Search Results (151)

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

Backgrounds/Objectives: Trabeculectomy is the gold standard for glaucoma drainage surgery, but it is associated with a risk of sight-threatening complications. The PreserFlo MicroShunt (PF) is a less invasive alternative that aims to reduce complications and simplify post-operative care. This study aimed to compare the effectiveness and safety of PF to trabeculectomy in the management of glaucoma. Methods: This was a retrospective cohort analysis of 95 eyes (48 PF, 47 trabeculectomy) from a single-center private practice in Brisbane, Australia. Data were collected from November 2017 to January 2024. Primary outcomes included intraocular pressure (IOP) and the number of medications. Secondary outcomes included best-corrected visual acuity (BCVA) and complications. Inverse probability of treatment weighting (IPTW) was applied to baseline covariates, and weighted regression and Cox proportional hazards models were then used to estimate treatment effects. Results: The two groups had comparable patient characteristics, although the PF group was older with worse visual field mean deviation. At 12 months, both procedures significantly reduced IOP and medications; however, differences were not statistically significant between groups (2.9 mmHg; 95%CI: −2.0, 7.9; p = 0.303, and 0.4; 95%CI: −0.13, 0.96; p = 0.138, respectively). The estimated probabilities of qualified success were comparable (74.9% PF vs. 72.5% trabeculectomy). Intra-operative stenting in PF eyes eliminated early post-operative hypotony. The incidence of open surgical revision in the PF group vs. the trabeculectomy group was 14.6% vs. 2.1% (p = 0.059, respectively). PF was associated with faster post-operative inflammation resolution (hazard ratio: 6.3; 95%CI: 2.8, 14.5; p < 0.001). Conclusions: Both PF and trabeculectomy are effective for glaucoma management. PF is a less invasive procedure with a lower rate of early hypotony when stented. Trabeculectomy has a tendency for lower IOP reduction and less requirement for open revision, although this did not reach statistical significance. This highlights the need for longer-term studies and improved techniques, such as more effective anti-fibrotic strategies. Full article

Background: This study aimed to evaluate the short-term outcomes of micropulse transscleral cyclophotocoagulation (MP-TSCPC) using the VITRA 810 in Japanese patients, focusing on intraocular pressure (IOP), medication score, complications, and ciliochoroidal effusion (CE). Methods: We retrospectively reviewed 37 eyes of 34 patients treated between March 2024 and March 2025. Postoperative IOP, glaucoma medication score, complications, and CE assessed by anterior segment OCT were analyzed. IOP changes were compared between CE-positive and CE-negative groups. Results: The mean preoperative IOP was 22.8 ± 7.1 mmHg, which decreased to 13.3 ± 6.8 mmHg at 1 week, 14.9 ± 7.4 mmHg at 1 month, 14.9 ± 5.8 mmHg at 3 months, and 15.0 ± 5.2 mmHg at 6 months (all p < 0.05 vs. baseline). CE was observed in 22 eyes (59.4%) and was associated with greater IOP reduction at 1 week and 1 month. Complications included mydriasis (24.3%), anterior chamber inflammation (24.3%), cystoid macular edema (5.4%), decreased visual acuity (8.1%), and phthisis bulbi (2.7%). Conclusions: VITRA 810 MP-TSCPC achieved significant short-term IOP reduction in Japanese patients. CE was linked to greater early IOP lowering. While generally safe, rare but severe complications such as phthisis bulbi require close monitoring. Full article

