Association of Retinal Thickness at Month 1 Post-Treatment with Later Thickness and Visual Acuity in Central Vein Occlusion.

PURPOSE: To investigate the association of retinal thickness 1 month post-randomization (1 month after first study injection with aflibercept or bevacizumab) with later retinal thickness, visual acuity, and number of treatments in eyes with central or hemiretinal vein occlusion enrolled in the SCORE2 trial. DESIGN: Cohort study using data from a randomized multicenter clinical trial. METHODS: Analysis included 350 SCORE2 participants through 2 years of follow-up. Main outcome measures are central subfield thickness (CST) on spectral domain optical coherence tomography, best-corrected visual acuity letter score (VALS), and number of treatments for macular edema. CST was classified as thin (≤216µm), medium (>216µm and ≤300µm), or thick (>300µm). RESULTS: At Month 1, 15% (51/350) of study eyes were in the thin CST class, 57% (199/350) in the medium CST class, and 29% (100/350) in the thick CST class. Of eyes with thin CST at Month 1, 89-96% were also thin during Months 2-12. Over all visits studied, the VALS of eyes in the medium Month 1 CST class was significantly greater than the Month 1 thin class. During Months 6-12 (p<0.001) and 12-24 (p <0.001), but not during Months 0-6 (p=0.36) when monthly treatment was protocol-specified, the mean number of treatments for macular edema per study eye was highest in the thick CST class and lowest in the thin CST class. The thin CST class is significantly more likely to have disorganization of the retinal inner layers inside the central subfield, more paracentral acute middle maculopathy at Month 1, and a history of anti-VEGF treatment prior to trial enrollment. CONCLUSIONS: Eyes with a thin CST at Month 1 were more likely to be in their Month 1 CST class during Months 2-12 than eyes in the thick or medium Month 1 CST classes. Eyes in the medium CST class had the best VALS, with fewest treatments in the thin class after Month 6. These findings suggest that having a post-treatment thin CST can be as detrimental to visual acuity as having a post-treatment thick CST.

The Wisconsin silicone oil study (report #1): anatomical and functional outcomes of repair of retinal detachment with proliferative vitreoretinopathy.

BACKGROUND: Silicone oil (SO) is a long-term tamponade for repair of complex retinal pathology but has limitations including late redetachment. This study describes our experience with SO tamponade for repair of retinal detachment with proliferative vitreoretinopathy (PVR), with attention to anatomic and functional outcomes. METHODS: Retrospective consecutive case series of eyes with retinal detachment (RD) complicated by proliferative vitreoretinopathy (PVR) receiving SO tamponade at the University of Wisconsin between 2013 and 2019. Group 1 defined as primary SO placement; Group 2 had SO placed after failing prior retinal detachment repair. RESULTS: Inclusion criteria of SO placement for repair of RD with PVR was met for 117 eyes. The final reattachment rate was 84% for all eyes, with no difference between Groups 1 and 2. Vision improvement was 2.1 lines for Group 1 (p = 0.06 from baseline) and 4.6 lines for Group 2 (p < 0.0001). The mean number of silicone oil placements was 1.4. Less improvement in vision was noted with repeat SO placement, though overall functional vision of 5/200 or better was achieved in 63.2% of patients. CONCLUSIONS: SO tamponade allows long-term anatomical stabilisation and substantial vision recovery in eyes with retinal detachment complicated by PVR. Rates of anatomic and functional success have improved significantly when compared to prior studies using oil tamponade for repair of PVR.

Real-World Safety Outcomes with Brolucizumab in Neovascular Age-Related Macular Degeneration: Findings from the IRIS® Registry.

