Illuminating Glaucoma: Linking Pupillary Light Responses to Functional and Structural Impairment in Ocular Hypertension and Primary Open-Angle Glaucoma
DOI:
https://doi.org/10.48560/rspo.38213Keywords:
Glaucoma, Open-Angle, Ocular Hypertension, Reflex, Pupillary, Retinal Ganglion Cells, Visual Field TestsAbstract
INTRODUCTION: This study assessed the relationship between the pupillary light reflex and both functional and structural loss in patients with ocular hypertension (OHT) and primary open-angle glaucoma (POAG), using automated pupillometry, a precise method for measuring pupillary responses. By examining this relationship, the study seeks to provide insights into how changes in pupillary function correspond to glaucoma development, potentially improving diagnostic and monitoring methods.
METHODS: A cross-sectional study enrolling OHT and POAG patients across the whole spectrum of disease severity was conducted. Monocular dynamic pupillary responses were recorded using an automatic quantitative pupillometry system. The relative amplitude of pupil constriction was calculated as the percentage change in pupil diameter from onset to peak constriction. All patients underwent standard automated perimetry and optical coherence tomography within one year before pupillometry, and the relationship between pupillary responses and these parameters was analyzed.
RESULTS: The study included 136 eyes from 68 subjects (mean age 68.6±10.268.6±10.2 years, 52.9% female). Significant correlations were found between all monocular pupillary light response parameters and structural and/or functional measurements, except for initial pupil diameter. When controlling for confounders (age and sex), the relative amplitude of pupil constriction remained significantly correlated with campimetric parameters - mean deviation (r=0.274,p=0.003r=0.274,p=0.003), pattern standard deviation (r=0.261,p=0.005r=0.261,p=0.005), and visual field index (r=0.281,p=0.002r=0.281,p=0.002). Retinal nerve fiber layer (r=0.271,p=0.003r=0.271,p=0.003) and retinal ganglion cell complex (r=0.208,p=0.025r=0.208,p=0.025) thickness were also significantly positively associated. Significant correlations were found between disease groups, particularly between the OHT group and early-stage POAG, for the relative amplitude (p=0.011p=0.011) and velocity (p=0.003p=0.003) of pupil constriction.
CONCLUSION: In glaucomatous eyes, reduced pupillary light responses were linked to more advanced visual field loss and structural retinal damage. These findings highlight automated pupillometry’s potential as a precise, non-invasive tool for detecting functional and structural impairments. Its ability to discern OHT from early-stage POAG further underscores its diagnostic value, allowing earlier intervention in at-risk patients. As the technology evolves, its increased accessibility could benefit both specialized clinics and community settings, enabling earlier diagnosis and better patient care.
Downloads
References
US Preventive Services Task Force. Screening for primary open-angle glaucoma: US Preventive Services Task Force recommendation statement. JAMA. 2022;327:1992-7. doi:10.1001/jama.2022.7013.
Allison K, Patel D, Alabi O. Epidemiology of glaucoma: the past, present, and predictions for the future. Cureus. 2020;12:e11686. doi: 10.7759/cureus.11686.
Tapply IH, Bourne RR, Chapter 2 - Epidemiology of glaucoma. In: Gillmann K, Mansouri K, editors. The Science of Glaucoma Management. New York: Academic Press; 2023. p. 17-34.
Prum BE Jr, Lim MC, Mansberger SL, et al. Primary open-angle glaucoma suspect Preferred Practice Pattern guidelines. Ophthalmology. 2016;123:112-51. doi:10.1016/j.ophtha.2015.10.055.
Stein JD, Khawaja AP, Weizer JS. Glaucoma in adults—screening, diagnosis, and management: a review. JAMA. 2021;325:164-74. doi:10.1001/jama.2020.21899.
Gunzenhauser R, Coleman AL. Glaucoma screening guidelines worldwide. J Glaucoma. 2024;338:8. doi: 10.1097/JG.000000000002362.
Fu DJ, Ademisoye E, Shih V, McNaught AI, Khawaja AP. Burden of glaucoma in the United Kingdom: a multicenter analysis of United Kingdom glaucoma services. Ophthalmology Glaucoma. 2023;6:106-15. doi: 10.1016/j.ogla.2022.08.007.
