Clinical Focus

  • Ophthalmology
  • Macular and Vitreoretinal Diseases

Academic Appointments

Administrative Appointments

  • Professor and Chairman, Stanford University School of Medicine - Ophthalmology (1997 - Present)

Honors & Awards

  • Lifetime Achievement Award, American Academy of Ophthalmology (2008)
  • Senior Honor Award, American Academy of Ophthalmology (2004)

Professional Education

  • Board Certification: Ophthalmology, American Board of Ophthalmology (1980)
  • Fellowship:University Of Miami - School of Medicine (1980) FL
  • Residency:Stanford University School of Medicine (1979) CA
  • Residency:Stanford University School of Medicine (1977) CA
  • Internship:Stanford University School of Medicine (1976) CA
  • Medical Education:Warren Alpert Medical School Brown University (1975) RI
  • AB, Brown University, Biology (1972)
  • MD, Brown University, Medicine (1975)
  • MMS, Brown University, Biochemical Pharmacology (1976)
  • Internship, Stanford University, Surgery (1976)
  • Residency, Stanford University, Ophthalmology (1979)
  • Fellowship, Bascom Palmer Eye Institute, Vitreoretinal Surgery (1980)

Research & Scholarship

Current Research and Scholarly Interests

Clinical Interest and Research
My primary areas of interest are in the diagnosis, medical and surgical treatment of vitreal retinal diseases. These principally include age-related macular degeneration and other diseases of the macula, and tractional syndromes, diabetic retinopathy, and complex forms of retinal detachment. I have been interested in the development of novel technology to diagnose and treat these diseases, including new forms of imaging, laser delivery systems, other microsurgical tools, and new drugs and drug delivery systems that inhibit new blood vessel growth, scarring and intraocular inflammation. I have been actively involved in translational research in the laboratory as well as technology transfer associated with that research for a variety of new therapies that have received FDA clearance and been introduced into clinical practice over the past 30 years.

Administrative and Community Service
I have served on the Board of Directors of a variety of voluntary education and service organizations, including the Corporation of Brown University, multiple scientific advisory boards and various philanthropic and research organizations.


2015-16 Courses

Stanford Advisees


All Publications

  • Panretinal Photocoagulation for Proliferative Diabetic Retinopathy AMERICAN JOURNAL OF OPHTHALMOLOGY Palanker, D., Blumenkranz, M. S. 2012; 153 (4): 780-781

    View details for Web of Science ID 000302387100035

    View details for PubMedID 22445637

  • Longterm cultures of the aged human RPE do not maintain epithelial morphology and high transepithelial resistance GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY Stanzel, B. V., Blumenkranz, M. S., Binder, S., Marmor, M. F. 2012; 250 (2): 313-315

    View details for DOI 10.1007/s00417-011-1624-x

    View details for Web of Science ID 000300290600021

    View details for PubMedID 21279375

  • Tennis partners. Retina (Philadelphia, Pa.) Flynn, H. W., Blumenkranz, M. S. 2012; 32: S12-4

    View details for DOI 10.1097/IAE.0b013e31823daa6f

    View details for PubMedID 22270764

  • Fifty Years of Ophthalmic Laser Therapy ARCHIVES OF OPHTHALMOLOGY Palanker, D. V., Blumenkranz, M. S., Marmor, M. F. 2011; 129 (12): 1613-1619

    View details for Web of Science ID 000297995000016

    View details for PubMedID 22159684

  • THE IMPACT OF PULSE DURATION AND BURN GRADE ON SIZE OF RETINAL PHOTOCOAGULATION LESION Implications for Pattern Density RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Palanker, D., Lavinsky, D., Blumenkranz, M. S., Marcellino, G. 2011; 31 (8): 1664-1669


    Shorter pulses used in pattern scanning photocoagulation (10-20 milliseconds [ms]) tend to produce lighter and smaller lesions than the Early Treatment Diabetic Retinopathy Study standard 100-ms exposures. Smaller lesions result in fewer complications but may potentially reduce clinical efficacy. It is worthwhile to reevaluate existing standards for the number and size of lesions needed.The width of the coagulated zone in patients undergoing retinal photocoagulation was measured using optical coherence tomography. Lesions of "moderate," "light," and "barely visible" clinical grades were compared for 100, 200, and 400 ?m spot sizes and pulse durations of 20 ms and 100 ms.To maintain the same total area as in 1,000 standard burns (100 ms, moderate) with a 400-?m beam, a larger number of 20-ms lesions are required: 1,464, 1,979, and 3,520 for moderate, light, and barely visible grades, respectively. Because of stronger relative effect of heat diffusion with a smaller beam, with 200 ?m this ratio increases: 1,932, 2,783, and 5,017 lesions of 20 ms with moderate, light, and barely visible grades correspond to the area of 1,000 standard burns.A simple formula is derived for calculation of the required spot spacing in the laser pattern for panretinal photocoagulation with various laser parameters to maintain the same total coagulated area.

    View details for Web of Science ID 000294456100027

    View details for PubMedID 21642898

  • Femtosecond laser capsulotomy JOURNAL OF CATARACT AND REFRACTIVE SURGERY Friedman, N. J., Palanker, D. V., Schuele, G., Andersen, D., Marcellino, G., Seibel, B. S., Battle, J., Feliz, R., Talamo, J. H., Blumenkranz, M. S., Culbertson, W. W. 2011; 37 (7): 1189-1198


    To evaluate a femtosecond laser system to create the capsulotomy.Porcine and cadaver eye studies were performed at OptiMedica Corp., Santa Clara, California, USA; the human trial was performed at the Centro Laser, Santo Domingo, Dominican Republic.Experimental and clinical study.Capsulotomies performed by an optical coherence tomography-guided femtosecond laser were evaluated in porcine and human cadaver eyes. Subsequently, the procedure was performed in 39 patients as part of a prospective randomized study of femtosecond laser-assisted cataract surgery. The accuracy of the capsulotomy size, shape, and centration were quantified and capsulotomy strength was assessed in the porcine eyes.Laser-created capsulotomies were significantly more precise in size and shape than manually created capsulorhexes. In the patient eyes, the deviation from the intended diameter of the resected capsule disk was 29 ?m ± 26 (SD) for the laser technique and 337 ± 258 ?m for the manual technique. The mean deviation from circularity was 6% and 20%, respectively. The center of the laser capsulotomies was within 77 ± 47 ?m of the intended position. All capsulotomies were complete, with no radial nicks or tears. The strength of laser capsulotomies (porcine subgroup) decreased with increasing pulse energy: 152 ± 21 mN for 3 ?J, 121 ± 16 mN for 6 ?J, and 113 ± 23 mN for 10 ?J. The strength of the manual capsulorhexes was 65 ± 21 mN.The femtosecond laser produced capsulotomies that were more precise, accurate, reproducible, and stronger than those created with the conventional manual technique.

    View details for DOI 10.1016/j.jcrs.2011.04.022

    View details for Web of Science ID 000292783100004

    View details for PubMedID 21700099

  • Critical appraisal of the clinical utility of the dexamethasone intravitreal implant (Ozurdex) for the treatment of macular edema related to branch retinal vein occlusion or central retinal vein occlusion. Clinical ophthalmology (Auckland, N.Z.) Chan, A., Leung, L., Blumenkranz, M. S. 2011; 5: 1043-1049


    Macular edema is a common cause of visual loss in patients with retinal vein occlusions. Ozurdex(®), a dexamethasone intravitreal implant, has been shown in randomized controlled trials to reduce macular edema and improve visual acuity in patients with either branch retinal vein occlusions or central retinal vein occlusions. It was approved in the United States in 2009. Since then, new therapeutic agents and clinical data have emerged. The purpose of this review is to critically evaluate the clinical utility of Ozurdex(®) in the current treatment strategy of macular edema related to retinal vein occlusion.