INTRODUCTION: To assess real-world safety outcomes for adults with neovascular age-related macular degeneration (nAMD) treated with brolucizumab from the US-based IRIS® (Intelligent Research in Sight) Registry. METHODS: In this retrospective study, 18,312 eyes (15,998 patients) treated with ≥ 1 intravitreal brolucizumab injections between 8 October 2019 (US launch date for brolucizumab) and 7 October 2021 were followed up for ≤ 2 years after first injection (index date). The study assessed the predefined incident ocular adverse events of intraocular inflammation (IOI), retinal vasculitis (RV), and retinal vascular occlusion (RO). RESULTS: Overall, 614/18,312 eyes (3.4%) experienced any IOI, RV, and/or RO event. Median (interquartile range [IQR]) time to an event was 84 (42-167) days; 77.4% of events (475/614) occurred within 6 months after index date. Median (IQR) number of brolucizumab injections before an event was 2 (1-4). For eyes with an adverse event and visual acuity (VA) data (n = 406), median (IQR) change in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from pre-event VA was 0 (- 7 to + 5) at the 6-month follow-up; 50 eyes (12.3%) had a VA loss of 10 or more ETDRS letters. Risk of an event (hazard ratio [95% confidence interval]) was decreased in eyes from male patients (0.61 [0.53-0.71]), from older patients (0.83 [0.76-0.90]), from treatment-naive patients (0.51 [0.38-0.69]), and from patients who started brolucizumab in the second year after launch (0.68 [0.53-0.86] vs. first year). CONCLUSION: In this large real-world brolucizumab safety study, 3.4% of eyes experienced an IOI, RV, and/or RO event. Among eyes that experienced an adverse event for which VA data were available, median ETDRS vision change was 0 letters (IQR - 7 to + 5).

Considerations for the Identification and Management of Geographic Atrophy: Recommendations from an Expert Panel.

Newly approved treatments for patients with geographic atrophy are changing the treatment paradigm, highlighting the need for eye care providers (ECPs) to have a set of recommendations on how to best manage GA patients. Here, we outline how to identify various stages of age-related macular degeneration including geographic atrophy (GA) by examining optimal management scenarios implicating various ECPs and reviewing treatment considerations for patients with GA. Early identification of GA will lead to optimal patient outcomes, while a standardized management scenario will reduce clinical burden among ECPs treating patients with GA.

OCT outcomes as biomarkers for disease status, visual function, and prognosis in diabetic macular edema.

OBJECTIVE: To evaluate disorganization of retinal inner layers (DRIL), as detected on spectral-domain optical coherence tomography (OCT) images, as a biomarker for diabetic macular edema (DME) activity, visual function, and prognosis in eyes with DME. DESIGN: Longitudinal prospective. METHODS: Post hoc correlation analyses were performed on data from a phase 2 clinical trial. Seventy-one eyes of 71 patients with treatment-naive DME received either suprachoroidally administered CLS-TA (proprietary formulation of a triamcinolone acetonide injectable suspension) combined with intravitreal aflibercept or intravitreal aflibercept with a sham suprachoroidal injection procedure. DRIL area, maximum horizontal extent of DRIL, ellipsoid zone (EZ) integrity, and the presence and location of subretinal (SRF) and intraretinal fluid (IRF) were evaluated at baseline and week 24 by certified reading centre graders. RESULTS: At baseline, the area and maximum horizontal extent of DRIL were negatively correlated with best-corrected visual acuity (BCVA; r = -0.25, p = 0.05 and r = -0.32, p =0.01, respectively). Mean baseline BCVA progressively worsened with each ordinal drop in EZ integrity, improved with the presence of SRF, and was invariant to the presence of IRF. DRIL area and maximum extent were significantly decreased at week 24 (-3.0 mm2 [p < 0.001] and -775.8 mm [p < 0.001], respectively. At week 24, decreases in the area and maximum horizontal extent of DRIL were positively correlated with increases in BCVA (r = -0.40, p = 0.003 and r = -0.30, p = 0.04). Improvements in BCVA at week 24 were no different between patients showing improvement in EZ, SRF, or IRF and those showing no improvement or worsening from baseline. CONCLUSIONS: DRIL area and DRIL maximum horizontal extent were demonstrated to be novel biomarkers for macular edema status, visual function, and prognosis in eyes with treatment-naive DME.

Month 60 Imaging Findings and Relationship to Treatment Outcomes Following Anti-VEGF Therapy for Macular Edema Due to Central or Hemi-Retinal Vein Occlusion.

