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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. [ABSTRACT FROM AUTHOR]

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AbstractPurposeMethodsResultsConclusionsTo identify risk factors and effect modifiers associated with intraocular inflammation (IOI) following brolucizumab injection.Our protocol was registered on PROSPERO (CRD42022382645). We searched six electronic databases (PubMed, Scopus, Web of Science, CENTRAL, EMBASE, and Google Scholar) to retrieve all studies that reported the occurrence of IOI following brolucizumab. Data are reported as mean difference with their corresponding 95% confidence intervals. All analyses were conducted per eye, and the risk of bias was assessed using the National Health Institute tool.Our analysis included 3527 eyes of 3469 patients of 33 papers. The mean age of the patients was 74 years (SD = 10.9, Range = 62.3–80.9). There were 1793 male patients (51.7%) and 1719 female patients (49.6%). The average follow-up period was 13.9 months (SD = 9.4). The mean number of injections was 4.5 (SD = 2.9) injections per eye; 1315 (37.3%) eyes had neovascular AMD, 189 (5.4%) had diabetic macular edema, and 129 (3.7%) eyes had polypoidal choroidal vasculopathy. Post-intervention, subretinal fluid, intraretinal fluid, and pigment epithelial detachment were significantly improved (46.5–11.3% of patients, 55.7–11.3% of patients, 24.7–7.1% of patients, respectively) (p < 0.001). Regarding visual acuity, there was an improvement with a mean difference of 0.12 (95% CI = 0.18–0.07, z = 4.38, p < 0.0001, 2064 eyes). The most common reported complication is IOI (n = 196, 6%). IOI was observed more in the elderly (76.3 ± 9.2 years), females (66%), and after the second injection.This systematic review provides valuable insights into risk factors and effect modifiers for IOI associated with brolucizumab treatment, aiding clinicians in optimizing patient care. Future studies should prioritize prospective, long-term investigations to further elucidate the safety profile of brolucizumab and refine its use in the management of retinal and choroidal vascular diseases. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate short-term outcomes of intravitreal injection of aflibercept 8 mg for neovascular age-related macular degeneration (nAMD). Study design: Retrospective, interventional case series. Methods: We retrospectively studied 35 eyes of 34 consecutive patients with nAMD, assessing best-corrected visual acuity (BCVA), foveal thickness (FT), and central choroidal thickness (CCT) before and 4 weeks after the initial intravitreal dose of aflibercept 8 mg. The rate of achieving a dry macula and the incidence of intraocular inflammation (IOI) at week 4 were also determined. Results: BCVA showed significant improvement, with significant reductions in FT and CCT 4 weeks after the initial injection of aflibercept 8 mg (all P < 0.01), with a dry macula being achieved in 20 eyes (57.1%). However, 3 eyes (8.6%) developed non-infectious IOI associated with retinal vasculitis, an adverse event not reported previously. The IOI in these eyes was relatively mild and treated with a posterior subtenon injection of triamcinolone acetonide with or without betamethasone eye drops, resulting in amelioration of IOI without any visual loss. Conclusions: Intravitreal aflibercept 8 mg appears to be effective for improving visual acuity and ameliorating exudative changes in eyes with nAMD. However, special attention should be given to the potential development of IOI associated with retinal vasculitis. [ABSTRACT FROM AUTHOR]

Purpose: We describe a case of intraocular inflammation and palpable purpura in a patient with Pasteurella multocida pneumonia. Methods: A 75-year-old pseudophakic woman with type-2 diabetes and chronic obstructive pulmonary disease complained of lower limb palpable purpura and right vision loss of five-day duration. On admission, right visual acuity was hand motion. Slit-lamp examination disclosed severe conjunctival and ciliary injection, corneal oedema, 3-mm hypopyon with heavy fibrin accumulation and blood clots, and synechiae to the IOL. Results: Chest computed tomography revealed interstitial pneumonia. Sputum culture yielded P. multocida. Amoxicillin/clavulanic tablets (1 g × 3/daily) and topical and systemic steroids were given. Later on, fluorescein angiography showed multiple choroidal lesions bilaterally. With the above-mentioned therapy, there was full recovery of the skin, lung, and eye lesions. Conclusion: This report emphasizes that P. multocida infection should be considered in patients with intraocular inflammation, palpable purpura, and interstitial pneumonia. A multidisciplinary approach is necessary for a correct diagnosis and management. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the characteristics of anterior uveitis in patients presenting with poorly controlled diabetes mellitus and with no other identifiable cause for their uveitis. A retrospective study of 121 eyes in 89 patients who presented at Auckland District Health Board with idiopathic acute anterior uveitis and uncontrolled diabetes between September 2009 and January 2022. The diagnosis of diabetes mellitus was known prior to presentation in 80 subjects (89.9%) and was discovered as a result of screening tests in the remainder. Mean HbA1c at presentation was 117.3 mmol/mol. Most uveitis was severe with 3+ (30 eyes, 25.4%) or 4+ cells (30 eyes, 25.4%) in the anterior chamber. Recurrence occurred in 22 eyes (18.2%) and was associated with elevated HbA1c. The visual prognosis was good with median visual acuity at 12 months of 6/7.5. Poorly controlled diabetes can be associated with acute anterior uveitis. [ABSTRACT FROM AUTHOR]

Abstract 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

Purpose: To investigate the long‐term efficacy and safety of intravitreal brolucizumab (BRZ) injections in patients with typical neovascular age‐related macular degeneration (typical nAMD) and polypoidal choroidal vasculopathy (PCV). Methods: This multicentre retrospective study included 401 eyes of 398 patients with nAMD who received BRZ injection(s), with a follow‐up duration of ≥12 months. Changes in best‐corrected visual acuity (BCVA), retinal fluid evaluation and central subfield thickness (CST) on optical coherence tomography were assessed. The efficacy of BRZ was compared between typical nAMD and PCV groups. Results: Analyses were conducted with 280 eyes of 278 patients with typical nAMD and 121 eyes of 120 patients with PCV (mean age, 71.1 ± 8.6 years). 29 eyes (7.2%) were treatment naïve. The mean follow‐up period was 15.3 ± 2.8 months; the mean number of BRZ injections within 1 year was 4.5 ± 1.7. BCVA was maintained during the follow‐up period, and CST significantly improved from the first injection month and was maintained for 12 months in both the typical nAMD and PCV groups. The dry macula proportion increased from 2.7% at baseline to 56.1% at 1 month and 42.9% at 12 months. Among the 18 eyes that underwent indocyanine green angiography both before and after treatment, 10 (55.6%) showed polyp regression. Overall, the incidence of intraocular inflammation (IOI), retinal vasculitis and occlusive retinal vasculitis was 9.4% (38 eyes), 1.2% (5 eyes) and 0.5% (2 eyes), respectively. IOI occurred from the first to the sixth injections, with an average IOI onset of 28.5 ± 1.4 days. All eyes achieved IOI resolution, although the two eyes with occlusive retinal vasculitis showed a severe visual decline after IOI resolution. Conclusion: Brolucizumab was effective in maintaining BCVA and managing fluid in eyes with nAMD for up to 1 year, exhibiting a high polyp regression rate. However, the not uncommon incidence of IOI and the severe visual decline caused by the rare occlusive retinal vasculitis following BRZ treatment underscore the importance of careful monitoring and timely management. [ABSTRACT FROM AUTHOR]

Context: Concerns about brolucizumab’s (Pagenax®) association with intraocular inflammation (IOI) limit its use despite its cost-effectiveness and efficacy. This multicentric study analyzes IOI incidence across 21 tertiary eyecare centers in India since its introduction in October 2020. Purpose: To determine the real-world incidence rate of IOI in Indian patients secondary to intravitreal brolucizumab across 21 tertiary eye care centers in India. Settings and Design: Retrospective multicentric, survey-based study. Methods: Data including number of patients treated, clinical indications, side effects encountered, and IOI case details was collected via Google Forms in 21 Indian tertiary eye care centers since October 2020. Mean, median, frequency, and standard deviation were calculated for statistical analysis. Results: All centers used pro re nata protocol for brolucizumab injections with a minimum injection interval of 8 weeks. The incidence of IOI was 0.79% (21 events out of 2655 eyes). Treatment indications included idiopathic polypoidal choroidal vasculopathy, neovascular age-related macular degeneration, diabetic macular edema, and off-label uses. IOI was experienced after the first injection (57%) in majority of cases with a median onset of 14 days (range: 1–65 days). IOI was mild in 28.5%, moderate in 33%, and severe in 38% of cases. Eighteen out of 21 IOI eyes recovered preinjection best corrected visual acuity or better. Conclusions: Our study found a lower IOI incidence (0.79%) with brolucizumab (Pagenax) in Indian patients compared to previously reported literature. IOI events were mostly mild to moderate, and post-treatment, most patients improved or maintained BCVA. Larger prospective multicentric studies with PRN dosing protocol are needed to confirm these findings.

