Lab Publications

Publications

  • Evaluation of Verteporfin as a Novel Antifibrotic Agent in a Rabbit Model of Glaucoma Filtration Surgery: A Pilot Study. Ophthalmology science Sun, M. T., Cotton, R. M., Charoenkijkajorn, C., Garcia-Sanchez, J., Dalal, R., Xia, X., Lin, J. H., Singh, K., Goldberg, J. L., Liu, W. W. 2024; 4 (3): 100448

    Abstract

    Verteporfin is a benzoporphyrin derivative which is Food and Drug Administration-approved for treatment of choroidal neovascularization in conjunction with photodynamic therapy. It has been shown to prevent fibrosis and scar formation in several organs and represents a promising novel antifibrotic agent for glaucoma surgery. The goal of this study is to determine the effect of verteporfin on wound healing after glaucoma filtration surgery.Preclinical study using a rabbit model of glaucoma filtration surgery.Eight New Zealand white rabbits underwent glaucoma filtration surgery in both eyes.Eyes were randomized into 4 study groups to receive a postoperative subconjunctival injection of 1 mg/mL verteporfin (n = 4), 0.4 mg/mL mitomycin C (MMC; n = 4), 0.4 mg/mL MMC + 1 mg/mL verteporfin (n = 4), or balanced salt solution (BSS) control (n = 4). Bleb survival, vascularity, and morphology were graded using a standard scale over a 30-day period, and intraocular pressure (IOP) was monitored. At 30 days postoperative or surgical failure, histology was performed to evaluate for inflammation, local toxicity, and scarring.The primary outcome measure was bleb survival. Secondary outcome measures were IOP, bleb morphology, and bleb histology.Compared to BSS control blebs, verteporfin-treated blebs demonstrated a trend toward increased surgical survival (mean 9.8 vs. 7.3 days, log rank P = 0.08). Mitomycin C-treated blebs survived significantly longer than verteporfin-treated blebs (log rank P = 0.009), with all but 1 MMC-treated bleb still surviving at postoperative day 30. There were no significant differences in survival between blebs treated with combination verteporfin + MMC and MMC alone. Mitomycin C-treated blebs were less vascular than verteporfin-treated blebs (mean vascularity score 0.3 ± 0.5 for MMC vs. 1.0 ± 0.0 for verteporfin, P < 0.01). Bleb histology did not reveal any significant toxicity in verteporfin-treated eyes. There were no significant differences in inflammation or scarring across groups.Although verteporfin remained inferior to MMC with regard to surgical survival, there was a trend toward increased survival compared with BSS control and it had an excellent safety profile. Further studies with variations in verteporfin dosage and/or application frequency are needed to assess whether this may be a useful adjunct to glaucoma surgery.Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

    View details for DOI 10.1016/j.xops.2023.100448

    View details for PubMedID 38261964

    View details for PubMedCentralID PMC10797546

  • Glaucoma tube shunt surgery with repeat penetrating keratoplasty in an aphakic patient. American journal of ophthalmology case reports Chiang, B., Wai, K., Naranjo, A., Smith, S., Rose-Nussbaumer, J., Liu, W. W. 2024; 36: 102145

    Abstract

    We present a complicated case of mixed mechanism glaucoma in the setting of failed corneal transplant and aphakia. The patient was a 54-year old male with HLA B27 uveitis and prior open globe injury. He was left aphakic after cataract extraction and had a subsequent corneal transplant for bullous keratopathy. Due to elevated intraocular pressure in the setting of a failed corneal graft, the decision was made to insert a pars plana tube shunt and perform repeat penetrating keratoplasty as a combined case with the glaucoma, cornea, and retina services. We illustrate the surgical steps and decision making and in this complex case.

