Search Results (68)

Background: Neovascular age-related macular degeneration (nAMD) remains a leading cause of irreversible central vision loss. Although anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed management, pivotal trials enrolled exclusively treatment-naïve patients, leaving clinicians without pooled evidence to guide switching decisions in previously treated eyes. This systematic review and meta-analysis assessed real-world visual, anatomical, durability, and safety outcomes following switching to aflibercept 8 mg in previously treated nAMD. Methods: Following PRISMA 2020 guidelines, we searched PubMed, Embase, Web of Science, CENTRAL, Scopus, and Google Scholar through April 2026. Studies reporting switching to aflibercept 8 mg with change in best-corrected visual acuity (BCVA), central subfield thickness (CST), or treatment interval were included. Continuous outcomes were pooled using random-effects models with Hartung–Knapp–Sidik–Jonkman adjustment; proportions were estimated using generalized linear mixed models. Methodological quality was evaluated using the JBI Critical Appraisal Checklist for Case Series. Certainty of evidence was assessed using GRADE. The protocol was registered with PROSPERO (CRD420261371334). Results: Twenty-one studies met inclusion criteria. BCVA remained stable (WMD: −0.017 logMAR; 95% CI: −0.027 to −0.007; +0.83 ETDRS letters; I² = 0%). CST decreased significantly (WMD: −21.5 µm; 95% CI: −29.3 to −13.7; I² = 56.0%), and treatment intervals extended by +1.79 weeks (95% CI: +1.32 to +2.27; I² = 74.3%). Intraretinal and subretinal fluid each resolved in 37.5% of eyes. Intraocular inflammation was rare across 9959 treated eyes, though this pool was not restricted to switched eyes, with no confirmed retinal vasculitis. Sensitivity analyses confirmed robustness across all co-primary estimates. GRADE certainty was low for BCVA and very low for CST and treatment interval. Conclusions: Low-certainty evidence suggests that switching to aflibercept 8 mg preserves visual acuity, while very-low-certainty evidence suggests reductions in central subfield thickness and modest extension of treatment intervals. Intraocular inflammation was rare, though safety denominators included non-switch eyes. These findings provide preliminary pooled estimates to inform switch decisions in previously treated eyes. Full article

Syphilitic panuveitis is a severe and diagnostically highly challenging manifestation of ocular syphilis. Its predominant posterior-segment involvement and its tendency to mimic noninfectious or viral uveitis may delay etiologic recognition and increase the risk of permanent vision loss. Rhegmatogenous retinal detachment (RRD) is a rare but vision-threatening complication that likely reflects advanced, inflammation-induced disruption of the vitreoretinal interface. A narrative literature review was conducted using the PubMed, Scopus, and Web of Science databases (January 2000 to 10 September 2025). Studies addressing the clinical presentation, imaging findings, pathophysiology, and management of syphilitic panuveitis and associated rhegmatogenous retinal detachment were analyzed. Infectious mimickers were also presented, with particular emphasis on West Nile virus (WNV). Evidence was synthesized qualitatively. Posterior uveitis and panuveitis are one of the most common ocular manifestations of syphilis. Posterior segment involvement in ocular syphilis is frequently bilateral, typically presenting with dense vitritis, retinal vasculitis, and optic neuropathy. RRD is a rare presenting complication, most often developing in areas of prior inflammatory retinitis and arising due to retinal necrosis, persistent vitreoretinal traction, and early proliferative vitreoretinopathy, which increases surgical complexity and may limit functional recovery. HIV coinfection often modifies disease severity. In relevant endemic or seasonal settings, WNV-associated ocular inflammation represents an important diagnostic pitfall. Syphilitic panuveitis should be considered early in patients presenting with unexplained posterior uveitis or panuveitis. Routine testing for syphilis and HIV in the uveitic laboratory palette, together with targeted evaluation for infectious mimickers, is essential to reduce diagnostic delay and avoid inappropriate immunosuppression. RRD should be recognized as a marker of advanced, inflammation-induced vitreoretinal interface damage requiring timely antimicrobial therapy and early involvement of vitreoretinal surgery. Full article

