Associations between steady-state pattern electroretinography and estimated retinal ganglion cell count in glaucoma suspects.

PURPOSE: To estimate retinal ganglion cell (RGC) count in glaucoma suspects (GS) and ascertain its relationships with steady-state pattern electroretinography (ssPERG) parameters. METHODS: In this prospective cross-sectional study, 22 subjects (44 eyes) were recruited at the Manhattan Eye, Ear, and Throat Hospital. Subjects underwent complete eye examinations, optical coherence tomography, standard automated perimetry, and ssPERG testing. Eyes were divided into two groups based upon clinical data: healthy subjects and GS. RGC count was estimated using the combined structure-function index. RESULTS: Estimated RGC count, average retinal nerve fiber layer thickness (ARNFLT), and average ganglion cell layer and inner plexiform layer thickness (GCIPLT) were reduced in GS eyes (p ≤ 0.001 for all parameters). Pearson correlations revealed that ssPERG magnitude and magnitudeD correlated with ARNFLT (r ≥ 0.53, p < 0.001), GCIPLT (r > 0.38, p < 0.011), and estimated RGC count (r > 0.46, p < 0.002). Six mediation analyses revealed that estimated RGC count mediated the relationships among ssPERG parameters, ARNFLT, and GCIPLT. CONCLUSION: Steady-state PERG parameters demonstrated linear correlations with estimated RGC count. The associations among ssPERG parameters and structural measures were mediated by estimated RGC count.

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.

PURPOSE: To derive and validate structure-function models for estimating retinal ganglion cell (RGC) count using optical coherence tomography (OCT) and steady-state pattern electroretinography (ssPERG) parameters in glaucoma suspects (GS) and preperimetric glaucoma (PPG). METHODS: In this prospective cross-sectional study, 25 subjects (50 eyes) were recruited at the Manhattan Eye, Ear, and Throat Hospital. Subjects underwent comprehensive eye examinations, OCT, standard automated perimetry (SAP), and ssPERG testing. Eyes were divided into three groups based on the Global Glaucoma Staging System: healthy (N = 30), GS (N = 10), and PPG (N = 10) eyes. The combined structure-function index (CSFI), which estimates retinal ganglion cell count (eRGCCSFI) from SAP and OCT parameters, was calculated in each study subject. Two prediction formulas were derived using a generalized linear mixed model (GLMM) to predict eRGCCSFI from ssPERG parameters, age, and average retinal nerve fiber layer thickness (ARNFLT) in 30 eyes selected at random (training group). GLMM predicted values were cross-validated with the remaining 20 eyes (validation group). RESULTS: The ARNFLT, ssPERG parameters magnitude (Mag) and magnitudeD (MagD), and eRGCCSFI were significantly different among study groups (ANOVA p ≤ 0.001). Pearson correlations demonstrated significant associations among ARNFLT, ssPERG parameters, and eRGCCSFI (r2 ≥ 0.31, p < 0.001). Two GLMMs predicted eRGCCSFI from Mag (eRGCMag) and MagD (eRGCMagD), respectively, with significant equations (F(3,18), F(3,19) ≥ 58.37, R2 = 0.90, p < 0.001). eRGCMag and eRGCMagD in the validation group (R2 = 0.89) correlated with eRGCCSFI similarly to the training group. Multivariate pairwise comparisons revealed that eRGCMag and eRGCMagD distinguished between healthy, GS, and PPG eyes (p ≤ 0.035), whereas independent Mag, MagD, and ARNFLT measures did not distinguish between GS and PPG eyes. CONCLUSION: This pilot study offers the first combined structure-function models for estimating RGC count using ssPERG parameters. RGC counts estimated with these models were generalizable, strongly associated with CSFI estimates, and performed better than individual ssPERG and OCT measures in distinguishing healthy, GS, and PPG eyes.

Correlations between Steady-State Pattern Electroretinogram and Humphrey Visual Field Analyzer Global Indices and Their Associations with Retinal Ganglion Cell Layer-Inner Plexiform Layer Thickness in Glaucoma Suspects.

