Deep Learning-Based Detection of Reticular Pseudodrusen in Age-Related Macular Degeneration on Optical Coherence Tomography.

Reticular pseudodrusen (RPD) signify a critical phenotype driving vision loss in age-related macular degeneration (AMD). Their detection is paramount in the clinical management of those with AMD, yet they remain challenging to reliably identify. We thus developed a deep learning (DL) model to segment RPD from 9,800 optical coherence tomography B-scans, and this model produced RPD segmentations that had higher agreement with four retinal specialists (Dice similarity coefficient [DSC]=0·76 [95% confidence interval [CI] 0·71-0·81]) than the agreement amongst the specialists (DSC=0·68, 95% CI=0·63-0·73; p <0·001). In five external test datasets consisting of 1,017 eyes from 812 individuals, the DL model detected RPD with a similar level of performance as two retinal specialists (area-under-the-curve of 0·94 [95% CI=0·92-0·97], 0·95 [95% CI=0·92-0·97] and 0·96 [95% CI=0·94-0·98] respectively; p ≥0·32). This DL model enables the automatic detection and quantification of RPD with expert-level performance, which we have made publicly available.

Severe Intraocular Inflammation After Intravitreal Injection of Faricimab: A Single-Site Case Series of Six Patients.

PURPOSE: To describe the patient characteristics and clinical course of severe intraocular inflammation (IOI) following intravitreal injection (IVT) of faricimab. DESIGN: Retrospective case series. METHODS: Case series at a single French academic center (Dijon University Hospital) where 263 patients were treated with faricimab IVT between January 9, 2024 and May 7, 2024. RESULTS: Over the 4-month period, a total of 1659 eyes (1338 patients) received anti-vascular endothelial growth factor (anti-VEGF) IVTs for a total of 3510 IVTs, of which 343 eyes (263 patients) received faricimab IVTs for a total of 971 IVTs. Overall, 6 pretreated eyes with neovascular age-related macular degeneration that were switched to faricimab developed severe unilateral IOI following faricimab IVT (1/162 injections [0.62%]), including 5 eyes presenting with a severe anterior and intermediate uveitis mimicking infectious endophthalmitis. All eyes were normotensive and presented with mild to moderate pain and predominantly moderate vitritis, associated with granulomatous keratic precipitates in 2 eyes and nonocclusive vasculitis in one eye. The clinical presentation, sterile vitreous sample culture, and rapid improvement with treatment made the diagnosis of infectious endophthalmitis unlikely. Four patients out of 6 did not recover their pre-IOI visual acuity, with an average visual loss of +0.2 logMAR. Two patients had positive antinuclear antibodies, including one with a history of cutaneous lupus. CONCLUSIONS: In this case series, we reported 6 cases of severe IOI after intravitreal faricimab over 4 months in a single French center with an estimated incidence rate of 0.6% per injection. Future real-world data will contribute to a better evaluation of the epidemiology of this rare inflammatory adverse event related to intravitreal faricimab.

Outcomes and Baseline Predictors of Failure in Primary Standalone Xen45 Gel Stent versus Trabeculectomy for Glaucoma.