PURPOSE: To evaluate imaging findings from SCORE2 participants through 60 months, to describe the degree of resolution or progression of these variables, and to correlate changes in these imaging findings to treatment outcomes such as visual acuity and the number of treatments administered. METHODS: SCORE2 participants were followed for up to 60 months. Visual acuity, injection frequency and imaging tests color fundus photography (CFP), optical coherence tomography (OCT), and ultra-widefield fluorescein angiography [UWFA]) were performed throughout this period. RESULTS: Less than 6% of eyes had subretinal fluid at month 60. Disorganization of the retinal inner layers (DRIL) was the most likely finding to persist, present in 96% of eyes at baseline and unchanged at 95% at month 60. For UWFA, at baseline, there was a mean of 5.0% non-perfusion area (95% CI: 3.3%-6.8%) in the NETWORC grid with little change to month 60. For the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, at baseline, there was a mean of 2.3% non-perfusion area (95% CI: 0.7%-3.9%) with little change to month 60. There was no correlation between any of the imaging variables at baseline and change in visual acuity to month 60 or in the number of injections following the variable treatment timeframe (month 12 to month 60). CONCLUSIONS: These analyses provide an anatomic explanation for persistent functional deficits many years following initial treatment. Clinical practice patterns should consider evaluation with these imaging tests to help explain persistent functional deficits in many eyes. Additionally, these 8 baseline imaging variables generally should not be relied on to predict visual acuity or intensity of treatment. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.

Visit Adherence and Visual Acuity in Study of COmparative Treatments for REtinal Vein Occlusion 2 (SCORE2).

PURPOSE: We quantify the association between visit adherence and visual acuity (VA) in retinal vein occlusions (CRVO). METHODS: The SCORE2 protocol included a visit every 4 weeks (every 28-35 days) during the first year. Visit adherence was measured as follows: number of missed visits, average and longest (avg and max days) visit interval, and average and longest (avg and max missed days) and unintended visit interval. Avg and max missed days were categorized as on time (0 days), late (>0-60 days), and very late (>60 days). The primary outcome was a change in the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity letter score (VALS) between baseline study visit and last attended visit during Year 1, using multivariate linear regression models controlling for numerous demographic and clinical factors. RESULTS: After adjustment, for each visit missed, patients lost 3.0 letters (95% CI: -6.2, 0.2) of vision (p = .07). On average, the 48 patients who missed at least 1 visit lost 9.4 letters (95% CI: -14.4, -4.3, p < .001) of vision after adjustment. Average days and maximal intervals between visits were not associated with changes in VALS (p > .22) for both comparisons. However, when a visit was missed, the average missed days between missed visits and the max missed interval were both associated with loss of VALS (both variables: 0 days missed as reference, late [1-60 days] -10.8 letters [95% CI: -16.9, -4.7], very late [>60 days] -7.3 letters [95% CI: -14.5, -0.2]; p = .003 for both). CONCLUSIONS: Visit adherence is associated with VALS outcomes in CRVO patients.

Intraocular Pressure in Eyes With Retinal Vein Occlusion Compared With Fellow Eyes: Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) Report 27.

This cohort study investigates intraocular pressure (IOP) in eyes with retinal vein occlusion (RVO) compared with fellow, unaffected eyes.

Efficacy and Safety of Brolucizumab for Diabetic Macular Edema: The KINGFISHER Randomized Clinical Trial.

