Evaluating the Effect of Hypoglycemic Agents on Diabetic Retinopathy Progression.

BACKGROUND AND OBJECTIVE: Newer hypoglycemics such as dipeptidyl peptidase 4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists have been increasingly used in diabetes. This study aimed to assess the relationship between usage of these hypoglycemic agents and effect on diabetic retinopathy (DR). MATERIALS AND METHODS: Using the Vestrum Health Retina Database, patients with DR with 1 year follow-up after use of a hypoglycemic agent were included and stratified by agent, including no pharmacotherapy. RESULTS: Of 60,649 eyes, in 1 year after hypoglycemic agent usage, progression rates from severe nonproliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) were the following: DPP-4 (17%), SGLT-2 (12%), GLP-1 (21%), metformin (18%), and none (20%). Progression rates from moderate NPDR to severe NPDR or PDR were the following: DPP-4 (11%), SGLT-2 (10%), GLP-1 (11%), metformin (10%), none (13%). Progression rates from mild NPDR to moderate/severe NPDR or PDR were the following: DPP-4 (6%), SGLT-2 (9%), GLP-1 (9%), metformin (7%), and none (10%). CONCLUSIONS: Within a large real-world database, patients prescribed GLP-1 agonists were found to have DR progression rates comparable to those of patients receiving no hypoglycemic agents. [Ophthalmic Surg Lasers Imaging Retina 2023; 54(3):158-165.].

Incidence of Retinal Artery and Vein Occlusions During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: To examine whether new cases of retinal artery occlusion (RAO) or retinal vein occlusion (RVO) increased during the coronavirus 209 (COVID-19) pandemic. PATIENTS AND METHODS: This was a retrospective cohort study of patients visiting retina clinics with a new diagnosis in two time periods: between January 1, 2019, and February 29, 2020 (the pre-COVID-19 period), and between March 1, 2020, and December 31, 2020 (the COVID-19 period). The key outcome was the percentage of newly diagnosed central RAO (CRAO), branch RAO (BRAO), central RVO (CRVO), and branch RVO (BRVO) seen in each period. RESULTS: The study population included 285,759 new patients in the pre-COVID-19 period and 156,427 new patients in the COVID-19 period. The overall number of new patients dropped dramatically during the first few months of the COVID-19 pandemic (24%, 66%, and 51% less new patients in March, April, and May 2020 than in the same months in 2019; P < .0001 for all 3 months). However, the decrease in the number of newly diagnosed patients with CRAO, CRVO, and BRAO during these months was less dramatic. As most states reopened in June and the number of patients in retina clinics started to increase, the newly diagnosed patients with these conditions as a percentage of all new diagnoses returned to similar trends as seen in the pre-COVID-19 period. CONCLUSIONS: The percentage of new cases of RAO and RVO with respect to all new diagnoses in retina clinics remained stable for the majority of the COVID-19 period. There was an increase in these percentages during the first few months of the COVID-19 pandemic, particularly for CRAO, CRVO, and BRAO, which may have led to the presumption that more patients presented with these conditions during the COVID-19 period evaluated in this study. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:22-30.

Quantifying burden of intravitreal injections: questionnaire assessment of life impact of treatment by intravitreal injections (QUALITII).

AIM: To quantify the areas of burden experienced by patients requiring repeated intravitreal injections (IVI) in the management of exudative retinal diseases. METHODS: The validated Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections survey was administered to patients at four retina clinical practices across four US states. The primary outcome measure was Treatment Burden Score (TBS), a single score assessing overall burden. RESULTS: Of 1416 (n=657 age-related macular degeneration; n=360 diabetic macular oedema/diabetic retinopathy; n=221 retinal vein occlusion; n=178 other/uncertain) patients, 55% were women with an average age of 70 years. Patients most frequently reported receiving IVI every 4-5 weeks (40%). The mean TBS was 16.1±9.2 (range 1-48; scale of 1-54), and the TBS was higher in patients with diabetic macular oedema and/or diabetic retinopathy (DMO/DR) (17.1) compared with those with age-related macular degeneration (15.5) or retinal venous occlusive (15.3) (p=0.028). Though the mean level of discomfort was quite low (1.86) (scale 0-6), 50% of patients reported experiencing side effects more than half of the visits. Patients having received fewer than 5 IVI reported higher mean anxiety levels before (p=0.026), during (p=0.050) and after (p=0.016) treatment compared with patients having received more than 50 IVI. After the procedure, 42% of patients reported restrictions from usual activities due to discomfort. Patients reported a high mean satisfaction rating of 5.46 (scale 0-6) with the care of their diseases. CONCLUSIONS: The mean TBS was moderate and highest among patients with DMO/DR. Patients with more total injections reported lower levels of discomfort and anxiety but higher disruption to daily life. Despite the challenges related to IVI, the overall satisfaction with treatment remained high.