Purpose: The purpose of this study was to investigate the utility of steady state pattern electroretinogram (ss-PERG) in detecting retinal ganglion cell (RGC) dysfunction in glaucoma suspects (GS) who had normal 24-2 Humphrey Visual Fields (HFA). Materials and Methods: This was a prospective cohort study of GS patients who were identified based on optic disc appearance with normal HFAs. Patients received a complete eye examination, standard automated perimetry (SAP), optical coherence tomography (OCT), and ss-PERG measurements. The ss-PERG parameters, Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio, were examined, along with their relationships between HFA and OCT measurements. Results: Twenty-five patients were included in this study, with a total of 49 eyes. Fifteen eyes had abnormal ss-PERG parameters and when compared to GS eyes with normal ss-PERG parameters, there were significant differences in HFA 24-2, retinal nerve fiber layer (RNFL) thickness, and ganglion cell layer and inner plexiform layer (GCL + IPL) thickness. All ss-PERG parameters were significantly correlated with 24-2 VF mean deviation (MD) and visual field index (VFI), as well as 10-2 VF MD after controlling for age, sex, intraocular pressure, central corneal thickness, and spherical equivalent. When controlled for age, spherical equivalent, and IOP, MagD/Mag ratio significantly contributed to the variance in average GCL + IPL thicknesses, whereas 24-2 VF MD and 10-2 VF MD did not. MagD/Mag ratio also significantly accounted for variance in all macular GCL + IPL sectors, while 10-2 VF MD did not. Conclusions: ss-PERG has significant correlations with HFA global indices and was predictive of GCL + IPL thickness in GS patients. Clinical Significance. ss-PERG may serve as a useful functional tool for detecting and measuring RGC dysfunction in GS. It appears to be more sensitive than HFA in the detection of early changes in GCL + IPL thicknesses and may be helpful to use in conjunction with current diagnostic studies to improve the ability of monitoring GS progression.

180° versus 360° Selective Laser Trabeculoplasty in Open Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-Analysis.

PRECIS: This systematic review and meta-analysis found that 360° selective laser trabeculoplasty (SLT) is significantly more effective than 180° SLT at reducing intraocular pressure at one month and one year follow-ups, without increased serious adverse event risk. PURPOSE: To determine the efficacy of 180° versus 360° selective laser trabeculoplasty (SLT) in adults with open angle glaucoma (OAG) and ocular hypertension (OHT). METHODS: A systematic review was performed using PubMed, Embase, and Scopus databases, from 1995 to December 30, 2023, for studies comparing 180° and 360° SLT in adults with OAG and OHT (PROSPERO ID: CRD42024497832). Meta-analyses were performed to calculate nominal percent and raw reductions in IOP between treatment groups at one-month, one-year, and two-year follow-ups, as well as success rates, defined as a 20% or greater IOP reduction. RESULTS: Nine studies with 1044 eyes were included; 491 received 180°SLT and 553 received 360° SLT. At the one-month follow-up, 360° SLT reduced IOP by 3.45% more (WMD=3.45; 95% CI: 2.02-4.88; P<0.00001) and 0.87 mmHg more (WMD=0.87; 95% CI: 0.35-1.38; P=0.0010). At the one-year follow-up, 360° SLT reduced IOP by 4.33% more (WMD=4.33; 95% CI: 2.35-6.32; P<0.0001) and 1.15 mmHg more (WMD=1.15; 95% CI: 0.25-2.04; P=0.01). At two years of follow up, 360° SLT reduced IOP by 4.86% more (WMD=4.86; 95% CI: -0.32, 10.0; P=0.07) and 1.25 mmHg more (WMD=1.25; 95% CI: -0.29, 2.79; P=0.11), however the difference was not statistically significant. Compared to 360° SLT, 180° SLT had a significantly lower success rate (OR=0.50; 95% CI: 0.35-0.72; P=0.0002). There was no difference in serious complications between interventions. CONCLUSION: 360° SLT is more effective than 180° SLT at lowering IOP at one-month and one-year follow-ups as well as achieving successful IOP control without increased risk of serious complications.

Posterior Pole Asymmetry Analysis as a Diagnostic Tool in Glaucoma Suspects: An Electrophysiological Approach.

Purpose: Spectral domain optical coherence tomography (SD-OCT) with posterior pole asymmetry analysis (PPAA) provides a mapping of posterior pole retinal thickness with asymmetry analysis between hemispheres of each eye. We investigated whether these structural abnormalities were correlated with functional retinal ganglion cell (RGC) loss, quantified by steady state pattern electroretinogram (ssPERG), in glaucoma suspects (GS). Methods: Twenty GS (34 eyes) were enrolled in a prospective study at the Manhattan Eye, Ear, and Throat Hospital. All subjects underwent ophthalmological examination, including Humphrey visual field, Spectralis Glaucoma Module Premium Edition (GMPE) SD-OCT PPAA, and ssPERG testing. The ability of ssPERG parameters (Magnitude [Mag, µv], MagnitudeD [MagD, µv], and MagD/Mag ratio) to predict PPAA thickness (total, superior, and inferior thickness, [µm]) was tested via adjusted multivariate linear regression analysis. Results: Mag explained 8% of variance in total PPAA change (F(1,29)=6.33, B=6.86, 95% CI: 1.29-12.44, p=0.018), 8% in superior PPAA change (F(1,29)=5.57, B=6.92, 95% CI: 0.92-12.92, p=0.025), and 7.1% in inferior PPAA change (F(1,29)=5.83, B=6.80, 95% CI: 1.04-12.56, p=0.022). Similarly, MagD explained 9.7% of variance in total PPAA change (F(1,29)=8.09, B=6.47, 95% CI: 1.82-11.13, p=0.008), 10% in superior PPAA change (F(1,29)=7.33, B=6.63, 95% CI: 1.62-11.63, p=0.011), and 8.5% in inferior PPAA change (F(1,29)=7.25, B=6.36, 95% CI: 1.53-11.18, p=0.012). MagD/Mag ratio and PPAA were not significantly associated. Conclusion: To the best of our knowledge, this is the first study demonstrating a positive relationship between RGC dysfunction and retinal thickness changes between the superior and inferior hemispheres. The detection of asymmetrical structural loss, combined with functional RGC assessment using ssPERG, may be an informative tool for early glaucoma diagnosis.