Importance: Despite the effectiveness of existing anti-vascular endothelial growth factor (VEGF) therapies, a need remains for further treatment options to improve response rates and/or reduce injection or monitoring frequency in patients with diabetic macular edema (DME). Objective: To evaluate the efficacy and safety of brolucizumab vs aflibercept dosed every 4 weeks in participants with DME. Design, Participants, and Setting: This 52-week, double-masked, phase 3 randomized clinical trial included treatment-naive adults and adults who had previously received anti-VEGF therapy. Data were collected from September 2019 to March 2020, and data were analyzed from April 2020 to February 2021. Intervention: Brolucizumab, 6 mg, intravitreal injection every 4 weeks or aflibercept, 2 mg, intravitreal injection every 4 weeks. Main Outcomes and Measures: Participants were randomized 2:1 to brolucizumab, 6 mg, or aflibercept, 2 mg. The primary end point was change from baseline in best-corrected visual acuity at week 52. Secondary end points were the proportion of participants with a 2-step improvement or greater from baseline in Diabetic Retinopathy Severity Scale score, the proportion of eyes with absence of both subretinal fluid and intraretinal fluid, change from baseline in central subfield thickness, and safety at week 52. Results: A total of 517 participants were randomized to brolucizumab (n = 346) or aflibercept (n = 171); 299 (57.8%) were male, and the mean (SD) age was 60.7 (10.2) years. Brolucizumab was noninferior to aflibercept in best-corrected visual acuity (Early Treatment Diabetic Retinopathy Study letter score) change from baseline at week 52 (brolucizumab, 12.2-letter improvement; aflibercept, 11.0-letter improvement; difference, 1.1; 95% CI, -0.6 to 2.9; noninferiority margin, 4; P < .001). Brolucizumab was superior to aflibercept for the proportion of eyes without subretinal and intraretinal fluid (brolucizumab, 144 of 346 [41.6%]; aflibercept, 38 of 171 [22.2%]; difference, 20.0%; 95% CI, 12.5to 28.6; P < .001) and mean central subfield thickness change from baseline at week 52 (brolucizumab, -237.8 µm; aflibercept, -196.5 µm; difference, -41.4; 95% CI, -58.9 to -23.8; P < .001). Incidence of intraocular inflammation was 4.0% (14 of 346) in the brolucizumab arm and 2.9% (5 of 171) in the aflibercept arm, incidence of retinal vasculitis was 0.9% (3 of 346) and 0.6% (1 of 171), respectively, and incidence of retinal vascular occlusion was 0.3% (1 of 346) and 0.6% (1 of 171). One participant in the brolucizumab arm had retinal artery occlusion. Conclusions and Relevance: In these study participants with DME, no clinically meaningful differences in visual outcomes were noted between the brolucizumab and aflibercept arms; some superior anatomic improvements were noted in the brolucizumab arm. No new safety concerns were identified. Trial Registration: ClinicalTrials.gov Identifier: NCT03917472.

Geographic Atrophy Management Consensus (GA-MAC): a Delphi panel study on identification, diagnosis and treatment.

BACKGROUND/AIMS: With a paradigm shift in geographic atrophy (GA) treatments now available, establishing consensus on the identification and diagnosis of the disease along with considerations for management of patients with GA will assist eye care professionals (ECP) in their day-to-day practices, leading to improved patient outcomes. METHODS: A modified Delphi panel process (Geographic Atrophy Management Consensus) consisting of three total surveys and one virtual live meeting held between survey 2 and survey 3. Data were collected from July to October 2022. Participants included expert members of the eye care community that have demonstrated outstanding leadership among peers: a steering committee with three ECPs and a 15-member panel divided between five optometrists, five comprehensive ophthalmologists and five retina specialists. Consensus on statements related to the management of patients with GA was calculated using the RAND/UCLA Appropriateness Method. RESULTS: At the conclusion of the third survey, consensus was reached on 91% of the 77 statements. Critical consensus topics include: (1) optical coherence tomography as the favoured method to diagnose and monitor GA, (2) preferred practice patterns regarding referral of patients to retina specialists and (3) treatment criteria given the advent of emerging therapeutics for GA. CONCLUSIONS: Generating awareness of early signs of disease development, progression and identifying the best tools to evaluate GA establishes ideal management and referral strategies. Given the paradigm shift in GA management driven by approved therapies, coupled with the fact that the disease is progressive resulting in devastating vision loss, these strategies are critical to ensure best overall outcomes.

OCT Grading System of Macular Infarction Predicts Vision in Participants With Central Retinal or Hemiretinal Vein Occlusion: A Secondary Analysis of SCORE2.

