Improvement of Pattern Electroretinogram Parameters Following Glaucoma Surgery 

Improvement of Pattern Electroretinogram Parameters Following Glaucoma Surgery | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Improvement of Pattern Electroretinogram Parameters Following Glaucoma Surgery Emmanuel Bettach, Leandro Oliverio, Kaweh Mansouri, André Mermoud This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8273114/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 9 You are reading this latest preprint version Abstract Purpose To assess the dynamics of Pattern Electroretinogram (PERG) parameters following glaucoma surgery in individuals with glaucomatous optic neuropathy. Methods The is a single center retrospective study. Preoperative PERG were conducted on moderate and advanced glaucoma patients scheduled for glaucoma surgery. Subsequently, the patients underwent an additional PERG a few months after the procedure. Comparative analysis focused on the PERG parameters (Mag, MagD and MagD/Mag ratio) before and after the glaucoma surgery in eyes achieving successful intraocular pressure (IOP) reduction post-operatively. Results The study enrolled 27 eyes from 24 consecutive patients who underwent successful glaucoma surgery between January 2021 and December 2023, each with both pre and post-operative PERG assessments. Postoperatively, there was a significant improvement of all the PERG parameters (0.94 ± 0.3 to 1.29 ± 0.3 µV, 0.54 ± 0.3 to 0.81 ± 0.41 µV, 0.54 ± 0.19 to 0.67 ± 0.26 for Mag, MagD and MagD/Mag ratio respectively, p < 0.01). Three patients who had no IOP reduction postoperatively showed no improvement of all PERG parameters following the surgery. Conclusions Glaucoma surgery, leading to effective IOP reduction, may demonstrate a positive impact on the functional activity of the retinal ganglion cells, as evidenced by the enhancement in PERG parameters post-operatively. Glaucoma Pattern electroretinogram Glaucoma surgery IOP Retinal Ganglion Cells Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Glaucoma is an optic neuropathy characterized by varying rates of progressive loss of retinal ganglion cells (RGCs).[ 1 ] The primary objective of glaucoma surgery is to decrease intraocular pressure (IOP) toward a target level to preserve visual function and prevent further loss of optic nerve axons.[ 2 ] It has been suggested that retinal ganglion cell (RGC) dysfunction occurs prior to their death, a condition that could be theoretically reversible by IOP reduction through glaucoma surgery.[ 3 ] The pattern electroretinogram (PERG) is a non-invasive method designed to assess the function of RGCs by measuring retinal response to a contrast reversing pattern.[ 4 ] Previous studies have demonstrated a significant reduction in pattern ERG amplitude in eyes with angle glaucoma compared to healthy eyes.[ 4 , 5 ] PERG abnormalities detected in eyes with ocular hypertension (OHT) or glaucoma suspects can indicate early functional damage, even when RNFL thickness and visual fields appear normal.[ 6 ] It has been shown that the PERG identified glaucoma patients 4 years before any changes in the visual field were detected.[ 7 ] Another study a found a significant correlation between PERG parameters and optic nerve rim area loss after adjusting for disc area in pre-perimetric glaucoma.[ 8 ] Gillmann et. al[ 9 ] showed good repeatability and the reproducibility of the Diopsys PERG parameters in healthy subjects at high contrast. The purpose of this study was to assess the dynamics of PERG parameters following glaucoma surgery in individuals with glaucomatous optic neuropathy. Methods Study population This retrospective observational clinical study was conducted at a single tertiary glaucoma center in Switzerland. This study was approved by the Swiss Ethics Committee on research involving humans (Vaud Canton, Switzerland) and followed the tenets of the Declaration of Helsinki. Informed consent was obtained from the enrolled patients. Medical records of consecutive patients with moderate to advanced glaucoma referred for preoperative evaluation for glaucoma surgery between January 2021 and December 2023 were reviewed. Patients who underwent a preoperative PERG (up to 6 months prior to surgery ) and subsequently an additional PERG after the surgical procedure (within 6 months - 12 months) were enrolled in the study. Patients younger than 18 years, those with best corrected visual acuity (BCVA) less than 0.5, less than 20% IOP reduction or IOP > 18 mmHg post-operatively, any ocular conditions affecting significantly the vision (e.g., corneal opacity, uveitis, macular pathology, non-glaucomatous optic neuropathy) were excluded. All subjects had a BCVA test and a comprehensive slit-lamp examination, including IOP measurement with Goldmann applanation tonometry. Additionally, visual field testing using the Octopus 900 Perimeter (Haag-Streit, Koeniz, Switzerland) and optical coherence tomography (OCT) with the Spectralis device (Heidelberg Engineering, Germany) were conducted. The treating ophthalmologist determined a target IOP for each eye, considering the baseline IOP and glaucoma severity. PERG metrics The PERG examination was conducted in a dark room with the Diopsys ARGOS (Diopsys Inc., Pine Brook, NJ). Hypoallergenic Silver/Silver Chloride ink skin sensors (Diopsys proprietary Skin Sensor) were placed on the lower eyelids of both eyes near the lid margins and the ground sensor (Diopsys EEG electrode) was attached to the central forehead area. All subjects wore their optimal prescription for a reading distance of 24 inches and were seated facing the stimulus monitor in a dark room. The pattern reversal stimulus comprised black-and-white square-wave horizontal gratings (24 degrees, 100% contrast, and 102.4 candelas/m² mean luminance), at a rate of 15 reversals per second for a duration of 25 seconds. The fixation target was a red cross measuring 50.79 arc minutes centered on the stimulus field. All recorded signals were processed through band pass filtration (0.5 to 100 Hz), amplification (gain = 20,000), and averaging (at least 150 frames). The program automatically discarded recording segments that were affected by excessive blinks or large eye saccades. Only tests with good signal quality indicators were included in the study. The device report displays the following parameters under high and low contrast conditions: Magnitude (Mag) (μV), MagD (μV), MagD/ Mag ratio, SNR (dB) and the number of artifacts. According to the manufacturer, Mag represents the highest amplitude of the PERG signal from the visual stimulus.[9] MagD is the average amplitude of all recorded 200ms sections, indicating phase variability during the signal acquisition period. The more consistent and repeatable the magnitudes and phases are throughout the test, the closer the value of MagD will be to the measured Mag. The MagD/Mag ratio measures the repeatability of the phase response; a ratio of 1 indicates a perfectly consistent signal in both magnitude and phase.