Ciliary Neurotrophic Factor for Macular Telangiectasia Type 2: Results From a Phase 1 Safety Trial EMILY Y. CHEW, TRACI E. CLEMONS, TUNDE PETO, FERENC B. SALLO, AVNER INGERMAN, WENG TAO, LAWRENCE SINGERMAN, STEVEN D. SCHWARTZ, NEAL S. PEACHEY, ALAN C. BIRD, AND THE MACTEL-CNTF RESEARCH GROUP  PURPOSE: To evaluate the safety and tolerability of intraocular delivery of ciliary neurotrophic factor (CNTF) using an encapsulated cell implant for the treat- ment of macular telangiectasia type 2.  DESIGN: An open-label safety trial conducted in 2 cen- ters enrolling 7 participants with macular telangiectasia type 2.  METHODS: The participant’s more severely affected eye (worse baseline visual acuity) received the high- dose implant of CNTF. Patients were followed for a period of 36 months. The primary safety outcome was a change in the parameters of the electroretinogram (ERG). Secondary efficacy outcomes were changes in vi- sual acuity, en face measurements of the optical coher- ence tomography of the disruption in the ellipsoid zone, and microperimetry when compared with baseline.  RESULTS: The ERG findings demonstrated a reduction in the amplitude of the scotopic b-wave in 4 participants 3 months after implantation (month 3). All parameters returned to baseline values by month 12 and remained so at month 36 with no clinical impact on dark adaptation. There was no change in visual acuity compared with base- line. The area of the defect as measured functionally by microperimetry and structurally by the en face OCT imaging of the ellipsoid zone loss appeared unchanged from baseline.  CONCLUSIONS: The intraocular delivery of CNTF in the encapsulated cell implant appeared to be safe and well tolerated in eyes with macular telangiectasia type 2. Further evaluation in a randomized controlled clinical trial is warranted to test for efficacy. (Am J Ophthalmol 2015;-:-–-. Ó 2015 by Elsevier Inc. All rights reserved.) I DIOPATHIC MACULAR TELANGIECTASIA TYPE 2 (MacTel) is a bilateral degenerative condition of un- known etiology with characteristic neurosensory atro- phy and perifoveal telangiectatic vessels that leak on fluorescein angiography. 1 Other characteristic lesions include loss of retinal transparency, crystalline deposits, a decrease or absence of macular pigment, and hyperplasia of the retinal pigment epithelium (RPE) in the macular area. The spectral-domain optical coherence tomography (OCT) assessments show disruption of the photoreceptor inner segment–outer segment junction line (IS/OS line) or ellipsoid zone (EZ) and hypo-reflective cavities in both the inner and outer retina. The natural course is a gradual progressive bilateral loss of vision, occasionally accompa- nied by subretinal neovascularization, leading to severe vision loss. 1 Genetic studies have suggested a MacTel gene locus on chromosome 1. 2 The natural course of gradual visual acuity loss in MacTel patients is approximately 1 letter per year (Clem- ons TE et al. IOVS, 2012; 53:ARVO e-abstract 982); how- ever, affected individuals have profoundly reduced visual function compared to a normal age-matched reference group. 3,4 This may be owing to the presence of bilateral lesions of photoreceptor disruption that begin temporal to the fovea, resulting in bilateral nasal scotomas and consequent prefixational blindness. A study correlating these visual field defects detected by microperimetry with OCT shows that the defects are closely associated with cavitation of the outer retina, indicating that loss of vision in MacTel is associated with structural changes at the level of photoreceptors. 5,6 Current evidence suggests that photoreceptor cell loss is intrinsic to the disorder rather than being consequent to the vascular changes. 7 Photoreceptor abnormality occurs early in the disorder and progression of photoreceptor cell loss may be detected on OCT with the loss of the IS/OS layer (ellipsoid zone). Measurement of the missing ellipsoid zone, captured as Accepted for publication Dec 11, 2014. From the National Eye Institute, National Institutes of Health, Bethesda, Maryland (E.Y.C.); The EMMES Corporation, Rockville, Maryland (T.E.C.); National Institute of Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology, London, United Kingdom (T.P.); Departments of Research and Development (F.B.S.) and Inherited Eye Disease (A.C.B.), Moorfields Eye Hospital, London, United Kingdom; University College London, Institute of Ophthalmology, London, United Kingdom (F.B.S.); ATIS Consultants, Scarsdale, New York (A.I.); Neurotech Pharmaceuticals, Cumberland, Rhode Island (W.T.); Retina Associates of Cleveland, Cleveland, Ohio (L.S.); University of California Los Angeles, Los Angeles, California (S.D.S.); Cleveland Clinic, Department of Ophthalmology, Cleveland Ohio (N.S.P.); and Louis Stokes Cleveland VA Medical Center, Cleveland, Ohio (N.S.P.). Inquiries to Emily Y. Chew, NIH, BLDG 10-CRC, RM 3-2531, 10 Center Drive - MSC1204, Bethesda MD 20892-1204; e-mail: echew@ nei.nih.gov 0002-9394/$36.00 http://dx.doi.org/10.1016/j.ajo.2014.12.013 1 Ó 2015 BY ELSEVIER INC.ALL RIGHTS RESERVED.