Short-Term Outcomes of Faricimab in Patients with Neovascular Age-Related Macular Degeneration on Prior Anti-VEGF Therapy.

PURPOSE: A subset of patients with neovascular age-related macular degeneration (nAMD) experience treatment burden and suboptimal response with anti-VEGF therapy. The aim of this study was to investigate the effect of switching to a novel, bispecific agent, faricimab, in patients with nAMD currently treated with anti-VEGF. DESIGN: Retrospective, noncomparative cohort study. SUBJECTS: Patients with nAMD previously treated with anti-VEGF and switched to intravitreal faricimab injection (IFI) at the Cleveland Clinic's Cole Eye Institute. METHODS: Switching and administration schedule of IFI was at the discretion of the clinician. Visual acuity (VA) and macular OCT parameters, including central subfield thickness (CST), maximum pigment epithelial detachment (PED) height, and presence of subretinal (SRF) or intraretinal fluid (IRF), were assessed at baseline (day of first IFI) and after each IFI. MAIN OUTCOME MEASURES: Central subfield thickness and presence of IRF or SRF after ≥ 3 IFIs. RESULTS: One hundred twenty-six eyes of 106 patients were included in the analysis with a mean follow-up time of 24.3 ± 5.2 weeks. Before switching to IFI, patients received a mean of either aflibercept (20.0 ± 8.4, mean ± standard deviation), bevacizumab (7 ± 8.9), ranibizumab (1.9 ± 8.5), or brolucizumab (0.3 ± 1.6) injections. The most common agent used before switching to IFI was aflibercept (n = 110, 87%), and the mean treatment interval with any anti-VEGF was 5.6 ± 1.6 weeks before switching. Central subfield thickness was reduced from baseline after the first IFI (266.8 ± 64.7 vs. 249.8 ± 58.6 µm, P = 0.02) and persisted over the 3 IFIs (P = 0.01). Pigment epithelial detachment height was reduced after the third IFI (249.6 ± 179.0 vs. 206.9 ± 130.0 µm, P = 0.01). The mean VA (62.9 vs. 62.7 approximate ETDRS letters, P = 0.42) and interval between injections (6.3 vs. 5.7 weeks, P = 0.16) was similar after the third IFI compared with baseline. Eleven (8.7%) eyes were switched back to their previous anti-VEGF, including 2 (1.6%) eyes from 1 patient with intraocular inflammation requiring cessation of IFI. There were no other adverse events from switching. CONCLUSIONS: Switching to faricimab resulted in a reduction in mean CST (-11.6 µm, P = 0.01) and PED height (-44.2 µm, P = 0.01) after 3 injections, with stable VA and at a similar treatment interval to prior anti-VEGF therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

The 2-Year Leakage Index and Quantitative Microaneurysm Results of the RECOVERY Study: Quantitative Ultra-Widefield Findings in Proliferative Diabetic Retinopathy Treated with Intravitreal Aflibercept.

Eyes with proliferative diabetic retinopathy (PDR) have been shown to improve in the leakage index and microaneurysm (MA) count after intravitreal aflibercept (IAI) treatment. The authors investigated these changes via automatic segmentation on ultra-widefield fluorescein angiography (UWFA). Forty subjects with PDR were randomized to receive either 2 mg IAI every 4 weeks (Arm 1) or every 12 weeks (Arm 2) through Year 1. After Year 1, Arm 1 switched to quarterly IAI and Arm 2 to monthly IAI through Year 2. By Year 2, the Arm 1 leakage index decreased by 43% from Baseline (p = 0.03) but increased by 59% from Year 1 (p = 0.04). Arm 2 decreased by 61% from Baseline (p = 0.008) and by 31% from Year 1 (p = 0.12). Both cohorts exhibited a significant decline in MAs from Baseline to Year 2 (871 to 410; p < 0.001; 776 to 207; p < 0.001, respectively). Subjects with an improved leakage and MA count showed a more significant improvement in the Diabetic Retinopathy Severity Scale (DRSS) score. Moreover, central subfield thickness (CST) was positively associated with changes in the leakage index. In conclusion, the leakage index and MA counts significantly improved from Baseline following IAI treatment, and monthly injections provided a more rapid and sustained reduction in these parameters compared with quarterly injections.

