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Purpose Explore the spectrum of clinical manifestations of pentosan polysulfate sodium (PPS) maculopathy observed across a range of practice settings. Design Multi-institutional retrospective study. Participants Patients exhibiting findings suggestive of PPS maculopathy identified from April 30, 2019, to December 4, 2020. Methods Members of the Macula Society submitted cases of presumed PPS maculopathy for consideration in this series. Diagnosis was confirmed by masked review of fundus imaging. Clinical characteristics of confirmed cases were summarized with descriptive statistics. Main Outcome Measures Pentosan polysulfate exposure characteristics and fundus imaging features. Results There were 74 patients with PPS maculopathy included in the current study. Median (interquartile range) age at diagnosis was 62.0 years (56.0–65.8). The median duration of exposure to PPS was 14.0 years (10.2–18.9), with a median cumulative exposure of 1.5 kg (0.9–2.4). The most common presenting symptom was decreased or blurry vision (66.2%), followed by prolonged dark adaption or nyctalopia (32.4%). The most common referral diagnosis was age-related macular degeneration (54.1%); 16.2% of patients were referred for suspected PPS maculopathy. Novel imaging findings emerged, including highly asymmetric disease in 2 patients and a prominent vitelliform maculopathy in 2 patients. Conclusions Most patients with PPS maculopathy exhibit characteristic findings on multimodal fundus imaging in the setting of high cumulative exposure to the oral drug. Some patients in the current study manifested novel imaging findings, expanding our understanding of the phenotypic spectrum of this condition. We recommend considering standardized ophthalmic screening of patients treated with PPS.

PURPOSE: To longitudinally assess the effect of anti-vascular endothelial growth factor (VEGF) treatment on ellipsoid zone (EZ) integrity, subretinal hyperreflective material (SHRM), and the sub-retinal pigment epithelium (sub-RPE) compartment in eyes with neovascular age-related macular degeneration (nAMD). DESIGN: This study was a post hoc analysis of the OSPREY clinical trial, a prospective, double-masked, phase 2 study comparing brolucizumab 6 mg with aflibercept 2 mg over 56 weeks. PARTICIPANTS: Participants with treatment-naïve nAMD at the initiation of the trial were included in the analysis. METHODS: Eyes were evaluated with spectral domain optical coherence tomography (SD-OCT) at 4-week intervals in the OSPREY trial (n=81). SD-OCT scans collected from each visit were automatically. segmented using a proprietary, machine learning enabled higher-order feature-extraction platform for retinal layer, SHRM, and sub-RPE boundary lines, which were evaluated and corrected as needed by masked trained graders. The current analysis focused only on subjects evaluated with Cirrus (Zeiss) platform, n=28). MAIN OUTCOME MEASURES: Outcome measures included change from baseline in EZ-RPE volume, EZ-RPE central subfield thickness (CST), total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume. The correlation between each of these measures and best corrected visual acuity (BCVA) at each visit was evaluated. RESULTS: EZ-RPE volume and EZ-RPE CST showed significant increases, and total EZ attenuation, SHRM volume, SHRM CST, and total sub-RPE volume showed significant decreases from baseline at each visit from Week 4–56 (P

To compare the variability between Snellen visual acuity (VA) and Early Treatment Diabetic Retinopathy (ETDRS) best-corrected VA (BCVA) measurements.Retrospective chart review.Eyes from subjects entering 12 prospective retinal trials in a large, urban retina practice.Eyes were included if a Snellen VA measurement was performed at the visit preceding trial screening and VA was better than counting fingers. Snellen VA and ETDRS BCVA were then converted to logarithm of the minimum angle of resolution (logMAR) units, and the variability between measurements was calculated.Outcome measures include VA variability among disease states, absolute VA, and central subfield thickness (CST).A total of 773 eyes of 413 subjects were identified with a mean of 27.2 days (median, 19; 95% confidence interval [CI], 25.1-29.3) between measurements. Mean Snellen and ETDRS measurements were 0.40 (20/50) and 0.27 logMAR (20/40), respectively. Overall, mean ETDRS BCVA was 6.1 letters better than Snellen VA (median, 5.8; 95% CI, 5.3-7.0; P0.05); 76.6% of eyes had improved ETDRS. Restricting the number of days between measurements did not result in any meaningful differences from this directionality. Among eyes with worse VA, variation was more pronounced than among eyes with better VA; eyes 20/25 or better were a mean +1.9 letters better on ETDRS testing (P0.05) and eyes 20/160 or worse were a mean +12.6 letters better on ETDRS testing (P0.05). Subgroup analyses by disease state found statistically significantly better vision measurements with the ETDRS protocol compared with Snellen in 4 of the 5 disease states studied. Although lens status did not affect the extent of discrepancy between ETDRS and Snellen measurements, amount of retinal edema (CST) did: increased CST correlated with increased variability.The ETDRS protocol BCVA measurement resulted in significantly better scores when compared with Snellen VA measurements. This difference was more pronounced among eyes with worse VA. Additionally, specific retinal disease states and anatomic variables such as extent of retinal edema (CST) may have a meaningful impact on the anticipated variability between ETDRS and Snellen VA measurement.