    View details for DOI 10.1016/j.ajoc.2024.102145

    View details for PubMedID 39263687

    View details for PubMedCentralID PMC11388665

  • Amniotic membrane graft to patch an overfiltering trabeculectomy flap. American journal of ophthalmology case reports Yang, M. C., Sun, M. T., Liu, W. W. 2024; 36: 102128

    Abstract

    Purpose: To describe the use of an amniotic membrane graft (AMG) with fibrin sealant to address an overfiltering trabeculectomy flap encountered intraoperatively.Observations: A 35-year-old female with severe primary open angle glaucoma underwent trabeculectomy with mitomycin C due to uncontrolled intraocular pressure (IOP). Intraoperatively, the elastic nature of the scleral flap led to overfiltration, causing persistent anterior chamber shallowing despite numerous sutures. To decrease but not completely shut down aqueous outflow through the trabeculectomy flap, we utilized AMG and fibrin sealant to stabilize the flap. Postoperatively, the patient had a formed anterior chamber, elevated bleb and significantly reduced IOP, without the need for additional glaucoma medications.Conclusions and importance: Amniotic membrane grafts (AMG) with fibrin sealant may help regulate aqueous flow efflux, maintain anterior chamber stability, and mitigate the risk of postoperative hypotony in trabeculectomy surgery. AMG was chosen in this setting given its anti-inflammatory, anti-fibrotic properties, as well as its optically clear nature to allow for post-operative visualization of the flap. AMG allows for early postoperative stabilization of the scleral flap without complete obstruction, and may be useful in patients at risk of early postoperative hypotony.

    View details for DOI 10.1016/j.ajoc.2024.102128

    View details for PubMedID 39139207

  • Mechanosensitive ion channels in glaucoma pathophysiology. Vision research Garcia-Sanchez, J., Lin, D., Liu, W. W. 2024; 223: 108473

    Abstract

    Force sensing is a fundamental ability that allows cells and organisms to interact with their physical environment. The eye is constantly subjected to mechanical forces such as blinking and eye movements. Furthermore, elevated intraocular pressure (IOP) can cause mechanical strain at the optic nerve head, resulting in retinal ganglion cell death (RGC) in glaucoma. How mechanical stimuli are sensed and affect cellular physiology in the eye is unclear. Recent studies have shown that mechanosensitive ion channels are expressed in many ocular tissues relevant to glaucoma and may influence IOP regulation and RGC survival. Furthermore, variants in mechanosensitive ion channel genes may be associated with risk for primary open angle glaucoma. These findings suggest that mechanosensitive channels may be important mechanosensors mediating cellular responses to pressure signals in the eye. In this review, we focus on mechanosensitive ion channels from three major channel families-PIEZO, two-pore potassium and transient receptor potential channels. We review the key properties of these channels, their effects on cell function and physiology, and discuss their possible roles in glaucoma pathophysiology.

    View details for DOI 10.1016/j.visres.2024.108473

    View details for PubMedID 39180975

  • Differential expression of PIEZO1 and PIEZO2 mechanosensitive channels in ocular tissues implicates diverse functional roles. Experimental eye research Zhu, Y., Garcia-Sanchez, J., Dalal, R., Sun, Y., Kapiloff, M. S., Goldberg, J. L., Liu, W. W. 2023: 109675

    Abstract

    PIEZO1 and PIEZO2 are mechanosensitive ion channels that regulate many important physiological processes including vascular blood flow, touch, and proprioception. As the eye is subject to mechanical stress and is highly perfused, these channels may play important roles in ocular function and intraocular pressure regulation. PIEZO channel expression in the eye has not been well defined, in part due to difficulties in validating available antibodies against PIEZO1 and PIEZO2 in ocular tissues. It is also unclear if PIEZO1 and PIEZO2 are differentially expressed. To address these questions, we used single-molecule fluorescence in situ hybridization (smFISH) together with transgenic reporter mice expressing PIEZO fusion proteins under the control of their endogenous promoters to compare the expression and localization of PIEZO1 and PIEZO2 in mouse ocular tissues relevant to glaucoma. We detected both PIEZO1 and PIEZO2 expression in the trabecular meshwork, ciliary body, and in the ganglion cell layer (GCL) of the retina. Piezo1 mRNA was more abundantly expressed than Piezo2 mRNA in these ocular tissues. Piezo1 but not Piezo2 mRNA was detected in the inner nuclear layer and outer nuclear layer of the retina. Our results suggest that PIEZO1 and PIEZO2 are differentially expressed and may have distinct roles as mechanosensors in glaucoma-relevant ocular tissues.

