DEFINING "STRONG" VERSUS "WEAK" RESPONSE TO ANTIVASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT FOR CENTER-INVOLVED DIABETIC MACULAR EDEMA.

BACKGROUND/PURPOSE: To define "strong" versus "weak" antivascular endothelial growth factor (anti-VEGF) treatment response in eyes with center-involved diabetic macular edema (CI-DME). METHODS: Exploratory analyses of three DRCR Retina Network randomized trials of eyes with CI-DME treated with aflibercept, bevacizumab, or ranibizumab. Thresholds of 5-, 10-, and 15-letter gain defined strong visual acuity (VA) response when baseline VA was 20/25-20/32, 20/40-20/63, or 20/80-20/320, respectively. Thresholds of 50, 100, or 200- µ m reduction defined strong anatomical response when baseline central subfield thickness (CST) was <75, ≥75 to <175, or ≥175- µ m above standard thresholds. Additional thresholds from regression equations were calculated. RESULTS: At 24 weeks, outcomes for strong response were achieved by 476 of 958 eyes (50%) for VA and 505 eyes (53%) for CST. At 104 weeks among the 32% of eyes with strong VA and CST response at 24 weeks, 195 of 281 (69%) maintained strong VA and CST response, whereas 20 (7%) had neither strong VA nor strong CST response. Outcomes rates were similar across protocols and when defined using regression equations. CONCLUSION: These phenotypes are suitable for efforts to identify predictive biomarkers for response to anti-VEGF therapy for DME and might facilitate comparison of treatment response among diverse cohorts with DME.

Improving Access to Eye Care: A Systematic Review of the Literature.

