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Hongxin Song, Austin Roorda, Jacque L Duncan, Mina M Chung; Cone loss in Type 2 Macular Telangiectasia Demonstrated by Adaptive Optics Scanning Laser Ophthalmoscopy in a Phase 1 Clinical Trial of Ciliary Neurotrophic Factor. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5933.
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Macular telangiectasia (MacTel) has been considered primarily a vascular disease, but recent evidence suggests that neuronal changes may occur early in disease development. The NT-501 ciliary neurotrophic factor (CNTF) implant (Neurotech USA, Inc.) uses encapsulated cell technology to deliver CNTF to the retina and has been shown to reduce photoreceptor cell loss in retinal degeneration. To study the rate of cone photoreceptor loss in MacTel treated with CNTF, we used AOSLO to examine patients enrolled in a Phase 1 clinical trial.
Three patients with MacTel were imaged using AOSLO at two centers. In each patient, the more severely affected eye had received the CNTF implant and the fellow eye served as a control. AOSLO imaging was conducted at baseline and 18 months after implantation in all 3 subjects. 1 subject was additionally imaged at 24 and 36 months. At least 10 regions of interest (ROIs) were selected and tracked across imaging sessions. Individual cones within each ROI were labeled. At each time point, at each ROI, the percent change in cone spacing from baseline was measured. The mean percent change was compared from baseline to each time point using one-way ANOVA, and the treated eyes were compared to controls using an independent t-test.
Combining the treated and control eyes from all 3 patients, AOSLO showed a statistically significant increase in cone spacing after 18 months (p<0.05). In 1 patient studied at 24 and 36 months, the increase was significant in the control (p<0.01) but not the treated eye (p=0.06) at 24 months, and significant in each eye at 36 months (p<0.01). The difference between treated and control eyes was not statistically significant at 18 months in the 3 patients studied (p =0.4). In 1 patient, the increase in cone spacing was significantly lower in the treated eye at 24 months (p =0.02) and 36 months (p=0.01).
Although MacTel has been classically defined by its clinically detectable changes in the retinal vasculature, AOSLO demonstrates that cone photoreceptor spacing increases with time in MacTel. AOSLO can provide a highly sensitive method to measure microscopic changes in MacTel in the clinical trial setting. Further study, including greater numbers of patients, is needed to determine whether the CNTF implant is effective in treating MacTel.
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