Rituximab for Autoimmune Retinopathy

目的：自身免疫性视网膜病变（AIR）是一种眼科疾病，其中自身抗体损伤视网膜及其组分，导致进行性视力丧失。AIR没有既定的治疗方法，但全身免疫抑制已显示出良好的反应。利妥昔单抗是一种特异性结合B淋巴细胞的免疫抑制剂。本研究的目的是探讨利妥昔单抗作为一种有效治疗AIR的安全性。 研究人群：5名AIR和至少一只眼睛的视力为20/200或更好的受试者将接受利妥昔单抗治疗。AIR必须通过免疫组化证实正常、未固定、冷冻恒河猴或人视网膜上的血清抗视网膜抗体，以及视野和视网膜电图（ERG）变化来证实。如果受试者在接受利妥昔单抗治疗前退出研究，则最多可入组7名受试者，以获得5名受试者纳入分析。 设计：研究时间为18个月。利妥昔单抗作为一个周期给药，包括两次单独的利妥昔单抗输注，每次1,000 mg，间隔两周。参与者将在基线时接受第一个利妥昔单抗周期，并在六个月后接受第二个周期的评估。治疗成功定义为与基线相比，ERG反应幅度改善25%或Humphrey视野分析仪HFA（30-2）平均偏差改善3分贝（dB）或Goldmann视野（GVF）现有暗点阈值改善> 0.5 log或GVF评估暗点面积改善25%。因此，参与者在本研究中最多可以接受两个周期。受试者将在每个周期首次输注后6周和3个月返回诊所进行安全性访视。在研究期间，研究访视将每三个月进行一次。 结果测量：主要结果是在基线后6个月内符合治疗成功定义的参与者人数。次要疗效结局包括视力的变化、9个月和12个月时治疗成功的数量、6个月、9个月和12个月时部分应答者的数量、HFA（30-2）或GVF证明的ERG或视野的变化、光学相干断层扫描（OCT）的变化、荧光素血管造影（FA）的变化、血清抗视网膜自身抗体或抗视网膜抗体染色的变化、色觉的变化、阳性视觉症状或夜盲症以及通过NEI视觉功能问卷评估的参与者生活质量的变化。对于入组前有2次ERG测量结果的受试者，将尝试比较研究前阶段的下降率与入组后阶段的下降率。安全性结局包括全身和眼部毒性、不良事件和感染的数量和严重程度，以及ETDRS字母评分损失15分的受试者比例。

Objective: Autoimmune retinopathy (AIR) is an ophthalmic disorder in which autoantibodies damage the retina and its components, causing progressive vision loss. AIR has no established treatment, but systemic immunosuppression has shown favorable responses. Rituximab is an immunosuppressive agent which binds specifically to B lymphocytes. The objective of this study is to investigate the safety of rituximab as an effective treatment for AIR. Study Population: Five participants with AIR and visual acuity of 20/200 or better in at least one eye will receive rituximab. AIR must be confirmed by immunohistochemical demonstration of serum anti-retinal antibodies on normal, unfixed, frozen rhesus monkey or human retinas, as well as visual field and electroretinography (ERG) changes. Up to seven participants may be enrolled in order to obtain the five participants to be included in the analysis if participants withdraw prior to receiving rituximab. Design: The study duration is 18 months. Rituximab is administered as a cycle consisting of two separate rituximab infusions of 1,000 mg each, two weeks apart. Participants will receive their first rituximab cycle at baseline and evaluated for a second cycle six months later. Treatment success is defined as experiencing a ≥ 25% improvement in ERG response amplitudes or ≥ 3 decibel (dB) improvement in mean deviation on Humphrey Field Analyzer HFA (30-2) or improvement in threshold values > 0.5 log in the existing scotomas on Goldmann Visual Field (GVF) or ≥ 25% improvement in the area of scotomas on GVF assessment as compared with baseline. As a result, participants could receive a maximum of two cycles in this study. Participants will return to the clinic six weeks and three months after their first infusion of each cycle for a safety visit. Study visits will continue every three months for the study duration. Outcome Measures: The primary outcome is the number of participants who meet the definition of treatment success within six months from baseline. Secondary efficacy outcomes include changes in visual acuity, the number of treatment successes at 9 and 12 months, the number of partial responders at 6, 9 and 12 months, changes in ERG or visual field as demonstrated by the HFA (30-2) or GVF, changes in optical coherence tomography (OCT), changes in fluorescein angiography (FA), changes in serum anti-retinal autoantibody or anti-retinal antibody staining, changes in color vision, positive visual symptoms or nyctalopia and changes in the participants quality-of-life as assessed by the NEI visual function questionnaire. For participants with ≥ 2 ERG measurements available prior to enrollment, an attempt will be made to compare the rate of decline pre-study period to the rate of decline post-enrollment period. Safety outcomes include the number and severity of systemic and ocular toxicities, adverse events, and infections and the proportion of participants with a loss of ≥ 15 ETDRS letter score.