PURPOSE: To compare safety, effectiveness, and baseline predictors of failure in standalone primary Xen45 gel stent (Xen) versus trabeculectomy (Trab) in glaucoma. DESIGN: Retrospective study. SUBJECTS: Subjects that underwent primary Xen or Trab augmented by mitomycin-C with at least 12 months follow-up. METHODS: Multinational observational study of eyes in the Fight Glaucoma Blindness international registry MAIN OUTCOME MEASURES: The primary outcome was success at 12 months defined by intraocular pressure (IOP) reduction ≥ 20% from baseline and ≤ threshold IOPs of 15, 18, and 21 mmHg with (qualified) or without (complete) medications and without secondary glaucoma surgery. Multivariable mixed effects Cox regression models were used to identify risk factors for failure in each cohort. RESULTS: A total of 701 eyes (Xen, 308; Trab, 393) of 596 subjects were included with baseline IOP being significantly higher (22.4 vs. 19.9 mmHg, P < 0.001) and baseline medications significantly lower in the Xen versus the Trab group (2.9 vs. 3.4, P < 0.001). Baseline visual field mean deviation was less severe in the Xen group (-9.47 vs. -13.04 dB, P < 0.001). The proportion of complete surgical success was significantly lower in the Xen versus Trab group across the 3 upper IOP limits at 12 months; 32% versus 52% at 15 mmHg, 37% versus 54% at 18 mmHg, and 39% versus 55% at 21 mmHg (P < 0.001). The incidence of postoperative numerical and symptomatic hypotony was lower in the Xen versus Trab group. In the Xen cohort, a higher failure rate was associated with Asian ethnicity (hazard ratio [HR], 1.97; 95% confidence interval (CI), 1.03-3.79) and use of oral acetazolamide at baseline (HR, 1.74; 95% CI, 1.13-2.70), whereas a lower failure rate was associated with diagnosis of ocular hypertension/open-angle glaucoma suspect (HR, 0.40; 95% CI, 0.20-0.82) and secondary open-angle glaucoma (HR, 0.46; 95% CI, 0.26-0.82). Exposure to prostaglandin analog was associated with greater failure in the Trab group (HR, 2.66; 95% CI, 1.18-6.01). CONCLUSIONS: There was significantly greater complete success at 12 months across all complete success definitions for Trab compared with Xen, whereas the rate of postoperative hypotony was significantly lower in the Xen group. Asian ethnicity and use of oral acetazolamide at baseline were associated with greater failure in Xen, whereas exposure to prostaglandin analog was associated with greater failure in Trab patients. Such baseline predictors of success and failure may help guide patient selection for subconjunctival minimally invasive glaucoma surgery in patients undergoing surgical intervention. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Treat-and-Extend Versus Pro re nata Regimens of Ranibizumab and Aflibercept in Neovascular Age-Related Macular Degeneration: A Comparative Study from Routine Clinical Practice.

INTRODUCTION: Anti-vascular endothelial growth factor (VEGF) is generally given using pro re nata or "treat-and-extend" (T&E) regimens for neovascular age-related macular degeneration (nAMD). Randomized clinical trials have reported that T&E is superior to Pro re nata (PRN), but results from clinical trials may not always be replicated in clinical practice. Real-world data comparing T&E and PRN regimens for nAMD are limited. The objective of this work was to report 24-month outcomes of PRN versus T&E regimens for ranibizumab and aflibercept to treat nAMD in routine clinical practice. METHODS: We conducted a retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project (FRB). Treatment-naïve eyes starting nAMD treatment with at least three injections using a T&E or PRN regimen were tracked by using the FRB. The primary outcome was the mean change in visual acuity (VA) measured by the number of letters read on a logarithm of the minimum angle of resolution chart at 2 years versus baseline. The secondary outcome was the number of injections at 2 years. RESULTS: From January 1, 2015 to January 31, 2019, 3313 eyes from 2948 patients with nAMD were included: 1243 eyes from 1065 patients were classified as PRN and 2070 eyes from 1935 patients started a T&E regimen. At 24 months, patients on the T&E regimen experienced significantly greater mean (95% confidence interval) improvement in VA than those on PRN (+ 4.2 [3.1, 5.2] vs. + 1.3 [0.1, 2.6] letters; p < 0.001), with more injections (14.9 standard deviation(SD) 4.3) vs. 9.8(SD 4.3); p < 0.001). CONCLUSIONS: Eyes treated with a T&E regimen had better VA outcomes from VEGF inhibitors than eyes treated PRN. This large real-world data assessment supports previous data from randomized clinical trials that the T&E regimen delivers better outcomes than PRN.

This study focused on comparing two methods of treating neovascular age-related macular degeneration, a common eye condition. The treatments used were ranibizumab and aflibercept. We looked at the reactive "pro re nata" method, where treatment is given sporadically and only when the condition reactivates, and the proactive "treat-and-extend" method, which aims to keep the disease inactive with the fewest treatments at regular intervals. The main aim was to determine which method provides the best vision outcomes over a 24-month period and the frequency of treatment required. We found that the treat-and-extend method resulted in a greater improvement in vision than the pro re nata method, although it did require more injections. This study highlights the effectiveness of the treat-and-extend method for neovascular age-related macular degeneration, suggesting it gets better outcomes despite requiring more injections.

