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.

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.

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.

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.

Relationship between optic disc hemorrhage and corneal hysteresis.

OBJECTIVE: To determine the relationship between optic disc hemorrhage (DH) and corneal hysteresis (CH). METHODS: Consecutive patients with prior or current photographic evidence of unilateral DH who had undergone CH measurement with the Ocular Response Analyzer (ORA; Reichert, Buffalo, NY) were enrolled. Eyes with a history of corneal disease, refractive surgery, or bilateral DH were excluded. Central corneal thickness (CCT), visual field data, 5 consecutive previous intraocular pressures (IOPs), and maximum documented peak IOP were obtained by chart review. Vertical cup-to-disc ratio (VCDR), the presence of neuroretinal rim notching, number of clock hours of beta zone parapapillary atrophy (ßPPA), and eye with greater ßPPA width were determined from photographs by 2 masked expert examiners. RESULTS: We identified and analyzed 49 patients with photographically documented unilateral DH. Compared to fellow non-DH eyes, eyes with DH had lower CH (8.7 ± 1.9 vs 9.2 ± 1.7; p = 0.002), higher IOP (15.6 ± 3.6 vs 14.3 ± 4.1; p = 0.017), and greater VCDR (0.79 ± 0.13 vs 0.68 ± 0.23; p < 0.001), but were similar with respect to CCT, ßPPA extent, rim notching, peak IOP, and visual field damage (all p > 0.05). Using multivariate conditional logistic regression analysis, only CH (p = 0.012) and VCDR (p = 0.004) predicted the laterality of the DH. CONCLUSIONS: Lower CH and greater VCDR are independently associated with DH. This suggests that CH may be a structural biomarker for an abnormality of the optic nerve complex that may be associated with progressive glaucoma. Eyes in which DH were detected had lower CH.

Outcomes of the Shunt Tube Exposure Prevention Study: A Randomized Clinical Trial.

PURPOSE: To compare the long-term safety and efficacy of amniotic membrane-umbilical cord (AM-UC) and pericardium patch grafts in reducing glaucoma shunt tube exposure. DESIGN: Multicenter, prospective, randomized clinical trial. PARTICIPANTS: Adults with uncontrolled glaucoma undergoing glaucoma drainage device (GDD) implantation. METHODS: Patients were randomized to receive GDD with either AM-UC or pericardium patch grafts to cover GDD tubes. Patients were followed up clinically with anterior segment (AS) OCT to assess patch graft stability and host-tissue integration prospectively. MAIN OUTCOME MEASURES: Tube exposure, graft thinning, and graft-related complications. RESULTS: A total of 81 eyes of 81 patients (50 women, 31 men) with a mean age of 67±13 years underwent GGD implantation using Baerveldt (n = 72) or Ahmed valve (n = 9). Tubes were inserted in the anterior chamber (n = 71), sulcus (n = 6), or pars plana (n = 4). Tube ligation was performed with Baerveldt GDD along with fenestration (n = 51) or orphan trabeculectomy (n = 21). Tubes were covered with AM-UC (n = 41) or pericardium (n = 40). The mean follow-up time was 29±8 months (range, 13-40 months). Tube exposure occurred in 1 eye (2%) in the AM-UC group at 3 months and in 2 eyes (5%) in the pericardium group at 2 and 6 months (P = 0.54). Sequential AS OCT showed better host-tissue integration and significantly less graft thinning in the AM-UC group. Early graft thinning (≤3 months) occurred in 5 eyes (12%) in the AM-UC group and in 17 eyes (43%) in the pericardium group (P = 0.002). Late thinning occurred in 2 eyes (5%) and 11 eyes (28%) in the AM-UC and pericardium groups, respectively (P = 0.007). Graft translucency and cosmetic appearance of the AM-UC graft were superior to those of the pericardium graft. No evidence of graft rejection or infection was associated with the patch grafts in either group. CONCLUSIONS: Amniotic membrane-umbilical cord grafts are well tolerated and offer an alternative to pericardium for safe and stable tube shunt coverage. Its high-tensile strength, low immunogenicity, and excellent host-tissue integration significantly reduced graft thinning.

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.

Glaucoma Diagnostic Capability of Circumpapillary Retinal Nerve Fiber Layer Thickness in Circle Scans With Different Diameters.

