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.

The African Descent and Glaucoma Evaluation Study (ADAGES) III: Contribution of Genotype to Glaucoma Phenotype in African Americans: Study Design and Baseline Data.

PURPOSE: To describe the study protocol and baseline characteristics of the African Descent and Glaucoma Evaluation Study (ADAGES) III. DESIGN: Cross-sectional, case-control study. PARTICIPANTS: Three thousand two hundred sixty-six glaucoma patients and control participants without glaucoma of African or European descent were recruited from 5 study centers in different regions of the United States. METHODS: Individuals of African descent (AD) and European descent (ED) with primary open-angle glaucoma (POAG) and control participants completed a detailed demographic and medical history interview. Standardized height, weight, and blood pressure measurements were obtained. Saliva and blood samples to provide serum, plasma, DNA, and RNA were collected for standardized processing. Visual fields, stereoscopic disc photographs, and details of the ophthalmic examination were obtained and transferred to the University of California, San Diego, Data Coordinating Center for standardized processing and quality review. MAIN OUTCOME MEASURES: Participant gender, age, race, body mass index, blood pressure, history of smoking and alcohol use in POAG patients and control participants were described. Ophthalmic measures included intraocular pressure, visual field mean deviation, central corneal thickness, glaucoma medication use, or past glaucoma surgery. Ocular conditions, including diabetic retinopathy, age-related macular degeneration, and past cataract surgery, were recorded. RESULTS: The 3266 ADAGES III study participants in this report include 2146 AD POAG patients, 695 ED POAG patients, 198 AD control participants, and 227 ED control participants. The AD POAG patients and control participants were significantly younger (both, 67.4 years) than ED POAG patients and control participants (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared with ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all P < 0.001). Family history of glaucoma did not differ between AD and ED POAG patients. CONCLUSIONS: With its large sample size, extensive specimen collection, and deep phenotyping of AD and ED glaucoma patients and control participants from different regions in the United States, the ADAGES III genomics study will address gaps in our knowledge of the genetics of POAG in this high-risk population.

Genetic Architecture of Primary Open-Angle Glaucoma in Individuals of African Descent: The African Descent and Glaucoma Evaluation Study III.

PURPOSE: To find genetic contributions to glaucoma in African Americans. DESIGN: Cross-sectional, case-control study. PARTICIPANTS: One thousand eight hundred seventy-five primary open-angle glaucoma (POAG) patients and 1709 controls, self-identified as being of African descent (AD), from the African Descent and Glaucoma Evaluation Study (ADAGES) III and Wake Forest School of Medicine. METHODS: MegaChip genotypes were imputed to Thousand Genomes data. Association of single nucleotide polymorphisms (SNPs) with POAG and advanced POAG was tested by linear mixed model correcting for relatedness and population stratification. Genetic risk scores were tested by receiver operator characteristic curves (ROC-AUCs). MAIN OUTCOME MEASURES: Primary open-angle glaucoma defined by visual field loss without other nonocular conditions (n = 1875). Advanced POAG was defined by age-based mean deviation of visual field (n = 946). RESULTS: Eighteen million two hundred eighty-one thousand nine hundred twenty SNPs met imputation quality of r2 > 0.7 and minor allele frequency > 0.005. Association of a novel locus, EN04, was observed for advanced POAG (rs185815146 ß, 0.36; standard error, 0.065; P < 3×10-8). For POAG, an AD signal was observed at the 9p21 European descent (ED) POAG signal (rs79721419; P < 6.5×10-5) independent of the previously observed 9p21 ED signal (rs2383204; P < 2.3×10-5) by conditional analyses. An association with POAG in FNDC3B (rs111698934; P < 3.9×10-5) was observed, not in linkage disequilibrium (LD) with the previously reported ED SNP. Additional previously identified loci associated with POAG in persons of AD were: 8q22, AFAP1, and TMC01. An AUC of 0.62 was observed with an unweighted genetic risk score comprising 11 SNPs in candidate genes. Two additional risk scores were studied by using a penalized matrix decomposition with cross-validation; risk scores of 50 and 400 SNPs were identified with ROC of AUC = 0.74 and AUC = 0.94, respectively. CONCLUSIONS: A novel association with advanced POAG in the EN04 locus was identified putatively in persons of AD. In addition to this finding, this genome-wide association study in POAG patients of AD contributes to POAG genetics by identification of novel signals in prior loci (9p21), as well as advancing the fine mapping of regions because of shorter average LD (FNDC3B). Although not useful without confirmation and clinical trials, the use of genetic risk scores demonstrated that considerable AD-specific genetic information remains in these data.

