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Purpose: This work assesses the clinical characteristics and outcomes of various treatment methods in managing rhegmatogenous retinal detachments secondary to retinal dialysis. Methods: In this retrospective, consecutive case series, patients presenting to a tertiary referral vitreoretinal service from 2015 to 2020 were chosen. The primary outcome measure was the single-surgery anatomic success (SSAS) rate in the first 90 days after surgery and overall SSAS rate until the last visit. Results: Eighty-six eyes of 84 patients were included. Mean (SD) age was 30 (14.8) years (range, 7-71 years). Fifty-nine (70%) patients were men and 55 eyes (64%) had a history of trauma. Dialysis occurred in the inferotemporal quadrant in 50 eyes (58%) of the entire cohort and 25 of 55 eyes (45%) with prior trauma. Fifty-one eyes (59.3%) were managed by scleral buckle (SB), 25 eyes (29.2%) with laser retinopexy, and 10 eyes (11.6%) with pars plana vitrectomy (PPV). The SSAS rate in the first 90 days after surgery was 94.1% (81 of 86 eyes), including 90.1% of eyes with SB, 100% of eyes with laser retinopexy, and 100% of eyes with PPV ( P = .07). The overall SSAS rate, however, was 89.5% (77 of 86) eyes, including 90.1% of eyes with SB, 84% of eyes with laser retinopexy, and 100% of eyes with PPV ( P = .4). Final attachment rate was 100% in the entire cohort. Conclusions: With careful consideration of underlying pathology, all 3 treatment modalities can provide high rates of anatomic and functional success.

Purpose To evaluate the effect of physician face mask use on rates and outcomes of post-injection endophthalmitis. Design Retrospective, comparative cohort study Methods . Setting Single-center Study Population Eyes receiving intravitreal anti-vascular endothelial growth factor injections from 7/1/2013 to 9/1/2019. Intervention Cases were divided into “face mask group” if face masks were worn by the physician during intravitreal injections or “no talking group” if no face mask was worn but a no talking policy was observed during intravitreal injections. Main Outcome Measures Rate of endophthalmitis, visual acuity, and microbial spectrum. Results Of 483,622 intravitreal injections administered, 168 out of 453,460 (0.0371%) cases of endophthalmitis occurred in the “no talking” group, and 9 out of 30,162 (0.0298%) cases occurred in the face mask group (odds ratio, 0.81; 95%CI, 0.41–1.57; p=0.527). Sixteen cases of oral flora-associated endophthalmitis were found in the “no talking” group (1 in 28,341 injections) compared to none in the face mask group (p=0.302). Mean logMAR visual acuity at presentation in cases that developed culture-positive endophthalmitis was significantly worse in the “no talking” group compared to the face mask group (17.1 lines lost from baseline acuity vs 13.4 lines lost; p=0.031), though no difference was observed at six months following treatment (p=0.479). Conclusion Physician face mask use did not influence the risk of post-injection endophthalmitis compared to a no talking policy. However, no cases of oral flora-associated endophthalmitis occurred in the face mask group. Future studies are warranted to assess the role of face mask use to reduce endophthalmitis risk, particularly due to oral flora., Highlights • Physician face mask use may not reduce the rate of post-injection endophthalmitis compared to a “no talking” policy • No cases of oral flora endophthalmitis were identified with physician face mask use • Visual outcomes following endophthalmitis were similar with physician face mask use compared to a “no talking” policy

Purpose Anatomically similar rhegmatogenous retinal detachments (RRDs) can be treated with scleral buckle (SB), pars plana vitrectomy (PPV), or SB combined with PPV (PPV/SB). This study compares moderately complex phakic primary RRD treated with SB, PPV, or PPV/SB to review anatomic and visual outcomes. Design Multicenter, retrospective, interventional cohort study. Participants Data were gathered on all patients from multiple retina practices in the United States with RRD in 2015 and >90 days of follow-up. The cohort of phakic patients with moderately complex RRD was analyzed. Methods A large and detailed database was generated. Eyes with findings that would bias toward PPV (vitreous hemorrhage, dense cataract, proliferative vitreoretinopathy, giant retinal tear, among others) were excluded. Age Main Outcome Measures Single surgery anatomic success (SSAS), defined as retinal attachment with no other RRD surgery within 90 days, is the main outcome measure. Final visual acuity is the secondary outcome measure. Pearson’s chi-square and analysis of variance were used to test treatment effect of surgery type on SSAS and vision. Results Single surgery anatomic success was noted in 155 of 169 SB cases (91.7%), 207 of 249 PPV cases (83.1%), and 271 of 297 PPV/SB cases (91.2%). Scleral buckle and PPV/SB were superior to PPV for SSAS (P = 0.0041). For macula-on or split cases, SB had significantly better visual outcomes than PPV or PPV/SB even after controlling for cataract (cases with minimal cataract at final follow-up or after cataract surgery) (P Conclusions For phakic moderately complex primary RRDs in this study of PPV versus SB versus PPV/SB, SB had the best visual outcomes, and PPV had the worst SSAS outcomes.

Purpose: This article compares 2-mg intravitreal triamcinolone (IVT) and 0.7-mg dexamethasone (DEX) implant for the treatment of diabetic macular edema in eyes that had a suboptimal response to antivascular endothelial growth factor therapy. Methods: A single-center, retrospective review was conducted of patients receiving either IVT between January 1, 2013, and January 1, 2018, or patients receiving DEX between October 1, 2015, and January 1, 2018. Visual acuity and central macular thickness (CMT) were recorded at visit of first injection and all subsequent visits. Results: Twenty-five eyes were included in the DEX group and 32 eyes were included in the IVT group. Change in vision from baseline was similar between DEX and IVT at 6-month follow-up (1.1 lines vs 2.3 lines, respectively; P = .24). Mean decrease in CMT from baseline was not different at 6-month follow-up (DEX: 120 µm vs IVT: 185 µm; P = .17). Conclusions: DEX and 2-mg IVT both achieved improvement in vision and CMT with no significant differences between treatment groups at 6-month follow-up.

To compare general ophthalmologists, retina specialists, and the EyeArt Artificial Intelligence (AI) system to the clinical reference standard for detecting more than mild diabetic retinopathy (mtmDR).Prospective, pivotal, multicenter trial conducted from April 2017 to May 2018.Participants were aged ≥ 18 years who had diabetes mellitus and underwent dilated ophthalmoscopy. A total of 521 of 893 participants met these criteria and completed the study protocol.Participants underwent 2-field fundus photography (macula centered, disc centered) for the EyeArt system, dilated ophthalmoscopy, and 4-widefield stereoscopic dilated fundus photography for reference standard grading.For mtmDR detection, sensitivity and specificity of EyeArt gradings of 2-field, fundus photographs and ophthalmoscopy grading versus a rigorous clinical reference standard comprising Reading Center grading of 4-widefield stereoscopic dilated fundus photographs using the ETDRS severity scale. The AI system provided automatic eye-level results regarding mtmDR.Overall, 521 participants (999 eyes) at 10 centers underwent dilated ophthalmoscopy: 406 by nonretina and 115 by retina specialists. Reading Center graded 207 positive and 792 eyes negative for mtmDR. Of these 999 eyes, 26 eyes were ungradable by the EyeArt system, leaving 973 eyes with both EyeArt and Reading Center gradings. Retina specialists correctly identified 22 of 37 eyes as positive (sensitivity 59.5%) and 182 of 184 eyes as negative (specificity 98.9%) for mtmDR versus the EyeArt AI system that identified 36 of 37 as positive (sensitivity 97%) and 162 of 184 eyes as negative (specificity of 88%) for mtmDR. General ophthalmologists correctly identified 35 of 170 eyes as positive (sensitivity 20.6%) and 607 of 608 eyes as negative (specificity 99.8%) for mtmDR compared with the EyeArt AI system that identified 164 of 170 as positive (sensitivity 96.5%) and 525 of 608 eyes as negative (specificity 86%) for mtmDR.The AI system had a higher sensitivity for detecting mtmDR than either general ophthalmologists or retina specialists compared with the clinical reference standard. It can potentially serve as a low-cost point-of-care diabetic retinopathy detection tool and help address the diabetic eye screening burden.