    View details for DOI 10.1016/j.exer.2023.109675

    View details for PubMedID 37820892

  • Mechanosensitive ion channel gene survey suggests potential roles in primary open angle glaucoma. Scientific reports Liu, W. W., Kinzy, T. G., Cooke Bailey, J. N., Xu, Z., Hysi, P., Wiggs, J. L. 2023; 13 (1): 15871

    Abstract

    Although glaucoma is a disease modulated by eye pressure, the mechanisms of pressure sensing in the eye are not well understood. Here, we investigated associations between mechanosensitive ion channel gene variants and primary open-angle glaucoma (POAG). Common (minor allele frequency > 5%) single nucleotide polymorphisms located within the genomic regions of 20 mechanosensitive ion channel genes in the K2P, TMEM63, PIEZO and TRP channel families were assessed using genotype data from the NEIGHBORHOOD consortium of 3853 cases and 33,480 controls. Rare (minor allele frequency < 1%) coding variants were assessed using exome array genotyping data for 2606 cases and 2606 controls. Association with POAG was analyzed using logistic regression adjusting for age and sex. Two rare PIEZO1 coding variants with protective effects were identified in the NEIGHBOR dataset: R1527H, (OR 0.17, P = 0.0018) and a variant that alters a canonical splice donor site, g.16-88737727-C-G Hg38 (OR 0.38, P = 0.02). Both variants showed similar effects in the UK Biobank and the R1527H also in the FinnGen database. Several common variants also reached study-specific thresholds for association in the NEIGHBORHOOD dataset. These results identify novel variants in several mechanosensitive channel genes that show associations with POAG, suggesting that these channels may be potential therapeutic targets.

    View details for DOI 10.1038/s41598-023-43072-3

    View details for PubMedID 37741866

    View details for PubMedCentralID PMC10517927

  • Managing primary open-angle glaucoma in the setting of suboptimal surgical outcomes in the fellow eye. Journal of cataract and refractive surgery Huang, M. J., Samuelson, T. W., De Francesco, T., Levin, A., Sieck, E., Gazzard, G., Porter, M., Gallardo, M., Chang, R. T., Liu, W. W., Chaya, C., Gulati, S., Shah, M. 2023; 49 (7): 764

    Abstract

    A 62-year-old woman with mild myopia presented to her local optometrist for a routine examination and was found to have intraocular pressure (IOP) of 30 mm Hg in both eyes and cupped nerves. She had a family history of glaucoma in her father. She was started on latanoprost in both eyes and was referred for a glaucoma evaluation. On initial evaluation, her IOP was 25 mm Hg in the right eye and 26 mm Hg in the left eye. Central corneal thickness measured 592 µm in the right eye and 581 µm in the left eye. Her angles were open to gonioscopy without any peripheral anterior synechia. She had 1+ nuclear sclerosis with a corrected distance visual acuity (CDVA) of 20/25 in the right eye and 20/30- in the left eye and uncorrected near visual acuity of J1+ in each eye. Her nerves were 0.85 mm in the right eye and 0.75 mm in the left eye. Optical coherence tomography (OCT) showed retinal nerve fiber layer thinning and a dense superior arcuate scotoma into fixation in her right eye, and superior and inferior arcuate scotomas in her left eye (Figures 1 and 2JOURNAL/jcrs/04.03/02158034-202307000-00019/figure1/v/2023-06-26T195222Z/r/image-tiffJOURNAL/jcrs/04.03/02158034-202307000-00019/figure2/v/2023-06-26T195222Z/r/image-tiff, Supplemental Figures 1 and 2, available at http://links.lww.com/JRS/A882 and http://links.lww.com/JRS/A883). She was successively trialed on fixed combination brimonidine-timolol, dorzolamide, and netarsudil, in addition to her latanoprost, but her IOP remained in the mid- to upper 20s in both eyes. The addition of acetazolamide lowered the pressure to 19 mm Hg in both eyes, but she tolerated it poorly. Methazolamide was also attempted with similar side effects. We elected to perform left eye cataract surgery combined with 360-degree viscocanaloplasty and insertion of a Hydrus microstent (Alcon Laboratories, Inc.). Surgery was uncomplicated with IOP of 16 mm Hg on postoperative day 1 with no glaucoma medications. However, by postoperative week 3, IOP returned to 27 mm Hg, and despite restarting latanoprost-netarsudil and finishing her steroid taper, IOP remained at 27 mm Hg by postoperative week 6. Brimonidine-timolol was added back to her left eye regimen and at postoperative week 8, IOP had elevated to 45 mm Hg. Maximizing her therapy with the addition of topical dorzolamide and oral methazolamide brought her IOP back down to 30 mm Hg. At that point, the decision was made to proceed with trabeculectomy of the left eye. The trabeculectomy was uneventful. However, postoperative attempts to augment filtration were rendered less successful by extremely thick Tenon layer. At her most recent follow-up the pressure in the left eye was mid-teens with brimonidine-timolol and dorzolamide. Her right eye IOP is in the upper 20s on maximum topical therapy. Knowing her postoperative course in the left eye, how would you manage the right eye? In addition to currently available options, would you consider a supraciliary shunt such as the MINIject (iSTAR) if such a device were U.S. Food and Drug Administration (FDA)-approved?