Background: The increasing prevalence of high-fat diets is associated with a rise in metabolic and neurodegenerative diseases. The retina and retinal pigment epithelium are metabolically active tissues exposed to oxidative stress, making them particularly vulnerable to lipid excess. Materials and Methods: A systematic literature review was conducted covering years until 2025 inclusive. Results: High-fat diets lead to cholesterol accumulation and lipid metabolism disturbances in the retina, retinal pigment epithelium, and ocular vessels. They activate inflammatory and oxidative stress pathways, resulting in structural and functional damage. Omega-3 deficiency exacerbates inflammation, while supplementation improves the tear film stability, corneal epithelial function, intraocular pressure regulation, and exerts neuroprotective effects. Conclusions: High-fat diets represent a significant risk factor for ocular diseases by disrupting lipid metabolism, enhancing inflammation, and inducing oxidative stress. Omega-3 fatty acid supplementation reduces inflammation and supports ocular functions. Full article

Background: Macular edema (ME) secondary to retinal vein occlusion (RVO) is a significant cause of vision impairment. Many patients show suboptimal responses to anti-vascular endothelial growth factor (anti-VEGF) monotherapy, prompting the exploration of alternative treatments. Faricimab is a bispecific antibody that targets VEGF-A and angiopoietin-2. We report 9-month real-world outcomes of switching to faricimab in therapy-resistant RVO-associated ME. Methods: In this retrospective study at a single tertiary center, patients with persistent or recurrent ME despite prior treatments (ranibizumab, aflibercept, or dexamethasone implant) were switched to faricimab. All eyes received a loading phase of four monthly faricimab injections, followed by a treat-and-extend regimen individualized per response. Key outcomes included best-corrected visual acuity (BCVA, logMAR), the central subfield thickness (CST, μm), and the intraretinal fluid (IRF) status on optical coherence tomography, assessed from the baseline (month 0, mo0) through the loading phase (mo1–mo3) and at month 9 (mo9). Results: Nineteen eyes (19 patients, mean age 64.8 years) were analyzed. The median BCVA improved from 0.20 to 0.00 logMAR by month 3 (p < 0.01) and was maintained at month 9. The median CST decreased from 325 μm at the baseline to 285 μm at month 3 (p < 0.01) and remained at 285 μm at month 9. IRF was present in 100% of eyes at the baseline, 26% at month 3, and 26% at month 9 (p < 0.01 for the baseline vs. month 9). Among eyes previously on anti-VEGF therapy (n = 14), the median treatment interval increased from 45.50 days at the baseline to 56.50 days at month 9 (p = 0.01; δ = 0.86). No intraocular inflammation or other adverse events were observed in this cohort over nine months. Conclusions: In this retrospective series, switching to faricimab was associated with improvements in vision and retinal anatomy that were maintained over 9 months; injection intervals were extended in a subset of eyes. These exploratory findings warrant confirmation in larger, controlled studies to define long-term effectiveness, safety, and dosing strategies. 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

Background/Objectives: We report the development of a novel intraocular sustained-release implantable pharmaceutical formulation, designed to be placed in the anterior chamber of the eye after cataract surgery. The device is intended to reduce postoperative inflammation, and to prevent opportunistic bacterial infections that may lead to endophthalmitis. Methods: The implants were produced via hot-melt extrusion, using a twin-screw extruder to process a homogeneous mixture of polylactide-co-glycolic acid, moxifloxacin hydrochloride (MOX HCl) and dexamethasone (DEX). Quality control tests included drug content determination, release rate profile evaluation, and several instrumental characterization techniques (scanning electron microscopy (SEM), confocal Raman microscopy, differential scanning calorimetry, and X-ray diffraction). Long-term and accelerated stability tests were also performed, following ICH guidelines. Sterilization was achieved by exposing samples to gamma radiation. In vivo exploratory studies were carried out in healthy rabbits to evaluate the safety and overall performance of the implantable formulation. Results: In terms of quality control, drug content was found to be homogeneously distributed throughout the implants, and it also met the label claim. In vitro release rate was constant for MOX HCl, but non-linear for DEX, increasing over time. In vivo preliminary tests showed that the inserts completely biodegraded within approximately 20 days. No clinical signs of anterior segment toxic syndrome or statistically significant intraocular pressure differences were found between treatment and control groups. Conclusions: The implants developed in this study can act as sustained-release depots for the delivery of both DEX and MOX HCl, and are biocompatible with ocular structures. Full article