[10] Lower ratios suggest potential dysfunction. Perfect waves have three identical sinusoidal waves, while pathologic waves are irregular. An example of a normal PERG printout is shown in Figure 1. Statistical analysis Data on patients’ demographics and the following parameters were recorded: BCVA, IOP, visual field mean deviation (MD) and high contrast pattern-ERG parameters (Mag, MagD, and MagD/Mag ratio) before and after glaucoma surgery. Data were recorded in Microsoft 8 Excel (version 2023.2.1414) and statistical analysis was performed using Prism 8.0 (GraphPad Software, San Diego, CA). The statistical difference of the clinical and PERG parameters before and after surgery was assessed using the Wilcoxon signed-rank test. All the tests were two-tailed, with a statistically significant P-value set at < 0.05. The comparison between pre- and post-operative data was based on a paired t-test. Results In total, clinical records of 49 eyes from 42 consecutive patients with a PERG test before and after glaucoma surgery were reviewed during the study period. Of these, 22 eyes from 21 patients were excluded due to high myopia (5), maculopathy (6), no significant IOP reduction post-operatively (e.g. < 20% reduction) (3), OHT with no glaucomatous optic neuropathy (4) and poor PERG quality (4). Twenty-seven eyes of 24 patients met the inclusion criteria and constituted the current study group (Fig. 2 ). The baseline demographic and clinical characteristics of the study population are summarized in Table 1. Primary open-angle glaucoma (POAG) was the most common diagnosis with 13 eyes (48.1%), followed by pseudo-exfoliative glaucoma (PEXG) with 6 eyes (22.2%), primary angle-closure glaucoma (PACG) with 5 eyes (18.5%), secondary angle-closure glaucoma with 2 eyes (7.4%) and 1 eye with traumatic glaucoma (3.7%). The preoperative PERG was conducted on average 4.6 ± 3.1 weeks before the surgical procedures. The glaucoma surgeries performed were 23 (85.2%) deep sclerectomies and 4 (14.8%) drainage tubes. Four procedures (15%) were combined with cataract surgery. The postoperative PERG was carried out on average 28.1 ± 6.4 weeks after surgeries. The mean IOP decreased significantly from 20.7 ± 4.7 mmHg at baseline to 11.1 ± 2.3 mmHg (-46.4%, p < 0.001) at 28.1 ± 6.4 weeks after glaucoma surgery, while mean BCVA was unchanged (0.93 pre- and post-operatively). All high contrast PERG parameters significantly increased postoperatively (0.94 ± 0.3 to 1.29 ± 0.3 µV, 0.54 ± 0.3 to 0.81 ± 0.41 µV, 0.54 ± 0.19 to 0.67 ± 0.26 for Mag, MagD and MagD/Mag ratio respectively, all p < 0.05) as shown in table 2. An example of the PERG printout before and after successful glaucoma surgery showing an improvement of all the parameters is displayed in Fig. 3 . Three patients who had no IOP reduction postoperatively (17.3 ± 1.5 mmHg at baseline to 18.6 ± 1.5 mmHg postoperatively) also showed no improvement of all PERG parameters following the surgery (0.83 ± 0.24 to 0.73 ± 0.11 µV, 0.52 ± 0.29 to 0.36 ± 0.24 µV, 0.55 ± 0.25 to 0.48 ± 0.3 for Mag, MagD and MagD/Mag ratio respectively). An example of a PERG of one of these eyes is shown in Fig. 4 . Discussion The primary goal of glaucoma surgery is to consistently lower IOP to prevent further damage to the optic nerve.[11] Clinical practice generally assumes that vision loss in glaucoma is irreversible. However, there is some evidence indicating that reversible functional changes may occur prior to cell death and permanent vision loss.[12] PERG is an electrophysiological test that primarily assesses the function of the RGC layer, making it valuable for evaluating eyes with glaucoma.[4] The association between PERG abnormalities and glaucoma risk factors has been demonstrated, indicating PERG's potential predictive value for the onset and progression of the disease.[13] In the current study, we observed an improvement in all the measurable PERG parameters and the waves pattern and regularity approximately 7 months following successful glaucoma surgery in eyes that achieved the target IOP, suggesting a possible enhancement of the RGC function post-operatively. In addition, none of the PERG parameters improved in the 3 eyes with no IOP reduction postoperatively. These results may support the theory of reversible functional damage to RGCs in glaucoma, suggesting that reducing IOP could potentially improve their function. Furthermore, the PERG may have clinical value in monitoring glaucoma patients and providing objective information on RGC function, allowing treatment adaptation accordingly. A previous study showed that the progressive decline in RGC function in early glaucoma can potentially be interrupted by lowering IOP, as indicated by PERG measurements.[14] Another study found that in glaucomatous eyes with early visual field impairment, lowering IOP with medical treatment can lead to at least partial restoration of PERG-derived retinal ganglion cell function.[15] Sehi et al.[16] conducted a study to prospectively assess the impact of surgical IOP reduction on RGC function using PERG optimized for glaucoma screening (PERGLA), showing significant improvement in PERGLA amplitude 3 months post-operatively, indicating a possible reversal of RGC dysfunction. Several studies have previously documented improvements in the appearance of glaucomatous optic nerves in adults following a reduction in IOP.[17–19] However, improvement of VF after glaucoma treatment is controversial with important variations between studies. Wright et al.[20] found an enhancement of central and peripheral VF sensitivity in 30 eyes after 3 months following glaucoma surgery. A previous study observed an improvement in the visual field after glaucoma treatment, correlating with the degree of IOP reduction.[21] In contrast, other studies found a reduction of VF progression after glaucoma surgery but no improvement.