Intraocular Inflammation Research Articles

Bilateral Idiopathic Neuroretinitis

Background/Objectives: Neuroretinitis (NR) is a rare inflammatory condition characterized by sudden vision loss, optic disc edema and macular star appearance predominantly affecting individuals in their third and fourth decades of life. Methods: This paper describes the case of 33-year-old Caucasian man with no significant medical history complaining of decreased vision for about a week. Results: The ophthalmological exam revealed best-corrected visual acuity (BCVA) for the right eye (RE) of 0.8 (decimal notation) and of 0.9 for the left eye (LE). Intraocular pressure (IOP) was 20 mmHg in RE and 18 mmHg in LE. Slit-lamp examination of both eyes (OU) showed no evidence of intraocular inflammation in the anterior chamber or vitreous cavity. Examination of the posterior pole of the right eye showed bilateral papilledema with an incomplete macular fan pattern. Conclusions: Despite extensive laboratory tests, including serologic and imaging investigations, a definitive etiology remained unclear. It is very important to differentiate NR from other optic nerve disorders, requiring careful clinical evaluation and observation of the evolution of symptoms.

Clinical and Genetic characteristics of patients with Peripheral Retinal Fleck in Koreans.

To describe the clinical and genetic features of Korean patients with peripheral retinal flecks unrelated to aging. A retrospective analysis was conducted on the clinical characteristics of patients with symmetric peripheral retinal flecks. Age-related deposits such as reticular pseudodrusen were excluded, as well as secondary deposits related to intraocular inflammation, tumor, and drug toxicity. Multimodal imaging, electrophysiological examinations, and genetic testing were analyzed. A total of 10 patients (2 males and 8 females) with bilateral peripheral flecks were enrolled in this study. A mean age at diagnosis was 30.5±19.6 years (4-59 years). Within the 10 patients, 6 were genetically confirmed with monogenic retinal disorders. Biallelic pathogenic variants in RDH5 were found in 5 patients, and 1 patient was diagnosed with retinopathy related to Alport syndrome due to a pathogenic variant in COL4A5. Although not genetically confirmed, one case associated with nanophthalmos and another case showing chorioretinal mottling in a carrier of ocular albinism have been identified. In one patient, genetic testing also revealed unknown causes. The mean logMAR initial visual acuity was 0.12±0.18 and 0.07±0.18 in right and left eyes, respectively. Night blindness was reported by 4 patients (40%), with 3 showing decreased or delayed rod response in electroretinogram, particularly those with RDH5 mutations. Differences in the deposit layers and the patterns of flecks were observed on multimodal imaging. In the study population, we observed various causes and clinical differences in the retinal fleck patterns among Koreans, including RDH5-related fundus albipunctatus and Alport syndrome. Despite reports of night blindness symptoms in some cases, all patients demonstrated satisfactory corrected visual acuity.

Occlusive retinal vasculitis and scleritis following brolucizumab treatment: A case report.

Brolucizumab is an anti-vascular endothelial growth factor agent. Clinical trials have demonstrated excellent efficacy of brolucizumab for neovascular age-related macular degeneration in terms of both visual and anatomic outcomes. However, compared with conventional anti-vascular endothelial growth factor therapy, this new treatment has a higher incidence of complications, particularly the development of occlusive retinal vasculitis. In this case report, we describe a patient who developed occlusive retinal vasculitis following brolucizumab treatment for age-related macular degeneration, followed by scleritis 141 days later. A 67-year-old Japanese man with a diagnosis of polypoidal choroidal vasculopathy in his right eye has received 18 intravitreal injections of aflibercept in the past 4 years. Because of a decline in treatment efficacy, intravitreal brolucizumab injection (IVBr) was initiated. However, 17 days after the second IVBr, the patient developed extensive occlusive retinal vasculitis with intraocular inflammation. Occlusive retinal vasculitis in the right eye was diagnosed as a complication of brolucizumab therapy. Corticosteroid treatment was initiated. The occlusive retinal vasculitis resolved 121 days after the second IVBr, and corticosteroid treatment was discontinued on day 138. However, on day 158 after the second IVBr, scleritis with intraocular inflammation developed. By day 184 after the second IVBr, both the scleritis and intraocular inflammation had resolved with the resumption of topical corticosteroid treatment. This case underscores the potential for brolucizumab-induced scleritis and emphasizes the importance of recognizing and promptly managing this complication. Furthermore, it highlights the need for long-term careful follow-up in patients who develop occlusive retinal vasculitis after brolucizumab treatment.