Wagner IV, Stewart MW, Dorairaj SK. Updates on the diagnosis and management of glaucoma. Mayo Clin Proc Innov Qual Outcomes. 2022;6:618-35. doi: 10.1016/j.mayocpigo.2022.09.007.
Jayaram H, Kolko M, Friedman DS, Gazzard G. Glaucoma: now and beyond. Lancet. 2023;402:1788-801. doi: 10.1016/S0140-6736(23)01289-8.
Charalel RA, Lin HS, Singh K. Glaucoma screening using relative afferent pupillary defect. J Glaucoma. 2014;23:169-73. doi: 10.1097/JG.000136318269742.
Hennessy AL, Katz J, Ramakrishnan R, Krishnadas R, Thulasiraf RD, Tielsch JM, et al. The utility of relative afferent pupillary defect as a screening tool for glaucoma: prospective examination of a large population-based study in a South Indian population. Br J Ophthalmol. 2011;95:1203-6. doi: 10.1136/bjo.2010.194217.
Martucci A, Cesareo M, Napoli D, Sorge RP, Ricci F, Mancino R, et al. Evaluation of pupillary response to light in patients with glaucoma: a study using computerized pupillometry. Int Ophthalmol. 2014;34:1241-7. doi: 10.1007/s10792-014-9920-1.
Kelbsch C, Strasser T, Chen Y, Feigl B, Gamlin PD, Kardon R, et al. Standards in pupillography. Front Neurol. 2019;10:129. doi: 10.3389/fneur.2019.00129. Erratum in: Front Neurol. 2019;10:371. doi: 10.3389/fneur.2019.00371.
Rukmini AV, Milea D, Gooley JJ. Chromatic pupillometry methods for assessing photoreceptor health in retinal and optic nerve diseases. Front Neurol. 2019;10:76. doi: 10.3389/fneur.2019.00076.
Chang DS, Arora KS, Boland MV, Supakontanasan W, Friedman DS. Development and validation of an associative model for the detection of glaucoma using pupillography. Am J Ophthalmol. 2013;156:1285-96.e2. doi: 10.1016/j.ajo.2013.07.026.
Suo L, Zhang D, Qin X, Li A, Zhang C, Wang Y. Evaluating state-of-the-art computerized pupillary assessments for glaucoma detection: a systematic review and meta-analysis. Front Neurol. 2020;11:777. doi: 10.3389/fneur.2020.00777.
Chang DS, Boland MV, Arora KS, Supakontanasan W, Chen BB, Friedman DS. Symmetry of the pupillary light reflex and its relationship to retinal nerve fiber layer thickness and visual field defect. Invest Ophthalmol Vis Sci. 2013;54:5596-601. doi: 10.1167/iovs.13-12142.
Pradhan ZS, Rao HL, Puttiahi NK, Kadambi SV, Dasari S, Reddy HB, et al. Predicting the magnitude of functional and structural damage in glaucoma from monocular pupillary light responses using automated pupillography. J Glaucoma. 2017;26:409-14. doi: 10.1097/JIG.0000000000000634.
Gracilelli CP, Duque-Chica GL, Moura AL, Nagy BY, de Melo GR, Roizenhalt M, 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. doi: 10.1167/iovs.14-15146.
Chang DS, Arora K, Boland MV, Friedman DS. The relationship between quantitative pupillometry and estimated ganglion cell counts in patients with glaucoma. J Glaucoma. 2019;28:238-42. doi: 10.1097/JIG.0000000000001183.
Tatham AJ, Meira-Freitas D, Weinreb RN, Marvasti AH, Zangwill LM, Medeiros FA. Estimation of retinal ganglion cell loss in glaucomatous eyes with a relative afferent pupillary defect. Invest Ophthalmol Vis Sci. 2014;55:513-22. doi: 10.1167/iovs.13-12921.
Bayraktar S, Hondur G, Sekeroglu MA, Sen E. Evaluation of static and dynamic pupillary functions in early-stage primary open-angle glaucoma. J Glaucoma. 2023;32(7). doi: 10.1097/JIG.000000000002212.
Chang DS, Xu L, Boland MV, Friedman DS. Accuracy of pupil assessment for the detection of glaucoma: a systematic review and meta-analysis. Ophthalmology. 2013;120:2217-25. doi: 10.1016/j.ophtha.2013.04.012.