    View details for DOI 10.2147/OPTH.S13775

    View details for PubMedID 21845032

  • 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


    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) ?m 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

  • Femtosecond Laser-Assisted Cataract Surgery with Integrated Optical Coherence Tomography SCIENCE TRANSLATIONAL MEDICINE Palanker, D. V., Blumenkranz, M. S., Andersen, D., Wiltberger, M., Marcellino, G., Gooding, P., Angeley, D., Schuele, G., Woodley, B., Simoneau, M., Friedman, N. J., Seibel, B., Batlle, J., Feliz, R., Talamo, J., Culbertson, W. 2010; 2 (58)


    About one-third of people in the developed world will undergo cataract surgery in their lifetime. Although marked improvements in surgical technique have occurred since the development of the current approach to lens replacement in the late 1960s and early 1970s, some critical steps of the procedure can still only be executed with limited precision. Current practice requires manual formation of an opening in the anterior lens capsule, fragmentation and evacuation of the lens tissue with an ultrasound probe, and implantation of a plastic intraocular lens into the remaining capsular bag. The size, shape, and position of the anterior capsular opening (one of the most critical steps in the procedure) are controlled by freehand pulling and tearing of the capsular tissue. Here, we report a technique that improves the precision and reproducibility of cataract surgery by performing anterior capsulotomy, lens segmentation, and corneal incisions with a femtosecond laser. The placement of the cuts was determined by imaging the anterior segment of the eye with integrated optical coherence tomography. Femtosecond laser produced continuous anterior capsular incisions, which were twice as strong and more than five times as precise in size and shape than manual capsulorhexis. Lens segmentation and softening simplified its emulsification and removal, decreasing the perceived cataract hardness by two grades. Three-dimensional cutting of the cornea guided by diagnostic imaging creates multiplanar self-sealing incisions and allows exact placement of the limbal relaxing incisions, potentially increasing the safety and performance of cataract surgery.

    View details for DOI 10.1126/scitranslmed.3001305

    View details for Web of Science ID 000288441800003

    View details for PubMedID 21084720



    The purpose of this study was to evaluate the correlation between best-corrected visual acuity (BCVA) and macular thickness in patients with persistent macular edema treated with a dexamethasone intravitreal drug delivery system (dexamethasone DDS).In a randomized, multicenter, controlled, parallel-group, dose-ranging study, patients with macular edema lasting at least 90 days despite treatment were randomized to observation or treatment with 350- or 700-microg dexamethasone DDS. Macular thickness was assessed in 80 patients using optical coherence tomography. Best-corrected visual acuity was measured using Early Treatment Diabetic Retinopathy Study methodology.At baseline, macular thickness was significantly inversely correlated with BCVA (r = -0.406, P < 0.001). Patients treated with 350- or 700-microg dexamethasone DDS showed a significant decrease in macular thickness from baseline to Day 90 (P = 0.002). In the 700-microg dexamethasone DDS treatment group, there was a modest inverse correlation between changes in macular thickness from baseline to Day 90 and improvement in BCVA (r = -0.530, P = 0.009). In the 350-microg dexamethasone DDS treatment group, the correlation was weaker and not statistically significant (r = -0.206, P = 0.304).The correlation between baseline BCVA and macular thickness in patients with persistent macular edema was modest. Improvement in BCVA after treatment with 700-microg dexamethasone DDS was consistent with changes in macular thickness measured using optical coherence tomography.

    View details for DOI 10.1097/IAE.0b013e3181dcfaf3

    View details for Web of Science ID 000279635600015

    View details for PubMedID 20616686

  • Optimal current and future treatments for diabetic macular oedema Blumenkranz, M. S. NATURE PUBLISHING GROUP. 2010: 428-434


    Diabetic retinopathy is the most common cause of vision loss in working-age adults. Both inflammation and vascular endothelial growth factor (VEGF) play a critical role, modern and emerging treatments have centred on both laser photocoagulation and new pharmacologic strategies to improve the prognosis. Focal and grid photocoagulation, as described in the ETDRS trials, remain the gold standard of treatment. New classes of agents include long-acting steroid formulations delivered as intravitreal injections and also anti-VEGF agents. In addition, studies are under way to evaluate potential benefits from other novel agents, including those acting on the mammalian target of rapamycin pathway. In limited numbers of direct head-to-head comparisons, both steroids and anti-VEGF agents appear to be superior to conventional photocoagulation in reducing macular oedema in the first 4-6 months after treatment, although laser photocoagulation appears to be superior at time points of 1-2 years. In addition, there appear to be significant potential long-term complications of steroids including cataracts and glaucoma that may limit their use in certain patients. New methods of the laser delivery including shorter pulse durations and pattern scanning may also improve the effectiveness and risk profile of laser from the patient prospective. Finally, multi-modality therapy may play an increasingly important role.

    View details for DOI 10.1038/eye.2009.335

    View details for Web of Science ID 000275447200005

    View details for PubMedID 20075969

  • Photoacoustic ocular imaging OPTICS LETTERS de la Zerda, A., Paulus, Y. M., Teed, R., Bodapati, S., Dollberg, Y., Khuri-Yakub, B. T., Blumenkranz, M. S., Moshfeghi, D. M., Gambhir, S. S. 2010; 35 (3): 270-272


    We developed a photoacoustic ocular imaging device and demonstrated its utility in imaging the deeper layers of the eye including the retina, choroid, and optic nerve. Using safe laser intensity, the photoacoustic system was able to visualize the blood distribution of an enucleated pig's eye and an eye of a living rabbit. Ultrasound images, which were simultaneously acquired, were overlaid on the photoacoustic images to visualize the eye's anatomy. Such a system may be used in the future for early detection and improved management of neovascular ocular diseases, including wet age-related macular degeneration and proliferative diabetic retinopathy.

    View details for Web of Science ID 000274196100001

    View details for PubMedID 20125691

  • Photodynamic Therapy With and Without Adjunctive Intravitreal Triamcinolone Acetonide: A Retrospective Comparative Study OPHTHALMIC SURGERY LASERS & IMAGING Chan, A., Blumenkranz, M. S., Wu, K. H., Wang, G., Berker, N., Parast, L. M., Sanislo, S. R. 2009; 40 (6): 561-569


    To compare photodynamic therapy (PDT) with and without adjunctive intravitreal triamcinolone acetonide (IVTA) in the treatment of choroidal neovascularization secondary to age-related macular degeneration.Sixty-six eyes received PDT with IVTA and 73 eyes received PDT only. Outcome measures included changes in visual acuity and greatest linear dimension (GLD), the presence of angiographic leakage, the re-treatment rate, and adverse events.Patients treated with PDT with IVTA had reduced mean GLD compared to patients treated with PDT only at all study time points (3 [P = .0049], 6 [P = .003], and 12 [P = .05] months). Forty-four percent of patients in the PDT with IVTA group and 22% of patients in the PDT only group achieved angiographic closure at 3 months (P = .027). There were no significant differences in the final visual acuity outcome or the re-treatment rate between the two groups.PDT with IVTA therapy has a favorable outcome on GLD. There is a modest improvement in visual acuity with PDT with IVTA therapy, which diminishes over time.

    View details for DOI 10.3928/15428877-20091030-05

    View details for Web of Science ID 000272510500006

    View details for PubMedID 19928721

  • Healing of Retinal Photocoagulation Lesions INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Paulus, Y. M., Jain, A., Gariano, R. F., Stanzel, B. V., Marmor, M., Blumenkranz, M. S., Palanker, D. 2008; 49 (12): 5540-5545


    To systematically assess the changes in retinal morphology during the healing of retinal photocoagulation lesions of various clinical grades.Rabbits were irradiated with a 532-nm Nd:YAG laser with a beam diameter of 330 microm at the retinal surface, a power of 175 mW, and pulse durations between 5 and 100 ms. Retinal lesions were clinically graded 1 minute after placement as invisible, barely visible, light, moderate, intense, very intense, and rupture and were assessed histologically at six time points from 1 hour to 4 months.At all pulse durations, the width of the retinal lesions decreased over time. At clinical grades of light and more severe (pulse durations, 10-100 ms), retinal scarring stabilized at 1 month at approximately 35% of the initial lesion diameter. Lesions clinically categorized as barely visible and invisible (pulse durations of 7 and 5 ms) exhibited coagulation of the photoreceptor layer but did not result in permanent scarring. In these lesions, photoreceptors completely filled in the damaged areas by 4 months.The decreasing width of the retinal damage zone suggests that photoreceptors migrating from unaffected areas fill in the gap in the photoreceptor layer. Laser photocoagulation parameters can be specified to avoid not only the inner retinal damage, but also permanent disorganization and scarring in the photoreceptor layer. These data may facilitate studies to determine those aspects of laser treatment necessary for beneficial clinical response and those that result in extraneous retinal damage.

