Journal of Current Glaucoma Practice

Register      Login

VOLUME 17 , ISSUE 4 ( October-December, 2023 ) > List of Articles


Retinal Ganglion Cell Functional Recovery after Intraocular Pressure Lowering Treatment Using Prostaglandin Analogs in Glaucoma Suspects: A Prospective Pilot Study

Andrew Tirsi, Vasiliki Gliagias, Hosam Sheha, Bhakti Patel, Julie Moehringer, Joby Tsai, Rohun Gupta, Stephen A Obstbaum, Celso Tello

Keywords : Ganglion cell layer + inner plexiform layer, Glaucoma suspects, Intraocular pressure treatment, Pattern electroretinogram, Retinal ganglion cells, Retinal nerve fiber layer thickness

Citation Information : Tirsi A, Gliagias V, Sheha H, Patel B, Moehringer J, Tsai J, Gupta R, Obstbaum SA, Tello C. Retinal Ganglion Cell Functional Recovery after Intraocular Pressure Lowering Treatment Using Prostaglandin Analogs in Glaucoma Suspects: A Prospective Pilot Study. J Curr Glaucoma Pract 2023; 17 (4):178-190.

DOI: 10.5005/jp-journals-10078-1423

License: CC BY-NC 4.0

Published Online: 17-01-2024

Copyright Statement:  Copyright © 2023; The Author(s).


Aim and background: To evaluate the ability of pattern electroretinogram (PERG) to detect improvement of retinal ganglion cell (RGC) function in glaucoma suspects (GS) after medically reducing intraocular pressure (IOP) using prostaglandin analog drops. Materials and methods: Six subjects (eight eyes) received topical IOP lowering treatment based on their clinical examination and were observed at Manhattan Eye, Ear & Throat Hospital over an average of 3.1 ± 2.2 months. During this time, participants underwent a full ophthalmologic exam and were evaluated with a Humphrey visual field analyzer (HFA) 24–2 [24–2 mean deviation (MD), 24–2 pattern standard deviation (PSD), and 24–2 visual field indices (VFI)], Diopsys NOVA PERG optimized for glaucoma [magnitude (Mag), magnitudeD (MagD), and magnitudeD/magnitude ratio (MagD/Mag ratio)] and optical coherence tomography (OCT)-derived average retinal nerve fiber layer thickness (avRNFLT) and average ganglion cell layer + inner plexiform layer (avGCL + IPL) thicknesses at baseline visit (pretreatment) and 3 months later (posttreatment). Goldman applanation tonometry was used to measure IOP at each visit. Paired sample t-tests were conducted to determine the statistical significance of the change in IOP, HFA indices, PERG parameters, and OCT thickness measurements between the two visits. Results: Lowering IOP by 22.29% resulted in a significant increase (32.98 and 15.49%) in MagD [t (7) = −3.174, 95% confidence interval (CI) = −0.53, −0.08, p = 0.016] and MagD/Mag ratio [t (7) = −3.233, 95% CI = −0.20, −0.03, p = 0.014], respectively. There was a positive percentage change for all variables of interest, however, 24–2 MD, Mag, avRNFLT, and GCL+ IPLT did not reach statistical significance. Conclusion: After reducing IOP by 22.29% for a duration of 3.1 months, the PERG parameters, MagD and MagD/Mag ratio, significantly improved by 32.98 and 15.49%, respectively. Clinical significance: Pattern electroretinogram (PERG) may be a crucial tool for clinicians to locate a window of opportunity in which degenerating yet viable RGCs could be rescued from irreversible damage. We suggest consideration of PERG as a tool in early retinal ganglion cell (RGC) dysfunction detection as well as for monitoring IOP lowering treatment.

