非感染性葡萄膜炎的系统治疗进展

葡萄膜炎是发生于眼内组织的炎症反应。其中,非感染性葡萄膜炎是T细胞介导的自身免疫性炎症反应。尽管非感染性葡萄膜炎的系统治疗方案多种多样,但主要原理都是抑制自身免疫反应。在本综述中,我们回顾了非感染性葡萄膜炎系统治疗的历史,详细叙述了系统治疗的现状,总结了各治疗方案的利弊,同时对非感染性葡萄膜炎的系统治疗进行一定的展望。     

Corneal esthesiometry and sub-basal nerves morphological changes in herpes simplex virus keratitis/uveitis patients

AIM: To describe and compare corneal sensation and morphological changes of sub-basal corneal nerves by in vivo laser scanning confocal microscopy (LSCM) in herpes simplex virus (HSV) keratitis/uveitis and contralateral, clinically unaffected eyes. METHODS: A prospective clinical study included 30 HSV eyes and 30 contralateral eyes of 30 patients, diagnosed with unilateral HSV keratitis/uveitis. Both eyes underwent a complete ophthalmological examination, Cochet-Bonnet aesthesiometry and LSCM of the central cornea, using the Heidelberg Retina Tomograph III Rostock Cornea Module. After 6mo, the same examination of the HSV affected and contralateral, clinically unaffected eyes was performed. RESULTS: HSV eyes, as compared to contralateral eyes, demonstrated a significant decrease in mean corneal sensation (3.1±1.6 vs 5.3±0.8 cm), total nerve fibres number (5.7±4.4 vs 15.1±5.4), nerve branches (3.4±3.0 vs 8.4±4.7), main nerve trunks (2.3±1.6 vs 5.8±2.2), and nerve fibres density (7.5±5.6 vs 18.1±5.3 mm/mm2, P<0.05). There was no significant difference between keratitis and uveitis eyes in mean corneal sensation and nerve fibres parameters. After 6mo, corneal sensation and sub-basal nerve fibres parameters were increased significantly, but did not reach the parameters of contralateral, clinically unaffected eyes. CONCLUSION: Corneal aesthesiometry and LSCM in HSV affected eyes reveals a significant decrease of corneal sensation and sub-basal nerve fibres which recovers at 6mo but does not reach the normal level.     

Next-generation calcineurin inhibitors for ophthalmic indications

Calcineurin inhibitors (CNIs) are potent immunosuppressants that reversibly inhibit T-cell proliferation and prevent the release of pro-inflammatory cytokines by blocking the activity of calcineurin, a ubiquitous enzyme that is found in cell cytoplasm. CNIs can be highly effective in immune-mediated ophthalmic diseases such as uveitis, dry eye syndrome and inflammatory blepharitis, as well as for the prevention of rejection in corneal transplants. ISA-247/LX-211 is a novel CNI that is in Phase III clinical development for the treatment of various forms of non-infectious uveitis. ISA-247/LX-211 is a rationally designed analog of ciclosporin A that exhibits more predictable pharmacokinetic and pharmacodynamic properties and a 4-fold greater calcineurin inhibition than its parent compound, ciclosporin A. ISA-247/LX-211 has been observed to be effective, well-tolerated, and safe in early clinical trials, exhibiting a much wider therapeutic window compared with classic CNIs, such as ciclosporin A and tacrolimus. An alternative approach to widening the therapeutic window for the therapy of ophthalmic disorders lies in local delivery of CNIs through polymeric implants that release the drug over long periods of time. The silicone matrix episcleral implant LX-201 is in Phase III development at present for the prevention of rejection in high-risk cornea transplantation.     

Gut microbiota as a source of a surrogate antigen that triggers autoimmunity in an immune privileged site

Recent discoveries on the role of commensal microbiota have significantly changed our understanding of human physiology. The host-microbiota interplay is now an important aspect to take into account to understand immune responses and immunological diseases. Autoimmune uveitis is a sight-threatening disease that arises without a known infectious etiology. It is unknown where and how autoreactive T cells become primed to trigger disease in the eye, which is an immune privileged site. We recently reported data supporting the notion that retina-specific T cells receive a signal in the gut from commensal microbiota-derived cross-reactive antigen(s) and trigger autoimmune uveitis in the R161H mouse model. Here we discuss our published findings, as well as our recent attempts to identify the responsible microbe(s) by using different antibiotic treatments, 16S rDNA sequencing and homology searches for candidate antigenic mimic(s) of the retinal antigen.     

Immunosuppressive Treatment of Non-infectious Uveitis: History and Current Choices

Non-infectious uveitis is one of the leading causes of preventable blindness worldwide. Long-term immunosuppressive treatment is generally required to achieve durable control of inflammation in posterior and panuveitis. Although systemic corticosteroids have been the gold standard of immunosup- pressive treatment for uveitis since first introduced in 1950s, its side effects of long-term use often warrant an adjuvant treatment to reduce the dosage/duration of corticosteroids needed to maintain disease control. Conventional immunosuppressive drugs, classified into alkylating agent, antimetabolites and T cell inhibitors, have been widely used as corticosteroid-sparing agents, each with characteristic safety/tolerance profiles on different uveitis entities. Recently, biologic agents, which target specific molecules in immunopathogenesis of uveitis, have gained great interest as alternative treatments for refractory uveitis based on their favorable safety and effectiveness in a variety of uveitis entities. However, lack of large randomized controlled clinical trials, concerns about efficacy and safety of long-term usage, and economic burden are limiting the use of biologics in non-infectious uveitis. Local administration of immunosuppressive drugs (from corticosteroids to biologics) through intraocular drug delivery systems represent another direction for drug development and is now under intense investigation, but more evidences are needed to support their use as regular alternative treatments for uveitis. With the numerous choices belonging to different treatment modalities (conventional immunosuppressive agents, biologics and local drug delivery systems) on hand, the practice patterns have been reported to vary greatly from center to center. Factors influence uveitis specialists' choices of immunosuppressive agents may be complex and may include personal familiarity, treatment availability, safety/tolerability, effectiveness, patient compliance, cost concerns and suggestions from related specialists such as rheumatologists and pediatricians. The focus of this review is to provide an overview of each treatment modality on safety/tolerability and effectiveness, which are believed to be the two most important factors affecting treatment decision making.     