Purpose To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for neovascular age-related macular degeneration (nAMD) treatment. Design Phase 2, multicenter, randomized, active treatment–controlled clinical trial. Participants Patients diagnosed with nAMD within 9 months who had received 2 or more prior anti–vascular endothelial growth factor intravitreal injections and were responsive to treatment. Methods Patients were randomized 3:3:3:2 to receive the PDS filled with ranibizumab 10 mg/ml, 40 mg/ml, 100 mg/ml, or monthly intravitreal ranibizumab 0.5-mg injections. Main Outcome Measures Time to first implant refill assessed when the last enrolled patient completed the month 9 visit (primary efficacy end point), improvement in best-corrected visual acuity (BCVA) and central foveal thickness (CFT), and safety. Results The primary analysis population was 220 patients, with 58, 62, 59, and 41 patients in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. Median time to first implant refill was 8.7, 13.0, and 15.0 months in the PDS 10-mg/ml, PDS 40-mg/ml, and PDS 100-mg/ml arms, respectively. At month 9, the adjusted mean BCVA change from baseline was ‒3.2 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, ‒0.5 ETDRS letters, +5.0 ETDRS letters, and +3.9 ETDRS letters in the PDS 10-mg/ml, PDS 40-mg/ml, PDS 100-mg/ml, and monthly intravitreal ranibizumab 0.5-mg arms, respectively. At month 9, the adjusted mean CFT change from baseline was similar in the PDS 100-mg/ml and monthly intravitreal ranibizumab 0.5-mg arms. The optimized PDS implant insertion and refill procedures were generally well tolerated. After surgical procedure optimization, postoperative vitreous hemorrhage rate was 4.5% (7/157; 1 event classified as serious). There was no evidence of implant clogging. Conclusions In the phase 2 Ladder trial, the PDS was generally well tolerated and demonstrated a dose response across multiple end points in patients with nAMD. The PDS 100-mg/ml arm showed visual and anatomic outcomes comparable with monthly intravitreal ranibizumab 0.5-mg injections but with a reduced total number of ranibizumab treatments. The PDS has the potential to reduce treatment burden in nAMD while maintaining vision.

Recent reports of retinal vasculitis (some cases were also occlusive) after brolucizumab injection has ignited a poorly understood immunogenicity alert in the form of intraocular inflammation and r...

Purpose To investigate the effect of the coronavirus disease 2019 (COVID-19) pandemic on the clinical presentation of acute, primary rhegmatogenous retinal detachment (RRD). Design Single-center, consecutive case series with historical controls. Participants Consecutive patients seeking treatment for primary RRD in a 50-day period during the COVID-19 pandemic (March 9–April 27, 2020) and the corresponding 50-day period during the previous year (March 4–April 22, 2019) in the United States. Methods The cohorts were compared to assess demographic variables and clinical presentations. Multivariate logistic regression was used to identify factors predictive of presenting macular attachment status. Main Outcome Measures The primary outcome was the proportion of patients with macula-on RRD at presentation. Secondary outcomes included visual acuity (VA), duration of symptoms before presentation, proportion seeking treatment within 1 day of symptom onset, and presence of primary proliferative vitreoretinopathy (PVR). Results Eighty-two patients were included in the 2020 cohort compared with 111 patients in the 2019 primary control cohort. Demographic factors were similar between the groups. Significantly fewer patients demonstrated macula-on RRD in the 2020 cohort (20/82 patients [24.4%]) than in the 2019 cohort (55/111 patients [49.5%]; P = 0.001). Patients in the 2020 cohort showed worse median VA at presentation (1.00 logarithm of the minimum angle of resolution [logMAR; Snellen equivalent, 20/200] in 2020 vs. 0.48 logMAR [Snellen equivalent, 20/60] in 2019; P = 0.008), fewer patients sought treatment within 1 day of symptoms (16/80 patients [19.5%] in 2020 vs. 41/106 patients [36.9%] in 2019; P = 0.005), and a greater proportion demonstrated primary PVR (11/82 patients [13.4%] in 2020 vs. 5/111 patients [4.5%] in 2019; P = 0.03). In multivariate analysis, younger age (P = 0.03) and established patient status (P = 0.02) were independent predictors of macula-on status in the 2020 cohort. Conclusions Patients with primary RRD during the 2020 COVID-19 pandemic were less likely to have macula-on disease and more likely to delay seeking treatment and to show worse vision and PVR.

To identify differences in preoperative characteristics and intraoperative approaches between surgeons with higher versus lower single surgery success rates (SSSR) for repair of rhegmatogenous retinal detachments (RRDs).This study is a sub-analysis of subjects who underwent RRD repair in the Primary Retinal Detachment Outcomes (PRO) study, a multi-institutional, retrospective comparative interventional study. The PRO study examined consecutive primary RRD surgeries from January 1, 2015 through December 31, 2015. The primary outcome was variations in surgical approach to different types of RRDs with secondary analyses of pre and intraoperative metrics for surgeons with SSSR 90% compared to those80% who performed at least 40 operations during the study period.A total of 689 surgeries were included in the analysis. The mean SSSR was 94% for the higher tier and 75% for the lower tier (p 0.0001). Surgeons with90% SSSR were more likely to have graduated fellowship more recently (p = 0.0025), use less perfluorocarbon liquid (p 0.0001), perform less 360 degree laser retinopexy (p 0.0001), and perform a higher percentage of primary buckles and combined PPV/SB (p 0.0001). For pseudophakic eyes there was no difference between PPV and PPV/SB use (p = 0.6211).Surgeons with high SSSR typically performed SB as well as combination PPV/SB for more RRDs. Similar numbers of PPV and PPV/SB were performed for pseudophakic eyes, suggesting that the difference in SSSR between the two groups may be related to a combination of preoperative and intraoperative decisions as well as differences in technique.

