Theodore Leng, MD, FACS

All Publications

• Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration: Secondary Analysis of a Randomized Clinical Trial JAMA OPHTHALMOLOGY Hallak, J. A., de Sisternes, L., Osborne, A., Yaspan, B., Rubin, D. L., Leng, T. 2019; 137 (7): 738–44

  View details for DOI 10.1001/jamaophthalmol.2019.0868

  View details for Web of Science ID 000481513900003

• Imaging, Genetic, and Demographic Factors Associated With Conversion to Neovascular Age-Related Macular Degeneration: Secondary Analysis of a Randomized Clinical Trial. JAMA ophthalmology Hallak, J. A., de Sisternes, L., Osborne, A., Yaspan, B., Rubin, D. L., Leng, T. 2019

  Abstract

  Importance: Risk factors associated with the development of neovascular age-related macular degeneration (AMD) have been identified. However, population size and methods to integrate imaging, genetic, and demographic factors associated with conversion to neovascular AMD are limited, specifically when treatment is administered in 1 eye.Objective: To determine the imaging, genetic, and demographic factors associated with conversion from nonneovascular to neovascular AMD in fellow eyes.Design, Setting, and Participants: This post hoc secondary analysis of the 24-month phase 3 multicenter, double-masked, active treatment-controlled HARBOR trial included 686 fellow eyes with nonneovascular AMD at baseline. Imaging features describing the presence, number, extent, density, and relative reflectivity of drusen were automatically extracted from spectral-domain optical coherence tomography scans. Genetic analysis included 34 single-nucleotide polymorphisms. Least absolute shrinkage and selection operator regression was performed to narrow imaging features. Survival analysis and Cox proportional hazards regression were performed to determine the association of the selected imaging features and genetic and demographic factors with conversion to neovascular AMD. Data were collected from November 2016 through October 2017 and analyzed from October 2017 through October 2018.Exposure: Nonneovascular AMD in the fellow eye.Main Outcomes and Measures: Features associated with conversion to neovascular AMD. Hazard ratios (HRs) and their 95% CIs were calculated.Results: Among the 686 fellow eyes included in the analysis (406 [59.2%] women; mean [SD] age, 78.12 [8.28] years), 154 (22.4%) converted to neovascular AMD. Female sex was significantly associated with conversion to neovascular AMD (HR,1.57; 95% CI, 1.11-2.20; P=.009). After controlling for demographic and treatment effects, drusen area within 3 mm of the fovea (HR, 1.45; 95% CI, 1.24-1.69; HR for 1-SD increase, 1.36 [95% CI, 1.20-1.54]) and mean drusen reflectivity (HR, 3.97; 95% CI, 1.11-14.18; HR for 1-SD increase, 1.32 [95% CI, 1.02-1.71]) were significantly associated with conversion to neovascular AMD. In addition, 1 genetic variant (rs61941274) was found to be associated with conversion to neovascular AMD.Conclusions and Relevance: Two imaging features (total en face area of drusen restricted to a circular area 3 mm from the fovea and mean drusen reflectivity) and 1 genetic variant (ACAD10 locus) were associated with conversion to neovascular AMD. Drusen characteristics may be associated with conversion to neovascular AMD despite treatment in 1 eye.Trial Registration: ClinicalTrials.gov identifier: NCT00891735.

  View details for PubMedID 31021381

• Preventing Progression in Nonexudative Age-Related Macular Degeneration With Subthreshold Laser Therapy: A Systematic Review OPHTHALMIC SURGERY LASERS & IMAGING RETINA Eng, V. A., Wood, E. H., Boddu, S., Karth, P. A., Leng, T. 2019; 50 (3): E61–E70

  Abstract

  Age-related macular degeneration (AMD) is the leading cause of irreversible blindness among the elderly in developed countries. Subthreshold retinal laser therapy is a new technique that targets drusen - a marker of nonexudative AMD - without causing incidental retinal damage associated with conventional laser photocoagulation. This review summarizes published literature on subthreshold retinal laser therapy as prophylactic treatment of nonexudative AMD.A literature search of the PubMed, Medline, and Embase databases was conducted from January 1997 to April 2018. Studies were analyzed based upon study design, laser parameters, drusen reduction, changes in visual acuity (VA), and the development of choroidal neovascularization (CNV) and/or geographic atrophy (GA).Twelve studies involving 2,481 eyes treated with subthreshold retinal laser therapy were included in this review. Treatment led to increased drusen reduction, and studies with significant VA improvement were associated with significant drusen reduction. There was no significant change in the risk of developing CNV or GA.Subthreshold retinal laser therapy is effective for reducing drusen and potentially improving vision in patients with nonexudative AMD. This therapy does not show benefits in reducing development of CNV or GA. Thus, its long-term efficacy to prevent progression to advanced AMD cannot yet be recommended. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:e61-e70.].

  View details for DOI 10.3928/23258160-20190301-13

  View details for Web of Science ID 000462056800003

  View details for PubMedID 30893458

• Thomas A. Swift's Electric Rifle Injuries to the Eye and Ocular Adnexa: The Management of Complex Trauma. Ophthalmology. Retina Moysidis, S. N., Koulisis, N., Rodger, D. C., Chao, J. R., Leng, T., de Carlo, T., Burkemper, B., Ediriwickrema, L. S., George, M. S., Jiang, Y., Bohm, K. J., Gulati, S., Torres, R. J., Meallet, M. A., Moshfeghi, A. A., Flynn, H. W., Mieler, W. F., Williams, G. A., Humayun, M. S., Eliott, D. 2019; 3 (3): 258–69

  Abstract

  To report the ocular and adnexal injuries sustained by patients with Thomas A. Swift's electric rifles (TASER; TASER International, Scottsdale, AZ), review the literature, and discuss the management of this complex trauma.Multicenter, retrospective case series and literature review.Seventeen eyes of 16 patients (5 eyes of 5 patients treated at 3 institutions, and 12 eyes of 11 previously reported cases).The clinical data of 17 eyes were pooled. Spearman's correlation coefficient was used to assess the association between the extent of TASER injury and patient outcomes.Extent of TASER injury (zone of injury, penetrating vs. perforating) and association with patient outcomes (visual acuity [VA] and retinal detachment [RD]).In our cohort, 4 patients were transported by law enforcement and 1 was transferred from a community hospital. Four patients were taken to the operating room for TASER removal and globe repair; 1 patient underwent removal in the emergency room. Of 17 pooled cases, 12 (71%) involved open-globe injury. Of these, there was a high rate of zone 3 injuries (100%; n = 12) and a high incidence of RD (73%; 8 of 11, eviscerated eye excluded). Among patients with closed-globe injury (n = 5), 1 patient demonstrated exudative RD and 1 patient demonstrated retinal dialysis with RD. Of 10 patients with RD, 1 (10%) achieved resolution with monitoring (exudative RD); 1 (10%) underwent cryopexy and pneumatic retinopexy; 3 (30%) underwent vitrectomy, and 5 (50%) with poor prognosis did not undergo vitreoretinal surgery. In the 3 patients who underwent vitrectomy, all 3 (100%) demonstrated redetachment resulting from proliferative vitreoretinopathy and required additional surgery. Visual acuity on presentation was significantly correlated with final VA (ρ = 0.783; P = 0.02). Men (94%) were more likely than women (6%) to sustain TASER trauma. Median age was 26 years. There was a 50% rate of loss to follow-up.Thomas A. Swift's electric rifle injuries to the eyes or ocular adnexa represent complex trauma. Zone 3 injuries are common. The visual prognosis is guarded, and eyes may require multiple surgeries to preserve vision. Patients are at high risk for loss to follow-up by way of incarceration.

  View details for PubMedID 31014704

• Automatically Determining the Confocal Parameters From OCT B-Scans for Quantification of the Attenuation Coefficients IEEE TRANSACTIONS ON MEDICAL IMAGING Dwork, N., Smith, G. T., Leng, T., Pauly, J. M., Bowden, A. K. 2019; 38 (1): 261–68

  Abstract

  The attenuation coefficient is a relevant biomarker for many diagnostic medical applications. Recently, the Depth-Resolved Confocal (DRC) technique was developed to automatically estimate the attenuation coefficients from Optical Coherence Tomography (OCT) data with pixel-level resolution. However, DRC requires that the confocal function parameters (i.e., focal plane location and apparent Rayleigh range) be known a priori. In this paper, we present the autoConfocal algorithm: a simple, automatic method for estimating those parameters directly from OCT imagery when the focal plane is within the sample. We present autoConfocal+DRC results on phantom data, ex-vivo biological tissue data, and in-vivo clinical data.

  View details for DOI 10.1109/TMI.2018.2861570

  View details for Web of Science ID 000455110500025

  View details for PubMedID 30072317

• Reductions in final visual acuity occur even within the first 3 days after a macula-off retinal detachment. The British journal of ophthalmology Greven, M. A., Leng, T., Silva, R. A., Leung, L. B., Karth, P. A., Moshfeghi, D. M., Sanislo, S. R., Schachar, I. H. 2018

  Abstract

  PURPOSE: To determine if final visual acuity (VA) is affected by duration of macular detachment (DMD) within the first week of macula-off retinal detachment (RD).METHODS: This is a retrospective study of eyes that underwent repair within 7 days with vitrectomy or vitrectomy with scleral buckle for macula-off RD at Stanford University Hospital between 1 May 2007 and 1 May 2017. A generalised linear model was constructed using DMD, postoperative lens status, preoperative VA, patient age and surgeon as the independent variables and the final VA as the dependent variable. The main outcome measure was the final VA.RESULTS: Seventy-nine eyes met the entry criteria. Group 1 included 52 eyes with RD repaired within 3 days of DMD, and group 2 included 27 eyes repaired between 4 and 7 days of DMD. The average final VA in group 1 eyes was logarithm of the minimum angle of resolution (logMAR) 0.21 (Snellen 20/33) and in group 2 eyes was logMAR 0.54 (Snellen 20/69). In group 1 and group 2 eyes, preoperative VA (p=0.017and p=0.007), DMD (p=0.004 and p=0.041) and final lens status (p<0.0001and p<0.001) predicted postoperative VA. Post-hoc analysis showed significant differences in final VA between detachments of 1day vs 3 days (p=0.0009).CONCLUSION: DMD affects the final VA even among patients whose DMD is <3 days. Based on these results, interventions that shorten DMD, including those occurring within the first 3days, may result in improved long-term VA outcomes.

  View details for PubMedID 30504489

• Micro-RNAs in the pathogenesis of epiretinal membrane (ERM) formation Kaidonis, G., Stary, C. M., Leng, T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442932805293

• Automatic identification of referral-warranted diabetic retinopathy using deep learning on mobile phone images Leng, T., Greven, M., Smith, S., Ludwig, C., Chang, R., Gargeya, R. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912505027

• Progressive Reductions in Acuity Occur even within the First Three Days After a Macula-Off Retinal Detachment Greven, M., Leng, T., Leung, L., Moshfeghi, D. M., Sanislo, S., Silva, R., Schachar, I. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2018

  View details for Web of Science ID 000442912503092

• Beyond Retinal Layers: A Deep Voting Model for Automated Geographic Atrophy Segmentation in SD-OCT Images TRANSLATIONAL VISION SCIENCE & TECHNOLOGY Ji, Z., Chen, Q., Niu, S., Leng, T., Rubin, D. L. 2018; 7 (1): 1

  Abstract

  To automatically and accurately segment geographic atrophy (GA) in spectral-domain optical coherence tomography (SD-OCT) images by constructing a voting system with deep neural networks without the use of retinal layer segmentation.An automatic GA segmentation method for SD-OCT images based on the deep network was constructed. The structure of the deep network was composed of five layers, including one input layer, three hidden layers, and one output layer. During the training phase, the labeled A-scans with 1024 features were directly fed into the network as the input layer to obtain the deep representations. Then a soft-max classifier was trained to determine the label of each individual pixel. Finally, a voting decision strategy was used to refine the segmentation results among 10 trained models.Two image data sets with GA were used to evaluate the model. For the first dataset, our algorithm obtained a mean overlap ratio (OR) 86.94% ± 8.75%, absolute area difference (AAD) 11.49% ± 11.50%, and correlation coefficients (CC) 0.9857; for the second dataset, the mean OR, AAD, and CC of the proposed method were 81.66% ± 10.93%, 8.30% ± 9.09%, and 0.9952, respectively. The proposed algorithm was capable of improving over 5% and 10% segmentation accuracy, respectively, when compared with several state-of-the-art algorithms on two data sets.Without retinal layer segmentation, the proposed algorithm could produce higher segmentation accuracy and was more stable when compared with state-of-the-art methods that relied on retinal layer segmentation results. Our model may provide reliable GA segmentations from SD-OCT images and be useful in the clinical diagnosis of advanced nonexudative AMD.Based on the deep neural networks, this study presents an accurate GA segmentation method for SD-OCT images without using any retinal layer segmentation results, and may contribute to improved understanding of advanced nonexudative AMD.

  View details for PubMedID 29302382

• Automated detection of foveal center in SD-OCT images using the saliency of retinal thickness maps MEDICAL PHYSICS Niu, S., Chen, Q., de Sisternes, L., Leng, T., Rubin, D. L. 2017; 44 (12): 6390–6403

  View details for DOI 10.1002/mp.12614

  View details for Web of Science ID 000425379200027

• Valved 25-Gauge Cannula for Vitreous Tap and Injection OPHTHALMIC SURGERY LASERS & IMAGING RETINA Leng, T., Moshfeghi, D. M. 2017; 48 (11): 916–17

  Abstract

  To describe a technique that reduces patient discomfort by using a valved 25-gauge trocar for vitreous tap and intravitreal injection of medications in previously vitrectomized eyes with suspected infectious endophthalmitis.A commercially available 25-gauge valved entry system is used to enter the vitreous cavity. A 25-gauge needle attached to a syringe is used to obtain a vitreous specimen for microbiological access and administer intravitreal injections of antibiotics and steroids. No vitreous volume is lost during these procedures because of the cannula's valve. At the completion of the tap and injections, the cannula is removed with forceps and the single wound tamponaded with a cotton-tipped applicator.With this method, a vitreous tap and injection of pharmacologic agents only requires one piercing through the sclera, instead of the usual four piercings.With this new technique, it is possible to enhance patient comfort, decreased pain, and reduce trauma to the conjunctiva. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:916-917.].

  View details for DOI 10.3928/23258160-20171030-07

  View details for Web of Science ID 000418012200007

  View details for PubMedID 29121361

• En Face Optical Coherence Tomography Angiography Imaging Versus Fundus Photography in the Measurement of Choroidal Nevi OPHTHALMIC SURGERY LASERS & IMAGING RETINA Lee, M. D., Kaidonis, G., Kim, A. Y., Shields, R. A., Leng, T. 2017; 48 (9): 741–47

  Abstract

  Choroidal nevi are common benign intraocular tumors with a small risk of malignant transformation. This retrospective study investigates the use of en face spectral-domain optical coherence tomography angiography (SD-OCTA) in determining the clinical features and measurement of choroidal nevi.Patients with choroidal nevi were imaged with both OCTA and a fundus photography device. Greatest longitudinal dimension (GLD), perpendicular dimension (PD), and the GLD/PD ratio were assessed on each device. Inter-device variation and intra- and inter-rater reliability analyses were performed.Fourteen patients with choroidal nevi were included. No significant difference between the GLD/PD ratio as measured by all three devices was found (Chi-square = 2.8, 2 df, P = .247). Intraclass correlation coefficients were greater than 0.7 for repeated measures on all devices, suggesting good repeatability and reproducibility.This study demonstrated inter-device consistency and high intra- and inter-rater reliability when measuring choroidal nevi. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:741-747.].

  View details for DOI 10.3928/23258160-20170829-09

  View details for Web of Science ID 000416072300008

  View details for PubMedID 28902335

• The superficial and deep retinal capillary plexus in cases of fovea plana imaged by spectral-domain optical coherence tomography angiography. American journal of ophthalmology case reports Kaidonis, G., Silva, R. A., Sanislo, S. R., Leng, T. 2017; 6: 41–44

  Abstract

  Purpose: To describe the appearance of the superficial and deep retinal capillary plexi in three patients with fovea plana of differing severity using spectral-domain optical coherence tomography angiography (OCTA).Observations: In the first case of grade 1 fovea plana (a patient with 20/25 vision), OCTA showed an orderly branching pattern of vessels from the superficial and deep retinal plexi extending to the center of the fovea. The second case of grade 3 fovea plana (20/30 vision) showed some disruption of the orderly vascular pattern with small caliber vessels from both superficial and deep layers densely covering the fovea center. Case 3 represented a patient with grade 4 fovea plana associated with PAX6 mutation and poor visual acuity. OCTA revealed a disorganized pattern of large and small caliber vessels from the superficial capillary network extending into the center of the fovea.Conclusions and importance: Previously available imaging modalities were unable to specifically target different layers of the retinal vasculature. Using OCTA we have been able to show progressive changes in the vascular pattern in the deep and superficial retinal layers of patients with different grades of fovea plana. This novel imaging technique may play a role in the classification and assessment of patients with fovea plana.