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-Degree Selective Laser Trabeculoplasty in Open Angle Glaucoma and Ocular Hypertension: A Systematic Review and Meta-Analysis.

PRCIS: This systematic review and meta-analysis found that 360-degree selective laser trabeculoplasty (SLT) is significantly more effective than 180-degree SLT at reducing intraocular pressure at 1-month and 1-year follow-ups without increased serious adverse event risk. PURPOSE: To determine the efficacy of 180- versus 360-degree 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-degree SLT in adults with OAG and OHT (PROSPERO ID: CRD42024497832). Meta-analyses were performed to calculate nominal percent and raw reductions in intraocular pressure (IOP) between treatment groups at 1-month, 1-year, and 2-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-degree SLT, and 553 received 360-degree SLT. At the 1-month follow-up, 360-degree SLT reduced IOP by 3.45% more (WMD=3.45; 95% CI: 2.02-4.88; P <0.00001) and 0.87 mm Hg more (WMD=0.87; 95% CI: 0.35-1.38; P =0.0010). At the 1-year follow-up, 360-degree SLT reduced IOP by 4.33% more (WMD=4.33; 95% CI: 2.35-6.32; P <0.0001) and 1.15 mm Hg more (WMD=1.15; 95% CI: 0.25-2.04; P =0.01). At 2 years of follow-up, 360-degree SLT reduced IOP by 4.86% more (WMD=4.86; 95% CI: -0.32, 10.0; P =0.07) and 1.25 mm Hg more (WMD=1.25; 95% CI: -0.29, 2.79; P =0.11); however, the difference was not statistically significant. Compared with 360-degree SLT, 180-degree 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. CONCLUSIONS: 360-degree SLT is more effective than 180-degree SLT at lowering IOP at 1-month and 1-year follow-ups as well as achieving successful IOP control without increased risk of serious complications.

Outcomes of Micropulse Laser Trabeculoplasty Compared to Selective Laser Trabeculoplasty: A Systematic Review and Meta-Analysis.

Purpose: To perform a meta-analysis and systematic review to compare the efficacy and complications of micropulse laser trabeculoplasty (MLT) and selective laser trabeculoplasty (SLT) in adult patients with open-angle glaucoma (OAG) and ocular hypertension (OHT). Methods: We performed a systematic review utilizing PubMed, Embase, and Scopus, on April 8, 2024. Meta-analyses were performed for the mean change in intraocular pressure (IOP) at one-month, six-month, and one-year follow-up visits, rate of IOP spikes (>5 mmHg increase from the pre-procedure baseline IOP), rate of treatment failure (<20% or <3 mmHg reduction in IOP or requiring additional medications or procedures), and mean change in number of medications. Results: Six studies, with a total of 593 eyes, were included: 283 underwent MLT, while 310 underwent SLT. A statistically significant difference in the efficacy of MLT versus SLT at one-month and six-month follow-ups was present, with SLT reducing IOP by 0.83 mmHg (95% CI: 0.20, 1.47; P = 0.01) more and 0.55 mmHg (95% CI: 0.02, 1.08; P = 0.04) more than MLT, respectively. At the one-year follow-up, there was no significant disparity in IOP reduction between SLT and MLT (WMD = 0.16; 95% CI: -0.40, 0.71; P = 0.58). There was a significantly lower rate of IOP spikes in the MLT treatment group (RR = 0.37; 95% CI: 0.16, 0.89; P = 0.03). There was no statistically significant difference in the rate of treatment failures (RR = 1.05; 95% CI: 0.68, 1.62; P = 0.84) or number of topical medications reduced (WMD = 0.06; 95% CI: -0.13, 0.26; P = 0.53). Conclusion: While SLT may offer greater short-term reductions in IOP, it may be associated with more postoperative IOP spikes when compared to MLT. At one-year follow-up, there were no significant differences in IOP reduction or failure rates between the MLT and SLT groups.