PURPOSE: To compare varying circumpapillary optical coherence tomographic (OCT) scan diameters for glaucoma diagnosis. MATERIALS AND METHODS: Prospective, cross-sectional, observational study. Circumpapillary retinal nerve fiber layer thickness (RNFLT) was measured using spectral-domain OCT in 1 randomly selected eye. Scans with diameters of 3.5, 4.1, and 4.7 mm were obtained, each with 7 parameters: mean global (G) RNFLT and mean RNFLT for the temporal-inferior (TI), nasal-inferior (NI), temporal-superior (TS), nasal-superior (NS), nasal (N), and temporal (T) sectors. Areas under the receiver operating characteristic curve (AUCs) were calculated. RESULTS: Mean age was 55±18 years in 68 healthy eyes and 59±15 years in 95 glaucomatous eyes (P=0.12). Visual field mean deviation was -7.55±6.61 dB in glaucomatous eyes. In all 3 circle scans, mean TI RNFLT had the greatest AUC (0.974 to 0.983), followed by mean G RNFLT (0.949 to 0.956). The AUC of mean TI RNFLT in the 4.1-mm scan (0.983) was greater than the AUCs of mean TI RNFLTs in the 4.7- (0.978; P=0.128) and 3.5-mm (0.974; P=0.049) scans. The AUC of mean TI RNFLT in the 4.1-mm scan (0.983) was greater than the AUCs of mean G RNFLTs in the 3.5- (0.954; P=0.011), 4.1- (0.956; P=0.016), and 4.7-mm (0.949; P=0.011) scans. In 2 eyes with large parapapillary atrophy, RNFL segmentation error was noted only in the 3.5-mm scan in the area of parapapillary atrophy. CONCLUSIONS: Further investigations to find the spectral-domain OCT circle scan diameter with the best diagnostic capability and the least artifacts are warranted, especially focusing on larger-than-conventional circle scans.

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.

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 Diagnostic Capability of Global and Regional Measurements of Isolated Ganglion Cell Layer and Inner Plexiform Layer.

PURPOSE: To compare glaucoma diagnostic capability of global/regional macular layer parameters in different-sized grids. MATERIALS AND METHODS: Serial horizontal spectral-domain optical coherence tomography scans of macula were obtained. Automated macular grids with diameters of 3, 3.45, and 6 mm were used. For each grid, 10 parameters (total volume; average thicknesses in 9 regions) were obtained for 5 layers: macular retinal nerve fiber layer (mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), ganglion cell-inner plexiform layer (GCIPL; GCL+IPL), and ganglion cell complex (GCC; mRNFL+GCL+IPL). RESULTS: Sixty-nine normal eyes (69 subjects) and 87 glaucomatous eyes (87 patients) were included. For the total volume parameter, the area under the receiver operating characteristic curves (AUCs) in 6-mm grid were larger than the AUCs in 3- and 3.45-mm grids for GCL, GCC, GCIPL, and mRNFL (all P<0.020). For the average thickness parameters, the best AUC in 6-mm grid (T2 region for GCL, IPL, and GCIPL; I2 region for mRNFL and GCC) was greater than the best AUC in 3-mm grid for GCL, GCC, and mRNFL (P<0.045). The AUC of GCL volume (0.920) was similar to those of GCC (0.920) and GCIPL (0.909) volume. The AUC of GCL T2 region thickness (0.942) was similar to those of GCC I2 region (0.942) and GCIPL T2 region (0.934) thickness. CONCLUSIONS: Isolated macular GCL appears to be as good as GCC and GCIPL in glaucoma diagnosis, while IPL does not. Larger macular grids may be better at detecting glaucoma. Each layer has a characteristic region with the best glaucoma diagnostic capability.

Lamina cribrosa depth in different stages of glaucoma.

PURPOSE: To compare lamina cribrosa (LC) depth between normal eyes and eyes with different stages of treated glaucoma. METHODS: Serial enhanced depth imaging (EDI) optical coherence tomography (OCT) B-scans of the optic nerve head were obtained. To generate the mean LC depth for each eye, LC depths were measured in 11 equally spaced horizontal B-scans and averaged. The mean LC depth was compared among normal, preperimetric, mild-to-moderate, and severe glaucoma groups. Among patients with visual field (VF) loss, correlation analysis was performed (1) between mean LC depth and VF mean deviation (MD), and (2) between mean LC depth and retinal nerve fiber layer (RNFL) thickness. RESULTS: Eighty-six normal eyes (age, 56 ± 14 years), 47 preperimetric glaucoma eyes (age, 60 ± 16 years), 55 mild-to-moderate glaucoma eyes (age, 59 ± 16 years; VF MD, -6.0 ± 3.2 dB), and 60 severe glaucoma eyes (age, 59 ± 17 years; VF MD, -19.7 ± 6.1 dB) were included. Mean LC depth was significantly greater in preperimetric glaucoma than in normal eyes (390 vs. 344 µm, P = 0.004) and in mild-to-moderate than in preperimetric glaucoma eyes (448 vs. 390 µm, P = 0.001). However, no significant difference was observed between mild-to-moderate and severe glaucoma eyes (448 vs. 437 µm, P = 0.52). No correlation was observed between LC depth and VF MD (P = 0.56) or RNFL thickness (P = 0.90) in glaucomatous eyes with VF loss. CONCLUSIONS: In treated glaucoma, posterior LC displacement occurs mostly in the preperimetric and mild-to-moderate glaucoma stages. This warrants further investigation of LC depth as a parameter to monitor glaucoma progression in the early stages.