  View details for PubMedID 29260054

• Automated intraretinal segmentation of SD-OCT images in normal and age-related macular degeneration eyes BIOMEDICAL OPTICS EXPRESS de Sisternes, L., Jonna, G., Moss, J., Marmor, M. F., Leng, T., Rubin, D. L. 2017; 8 (3): 1926-1949

  Abstract

  This work introduces and evaluates an automated intra-retinal segmentation method for spectral-domain optical coherence (SD-OCT) retinal images. While quantitative assessment of retinal features in SD-OCT data is important, manual segmentation is extremely time-consuming and subjective. We address challenges that have hindered prior automated methods, including poor performance with diseased retinas relative to healthy retinas, and data smoothing that obscures image features such as small retinal drusen. Our novel segmentation approach is based on the iterative adaptation of a weighted median process, wherein a three-dimensional weighting function is defined according to image intensity and gradient properties, and a set of smoothness constraints and pre-defined rules are considered. We compared the segmentation results for 9 segmented outlines associated with intra-retinal boundaries to those drawn by hand by two retinal specialists and to those produced by an independent state-of-the-art automated software tool in a set of 42 clinical images (from 14 patients). These images were obtained with a Zeiss Cirrus SD-OCT system, including healthy, early or intermediate AMD, and advanced AMD eyes. As a qualitative evaluation of accuracy, a highly experienced third independent reader blindly rated the quality of the outlines produced by each method. The accuracy and image detail of our method was superior in healthy and early or intermediate AMD eyes (98.15% and 97.78% of results not needing substantial editing) to the automated method we compared against. While the performance was not as good in advanced AMD (68.89%), it was still better than the manual outlines or the comparison method (which failed in such cases). We also tested our method's performance on images acquired with a different SD-OCT manufacturer, collected from a large publicly available data set (114 healthy and 255 AMD eyes), and compared the data quantitatively to reference standard markings of the internal limiting membrane and inner boundary of retinal pigment epithelium, producing a mean unsigned positioning error of 6.04 ± 7.83µm (mean under 2 pixels). Our automated method should be applicable to data from different OCT manufacturers and offers detailed layer segmentations in healthy and AMD eyes.

  View details for DOI 10.1364/BOE.8.001926

  View details for Web of Science ID 000395942600047

  View details for PubMedCentralID PMC5480589

• Individual Drusen Segmentation and Repeatability and Reproducibility of Their Automated Quantification in Optical Coherence Tomography Images. Translational vision science & technology de Sisternes, L., Jonna, G., Greven, M. A., Chen, Q., Leng, T., Rubin, D. L. 2017; 6 (1): 12-?

  Abstract

  To introduce a novel method to segment individual drusen in spectral-domain optical coherence tomography (SD-OCT), and evaluate its accuracy, and repeatability/reproducibility of drusen quantifications extracted from the segmentation results.Our method uses a smooth interpolation of the retinal pigment epithelium (RPE) outer boundary, fitted to candidate locations in proximity to Bruch's Membrane, to identify regions of substantial lifting in the inner-RPE or inner-segment boundaries, and then separates and evaluates individual druse independently. The study included 192 eyes from 129 patients. Accuracy of drusen segmentations was evaluated measuring the overlap ratio (OR) with manual markings, also comparing the results to a previously proposed method. Repeatability and reproducibility across scanning protocols of automated drusen quantifications were investigated in repeated SD-OCT volume pairs and compared with those measured by a commercial tool (Cirrus HD-OCT).Our segmentation method produced higher accuracy than a previously proposed method, showing similar differences to manual markings (0.72 ± 0.09 OR) as the measured intra- and interreader variability (0.78 ± 0.09 and 0.77 ± 0.09, respectively). The automated quantifications displayed high repeatability and reproducibility, showing a more stable behavior across scanning protocols in drusen area and volume measurements than the commercial software. Measurements of drusen slope and mean intensity showed significant differences across protocols.Automated drusen outlines produced by our method show promising accurate results that seem relatively stable in repeated scans using the same or different scanning protocols.The proposed method represents a viable tool to measure and track drusen measurements in early or intermediate age-related macular degeneration patients.

  View details for DOI 10.1167/tvst.6.1.12

  View details for PubMedID 28275527

  View details for PubMedCentralID PMC5338477

• Spectral Domain Optical Coherence Tomography Angiography in Stargardt's Macular Dystrophy. Ophthalmology. Retina Lee, M., Kaidonis, G., Leng, T. 2017; 1 (5): 452–54

  View details for PubMedID 31047578

• Automated detection of foveal center in SD-OCT images using the saliency of retinal thickness maps. Medical physics Niu, S., Chen, Q., de Sisternes, L., Leng, T., Rubin, D. L. 2017; 44 (12): 6390–6403

  Abstract

  To develop an automated method based on saliency map of the retinal thickness map to determine foveal center in spectral-domain optical coherence tomography (SD-OCT) images.This paper proposes an automatic method for the detection of the foveal center in SD-OCT images. Initially, a retinal thickness map is generated by considering the axial distance between the internal limiting membrane (ILM) and the Bruch's membrane (BM). Both the ILM and BM boundaries are automatically segmented by a known retinal segmentation technique. The macular foveal region is identified as a salient feature in the retinal thickness map, and segmented by the saliency detection method based on a human vision attention model. Finally, the foveal center is identified by searching for the lowest point from the determined macular fovea region.Experimental results in 39 scans from 35 healthy eyes and 58 scans from 29 eyes diagnosed with several stages of age-related macular degeneration (AMD), from mild or intermediate stages to severe dry or wet stages, demonstrated that the proposed method achieves good performance. The mean radial distance error of the automatically detected foveal center locations when compared to consensus manual determination established by repeated sessions from two expert readers was 52 ± 56 μm for the normal eyes and 73 ± 63 μm for AMD eyes.The proposed algorithm was more effective for detecting the foveal center automatically in SD-OCT images than the state-of-art methods.

  View details for PubMedID 28976639

• Automated intraretinal segmentation of SD-OCT images in normal and age-related macular degeneration eyes. Biomedical optics express de Sisternes, L., Jonna, G., Moss, J., Marmor, M. F., Leng, T., Rubin, D. L. 2017; 8 (3): 1926–49

  Abstract

  This work introduces and evaluates an automated intra-retinal segmentation method for spectral-domain optical coherence (SD-OCT) retinal images. While quantitative assessment of retinal features in SD-OCT data is important, manual segmentation is extremely time-consuming and subjective. We address challenges that have hindered prior automated methods, including poor performance with diseased retinas relative to healthy retinas, and data smoothing that obscures image features such as small retinal drusen. Our novel segmentation approach is based on the iterative adaptation of a weighted median process, wherein a three-dimensional weighting function is defined according to image intensity and gradient properties, and a set of smoothness constraints and pre-defined rules are considered. We compared the segmentation results for 9 segmented outlines associated with intra-retinal boundaries to those drawn by hand by two retinal specialists and to those produced by an independent state-of-the-art automated software tool in a set of 42 clinical images (from 14 patients). These images were obtained with a Zeiss Cirrus SD-OCT system, including healthy, early or intermediate AMD, and advanced AMD eyes. As a qualitative evaluation of accuracy, a highly experienced third independent reader blindly rated the quality of the outlines produced by each method. The accuracy and image detail of our method was superior in healthy and early or intermediate AMD eyes (98.15% and 97.78% of results not needing substantial editing) to the automated method we compared against. While the performance was not as good in advanced AMD (68.89%), it was still better than the manual outlines or the comparison method (which failed in such cases). We also tested our method's performance on images acquired with a different SD-OCT manufacturer, collected from a large publicly available data set (114 healthy and 255 AMD eyes), and compared the data quantitatively to reference standard markings of the internal limiting membrane and inner boundary of retinal pigment epithelium, producing a mean unsigned positioning error of 6.04 ± 7.83µm (mean under 2 pixels). Our automated method should be applicable to data from different OCT manufacturers and offers detailed layer segmentations in healthy and AMD eyes.

  View details for PubMedID 28663874

• Manual Removal of Intraocular Lens Silicone Oil Droplets and Dystrophic Calcifications Using a Nitinol Loop: A Case Series. Ophthalmic surgery, lasers & imaging retina Moussa, K., Leng, T., Oatts, J. T., Bhisitkul, R. B., Hwang, D. G., Stewart, J. M. 2017; 48 (5): 422–26

  Abstract

  Deposition of dystrophic calcifications on the posterior surface of silicone intraocular lenses (IOLs) has been reported in patients with asteroid hyalosis. Accumulation of silicone oil droplets on the posterior surface of silicone IOLs in silicone-filled eyes has also been reported. Recently, a novel technique to manually remove dystrophic calcifications using a nickel titanium loop (Finesse Flex Loop; Alcon, Fort Worth, TX) was described, obviating the need for IOL exchange. Here, the authors report their outcomes with this technique in five eyes with IOL dystrophic calcifications as well as one eye with IOL silicone oil droplet accumulation. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:422-426.].

  View details for DOI 10.3928/23258160-20170428-09

  View details for PubMedID 28499054

• Automated Identification of Diabetic Retinopathy Using Deep Learning. Ophthalmology Gargeya, R., Leng, T. 2017

  Abstract

  Diabetic retinopathy (DR) is one of the leading causes of preventable blindness globally. Performing retinal screening examinations on all diabetic patients is an unmet need, and there are many undiagnosed and untreated cases of DR. The objective of this study was to develop robust diagnostic technology to automate DR screening. Referral of eyes with DR to an ophthalmologist for further evaluation and treatment would aid in reducing the rate of vision loss, enabling timely and accurate diagnoses.We developed and evaluated a data-driven deep learning algorithm as a novel diagnostic tool for automated DR detection. The algorithm processed color fundus images and classified them as healthy (no retinopathy) or having DR, identifying relevant cases for medical referral.A total of 75 137 publicly available fundus images from diabetic patients were used to train and test an artificial intelligence model to differentiate healthy fundi from those with DR. A panel of retinal specialists determined the ground truth for our data set before experimentation. We also tested our model using the public MESSIDOR 2 and E-Ophtha databases for external validation. Information learned in our automated method was visualized readily through an automatically generated abnormality heatmap, highlighting subregions within each input fundus image for further clinical review.We used area under the receiver operating characteristic curve (AUC) as a metric to measure the precision-recall trade-off of our algorithm, reporting associated sensitivity and specificity metrics on the receiver operating characteristic curve.Our model achieved a 0.97 AUC with a 94% and 98% sensitivity and specificity, respectively, on 5-fold cross-validation using our local data set. Testing against the independent MESSIDOR 2 and E-Ophtha databases achieved a 0.94 and 0.95 AUC score, respectively.A fully data-driven artificial intelligence-based grading algorithm can be used to screen fundus photographs obtained from diabetic patients and to identify, with high reliability, which cases should be referred to an ophthalmologist for further evaluation and treatment. The implementation of such an algorithm on a global basis could reduce drastically the rate of vision loss attributed to DR.

  View details for PubMedID 28359545

• Significant Bilateral Response in Diabetic Macular Edema After Single Unilateral Intravitreal Aflibercept Injection. Ophthalmic surgery, lasers & imaging retina Rahimy, E., Nyong'o, O., Leng, T. 2017; 48 (2): 167-169

  Abstract

  A 61-year-old patient with bilateral, treatment-naïve, diffuse diabetic macular edema (DME) that had been progressing during the previous 12 months received a single intravitreal injection of aflibercept (Eylea; Regeneron, Tarrytown, NY) to the left eye. At 2-week follow-up, noticeable bilateral improvement of the DME was observed by spectral-domain optical coherence tomography imaging with commensurate improvement of visual acuity to 20/30 bilaterally. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:167-169.].

  View details for DOI 10.3928/23258160-20170130-11

  View details for PubMedID 28195620

• Retinotomy Closure Following Subretinal Stem Cell Transplant With a 30-Gauge Needle. Ophthalmic surgery, lasers & imaging retina Ludwig, C. A., Leng, T. 2016; 47 (9): 869-873

  Abstract

  The authors report two cases of posterior retinotomy closure following subretinal stem cell transplantation for age-related macular degeneration with a 30-gauge needle - a larger bore needle than those used in prior studies. Partial retinotomy closure was seen on optical coherence tomography within 24 hours in one patient, whereas complete closure occurred by the 5-month and 1-year follow-up visits. A trace retinal hemorrhage occurred in one case, with resolution by 12 weeks. These findings demonstrate the likelihood of uncomplicated, spontaneous retinotomy closure following subretinal stem cell transplantation with a 30-gauge needle. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:869-873.].

  View details for DOI 10.3928/23258160-20160901-12

  View details for PubMedID 27631485

• Fully Automated Prediction of Geographic Atrophy Growth Using Quantitative Spectral-Domain Optical Coherence Tomography Biomarkers. Ophthalmology Niu, S., de Sisternes, L., Chen, Q., Rubin, D. L., Leng, T. 2016; 123 (8): 1737-1750

  Abstract

  To develop a predictive model based on quantitative characteristics of geographic atrophy (GA) to estimate future potential regions of GA growth.Progression study and predictive model.One hundred eighteen spectral-domain (SD) optical coherence tomography (OCT) scans of 38 eyes in 29 patients.Imaging features of GA quantifying its extent and location, as well as characteristics at each topographic location related to individual retinal layer thickness and reflectivity, the presence of pathologic features (like reticular pseudodrusen or loss of photoreceptors), and other known risk factors of GA growth, were extracted automatically from 118 SD OCT scans of 38 eyes from 29 patients collected over a median follow-up of 2.25 years. We developed and evaluated a model to predict the magnitude and location of GA growth at given future times using the quantitative features as predictors in 3 possible scenarios.Potential regions of GA growth.In descending order of out-of-bag feature importance, the most predictive SD OCT biomarkers for predicting the future regions of GA growth were thickness loss of bands 11 through 14 (5.66), reflectivity of bands 11 and 12 (5.37), thickness of reticular pseudodrusen (5.01), thickness of bands 5 through 11 (4.82), reflectivity of bands 7 through 11 (4.78), GA projection image (4.73), increased minimum retinal intensity map (4.59), and GA eccentricity (4.49). The predicted GA regions in the 3 tested scenarios resulted in a Dice index mean ± standard deviation of 0.81±0.12, 0.84±0.10, and 0.87±0.06, respectively, when compared with the observed ground truth. Considering only the regions without evidence of GA at baseline, predicted regions of future GA growth showed relatively high Dice indices of 0.72±0.18, 0.74±0.17, and 0.72±0.22, respectively. Predictions and actual values of GA growth rate and future GA involvement in the central fovea showed high correlations.Experimental results demonstrated the potential of our predictive model to predict future regions where GA is likely to grow and to identify the most discriminant early indicator (thickness loss of bands 11 through 14) of regions susceptible to GA growth.

  View details for DOI 10.1016/j.ophtha.2016.04.042

  View details for PubMedID 27262765

• En Face Imaging of Epiretinal Membranes and the Retinal Nerve Fiber Layer Using Swept-Source Optical Coherence Tomography. Ophthalmic surgery, lasers & imaging retina Greven, M. A., Elkin, Z., Nelson, R. W., Leng, T. 2016; 47 (8): 730-734

  Abstract

  To describe en face swept-source optical coherence tomography (SS-OCT) imaging of epiretinal membranes (ERMs) and the underlying retinal nerve fiber layer (RNFL).SS-OCT images were captured in nine eyes with ERMs. These SS-OCT en face images were qualitatively compared to spectral-domain OCT (SD-OCT) en face images. Using SS-OCT, en face images of the RNFL were obtained, if possible.En face SS-OCT images of ERMs were obtained in all nine eyes of eight individuals with clinically diagnosed ERMs that were superior to SD-OCT images. Clear en face images of the RNFL were acquired in seven of nine eyes (78%) using SS-OCT.SS-OCT is a novel method for generating en face images of ERMs. Compared with SDOCT en face images, SS-OCT could more clearly identify the plaques and folds of ERMs and underlying defects in the RNFL. Such images could be useful for surgical planning and assessment of the integrity of the underlying RNFL. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:730-734.].

  View details for DOI 10.3928/23258160-20160808-06

  View details for PubMedID 27548450

• 8 Questions with Dr. Moshfeghi. Ophthalmic surgery, lasers & imaging retina Leng, T., Moshfeghi, D. M. 2016; 47 (8): 786-788

  View details for DOI 10.3928/23258160-20160808-15

  View details for PubMedID 27548459

• PROSPECTIVE TRIAL OF ENDOGENOUS FUNGAL ENDOPHTHALMITIS AND CHORIORETINITIS RATES, CLINICAL COURSE, AND OUTCOMES IN PATIENTS WITH FUNGEMIA RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Paulus, Y. M., Cheng, S., Karth, P. A., Leng, T. 2016; 36 (7): 1357-1363

  Abstract

  Former studies have found rates of endogenous endophthalmitis ranging from 0% to 37% in patients with fungemia. This study sought to prospectively determine the rate and risk factors for endogenous chorioretinitis and endophthalmitis in patients with fungemia.A prospective cohort study was performed of consecutive adult inpatients at a single site from 2010 to 2013 of patients with positive blood cultures for fungus. One hundred and nineteen pieces of information were gathered for each patient.A total of 125 patients were enrolled in the study with 7 positive cases of chorioretinitis for a rate of 5.6%. Of these positive cases, 2 patients had endophthalmitis for a rate of 1.6%. Two patients who had a negative initial examination subsequently had a positive examination; 57% of the chorioretinitis patients who could report symptoms were asymptomatic, 57% of the chorioretinitis patients died, and 32% of negative cases died. Prolonged hospitalization, altered mental status, total parenteral nutrition, and gastrointestinal surgery were protective on univariate but not multivariate analysis.Despite modern antifungal therapy, fungal chorioretinitis and endophthalmitis continue to occur in patients with positive fungal cultures. Two dilated ophthalmic examinations should still be considered even in asymptomatic patients with fungemia.