Purpose To evaluate the safety and efficacy of the Port Delivery System with ranibizumab (PDS) for the treatment of neovascular age-related macular degeneration (nAMD). Design Phase 3, open-label, randomized, visual acuity assessor–masked noninferiority and equivalence trial. Participants Patients with nAMD diagnosed within 9 months of screening previously treated with and responsive to anti–vascular endothelial growth factor therapy. Methods Patients were randomized 3:2 to treatment with the PDS with ranibizumab 100 mg/ml with fixed 24-week (Q24W) refill-exchanges (PDS Q24W) or intravitreal ranibizumab 0.5-mg injections every 4 weeks (monthly ranibizumab). Main Outcome Measures Primary end point was change in best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study letter (letters) score from baseline averaged over weeks 36 and 40 (noninferiority margin,–4.5 letters; equivalence margin, ±4.5 letters). Results Archway enrolled 418 patients; 251 were randomized to and 248 received treatment with the PDS Q24W, and 167 were randomized to and received treatment with monthly ranibizumab. Baseline BCVA was 74.4 letters (PDS Q24W arm) and 75.5 letters (monthly ranibizumab arm; Snellen equivalent, 20/32). Adjusted mean change in BCVA score from baseline averaged over weeks 36 and 40 was +0.2 letters (standard error [SE], 0.5 letters) in the PDS Q24W arm and +0.5 letters (SE, 0.6 letters) in the monthly ranibizumab arm (difference, –0.3 letters; 95% confidence interval, –1.7 to 1.1 letters). PDS Q24W was both noninferior and equivalent to monthly ranibizumab. Of 246 PDS-treated patients assessed for supplemental ranibizumab treatment, 242 (98.4%) did not receive supplemental ranibizumab treatment before the first refill-exchange procedure, including 4 patients who discontinued treatment before the first refill-exchange procedure. Prespecified ocular adverse events of special interest were reported in 47 patients (19.0%) in the PDS Q24W arm and 10 patients (6.0%) in the monthly ranibizumab arm, which included, in the former arm, 4 (1.6%) endophthalmitis cases, 2 (0.8%) retinal detachments, 13 (5.2%) vitreous hemorrhages, 6 (2.4%) conjunctival erosions, and 5 (2.0%) conjunctival retractions. Most ocular adverse events in the PDS Q24W arm occurred within 1 month of implantation. Conclusions Archway met its primary objective and PDS Q24W demonstrated noninferior and equivalent efficacy to monthly ranibizumab, with 98.4% of PDS-treated patients not receiving supplemental treatment in the first 24-week interval.

Purpose To investigate bacterial dispersion with patient face mask use during simulated intravitreal injections. Design Prospective cross-sectional study MethodsSetting Single-center Study Population Fifteen healthy subjects were recruited Intervention Each participant was instructed not to speak for 2-minutes, simulating a “no-talking” policy, while in an ophthalmic examination chair with an blood agar plate secured to the forehead and wearing various face masks (no mask, loose fitting surgical mask, tight-fitting surgical mask without tape, tight-fitting surgical mask with adhesive tape securing the superior portion of the mask, N95 mask, and cloth mask). Each scenario was then repeated while reading a 2-minute script, simulating a talking patient. Main Outcome Measures Number of colony-forming units (CFU) and microbial species. Results During the “no-talking” scenario, subjects wearing a tight-fitting surgical mask with tape developed fewer CFUs compared to subjects wearing the same mask without tape (difference, 0.93CFU; 95%CI, 0.32–1.55; P=.003). During the speech scenarios, subjects wearing a tight-fitting surgical mask with tape had significantly fewer CFUs compared to subjects without a face mask (difference, 1.07CFU; P=.001), subjects with a loose face mask (difference, 0.67; P=.034), and subjects with a tight face mask without tape (difference, 1.13; P.99) and “speech” (P=.831) scenarios. No oral flora was isolated in “no-talking” scenarios, but was isolated in 8/75 (11%) cultures in speech scenarios (P=.02). Conclusion Addition of tape to the superior portion of a patient’s face mask reduced bacterial dispersion during simulated intravitreal injections, and had no difference in bacterial dispersion compared to wearing N95 masks., Highlights • Patient face mask use may alter bacterial dispersion around the eye during intravitreal injections. • There was significantly more bacterial dispersion when wearing a tight-fitting face mask without tape compared to wearing a tight-fitting mask with tape. • There was no difference in bacterial dispersion between tight-fitting surgical masks with tape and N95 masks. • Taping the superior portion of a patient’s face mask may limit bacterial dispersion when performing intravitreal injections.

Purpose To evaluate the incidence of unexpected management changes on the first day after pars plana vitrectomy (PPV) for retinal detachment repair. Design Retrospective cohort study. Methods The medical and billing records of a large academic private practice were electronically queried for all cases of PPV for retinal detachment performed between January 1, 2017, and December 31, 2017. All cases of PPV for rhegmatogenous or tractional retinal detachment with completed postoperative day 1 (POD1) and postoperative week 1 (POW1) visits were included. The preoperative consultation, operative report, and POD1 and POW1 (postoperative days 5-14) visits were reviewed. Main outcome measures were incidence of unexpected management changes (change in or extended positioning, additional procedure, change in drop regimen, or shortened interval follow-up) at the POD1 visit after uncomplicated PPV for retinal detachment. Results Overall, 418 surgeries from 364 eyes and 355 patients were included. Eleven cases (2.6%) had an intraocular pressure (IOP) over 30 mm Hg at POD1. IOP-lowering drops were prescribed for 30 cases (7.2%). Silicone oil tamponade was positively associated with high IOP at POD1 (relative risk = 3.23, 95% confidence interval 0.96-10.84, P = 0.06). No additional management changes were made besides treating elevated IOP. Conclusions Management changes on POD1 after vitrectomy for retinal detachment repair are relatively uncommon and were solely IOP related in this patient group. There may be flexibility regarding the type of POD1 encounter necessary, including an IOP check with an ophthalmic technician or non–retinal eye care provider. Larger, prospective studies are needed to better determine the most efficient follow-up routine.

The management and outcome of retinal disorders was revolutionised with the advent of ocular anti-vascular endothelial growth factor (VEGF) therapies including US Food and Drug Administration (FDA)-approved ranibizumab (Lucentis; Genentech, South San Francisco, CA, USA) and aflibercept (Eylea; Regeneron, Tarrytown, NY, USA) and off-label bevacizumab (Avastin; Genentech). With the widespread adoption of these treatments over the last decade or so, the blindness attributable to neovascular age-related macular degeneration (nAMD) has been reduced by 50%–72%.1 The real-world studies though have highlighted a few restrictions to the approved regimens, primarily the required monthly injections and follow-up visits.2 Multiple treatment regimens have been introduced in recent years to reduce the frequency of anti-VEGF agent dosing while attempting to maintain efficacy comparable to monthly or bimonthly fixed treatment protocols by individualising therapy. The most practised individualised approaches are treat-and-extend and pro-re-nata protocols. Unfortunately, despite relatively good visual outcomes over 1–2 years in prospective studies with these individualised regimens, real-world studies typically show loss of initial visual gains over time.3 Brolucizumab (Beovu, Novartis), recently approved by the FDA on 7 October 2019, was followed by European Commission approval for use in the European Union on 17 February 2020, for the treatment of nAMD. To date, apart from FDA and European Medicines Agency, the molecule has also been granted marketing approval in Japan, Australia, Argentina, Switzerland and India. It gives another anti-VEGF option to treating physicians. Based on the clinical trial data from HAWK and HARRIER, brolucizumab demonstrated superior anatomic results with greater fluid resolution and similar best-corrected visual acuity compared to aflibercept with the possibility to extend the dosing regimen to q12-week intervals potentially reducing treatment burden.4 Brolucizumab is the first humanised single-chain antibody fragment to be approved for therapeutic use across the field of medicine. This is the smallest functional subunit …

