Datiles Manuel B, Ansari Rafat R, Yoshida Junko, Brown Holly, Zambrano Andrea I, Tian Jing, Vitale Susan, Zigler J Samuel, Ferris Frederick L, West Sheila K, Stark Walter J
National Eye Institute, National Institutes of Health, Bethesda, Maryland.
National Aeronautics and Space Administration-John H. Glenn Research Center, Cleveland, Ohio.
Ophthalmology. 2016 Feb;123(2):248-254. doi: 10.1016/j.ophtha.2015.10.007. Epub 2015 Nov 3.
To conduct a longitudinal study on age-related nuclear cataracts using dynamic light scattering (DLS) to determine if cataract progression is associated with loss of the unbound form of the lens molecular chaperone protein, α-crystallin.
Natural history and cohort study.
Patients 30 years of age or older of either gender seeking treatment at the Wilmer Eye Institute Cornea-Cataract Department.
All patients underwent a comprehensive dilated eye examination every 6 months, including slit-lamp grading of their lenses using the Age-Related Eye Disease Study (AREDS) clinical lens grading system and obtaining an estimate of unbound α-crystallin level in the nucleus, the α-crystallin index (ACI), using the National Aeronautics and Space Administration-National Eye Institute DLS device. We used a random effects statistical model to examine the relationship of lens opacity changes over time with ACI changes.
α-Crystallin Index (ACI) and AREDS nuclear cataract grade.
Forty-five patients (66 eyes) 34 to 79 years of age with AREDS nuclear lens grades of 0 to 3.0 were followed up every 6 months for a mean of 19 months (range, 6-36 months). We found that lenses with the lowest baseline levels of ACI had the most rapid progression of cataracts, whereas lenses with higher ACI at baseline had no or slower cataract progression. Lenses that lost α-crystallin at the highest rates during the study also had faster progression of nuclear cataracts than lenses with a slower rate of ACI loss. Kaplan-Meier survival curves showed that lenses with the lowest initial ACI had the highest risk of undergoing cataract surgery.
This longitudinal study corroborates our previous cross-sectional study finding that higher levels of unbound α-crystallin as assessed by ACI are associated with lower risk of cataract formation and that loss of ACI over time is associated with cataract formation and progression. This study suggested that assessment of ACI with the DLS device could be used as a surrogate for lens opacity risk in clinical studies, and for assessing nuclear cataract events in studies where cataract development may be a side effect of a drug or device.
使用动态光散射(DLS)对年龄相关性核性白内障进行纵向研究,以确定白内障进展是否与晶状体分子伴侣蛋白α-晶状体蛋白的游离形式丧失有关。
自然史和队列研究。
在威尔默眼科研究所角膜-白内障科寻求治疗的30岁及以上的男女患者。
所有患者每6个月进行一次全面的散瞳眼部检查,包括使用年龄相关性眼病研究(AREDS)临床晶状体分级系统对其晶状体进行裂隙灯分级,并使用美国国家航空航天局-美国国立眼科研究所DLS设备获得核内游离α-晶状体蛋白水平的估计值,即α-晶状体蛋白指数(ACI)。我们使用随机效应统计模型来研究晶状体混浊度随时间的变化与ACI变化之间的关系。
α-晶状体蛋白指数(ACI)和AREDS核性白内障分级。
45例年龄在34至79岁之间、AREDS核性晶状体分级为0至3.0的患者(66只眼)每6个月随访一次,平均随访19个月(范围6至36个月)。我们发现,基线ACI水平最低的晶状体白内障进展最快,而基线ACI水平较高的晶状体无白内障进展或进展较慢。在研究期间α-晶状体蛋白丧失率最高的晶状体,其核性白内障进展也比ACI丧失率较慢的晶状体更快。Kaplan-Meier生存曲线显示,初始ACI最低的晶状体接受白内障手术的风险最高。
这项纵向研究证实了我们之前横断面研究的结果,即通过ACI评估的较高水平的游离α-晶状体蛋白与较低的白内障形成风险相关,且随着时间的推移ACI的丧失与白内障的形成和进展相关。这项研究表明,使用DLS设备评估ACI可在临床研究中用作晶状体混浊风险的替代指标,并可在白内障发展可能是药物或器械副作用的研究中用于评估核性白内障事件。