Longitudinal Higher-Order OCT Assessment of Quantitative Fluid Dynamics and the Total Retinal Fluid Index in Neovascular AMD.

Purpose: The purpose of this study was to evaluate the feasibility of assessing quantitative longitudinal fluid dynamics and total retinal fluid indices (TRFIs) with higher-order optical coherence tomography (OCT) for neovascular age-related macular degeneration (nAMD). Methods: A post hoc image analysis study was performed using the phase II OSPREY clinical trial comparing brolucizumab and aflibercept in nAMD. Higher-order OCT analysis using a machine learning-enabled fluid feature extraction platform was used to segment intraretinal fluid (IRF) and subretinal fluid (SRF) volumetric components. TRFI, the proportion of fluid volume against total retinal volume, was calculated. Longitudinal fluid metrics were evaluated for the following groups: all subjects (i.e. treatment agnostic), brolucizumab, and aflibercept. Results: Mean IRF and SRF volumes were significantly reduced from baseline at each timepoint for all groups. Fluid feature extraction allowed high-resolution assessment of quantitative fluid burden. A greater proportion of brolucizumab participants achieved true zero and minimal fluid (total fluid volume between 0.0001 and 0.001mm3) versus aflibercept participants at week 40. True zero fluid during q12 brolucizumab dosing was achieved in 36.6% to 38.5%, similar to the 25.6% to 38.5% during the corresponding q8 aflibercept cycles. TRFI was significantly reduced from baseline in all groups. Conclusions: Higher-order OCT analysis demonstrates the feasibility of fluid feature extraction and longitudinal volumetric fluid burden and TRFI characterization in nAMD, supporting a unique opportunity for fluid burden assessment and the impact on outcomes. Translational Relevance: Detection and characterization of disease activity is vital for optimal treatment of nAMD. Longitudinal assessment of fluid dynamics and the TRFI provide important proof of concept for future automated tools in characterizing disease activity.

Longitudinal Assessment of Ellipsoid Zone Mapping Parameters in Retinal Venous Occlusive Disease With Associated Macular Edema.

Purpose: This work evaluated the longitudinal dynamics of ellipsoid zone (EZ) integrity in retinal vein occlusion (RVO) with macular edema and their relation to outcomes. Methods: Clinical characteristics and optical coherence tomography data of patients with RVO and associated macular edema were collected at baseline and at 3 and 12 months. Macular cube scans were exported into EZ and retinal-layer analysis software. Longitudinal EZ parameters and visual acuity (VA) outcomes were regressed and correlated. Results: The study included 108 eyes of 108 patients; all eyes were treated with antivascular endothelial growth factor therapy at the baseline visit. VA improved from 20/97 at baseline to 20/52 at 3 months and 12 months (P < .001), correlating with EZ integrity at each time point (P < .001). At 12 months following initiation of antivascular endothelial growth factor therapy, EZ partial attenuation and EZ total attenuation improved over 12 months from 16.4% to 8.5% (P < .001) and from 12.3% to 5.9% (P < .001), respectively. VA improvement from baseline to 12 months correlated with improvement of EZ partial and total attenuation (P < .001). Baseline EZ characteristics did not predict VA outcomes, but at 3 months, EZ parameters did predict improvement in visual outcomes by 12 months (P < .01). Conclusions: EZ and outer retinal integrity are correlated with functional outcomes in RVO. Following treatment, EZ integrity improves and is associated with functional improvement. In RVO baseline, EZ features were not associated with 1-year VA outcomes, but evaluation of EZ integrity at 3 months was linked to 1-year outcomes.

Patient-Reported Complications after Intravitreal Injection and Their Predictive Factors.

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

Longitudinal panretinal microaneurysm dynamics on ultra-widefield fluorescein angiography in eyes treated with intravitreal aflibercept for proliferative diabetic retinopathy in the recovery study.