PURPOSE: The goals were to develop a working and inclusive definition of access to eye care, identify gaps in the current system that preclude access, and highlight recommendations that have been identified in prior studies. This manuscript serves as a narrative summary of the literature. CLINICAL RELEVANCE: Health care disparities continue to plague the nation's well-being, and eye care is no exception. Inequities in eye care negatively affect disease processes (i.e., glaucoma, cataracts, diabetic retinopathy), interventions (surgical treatment, prescription of glasses, referrals), and populations (gender, race and ethnicity, geography, age). METHODS: A systematic review of the existing literature included all study designs, editorials, and opinion pieces and initially yielded nearly 2500 reports. To be included in full-text review, an article had to be US-based, be written in English, and address 1 or more of the key terms "barriers and facilitators to health care," "access," and "disparities in general and sub-specialty eye care." Both patient and health care professional perspectives were included. One hundred ninety-six reports met the inclusion criteria. RESULTS: Four key themes regarding access to eye care from both patient and eye care professional perspectives emerged in the literature: (1) barriers and facilitators to access, (2) utilization, (3) compliance and adherence, and (4) recommendations to improve access. Common barriers and facilitators included many factors identified as social determinants of health (i.e., transportation, insurance, language, education). Utilization of eye care was largely attributable to having coverage for eye care, recommendations from primary care professionals, and improved health status. Geographic proximity, age, and lack of transportation surfaced as factors for compliance and adherence. There were a variety of recommendations to improve access to eye care, including improving presence in community health clinics, reimbursement for physicians, and funding of community-based programs such as DRIVE and REACH. CONCLUSIONS: The eye care profession has abundant evidence of the disparities that continue to affect marginalized communities. Improving community-based programs and clinics, addressing social determinants of health, and acknowledging the effects of discrimination and bias on eye care serve as ways to improve equity in this field.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to AMD accounts for most cases of AMD-related severe vision loss. Intravitreous injection of anti-vascular endothelial growth factor (anti-VEGF) agents aims to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, to improve vision. OBJECTIVES: • To investigate ocular and systemic effects of, and quality of life associated with, intravitreous injection of three anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) versus no anti-VEGF treatment for patients with neovascular AMD• To compare the relative effects of one of these anti-VEGF agents versus another when administered in comparable dosages and regimens SEARCH METHODS: To identify eligible studies for this review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (searched January 31, 2018); MEDLINE Ovid (1946 to January 31, 2018); Embase Ovid (1947 to January 31, 2018); the Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to January 31, 2018); the International Standard Randomized Controlled Trials Number (ISRCTN) Registry (www.isrctn.com/editAdvancedSearch - searched January 31, 2018); ClinicalTrials.gov (www.clinicaltrials.gov - searched November 28, 2018); and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en - searched January 31, 2018). We did not impose any date or language restrictions in electronic searches for trials. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or versus a control treatment (e.g. sham treatment, photodynamic therapy), in which participants were followed for at least one year. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We compared outcomes using risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 16 RCTs that had enrolled a total of 6347 participants with neovascular AMD (the number of participants per trial ranged from 23 to 1208) and identified one potentially relevant ongoing trial. Six trials compared anti-VEGF treatment (pegaptanib, ranibizumab, or bevacizumab) versus control, and 10 trials compared bevacizumab versus ranibizumab. Pharmaceutical companies conducted or sponsored four trials but funded none of the studies that evaluated bevacizumab. Researchers conducted these trials at various centers across five continents (North and South America, Europe, Asia, and Australia). The overall certainty of the evidence was moderate to high, and most trials had an overall low risk of bias. All but one trial had been registered prospectively.When compared with those who received control treatment, more participants who received intravitreous injection of any of the three anti-VEGF agents had gained 15 letters or more of visual acuity (risk ratio [RR] 4.19, 95% confidence interval [CI] 2.32 to 7.55; moderate-certainty evidence), had lost fewer than 15 letters of visual acuity (RR 1.40, 95% CI 1.27 to 1.55; high-certainty evidence), and showed mean improvement in visual acuity (mean difference 6.7 letters, 95% CI 4.4 to 9.0 in one pegaptanib trial; mean difference 17.8 letters, 95% CI 16.0 to 19.7 in three ranibizumab trials; moderate-certainty evidence) after one year of follow-up. Participants treated with anti-VEGF agents showed improvement in morphologic outcomes (e.g. size of CNV, central retinal thickness) compared with participants not treated with anti-VEGF agents (moderate-certainty evidence). No trial directly compared pegaptanib versus another anti-VEGF agent and followed participants for one year; however, when compared with control treatments, ranibizumab and bevacizumab each yielded larger improvements in visual acuity outcomes than pegaptanib.Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same RCTs compared the same regimens with respect to gain of 15 or more letters of visual acuity (RR 0.95, 95% CI 0.81 to 1.12; high-certainty evidence) and loss of fewer than 15 letters of visual acuity (RR 1.00, 95% CI 0.98 to 1.02; high-certainty evidence); results showed similar mean improvement in visual acuity (mean difference [MD] -0.5 letters, 95% CI -1.5 to 0.5; high-certainty evidence) after one year of follow-up, despite the substantially lower cost of bevacizumab compared with ranibizumab. Reduction in central retinal thickness was less among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -11.6 µm, 95% CI -21.6 to -1.7; high-certainty evidence); however, this difference is within the range of measurement error, and we did not interpret it to be clinically meaningful.Ocular inflammation and increased intraocular pressure (IOP) after intravitreal injection were the most frequently reported serious ocular adverse events. Researchers reported endophthalmitis in less than 1% of anti-VEGF-treated participants and in no cases among control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to show a meaningful difference between groups (evidence of low- to moderate-certainty). Investigators rarely measured and reported data on visual function, quality of life, or economic outcomes. AUTHORS' CONCLUSIONS: Results of this review show the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; studies show that ranibizumab and bevacizumab improved visual acuity in some eyes that received these agents and were equally effective. Available information on the adverse effects of each medication does not suggest a higher incidence of potentially vision-threatening complications with intravitreous injection of anti-VEGF agents compared with control interventions; however, clinical trial sample sizes were not sufficient to estimate differences in rare safety outcomes. Future Cochrane Reviews should incorporate research evaluating variable dosing regimens of anti-VEGF agents, effects of long-term use, use of combination therapies (e.g. anti-VEGF treatment plus photodynamic therapy), and other methods of delivering these agents.