Amelioration of Endotoxin-Induced Uveitis in Rabbit by Topical Administration of Tacrolimus Proglycosome Nano-Vesicles

This work was aimed to improve the efficacy of tacrolimus in the treatment of endotoxin-induced uveitis (EIU) using propylene glycol modified lipid vesicles termed as proglycosome nano-vesicles (PNVs). PNVs were prepared by modified film hydration method. Experimental uveitis in rabbit eye was induced by an intravitreal injection of 20 μL of the endotoxin solution containing 100 ng of lipopolysaccharide endotoxin. In vivo efficacy of PNVs was determined by studying clinical symptoms of uveitis using slit lamp examination and by quantitatively measuring levels of tumor necrosis factor-alpha, interleukin-6, leukocytes and total proteins in aqueous humor, 24 h after intravitreal injection of endotoxin. Comparison was made with healthy, untreated and tacrolimus solution treated eyes. PNVs developed were nano-sized, deformable and showed sustained release of tacrolimus over period of 12 h. In vivo results indicated statistically significant difference between the effects of PNVs in the treatment of EIU compared to tacrolimus. PNV treatment not only subsides clinical symptoms of uveitis but also prevented breakdown of blood aqueous barrier. Tacrolimus loaded PNVs are potential new topical treatment for uveitis.     

Ocular Inflammation Associated with Polymyalgia Rheumatica without Concomitant Giant-Cell Arteritis: A Report of Three Cases

Purpose: We report three cases of ocular inflammation and polymyalgia rheumatica without concomitant giant-cell arteritis.

Methods: Report of three cases.

Results: Polymyalgia rheumatica onset was at a mean age of 66.7?years, and ocular inflammation, which developed 7–21 months later, was bilateral in all patients. Ocular inflammation presented as episcleritis, scleritis, or anterior uveitis, and it emerged during the tapering of low-dose prednisolone prescribed for polymyalgia rheumatica in all patients. Recurrence of ocular inflammation was observed in two patients.

Conclusions: Ocular inflammation associated with polymyalgia rheumatica was often bilateral and occurred during steroid tapering. Although this presentation is relatively uncommon, polymyalgia rheumatica should be considered in the differential diagnosis of older patients presenting with ocular inflammation, especially those with proximal myalgia and elevated inflammatory markers.     

Initial misdiagnosis of Vogt-Koyanagi-Harada disease

Purpose

To report the initial misdiagnosis of patients with Vogt–Koyanagi–Harada (VKH) disease.

吊顶灯辅助下25G微创玻璃体切割手术治疗眼弓蛔虫病的疗效

目的：探讨吊顶灯辅助下25G微创玻璃体切割手术治疗眼弓蛔虫病（OT）的疗效，并分析术后并发 症。方法：回顾性系列病例研究。选择2014年12月至2019年2月在徐州市立医院眼科确诊为OT的 患者27例（27眼）。所有患者经过1～2个月的全身或局部皮质类固醇治疗后接受了25G微创玻璃体 切割手术，避开周边病灶区放置灌注管和吊顶灯，切除玻璃体及牵拉条索，根据术中视网膜情况予 激光光凝、气液交换、玻璃体腔填充空气或C3F8或硅油，部分联合晶状体摘除、环扎术。分析患者 的临床特征、光学相干断层扫描（OCT）、眼底照相检查、治疗情况和术后并发症等，计算术后随访 期内葡萄膜炎复发率和一次性视网膜解剖复位率。对手术前与末次随访最佳矫正视力（BCVA）进行 t检验分析。结果：27例患者中周边部肉芽肿型11眼，后极部肉芽肿型11眼，眼内炎型5眼。伴视网 膜前膜（ERM）23眼；伴牵拉性视网膜脱离（TRD）13眼，其中TRD合并ERM 11眼，单纯TRD 2眼。 术后随访6～44（17.6±11.0）个月。术后早期低眼压4眼（15%），高眼压1眼（4%）。伴TRD的13眼中 11眼经一次手术即实现解剖复位，一次性视网膜复位率为85%；伴ERM的23眼中术后复发2眼（9%）； 术后视网膜脱离2眼（7%），术后并发白内障3眼（11%）。27眼中有4眼（15%）于术后1～5个月炎症复发， 其中1眼经再次手术后炎症消退，另外3眼予全身及局部皮质类固醇治疗2个月内炎症得到控制。术 前及术后末次随访BCVA（logMAR）分别为1.46±0.66、1.13±0.66，术后视力较术前明显提高，差 异有统计学意义（t=4.009，P<0.001）。结论：吊顶灯辅助下25G微创玻璃体切割手术治疗眼弓蛔虫病 可有效控制葡萄膜炎症，获得较满意的疗效。