BACKGROUND/AIMS: Quantifying microaneurysms (MAs) turnover may be an objective measure for therapeutic response in diabetic retinopathy. This study assesses changes in MA counts on ultra-widefield fluorescein angiography (UWFA) in subjects undergoing treatment with intravitreal aflibercept injection (IAI) for proliferative diabetic retinopathy (PDR) in the Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy(RECOVERY) study using an automated MA detection platform. METHODS: RECOVERY is a prospective study that enrolled 40 subjects with PDR randomised 1:1 to receive 2 mg IAI every 4 weeks(q4wk) or every 12 weeks (q12wk). UWFA images were obtained at baseline, 6 months and 1 year. Images were analysed using an automated segmentation platform to detect and quantify MAs. Zones 1, 2 and 3 correspond to the macula, mid-periphery and far-periphery, respectively. RESULTS: The q4wk cohort demonstrated a significant decline in MAs in all zones and panretinally at baseline versus month 6, baseline versus year 1, and month 6 versus year 1 (-20.0% to -61.8%; all p<0.001). In the q12wk cohort, baseline versus month 6 showed a significant decline panretinally (mean: -34.2%; p<0.001) and in zone 3 (mean -44.18%; p<0.001). Addiitonally, baseline to year 1 in the q12wk group demonstrated significant decline panretinally (mean: -47.7%; p<0.001) and in zone 3 (mean: -59.8%; p<0.001). All zones demonstrated significantly decline from month 6 to year 1 in the q12wk group. CONCLUSION: Therapy with IAI demonstrates significantly reduced panretinal MA counts in PDR at 1 year in both treatment groups. The use of automated platforms to detect and quantify MAs may provide a novel imaging marker for evaluating disease activity and therapeutic impact. TRIAL REGISTRATION NUMBER: NCT02863354.

CONSEQUENCES OF LAPSES IN TREATMENT WITH VASCULAR ENDOTHELIAL GROWTH FACTOR INHIBITORS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION IN ROUTINE CLINICAL PRACTICE.

PURPOSE: Evaluating outcomes in patients receiving intravitreal antivascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration whom experience a lapse in treatment. METHODS: A retrospective chart review evaluating 3,304 patients ≥18 years who experienced treatment lapses ≥3 months compared with control counterparts. Demographic information, macular thickness as measured by central subfield thickness, and visual acuity were collected at baseline, the first postlapse appointment, and at 3, 6, and 12 months after the lapse for the study group. RESULTS: Lapse (n = 241) and control patients (n = 241) had similar baseline visual acuity and central subfield thickness (Early Treatment Diabetic Retinopathy Study: 58.9 ± 20.2 [20/63] vs. 59.2 ± 20.1 [20/63]; central subfield thickness: 252.4 ± 63.2 µm vs. 259.8 ± 66.2 µm, P = 0.21). Analysis revealed that lapse patients experienced a significant increase in central subfield thickness after lapse when compared with controls (279.4 ± 86.9 µm vs. 253.7 ± 65.9 µm, P < 0.01), which normalized on resumption of treatment (259.1 ± 79 µm vs. 246.8 ± 57.6 µm, P = 0.06). Study patients also experienced loss in the visual acuity after lapse when compared with controls (52.9 ± 23.6 Early Treatment Diabetic Retinopathy Study [20/100] vs. 59.9 ± 20.8 [20/63] Early Treatment Diabetic Retinopathy Study, P < 0.01) that did not recover through 12 months of follow-up. CONCLUSION: Patients with neovascular age-related macular degeneration who have lapses in care are at risk for poorer outcomes. Although macular thickness normalizes on resumption of treatment, their decline in the visual acuity does not recover.

Effects of Quality Improvement Education in Diabetic Retinopathy on Routine Clinical Practice Patterns of Optometrists.