Abstract Background Non-infectious uveitis affecting the posterior segment of the eye (NIU-PS) is an inflammatory disease, which can significantly impair visual acuity if not adequately treated. Fluocinolone-acetonide sustained-release-0.2 µg/day intravitreal (FAc) implants are indicated for prevention of relapse in recurrent NIU-PS. The aim here was to provide treating clinicians with some consensus-based-recommendations for the clinical management of patients with NIU-PS with 0.2 µg/day FAc implants. Methods A European-clinical-expert-group agreed to develop a consensus report on different issues related to the use of FAc implants in patients with NIU-PS. Results The Clinical-expert-panel provided specific recommendations focusing on clinical presentation (unilateral/bilateral) of the NIU-PS; systemic involvement of NIU-PS and the lens status. Treatment algorithms were developed; one that refers to the management of patients with NIU-PS in clinical practice and another that establishes the best clinical scenarios for the use of FAc implants, both as monotherapy and as adjuvant therapy. Additionally, the Clinical-expert-panel has provided recommendations about the use of the FAc implants in a clinical-setting. The Clinical-expert-panel also considered the safety profile of FAc implants and their possible implications in the daily practice. Conclusions As more clinical experience has been gained using FAc implants, it was necessary to update the clinical recommendations that guide patient management in the clinic. The current consensus document addresses relevant issues related to the use of FAc implants on different types of patients with various etiologies of NIU-PS, and was conducted to standardize approaches to help specialists obtain better clinical outcomes.

To report the outcomes of intracameral tissue plasminogen activator (tPA) use during uveitic cataract surgery. Retrospective case series from a single United States tertiary center of 36 eyes from 31 consecutive patients with established uveitis who received intraoperative intracameral tPA during cataract surgery between 2016 and 2020. Mean visual acuity (VA) improved from logMAR 1.0 ± 0.7 preoperatively to logMAR 0.7 ± 0.8 by POM12. VA improved from baseline postoperatively (POM1 p = 0.0002, POM6 p = 0.006 and POM12 p = 0.007). Minimal to no anterior chamber inflammation was achieved in 47.2% of the eyes by POW1 and 80.0% of the eyes by POM1. Mean clock-hours of posterior synechiae improved from 8.2 ± 3.8 preoperatively to 0.1 ± 0.6 by POM12. Six eyes developed hyphema and/or vitreous hemorrhage, four of which resolved spontaneously. Adjunctive intracameral tPA during uveitic cataract surgery improves VA and intraocular inflammation, but risks postoperative hemorrhage. Intraoperative tPA as adjunctive anti-inflammatory therapy warrants randomized prospective studies. [ABSTRACT FROM AUTHOR]

To investigate predisposing immunosuppressive conditions causing cytomegalovirus retinitis (CMVr) and risk factors for delayed diagnosis in patients diagnosed between 2008 and 2018 in the Swedish population of 10 million. Sixty-three consecutive patients (100 eyes) were diagnosed with CMVr. The most common immunosuppressive state predisposing for CMVr was hematopoietic stem cell transplant recipients (27%) and hematological malignancy (24%). Two patients (3.2%) had no other predisposing factor than diabetes mellitus (DM). Patients with delayed diagnosis (≤30 days) were older than those with earlier diagnosis, mean age 68.7 (±9.8) and 48.8 (±17.6), respectively, p =.001. Signs of intraocular inflammation (IOI) were seen in 42 (70%) of cases and more common in delayed than early diagnosis, 16 (89%) and 21 (60%) respectively (p =.03). Delayed diagnosis was more common in older individuals with signs of IOI. DM may be a risk factor for CMVr, and clinical signs can be mistaken for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Background: Non-infectious uveitis affecting the posterior segment of the eye (NIU-PS) is an inflammatory disease, which can significantly impair visual acuity if not adequately treated. Fluocinolone-acetonide sustained-release-0.2 µg/day intravitreal (FAc) implants are indicated for prevention of relapse in recurrent NIU-PS. The aim here was to provide treating clinicians with some consensus-based-recommendations for the clinical management of patients with NIU-PS with 0.2 µg/day FAc implants. Methods: A European-clinical-expert-group agreed to develop a consensus report on different issues related to the use of FAc implants in patients with NIU-PS. Results: The Clinical-expert-panel provided specific recommendations focusing on clinical presentation (unilateral/bilateral) of the NIU-PS; systemic involvement of NIU-PS and the lens status. Treatment algorithms were developed; one that refers to the management of patients with NIU-PS in clinical practice and another that establishes the best clinical scenarios for the use of FAc implants, both as monotherapy and as adjuvant therapy. Additionally, the Clinical-expert-panel has provided recommendations about the use of the FAc implants in a clinical-setting. The Clinical-expert-panel also considered the safety profile of FAc implants and their possible implications in the daily practice. Conclusions: As more clinical experience has been gained using FAc implants, it was necessary to update the clinical recommendations that guide patient management in the clinic. The current consensus document addresses relevant issues related to the use of FAc implants on different types of patients with various etiologies of NIU-PS, and was conducted to standardize approaches to help specialists obtain better clinical outcomes. [ABSTRACT FROM AUTHOR]

Purpose: This study was planned to compare the clinical results and optical coherence tomography (OCT) data of patients who underwent adalimumab (ADA), infliximab (IFX) and switched protocols between these two methods in cases of Behçet's associated uveitis (BAU). Methods: The patients with BAU who were treated with anti-TNF-a agents for at least one year were qualified for the chart review. The outcome parameters were the steroid-free remission state, the best-corrected visual acuity (BCVA), the central macular thickness (CMT), and the subfoveal choroidal thickness (SFCT) of the patients at the last visit. Results: After a mean follow-up of 16.60 months, the rate of active inflammation decreased from 63.6% to 15.1%. Mean BCVA increased, mean CMT and mean SFCT decreased significantly at the last visit (P < 0.001, P < 0.001, respectively). Conclusion: Anti-TNF-a treatment and switching protocols between these two agents effectively and safely control intraocular inflammation in BAU patients. [ABSTRACT FROM AUTHOR]