PURPOSE: To determine whether macular infarction measured as hyper-reflectivity of the middle and inner retinal layers predicts long-term visual acuity outcomes in participants with central retinal vein occlusion (CRVO) or hemi-retinal vein occlusion (HRVO). DESIGN: Clinical cohort study using post hoc secondary analysis of phase 3 clinical trial data. METHODS: This post hoc secondary analysis of the phase 3 Study of COmparative Treatments for REtinal Vein Occlusions 2 (SCORE2) clinical trial included 310 of the 362 participants with macular edema secondary to CRVO/HRVO who were randomized to injections of aflibercept or bevacizumab. Month 01 (M01) optical coherence tomography (OCT) images were analyzed using the following grading scheme: no infarction (grade 0), only middle retinal infarction (grade 1), diffuse middle and patchy inner retinal infarction (grade 2), and diffuse middle and inner retinal infarction (grade 3). Visual acuity letter score (VALS), central subfield thickness (CST), and number of anti-vascular endothelial growth factor (anti-VEGF) injections were correlated with the infarction severity grade at month 01. RESULTS: More severe macular infarction, with both middle and inner retinal layer hyper-reflectivity (ie, grades 2 and 3), was associated with worse M00 VALS and was predictive of VALS at M01 to M60 (P < .001). More severe infarction was associated with greater CST at presentation; however, after the first anti-VEGF injection, CST decreased and was similar across all grades at all time points (P > .05) with similar number of injections. CONCLUSIONS: Participants with more severe macular infarction at M01, as graded with OCT, exhibited worse visual outcomes despite significantly improved macular edema from month 6 to 5 years. This suggests that macular infarction may drive visual acuity after retinal fluid is treated with anti-VEGF.

High Variation in Inner Retinal Reflectivity Predicts Poor Visual Outcome in Patients With Central Retinal Vein Occlusion: SCORE2 Report 21.

Purpose: To assess the association of a novel spectral domain optical coherence tomography biomarker with 6-month visual acuity in in the Study of COmparative Treatments for REtinal Vein Occlusion 2. Methods: Spectral domain optical coherence tomography volume scans were evaluated for inner retinal hyperreflectivity, quantified by optical intensity ratio (OIR) and OIR variation. Baseline visual acuity letter score (VALS), baseline OCT biomarkers, and month 1 OIR were correlated with VALS at month 6. Regression trees, a machine learning technique yielding readily interpretable models, were used to assess for variable interaction. Results: Only baseline VALS correlated positively with month 6 VALS in multivariate regression. Regression trees detected a novel functional and anatomical interaction in a subgroup. Among patients with a baseline VALS worse than 43, those with an OIR variation at month 1 of more than 0.09 had a mean of 13 fewer letters of vision at 6 months compared with patients with an OIR variation of 0.09 or less. Conclusions: Baseline VALS was the strongest predictor of month 6 VALS. Regression tree analysis detected an interaction effect, in which higher OIR variation at month 1 predicted worse 6-month VALS in patients with low VALS at baseline. OIR variation may serve as a predictor for poor visual outcome despite treatment of macular edema secondary to retinal vein occlusion in patients with poor vision at baseline. Translational Relevance: Pixel heterogeneity in three-dimensional OCT data may serve as measure of disruption of the retinal laminations, and this factor may carry visually prognostic value.

Cost-Utility Comparison of Bevacizumab and Aflibercept in the Treatment of Central or Hemiretinal Vein Occlusion in the SCORE2 Trial.

Importance: Retinal vein occlusion is the second most common retinal vascular disease. Bevacizumab was demonstrated in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2) to be noninferior to aflibercept with respect to visual acuity in study participants with macular edema due to central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) following 6 months of therapy. In this study, the cost-utility of bevacizumab vs aflibercept for treatment of CRVO is evaluated. Objective: To investigate the relative cost-effectiveness of bevacizumab vs aflibercept for treatment of macular edema associated with CRVO or HRVO. Design, Setting, and Participants: This economic evaluation study used a microsimulation cohort of patients with clinical and demographic characteristics similar to those of SCORE2 participants and a Markov process. Parameters were estimated and validated using a split-sample approach of the SCORE2 population. The simulated cohort included 5000 patients who were evaluated 100 times, each with a different set of characteristics randomly selected based on the SCORE2 trial. SCORE2 data were collected from September 2014 October 2019, and data were analyzed from October 2019 to July 2021. Interventions: Bevacizumab (followed by aflibercept among patients with a protocol-defined poor or marginal response to bevacizumab at month 6) vs aflibercept (followed by a dexamethasone implant among patients with a protocol-defined poor or marginal response to aflibercept at month 6). Main Outcomes and Measures: Incremental cost-utility ratio. Results: The simulation demonstrated that patients treated with aflibercept will have an expected cost $18 127 greater than those treated with bevacizumab in the year following initiation. When coupled with the lack of clinical superiority over bevacizumab (ie, patients treated with bevacizumab had a gain over aflibercept in visual acuity letter score of 4 in the treated eye and 2 in the fellow eye), these results demonstrate that first-line treatment with bevacizumab dominated aflibercept in the simulated cohort of SCORE2 participants. At current price levels, aflibercept would be considered the preferred cost-effective option only if treatment restored the patient to nearly perfect health. Conclusions and Relevance: While there will be some patients with CRVO-associated or HRVO-associated macular edema who will benefit from first-line treatment with aflibercept rather than bevacizumab, given the minimal differences in visual acuity outcomes and large cost differences for bevacizumab vs aflibercept, first-line treatment with bevacizumab is cost-effective for this condition.