SIGNIFICANCE: Optometrists play a preventive role in diabetic care by detecting early signs of diabetic retinopathy (DR), a leading cause of blindness in adults. This study demonstrates that additional training can improve optometrists' ability to assess the presence and severity of DR in individuals with diabetes. PURPOSE: This study aimed to determine the impact of a quality improvement intervention involving education, assessment, and feedback on improving the evaluation and referral patterns of optometrists with regard to their patients with diabetes. METHODS: A pre-interventional and post-interventional analysis of optometrist practices was conducted through a retrospective chart review of diabetic patient encounters from July 2018 to March 2019. Dilated fundus examination (DFE) documentation, follow-up scheduling, referral practices, and usage of various imaging modalities were collected from patient records. Concordance of DR severity recordings between DFE findings, assessment and plan notes, and International Classification of Diseases codes was calculated. RESULTS: After intervention, the proportion of optometrists who conducted a DFE significantly increased from 79.5 (95% confidence interval [CI], 77.3 to 81.7%) to 84.4% (95% CI, 82.4 to 86.4%). In addition, the rate of improper follow-up instructions decreased from 13.8 (95% CI, 12.0 to 15.7%) to 10.8% (95% CI, 9.2 to 12.6%), and the decrease was significant (P = .02). Although overall referrals decreased from 19.8 (95% CI, 17.6 to 21.9%) to 14.6% (95% CI, 12.6 to 16.5%), optometrists were as likely to refer to retinal specialists. Finally, concordance between documented DFE findings, assessment and plan notes, and International Classification of Diseases codes significantly increased from 78.8 (95% CI, 76.5 to 81.0%) to 88.7% (95% CI, 86.9 to 90.4%). CONCLUSIONS: Providing optometrists education in screening and assessing DR is effective in improving diabetic patient care.

Twenty-Four-Month OCTA Assessment in Diabetic Patients Undergoing Fixed-Interval Intravitreal Aflibercept Therapy.

BACKGROUND AND OBJECTIVE: Evaluate capillary perfusion density (CPD) in patients with diabetic macular edema (DME) undergoing fixed intravit-real aflibercept injections (IAI) through 24 months. PATIENTS AND METHODS: Prospective, interventional, single-arm study enrolling 20 patients with persistent DME. Patients received IAI every 4 weeks until DME resolution followed by extension to every 8 weeks. Optical coherence tomography angiography was obtained at baseline, 6, 12, and 24 months. RESULTS: Sixteen of 20 eyes completed the study. Baseline mean central subfield thickness was 420 µm, which improved to 251 µm (P < .001). The mean best-corrected visual acuity (BCVA) improved by 5.5 letters (P = .042). The whole superficial CPD decreased by 5.3% (P = .001) and the deep CPD decreased by 4.4% (P = .009). Better BCVA correlated with less CPD loss within the superficial parafovea (r = +0.66 [0.23, 0.88]; P = .006) and whole (r = +0.60 [0.12, 0.85]; P = .017) areas. CONCLUSION: Superficial and deep CPD decreased despite fixed IAI through 24 months. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:448-455.].

Hickam's Dictum: Pseudoxanthoma elasticum and Usher syndrome in a single patient.

BACKGROUND: To report the case of a patient with two distinct genetic systemic diseases - pseudoxanthoma elasticum (PXE) and Usher syndrome - confirmed by genetic testing. MATERIALS AND METHODS: Single Retrospective Case Report. RESULTS: A 36-year-old woman presented with acute central vision loss of the left eye (OS). Fundus exam revealed choroidal neovascularization OS in the setting of angioid streaks secondary to an underlying diagnosis of PXE. Unexpectedly, she also exhibited peripheral bony spicules with significant visual field constriction. Physical exam revealed skin papules on her neck and hearing loss. The presence of angioid streaks and skin findings was compatible with PXE; the etiology of her pigmentary retinopathy and hearing loss was elucidated using genetic testing. The patient was found to be compound heterozygous for pathogenic variants in both the ABCC6 and USH2A genes, confirming the diagnosis of two rare disorders in a single patient. CONCLUSIONS: PXE and Usher syndrome are rare systemic disorders that cause distinctive retinal abnormalities. This report highlights the importance of genetic testing in diagnosing uncommon hereditary retinal disorders and outlines the progression of disease over 6 years.

The Short-term Effect of a Single Lapse in Anti-Vascular Endothelial Growth Factor Treatment for Diabetic Macular Edema Within Routine Clinical Practice.