Introduction: To assess real-world safety outcomes for adults with neovascular age-related macular degeneration (nAMD) treated with brolucizumab from the US-based IRIS® (Intelligent Research in Sight) Registry. Methods: In this retrospective study, 18,312 eyes (15,998 patients) treated with ≥ 1 intravitreal brolucizumab injections between 8 October 2019 (US launch date for brolucizumab) and 7 October 2021 were followed up for ≤ 2 years after first injection (index date). The study assessed the predefined incident ocular adverse events of intraocular inflammation (IOI), retinal vasculitis (RV), and retinal vascular occlusion (RO). Results: Overall, 614/18,312 eyes (3.4%) experienced any IOI, RV, and/or RO event. Median (interquartile range [IQR]) time to an event was 84 (42–167) days; 77.4% of events (475/614) occurred within 6 months after index date. Median (IQR) number of brolucizumab injections before an event was 2 (1–4). For eyes with an adverse event and visual acuity (VA) data (n = 406), median (IQR) change in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from pre-event VA was 0 (− 7 to + 5) at the 6-month follow-up; 50 eyes (12.3%) had a VA loss of 10 or more ETDRS letters. Risk of an event (hazard ratio [95% confidence interval]) was decreased in eyes from male patients (0.61 [0.53–0.71]), from older patients (0.83 [0.76–0.90]), from treatment-naive patients (0.51 [0.38–0.69]), and from patients who started brolucizumab in the second year after launch (0.68 [0.53–0.86] vs. first year). Conclusion: In this large real-world brolucizumab safety study, 3.4% of eyes experienced an IOI, RV, and/or RO event. Among eyes that experienced an adverse event for which VA data were available, median ETDRS vision change was 0 letters (IQR − 7 to + 5). [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess the efficacy and safety of adalimumab in pediatric patients with chronic non-infectious posterior uveitis and panuveitis (not associated with juvenile idiopathic arthritis). Methods: The medical records of children (< 18 years old) with chronic non-infectious posterior uveitis and panuveitis were collected and analyzed in this retrospective cohort study. Children were allocated to a conventional adalimumab-free treatment (CT) or adalimumab (ADA) group based on whether they additionally received adalimumab. Results: In total, 69 children (138 eyes) were included, with 21 (42 eyes) and 48 (96 eyes) in the CT and ADA groups, respectively. During the average follow-up period of 24 months, the improvement in all ocular parameters (best-corrected visual acuity, intraocular inflammation, fluorescein angiography score) was better in the ADA group than in the CT group, except for changes in central macular thickness, which did not significantly differ between the groups. The mean time of first alleviation, which was after 1.03 ± 0.12 months of therapy, was earlier in the ADA group than in the CT group (2.30 ± 0.46 months). In the ADA group, 90.6% of children had remission within 3 months, and 47.9% had no relapse during follow-up. Cough and cold were the most common adverse events in the ADA group; however, the number of adverse events was similar between both the groups. Conclusions: Adalimumab was effective in the treatment of chronic noninfectious posterior uveitis and panuveitis in pediatric patients, and disease inactivity was accomplished in the majority of the patients, thereby improving visual outcomes and maintaining disease stability. Adverse events were limited and tolerable. [ABSTRACT FROM AUTHOR]

Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period (p < 0.01). An IOP increase (p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older (p = 0.004) and had been treated with more dexamethasone (DEX) implants (p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone (p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 (p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures. [ABSTRACT FROM AUTHOR]

AimMaterials & MethodsResultsConclusionWe report a unique finding of iris nodules in a woman with endogenous endophthalmitis due to Acinetobacter baumannii with no history of ocular surgery or trauma and good visual outcome.Retrospective case report.A 39-year-old woman with a history of type 2 diabetes mellitus presented with a decrease in vision in the right eye of 1-month duration. On examination, her BCVA was CF2m (OD) and 6/6 (OS). Right eye examination showed medium-to-large-sized keratic precipitates, iris nodules, and vitritis. PCR on the aqueous showed faint positivity for Propionibacterium acne and was negative to panfungal genome. Despite two intravitreal injections of vancomycin (1 mg/0.1 ml) and intravenous cefazolin 1 g bd for 5 days, there was progression to hypopyon. Vitrectomy with lensectomy was done. The vitreous culture grew Acinetobacter baumannii. She was given multiple intravitreal ceftazidime (2.25 mg/0.1 ml) with dexamethasone (0.4 mg/0.1 ml) injections. She was also put on tab bactrim DS twice a day for 3 months along with tab doxycycline 100 mg twice a day for 3 months by the infectious disease specialist. As the inflammation improved, the iris nodules were the last to resolve completely in 6 weeks. At 15-month follow-up, her eye was quiet, and vision was 6/9 (OD) with aphakic correction.We report a rare finding of iris nodules in a patient with culture proven Acinetobacter baumannii endogenous endophthalmitis. [ABSTRACT FROM AUTHOR]

Abstract Background To report a case of central retinal artery occlusion (CRAO) after intravitreal injection of brolucizumab for a treatment-naïve neovascular age-related macular degeneration (nAMD) patient without comorbid cardiovascular disease history. Case presentation A 79-year-old Asian male without a cardiovascular disease history such as diabetes or hypertension underwent three times of monthly consecutive intravitreal brolucizumab injections for treatment of progressed nAMD in his left eye. Two days after the third injection, the patient presented with acute painless visual loss. Typical retinal whitening with a cherry red spot was observed on the fundus photograph, and retinal swelling with hyper-reflectivity was also identified on the optical coherence tomography (OCT) scan. On the fundus fluorescein angiography, arm-to-retina time and arteriovenous transit time were remarkedly delayed, but clinical findings suggesting an intraocular inflammation (IOI) were not observed. Therefore, CRAO was diagnosed, and anterior chamber paracentesis was administrated immediately. However, there had been no improvement in visual acuity during the follow-up period of three months, despite prolonged oral steroid and anti-platelet agent medication. Conclusions In rare cases, patients without cardiovascular comorbidities can develop CRAO after intravitreal brolucizumab injection without gross evidence of IOI. Therefore, CRAO should always be in consideration and careful observation is required after intravitreal brolucizumab injection for nAMD patients with old age, even if the patient does not have any other cardiovascular disease history.

Abstract Introduction This study aimed to assess the efficacy and safety of adalimumab in pediatric patients with chronic non-infectious posterior uveitis and panuveitis (not associated with juvenile idiopathic arthritis). Methods The medical records of children (

Abstract Introduction To assess real-world safety outcomes for adults with neovascular age-related macular degeneration (nAMD) treated with brolucizumab from the US-based IRIS® (Intelligent Research in Sight) Registry. Methods In this retrospective study, 18,312 eyes (15,998 patients) treated with ≥ 1 intravitreal brolucizumab injections between 8 October 2019 (US launch date for brolucizumab) and 7 October 2021 were followed up for ≤ 2 years after first injection (index date). The study assessed the predefined incident ocular adverse events of intraocular inflammation (IOI), retinal vasculitis (RV), and retinal vascular occlusion (RO). Results Overall, 614/18,312 eyes (3.4%) experienced any IOI, RV, and/or RO event. Median (interquartile range [IQR]) time to an event was 84 (42–167) days; 77.4% of events (475/614) occurred within 6 months after index date. Median (IQR) number of brolucizumab injections before an event was 2 (1–4). For eyes with an adverse event and visual acuity (VA) data (n = 406), median (IQR) change in Early Treatment of Diabetic Retinopathy Study (ETDRS) letters from pre-event VA was 0 (− 7 to + 5) at the 6-month follow-up; 50 eyes (12.3%) had a VA loss of 10 or more ETDRS letters. Risk of an event (hazard ratio [95% confidence interval]) was decreased in eyes from male patients (0.61 [0.53–0.71]), from older patients (0.83 [0.76–0.90]), from treatment-naive patients (0.51 [0.38–0.69]), and from patients who started brolucizumab in the second year after launch (0.68 [0.53–0.86] vs. first year). Conclusion In this large real-world brolucizumab safety study, 3.4% of eyes experienced an IOI, RV, and/or RO event. Among eyes that experienced an adverse event for which VA data were available, median ETDRS vision change was 0 letters (IQR − 7 to + 5).

Abstract Background This study reports the first cases of scleritis following intravitreal brolucizumab (IVBr) injection for nAMD, emphasizing the need to be aware of the possibility of scleritis following IVBr injections. Case presentation Case 1. A 74-year-old Japanese man with nAMD complained of conjunctivitis and decreased vision in the right eye 8 days after his eighth IVBr injection. Examination revealed scleritis without anterior inflammation. Topical 0.1% betamethasone and 0.3% gatifloxacin eye drops were started. The scleritis worsened in the following 2 weeks and became painful. He underwent sub-Tenon’s capsule triamcinolone acetonide (STTA) injection. Two days later, he returned with a complaint of severe vision loss. Fundus examination revealed retinal artery occlusion, vasculitis, and vitreous opacity in the right eye. Vitreous surgery was performed. Case 2. An 85-year-old Japanese woman with nAMD in the right eye complained of reddening of the eye 27 days after her fifth IVBr injection. Examination showed conjunctivitis and scleritis without anterior inflammation in the right eye. She was started on 0.1% fluorometholone and 0.5% levofloxacin hydrate eye drops. The scleritis worsened in the following 3 weeks. Her treatment was switched to 0.1% betamethasone eye drops. One month later, the scleritis had improved and a sixth IVBr injection was administered. There was no worsening of the scleritis at that time. However, 1 month after a seventh IVBr injection, she complained of severe hyperemia and decreased vision. Fundus examination revealed vitreous opacification. She underwent STTA, and the vitreous opacity improved in 24 days. Case 3. A 57-year-old Japanese man with nAMD complained of pain and decreased vision in the right eye 21 days after a fourth IVBr injection. Examination revealed scleritis with high intraocular pressure but no anterior chamber or fundus inflammation. STTA and topical eye drops were performed. One month later, scleritis improved but visual acuity didn’t due to progression of nAMD. Conclusions Intraocular inflammation following IVBr injection may progress to the posterior segment. Scleritis can occur after IVBr injection, and topical eye drops alone may not be sufficient for initial treatment. Clinicians should consider the possibility of scleritis in patients with worsening inflammation after IVBr injection.