  View details for DOI 10.1097/IAE.0000000000000919

  View details for Web of Science ID 000378595100036

  View details for PubMedID 26655621

• Factors Associated With Poor Response to Aflibercept After Switching From Ranibizumab or Bevacizumab in Neovascular Age-related Macular Degeneration OPHTHALMIC SURGERY LASERS & IMAGING RETINA Cheng, S., Leng, T. 2016; 47 (5): 458-465

  Abstract

  The purpose of this study was to analyze demographic and ocular features of patients with age-related macular degeneration who failed aflibercept (Eylea; Regeneron, Tarrytown, NY) treatment after switching from ranibizumab (Lucentis; Genentech, South San Francisco, CA) or bevacizumab (Avastin; Genentech, South San Francisco, CA).Retrospective chart review of patients treated with aflibercept at the Byers Eye Institute from November 2011 to August 2014. Patient visual acuity was noted prior to aflibercept; after 1, 3, and 12 months; and on the most recent visit. Patients who improved vision after switching were compared to patients who lost vision. Demographic and imaging features were analyzed using univariate and multivariate statistics.Patients who lost vision had significantly higher BMI (P = .013, multivariate) and geographic atrophy (P = .0381, univariate; P = .1, multivariate) compared to patients who improved vision.BMI and geographic atrophy may be considered as potential indicators for poor response to aflibercept after switching from ranibizumab or bevacizumab. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:458-465.].

  View details for DOI 10.3928/23258160-20160419-09

  View details for Web of Science ID 000378847000007

  View details for PubMedID 27183550

• Spectral-Domain Optical Coherence Tomography Angiography of Central Retinal Artery Occlusion OPHTHALMIC SURGERY LASERS & IMAGING RETINA Damento, G., Chen, M. H., Leng, T. 2016; 47 (5): 467-470

  Abstract

  The authors report the use of optical coherence tomography angiography (OCTA) to determine retinal blood flow in a patient with central retinal artery occlusion (CRAO). Spectral-domain OCTA (SD-OCTA) was performed on an eye with CRAO. En face vascular images were constructed using an optical microangiography algorithm. The retinal vasculature was clearly imaged with high fidelity; areas of perfused retina were identified with exquisite detail. This study supports use of OCTA in diagnosing and monitoring CRAOs. Future research is warranted to recognize full potential of this imaging modality. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:467-470.].

  View details for DOI 10.3928/23258160-20160419-10

  View details for Web of Science ID 000378847000008

  View details for PubMedID 27183551

• AFLIBERCEPT FOR THE TREATMENT OF RETINAL PIGMENT EPITHELIAL DETACHMENTS. Retina (Philadelphia, Pa.) He, L., Silva, R. A., Moshfeghi, D. M., Blumenkranz, M. S., Leng, T. 2016; 36 (3): 492-498

  Abstract

  To compare anatomical and visual acuity outcomes of eyes with persistent pigment epithelial detachments (PEDs) secondary to exudative age-related macular degeneration despite ranibizumab or bevacizumab treatment.After institutional review board approval, 40 eyes with PEDs switched from ranibizumab or bevacizumab to intravitreal aflibercept were compared for logMAR visual acuity, central subfield thickness on spectral domain optical coherence tomography, and PED height. Using paired t-tests, these parameters at baseline, after 3 consecutive injections, and 1 year after the switch were compared.Baseline visions of 20/61 ± 3.99 lines declined after 3 injections with aflibercept by 0.39 ± 2.43 lines (P = 0.32) and continued to fall after 1 year by 1.27 ± 3.48 lines (P = 0.03). Central subfield thickness was reduced after 3 injections (9.1 ± 52.0 μm, P = 0.27) and after 1 year (24.4 ± 55.3 μm, P = 0.01). The height of PEDs decreased by 31.7 ± 71.53 μm (P = 0.008) after 3 injections and by 47.81 ± 77.94 μm (P < 0.001) after 1 year.Switching to aflibercept from ranibizumab or bevacizumab resulted in a reduction in the height of PED and central subfield thickness, but a trend toward worse visual acuity 1 year after the switch.

  View details for DOI 10.1097/IAE.0000000000000749

  View details for PubMedID 26398694

• Multi-Modal Longitudinal Evaluation of Subthreshold Laser Lesions in Human Retina, Including Scanning Laser Ophthalmoscope-Adaptive Optics Imaging. Ophthalmic surgery, lasers & imaging retina Wood, E. H., Leng, T., Schachar, I. H., Karth, P. A. 2016; 47 (3): 268-275

  Abstract

  Subthreshold retinal laser therapy is efficacious for a variety of retinovascular disorders. Currently, it is unknown which laser parameters can ensure no detectable damage to human retina tissue.One informed physician participant with a normal retina was treated with three levels (75%, 50%, and 25%) of subthreshold 577-nm laser (PASCAL; Topcon, Santa Clara, CA) at 20-millisecond (ms) duration and 100 µm spot size. Several high-resolution retinal imaging modalities, including spectral-domain optical coherence tomography (SD-OCT) and scanning laser ophthalmoscope-adaptive optics (SLO-AO), were used to longitudinally image retinal laser lesions during a 9-month period.SLO-AO and SD-OCT imaging of subthreshold laser therapy in human retina showed no cone cell or RPE damage at all time points during a 9-month period using the 25% threshold power 577-nm laser in the human retina.It is likely that subthreshold laser therapy with 577-nm laser at 20-ms duration in the human retina is safe at the 25% of threshold power level. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:268-275.].

  View details for DOI 10.3928/23258160-20160229-10

  View details for PubMedID 26985801

• Mobile Health in the Retinal Clinic Population: Access to and Interest in Self-Tracking. Ophthalmic surgery, lasers & imaging retina Ludwig, C. A., Callaway, N. F., Park, J. H., Leng, T. 2016; 47 (3): 252-257

  Abstract

  Implementation of mobile health-tracking programs for retinal pathology requires both access to mobile devices and patient motivation to participate in self-tracking. The authors' study aimed to evaluate the prevalence of smartphone and tablet ownership and patient interest in self-tracking among a retinal clinic population.This is an institutional, prospective, cross-sectional survey of 103 retinal clinic outpatients. Consenting patients underwent a one-on-one interview conducted in the examination room during their waiting period by one researcher.Overall, 75 of 103 participants (72.2%) reported either owning a smartphone and/or tablet or having access at their household to a device that could be used to track eye health. The majority of participants (69 of 103 participants; 67%) reported interest in using a mobile application (smartphone or tablet) to track their eye health.These data suggest strong patient interest in the use of mobile devices to track eye health. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:252-257.].

  View details for DOI 10.3928/23258160-20160229-08

  View details for PubMedID 26985799

• THINKING LEAN: Improving Vitreoretinal Clinic Efficiency by Decentralizing Optical Coherence Tomography. Retina (Philadelphia, Pa.) Callaway, N. F., Park, J. H., Maya-Silva, J., Leng, T. 2016; 36 (2): 335-341

  Abstract

  Patients in vitreoretinal clinic have long wait times that could be reduced by improving the efficiency of patient flow. The objective of this study was to determine whether decentralizing optical coherence tomography (OCT) into the technicians' room would reduce patient wait times and improve clinic efficiency.Randomized, single-center, clinical trial for 1 month without follow-up at Byers Eye Institute at Stanford. Subjects were return patients of three vitreoretinal specialists in March 2013. The intervention consisted of decentralizing OCT devices from the central photography suite into the technician screening rooms. Total clinic times and total wait times throughout subject appointments were recorded and compared with the control group (centralized photography suite). Secondary outcomes included frequency of injections, procedures, and primary diagnosis codes.Decentralized OCT reduced patient wait times by 74% and reduced total clinic appointment time by 36%. Subjects in the intervention arm experienced significantly reduced total wait time (mean difference = 15.9 minutes, P < 0.0001) and total time in clinic (mean difference = 22.9 minutes, P < 0.0001).Decentralized OCT represents the application of lean process concepts to improve vitreoretinal clinic efficiency. Decentralized OCT reduced both the total wait time and total time in clinic for return patients in a vitreoretinal clinic.

  View details for DOI 10.1097/IAE.0000000000000712

  View details for PubMedID 26815931

• Improving Vitreoretinal Clinic Efficiency by Decentralizing Optical Coherence Tomography RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Callaway, N. F., Park, J. H., Maya-Silva, J., Leng, T. 2016; 36 (2): 335-341

  Abstract

  Patients in vitreoretinal clinic have long wait times that could be reduced by improving the efficiency of patient flow. The objective of this study was to determine whether decentralizing optical coherence tomography (OCT) into the technicians' room would reduce patient wait times and improve clinic efficiency.Randomized, single-center, clinical trial for 1 month without follow-up at Byers Eye Institute at Stanford. Subjects were return patients of three vitreoretinal specialists in March 2013. The intervention consisted of decentralizing OCT devices from the central photography suite into the technician screening rooms. Total clinic times and total wait times throughout subject appointments were recorded and compared with the control group (centralized photography suite). Secondary outcomes included frequency of injections, procedures, and primary diagnosis codes.Decentralized OCT reduced patient wait times by 74% and reduced total clinic appointment time by 36%. Subjects in the intervention arm experienced significantly reduced total wait time (mean difference = 15.9 minutes, P < 0.0001) and total time in clinic (mean difference = 22.9 minutes, P < 0.0001).Decentralized OCT represents the application of lean process concepts to improve vitreoretinal clinic efficiency. Decentralized OCT reduced both the total wait time and total time in clinic for return patients in a vitreoretinal clinic.

  View details for DOI 10.1097/IAE.0000000000000712

  View details for Web of Science ID 000369513500014

• Automated geographic atrophy segmentation for SD-OCT images using region-based C-V model via local similarity factor BIOMEDICAL OPTICS EXPRESS Niu, S., de Sisternes, L., Chen, Q., Leng, T., Rubin, D. L. 2016; 7 (2): 581-600

  Abstract

  Age-related macular degeneration (AMD) is the leading cause of blindness among elderly individuals. Geographic atrophy (GA) is a phenotypic manifestation of the advanced stages of non-exudative AMD. Determination of GA extent in SD-OCT scans allows the quantification of GA-related features, such as radius or area, which could be of important value to monitor AMD progression and possibly identify regions of future GA involvement. The purpose of this work is to develop an automated algorithm to segment GA regions in SD-OCT images. An en face GA fundus image is generated by averaging the axial intensity within an automatically detected sub-volume of the three dimensional SD-OCT data, where an initial coarse GA region is estimated by an iterative threshold segmentation method and an intensity profile set, and subsequently refined by a region-based Chan-Vese model with a local similarity factor. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to quantitatively evaluate the automated segmentation algorithm. We compared results obtained by the proposed algorithm, manual segmentation by graders, a previously proposed method, and experimental commercial software. When compared to a manually determined gold standard, our algorithm presented a mean overlap ratio (OR) of 81.86% and 70% for the first and second data sets, respectively, while the previously proposed method OR was 72.60% and 65.88% for the first and second data sets, respectively, and the experimental commercial software OR was 62.40% for the second data set.

  View details for DOI 10.1364/BOE.7.000581

  View details for Web of Science ID 000369247000029

  View details for PubMedCentralID PMC4771473

• Noninvasive detection of microaneurysms in diabetic retinopathy by swept-source optical coherence tomography. Clinical ophthalmology (Auckland, N.Z.) Cheng, S., Leng, T. 2016; 10: 1791-1795

  Abstract

  A method of identifying retinal vascular microaneurysms (MAs) in nonproliferative diabetic retinopathy (NPDR) using swept-source optical coherence tomography (SS-OCT).SS-OCT images were acquired in 17 eyes with NPDR using prototype SS-OCT device and fluorescein angiography (FA) images were obtained simultaneously. MAs identified on SS-OCT slabs were correlated to MAs identified on FA.MAs were identified in SS-OCT slabs in 15/17 eyes, resulting in NPDR diagnosis rate of 88%. Mean number of MAs identified on FA was 11.7±11.9 (total 199) and was 8.1±9.3 (total 137) on SS-OCT. Wilcoxon rank sum test showed no significant difference in MAs detected on SS-OCT and FA (P=0.2995) across eyes. Wilcoxon rank sum test showed SS-OCT detected slightly fewer MAs than FA per eye (3.65 less, P=0.0009).SS-OCT visualization of MAs could serve as a tool for diagnosing NPDR, and possibly applied as an imaging biomarker for population-based diabetic retinopathy screening.

  View details for PubMedID 27695284

• Automated geographic atrophy segmentation for SD-OCT images using region-based C-V model via local similarity factor. Biomedical optics express Niu, S., de Sisternes, L., Chen, Q., Leng, T., Rubin, D. L. 2016; 7 (2): 581–600

  Abstract

  Age-related macular degeneration (AMD) is the leading cause of blindness among elderly individuals. Geographic atrophy (GA) is a phenotypic manifestation of the advanced stages of non-exudative AMD. Determination of GA extent in SD-OCT scans allows the quantification of GA-related features, such as radius or area, which could be of important value to monitor AMD progression and possibly identify regions of future GA involvement. The purpose of this work is to develop an automated algorithm to segment GA regions in SD-OCT images. An en face GA fundus image is generated by averaging the axial intensity within an automatically detected sub-volume of the three dimensional SD-OCT data, where an initial coarse GA region is estimated by an iterative threshold segmentation method and an intensity profile set, and subsequently refined by a region-based Chan-Vese model with a local similarity factor. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to quantitatively evaluate the automated segmentation algorithm. We compared results obtained by the proposed algorithm, manual segmentation by graders, a previously proposed method, and experimental commercial software. When compared to a manually determined gold standard, our algorithm presented a mean overlap ratio (OR) of 81.86% and 70% for the first and second data sets, respectively, while the previously proposed method OR was 72.60% and 65.88% for the first and second data sets, respectively, and the experimental commercial software OR was 62.40% for the second data set.

  View details for PubMedID 26977364

• Optical Coherence Tomography-Guided Short-Duration Positioning after Macular Hole Surgery. Ophthalmology. Retina Greven, M. A., Cheng, S., Leng, T. 2016; 1 (2): 176–78.e1

  View details for PubMedID 31047280

• Automated segmentation of optic disc in SD-OCT images and cup-to-disc ratios quantification by patch searching-based neural canal opening detection OPTICS EXPRESS Wu, M., Leng, T., de Sisternes, L., Rubin, D. L., Chen, Q. 2015; 23 (24): 31216-31229

  Abstract

  Glaucoma is one of the most common causes of blindness worldwide. Early detection of glaucoma is traditionally based on assessment of the cup-to-disc (C/D) ratio, an important indicator of structural changes to the optic nerve head. Here, we present an automated optic disc segmentation algorithm in 3-D spectral domain optical coherence tomography (SD-OCT) volumes to quantify this ratio. The proposed algorithm utilizes a two-stage strategy. First, it detects the neural canal opening (NCO) by finding the points with maximum curvature on the retinal pigment epithelium (RPE) boundary with a spatial correlation smoothness constraint on consecutive B-scans, and it approximately locates the coarse disc margin in the projection image using convex hull fitting. Then, a patch searching procedure using a probabilistic support vector machine (SVM) classifier finds the most likely patch with the NCO in its center in order to refine the segmentation result. Thus, a reference plane can be determined to calculate the C/D radio. Experimental results on 42 SD-OCT volumes from 17 glaucoma patients demonstrate that the proposed algorithm can achieve high segmentation accuracy and a low C/D ratio evaluation error. The unsigned border error for optic disc segmentation and the evaluation error for C/D ratio comparing with manual segmentation are 2.216 ± 1.406 pixels (0.067 ± 0.042 mm) and 0.045 ± 0.033, respectively.

  View details for DOI 10.1364/OE.23.031216

  View details for Web of Science ID 000366614100094

  View details for PubMedID 26698750

• Intraocular Nematode Affixed to Posterior Lens Capsule. Ophthalmic surgery, lasers & imaging retina Karth, P. A., Swinney, C. C., Moshfeghi, D. M., Yannuzzi, L. A., Pang, C. E., Leng, T. 2015; 46 (10): 1066-1067

  Abstract

  The clinical presentation of an intraocular nematode unusually affixed to the posterior lens capsule is described. A 64-year-old female patient presented with a 7-year history of gradually declining vision and enlarging central scotoma, but no inflammation. On follow-up 2 years later, vision had further declined and a non-motile, 8-mm nematode was seen affixed to the posterior lens capsule that remained unchanged through final follow-up. The patient disclosed having resided in Africa as a child. Systemic review revealed no evidence of extraocular involvement. Nematode carcasses may remain preserved in the human eye for extended periods without ongoing inflammation.