ETDRS Grading of Diabetic Retinopathy: Still the Gold Standard?

This article aims to provide a narrative history of the evolution, modification, and legacy of the Early Treatment Diabetic Retinopathy Study classification system.

A proteomic approach to understanding the pathogenesis of idiopathic macular hole formation.

Idiopathic macular holes (IMH) are full-thickness defects of retinal tissue that cause severe vision loss due to disruption of the anatomic fovea. Abnormal vitreous traction is involved in the formation of macular holes. Both glial cells and hyalocytes contribute to epiretinal membrane formation in IMH. In order to gain further insight into the pathophysiology of IMH, we conducted a discovery phase investigation of the vitreous proteome in four patients with macular holes and six controls using one-dimensional gel fractionation and liquid chromatography-tandem mass spectrometry analyses on an Orbitrap Elite mass spectrometer. Of a total of 5912 vitreous proteins, 32 proteins had increased and 39 proteins had decreased expression in IMH compared with controls, using a false discovery rate approach with p value < 0.001 and q value < 0.05. IMH was associated with increased expression of proteins in the complement pathway, α-2-macroglobulin, a major inducer of Müller glial cell migration, fibrinogen, and extracellular matrix proteins, and decreased expression of proteins involved in protein folding and actin filament binding. A proteomic approach revealed proteins and biological pathways that may be involved in the pathogenesis of IMH and could be targeted for future studies.

Intravitreal Bevacizumab Versus Ranibizumab for Treatment of Neovascular Age-Related Macular Degeneration: Findings from a Cochrane Systematic Review.

TOPIC: To summarize the relative effects of bevacizumab (Avastin; Genentech, Inc, South San Francisco, CA) and ranibizumab (Lucentis; Genentech, Inc.), using findings from a Cochrane Eyes and Vision Group systematic review. CLINICAL RELEVANCE: Neovascular age-related macular degeneration (NVAMD) is the most common cause of uncorrectable vision loss among the elderly in developed countries. Bevacizumab and ranibizumab are the most frequently used anti-vascular endothelial growth factor (VEGF) agents injected intravitreally to treat NVAMD. METHODS: For this systematic review, we included only randomized controlled trials in which the 2 anti-VEGF agents had been compared directly. The primary outcome was 1-year gain in best-corrected visual acuity (BCVA) of ≥15 letters. We followed Cochrane methods for trial selection, data extraction, and data analyses. Relative effects of bevacizumab versus ranibizumab are presented as estimated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). RESULTS: We identified 6 eligible randomized controlled trials with 2809 participants. The proportion of eyes that gained ≥15 letters of BCVA by 1 year was similar for the 2 agents when the same regimens were compared (RR, 0.90; 95% CI, 0.73-1.11). The mean change in BCVA from baseline also was similar (MD, -0.5 letter; 95% CI, -1.6 to +0.6). Other BCVA and quality of life outcomes were similar for the 2 agents. One-year treatment cost with ranibizumab was 5.1 and 25.5 times the cost for bevacizumab in the 2 largest trials. Ocular adverse events were uncommon (<1%), and rates were similar for the 2 agents. CONCLUSIONS: We found no important difference in effectiveness or safety between bevacizumab and ranibizumab for NVAMD treatment, but there was a large cost difference.

Evaluation of real-world mobility in age-related macular degeneration.

BACKGROUND: Previous research has suggested an association between poor vision and decreased mobility, including restricted levels of physical activity and travel away from home. We sought to determine the impact of age-related macular degeneration (AMD) on these measures of mobility. METHODS: Fifty-seven AMD patients with bilateral, or severe unilateral, visual impairment were compared to 59 controls with normal vision. All study subjects were between the ages of 60 and 80. Subjects wore accelerometers and cellular network-based tracking devices over 7 days of normal activity. Number of steps taken, time spent in moderate-to-vigorous physical activity (MVPA), number of excursions from home, and time spent away from home were the primary outcome measures. RESULTS: In multivariate negative binomial regression models adjusted for age, gender, race, comorbidities, and education, AMD participants took fewer steps than controls (18% fewer steps per day, p = 0.01) and spent significantly less time in MVPA (35% fewer minutes, p < 0.001). In multivariate logistic regression models adjusting for age, sex, race, cognition, comorbidities, and grip strength, AMD subjects showed an increased likelihood of not leaving their home on a given day (odds ratio = 1.36, p = 0.04), but did not show a significant difference in the magnitude of time spent away from home (9% fewer minutes, p = 0.11). CONCLUSION: AMD patients with poorer vision engage in significantly less physical activity and take fewer excursions away from the home. Further studies identifying the factors mediating the relationship between vision loss and mobility are needed to better understand how to improve mobility among AMD patients.