SCORE2 Report 24: Nonlinear Relationship of Retinal Thickness and Visual Acuity in Central Retinal and Hemiretinal Vein Occlusion.

PURPOSE: To investigate whether a nonlinear association between central subfield thickness (CST) on spectral-domain OCT and concurrent visual acuity letter score (VALS) exists in eyes treated initially with aflibercept or bevacizumab for macular edema associated with central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). DESIGN: Long-term follow-up after a randomized clinical trial from 64 centers in the United States. PARTICIPANTS: Participants were followed up to 60 months and treated at investigator discretion after completing the 12-month treatment protocol. METHODS: Two-segment linear regression models were compared with simple linear regression models of VALS on CST. Pearson correlation coefficients were calculated to assess strength of CST and VALS associations. MAIN OUTCOME MEASURES: Central subfield thickness was measured by OCT and VALS by the electronic Early Treatment Diabetic Retinopathy Study methodology. RESULTS: Estimated inflection points, reflecting turning points at which the CST and VALS association changes from positive to negative, calculated at 7 postbaseline visits, range from 217 to 256 µm. A strongly positive correlation exists to the left of each estimated inflection point, ranging from 0.29 (P < 0.01 at month 60) to 0.50 (P < 0.01 at month 12), and a strongly negative correlation exists to the right of each estimated inflection point, ranging from -0.43 (P < 0.01 at month 1) to -0.74 (P < 0.01 at month 24). Randomization statistical tests showed that 2-segment models are favored over 1-segment models for all postbaseline months (P < 0.001 for all tests performed). CONCLUSIONS: The relationship between CST and VALS in eyes with CRVO or HRVO after treatment with anti-vascular endothelial growth factor (VEGF) therapy is not simply linear. The usually modest correlations between OCT-measured CST and visual acuity belie strong left and right correlations present in 2-segment models. Post-treatment CST close to the estimated inflection points showed the best expected VALS. The SCORE2 participants with a post-treatment CST after treatment close to the estimated inflection points of 217 to 256 µm showed the best VALS. In patients treated with anti-VEGF for macular edema associated with CRVO or HRVO, a thinner retina is not always associated with better VALS. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

One-Year Brolucizumab Outcomes in Neovascular Age-Related Macular Degeneration from a Large United States Cohort in the IRIS® Registry.