Objective To investigate the effect of the COVID-19 pandemic on the clinical presentation of acute, primary rhegmatogenous retinal detachment (RRD). Design Single-center, consecutive case series with historical controls. Subjects Consecutive patients presenting with primary RRD in a 50-day period during the USA COVID-19 pandemic (March 9th - April 27th, 2020) and the corresponding 50-day period in the previous year (March 4th - April 22th, 2019). Methods The cohorts were compared to assess demographic variables and clinical presentations. Multivariate logistic regression was used to identify factors predictive of presenting macular attachment status. Main Outcome Measure The primary outcome was the proportion of patients with macula-on RRD at presentation. Secondary outcomes included visual acuity (VA), duration of symptoms prior to presentation, proportion presenting within one day of symptom onset, and presence of primary proliferative vitreoretinopathy (PVR). Results Eighty-two patients were included in the 2020 cohort compared to 111 patients in the 2019 primary control cohort. Demographic factors were similar between the groups. Significantly fewer patients presented with macula-on RRD in the 2020 cohort (20/82 patients, 24.4%) than in 2019 (55/111 patients, 49.5%, p = 0.001). Patients in the 2020 cohort had worse median VA at presentation (LogMAR 1.00, Snellen 20/200 in 2020 versus LogMAR 0.48, Snellen 20/60 in 2019, p = 0.008), fewer patients presenting within one day of symptoms (16/80 patients [19.5%] in 2020 versus 41/106 patients [36.9%] in 2019, p = 0.005), and a greater proportion with primary PVR (11/82 patients [13.4%] in 2020 versus 5/111 patients [4.5%] in 2019, p = 0.03). In multivariate analysis, younger age (p = 0.03) and established patient status (p = 0.02) were independent predictors of macula-on status in the 2020 cohort. Conclusions Patients with primary RRD during the 2020 COVID-19 pandemic were less likely to be macula-on and more likely to have delayed presentation, worse vision, and PVR., Highlights We report a significant decrease in macula-on presentation among patients with acute rhegmatogenous retinal detachments during the COVID-19 pandemic when compared to a similar group of control patients from the prior year.

Importance Diabetic retinopathy (DR) is a leading cause of blindness in adults worldwide. Early detection and intervention can prevent blindness; however, many patients do not receive their recommended annual diabetic eye examinations, primarily owing to limited access. Objective To evaluate the safety and accuracy of an artificial intelligence (AI) system (the EyeArt Automated DR Detection System, version 2.1.0) in detecting both more-than-mild diabetic retinopathy (mtmDR) and vision-threatening diabetic retinopathy (vtDR). Design, Setting, and Participants A prospective multicenter cross-sectional diagnostic study was preregistered (NCT03112005) and conducted from April 17, 2017, to May 30, 2018. A total of 942 individuals aged 18 years or older who had diabetes gave consent to participate at 15 primary care and eye care facilities. Data analysis was performed from February 14 to July 10, 2019. Interventions Retinal imaging for the autonomous AI system and Early Treatment Diabetic Retinopathy Study (ETDRS) reference standard determination. Main Outcomes and Measures Primary outcome measures included the sensitivity and specificity of the AI system in identifying participants’ eyes with mtmDR and/or vtDR by 2-field undilated fundus photography vs a rigorous clinical reference standard comprising reading center grading of 4 wide-field dilated images using the ETDRS severity scale. Secondary outcome measures included the evaluation of imageability, dilated-if-needed analysis, enrichment correction analysis, worst-case imputation, and safety outcomes. Results Of 942 consenting individuals, 893 patients (1786 eyes) met the inclusion criteria and completed the study protocol. The population included 449 men (50.3%). Mean (SD) participant age was 53.9 (15.2) years (median, 56; range, 18-88 years), 655 were White (73.3%), and 206 had type 1 diabetes (23.1%). Sensitivity and specificity of the AI system were high in detecting mtmDR (sensitivity: 95.5%; 95% CI, 92.4%-98.5% and specificity: 85.0%; 95% CI, 82.6%-87.4%) and vtDR (sensitivity: 95.1%; 95% CI, 90.1%-100% and specificity: 89.0%; 95% CI, 87.0%-91.1%) without dilation. Imageability was high without dilation, with the AI system able to grade 87.4% (95% CI, 85.2%-89.6%) of the eyes with reading center grades. When eyes with ungradable results were dilated per the protocol, the imageability improved to 97.4% (95% CI, 96.4%-98.5%), with the sensitivity and specificity being similar. After correcting for enrichment, the mtmDR specificity increased to 87.8% (95% CI, 86.3%-89.5%) and the sensitivity remained similar; for vtDR, both sensitivity (97.0%; 95% CI, 91.2%-100%) and specificity (90.1%; 95% CI, 89.4%-91.5%) improved. Conclusions and Relevance This prospective multicenter cross-sectional diagnostic study noted safety and accuracy with use of the EyeArt Automated DR Detection System in detecting both mtmDR and, for the first time, vtDR, without physician assistance. These findings suggest that improved access to accurate, reliable diabetic eye examinations may increase adherence to recommended annual screenings and allow for accelerated referral of patients identified as having vtDR.

Purpose To describe a case of central retinal vein occlusion (CRVO) in a young adult found to have elevated homocysteine after bariatric surgery and to review risk factors for CRVO in younger patients. Observations An 18-year-old female presented with a CRVO and severe cystoid macular edema (CME). She was normotensive, not on medications, and without known heritable hypercoagulable disease. Her medical history was notable for bariatric surgery and subsequently she was found to have nutritional deficiency, anemia, and elevated homocysteine. Her elevated homocysteine may have induced a hypercoaguable state that predisposed her to developing a CRVO. Treatment with bevacizumab dramatically improved her macular edema and visual acuity. Nutritional supplementation was initiated. Conclusions Elevated homocysteine in the setting of nutritional deficiency from prior bariatric surgery may cause a hypercoaguable state and is a potential risk factor for CRVO. Importance With the increasing prevalence of obesity and bariatric surgery, it is important to consider associated nutrient deficiency as a potential cause of induced hypercoagulability and increased risk for CRVO. Identification of these at-risk patients is especially important given this condition is easily treatable and may be present in younger individuals. To the best of our knowledge, this is the first reported case of a CRVO with elevated homocysteine in the setting of nutrient deficiencies from laparoscopic sleeve gastrectomy.

The antivascular endothelial growth factor agents have brought a paradigm shift in the treatment strategy of neovascular age-related macular degeneration (nAMD) by making the approach more interventional. Optical coherence tomography (OCT) is the critical clinical tool used for assessing the lesion activity and the need for therapy, and the presence of fluid is the key biomarker. We have noticed that there has been a lot of discussion and analysis to understand the fluid seen on spectral-domain OCT (SD-OCT) in the recent past. Most of the data and interpretation are based on the post hoc analysis of the Comparison of Age-Related Macular Degeneration Treatment Trials and VIEW 2 trials.1 2 Understanding the tolerance towards subretinal fluid (SRF) was demonstrated by the FLUID trial.3 The recent post hoc analysis of HARBOR trial measured the artificial intelligence-based fluid volume (IRF and SRF) and its prognostic value.4 Common interpretation and perception on the basis of evidences described above say that intraretinal fluid (IRF) either at baseline or at any stage of the treatment is a sign of poor visual prognosis in the long term. On the contrary, some amount of SRF can be tolerated. Subretinal pigment epithelial (sub-RPE) fluid can also be carefully monitored if associated with good visual acuity. However, this may not be completely true for the entire spectrum of nAMD. Jung et al 5 reported the incidence of the three subtypes of neovascularisation in AMD with the use of SD-OCT. They found that type 3 macular neovascularisation (MNV) comprised 28%–34% of eyes with neovascular AMD which is much higher than what was …

