PurposeTo evaluate retinal toxicity of ziv-aflibercept, a drug that had been approved for use for patients with colon cancer.MethodsTwenty-two albino rabbits were injected intravitreally with 0.1 mL of ziv-aflibercept solution into the experimental eye and 0.1-mL saline into the control eye. Twelve were used for electroretinogram (ERG) at 4-weeks follow-up. An additional 10 rabbits were used for testing penetration of ziv-aflibercept into the retina during follow-up. The visual-evoked potential (VEP) was recorded after 4 weeks of ERG follow-up. Glial fibrillary acidic protein (GFAP) immunocytochemistry and retinal histology were performed after the termination of the follow-up period.ResultsThe ERG responses of the experimental eyes did not show signs of permanent functional damage. The VEP responses of the experimental eyes were of normal pattern and amplitude, and were similar to those recorded by stimulation of the control eyes. Histologic studies of both experimental and control eyes did not show signs of structural damage. However, GFAP expression was increased in retinal Müller cells of the experimental eyes and not of the control eyes. Retinal penetration of ziv-aflibercept, as indicated by positive antihuman immunoreactivity, was observed 1 day postinjection and was strengthened during the next 7 days. At 14 days postinjection, ziv-aflibercept was not detected.ConclusionsZiv-aflibercept was found to be nontoxic to the retina of rabbits based on electrophysiologic testing and histologic examination. However, GFAP immunocytochemistry suggests mild retinal stress caused by the drug.Translational RelevanceIf proven safe, ziv-aflibercept may be a new affordable treatment option in conditions involving neovascularization and macular edema.

Behçet disease (BD) is a multisystemic disease that commonly involves the eyes. Although it affects patients in all age groups, data on ocular disease by age of onset are limited. This retrospective, multicenter study aimed to compare epidemiology, systemic and ocular manifestations, treatments and outcomes between three age groups: juvenile (<18 years), adult (18–39 years) and late (≥40 years) disease onset. The study included 175 ocular BD patients (303 eyes) from Israel and Palestine: juvenile-onset (n = 25, 14.3%), adult-onset (n = 120, 68.6%) and late-onset (n = 30, 17.1%). Most patients in all groups were male. Systemic manifestations were similar in all groups. Systemic co-morbidities were more common in late-onset patients. Bilateral panuveitis was the most common ocular manifestation in all patients. Non-occlusive retinal vasculitis, peripheral vessel occlusions, cataract and elevated intraocular pressure were found more commonly among juvenile-onset eyes. Anterior uveitis and macular ischemia were most common among late-onset eyes, while branch retinal vein occlusion was most common in adult and late-onset eyes. All patients were treated with corticosteroids. Methotrexate, immunomodulatory combinations and biologic treatments were more commonly used for juvenile-onset patients. All groups had a similar visual outcome. Our study showed that patients with ocular BD have varied ocular manifestations and require different treatments according to age of disease onset, but visual outcome is similar.

The literature on retinal vascular occlusions in Behçet disease (BD) patients is limited. The aim of this study is to thoroughly investigate retinal vascular occlusions among ocular BD patients. Methods: Retrospective, multicentre case-control study. Three-hundred and three eyes of 175 patients with ocular BD, from 13 hospitals in Israel and Palestine, were included. Patients were assigned into two groups according to the presence of retinal vascular occlusion. Epidemiology, systemic and ocular manifestations, treatments and outcomes were compared between the groups and risk factors for retinal vascular occlusions were identified. Results: One hundred twenty-five patients (71.4%) were male. The mean age at presentation was 28.2 ± 0.86 years. Retinal vascular occlusions were found in 80 eyes of 54 (30.9%) patients, including branch retinal vein occlusion (51.3%), peripheral vessels occlusions (32.5%), central retinal vein occlusion (13.8%) and arterial occlusions (7.5%). Systemic manifestations were similar among both groups. Anterior uveitis was more common in non-occlusive eyes (p < 0.01). Non-occlusive retinal vasculitis (p = 0.03) and ocular complications were more common in occlusive eyes (p < 0.01). Treatments including mycophenolate mofetil, Infliximab or a combination therapy of anti-metabolite and calcineurin inhibitor were more | M ET HOD SThis is a multicentre retrospective study, including 13 tertiary and non-tertiary medical centres, from Israel