PURPOSE: Diabetic macular edema (DME) is a leading cause of vision loss in diabetics. Anti-vascular endothelial growth factor (VEGF) therapy has been shown to be an effective treatment option for DME, although the injections are costly and require frequent visits, which increases the risk for unintended treatment lapses. The aim of this study is to characterize the effects of an unintended treatment lapse in patients with DME undergoing anti-VEGF therapy. DESIGN: Retrospective, comparative case series. METHODS: This retrospective chart review compared patients seen in a multicenter institutional practice with DME exhibiting an unintended minimum 3-month lapse in anti-VEGF treatment, with a control group of DME patients receiving regular anti-VEGF treatment without lapses. The primary outcome was difference in central subfield thickness (CST) between the control group and the treatment lapse group at 6 months following treatment lapse. RESULTS: A total of 164 patients were evaluated, 82 patients in the treatment lapse group and 82 patients in the control group. The average age was 65 years, and the average lapse in treatment was 6.2 ± 3.5 months (range 3-24 months). Comparison of data between the lapse and control groups revealed no significant differences in CST (359.9 ± 108.3 µm and 335.4±94.6 µm, respectively, P = .066) or in visual acuity (66.5 ± 14.3 and 68.9 ± 14.5, respectively, P = .136). Limitations included a relatively small sample size, retrospective nature, and only a single lapse being evaluated. CONCLUSIONS: An unintended, single, relatively short-term lapse in anti-VEGF treatment in patients with DME did not appear to result in significant anatomic or visual compromise upon resumption of regular follow-up and treatment.

Use of OCTA Capillary Perfusion Density Measurements to Detect and Grade Macular Ischemia.

BACKGROUND AND OBJECTIVE: To compare optical coherence tomography angiography (OCTA) capillary perfusion density (CPD) measurements of normal eyes and eyes with macular ischemia (MI). PATIENTS AND METHODS: AVATAR is an institutional review board-approved, prospective, observational imaging study using the Avanti RTVue XR HD. OCTA reports were reviewed for the presence of MI. Qualitative MI grading was performed, and CPD metrics in the superficial and deep fovea and parafovea were analyzed. A normal eye cohort was identified for comparative assessment. RESULTS: The MI and normal cohorts included 55 and 58 eyes, respectively. Compared to normal eyes, eyes with MI had significantly lower CPD values in all regions. There was a statistically significant correlation between qualitative MI grade and VA in the superficial (P = .003) and deep plexuses (P = .029). Only deep parafoveal CPD values demonstrated correlation with VA (P = .043). CONCLUSIONS: Eyes with MI determined by masked qualitative OCTA grading demonstrated significantly reduced CPD values compared to normal eyes. Categorical assessment of MI severity correlated with VA. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S30-S36.].

Macular Atrophy Affecting Visual Outcomes in Patients Undergoing Anti-VEGF Treatment in Routine Clinical Practice.

BACKGROUND AND OBJECTIVE: To explore how baseline macular atrophy (MA) affects visual acuity (VA) in patients receiving intravitreal anti-vascular endothelial growth factor (VEGF) injections for neovascular age-related macular degeneration (nAMD). PATIENTS AND METHODS: A retrospective, case control series. Patients were grouped into three cohorts based on baseline spectral-domain optical coherence tomography image findings: foveal MA, nonfoveal MA, and no MA. Outcomes were assessed at 1, 2, and 3 years following anti-VEGF therapy. RESULTS: No differences existed in MA growth between eyes with foveal and nonfoveal MA (0.89 mm2 [95% confidence interval (CI), 0.64-1.14] vs. 0.88 mm2 [95% CI, 0.72-1.05]) after adjusting for baseline lesion sizes at 3 years. Foveal MA patients lost an average of 19.4 ETDRS letters (95% CI, -30.8 to -8.0) after 3 years. Nonfoveal MA patients gained an average of 1.1 ETDRS letters (95% CI, -6.8 to 9.0), and patients without MA averaged a gain of 9.7 ETDRS letters (95% CI, 5.5-14.0). CONCLUSION: In patients with nAMD receiving anti-VEGF in routine clinical practice, presence of baseline foveal MA was associated with significant vision loss. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:68-75.].

RETINAL LEAKAGE INDEX DYNAMICS ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY IN EYES TREATED WITH INTRAVITREAL AFLIBERCEPT FOR PROLIFERATIVE DIABETIC RETINOPATHY IN THE RECOVERY STUDY.