    View details for DOI 10.1167/iovs.08-1928

    View details for Web of Science ID 000261193900049

    View details for PubMedID 18757510

  • Severe surfing-related ocular injuries: the Stanford Northern Californian experience BRITISH JOURNAL OF SPORTS MEDICINE Zoumalan, C. I., Blumenkranz, M. S., McCulley, T. J., Moshfeghi, D. M. 2008; 42 (10): 855-857


    There is a growing body of literature describing severe surfing-related ocular injuries that result in permanent vision loss. We describe three severe surfing-related ocular injuries that occurred on beaches in northern California. One particular case stresses the need to tailor treatment to the patient and injury because of the possibility of good outcomes despite severe injury. Attention should also be directed towards commercially available safety gear and providing additional safety measures to prevent other orbital and ocular injuries.

    View details for DOI 10.1136/bjsm.2007.041657

    View details for Web of Science ID 000259995400017

    View details for PubMedID 18198199

  • Surveillance for potential adverse events associated with the use of intravitreal bevacizumab for retinal and choroidal vascular disease RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Wong, L. J., Desai, R. U., Jain, A., Feliciano, D., Moshfeghi, D. M., Sanislo, S. R., Blumenkranz, M. S. 2008; 28 (8): 1151-1158


    To systematically study potential adverse events associated with the use of intraocular bevacizumab at a single medical center.Retrospective study of all consecutive patients receiving intraocular bevacizumab injections at the Stanford University Department of Ophthalmology between November 15, 2005 and July 14, 2006. Bevacizumab was given for exudative age-related macular degeneration, retinal vascular occlusion, diabetic macular edema, neovascular glaucoma, and five other indications.We analyzed medical records of 186 subjects (203 eyes) who received a total of 578 injections of 1.25 mg of bevacizumab. The average follow-up was approximately 6 months. Five eyes with exudative age-related macular degeneration developed retinal pigment epithelial (RPE) tears, all with preexisting RPE detachments. These five eyes represented 2.9% of all age-related macular degeneration eyes treated and 7% of the age-related macular degeneration eyes with preexisting RPE detachments at initiation of treatment. Other adverse events were rare and included retinal ischemia, subretinal hemorrhage, vitreous hemorrhage, ocular irritation or pain, worsened hypertension, and headache. No death or thromboembolic events were observed.Intraocular bevacizumab appears to be well tolerated for the treatment of a variety of retinal and choroidal vascular diseases. RPE tears may occur when treating choroidal neovascularization, particularly in patients with preexisting RPE detachment.

    View details for Web of Science ID 000259329100018

    View details for PubMedID 18685542

  • Bacterial contamination of ocular surface and needles in patients undergoing intravitreal injections RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES De Caro, J. J., Ta, C. N., Ho, H. V., Cabael, L., Hu, N., Sanislo, S. R., Blumenkranz, M. S., Moshfeghi, D. M., Jack, R., de Kaspar, H. M. 2008; 28 (6): 877-883


    To evaluate potential sources of bacterial contamination during intravitreal (IVT) injection procedures.Patients scheduled for IVT injection were asked to enroll in the study at the California Vitreoretinal Center (Menlo Park, CA) and the Vantage Eye Center (Salinas, CA) between October 2004 and April 2005. A total of 104 patients participated in the study, with a total of 118 IVT injection procedures performed on 107 eyes. Standard microbiological techniques were used to culture, identify, and quantify bacterial contamination of injection needles and the bulbar conjunctiva at the injection site in patients undergoing IVT injections. The main outcomes measured were type and quantity of bacterial isolates.Two (2%) of 114 needles collected were contaminated with bacteria. The prevalence of bacterial contamination of the injection site on the bulbar conjunctiva was 43% before prophylaxis on the day of the injection with topical antibiotics and povidone-iodine, with a statistically significant reduction to 13% after prophylaxis (P < 0.0001). Coagulase-negative Staphylococcus, the most common bacterium isolated from the ocular surface, was isolated from both culture-positive needles.IVT injection needles became contaminated with bacteria during the injection procedure. Although the contamination rate was low, this supports a mechanism of postinjection endophthalmitis in which there is direct inoculation of ocular surface flora into the vitreous cavity by the injection needle.

    View details for Web of Science ID 000256714300014

    View details for PubMedID 18536606

  • Effect of pulse duration on size and character of the lesion in retinal photocoagulation ARCHIVES OF OPHTHALMOLOGY Jain, A., Blumenkranz, M. S., Paulus, Y., Wiltberger, M. W., Andersen, D. E., Huie, P., Palanker, D. 2008; 126 (1): 78-85


    To systematically evaluate the effects of laser beam size, power, and pulse duration of 1 to 100 milliseconds on the characteristics of ophthalmoscopically visible retinal coagulation lesions.A 532-nm Nd:YAG laser was used to irradiate 36 retinas in Dutch Belt rabbits with retinal beam sizes of 66, 132, and 330 mum. Lesions were clinically graded 1 minute after placement, their size measured by digital imaging, and their depth assessed histologically at different time points.Retinal lesion size increased linearly with laser power and logarithmically with pulse duration. The width of the therapeutic window, defined by the ratio of the threshold power for producing a rupture to that of a mild coagulation, decreased with decreasing pulse durations. For 132- and 330-mum retinal beam sizes, the therapeutic window declined from 3.9 to 3.0 and 5.4 to 3.7, respectively, as pulse duration decreased from 100 to 20 ms. At pulse durations of 1 millisecond, the therapeutic window decreased to unity, at which point rupture and a mild lesion were equally likely to occur.At shorter pulse durations, the width and axial extent of the retinal lesions are smaller and less dependent on variations in laser power than at longer durations. The width of the therapeutic window, a measure of relative safety, increases with the beam size.Pulse durations of approximately 20 milliseconds represent an optimal compromise between the favorable impact of speed, higher spatial localization, and reduced collateral damage on one hand, and sufficient width of the therapeutic window (> 3) on the other.

    View details for Web of Science ID 000252312800011

    View details for PubMedID 18195222

  • Endogenous Scedosporium apiospermum endophthalmitis ARCHIVES OF OPHTHALMOLOGY Jain, A. T., Egbert, P., McCulley, T. J., Blumenkranz, M. S., Moshfeghi, D. M. 2007; 125 (9): 1286-1289

    View details for Web of Science ID 000249342100023

    View details for PubMedID 17846376

  • Role of genetic factors and inflammation in age-related macular degeneration RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Moshfeghi, D. M., Blumenkranz, M. S. 2007; 27 (3): 269-275


    Complement factor H (CFH) has been implicated in the predisposition to advanced forms of age-related macular degeneration (AMD). The purpose of this review is to highlight recent discoveries implicating single nucleotide polymorphisms on 1q32, 6p21, and 10q26 in the risk for development of AMD. In addition, the central role of CFH in the complement cascade and its role in the inflammatory hypothesis for AMD are reviewed.

    View details for Web of Science ID 000246985100001

    View details for PubMedID 17460581

  • A novel His158Arg mutation in TIMP3 causes a late-onset form of Sorsby fundus dystrophy AMERICAN JOURNAL OF OPHTHALMOLOGY Lin, R. J., Blumenkranz, M. S., Binkley, J., Wu, K., Vollrath, D. 2006; 142 (5): 839-848


    To describe the phenotype and genotype of a family with suspected Sorsby fundus dystrophy (SFD).Case reports and results of deoxyribonucleic acid (DNA) analysis.Clinical features were determined by complete ophthalmologic examination or by review of medical records. Mutational analysis of the tissue inhibitor of metalloproteinase (TIMP)3 gene was performed by DNA resequencing. Biochemical properties of the mutant TIMP3 protein were studied, and phylogenetic and molecular modeling analyses of TIMP proteins were performed.Fundi of four affected family members demonstrated active or regressed bilateral choroidal neovascularization, whereas another affected individual displayed severe diffuse pigmentary degeneration associated with nyctalopia characteristic of SFD. Onset of disease occurred in the fifth to seventh decades of life. A heterozygous His158Arg mutation was found in seven affected family members and was absent from an unaffected member and 98 unrelated controls. Bioinformatic analyses indicate that histidine 158 is an evolutionarily conserved residue in most vertebrate TIMP homologs and predict that substitution by arginine disrupts TIMP3 function. The mutant protein appears to be expressed by fibroblasts from an affected family member. Molecular modeling suggests that TIMP3 residue 158 may be part of a protein-protein interaction interface.A novel mutation in TIMP3 causes a late-onset form of SFD in this family. His158Arg is the first reported TIMP3 SFD coding sequence mutation that does not create an unpaired cysteine. Further study of this unusual mutation may provide insight into the mechanism of SFD pathogenesis.