This pharmacovigilance study drew upon the U.S. Food and Drug Administration’s Adverse Event Reporting System (FAERS) database to compare the reporting patterns of ocular and systemic adverse events (AEs) for the 2 mg (standard-dose [SD]) and 8 mg (high-dose [HD]) formulations of aflibercept given for any ocular indication. Disproportionality analysis, including reporting odds ratios (ROR), was used to compare each dose individually to the background reporting rate for the AE. Statistical significance of the RORs was evaluated using Bonferroni correction, alongside signal detection based on Evans criteria, and Bayesian information components. The Breslow–Day test was used to conduct a head-to-head comparison of RORs between each dose. We identified 953 SD and 314 HD AE reports within the 750-day period after the approval of HD by the U.S. Food and Drug Administration (FDA; 8/18/2023). Compared to SD, HD had a higher ROR for endophthalmitis (HD: ROR 767.56 [95% CI, 466.11–1263.95]; SD: ROR 331.64 [95% CI, 216.71–507.51]), eye inflammation (HD: ROR 118.45 [95% CI, 55.85–251.20]; SD: 43.98 [95% CI, 21.87–88.44]), retinal vasculitis (HD: ROR 769.87 [95% CI, 337.13–1758.04]; SD: ROR 124.80 [95% CI, 39.67–392.63]), and systemic vasculitis (HD: ROR 28.40 [95% CI, 14.63–55.14]; SD: ROR 4.05 [1.52–10.82]). These results, based on FAERS, indicate associations rather than causal relationships. Further studies are needed to quantify the absolute risks and elucidate the mechanisms underlying differences in safety signals, if any. Full article

Background/Objectives: The PHOTON trial established the efficacy of aflibercept 8 mg using fixed-interval dosing in treatment-naïve patients; however, real-world evidence regarding pro re nata (PRN) regimens in switch cases remains limited. This pilot study evaluated the short-term efficacy and safety of switching to aflibercept 8 mg with PRN dosing in eyes with DME. Methods: This retrospective study included 20 eyes from 12 patients with DME who switched to aflibercept 8 mg and were followed for 6 months. Patients received initial induction doses (1–3 injections based on predetermined anatomical and functional criteria) followed by PRN dosing based on clinical findings. Primary outcomes were changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). Treatment intervals and injection frequency were also analyzed. Results: Mean logMAR BCVA was maintained from baseline (0.242 ± 0.252) throughout the follow-up period: 0.164 ± 0.218 at 1 month, 0.138 ± 0.241 at 2 months, 0.145 ± 0.204 at 3 months, 0.143 ± 0.181 at 4 months, 0.149 ± 0.166 at 5 months, and 0.180 ± 0.224 at 6 months. No statistically significant changes in BCVA from baseline were observed at any time point. Mean CRT decreased from baseline (369.6 ± 138.3 μm) at all follow-up time points: 251.5 ± 82.1 μm at 1 month, 269.1 ± 104.5 μm at 2 months, 255.8 ± 67.8 μm at 3 months, 275.2 ± 76.6 μm at 4 months, 301.4 ± 81.2 μm at 5 months, and 302.7 ± 86.8 μm at 6 months. Statistically significant reductions in CRT were observed at 1 through 4 months (1 month: p = 0.000010; 2 months: p = 0.000243; 3 months: p = 0.000035; 4 months: p = 0.000597), whereas the reductions at 5 months (p = 0.0317) and 6 months (p = 0.0424) were not statistically significant. The mean number of injections over 6 months was 1.45 ± 1.05 (median 1; range 1–4), with 70% of eyes achieving treatment intervals ≥ 4 months. Five eyes (25%) required only the switching dose with no additional treatment during follow-up. No intraocular inflammation or retinal vasculitis was observed. Conclusions: Switching to aflibercept 8 mg with PRN dosing provided sustained anatomical improvement and maintained visual acuity in DME, with one quarter of the cases maintaining these outcomes with only a single additional injection. These real-world findings from a pilot study suggest that the PRN approach appears feasible and effective in real-world practice, offering a practical treatment option that may help reduce treatment burden while maintaining disease control. Full article