The last decade has seen a paradigm shift in the management of neovascular age-related macular degeneration (nAMD) with the introduction of biologicals that inhibit vascular endothelial growth factor (VEGF). These agents, similar to biologicals have imposed a major burden on all healthcare systems. Patients are not only financially strained by the cost of intravitreal injections that require repeated administrations but multiple visits to the hospital compromise quality of life. The recognition of this burden has to some extent led to a shift in the dosing strategy from fixed monthly (of ranibizumab) or 8-weekly dosing (of aflibercept) to pro-re-nata and treat-and-extend (T&E) protocols.1 After the three initial loading doses, re-injection decisions are made based on the presence of fluid on optical coherence tomography (OCT). The OCT is a tool that demonstrates structural changes in the macular retina arising from leakage in the nAMD lesion or occurring as part of the sequelae of chronicity of the pathology. Leakage of fluid and blood constituents representing lesion activity is interpreted by detecting signs (biomarkers) seen on OCT. The presence of clear hypo-reflective regions within the intraretinal layers is considered to represent fluid accumulation. Depending on the location of these regions of hypo-reflectivity, they can be compartmentalised into intraretinal fluid (IRF), subretinal fluid (SRF) and subretinal pigment epithelial fluid. Multiple post hoc analyses of major trials such as the Comparison of AMD Treatments Trials (CATT) and VIEW 2 have shown that presence of IRF, either foveal or extra-foveal during the …

ObjectiveTo understand patient burden of treatment of repeated intravitreal injections (IVI) in the management of exudative retinal diseases.Methods and analysisParticipants were sampled from a large urban retina specialty practice in Houston, Texas, USA, based on history of ongoing receipt of IVI. The 50-item Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections questionnaire was developed to evaluate the patient experience including discomfort, anxiety, inconvenience and satisfaction. Categorial principal components analysis (CATPCA) was performed to assess construct validity and internal consistency. A subset of these items was used to establish a measure of total treatment burden, referred to as the IVI Treatment Burden Score (TBS).Results142 patients participated in this study. CATPCA analysis revealed five dimensions of patient burden: disruption of normal routine or capacity, anxiety, frequency of visits, chronicity of disease and perceived treatment value or satisfaction. Together, these dimensions accounted for 67% of variance explained. Cronbach’s alpha was 0.97. The most frequently cited cause of discomfort was the feeling after anaesthetic wore off. The most common source of anxiety was fear of injection and associated discomfort or pain. Regarding inconvenience, patients reported temporary postinjection debilitation, requiring an average of 8 hours for recovery per treatment. The most frequently identified sources of satisfaction were confidence in the provider or treatment and interactions with staff.ConclusionsUnderstanding and quantifying the patient burden associated with repeated IVI for exudative retinal diseases can reveal opportunities to improve delivery methods. The TBS could serve to inform strategies to maximise treatment adherence and optimise patient experiences.

PurposeTo investigate the role of baseline demographics, disease characteristics, and treatment responses to ranibizumab during RIDE/RISE in predicting long-term treatment frequency with a criteria-based pro re nata (PRN) regimen during the open-label extension (OLE).DesignPooled, retrospective, post hoc analysis from the phase III, randomized RIDE/RISE studies and subsequent OLE.ParticipantsFive hundred patients enrolled in the OLE after completion of the 36-month RIDE/RISE studies.MethodsSummary statistics of RIDE/RISE baseline characteristics and treatment responses were generated by PRN ranibizumab 0.5 mg annualized injection frequency in the OLE (0 and >7 annualized injections). Univariable regression and analysis of variance, and multivariable analysis of covariance were performed on the annualized number of ranibizumab injections administered during the OLE versus baseline characteristics and response to treatment during the RIDE/RISE studies.Main Outcome MeasuresAssociation of patient characteristics and responses to treatment during RIDE/RISE with the observed ranibizumab treatment burden during the OLE.ResultsDuring the OLE, 121 patients required no treatment, 132 required >0 to ≤3 annualized injections, 159 required >3 to ≤7 annualized injections, and 88 required >7 annualized injections. Parameters identified in the multivariable analysis as related to the annualized number of injections included the total number of rescue focal macular lasers received during the core studies (P = 0.0203), central foveal thickness at baseline (P = 0.0002) and month 36 (P < 0.0001), fluorescein leakage area at month 36 (P = 0.0137), and glycated hemoglobin (HbA1c) levels at month 36 (P = 0.0054). Patients receiving 0 versus >7 annualized injections during the OLE had, on average, a shorter duration of diabetes and diabetic macular edema (DME) at baseline, were less likely to have proliferative diabetic retinopathy at baseline, received fewer rescue focal macular laser treatments, and were more likely to experience diabetic retinopathy severity scale improvement of ≥2 steps.ConclusionsPatients who received less frequent injections during the RIDE/RISE OLE tended to have less advanced disease at baseline and responded better to initial ranibizumab treatment, suggesting that earlier anti–vascular endothelial growth factor treatment of center-involving DME with visual acuity loss may decrease long-term treatment burden.

Purpose To compare anatomic and functional outcomes in eyes with proliferative diabetic retinopathy (PDR) that were lost to follow-up (LTFU) for more than 6 months after treatment with either intravitreal injection (IVI) of anti–vascular endothelial growth factor (VEGF) agents or panretinal photocoagulation (PRP). Design Retrospective cohort study. Participants Fifty-nine patients who were LTFU immediately after treatment for more than 6 months between September 2013 and September 2016. Methods Patients with eyes receiving either intravitreal anti-VEGF treatment or PRP with the next follow-up visit occurring more than 6 months after treatment were identified. Visual acuity (VA) and anatomic outcomes at the visit before being LTFU, the return visit, the 6-month visit after return, the 12-month visit after return, and the final visit were gathered and compared between the 2 treatment groups. Main Outcomes Measures Visual acuity and anatomic outcomes. Results Seventy-six eyes of 59 patients were included in the study, of which 30 received IVI with anti-VEGF and 46 received PRP. In the anti-VEGF group, mean VA worsened significantly when comparing the visit before being LTFU (0.43±0.38 logarithm of the minimum angle of resolution [logMAR]) with the return visit (0.97±0.80 logMAR; P = 0.001) as well as with the final visit (0.92±0.94 logMAR; P = 0.01). In the PRP group, mean VA worsened significantly when comparing the visit before being LTFU (0.42±0.34 logMAR) with the return visit (0.62±0.64 logMAR; P = 0.03). However, no significant difference was observed at the final visit (0.46±0.47 logMAR; P = 0.38). There was a significantly greater number of eyes with tractional retinal detachment in the IVI group compared with the PRP group at the final visit (10 vs. 1, respectively; P = 0.005). There was a significantly greater incidence of neovascularization of the iris in the IVI arm compared with the PRP arm at the final visit (4 vs. 0, respectively; P = 0.02). Conclusions Eyes with PDR that received only intravitreal anti-VEGF demonstrated worse anatomic and functional outcomes after being LTFU compared with eyes that received PRP. Given the potential sequelae of being LTFU, the choice of treatment for PDR must be considered carefully.

