Chromatic Pupillometry – a New Technique for Assessing Function in Glaucoma?

Abstract

Chromatic pupillometry allows quantification of photoreceptor-driven (extrinsic) and melanopsin-driven (intrinsic) responses of the intrinsic-photosensitive retinal ganglion cells (ipRGCs). This small subpopulation of retinal ganglion cells is also affected by glaucoma, making chromatic pupillometry a potential diagnostic tool. Studies show reduced phasic and tonic responses in glaucoma patients. The diagnostic value in earlier studies depended on the technical details and the study design. The purpose of this article is to give an introduction into the principles of chromatic pupillometry and to discuss the potential applications in the management of glaucoma.

Key words

glaucoma - pupillometry - retinal ganglion cells - neuroophthalmology

• References/Literatur

• 1 Casson RJ, Chidlow G, Wood JPM. et al. Definition of glaucoma: clinical and experimental concepts. Clin Experiment Ophthalmol 2012; 40: 341-349
• 2 Camp AS, Weinreb RN. Will Perimetry Be Performed to Monitor Glaucoma in 2025?. Ophthalmology 2017; 124 (12S): S71-S75
• 3 Hood DC, Kardon RH. A framework for comparing structural and functional measures of glaucomatous damage. Prog Retin Eye Res 2007; 26: 688-710
• 4 Lämmer R, Huchzermeyer C. [Value of Perimetric Measurements for Glaucoma Detection]. Klin Monbl Augenheilkd 2021;
• 5 Fry LE, Fahy E, Chrysostomou V. et al. The coma in glaucoma: Retinal ganglion cell dysfunction and recovery. Prog Retin Eye Res 2018; 65: 77-92
• 6 Bach M, Brigell MG, Hawlina M. et al. ISCEV standard for clinical pattern electroretinography (PERG): 2012 update. Doc Ophthalmol 2013; 126: 1-7
• 7 Frishman L, Sustar M, Kremers J. et al. ISCEV extended protocol for the photopic negative response (PhNR) of the full-field electroretinogram. Doc Ophthalmol 2018; 136: 207-211
• 8 Dacey DM. Parallel pathways for spectral coding in primate retina. Annu Rev Neurosci 2000; 23: 743-775
• 9 Kim US, Mahroo OA, Mollon JD. et al. Retinal Ganglion Cells – Diversity of Cell Types and Clinical Relevance. Front Neurol 2021; 12: 661938
• 10 Rodiek RW. The First Steps in Seeing. Sunderland, Massachusetts: Sinauer Associates, Inc.; 1998
• 11 Lee BB, Sun H, Zucchini W. The temporal properties of the response of macaque ganglion cells and central mechanisms of flicker detection. J Vis 2007;
• 12 Sample PA. Short-wavelength automated perimetry: itʼs role in the clinic and for understanding ganglion cell function. Prog Retin Eye Res 2000; 19: 369-383
• 13 Anderson AJ, Johnson CA. Frequency-doubling technology perimetry. Ophthalmol Clin North Am 2003; 16: 213-225
• 14 Frisén L. New, sensitive window on abnormal spatial vision: rarebit probing. Vision Res 2002; 42: 1931-1939
• 15 Frisén L. High-pass resolution perimetry. A clinical review. Doc Ophthalmol 1993; 83: 1-25
• 16 Swanson WH, Sun H, Lee BB. et al. Responses of Primate Retinal Ganglion Cells to Perimetric Stimuli. Invest Ophthalmol Vis Sci 2011; 52: 764-771
• 17 Quigley HA, Dunkelberger GR, Green WR. Chronic human glaucoma causing selectively greater loss of large optic nerve fibers. Ophthalmology 1988; 95: 357-363
• 18 Johnson CA. Selective versus nonselective losses in glaucoma. J Glaucoma 1994; 3 (Suppl. 01) S32-S44
• 19 Dacey DM, Liao HW, Peterson BB. et al. Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN. Nature 2005; 433: 749-754