  View details for DOI 10.3928/23258160-20151027-16

  View details for PubMedID 26599254

• Short-Term Outcomes of Aflibercept Therapy for Diabetic Macular Edema in Patients With Incomplete Response to Ranibizumab and/or Bevacizumab. Ophthalmic surgery, lasers & imaging retina Wood, E. H., Karth, P. A., Moshfeghi, D. M., Leng, T. 2015; 46 (9): 950-954

  Abstract

  Aflibercept is a vascular endothelial growth factor (VEGF) inhibitor recently approved by the U.S. Food and Drug Administration for the treatment of diabetic macular edema (DME). Currently, the effect of switching to aflibercept from other anti-VEGF agents for DME is unknown.In this prospective, interventional case series, DME patients with persistent retinal fluid despite regular (every 4 to 6 weeks) intravitreal injection (IVI) with ranibizumab 0.3 mg, and/or bevacizumab 1.25 mg were switched to IVI aflibercept 2 mg. Collected data included visual acuity, central subfield foveal thickness (CSFT), and the area of thickest edema on registered spectral-domain optical coherence tomography (SD-OCT).At 1 month after the first aflibercept IVI, 79% (11 of 14 eyes) showed anatomic improvement with a 23% decrease in average CSFT from 421 µm to 325 µm (P < .0132).A majority of patients with DME with persistent fluid on SD-OCT despite regular ranibizumab 0.3 mg and/or bevacizumab 1.25 mg IVIs showed a positive anatomic response to IVI aflibercept 2 mg. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:950-954.].

  View details for DOI 10.3928/23258160-20151008-08

  View details for PubMedID 26469235

• Restricted Summed-Area Projection for Geographic Atrophy Visualization in SD-OCT Images TRANSLATIONAL VISION SCIENCE & TECHNOLOGY Chen, Q., Niu, S., Shen, H., Leng, T., de Sisternes, L., Rubin, D. L. 2015; 4 (5)

  Abstract

  To enhance the rapid assessment of geographic atrophy (GA) across the macula in a single projection image generated from three-dimensional (3D) spectral-domain optical coherence tomography (SD-OCT) scans by introducing a novel restricted summed-area projection (RSAP) technique.We describe a novel en face GA visualization technique, the RSAP, by restricting the axial projection of SD-OCT images to the regions beneath the Bruch's membrane (BM) boundary and also considering the choroidal vasculature's influence on GA visualization. The technique analyzes the intensity distribution beneath the retinal pigment epithelium (RPE) layer to fit a cross-sectional surface in the sub-RPE region. The area is taken as the primary GA projection. A median filter is then adopted to smooth the generated GA projection image. The RSAP technique was evaluated in 99 3D SD-OCT data sets from 27 eyes of 21 patients presenting with advanced nonexudative age-related macular degeneration and GA. We used the mean difference between GA and background regions and GA separability metric to measure GA contrast and distinction in the generated images, respectively. We compared our results with two existing GA projection techniques, the summed-voxel projection (SVP) and Sub-RPE Slab techniques.Comparative results demonstrate that the RSAP technique is more effective in displaying GA than the SVP and Sub-RPE Slab. The average of the mean difference between GA and background regions and the GA separability based on SVP, Sub-RPE Slab, and RSAP were 0.129/0.880, 0.238/0.919, and 0.276/0.938, respectively.The RSAP technique was more effective for GA visualization than the conventional SVP and Sub-RPE Slab techniques. Our technique decreases choroidal vasculature influence on GA projection images by analyzing the intensity distribution characteristics in sub-RPE regions. The generated GA projection image with the RSAP technique has improved contrast and distinction.Our method for automated generation of GA projection images from SD-OCT images may improve the visualization of the macular abnormalities and the management of GA.

  View details for DOI 10.1167/tvst.4.5.2

  View details for Web of Science ID 000388661700002

  View details for PubMedID 26347016

  View details for PubMedCentralID PMC4559218

• Fabrication of healthy and disease-mimicking retinal phantoms with tapered foveal pits for optical coherence tomography. Journal of biomedical optics Lee, G. C., Smith, G. T., Agrawal, M., Leng, T., Ellerbee, A. K. 2015; 20 (8): 85004-?

  View details for DOI 10.1117/1.JBO.20.8.085004

  View details for PubMedID 26287985

• Fabrication of healthy and disease-mimicking retinal phantoms with tapered foveal pits for optical coherence tomography. Journal of biomedical optics Lee, G. C., Smith, G. T., Agrawal, M., Leng, T., Ellerbee, A. K. 2015; 20 (8): 85004-?

  View details for DOI 10.1117/1.JBO.20.8.085004

  View details for PubMedID 26287985

• Visual Prognosis of Eyes Recovering From Macular Hole Surgery Through Automated Quantitative Analysis of Spectral-Domain Optical Coherence Tomography (SD-OCT) Scans. Investigative ophthalmology & visual science de Sisternes, L., Hu, J., Rubin, D. L., Leng, T. 2015; 56 (8): 4631-4643

  Abstract

  To determine the value of topographic spectral-domain optical coherence tomography (SD-OCT) imaging features assessed after macular hole repair surgery in predicting visual acuity (VA) outcomes.An automated algorithm was developed to topographically outline and quantify area, extent, and location of defects in the ellipsoid zone (EZ) band and inner retina layers in SD-OCT scans. We analyzed the correlation of these values with VA in longitudinal observations from 35 patients who underwent successful macular hole surgery, in their first observation after surgery (within 2 months), and in a single observation within 6 to 12 months after surgery. Image features assessed at the first visit after surgery were also investigated as possible predictors of future VA improvement.Significant correlation with longitudinal VA was found for the extent, circularity, and ratio of defects in EZ band at the fovea and parafoveal regions. The ratio of defects in EZ band at the fovea, temporal-inner, and inferior-inner macula regions showed significant strong correlation with VA within 6 to 12 months post surgery. Patients with worse vision outcome at such time also had a significantly higher rate of inner retinal defects in the superior-outer region in their first postsurgery observation.A lowering extent of EZ band defects in the foveal and parafoveal regions is a good indicator of postsurgery VA recovery. Attention should also be given to postsurgical alterations in the inner retina, as patients with more extensive atrophic changes appear to have slower or worse VA recovery despite closure of the macular hole.

  View details for DOI 10.1167/iovs.14-16344

  View details for PubMedID 26200503

  View details for PubMedCentralID PMC4515949

• Application of Improved Homogeneity Similarity-Based Denoising in Optical Coherence Tomography Retinal Images JOURNAL OF DIGITAL IMAGING Chen, Q., de Sisternes, L., Leng, T., Rubin, D. L. 2015; 28 (3): 346-361

  Abstract

  Image denoising is a fundamental preprocessing step of image processing in many applications developed for optical coherence tomography (OCT) retinal imaging-a high-resolution modality for evaluating disease in the eye. To make a homogeneity similarity-based image denoising method more suitable for OCT image removal, we improve it by considering the noise and retinal characteristics of OCT images in two respects: (1) median filtering preprocessing is used to make the noise distribution of OCT images more suitable for patch-based methods; (2) a rectangle neighborhood and region restriction are adopted to accommodate the horizontal stretching of retinal structures when observed in OCT images. As a performance measurement of the proposed technique, we tested the method on real and synthetic noisy retinal OCT images and compared the results with other well-known spatial denoising methods, including bilateral filtering, five partial differential equation (PDE)-based methods, and three patch-based methods. Our results indicate that our proposed method seems suitable for retinal OCT imaging denoising, and that, in general, patch-based methods can achieve better visual denoising results than point-based methods in this type of imaging, because the image patch can better represent the structured information in the images than a single pixel. However, the time complexity of the patch-based methods is substantially higher than that of the others.

  View details for DOI 10.1007/s10278-014-9742-8

  View details for Web of Science ID 000354950200014

  View details for PubMedID 25404105

• Experience With Aflibercept for the Treatment of Neovascular Age-Related Macular Degeneration. Ophthalmic surgery, lasers & imaging retina He, L., Silva, R. A., Ayoub, N., Moshfeghi, D. M., Leng, T. 2015; 46 (5): 542-549

  Abstract

  Describe visual and anatomic outcomes of eyes with exudative age- related macular degeneration (AMD) after treatment with aflibercept.Eyes treated with intravitreal injections of aflibercept for exudative AMD were retrospectively reviewed to compare visual acuity and central subfield thickness (CST) on optical coherence tomography.A total of 142 eyes receiving aflibercept were previously treated with bevacizumab or ranibizumab intravitreal injections. Baseline vision was 20/73 ± 5.18 lines when switched to aflibercept. It improved by 0.2 ± 1.91 lines (P =.14) after three injections but decreased by 0.45 ± 2.9 lines (P = .06) after 1 year of follow-up. The reduction in CST was 9.9 ± 46.5 µm (P = .06) after three injections and grew to 19.3 ± 50.6 µm (P = .002), a statistically significant amount, after 1 year.Switching to aflibercept resulted in no clinically significant differences in visual acuity after 1 year. There was a significant reduction in CST, but this may not be clinically significant.

  View details for DOI 10.3928/23258160-20150521-05

  View details for PubMedID 26057757

• SUNDROP: six years of screening for retinopathy of prematurity with telemedicine. Canadian journal of ophthalmology. Journal canadien d'ophtalmologie Wang, S. K., Callaway, N. F., Wallenstein, M. B., Henderson, M. T., Leng, T., Moshfeghi, D. M. 2015; 50 (2): 101-106

  Abstract

  To report the 6-year results of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) initiative in the context of telemedicine screening initiatives for retinopathy of prematurity (ROP).A retrospective analysis.Premature newborns requiring ROP screening at 6 neonatal intensive care units from December 1, 2005, to November 30, 2011.Infants were evaluated via remote retinal photography by an ROP specialist. A total of 608 preterm infants meeting ROP examination criteria were screened with the RetCam II/III (Clarity Medical Systems, Pleasanton, Calif.). Primary outcomes were treatment-warranted ROP (TW-ROP) and adverse anatomical events.During the 6 years, 1216 total eyes were screened during 2169 examinations, generating 26 970 retinal images, an average of 3.56 examinations and 44.28 images per patient. Twenty-two (3.6%) of the infants screened met criteria for TW-ROP. Compared with bedside binocular ophthalmoscopy, remote interpretation of RetCam II/III images had a sensitivity of 100%, specificity of 99.8%, positive predicative value of 95.5%, and negative predicative value of 100% for the detection of TW-ROP. No adverse anatomical outcomes were observed for any enrolled patient.The 6-year results for the SUNDROP telemedicine initiative were highly favourable with respect to diagnostic accuracy. Telemedicine appears to be a safe, reliable, and cost-effective complement to the efforts of ROP specialists, capable of increasing patient access to screening and focusing the resources of the current ophthalmic community on infants with potentially vision-threatening disease.

  View details for DOI 10.1016/j.jcjo.2014.11.005

  View details for PubMedID 25863848

• Acute Retinal Necrosis Secondary to Herpes Simplex Virus Type 2 in Neonates OPHTHALMIC SURGERY LASERS & IMAGING RETINA Venincasa, V. D., Emanuelli, A., Leng, T., Perlini, E., Villegas, V., Diaz-Barbosa, M., Gutierrez, M., Miller, D., Berrocal, A. M. 2015; 46 (4): 499-501

  Abstract

  Acute retinal necrosis (ARN) should be in the differential diagnosis of a neonate who presents with vitritis. This report includes three cases of neonatal ARN at the Bascom Palmer Eye Institute from 2004 to 2009. Medical treatment with acyclovir helped reduce sequelae of herpes simplex virus (HSV) 2 infection. Patients with ARN are at risk for retinal detachment and blindness. Although mothers are screened during pregnancy, they are at risk of reactivation or primary contraction of HSV. A neonate presenting with vitritis should raise suspicion of ARN. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:499-501.].

  View details for DOI 10.3928/23258160-20150422-18

  View details for Web of Science ID 000359292300018

  View details for PubMedID 25932732

• Risk factors for respiratory depression in patients undergoing retrobulbar block for vitreoretinal surgery. Ophthalmic surgery, lasers & imaging retina Silva, R. A., Leng, J. C., He, L., Brock-Utne, J. G., Drover, D. R., Leng, T. 2015; 46 (2): 243-247

  Abstract

  To determine the risk factors for respiratory depression during retrobulbar block administration before vitreoretinal surgery.Prospective, observational case series of 113 patients undergoing monitored anesthesia care and retrobulbar block before vitreoretinal surgery at a tertiary medical center.Chin lift, jaw thrust, and bag mask ventilation were performed in eight (7.1%), nine (8%), and six (5.3%) patients, respectively. No patients required intubation. Age, sex, body mass index, history of obstructive sleep apnea, American Society of Anesthesiologists physical status level, and baseline oxygen saturation were not predictive of airway intervention. Of the four anesthetic agents utilized (midazolam, fentanyl, alfentanil, and propofol), only propofol and fentanyl were associated with an increased risk for clinically significant apnea. Use of three medications for sedation was associated with a 5.4-fold increase in the relative risk of requiring a respiratory rescue intervention.During preoperative sedation for retrobulbar block administration, the use of propofol, fentanyl, or a combination of three anesthetics is associated with a statistically significant increase in the risk for respiratory depression requiring resuscitation. [Ophthalmic Surg Lasers Imaging Retina. 2015;46:243-247.].

  View details for DOI 10.3928/23258160-20150213-22

  View details for PubMedID 25707051

• Manual Removal of Dystrophic Calcifications From Silicone Intraocular Lenses Using a 27-Gauge Nitinol Loop With Concave Tines. Retina (Philadelphia, Pa.) Schachar, I., Leng, T. 2015; 35 (12): 2650–51

  View details for PubMedID 26274039

• West African Crystalline Maculopathy in Sickle Cell Retinopathy. Case reports in ophthalmological medicine Kung, J. S., Leng, T. 2015; 2015: 910713-?

  Abstract

  Purpose. To describe the first reported case of West African crystalline maculopathy (WACM) from a member of the Benin tribe and explore the association with sickle cell retinopathy. Methods. Full ophthalmic examination and high-resolution ocular coherence tomographic imaging. Patients. 61-year-old patient from an academic retina practice. Results. The patient demonstrated bilateral yellow-green birefringent crystals localized to the inner retina on optical coherence tomography, as well as sickle cell-related neovascularization in the right eye. She reported no consumption of kola nuts. Conclusions. Associated retinal vascular disease may be important in the pathogenesis of crystalline maculopathy.

  View details for DOI 10.1155/2015/910713

  View details for PubMedID 26788391

  View details for PubMedCentralID PMC4695655

• Idiopathic pigmented vitreous cyst. Acta ophthalmologica Ludwig, C. A., Leng, T. 2015

  View details for PubMedID 26095667

• Stem cell treatments: What's happening in 2015 Retinal Physician Leng, T. 2015: 48-50
• A FALSE COLOR FUSION STRATEGY FOR DRUSEN AND GEOGRAPHIC ATROPHY VISUALIZATION IN OPTICAL COHERENCE TOMOGRAPHY IMAGES RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Chen, Q., Leng, T., Niu, S., Shi, J., de Sisternes, L., Rubin, D. L. 2014; 34 (12): 2346-2358

  Abstract

  To display drusen and geographic atrophy (GA) in a single projection image from three-dimensional spectral domain optical coherence tomography images based on a novel false color fusion strategy.We present a false color fusion strategy to combine drusen and GA projection images. The drusen projection image is generated with a restricted summed-voxel projection (axial sum of the reflectivity values in a spectral domain optical coherence tomography cube, limited to the region where drusen is present). The GA projection image is generated by incorporating two GA characteristics: bright choroid and thin retina pigment epithelium. The false color fusion method was evaluated in 82 three-dimensional optical coherence tomography data sets obtained from 7 patients, for which 2 readers independently identified drusen and GA as the gold standard. The mean drusen and GA overlap ratio was used as the metric to determine accuracy of visualization of the proposed method when compared with the conventional summed-voxel projection, (axial sum of the reflectivity values in the complete spectral domain optical coherence tomography cube) technique and color fundus photographs.Comparative results demonstrate that the false color image is more effective in displaying drusen and GA than summed-voxel projection and CFP. The mean drusen/GA overlap ratios based on the conventional summed-voxel projection method, color fundus photographs, and the false color fusion method were 6.4%/100%, 64.1%/66.7%, and 85.6%/100%, respectively.The false color fusion method was more effective for simultaneous visualization of drusen and GA than the conventional summed-voxel projection method and color fundus photographs, and it seems promising as an alternative method for visualizing drusen and GA in the retinal fundus, which commonly occur together and can be confusing to differentiate without methods such as this proposed one.