David Boyer,1 K Bailey Freund,2 Carl Regillo,3 Marc H Levy,4 Sumit Garg5 1Retina-Vitreous Associates Medical Group, Beverly Hills, CA, 2Vitreous-Retina-Macula Consultants of New York, New York, NY; 3Wills Eye Institute, Philadelphia, PA, 4Sarasota Retina Institute, Sarasota, FL, 5The Gavin Herbert Eye Institute (University of California, Irvine) Irvine, CA, USA Background: The purpose of this study was to evaluate the long-term results of an implantable miniature telescope (IMT) in patients with bilateral, end-stage, age-related macular degeneration (AMD).Methods: A prospective, open-label, multicenter clinical trial with fellow eye controls enrolled 217 patients (mean age 76 years) with AMD and moderate-to-profound bilateral central visual acuity loss (20/80–20/800) resulting from untreatable geographic atrophy, disciform scars, or both. A subgroup analysis was performed with stratification for age (patient age 65 to 30 days after surgery (7/70; 10%) and persistent corneal edema (3/70; 4.3%); and in group 2 were a decrease in BCDVA in the implanted eye or IMT removal (10/127 each; 7.9%), corneal edema >30 days after surgery (9/127; 7.1%), and persistent corneal edema (6/127; 4.7%). Significant adverse events included four corneal transplants, comprising two (2.9%) in group 1 and two (1.6%) in group 2. At 60 months, one patient in group 1 (3.2%) and three patients in group 2 (9.4%) had lost ≥2 lines of vision. The IMT was removed in one (1.4%) and ten (7.9%) patients in group 1 and group 2, respectively. Mean ECD loss was 20% at 3 months. Chronic loss was 3% per year. ECD loss was less in group 1 than in group 2 (35% versus 40%, respectively) at 60 months.Conclusion: Long-term results show substantial retention of improvement in BDCVA. Chronic ECD loss was consistent with that reported for conventional intraocular lenses. The IMT performed as well in group 1 (the younger group) as it did in group 2 through month 60. Younger patients retained more vision than their older counterparts and had fewer adverse events. Although not a specified outcome for this study, patients younger than 65 years also fared better than those in group 2 and retained more vision with fewer adverse events through month 60. Keywords: end-stage age-related macular degeneration, implantable miniature telescope, low vision

Purpose To assess anatomic and visual outcomes of ocriplasmin use for symptomatic vitreomacular adhesion (VMA). Design Retrospective chart review. Methods Macula Society members were surveyed online to collect data on ocriplasmin for symptomatic VMA. Clinical and optical coherence tomography data were collected using standardized data entry forms. Results There were 208 patients (208 eyes) with symptomatic VMA followed at least 3 weeks after receiving ocriplasmin. At baseline, VMA was focal (

Objective To report short-term visual and anatomic outcomes of patients who were switched to aflibercept for persistent macular edema associated with central retinal vein occlusion (CRVO). Methods Retrospective, consecutive, interventional case series of 17 patients with persistent macular edema secondary to CRVO (defined as intraretinal edema and either Results The mean age was 77 years, and the mean VA at CRVO diagnosis was 20/135 with a CFT of 523.4 µm. Mean number of injections before switching to aflibercept was 12.9 (range: 3–40) and mean number of months of anti-VEGF treatment before switching to aflibercept was 18.7. Mean VA at switch to aflibercept was 20/182 ( p = 0.50) with mean CFT of 547.9 µm ( p = 0.66). Mean aflibercept injections were 4.0, and mean follow-up from switch to last follow-up was 5.2 months. Final mean VA was 20/115 ( p = 0.017), with a CFT of 315.2 µm ( p = 0.0012). Of the patients, 35.2% gained ≥3 lines. 29% of patients had complete resolution of macular edema, and the mean change in CFT was −233 µm. Conclusions Aflibercept appears to have a beneficial effect on anatomic and VA outcomes in a subset of patients with macular edema secondary to CRVO that is refractory to treatment with bevacizumab and/or ranibizumab.

Purpose The Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) was developed to restore some vision to patients blind as a result of retinitis pigmentosa (RP) or outer retinal degeneration. A clinical trial was initiated in 2006 to study the long-term safety and efficacy of the Argus II System in patients with bare or no light perception resulting from end-stage RP. Design Prospective, multicenter, single-arm clinical trial. Within-patient controls included the nonimplanted fellow eye and patients’ native residual vision compared with their vision with the Argus II. Participants Thirty participants in 10 centers in the United States and Europe. Methods The worse-seeing eye of blind patients was implanted with the Argus II. Patients wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Secondary measures included functional vision performance on objectively scored real-world tasks. Results Twenty-four of 30 patients remained implanted with functioning Argus II Systems at 5 years after implantation. Only 1 additional serious adverse event was experienced after the 3-year time point. Patients performed significantly better with the Argus II on than off on all visual function tests and functional vision tasks. Conclusions The 5-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind as a result of RP. The Argus II is the first and only retinal implant to have market approval in the European Economic Area, the United States, and Canada. © 2016 American Academy of Ophthalmology

PURPOSE A review of treat-and-extend regimens (TERs) with intravitreal anti-vascular endothelial growth factor agents in retinal diseases. METHODS There is a lack of consensus on the definition and optimal application of TER in clinical practice. This article describes the supporting evidence and subsequent development of a generic algorithm for TER dosing with anti-vascular endothelial growth factor agents, considering factors such as criteria for extension. RESULTS A TER algorithm was developed; TER is defined as an individualized proactive dosing regimen usually initiated by monthly injections until a maximal clinical response is observed (frequently determined by optical coherence tomography), followed by increasing intervals between injections (and evaluations) depending on disease activity. The TER regimen has emerged as an effective approach to tailoring the dosing regimen and for reducing treatment burden (visits and injections) compared with fixed monthly dosing or monthly visits with optical coherence tomography-guided regimens (as-needed or pro re nata). It is also considered a suitable approach in many retinal diseases managed with intravitreal anti-vascular endothelial growth factor therapy, given that all eyes differ in the need for repeat injections. CONCLUSION It is hoped that this practical review and TER algorithm will be of benefit to health care professionals interested in the management of retinal diseases.

© 2015 American Academy of Ophthalmology. Purpose Retinitis pigmentosa (RP) is a group of inherited retinal degenerations leading to blindness due to photoreceptor loss. Retinitis pigmentosa is a rare disease, affecting only approximately 100 000 people in the United States. There is no cure and no approved medical therapy to slow or reverse RP. The purpose of this clinical trial was to evaluate the safety, reliability, and benefit of the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc, Sylmar, CA) in restoring some visual function to subjects completely blind from RP. We report clinical trial results at 1 and 3 years after implantation. Design The study is a multicenter, single-arm, prospective clinical trial. Participants There were 30 subjects in 10 centers in the United States and Europe. Subjects served as their own controls, that is, implanted eye versus fellow eye, and system on versus system off (native residual vision). Methods The Argus II System was implanted on and in a single eye (typically the worse-seeing eye) of blind subjects. Subjects wore glasses mounted with a small camera and a video processor that converted images into stimulation patterns sent to the electrode array on the retina. Main Outcome Measures The primary outcome measures were safety (the number, seriousness, and relatedness of adverse events) and visual function, as measured by 3 computer-based, objective tests. Results A total of 29 of 30 subjects had functioning Argus II Systems implants 3 years after implantation. Eleven subjects experienced a total of 23 serious device- or surgery-related adverse events. All were treated with standard ophthalmic care. As a group, subjects performed significantly better with the system on than off on all visual function tests and functional vision assessments. Conclusions The 3-year results of the Argus II trial support the long-term safety profile and benefit of the Argus II System for patients blind from RP. Earlier results from this trial were used to gain approval of the Argus II by the Food and Drug Administration and a CE mark in Europe. The Argus II System is the first and only retinal implant to have both approvals.