Background: To report a case of central retinal artery occlusion (CRAO) after intravitreal injection of brolucizumab for a treatment-naïve neovascular age-related macular degeneration (nAMD) patient without comorbid cardiovascular disease history. Case presentation: A 79-year-old Asian male without a cardiovascular disease history such as diabetes or hypertension underwent three times of monthly consecutive intravitreal brolucizumab injections for treatment of progressed nAMD in his left eye. Two days after the third injection, the patient presented with acute painless visual loss. Typical retinal whitening with a cherry red spot was observed on the fundus photograph, and retinal swelling with hyper-reflectivity was also identified on the optical coherence tomography (OCT) scan. On the fundus fluorescein angiography, arm-to-retina time and arteriovenous transit time were remarkedly delayed, but clinical findings suggesting an intraocular inflammation (IOI) were not observed. Therefore, CRAO was diagnosed, and anterior chamber paracentesis was administrated immediately. However, there had been no improvement in visual acuity during the follow-up period of three months, despite prolonged oral steroid and anti-platelet agent medication. Conclusions: In rare cases, patients without cardiovascular comorbidities can develop CRAO after intravitreal brolucizumab injection without gross evidence of IOI. Therefore, CRAO should always be in consideration and careful observation is required after intravitreal brolucizumab injection for nAMD patients with old age, even if the patient does not have any other cardiovascular disease history. [ABSTRACT FROM AUTHOR]

Background: This study reports the first cases of scleritis following intravitreal brolucizumab (IVBr) injection for nAMD, emphasizing the need to be aware of the possibility of scleritis following IVBr injections. Case presentation: Case 1. A 74-year-old Japanese man with nAMD complained of conjunctivitis and decreased vision in the right eye 8 days after his eighth IVBr injection. Examination revealed scleritis without anterior inflammation. Topical 0.1% betamethasone and 0.3% gatifloxacin eye drops were started. The scleritis worsened in the following 2 weeks and became painful. He underwent sub-Tenon's capsule triamcinolone acetonide (STTA) injection. Two days later, he returned with a complaint of severe vision loss. Fundus examination revealed retinal artery occlusion, vasculitis, and vitreous opacity in the right eye. Vitreous surgery was performed. Case 2. An 85-year-old Japanese woman with nAMD in the right eye complained of reddening of the eye 27 days after her fifth IVBr injection. Examination showed conjunctivitis and scleritis without anterior inflammation in the right eye. She was started on 0.1% fluorometholone and 0.5% levofloxacin hydrate eye drops. The scleritis worsened in the following 3 weeks. Her treatment was switched to 0.1% betamethasone eye drops. One month later, the scleritis had improved and a sixth IVBr injection was administered. There was no worsening of the scleritis at that time. However, 1 month after a seventh IVBr injection, she complained of severe hyperemia and decreased vision. Fundus examination revealed vitreous opacification. She underwent STTA, and the vitreous opacity improved in 24 days. Case 3. A 57-year-old Japanese man with nAMD complained of pain and decreased vision in the right eye 21 days after a fourth IVBr injection. Examination revealed scleritis with high intraocular pressure but no anterior chamber or fundus inflammation. STTA and topical eye drops were performed. One month later, scleritis improved but visual acuity didn't due to progression of nAMD. Conclusions: Intraocular inflammation following IVBr injection may progress to the posterior segment. Scleritis can occur after IVBr injection, and topical eye drops alone may not be sufficient for initial treatment. Clinicians should consider the possibility of scleritis in patients with worsening inflammation after IVBr injection. [ABSTRACT FROM AUTHOR]

Background and objective: Intravitreal injection of anti-VEGF agents is the first-line treatment for patients with neovascular-age related macular degeneration (nAMD). One unique serious adverse event that may be associated with these agents is intraocular inflammation (IOI). The main purpose of this analysis was to evaluate the potential presence of texture-based radiomics features characterizing heterogeneity within the vitreous compartment of spectral domain optical coherence tomography (SD-OCT) images that may precede or develop in association with IOI and might serve as OCT biomarkers for IOI. Methods: This is a post-hoc analysis of a subset of cases (N = 67) involving IOI, endophthalmitis, and/or retinal vascular occlusion in the phase 3 HAWK trial. These were investigator determined diagnoses that were also confirmed by the safety review committee. Intraocular inflammation was any signs of inflammation within the eye, endophthalmitis was inflammation associated with presumed infection, and retinal vascular occlusions consisted of intraocular inflammation with concurrent vascular occlusions/vasculitis. Out of 67 eyes, 34 belonged to the Safety group with an IOI event and 33 were propensity-matched Controls. A total of 481 texture-based radiomics features were extracted from the vitreous compartment of the SD-OCT scans at pre-IOI time point (i.e., much earlier than the actual event). Most discriminating five features, selected by the Wilcoxon Rank Sum feature selection were evaluated using Random Forest (RF) classifier on the training set (Str, N = 47) to differentiate between the two patient groups. Classifier performance was subsequently validated on the independent test set (St, N = 20). Additionally, the classifier performance in discriminating the Control and Safety group was also validated on St at the IOI event timepoint. Results: The RF classifier yielded area under the Receiver Operating Characteristics curve (AUC) of 0.76 and 0.81 on St using texture-based radiomics features at pre-IOI and event time-point, respectively. Conclusions: In this analysis, the presence of a pre-IOI safety signal was detected in the form of textural heterogeneity within the vitreous compartment even prior to the actual event being identified by the investigator. This finding may help the clinicians to assess for underlying posterior inflammation.

Real-world studies concerning different populations are valuable and bring new information regarding different regimens of Brolucizumab injections and their adverse reactions. The present study investigates the efficacy of a pro-re-nata regimen (PRN) for neovascular Age-related Macular Degeneration (nAMD). Separate from the main statistics we report the use of Brolucizumab in central serous chorioretinopathy (CSC).A retrospective observational single-center study was conducted on 82 eyes treated with Brolucizumab between 2021 and 2023, for nAMD. Patients were injected at intervals of at least 2 months after the loading phase. In 9 (3–20) months follow-up, only 0.26 % adverse reactions were noticed, with good resolution of retinal fluid (significant reduction of CST on SD-OCT, −72.50μ, p

Introduction: Here, we report a case of severe intraocular inflammation (IOI) and prominent choroidal thinning following the initial intravitreal brolucizumab injection (IVBr). Case Presentation: The patient was a 75-year-old Japanese man with type 2 age-related macular degeneration of both eyes. Until 2015, he had undergone two intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and two photodynamic therapies in his right eye. His decimal best-corrected visual acuity (BCVA) was 0.1 in the right eye and 0.1 in the left eye. Central choroidal thickness (CCT) measured 240 μm in his right eye. IVBr was administered to the right eye. The patient reported pain in the right eye 23 days after the injection. On day 26, panuveitis and retinal vasculitis were observed in the right eye. CCT measured 436 μm. On the same day, a sub-tenon triamcinolone injection was administered. On day 42, retinal inflammation remained at a similar level. The CCT decreased to 164 μm. On day 68, the intraocular pressure (IOP) in the right eye increased to 39 mm Hg, and IOI persisted. On day 89, the patient’s eye pain disappeared, and the IOP decreased to 13 mm Hg. On day 225, the IOI and symptoms were completely resolved. The decimal BCVA was 0.04 in the right eye, and CCT measured 84 μm. Conclusion: Brolucizumab is a highly effective anti-VEGF drug; however, it has the potential to induce inflammation in tissues adjacent to the retina and may occasionally cause irreversible sequelae.