PURPOSE: To evaluate visual acuity (VA) and injection intervals in patients with neovascular age-related macular degeneration (nAMD) after 12 months of brolucizumab therapy in clinical practice. DESIGN: Retrospective cohort study. PARTICIPANTS: Adults in the United States-based IRIS® Registry (Intelligent Research in Sight) with nAMD who received brolucizumab exclusively for 12 months (2308 eyes of 2079 patients). METHODS: Observational study of eyes with a first injection of brolucizumab (index), followed by 2 or more brolucizumab injections over the following 12 months without switching to another anti-vascular endothelial growth factor (VEGF) agent. MAIN OUTCOME MEASURES: Primary outcomes were change in best recorded VA and, for eyes receiving prior anti-VEGF therapy (treatment-experienced eyes), the difference between the brolucizumab injection interval at 12 months and the anti-VEGF injection interval before switching. The interval before switching was defined as the time between the prior anti-VEGF and index brolucizumab injections; brolucizumab interval was the time between the closest injection to day 365 and the preceding injection. Secondary outcomes included incident adverse events. RESULTS: Overall VA at index was 61.6 ± 18.4 Early Treatment Diabetic Retinopathy Study letters; 83.7% of treatment-naive eyes (184/220) and 86.1% of treatment-experienced eyes (1797/2088) showed stable (< 10 letters gained or lost) or improved (≥ 10 letters gained) VA at 12 months. Among treatment-experienced eyes receiving a prior anti-VEGF injection within 365 days before index, 29.5% (594/2015) showed an interval before switching of 8 weeks or more (mean, 7.6 ± 5.5 weeks), whereas 83.1% (1734/2015) showed a brolucizumab injection interval at 12 months of 8 weeks or more (mean, 10.3 ± 4.0 weeks). In all, 77.1% of treatment-experienced eyes (1554/2015) showed an interval extension of 1 week or more; of these, 55.4% (861/1554) showed an extension of 4 weeks or more. CONCLUSIONS: In this community-based study, at 12 months, brolucizumab treatment prolonged the interval between anti-VEGF injections for most treatment-experienced eyes, particularly those with shorter intervals before switching, while maintaining or improving VA. With careful balancing of the benefits and risks, switching to brolucizumab treatment may offer the advantage of extending the treatment interval for patients with a high anti-VEGF therapy burden. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Factors Linked to Injection Interval Extension in Eyes with Wet Age-Related Macular Degeneration Switched to Brolucizumab.

PURPOSE: To evaluate factors associated with anti-vascular endothelial growth factor (VEGF) injection interval extension in patients with neovascular age-related macular degeneration (nAMD) switched to brolucizumab treatment. DESIGN: Retrospective, observational cohort study. PARTICIPANTS: Adults in the United States-based IRIS® Registry (Intelligent Research in Sight) with nAMD who switched from another anti-VEGF agent to brolucizumab-only treatment for ≥ 12 months from October 8, 2019, through November 26, 2021. METHODS: Univariable and multivariable analyses examined associations of demographic and clinical characteristics with the likelihood of interval extension after switching to brolucizumab therapy. MAIN OUTCOME MEASURES: Eyes were classified as either extenders or nonextenders at 12 months. Extenders were eyes that achieved (1) an extension of ≥ 2 weeks in the brolucizumab injection interval at 12 months versus the interval before switching (time between the last known prior anti-VEGF injection and first [index] brolucizumab injection) and (2) stable (< 10 letters gained or lost) or improved (≥ 10 letters gained) visual acuity (VA) at 12 months versus VA at index injection. RESULTS: Of 2015 eyes among 1890 patients who switched to brolucizumab treatment, 1186 (58.9%) were extenders. In univariable analyses, demographic and clinical characteristics were comparable between extenders and nonextenders, except that extenders had shorter intervals before switching versus nonextenders (mean, 5.9 ± 2.1 weeks vs. 10.1 ± 7.6 weeks, respectively). In multivariable logistic regression modeling, a shorter interval before switching was associated significantly and positively with interval extension with brolucizumab therapy (adjusted odds ratio, 5.6 for interval before switching of < 8 weeks versus ≥ 8 weeks; 95% confidence interval, 4.5-6.9; P < 0.001), and eyes with an index VA of 40 to 65 letters were significantly less likely to be extenders than eyes in the higher (better) index VA categories. CONCLUSIONS: Length of the treatment interval before switching was the characteristic associated most strongly with successful interval extension with brolucizumab. Treatment-experienced patients who required more frequent injections (i.e., shorter intervals before switching) showed the greatest extensions when switching to brolucizumab. With careful consideration of benefits and risks, brolucizumab may be a valuable option for patients with higher treatment burdens because of the need for frequent injections. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Progression of Stargardt Disease as Determined by Fundus Autofluorescence Over a 24-Month Period (ProgStar Report No. 17).