Is preoperative ciliary body and iris anatomical configuration a predictor of malignant glaucoma development?

BACKGROUND: To investigate anatomical configuration of ciliary body and iris using ultrasound biomicroscopy as a predictor of malignant glaucoma development. DESIGN: Retrospective study in a tertiary care hospital. PARTICIPANTS: Cohort of 31 consecutive patients diagnosed with post-surgical malignant glaucoma. METHODS: Anterior chamber angle, iris and ciliary body configuration of involved eyes that had ultrasound biomicroscopy evaluation prior to the malignant glaucoma onset were evaluated. In cases with no presurgical ultrasound biomicroscopy exam of the involved eye, images from the fellow eye (imaged within 6 months) were analysed. MAIN OUTCOME MEASURES: Qualitative parameters. RESULTS: Thirty-one eyes (31 patients) had confirmed malignant glaucoma between 1996 and 2008. Most patients were women (65%) and had an anatomical narrow angle or angle-closure glaucoma (77%). Mean intraocular pressure at diagnosis was 30.4 ± 13.5 mmHg. The most common operation was trabeculectomy with mitomycin C (55%, 17/31 eyes), combined (3/17) or not (14/17) with cataract extraction and intraocular lens implantation. Among these 31 cases, we were able to evaluate the ultrasound biomicroscopy images of 13 patients (13 eyes) including involved eyes imaged prior to the malignant glaucoma onset or eligible fellow eyes. A narrow angle with or without iridotrabecular contact was found in all eyes. A large and/or anteriorly positioned ciliary body associated with an iris root angulating forward and centrally, revealing a plateau iris configuration, was noticed in 85% (11/13) of these eyes. CONCLUSION: Identification of plateau iris configuration by ultrasound biomicroscopy should be considered as a possible predictor of post-operative malignant glaucoma development.

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.

Enhanced depth imaging optical coherence tomography of deep optic nerve complex structures in glaucoma.

OBJECTIVE: To assess the usefulness of enhanced depth imaging (EDI) optical coherence tomography (OCT) for evaluating deep structures of the optic nerve complex (ONC; optic nerve head and peripapillary structures) in glaucoma. DESIGN: Prospective, observational study. PARTICIPANTS: Seventy-three established glaucoma patients (139 eyes) with a range of glaucomatous damage. METHODS: Serial horizontal and vertical EDI OCT images of the ONC were obtained from both eyes of each participant. Deep ONC structures, including the lamina cribrosa (LC), short posterior ciliary artery (SPCA), central retinal artery (CRA), central retinal vein (CRV), peripapillary choroid and sclera, and subarachnoid space around the optic nerve, were investigated for their visibility and morphologic features. MAIN OUTCOME MEASURES: Deep ONC structures identified in EDI OCT images. RESULTS: Visual field mean deviation of 139 included eyes was -11.8 ± 8.6 dB (range, -28.70 to -2.01 dB). The anterior laminar surface was identified in all eyes in the central laminar area and in 91 (65%) eyes in the periphery beneath the neuroretinal and scleral rims or vascular structures. The LC pores with various shapes and sizes were visualized in 106 (76%) eyes, mainly in the central and temporal areas of the LC. Localized LC lesions seen on optic disc photographs were identified as focal LC defects (partial loss of LC tissue) in the EDI OCT images. The locations of the CRA and CRV were identified in all eyes. In the LC, the CRA maintained a straight shape with a consistent caliber, but the CRV (and tributaries) assumed a more irregular shape. The SPCAs, their branches through the emissary canals in the sclera, or both were visualized in 120 (86%) eyes. The subarachnoid space around the optic nerve was identified with varying degrees of clarity in 25 eyes (18%): 17 had high myopia and extensive parapapillary atrophy. Intrachoroidal cavitation or choroidal schisis, which had been unrecognized clinically, was identified in 2 eyes (1%) with high myopia. CONCLUSIONS: Enhanced depth imaging OCT was able to visualize a wide variety of deep ONC structures in glaucoma patients and may be helpful in detecting, conceptualizing, and understanding basic and complicated in vivo anatomic and pathologic features of the ONC in glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Rates of visual field progression in distinct optic disc phenotypes.