Purpose: To determine the effect of phacoemulsification surgery, which is one of the types of cataract surgery by using ultrasonic power to break up the crystalline lens and clean it with vacuum, on anterior chamber flare (ACF) and choroidal vascular index (CVI). Methods: For this cross-sectional study, patients were included if they had cataract with nucleus hardness grade 2 or 3, no systemic inflammatory disease, and not use of anti-inflammatory drugs/prostaglandins preoperatively. ACF using a laser flare meter and CVI in patients underwent uncomplicated phacoemulsification was recorded preoperatively, on the postoperative 1st day, 1st week, and 1st month. Results: Fifty-six eyes were included. ACF was 9.00 ± 2.90 ph/ms preoperatively. Although ACF increased significantly on postoperative day-1 (39.38 ± 23.31ph/ms) and decreased gradually until the 1st month (14.03 ± 6.03ph/ms) after the operation, it was still significantly higher at the 1st month (p < 0.001). Macular and peripapillary CVI increased significantly on postoperative day-1 (0.64 ± 0.03/0.63 ± 0.05) and week-1 (0.64 ± 0.04/0.62 ± 0.04) (p = 0.01, p < 0.001); the postoperative 1st month was similar to the preoperative one (0.59 ± 0.06/0.58 ± 0.06). The relationship between the change in ACF and the change in CVI was not significant. Conclusion: Phacoemulsification causes raises in ACF and CVI due to increased intraocular inflammation. The fact that ACF was significantly higher in postoperative month-1 and CVI returned to its preoperative value suggests that the effect of uncomplicated phacoemulsification surgery on the increase in inflammation in the anterior segment lasts longer than in the posterior segment. These results suggest that ACF and CVI follow-up may be clinically important in the follow-up of postoperative inflammation. [ABSTRACT FROM AUTHOR]

Intraocular inflammations (IOIs) have been reported to occur after intravitreal injections of brolucizumab, and one of their causes has been suggested to be drug-specific features. We evaluated the anterior chamber by the aqueous flare value (AFV) and the retina by flicker electroretinography (ERG) after the initial intravitreal injection of aflibercept (IVA), brolucizumab (IVBr), or faricimab (IVF) for neovascular age-related macular degeneration (nAMD). The AFV and flicker ERGs were determined before, 2 weeks after, and 4 weeks after the injections in 14 eyes of 14 patients for each drug. After the injections, none of the patients had an IOI, but the AFV increased significantly in the IVA and IVF groups. The increase in the IVF group was +4.6 photon count/ms, which was significantly greater than in the other groups, but was not clinically significant. The implicit time was significantly prolonged in the IVBr group but unchanged in the IVA and IVF groups. These results suggest that brolucizumab, administered at high molar doses, may cause transient retinal disturbances that are not detectable by general ophthalmologic examinations but affect the implicit ERG times. [ABSTRACT FROM AUTHOR]

To assess the efficacy of adalimumab (ADA) on visual acuity (VA), ocular inflammation, vitreous haze and central macular thickness (CMT) in pediatric refractory non-infectious uveitis. Thirty-one eyes of 16 pediatric patients with uveitis of various etiologies were treated with ADA. VA, intraocular active inflammatory cells, vitreous haze, and CMT were evaluated at the baseline and 2nd, 4th, 12th, and 24th weeks following ADA treatment. Twenty-three of 31 eyes had active and the remaining 8 eyes had inactive uveitis (with frequent relapse) before ADA therapy. VA (LogMAR) increased at 12th week following ADA treatment (p<.001). Intraocular inflammation degrees significantly improved within 4 weeks (p<.001). Vitreous haze decreased at fourth week and stabilized at 12th week (p=.038). CMT started to decrease within weeks and stabilized at 12th week (p=.006). ADA was found to be safe and effective to suppress intraocular inflammation in pediatric non-infectious uveitis, which prevented sight-threatening complications. [ABSTRACT FROM AUTHOR]

Purpose: To investigate baseline characteristics associated with the incidence of intraocular inflammation (IOI) after the intravitreal injection of brolucizumab (IVBr) for the treatment of neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 66 eyes of 62 consecutive patients with nAMD who received IVBr (18 eyes were treatment naïve and 48 eyes had switched from other anti-vascular endothelial growth factor [VEGF] therapy). Baseline clinical characteristics were compared in non-IOI and IOI groups. Results: Although a dry macula was achieved at a high rate even 6 months after IVBr, IOI occurred in 8 of 66 eyes (12.1%; all had switched therapy) during the study period. Baseline characteristics including age, sex, nAMD type, lens status, visual acuity, central macular thickness, and a history of diabetes did not differ between the groups. The number of previous anti-VEGF injections before IVBr was greater in the IOI group (P = 0.004), and the ratio of patients with a laser flare-cell photometry (LFCP) value over 15 photon count per millisecond (pc/ms) was higher in the IOI group (P = 0.017). Multivariate logistic regression analysis showed that a greater number of previous anti-VEGF injections (odds ratio [OR]: 1.12, P = 0.006; area under the curve: 0.82, cut-off score: 14.0) and an LFCP value over 15 pc/ms (OR: 81.6, P = 0.031) were significantly associated with the incidence of IOI after IVBr. Conclusion: A number of previous anti-VEGF injections greater than 14 and an LFCP value more than 15 pc/ms might be useful predictors of the incidence of IOI after IVBr in eyes with nAMD. [ABSTRACT FROM AUTHOR]

To compare endothelial toxicity and efficacy of two local steroid injections (intracameral triamcinolone acetonide and subconjunctival dexamethasone) in controlling postoperative inflammation following pars plana vitrectomy (PPV) combined with phacoemulsification cataract surgery. This cohort included 54 patients that underwent combined surgery and received either intracameral triamcinolone acetonide injections (n = 27, IC-TA group) or subconjunctival dexamethasone (n = 27, Sc-Dex group) injections at the end of the surgery. All participants had at least 4 months or longer follow-up. A detailed ophthalmologic examination including intraocular pressure (IOP) measurement and specular microscopy was performed at every visit. Endothelial cell density (ECD) reduced significantly in IC-TA group postoperatively (2418 vs. 2249, p = 0.019), while it did not change significantly in Sc-Dex group (2541 vs. 2492, p = 0.247). Postoperative ECD was also significantly lower in IC-TA group compared to Sc-Dex group (p = 0.011). Preoperative and postoperative IOP values remained unchanged both in IC-TA and Sc-Dex groups (p = 0.424 and p = 0.523, respectively). However, 4 patients in IC-TA group and 5 patients in the Sc-Dex group needed glaucoma medications. The postoperative need for glaucoma medications was similar between the groups (p = 0.347). Postoperative inflammation was well controlled in both groups and none of the patients developed fibrin membrane or synechiae postoperatively. Both treatments were effective in controlling postoperative inflammation, but patients in IC-TA group experienced significantly higher endothelial loss. Sc-Dex injections are safer in terms of endothelial loss and preferable to control postoperative inflammation following complex intraocular surgeries. [ABSTRACT FROM AUTHOR]