Rates of Suspected Endophthalmitis Following Intravitreal Injections in Clinical Practices in the United States.

BACKGROUND AND OBJECTIVE: To evaluate rates of suspected endophthalmitis following intravitreal injections of aflibercept, bevacizumab, ranibizumab (vial and pre-filled), dexamethasone implant, and triamcinolone in clinical practice. PATIENTS AND METHODS: Retrospective study of aggregated electronic medical records from the Vestrum Health Database. Eyes with a diagnosis of suspected endophthalmitis based on billing codes between January 2013 and June 2019 were included. RESULTS: Total number of injections, suspected endophthalmitis cases, and medication rate, respectively, were: aflibercept (1,412,699; 687; 0.049%); bevacizumab (1,467,722; 379; 0.026%); ranibizumab vial (884,061; 233; 0.026%), ranibizumab pre-filled (427,763; 96; 0.022%); dexamethasone implant (49,464; 53; 0.107%); and triamcinolone (75,038; 110; 0.147%). Rates were lower for bevacizumab and ranibizumab (vial and pre-filled) compared to aflibercept, dexamethasone implant, and triamcinolone (P < .05). Triamcinolone had a higher rate compared to all of the other medications (P < .05). CONCLUSIONS: Suspected endophthalmitis rates following anti-vascular endothelial growth factor injections in clinical practice were similar to reported rates in clinical trials. Rates of suspected endophthalmitis following steroid injections trended higher with significantly higher rates with triamcinolone. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:312-318.].

Characterizing Progression to Neovascular AMD in Fellow Eyes of Patients Treated With Intravitreal Anti-VEGF Injections.

BACKGROUND AND OBJECTIVE: The purpose of this study was to assess the real-world incidence of conversion to bilateral neovascular age-related macular degeneration (nAMD) following treatment initiation of nAMD in the initial eye. PATIENTS AND METHODS: This was a retrospective cohort of electronic health records from retinal centers across the United States (Vestrum Database) of all patients with unilateral nAMD treated with anti-vascular endothelial growth factor therapy. RESULTS: A total of 22,553 patients with unilateral nAMD were included. Fellow eyes of 8,522 patients (38%) converted to nAMD. Among these, 2,639 (12%), 2,030 (9%), and 1,802 (8%) patients converted in Years 1, 2, and 3, respectively, after diagnosis in the first eye. Fellow eyes had better vision at conversion and 1 year following conversion. CONCLUSIONS: The fellow eye should be monitored at regular intervals to detect signs of neovascularization. Fellow eyes presented with significantly better vision at diagnosis than the initial eye and maintained better visual acuity with less injections. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:123-128.].

Characterizing New-Onset Exudation in the Randomized Phase 2 FILLY Trial of Complement Inhibitor Pegcetacoplan for Geographic Atrophy.