Background/Objectives: Diabetic macular edema (DME) are major causes of visual impairment worldwide, with vascular endothelial growth factor (VEGF) playing a central role in disease pathogenesis. Intravitreal anti-VEGF therapy is the current standard of care for center-involving DME. Methods: This narrative review summarizes and compares the pharmacological properties, clinical efficacy, safety, and real-world performance of aflibercept and brolucizumab in the treatment of DME, based on randomized controlled trials and observational studies published between 2014 and 2025. Results: Both agents demonstrate significant improvements in visual acuity and retinal anatomy. Brolucizumab has shown non-inferior visual outcomes and, in several studies, greater reductions in central retinal thickness with the potential for extended dosing intervals, suggesting reduced treatment burden. However, post-marketing data have identified an increased risk of intraocular inflammation, including retinal vasculitis and retinal vascular occlusion, associated with brolucizumab, which has influenced its clinical use. Conclusions: Both aflibercept and brolucizumab are effective anti-VEGF therapies for diabetic macular edema, but they differ in durability and safety considerations. Aflibercept remains a reliable first-line option for many patients, while brolucizumab may be considered in carefully selected cases where treatment burden is a priority. Individualized treatment selection based on clinical characteristics, patient preferences, and safety considerations is essential for optimizing long-term outcomes. Full article

Experimental autoimmune uveitis (EAU) in rats is a pivotal model for understanding the immunological mechanisms of human uveitis and developing therapies. In humans, optical coherence tomography (OCT) allows for the in vivo detection of characteristic findings in active uveitis, as well as sequelae of inflammation. The objective of this study was to correlate OCT findings in patients with uveitis with retinal histologies from two rat models of EAU caused by T cells with different autoantigen specificities and well-known underlying immunological pathomechanisms. Patients with various noninfectious uveitis subtypes underwent imaging using an ultra-widefield swept source or conventional OCT. Histological cryosections from rat eyes with experimental autoimmune uveitis were stained for T cell and/or macrophage markers. Typical human OCT findings were reproduced in the experimental animal model. Hyperreflective signals observed on OCT corresponded to lymphocyte infiltration in histological sections. This infiltration was typically found as vasculitis in the perivascular regions and snowballs in the posterior hyaloid. There was lymphocyte and macrophage infiltration of the retina through the retinal vessels and the retinal pigment epithelium. Comparing in vivo OCT imaging of human uveitis with corresponding histologies from rat models improves our understanding of the type of inflammation, extent of tissue destruction, and immunopathogenesis. Full article

Varicella-Zoster Virus (VZV) is one of the most important pathogens in ophthalmology. Reactivation may involve the adnexa (blepharoconjunctivitis, pseudomembranous conjunctivitis), cornea (dendritic keratitis, nummular and necrotizing stromal keratitis, disciform endotheliitis, neurotrophic ulcers, mucous-plaque keratitis) and sclera (episcleritis, anterior scleritis). Uveal inflammation ranges from anterior uveitis—with iris atrophy, trabeculitis-induced glaucoma and complicated cataract—to posterior necrotizing syndromes: acute retinal necrosis in immunocompetent hosts and progressive outer retinal necrosis in immunosuppressed patients, often complicated by occlusive vasculitis, macular edema, retinal detachment and phthisis. Optic nerve and cranial nerve involvement (optic neuritis, neuroretinitis, III/IV/VI palsies) and orbital inflammation may occur even without cutaneous signs (“zoster sine herpete”), making PCR-based intraocular diagnostics essential. Management relies on early, high-dose antivirals (acyclovir or valacyclovir), judicious corticosteroids and timely surgical intervention when required. Universal childhood varicella vaccination and recombinant zoster vaccination in adults ≥50 years have reduced VZV incidence and ocular complications in settings with high vaccine coverage, though rare post-vaccine keratitis or uveitis underscore the need for ongoing vigilance. In this review, we synthesize current knowledge on varicella-zoster virus ocular disease, with a focus on host–pathogen interactions that drive both injury and defense. Full article