PURPOSE: Characterization of leakage indices on ultra-widefield fluorescein angiography in proliferative diabetic retinopathy treated with intravitreal aflibercept. METHODS: Prospective study enrolling subjects for treatment of proliferative diabetic retinopathy randomized 1:1 to receive 2-mg intravitreal aflibercept every 4 weeks (2q4) or every 12 weeks (2q12). Ultra-widefield fluorescein angiography images obtained at baseline, 24, and 48 weeks were analyzed using a semiautomated leakage segmentation platform. Panretinal and zonal leakage indices were calculated. RESULTS: Forty eyes of 40 subjects were included, and mean age was 48 ± 12.1 years. Mean number of injections was 11 ± 1.7 in the 2q4 arm and 4 ± 0.4 in the 2q12 arm. Median baseline leakage index in the 2q4 and 2q12 groups was 5.1% and 4.3%, respectively (P = 0.28). At 24 and 48 weeks, the 2q4 group significantly improved to 1.1% (-79%, P < 0.0001). At Week 24, the 2q12 group demonstrated nonsignificant improvement (3.4%; -21%, P = 0.47); by Week 48, improvement was significant (1.4%; -68%, P = 0.02). The 2q4 group resulted in lower leakage index compared with the 2q12 group at 24 weeks (1.1% vs. 3.4%, respectively; P = 0.008), but by 48 weeks, leakage index was similar between both groups (1.1% vs. 1.4%, respectively; P = 0.34). CONCLUSION: Proliferative diabetic retinopathy treated with intravitreal aflibercept demonstrated significant leakage index reductions at 1 year. Monthly dosing provided more rapid reduction in leakage index compared with quarterly dosing. TRIAL REGISTRATION: RECOVERY study (NCT02863354); https://clinicaltrials.gov/ct2/show/NCT02863354.

Diabetic Macular Edema Treated With Intravitreal Aflibercept Injection After Treatment With Other Anti-VEGF Agents (SWAP-TWO Study)-12-Month Analysis.

Purpose: This article reports 12-month outcomes of patients with diabetic macular edema previously treated with other antivascular endothelial growth factor agents and transitioned to fixed dosing of intravitreal aflibercept (IAI). Methods: This prospective, single-arm study enrolled patients to receive IAI 2 mg (0.05 mL) every 4 weeks until optical coherence tomography demonstrated no fluid. Patients then received fixed dosing of IAI 2 mg once every 8 weeks through 12 months. Primary outcome was mean absolute change from baseline central subfield thickness (CST) at 12 months measured by optical coherence tomography. Results: Twenty eyes were enrolled. At baseline, best-corrected visual acuity was 70.0 letters, mean CST was 419.7 µm ± 92.0, superficial capillary perfusion density (CPD) was 46.0 ± 4.2%, and deep CPD was 50.8 ± 4.3%. At 12 months, the mean CST improved to 287.2 µm ± 80.2 (P < .001), superficial CPD decreased to 43.6 ± 4.8% (P = .04), and deep CPD decreased to 47.6 ± 4.8% (P = .05). Conclusions: Patients who switched to fixed dosing of IAI demonstrated significant anatomic improvements in CST at 12 months. CPD values decreased significantly both in superficial and deep layers without significant changes in vision.

Comparative Assessment of Widefield Fundus Autofluorescence Patterns in Retinoschisis and Retinal Detachment.

Purpose: This article characterizes widefield fundus autofluorescence (WF-FAF) patterns in retinoschisis (RS), retinal detachment (RD), and combined retinoschisis-detachment (RS/RD), and to correlate them with spectral-domain optical coherence tomography (SD-OCT) findings. Methods: A retrospective case series of 13 eyes with senile RS, RD, or RS/RD is presented. One eye underwent imaging of 2 areas within the retina, resulting in 14 data points. Independent, masked graders classified pathology on SD-OCT as RS, RD, or RS/RD and graded WF-FAF images for either hypoautofluorescent areas or mixed autofluorescence (AF) (hyper-AF, iso-AF, hyper-AF with hypo-AF, hyper-AF with iso-AF, or hypo-AF with iso-AF). Results: There was no statistically significant correlation between the autofluorescence pattern and the type of retinal abnormality (P = .74). Conclusions: High variability was found in the characterization of WF-FAF in patients with RS and RD. SD-OCT remains the criterion-standard imaging modality in distinguishing RS from RD in clinically ambiguous cases.

