Twins with Senior-Loken syndrome

Senior-Loken syndrome is a rare entity that combines familial juvenile nephronophthisis with retinal dystrophy. The eye disease may be congenital amaurosis of Leber type or pigmentary retinal degeneration and electroretinogram (ERG) helps in the diagnosis of these varieties. The disease progresses inexorably to chronic renal failure. Here is a case of twins with Senior-Loken syndrome emphasizing the importance of ophthalmic examination in children with renal failure, for determining a correct diagnosis.     

针刺治疗视网膜色素变性的组穴规律分析

目的:基于数据挖掘技术分析文献中针刺治疗视网膜色素变性穴位的组方规律。方法:检索国家知识基础设施数据库（CNKI）、中国学术期刊数据库（CSPD）、中文科技期刊数据库（CCD）文献中治疗视网膜色素变性所使用的穴位处方,使用中医传承计算平台（V3.1）进行数据挖掘,分析针刺治疗视网膜色素变性的取经、选穴和配伍规律。结果:共纳入文献47篇,应用频次前5位的腧穴为球后、睛明、太阳、足三里、合谷;奇穴选用频次最高,经脉选用频次前3位依次为足太阳膀胱经、足少阳胆经、足阳明胃经;取穴部位以头颈部选取最多;其次为下肢部和上肢部。结论:针刺治疗视网膜色素变性的核心经脉为足太阳膀胱经、足少阳胆经及足阳明胃经,核心组穴为球后、睛明及太阳,配以足三里、合谷、光明、三阴交等穴,其取穴规律以局部取穴以及邻近取穴直达病所为主,远端取穴以足三里、合谷等辅以调理脏腑经络。     

Focal Choroidal Excavation in Retinal Dystrophies

Aim: To investigate the presence of focal choroidal excavation (FCE) in patients with retinitis pigmentosa (RP), Stargardt’s disease (STGD), and Best disease in the Indian population. Methods: This retrospective consecutive case series included 309 eyes of 157 patients with RP (183 eyes), STGD (93 eyes), and Best disease (33 eyes) with good-quality, enhanced-depth spectral domain optical coherence tomography scans. Comprehensive ophthalmic examination data were collected. Characteristics of FCE, including location of FCE, type (conforming and non-conforming), maximal width, and depth, were noted. Results: FCE was found in 2 out of 33 (6%) eyes with Best disease and no FCE was found in eyes with RP or STGD. The location of the FCE was extrafoveal in both cases. The first case had non-conforming FCE while the second case had the conforming type and the FCE occurred in association with choroidal neovascularization in the second case. The first case maintained good visual acuity of 20/20 over the entire period of follow-up (14 months), while the second case had a visual acuity of 20/200 at the last follow-up (three years) due to scarred choroidal neovascular membranes. The FCE showed no change in both eyes over the entire duration of follow-up. Conclusion: Focal choroidal excavation was found in 6% of eyes with Best disease, which remained stable throughout follow up. Eyes with RP and STGD did not have any FCE. Further studies are required to determine the role of vitelliform material in FCE development in Best disease.     

Progress in treating inherited retinal diseases: Early subretinal gene therapy clinical trials and candidates for future initiatives

Due to improved phenotyping and genetic characterization, the field of ‘incurable’ and ‘blinding’ inherited retinal diseases (IRDs) has moved substantially forward. Decades of ascertainment of IRD patient data from Philadelphia and Toronto centers illustrate the progress from Mendelian genetic types to molecular diagnoses. Molecular genetics have been used not only to clarify diagnoses and to direct counseling but also to enable the first clinical trials of gene-based treatment in these diseases. An overview of the recent reports of gene augmentation clinical trials by subretinal injections is used to reflect on the reasons why there has been limited success in this early venture into therapy. These first-in human experiences have taught that there is a need for advancing the techniques of delivery of the gene products - not only for refining further subretinal trials, but also for evaluating intravitreal delivery. Candidate IRDs for intravitreal gene delivery are then suggested to illustrate some of the disorders that may be amenable to improvement of remaining central vision with the least photoreceptor trauma. A more detailed understanding of the human IRDs to be considered for therapy and the calculated potential for efficacy should be among the routine prerequisites for initiating a clinical trial.     

Clinical and Electrophysiologic Characteristics of a Large Kindred with X-Linked Retinitis Pigmentosa Associated with the RPGR Locus

Purpose: To phenotypically and genotypically characterize a large Puerto Rican kindred with X-linked retinitis pigmentosa associated with a novel RP GTPase regulator (RPGR) genotype.

Methods: A total of 100 family members of a single kindred with X-linked RP were evaluated with ophthalmic examinations and blood DNA analysis. Visual fields, OCT, and full-field ERG were obtained on all affected males and carriers.

Results: Of the 100 family members examined, 13 were affected males and 18 were carriers. A deletion of 2 base pair of the RPGR gene in the ORF15 region at position c.2267-2268 (Lys756del2aaAG hemi) was identified with the affected and carriers. Best eye visual acuity was correlated with age (Spearman coefficient?=?0.95) with hand-motion acuity by age 35 and light perception to no light perception by age 50–60. Visual fields were minimally plottable by age 40, and ERG responses reached non-detectable levels by late teens. Carriers had no or mild visual symptoms. All carriers had visual acuity of at least 20/50 or better in one eye, and the amount of retinal degeneration was variable with ERG responses ranging from severely impaired to normal.