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

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. How to cite this article: Tirsi A, Gliagias V, Sheha H, et al. 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.

Pattern Electroretinogram Parameters and their Associations with Optical Coherence Tomography in Glaucoma Suspects.

Aim: To investigate whether steady state pattern electroretinogram (ssPERG) could identify retinal ganglion cell (RGC) dysfunction, and to assess the relationship between ssPERG with optical coherence tomography (OCT) measurements in glaucoma suspects (GS). Materials and methods: This was a prospective cohort study of GS, identified based on suspicious optic disk appearance and glaucoma risk factors. Complete eye exam, Standard automated perimetry, OCT, and ssPERG were performed. Magnitude (Mag), Magnitude D (MagD), and MagD/Mag ratio were subsequently used in the correlation and linear regression analyses between ssPERG parameters and the RNFL, GCL/IPL, and macular thicknesses measurements. Results: Forty-nine eyes of 26 patients were included. Mag and MagD were significantly correlated with the superior, inferior, and average RNFL thicknesses (avRNFLT). All ssPERG parameters were significantly correlated with the average and minimum GCL/IPL thicknesses and the inner macular sector thicknesses. Mag and MagD significantly predicted the superior, inferior, and avRNFLT in the regression analysis. All ssPERG parameters were predictive of GCL/IPL thickness in all sectors as well as the average and minimum GCL/IPL thicknesses. All ssPERG parameters were predictive of all inner macular sector thicknesses and MagD was also predictive of some outer macular sector thicknesses as well. Conclusion: ssPERG has significant correlations with and is predictive of RNFL, GCL/IPL, and macular thicknesses in glaucoma suspects. Clinical significance: ssPERG may serve as a useful objective functional tool for identifying and following the progression of disease in glaucoma suspects. How to cite this article: 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.

Pattern Electroretinogram Parameters Are Associated with Optic Nerve Morphology in Preperimetric Glaucoma after Adjusting for Disc Area.

PURPOSE: We examined the relationships between pattern electroretinogram and optical coherence tomography derived optic nerve head measurements, after controlling for disc area. METHODS: Thirty-two eyes from 20 subjects with preperimetric glaucoma underwent pattern electroretinogram and optical coherence tomography. Pattern electroretinogram parameters (Magnitude, MagnitudeD, and MagnitudeD/Magnitude ratio) and optic nerve head measurements (rim area, average cup to disc ratio, vertical cup to disc ratio, cup volume, retinal nerve fiber layer thickness sectors, and Bruch's membrane opening-minimum rim width thickness sectors) were analyzed after controlling for disc area. RESULTS: Magnitude and MagnitudeD were significantly associated with rim area (r ≥ 0.503, p ≤ 0.004). All pattern electroretinogram parameters significantly correlated with Bruch's membrane opening-minimum rim width sectors-temporal superior and nasal inferior (r = 0.400, p=0.039)-and retinal nerve fiber layer sectors-superior, nasal superior, and inferior (r ≥ 0.428, p ≤ 0.026). Magnitude and MagnitudeD explained an additional 26.8% and 25.2% of variance in rim area (B = 0.174 (95% CI: 0.065, 0.283), p=0.003, and B = 0.160 (95% CI: 0.056, 0.265), p=0.004), respectively. MagnitudeD and MagnitudeD/Magnitude ratio explained an additional 13.4% and 12.8% of the variance in Bruch's membrane opening-minimum rim width global (B = 38.921 [95% CI: 3.872, 73.970], p=0.031, and B = 129.024 (95% CI: 9.589, 248.460), p=0.035), respectively. All Bruch's membrane opening-minimum rim width sectors and retinal nerve fiber layer sectors (nasal superior, nasal inferior, and inferior) were significantly correlated with rim area (r ≥ 0.389, p ≤ 0.045). CONCLUSION: PERG abnormalities can predict rim area loss in preperimetric glaucoma after controlling for disc area. We recommend controlling for disc area to increase diagnostic accuracy in early glaucoma.