Quantitative Ultra-Widefield Angiographic Features and Associations with Diabetic Macular Edema.

PURPOSE: To examine the relationship between diabetic macular edema (DME) and quantitative ultra-widefield fluorescein angiography (UWFA) metrics of ischemia, leakage, and microaneurysms. DESIGN: Retrospective image analysis study. PARTICIPANTS: Eyes with diabetic retinopathy that had undergone spectral-domain OCT, UWFA, and ultra-widefield fundus photography. METHODS: OCT images were analyzed to determine the presence or absence of DME, central subfield thickness (CST), and subretinal fluid. Using a semiautomated analysis platform, UWFA images were segmented for ischemia, leakage, and microaneurysms with manual correction as needed. Clinical variables, including age, gender, race, hemoglobin A1C levels, blood pressure, cholesterol levels, use of blood thinners, smoking status, and lens status also were evaluated. MAIN OUTCOME MEASURES: Factors associated with the presence and severity of DME. RESULTS: A total of 304 eyes (156 right eyes, 148 left eyes) from 178 diabetic patients were analyzed in the study. Panretinal leakage index, microaneurysm count, and ischemic index were not significantly different between eyes with and without DME in univariate assessment. Zonal assessments of macular microaneurysms and macular leakage index values revealed that eyes with DME showed a significantly higher microaneurysm count (P = 0.001) and leakage index (P < 0.0001) in the posterior pole compared with eyes without DME. Severity of macular thickening (i.e., CST) was associated significantly with macular leakage index and posterior pole microaneurysm count (P = 0.0002 and P = 0.03, respectively). In addition to posterior pole leakage index and microaneurysm count, DME was associated with older age (P < 0.01), higher systolic blood pressure (P < 0.001), and white race (P = 0.03). Multivariate assessment confirmed the independent association of presence of DME with macular leakage index and macular microaneurysm count (P < 0.01). CONCLUSIONS: Quantitative measures of leakage index and microaneurysm count in the posterior pole on UWFA images were associated with the presence and severity of DME. Panretinal analyses were not linked to DME as strongly. Additional research is needed to determine the role of quantitative UWFA in predicting DME development and characterizing patient prognosis.

Longitudinal Panretinal Leakage and Ischemic Indices in Retinal Vascular Disease after Aflibercept Therapy: The PERMEATE Study.

PURPOSE: To characterize the longitudinal panretinal retinal vascular dynamics in diabetic macular edema (DME) and retinal vein occlusion (RVO) over a 12-month period while being treated with intravitreal aflibercept injections (IAIs). DESIGN: Prospective open-label study (clinicaltrials.gov identifier, NCT02503540). PARTICIPANTS: Thirty-one treatment-naive eyes with foveal-involving retinal edema secondary to DME and RVO. METHODS: Participants received 2 mg IAI every 4 weeks for the first 6 months, followed by 2 mg every 8 weeks. Ultra-widefield fluorescein angiography (UWFA; California Optos [Optos, Dunfermline, United Kingdom]) and spectral-domain OCT (Cirrus; Zeiss, Oberkochen, Germany) scans were obtained and analyzed using a novel quantitative assessment platform. Visual acuity, central subfield thickness, and adverse events also were collected. MAIN OUTCOME MEASURES: The primary end point was the mean change in panretinal leakage index at month 12 from baseline as measured by UWFA. RESULTS: Mean age was 67.1 years. At month 12, visual acuity significantly improved by a mean of 18.4±21.4 letters (P < 0.0001), and central subfield thickness also improved significantly, with a mean reduction of 301.3±250.3 µm (P < 0.0001). Mean panretinal leakage index improved significantly, decreasing from 3.4% at baseline to 0.5% at month 6 (P <0.0001) and 0.4% at month 12 (P < 0.0001). Panretinal ischemic index did not demonstrate any significant change but showed a nonsignificant increase from 5.5% at baseline to 6.1% at month 6 (P = 0.315) and 8.7% at month 12 (P = 0.193). Eyes with DME showed a decrease in leakage index from 3.5±2.7% at baseline to 1.6±0.8% at month 12 (P = 0.018) and overall stability in ischemic index from 5.0±4.1% at baseline to 4.7±3.5% at month 12 (P = 0.689). Participants with RVO showed a decrease in leakage index from 3.3±1.1% at baseline to 0.02±0.03% at 12 months (P < 0.0001) and a nonsignificant increase in ischemic index from 5.9±4.5% at baseline to 12.6±9.8% at month 12 (P = 0.172). CONCLUSIONS: Intravitreal aflibercept injections resulted in a dramatic reduction in panretinal leakage index. Panretinal ischemic index did not improve and trended toward worsening.