Driving habits in older patients with central vision loss.

OBJECTIVE: To determine if central visual loss is associated with driving cessation, driving restriction, or other-driver preference. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty-four subjects with bilateral visual loss (<20/32 in better eye) or severe unilateral visual loss (<20/200) from age-related macular degeneration (AMD) and 58 normally sighted controls between 60 and 80 years of age. METHODS: Participants self-reported driving habits. Other-driver preference was defined as preferring that another drive when there is more than 1 driver in the car. Subjects reporting 2 or more driving limitations were considered to have restricted their driving. MAIN OUTCOME MEASURES: Self-reported driving cessation, other-driver preference, and driving restriction. RESULTS: Age-related macular degeneration subjects were older (74.7 vs. 69.7 years), had worse visual acuity (VA; mean better-eye VA, 0.43 vs. 0.08 logarithm of minimum angle of resolution [logMAR]) and contrast sensitivity (CS; 1.4 vs. 1.9 log units of CS [logCS]), and were more likely to be white when compared with controls (P<0.001 for all). Drivers with AMD-related vision loss were more likely to avoid driving over longer distances, beyond 1 hour, at night, and in unfamiliar conditions (P < 0.05 for all). In multivariate models, driving cessation was associated with worse better-eye VA (odds ratio [OR], 1.5 per 1-line decrement in VA; P<0.001) and worse binocular CS (OR, 1.36 per 0.1 logCS increment; P = 0.005); however, AMD group status was not associated with driving cessation (OR, 1.9; P = 0.35). Factors predicting driving restriction were AMD (OR, 9.0; P = 0.004), worse vision (OR, 2.5 per line of VA loss; P<0.001), lower CS (OR, 2.2 per 0.1-logCS increment; P<0.001), and female gender (OR, 27.9; P = 0.002). Other-driver preference was more common with worse vision (OR, 1.6 per 0.1-logMAR increment; P = 0.003), female gender (OR, 4.5; P = 0.02), and being married (OR, 3.8; P = 0.04). CONCLUSIONS: Most patients with AMD-related central vision loss continue to drive, but demonstrate significant driving restrictions, especially with more severe VA and CS loss. Future work should determine which driving adaptations the visually impaired best balance safety and independence.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the most common cause of uncorrectable severe vision loss in people aged 55 years and older in the developed world. Choroidal neovascularization (CNV) secondary to neovascular AMD accounts for most AMD-related severe vision loss. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, aim to block the growth of abnormal blood vessels in the eye to prevent vision loss and, in some instances, improve vision. OBJECTIVES: To investigate: (1) the ocular and systemic effects of, and quality of life associated with, intravitreally injected anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) for the treatment of neovascular AMD compared with no anti-VEGF treatment; and (2) the relative effects of one anti-VEGF agent compared with another when administered in comparable dosages and regimens. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) (2014, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to March 2014), EMBASE (January 1980 to March 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to March 2014), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 27 March 2014. SELECTION CRITERIA: We included randomized controlled trials (RCTs) that evaluated pegaptanib, ranibizumab, or bevacizumab versus each other or a control treatment (e.g., sham treatment or photodynamic therapy). All trials followed participants for at least one year. DATA COLLECTION AND ANALYSIS: Two review authors independently screened records, extracted data, and assessed risks of bias. We contacted trial authors for additional data. We analyzed outcomes as risk ratios (RRs) or mean differences (MDs). We used the standard methodological procedures expected by The Cochrane Collaboration. MAIN RESULTS: We included 12 RCTs including a total of 5496 participants with neovascular AMD (the number of participants per trial ranged from 28 to 1208). One trial compared pegaptanib, three trials ranibizumab, and two trials bevacizumab versus controls; six trials compared bevacizumab with ranibizumab. Four trials were conducted by pharmaceutical companies; none of the eight studies which evaluated bevacizumab were funded by pharmaceutical companies. The trials were conducted at various centers across five continents (North and South America, Europe, Asia and Australia). The overall quality of the evidence was very good, with most trials having an overall low risk of bias.When compared with control treatments, participants who received any of the three anti-VEGF agents were more likely to have gained 15 letters or more of visual acuity, lost fewer than 15 letters of visual acuity, and had vision 20/200 or better after one year of follow up. Visual acuity outcomes after bevacizumab and ranibizumab were similar when the same regimens were compared in the same RCTs, despite the substantially lower cost for bevacizumab compared with ranibizumab. No trial directly compared pegaptanib with other anti-VEGF agents; however, when compared with controls, ranibizumab or bevacizumab yielded larger improvements in visual acuity outcomes than pegaptanib.Participants treated with anti-VEGFs showed improvements in morphologic outcomes (e.g., size of CNV or central retinal thickness) compared with participants not treated with anti-VEGF agents. There was less reduction in central retinal thickness among bevacizumab-treated participants than among ranibizumab-treated participants after one year (MD -13.97 µm; 95% confidence interval (CI) -26.52 to -1.41); however, this difference is within the range of measurement error and we did not interpret it as being clinically meaningful.Ocular inflammation and increased intraocular pressure after intravitreal injection were the most frequently reported serious ocular adverse events. Endophthalmitis was reported in fewer than 1% of anti-VEGF treated participants; no cases were reported in control groups. The occurrence of serious systemic adverse events was comparable across anti-VEGF-treated groups and control groups; however, the numbers of events and trial participants may have been insufficient to detect a meaningful difference between groups. Data for visual function, quality of life, and economic outcomes were sparsely measured and reported. AUTHORS' CONCLUSIONS: The results of this review indicate the effectiveness of anti-VEGF agents (pegaptanib, ranibizumab, and bevacizumab) in terms of maintaining visual acuity; ranibizumab and bevacizumab were also shown to improve visual acuity. The information available on the adverse effects of each medication do not suggest a higher incidence of potentially vision-threatening complications with intravitreal injection compared with control interventions; however, clinical trial sample sizes may not have been sufficient to detect rare safety outcomes. Research evaluating variable dosing regimens with anti-VEGF agents, effects of long-term use, combination therapies (e.g., anti-VEGF treatment plus photodynamic therapy), and other methods of delivering the agents should be incorporated into future Cochrane reviews.