Background: Glaucoma is a progressive optic neuropathy marked by retinal ganglion cells (RGCs), apoptosis, vascular insufficiency, oxidative stress, mitochondrial dysfunction, excitotoxicity, and neuroinflammation. While intraocular pressure (IOP) reduction remains the primary intervention, many patients continue to lose vision despite adequate pressure control. Emerging neuroprotective agents—citicoline, coenzyme Q10 (CoQ10), pyruvate, nicotinamide, pyrroloquinoline quinone (PQQ), homotaurine, berberine, and gamma-aminobutyric acid (GABA)—target complementary pathogenic pathways in experimental and clinical settings. Methods: This literature review synthesizes current evidence on glaucoma neuroprotection, specifically drawing on the most relevant and recent studies identified via PubMed. Results: Citicoline enhances phospholipid synthesis, stabilizes mitochondrial membranes, modulates neurotransmitters, and improves electrophysiological and visual field outcomes. CoQ10 preserves mitochondrial bioenergetics, scavenges reactive oxygen species, and mitigates glutamate-induced excitotoxicity. Pyruvate supports energy metabolism, scavenges reactive oxygen species, and restores metabolic transporter expression. Nicotinamide and its precursor nicotinamide riboside boost NAD⁺ levels, protect against early mitochondrial dysfunction, and enhance photopic negative response amplitudes. PQQ reduces systemic inflammation and enhances mitochondrial metabolites, while homotaurine modulates GABAergic signaling and inhibits β-amyloid aggregation. Berberine attenuates excitotoxicity, inflammation, and apoptosis via the P2X7 and GABA-PKC-α pathways. Preclinical models demonstrate synergy when agents are combined to address multiple targets. Clinical trials of fixed-dose combinations—such as citicoline + CoQ10 ± vitamin B3, citicoline + homotaurine ± vitamin E or PQQ, and nicotinamide + pyruvate—show additive improvements in RGCs’ electrophysiology, visual function, contrast sensitivity, and quality of life without altering IOP. Conclusions: A multi-targeted approach is suitable for glaucoma’s complex neurobiology and may slow progression more effectively than monotherapies. Ongoing randomized controlled trials are essential to establish optimal compound ratios, dosages, long-term safety, and structural outcomes. However, current evidence remains limited by small sample sizes, heterogeneous study designs, and a lack of long-term real-world data. Integrating combination neuroprotection into standard care holds promise for preserving vision and reducing the global burden of irreversible glaucoma-related blindness. Full article

Glaucoma is traditionally classified as an ocular disease characterized by progressive retinal ganglion cell (RGC) loss and optic nerve damage. However, emerging evidence suggests that its pathophysiology may extend beyond the eye, involving trans-synaptic neurodegeneration along the visual pathway and structural changes within central brain regions, including the lateral geniculate nucleus and visual cortex. In this narrative review, we have used the phrase ‘brain involvement’ to underscore central changes that accompany or follow retinal ganglion cell loss; we have not intended to redefine glaucoma as a primary cerebral disorder. Neuroimaging studies and neurocognitive assessments in adult glaucoma patients, primarily older individuals with primary open-angle glaucoma reveal that glaucoma patients may exhibit alterations in brain connectivity and cortical thinning, aligning it more closely with neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. This evolving neurocentric perspective raises important questions regarding shared mechanisms—such as mitochondrial dysfunction, chronic inflammation, and impaired axonal transport—that may link glaucomatous optic neuropathy to central nervous system (CNS) pathology. These insights open promising therapeutic avenues, including the repurposing of neuroprotective and neuroregenerative agents, targeting not only intraocular pressure (IOP) but also broader CNS pathways. Furthermore, neuroimaging biomarkers and brain-targeted interventions may play a future role in diagnosis, prognosis, and individualized treatment. This review synthesizes current evidence supporting glaucoma as a CNS disease, explores the mechanistic overlap with neurodegeneration, and discusses the potential clinical implications of glaucoma within a neuro-ophthalmologic paradigm. Full article