  1. Porciatti V. Electrophysiological assessment of retinal ganglion cell function. Exp Eye Res 2015;141:164–170. DOI: 10.1016/j.exer.2015.05.008
  2. Križaj D. Webvision: The Organization of the Retina and Visual System. 2019.
  3. Jafarzadehpour E, Radinmehr F, Pakravan M, et al. Pattern electroretinography in glaucoma suspects and early primary open angle glaucoma. J Ophthalmic Vis Res 2013;8(3):199–206. PMID: 24349662.
  4. Kass MA, Heuer DK, Higginbotham EJ, et al. The ocular hypertension treatment study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol 2002;120:701–713. DOI: 10.1001/archopht.120.6.701
  5. Tan JC, Kaufman PL. Primary open angle glaucoma. In: Yanoff M, Duker JS (Eds). Ophthalmology, 5th edition. Philadelphia, Pennsylvania, United States: Saunders, Elsevier; 2019. pp. 1057–1060.
  6. Ventura LM, Porciatti V. Restoration of retinal ganglion cell function in early glaucoma after intraocular pressure reduction: a pilot study. Ophthalmology 2005;112(1):20–27. DOI: 10.1016/j.ophtha.2004.09.002
  7. Kerrigan-Baumrind L, Quigley H, Pease M, et al. Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Invest Ophthalmol Vis Sci 2000;41(3):741–748. PMID: 10711689.
  8. Tirsi A, Gliagias V, Moehringer J, et al. Pattern electroretinogram parameters are associated with optic nerve head morphology abnormalities in pre-perimetric glaucoma after controlling for disc area. J Ophthalmol 2021;2021:8025337. DOI: 10.1155/2021/8025337
  9. Medeiros FA, Zangwill LM, Bowd C, et al. The structure and function relationship in glaucoma: implications for detection of progression and measurement of rates of change. Invest Ophthalmol Vis Sci 2012;53(11):6939–6946. DOI: 10.1167/iovs.12-10345
  10. Gillmann K, Mansouri K, Rao HL, et al. A prospective evaluation of the repeatability and reliability of new steady-state pattern electroretinogram parameters. J Glaucoma 2018;27(12):1079–1085. DOI: 10.1097/IJG.0000000000001103
  11. Kreft D, Doblhammer G, Guthoff RF, et al. Prevalence, incidence, and risk factors of primary open-angle glaucoma - a cohort study based on longitudinal data from a German public health insurance. BMC Public Health 2019;19(1):851. DOI: 10.1186/s12889-019-6935-6
  12. Kuang TM, Zhang C, Zangwill LM, et al. Estimating lead time gained by optical coherence tomography in detecting glaucoma before development of visual field defects. Ophthalmology 2015;122(10):2002–2009. DOI: 10.1016/j.ophtha.2015.06.015
  13. Banitt MR, Ventura LM, Feuer WJ, et al. Progressive loss of retinal ganglion cell function precedes structural loss by several years in glaucoma suspects. Invest Ophthalmol Vis Sci 2013;54(3):2346–2352. DOI: 10.1167/iovs.12-11026
  14. Porciatti V, Ventura LM. Normative data for a user-friendly paradigm for pattern electroretinogram recording. Ophthalmology 2004;111(1):161–168. DOI: 10.1016/j.ophtha.2003.04.007
  15. Sehi M, Grewal DS, Goodkin ML, et al. Reversal of retinal ganglion cell dysfunction after surgical reduction of intraocular pressure. Ophthalmology 2010;117(12):2329–2336. DOI: 10.1016/j.ophtha.2010.08.049
  16. Fortune B, Bui BV, Morrison JC, et al. Selective ganglion cell functional loss in rats with experimental glaucoma. Invest Ophthalmol Vis Sci 2004;45(6):1854–1862. DOI: 10.1167/iovs.03-1411
  17. Hare WA, Hau T. Effects of APB, PDA, and TTX on ERG responses recorded using both multifocal and conventional methods in monkey. Effects ofAPB, PDA, and TTX on monkey ERG responses. Doc Ophthalmol 2002;105(2): 189–222. DOI: 10.1023/a:1020553020264
  18. Hood DC, Frishman LJ, Viswanathan S, et al. Evidence for a ganglion cell contribution to the primate electroretinogram (ERG): effects of TTX on the multifocal ERG in macaque. Vis Neurosci 1999;16(3):411–416. DOI: 10.1017/s0952523899163028
  19. Viswanathan S, Frishman L, Robson J. The uniform field and pattern erg in macaques with experimental glaucoma: removal of spiking activity. Invest Ophthalmol Vis Sci 2000;41:2797–2810. PMID: 10937600.
