Ophthalmology 2023;130:413-422 ª 2022 by the American Academy of Ophthalmology. This is an open access article under the CC BY license .

中文摘要

這篇文章介紹了RP2視網膜病變的臨床表現和分子遺傳學。這項研究收集了大型患者群體的數據，並發現了28個疾病引起的變異，其中有20個變異以前並未被臨床確定。在RP2病變中觀察到了一系列的自由基螢光（FAF）表現，從正常到進階萎縮都有。在此研究中，RP2視網膜病變是一種兒童期開始的、進展快速的視網膜退化症，通常早期涉及黃斑，大多數情況下在26歲以前已經完全失去橢圓區(ellipsoid zone )。本文介紹了這種罕見疾病的特徵和表現，對臨床診斷和治療有所啟示。

English Abstract

The study aimed to provide a clinical and genetic analysis of a large cohort of RP2-associated retinopathy patients to identify the phenotype-genotype correlation and prognosis. Molecular genetic testing and clinical findings including best-corrected visual acuity were examined, and twenty-eight disease-causing variants were identified, with 20 not previously clinically characterized. No patient with childhood-onset disease had an identifiable ellipsoid zone (EZ) after the age of 26 years. This study highlights that RP2 retinopathy is predominantly childhood-onset, rapidly progressive retinal degeneration, with macular involvement, and early complete loss of EZ in most cases. The study concludes that natural history data in genetically proven patients with RP2-associated retinopathy is limited, and future prospective natural history studies that monitor patients from a young age are vital to establish prognosis, phenotype-genotype correlations, and meaningful endpoints for trials.

Ophthalmology Volume 130, Number 4, April 2023

中文摘要

本文旨在探討罕見的ROSAH（視網膜萎縮，視神經水腫，脾臟肥大，無汗和頭痛）症候群患者的眼部表徵，該症候群是一種罕見的常染色體显性疾病，以視網膜萎縮，視神經水腫，脾臟肥大，無汗和頭痛為特徵。本研究包括11名患有ROSAH症候群且ALPK1基因突變的患者。研究結果表明，ROSAH症候群患者的視覺功能變化有三個主要因素：包括視神經受損，包括眼內發炎含囊狀黃斑水腫(cystoid macular edema)以及視網膜退化。在這些患者中觀察到可變的眼內發炎症跡象或後遺症，包括角膜沉澱，帶状角膜病變，前房細胞，囊狀黃斑水腫和FAG的视網膜血管炎。此外，十名患者呈現視神經盤突起，OCT可看到peripapillary厚度增加。結果顯示，ROSAH症候群患者的視覺功能變化與視神經，眼內炎症，包括囊狀黃斑水腫，以及視網膜退化有關。

English Abstract

This article aims to investigate the ocular manifestations of the rare ROSAH (Retinal dystrophy, Optic disc Swelling, Splenomegaly, Anhidrosis, and Headache) syndrome, a rare autosomal dominant disorder characterized by retinal dystrophy, optic disc swelling, splenomegaly, anhidrosis, and headache. This study included 11 patients with ROSAH syndrome and mutations in the ALPK1 gene. The results showed that there were three main factors contributing to the visual functional changes in ROSAH syndrome patients, including optic nerve damage, intraocular inflammation involving cystoid macular edema, and retinal degeneration. Variable signs or sequelae of intraocular inflammation were observed in these patients, including corneal deposits, band keratopathy, anterior chamber cells, cystoid macular edema, and retinal vasculitis on fluorescein angiography. Additionally, ten patients showed optic disc elevation and increased peripapillary thickness on OCT. These results suggest that the visual functional changes in ROSAH syndrome patients are associated with optic nerve, intraocular inflammation involving cystoid macular edema, and retinal degeneration.

JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2023.0709
Published online April 6, 2023

中文摘要

這篇文章是一項階段三的多中心、隨機、雙盲、安慰劑對照的臨床試驗，旨在評估一種無水的0.1%cyclosporine環孢素眼用溶液（CyclASol [Novaliq GmbH]）每日兩次用於治療中度至重度乾眼症的療效、安全性和耐受性。研究對象是從2020年12月5日至2021年10月8日在27個臨床中心招募的834名乾眼症患者，他們在使用人工淚液14天後被隨機分配到環孢素組或安慰劑組，並持續治療29天。研究的主要終點是第29天時與基線相比的total corneal fluorescein staining（tCFS）和dryness score（0-100 visual analog scale）的變化。結果顯示，環孢素組在tCFS和dryness score (dryness and blurred vision)方面均顯著優於安慰劑組（P < .001），並且具有快速起效和良好耐受性的特點。研究結論是，無水的0.1%環孢素眼用溶液每日兩次用於治療中度至重度乾眼症是有效和安全的。

English Abstract

This article is a phase 3, multicenter, randomized, double-masked, vehicle-controlled clinical trial that aims to evaluate the efficacy, safety, and tolerability of a water-free cyclosporine ophthalmic solution, 0.1% (CyclASol [Novaliq GmbH]), applied twice daily in dry eye disease (DED) compared with vehicle. The study participants were 834 patients with moderate to severe DED who were recruited from 27 clinical centers from December 5, 2020, to October 8, 2021. They were randomly assigned to cyclosporine or vehicle groups after using artificial tears for 14 days and continued treatment for 29 days. The primary outcomes were changes from baseline in total corneal fluorescein staining (tCFS, 0-15 National Eye Institute scale)) and in dryness score (0-100 visual analog scale) at day 29. The results showed that cyclosporine group had significantly better outcomes than vehicle group in tCFS and dryness score about dryness and blurred vision (P < .001), and had a rapid onset (2 weeks) of action and a good tolerability profile. The study concluded that water-free cyclosporine ophthalmic solution, 0.1%, applied twice daily was effective and safe for the treatment of moderate to severe DED.

