Incidence, clinical features, risk factors, and outcomes of Intraocular inflammation following Brolucizumab in Indian eyes – A multicentric study

Purpose: To report the incidence, clinical features, potential risk factors, and outcomes of intraocular inflammation (IOI) following brolucizumab in Indian eyes. Methods: All consecutive patients diagnosed with brolucizumab?induced IOI from 10 centers in eastern India between October 2020 and April 2022 were included. Results: Of 758 injections given during the study period across centers, 13 IOI events (1.7%) were recorded attributable to brolucizumab. The IOI occurred after the first dose in two eyes (15%) (median 45 days after brolucizumab), second dose in six eyes (46%) (median = 8.5 days), and third dose (39%) in the remaining five eyes (median 7 days). Reinjections of brolucizumab were administered at a median interval of 6 weeks (interquartile range = 4–10 weeks) in the 11 eyes, where IOI occurred after the second or third dose. Eyes that experienced IOI after the third dose had received a significantly greater number of previous antivascular endothelial growth factor injections (median = 8) compared to those who developed it after the first or second dose (median = 4) (P = 0.001). Anterior chamber cells were seen in almost all eyes (n = 11, 85%), while peripheral retinal hemorrhages were seen in two eyes, and one eye showed branch artery occlusion. Two?thirds of patients (n = 8, 62%) recovered with a combination of topical and oral steroids, while remaining recovered with topical steroids alone. Irreversible visual loss was not seen in any eye, and median vision recovered to pre?IOI levels by 3 months’ time point. Conclusion: Brolucizumab?induced IOI was relatively rare, occurring in 1.7% of eyes, was more common after the second or third injection, especially in those who required frequent reinjections every 6 weeks, and occurred earlier with increasing number of previous brolucizumab injections. Continued surveillance is necessary even after repeated doses of brolucizumab.

Firocoxib on aqueous humor prostaglandin E 2 levels for controlling experimentally-induced breakdown of blood-aqueous barrier in healthy and Toxoplasma gondii -seropositive cats / Efeitos do firocoxib sobre os níveis de prostaglandina E 2 no humor aquoso de gatos saudáveis e com sorologia positiva para toxoplasmose mediante quebra da barreira hematoaquosa experimentalmente induzida

ABSTRACT: This study aimed to evaluate the effects of firocoxib for controlling experimentally-induced breakdown of the blood-aqueous barrier in healthy and Toxoplasma gondii -seropositive cats. Thirty two cats with no ocular abnormalities were used. Groups (n=8/each) were formed with healthy cats that received 5mg g-1 of oral firocoxib (FH) or no treatment (CH) on day 0; seropositive cats for anti -T. gondii specific immunoglobulin G (IgG) were grouped (n=8/each) and treated in a similar fashion (FT and CT). On day 1, cats of all groups received the same treatment protocol, and 1h later, aqueocentesis was performed under general anesthesia (M0). Following 1h, the same procedure was repeated (M1). Quantitation of aqueous humor total protein and prostaglandin E2 (PGE2) were determined. Aqueous samples of seropositive cats were tested for anti- T. gondii specific IgG. In M0, aqueous samples of CT showed a significantly higher concentration of PGE2 in comparison with other groups (P<0.05). In all groups, PGE2 concentration increased significantly from M0 to M1 (P=0.001). PGE2 values did not change significantly between groups in M1 (P=0.17). Anti- T. gondii specific IgG were reported only in samples of M1, and aqueous titers did not change significantly between FT and CT (P=0.11). Although we have observed that aqueous humor PGE2 levels were significantly higher in cats of CT group during M0, such increase was not able to break the blood-aqueous barrier and cause anterior uveitis. Firocoxib did not prevent intraocular inflammation after aqueocentesis, in healthy and toxoplasmosis-seropositive cats.

