Raymond P Najjar1, Sourabh Sharma2, Eray Atalay3, Annadata V Rukmini4, Christopher Sun5, Jing Zhan Lock4, Mani Baskaran6, Shamira A Perera6, Rahat Husain5, Ecosse Lamoureux7, Joshua J Gooley8, Tin Aung9, Dan Milea10. 1. Singapore Eye Research Institute, Singapore; Ophthalmology and Visual Sciences Program, Duke-NUS Medical School, Singapore. 2. Singapore Eye Research Institute, Singapore; Singapore National Eye Center, Singapore. 3. Singapore Eye Research Institute, Singapore; Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey. 4. Singapore Eye Research Institute, Singapore. 5. Singapore National Eye Center, Singapore. 6. Singapore Eye Research Institute, Singapore; Ophthalmology and Visual Sciences Program, Duke-NUS Medical School, Singapore; Singapore National Eye Center, Singapore. 7. Singapore Eye Research Institute, Singapore; Ophthalmology and Visual Sciences Program, Duke-NUS Medical School, Singapore; Office of Clinical Sciences, Duke-NUS Medical School, Singapore. 8. Program in Neuroscience and Behavioral Disorders, Duke-NUS Medical School, Singapore. 9. Singapore Eye Research Institute, Singapore; Ophthalmology and Visual Sciences Program, Duke-NUS Medical School, Singapore; Singapore National Eye Center, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 10. Singapore Eye Research Institute, Singapore; Ophthalmology and Visual Sciences Program, Duke-NUS Medical School, Singapore; Singapore National Eye Center, Singapore. Electronic address: dan.milea@snec.com.sg.
Abstract
PURPOSE: To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of -6 decibels or better on automated perimetry. METHODS: Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography. MAIN OUTCOME MEASURES: Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis. RESULTS: Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm2/s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG. CONCLUSIONS: Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease.
PURPOSE: To evaluate the ability of chromatic pupillometry to reveal abnormal pupillary responses to light in patients with early-stage primary open-angle glaucoma (POAG) and to test whether the degree of pupillometric impairment correlates with structural hallmarks of optic nerve damage in the disease. DESIGN: Cross-sectional study. PARTICIPANTS: Forty-six patients with early-stage POAG (63.4±8.3 years, 63% male, 87% ethnic-Chinese) and 90 age-matched healthy controls (61.4±8.6 years, 34% male, 89% ethnic-Chinese). Patients with POAG had a visual field mean deviation (VFMD) of -6 decibels or better on automated perimetry. METHODS: Each participant underwent a monocular 2-minute exposure to blue light (462 nm) followed by another 2-minute exposure to red light (638 nm) using a modified Ganzfeld dome equipped with a light-emitting diode lighting system. The light stimuli intensity was increased logarithmically to evaluate the combined extrinsic and intrinsic response of intrinsically photosensitive retinal ganglion cells (ipRGCs). Light-induced changes in horizontal pupil diameter were assessed monocularly using infrared pupillography. MAIN OUTCOME MEASURES: Baseline-adjusted, light-induced pupillary constriction amplitudes were calculated, and individual irradiance-response curves were constructed for each stimulus. Pupillary constriction amplitudes were compared between groups and across light intensities using a linear mixed model analysis. The linear relationship between pupillometric parameters and different structural and functional features of glaucoma was assessed using Pearson's correlation analysis. RESULTS: Light-induced pupillary constriction was reduced in patients with early-stage POAG compared with controls at moderate to high irradiances (≥11 Log photons/cm2/s) of blue (P = 0.003) and red (P < 0.001) light. Maximal pupillary constriction amplitude was correlated with retinal nerve fiber layer thickness (RNFL) thickness (blue: r = 0.51, P < 0.001; red: r = 0.45, P = 0.002) in patients with POAG but not in controls. Conversely, pupillometric parameters were not correlated with visual field scores in patients with early-stage POAG. CONCLUSIONS:Patients with early-stage POAG exhibit reduced pupillary responses to moderate and high irradiances of blue and red lights. This wavelength-independent functional alteration correlates with structural thinning of the RNFL and could be the consequence of dysfunction or loss of melanopsin expressing ipRGCs in the early stages of the disease.
Authors: Carina Kelbsch; Torsten Strasser; Yanjun Chen; Beatrix Feigl; Paul D Gamlin; Randy Kardon; Tobias Peters; Kathryn A Roecklein; Stuart R Steinhauer; Elemer Szabadi; Andrew J Zele; Helmut Wilhelm; Barbara J Wilhelm Journal: Front Neurol Date: 2019-02-22 Impact factor: 4.003
Authors: A V Rukmini; Milton C Chew; Maxwell T Finkelstein; Eray Atalay; Mani Baskaran; Monisha E Nongpiur; Joshua J Gooley; Tin Aung; Dan Milea; Raymond P Najjar Journal: Sci Rep Date: 2019-03-20 Impact factor: 4.379
Authors: Anton Sonntag; Carina Kelbsch; Ronja Jung; Helmut Wilhelm; Torsten Strasser; Tobias Peters; Krunoslav Stingl; Barbara Wilhelm Journal: Int Ophthalmol Date: 2021-11-26 Impact factor: 2.029