[22,23] The discrepancies between these results can be attributed to the challenges in assessing visual field improvement, as there is uncertainty about the appropriate index for analysis and the test's subjective component. Our study has some limitations other than its retrospective nature. First, postoperative PERG data were missing for some eyes and therefore could not be included in the analysis. Second, an insufficient number of patients without postoperative IOP reduction could be enrolled to constitute a control group. Third, 4 glaucoma surgeries were combined with phacoemulsification, which could potentially influence the PERG results. However, the cataracts in these eyes were not advanced, and the preoperative visual acuity was better than 0.7. Therefore, it is reasonable to assume that the impact of cataracts on the PERG results was negligible. In conclusion, our study demonstrated significant improvement across all PERG parameters several months after glaucoma surgery with successful IOP reduction. These findings support the theory of partially reversible functional damage to RGCs in glaucoma and highlight the potential for functional enhancement with effective IOP management. Electrophysiologic follow-up in the glaucoma patients can provide valuable elements for determining the target IOP, for the prevention of further glaucoma-related damage and promoting optimal RGC function recovery. Further studies are needed to determine whether there is a correlation between the positive evolution of PERG following consistent IOP reduction and potential changes in the visual field. What was known before RGC dysfunction in glaucoma occur prior to their death. PERG is a non-invasive method designed to assess the function of RGCs. The goal of glaucoma surgery is to decrease IOP to prevent further loss of optic nerve axons. What this study adds The PERG parameters improved following successful glaucoma surgery. Consistent and effective IOP reduction in eyes with glaucoma may possibly enhance the function of RGC. The PERG may be a useful tool to follow glaucoma progression and determine the target IOP. Declarations Author Contribution All authors reviewed the manuscript Acknowledgement Acknowledgements: Daniela Gallo Castro for the coordination References Vrabec JP, Levin LA. The neurobiology of cell death in glaucoma. Eye . 2007;21:S11–4. doi: 10.1038/sj.eye.6702880 Weinreb RN, Aung T, Medeiros FA. The Pathophysiology and Treatment of Glaucoma. JAMA . 2014;311:1901. doi: 10.1001/jama.2014.3192 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. doi: 10.1016/j.preteyeres.2018.04.001 Tafreshi A, Racette L, Weinreb RN, et al. Pattern Electroretinogram and Psychophysical Tests of Visual Function for Discriminating Between Healthy and Glaucoma Eyes. Am J Ophthalmol . 2010;149:488–95. doi: 10.1016/j.ajo.2009.09.027 Nesher R, Trick GL. The pattern electroretinogram in retinal and optic nerve disease. Documenta Ophthalmologica . 1991;77:225–35. doi: 10.1007/BF00161370 Forte R, Ambrosio L, Bonavolontà P, et al. Pattern electroretinogram optimized for glaucoma screening (PERGLA) and retinal nerve fiber thickness in suspected glaucoma and ocular hypertension. Documenta Ophthalmologica . 2010;120:187–92. doi: 10.1007/s10633-009-9211-8 Bode SFN, Jehle T, Bach M. Pattern Electroretinogram in Glaucoma Suspects: New Findings from a Longitudinal Study. Investigative Opthalmology & Visual Science . 2011;52:4300. doi: 10.1167/iovs.10-6381 Tirsi A, Gliagias V, Moehringer J, et al. Pattern Electroretinogram Parameters Are Associated with Optic Nerve Morphology in Preperimetric Glaucoma after Adjusting for Disc Area. J Ophthalmol . 2021;2021:1–12. doi: 10.1155/2021/8025337 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;27:1079–85. doi: 10.1097/IJG.0000000000001103 Resende AF, Sanvicente CT, Eshraghi H, et al. Test–retest repeatability of the pattern electroretinogram and flicker electroretinogram. Documenta Ophthalmologica . 2019;139:185–95. doi: 10.1007/s10633-019-09707-5 Lim R. The surgical management of glaucoma: A review. Clin Exp Ophthalmol . 2022;50:213–31. doi: 10.1111/ceo.14028 Ahmed OM, Waisbourd M, Spaeth GL, et al. Improvement in structure and visual function in patients with glaucoma: the possible key to better treatment? Surv Ophthalmol . 2021;66:644–52. doi: 10.1016/j.survophthal.2020.12.004 VENTURA L, PORCIATTI V, ISHIDA K, et al. Pattern electroretinogram abnormality and glaucoma. Ophthalmology . 2005;112:10–9. doi: 10.1016/j.ophtha.2004.07.018 Ventura LM, Feuer WJ, Porciatti V. Progressive Loss of Retinal Ganglion Cell Function Is Hindered with IOP-Lowering Treatment in Early Glaucoma. Investigative Opthalmology & Visual Science . 2012;53:659. doi: 10.1167/iovs.11-8525 VENTURA L, PORCIATTI V. Restoration of retinal ganglion cell function in early glaucoma after intraocular pressure reductionA pilot study. Ophthalmology . 2005;112:20–7. doi: 10.1016/j.ophtha.2004.09.002 Sehi M, Grewal DS, Goodkin ML, et al. Reversal of Retinal Ganglion Cell Dysfunction after Surgical Reduction of Intraocular Pressure. Ophthalmology . 2010;117:2329–36. doi: 10.1016/j.ophtha.2010.08.049 Schwartz B, Takamoto T, Nagin P. Measurements of Reversibility of Optic Disc Cupping and Pallor in Ocular Hypertension and Glaucoma. Ophthalmology . 1985;92:1396–407. doi: 10.1016/S0161-6420(85)33850-2 Pederson JE, Herschler J. Reversal of Glaucomatous Cupping in Adults. Archives of Ophthalmology . 1982;100:426–31. doi: 10.1001/archopht.1982.01030030428008 Quigley HA. Results, with Trabeculotomy and Study of Reversible Cupping. Ophthalmology . 1982;89:219–26. doi: 10.1016/S0161-6420(82)34803-4 Wright TM, Goharian I, Gardiner SK, et al. Short-Term Enhancement of Visual Field Sensitivity in Glaucomatous Eyes Following Surgical Intraocular Pressure Reduction. Am J Ophthalmol . 2015;159:378-385.e1. doi: 10.1016/j.ajo.2014.11.012 Katz LJ, Spaeth GL, Cantor LB, et al. Reversible Optic Disk Cupping and Visual Field Improvement in Adults With Glaucoma. Am J Ophthalmol . 1989;107:485–92. doi: 10.1016/0002-9394(89)90492-3 Yamazaki Y, Hayamizu. Effect of trabeculectomy on retrobulbar circulation and visual field progression in patients with primary open-angle glaucoma. Clinical Ophthalmology . 2012;1539. doi: 10.2147/OPTH.S36331 Yuen D, Buys YM. Disc photography and heidelberg retinal tomography documentation of reversal of cupping following trabeculectomy. Graefe’s Archive for Clinical and Experimental Ophthalmology . 2010;248:1671–3. doi: 10.1007/s00417-010-1422-x Tables Table 1. Demographic characteristics of the study population Characterisic Value Number of eyes (patients) 27 (24) Age (y), mean ± SD (median) 68.8 ± 13.1 (74.5) Female, n (%) 17 (70.8) Phakic, n (%) 14 (51.8) Laterality OD, n (%) 13 (48.1) Baseline VF MD (dB) mean ± SD (median) 8.5 ± 6.3 (7) POAG n (%) PEXG n (%) PACG n (%) SACG n (%) Traumatic glaucoma n (%) 13 (48.1) 6 (22.2) 5 (18.5) 2 (7.4) 1 (3.7) VF = Visual field; MD = Mean deviation POAG = Primary open angle glaucoma; PEXG = Pseudoexfoliative glaucoma; PACG = Primary angle closure glaucoma; SACG = Secondary angle closure glaucoma Table 2. Change of clinical data and PERG parameters before and after glaucoma surgery Variable Before After Difference P-value BCVA (decimal) 0.93 ± 0.14 (1) 0.93 ± 0.07 (1) 0 0.97 IOP (mmHg) 20.7 ± 4.7 11.1 ± 2.3 -9.5 ± 4.6 <0.0001 Mag (μV) 0.94 ± 0.3 (0.91) 1.29 ± 0.3 (1.28) 0.34 ± 0.3 <0.0001 MagD (μV) 0.54 ± 0.3 (0.48) 0.81 ± 0.41 (0.76) 0.26 ± 0.32 <0.05 MagD/Mag ratio 0.54 ± 0.19 (0.57) 0.67 ± 0.26 (0.72) 0.15 ± 0.27 <0.05 BCVA = Best corrected visual acuity; IOP = Intraocular pressure Values are given as mean ± SD (median) Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 16 Dec, 2025 Reviews received at journal 16 Dec, 2025 Reviews received at journal 12 Dec, 2025 Reviewers agreed at journal 12 Dec, 2025 Reviewers agreed at journal 07 Dec, 2025 