Two-year outcomes of Xen 45 gel stent implantation in patients with open-angle glaucoma: real-world data from the Fight Glaucoma Blindness registry.

OBJECTIVE: To evaluate efficacy and safety outcomes of the Xen 45 gel stent implant over 24 months of follow-up. METHODS: A retrospective analysis of prospectively collected data from the Fight Glaucoma Blindness observational registry. Complete success (CS) was defined as intraocular pressure (IOP) reduction ≥20% from preoperative and an IOP ≤18 mm Hg and ≥6 mm Hg with no secondary procedure at 2 years and without IOP-lowering medications. Qualified success (QS) was defined similarly, allowing the use of IOP-lowering medications. RESULTS: The Xen 45 gel stent implant was implanted in 646 eyes of 515 patients. Preoperative IOP was 21.4±7.6 (mean±SD) mm Hg on 2.7±1.3 IOP-lowering medication and mean deviation was -10.2±8.4 dB. After 24-month follow-up, IOP was 16.8±7.3 mm Hg (mean reduction of 21.7%) on 1.2±1.4 IOP-lowering medications. CS and QS rates at 24 months were 26% and 48%, respectively. CS and QS were higher in the Xen stand-alone group (33% and 52%, respectively) than in the Xen+cataract group (16% and 42%, respectively). Bleb needling was performed in 28.4% of cases, and 18% underwent a secondary procedure. CONCLUSIONS: The Xen 45 gel stent implant offers acceptable long-term efficacy for the treatment of open-angle glaucoma. However, there is a significant rate of reoperation and needling, and outcomes are less effective if combined with cataract surgery.

Three-Year Outcomes of VEGF Inhibitors in Naive Branch Retinal Vein Occlusion: Fight Retinal Blindness!

PURPOSE: To evaluate the 3-year outcomes of VEGF inhibitors in the treatment of cystoid macular edema due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes. DESIGN: Multicenter, international, BRVO database study. SUBJECTS: Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting. METHODS: Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, central subfield thickness (CST), treatments, number of injections, and visits data was collected using a validated web-based tool. MAIN OUTCOME MEASURES: Visual acuity gain at 3 years in logarithm of the minimum angle of resolution letters. Secondary outcome measures included anatomical results, treatment pattern, and percentage of completers. A subgroup analysis by study drug was conducted for clinical outcomes. RESULTS: Mean adjusted VA change was +11 letters (95% confidence interval 9-13), mean adjusted change in CST was -176 µm (-193, -159). Median number of injections/visits was 16 of 24 at 3 years of follow-up. Most eyes received VEGF inhibitors exclusively (89%, n = 677) and as a monotherapy in 71% (n = 538). Few eyes were switched to steroids (11%, n = 83). Suspensions in treatment >180 days occurred in 26% of study eyes. Aflibercept showed greater CST reductions (-147 vs. -128 vs. -114 µm; P < 0.001) and significantly lower switching rates (14% vs. 38% vs. 33%; P < 0.001) compared with ranibizumab and bevacizumab, respectively. CONCLUSIONS: This international study of 3-year BRVO outcomes after starting treatment with VEGF inhibitors found adequate visual and anatomical results in routine clinical care. Visual outcomes were similar among the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

One-Year Anti-VEGF Therapy Outcomes in Diabetic Macular Edema Based on Treatment Intensity: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To compare 1-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal VEGF inhibitor injections were delivered. DESIGN: Cohort study. PARTICIPANTS: There were 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy from October 31, 2015 to October 31, 2021 from the Fight Retinal Blindness! international outcomes registry. METHODS: Eyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n = 1172) versus Group B with greater than the median (n = 1116). MAIN OUTCOME MEASURES: Mean visual acuity (VA) change after 12 months of treatment. RESULTS: The mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8-4.4) letters for eyes in Group A versus 5.2 (4.4-5.9) letters for eyes in Group B (P = 0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76 to -61) µm and -85 (-92 to -78) µm for eyes in Group A versus Group B, respectively (P = 0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (P < 0.001). Additionally, eyes that received more injections had a moderately greater CST reduction. CONCLUSIONS: This registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Initial response and 12-month outcomes after commencing dexamethasone or vascular endothelial growth factor inhibitors for retinal vein occlusion in the FRB registry.