Sterile Intraocular Inflammation Associated With Faricimab

Randomized clinical trials are conducted to establish both drug safety and efficacy. However, evidence of adverse events associated with these drugs in the clinical practice setting can be of value at generating hypotheses regarding less common safety issues, even if causality cannot be determined. To present and analyze cases of intraocular inflammation associated with faricimab therapy in patients referred to a single European institution. This was a review starting in April of 2024 of an observational case series. Patients were from a single academic-based tertiary referral center in Switzerland. Included in the analysis were patients referred for intraocular inflammation soon after receiving a faricimab intravitreal injection between June 1, 2022, and March 5, 2024. Faricimab, 6 mg (0.05 mL of a 120-mg/mL solution), administrated for neovascular age-related macular degeneration or diabetic macular edema. The systemic and ocular histories and imaging data available were reviewed. The following were evaluated: visual acuity measured with habitual correction using the Early Treatment of Diabetic Retinopathy Study charts before and after the event; intraocular pressure; patient symptoms; anterior, intermediate, or posterior location of the intraocular inflammation; and the presence of retinal vasculitis. Multimodal imaging including color fundus photographs, fluorescein angiograms, indocyanine green angiograms, and optical coherence tomography were reviewed. A total of 12 eyes from 7 patients (mean [SD] age, 73.3 [16.7] years; 4 female [57.1%]) over 22 months were identified as having noninfectious intraocular inflammation after intravitreal faricimab injections. Among these cases, in 2 eyes, retinal vasculitis was present together with anterior and posterior inflammation. One of the 2 eyes had an occlusive form of vasculitis of the arteries and veins, leading to subsequent macular capillary nonperfusion and clinically relevant irreversible vision deterioration from 20/80 to 20/2000. The remaining eyes were characterized by moderate anterior segment inflammation without substantial vision changes. The intraocular inflammation event occurred after a median (IQR) of 3.5 (2.0-4.3) faricimab injections. The median (IQR) interval between the last faricimab injection and the diagnosis of inflammation was 28 (24-38) days. Increased intraocular pressure of 30 mm Hg or higher was found in 3 eyes. This case series highlights the occurrence of rare, but potentially severe, intraocular inflammation associated with faricimab therapy. Although these findings do not prove causality and can only generate hypotheses for future investigations, these results suggest the importance of continuous surveillance and monitoring for patients undergoing faricimab therapy to promptly identify and manage potential adverse events.

Pharmacological Advances in Glaucoma Management

Glaucoma is the leading cause of global irreversible blindness, with clinical diagnosis related to population-based low vision standards and subsequently to diminished vision-related quality of life. The main objective of the present study is to review the updates regarding pharmacological advances in glaucoma management. Pharmacological management to reduce intraocular pressure and inflammation and improve retinal ganglion cell survival has a significant impact on the overall management of glaucoma. The changes in the therapeutic pipelines include the targeting of both traditional and novel molecules. New medications in the offing either improve the already established targets or focus on newer avenues to confer better anti-glaucomatous effects with minimal side effects.

