Vogt-Koyanagi-Harada Disease Associated with Hepatitis B Vaccination

Purpose: To report a case of Vogt–Koyanagi–Harada (VKH) disease associated with hepatitis B vaccination.

Methods: Case report.

Results: A 43-year-old Caucasian male presented with a three-week history of blurry vision, pain, photophobia, and redness in both eyes. Three days prior to the onset of symptoms, he had received the hepatitis B virus vaccine. Clinical evaluation revealed multifocal placoid lesions in the posterior pole, choroidal thickening, and serous macular detachment. Targeted laboratory investigations were negative for infectious or autoimmune markers. After treatment with oral corticosteroids, the patient had resolution of symptoms with near-total recovery of visual function. The patient later reported systemic findings of hearing loss, tinnitus, and integumentary changes. A diagnosis of VKH disease was made and inflammation was managed with oral corticosteroids followed by methotrexate for long-term disease control.

Conclusions: VKH disease is an inflammatory condition primarily affecting the choroid, retinal pigment epithelium, and outer retina. The underlying etiology is unclear, but it can be associated with a viral prodrome suggesting an infectious trigger in a genetically susceptible individual. Our case suggests that hepatitis B vaccination may trigger a similar inflammatory response.     

葡萄膜炎并发白内障患者晶状体前囊膜中NLRP3炎症小体相关蛋白的表达和前囊膜超微结构改变

目的　探究葡萄膜炎并发白内障患者晶状体前囊膜中NLRP3炎症小体相关蛋白的表达和前囊膜超微结构改变。方法　随机选取2018年8月至2019年6月在我院诊治的葡萄膜炎并发白内障患者17例(22眼)作为试验组；老年性白内障患者10例(18眼)作为对照组。均于白内障超声乳化手术中环形撕囊获取前囊膜。采用免疫组织化学法检测两组患者晶状体前囊膜NLRP3炎症小体的三个组成结构NLRP3、Caspase-1和接头蛋白ASC的蛋白表达，并对前囊膜进行电镜观察。结果　两组患者晶状体前囊膜中均有NLRP3炎症小体相关蛋白的表达；试验组晶状体前囊膜中NLRP3、Caspase-1及接头蛋白ASC（光密度值分别为0.383±0.067、0.313±0.058、0.335±0.035）表达水平均明显高于对照组（光密度值分别为0.330±0.085、0.271±0.039、0.268±0.036）（均为P<0.05）。试验组患者前囊膜的晶状体上皮细胞可见明显的细胞核固缩，染色质浓缩边集，细胞核膜皱褶、轻度增宽，线粒体形态基本正常、部分线粒体嵴突消失，细胞质中可见典型的凋亡小体。对照组有轻度凋亡改变。结论　NLRP3炎症小体可能参与了葡萄膜炎并发白内障的发病过程，细胞凋亡是葡萄膜炎并发白内障的重要病理改变。     

Dexamethasone for ocular inflammation

Introduction: Corticosteroids, administered systemically and periocularly, have long been used to treat intermediate and posterior segment noninfectious uveitis. In addition to systemic immunosuppressive medications, these therapies are used to reduce inflammation, prevent structural complications and prevent long-term visual loss in patients with uveitis. While systemic immunosuppressive therapies carry their own set of side effects, treatment with local steroids is associated with the risk of development of cataract and glaucoma.

Areas covered: Intravitreal delivery of fluocinolone acetonide via a sustained-release implant (Retisert) was approved by the FDA in 2005 for the treatment of noninfectious intermediate and posterior uveitis. Recently, the FDA also approved the biodegradable dexamethasone implant (Ozurdex) for the treatment of noninfectious uveitis involving the posterior segment.

Expert opinion: The single injection, 26-week data indicate that the implant is well tolerated and produces meaningful improvements in intraocular inflammation and visual acuity that persist through 6 months. The available 6-month data also indicate that this implant confers much less of a risk of ocular hypertension than other forms of intraocular steroid therapy. However, future longer-term trials are needed to evaluate the efficacy and safety data in patients who receive multiple injections. The newly approved dexamethasone implant, Ozurdex, is a useful addition to our local armamentarium in the treatment of noninfectious intermediate and posterior uveitis given its efficacy, safety, and ease of use in the outpatient setting.     