Background/Objectives: To evaluate the incidence, characteristics, and clinical outcomes of intraocular inflammation (IOI) associated with intravitreal faricimab (IVF) in patients with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Methods: Following PRISMA guidelines, a comprehensive search of PubMed, Web of Science, Scopus, Embase, and CENTRAL databases was performed from their inception to February 2025. Using the random-effects model, weighted proportions, standardized mean differences, and weighted log odds ratios (OR) were pooled and calculated. A two-tailed p-value of <0.05 was considered statistically significant. The χ² (z) test and the Higgins I² test were used to assess studies heterogeneity. Results: We conducted a systematic review and meta-analysis of 24 studies (4761 patients; 5652 eyes). The most common diagnoses were nAMD (n = 4782, 94.6%) and DME (n = 845, 37.1%). The pooled proportion for IOI incidence in eyes receiving IVF was 3.0% (95% CI: 1.0–6.0). The odds of developing IOI did not differ significantly between the DME and nAMD groups (OR: 1.13, p = 0.78). Unspecified IOI was the most common sign (n = 210, 2.9% [95% CI: 1.2–7.3]), followed by anterior uveitis (n = 80, 1.9% [95% CI: 0.1–34.8]), vitritis (n = 63, 2.9% [95% CI: 0.2–32.1]), retinal hemorrhage (n = 27, 0.7% [95% CI: 0.0–15.3]), and endophthalmitis (n = 8, 0.5% [95% CI: 0.3–1.1]). Conclusions: While IVF demonstrates therapeutic efficacy, our findings highlight a clinically relevant risk of IOI. We, therefore, recommend vigilant clinical monitoring in patients receiving this therapy. Full article

Objectives: To evaluate the utility of widefield montage swept-source OCT angiography (SS-OCTA) in detecting and monitoring retinal vasculitis beyond the posterior pole. Methods: Prospective case series. Patients with clinically diagnosed retinal vasculitis imaged with a same-day widefield SS-OCTA montage and ultra-widefield fluorescein angiography (FA) at 2 or more visits. Five overlapping 12 × 12 mm SS-OCTA scans were acquired to provide imaging of the posterior pole and each quadrant of the near periphery. A color retinal thickness map was superimposed on each 12 × 12 mm en-face flow scan with a customized segmentation to demonstrate perivascular retinal thickening. A composite “montage” image was then created by combining the scans to allow for analysis of the macula and near periphery. Findings were then correlated with the same-day FA, the current “gold standard” diagnostic tool for retinal vasculitis, to assess diagnostic efficacy. Results: SS-OCTA demonstrated perivascular thickening in both the posterior pole and peripheral retina in 30 eyes of 16 patients and was found to be an effective diagnostic tool with good correlation to findings on fluorescein angiography for monitoring retinal vasculitis over time. Conclusions: The widefield SS-OCTA montage expands the visualization of retinal vasculitis into the near periphery, providing a noninvasive tool that may complement FA in the diagnosis and monitoring of retinal vasculitis. Full article

Background: Central retinal artery occlusion (CRAO) is an ophthalmic emergency attributed to a vessel occlusion with an embolus or a thrombus and may occur during the hypercoagulable state, inflammation, or vasculitis. CRAO may occur in children; however its incidence is very rare. Most pediatric cases have detectable etiologies. Case Presentation: We describe the case of an otherwise-healthy six-year-old female, who presented with the sudden and complete vision loss of the left eye lasting over twelve hours after a six-day chickenpox exanthema, followed by a high fever. All the ophthalmological, laboratory, and instrumental investigations led to the diagnosis of a left CRAO. Laboratory testing was unremarkable except for the transient elevation of D dimers (1363 µg/L), IgM anticardiolipin antibodies (238.5 CU), and IgG anti-beta-2 glycoprotein-1 antibodies (76.1 CU) on admission. Thrombolytic treatment was not exerted because of late presentation to the hospital. Treatment with steroids, antiviral medications, antibiotics, and anticoagulants was obtained, but the visual outcome was poor during the hospitalization and at the last follow-up. We could not ascribe features of this case to any etiological condition apart from the documented ongoing chickenpox infection. Conclusions: This is the first case report of CRAO in a child with transient aPL elevation and acute chickenpox infection. Full article

