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Rishi P Singh, Sunil K Srivastava, Justis P Ehlers, Fabiana Q Silva, Rumneek Bedi, Andrew P Schachat, Peter K Kaiser Cole Eye Institute, Cleveland Clinic, Cleveland, OH, USA Summary statement: In subjects with active exudative age-related macular degeneration, treating with a fixed intravitreal aflibercept injection dosing regimen for 12 months demonstrated improved anatomic and vision endpoints from baseline.Purpose: Switching therapies in neovascular age-related macular degeneration (AMD) may offer an advantage for some patients. This study evaluates the efficacy of intravitreal aflibercept injection (IAI) in subjects previously treated with ranibizumab and/or bevacizumab.Methods: Subjects (n=26) were given monthly 2 mg of IAI for 3 months, followed by 2 mg once in every 2 months for up to 12 months. The mean absolute change from baseline in central subfield thickness (CST) measured by optical coherence tomography and the mean change from baseline in best-corrected visual acuity (BCVA) early treatment in diabetic retinopathy study (ETDRS) letter score were obtained. Additionally, the percentage of subjects who gained or lost ≥15 letters of vision and the percentage of subjects who are 20/40 or better or 20/200 or worse were evaluated.Results: There was a mean decrease in CST of -50.3 µm (P

Singh RP, Srivastava SK, Ehlers JP, et al. Clin Ophthalmol. 2015;9:1759–1766.On page 1763, Figure 4 has been amended. Read the original article

Background: This study evaluated the association of age-related lens opacities with the use of nutritional supplements and demographic factors among 4314 black participants (> or = 40 years) in the population-based Barbados Eye Study.Methods: Lenses were classified at the slit lamp by the Lens Opacities Classification System II (LOCS II); a score > or = 2 was used to define the presence of gradable lens opacities, by type. Lens changes also included prior cataract surgery or cataract too advanced to grade. Associations with risk factors were evaluated by logistic regression analyses.Results: The study identified 1800 individuals with lens changes in at least one eye; 229 had nuclear opacities only; 851 had cortical opacities only. Older age and indicators of lower socioeconomic status (low education and/or non-professional occupation), were positively associated with both nuclear (odds ratio [OR] = 1.90) and cortical (OR = 1.47) opacities. Women had an increased risk of cortical opacities (OR = 1.41). Regular users of nutritional supplements were less likely to have lens changes (OR = 0.78) and, specifically, cortical opacities (OR = 0.77). The association with nutritional supplements was present in those < 70 years, but not at older ages.Conclusions: The study supports the association of lower socioeconomic status with lens changes, including nuclear and cortical lens opacities. The findings also suggest that regular users of nutritional supplements have a one-fourth lower risk of lens changes and particularly, of cortical opacities; a result seen at ages under 70 years. The associations with potentially modifiable factors indicate the need for further evaluations, given the high prevalence of lens opacities. [ABSTRACT FROM AUTHOR]

Objective: This study quantifies change in best visual acuity (BVA) over the preoperative period and assesses factors associated with postoperative outcomes., Design: Retrospective chart review conducted at a single institution., Participants: A total of 691 patients underwent cataract surgery and had a preoperative assessment 0-30 days prior to surgery following their surgical evaluation., Methods: Baseline demographics and past medical and clinical data were collected through electronic medical record query. BVA was noted at initial surgical evaluation, preoperative assessment, and nearest postoperative assessment., Results: A total of 691 patients (911 eyes) were included with mean BVAs at the initial evaluation, preoperative assessment, and postoperative assessment of 68.3 ± 16.8, 64.6 ± 18.5, and 81.1 ± 12.0 ETDRS letters, respectively. Mean BVA was significantly higher postoperatively compared with the preoperative assessment and initial evaluation (p < 0.0001). There was a mean of 53.8 days between initial surgical evaluation and surgery date and a mean of 49.9 days between the preoperative assessment and initial surgical evaluation. The mean interval between the preoperative assessment and surgery was 11.7 days. In the preoperative period, 9.1% of eyes experienced worsening of BVA by >3 lines and 0.9% experienced improvement of BVA by >3 lines. Time to surgery was significantly associated with change in postoperative BVA (effect size, -0.03 ETDRS letters; p = 0.015) but was not significant on multiple linear regression. BVA at initial evaluation, glaucoma, and glaucoma surgery were all significantly associated with postoperative outcomes., Conclusion: Most eyes experienced stable vision in the preoperative period for cataract surgery. On average, patients with high BVAs at the time of initial surgical evaluation may be able to defer surgery without the risk of poorer surgical outcomes., (Copyright © 2023 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Disorganization of retinal inner layers (DRIL) is a potential spectral-domain optical coherence tomography (SD-OCT) imaging biomarker with clinical utility in diabetic retinopathy (DR)., Patients and Methods: A cross-sectional study was conducted at a large academic center. The cohort was composed of 1,175 patients with type 2 diabetes with and without retinopathy on initial examination between September 2009 and January 2019 ( n = 2,083 eyes). DR risk and progression factors were obtained from the medical record. Trained graders masked to patients' clinical histories evaluated SD-OCT scans for DRIL., Results: Of 2,083 eyes, 28.1% ( n = 585) demonstrated presence of DRIL with high interrater reliability ( K = 0.88, 95% CI 0.86-0.90). DRIL was associated with worse visual acuity (VA) ( P < 0.001) and DR severity ( P < 0.0001). Insulin users had more severe DR ( P < 0.0001). DR-related factors, race (Black, White) and sex (male) were significantly associated with DRIL ( P < 0.05)., Conclusions: DRIL was strongly associated with DR severity and worse VA, supporting its utility as an unfavorable prognostic indicator. [ Ophthalmic Surg Lasers Imaging Retina 2023;54:692-700.] .