• 20 Rukmini AV, Milea D, Aung T. et al. Pupillary responses to short-wavelength light are preserved in aging. Sci Rep 2017; 7: 43832
• 21 Feigl B, Mattes D, Thomas R. et al. Intrinsically photosensitive (melanopsin) retinal ganglion cell function in glaucoma. Invest Ophthalmol Vis Sci 2011; 52: 4362-4367
• 22 Obara EA, Hannibal J, Heegaard S. et al. Loss of Melanopsin-Expressing Retinal Ganglion Cells in Severely Staged Glaucoma Patients. Invest Ophthalmol Vis Sci 2016; 57: 4661-4667
• 23 Li RS, Chen BY, Tay DK. et al. Melanopsin-Expressing Retinal Ganglion Cells Are More Injury-Resistant in a Chronic Ocular Hypertension Model. Invest Ophthalmol Vis Sci 2006; 47: 2951-2958
• 24 Honda S, Namekata K, Kimura A. et al. Survival of Alpha and Intrinsically Photosensitive Retinal Ganglion Cells in NMDA-Induced Neurotoxicity and a Mouse Model of Normal Tension Glaucoma. Invest Ophthalmol Vis Sci 2019; 60: 3696-3707
• 25 Kelbsch C, Strasser T, Chen Y. et al. Standards in Pupillography. Front Neurol 2019; 10: 129
• 26 Suo L, Zhang D, Qin X. et al. Evaluating State-of-the-Art Computerized Pupillary Assessments for Glaucoma Detection: A Systematic Review and Meta-Analysis. Front Neurol 2020; 11: 777
• 27 Najjar RP, Rukmini AV, Finkelstein MT. et al. Handheld chromatic pupillometry can accurately and rapidly reveal functional loss in glaucoma. Br J Ophthalmol 2023; 107: 663-670
• 28 Huchzermeyer C, Kremers J. Selective Stimulation of the Different Photoreceptor Classes by Silent Substitution in Psychophysical and Electroretinographic Measurements. Klin Monbl Augenheilkd 2022; 239: 1433-1439
• 29 Zele AJ, Adhikari P, Cao D. et al. Melanopsin and Cone Photoreceptor Inputs to the Afferent Pupil Light Response. Front Neurol 2019; 10: 529
• 30 Yoshikawa T, Obayashi K, Miyata K. et al. Association Between Postillumination Pupil Response and Glaucoma Severity: A Cross-Sectional Analysis of the LIGHT Study. Invest Ophthalmol Vis Sci 2022; 63: 24
• 31 Ramirez AI, de Hoz R, Salobrar-Garcia E. et al. The Role of Microglia in Retinal Neurodegeneration: Alzheimerʼs Disease, Parkinson, and Glaucoma. Front Aging Neurosci 2017; 9: 214
• 32 Gracitelli CPB, Duque-Chica GL, Moura AL. et al. A positive association between intrinsically photosensitive retinal ganglion cells and retinal nerve fiber layer thinning in glaucoma. Invest Ophthalmol Vis Sci 2014; 55: 7997-8005
• 33 Kelbsch C, Maeda F, Strasser T. et al. Pupillary responses driven by ipRGCs and classical photoreceptors are impaired in glaucoma. Graefes Arch Clin Exp Ophthalmol 2016; 254: 1361-1370
• 34 Quan Y, Duan H, Zhan Z. et al. Evaluation of the Glaucomatous Macular Damage by Chromatic Pupillometry. Ophthalmol Ther 2023; 12: 2133-2156
• 35 Rukmini AV, Milea D, Baskaran M. et al. Pupillary Responses to High-Irradiance Blue Light Correlate with Glaucoma Severity. Ophthalmology 2015; 122: 1777-1785
• 36 Adhikari P, Zele AJ, Thomas R. et al. Quadrant Field Pupillometry Detects Melanopsin Dysfunction in Glaucoma Suspects and Early Glaucoma. Sci Rep 2016; 6: 33373
• 37 Kelbsch C, Stingl K, Kempf M. et al. Objective Measurement of Local Rod and Cone Function Using Gaze-Controlled Chromatic Pupil Campimetry in Healthy Subjects. Transl Vis Sci Technol 2019; 8: 19
• 38 Kelbsch C, Stingl K, Jung R. et al. How lesions at different locations along the visual pathway influence pupillary reactions to chromatic stimuli. Graefes Arch Clin Exp Ophthalmol 2022; 260: 1675-1685