Imaging endpoints for clinical trials in MacTel type 2

INTRODUCTION: Macular Telangiectasia type 2 (MacTel) is a bilateral neurodegenerative disease associated with dysfunction in the serine and lipid metabolism resulting in loss of Muller cells and photoreceptors. Typical structural changes include vascular abnormalities, loss of retinal transparency, redistribution of macular pigment and thinning of the central retina with photoreceptor loss. The presence and extent of photoreceptor loss, as visible on Optical Coherence Tomography (OCT) ("disease severity scale"), correlate with functional loss and the limitation of photoreceptor loss appears to be the most promising therapeutic approach. Ongoing clinical trials of ciliary neurotrophic factor (CNTF) implants for the treatment of MacTel are using this outcome to evaluate efficacy. An ideal outcome measure provides the ability to quantify the extent of the disease progression with precision and reproducibility.

METHODS: This review describes the changes and findings on different imaging techniques including fluorescein- and OCT angiography, blue light reflectance, 1- and 2-wavelength autofluorescence and OCT.

RESULTS: The possibilities of objective quantification of the severity of MacTel and correlation with functional characteristics such as best-corrected visual acuity (BCVA) and microperimetry and their applications as quantitative imaging endpoints for clinical treatment trials are discussed. OCT and especially en face OCT could be demonstrated as precise and reproducible methods to quantify the area of photoreceptor loss, which correlated highly significantly with functional loss in microperimetry.

CONCLUSION: The analysis of the area of photoreceptor loss on en face OCT is the most reliable imaging endpoint for treatment trials in MacTel. This method is already being used in ongoing randomized trials.