Introduction: Here, we report a case of severe intraocular inflammation (IOI) and prominent choroidal thinning following the initial intravitreal brolucizumab injection (IVBr). Case Presentation: The patient was a 75-year-old Japanese man with type 2 age-related macular degeneration of both eyes. Until 2015, he had undergone two intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections and two photodynamic therapies in his right eye. His decimal best-corrected visual acuity (BCVA) was 0.1 in the right eye and 0.1 in the left eye. Central choroidal thickness (CCT) measured 240 μm in his right eye. IVBr was administered to the right eye. The patient reported pain in the right eye 23 days after the injection. On day 26, panuveitis and retinal vasculitis were observed in the right eye. CCT measured 436 μm. On the same day, a sub-tenon triamcinolone injection was administered. On day 42, retinal inflammation remained at a similar level. The CCT decreased to 164 μm. On day 68, the intraocular pressure (IOP) in the right eye increased to 39 mm Hg, and IOI persisted. On day 89, the patient’s eye pain disappeared, and the IOP decreased to 13 mm Hg. On day 225, the IOI and symptoms were completely resolved. The decimal BCVA was 0.04 in the right eye, and CCT measured 84 μm. Conclusion: Brolucizumab is a highly effective anti-VEGF drug; however, it has the potential to induce inflammation in tissues adjacent to the retina and may occasionally cause irreversible sequelae. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the effectiveness of the 0.19-mg fluocinolone acetonide (FAc) implant by multimodal measurements in patients with non-infectious uveitis (NIU) in a real-world setting in Spain. Methods: A prospective study of patients who had NIU including uveitic macular oedema (UME) with ≥ 12 months follow-up was done. Exclusion criteria include infectious uveitis and uncontrolled glaucoma or ocular hypertension requiring more than 2 medications. Effectiveness was assessed using a multicomponent outcome measure that included nine outcomes. Effectiveness was defined as all components being met at every timepoint. Secondary outcome measures were onset or progression of glaucoma and investigator-reported adverse events. Results: Twenty-six eyes from 22 patients were included, with 96.2% having an indication including UME. During the 12-month study, the FAc implant was effective in 15 (57.7%) eyes, reaching effectiveness as soon as 2 weeks post-implantation. Mean best-corrected visual acuity and mean central macular thickness (CMT) were significantly improved vs. baseline at all timepoints (all comparisons p < 0.01). During the 12-month study, inflammation markers (anterior chamber cells and vitreous haze) had also significantly declined. Factors predicting effectiveness at month 12 were systemic corticosteroid dose pre-FAc, higher immunomodulatory therapy (IMT) load at baseline and thicker retinal nerve fibre layer (RNFL) at baseline (all p < 0.05). Factors predicting failure were male gender, thinner RNFL at baseline and treatment ineffectiveness at 1 month (all p < 0.05). In parallel, corticosteroid and IMT use also declined significantly. No significant increase in IOP was detected. Conclusion: The FAc implant is safe and effective at treating NIU over 12 months in a real-world setting in Spain. [ABSTRACT FROM AUTHOR]

Purpose: This study was planned to compare the clinical results and optical coherence tomography (OCT) data of patients who underwent adalimumab (ADA), infliximab (IFX) and switched protocols between these two methods in cases of Behçet’s associated uveitis (BAU). Methods: The patients with BAU who were treated with anti-TNF-α agents for at least one year were qualified for the chart review. The outcome parameters were the steroid-free remission state, the best-corrected visual acuity (BCVA), the central macular thickness (CMT), and the subfoveal choroidal thickness (SFCT) of the patients at the last visit. Results: After a mean follow-up of 16.60 months, the rate of active inflammation decreased from 63.6% to 15.1%. Mean BCVA increased, mean CMT and mean SFCT decreased significantly at the last visit (P < 0.001, P < 0.001, respectively). Conclusion: Anti-TNF-α treatment and switching protocols between these two agents effectively and safely control intraocular inflammation in BAU patients.

Nicholas J Saba,1 Scott D Walter2 1Department of Ophthalmology, SUNY Downstate Medical Center, Brooklyn, NY, USA; 2Retina Consultants, PC, Hartford, CT, USACorrespondence: Scott D Walter, Retina Consultants, PC, 43 Woodland Street, Hartford, CT, USA, 06105, Tel +1860-206-2237, Fax +1860-409-7803, Email swalter@retinact.comImportance: Brolucizumab (Beovu®) is an anti-vascular endothelial growth factor (anti-VEGF) agent approved for the treatment of neovascular age-related macular degeneration (nvAMD). Brolucizumab was marketed for its noninferiority to aflibercept and its potential for greater durability. However, post-marketing utilization has been tempered by safety concerns.Objective: We evaluate the visual and anatomic efficacy of brolucizumab, examine changes in treatment intervals after switching to brolucizumab, and estimate the incidence of drug-related adverse events in the real world.Design, Setting, and Participants: This was a retrospective consecutive case series of 626 eyes (543 patients) with nvAMD treated with 1438 brolucizumab injections at a single retina practice between 10/1/2019 and 5/15/2020.Main Outcomes and Measures: Changes in visual acuity (VA); anatomic outcomes assessed by optical coherence tomography (OCT) including central subfield thickness (CST), macular volume (MV), presence of intraretinal fluid (IRF), subretinal fluid (SRF), and serous pigment epithelial detachment (sPED) on foveal line scans; treatment intervals before and after receiving brolucizumab; and the incidence of brolucizumab-related adverse events.Results: The majority of eyes (N = 531, 89.7%) had received prior anti-VEGF therapy with aflibercept, ranibizumab, and/or bevacizumab. VA improved in treatment-naïve eyes (+3.7 letters, p = 0.04), and was maintained in previously treated eyes. There were significant improvements in all anatomic outcomes in both groups (p < 0.001). We observed a 4.8% incidence of intraocular inflammation (IOI) and a 0.6% incidence of retinal vasculitis. The average treatment interval increased from 6.3 to 6.8 weeks (p = 0.001).Conclusions and Relevance: Brolucizumab treatment was associated with VA improvement in naïve eyes and maintenance of VA in previously treated eyes. Switching to brolucizumab was associated with improved anatomic outcomes and extended treatment intervals in most eyes. We observed a similar incidence of IOI and a lower incidence of retinal vasculitis compared to the Safety Review Committee’s analysis of HAWK and HARRIER.Keywords: Beovu, brolucizumab, anti-VEGF, intraocular inflammation, retinal vasculitis

Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period (p < 0.01). An IOP increase (p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older (p = 0.004) and had been treated with more dexamethasone (DEX) implants (p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone (p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 (p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures.

Abstract Introduction Intraocular inflammation (IOI)-related adverse events (AEs) that may result in severe vision loss have been associated with the anti-vascular endothelial growth factor brolucizumab. In this study, we investigate the timing, management and resolution of IOI-related AEs in a large cohort of patients treated with at least one injection of brolucizumab in routine clinical practice. Methods Retrospective review of medical records from patients with neovascular age-related macular degeneration treated with ≥ 1 brolucizumab injection between October 2019 and November 2021 at the Retina Associates of Cleveland, Inc. clinics. Results Of the 482 eyes included in the study, IOI-related AEs occurred in 22 (4.6%) eyes. Four (0.8%) eyes developed retinal vasculitis (RV) and of these, 2 (0.4%) had concomitant retinal vascular occlusion (RO). Most eyes [14/22 (64%)] developed the AE within 3 months and 4/22 (18%) within 3–6 months of the first brolucizumab injection. The median [interquartile range (IQR)] time from the last brolucizumab injection to development of the IOI-related AE was 13 (4–34) days. At the time of event, 3 (0.6%) eyes with IOI (no RV/RO) developed severe vision loss of ≥ 30 ETDRS letters, and a further 5 (1.0%) eyes (1 with IOI + RV, 1 with IOI + RV + RO) developed moderate vision loss of ≥ 15 letters compared with their last visual acuity (VA) prior to the AE. The median (IQR) vision loss was −6.8 (−19.9, –0.0) letters. Taking the best VA at either 3 or 6 months after AE resolution (or stability for occlusive events), VA decreased by ≥ 5 letters compared with prior to the AE in 3 (14%) of the 22 affected eyes, and was preserved (

Ella H Leung, Daniel J Oh, Shannon E Alderson, Joshlynn Bracy, Mia McLeod, Litzi I Perez, Alexander Bottini, David Chin Yee, Krishna Mukkamala Georgia Retina, Atlanta, GA, USACorrespondence: Ella H Leung, 833 Campbell Hill St NW, Suite 300, Marietta, GA, 30060, USA, Tel +1 770-218-1888, Email eleung@garetina.comPurpose: To evaluate the initial efficacy and safety of intravitreal faricimab in eyes previously treated for neovascular age-related macular degeneration (nARMD).Patients and methods: A retrospective review of all patients with nARMD previously treated with anti-vascular endothelial growth factor (anti-VEGF) injections who received at least 3 intravitreal faricimab injections with at least 3 months of follow-up.Results: A total of 190 eyes were included. Patients received a mean of 34.2± 23 anti-VEGF injections over 182.41± 128 weeks prior to switching to faricimab. Patients then received a mean of 6.99± 2.3 faricimab injections with an average 34.88± 8.2 weeks of follow-up. The mean best corrected visual acuities improved from 0.33± 0.32 logMAR &ap;20/43 to 0.27± 0.32 logMAR &ap;20/37 (P=0.0022). The central subfield thickness (CST) improved from 312± 87μm to 287± 71μm (P< 0.0001). At the last clinical visit, 24% had no subretinal fluid or intraretinal fluid on optical coherence tomography. The mean dosing interval between the last two consecutive faricimab injections (7.64± 6.2 weeks) was significantly longer than that for ranibizumab (5.16± 2.0 weeks, P< 0.001) or aflibercept (5.57± 3.6 weeks, P< 0.001). No patients developed idiopathic intraocular inflammation.Conclusion: Intravitreal faricimab was associated with improved vision and CSTs, even in treatment-resistant nARMD eyes. The mean last dosing interval for faricimab was longer than for ranibizumab or aflibercept. No significant adverse events were directly attributed to faricimab during the study.Keywords: faricimab, intravitreal injection, neovascular age-related macular degeneration, intraocular inflammation, anti-vascular endothelial growth factor