  View details for Web of Science ID 000345911300010

  View details for PubMedID 25062439

• Quantitative SD-OCT imaging biomarkers as indicators of age-related macular degeneration progression. Investigative ophthalmology & visual science de Sisternes, L., Simon, N., Tibshirani, R., Leng, T., Rubin, D. L. 2014; 55 (11): 7093-7103

  Abstract

  Purpose: We developed a statistical model based on quantitative characteristics of drusen to estimate the likelihood of conversion from early and intermediate age-related macular degeneration (AMD) to its advanced exudative form (AMD progression) in the short term (less than 5 years), a crucial task to enable early intervention and improve outcomes. Methods: Image features of drusen quantifying their number, morphology, and reflectivity properties, as well as the longitudinal evolution in these characteristics, were automatically extracted from 2146 spectral domain optical coherence tomography (SD-OCT) scans of 330 AMD eyes in 244 patients collected over a period of 5 years, with 36 eyes showing progression during clinical follow-up. We developed and evaluated a statistical model to predict the likelihood of progression at pre-determined times using clinical and image features as predictors. Results: Area, volume, height, and reflectivity of drusen were informative features distinguishing between progressing and non-progressing cases. Discerning progression at follow-up (mean 6.16 months) resulted in a mean area under the receiver operating characteristic curve (AUC) of 0.74 ((0.58, 0.85) 95% confidence interval (CI)). The maximum predictive performance was observed at 11 months after a patient's first early AMD diagnosis, with mean AUC 0.92 ((0.83, 0.98) 95% CI). Those eyes predicted to progress showed a much higher progression rate than those predicted not to progress at any given time from the initial visit. Conclusions: Our results demonstrate the potential ability of our model to identify those AMD patients at risk of progressing to exudative AMD from an early or intermediate stage.

  View details for DOI 10.1167/iovs.14-14918

  View details for PubMedID 25301882

• Optic nerve pit-associated choroidal cleft. JAMA ophthalmology Silva, R. A., Chang, R. T., Moshfeghi, D. M., Leng, T. 2014; 132 (9): 1142-?

  View details for DOI 10.1001/jamaophthalmol.2014.174

  View details for PubMedID 25058335

• An improved optical coherence tomography-derived fundus projection image for drusen visualization. Retina (Philadelphia, Pa.) Chen, Q., Leng, T., Zheng, L. L., Kutzscher, L., de Sisternes, L., Rubin, D. L. 2014; 34 (5): 996-1005

  Abstract

  To develop and evaluate an improved method of generating en face fundus images from three-dimensional optical coherence tomography images which enhances the visualization of drusen.We describe a novel approach, the restricted summed-voxel projection (RSVP), to generate en face projection images of the retinal surface combined with an image processing method to enhance drusen visualization. The RSVP approach is an automated method that restricts the projection to the retinal pigment epithelium layer neighborhood. Additionally, drusen visualization is improved through an image processing technique that fills drusen with bright pixels. The choroid layer is also excluded when creating the RSVP to eliminate bright pixels beneath drusen that could be confused with drusen when geographic atrophy is present. The RSVP method was evaluated in 46 patients and 3-dimensional optical coherence tomography data sets were obtained from 8 patients, for which 2 readers independently identified drusen as the gold standard. The mean drusen overlap ratio was used as the metric to determine the accuracy of visualization of the RSVP method when compared with the conventional summed-voxel projection technique.Comparative results demonstrate that the RSVP method was more effective than the conventional summed-voxel projection in displaying drusen and retinal vessels, and was more useful in detecting drusen. The mean drusen overlap ratios based on the conventional summed-voxel projection method and the RSVP method were 2.1% and 89.3%, respectively.The RSVP method was more effective for drusen visualization than the conventional summed-voxel projection method, and it may be useful for macular assessment in patients with nonexudative age-related macular degeneration.

  View details for DOI 10.1097/IAE.0000000000000018

  View details for PubMedID 24177190

• Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): Five Years of Screening With Telemedicine. Ophthalmic surgery, lasers & imaging retina Fijalkowski, N., Zheng, L. L., Henderson, M. T., Wang, S. K., Wallenstein, M. B., Leng, T., Moshfeghi, D. M. 2014; 45 (2): 106-113

  View details for DOI 10.3928/23258160-20140122-01

  View details for PubMedID 24444469

• Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): five years of screening with telemedicine. Ophthalmic surgery, lasers & imaging retina Fijalkowski, N., Zheng, L. L., Henderson, M. T., Wang, S. K., Wallenstein, M. B., Leng, T., Moshfeghi, D. M. 2014; 45 (2): 106-113

  Abstract

  To report the 5-year results of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative.Infants requiring retinopathy of prematurity (ROP) screening at six neonatal intensive care units from December 1, 2005, to November 30, 2010, were evaluated with remote retinal photography by an ROP specialist. Every infant received outpatient binocular indirect ophthalmoscope examinations until termination criteria were achieved or until treatment. Outcomes were treatment-warranted ROP (TW-ROP, ETROP type 1) and adverse anatomical events.Five hundred eleven infants (1,022 eyes) were screened. Fifteen infants had TW-ROP and underwent laser photocoagulation. The TW-ROP cohort had significantly lower birth weight and gestational age (both P < .001). No patient progressed to adverse anatomical outcomes and no case of TW-ROP was missed. Tele-medicine had 100% sensitivity, 99.8% specificity, 93.8% positive predictive value, and 100% negative predictive value for detection of TW-ROP.Telemedicine demonstrates high diagnostic accuracy for detection of TW-ROP and can complement ROP screening. [Ophthalmic Surg Lasers Imaging Retina. 2014;45:106-113.].

  View details for DOI 10.3928/23258160-20140122-01

  View details for PubMedID 24444469

• Retinal breaks due to intravitreal ocriplasmin. Clinical ophthalmology (Auckland, N.Z.) Silva, R. A., Moshfeghi, D. M., Leng, T. 2014; 8: 1591-1594

  Abstract

  Ocriplasmin represents a new treatment option for numerous vitreoretinopathies involving an abnormal vitreomacular interface. While the drug may circumvent the traditional risks of surgical treatment, pharmacologic vitreolysis is not devoid of risk itself. This report presents two cases, one of vitreomacular traction syndrome and the other of a full-thickness macular hole, both of which were treated with an intravitreal injection of ocriplasmin. Notably, in both cases, vitreomacular traction of the macula appears to have been alleviated; however, failure to completely relieve vitreoretinal traction from the peripheral retina generated retinal breaks with one patient eventually developing a macula-involving retinal detachment. Thus, even in instances of 'successful' pharmacologic treatment of vitreomacular traction, continued follow-up evaluation is essential.

  View details for DOI 10.2147/OPTH.S68037

  View details for PubMedID 25210426

• Multimodal imaging and multifocal electroretinography demonstrate autosomal recessive Stargardt disease may present like occult macular dystrophy. Retina (Philadelphia, Pa.) Sisk, R. A., Leng, T. 2014; 34 (8): 1567–75

  Abstract

  To describe multimodal imaging and electrophysiologic characteristics of an unusual subset of patients with genetically confirmed autosomal recessive Stargardt disease (STGD1) who exhibited a central form of cone dysfunction resembling occult macular dystrophy that preceded the development of lipofuscin flecks, atrophy of retinal pigment epithelium (RPE), or full-field electroretinography abnormalities.Retrospective, observational descriptive case series.Five patients with compound heterozygous ABCA4 mutations presented with bilateral visual acuity reduction, normal-appearing fundi, and blocked choroidal fluorescence on fluorescein angiography. One sibling each of two probands with identical genotypes was also included for analysis. Full-field electroretinography testing was normal in all patients, but multifocal electroretinography demonstrated centripetally depressed amplitudes exceeding areas of fundus autofluorescence, infrared imaging, and spectral domain optical coherence tomography abnormalities. Spectral domain optical coherence tomography initially revealed disruption of the inner segment ellipsoid band accompanying an ovoid hypofluorescent foveolar lesion. Progression to later stages was accompanied by the loss of the foveal photoreceptor outer segments, creating foveal cavitation with preservation of the RPE. Fundus autofluorescence and infrared imaging demonstrated corresponding bull's eye lesions. Over time, the foveal potential space on spectral domain optical coherence tomography collapsed, and three patients developed RPE atrophy and visible lipofuscin flecks. The flecks were detectable by fundus autofluorescence and infrared imaging earlier than by biomicroscopy. From these findings, a staging system for this subset of Stargardt disease presenting with central cone dysfunction was developed and presented herein.Autosomal recessive Stargardt disease may present as a central cone dysfunction syndrome before the development of lipofuscin flecks, atrophy of RPE, or full-field electroretinography abnormalities. If emerging therapies for Stargardt disease succeed, early recognition and treatment of patients with preserved foveal photoreceptor and RPE cell bodies may yield a more favorable visual prognosis.

  View details for PubMedID 24743636

• Automated drusen segmentation and quantification in SD-OCT images. Medical image analysis Chen, Q., Leng, T., Zheng, L., Kutzscher, L., Ma, J., de Sisternes, L., Rubin, D. L. 2013; 17 (8): 1058-1072

  Abstract

  Spectral domain optical coherence tomography (SD-OCT) is a useful tool for the visualization of drusen, a retinal abnormality seen in patients with age-related macular degeneration (AMD); however, objective assessment of drusen is thwarted by the lack of a method to robustly quantify these lesions on serial OCT images. Here, we describe an automatic drusen segmentation method for SD-OCT retinal images, which leverages a priori knowledge of normal retinal morphology and anatomical features. The highly reflective and locally connected pixels located below the retinal nerve fiber layer (RNFL) are used to generate a segmentation of the retinal pigment epithelium (RPE) layer. The observed and expected contours of the RPE layer are obtained by interpolating and fitting the shape of the segmented RPE layer, respectively. The areas located between the interpolated and fitted RPE shapes (which have nonzero area when drusen occurs) are marked as drusen. To enhance drusen quantification, we also developed a novel method of retinal projection to generate an en face retinal image based on the RPE extraction, which improves the quality of drusen visualization over the current approach to producing retinal projections from SD-OCT images based on a summed-voxel projection (SVP), and it provides a means of obtaining quantitative features of drusen in the en face projection. Visualization of the segmented drusen is refined through several post-processing steps, drusen detection to eliminate false positive detections on consecutive slices, drusen refinement on a projection view of drusen, and drusen smoothing. Experimental evaluation results demonstrate that our method is effective for drusen segmentation. In a preliminary analysis of the potential clinical utility of our methods, quantitative drusen measurements, such as area and volume, can be correlated with the drusen progression in non-exudative AMD, suggesting that our approach may produce useful quantitative imaging biomarkers to follow this disease and predict patient outcome.

  View details for DOI 10.1016/j.media.2013.06.003

  View details for PubMedID 23880375

• Semi-automatic geographic atrophy segmentation for SD-OCT images BIOMEDICAL OPTICS EXPRESS Chen, Q., de Sisternes, L., Leng, T., Zheng, L., Kutzscher, L., Rubin, D. L. 2013; 4 (12): 2729-2750

  Abstract

  Geographic atrophy (GA) is a condition that is associated with retinal thinning and loss of the retinal pigment epithelium (RPE) layer. It appears in advanced stages of non-exudative age-related macular degeneration (AMD) and can lead to vision loss. We present a semi-automated GA segmentation algorithm for spectral-domain optical coherence tomography (SD-OCT) images. The method first identifies and segments a surface between the RPE and the choroid to generate retinal projection images in which the projection region is restricted to a sub-volume of the retina where the presence of GA can be identified. Subsequently, a geometric active contour model is employed to automatically detect and segment the extent of GA in the projection images. Two image data sets, consisting on 55 SD-OCT scans from twelve eyes in eight patients with GA and 56 SD-OCT scans from 56 eyes in 56 patients with GA, respectively, were utilized to qualitatively and quantitatively evaluate the proposed GA segmentation method. Experimental results suggest that the proposed algorithm can achieve high segmentation accuracy. The mean GA overlap ratios between our proposed method and outlines drawn in the SD-OCT scans, our method and outlines drawn in the fundus auto-fluorescence (FAF) images, and the commercial software (Carl Zeiss Meditec proprietary software, Cirrus version 6.0) and outlines drawn in FAF images were 72.60%, 65.88% and 59.83%, respectively.

  View details for DOI 10.1364/BOE.4.002729

  View details for Web of Science ID 000328078300002

  View details for PubMedID 24409376

  View details for PubMedCentralID PMC3862151

• Traumatic airbag maculopathy. JAMA ophthalmology Kung, J., Leung, L. B., Leng, T., Liao, Y. J. 2013; 131 (5): 685-687

  View details for DOI 10.1001/jamaophthalmol.2013.883

  View details for PubMedID 23699847

• Quantitative evaluation of drusen on photographs. Ophthalmology Rubin, D. L., de Sisternes, L., Kutzscher, L., Chen, Q., Leng, T., Zheng, L. L. 2013; 120 (3): 644-644 e2

  View details for DOI 10.1016/j.ophtha.2012.09.052

  View details for PubMedID 23714606

• Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP): Four-years of Screening with Telemedicine CURRENT EYE RESEARCH Fijalkowski, N., Zheng, L. L., Henderson, M. T., Wallenstein, M. B., Leng, T., Moshfeghi, D. M. 2013; 38 (2): 283-291

  Abstract

  To report the four-year experience of the Stanford University Network for Diagnosis of Retinopathy of Prematurity (SUNDROP) telemedicine initiative, which was developed to reduce the risk of blindness from retinopathy of prematurity (ROP).A retrospective analysis of the SUNDROP archival data between 12/1/2005 and 11/30/2009. A total of 410 consecutively enrolled infants meeting ROP screening criteria had nurse-obtained fundoscopic images evaluated remotely by an ROP specialist. Every infant then received at least one dilated bedside binocular indirect ophthalmoscope (BIO) examination within one week of discharge. All infants were then followed with both telemedicine images and bedside evaluation in clinic according to recommended screening timelines. Primary outcomes were treatment-warranted ROP (TW-ROP), defined as Early Treatment of ROP Type 1, and adverse anatomical outcomes.The SUNDROP telemedicine screening initiative has not missed any TW-ROP in its four-year evaluation period. A total of 410 infants (820 eyes) were imaged, resulting in 1486 examinations and 18,097 unique images. An average of 12.2 images were obtained per patient. Fourteen infants met TW-ROP criteria on telemedicine examination. After bedside evaluation, 13 infants required laser photocoagulation and one was followed until he spontaneously regressed. Infants with TW-ROP had a significantly lower gestational age (24.9 weeks), birth weight (658.7 grams), and were more likely to be male than the no TW-ROP cohort (all p values <0.00001). Telemedicine had a calculated sensitivity of 100%, specificity of 99.8%, positive predicative value of 92.9% and negative predictive value of 100% for the detection of TW-ROP. No patient progressed to retinal detachment or any adverse anatomical outcome.The SUNDROP initiative demonstrated a high degree of diagnostic reliability and was able to capture all infants with TW-ROP. Telemedicine offers a cost-effective, reliable and accurate screening methodology for identifying infants with TW-ROP without sacrificing quality of care.

  View details for DOI 10.3109/02713683.2012.754902

  View details for Web of Science ID 000314900400008

  View details for PubMedID 23330739

• Abundance of myelinated nerve fibers. JAMA ophthalmology Leng, T., Nyong'o, O. L. 2013; 131 (2): 245-?

  View details for DOI 10.1001/jamaophthalmol.2013.583

  View details for PubMedID 23411895

• Antibiotic controversies in vitreoretinal practice Retinal Physician Karth, P. A., Leng, T. 2013: 22-25
• Management of suspected endogenous endophthalmitis Retina Today Leng, T. 2013; 8 (6): 32-33
• Carbon nanotube bucky paper as an artificial support membrane for retinal cell transplantation. Ophthalmic surgery, lasers & imaging retina Leng, T., Fishman, H. A. 2013; 44 (1): 73-76

  Abstract

  Transplantation of epithelial cells on a substrate to rescue diseased retinal cells is an experimental therapy for age-related macular degeneration. Carbon nanotube bucky paper was tested for cell transplantation into the retina.Bucky paper was prepared and human RPE cells cultured on its surface demonstrating its utility as a cell transplantation substrate. Bucky paper was implanted underneath 9 rabbit retinas using a standard 3-port pars plana vitrectomy and subretinal bleb. A 1 mm retinotomy was created through which Bucky paper precut to fit was inserted with the subretinal forceps, into the subretinal bleb. The retina was reattached by airfluid exchange.By light microscopy, RPE cells demonstrated normal morphology and growth patterns on the bucky paper surface. Scanning electron microscopy confirmed a confluent monolayer of cells, and indicated the formation of microvilli on the apical surface. Bucky paper remained flat in the subretinal space after 2 weeks, the retina fully attached without edema or inflammation.Bucky paper possesses the necessary attributes for therapeutic cell transplantation in the eye.