Helicobacter pylori and Its Treatment Impact on Immune-Mediated Ocular Diseases

ABSTRACT Purpose Helicobacter pylori (HP), which colonizes exclusively in the gastrointestinal tract, has been reported to dysregulate the immune response and gives rise to several extra-gastrointestinal autoimmune disorders. However, the relationship between HP and immune-mediated ocular diseases remains ambiguous. This study aims to clarify the association between immune-mediated ocular diseases and HP infection, as well as the impact of HP treatment on the incidence of immune-mediated ocular diseases. Methods This is a retrospective population-based study using National Health Insurance Research Database in Taiwan. Patients with newly diagnosed peptic ulcer disease or HP infection between 2009 and 2015 were identified as HP group and compared to the non-HP group with one-to-one exact matching. Moreover, the incident risk of immune-mediated ocular diseases and its two subgroups (ocular surface and orbital inflammation group, intraocular inflammation group) were compared in HP patients with or without treatment. Results A total of 1,030,119 subjects in the non-HP group and 1,030,119 patients in the HP group were enrolled. The incidence rate of immune-mediated ocular diseases was significantly higher in the HP group (95% confidence interval (CI): 2.534–2.547). The incident rate ratio was significantly higher in HP with treatment than without treatment (HR: 1.654, 95% CI: 1.641–1.668). The Cox proportional hazards regression model demonstrated a significantly increased HR of immune-mediated ocular diseases in HP treated group (HR: 2.265, 95% CI: 2.024–2.534) and less increased HR in HP non-treated group (HR: 1.427, 95% CI: 1.273–1.598) when comparing to non-HP group. Subgroup analysis demonstrated a significantly higher incidence rate of ocular surface and orbital inflammation as well as intraocular inflammation in the HP group. Conclusion This study illustrated a higher incidence of immune-mediated ocular diseases in HP infection, and a heightened risk following HP eradication.

Incidence of intraocular inflammation and its risk factors in patients treated with brolucizumab: a nationwide cohort study

This study aimed to evaluate the incidence of clinically significant intraocular inflammation (csIOI) after treatment with intravitreal injection (IVI) of brolucizumab and identify csIOI risk factors. We categorized 60,966 South Korean patients from a nationwide population-based cohort into 4 groups: groups 1 (Ranibizumab), 2 (Aflibercept), 3 (Brolucizumab), and 4 (switched to brolucizumab). We used the Kaplan–Meier method to estimate the cumulative incidence of csIOI in each group and calculated the hazard ratios (HRs) and 95% confidence intervals (CIs). We constructed a multivariate model using forward selection methods to identify risk factors for csIOI. The cumulative incidence of csIOI within 180 days of the index date in groups 1, 2, 3, and 4 was 0.36% (67/18,537), 0.49% (186/37,951), 3.47% (38/1,095), and 3.69% (125/3,383), respectively. Multivariate analysis revealed a significant increase in csIOI risk in groups 3 (HR 11.08, 95% CI 7.42–16.53, P < 0.001) and 4 (HR 10.40, 95% CI 7.67–14.09, P < 0.001). History of retinal vascular occlusion (HR 1.56, 95% CI 1.01–2.40, P = 0.043) significantly increased csIOI risk after brolucizumab IVI treatment; female sex (HR 0.78, 95% CI 0.64–0.96, p = 0.020) and diabetes (HR 0.72, 95% CI 0.58–0.90, p = 0.004) decreased the risk. csIOI incidence was higher after brolucizumab IVI treatment than after ranibizumab and aflibercept IVI treatment. Retinal vein occlusion history, female sex, and diabetes are associated with csIOI after brolucizumab IVI treatment.

Early real-world experience with intravitreal Faricimab for neovascular AMD: FAN study

PurposeThis study presents real-world experiences and clinical outcomes of patients who switched to faricimab after prior treatment with other anti-vascular endothelial growth factor medication for patients with neovascular age-related macular degeneration (nAMD) in 2022. DesignWe evaluated all consecutive patients that received an intravitreal injection (IVI) with faricimab for nAMD and had complete follow-up visits after at least three IVI. MethodsFunctional and structural parameters including best-corrected visual acuity (BCVA, logMAR), foveal centre point (FCP, µm), central subfield retinal thickness (CSRT, µm) and macular volume (mm3) were evaluated after three (n=71) and five (n=57) faricimab injections with complete follow-up visits. ResultsWe included 71 eyes of 63 patients. Mean BCVA at baseline was 0.49 logMAR (0 – 1.6) and did not change significantly after five faricimab injections (p=0.33). Significant reductions were seen for FCP, CSRT and macular volume after the first five consecutive injections when compared to baseline (p<0.0001 respectively). FCP was 388.35 µm (173-924 µm) at baseline and decreased to 279.16 µm (97 – 667) at visit 5. CSRT was 370.68 µm (202 – 1074) and decreased to 307.75 µm (168 – 590) at visit 5. Macular volume was reduced from 2.59 mm3 (1.83 – 4.90) to 2.31 mm3 (1.80 – 3.19) at visit 5. Intraocular inflammation was observed in one eye showing anterior chamber cells that resolved with topical corticosteroid treatment. ConclusionsThe results of the FAN (FAricimab for Neovascular AMD) study indicate that faricimab improves structural outcomes in patients with recalcitrant fluid due to nAMD with no major complications observed.

