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Noninvasive Detection of Mitochondrial Dysfunction in Ocular Hypertension and Primary Open-angle Glaucoma

Geyman, Lawrence S., MD*,†; Suwan, Yanin, MD†,‡; Garg, Reena, MD; Field, Matthew G., PhD§; Krawitz, Brian D., MD*,†; Mo, Shelley, MD*,†; Pinhas, Alexander, MD†,∥; Ritch, Robert, MD; Rosen, Richard B., MD*,†

doi: 10.1097/IJG.0000000000000980
Original Studies

Purpose: To assess mitochondrial dysfunction in vivo in ocular hypertension (OHT) and primary open-angle glaucoma (POAG) using retinal metabolic analysis.

Patients and Methods: This was an observational, cross-sectional study performed from November 2015 to October 2016 at the New York Eye and Ear Infirmary of Mount Sinai. Thirty-eight eyes with varying stages of POAG, 16 eyes with OHT, and 32 control eyes were imaged on a custom fundus camera modified to measure full retinal thickness fluorescence at a wavelength optimized to detect flavoprotein fluorescence (FPF). Optical coherence tomography was used to measure the retinal ganglion cell-plus layer (RGC+) thickness. Macular FPF and the ratio of macular FPF to RGC+ thickness were the primary outcome variables and were compared among the three groups using an age-adjusted linear regression model. A mixed-effects model was used to assess correlations between FPF variables and clinical characteristics.

Results: Both macular FPF and the macular FPF/RGC+ thickness ratio were significantly increased in OHT compared with control eyes (P<0.05 and <0.01, respectively). In POAG eyes, macular FPF was not significantly increased compared with controls (P=0.24). However, the macular FPF/RGC+ thickness ratio in POAG eyes was significantly increased compared with controls (P<0.001). FPF was significantly correlated to age in POAG eyes.

Conclusions: Despite lacking clinical evidence of glaucomatous deterioration, OHT eyes displayed significantly elevated macular FPF, suggesting that mitochondrial dysfunction may be detected before structural changes visible on current clinical imaging. Our preliminary results suggest that macular FPF analysis may prove to be a useful tool in assessing and evaluating OHT and POAG eyes.

*Icahn School of Medicine at Mount Sinai

Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York

Department of Ophthalmology, State University of New York Downstate Medical Center, Brooklyn, NY

Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

§Leonard M. Miller School of Medicine, University of Miami, Miami, FL

Supported by the New York Eye and Ear Infirmary Chairman’s Research Fund, New York, NY; the Marrus Family Foundation, New York, NY; and the Lary Stromfeld Research Fund of the New York Glaucoma Research Institute, New York, NY. The sponsor or funding organization had no role in the design and conduct of this research.

L.S.G.: planning, conduct, reporting. Y.S.: planning, conduct, reporting. R.G.: planning, conduct, reporting. M.G.F.: planning, reporting. B.D.K.: conduct, reporting. S.M.: conduct, reporting. A.P.: planning, reporting. R.R.: planning, reporting. R.B.R.: planning, reporting.

Presented in part at the Association for Research in Vision and Ophthalmology Annual Meeting (Geyman L, Pinhas A, Krawitz B, Mo S, Field M, Rosen RB. Mitochondrial Flavoprotein Fluorescence in Glaucoma Suspects, Primary Open-Angle Glaucoma, and Healthy Controls. ARVO Annual Meeting, May 2016, Seattle, WA). R.B.R. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Disclosure: M.G.F.: reports consultancy for and an equity stake in OcuSciences Inc. R.R.: reports personal fees from iSonic Medical, personal fees from Sensimed AG, personal fees from Aeon Astron, nonfinancial support from GLIA, LLC, other support from Xoma (US), LLC, other support from Guardion Health Sciences, other support from Mobius Therapeutics, other support from Intelon Optics, personal fees from Ocular Instruments Inc., ownership interest from Diopsys Inc., and ownership interest from International Eye Wellness Institute, outside the submitted work. R.B.R.: reports personal fees from Nano Retina Inc., personal fees from Ocata Therapeutics Inc., personal fees from Optovue Inc., ownership interest from Guardion Health, Opticology, and GlaucoHealth outside the submitted work. The remaining authors declare no conflict of interest.

Reprints: Richard B. Rosen, MD, 310 East 14th Street, 5th Floor, South Building, New York, NY, 10003 (e-mail: rrosen@nyee.edu).

Received December 26, 2017

Accepted April 30, 2018

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