  View details for DOI 10.3928/23258160-20121221-16

  View details for PubMedID 23410811

• FOVEAL CAVITATION AS AN OPTICAL COHERENCE TOMOGRAPHY FINDING IN CENTRAL CONE DYSFUNCTION RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., Marmor, M. F., Kellner, U., Thompson, D. A., Renner, A. B., Moore, W., Sowden, J. C. 2012; 32 (7): 1411-1419

  Abstract

  To describe a distinctive foveal cavitation as seen by spectral-domain optical coherence tomography in certain cone dysfunction syndromes.Observational case series. Patients were evaluated by dilated fundus examination, fundus photography, fundus autofluorescence, full-field electroretinogram, multifocal electroretinogram, spectral-domain optical coherence tomography, color vision testing, fluorescein angiography, Goldmann visual field testing, and molecular genetic analysis.We present eight patients with foveal cavitation in association with presumed cone dysfunction. This was characterized on spectral-domain optical coherence tomography by a gap in the subfoveal outer segment layer without more diffuse retinal thinning. There were 5 patients of age 10 years to 27 years and 3 patients of age 49 years to 52 years, with a 1.5- to 38-year history of bilateral visual loss. A small foveal oval-shaped area of reduced foveal fundus autofluorescence, surrounded by increased fundus autofluorescence, was seen in the younger patients, and a broad circle of increased fundus autofluorescence in the older patients. The multifocal electroretinogram always showed central amplitude reduction, but there were varying degrees of cone dysfunction on full-field electroretinogram. There were mild abnormalities on desaturated color vision testing. The family history was noncontributory in all cases. None of the cases were congenital. ABCA4 gene mutations were identified in three of five patients tested; CNGB3 testing was negative in these patients.Cone dysfunction syndromes typically show retinal thinning on optical coherence tomography imaging, although several case reports have noted focal outer retinal loss. Our case series shows that a distinctive optical coherence tomography finding, foveal cavitation, may be a clue to cone dysfunction syndromes, but is not specific to any one hereditary disorder or age group.

  View details for DOI 10.1097/IAE.0b013e318236e4ea

  View details for PubMedID 22466470

• Cannula-Based 25-Gauge Vitreous Tap And Injection: A New Surgical Technique RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Chan, A., Leng, T., Moshfeghi, D. M. 2012; 32 (5): 1021-1022

  View details for DOI 10.1097/IAE.0b013e318248e6ba

  View details for PubMedID 22311272

• Effect of Lidocaine Gel Anesthesia on Endophthalmitis Rates Following Intravitreal Injection OPHTHALMIC SURGERY LASERS & IMAGING Lad, E. M., Maltenfort, M. G., Leng, T. 2012; 43 (2): 115-120

  Abstract

  To determine whether the use of lidocaine gel before application of povidone-iodine affects endophthalmitis rates following intravitreal injections.Retrospective consecutive case series of all intravitreal injections and post-intravitreal injection endophthalmitis cases at one institution from 2000 to 2009. A review of medical records of post-intravitreal injection endophthalmitis cases was performed to determine whether lidocaine gel was applied prior to povidone-iodine antisepsis and to analyze the clinical course and outcomes.A total of 8,802 intravitreal injections were administered during the study period. When no lidocaine gel was used prior to povidone-iodine antisepsis, four cases of endophthalmitis following 4,120 intravitreal injections (0.097%) were recorded. When 2% lidocaine gel was applied before povidone-iodine, four cases of endophthalmitis following 4,682 intravitreal injections (0.085%) were observed (P = 1.00, odds ratio = 1.12).The use of lidocaine gel prior to povidone-iodine antisepsis did not significantly alter post-intravitreal injection endophthalmitis rates.

  View details for DOI 10.3928/15428877-20120119-01

  View details for Web of Science ID 000305342900004

  View details for PubMedID 22283227

• REDUCING ORAL FLORA CONTAMINATION OF INTRAVITREAL INJECTIONS WITH FACE MASK OR SILENCE RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Doshi, R. R., Leng, T., Fung, A. E. 2012; 32 (3): 473-476

  Abstract

  To provide experimental evidence to support or refute the proposition that the use of surgical face masks and/or avoidance of talking can decrease the dispersion of respiratory flora during an intravitreal injection.Ten surgeons recited a 30-second standardized script with blood agar plates positioned 30 cm below their mouths. The plates were divided into 4 groups, with 10 plates per group. In Group 1, participants did not wear a face mask. In Group 2, participants wore a standard surgical mask. In Group 3, no mask was worn, but plates were pretreated with 5% povidone-iodine. In Group 4, no mask was worn, and participants remained silent for 30 seconds. The plates were then incubated at 37°C for 24 hours, and the number of colony-forming units (CFUs) was determined.Mean bacterial growth were as follows: Group 1, 8.6 CFUs per subject; Group 2, 1.1 CFUs per subject; Group 3, 0.1 CFUs per subject; and Group 4, 2.4 CFUs per subject. Differences between the groups were statistically significant (P < 0.05), with the exception of Group 2 versus Group 4 (P = 0.115).The use of a face mask and avoidance of talking each significantly decreased the dispersion of bacteria. Even without these interventions, plates pretreated with povidone-iodine demonstrated the least bacterial growth.

  View details for DOI 10.1097/IAE.0B013E31822C2958

  View details for Web of Science ID 000300907200007

  View details for PubMedID 22374155

• The influence of medical school and residency training program upon choice of an academic career and academic productivity among otolaryngology faculty in the United States of America: Our experience of 1433 academic otolaryngologists CLINICAL OTOLARYNGOLOGY Leng, T., Jaben, K. A., Zheng, L., Yang, J., Paulus, Y. M., Moshfeghi, A. A., Maltenfort, M. G., Campbell, P. G., Ratliff, J. K., Moshfeghi, D. M. 2012; 37 (1): 58-62

  View details for DOI 10.1111/j.1749-4486.2011.02402.x

  View details for Web of Science ID 000301779300008

  View details for PubMedID 22433138

• Intravitreal dexamethasone in the management of delayed-onset bleb-associated endophthalmitis. International journal of inflammation Jacobs, D. J., Pathengay, A., Flynn, H. W., Leng, T., Miller, D., Shi, W. 2012; 2012: 503912-?

  Abstract

  Purpose. To report the visual acuity (VA) outcomes and culture results of delayed-onset bleb-associated endophthalmitis (BAE) with and without intravitreal dexamethasone (IVD). Methods. Retrospective nonrandomized comparative case series of BAE at Bascom Palmer Eye Institute between January 1, 1996 and December 31, 2009. Clinical data were compared using the 2-sided Student's t-test for patients who received IVD and patients who did not receive IVD. Results. 70/83 (84%) received IVD, and 13/83 (16%) did not receive IVD. Mean baseline VA was 20/90 in the IVD group and 20/70 in the group that did not receive IVD (P = 0.57). Mean presenting VA was 0.9/200 in the IVD group and 1.7/200 in the group that did not receive IVD (P = 0.23). Repeat cultures were positive in 2/70 (3%) IVD cases and 1/13 (8%) cases that did not receive IVD (P = 0.57). Mean VA at 1 month was 5/200 in the IVD group and 1.8/200 in the group that did not receive IVD, logMARΔ of 0.85 and 1.56, respectively (P = 0.02). Mean VA at 3 months was 7/200 in the IVD group and 3/200 in the group that did not receive IVD, logMARΔ of 0.74 and 1.33, respectively (P = 0.14). Conclusion. In the current study of BAE, IVD was associated with improved short-term VA outcomes without an increased rate of persistent infection.

  View details for DOI 10.1155/2012/503912

  View details for PubMedID 22288020

  View details for PubMedCentralID PMC3263617

• Two cases of X-linked retinoschisis with different spectral domain optical coherence tomography findings. Clinical ophthalmology (Auckland, N.Z.) Leng, T. 2012; 6: 1563-1565

  Abstract

  Spectral domain optical coherence tomography was used to image the maculae of two brothers who had the diagnosis of X-linked retinoschisis maculopathy. One patient demonstrated a large foveal cyst in one eye and a lamellar macular hole in the fellow eye. The second patient demonstrated small retinal cysts in multiple layers of the retina. Spectral domain optical coherence tomography allowed high-resolution imaging and characterization of the features in X-linked retinoschisis in these patients, and it highlighted the variability of the same genetic disease, even in one family.

  View details for DOI 10.2147/OPTH.S36756

  View details for PubMedID 23055679

  View details for PubMedCentralID PMC3460697

• Medical School and Residency Influence on Choice of an Academic Career and Academic Productivity Among US Neurology Faculty ARCHIVES OF NEUROLOGY Campbell, P. G., Lee, Y. H., Bell, R. D., Maltenfort, M. G., Moshfeghi, D. M., Leng, T., Moshfeghi, A. A., Ratliff, J. K. 2011; 68 (8): 999-1004

  Abstract

  To evaluate the effectiveness of medical schools and neurology training programs in the United States by determining their contribution to academic neurology in terms of how many graduates choose academic careers and their respective influence on current medical knowledge through bibliometric analysis.Biographical information from current faculty members of neurology training programs in the United States was obtained through an Internet-based search of departmental Web sites. Collected variables included medical school attended, residency program completed, and current academic rank. For each faculty member, ISI Web of Science and Scopus h -indices were also collected.Data from academic neurologists from 120 training programs with 3249 faculty members were collected. All data regarding training program and medical school education were compiled and analyzed by the institution from which each individual graduated. The 20 medical schools and neurology residency training programs producing the greatest number of graduates remaining in academic practice and the mean h -indices are reported. More medical school graduates of the Columbia University College of Physicians and Surgeons chose to enter academic neurology practice than the graduates of any other institution. Analyzed by residency training program attended, New York Presbyterian Hospital (Columbia University), Mayo Clinic (Rochester, Minnesota), and Mount Sinai Medical Center (New York, New York) produced the most graduates remaining in academics.This retrospective, longitudinal cohort study examines through quantitative measures the academic productivity and rank of academic neurologists. The results demonstrate that several training programs excel in producing a significantly higher proportion of academically active neurologists.

  View details for DOI 10.1001/archneurol.2011.67

  View details for Web of Science ID 000293647500005

  View details for PubMedID 21482917

• Medical school and residency influence on choice of an academic career and academic productivity among neurosurgery faculty in the United States Clinical article JOURNAL OF NEUROSURGERY Campbell, P. G., Awe, O. O., Maltenfort, M. G., Moshfeghi, D. M., Leng, T., Moshfeghi, A. A., Ratliff, J. K. 2011; 115 (2): 380-386

  Abstract

  Factors determining choice of an academic career in neurological surgery are unclear. This study seeks to evaluate the graduates of medical schools and US residency programs to determine those programs that produce a high number of graduates remaining within academic programs and the contribution of these graduates to academic neurosurgery as determined by h-index valuation.Biographical information from current faculty members of all accredited neurosurgery training programs in the US with departmental websites was obtained. Any individual who did not have an American Board of Neurological Surgery certificate (or was not board eligible) was excluded. The variables collected included medical school attended, residency program completed, and current academic rank. For each faculty member, Web of Science and Scopus h-indices were also collected.Ninety-seven academic neurosurgery departments with 986 faculty members were analyzed. All data regarding training program and medical school education were compiled and analyzed by center from which each faculty member graduated. The 20 medical schools and neurosurgical residency training programs producing the greatest number of graduates remaining in academic practice, and the respective individuals' h-indices, are reported. Medical school graduates of the Columbia University College of Physicians and Surgeons chose to enter academics the most frequently. The neurosurgery training program at the University of Pittsburgh produced the highest number of academic neurosurgeons in this sample.The use of quantitative measures to evaluate the academic productivity of medical school and residency graduates may provide objective measurements by which the subjective influence of training experiences on choice of an academic career may be inferred. The top 3 residency training programs were responsible for 10% of all academic neurosurgeons. The influence of medical school and residency experiences on choice of an academic career may be significant.

  View details for DOI 10.3171/2011.3.JNS101176

  View details for Web of Science ID 000293145100037

  View details for PubMedID 21495810

• Povidone-Iodine Before Lidocaine Gel Anesthesia Achieves Surface Antisepsis Annual Meeting of the Retina-Society Doshi, R. R., Leng, T., Fung, A. E. SLACK INC. 2011: 346–49

  Abstract

  Viscous lidocaine interferes with ocular surface antisepsis. The current study was designed to evaluate the impact on surface antisepsis of different application sequences with lidocaine gel and povidone-iodine solution.Blood agar plates inoculated with Staphylococcus epidermidis were treated with varying sequences of 2% lidocaine gel and 5% povidone-iodine solution. The plates were then incubated at 37°C for 24 hours and bacterial growth was determined.Plates on which povidone-iodine was applied alone or prior to lidocaine gel demonstrated no bacterial growth regardless of whether the antiseptic was retained on the plate for 5 seconds or for 30 seconds. There was no statistically significant difference between bacterial growth on plates not treated with povidone-iodine and on plates treated with lidocaine gel alone or prior to povidone-iodine (P = .553 and P = .485, respectively).Povidone-iodine effectively reduces bacterial counts when applied alone or prior to lidocaine gel. Lidocaine gel was confirmed to be a barrier to antisepsis when administered prior to povidone-iodine.

  View details for DOI 10.3928/15428877-20110210-02

  View details for Web of Science ID 000305342000012

  View details for PubMedID 21366185

• SELECTIVE RETINAL THERAPY WITH MICROSECOND EXPOSURES USING A CONTINUOUS LINE SCANNING LASER RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Paulus, Y. M., Jain, A., Nomoto, H., Sramek, C., Gariano, R. F., Andersen, D., Schuele, G., Leung, L., Leng, T., Palanker, D. 2011; 31 (2): 380-388

  Abstract

  To evaluate the safety, selectivity, and healing of retinal lesions created using a continuous line scanning laser.A 532-nm Nd:YAG laser (PASCAL) with retinal beam diameters of 40 μm and 66 μm was applied to 60 eyes of 30 Dutch-belted rabbits. Retinal exposure duration varied from 15 μs to 60 μs. Lesions were acutely assessed by ophthalmoscopy and fluorescein angiography. Retinal pigment epithelial (RPE) flatmounts were evaluated with live-dead fluorescent assay. Histological analysis was performed at 7 time points from 1 hour to 2 months.The ratios of the threshold of rupture and of ophthalmoscopic visibility to fluorescein angiography visibility (measures of safety and selectivity) increased with decreasing duration and beam diameter. Fluorescein angiography and live-dead fluorescent assay yielded similar thresholds of RPE damage. Above the ophthalmoscopic visibility threshold, histology showed focal RPE damage and photoreceptor loss at 1 day, without inner retinal effects. By 1 week, photoreceptor and RPE continuity was restored. By 1 month, photoreceptors appeared normal.: Retinal therapy with a fast scanning continuous laser achieves selective targeting of the RPE and, at higher power, of the photoreceptors without permanent scarring or inner retinal damage. Continuous scanning laser can treat large retinal areas within standard eye fixation time.

  View details for DOI 10.1097/IAE.0b013e3181e76da6

  View details for Web of Science ID 000286586500024

  View details for PubMedID 20930656

• DELAYED-ONSET BLEB-ASSOCIATED ENDOPHTHALMITIS (1996-2008) Causative Organisms and Visual Acuity Outcomes RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., Miller, D., Flynn, H. W., Jacobs, D. J., Gedde, S. J. 2011; 31 (2): 344-352

  Abstract

  The purpose of this study was to report the clinical features, organisms, and outcomes of patients with delayed-onset bleb-associated endophthalmitis.Retrospective consecutive case series. Patients who were treated for delayed-onset bleb-associated endophthalmitis between January 1, 1996, and July 1, 2008, at a single institution were included. Information on visual acuities, clinical characteristics, causative organisms, and treatment outcomes were collected. Infections within 1 month of glaucoma filtering surgery, inadvertent filtering blebs after cataract surgery, and patients with glaucoma drainage devices were excluded.A total of 71 eyes from 68 patients were identified. An adjunctive antifibrotic agent was used in 48 eyes (68%). The mean time between surgery and endophthalmitis was 4.8 years (range, 0.1-16; standard deviation, 3.6). The average follow-up time after initial treatment was 37 months (range 1-144; standard deviation, 41). At presentation, 17 eyes (24%) had a bleb leak. Fifty-seven eyes (83%) were culture positive. The most common causative organisms were Streptococcus species in 20 eyes (30%), gram-negative organisms in 19 eyes (28%), and coagulase-negative Staphylococcus in 12 eyes (18%). All gram-positive isolates were sensitive to vancomycin. Nine eyes (13%) eventually underwent evisceration or enucleation secondary to pain and/or poor vision. The main outcome measure was best-corrected visual acuity at the last follow-up examination. Final visual acuities in the initial tap/inject group (n = 45) versus the initial vitrectomy group (n = 24) were as follows: ≥ 20/40 (29% vs. 4.2%), 20/50 to 20/400 (36% vs. 29%), and <5/200 (36% vs. 62%).Streptococcus species and gram-negative organisms were the most common causative isolates identified in this case series of delayed-onset bleb-associated endophthalmitis. Despite treatment of the infection, visual outcomes were generally poor.

