Michael Waisbourd

Treatment of diabetic retinopathy with anti‐VEGF drugs

The aim of this review is to summarize the latest developments in the treatment of diabetic retinopathy (DR) with anti‐vascular endothelial growth factor (VEGF) drugs. We reviewed recent studies that evaluated the role of the anti‐VEGF agents bevacizumab, ranibizumab and pegaptanib in the treatment of DR. There was only one large randomized controlled trial that evaluated the role of ranibizumab in diabetic macular oedema (DME). Other prospective and retrospective studies provided important insight into the role of anti‐VEGF drugs in DR, but most of them were not conducted in large scales. The growing evidence indicates that anti‐VEGF drugs are beneficial in DR, especially in DME. Further studies are needed to fully evaluate the role of these agents, especially in proliferative DR and in DR candidates for vitrectomy surgery.

Targeting vascular endothelial growth factor: a promising strategy for treating age-related macular degeneration.

Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the industrialised world. While treatment options for advanced AMD have been rather limited until recently, the introduction of intravitreal injections of anti-angiogenic agents appears to be a promising and revolutionary mode of treatment for this blinding disease. Vascular endothelial growth factor (VEGF) appears to play a pivotal role in the pathogenesis of choroidal neovascularisation, one of the cornerstones of advanced AMD. Pegaptanib, the first anti-VEGF treatment approved for AMD patients, is a VEGF-neutralising aptamer that specifically inhibits one isoform of VEGF (VEGF-165). Although evidence suggested that pegaptanib was superior to previous treatment options, results with this agent were still unsatisfactory. Ranibizumab is a humanised anti-VEGF monoclonal antibody fragment that inhibits all isotypes of VEGF. This new drug has demonstrated a high efficacy profile in terms of inhibiting disease progression and even improving visual acuity. Bevacizumab is a full-length anti-VEGF antibody that was originally approved for use in metastatic colon cancer and is under investigation as a low-cost off-label alternative for patients with AMD. There is growing evidence that this drug may be an effective and safe alternative to the more expensive ranibizumab, although prospective multicentre trials are required to fully investigate this issue. Undoubtedly, the concept of directly injecting anti-VEGF drugs into the vitreal cavity brings new hope to many AMD patients.

Long-term evaluation of patients treated with dexamethasone intravitreal implant for macular edema due to retinal vein occlusion

PurposeTo evaluate the long-term visual prognosis and complications of patients who received intravitreal Ozurdex injections for the treatment of macular edema (ME) due to retinal vein occlusion (RVO).MethodsA total of 17 patients who received Ozurdex injections in our institution as part of the GENEVA study were recalled for examination. Recorded parameters included final visual acuity (VA), final retinal thickness by optical coherence tomography, persistence of ME, and the occurrence of any complications.ResultsMean follow-up time was 50.5 months. Patients with branch RVO (BRVO) had a more favorable prognosis than central RVO (CRVO), and their mean VA had improved significantly, whereas the mean VA for the patients with CRVO did not improve significantly. Retinal thickness had reduced significantly in the whole group and in each subgroup separately. Complications included 10 patients with cataract progression, 1 with elevated intraocular pressure, and 1 with neovascularization and vitreous hemorrhage.ConclusionsThis is the first reported long-term evaluation of patients treated with Ozurdex. Our results indicate that it has favorable long-term safety profile, and may have a beneficial effect on the visual prognosis in BRVO even in the absence of continuous treatment. Further research is required to establish the optimal retreatment schedule for Ozurdex.

Primary angle-closure glaucoma: an update

Primary angle‐closure glaucoma is potentially a devastating disease, responsible for half of glaucoma‐related blindness worldwide. Angle closure is characterized by appositional approximation or contact between the iris and trabecular meshwork. It tends to develop in eyes with shallow anterior chambers, anteriorly positioned or pushed lenses, and angle crowding. Risk of primary angle‐closure glaucoma is high among women, the elderly and the hyperopic, and it is most prevalent in Asia. Investigation into genetic mechanisms of glaucoma inheritance is underway. Diagnosis relies on gonioscopy and may be aided by anterior segment optical coherence tomography and ultrasound biomicroscopy. Treatment is designed to control intraocular pressure while monitoring changes to the angle and optic nerve head. Treatment typically begins with medical management through pressure‐reducing topical medications. Peripheral iridotomy is often performed to alleviate pupillary block, while laser iridoplasty has been found effective for mechanisms of closure other than pupillary block, such as plateau iris syndrome. Phacoemulsification, with or without goniosynechialysis, both in eyes with existing cataracts and in those with clear lenses, is thus far a viable treatment alternative. Long‐term research currently underway will examine its efficacy in cases of angle closure in early stages of the disease. Endoscopic cyclophotocoagulation is another treatment option, which can be combined with cataract surgery. Trabeculectomy remains effective therapy for more advanced cases.