Eplerenone for the treatment of chronic central serous chorioretinopathy: 3-year clinical experience.

BACKGROUND/AIMS: The efficacy of mineralocorticoid receptor antagonist eplerenone to treat chronic central serous chorioretinopathy (CSCR) has been established. However, previous studies have been limited by small cohort size and short follow-up duration. This study aims to report 3-year clinical outcomes of patients treated with eplerenone for chronic CSCR. METHODS: Institutional review board-approved retrospective chart analysis at a single institution from 2012 to 2018. Baseline best-corrected visual acuity and anatomical measurements related to degree of subretinal fluid (SRF) were collected at eplerenone initiation. Follow-up data were collected at the closest date to 12, 24 and 36 months. RESULTS: Data were obtained for 100 eyes of 83 patients at 1-year (mean 11.18 ± 4.00 months), 49 eyes at 2-year (24.01 ± 3.33 months) and 33 eyes at 3-year (mean 35.5 ± 7.89 months) follow-up visits. The rate of complete SRF resolution was 31%, 28% and 33%, respectively. At final follow-up, logarithm of the minimum angle of resolution visual acuity change from baseline was +0.10 ± 0.24 (p = 0.130). Average change from baseline at final follow-up for central subfield thickness was -97 ± 140.6 µm (p < 0.001), cube volume was -1.07 ± 1.71 mm3 (p < 0.001), macular thickness -28. 5 ± 47.5 µm (p < 0.001), maximum SRF height was -95.6 ± 160.5 µm (p < 0.001) and maximum SRF diameter was -1169.0 ± 1638.7 µm (p = 0.008). CONCLUSION: Anatomical improvement occurs primarily within the first year of eplerenone treatment for chronic CSCR.

Repeatability of automated leakage quantification and microaneurysm identification utilising an analysis platform for ultra-widefield fluorescein angiography.

Background/aimsUltra-widefield fluorescein angiography (UWFA) provides unique opportunities for panretinal assessment of retinal diseases. The objective quantification of UWFA features is a labour-intensive manual process, limiting its utility. The present study assesses the consistency/repeatability of an automated assessment platform for the characterisation of retinal vascular features, quantification of microaneurysms (MA) and leakage foci in UWFA images. METHODS: An Institutional Review Board-approved retrospective image analysis study was performed on UWFA images. For each eye, two arteriovenous-phase images and two late-phase images were selected. Automated assessment was performed for retinal vascular features, MA identification and leakage segmentation. Panretinal and zonal assessment of metrics was performed. RESULTS: There was a significant correlation between paired time points for retinal vessel area and vessel length on early images (Pearson r=0.92, p<0.0001; Pearson r=0.94, p<0.0001) and late images (Pearson r=0.92, p<0.0001; Pearson r=0.92, p<0.0001, respectively). Panretinal and zonal MA counts demonstrated high repeatability between images (all p<0.0001). Similarly, panretinal leakage area and zonal leakage areas were highly correlated (all p<0.001). CONCLUSION: This automated algorithm demonstrated very strong intrastudy correlation between paired time points in the same phases of the angiogram for quantifying retinal vascular characteristics, MA count and leakage parameters in UWFA images. These findings suggest significant flexibility in the platform for consistency in evaluating metrics over time and is encouraging for longitudinal assessment opportunities.