Purpose: The intravitreal injection (IVI) of pharmacologic agents is the most commonly performed ocular procedure and is associated with a host of complications. Most IVI-related complications data are derived from randomized controlled clinical trials, which report a high adverse event rate. The nature of these protocol-driven trials limit their applicability to the diverse circumstances seen in routine clinical practice. The goal of this study was to determine the prevalence of patient-reported IVI-related complications, their risk factors, and the manner in which patients sought treatment at a tertiary eye care center., Design: Retrospective, institutional review board-approved study., Participants: Forty-four thousand seven hundred thirty-four injections in 5318 unique patients at the Cleveland Clinic Cole Eye Institute from 2012 through 2016., Methods: Intravitreal injection., Main Outcome Measures: Complication occurrence within 15 days of injection., Results: From 2012 through 2016, a total of 44734 injections were performed in 5318 unique patients. Overall, complication rates were low, representing 1.9% of all injections, with 1031 unique complications in 685 patients (12.9%). The most common minor complications, or those not requiring intervention, were irritation (n = 312) and subconjunctival hemorrhage (n = 284). The most common serious complications, or those requiring intervention, were corneal abrasion (n = 46) and iritis (n = 31). Most complications (66%) were managed adequately by a telephone or Epic (Epic Systems Corp., Verona, WI) electronic message encounter only. Importantly, no injection protocol parameter, such as type of anesthesia, preparation, or post-injection medication, increased the risk of a complication. However, a patient's gender, age, number of previous injections, and provider strongly influenced the risk of patient-reported complications., Conclusions: Overall, complication rates seen in routine clinical practice were low compared with clinical trial reporting. Providers should feel confident in the safety and administration of IVI during times when follow-up office visits and resources may be limited. When performing an IVI, factors such as a patient's gender, age, number of previous injections, and provider must be taken into account to ensure the best possible outcomes., (Copyright © 2020 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the frequency and predictors of local treatment failure and enucleation after iodine 125 (I 125 ) brachytherapy in patients with choroidal melanoma treated and followed up in a large randomized clinical trial., Design: Prospective, noncomparative, interventional case series within a randomized, multicenter clinical trial., Participants: Patients enrolled in the Collaborative Ocular Melanoma Study (COMS) trial of enucleation versus brachytherapy between February 1987 and July 1998; tumors measured 2.5 to 10.0 mm in apical height and no more than 16.0 mm in longest basal dimension., Methods: I 125 brachytherapy was administered via episcleral plaque according to a standard protocol. Follow-up ophthalmic evaluations, including ophthalmic ultrasound and fundus photography, were performed according to a standard protocol at baseline, every 6 months thereafter for 5 years, and subsequently at annual intervals. Survival analysis methods were used to estimate the cumulative risk of postirradiation treatment failure and enucleation. Factors associated with treatment failure and enucleation of plaqued eyes were evaluated using Cox proportional hazards analysis., Main Outcome Measures: Reports of enucleation and of local treatment failure, defined as tumor growth, recurrence, or extrascleral extension, derived from clinical reports based on echographic and photographic documentation., Results: As of September 30, 2000, 638 of the 650 patients randomized to brachytherapy and so treated had been followed up for 1 year or longer, and 411 had been followed up for at least 5 years. Sixty-nine eyes were enucleated during the first 5 years after brachytherapy, and treatment failure was reported for 57 eyes. The Kaplan-Meier estimate of proportion of patients undergoing enucleation by 5 years was 12.5% (95% confidence interval [CI], 10.0%-15.6%); the risk of treatment failure was 10.3% (95% CI, 8.0%-13.2%). Treatment failure was the most common reason for enucleation within 3 years of treatment; beyond 3 years, ocular pain was most common. Risk factors for enucleation were greater tumor thickness, closer proximity of the posterior tumor border to the foveal avascular zone, and poorer baseline visual acuity in the affected eye. Risk factors for treatment failure were older age, greater tumor thickness, and proximity of the tumor to the foveal avascular zone. Local treatment failure was associated weakly with reduced survival after controlling for baseline tumor and personal characteristics (adjusted risk ratio, 1.5; P = 0.08)., Conclusions: Local treatment failure and enucleation were relatively infrequent events after I 125 brachytherapy within the COMS. Treatment failure typically occurred early and was associated weakly with poorer survival. The COMS randomized trial documented the absence of a clinically or statistically significant difference in survival for patients randomly assigned to enucleation versus brachytherapy. This analysis documents the efficacy of brachytherapy to achieve sustained local tumor control and to conserve the globe., (Copyright © 2020. Published by Elsevier Inc.)