    View details for DOI 10.1016/j.ajo.2006.06.003

    View details for Web of Science ID 000242142900019

    View details for PubMedID 16989765

  • Semiautomated patterned scanning laser for retinal photocoagulation RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Blumenkranz, M. S., Yellachich, D., Andersen, D. E., Wiltberger, M. W., Mordaunt, D., Marcellino, G. R., Palanker, D. 2006; 26 (3): 370-376

    View details for Web of Science ID 000241684700024

    View details for PubMedID 16508446

  • Antibiotic susceptibility of preoperative normal conjunctival bacteria AMERICAN JOURNAL OF OPHTHALMOLOGY de Kaspar, H. M., Koss, M. J., Blumenkranz, M. S., Ta, C. N. 2005; 139 (4): 730-733


    To determine the antibiotic susceptibility of preoperative conjunctival bacterial flora.In vitro study.Antibiotic susceptibility of conjunctival bacterial strains isolated from 164 patients undergoing intraocular surgery was determined using the Kirby-Bauer disk-diffusion technique.Among the 162 bacteria isolated, 124 (76%) were coagulase-negative staphylococci (CNS), with 2% resistant to gatifloxacin and moxifloxacin, and none were resistant to vancomycin or minocycline. Other bacteria isolated were 19 Staphylococcus aureus (S. aureus), 8 Streptococcus Group D, and 11 gram-negative rods. Most S. aureus (>85%) were susceptible to all antibiotics except for the penicillin and macrolide groups. No streptococci were resistant to gatifloxacin, levofloxacin, moxifloxacin, mezlocillin, imipenem, or vancomycin. None of the gram-negative rods were resistant to the fluoroquinolones. Approximately one half of all bacteria were resistant to erythromycin. One in three patients harbored multi-resistant bacteria (resistant to > or = five antibiotics).Newer-generation fluoroquinolones provide excellent broad-spectrum coverage against conjunctival bacterial flora.

    View details for Web of Science ID 000228222300031

    View details for PubMedID 15808182

  • New therapy for central retinal vein occlusion - Are intravitreal steroids a possible answer? ARCHIVES OF OPHTHALMOLOGY Blumenkranz, M. S. 2005; 123 (2): 259-261

    View details for Web of Science ID 000226755000018

    View details for PubMedID 15710826

  • 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


    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 Web of Science ID 000224678200039

    View details for PubMedID 15505066

  • Migration of retinal cells through a perforated membrane: Implications for a high-resolution prosthesis INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Palanker, D., Huie, P., Vankov, A., Aramant, R., Seiler, M., Fishman, H., Marmor, M., Blumenkranz, M. 2004; 45 (9): 3266-3270


    One of the critical difficulties in design of a high-resolution retinal implant is the proximity of stimulating electrodes to the target cells. This is a report of a phenomenon of retinal cellular migration into a perforated membrane that may help to address this problem.Mylar membranes with an array of perforations (3-40 microm in diameter) were used as a substrate for in vitro retinal culture (chicken, rats) and were also transplanted into the subretinal space of adult RCS rats. A membrane was also constructed with a seal on one side to restrict the migration.Retinal tissue in vitro grew within 3 days through perforations of greater than 5 microm in diameter when the membranes were positioned on the photoreceptor side, but no migration occurred if the implant was placed on the inner retinal surface. Histology with light microscopy and transmission electron microscopy (TEM) demonstrated that migrating cells retain neuronal structures for signal transduction. Similar growth of RCS rat retinal cells occurred in vivo within 5 days of implantation. A basal seal kept the migrating tissue within a small membrane compartment.Retinal neurons migrate within a few days into perforations (> 5 microm in diameter) of a membrane placed into the subretinal space. This may provide a means of gaining close proximity between electrodes in a retinal prosthetic chip and target cells, and thus allow a greater density of stimulating elements to subserve higher resolution. Further studies are needed to explore the long-term stability of the retinal migration.

    View details for DOI 10.1167/iovs.03-1327

    View details for Web of Science ID 000223500900055

    View details for PubMedID 15326150

  • Localized chemical release from an artificial synapse chip PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Peterman, M. C., Noolandi, J., Blumenkranz, M. S., Fishman, H. A. 2004; 101 (27): 9951-9954


    A device that releases chemical compounds in small volumes and at multiple, well defined locations would be a powerful tool for clinical therapeutics and biological research. Many biomedical devices such as neurotransmitter-based prostheses or drug delivery devices require precise release of chemical compounds. Additionally, the ability to control chemical gradients will have applications in basic research such as studies of cell microenvironments, stem cell niches, metaplasia, or chemotaxis. We present such a device with repeatable delivery of chemical compounds at multiple locations on a chip surface. Using electroosmosis to drive flow through microfluidic channels, we pulse minute quantities of a bradykinin solution through four 5-microm apertures onto PC12 cells and show stimulation of individual cells using a Ca(2+)-sensitive fluorescent dye. We also present basic computational results with experimental verification of both fluid ejection and fluid withdrawal by imaging pH changes by using a fluorescent dye. This "artificial synapse chip" is a prototype neural interface that introduces a new paradigm for neural stimulation, with eventual application in treating macular degeneration and other neurological disorders.

    View details for DOI 10.1073/pnas.0402089101

    View details for Web of Science ID 000222534200003

    View details for PubMedID 15218102

  • Three-day application of topical ofloxacin reduces the contamination rate of microsurgical knives in cataract surgery - A prospective randomized study OPHTHALMOLOGY de Kaspar, H. M., Chang, R. T., Shriver, E. M., Singh, K., Egbert, P. R., Blumenkranz, M. S., Ta, C. N. 2004; 111 (7): 1352-1355


    To determine the rate of contamination of microsurgical knives during cataract surgery and the benefit of a 3-day versus a 1-hour preoperative application of topical ofloxacin in reducing the contamination rate.Prospective, randomized controlled trial.Seventy-eight eyes of 75 patients were randomly assigned to control (39 eyes) or study groups (39 eyes).All patients from both groups received 0.3% topical ofloxacin 1 hour before surgery, 5% povidone-iodine (PVI) scrub of the periorbital area, and 2 drops of PVI onto the ocular surface preoperatively. The patients in the study group also received ofloxacin 4 times a day for 3 days before surgery.Microsurgical knives were placed in blood culture broth media immediately after the incision had been made. The number of positive cultures and types of bacteria isolated were determined.Ten of 39 knives (26%) in the control group were found to be positive for bacterial growth compared with only 2 of 39 (5%) in the study group (P = 0.028).The initial paracentesis incision frequently results in contamination of the microsurgical knife and may serve as a mechanism for introducing bacteria from the ocular surface into the anterior chamber. The application of topical ofloxacin for 3 days before surgery significantly reduces the contamination rate of the microsurgical knives, compared with a preoperative application of ofloxacin given 1 hour before surgery.

    View details for Web of Science ID 000222418900017

    View details for PubMedID 15234136

  • 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


    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

  • Controlling cell adhesion on human tissue by soft lithography LANGMUIR Lee, C. J., Blumenkranz, M. S., Fishman, H. A., Bent, S. F. 2004; 20 (10): 4155-4161


    Soft lithographic techniques are widely used for fundamental biological applications. This study investigates the extension of soft lithography for use on human tissue to create a biological implant by systematically studying the effect of pattern size on cellular morphology. We focus on mimicking a key layer of the physiological retina with an organized monolayer of epithelial cells to act as a new treatment for age-related macular degeneration. We show that epithelial cells can be confined to cytophilic islands defined on lens capsule by the inhibitory polymer poly(vinyl alcohol). In addition, as the size of the cytophilic islands grows, both the fraction of islands with cells attached and the number of cells adhered to each island increase. High densities of cell adhesion and single cell attachment per island were achieved with a 25 microm pattern size. Over time, the cells spread over the 5 microm wide barriers to form a confluent monolayer that may eventually serve as a functional retinal implant. With the ability to apply soft lithography to tissue samples, human tissue may become a universal membrane substrate for other ocular diseases or in tissue engineering applications elsewhere in the body.