BACKGROUND: To determine if optic disc phenotype is correlated with the rate of glaucomatous visual field progression. DESIGN: Retrospective cohort. PARTICIPANTS OR SAMPLES: Treated glaucoma patients. METHODS: The optic disc stereophotographs of glaucoma patients were reviewed by two investigators masked to all clinical and perimetric data. Each disc was classified as focal ischaemic, myopic, senile sclerotic and generalized enlargement. Visual field progression (defined as at least two adjacent test points in the same hemifield progressing by more than 1.0 dB/year at P < 0.01) was evaluated using automated pointwise linear regression. MAIN OUTCOME MEASURES: Association between optic disc phenotypes and other clinical variables and rates of visual field progression. RESULTS: 264 optic disc stereophotographs (127 generalized enlargement, 41 focal ischaemic, 54 myopic and 42 senile sclerotic) were evaluated. In the univariate analyses, it was found that patients with senile sclerotic discs were older (p = 0.002) and those with generalized enlargement had better baseline visual field mean deviation (p < 0.001) and higher intraocular pressure (p = 0.006) compared with the other groups. More disc haemorrhages were detected in the focal ischaemic and senile sclerotic groups (p = 0.010). After adjusting for other risk factors (intraocular pressure, age, central corneal thickness, disc haemorrhage), there were no differences among groups regarding the risk (p = 0.58) and velocity (p = 0.21) of visual field progression. CONCLUSIONS: Visual field progression was similar among the four optic disc phenotypes in treated glaucoma after adjusting for other known risk factors. The division of disc appearance into clinical phenotypes does not appear to provide independent information regarding the risk of progression in clinical practice.

The region of largest ß-zone parapapillary atrophy area predicts the location of most rapid visual field progression.

PURPOSE: To determine if visual field (VF) progression occurs most rapidly in the region of largest ß-zone parapapillary atrophy (PPA). DESIGN: Retrospective cohort. PARTICIPANTS: One hundred twenty-five patients from the New York Glaucoma Progression Study with both ß-zone PPA and VF progression. METHODS: Treated open-angle glaucoma patients with 8 or more Swedish Interactive Threshold Algorithm Standard 24-2 VFs (Humphrey Field Analyzer II; Carl Zeiss Meditec, Inc., Dublin, CA) in either eye were identified. Eyes with optic disc photographs, ß-zone PPA, less than 6 diopters myopia, and VF progression were studied. Visual field progression was defined using trend analysis as the presence of at least 2 adjacent progressing points in the same hemifield using standard pointwise linear regression (PLR) criteria. MAIN OUTCOME MEASURES: The correlation between ß-zone PPA and location of most rapid future VF progression. RESULTS: One hundred twenty-five eyes (125 patients; mean age, 71.9 ± 12.3 years; 58% women; 75% European descent) with ß-zone PPA and VF progression were enrolled. The mean follow-up was 6.8 ± 1.7 years and the mean number of VFs was 12.5 ± 3.6. Ninety-three patients (74%) had more ß-zone PPA inferiorly and 32 patients (26%) had more ß-zone PPA superiorly. The fastest VF progression occurred in the superior hemifield in 77 patients (62%) and in the inferior hemifield in 48 (38%) patients. Patients with superior VF progression had a superior localized mean rate of progression of -1.57 ± 1.7 dB/year, and patients with inferior VF progression had an inferior localized mean rate of -0.94 ± 1.4 dB/year (P = 0.012). The mean number of points reaching the predefined PLR end points was 5.6±7.5 for the superior VF hemifield and 3.0±4.9 for the inferior hemifield (P = 0.006). The hemifield with more points reaching PLR progression end points, with fastest average velocity of progression, or both was spatially consistent with the location of largest ß-zone PPA in 89 (71%) patients (P = 0.0001, Fisher exact test; κ = 0.35; 95% confidence interval, 0.17-0.53). CONCLUSIONS: In treated glaucoma patients with ß-zone PPA and VF progression, the location of largest ß-zone PPA typically correlates spatially with the region of the most rapid future VF progression. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Initial parafoveal versus peripheral scotomas in glaucoma: risk factors and visual field characteristics.