OBJECTIVES: To evaluate clinical characteristics of eyes in which investigator-determined new-onset exudative age-related macular degeneration (eAMD) developed during the FILLY trial. DESIGN: Post hoc analysis of the phase 2 study of intravitreal pegcetacoplan in geographic atrophy (GA). SUBJECTS: Patients with GA secondary to age-related macular degeneration (AMD), n = 246. INTERVENTION: Either 15 mg intravitreal pegcetacoplan or sham given monthly or every other month for 12 months followed by a 6-month off-treatment period. MAIN OUTCOME MEASURES: Time of new eAMD onset in the study eye, history of eAMD in the fellow eye, presence of double-layer sign (DLS) on structural OCT in the study eye, changes in retinal anatomic features by structural OCT and fluorescein angiography (FA), and changes in visual acuity. RESULTS: Exudation was reported in 26 study eyes across treatment groups over 18 months. Mean time to eAMD diagnosis was 256 days (range, 31-555 days). Overall, a higher proportion of patients with a baseline history of eAMD in the fellow eye (P = 0.016) and a DLS in the study eye (P = 0.0001) demonstrated eAMD. Among study eyes in which eAMD developed, 18 of 26 (69%) had history of fellow-eye eAMD and 19 of 26 (73.1%) had DLS at baseline, compared with 76 of 217 study eyes (35%; P = 0.0007) and 70 of 215 study eyes (32.5%; P < 0.0001), respectively, in which eAMD did not develop. All 21 patients with structural OCT imaging at the time of eAMD diagnosis demonstrated subretinal fluid, intraretinal cysts, or both consistent with exudation. Among 17 patients who underwent FA at eAMD diagnosis, 10 showed detectable macular neovascularization (MNV), all occult lesions. Development of eAMD did not have an appreciable impact on visual acuity, and all patients responded to anti-vascular endothelial growth factor (VEGF) therapy. CONCLUSIONS: Intravitreal pegcetacoplan slowed the rate of GA growth and was associated with an unexpected dose-dependent increased incidence of eAMD with no temporal clustering of onset. Exudative AMD seemed to be associated with baseline eAMD in the contralateral eye and a DLS, suggestive of nonexudative MNV, in the study eye. The safety profile of pegcetacoplan was acceptable to proceed to phase 3 studies without adjustments to enrollment criteria.

Intravitreal Aflibercept Injection vs Sham as Prophylaxis Against Conversion to Exudative Age-Related Macular Degeneration in High-risk Eyes: A Randomized Clinical Trial.

IMPORTANCE: Anti-vascular endothelial growth factor (VEGF) agents may provide a prophylactic effect in high-risk eyes with intermediate dry age-related macular degeneration (AMD) against conversion to exudative AMD (eAMD), lowering the risk of vision loss. OBJECTIVE: To evaluate intravitreal aflibercept injection (IAI) as prophylaxis against the conversion to eAMD in high-risk eyes at 24 months. DESIGN, SETTING, AND PARTICIPANTS: This single-masked, sham-controlled, randomized clinical trial performed at 4 US clinical sites enrolled patients with intermediate AMD in 1 eye (study eye), defined as presence of more than 10 medium drusen (≥63 to <125 µm), at least 1 large druse (≥125 µm), and/or retinal pigmentary changes, and eAMD in the fellow eye. Patients were treated from June 23, 2015, to March 13, 2019. INTERVENTIONS: Intravitreal aflibercept injection (2 mg) or sham quarterly injection for 24 months (1:1 randomization). MAIN OUTCOMES AND MEASURES: The primary end point was the proportion of patients with conversion to eAMD at month 24 characterized by development of choroidal neovascularization, as assessed by leakage on fluorescein angiography and fluid on spectral-domain optical coherence tomography by an independent masked reading center. RESULTS: Of 128 patients enrolled, 127 (63 in the IAI group and 64 in the sham group) were included in the primary analysis (68 men [53.5%]; mean [SD] age, 76.5 [8.1] years). Baseline demographic and clinical characteristics were balanced between the groups. By month 24, 6 patients (9.5%) in the IAI group and 7 (10.9%) in the sham group developed eAMD (P = .98). Patients with a history of eAMD for longer than 2 years in their fellow eye at baseline showed a lower rate of conversion to eAMD in the study eye compared with those with a history of eAMD for 2 years or less in the fellow eye. Safety was consistent with previous studies involving intravitreal anti-VEGF injections. CONCLUSIONS AND RELEVANCE: In this evaluation of quarterly anti-VEGF exposure as prophylaxis to reduce conversion of eyes with high-risk dry AMD to eAMD, the rates of conversion were not lower in the IAI group compared with the sham treatment group at month 24. Understanding the mechanism of conversion to eAMD and therapies that could prevent this event remains an important unmet need. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02462889.

Increasing Incidence and Prevalence of Common Retinal Diseases in Retina Practices Across the United States.