    View details for DOI 10.1097/j.jcrs.0000000000001221

    View details for PubMedID 37390324

  • Correlation between central visual field defects and stereopsis in patients with early to moderate visual field loss. Ophthalmology. Glaucoma Liu, W. W., Shalaby, W. S., Shiuey, E. J., Raghu, R., Petkovsek, D., Myers, J. S., Wizov, S. S., Spaeth, G. L., Shukla, A. G. 2023

    Abstract

    To investigate an association between stereoacuity and the presence of central visual field defects (CVFDs) due to glaucoma.Prospective, cross-sectional cohort study.Participants with early to moderate glaucoma with visual acuity better than 20/40, less than 2-line difference in visual acuity between eyes, and 2 reliable Humphrey VFs (24-2 SITA standard) with mean deviation (MD) in the worse eye better than -12dB.Stereoacuity was measured using the Titmus stereo test. Participants with a significant field defect (P<0.5%) in any one of the central four points in the 24-2 SITA standard total deviation map in either eye were classified as having a CVFD. Vision-related quality of life (VR-QOL) was measured by the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores. Logistic regression was used to determine the association between level of stereoacuity and age, gender, race, glaucoma type, presence of CVFDs, visual acuity, contrast sensitivity, and visual field MD.Stereoacuity in the CVFD and no CVFD groups.Sixty-five participants met the inclusion criteria. The mean age was 64.3 ± 8.0 years and 64.6% were women. Median stereoacuity was 60 arc sec (inter-quartile range 40-120). Forty-two (65%) patients had CVFDs and 23 (35%) patients did not. Median stereoacuity for the CVFD group was worse than the non-CVFD group (60 arc sec (IQR 50-140) vs. 40 arc sec (IQR 40-80); p=0.001), respectively. The non-CVFD group had a higher percentage of participants with normal stereopsis compared to the non-CVFD group (61% vs 21%, p=0.001). Multivariable analysis found that the presence of CVFDs was associated with worse stereopsis level (odds ratio 4.49, p=0.021). The CVFD group had a lower VFQ-25 composite score (84.0 vs 91.4, p=0.004), and lower VFQ-25 sub-scale scores for general vision, near activities, and mental health (P<0.05).CVFDs were associated with increased odds of poor stereoacuity in patients with early to moderate glaucomatous VF loss. Specifically, patients without CVFDs are more likely to have normal stereopsis and higher VR-QOL than those with CVFDs. Patients with CVFDs should be counseled regarding how depth perception difficulties may affect daily living.

    View details for DOI 10.1016/j.ogla.2023.04.003

    View details for PubMedID 37080537