Bhowmik S, Arjunan SP, Sarossy M, Radcliffe P, Kumar DK. Pupillometric recordings to detect glaucoma. Physiol Meas. 2021;42. doi: 10.1088/1361-6579/abt05c.
Najjar RP, Rukmini AV, Finkelstein MT, Nusimovici S, Mani B, Nongpiur ME, et al. Handheld chromatic pupillometry can accurately and rapidly reveal functional loss in glaucoma. Br J Ophthalmol. 2023;107:663-70. doi: 10.1136/bjophthalmol-2021-319938.
Kalaboukhova L, Fridhammar V, Lindblom B. Relative afferent pupillary defect in glaucoma: a pupillometric study. Acta Ophthalmol Scand. 2007;85:519-25. doi: 10.1111/j.1600-0420.2006.00863.
Ozeki N, Yuki K, Shiba D, Tsubota K. Pupillographic evaluation of relative afferent pupillary defect in glaucoma patients. Br J Ophthalmol. 2013;97:1538-42. doi: 10.1136/bjophthalmol-2013-303825.
Sarezky D, Krupin T, Cohen A, Stewart CW, Volpe NJ, Tanna AP. Correlation between intereye difference in visual field mean deviation values and relative afferent pupillary response as measured by an automated pupillometer in subjects with glaucoma. J Glaucoma. 2014;23:419-23. doi: 10.1097/JIG.000013e3182711522.
Sarezky D, Volpe NJ, Park MS, Tanna AP. Correlation between inter-eye difference in average retinal nerve fiber layer thickness and afferent pupillary response as measured by an automated pupillometer in glaucoma. J Glaucoma. 2016;25:312-6. doi: 10.1097/JIG.000000000000213.
Rao HL, Kadambi SV, Mehta P, Dasari S, Puttiahi NK, Pradhan ZS, et al. Diagnostic ability of automated pupillography in glaucoma. Curr Eye Res. 2017;42:743-7. doi: 10.1080/02713683.2016.1238944.
Pinheiro HM, Camilo ENR, Paranhos A Jr, Fonseca AU, Laureano GT, Costa RM. Evaluating machine learning techniques for enhanced glaucoma screening through Pupillary Light Reflex analysis. Array. 2024;100359. doi:10.1016/j.array.2024.100359
Quan Y, Duan H, Zhan Z, Shen Y, Lin R, Liu T, et al. Binocular head-mounted chromatic pupillometry can detect structural and functional loss in glaucoma. Front Neurosci. 2023;17:1187619. doi: 10.3389/fnins.2023.1187619.
Finkelstein MT, Nongpiur ME, Husain R, Perera S, Baskaran M, Wong TT, et al. Handheld chromatic pupillometry can reliably detect functional glaucomatous damage in eyes with high myopia. Br J Ophthalmol. 2024;108:818-25. doi: 10.1136/bjo-2023-323878.
Barry C, De Souza J, Xuan Y, Holden J, Granholm E, Wang EJ. At-Home Pupillometry Using Smartphone Facial Identification Cameras. Proc SIGCHI Conf Hum Factor Comput Syst. 2022;2022:235. doi: 10.1145/3491102.3502493
Maxim A, Kush S, Kehne T, Niichian P, Gulck B, McGrath L, et al. Smartphone Pupillometry Use in Neurodegenerative Disease: A Clinical Pilot Study. Neurology. 2024;102. doi: 10.1212/WNL.00000000002056
Stelandre A, Rouland JF, Lorenceau J. Evaluation d'une methode pupillométrique pour la détection du glaucoma. J Fr Ophthalmol. 2023;46:475-94. doi: 10.1016/j.fro.2022.06.006.
Tekin K, Sekeroglu MA, Kiziltoprak H, Doguizi S, Inane M, Yilmazbas P. Static and dynamic pupillometry data of healthy individuals. Clin Exp Optom. 2018;101:659-65. doi: 10.1111/cxo.12659.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Revista Sociedade Portuguesa de Oftalmologia
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Do not forget to download the Authorship responsibility statement/Authorization for Publication and Conflict of Interest.
The article can only be submitted with these two documents.
To obtain the Authorship responsibility statement/Authorization for Publication file, click here.
To obtain the Conflict of Interest file (ICMJE template), click here