BACKGROUND AND OBJECTIVE: To provide an updated estimate of incidence and prevalence of the foremost retinal diseases in the U.S. PATIENTS AND METHODS: Retrospective study of the Vestrum Health Database evaluating eyes with diagnoses of wet or dry age-related macular degeneration (AMD), diabetic macular edema (DME), diabetic retinopathy (DR), branch or central retinal vein occlusion (BRVO; CRVO) from January 2014 to December 2019 across 58 retina practices. RESULTS: Of the 3,086,791 eyes examined, 490,881 (15.9%) had dry AMD, 294,041 (9.5%) wet AMD, 270,703 (8.8%) DME, 254,690 (8.3%) DR without DME, 73,617 (2.4%) BRVO, and 50,670 (1.6%) CRVO. Dry AMD had the highest incidence. These diseases comprised 61.0% of total prevalence and 54.3% of incidence among patients at the retina practices analyzed. CONCLUSIONS: Based on a diverse database, these diseases comprised the majority of U.S. retina practice cases, with increasing annual incidences. AMD is the most common diagnosis, then diabetic eye disease. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:29-36.].

Outcomes by Baseline Choroidal Neovascularization Features in Age-Related Macular Degeneration: A Post Hoc Analysis of the VIEW Studies.

PURPOSE: To assess the influence of baseline choroidal neovascularization (CNV) features on visual change and fluid resolution after anti-vascular endothelial growth factor (VEGF) treatment of eyes with neovascular age-related macular degeneration (nAMD). DESIGN: Post hoc analysis of 52-week data from the phase 3 Vascular Endothelial Growth Factor VEGF Trap-Eye: Investigation of Efficacy and Safety in Wet Age-Related Macular Degeneration (AMD) Studies (VIEW) 1 and 2 clinical trials. PARTICIPANTS: One thousand eight hundred four patients with nAMD. METHODS: Integrated data from VIEW 1 and 2 of 1804 eyes receiving intravitreal aflibercept injections (IAIs) 2 mg every 4 weeks, IAIs 2 mg every 8 weeks after 3 initial monthly doses, and ranibizumab every 4 weeks with documented baseline CNV type, total area, and leakage area were analyzed. Time to an event and cumulative incidence were evaluated by Kaplan-Meier analysis, and relative risks were estimated using proportional hazards analysis. MAIN OUTCOMES MEASURES: Cumulative incidence of time to first sustained vision gain of 15 or more Early Treatment Diabetic Retinopathy Study letters, vision loss of more than 5 Early Treatment Diabetic Retinopathy Study letters from baseline, as well as first sustained absence of retinal fluid and intraretinal fluid as evaluated by OCT with respect to CNV type, total CNV, and leakage area. RESULTS: Eyes with predominantly classic CNV (mean best-corrected visual acuity [BCVA], 48.2 letters at baseline) showed a higher incidence rate of first sustained gain of 15 letters or more than eyes with occult CNV (mean BCVA, 57.9 letters at baseline; P < 0.01). Eyes with occult CNV at baseline showed higher incidence rates of first sustained absence of retinal fluid and of intraretinal fluid than eyes with predominantly classic CNV (both P < 0.01). With increasing baseline CNV total area and leakage area, the incidence rate of first sustained gain of 15 letters or more decreased. CONCLUSIONS: This post hoc analysis provided additional evidence for the role of baseline CNV features (CNV type, total area, and leakage area) in influencing visual and anatomic outcomes in eyes with nAMD after anti-VEGF treatment.

Impact of Systemic Dipeptidyl Peptidase-4 Inhibitor Use in Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: To evaluate impact of baseline systemic dipeptidyl peptidase-4 (DPP-4) inhibitor use in diabetic macular edema (DME). PATIENTS AND METHODS: This was a post hoc exploratory analysis of previously completed randomized, controlled clinical trials (VISTA and VIVID) in patients with DME evaluating intravitreal aflibercept injection (IAI) every 4 weeks (2q4) or every 8 weeks (2q8) or macular laser photocoagulation. RESULTS: Overall, a small number of patients (12.2% [n = 35], 9.7% [n = 28], and 15.4% [n = 44]) in the laser control, 2q4, and 2q8 groups reported baseline DPP-4 inhibitor use. There were no differences in changes from baseline in best-corrected visual acuity, central subfield thickness, or rates of 2-or-greater-step improvement in Diabetic Retinopathy Severity Scale score based on DPP-4 inhibitor use within each treatment group. CONCLUSION: DPP-4 inhibitor use at baseline did not influence the magnitude of visual and anatomic benefit in patients with DME being treated with IAI or laser. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:226-234.].

