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PURPOSE To characterize the in vivo effect of cyclopentolate on the microstructure of Schlemm canal (SC) in healthy eyes. METHODS For healthy subjects, 81 serial horizontal enhanced depth imaging optical coherence tomography B-scans (interval between scans, ∼35 μm) of the nasal corneoscleral limbal area were obtained before and 1 hour after cyclopentolate 1% administration in 1 eye. The structures of aqueous and blood vessels in each scan were used as landmarks to select 50 overlapping scans between the 2 sets of 81 serial scans (before and after cyclopentolate administration). The SC cross-sectional area was measured in each of the 50 selected scans. After 3-dimensional reconstruction, SC volume was determined. RESULTS Twelve eyes (12 healthy subjects) were imaged successfully before and after cyclopentolate administration. Mean age was 27.8±4.9 years (range, 25 to 38 y). Following cyclopentolate administration, mean intraocular pressure did not change significantly (13.9±1.5 to 14.2±1.5 mm Hg; P=0.19). Mean SC cross-sectional area decreased by 17%, from 3563±706 to 2959±460 μm (P

PURPOSE The purpose of this study was to assess the relationship between the rate of the glaucomatous visual field (VF) worsening and baseline age and baseline VF mean deviation (MD). DESIGN This study was a retrospective, multisite cohort. PARTICIPANTS A total of 84,711 reliable Swedish Interactive Thresholding Algorithm 24-2 VF tests from 8167 eyes from 5644 patients with ≥6 VF tests, ≥5 years of follow-up, baseline age 18 years or above and baseline MD ≥-10 dB, and at least 2 abnormal VF tests were included from the Glaucoma Research Network Database. METHODS The global mean deviation rates (MDRs) and pointwise total deviation rates (TDRs) of VF progression (dB/y) were calculated for each eye using linear regression. The relationships between MDR and baseline age and MD were determined using linear mixed-effects models and logistic regression, with rapid progression defined as an MDR≤-1.0 dB/y. The relationships between TDR and baseline age and baseline MD were determined using linear mixed-effects models. MAIN OUTCOME MEASURES Coefficients of the regression models. RESULTS In individual mixed-effects models both baseline age (β=-0.0079 dB/y; P

PurposeTo develop and evaluate a deep learning system for differentiating between eyes with and without glaucomatous visual field damage (GVFD) and predicting the severity of GFVD from spectral domain OCT (SDOCT) optic nerve head images.DesignEvaluation of a diagnostic technology.ParticipantsA total of 9765 visual field (VF) SD OCT pairs collected from 1194 participants with and without GVFD (1909 eyes).MethodsDeep learning models were trained to use SD OCT retinal nerve fiber layer (RNFL) thickness maps, RNFL en face images, and confocal scanning laser ophthalmoscopy (CSLO) images to identify eyes with GVFD and predict quantitative VF mean deviation (MD), pattern standard deviation (PSD), and mean VF sectoral pattern deviation (PD) from SD OCT data.Main outcome measuresDeep learning models were compared with mean RNFL thickness for identifying GVFD using area under the curve (AUC), sensitivity, and specificity. For predicting MD, PSD, and mean sectoral PD, models were evaluated using R2 and mean absolute error (MAE).ResultsIn the independent test dataset, the deep learning models based on RNFL en face images achieved an AUC of 0.88 for identifying eyes with GVFD and 0.82 for detecting mild GVFD significantly (P < 0.001) better than using mean RNFL thickness measurements (AUC= 0.82 and 0.73, respectively). Deep learning models outperformed standard RNFL thickness measurements in predicting all quantitative VF metrics. In predicting MD, deep learning models based on RNFL en face images achieved an R2 of 0.70 and MAE of 2.5 decibels (dB) compared with 0.45 and 3.7 dB for RNFL thickness measurements. In predicting mean VF sectoral PD, deep learning models achieved high accuracy in the inferior nasal (R2= 0.60) and superior nasal (R2= 0.67) sectors, moderate accuracy in inferior (R2= 0.26) and superior (R2= 0.35) sectors, and lower accuracy in the central (R2=0.15) and temporal (R2= 0.12) sectors.ConclusionsDeep learning models had high accuracy in identifying eyes with GFVD and predicting theseverity of functional loss from SD OCT images. Accurately predicting the severity of GFVD from SD OCT imaging can help clinicians more effectively individualize the frequency of VF testing to the individual patient.