Intravitreal faricimab for treatment naïve patients with neovascular age-related macular degeneration: a real-world prospective study

BackgroundIntravitreal faricimab, a bispecific antibody targeting both angiopoietin-2 (Ang-2) and vascular endothelial growth factor-A (VEGF-A), was recently introduced for the treatment of neovascular age-related macular degeneration (nAMD), diabetic macular oedema and cystoid macular oedema secondary to retinal vein occlusion. The aim of our study was to assess the efficacy, safety and durability of intravitreal faricimab in a real-world cohort of treatment-naïve patients with nAMD.MethodsSingle-centre, prospective cohort study of 21 eyes from 19 treatment-naïve nAMD patients who were treated with intravitreal faricimab from October 2022 to April 2024. Patients underwent a loading dose (LD) of 4 monthly faricimab injections followed by a treat-and-extend regimen. Primary outcomes included best-corrected visual acuity (BCVA) and structural parameters from spectral-domain optical coherence tomography (SD-OCT). Secondary outcomes included the proportion of eyes achieving a dry macula, maximal fluid-free interval and intended interval at last follow-up.ResultsThe study included 21 eyes of 19 patients (mean age 83.1 years). After LD, 93.3% of eyes achieved a dry macular SD-OCT scan within a median time of 8 weeks. At the first extension, 53% of eyes remained dry, while 47% showed fluid recurrence. Long-term analysis (n = 14) revealed significant reductions in macular volume (MV), central subfield thickness (CST), and pigment epithelial detachment (PED) height over a median follow-up of 64.9 weeks, with sustained visual and anatomical improvements. Median BCVA, CST, and MV at the final follow-up were significantly improved from baseline (p < 0.01). The intended interval between injections was ≥ 12 weeks in 42.86% of eyes. No cases of intraocular inflammation were observed, although 10% experienced retinal pigment epithelial tears.ConclusionsIntravitreal faricimab demonstrated favourable efficacy, safety, and durability outcomes in a real-world cohort of treatment-naïve nAMD patients.

Uveitis: A snapshot in the MOG antibody spectrum.

Despite the commonly observed association of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies with bilateral optic neuritis, their connection to uveitis is largely unexplored. The presented case involves a 41-year-old male with uveitis and bilateral optic neuritis, subsequently diagnosed with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). This case, characterized by bilateral optic neuritis associated to anti-MOG antibodies and the concurrent onset of unilateral anterior uveitis, provides further evidence concerning the features of intraocular inflammation in MOGAD. The patient's treatment response, including the use of rituximab due to contraindications to oral steroids, emphasizes the importance of personalized management strategies in MOGAD-associated ocular manifestations.

One-Year Real-World Outcomes of Intravitreal Faricimab for Previously Treated Neovascular Age-Related Macular Degeneration.

This study assessed the efficacy, durability, and safety of faricimab in patients with neovascular age-related macular degeneration (nAMD), previously treated with aflibercept or ranibizumab with unsatisfactory results. This was a single-center, prospective cohort study of all consecutive patients with nAMD switched to intravitreally administered faricimab from traditional anti-vascular endothelial growth factor (anti-VEGF) treatments between September 2022 and April 2023 because of unsatisfactory response (maximal fluid-free interval ≤ 8weeks). Faricimab was administered with a loading dose of four 4-weekly injections, followed by a treat-and-extend regimen. The primary outcome measures were maximum fluid-free interval after the switch and last assigned treatment interval. Secondary outcome measures included best-corrected visual acuity (BCVA) and structural optical coherence tomography parameters. Thirty-three eyes of 33 patients were included. Patients were followed for a median of 72weeks [interquartile range 61, 76]. Median maximum fluid-free treatment interval after switch to faricimab and the last assigned interval were significantly longer than before the switch (7 vs. 4weeks, p < 0.001 and 8 vs. 5weeks, p < 0.001, respectively). Significant improvements in central subfield thickness (353 vs. 281µm), macular volume (2.46 vs. 2.16mm3), and pigment epithelial detachment height (198 vs. 150µm) were observed (all p < 0.001). BCVA remained stable at 0.4 versus 0.3logMAR before switch (p = 0.190). One eye (3%) developed intraocular inflammation and one eye (3%) developed a retinal pigment epithelium tear. Faricimab improved anatomical outcomes and allowed longer treatment intervals in patients with nAMD previously treated with other anti-VEGF therapies with unsatisfactory response, reducing treatment burden. A favorable safety profile was observed.