    View details for DOI 10.1021/la035467c

    View details for Web of Science ID 000221319400049

    View details for PubMedID 15969410

  • The challenge of determining aqueous contamination rate in anterior segment intraocular surgery AMERICAN JOURNAL OF OPHTHALMOLOGY Ta, C. N., Egbert, P. R., Singh, K., Blumenkranz, M. S., de Kaspar, H. M. 2004; 137 (4): 662-667


    To determine aqueous contamination rate in anterior segment intraocular surgery using two different techniques of obtaining aqueous fluid and to assess whether a 3-day application of topical 0.3% ofloxacin reduces this contamination rate compared with a 1-hour application.Randomized clinical trial.One hundred and thirty-three eyes of 130 patients undergoing anterior segment intraocular surgery were randomized to either control (64 eyes received topical ofloxacin 1 hour before surgery) or study groups (69 eyes received topical ofloxacin four times a day for 3 days before surgery in addition to 1 hour preoperatively). Eyes in both groups received a periorbital iodine scrub and two drops of topical 5% iodine. Aqueous fluid was obtained at the beginning and conclusion of surgery using a cannula passed through a paracentesis or a needle passed through clear cornea. The aqueous, cannula, and needles were inoculated in blood culture media broth and bacterial growth was identified.Overall, eight of 89 aqueous samples (9%) obtained using a cannula at the beginning of surgery were culture-positive. Similarly, six of 41 aqueous samples (15%) obtained through a needle through clear cornea at the beginning of surgery showed contamination. At the conclusion of surgery, nine of 112 samples (8%) showed positive cultures. There was no difference in the aqueous contamination rates between the control and study groups.Despite the use of a needle to obtain aqueous fluid at the beginning of surgery before creating a paracentesis, the aqueous contamination rate remained higher than that found at the conclusion of surgery. A 3-day application of topical ofloxacin before surgery did not reduce the anterior chamber aqueous contamination rate relative to a 1-hour application.

    View details for DOI 10.1016/j.ajo.2003.11.057

    View details for Web of Science ID 000220762800009

    View details for PubMedID 15059705

  • Fluid flow past an aperture in a microfluidic channel ANALYTICAL CHEMISTRY Peterman, M. C., Noolandi, J., Blumenkranz, M. S., Fishman, H. A. 2004; 76 (7): 1850-1856


    Electroosmotically driven flow in neurotransmitter-based retinal prostheses offers a novel approach to interfacing the nervous system. Here, we show that electroosmotically driven flow in a microfluidic channel can be used either to eject or to withdraw fluid through a small aperture in the channel wall. We study this fluid movement numerically using a finite-element method and experimentally using microfabricated channels and apertures. Two devices are used to test the concept of fluid ejection and withdrawal: (1) a single, large channel with four apertures and (2) a prototype neural interface with four individually addressable apertures. We compared experimental and numerical results in microchannels using the observed pH dependence of the fluorescent dye fluorescein, finding good agreement between the results. Because of the simplicity and rapid response of electroosmotic flow, this technique may be useful for neurotransmitter-based neural interfaces.

    View details for DOI 10.1021/ac035154m

    View details for Web of Science ID 000220618400016

    View details for PubMedID 15053643

  • 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


    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

  • Antibiotic resistance patterns of ocular bacterial flora - A prospective study of patients undergoing anterior segment surgery OPHTHALMOLOGY Ta, C. N., Chang, R. T., Singh, K., Egbert, P. R., Shriver, E. M., Blumenkranz, M. S., de Kaspar, H. M. 2003; 110 (10): 1946-1951


    To determine the antibiotic susceptibility patterns of conjunctival bacterial flora isolated preoperatively from patients undergoing anterior segment surgery.Prospective observational study.One hundred fifty-six eyes from 139 patients scheduled for anterior segment surgery were enrolled over a 6-month period from August 2001 to February 2002.Conjunctival cultures were obtained on the day of surgery before povidone-iodine or antibiotic application.Bacterial isolates were identified and tested for antibiotic susceptibility using the Kirby-Bauer disc-diffusion technique.Among the 156 eyes studied, 36 were from patients who had undergone either bilateral surgery or more than one surgery in the same eye. Only the first eyes of the 120 patients that underwent initial ocular surgery were included in our analysis. Of these 120 eyes, 21 (18%) showed no bacterial growth. Of the 143 bacterial strains isolated from the remaining 99 eyes, 112 (78%) were coagulase-negative staphylococci (CNS). Among the CNS, greater than 90% were susceptible to cefotaxime, levofloxacin, imipenem, meropenem, vancomycin, and each of the aminoglycosides except neomycin. Between 70% and 90% of the CNS were susceptible to cefazolin, neomycin, ciprofloxacin, ofloxacin, norfloxacin, and chloramphenicol. Less than 70% of the isolated CNS were sensitive to the penicillin analogues, ceftazidime, erythromycin, and tetracycline.Preoperative conjunctival isolates of CNS seem to be most sensitive to vancomycin, the aminoglycosides (except neomycin), and levofloxacin.

    View details for DOI 10.1016/S0161-6420(03)00735-8

    View details for Web of Science ID 000185615400015

    View details for PubMedID 14522770

  • Risk factors for antibiotic-resistant conjunctival bacterial flora in patients undergoing intraocular surgery GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY de Kaspar, H. M., Shriver, E. M., Nguyen, E. V., Egbert, P. R., Singh, K., Blumenkranz, M. S., Ta, C. N. 2003; 241 (9): 730-733


    The purpose of this study was to determine if patients with certain risk factors are more likely to harbor conjunctival bacterial flora resistant to multiple antibiotics.In this prospective study, detailed medical history and slit-lamp examination were performed on all patients prior to intraocular surgery. Patients with local risk factors were defined as those with chronic blepharitis, conjunctivitis or discharge. Those with systemic risk factors were patients with diabetes, autoimmune, immunodeficient or skin disorders, asthma and those taking immunosuppressant medications. Conjunctival cultures were obtained prior to preoperative antibiotics and povidone-iodine. Bacteria isolated were identified and antibiotic susceptibility was determined. Bacteria resistant to five or more antibiotics were defined as multi-resistant (MR).Among the 207 patients enrolled in the study, 73 patients had local risk factors. Of these patients, 32 patients (44%) carried MR organisms, compared to 32 of the 134 patients (24%) without local risk factors (P=0.0049). Thirty-two of 71 patients (45%) with systemic risk factors harbored MR organisms, compared to 32 of 136 patients (24%) without systemic risk factors (P=0.0025). Seventeen of 93 patients (18%) who had neither local nor systemic risk factors had MR organisms on their conjunctiva. In contrast, 17 of the 30 patients (57%) with both local and systemic risk factors (57%) carried MR bacteria (P=0.0001).Patients with local and/or systemic risk factors are more likely to harbor MR organisms. This may be one mechanism for the reported increased risk of postoperative endophthalmitis in this group of patients.

    View details for DOI 10.1007/s00417-003-0742-5

    View details for Web of Science ID 000186037100008

    View details for PubMedID 12928904

  • Localized neurotransmitter release for use in a prototype retinal interface INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Peterman, M. C., Bloom, D. M., Lee, C., Bent, S. F., Marmor, M. E., Blumenkranz, M. S., Fishman, H. A. 2003; 44 (7): 3144-3149


    Current neural prostheses use electricity as the mode of stimulation, yet information transfer in neural circuitry is primarily through chemical transmitters. To address this disparity, this study was conducted to devise a prototype interface for a retinal prosthetic based on localized chemical delivery. The goal was to determine whether fluidic delivery through microfabricated apertures could be used to stimulate at single-cell dimensions.A drug delivery system was microfabricated based on a 5- or 10- microm aperture in a 500-nm thick silicon nitride membrane to localize and limit transmitter release. The aperture overlies a microfluidic delivery channel in a silicone elastomer. To demonstrate the effectiveness of this transmitter-based prosthesis, rat pheochromocytoma cells (PC12 cell line) were grown on the surface of the device to test the precision of stimulation, using bradykinin as a stimulant and measuring fluorescence from the calcium indicator, fluo-4.The extent of stimulation could be controlled accurately by varying the concentration of stimulant, from a single cell adjacent to the aperture to a broad area of cells. The stimulation radius was as small as 10 microm, corresponding to stimulation volumes as small as 2 pL. The relationship between the extent of stimulation and concentration was linear.The demonstration of localized chemical stimulation of excitable cells illustrates the potential of this technology for retinal prostheses. Although this is only a proof of concept of neurotransmitter stimulation for a retinal prosthesis, it is a significant first step toward mimicking neurotransmitter release during synaptic transmission.