Detection of new-onset choroidal neovascularization using optical coherence tomography: the AMD DOC Study.

PURPOSE: To determine the sensitivity of time domain optical coherence tomography (OCT) in detecting conversion to neovascular age-related macular degeneration (AMD) in eyes at high risk for choroidal neovascularization (CNV), compared with detection using fluorescein angiography (FA) as the gold standard. DESIGN: Prospective, multicenter, observational study. PARTICIPANTS: Individuals aged ≥50 years with nonneovascular AMD at high risk of progressing to CNV in the study eye and evidence of neovascular AMD in the fellow eye. METHODS: At study entry and every 3 months through 2 years, participants underwent best-corrected visual acuity, supervised Amsler grid testing, preferential hyperacuity perimetry (PHP) testing, stereoscopic digital fundus photographs with FA, and OCT imaging. A central Reading Center graded all images. MAIN OUTCOMES MEASURES: The sensitivity of OCT in detecting conversion to neovascular AMD by 2 years, using FA as the reference standard. Secondary outcomes included comparison of sensitivity, specificity, positive predictive value, and negative predictive value of OCT, PHP, and supervised Amsler grid relative to FA for detecting incident CNV. RESULTS: A total of 98 participants were enrolled; 87 (89%) of these individuals either completed the 24-month visit or exited the study after developing CNV. Fifteen (17%) study eyes had incident CNV confirmed on FA by the Reading Center. The sensitivity of each modality for detecting CNV was: OCT 0.40 (95% confidence interval [CI], 0.16-0.68), supervised Amsler grid 0.42 (95% CI, 0.15-0.72), and PHP 0.50 (95% CI, 0.23-0.77). Treatment for incident CNV was recommended by the study investigator in 13 study eyes. Sensitivity of the testing modalities for detection of CNV in these 13 eyes was 0.69 (95% CI, 0.39-0.91) for OCT, 0.50 (95% CI, 0.19-0.81) for supervised Amsler grid, and 0.70 (95% CI, 0.35-0.93) for PHP. Specificity of the OCT was higher than that of the Amsler grid and PHP. CONCLUSIONS: Time-domain OCT, supervised Amsler grid, and PHP have low to moderate sensitivity for detection of new-onset CNV compared with FA. Optical coherence tomography has greater specificity than Amsler grid or PHP. Among fellow eyes of individuals with unilateral CNV, FA remains the best method to detect new-onset CNV.

Are Dilated Fundus Examinations Needed for OCT-Guided Retreatment of Exudative Age-Related Macular Degeneration? A Prospective, Randomized, Pilot Study.

PURPOSE: To report findings when dilated fundus examination (DFE) is omitted from follow-up of patients receiving anti-VEGF injections for neovascular age-related macular degeneration (NVAMD). DESIGN: Randomized pilot study. PARTICIPANTS: NVAMD patients with two or more injections of anti-VEGF within prior six months who were expected to require treatment for at least eight more months. METHODS AND INTERVENTIONS: Participants were assigned to either retinal imaging and DFE or retinal imaging without a DFE except at 16 weeks and 32 weeks and at study completion. OUTCOMES: Primary safety outcomes were change in usual-corrected visual acuity (UCVA) and central subfield thickness (CST). Primary efficacy outcomes included time spent in clinic and patient satisfaction with clinic visits. RESULTS: The 66 participants had mean baseline UCVA of 20/50 in the study eye. Median change in UCVA from baseline to each clinic visit in each arm was "no change". Mean change in CST was less than 15 microns from baseline to any follow-up clinic visit. Time spent in the clinic at follow-up visits averaged 20 minutes less for participants in the Imaging Only group than those in the Full Exam group. More participants in the Imaging Only group were satisfied with the time spent in clinic and with the clinic visits overall than participants in the Full Exam group: means of 71 vs 91 minutes, respectively, per clinic visit. CONCLUSION: Based on findings from this randomized pilot study, follow-up retina clinic visits for established patients who have NVAMD and are under treatment with intravitreous injection of anti-VEGF agents could be streamlined by implementing longer intervals between DFE and by relying on imaging alone to make most decisions regarding the need for retreatment, thereby reducing the time spent by patients in clinic and increasing their satisfaction with care received, without excess adverse events. TRIAL REGISTRATION: NCT02251366.

Prevalence and causes of clinically detectable uveitic serous retinal detachment.

PURPOSE: To describe the prevalence and causes of clinically detectable uveitic serous retinal detachment (SRD). METHODS: Retrospective chart review of a large clinic-based series. RESULTS: Serous retinal detachment was present in 78 of the 2761 (2.8%) patients. Vogt-Koyanagi-Harada (VKH) disease was the most commonly identified cause (38/78, 48.7%). Less common associated etiologies included toxoplasmic retinochoroiditis (8/78, 10.3%), sarcoidosis (5/78, 6.4%), intraocular lymphoma (4/78, 5.1%), presumed tuberculosis (3/78, 3.8%), and posterior scleritis (2/78, 2.6%). Fifteen patients (19.2%) with uveitic SRD at presentation had no identifiable etiology and were labeled idiopathic or indeterminant. Thirty of the 38 patients with VKH disease (78.9%) had positive neurological and/or integumentary findings, and therefore constituted either complete or incomplete subtypes of the disease. The remaining eight (21.1%) had presumed/ocular VKH disease limited to the eye. CONCLUSION: While VKH disease by far is the most common cause of clinically detectable uveitic SRD, a number of other non-infectious and infectious inflammatory disorders were also associated with this distinctive clinical finding.