Dynamics of Treatment Response to Faricimab for Diabetic Macular Edema.

This study analyzes the dynamics of short-term treatment response to the first intravitreal faricimab injection in eyes with diabetic macular edema (DME). This retrospective, single-center, clinical trial was conducted at the Department of Ophthalmology, University Hospital Zurich. Patients with treatment-naïve and pretreated DME were included. Patient chart data and imaging were analyzed. Safety and efficacy (corrected visual acuity (CVA), central subfield thickness (CST), and signs of intraocular inflammation (IOI)) of the first faricimab intravitreal therapy (IVT) were evaluated weekly until 4 weeks after injection. Forty-three eyes (81% pretreated) of 31 patients were included. Four weeks after the first faricimab IVT, CVA remained stable and median CST (µm) decreased significantly (p < 0.001) from 325.0 (293.5-399.0) at baseline to 304.0 (286.5-358.0). CVA at week 4 was only associated with baseline CVA (p < 0.001). CST was the only predictive variable (p = 0.002) between baseline and week 4 CST. Weekly safety assessments did not show any sign of clinically significant IOI. This study suggests faricimab is an effective treatment for (pretreated) DME, showing structural benefit 1 month following the first injection without short-term safety signals.

α-Klotho prevents diabetic retinopathy by reversing the senescence of macrophages

BackgroundDiabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus (DM) and a significant cause of acquired blindness in the working-age population worldwide. Aging is considered as an important risk factor for DR development. Macrophages in aged mice bear typical M2 marker proteins but simultaneously express a pro-inflammatory factor profile. This may explain why the level of intraocular inflammation does not decrease during proliferative diabetic retinopathy (PDR) despite the occurrence of neovascularization and fibrosis (M2 activation). α-Klotho (KL) was originally discovered as a soluble anti-aging factor, which is mainly expressed in kidney tubular epithelium, choroid plexus in the brain and secreted in the blood. However, the role of KL in DR pathophysiology has not been previously reported.MethodsType 1 (streptozotocin [STZ]-induced) and type 2 (a high-fat diet along with a low dose of STZ) diabetic mouse models were established and injected with or without KL adenovirus via the tail vein for 12 weeks. Vldlr−/− mice were injected intravitreally with or without soluble KL protein from P8 to P15. The retinal structure and function were analyzed by electroretinogram and optical coherence tomography. The neovascular lesions were analyzed by retinal flat mount and RPE flat mount. The senescence markers, macrophage morphology, and KL expression levels were detected by immunofluorescence staining. A cell model was constructed using RAW264.7 cells stimulated by 4-hydroxynonenal (4HNE) and transfected with or without KL adenovirus. The senescence-associated secretory phenotypes were detected by qRT-PCR. Senescence was detected by SA-β-Gal staining. Serum, aqueous humor, and vitreous humor KL levels of proliferative diabetic retinopathy (PDR) patients were measured by enzyme‐linked immunosorbent assay. Quantitative proteomics and bioinformatics were applied to predict the change of proteins and biological function after overexpression of KL in macrophages. The effects of KL on the HECTD1 binding to IRS1 were analyzed by bioinformatics, molecular docking, and Western Blot.ResultsSerum, aqueous humor, and vitreous humor KL levels were lower in patients with PDR than in those with cataracts. KL relieved the retinal structure damage, improved retina function, and inhibited retinal senescence in diabetic mice. KL administration attenuated the neovascular lesions in VLDLR−/− mice by decreasing the secretion of VEGFA and FGF2 from macrophages. KL also protected RAW264.7 cells from 4HNE-induced senescence. Additionally, it inhibited E3 ubiquitin ligase HECTD1 expression in both diabetic mouse peripheral blood mononuclear cells and 4HNE-treated RAW264.7 cells. KL inhibited HECTD1 binding to IRS1 and reduced the ubiquitination of IRS1.ConclusionsMacrophage aging is involved in DM-induced retinopathy. KL alleviates DM-induced retinal macrophage senescence by downregulating HECTD1 and decreasing IRS1 ubiquitination and degradation. Meanwhile, KL administration attenuated the neovascular lesions by altering the activation state of macrophages and decreasing the expression of VEGFA and FGF2.