Graves’ orbitopathy (GO) is a debilitating autoimmune disorder that may require surgical orbital decompression in severe cases with risk of proptosis and optic neuropathy. This report presents a case treated with navigation-assisted three-wall orbital decompression, planned with preoperative imaging and assessed using postoperative analysis. Intraoperative navigation enabled precise localization of critical structures, improving osteotomy execution. Postoperatively, orbital volume increased by 3.5 cm³ (right eye) and 4.0 cm³ (left eye), while proptosis was reduced by 6 mm in both eyes. These changes correlated with intraocular pressure normalization and functional improvement. This was further supported by a postoperative Clinical Activity Score (CAS) of 0, indicating active orbital inflammation. Image-guided surgery (IGS) achieved an average proptosis reduction of 3.8 mm, slightly superior to that of non-guided techniques. Although IGS enhances precision and functional outcomes, it requires longer surgical time and incurs higher costs, highlighting the need for prospective studies on long-term efficacy This case supports the importance of integrating advanced imaging and navigation-assisted techniques in GO management to improve both functional and aesthetic outcomes. Full article

Combined trabeculectomy–phacoemulsification is known to provoke more inflammation and yield a poorer long-term efficacy than trabeculectomy alone. This study evaluates whether a similar trend exists for Ahmed glaucoma valve implantation when performed with or without concurrent phacoemulsification. We retrospectively analyzed 51 eyes from patients who underwent either Ahmed-Alone (n = 25) or PhacoAhmed (n = 26) surgery over a 5-year period. The primary outcomes included intraocular pressure (IOP), the use of IOP-lowering medications, and the need for further surgical intervention. Absolute success was defined as IOP reduction > 20% and IOP < 21 mmHg without medication; relative success allowed for continued pharmacologic therapy. Both groups showed a significant IOP reduction, with similar final mean IOP values (Ahmed-Alone: 14.02 ± 4.76 mmHg; PhacoAhmed: 13.89 ± 4.17 mmHg; p = 0.99) and comparable reductions in medication use (p = 0.52). Reinterventions occurred less frequently and later in the PhacoAhmed group (12% vs. 27.3%; median time: 27.1 vs. 12 months). Absolute success was not achieved in any PhacoAhmed case but occurred in 9.3% of Ahmed-Alone cases; relative success rates were similar (83.3% vs. 81.4%; p = 0.291). These findings suggest that combining phacoemulsification with Ahmed valve implantation does not significantly alter efficacy or safety profiles. Additional prospective studies are warranted to assess long-term outcomes. Full article

We report a case of herpes simplex virus type 1 (HSV-1) anterior uveitis evolving into an acute iris transillumination-like syndrome with secondary pigmentary glaucoma, highlighting diagnostic challenges and treatment considerations. A 61-year-old immunocompetent woman presented with unilateral anterior uveitis characterized by keratic precipitates and mild anterior chamber inflammation. The condition was initially treated with topical and subconjunctival corticosteroids without antiviral therapy. After an initial resolution of symptoms, upon the cessation of treatment, the patient developed features resembling unilateral acute iris transillumination (UAIT) syndrome with elevated intraocular pressure, diffuse pigment dispersion, and progressive iris transillumination defects. Aqueous polymerase chain reaction (PCR) testing confirmed the presence of HSV-1. Despite the initiation of antiviral therapy, the condition progressed to severe pigmentary glaucoma, with unreliable intraocular pressure measurements due to prior LASIK surgery. Cataract extraction, pars plana vitrectomy, and Ahmed valve implantation were performed, with only partial recovery of visual acuity. This case illustrates that HSV-1 uveitis can mimic or transition into a UAIT-like syndrome, possibly due to steroid use without concurrent antiviral treatment, which may exacerbate viral replication and damage to the iris pigment epithelium. Aqueous PCR testing aids in differential diagnosis, but indicative medical history and clinical findings should remain instrumental. Clinicians should maintain a high index of suspicion for herpetic etiology in anterior uveitis cases and initiate prompt antiviral treatment to prevent potentially sight-threatening complications. Full article

