Ciliary neurotrophic factor for macular telangiectasia type 2: results from a phase 1 safety trial.

PURPOSE: To evaluate the safety and tolerability of intraocular delivery of ciliary neurotrophic factor (CNTF) using an encapsulated cell implant for the treatment of macular telangiectasia type 2. DESIGN: An open-label safety trial conducted in 2 centers 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 visual acuity, en face measurements of the optical coherence 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 baseline. 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.

Anti-retinal antibodies in patients with macular telangiectasia type 2.

PURPOSE: Macular telangiectasia type 2 (MacTel-2) is a retinal disease that can cause loss of central vision. To gain better understanding of the etiology and pathogenesis of MacTel-2, we investigated antigens that prompt the generation of retinal autoantibodies in the serum of patients with MacTel-2. METHODS: We screened for the presence of retinal autoantibodies in 45 serum samples collected from patients with MacTel-2 and 58 serum samples from healthy control subjects by Western blot. We then isolated and identified three retinal proteins that are putative targets of three of the most frequently detected autoantibodies in the serum of patients with MacTel-2 using chromatographic fractionation and liquid chromatography coupled to tandem mass spectrometry. We also validated the retinal location of the three antigens by immunohistochemisty using MacTel-2 sera as primary antibodies and commercial antibodies. RESULTS: Retinal autoantibodies were detected in a significantly higher proportion of patients with MacTel-2 than in controls (31 of 45 [69%] vs. 9 of 58 [16%], P < 0.0001). The three antigens that were targeted by the most frequently detected MacTel-2 autoantibodies were identified as glycogen debranching enzyme (hereafter AGL, named for the gene symbol AGL), retinol-binding protein 3 (RBP3), and creatine kinase type B (CK-B); autoantibodies against these antigens were found in four, eleven, and nine MacTel-2 serum samples, respectively. CONCLUSIONS: We found that most patients with MacTel-2 possess retinal autoantibodies, the most prevalent of which were directed against AGL, RBP3, and CK-B. The localization of retinal proteins bound by AGL, RBP3, and CK-B autoantibodies is consistent with their putative physiological functions. These findings provide potentially novel mechanisms for the etiology and pathogenesis of MacTel-2.