Sensitivity and specificity of short-duration transient visual evoked potentials (SD-tVEP) in discriminating normal from glaucomatous eyes.

PURPOSE: To evaluate the ability of the short-duration transient visual evoked potential (SD-tVEP) to discriminate between healthy eyes and eyes with early to advanced glaucomatous visual field loss. METHODS: We tested 30 eyes of 30 healthy controls and 45 eyes of 35 glaucoma patients. Normal eyes had 20/30 or better visual acuity and normal 24-2 Swedish interactive thresholding algorithm (SITA) Standard visual fields. Glaucoma was staged as mild (mean deviation, MD > -6.0 dB), moderate (MD between -6.0 and -12.0 dB), and severe (MD < -12.0 dB). There were 15 eyes in each group. SD-tVEPs were recorded using the Diopsys NOVA-LX System. Each eye was stimulated with a low (Lc) and a high (Hc) Michelson contrast checkerboard pattern. Each test resulted in an Lc and an Hc SD-tVEP response. Each response was evaluated for overall waveform quality, P100 latency, and P100 amplitude referenced to the N75. The sensitivity, specificity, negative predictor value (NPV), and positive predictor value (PPV) were calculated. RESULTS: Lc latency showed the highest accuracy for discrimination using receiver operating characteristic curves for high and low contrast parameters. The analysis for all subjects resulted in a 91.1% sensitivity, 93.3% specificity, 95.3% PPV, and an 87.5% NPV. Evaluating the mean Lc latency of the mild, moderate, and severe glaucoma patients against controls showed discrimination consistent with the glaucoma severity. CONCLUSIONS: Short-duration transient VEP objectively identified decreased visual function and discriminated between healthy and glaucomatous eyes, and also showed good differentiation between healthy eyes and those with early visual field loss. VEP may be useful for early diagnosis of glaucoma.

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.

Optic disc progression and rates of visual field change in treated glaucoma.

PURPOSE: To investigate the relationship between optic disc progression and rates of visual field (VF) change in patients with treated glaucoma. METHODS: Glaucoma patients with repeatable VF loss, ≥8 SITA-Standard 24-2 VF tests and good quality optic disc stereophotographs evaluated over a 10-year period were included. Optic disc photographs were reviewed for signs of glaucoma progression (neuroretinal rim change, widening of retinal nerve fibre layer defect, disc haemorrhage and enlargement of beta-zone parapapillary atrophy) by two glaucoma specialists masked to their temporal sequence. Disagreements were adjudicated by a third grader. VF progression was evaluated using automated pointwise linear regression (PLR) and defined as at least two adjacent test points progressing >1.0 dB/year at p < 0.01. VF progression outcomes were compared with photograph review results. RESULTS: Three-hundred and eighty nine eyes (389 patients; mean age 64.9 ± 13.0 years; mean baseline MD, -7.1 ± 5.1 dB) were included. Most patients had primary open angle glaucoma (54%). Eighty-two eyes (21%) had confirmed optic disc progression and 115 eyes (29%) met the VF PLR criteria. Eyes with documented optic disc progression had more rapid rates of VF change (-0.66 ± 0.7 versus -0.36 ± 0.7 dB/year, p < 0.01) and met the VF PLR endpoint more often (univariate OR = 1.85, p = 0.02; multivariate OR = 1.78, p = 0.03) than eyes without optic disc progression. There was moderate spatial consistency between the location of the optic disc progression and the hemifield with more rapid progression (81%, kappa = 0.40). CONCLUSIONS: Treated glaucomatous eyes with documented optic disc progression are at increased risk of diminished visual function over time and may require more aggressive therapy to prevent future vision loss. Among the indicators of structural progression, disc haemorrhage was the single most significant predictor for VF deterioration.