Background: Concerns of intraocular inflammation associated with intravitreal administration of anti-VEGF drugs have been risen and the exact mechanism is not yet elucidated. Objective: To explore the relationship between immunogenicity and intraocular inflammation in intravitreal anti-VEGF drugs. Methods: This review examines the immunogenicity of individual intravitreal anti-VEGF drugs and their potential link to intraocular inflammation. Results: We suggest that the main cause of intraocular inflammation is the presence of pre-existing and treatment-induced antidrug antibodies, along with considerations related to the molecular structure, which includes the drug's format and size. Conclusions: Researchers and clinicians involved in the advancement of new anti-VEGF drugs should take into consideration the factors related to intraocular inflammation that have been discussed.

Purpose: The aim of this analysis was to characterize the spectrum of inflammatory changes arising from brolucizumab use in routine clinical practice. Design: Retrospective analysis of fluorescein angiography (FA), fundus photography (FP) and OCT images taken at the time of adverse event. Subjects: Brolucizumab-treated patients with neovascular age-related macular degeneration with retinal vasculitis (RV) and/or retinal vascular occlusion (RO) reported to Novartis Patient Safety between February 2020 and January 2021. Methods: Ocular images were reviewed by an external reading center using predefined grading lists for FA, FP, and OCT. Main Outcome Measures: Classification of images, the most common imaging features of RV and/or RO by each imaging modality, and the anatomical location of the adverse event in relation to the macula. Results: Gradable images (N = 475; 222 eyes; 198 patients) were classified as RV only (n = 72); RO only (n = 9), RV + RO (n = 63); posterior segment intraocular inflammation (n = 31); or none by imaging (n = 47). Of the 144 eyes with RV and/or RO, the most common imaging features were vascular leakage on FA, perivascular sheathing on FP, and hyperreflective dots in the vitreous humor on OCT. Retinal vascular occlusion was mainly branched and arterial, affecting multiple vessels. Conclusions: Although no distinct inflammatory phenotype pathognomonic to brolucizumab-related inflammation was identified, this study increases our understanding of the spectrum of posterior segment inflammatory changes that may occur in brolucizumab-treated neovascular age-related macular degeneration patients, highlighting the potential value of widefield retinal imaging and angiography to detect these inflammatory adverse events. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Introduction: Intraocular inflammation (IOI)-related adverse events (AEs) that may result in severe vision loss have been associated with the anti-vascular endothelial growth factor brolucizumab. In this study, we investigate the timing, management and resolution of IOI-related AEs in a large cohort of patients treated with at least one injection of brolucizumab in routine clinical practice. Methods: Retrospective review of medical records from patients with neovascular age-related macular degeneration treated with ≥ 1 brolucizumab injection between October 2019 and November 2021 at the Retina Associates of Cleveland, Inc. clinics. Results: Of the 482 eyes included in the study, IOI-related AEs occurred in 22 (4.6%) eyes. Four (0.8%) eyes developed retinal vasculitis (RV) and of these, 2 (0.4%) had concomitant retinal vascular occlusion (RO). Most eyes [14/22 (64%)] developed the AE within 3 months and 4/22 (18%) within 3–6 months of the first brolucizumab injection. The median [interquartile range (IQR)] time from the last brolucizumab injection to development of the IOI-related AE was 13 (4–34) days. At the time of event, 3 (0.6%) eyes with IOI (no RV/RO) developed severe vision loss of ≥ 30 ETDRS letters, and a further 5 (1.0%) eyes (1 with IOI + RV, 1 with IOI + RV + RO) developed moderate vision loss of ≥ 15 letters compared with their last visual acuity (VA) prior to the AE. The median (IQR) vision loss was −6.8 (−19.9, –0.0) letters. Taking the best VA at either 3 or 6 months after AE resolution (or stability for occlusive events), VA decreased by ≥ 5 letters compared with prior to the AE in 3 (14%) of the 22 affected eyes, and was preserved (< 5-letter loss) in 18 (82%) eyes. Conclusions: In this real-world study, most IOI-related AEs occurred early after brolucizumab treatment initiation. With appropriate monitoring and management of IOI-related AEs, vision loss associated with brolucizumab may be limited. [ABSTRACT FROM AUTHOR]

Background and Objectives: Brolucizumab (IVBr) is a recently introduced anti-vascular endothelial growth factor (anti-VEGF) which has been found to be very effective in treating neovascular age-related macular degeneration (nAMD). We reported our findings in a case of nAMD that developed intraocular inflammation (IOI) after IVBr injections. Materials and Methods: A 79-year-old man was referred to our hospital complaining of reduced vision in both eyes of one-month's duration. His decimal best-corrected visual acuity (BCVA) was 0.9 in the right eye and 1.0 in the left eye. He was diagnosed with nAMD in the left eye and was treated with intravitreal aflibercept (IVA). Despite the three-monthly IVA injections, the serous retinal pigment epithelial detachment (PED) and subretinal fluid (SRF) remained, and the VA gradually decreased to 0.1. Because of the patient being refractory to aflibercept treatment, we switched to 3-monthly IVBr injections. The BCVA gradually improved to 0.3 and optical coherence tomography (OCT) showed an absence of the serous PED and SRF. Three weeks after his third IVBr, he returned to our hospital with a complaint of reduced vision in his left eye that he first noted two weeks earlier. Our examination of the left eye showed signs of IOI mainly in the anterior chamber. The inflammation improved with topical steroids but the treatment of the IOI was delayed for two weeks. The patient was instructed that it was important to begin the treatment as soon as the symptoms of IOI developed. We then performed the Mini-Mental State Examination (MMSE), and his score indicated that he had cognitive impairment. Conclusions: We concluded that before beginning IVBr treatment in nAMD patients, a careful assessment must be made of the cognitive status of the patient. [ABSTRACT FROM AUTHOR]