Stem cell therapy for glaucoma: Science or snake oil?

In recent years there has been substantial progress in developing stem cell treatments for glaucoma. As a downstream approach that targets the underlying susceptibility of retinal ganglion and trabecular meshwork cells, stem cell therapy has the potential to both replace lost, and protect damaged, cells by secreting neurotrophic factors. A variety of sources, including embryonic cells, adult cells derived from the central nervous system, and induced pluripotent stem cells show promise as therapeutic approaches. Even though safety concerns and ethical controversies have limited clinical implementation, some institutions have already commercialized stem cell therapy and are using direct-to-consumer advertising to attract patients with glaucoma. We review the progress of stem cell therapy and its current commercial availability.

The Impact of Visual Field Clusters on Performance-based Measures and Vision-Related Quality of Life in Patients With Glaucoma

PURPOSE To investigate how visual field (VF) clusters affect performance-based measures of the ability to perform activities of daily living and subjective measures of vision-related quality of life (QoL) in patients with glaucoma. DESIGN Prospective, cross-sectional study. METHODS setting: Institutional - Wills Eye Hospital. STUDY POPULATION 322 eyes of 161 patients with moderate-stage glaucoma. OBSERVATION VF tests were conducted using the Humphrey 24-2 Swedish Interactive Thresholding Algorithm standard perimeter. The VFs of each patient were divided into 5 clusters: nasal, temporal, central, paracentral, and peripheral. The score for each cluster was the averaged total deviation scores of all tested points within the cluster. Each cluster score was correlated with performance-based measures of visual function and subjective assessment of vision-related QoL. MAIN OUTCOME MEASURES The Compressed Assessment of Ability Related to Vision, the National Eye Institute Visual Functioning Questionnaire 25 (NEI VFQ-25), and the Modified Glaucoma Symptom Scale. RESULTS The central VF cluster in the better eye was positively correlated with all Compressed Assessment of Ability Related to Vision (performance-based measure) subscales. The strongest correlation for the better eye was between the central VF cluster and total Compressed Assessment of Ability Related to Vision score (0.39, P < .001). The inferior VF hemisphere in both eyes was positively correlated with most Compressed Assessment of Ability Related to Vision subscales. Central VF clusters in the better eye were positively correlated with a majority of the NEI VFQ-25 subscales. There were no significant correlations between VF clusters and Modified Glaucoma Symptom Scale subscales. CONCLUSIONS Scores of central VF defects in the better eye and inferior hemisphere defects in both eyes were positively correlated with performance-based measures of the ability to perform activities of daily living. Glaucoma patients with central defects in the better eye were more likely to have reduced scores on assessments of vision-related QoL.

Tube shunt coverage with gamma-irradiated cornea allograft (VisionGraft).

Purpose To investigate the clinical outcomes of tube shunt coverage using sterile gamma-irradiated cornea allograft. Patients and methods The Wills Eye Hospital Glaucoma Research Center retrospectively reviewed the medical records of 165 patients who underwent glaucoma tube shunt procedures using sterile gamma-irradiated cornea allograft (VisionGraft) between December 2012 and November 2013. Demographic characteristics, type of tube shunt, and position were noted. Complications were recorded at 1 day; 1 week; 1, 3, 6, and 12 months; and on the final postoperative visit. Results One hundred and sixty-nine eyes of 165 patients were included. The mean follow-up time was 4.8±3.5 (ranging from 1 to 16) months. There was no evidence of immunological reaction, infection, or exposure in 166 eyes (98.2%). Three eyes (1.8%) experienced graft or tube exposure within the first 3 postoperative months. Two of the cases had underlying diseases: bullous pemphigoid and chronic allergic conjunctivitis. Conclusion Coverage of tube shunts using gamma-irradiated cornea allograft had a low exposure rate and was well tolerated. The graft can be stored long term at room temperature and has an excellent postoperative cosmetic appearance.