Background/aims: The efficacy of mineralocorticoid receptor antagonist eplerenone to treat chronic central serous chorioretinopathy (CSCR) has been established. However, previous studies have been limited by small cohort size and short follow-up duration. This study aims to report 3-year clinical outcomes of patients treated with eplerenone for chronic CSCR., Methods: Institutional review board-approved retrospective chart analysis at a single institution from 2012 to 2018. Baseline best-corrected visual acuity and anatomical measurements related to degree of subretinal fluid (SRF) were collected at eplerenone initiation. Follow-up data were collected at the closest date to 12, 24 and 36 months., Results: Data were obtained for 100 eyes of 83 patients at 1-year (mean 11.18 ± 4.00 months), 49 eyes at 2-year (24.01 ± 3.33 months) and 33 eyes at 3-year (mean 35.5 ± 7.89 months) follow-up visits. The rate of complete SRF resolution was 31%, 28% and 33%, respectively. At final follow-up, logarithm of the minimum angle of resolution visual acuity change from baseline was +0.10 ± 0.24 (p = 0.130). Average change from baseline at final follow-up for central subfield thickness was -97 ± 140.6 µm (p < 0.001), cube volume was -1.07 ± 1.71 mm 3 (p < 0.001), macular thickness -28. 5 ± 47.5 µm (p < 0.001), maximum SRF height was -95.6 ± 160.5 µm (p < 0.001) and maximum SRF diameter was -1169.0 ± 1638.7 µm (p = 0.008)., Conclusion: Anatomical improvement occurs primarily within the first year of eplerenone treatment for chronic CSCR., Competing Interests: Competing interests: DP, DG, FC and GH: None to Declare. AB reports grants from Regeneron, personal fees from VINDICO, MCME Global, outside the submitted work; AR reports personal fees from Allergan, Alcon, Zeiss, outside the submitted work; AS reports personal fees and other from American Academy of Ophthalmology, outside the submitted work; In addition, AS has a patent Elsevier with royalties paid and may receive possible future payments (none to-date) from Easton Capital. JE reports personal fees from Bioptigen, Leica, Zeiss, Alcon, Santen, grants and personal fees from Thrombogenics, Genentech, grants from Regeneron, outside the submitted work; JE has a patent Bioptigen issued. PK personal fees from Bausch and Lomb, Novartis, Carl Zeiss Meditec, Topcon, Allergan, outside the submitted work. RS reports grants and personal fees from Genentech/Roche, Alcon/Novartis, grants from Apellis, personal fees from Optos, Zeiss, from Biogen, grants and personal fees from Regeneron Pharmaceuticals, Inc., outside the submitted work; SKS reports grants and personal fees from Bausch and Lomb, Leica, Santen, grants and personal fees from Carl Zeiss Meditec, grants from Allergan, outside the submitted work; SKS has a patent Bioptigen and Synergetics issued. SS reports personal fees from Allergan, outside the submitted work., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objective: To identify choroidal neovascular membrane (CNVM) associated with spectral-domain optical coherence tomography (SD-OCT)-defined pigment epithelial detachment (PED) using SD-OCT angiography (SD-OCTA)., Patients and Methods: Sixty-nine patients with same-day OCT and OCTA imaging were reviewed, and 41 eyes of 29 patients with PEDs were included. OCTs were analyzed for PED type, fluid, and subretinal hyperreflective material (SHRM)., Results: Twenty-seven eyes (66%) demonstrated CNVM on OCTA beneath all subtypes of PED. Twenty-two eyes (75.9%) with fluid or SHRM demonstrated CNVM on OCTA (P = .036). Fluid corresponded in a statistically significant manner with treatment (P = .0032), whereas SHRM did not (P = .613). OCTA-defined CNVM showed borderline statistically significant correlation to treatment (P = .05). Increased choroidal flow signal seen in 50% of eyes did not demonstrate statistically significant correlation to the presence of fluid on SD-OCT (P = .2798) or treatment decision (P = .678). A subset of 14 untreated eyes with CNVM was analyzed, 21% of which required treatment at subsequent visits., Conclusions: OCTA-defined CNVM was seen in all subtypes of PED in clinically active and inactive disease. The role of OCTA in predicting need for treatment remains to be established. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:620-626.]., (Copyright 2019, SLACK Incorporated.)

Purpose: Although intravitreal anti-vascular endothelial growth factor (VEGF) injection has become the mainstay treatment for neovascular age-related macular degeneration (nAMD), emerging studies suggest that anti-VEGF may be correlated with the development of macular atrophy (MA) in chronic therapy. The purpose of the current study is to determine the prevalence and progression of MA in nAMD treated with chronic anti-VEGF in a routine clinical practice., Design: Retrospective cohort., Participants: Patients with nAMD who were previously treatment-naïve and treated with anti-VEGF at the Cole Eye Institute for at least 4 years., Methods: This is chart review on anti-VEGF treated patients with nAMD with baseline and yearly follow-up spectral domain-OCT for at least 4 years. Retinal pigment epithelium subillumination analysis was used to automate identification of atrophy. Segmentation errors were manually corrected by 4 expert raters using a standardized grading protocol to quantify MA size. Patient baseline characteristics and treatment course were analyzed to identify predictive factors for the development of MA., Main Outcome Measures: MA growth rate and prevalence in cohorts with and without baseline atrophy., Results: A total of 79 eyes from 66 patients (79.8±7.4 years, 63% were female) with nAMD and 4 years of follow-up with anti-VEGF injections were identified. The mean baseline visual acuity was 0.48±0.25 logarithm of the minimum angle of resolution (20/60 Snellen equivalent), and the mean final visual acuity was 0.48±0.49 logarithm of the minimum angle of resolution (20/44 Snellen equivalent, P = 0.23). The average number of injections was 19.8±9.8. MA was observed in 12.7% of eyes at baseline with an average annual growth rate of 0.7±0.5 mm 2 . In eyes without baseline MA, atrophy developed in 53.6% eyes by year 4 with a growth rate of 0.2±0.4 mm 2 per year. Multiple linear regression analysis revealed that the progression of MA was positively correlated with age (R = 0.02, P = 0.009)., Conclusions: More than half of patients with nAMD treated with anti-VEGF injections for 4 years developed new MA. Atrophy progression was most strongly correlated with age, which suggests that baseline disease characteristics may be more predictive of MA progression than cumulative anti-VEGF treatment., (Copyright © 2017 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To assess the efficacy of ranibizumab for persistent diabetic macular edema (DME) previously treated with bevacizumab and compare monthly vs treat-and-extend (TAE) dosing., Design: 12-month, open-label, prospective randomized comparative dosing study., Participants: 27 participants with persistent foveal-involving DME recently treated with bevacizumab., Methods: All subjects were to receive three initial monthly 0.3 mg ranibizumab injections before randomization to monthly (n=15) or TAE (n=12) injection protocols over 12 months. Treatment interval was extended by two weeks up to a maximum interval of 12 weeks in the TAE group if central subfield thickness (CST) was ≤ 300 μm or complete absence of intraretinal or subretinal fluid on the macular cube was observed. Follow-up interval was decreased by 2 weeks if CST increased above 300 μm with associated intraretinal and/or subretinal fluid., Main Outcome Measures: Change in Early Treatment of Diabetic Retinopathy Study (ETDRS) best corrected visual acuity (BCVA), CST, adverse events., Results: Prior to study enrollment, subjects received an average of 8.6 bevacizumab injections. At month 12, mean ETDRS BCVA improved by + 5.3 letters (p<0.05) and mean CST decreased by -99.6 μm (p<0.01) in all patients. At study exit, 18.5 % of subjects gained ≥ 3 lines of vision and 3.7% of subjects lost ≥ 3 lines. Patients treated via the TAE protocol gained +8.4 letters and decreased CST by -120.2 μm whereas those treated by monthly injection gained +2.7 letters and decreased CST by -83.1 μm at month 12., Conclusions: Following conversion to ranibizumab in eyes with persistent DME refractory to bevacizumab, significant functional and anatomic improvements were noted. Visual and anatomical outcomes were similar in TAE and monthly treatment protocols., Competing Interests: Conflict of Interest Statement: JPE and RPS are consultants for Alcon. JPE and RPS receive research support from Genentech and Regeneron. SKS receives research support from Allergan. No other specific conflicts of interest exist related to this study for any of the other authors.

