Department of Ophthalmology, Division of Preventive Medicine and Public Health, University of California at San Francisco, CA, USA.
Invest Ophthalmol Vis Sci. 2011 Apr 6;52(5):2219-26. doi: 10.1167/iovs.10-6479.
To study cone photoreceptor structure and function in patients with inherited retinal degenerations treated with sustained-release ciliary neurotrophic factor (CNTF).
Two patients with retinitis pigmentosa and one with Usher syndrome type 2 who participated in a phase 2 clinical trial received CNTF delivered by an encapsulated cell technology implant in one eye and sham surgery in the contralateral eye. Patients were followed longitudinally over 30 to 35 months. Adaptive optics scanning laser ophthalmoscopy (AOSLO) provided high-resolution images at baseline and at 3, 6, 12, 18, and 24 months. AOSLO measures of cone spacing and density and optical coherence tomography measures of retinal thickness were correlated with visual function, including visual acuity (VA), visual field sensitivity, and full-field electroretinography (ERG).
No significant changes in VA, visual field sensitivity, or ERG responses were observed in either eye of the three patients over 24 months. Outer retinal layers were significantly thicker in CNTF-treated eyes than in sham-treated eyes (P < 0.005). Cone spacing increased by 2.9% more per year in sham-treated eyes than in CNTF-treated eyes (P < 0.001, linear mixed model), and cone density decreased by 9.1%, or 223 cones/degree(2) more per year in sham-treated than in CNTF-treated eyes (P = 0.002, linear mixed model).
AOSLO images provided a sensitive measure of disease progression and treatment response in patients with inherited retinal degenerations. Larger studies of cone structure using high-resolution imaging techniques are urgently needed to evaluate the effect of CNTF treatment in patients with inherited retinal degenerations.
研究接受睫状神经营养因子（CNTF）缓释治疗的遗传性视网膜退行性病变患者的视锥细胞结构和功能。
两名参加 2 期临床试验的色素性视网膜炎患者和 1 名 Usher 综合征 2 型患者，一只眼接受包裹细胞技术植入物的 CNTF 治疗，另一只眼接受假手术。患者在 30 至 35 个月的时间内进行了纵向随访。自适应光学扫描激光检眼镜（AOSLO）在基线和 3、6、12、18 和 24 个月时提供高分辨率图像。AOSLO 测量的视锥细胞间距和密度以及视网膜厚度的光学相干断层扫描测量值与视觉功能相关，包括视力（VA）、视野敏感度和全视野视网膜电图（ERG）。
在 24 个月内，三名患者的双眼均未观察到 VA、视野敏感度或 ERG 反应的显著变化。CNTF 治疗眼的外视网膜层明显比假手术治疗眼厚（P < 0.005）。与 CNTF 治疗眼相比，假手术治疗眼的视锥细胞间距每年增加 2.9%（P < 0.001，线性混合模型），视锥细胞密度每年减少 9.1%，即每年减少 223 个视锥细胞/度（2）（P = 0.002，线性混合模型）。
AOSLO 图像为遗传性视网膜退行性病变患者的疾病进展和治疗反应提供了一种敏感的测量方法。迫切需要使用高分辨率成像技术对视锥细胞结构进行更大规模的研究，以评估 CNTF 治疗遗传性视网膜退行性病变患者的效果。