Purpose: To identify the inflammatory cytokine profile in the aqueous humor (AH) of patients with intraocular inflammation (IOI) after intravitreal administration of brolucizumab (IVBr) for neovascular age-related macular degeneration. Methods: Eight eyes from seven patients with IOI after initial IVBr (IVBrIOI +) were enrolled. Sixteen eyes from 16 patients without IOI after IVBr (IVBrIOI −) and aflibercept (IVA) were used as controls. AH samples were analyzed using a multiplex immunoassay. Results: C–C motif chemokine ligand (CCL)2, C-X-C motif chemokine ligand (CXCL)1, CXCL10, CXCL13, interleukin (IL)-6, IL-8, IL-10, matrix metalloproteinase (MMP)-1, MMP-9, granulocyte colony-stimulating factor (G-CSF), granulocyte–macrophage colony-stimulating factor (GM-CSF), intercellular adhesion molecule (ICAM)-1, E-selectin, and P-selectin levels were significantly higher in IVBrIOI + than in IVBrIOI − and IVA. Vascular endothelial growth factor (VEGF) was significantly lower in IVBrIOI − compared to that in IVBrIOI + and IVA. In the IVBrIOI + group, there were significant correlations between CCL2, CXCL1, IL-6, IL-8, IL-10, G-CSF, GM-CSF, ICAM-1, and E-selectin, which also exhibited significant correlations in the IVBrIOI − group. Conclusion: The number of inflammatory cytokines increases during IOI, which is associated with type IV hypersensitivity and vascular inflammation. Some cytokines exhibit correlations even in non-inflamed eyes, indicating a subclinical response to IVBr. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study is to explore the clinical features and associated factors of intraocular inflammation (IOI) following intravitreal brolucizumab (IVBr) administration for neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 87 eyes from 87 Japanese patients with nAMD who were followed up for 5 months after the initial administration of IVBr as switching therapy. Clinical pictures of IOI post-IVBr and changes in best corrected visual acuity (BCVA) at 5 months were evaluated between eyes with and without IOI (non-IOI). The association between IOI and baseline factors (age, sex, BCVA, hypertension, and/or arteriosclerotic changes in the fundus, subretinal hyperreflective material [SHRM], and macular atrophy) was evaluated. Results: Of the 87 eyes, 18 (20.6%) developed IOI and 2 (2.3%) developed retinal artery occlusion. There were 9 (50%) cases of posterior or pan-uveitis among eyes with IOI. The mean interval from initial IVBr administration to IOI was 2 months. The mean changes in logMAR BCVA at 5 months were significantly worse in IOI eyes than in non-IOI eyes (0.09 ± 0.22 vs. − 0.01 ± 0.15, P = 0.03). There were 8 (44.4%) and 7 (10.1%) cases of macular atrophy and 11 (61.1%) and 13 (18.8%) cases of SHRM in the IOI and non-IOI groups, respectively. SHRM and macular atrophy were significantly associated with IOI (P = 0.0008 and P = 0.002, respectively). Conclusion: In IVBr therapy for nAMD, eyes with SHRM and/or macular atrophy should be observed more meticulously, given the increased risk of developing IOI, which is associated with insufficient BCVA gain. [ABSTRACT FROM AUTHOR]

Short chain fatty acids (SCFAs) are produced by gut microbiota as fermentation products of digestion-resistant oligosaccharides and fibers. Their primary roles are functioning as major energy sources for colon cells and assisting in gut homeostasis by immunomodulation. Recent evidence suggests that they affect various organs both at cellular and molecular levels, and regulate functions in distance sites including gene expression, cell proliferation, cell differentiation, apoptosis and inflammation. In this study, we examined whether SCFAs are present in the mouse eye and whether SCFAs affect inflammatory responses of the eye and retinal astrocytes (RACs). We observed that intra-peritoneal injected SCFAs were detected in the eye and reduced intraocular inflammation induced by lipopolysaccharide (LPS). Moreover, SCFAs displayed two disparate effects on LPS-stimulated RACs - namely, cytokine and chemokine production was reduced, but the ability to activate T cells was enhanced. Our results support the existence of gut-eye cross talk and suggest that SCFAs can cross the blood-eye-barrier via the systemic circulation. If applied at high concentrations, SCFAs may reduce inflammation and impact cellular functions in the intraocular milieu.

Early poor outcomes of intraocular inflammation (IOI) after intravitreal brolucizumab (IVB) have negatively affected the use of brolucizumab in clinical routine. We wished to identify factors related to the treatment details of IOI involving the posterior segment resulting from IVB for neovascular AMD (nAMD), if these were reported in detail. Articles were retrieved from PubMed, Scopus, ClinicalTrials, and CENTRAL using the following search terms: AND AND . The risk of bias was rated using the JBI Critical Appraisal Tool. We included 31 reports (41 patients and 46 eyes). Patients were 75.9 ± 8.5 years, and 58.5% were female. IOI occurred 41.7 ± 37.5 (median 37.0) days after treatment initiation with 2.0 ± 1.3 (1–6) IVB injections. A mean change in visual acuity of −14.6 ± 21.0 (median −6.5) letters was reported. The mean time from first IOI signs to the initiation of any anti-inflammatory treatment was 3.3 ± 6.2 days, with 63% of the patients receiving systemic corticosteroids as standard treatment. Finally, a period effect was observed, with a change in visual acuity of −25.3 ± 27.1 and −2.6 ± 7.3 letters in the chronologically first and last third, respectively, of treated eyes (effect size: r = 0.71; p = 0.006). Functional outcomes markedly improved with increasing experience in managing IOI. [ABSTRACT FROM AUTHOR]

Uveitis in childhood poses a distinct challenge, mainly because of the insidious onset and chronic course of intraocular inflammation in most cases, which may result in permanent visual loss due to delayed diagnosis and treatment. Although anterior uveitis, frequently associated with juvenile idiopathic arthritis, is the most common form of ocular involvement, idiopathic intermediate uveitis (pars planitis) is also a common uveitic entity in childhood. Posterior or panuveitis of a variety of noninfectious or infectious etiologies may be seen as well. Pediatric uveitis needs to be closely monitored since serious ocular complications such as intraocular pressure elevation, cataract, and macular edema may rapidly develop due to inadequately controlled inflammation and/or the use of corticosteroids. Methotrexate is generally the firstline corticosteroid-sparing agent, and adalimumab is the first-line biologic in refractory cases of noninfectious uveitis. A multidisciplinary approach is essential to monitor systemic disease associations, treatment response, and adverse events in children with uveitis. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effectiveness of pars plana vitrectomy (PPV) without macular intervention on uveitis eyes with persistent vitreous inflammation/opacities in terms of visual acuity (VA), intraocular inflammation and macular profile. Methods: We carried out a single-center retrospective study of patients with uveitic eyes that underwent PPV without intervention on the macula due to persistent vitreous inflammation/opacities. The primary outcome measures were best-corrected visual acuity (BCVA), intraocular inflammation and macular profile at 3, 12 and 24 months after surgery. Results: Twenty-seven eyes of twenty-six patients were analyzed. Overall, 77.8% had an improvement of VA (55% by 0.3 LogMAR or more); 62.5% of patients had no intraocular inflammation, and the number of patients on systemic steroids and second-line immunosuppressives was reduced by 26% at 12 months; 87.5% of patients had resolution of macular oedema at 12 months. Conclusion: PPV for persistent vitreous inflammation/opacities is safe and effective, showing beneficial outcomes in terms of improvement of BCVA and the reduction in inflammation. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the study was to determine the short-term real-world safety and efficacy of intravitreal brolucizumab injections in Korean patients with neovascular age-related macular degeneration (nAMD). Methods: This multicenter retrospective study involved 294 eyes (treatment naïve 20 eye [6.8%] and nontreatment naïve 274 eyes [93.2%]) of 290 patients from 13 hospitals or retinal centers in South Korea. Patients with nAMD who received brolucizumab injection(s) between April 1 and November 30, 2021, with a follow-up ≥1 month, were included. Primary outcomes were safety, incidence of intraocular inflammation (IOI), and potential risk factors. The secondary outcome was efficacy, i.e., change in best-corrected visual acuity (BCVA) and optical coherence tomography-measured macular thickness and retinal fluid. Results: The mean age was 71.63 ± 8.66. The follow-up period was 2.38 ± 0.79 months. The mean number of brolucizumab injections during the follow-up was 1.52 ± 0.58. The overall incidence of IOI was 13.9% (n = 41 eyes). Most IOI cases were of anterior uveitis (8.8%, 26 eyes), followed by retinal vasculitis (2.4%, seven eyes) and occlusive retinal vasculitis (0.3%, one eye). Most eyes showed IOI resolution (n = 40, 97.5%) and BCVA restoration (n = 39, 95.1%) with or without corticosteroid treatment during the follow-up. Age, sex, IOI history, or other anti-vascular endothelial growth factor injection histories were not associated with the occurrence of IOI. However, only thin subfoveal choroidal thickness (SFCT) was associated with the occurrence of IOI (odds ratio = 0.995, p = 0.020). BCVA at 1 month improved from baseline (baseline 0.518 ± 0.356 vs. 1 month 0.503 ± 0.383, p = 0.023), but the improvement was not maintained. Anatomical improvement was significant after 3 months. Conclusion: In Korean patients with nAMD, the incidence of IOI following brolucizumab injections was 13.9%. IOI was well-controlled with or without steroid treatment. Most IOI eyes (95.1%) were restored to the level of vision before. IOI occurrence and occlusive vasculitis was rare. In the short term, brolucizumab injection effectively improved vision at 1 month and dried retinal fluid for 3 months. [ABSTRACT FROM AUTHOR]