THE DOSE-DEPENDENT MACULAR THICKNESS CHANGES ASSESSED BY FD-OCT IN PATIENTS WITH RETINITIS PIGMENTOSA TREATED WITH CILIARY NEUROTROPHIC FACTOR SUMAN PILLI, MD, ROBERT J. ZAWADZKI, PHD, DAVID G. TELANDER, MD, PHD Purpose: To evaluate the effect of intravitreal ciliary neurotrophic factor (CNTF) implant on mean macular thickness (MMT) in eyes with retinitis pigmentosa using high-resolution Fourier domain optical coherence tomography imaging. Methods: A cohort of 8 patients (CNTF-3: n = 5; CNTF-4: n = 3) enrolled in Neurotech sponsored Phase 2 clinical trial underwent Fourier domain optical coherence tomography imaging. A $3% change in MMT from baseline or fellow eye was considered as a measur- able change. Results: Two patients enrolled in the CNTF-3 study received low-dose implant. At 18 months, a change in MMT from -4.47 mm to 6 mm from baseline was noted. Six patients received high-dose implant (CNTF-3: n = 3; CNTF-4: n = 3). In CNTF-3 group, 1 eye showed an increase in MMT by 19.25 mm (+7.6%) from baseline at 18 months. In CNTF-4 group, 1 eye had an increase in MMT of 27.08 mm (+11%) from baseline at 30 months; second eye had increase in MMT of 31.36 mm (+12%) from contralateral eye. Amongst these 3 respon- sive high-dose implant eyes, overall thickening of the retina could not be attributed to any specific retinal layer. Conclusion: A heterogeneous dose-dependent response on MMT was noted in eyes treated using intravitreal CNTF implant for retinitis pigmentosa. We recommend corrobo- ration of our findings with Neurotech sponsored clinical trial results. RETINA 34:1384–1390, 2014 C iliary neurotrophic factor (CNTF) is a neurocyto- kine with multiple actions on the retina, which includes the differentiation of the developing photore- ceptor cells, expressing bipolar cell markers, promot- ing müller glia differentiation, and protecting retinal neurons from degeneration. 1–5 It acts by binding to its a-receptor and 2 signal-transducing transmembrane subunits, namely leukemia inhibitory factor rece- ptor (LIFRb) and glycoprotein (gp) 130. 6 The CNTF a-receptor is expressed on the Müller cell membrane and on rod and cone photoreceptors cells. 7 In Phase 1 clinical trial, the CNTF delivered by encapsulated cell line through an intraocular implant was found to be safe in patients, and visual acuity improvement was noted in three of the seven eyes. 7 Based on these observations, 2 Phase 2, multicenter randomized sham-controlled dose-ranging studies (CNTF-3 and CNTF-4) were conducted to evaluate the safety and efficacy of CNTF secreting (NT-501) implants in pa- tients with retinitis pigmentosa (RP) sponsored by Neurotech Pharmaceuticals, Inc. The CNTF-3 trial focused on patients with RP with vision between 20/ 60 and 20/320, and used central visual acuity changes as a primary outcome over an 18-month duration. The CNTF-4 study enrolled patients with RP with visual acuities better than 20/60 and measured visual field changes as a primary outcome with a 30-month dura- tion. The initial 12-month analysis of patients enrolled From the Department of Ophthalmology & Vision Science, Uni- versity of California Davis Eye Center, Sacramento, California. Supported by the National Eye Institute (Grant EY 014743) and Research to Prevent Blindness Unrestricted Departmental Grant. None of the authors have any conflicting interests to disclose. Reprint requests: David Telander, MD, PhD, c/o Retinal Consultants Medical Group 3939 J Street, Suite 106 Sacramento, CA 95819; e-mail: david.telander@yahoo.com 1384