    View details for DOI 10.1167/iovs.02-1097

    View details for Web of Science ID 000183795800048

    View details for PubMedID 12824264

  • Precision and safety of the pulsed electron avalanche knife in vitreoretinal surgery ARCHIVES OF OPHTHALMOLOGY MILLER, J. M., Palanker, D. V., Vankov, A., Marmor, M. F., Blumenkranz, M. S. 2003; 121 (6): 871-877


    We have developed a new surgical instrument, called the pulsed electron avalanche knife (PEAK; Carl Zeiss Meditec, Jena, Germany), for precise, "cold," and tractionless dissection of tissue in liquid media.To evaluate the 3-dimensional damage zone induced by the PEAK compared with 2 other standard intraocular surgical instruments, diathermy and retinal scissors.Damage zone and minimum safe distance were measured in vitro on chick chorioallantoic membrane and in vivo on rabbit retina with the use of propidium iodide staining.The PEAK produced a paracentral zone of cellular structure disruption surrounding a crater and a peripheral zone of structurally intact but abnormally permeable cells. The instrument induced a damage radius that varied from 55 to 300 micro m for the range of voltages and pulses typically used during surgery. For comparison, damage radius for microsurgical scissors was 50 micro m, and for diathermy, 400 to 850 micro m. The PEAK also damaged tissue up to 1.4 mm away by the creation of water flow that formed at the tip of convex probes during collapse of a cavitation bubble. Concave probes, which prevent formation of the water jet, eliminated this effect.The PEAK operated well within accept-able safety limits and may greatly facilitate both posterior segment surgeries (eg, membrane dissection and sheathotomy) and anterior segment procedures (eg, capsulotomy, nonpenetrating trabeculectomy, and iridectomy).

    View details for Web of Science ID 000183408600017

    View details for PubMedID 12796261

  • Retinal evaluation of patients on chronic amiodarone therapy RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Shaikh, S., Shaikh, N., Chun, S. H., Spin, J. M., Blumenkranz, M. S., Marmor, M. F. 2003; 23 (3): 354-359


    To determine whether retinal electrophysiologic changes can be detected and correlated with funduscopic findings in patients with the long-term use of amiodarone.Eleven patients ranging in age from 52 to 67 years were recruited from the Stanford University Medical Center Department of Cardiology for ophthalmologic examination. Patients had received amiodarone at various dosages ranging from 100 to 800 mg daily for at least 15 months. Clinical indications for the use of amiodarone included atrial fibrillation, ventricular arrhythmias, and congestive heart failure. All patients underwent retinal electrophysiology studies (full-field and multifocal electroretinograms) in addition to a complete ophthalmologic examination and fluorescein angiography.No patients were found to have significant vision loss. Funduscopic examination and fluorescein angiography showed mild age-related changes in four patients, three of whom had nonspecific foveal pigmentary alterations. Multifocal and full-field electroretinograms were mostly unremarkable, and the mildly subnormal findings in a few patients showed no consistent pattern to suggest a toxic cause. Dosage, duration of amiodarone exposure, patient age, and underlying cardiac disease did not appear to correlate with these findings.No significant adverse retinal funduscopic changes or electrophysiologic effects could be correlated with amiodarone exposure in this small series of patients. Routine electrophysiologic and funduscopic screening of patients receiving amiodarone does not seem warranted, although future prospective controlled studies may be required to exclude the possibility of progressive abnormalities in patients with preexisting age-related macular degeneration.

    View details for Web of Science ID 000183932600011

    View details for PubMedID 12824836

  • 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


    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 Web of Science ID 000179737900014

    View details for PubMedID 12470147

  • Prospective randomized comparison of 3-day versus 1-hour preoperative ofloxacin prophylaxis for cataract surgery OPHTHALMOLOGY Ta, C. N., Egbert, P. R., Singh, K., Shriver, E. M., Blumenkranz, M. S., de Kaspar, H. M. 2002; 109 (11): 2036-2040


    To determine the efficacy of reducing conjunctival bacterial flora with topical ofloxacin when given for 3 days compared with 1 hour before surgery.Prospective, randomized, controlled trial.Ninety-two eyes from 89 patients were randomized to a control group (48 eyes) or study group (44 eyes).All patients from both groups received topical ofloxacin 0.3% 1 hour before surgery and a 5% povidone iodine scrub of the periorbital area before surgery. The patients in the study group received additional ofloxacin four times daily for 3 days before surgery.Conjunctival cultures were obtained at five separate time points and were inoculated in solid and liquid culture media. The presence of bacteria was determined, quantified, and identified.Forty-two percent of eyes in the control group had positive conjunctival culture immediately before surgery, compared with 19% of eyes in the study group (P < 0.05). Immediately after surgery, 34% and 14% of eyes had positive cultures in the control and study groups, respectively (P < 0.05). Quantitatively, fewer bacteria were isolated from eyes in the study group compared with those in the control group for culture samples that were obtained both before povidone iodine scrub and at the conclusion of surgery (P

    View details for Web of Science ID 000178778600032

    View details for PubMedID 12414411

  • Treatment of central retinal vein occlusion by vitrectomy with lysis of vitreopapillary and epipapillary adhesions, subretinal peripapillary tissue plasminogen activator injection, and photocoagulation AMERICAN JOURNAL OF OPHTHALMOLOGY Lam, H. D., Blumenkranz, M. S. 2002; 134 (4): 609-611


    To report a case of subretinal peripapillary tissue plasminogen activator (tPA) injection with vitreopapillary and epipapillary membrane dissection and peripheral photocoagulation in the treatment of central retinal vein occlusion.Interventional case report.A 79-year-old woman with a history of branch vein occlusion in the left eye presented with visual loss in the right eye for 4 months secondary to unresolved central retinal vein occlusion. She underwent vitrectomy, right eye, with lysis of vitreopapillary and epipapillary adhesions and hyaloid separation, subretinal peripapillary tissue tPA injection, peripheral photocoagulation, and air-fluid exchange.Postoperatively, funduscopic and fluorescein angiographic features of venous obstruction improved rapidly, with prompt reduction in intraretinal hemorrhages and disk and macular edema. The patient reported subjective improvement of vision in her right eye, although measured improvement was modest, from finger counting to 20/400.Subretinal administration of tPA, lysis of adhesions, and endophotocoagulation may be of value in resolving the obstructive component of selected cases of chronic central retinal vein occlusion associated with vitreopapillary and epipapillary traction.

    View details for Web of Science ID 000178446100019

    View details for PubMedID 12383824

  • CME photodynamic therapy for choroidal neovascularization - A review RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Woodburn, K. W., Engelman, C. J., Blumenkranz, M. S. 2002; 22 (4): 391-405


    To review the biophysical basis and current state of therapy for photodynamic closure of subfoveal choroidal neovascularization in the eye.A review of the literature is included, which encompasses the chemical structure, biophysical mechanism of action, range of available agents, status of clinical trials, clinical indications, results of treatments, complications, and future directions.Photodynamic therapy has been shown to be effective in closing both experimental choroidal neovascularization in animal models as well as subfoveal choroidal neovascularization in humans. The therapy results in temporary closure of choroidal new vessels for a period of approximately 1 to 4 weeks. By 12 weeks, most patients have reperfusion or reproliferation of choroidal new vessels resulting in the need for retreatment to achieve continued closure and visual stabilization. Differences exist in the quantum yield, clinical efficiency, and light and sensitizer dose requirements between different classes of agents. Further clinical trials will be required to determine the optimal form of therapy, with verteporfin (Visudyne) as the only currently approved agent. Other agents, including tin etiopurpurin (Purlytin) and motexafin lutetium (Optrin), are currently undergoing phase III, and phase II trials, respectively.Photodynamic therapy is a promising treatment modality shown to be effective in achieving closure and stabilization of vision loss compared with placebo control in eyes with subfoveal choroidal neovascularization.