Background/Objectives: Brolucizumab is a humanized single-chain antibody fragment with a molecular weight of approximately 26 kilodaltons (scFv, ~26 kDa) targeting all VEGF-A isoforms. Intravitreal brolucizumab (6 mg) is FDA-approved for neovascular age-related macular degeneration (nAMD) (2019) and diabetic macular edema (DME) (2022). We systematically review the literature on brolucizumab for nAMD and DME, focusing on efficacy, safety, pharmacokinetics, real-world outcomes, and cost-effectiveness in adult and pediatric patients. Methods: Our method involves a comprehensive literature search of PubMed, Embase, Scopus, Cochrane, and related databases (through late 2024) using terms including “brolucizumab,” “Beovu,” “neovascular AMD,” “diabetic macular edema,” “safety,” “pharmacokinetics,” and “pediatric.” High-quality clinical trials, meta-analyses, regulatory documents, and real-world studies were prioritized. Results: In pivotal Phase III trials (HAWK/HARRIER for nAMD), brolucizumab 6 mg demonstrated non-inferior visual acuity (VA) gains to aflibercept, with >50% of eyes maintained on 12-week dosing and greater retinal fluid reduction. In DME trials (KESTREL/KITE), brolucizumab was similarly non-inferior to aflibercept for VA and showed superior anatomic drying, with 33–48% of eyes maintained on ≥12-week intervals. However, brolucizumab use has been associated with intraocular inflammation (IOI), retinal vasculitis, and vascular occlusion: clinical trials and post hoc analyses reported higher rates of these events than comparator agents. Real-world cohorts found IOI in ~4–10% of treated eyes, often occurring early (within 3 months) after initiation. Conclusions: In conclusion, Brolucizumab is an effective anti-VEGF option for nAMD and DME, providing durable anatomic control with fewer injections. Non-inferior vision outcomes and superior fluid resolution have been demonstrated. However, it carries a distinct risk of IOI and occlusive vasculitis, necessitating careful patient selection, dosing, and monitoring. Full article

Neovascular age-related macular degeneration (nAMD) is a significant cause of vision loss globally, with intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents forming the cornerstone of treatment. Despite advances, the considerable treatment burden associated with frequent injections and the occurrence of suboptimal responses in some patients highlight an ongoing need for more effective and durable therapeutic options. Faricimab, a bispecific antibody that targets both VEGF-A and angiopoietin-2 (Ang-2), has been developed to address these challenges by promoting greater vascular stability and potentially offering extended treatment intervals. This review synthesizes current evidence from pivotal clinical trials (TENAYA/LUCERNE), real-world studies, meta-analyses, and case reports on the efficacy, durability, and safety of intravitreal faricimab for nAMD. Key efficacy outcomes, such as changes in best-corrected visual acuity and anatomical parameters (e.g., central subfield thickness, retinal fluid dynamics, pigment epithelial detachment morphology), are evaluated in both treatment-naïve and previously treated/treatment-resistant nAMD populations. The safety profile, including intraocular inflammation, retinal vasculitis, retinal pigment epithelium tears, and systemic adverse events, is also comprehensively addressed. Faricimab has demonstrated non-inferior visual outcomes compared to aflibercept 2 mg, alongside robust anatomical improvements and a significant potential for reduced treatment frequency, thereby lessening patient and healthcare system burden. While generally well-tolerated, ongoing monitoring for adverse events remains essential. Full article