Transcription factor EGR2 alleviates autoimmune uveitis via activation of GDF15 to modulate the retinal microglial phenotype

Uveitis is a vision-threatening disease primarily driven by a dysregulated immune response, with retinal microglia playing a pivotal role in its progression. Although the transcription factor EGR2 is known to be closely associated with uveitis, including Vogt-Koyanagi-Harada disease and Behcet's disease, and is essential for maintaining the dynamic homeostasis of autoimmunity, its exact role in uveitis remains unclear. In this study, diminished EGR2 expression was observed in both retinal microglia from experimental autoimmune uveitis (EAU) mice and inflammation-induced human microglia cell line (HMC3). We constructed a mice model with conditional knockout of EGR2 in microglia and found that EGR2 deficiency resulted in increased intraocular inflammation. Meanwhile, EGR2 overexpression downregulated the expression of inflammatory cytokines as well as cell migration and proliferation in HMC3 cells. Next, RNA sequencing and ChIP-PCR results indicated that EGR2 directly bound to its downstream target growth differentiation factor 15 (GDF15) and further regulated GDF15 transcription. Furthermore, intravitreal injection of GDF15 recombinant protein was shown to ameliorate EAU progression in vivo. Meanwhile, knockdown of GDF15 reversed the phenotype of EGR2 overexpression-induced microglial inflammation in vitro. In summary, this study highlighted the protective role of the transcription factor EGR2 in AU by modulating the microglial phenotype. GFD15 was identified as a downstream target of EGR2, providing a unique target for uveitis treatment.

Brolucizumab in patients with neovascular age-related macular degeneration: Real-life outcomes from a tertiary care eye hospital.

To report real-world clinical evidence of brolucizumab in treating neovascular age-related macular degeneration (nAMD). This study included 37 eyes with nAMD treated with intravitreal injections of brolucizumab. The main outcomes were best corrected visual acuity (BCVA) changes, central retinal thickness (CRT), and serious ocular adverse events. Intraretinal fluid (IRF) and subretinal fluid (SRF), subretinal hyperreflective material (SHRM), pigment epithelial detachments (PEDs), hyperreflective foci, macular atrophy, and retinal pigment epithelial tears were evaluated. The mean BCVA of all patients showed a post-treatment value of 0.47 ± 0.33 log of minimum angle of resolution (LogMAR), compared to a baseline measure of 0.50 ± 0.28 LogMAR (P = 0.372). For treatment-naïve patients, a non-statistically significant improvement in BCVA was observed (P = 0.116). Both treatment-naive patients and the entire patient cohort exhibited a statistically significant improvement in the mean CRT after injections. Majority of patients exhibited improvements in optical coherence tomography findings, specifically in the resolution of IRF, SRF, SHRM, and PEDs. Four eyes experienced ocular adverse events in the form of intraocular inflammation. Brolucizumab did not yield a substantial improvement in BCVA, but it exhibited efficacy in reducing CRT in the entire study population and treatment-naive patients with nAMD. Our study identified intraocular inflammation as a significant adverse event with brolucizumab. Thus, precise patient selection, education, and vigilant inflammation monitoring are crucial for patients undergoing this treatment.