Conclusions: Profound visual loss occurred by the second decade of life with progression to near no light perception by age 60 in this kindred of X-linked RP associated with the RPGR genotype. Female carriers maintained visual acuity with age and were identifiable by clinical and ERG examination. The information from this study is important to determine the optimal age for intervention, as new RP treatments are being developed and tested.     

Atteintes ophtalmologiques des infections virales

Viral infections may involve all ocular tissues and may have short and long-term sight-threatening consequences. Among them, ocular infections caused by herpesviruses are the most frequent. HSV-1 keratitis and kerato-uveitis affect approximately are the leading cause of infectious blindness in the Western world, mainly because of corneal opacification caused by recurrences. For this reason, they may warrant long-term antiviral prophylaxis. Herpes zoster ophthalmicus, accounts for 10 to 20% of all shingles locations and can be associated with severe ocular involvement (keratitis, kerato-uveitis) of which a quarter becomes chronic/recurrent. Post herpetic neuralgias in the trigeminal territory can be particularly debilitating. Necrotizing retinitis caused by herpesviruses (HSV, VZV, CMV) are seldom, but must be considered as absolute visual emergencies, requiring urgent intravenous and intravitreal antiviral treatment. Clinical pictures depend on the immune status of the host. Adenovirus are the most frequent cause of infectious conjunctivitis. These most often benign infections are highly contagious and may be complicated by visually disabling corneal lesions that may last over months or years. Some arboviruses may be associated with inflammatory ocular manifestations. Among them, congenital Zika infections may cause macular or optic atrophy. Conjunctivitis is frequent during the acute phase of Ebola virus disease. Up to 15% of survivors present with severe chronic inflammatory ocular conditions caused by viral persistence in uveal tissues. Finally, COVID-19-associated conjunctivitis can precede systemic disease, or even be the unique manifestation of the disease. Utmost caution must be taken because of viral shedding in tears.     

碘酸钠诱导大鼠视网膜损伤的病理改变和SOD、CAT的变化

目的: 探讨不同剂量碘酸钠诱导大鼠视网膜损伤过程中的病理形态改变及抗氧化系统中超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性的改变。方法: SD大鼠80只,随机分为4组(每组20只),即40 mg/kg、50 mg/kg、60 mg/kg碘酸钠造模组和正常对照组。在造模后第1、4、7、14 d取大鼠右眼进行病理检查;取左眼视网膜,检测SOD和CAT的活性。结果: 病理结果显示,与对照组比较,第1 d,40 mg/kg和50 mg/kg碘酸钠造模组视网膜各层未见损伤,60 mg/kg碘酸钠造模组出现视网膜色素上皮层损伤、外核层细胞排列紊乱;第4、7、14 d,各剂量组均出现明显损伤,且损伤程度比第1 d和对照组明显加重,呈现外核层细胞波浪状改变和外核层厚度减少(P＜0.05或P＜0.01)。生化检测结果显示,与对照组比较,第1、4 d,60 mg/kg碘酸钠造模组视网膜组织SOD、CAT的活性均显著下降(P＜0.05);第7、14 d,各剂量组视网膜SOD、CAT活性均呈明显下降趋势(P＜0.05或P＜0.01)。结论: 40 mg/kg、50 mg/kg和60 mg/kg的碘酸钠均可导致大鼠视网膜色素上皮层和外核层细胞损伤,并使大鼠视网膜抗氧化系统受损。碘酸钠用量越大,视网膜细胞损伤出现时间越早、程度越重。     

Bright cyclic light accelerates photoreceptor cell degeneration in tubby mice

Photoreceptor cell death is an irreversible, pathologic event in many blinding retinal diseases including retinitis pigmentosa, age-related macular disease, and retinal detachment. Light exposure can exacerbate a variety of human retinal diseases by increasing the rate of photoreceptor cell death. In the present study, we characterize the kinetics of photoreceptor cell death in Tubby (homozygous tub/tub, which have inherited, progressive retinal degeneration) mice born and raised in a bright cyclic light environment. Our data show that raising tub/tub mice in a bright cyclic light environment induces rapid loss of photoreceptors. This effect can be slowed, but not prevented, by raising animals in constant darkness, which suggests the involvement of phototransduction in the accelerated death of photoreceptors in this animal. We further demonstrated that the activities of cytosolic cytochrome c and caspases-3 and -9 were significantly increased in the retinas of tub/tub mice. Raising animals in darkness significantly reduced the increased activities of caspases-3 and -9, as well as cytosolic cytochrome c. We also observed that rhodopsin, a phototransduction protein, is not restricted to the rod outer segment, but is distributed throughout the rod cell, including the inner segments, cell bodies, and synapses. In addition, the light-dependent translocation and compartmentalization of arrestin and transducin are affected by the tubby mutation. Our results support the interpretation that problems in protein trafficking in the photoreceptors of the tub/tub mouse may contribute to retinal degeneration.     

应用连锁分析方法对X连锁型视网膜色素变性进行基因诊断的研究

目的 探讨用连锁分析方法对Ｘ连锁型视网膜色素变性（ＲＰ）进行基因诊断的可行性。方法 选用ＲＰ３及ＲＰ２所在染色体区间,即Ｘｐ２１．１￣ｐ１１．２３的１０个微卫星染色体位标,对Ｘ连锁型ＲＰ家系了连锁分析,通过家系成员的单倍型分析,确定致病基因所在的染色体位置,进而判定欲检修个体是否携带该染色体区段。结果 确定４个Ｘ 锁隐性ＲＰ家系致病基因在ＲＰ３和ＲＰ２的染色体区间,对家系中的年幼女性是否为携带者。