OBJECTIVE: To assess risk factors for an initial parafoveal scotoma (IPFS) compared with an initial nasal step (INS) in glaucoma. DESIGN: Retrospective, observational study. PARTICIPANTS: Sixty-nine patients with glaucoma with an isolated IPFS and 53 patients with an isolated INS. METHODS: On the basis of 2 reliable, consistent 24-2 Swedish interactive threshold algorithm standard visual fields (VFs), 2 groups of patients with glaucoma were studied: those with an IPFS in 1 hemifield (≥3 adjacent points with P<5% within the central 10 degrees of fixation, ≥1 point with P<1% lying at the innermost paracentral points, and no VF abnormality outside the central 10 degrees) and those with an INS in 1 hemifield (≥3 adjacent points with P<5% in the nasal periphery outside 10 degrees of fixation, the nasal-most point with P<1%, and no VF abnormality within the central 10 degrees). Clinical characteristics and systemic factors were recorded from charts and compared between the 2 groups. MAIN OUTCOME MEASURES: Maximum untreated intraocular pressure (IOP), disc hemorrhage (DH) detection during follow-up, systemic risk factors, and VF mean deviation (MD) and pattern standard deviation (PSD). RESULTS: Maximum untreated IOP (21.6±4.5 vs. 28.3±9.6 mmHg; P<0.001) was significantly lower, and frequency of DH detection (44% vs. 17%; P=0.001) and systemic risk factors (hypotension, migraine, Raynaud's phenomenon, and sleep apnea; 16%, 23%, 24%, and 9% vs. 0%, 4%, 9%, and 0%; P=0.001, 0.002, 0.025, and 0.030, respectively) were significantly higher in patients with an IPFS than in patients with an INS. There were no significant differences in age, gender, family history of glaucoma, refractive error, central corneal thickness, and disc area between the 2 groups (all P>0.1). Mean deviation was similar between the 2 groups (P=0.346), but PSD was significantly greater in the IPFS group than in the INS group (P=0.043). CONCLUSIONS: Eyes with an IPFS differ from those with an INS. These findings may help clinicians identify patients at higher risk of early central field loss.

Short-duration transient visual evoked potential for objective measurement of refractive errors.

This study examined effects of uncorrected refractive errors (RE) in a short-duration transient visual evoked potential (SD t-VEP) system and investigated their role for objective measurement of RE. Refractive errors were induced by means of trial lenses in 35 emmetropic subjects. A synchronized single-channel EEG was recorded for emmetropia, and each simulated refractive state to generate 21 VEP responses for each subject. P100 amplitude (N75 trough to P100 peak) and latency were identified by an automated post-signal processing algorithm. Induced hypermetropia and myopia correlated strongly with both P100 amplitude and latency. To minimize the effect of baseline shift and waveform fluctuations, a VEP scoring system, based on software-derived P100 latency, amplitude and waveform quality, was used to estimate the RE. Using the VEP scores, a single VEP response had a high sensitivity and specificity for discerning emmetropia, small RE (<2 diopter) within a 2 diopter range and large RE (2-14 diopter) within a 4 diopter range. The VEP scoring system has a potential for objective screening of RE and for a more accurate 3-step objective refraction.

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.

Beta-Zone parapapillary atrophy and the velocity of glaucoma progression.