Interim safety and efficacy of gene therapy for RLBP1-associated retinal dystrophy: a phase 1/2 trial

Gene therapy holds promise for treatment of inherited retinal dystrophies, a group of rare genetic disorders characterized by severe loss of vision. Here, we report up to 3-year pre-specified interim safety and efficacy results of an open-label first-in-human dose-escalation phase 1/2 gene therapy clinical trial in 12 patients with retinal dystrophy caused by biallelic mutations in the retinaldehyde-binding protein 1 (RLBP1) gene of the visual cycle. The primary endpoints were systemic and ocular safety and recovery of dark adaptation. Secondary endpoints included microperimetry, visual field sensitivity, dominant eye test and patient-reported outcomes. Subretinal delivery of an adeno-associated viral vector (AAV8-RLBP1) was well tolerated with dose-dependent intraocular inflammation which responded to corticosteroid treatment, and focal atrophy of the retinal pigment epithelium as the dose limiting toxicity. Dark adaptation kinetics, the primary efficacy endpoint, improved significantly in all dose-cohorts. Treatment with AAV8-RLBP1 resulted in the resolution of disease-related retinal deposits, suggestive of successful restoration of the visual cycle. In conclusion, to date, AAV8-RLBP1 has shown preliminary safety and efficacy in patients with RLBP1-associated retinal dystrophy. Trial number: NCT03374657.

Clinical Features of Behçet’s Disease Uveitis

Abstract: Behçet’s disease (BD) is a chronic, multisystemic vasculitis first described by Professor Hulusi Behçet in 1937. It is characterized by recurrent inflammatory attacks affecting multiple organs, with uveitis being a significant and severe complication that can lead to blindness. BD typically emerges between the ages of 20 and 30 years, with a higher prevalence in males and rare occurrences in children. The prevalence and severity of BD and its ocular symptoms tend to diminish with age. In Turkey, BD is a leading cause of noninfectious uveitis, and its prevalence varies across different regions. Ocular involvement, seen in up to 90% of BD patients, often appears 2–4 years after disease onset and may be the initial sign in 10%–20% of cases. BD uveitis is characterized by recurrent nongranulomatous panuveitis and retinal vasculitis, typically affecting both eyes. Diagnostic tools such as fluorescein angiography (FA), optical coherence tomography (OCT), and laser flare photometry (LFP) are essential for monitoring disease activity and guiding treatment. FA is crucial for identifying occlusive and leaky vasculitis, while OCT helps in detecting macular complications and visualizing retinal infiltrates and their sequelae. LFP quantitatively evaluates intraocular inflammation. Recognizing the ocular manifestations of BD early is vital for accurate diagnosis and effective management. This review highlights the clinical features, diagnostic tools, and importance of early diagnosis in managing BD uveitis.

Fine particulate matter potentiates Th17-cell pathogenicity in experimental autoimmune uveitis via ferroptosis

The effect of fine particulate matter (PM2.5) on the development of uveitis remains unclear. Therefore, this study was designed to investigate the role of PM2.5 in experimental autoimmune uveitis (EAU) and its potential mechanism. Our results showed that PM2.5 could exacerbate the activity of EAU, as evidenced by severer clinical and pathological changes, correlated with elevated Th17 cells frequency and IL-17A expression. Proteomic analysis revealed ferroptosis was the most significant pathway. In vivo, the levels of Fe2+, ROS, lipid ROS, and malondialdehyde, as well as the expression of TFRC, HMOX1, FTH1, and FTL1 in CD4+ T cells were increased, while GSH/GSSG ratio and the expression of ACSL1 and GPX4 were decreased after PM2.5 exposure. In vitro, the expression of TFRC and HMOX1 were increased, while the expression FTH1, FTL1, ACSL1, and GPX4 were decreased after PM2.5 exposure. Ferrostatin-1 effectively alleviated PM2.5-induced intraocular inflammation and suppressed the frequency of Th17 cells. These results suggest that PM2.5 could aggravate intraocular inflammation and immune response in EAU mice through ferroptosis. Ferroptosis could be a potential marker for the prevention and treatment of uveitis.

Inflammation and Vasculitis Related to Brolucizumab.