    View details for Web of Science ID 000177437200001

    View details for PubMedID 12172104

  • The sensitivity and specificity of single-field nonmydriatic monochromatic digital fundus photography with remote image interpretation for diabetic retinopathy screening: A comparison with ophthalmoscopy and standardized mydriatic color photography AMERICAN JOURNAL OF OPHTHALMOLOGY Lin, D. Y., Blumenkranz, M. S., Brothers, R. J., Grosvenor, D. M. 2002; 134 (2): 204-213


    To evaluate single-field digital monochromatic nonmydriatic fundus photography as an adjunct in the screening of diabetic retinopathy.Prospective, comparative, observational case series.Patients with type I and type II diabetes mellitus (n = 197) were sequentially evaluated by three different techniques: single-field digital monochromatic nonmydriatic photography; dilated ophthalmoscopy by an ophthalmologist; and seven Early Treatment Diabetic Retinopathy Study (ETDRS) standardized 35-mm color stereoscopic mydriatic images. The seven stereoscopic color photographs served as the reference standard and were compared with either ophthalmoscopy or a single digital photograph transmitted electronically to a reading site. Levels of agreement were determined by kappa analyses. The sensitivity and specificity of the three methods were compared based on a threshold for referral to further ophthalmologic evaluation (ETDRS level > or =35).There was highly significant agreement (kappa = 0.97, P =.0001) between the degree of retinopathy detected by a single nonmydriatic monochromatic digital photograph and that seen in seven standard 35-mm color stereoscopic mydriatic fields. The sensitivity of digital photography compared with color photography was 78%, with a specificity of 86%. Agreement was poor (kappa = 0.40, P =.0001) between mydriatic ophthalmoscopy and the seven-field standard 35-mm color photographs. Sensitivity of ophthalmoscopy compared with color photography was 34%, with a specificity of 100%.A single nonmydriatic monochromatic wide-field digital photograph of the disk and macula was more sensitive for diabetic retinopathy screening than mydriatic ophthalmoscopy, the currently accepted screening method. When adjudicated by standard seven-field color photographs, the higher sensitivity of digital photography primarily reflected the reduced sensitivity of ophthalmoscopy in detecting early retinopathy.

    View details for Web of Science ID 000177169300008

    View details for PubMedID 12140027

  • Effects of the pulsed electron avalanche knife on retinal tissue ARCHIVES OF OPHTHALMOLOGY Palanker, D. V., Marmor, M. F., Branco, A., Huie, P., MILLER, J. M., Sanislo, S. R., Vankov, A., Blumenkranz, M. S. 2002; 120 (5): 636-640


    To evaluate the precision of retinal tissue dissection by the pulsed electron avalanche knife (PEAK) and to assess possible toxic effects from this device.To demonstrate precision of cutting, bovine retina (in vitro) and rabbit retina (in vivo) were incised with the PEAK. Samples were examined by scanning electron microscopy and histologic examination (light microscopy). To evaluate possible toxic effects in rabbit eyes, 30 000 pulses were delivered into the vitreous 1 cm above the retina. Histologic examinations and electroretinography were performed at intervals up to 1 month after exposure.Cuts in postmortem bovine retina showed extremely sharp edges with no signs of thermal damage. Full-thickness cuts in living attached rabbit retina were similarly sharp and were typically less than 100 microm wide. No signs of retinal toxic effects were detected by histologic examination or electroretinography.The PEAK is capable of precise cutting through retinal tissue, and there are no demonstrable retinal toxic effects from its use. The precision and tractionless nature of PEAK cutting offers advantages over mechanical tools and laser-based instrumentation. We believe this new device will prove useful in a variety of vitreoretinal surgical applications.

    View details for Web of Science ID 000175503400015

    View details for PubMedID 12003616

  • Pulsed Electron Avalanche Knife (PEAK) for intraocular surgery INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE Palanker, D. V., MILLER, J. M., Marmor, M. F., Sanislo, S. R., Huie, P., Blumenkranz, M. S. 2001; 42 (11): 2673-2678


    To develop a better and more economical instrument for precise, tractionless, "cold" cutting during intraocular surgery. The use of highly localized electric fields rather than laser light as the means of tissue dissection was investigated.A high electric field at the tip of a fine wire can, like lasers, initiate plasma formation. Micrometer-length plasma streamers are generated when an insulated 25 micron (microm) wire, exposed to physiological medium at one end, is subjected to nanosecond electrical pulses between 1 and 8 kV in magnitude. The explosive evaporation of water in the vicinity of these streamers cuts soft tissue without heat deposition into surrounding material (cold cutting). Streamers of plasma and the dynamics of water evaporation were imaged using an inverted microscope and fast flash photography. Cutting effectiveness was evaluated on both polyacrylamide gels, on different tissues from excised bovine eyes, and in vivo on rabbit retina. Standard histology techniques were used to examine the tissue.Electric pulses with energies between 150 and 670 microJ produced plasma streamers in saline between 10 and 200 microm in length. Application of electric discharges to dense (10%) polyacrylamide gels resulted in fracturing of the gel without ejection of bulk material. In both dense and softer (6%) gels, layer by layer shaving was possible with pulse energy rather than number of pulses as the determinant of ultimate cutting depth. The instrument made precise partial or full-thickness cuts of retina, iris, lens, and lens capsule without any evidence of thermal damage. Because different tissues require distinct energies for dissection, tissue-selective cutting on complex structures can be performed if the appropriate pulse energies are used; for example, retina can be dissected without damage to the major retinal vessels.This instrument, called the Pulsed Electron Avalanche Knife (PEAK), can quickly and precisely cut intraocular tissues without traction. The small delivery probe and modest cost make it promising for many ophthalmic applications, including retinal, cataract, and glaucoma surgery. In addition, the instrument may be useful in nonophthalmic procedures such as intravascular surgery and neurosurgery.

    View details for Web of Science ID 000171433300037

    View details for PubMedID 11581215

  • Adjuvant methods in macular hole surgery: Intraoperative plasma-thrombin mixture and postoperative fluid-gas exchange OPHTHALMIC SURGERY AND LASERS Blumenkranz, M. S., Ohana, E., Shaikh, S., Chang, S., Coll, G., Morse, L. S., De Bustros, S. 2001; 32 (3): 198-207


    The optimal method for surgical management of idiopathic macular holes remains unknown. Adjuvant methods including intraoperative cytokines and postoperative fluid-gas exchange with and without laser have been described. We report on the safety and final results of routine intraoperative autologous plasma-thrombin mixture and postoperative fluid-gas exchange when necessary as an adjunct to the surgical therapy of this disease.A consecutive series of 114 patients (mean age 66.9 years) with primary idiopathic full thickness Stage II, III, and IV macular holes were primarily treated by vitrectomy, fluid/perfluorocarbon gas exchange, and application of autologous plasma-thrombin mixture to the macular hole. Visible epiretinal membranes were peeled but the normal appearing internal limiting membrane was not routinely stripped. Outcome measures included final Snellen visual acuity, rate of macular hole closure, complications, and number of supplemental procedures performed.Closed at one month, were 110 of 121 (91%) macular holes, including two that underwent repeat fluid/gas exchange and laser within the first two weeks after surgery. At the time of final follow-up (mean: 10.9 months), 110 of 121 (91%) macular holes were closed. This included 8 of 9 eyes that had reopening of the macular hole between one and 21 months successfully treated by repeat fluid-gas exchange and 2 eyes that underwent a second successful pars plana vitrectomy, membrane peeling, and repeat fluid-gas exchange. Overall, 98 of 121 eyes overall (81%) were successfully treated by a single surgery; 94 of 121 (78%) achieved two lines or greater of visual improvement; 83 of 121 (69%) achieved 20/70 or better vision; and 47 eyes (39%) achieved 20/40 or better vision. Complications in this series included infectious endophthalmitis (1 eye), intraoperative retinal break (2 eyes), late retinal detachment (5 eyes), transient mild intraocular pressure elevation (46 eyes), inflammatory response (six eyes), epiretinal membrane (6 eyes), intraretinal hemorrhages (1 eye), and cataract (33 of 99 phakic eyes underwent cataract extraction during the follow-up).A combination of intravitreal perfluorocarbon gas and autologous plasma-thrombin mixture (tissue glue) was well tolerated in most patients and did not result in any specific long-term complications. The use of supplemental fluid-gas exchange when necessary improved the final success rate. Further well-controlled and randomized studies will be required to determine the efficacy of this as an adjunct or alternative to other methods of treatment for macular holes.