Reviewers invited by journal 06 Dec, 2025 Editor assigned by journal 04 Dec, 2025 Submission checks completed at journal 04 Dec, 2025 First submitted to journal 03 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8273114","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":557728511,"identity":"7f37c31f-6251-48d8-965a-57663f4263e8","order_by":0,"name":"Emmanuel Bettach","email":"","orcid":"","institution":"Montchoisi Clinic","correspondingAuthor":false,"prefix":"","firstName":"Emmanuel","middleName":"","lastName":"Bettach","suffix":""},{"id":557728512,"identity":"06838d64-81bc-425d-b3e2-54aef596cf4a","order_by":1,"name":"Leandro Oliverio","email":"","orcid":"","institution":"Montchoisi 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13:20:25","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":70369,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8273114/v1/b1f6bdb6da92903ed91a2d5a.html"},{"id":98428779,"identity":"f239ad3a-a824-447d-8270-4c1943b29be6","added_by":"auto","created_at":"2025-12-17 16:42:23","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":621905,"visible":true,"origin":"","legend":"\u003cp\u003eRecording report of PERG of both eyes in a healthy subject: The quality marker confirms normal quality of the recording (star). The vertical axis of the PERG graph indicates the measure and amplitude in microvolts. The horizontal axis displays the time measured in milliseconds with a range of 0 to 200 ms. Normal waveforms with regular, sinusoidal and similar waves recorded under high (100% - upper arrow) and low contrast (85% - lower arrow) conditions over the 200 ms section. Magnitude values are displayed in the data table under high (100%) and low (85%) contrast, normal values are presented with a green background (arrowhead)\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-8273114/v1/7e41acf3e44f30b4a9745c7b.png"},{"id":98428894,"identity":"26ed0e11-b058-40f2-b29a-aeb783335f18","added_by":"auto","created_at":"2025-12-17 16:42:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":325327,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of the study results\u003c/p\u003e","description":"","filename":"Fig2.png","url":"https://assets-eu.researchsquare.com/files/rs-8273114/v1/4cc98ec6417fef21f1cbe3a1.png"},{"id":98072843,"identity":"3778e0ab-5c8c-47ab-8948-5a8748e33161","added_by":"auto","created_at":"2025-12-12 13:20:25","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":820525,"visible":true,"origin":"","legend":"\u003cp\u003eRecording report of PERG of the left eye of a patient before and after successful glaucoma surgery: A: PERG before the glaucoma surgery, irregular waves with low magnitude values (borderline values displayed in yellow and low values in red in the table)\u003c/p\u003e\n\u003cp\u003eB: PERG 6 month after glaucoma surgery with target IOP achievement, significant improvement of waves regularity and sinusoidality and magnitude values displayed in the table.\u003c/p\u003e","description":"","filename":"Fig3.png","url":"https://assets-eu.researchsquare.com/files/rs-8273114/v1/34149ae030fcee98eb656a17.png"},{"id":98429551,"identity":"7b8e788c-6352-4d9b-86c2-9d3ff789cd78","added_by":"auto","created_at":"2025-12-17 16:43:41","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":681178,"visible":true,"origin":"","legend":"\u003cp\u003eRecording report of PERG of the left eye of a patient before and after unsuccessful glaucoma surgery. A: PERG before the glaucoma surgery, irregular waves with low magnitude values displayed in the table.\u003c/p\u003e\n\u003cp\u003eB: PERG a year after unsuccessful glaucoma surgery with no target IOP achievement, no improvement and some worsening in the waves pattern and magnitude values in the table.\u003c/p\u003e","description":"","filename":"Fig4.png","url":"https://assets-eu.researchsquare.com/files/rs-8273114/v1/792126be4bafe4a349bd746f.png"},{"id":98623669,"identity":"8e43a4f5-fff3-4d98-9285-909d15bb3ab1","added_by":"auto","created_at":"2025-12-19 17:07:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2350530,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8273114/v1/ae993662-9558-42d0-a69e-eaa6ee73ca3b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Improvement of Pattern Electroretinogram Parameters Following Glaucoma Surgery ","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGlaucoma is an optic neuropathy characterized by varying rates of progressive loss of retinal ganglion cells (RGCs).[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The primary objective of glaucoma surgery is to decrease intraocular pressure (IOP) toward a target level to preserve visual function and prevent further loss of optic nerve axons.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] It has been suggested that retinal ganglion cell (RGC) dysfunction occurs prior to their death, a condition that could be theoretically reversible by IOP reduction through glaucoma surgery.[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe pattern electroretinogram (PERG) is a non-invasive method designed to assess the function of RGCs by measuring retinal response to a contrast reversing pattern.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Previous studies have demonstrated a significant reduction in pattern ERG amplitude in eyes with angle glaucoma compared to healthy eyes.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] PERG abnormalities detected in eyes with ocular hypertension (OHT) or glaucoma suspects can indicate early functional damage, even when RNFL thickness and visual fields appear normal.[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] It has been shown that the PERG identified glaucoma patients 4 years before any changes in the visual field were detected.[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Another study a found a significant correlation between PERG parameters and optic nerve rim area loss after adjusting for disc area in pre-perimetric glaucoma.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Gillmann et. al[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] showed good repeatability and the reproducibility of the Diopsys PERG parameters in healthy subjects at high contrast.\u003c/p\u003e\u003cp\u003eThe purpose of this study was to assess the dynamics of PERG parameters following glaucoma surgery in individuals with glaucomatous optic neuropathy.