  View details for DOI 10.1097/IAE.0b013e3181e09810

  View details for PubMedID 20838358

• The vitreous trap: a simple, surgeon-controlled technique for obtaining undiluted vitreous and subretinal specimens during pars plana vitrectomy. Retina (Philadelphia, Pa.) Moshfeghi, A. A., Albini, T. A., Kitchens, J. W., Leng, T., Moshfeghi, D. M. 2011; 31 (2): 426-427

  View details for DOI 10.1097/IAE.0b013e318200c125

  View details for PubMedID 21233788

• Improving the therapeutic window of retinal photocoagulation by spatial and temporal modulation of the laser beam JOURNAL OF BIOMEDICAL OPTICS Sramek, C., Leung, L., Leng, T., Brown, J., Paulus, Y. M., Schuele, G., Palanker, D. 2011; 16 (2)

  Abstract

  Decreasing the pulse duration helps confine damage, shorten treatment time, and minimize pain during retinal photocoagulation. However, the safe therapeutic window (TW), the ratio of threshold powers for thermomechanical rupture of Bruch's membrane and mild coagulation, also decreases with shorter exposures. Two potential approaches toward increasing TW are investigated: (a) decreasing the central irradiance of the laser beam and (b) temporally modulating the pulse. An annular beam with adjustable central irradiance was created by coupling a 532-nm laser into a 200-μm core multimode optical fiber at a 4-7 deg angle to normal incidence. Pulse shapes were optimized using a computational model, and a waveform generator was used to drive a PASCAL photocoagulator (532 nm), producing modulated laser pulses. Acute thresholds for mild coagulation and rupture were measured in Dutch-Belted rabbit in vivo with an annular beam (154-163 μm retinal diameter) and modulated pulse (132 μm, uniform irradiance "flat-top" beam) with 2-50 ms pulse durations. Thresholds with conventional constant-power pulse and a flat-top beam were also determined. Both annular beam and modulated pulse provided a 28% increase in TW at 10-ms duration, affording the same TW as 20-ms pulses with conventional parameters.

  View details for DOI 10.1117/1.3542045

  View details for Web of Science ID 000288939200056

  View details for PubMedID 21361711

• Retinopathy of prematurity in an infant with Aicardi's syndrome EYE Leng, T., Moshfeghi, D. M. 2011; 25 (2): 257-258

  View details for DOI 10.1038/eye.2010.189

  View details for Web of Science ID 000287187300025

  View details for PubMedID 21151036

  View details for PubMedCentralID PMC3169236

• Delayed-onset bleb-associated endophthalmitis: presentation and outcome by culture result. Clinical ophthalmology (Auckland, N.Z.) Jacobs, D. J., Leng, T., Flynn, H. W., Shi, W., Miller, D., Gedde, S. J. 2011; 5: 739-744

  Abstract

  To determine how culture results are associated with clinical presentations and outcomes in delayed-onset bleb-associated endophthalmitis (BAE).Retrospective consecutive case series of BAE at Bascom Palmer Eye Institute between January 1, 1996 and December 31, 2009. All patients had prior glaucoma filtering surgery. BAE was defined as intraocular infection with vitreous involvement receiving treatment with intravitreal antibiotics. Visual acuity (VA) outcomes and other clinical data were grouped by culture result and compared using the 2-sided Student's t-test.Mean logMAR change at 3 months after treatment (3-month logMARΔ).Eighty-six eyes of 85 patients were identified. Two eyes were primarily eviscerated. Fifty-three (63%) eyes were culture-positive with the following organisms: Streptococcus, 21 (25%); coagulase-negative Staphylococcus, 9 (11%); Enterococcus, 6 (7%); Gram-negative, 15 (18%); Moraxella, 8 (10%); Pseudomonas, 3 (4%); and Serratia, 3 (4%). Presenting logMAR VA: culture-positive worse than culture-negative cases (2.45 vs 2.19, P = 0.05). Presenting intraocular pressure (IOP): culture-positive higher than culture-negative cases (24 mmHg vs 14 mmHg, P = 0.002). Poor presenting view of the fundus: Streptococcus worse than coagulase-negative Staphylococcus cases (90% vs 44%, P = 0.006), Pseudomonas and Serratia worse than Moraxella cases (100% vs 50%, P = 0.04). Three month logMARΔ: culture-positive worse than culture-negative cases (1.03 vs 0.43, P = 0.02), Streptococcus worse than coagulase-negative Staphylococcus cases (1.44 vs 0.31, P = 0.004), Pseudomonas and Serratia worse than coagulase-negative Staphylococcus cases (2.41 vs 0.31, P = 0.001), Pseudomonas and Serratia worse than Moraxella cases (2.41 vs 0.04, P = 0.001). A culture result of Streptococcus or Serratia was present in 6 of 7 eyes that received an additional treatment of enucleation or evisceration (P = 0.01).Culture-positive cases were associated with worse presenting VA, higher presenting IOP, and worse VA outcomes than culture-negative cases. Streptococcus, Pseudomonas, and Serratia cases were associated with poor presenting view of the fundus and worse VA outcomes than coagulase-negative Staphylococcus and Moraxella cases.

  View details for DOI 10.2147/OPTH.S17975

  View details for PubMedID 21691583

• Endogenous Candida albicans endophthalmitis following spontaneous abortion and IUD removal. Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye Doshi, R. R., Wender, J. D., Jumper, J. M., Sanislo, S. R., Leng, T. 2011; 42 Online: e132-4

  Abstract

  The authors report a rare case of a 32-year-old woman who developed endogenous Candida albicans endophthalmitis following spontaneous abortion and removal of a contraceptive intrauterine device. Considerations regarding diagnosis and management are presented based on a review of the literature.

  View details for DOI 10.3928/15428877-20111208-02

  View details for PubMedID 22165949

• Neovascularization in Purtscher's retinopathy. Clinical ophthalmology (Auckland, N.Z.) Chan, A., Fredrick, D. R., Leng, T. 2011; 5: 1585-1587

  Abstract

  We report a case of neovascularization secondary to Purtscher's retinopathy that showed minimal improvement with photocoagulation treatment. A 14-year-old boy with a history of cerebellar medulloblastoma presented with blurry vision and floaters after being struck by a motor vehicle while riding his bike. At presentation, visual acuity was 20/400 in his right eye and counting fingers in his left eye. Fundus examination showed disk edema, retinal whitening, and retinal hemorrhages in both eyes. Optical coherence tomography demonstrated thinning of the temporal retina and disruption of the inner segment-outer segment junction of the photoreceptor layer in the right eye and thickening and edema of the nasal macula, as well as a central foveal hyper-reflectivity, in the left eye. At the initial visit, there was no ischemia or neovascularization (NV). One month later, the patient developed NV of the disk and ischemia in the mid-periphery of the left eye. The patient underwent treatment with pan-retinal photocoagulation. The NV regressed, but visual outcome remained poor at his 5-month follow-up visit.

  View details for DOI 10.2147/OPTH.S26076

  View details for PubMedID 22125405

  View details for PubMedCentralID PMC3218168

• Photodynamic therapy rescue for subretinal fluid exacerbation after focal laser treatment in idiopathic central serous chorioretinopathy. The open ophthalmology journal Leng, T., Sanislo, S. R., Jack, R. L. 2011; 5: 6-9

  Abstract

  To report a case of subretinal leakage after focal laser treatment for idiopathic central serous chorioretinopathy (ICSC). This rare complication was successfully treated with photodynamic therapy (PDT).Interventional case report.A 36-year-old male presented with ICSC in his right eye. After a period of observation without resolution, he was treated with focal laser. That treatment resulted in a massive exacerbation of his subretinal fluid. PDT was successfully used to treat the severe exacerbation with rapid resolution of the subretinal fluid, improvement in visual acuity, decreased leakage on fluorescein angiography, and reduction of subretinal fluid on ophthalmoscopic exam and by optical coherence tomography.Ophthalmologists should consider the use of PDT in cases where focal laser causes an exacerbation of subretinal fluid in ICSC.

  View details for DOI 10.2174/1874364101105010006

  View details for PubMedID 21399767

• Kinetics of central macular thickness reduction in patients with macular edema after intravitreal drug therapy. Clinical ophthalmology (Auckland, N.Z.) He, L., Chan, A., Leng, T., Blumenkranz, M. S. 2011; 5: 1751-1758

  Abstract

  The purpose of this study was to characterize central macular thickness and retinal volume following intravitreal injections using time domain and spectral domain optical coherence tomography (TD-OCT and SD-OCT, respectively).Nine patients with macular edema secondary to diabetes or retinal vein occlusion treated with intravitreal triamcinolone 4.0 mg and/or bevacizumab 1.25 mg were enrolled. Central macular thickness and volume was measured by SD-OCT and TD-OCT scan at baseline, and 1, 3, 6, 24, 48 hours, and 1 week postinjection.Equations were derived to describe central macular thickness and volume reduction in the hours following intravitreal injection. Measurements of central macular thickness by SD-OCT were significantly reduced by 3 hours (P = 0.03) and retinal volume by 6 hours (P = 0.03). Central macular thickness measured 40.9 (28.6-53.2) μm thicker on the SD-OCT instrument while volume measured 3.47 (3.27-3.66) mm(3) higher.Significant central macular thickness and volume reductions occur in the first hours after injection with triamcinolone and/or bevacizumab.

  View details for DOI 10.2147/OPTH.S26631

  View details for PubMedID 22205836

  View details for PubMedCentralID PMC3245197

• Focal periocular carboplatin chemotherapy avoids systemic chemotherapy for unilateral, progressive retinoblastoma. Retina (Philadelphia, Pa.) Leng, T., Cebulla, C. M., Schefler, A. C., Murray, T. G. 2010; 30 (4): S66-8

  Abstract

  The purpose of this study was to report a case of a boy with unilateral, multifocal retinoblastoma who was successfully treated with periocular carboplatin injections for a tumor that progressed despite focal laser ablation.This is an interventional case report. A boy with a paternal history of retinoblastoma and in utero identification of an RB1 mutation was monitored beginning at 2 weeks of age. When the patient was 6 months old, the first tumor was detected and treatment with a direct, ablative, large spot-size diode laser was initiated. During a 38-month period of follow-up, the patient received 23 laser treatments and 3 periocular carboplatin injections (20 mg in 2 mL) to treat 3 tumors in 1 eye.Initially, diode laser ablation of the tumors produced a favorable involutional response of the tumors, associated with a decrease in size and vascularity. Despite aggressive treatment with 12 consecutive laser treatments for 9.7 months, progressive tumor growth was observed in the superonasal tumor, whereas the other 2 tumors remained quiescent. At that time, a series of three focal periocular injections of carboplatin were administered in combination with continued laser ablation. The tumor regressed with type 4 chorioretinal scarring. No systemic chemotherapy or radiation was required.This case of unilateral, multifocal retinoblastoma was successfully treated solely with diode laser ablation and rescue periocular injections of carboplatin after the failure of laser alone. A trial of periocular carboplatin with laser may be considered in cases of unilateral retinoblastoma that are resistant to laser ablation therapy alone.

  View details for PubMedID 20419851

• Intraoperative Use of Three-Dimensional Spectral-Domain Optical Coherence Tomography OPHTHALMIC SURGERY LASERS & IMAGING Ide, T., Wang, J., Tao, A., Leng, T., Kymionis, G. D., O'Brien, T. P., Yoo, S. H. 2010; 41 (2): 250-254

  Abstract

  To develop a prototype three-dimensional anterior segment spectral-domain optical coherence tomography (SD-OCT) device and demonstrate the feasibility of its use in the operating room.Single-institution interventional case series including six consecutive patients undergoing Descemet's stripping automated endothelial keratoplasty (DSAEK). The prototype anterior segment SD-OCT was used intraoperatively to search for the presence of interface fluid between the host cornea and the DSAEK graft.Anterior segment SD-OCT was successfully used intraoperatively during DSAEK. After the initial placement of the graft, no fluid was clinically apparent; however, interface fluid was identified by anterior segment SD-OCT in two of the six cases. After additional aspiration, all patients were fluid-free on follow-up anterior segment SD-OCT scanning.Intraoperative anterior segment SD-OCT was used successfully to find interface fluid that was clinically undetectable under the microscope. As such, all patients were able to leave the operating room with a fully attached graft.

  View details for DOI 10.3928/15428877-20100303-15

  View details for Web of Science ID 000275606400015

  View details for PubMedID 20307045

• Retinal capillary hemangioma in von Hippel-Lindau disease Arch Ophthalmol Leng T, Murray TG 2010; 128 (4): 425
• Branch retinal artery occlusion after septoplasty. Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye Leng, T., Moshfeghi, D. M. 2010; 41 Online: e1-2

  Abstract

  Loss of vision after uncomplicated rhinosurgery is a rare and uncommon complication. The authors describe a case of branch retinal artery occlusion after septoplasty in a 40-year-old otherwise healthy man. The likely etiology was injection of local anesthetics into the nasal mucosa during surgery. Vision loss could potentially have been prevented through the application of topical vasoconstrictive agents prior to anesthetic injection. Furthermore, slow injection and aspiration prior to injection could also help prevent inadvertent intraarterial injection.

  View details for DOI 10.3928/15428877-20101124-13

  View details for PubMedID 22785539

• Descemet Stripping Automated Endothelial Keratoplasty Tissue Preparation With Femtosecond Laser and Contact Lens CORNEA Ide, T., Yoo, S. H., Kymionis, G. D., Leng, T., Marini, C., Stanciu, N. A., O'Brien, T. P. 2010; 29 (1): 93-98

  Abstract

  To report a novel method of preparing planar Descemet stripping automated endothelial keratoplasty (DSAEK) tissue using a femtosecond laser with a hyperopic soft contact lens (Hyp-SCL).DSAEK tissue was prepared from 11 cadaveric porcine eyes. A femtosecond laser was used to create 400-microm flaps, with or without a Hyp-SCL, after which the eyes were imaged with anterior segment optical coherence tomography. The ratio of the mean central thickness (C) to the mean peripheral thickness (P) was calculated using the flap tool.Eleven eyes were cut (5 without, 5 with, and 1 without and with a Hyp-SCL). In all corneas, the cut interfaces were visualized by anterior segment optical coherence tomography. The mean C:P ratio of the flap made without a Hyp-SCL was 0.998 (range 0.968-1.03, SD = 0.254) compared with 0.904 (range 0.851-0.985, SD = 0.509) with a Hyp-SCL (P = 0.001), demonstrating that a cut made with a Hyp-SCL created a flap that was significantly more concave than that created without a Hyp-SCL, resulting in a more planar DSAEK graft. However, the C:P ratios calculated for DSAEK tissue made without (mean 0.998, range 0.965-1.02, SD = 0.0195) and with (mean 1.02, range 0.986-1.05, SD = 0.0250) a Hyp-SCL did not show significance (P = 0.07).Combining a femtosecond laser and a Hyp-SCL may aid in the creation of planar donor tissue for DSAEK. Clinically, this could reduce the amount of postoperative hyperopic shift, although further human corneal studies are warranted.

  View details for Web of Science ID 000273211500016

  View details for PubMedID 19907309

• Branch retinal artery occlusion after septoplasty. Ophthalmic surgery, lasers & imaging : the official journal of the International Society for Imaging in the Eye Leng, T., Moshfeghi, D. M. 2010; 41 Online: e1-2

  Abstract

  Loss of vision after uncomplicated rhinosurgery is a rare and uncommon complication. The authors describe a case of branch retinal artery occlusion after septoplasty in a 40-year-old otherwise healthy man. The likely etiology was injection of local anesthetics into the nasal mucosa during surgery. Vision loss could potentially have been prevented through the application of topical vasoconstrictive agents prior to anesthetic injection. Furthermore, slow injection and aspiration prior to injection could also help prevent inadvertent intraarterial injection.

  View details for DOI 10.3928/15428877-20101124-13

  View details for PubMedID 21117572

• SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY CHARACTERISTICS OF CUTICULAR DRUSEN RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., Rosenfeld, P. J., Gregori, G., Puliafito, C. A., Punjabi, O. S. 2009; 29 (7): 988-993

  Abstract

  To evaluate the appearance of cuticular drusen with spectral domain optical coherence tomography.Eyes of patients with cuticular drusen were imaged using a prototype spectral domain optical coherence tomography instrument with 5-microm axial resolution. Thickness maps were obtained after automated segmentation of the internal limiting membrane and retinal pigment epithelium layers using a proprietary algorithm. The volume of subretinal fluid (SRF) was calculated using a manual segmentation technique that involved drawing boundaries around the SRF. The repeatability of these measurements was tested by comparing the volume measurements from multiple scans performed on the same day in four eyes of three patients.Sixteen eyes from eight patients with cuticular drusen were scanned. Areas of decreased retinal thickness overlying drusen were best visualized using the three-dimensional retinal thickness map. The distribution and sawtooth pattern of cuticular drusen were best visualized using three-dimensional retinal pigment epithelium segmentation. Of the 16 eyes, 13 had SRF within the macula. In the eyes with macular SRF, characteristic excrescences were present along the outer retina and attenuation of the photoreceptor inner and outer segment boundary were observed in many areas. In areas where the retina was detached, the retinal pigment epithelium-Bruch's membrane complex appeared nodular or attenuated. The volumetric measurements of the SRF were performed using a manual segmentation with a 1.11% mean difference between repeated measurements on the same day (range, 0.47-1.68%; standard deviation, 0.55%).The sawtooth pattern of drusen and the presence of excrescences along the detached outer retina are characteristic features of cuticular drusen that should be helpful in confirming the diagnosis of this condition. The volumetric analysis of the SRF is repeatable and may be useful in following the clinical course of these patients.

  View details for Web of Science ID 000267955400013

  View details for PubMedID 19584657

• Retinal Vascular Tumor and Peripheral Retinal Vasculitis in the Setting of Systemic Tuberculosis OPHTHALMIC SURGERY LASERS & IMAGING Leng, T., Schefler, A. C., Murray, T. G. 2009; 40 (4): 409-412

  Abstract

  Tuberculosis commonly affects the eye by causing neovascularization, peripheral vasculitis, and choroidal tubercles. The authors describe a 28-year-old man with systemic tuberculosis who presented with a retinal vascular tumor, peripheral retinal vasculitis, retinal neovascularization, and vitreous hemorrhage causing acute vision loss. He was successfully treated with systemic anti-tuberculosis medications, retinal photocoagulation, and focal ablative diode laser to the tumor. Ophthalmologists should consider performing a purified protein derivative test and a chest x-ray for any patient with a history suspicious for tuberculosis who presents with a vascular tumor.