Prevention of Macular Edema in Patients With Diabetic Retinopathy Undergoing Cataract Surgery: The PROMISE Trial.

BACKGROUND AND OBJECTIVE: To determine the safety and efficacy of intravitreal aflibercept injection (IAI) in patients with diabetic retinopathy (DR) in the prevention of macular edema (ME) following cataract surgery. PATIENTS AND METHODS: This phase 2, prospective, interventional, single-masked, randomized trial at a single academic center included 30 patients who were 18 years of age or older with nonproliferative DR and undergoing cataract surgery with phacoemulsification. Patients received 2 mg intravitreal aflibercept (0.05 mL) or sham injection during cataract surgery. Main outcome measures included treatment adverse events (AEs), best-corrected visual acuity (BCVA), and incidence of ME (defined as presence of cystoid abnormalities as detected by optical coherence tomography at any follow-up visit), a 30% or greater increase from preoperative baseline in central subfield macular thickness, or a BCVA decrease of more than 5 ETDRS letters from Day 7 due to retinal thickening. RESULTS: There were similar incidences of AEs between the two groups and no clinically serious ocular AEs in either group. The IAI group had fewer ME events at Day 14 (13% vs. 53%; P = .022), but there was no significant difference in ME events at Day 30 (27% vs. 60%; P = .057), Day 60 (27% vs. 60%; P = .057), or Day 90 (40% vs. 67%; P = .161). Compared to the study group, the control group had a significantly greater increase in central subfield thickness (CST) at Day 30 (50.05 µm vs. 7.95 µm; P = .040) and Day 60 (56.45 µm vs. 3.02 µm; P = .010). However, the difference in CST between groups was no longer significant at Day 90 (50.31 µm vs. 18.48 µm; P = .12). There were no significant differences in BCVA gains between the IAI and sham group at the end of the follow-up period (Day 90, ETDRS letters: 9.88 vs. 8.52; P = .66). CONCLUSIONS: Use of IAI in patients with DR for prevention of ME following cataract surgery showed no significant AEs. Although there were significant differences in ME incidence and retinal thickness at periods of time, there was no clinically meaningful benefit in terms of VA. Further larger trials are needed to validate these findings. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:170-178.].

Outcomes in Patients with Diabetic Macular Edema Requiring Cataract Surgery in VISTA and VIVID Studies.

PURPOSE: To evaluate the impact of cataract surgery on visual and anatomic outcomes in patients with diabetic macular edema treated with intravitreal aflibercept injection (IAI) or laser control and who did not require rescue therapy. DESIGN: Post hoc analysis of 2 phase 3 trials, Study of Intravitreal Aflibercept Injection in Patients with Diabetic Macular Edema (VISTA) and Intravitreal Aflibercept Injection in Vision Impairment Due to DME (VIVID). PARTICIPANTS: Fifty-four patients (laser treatment, n = 11; IAI, n = 43) who underwent cataract surgery during the study period. METHODS: In VISTA and VIVID, patients received IAI 2 mg every 4 weeks, IAI 2 mg every 8 weeks after 5 monthly doses, or laser control through week 100. Starting at week 24, if rescue treatment criteria were met, IAI patients received laser therapy, and laser therapy patients received IAI 2 mg every 8 weeks (after 5 monthly doses). Patients who received rescue treatment before cataract surgery were excluded. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in the laser control and pooled IAI groups before and after cataract surgery. RESULTS: The cumulative incidence of cataract surgery did not depend on treatment group assignment (rate ratio, = 1.517; 95% confidence interval, 0.782-2.944; P = 0.2174). At the last study visit before surgery, BCVA was 62.2 and 56.9 letters and CRT was 342 µm and 301 µm in the laser control and IAI groups, respectively. At the first study visit after cataract surgery, BCVA was improved significantly in both the laser control and IAI groups to 73.5 letters (P = 0.010 compared with last visit before surgery) and 67.2 letters (P < 0.001 compared with last visit before surgery), respectively. Corresponding change in CRT was a modest increase to 364 µm (P > 0.05 compared with last visit before surgery) and 359 µm (P = 0.013 compared with last visit before surgery), respectively. CONCLUSIONS: Incidence of cataract surgery was similar in both treatment groups. Despite a modest worsening in CRT after cataract surgery, BCVA was improved in both treatment groups.

