Faricimab in Neovascular AMD Complicated by Pigment Epithelium Detachment: An AI-Assisted Evaluation of Early Morphological Changes.

INTRODUCTION: This study investigates the early temporal changes in pigment epithelial detachment (PED) morphology following treatment with faricimab in patients with neovascular age-related macular degeneration (nAMD). Utilizing an artificial intelligence (AI)-assisted approach, we provide a detailed quantification and characterization of the dynamics of these morphological changes. METHODS: A prospective observational study was conducted on 22 eyes from 22 treatment-naïve patients with nAMD-associated PED (presenting either type 1 or type 3 macular neovascularization). Participants were administered intravitreal faricimab (6 mg) at baseline and at days 30, 60, and 90. Comprehensive ophthalmic evaluations and spectral-domain optical coherence tomography (SD-OCT) imaging were conducted at baseline and at seven additional follow-up visits on days 1, 7, 14, 30, 60, 90, and 120. An AI-based automated segmentation algorithm was utilized to precisely quantify changes in PED volume, alongside intraretinal (IRF) and subretinal fluid (SRF) volumes, at each time point. RESULTS: Treatment with faricimab resulted in a significant reduction in mean PED volume, with an average decrease of 12% at day 1, 29% at day 7, 51% at day 14, 68% at day 30, 72% at day 60, 79% at day 90, and 84% at day 120 (p < 0.0001 for all time points). Similarly rapid and marked reductions were noted in both mean IRF (23.5% at day 1, 90.7% at day 14) and SRF (14.4% at day 1, 91.2% at day 14) volumes. The study also showed a statistically significant improvement in best-corrected visual acuity (BCVA) over the follow-up period, correlating with the reduction in PED volume. CONCLUSION: Faricimab demonstrates early and significant efficacy in improving PED architecture in patients with nAMD. The rapid morphological improvements observed in this study suggest faricimab may represent a valid therapeutic option for PEDs associated with nAMD.

External dacryocystorhinostomy: A critical overview of the current evidence.

PURPOSE: External dacryocystorhinostomy (ext-DCR) is still considered the gold standard in the treatment of distal lacrimal duct obstruction. Despite an overall high success rate, some patients do relapse after surgery and the ideal perioperative management has not been identified yet. The purpose of this study is to critically discuss the published evidence in the last five years on the medical and surgical management of external dacryocystorhinostomy. Furthermore, the drawbacks of the available literature and the perspectives in this field will be also highlighted. METHODS: Systematic review of the literature in the last 5 years by using PubMed and Google Scholar. RESULTS: A total of 64 articles were included. Many technical modifications and surgical refinements have been proposed but a formal comparison among the various techniques is hampered by methodological heterogeneity. The use of local anesthesia, and the perioperative adjunctive techniques to reduce the risk of restenosis are also gaining popularity but the level of evidence remains weak. CONCLUSION: Ext-DCR offers satisfactory clinical outcomes even though there are many gray areas that need to be addressed in future high-quality studies.

Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial.

