Genetic Penetrance of Macular Telangiectasia Type 2.

Importance: The apparent genetic penetrance of macular telangiectasia type 2 (MacTel) is important for gene discovery studies and for clinical risk assessment of affected individuals' family members. Objective: To determine the genetic penetrance of MacTel. Design, Setting, and Participants: Descriptive cross-sectional study of patients with MacTel at a tertiary referral eye center. From 2008 to 2016, consecutive patients with MacTel were independently identified, and all of their available siblings and parents were recruited. Seventeen probands with MacTel were included in the study who satisfied the requirement of having at least 1 parent or sibling willing and able to participate. Data from these 17 families were included for the analysis of apparent genetic penetrance. Main Outcomes and Measures: Determination of MacTel genetic penetrance in probands' parents and siblings. Results: Of 80 study participants, 50 (62.5%) were women. The mean (SD) age of study participants with MacTel was 61.2 (14.0) years (range, 23-81 years) and without MacTel was 60.7 (16.4) years (range, 24-92 years). There were 17 MacTel probands, and there was a high rate of enrollment of living siblings and parents: 52 of 71 living siblings (73%) and 11 of 12 parents (92%). Of 52 enrolled siblings, 9 (17%) were affected. Of 11 enrolled parents, 3 (27%) had MacTel. Apparent genetic penetrance was calculated to be 0.35 (95% CI, 0.14-0.6) by sibling analysis and 0.55 (95% CI, 0.02-1.00) by parent analysis. Combining the sibling and parent analyses, the apparent penetrance was calculated to be 0.38 (95% CI, 0.19-0.57). Conclusions and Relevance: The genetic penetrance of MacTel in rigorously phenotyped multiple large families is described. Families such as these could be critical for successful identification of MacTel genes.

MACULAR PIGMENT DISTRIBUTION RESPONSES TO HIGH-DOSE ZEAXANTHIN SUPPLEMENTATION IN PATIENTS WITH MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: To analyze macular pigment (MP) amount and distribution in patients with macular telangiectasia Type 2 receiving oral zeaxanthin supplementation in a randomized, open-label, interventional trial. METHODS: Eight macular telangiectasia Type 2 patients were randomized to 10 mg or 20 mg of zeaxanthin per day. At each visit, best-corrected visual acuity, contrast sensitivity, fundus biomicroscopy, color fundus photography, autofluorescence imaging, optical coherence tomography, and serum carotenoid levels were tested. Patients were assessed at baseline and after 6, 12, 18, and 24 months of zeaxanthin supplementation. Concentration of MP was analyzed and calculated from autofluorescence imaging obtained at 488-nm excitation wavelength. Serum carotenoid levels were obtained using high-performance liquid chromatography. RESULTS: The majority of patients had definite increases in the intensity of hypofluorescent ring of MP, but none of them deposited MP centrally at the fovea. Although some patients noted subjective improvements in vision, no objective improvements could be documented, and there were no changes in foveal optical coherence tomographic features. Yellowish, hypofluorescent crystals appeared in one patient's macular region with no change in visual acuity. These inner retinal crystals disappeared several months after discontinuing her 20-mg zeaxanthin supplement. CONCLUSION: Based on the current study, zeaxanthin supplementation does not result in any visual benefit in patients with macular telangiectasia Type 2 and does not reestablish a normal peaked distribution of MP in the fovea. One patient developed a novel, reversible, crystalline maculopathy in response to zeaxanthin supplementation that was reminiscent of canthaxanthin crystalline maculopathy.