Background/objectives: To compare the prevalence of intra-ocular inflammation (IOI) between brolucizumab and aflibercept in neovascular age-related macular degeneration (nAMD) after intra-vitreal injections (IVI) and to compare the IOI odds ratios (ORs) of both therapies with the prevalence of septic endophthalmitis after IVI that was previously reported in the literature. Methods: A total of 468 IVI of brolucizumab (117 eyes) were compared with 2884 IVI of aflibercept (305 eyes) regarding IOI and occlusive retinal vasculitis (RV) from December 2021 to June 2023 in this retrospective study. The OR was calculated for both anti-VEGF agents and was compared with the relative risk of septic endophthalmitis after IVI. Results: There were four eyes with unilateral IOI related to brolucizumab (3.42%), one presenting uveitis (0.85%), two vitritis (1.71%) and the last one presenting occlusive RV (0.85%), compared with two eyes presenting unilateral IOI (anterior uveitis, 0.66%) and none with RV from the aflibercept cohort. The incidence of IOI per injection with brolucizumab (0.855%) was significantly higher compared with aflibercept (0.069%, p = 0.004). The OR of IOI related to brolucizumab IVI compared with septic endophthalmitis was 20 times greater (1.49 for aflibercept, p = 0.646, versus 20.15 for brolucizumab, p < 0.001). The OR of RV with brolucizumab compared with septic endophthalmitis was 4.6. Conclusion: Data from our department suggest a much higher risk of IOI and occlusive retinal vasculitis after brolucizumab when compared with aflibercept. The risk of IOI and severe sight-threatening complications related to brolucizumab is greater than the risk of septic endophthalmitis after any IVI.

MERLIN: Two-Year Results of Brolucizumab in Participants with Neovascular Age-Related Macular Degeneration and Persistent Retinal Fluid

PurposeTo report the safety and efficacy of brolucizumab (Beovu®) 6 mg vs. aflibercept (Eylea®) 2 mg administered every 4 weeks in participants with neovascular age-related macular degeneration (nAMD) and persistent retinal fluid after the Week 52 primary endpoint analysis (from Week 52 up to Week 104, post-study termination). DesignMulticenter, randomized, double-masked Phase 3a study. ParticipantsParticipants with recalcitrant nAMD (persistent residual retinal fluid despite previous frequent anti-vascular endothelial growth factor treatment). MethodsStudy eyes were randomized 2:1 to intravitreal brolucizumab 6 mg or aflibercept 2 mg every 4 weeks for 100 weeks, or until study termination. Main Outcome MeasuresAll available efficacy (analysis of noninferiority in mean best-corrected visual acuity [BCVA], central subfield thickness [CST], fluid-free status [no intraretinal fluid and no subretinal fluid]), and safety data up to study termination, including data up to Week 104 for those participants who completed the study prior to its termination. All P values after Week 52 were nominal and reflect observed data for the efficacy analyses. ResultsBrolucizumab 6 mg every 4 weeks was noninferior to aflibercept 2 mg in mean BCVA change from baseline to Week 104 (least squares mean difference, -0.4 Early Treatment Diabetic Retinopathy Study letters; 95% confidence interval [CI], -3.7 to 3.0; P = 0.0169). The proportion of eyes with ≥15-letter loss was 6.2% for brolucizumab and 4.7% for aflibercept. (P = 0.0014), and a greater proportion of eyes were fluid free at Week 104 (52.5% brolucizumab vs. 28.2% aflibercept; 95% CI, 11.9−37.3; P < 0.001) in eyes treated with brolucizumab vs. aflibercept. Incidence of intraocular inflammation (IOI), including retinal vasculitis and retinal vascular occlusion, was 11.5% (0.8% and 2.2%) for brolucizumab vs 6.1% (0% and 0.6%) for aflibercept, respectively. ConclusionsConsistent with 52-week results, brolucizumab 6 mg every 4 weeks was noninferior in mean BCVA change with anatomic outcomes superior to aflibercept 2 mg every 4 weeks from baseline to Week 104 or study termination. The incidence of IOI, including retinal vasculitis and retinal vascular occlusion, was higher with brolucizumab vs. aflibercept; therefore, brolucizumab should not be used more frequently than every 8 weeks following the loading regimen.