  20. Papst N, Bopp M, Schnaudigel OE. The pattern evoked electroretinogram associated with elevated intraocular pressure. Graefes Arch Clin Exp Ophthalmol 1984;222(1):34–37. DOI: 10.1007/BF02133775
  21. Arden GB, O' Sullivan F. Longitudinal follow up of glaucoma suspects tested with pattern electroretinogram. Bull Soc Belge Ophtalmol 1992;244:147–154. PMID: 1363653.
  22. Nesher R, Trick GL, Kass MA, et al. Steady-state pattern electroretinogram following long term unilateral administration of timolol to ocular hypertensive subjects. Doc Ophthalmol 1990;75(2):101–109. DOI: 10.1007/BF00146546
  23. Falsini B, Colotto A, Porciatti V, et al. Follow-up study with pattern ERG in ocular hypertension and glaucoma patients under timolol maleate treatment. Clin Vision Sci 1992;7:341–347.
  24. Colotto A, Salgarello T, Giudiceandrea A, et al. Pattern electroretinogram in treated ocular hypertension: a cross-sectional study after timolol maleate therapy. Ophthalmic Res 1995;27(3):168–177. DOI: 10.1159/000267663
  25. Kremmer S, Tolksdorf-Kremmer A, Stodtmeister R. Simultane ableitung von VECP und muster-ERG bei küunstlicher erhöhung des augeninnendrucks. Ophthalmologica 1995;209:233–241. DOI: 10.1159/000310622
  26. Colotto A, Falsini B, Salgarello T, et al. Transiently raised intraocular pressure reveals pattern electroretinogram losses in ocular hypertension. Invest Ophthalmol Vis Sci 1996;37(13):2663–2670. PMID: 8977480.
  27. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the early manifest glaucoma trial. Arch Ophthalmol 2002;120(10):1268–1279. DOI: 10.1001/archopht.120.10.1268
  28. Karaśkiewicz J, Penkala K, Mularczyk M, et al. Evaluation of retinal ganglion cell function after intraocular pressure reduction measured by pattern electroretinogram in patients with primary open-angle glaucoma. Doc Ophthalmol 2017;134(2):89–97. DOI: 10.1007/s10633-017-9575-0
  29. Dietlein TS, Hermann MM, Jordan JF. The medical and surgical treatment of glaucoma. Dtsch Arztebl Int 2009;106(37):597–605. DOI: 10.3238/arztebl.2009.0597
  30. Sehi M, Grewal DS, Feuer WJ, et al. The impact of intraocular pressure reduction on retinal ganglion cell function measured using pattern electroretinogram in eyes receiving latanoprost 0.005% versus placebo. Vision Res 2011;51(2):235–242. DOI: 10.1016/j.visres.2010.08.036
  31. Al-Nosairy KO, Hoffmann MB, Bach M. Non-invasive electrophysiology in glaucoma, structure and function—a review. Eye (Lond) 2021;35(9):2374–2385. DOI: 10.1038/s41433-021-01603-0
  32. Wen JC, Lee CS, Keane PA, et al. Forecasting future humphrey visual fields using deep learning. PLOS One 2019;14(4):e0214875. DOI: 10.1371/journal.pone.0214875
  33. Tirsi A, Orshan D, Wong B, et al. Associations between steady-state pattern electroretinography and estimated retinal ganglion cell count in glaucoma suspects. Doc Ophthalmol 2022;145(1):11–25. DOI: 10.1007/s10633-022-09869-9
  34. Orshan D, Tirsi A, Sheha H, et al. Structure-function models for estimating retinal ganglion cell count using steady-state pattern electroretinography and optical coherence tomography in glaucoma suspects and preperimetric glaucoma: an electrophysiological pilot study. Doc Ophthalmol 2022;145(3):221–235. DOI: 10.1007/s10633-022-09900-z
  35. Tirsi A, Wong A, Zhu D, et al. Pattern electroretinogram parameters and their associations with optical coherence tomography in glaucoma suspects. J Curr Glaucoma Pract 2022;16(2):96–104. DOI: 10.5005/jp-journals-10078-1365
  36. Gandolfi SA, Cimino L, Sangermani C, et al. Improvement of spatial contrast sensitivity threshold after surgical reduction of intraocular pressure in unilateral high-tension glaucoma. Invest Ophthalmol Vis Sci 2005;46(1):197–201. DOI: 10.1167/iovs.04-0199
  37. Sehi M, Pinzon-Plazas M, Feuer WJ, et al. Relationship between pattern electroretinogram, standard automated perimetry, and optic nerve structural assessments. J Glaucoma 2009;18(8):608–617. DOI: 10.1097/IJG.0b013e31819afb5c