Changes in neovascular activity following fixed dosing with an anti-vascular endothelial growth factor agent over 52 weeks in the phase III VIEW 1 and VIEW 2 studies.

BACKGROUND/AIMS: To understand changes in disease activity as assessed by leakage and retinal fluid status in patients with neovascular age-related macular degeneration (nAMD) receiving fixed dosing with an anti-vascular endothelial growth factor (anti-VEGF) agent. METHODS: In the phase III VIEW 1 (NCT00509795) and VIEW 2 (NCT00637377) studies, eyes with nAMD were treated with intravitreal aflibercept or ranibizumab. Independent, masked reading centres determined the presence/absence of leakage (fluorescein angiography) and retinal fluid (optical coherence tomography) at baseline, week 24 and week 52. In this integrated, post hoc analysis of the VIEW studies, the relationship between leakage/fluid status and best-corrected visual acuity (BCVA) was assessed. The impact of baseline lesion type (predominantly classic (PC), minimally classic (MC), occult) was also evaluated. Data from all treatment groups were pooled. RESULTS: 2373 eyes were included in this analysis. At baseline, 95.4% of eyes presented with both leakage and fluid. By week 52, leakage and fluid were present in 16.0% of eyes. Mean BCVA gains at week 52 were numerically greater in eyes without leakage and fluid versus eyes with both leakage and fluid (10.3 vs 9.2 letters). At week 52, 11.6%, 15.3% and 20.1% of eyes with PC, MC and occult lesions, respectively, had both leakage and fluid present. CONCLUSION: In this post hoc analysis, fixed dosing with an anti-VEGF agent over 52 weeks eliminated disease activity (absence of both leakage and fluid) in most eyes. The effect of anti-VEGF treatment on leakage/fluid status favoured PC versus occult lesions.

Higher-Order Assessment of OCT in Diabetic Macular Edema from the VISTA Study: Ellipsoid Zone Dynamics and the Retinal Fluid Index.

PURPOSE: To investigate retinal fluid features and ellipsoid zone (EZ) integrity dynamics on spectral-domain OCT (SD-OCT) in eyes with diabetic macular edema (DME) treated with intravitreal aflibercept injection (IAI) in the VISTA-DME study. DESIGN: A post hoc subanalysis of a phase III, prospective clinical trial. PARTICIPANTS: Eyes received either IAI 2 mg every 4 weeks (2q4) or every 8 weeks after 5 initial monthly doses (2q8). METHODS: All eyes from the VISTA Phase III study in the IAI groups imaged with the Cirrus HD-OCT system (Zeiss, Oberkochen, Germany) were included. The OCT macular cube datasets were evaluated using a novel software platform to generate retinal layer and fluid boundary lines that were manually corrected for assessment of change in EZ parameters and volumetric fluid parameters from baseline. The retinal fluid index (i.e., proportion of the retinal volume consisting of cystic fluid) was also calculated at each time point. MAIN OUTCOME MEASURES: The feasibility of volumetric assessment of higher-order OCT-based retinal parameters and its correlation with best-corrected visual acuity (BCVA). RESULTS: Overall, 106 eyes of 106 patients were included. Specifically, 52 eyes of 52 patients were included in the IAI 2q4 arm, and 54 eyes of 54 patients were included in the IAI 2q8 arm. Ellipsoid zone integrity metrics significantly improved from baseline to week 100, including central macular mean EZ to retinal pigment epithelium (RPE) thickness (2q4: 26.6 µm to 31.6 µm, P < 0.001; 2q8: 25.2 µm to 31.4 µm, P < 0.001). At week 100, central macular intraretinal fluid volume was reduced by >65% (P < 0.001) and central macular subretinal fluid volume was reduced by >99% in both arms (P < 0.001). Central macular retinal fluid index (RFI) significantly improved in both arms (2q4: 17.9% to 7.2%, P < 0.001; 2q8: 19.8% to 4.2%, P < 0.001). Central macular mean EZ-RPE thickness (i.e., a surrogate for photoreceptor outer segment length) and central RFI were independently correlated with BCVA at multiple follow-up visits. CONCLUSIONS: Intravitreal aflibercept injection resulted in significant improvement in EZ integrity and quantitative fluid metrics in both 2q4 and 2q8 arms and correlated with visual function.