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eStudy population\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective observational clinical study was conducted at a single tertiary glaucoma center in Switzerland. This study was approved by the Swiss Ethics Committee on research involving humans (Vaud Canton, Switzerland) and followed the tenets of the Declaration of Helsinki. Informed consent was obtained from the enrolled patients. Medical records of consecutive patients with moderate to advanced glaucoma referred for preoperative evaluation for glaucoma surgery between January 2021 and December 2023 were reviewed. Patients who underwent a preoperative PERG (up to 6 months prior to surgery\u003cem\u003e)\u0026nbsp;\u003c/em\u003eand subsequently an additional PERG after the surgical procedure (within 6 months \u003cem\u003e-\u003c/em\u003e12 months) were enrolled in the study. Patients younger than 18 years, those with best corrected visual acuity (BCVA) less than 0.5, less than 20% IOP reduction or IOP \u0026gt; 18 mmHg post-operatively, any ocular conditions affecting significantly the vision (e.g., corneal opacity, uveitis, macular pathology, non-glaucomatous optic neuropathy) were excluded. All subjects had a BCVA test and a comprehensive slit-lamp examination, including IOP measurement with Goldmann applanation tonometry. Additionally, visual field testing using the Octopus 900 Perimeter (Haag-Streit, Koeniz, Switzerland) and optical coherence tomography (OCT) with the Spectralis device (Heidelberg Engineering, Germany) were conducted. The treating ophthalmologist determined a target IOP for each eye, considering the baseline IOP and glaucoma severity.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePERG metrics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe PERG examination was conducted in a dark room with the Diopsys ARGOS (Diopsys Inc., Pine Brook, NJ). Hypoallergenic Silver/Silver Chloride ink skin sensors (Diopsys proprietary Skin Sensor) were placed on the lower eyelids of both eyes near the lid margins and the ground sensor (Diopsys EEG electrode) was attached to the central forehead area. All subjects wore their optimal prescription for a reading distance of 24 inches and were seated facing the stimulus monitor in a dark room. The pattern reversal stimulus comprised black-and-white square-wave horizontal gratings (24 degrees, 100% contrast, and 102.4 candelas/m\u0026sup2; mean luminance), at a rate of 15 reversals per second for a duration of 25 seconds. The fixation target was a red cross measuring 50.79 arc minutes centered on the stimulus field. All recorded signals were processed through band pass filtration (0.5 to 100 Hz), amplification (gain = 20,000), and averaging (at least 150 frames). The program automatically discarded recording segments that were affected by excessive blinks or large eye saccades. Only tests with good signal quality indicators were included in the study. The device report displays the following parameters under high and low contrast conditions: Magnitude (Mag) (\u0026mu;V), MagD (\u0026mu;V), MagD/ Mag ratio, SNR (dB) and the number of artifacts. According to the manufacturer, Mag represents the highest amplitude of the PERG signal from the visual stimulus.[9] MagD is the average amplitude of all recorded 200ms sections, indicating phase variability during the signal acquisition period. The more consistent and repeatable the magnitudes and phases are throughout the test, the closer the value of MagD will be to the measured Mag. The MagD/Mag ratio measures the repeatability of the phase response; a ratio of 1 indicates a perfectly consistent signal in both magnitude and phase.[10] Lower ratios suggest potential dysfunction. Perfect waves have three identical sinusoidal waves, while pathologic waves are irregular. An example of a normal PERG printout is shown in Figure 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData on patients\u0026rsquo; demographics and the following parameters were recorded: BCVA, IOP, visual field mean deviation (MD) and high contrast pattern-ERG parameters (Mag, MagD, and MagD/Mag ratio) before and after glaucoma surgery. Data were recorded in Microsoft 8 Excel (version 2023.2.1414) and statistical analysis was performed using Prism 8.0 (GraphPad Software, San Diego, CA). The statistical difference of the clinical and PERG parameters before and after surgery was assessed using the Wilcoxon signed-rank test. All the tests were two-tailed, with a statistically significant P-value set at \u0026lt; 0.05. The comparison between pre- and post-operative data was based on a paired t-test.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn total, clinical records of 49 eyes from 42 consecutive patients with a PERG test before and after glaucoma surgery were reviewed during the study period. Of these, 22 eyes from 21 patients were excluded due to high myopia (5), maculopathy (6), no significant IOP reduction post-operatively (e.g. \u0026lt; 20% reduction) (3), OHT with no glaucomatous optic neuropathy (4) and poor PERG quality (4). Twenty-seven eyes of 24 patients met the inclusion criteria and constituted the current study group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The baseline demographic and clinical characteristics of the study population are summarized in Table\u0026nbsp;1. Primary open-angle glaucoma (POAG) was the most common diagnosis with 13 eyes (48.1%), followed by pseudo-exfoliative glaucoma (PEXG) with 6 eyes (22.2%), primary angle-closure glaucoma (PACG) with 5 eyes (18.5%), secondary angle-closure glaucoma with 2 eyes (7.4%) and 1 eye with traumatic glaucoma (3.7%).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe preoperative PERG was conducted on average 4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1 weeks before the surgical procedures. The glaucoma surgeries performed were 23 (85.2%) deep sclerectomies and 4 (14.8%) drainage tubes. Four procedures (15%) were combined with cataract surgery. The postoperative PERG was carried out on average 28.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 weeks after surgeries. The mean IOP decreased significantly from 20.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.7 mmHg at baseline to 11.1\u0026thinsp;\u0026plusmn;\u0026thinsp;2.3 mmHg (-46.4%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001) at 28.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 weeks after glaucoma surgery, while mean BCVA was unchanged (0.93 pre- and post-operatively). All high contrast PERG parameters significantly increased postoperatively (0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 to 1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 \u0026micro;V, 0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 to 0.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41 \u0026micro;V, 0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19 to 0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26 for Mag, MagD and MagD/Mag ratio respectively, all p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) as shown in table 2. An example of the PERG printout before and after successful glaucoma surgery showing an improvement of all the parameters is displayed in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThree patients who had no IOP reduction postoperatively (17.3\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 mmHg at baseline to 18.