Longitudinal Study of Cone Photoreceptors during Retinal Degeneration and in Response to Ciliary Neurotrophic Factor Treatment
Longitudinal Study of Cone Photoreceptors during Retinal Degeneration and in Response to Ciliary Neurotrophic Factor Treatment
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DOI：
10.1167/iovs.10-6479
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发表时间：
2011-04-01
影响因子：
4.4
通讯作者：
Duncan, Jacque L.
中科院分区：
文献类型：
--
作者：
Talcott, Katherine E.;Ratnam, Kavitha;Duncan, Jacque L.
目的.目的研究持续释放睫状神经营养因子（CNTF）治疗遗传性视网膜变性患者后视锥细胞结构和功能的变化。参与2期临床试验的2名视网膜色素变性患者和1名Usher综合征2型患者的一只眼睛接受了通过包封细胞技术植入物递送的CNTF，对侧眼睛接受了假手术。对患者进行了30至35个月的纵向随访。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测量的视锥间距和密度以及光学相干断层扫描测量的视网膜厚度与视功能相关，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，3名患者的任何一只眼睛都没有观察到VA、视野敏感度或ERG反应的显著变化。CNTF组视网膜外层厚度明显大于假手术组（P < 0.005）。假手术组的视锥细胞间距比CNTF组每年增加2.9%（P < 0.001，线性混合模型），视锥细胞密度比CNTF组每年减少9.1%或223个视锥细胞/度（P = 0.002，线性混合模型）。AOSLO图像为遗传性视网膜变性患者的疾病进展和治疗反应提供了敏感的测量方法。目前迫切需要使用高分辨率成像技术对锥细胞结构进行更大规模的研究，以评估CNTF治疗遗传性视网膜变性患者的效果。（ClinicalTrials.gov编号，NCT 00447980。）（Invest Ophthalmol维斯科学。2011;52：2219-2226）DOI：10.1167/iovs.10-6479
PURPOSE. To study cone photoreceptor structure and function in patients with inherited retinal degenerations treated with sustained-release ciliary neurotrophic factor (CNTF).METHODS. 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).RESULTS. 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).CONCLUSIONS. 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. (ClinicalTrials.gov number, NCT00447980.) (Invest Ophthalmol Vis Sci. 2011;52:2219-2226) DOI:10.1167/iovs.10-6479