Impact of Baseline Retinal Nonperfusion and Macular Retinal Capillary Nonperfusion on Outcomes in the COPERNICUS and GALILEO Studies.

PURPOSE: To evaluate the impact of baseline retinal capillary nonperfusion (RNP) and macular retinal capillary nonperfusion (MNP) status on outcomes at week 24 (W24). DESIGN: Post hoc analyses of 2 phase 3, randomized, double-masked, multicenter, sham-controlled studies. PARTICIPANTS: Three hundred sixty-six patients with macular edema secondary to central retinal vein occlusion randomized in COPERNICUS and GALILEO. METHODS: We randomized patients 3:2 to receive intravitreal aflibercept 2 mg every 4 weeks or sham injections until W24. RNP and MNP were assessed by a masked independent reading center. MAIN OUTCOME MEASURES: Proportion of patients with 10 disc areas (DA) or more of RNP and any degree of MNP at W24, relative risks of 10 DA or more of RNP or any degree of MNP at W24 developing, change from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) by baseline RNP and MNP status, and relationship between baseline RNP and MNP status. RESULTS: At baseline, 24.6% of patients showed 10 DA or more of RNP and 72.6% showed MNP, regardless of baseline RNP status. At W24, the pooled proportions of patients in the intravitreal aflibercept and sham groups with 10 DA or more of RNP were 11.6% and 29.0%, respectively (P = 0.0001); the respective proportions with any degree of MNP were 61.2% and 79.5% (P = 0.0008). Relative risks and 95% confidence intervals for intravitreal aflibercept versus sham were 0.4 (0.25-0.62) for 10 DA or more of RNP and 0.8 (0.68-0.90) for MNP, indicating a lower risk for these outcomes with intravitreal aflibercept than with sham. Mean BCVA change was greater in intravitreal aflibercept- versus sham-treated eyes, with less than 10 DA and 10 DA or more of RNP at baseline (+17.5 vs. +0.8 letters and +18.3 vs. -4.1 letters, respectively) and with and without baseline MNP (+15.7 vs. +0.3 letters and +17.1 vs. +0.4 letters, respectively). Agreement between baseline RNP and MNP status was low (κ = 0.12). The proportions of patients with 1 or more ocular serious adverse event in the intravitreal aflibercept- and sham-treated groups, respectively, were 3.2% and 11.3%. CONCLUSIONS: At W24, visual and anatomic improvements, including perfusion status, were greater in eyes treated with intravitreal aflibercept than in eyes treated with sham, regardless of baseline RNP or MNP status.

Lipid-Lowering Medications Are Associated with Lower Risk of Retinopathy and Ophthalmic Interventions among United States Patients with Diabetes.

PURPOSE: To evaluate the impact of lipid-lowering medications on diabetic retinopathy and diabetic complications requiring intervention in the US population. DESIGN: Retrospective cohort analysis. METHODS: Administrative insurance claims were drawn from the Truven MarketScan Commercial Claims and Encounters databases. Population consisted of beneficiaries with type 2 diabetes mellitus (T2DM). Main outcome measurements were any signs of diabetic retinopathy, as measured by diagnosis codes for nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), or diabetic macular edema (DME) and procedure codes for retinopathy treatments (anti-VEGF injections, laser therapy, and vitrectomy). RESULTS: A population of 269,782 patients diagnosed with T2DM between 2008 and 2015 were analyzed. A total of 99,233 patients (37%) were undergoing treatment with lipid-lowering medications. Approximately 6% of patients taking lipid-lowering medications had a diagnosis code for NPDR, PDR, or DME or a procedural code for intravitreal injections, pars plana vitrectomy (PPV) or laser treatment in their record following diagnosis with diabetes compared to 6.5% of patients who did not take lipid-lowering medications (P < 0.01). In adjusted time-to-event analyses, patients who took lipid-lowering medications prior to diagnosis of T2DM were less likely to progress to any retinopathy diagnosis (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.55-0.65) and less likely to receive any treatment for retinopathy (HR, 0.81; 95% CI, 0.78-0.84). These findings were significant at the aggregate level, at the individual level of diagnosis (NPDR HR, 0.63; 95% CI, 0.57-0.69; PDR HR, 0.45; 95% CI, 0.37-0.54; and DME HR, 0.39; 95% CI, 0.33-0.45), and at the level of each treatment category (anti-VEGF injection HR, 0.81; 95% CI, 0.78-0.84; laser HR, 0.62; 95% CI, 0.47-0.81; and vitrectomy HR, 0.71; 95% CI, 0.59-0.85). CONCLUSIONS: This study found consistent evidence that patients taking lipid-lowering medications were less likely to develop NPDR, PDR, or DME and modest evidence that these patients are less likely to receive intravitreal injections of anti-VEGF medication, laser treatments, or vitrectomy. The study validates the findings of studies that have used claims databases in East Asia in relatively homogeneous populations to estimate an association between statin use and retinopathy, replicating them in a US context in a large commercial claims database.