Background Medicare recently approved coverage of home telemonitoring for early detection of incident choroidal neovascularization (CNV) among patients with age-related macular degeneration (AMD), but no economic evaluation has yet assessed its cost-effectiveness and budgetary impact. Objectives To evaluate a home-based daily visual-field monitoring system using simulation methods and to apply the findings of the Home Monitoring of the Eye study to the US population at high risk for wet-form AMD. Design, Setting, and Participants In this economic analysis, an evaluation of the potential cost, cost-effectiveness, and government budgetary impact of adoption of a home-based daily visual-field monitoring system among eligible Medicare patients was performed. Effectiveness and visual outcomes data from the Age-Related Eye Disease Study 2 Home Monitoring of the Eye study, treatment data from the Wills Eye Hospital Treat & Extend study, and AMD progression data from the Age-Related Eye Disease Study 1 were used to simulate the long-term effects of telemonitoring patients with CNV in one eye or large drusen and/or pigment abnormalities in both eyes. Univariate and probabilistic sensitivity analysis and an alternative scenario using the Treat & Extend study control group outcomes were used to examine uncertainty in these data and assumptions. Interventions Home telemonitoring of patients with AMD for early detection of CNV vs usual care. Main Outcomes and Measures Incremental cost-effectiveness ratio, net present value of lifetime societal costs, and 10-year nominal government expenditures. Result Telemonitoring of patients with existing unilateral CNV or multiple bilateral risk factors for CNV (large drusen and retinal pigment abnormalities) incurs $907 (95% CI, −$6302 to $2809) in net lifetime societal costs, costs $1312 (95% CI, $222-$2848) per patient during 10 years from the federal government’s perspective, and results in an incremental cost-effectiveness ratio of $35 663 (95% CI, cost savings to $235 613) per quality-adjusted life-year gained. Conclusions and Relevance Home telemonitoring of patients with AMD who are at risk for CNV was cost-effective compared with scheduled examinations alone. Monitoring patients with existing CNV in one eye is cost saving, but monitoring is generally not cost-effective among patients with low risk of CNV, including those with no or few risk factors. With Medicare coverage, monitoring incurs budgetary expenditures for the government but is cost-saving for patients at high risk of AMD. Monitoring could be cost saving to society if monitoring reduced the frequency of scheduled examinations or led to a reduction of one or more injections of ranibizumab.

Importance Although anti–vascular endothelial growth factor treatment of neovascular age-related macular degeneration (AMD) results in improved vision overall, loss of substantial vision can occur. Understanding the processes that lead to loss of vision may lead to preventive strategies. Objective To determine the incidence, characteristics, causes, and baseline predictors of sustained visual acuity loss after 2 years of treatment with ranibizumab or bevacizumab for neovascular AMD. Design, Setting, and Participants A cohort study within a randomized clinical trial of participants in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). Interventions Participants were randomly assigned to treatment with ranibizumab or bevacizumab and to 2 years of monthly or as needed injections or monthly injections for 1 year and as needed injections the following year. Main Outcomes and Measures Sustained visual acuity loss, defined as loss of 15 or more letters from baseline at weeks 88 and 104. Results Among 1030 participants, 61 eyes (5.9%) developed sustained visual acuity loss in 2 years. Within this group, visual acuity decreased gradually over time, with a mean decrease of 2, 19, and 33 letters from baseline at 4 weeks, 1 year, and 2 years, respectively. At 2 years, eyes with sustained visual acuity loss had more scarring (60.0% vs 41.4%, P = .007), more geographic atrophy (GA) (31.6% vs 20.7%, P = .004), larger lesions (16 vs 8 mm 2 , P P P P P P = .006), larger area of choroidal neovascularization (OR for a >4-disc area vs ≤1-disc area, 3.91; 95% CI, 1.70-9.03; P = .007), and bevacizumab treatment (OR, 1.83; 95% CI, 1.07-3.14; P = .03). Conclusions and Relevance Sustained visual acuity loss was relatively rare in CATT. The development of foveal scar, pigmentary abnormalities, or GA contributed to most of the sustained visual acuity loss. Risk was 3% higher among eyes treated with bevacizumab. Treatment that targeted the prevention of scarring or GA may improve vision outcomes. Trial Registration clinicaltrials.gov Identifier:NCT00593450

Objective To evaluate the clinical utility of routinely using indocyanine green angiography (ICGA) with fluorescein angiography (FA) in detecting persistent or recurrent choroidal neovascularization (CNV). Design Prospective, consecutive case series. Participants Twenty-four eyes of 21 patients with exudative age-related macular degeneration (AMD) that had conventional laser treatment for CNV were examined. Intervention Fluorescein angiography and ICGA were performed together on all eligible eyes at the first post-treatment visit and all subsequent follow-up visits in which persistent or recurrent CNV was suspected clinically. Main outcome measures Choroidal neovascularization detection and delineation by each angiographic technique were measured. Results Of the 54 FA-ICGA study pairs performed over a 20-month investigation period, FA showed well-defined, ill-defined, and no CNV in 10 (19%), 19 (35%), and 25 (46%) eyes, respectively. Indocyanine green angiography had a high concordance rate at 70% and 88% when persistent or recurrent CNV was well-defined and absent, respectively, on FA and rarely added additional, clinically useful information in these settings, particularly in the former presentation. Of the 29 eyes that showed some evidence of CNV by FA, the neovascular complex was ill-defined in 19 (66%) eyes. When CNV was ill-defined by FA, the corresponding ICGA showed well-defined CNV in 9 (47%) of 19 eyes, in 5 of which the CNV was nonsubfoveal in location. Conclusions Persistent or recurrent CNV in AMD was frequently ill-defined by FA. Indocyanine green angiography was a valuable adjunct to FA by better delineating CNV in this specific setting. However, ICGA was not useful when the post-treatment FA showed well-defined CNV. Furthermore, ICGA was not helpful when the first post-treatment FA was negative and there were no ophthalmoscopic signs of exudation.

Purpose: To characterize the onset and type of neovascular events in eyes with central retinal vein occlusion (CRVO) undergoing serial anti-VEGF therapy. Methods: Consecutive eyes undergoing serial intravitreal bevacizumab or ranibizumab injections for treatment of CME secondary to CRVO were identified. Pertinent data was retrospectively collected and included type and onset of the neovascular event, and the treatment free interval from last injection until the neovascular event. Kaplan-Meier life table analysis was performed to determine the differential effects of baseline perfusion status, early initiation of anti-VEGF treatment (within 3 months of CRVO onset) versus later treatment, and continuous (1-month±2 weeks) versus discontinuous treatment interval (>1.5 months) on time until neovascular event. Results: Of 31 eligible eyes, 12 (39%) and 19 (61%) presented with perfused and ischemic CRVO, respectively. The mean duration from CRVO until the onset of any neovascular event was 17.0±10.3 months. The mean treatment-free interval prior to any neovascular event was 6.2±7.3 months. On average, 5.3±3.2 anti-VEGF injections were given prior to any neovascular event. Neovascularization of the iris or angle occurred in 18 eyes (58%), vitreous hemorrhage associated with neovascularization was observed in 9 eyes (29%) and neovascularization of the disc developed in 5 eyes (16%). Neovascular events showed a trend towards occurring later in eyes with perfused CRVO at baseline (log rank test, P =0.07). Conclusion: Neovascular events occur in eyes with CRVO undergoing serial anti-VEGF therapy, and these events may be delayed compared to the natural history of CRVO-associated neovascularization. Iris neovascularization occurred most frequently.