PURPOSE: Beta-Zone parapapillary atrophy (PPA) occurs more commonly in eyes with glaucoma. Rates of glaucomatous visual field (VF) progression in eyes with and without beta-zone PPA at the time of baseline assessment were compared. DESIGN: Retrospective, comparative study. PARTICIPANTS: Two hundred forty-five patients from the New York Glaucoma Progression Study. METHODS: Subjects with glaucomatous optic neuropathy and repeatable VF loss were assessed for eligibility. Eyes with a Heidelberg Retina Tomograph II (HRT) examination, at least 5 visual field tests after the HRT in either eye, optic disc photographs, and <6 diopters of myopia were enrolled. beta-Zone PPA was defined as a region of chorioretinal atrophy with visible sclera and choroidal vessels adjacent to the optic disc. Global rates of VF progression were determined by automated pointwise linear regression analysis. Univariate analysis included age, gender, ethnicity, central corneal thickness (CCT), refractive error, baseline mean deviation, baseline intraocular pressure (IOP), mean IOP, IOP fluctuation, disc area, rim area, rim area-to-disc area ratio, beta-zone PPA area, beta-zone PPA area-to-disc area ratio, and presence or absence of beta-zone PPA. MAIN OUTCOME MEASURES: The relationship between beta-zone PPA and the rate and risk of glaucoma progression. RESULTS: Two hundred forty-five eyes of 245 patients (mean age, 69.6+/-12.3 years) were enrolled. The mean follow-up was 4.9+/-1.4 years and the mean number of VFs after HRT was 9.3+/-2.7. beta-Zone PPA was present in 146 eyes (65%). Eyes with beta-zone PPA progressed more rapidly (-0.84+/-0.8 dB/year) than eyes without it (-0.51+/-0.6 dB/year; P<0.01). Multivariate regression showed significant influence of mean IOP (hazard ratio [HR], 1.11; P<0.01), IOP fluctuation (HR, 1.17; P = 0.02), and presence of beta-zone PPA (HR, 2.59; P<0.01) on VF progression. Moderate (0.5-1.5 dB/year; P = 0.01) and fast (>1.5 dB/year; P = 0.08) global rates of progression occurred more commonly in eyes with beta-zone PPA than in eyes without it. Thinner CCT (<525 microm) had a weak but significant correlation with presence of beta-zone PPA (kappa = 0.13). CONCLUSIONS: Eyes with beta-zone PPA are at increased risk for glaucoma progression and warrant close clinical surveillance.

Factors affecting rates of visual field progression in glaucoma patients with optic disc hemorrhage.

PURPOSE: Optic disc hemorrhage (DH) is an important risk factor for glaucoma progression. We sought to investigate factors affecting the rate of visual field (VF) progression after DH in glaucomatous eyes. DESIGN: Retrospective cohort study. PARTICIPANTS: Consecutive glaucoma patients from our Glaucoma Progression Study with > or =5 Swedish interactive threshold algorithm standard 24-2 VFs from 1999 through 2008. METHODS: Disc photographs of all patients were evaluated for the presence of DH. Exclusion criteria were conditions other than glaucoma likely to affect the VF and insufficient number of VFs to create a slope after DH detection. Automated pointwise linear regression was used to determine the rate of VF loss after DH detection. Fast progression was defined as a global VF loss of > or =1.5 dB/year. Factors associated with a fast rate of VF loss after the detection of the DH were evaluated. MAIN OUTCOME MEASURES: Assessed variables included baseline (age, gender, intraocular pressure [IOP], central corneal thickness, VF mean deviation [MD], presence of migraine, Raynaud's phenomenon, low blood pressure, and exfoliation syndrome) and intercurrent data (DH recurrence, fellow eye involvement, glaucoma surgery, and IOP reduction). Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for each variable. RESULTS: Seventy-six eyes (76 patients; mean age, 68.3+/-10.9 years) were enrolled. Mean IOP and VF MD at the time of the DH detection were 16.6+/-3.8 mmHg and -5.6+/-5.7 dB, respectively. The mean global progression rate after DH was -1.1+/-1.3 dB/year (mean follow-up, 3.8+/-2.8 years). A rate of progression of > or =1.5 dB/year was found in 20 (26%) eyes. Multivariate logistic regression analysis revealed larger baseline MD (OR, 1.11; 95% CI, 1.01-1.20; P = 0.03) and older age (OR, 1.06; 95% CI, 1.01-1.13; P = 0.04) to be significant risk factors for fast progression after DH. Eyes with a baseline MD worse than -4.0 dB had a 270% increased risk of fast progression compared with those with an MD better than -4.0 dB. CONCLUSIONS: The presence of a DH in older subjects with a worse VF predicted further VF global MD deterioration by more than 5 dB within 4 years. These eyes should undergo careful and frequent disease surveillance and consideration should be given to more aggressive treatment.

Repeatability of short-duration transient visual evoked potentials in normal subjects.