Background and Objective: In the ASSESS study, patients with neovascular age-related macular degeneration transitioned from other anti-vascular endothelial growth factor therapies to intravitreous aflibercept (Eylea; Regeneron, Tarrytown, NY) injections (IAI). The purpose was to determine the 36-month outcomes following the change from a fixed 24-month IAI dosing regimen to a routine clinical practice regimen., Patients and Methods: Patients were treated with a fixed bimonthly regimen for the first 2 years. In the third year, patients were managed according to routine clinical practice., Results: A total of 18 patients completed the 36 months and were considered for statistical analyses. At 36 months, a nonsignificant decrease of -37.8 μm in central subfield thickness and a nonsignificant gain of 5.8 letters from baseline were observed., Conclusion: Despite the significant visual and anatomical gains observed in the 2 years of fixed-dosing IAI, there was gradual decline in these improvements when patients were transitioned to a variable regimen. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:179-185.]., (Copyright 2018, SLACK Incorporated.)

Background and Objective: Previous literature assessing ocular hemorrhagic complications of anticoagulant/antiplatelet medications in routine clinical practice is limited. This study evaluates the prevalence of spontaneous ocular hemorrhagic events associated with anticoagulation/antiplatelet therapy., Patients and Methods: A retrospective study was performed to identify patients taking anticoagulants (rivaroxaban [Xarelto; Janssen Pharmaceuticals, Beerse, Belgium], bivalirudin [Angiomax; The Medicines Company, Parsippany, NJ], lepirudin [Refludan; Bayer HealthCare Pharmaceuticals, Berlin, Germany], dabigatran [Pradaxa; Boehringer Ingelheim, Ingelheim am Rhein, Germany], and argatroban) and antiplatelet agents (clopidogrel [Plavix; Bristol-Myers Squibb, New York City, NY], prasugrel [Effient; Lilly Medical, Indianapolis, IN], and ticagrelor [Brilinta; AstraZeneca, Cambridge, UK]) who presented for an eye examination. Location of hemorrhage, relevant systemic and ocular comorbidities, baseline demographics, and concomitant aspirin use were noted., Results: A total of 44 patients with spontaneous ocular hemorrhage were identified. Thirty patients had a single episode, whereas 14 patients had multiple episodes (two or more hemorrhagic events). Prevalence of spontaneous ocular hemorrhage on prasugrel (7.2%) and rivaroxaban (3.1%) was higher compared to dabigatran (1.9%), clopidogrel (2.0%), and ticagrelor (2.7%)., Conclusion: Prevalence of spontaneous ocular hemorrhage with use of anticoagulant/antiplatelet agents is higher in routine clinical practice as compared to previously reported literature. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:27-34.]., (Copyright 2018, SLACK Incorporated.)