白芍总苷辅助治疗系统性红斑狼疮伴发葡萄膜炎的疗效分析

目的观察分析白芍总苷辅助治疗系统性红斑狼疮伴发葡萄膜炎的临床效果。方法将2009年2月—2011年10月杭州市红十字会医院眼科门诊系统性红斑狼疮伴发葡萄膜炎患者78例随机分为治疗组和对照组,治疗组40例采用白芍总苷辅助西药结合治疗,对照组38例单用西药常规治疗,平均随访为6个月,比较评估2组治疗后的临床疗效。结果治疗组总有效率为95.00%,对照组总有效率为78.95%,2组治疗后临床疗效比较有显著差异(P<0.05)。结论白芍总苷辅助治疗系统性红斑狼疮伴发葡萄膜炎的效果满意,优于常规西药治疗。     

Uveitis in Mouse and Man

Uveitis is underappreciated as a sight-threatening cause of blindness. There are two broad causative classes of uveitis: infectious and non-infectious. Non-infectious uveitis is considered a prototypical autoimmune disorder based mainly on data from experimental models in the mouse. Several different experimental models exist that reflect the different types of uveitis in man (anterior, intermediate, and posterior uveitis). These models have demonstrated that uveitis is predominantly a Th1/Th17 mediated disease, although innate immune cells play a significant role both in induction of disease and in tissue damage. Most experimental models of uveitis rely on activation of the innate immune system by use of adjuvants that activate a range of pathogen recognition receptors (PRRs). This begs the question of the underlying role of initial and/or persistent infection, including latent infection, in immune-mediated uveitis in which active infection cannot be demonstrated. This further raises the possibility of pathogenic mechanisms such as antigenic cross-reactivity and molecular mimicry. Alternatively, residual/latent antigen from infectious agents may act as “endogenous” adjuvants for induction of immune reactions to damaged/altered self antigen, suggesting a commonality in pathogenesis for both infectious and non-infectious uveitis in man.     

Does switching anti-TNFα biologic agents represent an effective option in childhood chronic uveitis: The evidence from a systematic review and meta-analysis approach

Objective

To summarize the evidence regarding the effectiveness of switching to a second anti-TNFα treatment in children with autoimmune chronic uveitis (ACU), refractory to the first course of anti-TNFα treatment.

Methods

We conducted a systematic literature review between January 2000 and May 2013 to investigate the efficacy of a second anti-TNFα agent in the treatment of ACU in children (≤16 years) refractory to a first course of a single anti-TNFα treatment, topical and/or systemic steroid therapy and at least one DMARD. The primary outcome measure was the improvement of intraocular inflammation, as defined by the SUN working group criteria, at 6 (±2) months of treatment.

Results

Among 1086 identified articles, 128 were scrutinized: 10 observational studies, 6 on adalimumab (ADA), 3 on infliximab (INF), and 1 on both, were deemed eligible. Study cohort included 40 children (ADA = 34 and INF = 6), median age 8 years (range 3–16). Nine were males, 28 females (gender not reported in 3), 39/40 were affected by JIA. Seventeen children received etanercept: 11 were switched to ADA, the remaining 6 to INF. All 23 children who previously received INF were switched to ADA. Altogether, 30 children (24 on ADA, 6 on INF) of 40 responded to treatment: 0.75 (95% CI: 0.51–100) was the combined estimate of the proportion of subjects improving.

Conclusions

Despite the fact that no RCT is available and the number of cases is small, this review provides evidence that switching to a second anti-TNFα agent results in improvement of ocular activity for the 75% treated children     

Characterization of Gene Therapy Associated Uveitis Following Intravitreal Adeno-Associated Virus Injection in Mice

PurposeTo characterize the intraocular immune cell infiltrate induced by intravitreal adeno-associated virus (AAV) gene therapy.MethodsAAV vectors carrying plasmids expressing green fluorescent protein under the control of PR2.1 were injected intravitreally into AAV naive and AAV primed C57Bl/6 mice. Clinical inflammation was assessed using optical coherence tomography. Intraocular immune cell populations were identified and quantified by flow cytometry on days 1, 7, and 29 after intravitreal injection and compared with sham and fellow eye controls.ResultsOptical coherence tomography inflammation score and total CD45+ cell number were significantly higher in AAV injected eyes compared to uninjected fellow eye and sham injected controls. Clinically apparent inflammation (vitritis on optical coherence tomography) and cellular inflammation (CD45+ cell number) was significantly increased in AAV injected eyes and peaked around day 7. Vitritis resolved by day 29, but cellular inflammation persisted through day 29. On day 1, neutrophils and activated monocytes were the dominant cell populations in all AAV injected eyes. On day 7, eyes of AAV exposed animals had significantly more dendritic cells and T cells than eyes of AAV naive animals. By day 29, CD8– T cells were the dominant CD45+ cell population in AAV injected eyes.ConclusionsIntravitreal AAV injection in mice generates clinically evident inflammation that is mild and seems to resolve spontaneously. However, the total number of intraocular CD45+ cells, particularly T cells, remain elevated. Both innate and adaptive immune cells respond to intravitreal AAV regardless of prior immune status, but the adaptive response is delayed in AAV naive eyes.