Background and Clinical Significance: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome characterized by bilateral uveal melanocyte proliferation and progressive visual disturbance. While most commonly associated with solid tumors, its occurrence in hematologic malignancies is exceedingly rare. Case Presentation: We report a case of BDUMP in a 64-year-old male recently diagnosed with chronic myelomonocytic leukemia (CMML), who presented with subacute, painless bilateral blurred vision. Multimodal imaging revealed suggestive features of BDUMP, including orange-red subretinal patches, retinal pigment epithelium mottling, and diffuse choroidal thickening, consistent with early structural involvement despite preserved central vision. No intraocular mass or signs of inflammation were observed. The patient did not receive specific treatment for BDUMP, and visual acuity remained stable during follow-up. Conclusions: This case underscores the importance of considering BDUMP in the differential diagnosis of bilateral visual symptoms in patients with hematologic malignancies. Although rare, BDUMP may occur in the context of CMML. Recognition through multimodal imaging and interdisciplinary collaboration is essential, and further research is needed to clarify its pathogenesis and improve management strategies. Full article

Purpose: We aimed to investigate whether genetic variants susceptible to age-related macular degeneration (AMD) are associated with intraocular inflammation after brolucizumab administration in eyes that have exudative AMD. Methods: A total of 206 eyes from 206 patients (156 men/50 women, 74.0 ± 8.4 years; treatment-naïve, 128 [62.1%]; switching, 78 [37.9%]) were included in this study. All patients were treated with intravitreal brolucizumab at least once. The genotyping of ARMS2 A69S (rs10490924), CFH I62V (rs800292), CFH (rs1329428), SKIV2L (rs429608), C3 (rs2241394), cholesteryl ester transfer protein (CETP) (rs3764261), and ADAMTS9 (rs6795375) was performed using TaqMan technology. Results: Out of the 206 patients who were included, 21 eyes from 21 patients (10.2%) exhibited intraocular inflammation (IOI). Four (19.0%) exhibited severe IOI, including retinal vasculitis and/or retinal vascular occlusion, and 17 (81.0%) showed mild IOI. The frequency of the T allele of the CETP gene was significantly lower in patients who developed IOI compared to patients who did not develop IOI (T allele frequency: 9.5% vs. 23.5%, p = 0.036). After adjusting for confounding factors, the T allele remained significantly associated with protection against IOI (p = 0.028, 95% confidence interval: 0.098–0.88). Conclusions: The T allele of the CETP gene, a risk allele for AMD and the protective allele for atherosclerosis, may be associated with protection against IOI after brolucizumab administration in eyes that have exudative AMD. Full article

Angiopoietin-like proteins (ANGPTLs) represent a family of secreted glycoproteins that are extensively expressed in vivo and are integral to various pathophysiological processes, including glucose and lipid metabolism, stem cell proliferation, local inflammation, vascular permeability, and angiogenesis. Particularly interesting is ANGPTL4, which has been identified as a significant factor in the development and progression of diabetic retinopathy (DR), thus becoming a central focus of DR research. ANGPTLs modulate metabolic pathways, enhance vascular permeability, and facilitate pathological angiogenesis, in addition to causing intraocular inflammation. As promising molecular targets, ANGPTLs not only serve as biomarkers for predicting the onset and progression of DR but also present therapeutic potential through antibody-based interventions. This paper discusses the pathogenesis of DR and the potential applications of ANGPTLs in early diagnosis and targeted therapy. It provides references for advancing precision diagnosis and personalized treatment strategies through more profound ANGPTLs research in the future. Full article