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Structure and Function of Dysflective Cones in Healthy and Diseased Eyes

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Abstract Number: 1031

AuthorBlock: Ethan Bensinger1, Katharina G. Foote1,2, Jessica J. Wong2, Jacque L. Duncan2, Austin Roorda1
1School of Optometry and Vision Science Graduate Group, University of California Berkeley, Berkeley, California, United States; 2Ophthalmology, University of California San Francisco, San Francisco, California, United States;

DisclosureBlock: Ethan Bensinger, C.Light Technologies Code C (Consultant), Spouse - C.Light Technologies Code I (Personal Financial Interest), Spouse - C.Light Technologies Code P (Patent), Katharina G. Foote, Carl Zeiss Meditec, Inc. Code C (Consultant), Jessica J. Wong, None; Jacque L. Duncan, AGTC Code C (Consultant), California Institute for Regenerative Medicine Code C (Consultant), Foundation Fighting Blindness Code C (Consultant), Editas Medicine Code C (Consultant), Ionis Pharmaceuticals Code C (Consultant), Novelion Therapeutics Code C (Consultant), ProQR Therapeutics Code C (Consultant), SparingVision Code C (Consultant), Spark Therapeutics Code C (Consultant), Foundation Fighting Blindness Code S (Non-remunerative), Neurotech USA Inc Code S (Non-remunerative), Austin Roorda, C.Light Technologies Code I (Personal Financial Interest), USPTO#7,118,216 Code P (Patent), USPTO#6,890,076 Code P (Patent)

Purpose
To characterize the structure and function of dysflective cones in normal subjects and in patients with Macular Telangiectasia type 2 (MacTel). Dysflective cones exhibit measurable function but are not seen in confocal adaptive optics scanning laser ophthalmoscopy (AOSLO) images and lack inner/outer segment junction and cone outer segment tip reflections in optical coherence tomography (OCT) B-scans.

Methods
AOSLO and Adaptive Optics Microperimetry (AOMP) were used to assess the structure and function of areas identified as possible dysflective cones in 3 healthy subjects and 2 patients. AOMP thresholds were measured with 543 nm light (equally sensed by L and M cones) and computed as the average of 2, 35-trial adaptive staircase (QUEST) sessions. Due to the small size of the dysflective areas in healthy eyes (average area of 8.3 arcmin2) AOMP utilized a stimulus size of less than 1 arcmin, and transverse chromatic aberration was measured before and after testing to confirm that the stimulus remained on target. Patients, who had larger dysflective regions, were tested with a stimulus size of 3.45 arcmin. Suspected dysflective and normal-appearing cones at similar eccentricities were tested in each group. Whenever possible, subjects were imaged with confocal AOSLO, split detector AOSLO, and OCT.

Results
All subjects had measurable function in the dysflective cone area. 2 of the 3 healthy subjects showed no difference in function in the dysflective area compared to adjacent areas. Cones in one healthy subject’s dysflective area regained normal reflective properties after 2 weeks. The 3rd healthy subject had 3x reduced sensitivity within the dysflective area. Both patients had reduced, but measurable, sensitivity within the dysflective area. One patient had no measurable sensitivity in the middle of the lesion but measurable sensitivity at the dysflective border. These corresponded to regions in the split-detection images without and with visible inner segments, respectively.

Conclusions
For the first time (i) dysflective cones have been identified in healthy subjects and (ii) we observe instances where dysflective cones in healthy subjects regain normal reflective properties. Finally, we used split detector imaging to further refine the dysflective cone phenotype in MacTel patients, and suggest that visible inner segments are present in dysflective cones with measurable function.

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