  View details for DOI 10.3928/15428877-20096030-11

  View details for Web of Science ID 000268127800011

  View details for PubMedID 19634748

• ENDOPHTHALMITIS CAUSED BY PROTEUS SPECIES Antibiotic Sensitivities and Visual Acuity Outcomes RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., Flynn, H. W., Miller, D., Murray, T. G., Smiddy, W. E. 2009; 29 (7): 1019-1024

  Abstract

  The purpose of this study was to report the clinical presentation, causative organisms, antibiotic sensitivities, management, and visual acuity outcomes in patients with endophthalmitis caused by Proteus species at a university teaching hospital over a 24-year period.This was a retrospective consecutive case series. The Bascom Palmer Eye Institute Microbiology Laboratory database was reviewed to identify all patients with intraocular cultures positive for Proteus species between 1983 and 2007. Clinical records were reviewed to ascertain the clinical presentation, management, and visual acuity outcomes.In the 13 patients identified, all cases followed intraocular surgery, and 1 was associated with a recurrent corneal ulcer. Of the 1,751 organisms isolated from intraocular culture during the study period, 244 were Gram negative. Proteus species represented 5.3% of gram-negative organisms and <1% of the total isolates identified. Endophthalmitis developed 2 days to 14 days postoperatively (median, 3.5 days), and patients were observed 1 month to 61 months after presentation (median, 17 months). Presenting vision ranged from light perception to 20/200. Ten patients had positive cultures for Proteus mirabilis, and three patients had a growth of Proteus morganii. Four patients (31%) were infected with >1 organism. All Proteus isolates were sensitive to the antibiotics clinically administered, including cefazolin, ceftazidime, gentamicin, and the fluoroquinolones. Five patients (38%) initially received intravitreal injections of antibiotics alone, 1 received an anterior chamber washout in combination with intravitreal injections, and 7 patients (54%) received pars plana vitrectomy in combination with intravitreal injections. Two of the patients (15%) who received vitrectomies had either an intraocular lens or retained nuclear fragments removed. Six patients (46%) received additional antibiotic injections during the clinical course, and 6 patients (46%) underwent additional surgical procedures. Final visual acuity was better than light perception in 5 patients (38%) and was light perception or no light perception in 8 patients (62%). Only 4 patients (31%) had a final vision acuity > or =5/200.Despite prompt treatment with appropriate antibiotics, the clinical outcome for Proteus species endophthalmitis is often poor.

  View details for Web of Science ID 000267955400017

  View details for PubMedID 19584659

• Eyelid and orbital implant injury after enucleation OphthalmologyWeb Leng T 2009
• Subconjunctival Air Leakage After Descemet's Stripping Automated Endothelial Keratoplasty(DSAEK) in a Post-Trabeculectomy Eye. The open ophthalmology journal Ide, T., Yoo, S. H., Leng, T., O'Brien, T. P. 2009; 3: 1-2

  Abstract

  To report a case of subconjunctival air leakage from the anterior chamber (AC) into a trabeculectomy bleb after Descemet's stripping automated endothelial keratoplasty (DSAEK).An 89 year-old woman with a previous history of primary open angle glaucoma in her left eye and previous trabeculectomy with mitomycin C had DSAEK on the patient's left eye in order to treat her endothelial disease. During the DSAEK procedure, air was injected into the AC to aid in graft adherence.The day after the surgery, subconjunctival air leakage from the AC into a trabeculectomy bleb was observed.Although our patient did not have any complications from this leak, there exists the potential for hypotony, bleb-related infections, and dislocations of the DSAEK graft. Given the potential consequences, these patients should be monitored closely.

  View details for DOI 10.2174/1874364100903010001

  View details for PubMedID 19554220

• Three-dimensional spectral domain optical coherence tomography of a clear corneal cataract incision OPHTHALMIC SURGERY LASERS & IMAGING Leng, T., Lujan, B. J., Yoo, S. H., Wang, J. 2008; 39 (4): S132-S134

  Abstract

  A prototype 1,310-nm wavelength spectral domain optical coherence tomography (SD-OCT) instrument was constructed and mounted onto a conventional slit lamp for imaging of the anterior segment. The device had an axial resolution of 8 microm and was able to acquire real-time two-dimensional images at 14 frames/second and full three-dimensional datasets in approximately 7 seconds. An SD-OCT dataset of 100 B-scans, each consisting of 512 A-scans, was acquired from the left eye ofa patient who had undergone phacoemulsification with a clear corneal incision. The resulting dataset could be manipulated in three-dimensional space to analyze the geometry of the wound. Additionally, stromal edema and iris features were clearly imaged with the device. SD-OCT can be used to analyze clear corneal incisions to determine optimal wound construction technique and geometry as they relate to the prevention of complications such as postoperative wound leak, infection, and epithelial ingrowth.

  View details for Web of Science ID 000258283000025

  View details for PubMedID 18777882

• Glaucoma valves and shunts OphthalmologyWeb Leng T 2008
• A model retinal interface based on directed neuronal growth for single cell stimulation BIOMEDICAL MICRODEVICES Mehenti, N. Z., Tsien, G. S., Leng, T., Fishman, H. A., Bent, S. F. 2006; 8 (2): 141-150

  Abstract

  In this work, we use cell micropatterning technologies to direct neuronal growth to individual electrodes, and demonstrate that such an approach can achieve selective stimulation and lower stimulation thresholds than current field-effect based retinal prostheses. Rat retinal ganglion cells (RGCs) were purified through immunopanning techniques, and microcontact printing (microCP) was applied to align and pattern laminin on a microelectrode array, on which the RGCs were seeded and extended neurites along the pattern to individual electrodes. The stimulation threshold currents of RGCs micropatterned to electrodes were found to be significantly less than those of non-patterned RGCs over a wide range of electrode-soma distances, as determined with calcium imaging techniques. Moreover, the stimulation threshold for micropatterned cells was found to be independent of electrode-soma distance, and there was no significant effect of microCP on cell excitability. The effects of additional stimulation parameters, such as electrode size and pulse duration, on threshold currents were determined. The stimulation results quantitatively demonstrate the potential benefits of a retinal prosthetic interface based on directed neuronal growth.

  View details for DOI 10.1007/s10544-006-7709-3

  View details for Web of Science ID 000237486500006

  View details for PubMedID 16688573

• Full thickness retinal pigment epithelium explants proliferate into epithelial monolayers on synthetic Bruch's membrane substitutes Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Lombardi, L., Leng, T., Yeh, E., Molnar, F., Noolandi, J., Marmor, M. F., Fishman, H. A., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2005

  View details for Web of Science ID 000227980404442

• Synthetic Bruch's membrane substitutes: Comparisons after subretinal transplantation with cultured iris pigment epithelium Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Molnar, F. E., Lombardi, L., Berker, N., Yeh, E., Yellachich, D., Leng, T., Dalal, R., Marmor, M. F., Fishman, H. A., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2005

  View details for Web of Science ID 000227980404446

• Directed retinal nerve cell growth for use in a retinal prosthesis interface INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Leng, T., Wu, P., Mehenti, N. Z., Bent, S. F., Marmor, M. F., Blumenkranz, M. S., Fishman, H. A. 2004; 45 (11): 4132-4137

  Abstract

  Retinal prosthetic devices that use microelectrode arrays to stimulate retinal nerve cells may provide a viable treatment for degenerative retinal diseases. Current devices are based on electrical field-effect stimulation of remaining functional neural elements. However, the distance between target neurons and electrodes limits the potential density of electrodes and the ability to stimulate specific types of retinal neurons that contribute to visual perceptions. This study was conducted to investigate the use of microcontact printing (muCP) to direct cultured or explant retinal ganglion cell (RGC) neurites to precise and close stimulation positions and to evaluate the cell types that grow from a retinal explant.RGCs and whole retinal explants were isolated from postnatal day-7 Sprague-Dawley rats using immunopanning purification and microdissection, respectively. Aligned muCP was used to direct the growth of RGC neurites from pure cultures (n=105) and retinal explants (n=64) along laminin patterns and to individual microelectrodes. Immunofluorescence stains (n=39) were used to determine the cell types that grew out from the retinal explants.RGC neurite growth was directed reproducibly along aligned laminin micropatterns to individual microelectrodes in pure RGC cultures and from full-thickness explanted rat retinas in 92% of experiments, neurites from pure RGC cultures extended along the laminin lines with an average length of 263 +/- 118 microm (SD; n=27) after 24 hours. Neurites from retinal explants extended in more than 80% of experiments and were observed to grow to an average length of 279 +/- 78 microm (n=64) after 2 days in culture. These neurites grew up to 3 mm after 1 month of culture on the laminin micropatterns. Immunohistochemical stains demonstrated that extended processes from both RGCs and glial cells grew out of retinal explants onto stamped laminin lines.Using muCP to pattern surfaces with growth factors, individual neuronal processes from pure RGC culture and whole retinal explants can be directed to discrete sites on a microelectronic chip surface. By directing RGC neurite processes to specific sites, single cell stimulation becomes possible. This may allow discrete populations of retinal neurons to be addressed so that physiologic retinal processing of visual information can be achieved.

  View details for DOI 10.1167/iovs.03-1335

  View details for PubMedID 15505066

• The chick chorioallantoic membrane as a model tissue for surgical retinal research and simulation RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Leng, T., MILLER, J. M., Bilbao, K. V., Palanker, D. V., Huie, P., Blumenkranz, M. S. 2004; 24 (3): 427-434

  Abstract

  We describe the use of chick chorioallantoic membrane (CAM) as a model system for the study of the precision and safety of vitreoretinal microsurgical instruments and techniques.The CAM was prepared for experimentation with and without its inner shell membrane (ISM) attached for in vivo and in vitro experiments that simulated medical and surgical interventions on the retina.The CAM's ease of use, low cost, and anatomic structure make it a convenient model for surgical retinal and retinal vascular modeling.While CAM has been used extensively in the past for ocular angiogenesis studies, we describe the tissue as a useful tool for a variety of other applications, including (1) testing of novel surgical tools and techniques for cutting and coagulating retina and its vasculature, (2) testing vessel cannulation and injection techniques, (3) angiographic studies, and (4) endoscopic surgery.

  View details for Web of Science ID 000222156800014

  View details for PubMedID 15187666

• Fabrication and characterization of a carbon nanotube microelectrode array for retinal prostheses Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Wang, K., Dai, H., Leng, T., Mehenti, N. Z., Harris, J. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2004: U379–U379

  View details for Web of Science ID 000223338201366

• Retinal light processing using carbon nanotubes Official Gazette of the USPTO Patents Loftus D, Leng T, Fishman HA 2004; 1283 (5)
• The artificial synapse chip: A flexible retinal interface based on directed retinal cell growth and neurotransmitter stimulation ARTIFICIAL ORGANS Peterman, M. C., Mehenti, N. Z., Bilbao, K. V., Lee, C. J., Leng, T., Noolandi, J., Bent, S. F., Blumenkranz, M. S., Fishman, H. A. 2003; 27 (11): 975-985

  Abstract

  The Artificial Synapse Chip is an evolving design for a flexible retinal interface that aims to improve visual resolution of an electronic retinal prosthesis by addressing cells individually and mimicking the physiological stimulation achieved in synaptic transmission. We describe three novel approaches employed in the development of the Artificial Synapse Chip: (i) micropatterned substrates to direct retinal cell neurite growth to individual stimulation sites; (ii) a prototype retinal interface based on localized neurotransmitter delivery; and (iii) the use of soft materials to fabricate these devices. By patterning the growth of cells to individual stimulation sites, we can improve the selectivity of stimulation and decrease the associated power requirements. Moreover, we have microfabricated a neurotransmitter delivery system based on a 5- micro m aperture in a 500-nm-thick silicon nitride membrane overlying a microfluidic channel. This device can release neurotransmitter volumes as small as 2 pL, demonstrating the possibility of chemical-based prostheses. Finally, we have fabricated and implanted an equivalent device using soft flexible materials that conform to the retinal tissue more effectively. As many of the current retinal prosthesis devices use hard materials and electrical excitation at a lower resolution, our approach may provide more physiologic retinal stimulation.

  View details for Web of Science ID 000186491900003

  View details for PubMedID 14616516

• Wiggling subcutaneous lumps - Furuncular myiasis due to Dermatobia hominis larvae CLINICAL INFECTIOUS DISEASES Leng, T., Smith, D. S. 2003; 37 (4): 542-?

  View details for Web of Science ID 000184618900011

• A retinal interface based on neurite micropatterning for single cell stimulation Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Mehenti, N. Z., Peterman, M. C., Leng, T., Marmor, M. F., Blumenkranz, M. S., Bent, S. F. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U704–U704

  View details for Web of Science ID 000184607002529

• Cell demographics from full thickness retinal explant growth on micropatterned surfaces Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Wu, P., Mehenti, N. Z., Leng, T., Marmor, M. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2003: U692–U692

  View details for Web of Science ID 000184607002467

• Wiggling subcutaneous lumps. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America Leng, T., Smith, D. S. 2003; 37 (4): 542, 591–92

  View details for PubMedID 12905150

• Microcontact printing on human tissue for retinal cell transplantation ARCHIVES OF OPHTHALMOLOGY Lee, C. J., Huie, P., Leng, T., Peterman, M. C., Marmor, M. F., Blumenkranz, M. S., Bent, S. F., Fishman, H. A. 2002; 120 (12): 1714-1718

  Abstract

  To demonstrate that microcontact printing, a modern materials fabrication technique, can be used to engineer the surface of human tissue and to show that inhibitory molecules can be used to pattern the growth of retinal pigment epithelial cells or iris pigment epithelial cells on human lens capsule for transplantation.Photolithographic techniques were used to fabricate photoresist-coated silicon substrates into molds. Poly(dimethylsiloxane)stamps for microcontact printing were made from these molds. The poly(dimethylsiloxane) stamps were then used to "wet-transfer" growth inhibitory molecules to the surface of prepared human lens capsules that were obtained during cataract surgery. Human retinal pigment epithelial and rabbit iris pigment epithelial cells were grown on a lens capsule substrate in the presence and absence of a patterned array of inhibitory factors.We found that human lens capsule could be microprinted with a precision similar to that obtained on glass or synthetic polymers. Retinal pigment epithelial cells and iris pigment epithelial cells cultured onto an untreated lens capsule showed spreading and formed into fusiform-appearing cells. In contrast, cells cultured on a lens capsule with a hexagonal micropattern of growth inhibitory molecules retained an epithelioid form within the inhibitory hexagons.Inhibitory growth molecules can be micropatterned onto human lens capsule, and these micropatterns can control the organization of retinal pigment epithelial cells or iris pigment epithelial cells cultured onto the lens capsule surface.Microprinting on autologous human tissue may facilitate efforts to effectively organize cell cultures and transplantations for the replacement of vital ocular tissues such as the retinal pigment epithelium in age-related macular degeneration.

  View details for PubMedID 12470147

• Tissue engineered lens capsule as a substrate for IPE and RPE transplantation Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Fung, A. E., Lee, C. J., Leng, T., Bilbao, L. V., Peterman, M. C., Blumenkranz, M. S., Bent, S. F., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U973–U973

  View details for Web of Science ID 000184606700604

• Directed ganglion cell growth and stimulation with microcontact printing as a prototype visual prosthesis interface Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Leng, T., Huie, P., Mehenti, N. Z., Peterman, M. C., Lee, C. J., Marmor, M. F., Sanislo, S. R., Beni, S. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U1279–U1279

  View details for Web of Science ID 000184606701608

• A biodegradable matrix facilitates the use of lens capsule as a substrate for subretinal cell transplantation Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Bilbao, K. V., Leng, T., Fung, A. E., Huie, P., Sanislo, S. R., Marmor, M. F., Blumenkranz, M. S., Fishman, H. A. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U972–U972

  View details for Web of Science ID 000184606700593

• The artificial synapse chip: A novel interface for a retinal prosthesis based on neurotransmitter stimulation and nerve regeneration Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology Fishman, H. A., Peterman, M. C., Leng, T., Huie, P., Lee, C. J., Bloom, D. M., Sanislo, S. R., Marmor, M. F., Bent, S. F., Blumenkranz, M. S. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2002: U803–U803

  View details for Web of Science ID 000184606700013

• Novel interface to biological systems for retinal prosthetics Symposium on MEMS and BioMEMS held at the 2002 MRS Spring Meeting Peterman, M. C., Lee, C., Leng, T., Huie, P., Fishman, H. A. MATERIALS RESEARCH SOCIETY. 2002: 149–154

  View details for Web of Science ID 000178928100021

• A real world lesson The Bulletin of the Santa Clara County Medical Association Leng T 2001; 7 (6): 6-7
• Capillary electrophoresis coupled with RBL-2H3 cells as a single-cell biosensor Stanford University Department of Biological Sciences Honors Thesis Leng T, Zare RN 1999