BACKGROUND: Intravitreal aflibercept 8 mg could improve treatment outcomes and provide sustained disease control in patients with neovascular age-related macular degeneration (nAMD), with extended dosing compared with aflibercept 2 mg. METHODS: PULSAR is a phase 3, randomised, three-group, double-masked, non-inferiority, 96-week trial conducted across 223 sites worldwide. Adults with nAMD were randomised 1:1:1 to aflibercept 8 mg every 12 weeks (8q12), aflibercept 8 mg every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups. From week 16, patients in the aflibercept 8 mg groups had their dosing interval shortened if pre-specified dose regimen modification criteria denoting disease activity were met. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48. All patients with at least one dose of study treatment were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04423718) and is ongoing. FINDINGS: Of 1011 patients randomised to aflibercept 8q12 (n=336), 8q16 (n=338), or 2q8 (n=337) between Aug 11, 2020, and July 30, 2021, 1009 patients received study treatment (aflibercept 8q12 n=335; aflibercept 8q16 n=338; and aflibercept 2q8 n=336). Aflibercept 8q12 and 8q16 showed non-inferior BCVA gains versus aflibercept 2q8 (mean BCVA change from baseline +6·7 [SD 12·6] and +6·2 [11·7] vs +7·6 [12·2] letters). The least squares mean differences between aflibercept 8q12 versus 2q8 and 8q16 versus 2q8, respectively, were -0·97 (95% CI -2·87 to 0·92) and -1·14 (-2·97 to 0·69) letters (non-inferiority margin at 4 letters). The incidence of ocular adverse events in the study eye was similar across groups (aflibercept 8q12 n=129 [39%]; aflibercept 8q16 n=127 [38%]; and aflibercept 2q8 n=130 [39%]). INTERPRETATION: Aflibercept 8 mg showed efficacy and safety with extended dosing intervals, which has the potential to improve the management of patients with nAMD. FUNDING: Bayer AG and Regeneron Pharmaceuticals.

Submacular hemorrhage during neovascular age-related macular degeneration: a meta-analysis and meta-regression on the use of tPA and anti-VEGFs.

BACKGROUND: Submacular hemorrhage (SMH) associated with neovascular age-related macular degeneration (nAMD) precipitates rapid visual decline and impacts quality of life. Treatments vary, but combined recombinant tissue plasminogen activator (tPA) and anti-vascular endothelial growth factor (anti-VEGF) therapy has gained prominence as a viable treatment option. OBJECTIVES: This study aims to evaluate the efficacy of the combination of tPA and anti-VEGF. METHODS: We conducted a systematic review meta-analysis following PRISMA guidelines, focusing on studies examining tPA and anti-VEGF therapy in SMH secondary to nAMD. Outcomes measured were change in best-corrected visual acuity (BCVA) and success rate of SMH displacement. Meta-regression assessed the relative efficacy of intravitreal and subretinal delivery. RESULTS: Out of 257 initial reports, 22 studies involving 29 patient populations met inclusion criteria. Our analysis showed significant improvement in BCVA and a high rate of successful SMH displacement with combined tPA and anti-VEGF therapy. No significant differences were found between subretinal and intravitreal tPA administration. Furthermore, when evaluating the effects of subretinal versus intravitreal anti-VEGF administration in patients treated with subretinal tPA, the results indicated similar efficacy. CONCLUSIONS: Combined tPA and anti-VEGF therapy is effective in managing SMH in nAMD patients, significantly improving visual acuity and SMH displacement. The location of tPA and anti-VEGF delivery did not significantly impact outcomes.

Update on coronavirus disease 2019: Ophthalmic Manifestations and Adverse Reactions to Vaccination.

The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 was one of the most devastating public health issues in recent decades. The ophthalmology community is as concerned about the COVID-19 pandemic as the global public health community is, as COVID-19 was recognized to affect multiple organs in the human body, including the eyes, early in the course of the outbreak. Ophthalmic manifestations of COVID-19 are highly variable and could range from mild ocular surface abnormalities to potentially sight and life-threatening orbital and neuro-ophthalmic diseases. Furthermore, ophthalmic manifestations may also be the presenting or the only findings in COVID-19 infections. Meanwhile, global vaccination campaigns to attain herd immunity in different populations are the major strategy to mitigate the pandemic. As novel vaccinations against COVID-19 emerged, so were reports on adverse ophthalmic reactions potentially related to such. As the world enters a post-pandemic state where COVID-19 continues to exist and evolve as an endemic globally, the ophthalmology community ought to be aware of and keep abreast of the latest knowledge of ophthalmic associations with COVID-19 and its vaccinations. This review is a summary of the latest literature on the ophthalmic manifestations of COVID-19 and the adverse ophthalmic reactions related to its vaccinations.