This comprehensive review examines the multifaceted interactions between influenza viruses and the ocular system, integrating viral pathogenesis, clinical manifestations, and vaccine-related considerations. Influenza A subtypes (H7, H1N1, H5N1) and influenza B viruses induce a spectrum of ocular complications, from mild conjunctivitis—predominantly associated with H7 avian strains—to sight-threatening disorders like uveal effusion syndrome, acute macular neuroretinopathy, and optic neuritis. Experimental evidence confirms viral replication in human corneal and retinal cells, with H7N7 demonstrating unique tropism for ocular tissues via NF-κB-mediated inflammatory pathways. Clinical cases highlight direct viral invasion and immune-mediated mechanisms, such as Vogt–Koyanagi–Harada disease exacerbation and retinal vasculitis. Rarely, influenza vaccination has been linked to oculorespiratory syndrome, uveitis, and demyelinating events, though large-scale epidemiological studies (e.g., WHO safety reports) confirm vaccines’ favorable risk–benefit profile, distinguishing true adverse events from temporal associations. This synthesis emphasizes the need for ophthalmologists to prioritize surveillance during influenza seasons, integrating diagnostic tools like conjunctival RT-PCR and optical coherence tomography. Future research should focus on defining viral receptor-binding mechanisms in ocular tissues and developing targeted therapies for severe retinopathies, while reinforcing vaccination as a cornerstone of public health despite rare ocular risks. Full article

Dengue virus infection frequently involves the eye, manifesting with hemorrhages, uveal inflammation, retinal vascular changes and maculopathy. These ocular manifestations may arise during the acute febrile phase or emerge weeks later. Studies from endemic regions report that up to one-quarter of hospitalized patients develop eye-related symptoms. Furthermore, studies confirm a higher risk of new uveitis cases following dengue infection. Breakdown of the blood–ocular barrier—driven by antibody-mediated enhancement, complement activation and release of inflammatory mediators—leads to vascular leakage, tissue injury and ischemia. Diagnosis relies on clinical examination supplemented by imaging (OCT, angiography) and laboratory confirmation of dengue. Mild anterior inflammation often responds to topical steroids, while sight-threatening posterior disease requires systemic corticosteroids and, in refractory cases, immunomodulatory agents. Visual outcomes depend on the initial severity; anterior uveitis typically resolves without sequelae, whereas vasculitis or foveal involvement may leave lasting deficits. This review integrates the current understanding of dengue-related eye disease, emphasizing its varied presentations and the importance of early recognition. Further research into targeted, mechanism-based therapies is needed to optimize visual outcomes. Full article

Syphilis is a systemic infection with a broad spectrum of ocular involvement that can affect every segment of the eye. Clinical presentations range from interstitial keratitis, conjunctivitis, episcleritis, and scleritis to anterior, intermediate, and posterior uveitis; acute syphilitic posterior placoid chorioretinitis; retinitis; retinal vasculitis; neuroretinitis; optic neuritis; exudative retinal detachment; and optic nerve dysfunction. These manifestations may occur at any stage of infection and are frequently nonspecific, contributing to diagnostic delays. Diagnosis requires a high index of suspicion and is established by combined non-treponemal and treponemal serologic testing, with cerebrospinal fluid analysis when neurosyphilis is suspected. Multimodal imaging, including optical coherence tomography, fluorescein angiography, fundus autofluorescence, and visual field testing, enhances the detection of subclinical and atypical diseases. Management mandates prompt intravenous penicillin G, with adjunctive corticosteroids to mitigate Jarisch–Herxheimer reactions and control inflammation; ceftriaxone or doxycycline serve as alternatives for penicillin-allergic patients. Long-term follow-up with serial serologies and neurologic evaluation is essential to detect relapse or progression to neurosyphilis. Despite effective therapy, diagnostic delays contribute to irreversible visual loss in a significant proportion of cases. This review integrates current knowledge on ocular syphilis, emphasizing its varied presentations and the importance of early recognition to prevent vision-threatening complications, and calls for multidisciplinary, mechanism-based research to optimize outcomes. We conducted a literature search in Pubmed and Embase for articles published between 2000 and 2025, using the terms “ocular syphilis,” “syphilitic uveitis,” and “neurosyphilis,” with a focus on epidemiology, clinical features, diagnostics, therapeutics, and co-infections. Full article