  38. Bowd C, Vizzeri G, Tafreshi A, et al. Diagnostic accuracy of pattern electroretinogram optimized for glaucoma detection. Ophthalmology 2009;116(3):437–443. DOI: 10.1016/j.ophtha.2008.10.026
  39. Fredette MJ, Anderson DR, Porciatti V, et al. Reproducibility of pattern electroretinogram in glaucoma patients with a range of severity of disease with the new glaucoma paradigm. Ophthalmology 2008;115(6):957–963. DOI: 10.1016/j.ophtha.2007.08.023
  40. Holder GE, Brigell MG, Hawlina M, et al. ISCEV standard for clinical pattern electroretinography–2007 update. Doc Ophthalmol 2007;114(3):111–116. DOI: 10.1007/s10633-007-9053-1
  41. Jeon SJ, Park HL, Jung KI, et al. Relationship between pattern electroretinogram and optic disc morphology in glaucoma. PLoS One 2019;14(11):e0220992. DOI: 10.1371/journal.pone.0220992
  42. Liu M, Duggan J, Salt TE, et al. Dendritic changes in visual pathways in glaucoma and other neurodegenerative conditions. Exp Eye Res 2011;92(4):244–250. DOI: 10.1016/j.exer.2011.01.014
  43. Knight OJ, Chang RT, Feuer WJ, et al. Comparison of retinal nerve fiber layer measurements using time domain and spectral domain optical coherent tomography. Ophthalmology 2009;116(7):1271–1277. DOI: 10.1016/j.ophtha.2008.12.032
  44. Celebi AR, Mirza GE. Age-related change in retinal nerve fiber layer thickness measured with spectral domain optical coherence tomography. Invest Ophthalmol Vis Sci 2013;54(13):8095–8103. DOI: 10.1167/iovs.13-12634
  45. Wadhwani M, Bali SJ, Satyapal R, et al. Test-retest variability of retinal nerve fiber layer thickness and macular ganglion cell-inner plexiform layer thickness measurements using spectral-domain optical coherence tomography. J Glaucoma 2015;24(5):e109–115. DOI: 10.1097/IJG.0000000000000203
  46. Mwanza JC, Durbin MK, Budenz DL, et al. Profile and predictors of normal ganglion cell–inner plexiform layer thickness measured with frequency-domain optical coherence tomography. Invest Ophthalmol Vis Sci 2011;52(11):7872–7879. DOI: 10.1167/iovs.11-7896
  47. Porciatti V, Chou TH. Modeling retinal ganglion cell dysfunction in optic neuropathies. Cells 2021;10(6):1398. DOI: 10.3390/cells10061398
  48. Ahmad, SS. Glaucoma suspects: a practical approach. Taiwan J Ophthalmol 2018;8(2):74–81. DOI: 10.4103/tjo.tjo_106_17
  49. Shiga Y, Aizawa N, Tsuda S, et al. Preperimetric glaucoma prospective study (PPGPS): predicting visual field progression with basal optic nerve head blood flow in normotensive PPG eyes. Transl Vis Sci Technol 2018;7(1):11. DOI: 10.1167/tvst.7.1.11
  50. Kim SH, Jeoung JW, Park KH, et al. Correlation between retinal nerve fiber layer thickness and visual field sensitivity: diffuse atrophy imaging study. Ophthalmic Surg Lasers Imaging 2012;43(6 Suppl):S75–S82. DOI: 10.3928/15428877-20121001-01
  51. Kudrna JJ, Ferguson TJ, Swan RJ, et al. Short-term steady-state pattern electroretinography changes using a multi-pressure dial in ocular hypertensive, glaucoma suspect, and mild open-angle glaucoma patients: a randomized, controlled, prospective, pilot study. Ophthalmol Ther 2020;9(4):981–992. DOI: 10.1007/s40123-020-00302-5
  52. Ventura LM, Porciatti V, Ishida K, et al. Pattern electroretinogram abnormality and glaucoma. Ophthalmology 2005;112(1):10–19. DOI: 10.1016/j.ophtha.2004.07.018
  53. Porciatti V, Ventura LM. Physiologic significance of steady-state pattern electroretinogram losses in glaucoma: clues from simulation of abnormalities in normal subjects. J Glaucoma 2009;18(7):535–542. DOI: 10.1097/IJG.0b013e318193c2e1
  54. Gordon PS, Kostic M, Monsalve PF, et al. Long-term PERG monitoring of untreated and treated glaucoma suspects. Doc Ophthalmol 2020;141(2):149–156. DOI: 10.1007/s10633-020-09760-5
  55. Triolo G, Toft-Nielsen J, Monsalve P, et al. Physiological and noise components of the PERG intrinsic variability. Invest Ophthalmol Vis Sci 2015;56(7):467.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.