Aims: To compare anti-vascular endothelial growth factor (VEGF) treatment outcomes for macular oedema (ME) secondary to retinal vein occlusion (RVO) based on vitreoretinal interface (VRI) status., Methods: This retrospective case series includes treatment-naive eyes diagnosed with RVO and treated with anti-VEGF injections. Eyes were stratified based on international VRI classification schema at baseline into three groups-vitreomacular traction (group A), no posterior vitreous detachment (PVD) (group B) and PVD without vitreomacular attachment (group C). Fifty-two eyes were identified based on inclusion/exclusion criteria. The primary endpoint was change in central subfield thickness (CST) on optical coherence tomography at 6 months., Results: There were no statistically significant differences in baseline characteristics of patients with RVO when stratified by VRI subgroups. After 6 months of treatment, there was no statistically significant difference in the change in CST from baseline between VRI cohorts (p=0.11). There was a trend demonstrating the greatest improvement in CST in eyes in group A compared with eyes in groups B and C (-224.13 μm, -160.88 μm and -50.92 μm, respectively, p=0.11 between cohorts). Mean change in logarithm of the minimum angle of resolution visual acuity from baseline to month 6 in group A compared with groups B and C was -0.25, -0.14 and -0.13, respectively (p=0.64 between cohorts)., Conclusions: We did not identify an association between VRI status and treatment outcomes with anti-VEGF agents for ME secondary to RVO., Competing Interests: Competing interests: RPS: Regeneron (grants and personal fees), Alcon (grants and personal fees), Genentech (grants and personal fees), Shire (personal fees), Zeiss (grants), Biogen (personal fees), during the conduct of the study; JPE: Thrombogenics (grants and personal fees), Alcon (personal fees), Zeiss (personal fees), Leica (personal fees), Genentech (grants), Regeneron (grants), Santen (personal fees), Alimera (personal fees), outside the submitted work; APS: Cleveland Clinic (full-time employee), State of Ohio (part-time employee), Elsevier (Royalties), American Academy of Ophthalmology (Honorarium), Easton Capital (possible future payments, nothing to date); SKS: Santen (personal fees), Bausch and Lomb (grants and personal fees), Synergetics (personal fees), Zeiss (grants and personal fees), Sanofi (grants and personal fees), Optos (personal fees), Regeneron (grants and personal fees), Allergan (grants and personal fees), outside the submitted work; PKK: Alcon (personal fees), Bayer (personal fees), Regeneron (personal fees), Novartis (personal fees), Kanghong (personal fees), Thrombgenics (personal fees), outside the submitted work., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: The aim is to compare the therapeutic effects of three antivascular endothelial growth factor (VEGF) drugs (bevacizumab, aflibercept and ranibizumab) on fibrovascular pigment epithelial detachments (fvPEDs) in age-related macular degeneration (AMD)., Methods: This was a retrospective, comparative, consecutive case series of 88 unique eyes with fvPEDs in neovascular AMD treated with anti-VEGF monotherapy for a minimum of 6 months. All eyes were treatment naive. Diagnosis was confirmed retrospectively by fluorescein angiography and spectral-domain optical coherence tomography. Exclusion criteria included serous/drusenoid PEDs or patients who switched anti-VEGF. Mean follow-up across all therapies was 313.9±85.3 days., Results: Average age of all patients was 80.6 years. Baseline maximum subfoveal PED height was 326.8±185.1 μm, 394.5±238.6 μm and 258.0±145.3 μm for bevacizumab, aflibercept and ranibizumab, respectively (p=0.05). All patients had subretinal fluid, intraretinal fluid or a combination of the two at an initial presentation. Central retinal thickness decreased at all time points compared with baseline across all three anti-VEGF therapies. Subfoveal PED height decreased in patients treated with aflibercept at all time points and decreased in patients treated with bevacizumab at 1-month, 3-month and 6-month time points. Aflibercept reduced PED height more than bevacizumab at 1-month and 12-month follow-ups (p=0.02 and p=0.03, respectively) and ranibizumab at 1-month and 6-month follow-ups (p=0.03 and p=0.02, respectively). No differences in best-corrected visual acuity were appreciated at any time point between drugs., Conclusions: There was a significant reduction in subfoveal PED height for aflibercept and bevacizumab compared with baseline. A direct comparison of drugs demonstrated a beneficial reduction of PED height, albeit inconsistently, favouring aflibercept. There were no differences in visual acuity across the groups at any time point., Competing Interests: Competing interests: RPS: Regeneron (FS, C), Thrombogenics (FS, C), Alcon (FS, C) and Genentech (FS, C). AVR: Allergan (C). JPE: Bioptigen (C), Thrombogenics (R, C), Zeiss (C), Alcon (C) and Leica (C). SKS: Regeneron (C), Bausch and Lomb (C, FS), Clearside (C, FS), Novartis (FS), Allergan (FS), Carl Zeiss Meditec (C) and Santen (C). PKK: Genentech (R, C), Novartis (R, C), Regeneron (R, C), Bayer HealthCare Pharmaceuticals (C) and Kanghong Biotechnology (C). APS: Allergan (C), Bausch and Lomb (C), AnGes (C) and Elsevier (R)., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To evaluate alterations on optical coherence tomography angiography (OCT-A) and quantitatively assess alterations in the ellipsoid zone (EZ) in eyes with macular telangiectasia type 2 (MacTel type 2)., Methods: The Observational Assessment of Visualizing and Analyzing Vessels With Optical Coherence Tomography Angiography in Retinal Diseases study is an institutional review board-approved prospective, observational study investigating OCT-A in macular disease. Patients underwent spectral-domain (SD)-OCT and OCT-A imaging at a single visit. SD-OCT data were analyzed using a novel OCT EZ-mapping software to obtain linear, area, and volumetric measurements of the EZ-retinal pigment epithelium (RPE) complex across the macular cube. OCT-A retinal capillary density was measured using the Optovue Avanti split-spectrum amplitude-decorrelation angiography algorithm. EZ-RPE parameters were compared to age-matched, sex-matched controls., Results: Fourteen eyes of seven patients (mean age, 59 ± 6.5 years) were analyzed. Mean visual acuity was 20/45 (range, 20/20-20/150). EZ-RPE central foveal mean thickness was 27.8 ± 6.7 μm, EZ-RPE central foveal thickness was 22.1 ± 21.6 μm, EZ-RPE central foveal area was 0.17 ± 0.04 mm2, and EZ-RPE central subfield volume was 0.017 ± 0.012 mm3. Each of these measurements was significantly inversely correlated with visual acuity (P < 0.02). In addition, all of these measurements were significantly reduced compared to controls (all P ≤ 0.005). OCT-A showed a reduced parafoveal vessel density of 50.8% temporally compared to 53.8% nasally (P = 0.01) in the superficial vascular plexus. In the deep vascular plexus, similar findings were noted with a parafoveal vessel density of 56.7% temporally and 58.8% nasally (P = 0.01)., Conclusions: Abnormalities in EZ-RPE thickness, area, and volume are correlated with visual acuity in MacTel type 2, and may provide quantitative markers to measure disease progression and treatment response. OCT-A was a useful adjunct for determining disease severity.

Background and Objective: To determine outcomes of intravitreal ranibizumab (IVR) (Lucentis; Genentech, South San Francisco, CA) versus bevacizumab (IVB) (Avastin; Genentech, South San Francisco, CA) for treatment of macular edema (ME) secondary to retinal vein occlusion (RVO) in routine clinical practice., Patients and Methods: A retrospective study identified treatment-naïve patients with ME secondary to RVO where treatment with either IVB or IVR was initiated. Retreatment criteria were based on ophthalmic examination and/or spectral-domain optical coherence tomography findings., Results: Central RVO/hemi-RVO cohort: At 12 months, change in visual acuity (VA) (IVR: +12.9 letters, IVB +6.9 letters; P = .53), central subfield thickness (CST) (IVR: -144.1 μm, IVB: -153.9 μm; P = .88), and number of injections (IVR: 5.40 injections, IVB: 5.64 injections; P = .70) were not different between groups. Branch RVO cohort: At 12-month follow-up, no differences in change in VA (IVR: +15.2 letters, IVB: +10.6 letters; P = .46), CST (IVR: -23.1 μm, IVB: -91.4 μm; P = .16), or number of injections (IVR: 5.93 injections, IVB: 5.13 injections; P = .15) were noted., Conclusion: There is no notable difference in outcome between IVR and IVB when treating ME from RVO in routine clinical practice. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:465-472.]., (Copyright 2017, SLACK Incorporated.)