Evaluate the impact of intravitreal aflibercept (Eylea; Regeneron, Tarrytown, NY) on retinal nonperfusion (RNP) in eyes with proliferative diabetic retinopathy (PDR).Prospective, randomized clinical trial.Eyes with treatment-naïve PDR and extensive RNP without diabetic macular edema.Patients were randomized 1:1 to intravitreal 2 mg aflibercept every 4 weeks (monthly) or every 12 weeks (quarterly).The primary outcome measure was change in total RNP area (in square millimeters) from baseline to year 1. Secondary outcomes included ischemic index (ISI), diabetic retinopathy severity scale (DRSS) scores, visual acuity, central retinal thickness, and adverse events. The mean and 95% confidence interval were calculated for each outcome.Through 1 year, the monthly (n = 20) and quarterly (n = 20) cohorts received 11.0 and 3.95 mean aflibercept injections, and DRSS scores improved 2 steps or more in 74% and 67% of patients, respectively. Among all patients through 1 year, mean total area of RNP increased from 235 mmWidespread evidence of retinal reperfusion with aflibercept dosing of PDR eyes with extensive RNP was not identified, and therefore the primary outcome of the current study was not met. Nevertheless, zones of apparent reperfusion were detected in some patients, and a dose response was identified with a reduction of RNP progression with monthly compared to quarterly dosing.

Purpose To characterize choroidal neovascular (CNV) lesions and the corresponding change in visual acuity (VA) in eyes that converted to neovascular age-related macular degeneration (AMD) in the Age-Related Eye Disease Study 2–HOme Monitoring of the Eye Study. (AREDS2–HOME Study). Design Cohort study. Participants A total of 1520 participants at risk of developing CNV were enrolled, each of whom contributed 1 or both study eye(s) that had a best-corrected VA letter score of ≥54 letters (Snellen equivalent 20/60) and ≥1 large (≥125 μm) macular druse in the absence of neovascular AMD or central geographic atrophy. Methods A multicenter clinical trial comparing standard care (SC) versus SC plus ForeseeHome (FH; Notal Vision, Manassas, VA) monitoring strategy in the detection of neovascular AMD. Fluorescein angiograms (FA) and OCT were evaluated by an independent reading center (RC) from the visit in which the ophthalmologist identified progression to CNV (n = 82 eyes). Main Outcome Measures Development of CNV on OCT, FA, or both. Results The RC confirmed CNV in 67 of 82 eyes (82%); lesions were confirmed in 42 of 70 eyes (60%) with FA, 59 of 72 eyes (82%) with OCT, and on both images in 34 of 67 eyes (51%). Among the FA-confirmed cases, the median lesion size was 0.82 disc area (DA); lesions were subfoveal in 40.5%, occult CNV composition was present in 54.8%, and associated hemorrhage in 50%. Median (interquartile range [IQR]) lesion size on FA was 0.23 (0.0–0.91) DA versus 0.70 (0.0–1.50) DA, P = 0.051) in the FH and SC eyes, respectively. Among the OCT-confirmed cases median (IQR) center point thickness was 209 (175–274) μm, retinal pigment epithelial lesion complex was present in 86.4%, and subretinal fluid (SRF) was present in 76.3%. The median change in VA from baseline was –4.0 letters and –10.0 letters in the FH and SC eyes (P = 0.008) confirmed as CNV at the RC. Conclusions Incident CNV lesions were more prevalent on OCT images than on FA; however, the use of both OCT and FA enhanced detection of incident lesions. Lesions were smaller and associated with less vision loss among eyes in the FH group.

Purpose To compare the safety and efficacy of treatment with suprachoroidal triamcinolone acetonide (CLS-TA) plus intravitreal aflibercept vs. treatment with aflibercept alone in patients with macular edema due to retinal vein occlusion (RVO). Design Randomized masked controlled clinical trial. Subjects Forty-six patients with RVO. Methods Subjects were randomized 1:1 to suprachoroidal injection of CLS-TA plus intravitreal aflibercept (combination arm) or sham suprachoroidal injection plus aflibercept (aflibercept arm), followed by aflibercept as needed at months 1, 2, and 3 in each arm. Main Outcome Measures The primary efficacy end point was the number of protocol-required aflibercept re-treatments through month 3. Secondary outcomes included mean improvement from baseline best-corrected visual acuity (BCVA), central subfield thickness (CST), and the percentage of participants with CST ≤310 μm at each time point. Results The number of re-treatments were reduced in the combination arm compared with that in the aflibercept arm (23 vs. 9; −61%; P = 0.013) and the percentage of participants requiring no re-treatments was increased (78% vs. 30%; P = 0.003). The mean improvement from baseline BCVA letter score in combination vs. that in the aflibercept arms was 16.1 vs. 11.4 (P = 0.20) at month 1, 20.4 vs. 11.9 (P = 0.04) at month 2, and 18.9 vs. 11.3 (P = 0.09) at month 3. The mean baseline CST in the combination arm (731.1 μm) decreased into the normal range at month 1 (284.7 μm) and remained there at months 2 and 3 (272.4 μm and 285.4 μm). The mean baseline CST (727.5 μm) in the aflibercept arm decreased to 322.8 μm at month 1 and increased at months 2 and 3 (383.4 μm and 384.6 μm). Edema resolution (CST ≤ 310 μm) occurred in 87.0%, 87.0%, and 78.3% of participants in the combination arm at months 1, 2, and 3, respectively, vs. 56.5%, 47.8%, and 47.8% of participants in the aflibercept arm. In the combination arm, 1 participant had cataract progression and 4 (2 with preexistent glaucoma) had increased intraocular pressure that was controlled with topical medication. Conclusions Combination intravitreal aflibercept and suprachoroidal CLS-TA is well tolerated and significantly reduces the need for additional intravitreal aflibercept injections over a 3-month period in patients with RVO. Preliminary evidence suggests that combination therapy may sustain edema resolution and improve visual outcomes.