PURPOSE: To investigate whether there is an association between known age-related macular degeneration genetic risk variants in the CFH, ARMS2, and HTRA1 genes and response to anti-vascular endothelial growth factor (VEGF) (ranibizumab or bevacizumab) treatment for wet age-related macular degeneration. METHODS: A retrospective review of 150 patients with documented wet age-related macular degeneration based on clinical examination and fluorescein angiogram was performed. Patients received anti-VEGF therapy with ranibizumab and/or bevacizumab. Patients were genotyped for the single-nucleotide polymorphism rs1061170, rs10490924, rs3750848, rs3793917, rs11200638, and rs932275 and for the indel del443ins54 spanning the CFH, ARMS2, and HTRA1 genes. RESULTS: There were 57 patients who were characterized as negative responders to anti-VEGF therapy, and 93 patients who were characterized as positive responders. There was no significant difference in mean baseline visual acuity between the groups. Negative responders were followed for a mean duration of 24.0 months, while positive responders were followed for a mean duration of 22.0 months. Although the frequency of the at-risk alleles was higher in the positive responders when compared with the negative responder, this did not reach statistical significance. Additionally, there was no significant association between genotype and the number of injections or absolute change in visual acuity in both groups of responders. CONCLUSION: In our patient cohort, there was no statistically significant association between response to anti-VEGF therapy and the genotype in both positive-responder and negative-responder groups. Larger studies with more power are necessary to further determine whether a pharmacogenetic association exists between wet age-related macular degeneration and anti-VEGF therapy.

Purpose. To determine the relationship of six genetic variants (rs10490924, rs3750848, del443ins54, rs3793917, rs11200638, and rs932275) localized to the ARMS2-HTRA1 region of chromosome 10, region q26, as risk factors for age-related macular degeneration (AMD), to define the haplotype structure of these six loci, and to confirm their genetic association with the disease. Methods. Caucasian patients (n = 482) were stratified into categories based on AREDS (Age-Related Eye Disease Study) grading criteria (groups 0 and 1 served as the control, groups 3 and 4 contained subjects with AMD, and group 2 was excluded from the analysis). The six genetic variants in the ARMS2-HTRA1 region were genotyped and analyzed both independently and as a joint haplotype for association in subjects with disease (n = 291) compared with the control (n = 191). Results. The six high-risk alleles all showed a statistically significant association with AMD (the most significant SNP was rs10490924 [Por = 3.31 x 10(-5), OR = 1.86]; the least significant SNP was rs932275 [Por = 9.15 x 10(-5), OR = 1.78]). Multimarker analysis revealed that all six markers were in strong linkage disequilibrium with each other, and the two major haplotypes that captured98% of the genetic variation in the region were both significantly associated with the disease: One increased the risk of AMD and contained only risk alleles (Por = 2.20 x 10(-5)), and the other haplotype decreased the risk of AMD and contained only wild-type alleles (Por = 6.81 x 10(-5)). Furthermore, 36 individuals comprising both cases and controls were identified outside of these two major haplotypes, with at least one discordant marker. Conclusions. The results replicate the previously reported association between the high-risk alleles and AMD and independently confirm, for the first time, an association with AMD and the indel (del443ins54) polymorphism in a Caucasian population. Two major haplotypes that are associated with AMD and many minor novel haplotypes were identified. The novel haplotypes, identified from 36 cases and controls with discordant alleles spanning the ARMS2-HTRA1 region provide unique opportunities to gauge the relative phenotypic contributions of each of these genetic risk factors. With the identification of more discordant patients in the future, it may be possible to resolve the ongoing controversy as to which of the risk alleles and genes (ARMS2 vs. HTRA1) has the greatest impact on disease susceptibility. Future work should include the analysis of larger and more diverse populations, to further define the linkage structure of the region with a focus on phenotypic effects on AMD of the various haplotypes involving 10q26, as well as a functional analysis of the normal ARMS2 protein.

Objective: To better define the spectrum of patient characteristics and fundus findings in patients with a presumably unique clinical entity referred to as diabetic papillopathy. Design: Retrospective series. Setting: A university-based referral practice. Methods: We retrospectively reviewed the medical records of all diabetic patients with benign, transient disc swelling who were evaluated at our institution from 1986 to 1992. Data pertaining to patient demographics, visual acuity and symptoms, disc and retinal findings, ancillary test results, and clinical course were collected. Results: Twenty-seven eyes of 19 patients met the study definition of diabetic papillopathy. Patients were generally older (mean age, 50 years) and of a broader age range (19 to 79 years) compared with those in prior reports. Two thirds of patients had type II diabetes. Disc swelling was consistently hyperemic and, on average, resolved within 3.7 months. Macular edema was a frequent associated finding (70% of eyes) as was significant capillary nonperfusion (52% of tested eyes). Only four eyes (15%) had final visual acuities of less than 20/50 and each had prominent macular edema. Cup-disc ratio analysis of uninvolved eyes revealed a significantly small physiologic cup. Conclusions: The clinical profile of diabetic papillopathy can be expanded to include people who are older or have type II diabetes and that affected eyes commonly have macular edema or retinal vascular changes that can adversely affect the visual outcome. Last, a small physiologic cup may represent an anatomic predisposition to the condition.

Objective To determine the long-term safety of pars plana vitrectomy (PPV) in eyes with plaque-irradiated posterior uveal melanoma. Methods In this retrospective case series, patients with plaque-irradiated posterior uveal melanoma subsequently underwent PPV for vitreous hemorrhage. The main outcome measures are the rates of intraocular melanoma dissemination, extrascleral extension of melanoma, local melanoma recurrence, and systemic melanoma metastasis after PPV. Results Forty-seven eyes of 47 patients underwent PPV for vitreous hemorrhage after iodine 125–labeled plaque radiotherapy for choroidal melanoma. The mean interval between the onset of vitreous hemorrhage and PPV was 13 (median, 10; range, 0-52) months. The mean time from PPV to last follow-up was 5 (range, 0.5-16) years. There were no cases of intraocular melanoma dissemination or extrascleral extension of melanoma. One patient (2%) developed local choroidal melanoma recurrence (2 years after PPV and 5 years after initial plaque radiotherapy) and was successfully managed with transpupillary thermotherapy. Systemic melanoma metastasis occurred in 4 patients (9%) during a mean interval of 5 years after plaque radiotherapy. During follow-up, 43 patients (91%) were alive without systemic metastasis and 4 patients (9%) were alive with metastasis. Conclusion Management of vitreous hemorrhage by PPV in eyes with previously irradiated uveal melanoma appears to be safe and without increased risk for intraocular, local, orbital, or systemic dissemination of the tumor.