Aim: To determine the impact of initial visual acuity (VA) on anti-vascular endothelial growth factor (VEGF) treatment outcomes in patients with macular oedema secondary to retinal vein occlusions in routine clinical practice., Methods: A retrospective study was conducted at a single academic institution to identify 177 treatment naïve patients with macular oedema secondary to branch retinal vein occlusion (BRVO), hemiretinal vein occlusion (HRVO) and central retinal vein occlusion (CRVO) treated with intravitreal anti-VEGFs. Exclusion criteria included prior intravitreal injection or presence of active confounding ocular disease. Patients were stratified by initial VA; main outcomes measured were average change in VA and mean absolute change in central subfield thickness (CST) at 6 and 12 months., Results: Patients with BRVO with initial VA of 20/40 or better had no significant changes in average letters gained and CST from baseline (+2.6 letters, p=0.42; -48.94 µm, p=0.12) compared with patients with initial VA between 20/50 and 20/300 (+13.2 letters, p<0.001; -98.20 µm, p<0.001) after 12 months. Patients with CRVO/HRVO with initial VA of 20/320 or worse had the most improvement in average letters gained and CST from baseline (+42.2 letters, p<0.001; -182.84 µm, p=0.004) with anti-VEGF therapy compared with patients with initial VA between 20/50 and 20/300 (+9.4 letters, p=0.016; -160.87 µm, p<0.001) and patients with initial VA of 20/40 or better (-9.6 letters, p=0.14; -47.92 µm, p=0.38)., Conclusions: For macular oedema secondary to retinal vein occlusion, anti-VEGF treatment can result in a greater improvement in average letters gained and in CST for those with poor initial VA compared with those with better initial VA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: On clinical examination, it can be challenging to differentiate retinoschisis with outer retinal hole from schisis-detachment. This study examined the role of outer retinal hole spectral domain optical coherence tomography (SD-OCT) imaging in conjunction with imaging of the posterior schisis cavity edge in differentiating between these conditions., Methods: This is a retrospective case series. Out of 500 subjects with ICD-9 diagnoses of senile retinoschisis (361.10, 361.11, 361.12, 361.19) from January 2004 to December 2014, 62 had evidence of retinoschisis on fundus photography or optical coherence tomography (OCT). Six eyes of five patients had outer retinal holes documented by fundus photography (Optos, Marlborough, Massachusetts, USA) and SD-OCT (Carl Zeiss Meditec, Dublin, California, USA). The OCT morphology of outer retinal holes, subjects' symptomology, visual acuity, fundus examination, diagnosis and progression of the disease were analysed., Results: All five patients were women; the mean age was 67.4 years. The correct diagnosis was recorded in the chart in 50% of cases. All, but one, were asymptomatic with visual acuity ranging from 20/20 to 20/200. Three types of outer retinal hole OCT morphology in conjunction with imaging of the posterior schisis cavity edge were established. (1) Outer retinal hole with both edges down and attached to retinal pigment epithelium (RPE) and the edge of the cavity showing a split in neurosensory retina corresponded to isolated retinoschisis. The outer retinal hole with (2) one or (3) both edges detached from the RPE and the edge of the cavity showing complete separation of retina from RPE corresponded to schisis-detachment. One patient underwent scleral buckle surgery for schisis-detachment. Otherwise, no treatment was performed and no progression was noted with the longest OCT-documented follow-up of 26 months., Conclusions: The OCT morphology of outer retinal holes in conjunction with imaging of the posterior schisis cavity edge aids in the diagnosis of retinoschisis and schisis-detachment., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Purpose: To report the 24-month results and predictive factors for outcomes in patients transitioned from other anti-vascular endothelial growth factor agents to aflibercept for the treatment of exudative age-related macular degeneration (AMD)., Design: A prospective, single arm, investigator-initiated study., Participants: A total of 24 patients participated in the study and 87.5% (n = 21) completed the 24 month assessments. Patients were included if they had an active exudative AMD confirmed by fluorescein angiography, presence of fluid on spectral-domain optical coherence tomography (OCT) or new hemorrhage on clinical examination, Electronic Early Treatment Diabetic Retinopathy Study vision of 25 to 80 letters (Snellen equivalent of approximately 20/25-20/320), prior bevacizumab or ranibizumab injections within 3 months of enrollment, and an initial response on OCT defined as a decrease of retinal edema and/or subretinal fluid to anti-vascular endothelial growth factor injections., Methods: Patients were treated the first 3 months with 2 mg of intravitreal aflibercept monthly, followed by a fixed bimonthly schedule for 24 months. At each study visit, visual acuity and a spectral-domain OCT scanning of both eyes were performed., Main Outcome and Measures: The mean absolute change from baseline in central subfield thickness at month 24, mean change from baseline in best-corrected visual acuity (BCVA) score, change from baseline in macular volume, and cube average thickness by spectral-domain OCT. Additionally, predictive factors associated with final visual and anatomic outcomes at month 24., Results: A mean decrease in central subfield thickness of -41 μm (P = 0.004) was observed with a mean increase in ETDRS BCVA of +10.4 letters (P < 0.001). At study entry, BCVA was a significant predictive factor for BCVA change at month 24 (rho = -0.59; P = 0.003). Also, the duration between AMD diagnosis and study entry was a significant factor for central subfield thickness change at month 24 (rho = -0.51; P = 0.011)., Conclusions: In nonnaïve patients with active exudative AMD, treatment with a fixed intravitreal aflibercept dosing regimen for 24 months demonstrated sustained improvements in anatomy and vision in patients transitioned from other anti-vascular endothelial growth factor agents and stability when compared with 12-month outcomes. Patients who benefited most were those with worse vision at entry and longer duration of disease., (Copyright © 2016 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare retinal layer volumes using spectral-domain optical coherence tomography between eyes with hydroxychloroquine (HCQ) toxicity and control eyes., Methods: Using a previously validated algorithm, volumetric analysis from the macular cube scan of the ganglion cell layer, inner plexiform layer, inner nuclear layer, and outer retina (outer plexiform layer to retinal pigment epithelium) layers were compared in three sets of patients: patients with a clinical diagnosis of HCQ toxicity, age-matched patients taking HCQ but not manifesting overt toxicity, and age-matched control patients., Results: There were 14 patients in each group. The ganglion cell layer (P = 0.01), inner plexiform layer (P = 0.004), inner nuclear layer (P < 0.001), and outer plexiform layer to retinal pigment epithelium (P < 0.001) volumes were significantly reduced in HCQ toxicity eyes relative to the HCQ exposure eyes. There were no significant inner and outer retinal volume differences between the HCQ exposure group and group with no HCQ use (P > 0.05 for all layers). Increasing disease severity correlated with increasing volume loss in the inner retina (2.27 mm in early disease vs. 1.78 mm in advanced retinopathy, P = 0.02)., Conclusion: Hydroxychloroquine toxicity seems to result in both outer and inner retinal volumetric thinning compared with age-matched control patients and patients taking HCQ but not manifesting toxicity.