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5 mmHg postoperatively) also showed no improvement of all PERG parameters following the surgery (0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24 to 0.73\u0026thinsp;\u0026plusmn;\u0026thinsp;0.11 \u0026micro;V, 0.52\u0026thinsp;\u0026plusmn;\u0026thinsp;0.29 to 0.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.24 \u0026micro;V, 0.55\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25 to 0.48\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 for Mag, MagD and MagD/Mag ratio respectively). An example of a PERG of one of these eyes is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe primary goal of glaucoma surgery is to consistently lower IOP to prevent further damage to the optic nerve.[11]\u0026nbsp;Clinical practice generally assumes that vision loss in glaucoma is irreversible. However, there is some evidence indicating that reversible functional changes may occur prior to cell death and permanent vision loss.[12]\u0026nbsp;PERG is an electrophysiological test that primarily assesses the function of the RGC layer, making it valuable for evaluating eyes with glaucoma.[4]\u0026nbsp;The association between PERG abnormalities and glaucoma risk factors has been demonstrated, indicating PERG\u0026apos;s potential predictive value for the onset and progression of the disease.[13]\u003c/p\u003e\n\u003cp\u003eIn the current study, we observed an improvement in all the measurable PERG parameters and the waves pattern and regularity approximately 7 months following successful glaucoma surgery in eyes that achieved the target IOP, suggesting a possible enhancement of the RGC function post-operatively. In addition, none of the PERG parameters improved in the 3 eyes with no IOP reduction postoperatively.\u0026nbsp;These results may support the theory of reversible functional damage to RGCs in glaucoma, suggesting that reducing IOP could potentially improve their function.\u0026nbsp;Furthermore, the PERG may have clinical value in monitoring glaucoma patients and providing objective information on RGC function, allowing treatment adaptation accordingly.\u0026nbsp;A previous study showed that the progressive decline in RGC function in early glaucoma can potentially be interrupted by lowering IOP, as indicated by PERG measurements.[14]\u0026nbsp;Another study found that\u0026nbsp;in glaucomatous eyes with early visual field impairment, lowering IOP with medical treatment can lead to at least partial restoration of\u0026nbsp;PERG-derived\u0026nbsp;retinal ganglion cell function.[15]\u003csup\u003e\u0026nbsp;\u003c/sup\u003eSehi et al.[16] conducted a study to prospectively assess the impact of surgical IOP reduction on RGC function using PERG optimized for glaucoma screening (PERGLA), showing significant improvement in PERGLA amplitude 3 months post-operatively, indicating a possible reversal of RGC dysfunction.\u003c/p\u003e\n\u003cp\u003eSeveral studies have previously documented improvements in the appearance of glaucomatous optic nerves in adults following a reduction in IOP.[17\u0026ndash;19] However,\u0026nbsp;improvement of VF after glaucoma treatment is controversial with important variations between studies. Wright et al.[20] found an enhancement of central and peripheral VF sensitivity in 30 eyes after 3 months following glaucoma surgery.\u0026nbsp;A previous study observed an improvement in the visual field after glaucoma treatment, correlating with the degree of IOP reduction.[21]\u0026nbsp;In contrast, other studies found a reduction of VF progression after glaucoma surgery but no improvement.[22,23]\u003csup\u003e\u0026nbsp;\u003c/sup\u003eThe discrepancies between these results can be attributed to the challenges in assessing visual field improvement, as there is uncertainty about the appropriate index for analysis and the test\u0026apos;s subjective component.\u003c/p\u003e\n\u003cp\u003eOur study has some limitations other than its retrospective nature. First, postoperative PERG data were missing for some eyes and therefore could not be included in the analysis. Second,\u0026nbsp;an insufficient number of patients without postoperative IOP reduction could be enrolled to constitute a control group. Third, 4 glaucoma surgeries were combined with phacoemulsification, which could potentially influence the PERG results. However, the cataracts in these eyes were not advanced, and the preoperative visual acuity was better than 0.7. Therefore, it is reasonable to assume that the impact of cataracts on the PERG results was negligible.\u003c/p\u003e\n\u003cp\u003eIn conclusion, our study demonstrated significant improvement across all PERG parameters several months after glaucoma surgery with successful IOP reduction. These findings support the theory of partially reversible functional damage to RGCs in glaucoma and highlight the potential for functional enhancement with effective IOP management. Electrophysiologic follow-up in the glaucoma patients can provide valuable elements for determining the target IOP, for the prevention of further glaucoma-related damage and promoting optimal RGC function recovery. Further studies are needed to determine whether there is a correlation between the positive evolution of PERG following consistent IOP reduction and potential changes in the visual field.\u003c/p\u003e"},{"header":"What was known before","content":"\u003cul\u003e\n \u003cli\u003eRGC dysfunction in glaucoma occur prior to their death.\u003c/li\u003e\n \u003cli\u003ePERG is a non-invasive method designed to assess the function of RGCs.\u003c/li\u003e\n \u003cli\u003eThe goal of glaucoma surgery is to decrease IOP to prevent further loss of optic nerve axons.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eWhat this study adds\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThe PERG parameters improved following successful glaucoma surgery.\u003c/li\u003e\n \u003cli\u003eConsistent and effective IOP reduction in eyes with glaucoma may possibly enhance the function of RGC.\u003c/li\u003e\n \u003cli\u003eThe PERG may be a useful tool to follow glaucoma progression and determine the target IOP.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eAll authors reviewed the manuscript\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eAcknowledgements: Daniela Gallo Castro for the coordination\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVrabec JP, Levin LA. The neurobiology of cell death in glaucoma. \u003cem\u003eEye\u003c/em\u003e. 2007;21:S11\u0026ndash;4. doi: 10.1038/sj.eye.6702880\u003c/li\u003e\n\u003cli\u003eWeinreb RN, Aung T, Medeiros FA. The Pathophysiology and Treatment of Glaucoma. \u003cem\u003eJAMA\u003c/em\u003e. 2014;311:1901. doi: 10.1001/jama.2014.3192\u003c/li\u003e\n\u003cli\u003eFry LE, Fahy E, Chrysostomou V, \u003cem\u003eet al.