To compare baseline characteristics, initial response and 12-month efficacy and safety outcomes in eyes with branch and central retinal vein occlusion (BRVO and CRVO) treated with dexamethasone implants (DEX) or anti-vascular endothelial growth factor (anti-VEGF) we performed a multi-centre, retrospective and observational study using Fight Retinal Blindness! Registry. Of 725 eligible eyes, 10% received DEX initially with very frequent adjunctive anti-VEGF (BRVO-DEX 49%, CRVO-DEX 60%). The primary outcome of mean adjusted change in VA at 12 months with DEX and anti-VEGF initiated groups were not statistically significantly different (BRVO: DEX + 6.7, anti-VEGF + 10.6 letters; CRVO: DEX + 2.8, anti-VEGF + 6.8 letters). DEX initiated eyes had fewer injections and visits than anti-VEGF initiated eyes. The BRVO-DEX eyes had greater initial mean changes in VA and central subfield thickness (CST) and achieved inactivity sooner than BRVO-anti-VEGF eyes. The mean CST after the first three months was above 350 µm in all but the BRVO-anti-VEGF group, suggesting undertreatment. In routine care DEX is uncommonly used when available as initial treatment of BRVO and CRVO requiring supplemental anti-VEGF within the first year. The 12-month outcomes were similar, but DEX initiated eyes had fewer injections and visits but more episodes of raised IOP Vs those starting anti-VEGF.

European Unmet Needs in the Management of Neovascular Age-Related Macular Degeneration in Daily Practice: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To evaluate the proportion, predictors, and outcomes of patients with neovascular age-related macular degeneration (nAMD) treated with a high burden of VEGF inhibitor intravitreal (IVT) injections after 2 years in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project, of patients treated in European centers. PARTICIPANTS: Treatment-naïve eyes (1 eye per patient) starting VEGF inhibitors for nAMD from January 2017 to March 2020 with 24 months of follow-up. We analyzed the following 3 treatment-burden groups defined by the mean interval of the 3 closest injections to the 24-month visit: (1) those with a high-treatment burden had injection intervals ≤ 42 days, (2) those with a low-treatment burden had injection intervals between 43 and 83 days; and (3) those with tolerable treatment burden had injection intervals between 84 and 365 days. METHODS: Multinomial regression was used to evaluate baseline risk predictors of patients requiring a high-treatment burden. MAIN OUTCOME MEASURES: The proportion of patients that experienced a high-treatment burden at 2 years and its predictors. RESULTS: We identified 2038 eligible patients completing 2 years of treatment (2038/3943 patients [60%]) with a median (quartile 1, quartile 3) of 13 (10, 17) injections. The proportion of patients with a high-treatment burden was 25% (516 patients) at 2 years. Younger patients (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.96-0.99; P < 0.01) were more likely to have high-treatment burden, whereas eyes with type 3 choroidal neovascular lesions at baseline were significantly less likely (OR, 0.26; 95% CI, 0.13-0.52; P < 0.01). Regarding type of fluid, patients with subretinal fluid only at baseline (OR, 3.85; 95% CI, 1.34-11.01; P = 0.01) and persistent active intraretinal (OR, 1.56; 95% CI, 1.18-2.06; P < 0.01) or subretinal fluid only (OR, 2.21; 95% CI, 1.52-3.21; P < 0.01) after the loading phase had a higher risk of high treatment burden at 2 years. CONCLUSIONS: High treatment burden is a common issue in routine clinical practice in Europe, with a quarter of patients requiring injections of conventional VEGF inhibitors every 6 weeks at 2 years and 40% discontinuing treatment within 2 years. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.