To evaluate the within-session and inter-session repeatability of a new, short-duration transient visual evoked potential (SD-tVEP) device on normal individuals, we tested 30 normal subjects (20/20 visual acuity, normal 24-2 SITA Standard VF) with SD-tVEP. Ten of these subjects had their tests repeated within 1-2 months from the initial visit. Synchronized single-channel EEG was recorded using a modified Diopsys Enfant System (Diopsys, Inc., Pine Brook, New Jersey, USA). A checkerboard stimulus was modulated at two reversals per second. Two different contrasts of checkerboard reversal patterns were used: 85% Michelson contrast with a mean luminance of 66.25 cd/m(2) and 10% Michelson contrast with a mean luminance of 112 cd/m(2). Each test lasted 20 s. Both eyes, independently and together, were tested 10 times (5 times at each contrast level). The following information was identified from the filtered N75-P100-N135 complex: N75 amplitude, N75 latency, P100 amplitude, P100 latency, and Delta Amplitude (N75-P100). The median values for each eye's five SD-tVEP parameters were calculated and grouped into two data sets based on contrast level. Mean age was 27.3 +/- 5.2 years. For OD only, the median (95% confidence intervals) of Delta Amplitude (N75-P100) amplitudes at 10% and 85% contrast were 4.6 uV (4.1-5.9) and 7.1 uV (5.15-9.31). The median P100 latencies were 115.2 ms (112.0-117.7) and 104.0 ms (99.9-106.0). There was little within-session variability for any of these parameters. Intraclass correlation coefficients ranged between 0.64 and 0.98, and within subject coefficients of variation were 3-5% (P100 latency) and 15-30% (Delta Amplitude (N75-P100) amplitude). Bland-Altman plots showed good agreement between the first and fifth test sessions (85% contrast Delta Amplitude (N75-P100) delta amplitude, mean difference, 0.48 mV, 95% CI, -0.18-1.12; 85% contrast P100 latency delay, -0.82 ms, 95% CI, -3.12-1.46; 10% contrast Delta Amplitude (N75-P100) amplitude, 0.58 mV, 95% CI, -0.27-1.45; 10% contrast P100 latency delay, -2.05 mV, 95% CI, -5.12-1.01). The inter-eye correlation and agreement were significant for both SD-tVEP amplitude and P100 latency measurements. For the subset of eyes in which the inter-session repeatability was tested, the intraclass correlation coefficients ranged between 0.71 and 0.86 with good agreement shown on Bland-Altman plots. Short-duration transient VEP technology showed good within-session, inter-session repeatability, and good inter-eye correlation and agreement.

Recurrent disc hemorrhage does not increase the rate of visual field progression.

AIMS: To determine whether recurrent disc hemorrhage (DH) accelerates glaucomatous visual field (VF) loss compared to an isolated, single, detected DH. METHODS: We evaluated the disc photographs of consecutive patients with >/=5 SITA-Standard fields for DH. Group A had patients with a single DH in one eye, and group B had at least one recurrence in the same eye. Automated pointwise linear regression analysis was used to calculate rates of progression. Logistic regression was used to determine ocular or systemic variables associated with DH recurrence after baseline assessment. RESULTS: One hundred and seventeen patients were enrolled (group A = 72, group B = 45). The mean age was 67.1 +/- 10.8 years; most patients were women (65%) of European ancestry (92%) diagnosed with primary open-angle glaucoma (47%). The mean number of VF after the initial DH was 7.9 +/- 2.9, spanning a mean of 4.6 +/- 2.2 years. None of the ocular or systemic characteristics revealed a significant difference between groups. The mean global rate of progression (group A, -0.8 +/- 0.6 vs group B, -0.8 +/- 0.7 dB/year, p = 0.93) and number of eyes reaching a progression endpoint (group A, 70% vs group B, 73%, p = 0.80) did not differ between groups. Recurrent DH eyes showed a tendency to be followed longer, with a greater number of disc photographs, which was not significant in the multivariate analysis. The global rates of progression between groups remained non-significant even after adjusting to follow-up time and number of VF tests (p = 0.69). CONCLUSION: Recurrent DH does not result in a faster rate of VF progression compared to a single detected DH. Eyes with single or recurrent DH have similar risks for future disease progression.