\u003c/em\u003e The coma in glaucoma: Retinal ganglion cell dysfunction and recovery. \u003cem\u003eProg Retin Eye Res\u003c/em\u003e. 2018;65:77\u0026ndash;92. doi: 10.1016/j.preteyeres.2018.04.001\u003c/li\u003e\n\u003cli\u003eTafreshi A, Racette L, Weinreb RN, \u003cem\u003eet al.\u003c/em\u003e Pattern Electroretinogram and Psychophysical Tests of Visual Function for Discriminating Between Healthy and Glaucoma Eyes. \u003cem\u003eAm J Ophthalmol\u003c/em\u003e. 2010;149:488\u0026ndash;95. doi: 10.1016/j.ajo.2009.09.027\u003c/li\u003e\n\u003cli\u003eNesher R, Trick GL. The pattern electroretinogram in retinal and optic nerve disease. \u003cem\u003eDocumenta Ophthalmologica\u003c/em\u003e. 1991;77:225\u0026ndash;35. doi: 10.1007/BF00161370\u003c/li\u003e\n\u003cli\u003eForte R, Ambrosio L, Bonavolont\u0026agrave; P, \u003cem\u003eet al.\u003c/em\u003e Pattern electroretinogram optimized for glaucoma screening (PERGLA) and retinal nerve fiber thickness in suspected glaucoma and ocular hypertension. \u003cem\u003eDocumenta Ophthalmologica\u003c/em\u003e. 2010;120:187\u0026ndash;92. doi: 10.1007/s10633-009-9211-8\u003c/li\u003e\n\u003cli\u003eBode SFN, Jehle T, Bach M. Pattern Electroretinogram in Glaucoma Suspects: New Findings from a Longitudinal Study. \u003cem\u003eInvestigative Opthalmology \u0026amp; Visual Science\u003c/em\u003e. 2011;52:4300. doi: 10.1167/iovs.10-6381\u003c/li\u003e\n\u003cli\u003eTirsi A, Gliagias V, Moehringer J, \u003cem\u003eet al.\u003c/em\u003e Pattern Electroretinogram Parameters Are Associated with Optic Nerve Morphology in Preperimetric Glaucoma after Adjusting for Disc Area. \u003cem\u003eJ Ophthalmol\u003c/em\u003e. 2021;2021:1\u0026ndash;12. doi: 10.1155/2021/8025337\u003c/li\u003e\n\u003cli\u003eGillmann K, Mansouri K, Rao HL, \u003cem\u003eet al.\u003c/em\u003e A Prospective Evaluation of the Repeatability and Reliability of New Steady-state Pattern Electroretinogram Parameters. \u003cem\u003eJ Glaucoma\u003c/em\u003e. 2018;27:1079\u0026ndash;85. doi: 10.1097/IJG.0000000000001103\u003c/li\u003e\n\u003cli\u003eResende AF, Sanvicente CT, Eshraghi H, \u003cem\u003eet al.\u003c/em\u003e Test\u0026ndash;retest repeatability of the pattern electroretinogram and flicker electroretinogram. \u003cem\u003eDocumenta Ophthalmologica\u003c/em\u003e. 2019;139:185\u0026ndash;95. doi: 10.1007/s10633-019-09707-5\u003c/li\u003e\n\u003cli\u003eLim R. The surgical management of glaucoma: A review. \u003cem\u003eClin Exp Ophthalmol\u003c/em\u003e. 2022;50:213\u0026ndash;31. doi: 10.1111/ceo.14028\u003c/li\u003e\n\u003cli\u003eAhmed OM, Waisbourd M, Spaeth GL, \u003cem\u003eet al.\u003c/em\u003e Improvement in structure and visual function in patients with glaucoma: the possible key to better treatment? \u003cem\u003eSurv Ophthalmol\u003c/em\u003e. 2021;66:644\u0026ndash;52. doi: 10.1016/j.survophthal.2020.12.004\u003c/li\u003e\n\u003cli\u003eVENTURA L, PORCIATTI V, ISHIDA K, \u003cem\u003eet al.\u003c/em\u003e Pattern electroretinogram abnormality and glaucoma. \u003cem\u003eOphthalmology\u003c/em\u003e. 2005;112:10\u0026ndash;9. doi: 10.1016/j.ophtha.2004.07.018\u003c/li\u003e\n\u003cli\u003eVentura LM, Feuer WJ, Porciatti V. Progressive Loss of Retinal Ganglion Cell Function Is Hindered with IOP-Lowering Treatment in Early Glaucoma. \u003cem\u003eInvestigative Opthalmology \u0026amp; Visual Science\u003c/em\u003e. 2012;53:659. doi: 10.1167/iovs.11-8525\u003c/li\u003e\n\u003cli\u003eVENTURA L, PORCIATTI V. Restoration of retinal ganglion cell function in early glaucoma after intraocular pressure reductionA pilot study. \u003cem\u003eOphthalmology\u003c/em\u003e. 2005;112:20\u0026ndash;7. doi: 10.1016/j.ophtha.2004.09.002\u003c/li\u003e\n\u003cli\u003eSehi M, Grewal DS, Goodkin ML, \u003cem\u003eet al.\u003c/em\u003e Reversal of Retinal Ganglion Cell Dysfunction after Surgical Reduction of Intraocular Pressure. \u003cem\u003eOphthalmology\u003c/em\u003e. 2010;117:2329\u0026ndash;36. doi: 10.1016/j.ophtha.2010.08.049\u003c/li\u003e\n\u003cli\u003eSchwartz B, Takamoto T, Nagin P. Measurements of Reversibility of Optic Disc Cupping and Pallor in Ocular Hypertension and Glaucoma. \u003cem\u003eOphthalmology\u003c/em\u003e. 1985;92:1396\u0026ndash;407. doi: 10.1016/S0161-6420(85)33850-2\u003c/li\u003e\n\u003cli\u003ePederson JE, Herschler J. Reversal of Glaucomatous Cupping in Adults. \u003cem\u003eArchives of Ophthalmology\u003c/em\u003e. 1982;100:426\u0026ndash;31. doi: 10.1001/archopht.1982.01030030428008\u003c/li\u003e\n\u003cli\u003eQuigley HA. Results, with Trabeculotomy and Study of Reversible Cupping. \u003cem\u003eOphthalmology\u003c/em\u003e. 1982;89:219\u0026ndash;26. doi: 10.1016/S0161-6420(82)34803-4\u003c/li\u003e\n\u003cli\u003eWright TM, Goharian I, Gardiner SK, \u003cem\u003eet al.\u003c/em\u003e Short-Term Enhancement of Visual Field Sensitivity in Glaucomatous Eyes Following Surgical Intraocular Pressure Reduction. \u003cem\u003eAm J Ophthalmol\u003c/em\u003e. 2015;159:378-385.e1. doi: 10.1016/j.ajo.2014.11.012\u003c/li\u003e\n\u003cli\u003eKatz LJ, Spaeth GL, Cantor LB, \u003cem\u003eet al.\u003c/em\u003e Reversible Optic Disk Cupping and Visual Field Improvement in Adults With Glaucoma. \u003cem\u003eAm J Ophthalmol\u003c/em\u003e. 1989;107:485\u0026ndash;92. doi: 10.1016/0002-9394(89)90492-3\u003c/li\u003e\n\u003cli\u003eYamazaki Y, Hayamizu. Effect of trabeculectomy on retrobulbar circulation and visual field progression in patients with primary open-angle glaucoma. \u003cem\u003eClinical Ophthalmology\u003c/em\u003e. 2012;1539. doi: 10.2147/OPTH.S36331\u003c/li\u003e\n\u003cli\u003eYuen D, Buys YM. Disc photography and heidelberg retinal tomography documentation of reversal of cupping following trabeculectomy. \u003cem\u003eGraefe\u0026rsquo;s Archive for Clinical and Experimental Ophthalmology\u003c/em\u003e. 2010;248:1671\u0026ndash;3. doi: 10.1007/s00417-010-1422-x\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Demographic characteristics of the study population\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eCharacterisic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eValue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eNumber of eyes (patients)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e27 (24)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eAge (y), mean \u0026plusmn; SD (median)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e68.8 \u0026plusmn; 13.1 (74.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e17 (70.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003ePhakic, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e14 (51.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eLaterality \u0026nbsp;OD, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e13 (48.