RESUMO: Objetivou-se avaliar a eficácia do firocoxib no controle da quebra da barreira hematoaquosa experimentalmente induzida em gatos saudáveis e com sorologia positiva para toxoplasmose. Para tanto, utilizaram-se trinta e dois gatos sem alterações oculares, alocados em grupos (n=8/cada) compostos por gatos saudáveis que receberam tratamento prévio com 5mg g-1 de firocoxib oral (HF) ou sem nenhum tratamento (CH) no dia 0, e por gatos com sorologia positiva para toxoplasmose tratados de maneira similar (FT e CT). No dia 1, os gatos de todos os grupos receberam o mesmo protocolo de tratamento do dia anterior e, 1h depois, foram submetidos à paracentese da câmara anterior sob anestesia geral (M0). Após 1h, realizou-se nova paracentese (M1). Mediante a colheita de humor aquoso (M0 e M1), quantificaram-se os valores de proteína total e prostaglandina E2 (PGE2) das amostras. As amostras dos gatos com sorologia positiva para toxoplasmose foram também testadas para anticorpos anti- T. gondii IgG específicos. Em M0, as amostras de humor aquoso de CT apresentaram concentração de PGE2 significativamente superior aos demais grupos (P<0,05). Em todos os grupos, a concentração de PGE2 aumentou significativamente de M0 para M1 (P=0,001), no entanto, não houve diferença significativa entre os grupos em M1 (P=0,17). Anticorpos anti -T. gondii IgG específicos foram encontrados somente em amostras de M1, e os títulos não diferiram significativamente entre FT e CT (P=0,11). Valores de PGE2 significativamente superiores no CT durante M0 não foram capazes de induzir a quebra da barreira hematoaquosa e causar uveíte anterior nos gatos deste estudo. O firocoxib, por sua vez, não foi capaz de prevenir a quebra da barreira hematoaquosa após realização de paracente na câmara anterior em gatos saudáveis e com sorologia positiva para toxoplasmose.

Vitreoretinal lymphomas misdiagnosed as uveitis: Lessons learned from a case series.

Purpose: To present challenging cases of vitreoretinal lymphoma (VRL) that was misdiagnosed as uveitis because of the apparent intraocular inflammation. At the light of the new classification of intraocular lymphomas, we detail the characteristics that masqueraded the tumors and the clinical aspects that guided us to the correct diagnosis. Materials and Methods: We retrospectively reviewed the patients referred to our uveitis service between January 2006 and December 2014. Results: Seven patients referred with a presumptive diagnosis of idiopathic uveitis received a final diagnosis of VRL. The median time between the onset of symptoms and definitive diagnosis was 25 months for these complex cases. The median time from presentation at our clinic to final diagnosis was 1 month. The described clinical features including dense vitreous cells and subretinal infiltrates were characteristic and tend to be present in all these chronically ill patients. Vitreous samples were collected, and all demonstrated the pathognomonic tumor cells, the specific immunoglobulin heavy chain gene rearrangements, and an interleukin (IL)‑10 to IL‑6 ratio >1. Conclusion: VRLs are severe diseases with a poor prognosis that may be misdiagnosed as idiopathic inflammatory conditions of the eye. Treatment with steroids may occult the tumors and delay the correct diagnosis. Appropriate evaluation may prompt to a timely vitreous sampling and therefore to a faster diagnosis in these peculiar cases where the correct diagnosis was delayed by several months.

Vitreous Web after Pars Plana Vitrectomy and Bevacizumab Injection

PURPOSE: To report a case of vitreous inflammation (vitreous web) after intravitreal bevacizumab injection accompanying pars plana vitrectomy (PPV) for the treatment of proliferative diabetic retinopathy with vitreous hemorrhage. CASE SUMMARY: A 41-year-old female who underwent panretinal photocoagulation for diabetes mellitus (DM) retinopathy presented with decreased visual acuity in her right eye which was caused by vitreous hemorrhage. The patient underwent PPV with intravitreal bevacizumab injection. One day after surgery, the vitreous hemorrhage cleared and there was no inflammation in the anterior segment; however, multiple inflammatory white strands (vitreous web) were found in the vitreous cavity. She was diagnosed with non-infectious endophthalmitis and treated with topical steroid and additional oral steroids, resulting in clearance of the vitreous web on postoperative day 4. One month later, vitreous hemorrhage occurred in the other eye. PPV without bevacizumab injection cleared the vitreous hemorrhage with no evidence of vitreous web. CONCLUSIONS: Vitreous web-like inflammation can occur after intravitreal bevacizumab injection accompanying PPV for the treatment of DM vitreous hemorrhage. After eliminating infectious endophthalmitis based on lack of pain, conjunctival injection, anterior chamber hypopyon, and inflammatory cells, the web can be cleared without invasive intravitreal antibiotics injections.

