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.

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.

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.

A child with dendritiform eye lesions and developmental delay.

Purpose: Tyrosinemia Type II (Richner-Hanhart syndrome) is a rare autosomal recessive disease that occurs due to deficiency in the enzyme tyrosine aminotransferase and can result in an ulcerated keratitis. We present a case of a young patient with oculocutaneous tyrosinemia despite a negative newborn screen. Observations: A 15 month old boy with an uncomplicated birth history and negative newborn screen presented with a unilateral central irregular epithelial defect and hyperkeratotic lesions on his fingertips and soles. A month later, the patient developed bilateral dendritiform epithelial erosions. Following a series of antiviral, antibiotic, and lubricating treatments, there was a waxing and waning course of epithelial healing. After the patient was lost to follow up for one year, the patient presented with a new global developmental delay prompting further workup. Tyrosine and phenylalanine levels were ordered which confirmed a diagnosis of Tyrosinemia Type II, and the patient was started on a low-protein diet. A month later, the patient's epithelial defects and ocular symptoms were resolved. Conclusion and Importance: Presentation of a dendritiform epithelial erosion, whether unilateral or bilateral, accompanied by symptoms of developmental delay and palmoplantar hyperkeratotic lesions should prompt measurement of tyrosine and phenylalanine levels. As dermatologic lesions and variable developmental delay may not appear until later in the course of disease, diagnosis may depend on early recognition of ocular signs and symptoms even with negative newborn screening. Prompt diagnosis and diet modification is necessary to prevent developmental delay in this disease. To our knowledge, this is the first Tyrosinemia Type II case in the literature manifesting as an asynchronous bilateral eye disease.

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.

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.

Systemic immune response in squamous cell carcinoma of the head and neck: a comparative concordance index analysis.

PURPOSE: The objective of this study was to investigate the prognostic role of three inflammatory markers: the neutrophil to lymphocyte ratio (NLR), the lymphocyte to monocyte ratio (LMR), and the platelet to lymphocyte ratio (PLR) as prognostic indicators in squamous cell carcinoma of the head and neck (HNSCC). METHODS: Patients with HNSCC treated with primary surgery, with or without adjuvant radiochemotherapy were enrolled. The preoperative NLR, LMR, and PLR were recorded. Confounding variables were also recorded: age, sex, BMI, comorbidities, performance status, AJCC T and N stage and HPV status. Endpoints were overall survival (OS) and event-free survival (EFS). Survival analysis was performed using Kaplan-Meier analysis, and multivariable analysis was performed using Cox proportional hazards regression. Survival models were evaluated using Harrell's concordance index (c-index). RESULTS: NLR (p = 0.2413), PLR (p = 0.1593), and LMR (p = 0.0552) were not significantly associated with OS in the multivariable analysis. With regard to EFS, low LMR (HR = 2.95, 95% CI 1.54-5.65, p = 0.001), high PLR (HR = 2.68, 95% CI 1.42-5.09, p = 0.003), and high NLR (HR = 3.37, 95% CI 1.7-6.69, p < 0.001) were associated with EFS. The multivariable c-index was highest for LMR (0.762), followed by NLR (0.761) and PLR (0.739). CONCLUSION: The LMR, PLR, and NLR were not associated with OS, but were associated with EFS in HNSCC. These markers are easily obtainable, and in the age of individualized patient care and precision medicine, they might represent further risk stratification tools for HNSCC patients.