Progression in X-linked Retinitis Pigmentosa Due to ORF15-RPGR Mutations: Assessment of Localized Vision Changes Over 2 Years
Progression in X-linked Retinitis Pigmentosa Due to ORF15-RPGR Mutations: Assessment of Localized Vision Changes Over 2 Years
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DOI：
10.1167/iovs.18-24931
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发表时间：
2018-09-01
影响因子：
4.4
通讯作者：
Jacobson, Samuel G.
中科院分区：
文献类型：
--
作者：
Cideciyan, Artur V.;Charng, Jason;Jacobson, Samuel G.
目的.目的探讨X连锁视网膜色素变性（XLRP）患者的进展率及视杆细胞和视锥细胞敏感性的变化。对ORF 15-RPGR-XLRP患者（n = 15）进行了为期2年的前瞻性研究，在12度正方形网格上覆盖168度宽和84度高，在暗适应和光适应条件下对视野进行静态视野检查。估计视杆细胞和视锥细胞灵敏度损失的自然史和重测变异性。数据进行逐点分析，并在相邻基因座的约80 mm（2）（900 deg（2））大小的小区域内平均，代表局部基因治疗注射的可能范围。在大多数患者中，轻度至中度敏感性丧失的视网膜位点倾向于位于中至远周边视网膜。当在小区域内平均时，暗适应视杆视觉以平均每年2 dB的速度进展，重复性系数（CR）为6.3 dB，而白色刺激的光适应视锥视觉以平均每年0.9 dB的速度进展，CR为3.8 dB。对于入组早期临床试验的普通患者，预测在4.5年的视杆视力和6.1年的视锥视力中发生显著（α = 0.05）进展，把握度为80%。颞侧半野区域的定位和多例患者结果的分组将允许更短持续时间的试验设计。在暗适应条件下，在一个小区域内平均测量视杆细胞敏感性，显示出在最短时间内可检测到进展的最大潜力。
PURPOSE. To determine the progression rate and the variability of rod and cone sensitivities in patients with X-linked retinitis pigmentosa (XLRP) caused by mutations in ORF15-RPGR.METHODS. ORF15-RPGR-XLRP patients (n = 15) were studied prospectively over 2 years with static perimetry sampling the visual field under dark-adapted and light-adapted conditions on a 12 degrees square grid covering 168 degrees width and 84 degrees height. Natural history of rod and cone sensitivity loss and test-retest variability were estimated. Data were analyzed pointwise as well as averaged across small regions of neighboring loci of approximately 80 mm(2) (900 deg(2)) in size representing the likely extent of localized gene therapy injections.RESULTS. Retinal loci with mild to moderate loss of sensitivity tended to be in the mid-to farperipheral retina in most patients. When averaged across small regions, dark-adapted rod vision progressed at an average of 2 dB per year with a coefficient of repeatability (CR) of 6.3 dB, and light-adapted cone vision with white stimulus progressed at an average of 0.9 dB per year with a CR of 3.8 dB. For an average patient enrolled in an early-phase clinical trial, significant (alpha = 0.05) progression would be predicted to occur with 80% power in 4.5 years for rod vision and 6.1 years for cone vision. Localization of regions in the temporal hemifield and grouping of results from multiple patients would permit trial designs of shorter duration.CONCLUSIONS. Measurement of rod sensitivity under dark-adapted conditions averaged across a small region showed the greatest potential for detectability of progression in the shortest period.