Structured layer surface segmentation for retina OCT using fully convolutional regression networks.

Optical coherence tomography (OCT) is a noninvasive imaging modality with micrometer resolution which has been widely used for scanning the retina. Retinal layers are important biomarkers for many diseases. Accurate automated algorithms for segmenting smooth continuous layer surfaces with correct hierarchy (topology) are important for automated retinal thickness and surface shape analysis. State-of-the-art methods typically use a two step process. Firstly, a trained classifier is used to label each pixel into either background and layers or boundaries and non-boundaries. Secondly, the desired smooth surfaces with the correct topology are extracted by graph methods (e.g., graph cut). Data driven methods like deep networks have shown great ability for the pixel classification step, but to date have not been able to extract structured smooth continuous surfaces with topological constraints in the second step. In this paper, we combine these two steps into a unified deep learning framework by directly modeling the distribution of the surface positions. Smooth, continuous, and topologically correct surfaces are obtained in a single feed forward operation. The proposed method was evaluated on two publicly available data sets of healthy controls and subjects with either multiple sclerosis or diabetic macular edema, and is shown to achieve state-of-the art performance with sub-pixel accuracy.

Antagonism of vascular endothelial growth factor for macular edema caused by retinal vein occlusions: two-year outcomes.

PURPOSE: To determine the long-term effects of intraocular antagonism of vascular endothelial growth factor (VEGF) in patients with macular edema caused by retinal vein occlusions (RVOs). DESIGN: Prospective randomized trial. PARTICIPANTS: Twenty patients with macular edema caused by branch RVOs (BRVOs) and 20 patients with central RVOs (CRVOs). METHODS: After the month 3 primary end point, patients were seen every 2 months and received injections of an anti-VEGF agent as needed for recurrent edema. MAIN OUTCOME MEASURES: Mean change from baseline best-corrected visual acuity (BCVA) at month 24 with assessment of other parameters of visual function and center subfield thickness (foveal thickness [FTH]). RESULTS: For 17 patients with BRVO who completed 2 years of follow-up, the mean improvement from baseline in BCVA at month 24 was 17.8 letters compared with 15.6 letters at month 3. Improvement by at least 6, 3, or 2 lines occurred in 18%, 59%, and 76% of patients, respectively. The Snellen equivalent BCVA at month 24 was 20/40 or better in 10 patients. With an average of 2 injections of ranibizumab during year 2, the mean FTH at month 24 was 245.8 µm compared with 217.1 µm at month 3 and 481.5 µm at baseline. For 14 patients with CRVO who completed 2 years of follow-up, the mean improvement in BCVA at month 24 was 8.5 letters compared with 12.0 letters at month 3. Improvement by at least 6, 3, or 2 lines occurred in 14%, 21%, and 43% of patients, respectively. The Snellen equivalent BCVA at month 24 was 20/40 or better in 4 patients. With an average of 3.5 injections of ranibizumab in year 2, mean FTH at month 24 was 338 µm compared with 278 µm at month 3 and 533 µm at baseline. Duration of RVO >1 year at study entry and nonperfusion of perifoveal capillaries for 360 degrees correlated with reduced visual outcomes. CONCLUSIONS: Antagonism of VEGF provides substantial long-term benefit to patients with macular edema caused by RVO, but frequent injections are required in some patients with BRVO and most patients with CRVO.

Ranibizumab for macular edema due to retinal vein occlusions: implication of VEGF as a critical stimulator.