Ophthalmology 2023;130:354-360

中文摘要

這篇文章研究了在眼科提供者（Eye care providers, ECPs）中是否可以應用醫療保健供應短缺區域（Health Provider Shortage Areas, HPSAs），並研究了HPSA得分與視力損失和ECP密度之間的相關性。研究發現，HPSA得分與視覺障礙（Visual impairment, VI）（r = 0.38，P <0.0001）和ECP密度每個郡人口（r = e0.18，P <0.0001）之間存在統計上顯著但較弱的相關性。多變量回歸分析發現，在鄉村縣（adjusted odds ration [aOR]，2.47；confident interval[CI]，1.93-3.67；P <0.001）和具有不到高中教育程度的居民的流行病（aOR，1.21；95％ CI，1.19-1.25；P <0.001），65歲以上的居民（aOR，1.10；95％ CI，1.07-1.13；P <0.001）和未投保的居民（aOR，1.04；95％ CI，1.01-1.06；P <0.001）的郡中，ECP PAS（cid：2）75th百分位數（可及性較差）的機率更高。目前HPSAs，與ECP相關性薄弱。本研究提出了一種新的方法來識別有高度需求但ECP卻有限的縣市

English Abstract

The article examines whether Health Provider Shortage Areas (HPSAs) can be used to identify areas of eye care provider (ECP) shortage in the United States. The study found a weak correlation between HPSA scores and visual impairment and ECP density per county population. A new scoring system for patient accessibility to ECPs was modeled, which found a higher odds of ECP shortage in rural counties and counties with a greater prevalence of residents with less than a high school education, residents aged 65 years or older, and uninsured residents. The study emphasizes the importance of equitable and proportional patient accessibility to eye care services, especially as the number of visually impaired people in the US is expected to double by 2050. The study also identifies potential areas for improvement in eye care accessibility and recommends extending ECP coverage and improving eye education. The study uses sophisticated geographic information systems analysis to identify counties with ECP shortage and suggests potential policies to address this issue.

Considerations When Offering Minimally Proven Investigational Treatments

https://doi.org/10.1016/j.ophtha.2022.11.008
ISSN 0161-6420/22

中文摘要

這篇文章討論了醫生在提供未經嚴格評估的治療時應考慮的因素。許多常見的醫療干預從未進行嚴格評估，以確保其風險不超過其效益。在美國，多達73%的門診藥物處方off label use並沒有得到充分的科學支持。文章說明了醫生提供未經證實的治療時應平衡為沒有其他選擇的患者提供潛在的挽救生命的治療與遵守希波克拉底誓言，即doing no harm。作者強調，在提供未經證實的治療之前，醫生必須考慮個別的臨床情況，並警告患者缺乏充分的和有良好控制的臨床試驗數據，FDA用於確定是否有足夠的證據支持其有效性的數據。在提供未經證實的治療之前，應該滿足某些標準，例如，治療應提供比現有治療更大的益處，醫生必須具備相關的技能和知識。此外，治療的結果必須得到監控，包括副作用和併發症。文章還提到了應遵循的一些準則，例如美國眼科學會的道德準則和美國食品藥品監督管理局提供的指南，以確保患者福利和權利是在考慮使用未經證實的療法時的首要考慮因素。最後，作者還提醒醫生在決定使用未經證實的治療時，應考慮有限的醫療資源的社會成本和成本效益。

English Abstract

The article “Considerations When Offering Minimally Proven Investigational Treatments” discusses the challenges and ethical considerations that physicians face when providing unproven treatments to patients with life-threatening conditions. The article explains that many medical interventions lack rigorous evaluation to ensure their risks do not outweigh their benefits, and as a result, investigational treatments may be the only option for patients with severe, life-shortening conditions. Physicians must balance the need to provide access to potentially life-saving therapies against the Hippocratic oath of “first doing no harm.” The article provides examples of minimally proven investigational treatments, including surgical techniques, laser procedures, and off-label use of medications, that have been adopted by ophthalmologists before being substantiated. The authors argue that physicians must assess each individual clinical situation to determine whether an investigational treatment would be appropriate, and they must alert patients to the absence of adequate and well-controlled clinical trial data. The article emphasizes the importance of informed consent and the need for appropriate review mechanisms, including prospective institutional review board approval and the disclosure of financial and non-financial conflicts of interest. Ultimately, the article stresses that any decision on the use of unproven investigational therapies must involve a serious and thoughtful discussion of the risks and benefits with the patient, and treatment should be recommended only after careful consideration of the patient’s social, emotional, occupational, and physical needs, acknowledging the protection of potentially vulnerable patients.