To examine the relationship between glycemic control at baseline and response to anti-vascular endothelial growth factor treatment for diabetic macular edema (DME).Post hoc analysis of 2 similarly designed phase III trials, VISTA and VIVID.Patients with central-involved DME.Both VISTA and VIVID compared efficacy and safety of intravitreal aflibercept injection (IAI) with macular laser photocoagulation for DME. Current analysis focused on comparison within each treatment group in an integrated VISTA and VIVID dataset. Baseline hemoglobin A1c (HbA1c) was partitioned into 4 quartiles: 4.5% to6.7% (n = 233), 6.7% to7.4% (n = 206), 7.4% to8.6% (n = 209), and 8.6% to14.7% (n = 208). Outcomes were analyzed by mixed model for repeated measures. Intragroup differences were quantified by a regression model.Change from baseline best-corrected visual acuity (BCVA), central subfield thickness (CST), and HbA1c.In the IAI group, mean BCVA improvement from baseline did not depend on baseline HbA1c at week 52 (P = 0.1852), but seemed to be dependent at week 100 (P = 0.0425). The mean CST reduction from baseline was independent of baseline HbA1c at both weeks 52 (P = 0.1857) and 100 (P = 0.7346). Mean HbA1c change from baseline in IAI group was small across all HbA1c quartiles. In the laser group, the mean BCVA gain decreased with increasing baseline HbA1c at both weeks 52 (P = 0.0421) and 100 (P = 0.0001). Similarly, the mean CST decrease was greater with decreasing baseline HbA1c, at both weeks 52 (P = 0.0065) and 100 (P = 0.0162). The mean HbA1c change from baseline in the laser group was minimal across HbA1c quartiles, although glycemic control tended to worsen in upper quartiles.The benefit of IAI in patients with DME was less dependent on their presenting glycemic status as opposed to laser.

To evaluate a prospective treat-and-extend (TREX) management strategy compared with monthly dosing with intravitreal ranibizumab (Lucentis) in neovascular age-related macular degeneration (AMD).Prospective, randomized, multicenter clinical trial.Sixty patients with treatment-naïve neovascular AMD randomized 1:2 to monthly or TREX cohorts.Patients with Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) of 20/32 to 20/500 (Snellen equivalent) were randomized to receive intravitreal 0.5 mg ranibizumab monthly or, according to a TREX protocol, no less frequently than every 12 weeks. After interval extension, if recurrent exudative disease was identified, this maximum interval between treatments was rechallenged according to a strict prospective protocol.Change in ETDRS BCVA from baseline.Sixty patients were enrolled and 50 completed month 24, at which point mean ETDRS BCVA letter gains were similar: 10.5 and 8.7 for the monthly and TREX cohorts, respectively (P = 0.64). At month 24, 4 patients (20%) and 12 patients (30%) in the monthly and TREX cohorts, respectively, gained at least 15 letters (P = 0.41). No monthly cohort patient lost more than 2 letters, whereas 5 TREX cohort patients (13%) lost at least 15 letters. Anatomic improvements were similar between the cohorts. Through month 24, the mean number of injections administered was 25.5 (range, 22-27) and 18.6 (range, 10-25) for the monthly and TREX cohorts, respectively (P 0.001). Among TREX patients completing month 24, 14 (47%) were at an extension interval of 8 weeks or more, and the mean maximum tolerated extension was 8.5 weeks over the course of 2 years. Of the 26 TREX patients (65%) who demonstrated recurrent exudation upon interval extension, the first maximum extension interval was consistent in most eyes (n = 19 [73%]).The TREX neovascular AMD management protocol used with ranibizumab in the Treat-and-Extend Protocol in Patients with Wet Age-Related Macular Degeneration (TREX-AMD) study resulted in visual and anatomic gains comparable with those obtained with monthly dosing, and most patients randomized to TREX therapy demonstrated a relatively consistent maximum extension interval.