Macular edema is a major cause of vision loss in patients with central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). It is not clear how much of the edema is due to hydrodynamic changes from the obstruction and how much is due to chemical mediators. Patients with macular edema due to CRVO (n = 20) or BRVO (n = 20) were randomized to receive three monthly injections of 0.3 or 0.5 mg of ranibizumab. At the primary endpoint, month 3, the median improvement in letters read at 4 m was 17 in the 0.3-mg group and 14 in the 0.5-mg group for CRVO, and 10 and 18, respectively for the BRVO group. Optical coherence tomography (OCT) showed that compared to injections of 0.3 mg, injections of 0.5 mg of ranibizumab tended to cause more rapid reductions of central retinal thickening that lasted longer between injections, but in 3 months, excess central retinal thickening which is a quantitative assessment of the macular edema, was reduced by approximately 90% in all four treatment groups. There was no correlation between the amount of improvement and duration of disease or patient age at baseline, but there was some correlation between the aqueous vascular endothelial growth factor (VEGF) level at baseline and amount of improvement. These data indicate that excess production of VEGF in the retinas of patients with CRVO or BRVO is a major contributor to macular edema and suggest that additional studies investigating the efficacy of intraocular injections of ranibizumab are needed.

Risk factors for rhegmatogenous retinal detachment in the submacular surgery trials: SST report No. 22.

OBJECTIVE: To identify risk factors associated with the development of rhegmatogenous retinal detachment (RRD) in patients enrolled in the Submacular Surgery Trials. METHODS: One thousand fifteen patients with eligible subfoveal neovascular lesions in the study eye were assigned randomly to observation or to surgery. Eyes were examined at 3 months, 6 months, 12 months, and 24 months after enrollment to assess study outcomes and adverse events, including RRDs. Adverse events also were reported at other times as clinical personnel became aware of them. Potential risk factors for the development of RRD in study eyes were evaluated using recursive partitioning and logistic regression analysis. RESULTS: Among 506 eyes assigned to surgery, RRD developed in 44 (8.7%) compared with 4 (0.8%) of 509 eyes assigned to observation. Of the 44 eyes in which RRD developed, 27 had age-related macular degeneration (AMD) and large (>3.5 MPS disk areas) hemorrhagic subfoveal neovascular lesions at baseline and represented 16.1% of all eyes with such lesions assigned to surgery. Eyes with AMD and larger hemorrhagic lesions (>16 MPS disk areas) together with relatively poor visual acuity (best-corrected visual acuity < or =20/1280) had a higher risk of RRD (odds ratio = 6.2, 95% confidence interval: 2.2-16.7) compared with those with smaller lesions and better visual acuity at baseline. CONCLUSION: Poor visual acuity and very large, predominantly hemorrhagic subfoveal neovascular AMD lesion type were the greatest risk factors for RRD after submacular surgery. Submacular surgery should be undertaken in such eyes with full awareness of the risk of RRD during subsequent follow-up.

Risk factors for second eye progression to advanced age-related macular degeneration: SST report No. 21 Submacular Surgery Trials Research Group.

OBJECTIVE: To identify characteristics predictive of progression to advanced age-related macular degeneration (AMD) in second (fellow) eyes of participants in the Submacular Surgery Trials (SST) who had unilateral neovascular AMD at study entry. METHODS: Review of baseline fluorescein angiograms confirmed the absence of advanced AMD in 370 fellow eyes. All participants were eligible for 2 years of follow-up; follow-up angiograms of eyes at risk were evaluated to estimate incidence rates of advanced AMD. Baseline nonocular and ocular AMD characteristics were evaluated to identify those that predicted development of advanced AMD. RESULTS: Of 110 eyes that progressed to advanced AMD, choroidal neovascularization (CNV) developed in 98 eyes and foveal geographic atrophy (GA) in 15 eyes. No nonocular characteristic (age, gender, history of hypertension or smoking) or ocular feature of the study eye at baseline (lesion composition, lesion size, or visual acuity) was predictive of progression to advanced AMD in this cohort. Multivariate analysis identified three baseline fellow eye ocular features that had a significant and independent relationship with progression to advanced AMD: drusen size, focal hyperpigmentation, and nonfoveal GA. CONCLUSION: Recognition of factors that predict advanced AMD in the second eye may identify those individuals at greater risk of progression so that treatment can be provided before vision is severely compromised.