    View details for Web of Science ID 000168620300003

    View details for PubMedID 11371086

  • Transient improvement in visual acuity and macular edema in central retinal vein occlusion accompanied by inflammatory features after pulse steroid and anti-inflammatory therapy RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Shaikh, S., Blumenkranz, M. S. 2001; 21 (2): 176-178

    View details for Web of Science ID 000168148600013

    View details for PubMedID 11321147

  • Fluorescein angiographic findings in ocular siderosis AMERICAN JOURNAL OF OPHTHALMOLOGY Shaikh, S., Blumenkranz, M. S. 2001; 131 (1): 136-138


    To report a case of siderosis from a retained intraocular iron foreign body manifesting localized retinal capillary nonperfusion documented by fluorescein angiography.Case Report. In a 35-year-old man with decreased vision in the left eye, studies included fundus photography, fluorescein angiography, visual field testing, and electrophysiology. Surgical foreign body extraction and histopathologic examination were performed.Preoperatively, in the left eye, humphrey visual fields and electrophysiology testing revealed marked depression. Fluorescein angiography demonstrated nasal capillary nonperfusion with occlusion of the second- and third-order arterioles extending along a gradient from the foreign body. Microscopic examination of the lens capsule confirmed the diagnosis of siderosis secondary to a retained iron foreign body.Extensive capillary nonperfusion may be associated with a retained iron intraocular foreign body, as documented by fluorescein angiography.

    View details for Web of Science ID 000166429600024

    View details for PubMedID 11162994

  • Lutetium texaphyrin (lu-tex): A potential new agent for ocular fundus angiography and photodynamic therapy AMERICAN JOURNAL OF OPHTHALMOLOGY Blumenkranz, M. S., Woodburn, K. W., Qing, F., Verdooner, S., Kessel, D., Miller, R. 2000; 129 (3): 353-362


    To investigate the suitability of lutetium texaphyrin (lu-tex) as a fluorescence imaging agent in the delineation of retinal vascular and choroidal vascular diseases. The utilization of an efficient fluorescent molecule that is also a photosensitizer represents a unique opportunity to couple diagnosis and therapy.Fundus fluorescence angiography comparing lu-tex (motexafin lutetium, Optrin, Pharmacyclics Inc, Sunnyvale, California) with the conventional angiographic dyes, sodium fluorescein, and indocynanine green (ICG), was performed on the eyes of normal and laser-injured New Zealand white rabbits. Plasma pharmacokinetic data and plasma protein binding were assessed in addition to light microscopy of the retina in both imaged and laser-injured eyes.Normal retinal and choroidal vasculature was well delineated by lu-tex angiography. Experimentally induced choroidal and retinal vascular lesions were enhanced by lu-tex and demonstrated different staining patterns than fluorescein or ICG, particularly at the margins of the lesions. Lu-tex cleared rapidly from the plasma, with 39.7% bound to the high-density lipoprotein (HDL) fraction while 15.8% was bound to the low-density lipoprotein (LDL) fraction. No evidence of retinal toxicity after dye administration was observed by either ophthalmoscopy and fundus photography or by light microscopy.Lu-tex angiography is a potentially valuable method for retinal vascular and choroidal vascular evaluation, and it has advantages over fluorescein and ICG angiography. The same agent could conceivably be used for both the identification of abnormal vasculature and subsequent photodynamic treatment.

    View details for Web of Science ID 000085807500013

    View details for PubMedID 10704552

  • Fluorescein angiographic changes in acute toxic retinopathy associated with polypharmacy RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES Shaikh, S., Shaikh, N., Blumenkranz, M. S. 2000; 20 (6): 685-688

    View details for Web of Science ID 000167054900025

    View details for PubMedID 11131433

  • The role of digital fundus photography in diabetic retinopathy screening. Digital Diabetic Screening Group (DDSG). Diabetes technology & therapeutics Lin, D. Y., Blumenkranz, M. S., Brothers, R. 1999; 1 (4): 477-487


    The role of digital monochromatic nonmydriatic fundus photography as an adjunct in the diagnosis of diabetic retinopathy is evaluated.197 patients were sequentially evaluated by three different techniques: dilated ophthalmoscopy by an experienced ophthalmologist, performance of 7 standard color mydriatic stereo fields, and a single digital monochromatic nonmydriatic image incorporating the disc and macula. Stereo color photographs served as the reference standard and were compared to either ophthalmoscopy performed by a physician, or a single digital photograph transmitted electronically to a reading site and evaluated by a trained non-physician grader. Sensitivity and specificity of the three methods were compared. The decision as to whether or not to refer to an ophthalmologist for potential treatment (Kaiser modified ETDRS level > 21) was then chosen for analysis.A single nonmydriatic monochromatic digital photograph appeared equivalent to standard color photography and more sensitive than mydriatic ophthalmoscopy in the detection of diabetic retinopathy in this patient population. Sensitivity of digital photography compared with color photography was 78%, and the specificity 86% contrasted with comparable ratios of 34% and 100% for ophthalmoscopy versus color photography. No patient identified by ophthalmoscopy alone for referral based on retinopathy level of > 21 would have been missed by a single digital monochromatic photographic image.A single nonmydriatic monochromatic wide field digital photograph of the disc and macula in diabetic patients is a sensitive and cost-effective means for detecting diabetic retinopathy in high-risk populations.

    View details for PubMedID 11484714

  • Treatment of reopened macular hole after vitrectomy by laser and outpatient fluid-gas exchange OPHTHALMOLOGY Ohana, E., Blumenkranz, M. S. 1998; 105 (8): 1398-1403


    This study aimed to assess a new nonsurgical treatment for patients who have previously undergone vitrectomy for macular hole with either persistent or reopened holes.A prospective, noncomparative, consecutive case series.Fifteen patients (15 eyes) were studied.Patients were treated by an outpatient method consisting of laser photocoagulation to the foveal pigment epithelium followed by fluid-gas exchange with 20% perfluoropropane gas and prone positioning. Patients without known allergy were treated with two doses of oral Diamox (250 mg) and ciprofloxacin (500 mg).Visual acuity, intraocular pressure, anatomic status of the macular hole, and cataract were the principal outcome measures studied.Thirteen of 15 macular holes were closed successfully with 1 or more procedures. All patients with macular hole closure achieved two lines or greater of vision improvement on Snellen testing. Three patients (20%) achieved 20/40 and nine (60%) achieved 20/80 or better. Three patients required more than one procedure. Four patients developed mild transient ocular hypertension.The combination of office-based outpatient fluid-gas exchange and laser appears to be a safe and cost-effective alternative to repeat surgery in selected patients with persistent or reopened macular holes after vitrectomy, in whom there are no visible epiretinal membranes, or in whom return to the operating room is undesirable for medical or personal reasons.

    View details for Web of Science ID 000075231500019

    View details for PubMedID 9709749



    In the Silicone Study, 117 of 404 eyes (29%) with severe proliferative vitreoretinopathy (> or = C-3, full-thickness retinal folds in three or more quadrants) enrolled in the study were treated with vitrectomy, underwent a relaxing retinotomy, and were randomly assigned to treatment with long-acting gas or silicone oil. Forty-six eyes (20%) had undergone no previous vitrectomy (group 1); 71 eyes (42%) had undergone previous vitrectomy (group 2) with intraocular gas tamponade (P < .001). Group 1 eyes not undergoing retinotomy had better anatomic (six months) and visual (six and 24 months) outcomes and less hypotony (six months) than eyes that did regardless of tamponade (P < .05). For eyes undergoing retinotomy, silicone oil decreased the likelihood of hypotony (six months, P < .05). These differences were not found in group 2 eyes. We conclude that eyes undergoing a vitreous operation for the first time for the treatment of proliferative vitreoretinopathy can in most instances be successfully treated by conventional techniques without the need for relaxing retinotomy. Retinotomy may be required more often in patients undergoing repeat vitreous surgery for proliferative vitreoretinopathy, in which case both silicone oil and long-acting perflouropropane gas appear to be equally effective.

    View details for Web of Science ID A1993MF62400003

    View details for PubMedID 8238214