Importance: The Diabetic Retinopathy Clinical Research Network (DRCR Network), sponsored by the National Eye Institute, reported the results of a comparative effectiveness randomized clinical trial (RCT) evaluating the 3 anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept (2.0 mg), bevacizumab (1.25 mg), and ranibizumab (0.3 mg) for treatment of diabetic macular edema (DME) involving the center of the retina and associated with visual acuity loss. The many important findings of the RCT prompted the American Society of Retina Specialists to convene a group of experts to provide their perspective regarding clinically relevant findings of the study., Objectives: To describe specific outcomes of the RCT judged worthy of highlighting, to discuss how these and other clinically relevant results should be considered by specialists treating DME, and to identify unanswered questions that merit consideration before treatment., Evidence Review: The DRCR Network-authored publication on primary outcomes of the comparative effectiveness RCT at 89 sites in the United States. The study period of the RCT was August 22, 2012, to August 28, 2013., Findings: On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and with visual acuity impairment, including mean (SD) improvements by +13.3 (11.1) letters with aflibercept vs +9.7 (10.1) letters with bevacizumab (P < .001) and +11.2 (9.4) letters with ranibizumab (P = .03). Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept (+18.9 [11.5]) over bevacizumab (+11.8 [12.0]) or ranibizumab (14.2 [10.6]) 1 year later (P < .001 for interaction with visual acuity as a continuous variable, and P = .002 for interaction with visual acuity as a categorical variable). It is unknown whether different visual acuity outcomes associated with the use of the 3 anti-VEGF agents would be noted with other treatment regimens or with adequately repackaged bevacizumab, as well as in patients with criteria that excluded them from the RCT, such as persistent DME despite recent anti-VEGF treatment., Conclusions and Relevance: On average, all 3 anti-VEGF agents led to improved visual acuity in eyes with DME involving the center of the retina and visual acuity impairment. Worse visual acuity when initiating therapy was associated with greater visual acuity benefit of aflibercept over bevacizumab or ranibizumab 1 year later. Care needs to be taken when attempting to extrapolate outcomes of this RCT to differing treatment regimens. With access to adequately repackaged bevacizumab, many specialists might initiate therapy with bevacizumab when visual acuity is good (ie, 20/32 to 20/40 as measured in the DRCR Network), recognizing that the cost-effectiveness of bevacizumab outweighs that of aflibercept or ranibizumab.

Age-related macular degeneration (AMD) is the leading cause of severe vision loss in individuals over the age of 50 years. Choroidal neovascularization (CNV) is the hallmark of 'wet' or 'exudative' AMD, and is responsible for approximately 90% of cases of severe vision loss due to AMD. Vascular endothelial growth factor (VEGF) is a key component in the development and progression of wet AMD. Since the approval of ranibizumab in 2006, VEGF inhibitors have rapidly altered the treatment and standard of care for wet AMD. Ranibizumab, bevacizumab, and aflibercept are now the most widely used anti-VEGF agents for the treatment of wet AMD. This chapter discusses the pharmacologic properties, pharmacokinetics, safety, and efficacy of these medications, as well as revisits landmark clinical trials that establish these drugs as gold standards in care. While these medications have greatly and positively altered the way we treat AMD, there are still many economic and therapeutic limitations with our current therapy regimens. There continue to be advancements and innovations in exploring alternative and new treatment modalities, as well as combining existing treatment options to improve efficacy, and reduce cost and patient burden., (© 2016 S. Karger AG, Basel.)

Purpose: To determine provider compliance with hydroxychloroquine screening following the revised recommendations published in 2011 by the American Academy of Ophthalmology., Design: Evaluation of adherence to a screening protocol., Methods: Subjects were identified with hydroxychloroquine as a medication by electronic query at a large multispecialty ophthalmic practice. Patients were excluded if patients: (1) were screened by an outside physician; (2) lacked recorded height, weight, start date, or dosing; or (3) took hydroxychloroquine for malaria prophylaxis. Screening tests were stratified by ophthalmic subspecialty. Guidelines define proper screening as 1 subjective test-Humphrey visual field (HVF), and 1 objective test-spectral-domain optical coherence tomography (SD OCT), fundus autofluorescence (FAF), or multifocal electroretinography (mfERG). Adherence to guidelines was determined by categorizing practices as: (1) "appropriate"-consistent with guidelines; (2) "underscreened"-insufficient testing; or (3) "inappropriate"-no testing., Results: The study comprised 756 patients with a mean age of 56 years undergoing 1294 screening visits. Twenty-one patients received initial screenings outside the institution. Most common screening tests employed included SD OCT (56.6%), 10-2 HVF (55.0%), and Amsler grid (40.0%). Of the 735 initial screenings, 341 (46.4%) were appropriately screened, 204 (27.8%) underscreened, and 190 (25.9%) inappropriately screened. Of those who presented solely for screening (560), 307 (54.8%) were appropriately screened, 144 (25.7%) underscreened, and 109 (19.5%) inappropriately screened., Conclusions: Of patients presenting for hydroxychloroquine screening, 54.8% of patients received appropriate evaluation, indicating lack of adherence to guidelines. Overall, SD OCT and 10-2 HVF were the preferred screening modalities, with FAF and mfERG less frequently ordered., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To examine eplerenone (Inspra, Pfizer), a mineralocorticoid receptor antagonist, as a treatment option for chronic central serous chorioretinopathy (CSCR)., Methods: A retrospective consecutive case series was conducted for patients receiving oral eplerenone for chronic CSCR. At baseline and each follow-up visit, spectral domain optical coherence tomography (SD-OCT) imaging was performed, including manual measurements of the height and diameter size of subretinal fluid. The primary outcome measure was the reduction in subretinal fluid following initiation of therapy., Results: A total of 17 eyes of 13 patients treated with 25 and 50 mg of oral eplerenone per day were identified. Subretinal fluid (SRF) decreased over time following eplerenone therapy (P= 0.007 and P = 0.002, diameter and height respectively). Maximum SRF height decreased from a mean of 131.5 µm at baseline to 15.3 µm at day 181+. SRF diameter decreased from an average of 2174.4 µm at baseline to 46.9 µm at day 181+. LogMAR visual acuity improved from 0.42 (Snellen equivalent: 20/53) at baseline to 0.29 (Snellen equivalent: 20/39) at day 181+ (P = 0.024). Central subfield thickness (CST) decreased from 339.5 µm at baseline to 270.3 µm at day 181+ (P = 0.029)., Conclusion: Eplerenone therapy resulted in significant anatomic and visual improvements in eyes with chronic CSCR.