PURPOSE: To estimate the progression rate of atrophic lesions in Stargardt disease derived from fundus autofluorescence (FAF). DESIGN: International, multicenter, prospective cohort study. METHODS: A total of 259 participants aged ≥6 years with disease-causing variants in the ABCA4 gene were enrolled from 9 centers and followed over a 24-month period. FAF images were obtained every 6 months, and areas of definitely decreased autofluorescence (DDAF) and decreased autofluorescence (DAF) were quantified. Progression rates were estimated from linear mixed models with time as the independent variable. RESULTS: A total of 488 study eyes of 259 participants (88.8% with both eyes) were enrolled and images from 432 eyes were followed for 24 months. The overall estimated progression of DDAF was 0.74 mm2/y (95% CI 0.64-0.85, P < .0001) and that of DAF was 0.64 mm2/y (95% CI 0.57-0.71) over a 24-month period in univariate analysis. Growth rates were strongly dependent on baseline lesion area. After square root transformation, the DDAF growth rate was not dependent on baseline lesion radius (P = .11), whereas the DAF growth rate was dependent (P < .0001). Genotype was not found to significantly impact the growth rate of DDAF or DAF lesions. CONCLUSIONS: FAF may serve as a convenient monitoring tool and suitable end point for interventional clinical trials that aim to slow disease progression. DDAF and DAF lesion sizes at baseline are strong predicting factors for lesion area growth and can be partially accounted for by square root transformation.

IMPACT OF RETINAL FLUID-FREE MONTHS ON OUTCOMES IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: A Treatment Agnostic Analysis of the HAWK and HARRIER Studies.

PURPOSE: To assess the effect of the total number of fluid-free months after loading on visual and anatomical outcomes in neovascular age-related macular degeneration patients receiving anti-vascular endothelial growth factor therapy. METHODS: This post hoc analysis pooled patient-level data from the brolucizumab 6 mg (n = 718) and aflibercept 2 mg (n = 715) arms of the HAWK and HARRIER randomized clinical trials. Based on data from Weeks 12 to 96, patients were assigned to one of five categories based on fluid-free visits (FFVs; the total number of monthly visits at which they were observed to be without retinal fluid). Three definitions of "fluid-free" were explored based on the location of the fluid observed. RESULTS: Patients allocated to Categories 4 (15-21 FFV) and 5 (22 FFV, always dry) consistently had the best visual and anatomical outcomes at Week 96, whereas patients allocated to Categories 1 (0 FFV, never dry) and 2 (1-7 FFV) consistently had the worst visual and anatomical outcomes. Variability in retinal thickness over time was lowest in Categories 4 and 5. CONCLUSION: Absence of retinal fluid at more visits after loading has a positive association with visual and anatomic outcomes in neovascular age-related macular degeneration patients, regardless of fluid type.

In Vivo Longitudinal Measurement of Cone Photoreceptor Density in Intermediate Age-Related Macular Degeneration.

PURPOSE: To evaluate cone photoreceptor density in clinically unremarkable retinal regions in patients with age-related macular degeneration (AMD) using adaptive optics scanning laser ophthalmoscopy (AOSLO). DESIGN: Prospective case series with normal comparison group. METHODS: Ten eyes of 7 patients with intermediate AMD were studied, including 4 with predominantly subretinal drusenoid deposits (SDD) and 3 without SDD. Macular regions with a clinical absence of AMD-associated lesions were identified by cone packing structure on AOSLO and optical coherence tomography. Cone density was measured in 1174 clinically unremarkable regions within the central subfield (CSF), the inner (IR), and outer rings (OR) of the Early Treatment Diabetic Retinopathy Study grid over 39.6 ± 3.3 months and compared with age-matched normal values obtained in 17 participants. RESULTS: Cone density decreased at 98.3% of the examined locations over time in the eyes with AMD. In the CSF, IR, and OR, cones declined by -255 ± 135, -133 ± 45, and -59 ± 24 cones/degree2/year, respectively, in eyes with SDD, and by -212 ± 89, -83 ± 37, and -27 ± 18 cones/degree2/year, respectively, in eyes without SDD. The percentage of retinal loci with cone density lower than normal (Z score < -2) increased over the follow-up: from 42% at the baseline to 80% at the last visit in eyes with SDD and from 31% to 70% in eyes without SDD. CONCLUSIONS: AOSLO revealed cone photoreceptor loss in regions that appear otherwise unremarkable clinically. These findings may help explain the loss of mesopic sensitivity reported in these areas in eyes with intermediate AMD.