Visual impairment from uveitis in a reference hospital of Southeast Brazil: a retrospective review over a twenty years period / Deficiência visual em uveítes em hospital de referência da região sudeste do Brasil: uma revisão retrospectiva de 20 anos

PURPOSE: To identify the frequency and causes of uveitis leading to visual impairment in patients referred to the Low Vision Service - Department of Ophthalmology - UNIFESP, over a twenty years period. METHODS: In a retrospective study, medical records of 5,461 patients were reviewed. Data from the first clinical evaluation at the Low Vision Service were collected, patient's age, gender and cause of visual impairment were analyzed. Patients with uveitis had their chart reviewed for anatomical classification and clinical diagnosis. RESULTS: The mean age of the patients referred to the Low Vision Service was 42.86 years and the mean age of patients with uveitis diagnosis was 25.51 years. Retinal disorders were the most common cause of visual impairment (N=2,835 patients; 51.9%) followed by uveitis (862 patients, 15.7%). Uveitis was posterior in 792 patients (91.9% of uveitis) and toxoplasmosis was the most common diagnosis (765 patients, 88.7%). CONCLUSIONS: In our study, uveitis represents the second cause of visual impairment in patients referred for visual rehabilitation and toxoplasmic retinochoroiditis was the most common clinical diagnosis. It affects a young working age population with a relevant social and economic impact, but the early diagnosis and treatment can improve the quality of life of these patients.

OBJETIVO: Identificar a frequência e as causas de uveítes que resultam em deficiência visual, em pacientes encaminhados ao Serviço de Visão Sub-Normal do Departamento de Oftalmologia - UNIFESP, durante um período de 20 anos. MÉTODOS: Em um estudo retrospectivo foram revisados 5.461 prontuários. Foram coletados os dados da primeira avaliação clínica realizada no Setor de Visão Sub-Normal, que inclui idade do paciente, sexo e a causa da deficiência visual. Os registros clínicos dos pacientes com diagnóstico de uveíte foram revisados para classificação anatômica e diagnóstico. RESULTADOS: A média de idade dos pacientes encaminhados para o Setor de Visão Sub-Normal foi de 42.86 anos e a média de idade dos pacientes com diagnóstico de uveíte foi de 25.51 anos. As doenças retinianas foram as causas mais comuns de deficiência visual (N=2.835 pacientes; 51.9%), seguida por uveítes (N=862 pacientes, 15.7%). Foi observado uveíte posterior em 792 pacientes (91.9% dos casos de uveíte) e, dentre estes, toxoplasmose foi o diagnóstico mais comum (765 pacientes, 88.7%). CONCLUSÕES: Em nosso estudo, uveíte representa a segunda causa de deficiência visual nos pacientes encaminhados para reabilitação visual e retinocoroidite por toxoplasmose foi o diagnóstico clínico mais comum. Uveíte afeta uma população jovem e em idade laboral, portanto com relevante impacto social e econômico, mas o diagnóstico e tratamento precoce podem melhorar a qualidade de vida destes pacientes.

Inflammatory choroidal neovascular membrane in posterior uveitis—pathogenesis and treatment.

Choroidal neovascular membrane (CNVM) formation is a well-documented sight-threatening complication of posterior segment intraocular inflammation (PSII). The aim of this article is to review the basic and clinical science literature on the pathogenesis of CNVM formation in PSII and to present results of a case series. We searched the literature using the mesh terms- inflammation, CNVM, age-related macular degeneration, immunosuppression, photodynamic therapy, steroids, vascular endothelial growth factors and posterior uveitis. Additionally, we evaluated the visual outcome of and clinical response to our standard treatment protocol involving a combination treatment for young patients with inflammatory CNVM. The development of CNVM in PSII is promulgated by infiltrating myeloid cells as well as choroidal and retinal myeloid cell activation, subsequent vascular endothelial growth factors, cytokine and chemokine production and complement activation acting in consort to mediate angiogenic responses. No clear standard of care currently exists for the treatment of inflammatory CNVM and various combinations have been tried. Using our combination treatment, visual acuity improved in four, stabilized in one and worsened in four patients. Though significant advances have occurred in the understanding of the pathogenesis and management of this condition, optimizing therapeutic regimens will require further well-constructed prospective cohort series.