EVALUATING CONTRAST SENSITIVITY IN AGE-RELATED MACULAR DEGENERATION USING A NOVEL COMPUTER-BASED TEST, THE SPAETH/RICHMAN CONTRAST SENSITIVITY TEST.

Background: Contrast sensitivity (CS) is a valuable measure of visual function in patients with age-related macular degeneration (AMD). The authors aimed to compare a novel computer-based test (the Spaeth/Richman Contrast Sensitivity test) with Pelli–Robson test for evaluating CS in patients with AMD. Methods: In this prospective cross-sectional study, CS was evaluated in patients with various stages of AMD and healthy controls using Spaeth/Richman Contrast Sensitivity test and Pelli–Robson test. Spaeth/Richman Contrast Sensitivity test determined CS scores for 5 areas of vision for each eye (central, superonasal, superotemporal, inferonasal, and inferotemporal) and the total score. Test scores between the two methods were compared using mixed-effects linear regression. Spearmans rank correlation coefficient was used to determine correlations. Test–retest reliability was determined using the intraclass correlation coefficient. Results: Of 35 participants with AMD (54 eyes) and 34 controls (66 eyes), 51% were female and 93% were of European descent. The mean Spaeth/Richman Contrast Sensitivity test score for the central area and each of the 4 peripheral quadrants was significantly lower for patients with AMD versus controls (P < 0.001 for all). The mean Pelli–Robson score was also significantly lower in patients with AMD versus controls (P < 0.001). The intraclass correlation coefficient for Spaeth/Richman Contrast Sensitivity test total score and Pelli–Robson score was 0.87 and 0.92, respectively. Conclusion: Spaeth/Richman Contrast Sensitivity test, a novel Internet-based method of testing CS, had significantly lower scores for patients with AMD compared with controls for central and peripheral vision. This test is a valuable tool for assessing CS in AMD.

Selective laser trabeculoplasty as a first-line therapy: a review ☆

Poor adherence with glaucoma medications has been well documented. There remains a significant unmet need for a relatively safe intraocular pressure (IOP)-lowering procedure that minimizes or eliminates patient participation, and thus reduce the incidence of treatment failures attributable to nonadherence. Selective laser trabeculoplasty (SLT) offers several advantages: It effectively reduces IOP in most patients with open-angle glaucoma, it is cost-effective compared with eye drops, it can be repeated if needed, and it eliminates the issue of adherence to medications when used as an initial treatment. This article reviews the evidence supporting the use of SLT as a first-line therapy in glaucoma.

Topical Bevacizumab for Neovascular Glaucoma: A Pilot Study

Background/Aims: Bevacizumab (Avastin), an anti-vascular endothelial growth factor drug, has been successfully used in recent years to treat ocular pathologies, mostly by intravitreal administration. The aim of this study was to investigate the safety and efficacy of topically applied bevacizumab for the treatment of neovascular glaucoma (NVG). Methods: Patients with NVG were treated with topical bevacizumab (25 mg/ml) 4 times daily during 2 weeks. The following parameters were evaluated at baseline and on days 3, 7 and 14: visual acuity, slit-lamp examination, intraocular pressure (IOP), heart rate and systemic blood pressure. Iris neovascularization was documented using slit-lamp color photos at baseline and on day 14. Results: Eight eyes of 8 patients with NVG were evaluated. After the 2-week treatment, mean IOP was lowered from 34.9 mm Hg (SD 12.8) at baseline to 28.8 mm Hg (SD 9.9) on day 14, representing a mean reduction of 6.1 mm Hg (17.5%). Three patients had clinical regression of their iris neovascularization. Ocular adverse events were transient and included mild upper eyelid swelling, mild exacerbation of superficial punctate keratitis and mild corneal epithelial bullae in an already edematous cornea. There were no serious systemic adverse events. Conclusions: Topical application of bevacizumab may lower IOP and result in regression of neovascularization in patients with NVG.