Longitudinal Retinal Perfusion Status in Eyes with Diabetic Macular Edema Receiving Intravitreal Aflibercept or Laser in VISTA Study.

PURPOSE: To evaluate changes in retinal perfusion status with intravitreal aflibercept injection (IAI) and laser treatment in the phase 3 VISTA study of patients with diabetic macular edema (DME). DESIGN: Post hoc analysis of a double-masked, randomized, active-controlled, phase 3 trial. PARTICIPANTS: Patients with center-involved DME in the study eye. METHODS: VISTA randomized 466 patients to laser, IAI 2 mg every 4 weeks (2q4), or IAI 2 mg every 8 weeks after 5 monthly doses (2q8). One eye per patient was enrolled in the study. Retinal perfusion status was evaluated by fluorescein angiography based on the presence or absence of retinal nonperfusion (RNP) in quadrants intersecting at the optic nerve head by a masked independent reading center at weeks 24, 52, 72, and 100. Visual and anatomic outcomes were evaluated at all visits. In patients who received rescue treatment, data were censored from the time rescue treatment was given. MAIN OUTCOME MEASURES: Change in perfusion status from baseline through week 100. RESULTS: At week 100, the proportion of eyes with improvement in retinal perfusion (defined as a reduction from baseline in the total number of quadrants in which RNP is present) in the laser control, 2q4, and 2q8 groups was 14.6%, 44.7%, and 40.0%, respectively. The proportion of eyes that experienced worsening in retinal perfusion (defined as an increase from baseline in the total number of quadrants in which RNP is present) at week 100 in the laser control, 2q4, and 2q8 groups was 25.0%, 9.0%, and 8.6%, respectively. CONCLUSION: Post hoc analysis of the phase 3 VISTA study in patients with DME provides evidence that regular IAI dosing not only can slow worsening of retinal perfusion associated with diabetic retinopathy but also may be able to improve retinal perfusion in some cases by decreasing zones of RNP.

Difference in Treatment Effect Between Intravitreal Aflibercept Injection and Laser by Baseline Factors in Diabetic Macular Edema.

BACKGROUND AND OBJECTIVE: To evaluate the effect of baseline factors on differences in vision gains with intravitreal aflibercept injection (IAI) versus laser control in patients with diabetic macular edema (DME). PATIENTS AND METHODS: This was an integrated post-hoc subanalysis of two phase 3 trials (VISTA, VIVID) in patients with DME. Least square (LS) mean differences of patients treated with IAI compared to laser control in best-corrected visual acuity (BCVA) change from baseline at week 100 were evaluated for association with baseline demographics and baseline systemic disease characteristics. RESULTS: At week 100, LS mean differences in BCVA change from baseline with IAI compared to laser control were not significant for association with baseline age, gender, and race or status of glycosylated hemoglobin, body mass index, renal impairment, hypertension, cerebrovascular disease, and ischemic heart disease. CONCLUSION: Vision gains with IAI were significantly greater than laser control and were not influenced by demographics and systemic disease control at baseline. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:167-173.].

Extended (Every 12 Weeks or Longer) Dosing Interval With Intravitreal Aflibercept and Ranibizumab in Neovascular Age-Related Macular Degeneration: Post Hoc Analysis of VIEW Trials.

PURPOSE: To evaluate outcomes and disease characteristics in eyes with neovascular age-related macular degeneration that received intravitreal aflibercept injection (IAI) and ranibizumab every 12 weeks or longer (≥q12 weeks) or less than every 12 weeks (