Aim: To evaluate efficacy and safety of intravitreal aflibercept injection (IAI) in subjects who were previously treated with ranibizumab and/or bevacizumab for active exudative age-related macular degeneration (AMD)., Methods: Patients (n=26) were enrolled in a 12-month prospective, interventional, single arm, investigator-initiated study with planned 6-month interim analysis. Patients with active exudative AMD, previously treated with ranibizumab and/or bevacizumab, were treated with 2 mg IAI every month for the first 3 months, followed by a fixed dosing schedule of 2 mg IAI every 2 months. The primary study endpoint was the mean absolute change from baseline central subfield thickness (CST) at month 12 as measured by SDOCT. Secondary outcomes included mean change from baseline best-corrected visual acuity (BCVA) score, percentage of subjects who gained or lost greater than or equal to 15 letters of vision, percentage of subjects who are 20/40 or better, percentage of subjects who are 20/200 or worse, and the incidence of adverse events (AE) and serious AEs., Results: Planned 6-month interim analysis demonstrated a mean decrease in CST of 38.6 µm (p<0.001) and a mean increase in ETDRS BCVA of +5.9 letters (p<0.001). Fifteen percent of subjects experienced a greater than 15-letter improvement in visual acuity, 84.6% of patients gained visual acuity, and no patient lost 3 lines of vision from baseline. Forty-two percent of subjects were 20/40 or better, and 11.5% of subjects were 20/200 or worse at month 6. No serious ocular or systemic AEs were encountered., Conclusions: IAI-treated eyes demonstrated improved short-term functional and anatomic endpoints in subjects with active exudative AMD switching from previous anti-VEGF treatment when given in a fixed dosing scheme for 6 months., Trial Registration Number: NCT01617148., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Diabetic retinopathy (DR) is one of the leading causes of blindness in the working population worldwide. Vascular leakage, angiogenesis and neuronal degeneration are key features of DR. Current effective interventions for DR include treatment of systemic risk factors such as elevated blood glucose, blood pressure and dyslipidemia. Ocular treatments include vascular endothelial growth factor A (VEGF-A) inhibitors, laser photocoagulation and surgery. While anti-VEGF therapy has become as first-line treatment for diabetic macular edema (DME) that causes reduced vision, intravitreal glucocorticoids also have been shown to be efficacious in this situation. It has been reported that all the major pathological processes of DR are susceptible to glucocorticoid treatment. The effects of glucocorticoids on vascular leakage and angiogenesis may be mediated through their well established anti-inflammatory role. Alternatively, glucocorticoids may affect other mechanisms known to be activated in DR. Potential mechanisms for the anti-inflammatory effects of glucocorticoids include blockage of cytokine production and inhibition of leukocyte adhesion induced by VEGF-A. Glucocorticoids decrease the expression of VEGF-A directly, and increase the production, or decrease phosphorylation, of tight junction-associated proteins. Glucocorticoids have also been shown to be neuroprotective, in contrast to VEGF-A inhibitors which animal studies suggest may be neurotoxic. This review outlines the biological properties of synthetic glucocorticoids, with particular emphasis on the potential beneficial effect of combining glucocorticoids with anti-VEGF treatment for DME and DR.

Objective: To evaluate the anatomical and visual outcomes of patients treated with ocriplasmin for the treatment of symptomatic vitreomacular adhesion (sVMA), including vitreomacular traction syndrome and macular holes., Design: Retrospective, interventional, single centre, case series., Participants: Patients with sVMA., Intervention: Patients were treated with a single intravitreal injection of 0.125 mg ocriplasmin (Jetrea, Thrombogenics Inc, USA, Alcon/Novartis EU) with the reconstitution technique recommended by the manufacturer., Main Outcome Measures: The primary study endpoint was the resolution of sVMA by spectral domain optical coherence tomography (SDOCT) at day 28. Secondary outcome measures included time to vitreous release, visual acuity (VA), changes in the optical coherence tomography (OCT) thickness and structure and macular hole closure rate., Results: 17 patients were included in the study and resolution of vitreomacular adhesion (VMA) was verified by SDOCT in eight patients by day 28 (overall response rate of 47.1%, 8/17 eyes) with most patients experiencing VMA release by 7 days (41.2%, 7/17 eyes). Those who did not have VMA resolution showed no statistically significant change in VMA diameter as measured by horizontal and vertical 5-line raster scans at final follow-up (p=0.82 and p=0.75, respectively). The mean baseline Snellen VA was 20/49 and at final follow-up was 20/46 (p=0.59). The average central subfield thickness was 371 microns prior to treatment and 324 microns at final follow-up (range 191-767 microns, p=0.25). Patients meeting three of four positive predictors criteria (eg, no epiretinal membrane (ERM) at baseline, VMA diameter ≤1500 µm and phakic lens status) showed a response rate of 50.0% (seven of 14 patients); those meeting all four criteria (eg, younger than 65, no ERM at baseline, VMA diameter ≤1500 µm and phakic lens status) showed a response rate of 75.0% (three of four eyes). Transient outer segment ellipsoid zone loss was documented in seven patients and subretinal fluid presence following injection was noted in five patients. Four of the five patients with macular holes at baseline experienced resolution of their macular hole after injection., Conclusions: This is the first study to quantify the extent of outer retinal changes seen in patients receiving ocriplasmin. Our initial experience with ocriplasmin shows a significant anatomical effect and is accompanied by transient changes in the outer retinal structures visualised by SDOCT.