Insulin Sensitivity and Inflammation Mediate the Impact of Fitness on Cerebrovascular Health in Adolescents.

BACKGROUND/OBJECTIVES: To investigate in adolescents the relationships between retinal vessel diameter, physical fitness, insulin sensitivity, and systemic inflammation. METHODS: We evaluated 157 adolescents, 112 with excessive weight and 45 lean, all without type 2 diabetes mellitus. All received detailed evaluations, including measurements of retinal vessel diameter, insulin sensitivity, levels of inflammation, and physical fitness. RESULTS: Overweight/obese adolescents had significantly narrower retinal arteriolar and wider venular diameters, significantly lower insulin sensitivity, and physical fitness. They also had decreased levels of anti-inflammatory and increased levels of proinflammatory markers as well as an overall higher inflammation balance score. Fitness was associated with larger retinal arteriolar and narrower venular diameters and these relationships were mediated by insulin sensitivity. We demonstrate that inflammation also mediates the relationship between fitness and retinal venular, but not arterial diameter; insulin sensitivity and inflammation balance score jointly mediate this relationship with little overlap in their effects. CONCLUSIONS: Increasing fitness and insulin sensitivity and reducing inflammation among adolescents carrying excess weight may improve microvascular integrity. Interventions to improve physical fitness and insulin function and reduce inflammation in adolescents, a group likely to benefit from such interventions, may reduce not only cardiovascular disease in middle age, but also improve cerebrovascular function later in life.

Iridocorneal Endothelial Syndrome Presenting With Large Diurnal Intraocular Pressure Fluctuation.

PURPOSE OF THE STUDY: The purpose of the study was to report a case of iridocorneal endothelial syndrome with an initial presentation of a large diurnal fluctuation of intraocular pressure (IOP) which peaked early in the morning. METHODS: A 31-year-old white man had transient blurry vision oculus sinister (OS) upon awakening in the morning for the past 2 months. The blurry vision improved within 1 to 2 hours. Clinical examination, diurnal IOP measurements, and specular microscopy were performed to investigate the cause of his transient blurry vision. RESULTS: At 6 AM, IOP OS was 38 mm Hg with corneal edema and visual acuity of 20/30. At 8 AM, IOP OS decreased to 25 mm Hg with clear cornea and visual acuity of 20/20. Diurnal IOP measurements revealed a large fluctuation OS (18 mm Hg). Specular microscopy revealed pleomorphism, polymegathism, light peripheral borders and light/dark reversal of the corneal endothelium OS. IOP oculus dexter remained within normal limits with clear cornea and stable visual acuity throughout the diurnal measurements. CONCLUSIONS: In patients with consistent daily episodes of transient blurry vision, clinicians should suspect a large diurnal IOP fluctuation with high peak IOP. If symptoms and signs are unilateral, iridocorneal endothelial syndrome should be included in the differential diagnosis and corneal specular microscopy should be obtained.

Glaucoma Patient-Reported Concerns and Associated Factors.

PURPOSE: To assess the character and degree of concerns of glaucoma patients and identify demographic/clinical factors affecting the concerns. DESIGN: Prospective cross-sectional study. METHODS: A questionnaire that addressed patients' concerns was administered to consecutive glaucoma patients. Severity of concern was scored with a scale of 0-5 in order of increasing severity. Age, sex, intraocular pressure, visual field (VF) mean deviation (MD), number of antiglaucoma medications, history of glaucoma surgery, and employment status were recorded. RESULTS: Questionnaire results of 152 patients (mean VF MD, -8.03 ± 7.86 dB [better eye] and -16.06 ± 10.22 dB [worse eye]; mean age, 69 ± 14 years) were analyzed. Severity of concern was greatest for general eyesight (2.92/5.00) and visual symptoms (2.78/5.00), followed by activities (2.20/5.00) and socioeconomic factors (2.13/5.00), and then ocular symptoms (1.69/5.00) (P < .001). The most common concerns within each domain were blurry vision (32%), reading small print (34%), medical costs (26%), and dryness (32%). Concern about visual symptoms correlated with VF MD of the better eye (r = -0.258; P = .001) and worse eye (r = -0.233; P = .004). Concern about activities correlated with history of glaucoma surgery (r = 0.148; P = .023) and VF MD of the better eye (r = -0.284; P < .001) and worse eye (r = -0.295; P < .001). Concern about socioeconomic factors correlated with VF MD of the better eye (r = -0.245; P = .003) and age (r = -0.260; P = .001). CONCLUSIONS: Glaucoma patients reported varied degrees of concern regarding items associated with quality of life. Certain items may be more concerning than others. Severity of some concerns increased with more severe VF loss, prior glaucoma surgery, or younger age.