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003eBaseline VF MD (dB) \u0026nbsp;mean \u0026plusmn; SD (median)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e8.5 \u0026plusmn; 6.3 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003ePOAG \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003ePEXG \u0026nbsp;n (%)\u003c/p\u003e\n \u003cp\u003ePACG n (%)\u003c/p\u003e\n \u003cp\u003eSACG n (%)\u003c/p\u003e\n \u003cp\u003eTraumatic glaucoma n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 301px;\"\u003e\n \u003cp\u003e13 (48.1)\u003c/p\u003e\n \u003cp\u003e6 (22.2)\u003c/p\u003e\n \u003cp\u003e5 (18.5)\u003c/p\u003e\n \u003cp\u003e2 (7.4)\u003c/p\u003e\n \u003cp\u003e1 (3.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 601px;\"\u003e\n \u003cp\u003eVF = Visual field; MD = Mean deviation\u003c/p\u003e\n \u003cp\u003ePOAG = Primary open angle glaucoma; \u0026nbsp;PEXG = \u0026nbsp;Pseudoexfoliative glaucoma;\u0026nbsp;\u003c/p\u003e\n \u003cp\u003ePACG = Primary angle closure glaucoma; SACG = Secondary angle closure glaucoma\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eTable 2. Change of clinical data and PERG parameters before and after glaucoma surgery\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eBefore\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eAfter\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003eDifference\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eBCVA (decimal)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.93 \u0026plusmn; 0.14 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.93 \u0026plusmn; 0.07 (1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e0.97\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eIOP (mmHg)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e20.7 \u0026plusmn; 4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e11.1 \u0026plusmn; 2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e-9.5 \u0026plusmn; 4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eMag (\u0026mu;V)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.94 \u0026plusmn; 0.3 (0.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e1.29 \u0026plusmn; 0.3 (1.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.34 \u0026plusmn; 0.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026lt;0.0001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eMagD\u0026nbsp;(\u0026mu;V)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.54 \u0026plusmn; 0.3 (0.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.81 \u0026plusmn; 0.41 (0.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.26 \u0026plusmn; 0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003eMagD/Mag ratio\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 132px;\"\u003e\n \u003cp\u003e0.54 \u0026plusmn; 0.19 (0.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e0.67 \u0026plusmn; 0.26 (0.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 94px;\"\u003e\n \u003cp\u003e0.15 \u0026plusmn; 0.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 101px;\"\u003e\n \u003cp\u003e\u0026lt;0.05\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 601px;\"\u003e\n \u003cp\u003eBCVA = \u0026nbsp;Best corrected visual acuity; IOP = \u0026nbsp;Intraocular pressure\u003c/p\u003e\n \u003cp\u003eValues are given as mean \u0026plusmn; SD (median)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Glaucoma, Pattern electroretinogram, Glaucoma surgery, IOP, Retinal Ganglion Cells","lastPublishedDoi":"10.21203/rs.3.rs-8273114/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8273114/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eTo assess the dynamics of Pattern Electroretinogram (PERG) parameters following glaucoma surgery in individuals with glaucomatous optic neuropathy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThe is a single center retrospective study. Preoperative PERG were conducted on moderate and advanced glaucoma patients scheduled for glaucoma surgery. Subsequently, the patients underwent an additional PERG a few months after the procedure. Comparative analysis focused on the PERG parameters (Mag, MagD and MagD/Mag ratio) before and after the glaucoma surgery in eyes achieving successful intraocular pressure (IOP) reduction post-operatively.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe study enrolled 27 eyes from 24 consecutive patients who underwent successful glaucoma surgery between January 2021 and December 2023, each with both pre and post-operative PERG assessments. Postoperatively, there was a significant improvement of all the PERG parameters (0.94\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 to 1.29\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 \u0026micro;V, 0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3 to 0.81\u0026thinsp;\u0026plusmn;\u0026thinsp;0.41 \u0026micro;V, 0.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.19 to 0.67\u0026thinsp;\u0026plusmn;\u0026thinsp;0.26 for Mag, MagD and MagD/Mag ratio respectively, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). Three patients who had no IOP reduction postoperatively showed no improvement of all PERG parameters following the surgery.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eGlaucoma surgery, leading to effective IOP reduction, may demonstrate a positive impact on the functional activity of the retinal ganglion cells, as evidenced by the enhancement in PERG parameters post-operatively.\u003c/p\u003e","manuscriptTitle":"Improvement of Pattern Electroretinogram Parameters Following Glaucoma Surgery ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-12 13:20:20","doi":"10.21203/rs.3.rs-8273114/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-16T07:29:09+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-16T06:09:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-12T11:58:49+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"243770501394824637062098463900096303021","date":"2025-12-12T05:51:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"68854255685757163668683526481040272786","date":"2025-12-07T05:50:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-06T20:30:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-04T07:29:00+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-04T07:28:48+00:00","index":"","fulltext":""},{"type":"submitted","content":"International Ophthalmology","date":"2025-12-03T18:23:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"international-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"inte","sideBox":"Learn more about [International Ophthalmology](https://www.springer.com/journal/10792)","snPcode":"10792","submissionUrl":"https://submission.nature.com/new-submission/10792/3","title":"International Ophthalmology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"7d0db674-b4b8-41f4-b0ed-6f44d9c14847","owner":[],"postedDate":"December 12th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-10T14:24:34+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-12 13:20:20","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8273114","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8273114","identity":"rs-8273114","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}