PURPOSE To examine the frequency of paravascular defects (PDs) and macular epiretinal membranes (ERMs) in eyes categorized as having mild glaucoma or glaucoma suspect using en-face slab analysis of optical coherence tomography (OCT) scans. MATERIALS AND METHODS Fifty-seven glaucomatous eyes, 44 low-risk suspect eyes, and 101 healthy control eyes were included in the study. The 101 glaucomatous and suspect eyes had a mean deviation better than -6 dB on the 24-2 visual field, and a spherical refractive error between±6 D or axial length

Author(s): Yang, Hongli; Luo, Haomin; Gardiner, Stuart K; Hardin, Christy; Sharpe, Glen P; Caprioli, Joseph; Demirel, Shaban; Girkin, Christopher A; Liebmann, Jeffrey M; Mardin, Christian Y; Quigley, Harry A; Scheuerle, Alexander F; Fortune, Brad; Chauhan, Balwantray C; Burgoyne, Claude F | Abstract: Purpose:To quantify peripapillary choroidal thickness (PCT) and the factors that influence it in healthy participants who represent the racial and ethnic composition of the U.S. population. Methods:A total of 362 healthy participants underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head with a 24 radial B-scan pattern aligned to the fovea to Bruch's membrane opening axis. Bruch's membrane, anterior scleral canal opening (ASCO), and the anterior scleral surface were manually segmented. PCT was measured at 100, 300, 500, 700, 900, and 1100 μm from the ASCO globally and within 12 clock-hour sectors. The effects of age, axial length, intraocular pressure, ethnicity, sex, sector, and ASCO area on PCT were assessed by ANOVA and univariable and multivariable regressions. Results:Globally, PCT was thicker further from the ASCO border and thinner with older age, longer axial length, larger ASCO area, European descent, and female sex. Among these effectors, age and axial length explained the greatest proportion of variance. The rate of age-related decline increased further from the ASCO border. Sectorally, the inferior-temporal sectors were thinnest (10.7%-20.0% thinner than the thickest sector) and demonstrated a higher rate of age-related loss (from 15.6% to 20.7% faster) at each ASCO distance. Conclusions:In healthy eyes, PCT was thinnest in the inferior temporal sectors and thinner PCT was associated with older age, European descent, longer axial length, larger ASCO area, and female sex. Among these associations, age had the strongest influence, and its effect was greatest within the inferior temporal sectors.

PurposeTo assess anterior scleral canal opening (ASCO) offset relative to Bruch's membrane opening (BMO) (ASCO/BMO offset) so as to determine neural canal direction, obliqueness, and minimum cross-sectional area (NCMCA) in 362 healthy eyes.DesignCross-sectional study.MethodsAfter optical coherence tomography optic nerve head and retinal nerve fiber layer thickness (RNFLT) imaging, BMO and ASCO were manually segmented. Planes, centroids, size, and shape were calculated. Neural canal direction was defined by projecting the neural canal axis vector (connecting BMO and ASCO centroids) onto the BMO plane. Neural canal obliqueness was defined by the angle between the neural canal axis and the BMO plane perpendicular vector. NCMCA was defined by projecting BMO and ASCO points onto a neural canal axis perpendicular plane and measuring the area of overlap. The angular distance between superior and inferior peak RNFLT was measured, and correlations between RFNLT, BMO, ASCO, ASCO/BMO offset, and NCMCA were assessed.ResultsMean (SD) NCMCA was significantly smaller than either the BMO or ASCO area (1.33 (0.42), 1.82 (0.38), 2.22 (0.43) mm2, respectively), and most closely correlated to RNFLT (P < .001, R2= 0.158). Neural canal direction was most commonly superior-nasal (55%). Mean neural canal obliqueness was 39.4° (17.3°). The angular distance between superior and inferior peak RNFLT correlated to neural canal direction (P ≤ .008, R2= 0.093).ConclusionsASCO/BMO offset underlies neural canal direction, obliqueness, and NCMCA. RNFLT is more strongly correlated to NCMCA than to BMO or ASCO, and its peripapillary distribution is influenced by neural canal direction.

Patients with open-angle glaucoma manifest a chronic, idiopathic disease associated with progressive degeneration of the anterior optic nerve, known as glaucomatous optic neuropathy. Although elevated intraocular pressure is an important causative risk factor, only about half of the three million North Americans with glaucoma will manifest elevated intraocular pressure at a single measurement. Therefore, measurement of intraocular pressure alone is a poor screening technique for glaucoma. Like most biologic parameters, eye pressure fluctuates diurnally and with other endogenous and exogenous influences, including hydration, sleep, blood pressure, and body position. With multiple measurements at different testing sessions, many, but not all of these glaucoma subjects, will eventually exhibit elevated intraocular pressure at least part of the time.

Glaucoma is a chronic neurodegenerative disease of the optic nerve and a leading cause of irreversible blindness, worldwide. While the experimental research using animal models provides growing information about cellular and molecular processes, parallel analysis of the clinical presentation of glaucoma accelerates the translational progress towards improved understanding, treatment, and clinical testing of glaucoma. Optic nerve axon injury triggers early alterations of retinal ganglion cell (RGC) synapses with function deficits prior to manifest RGC loss in animal models of glaucoma. For testing the clinical relevance of experimental observations, this study analyzed the functional correlation of localized alterations in the inner plexiform layer (IPL), where RGCs establish synaptic connections with retinal bipolar and amacrine cells. Participants of the study included a retrospective cohort of 36 eyes with glaucoma and a control group of 18 non-glaucomatous subjects followed for two-years. The IPL was analyzed on consecutively collected macular SD-OCT scans, and functional correlations with corresponding 10–2 visual field scores were tested using generalized estimating equations (GEE) models. The GEE-estimated rate of decrease in IPL thickness (R = 0.36, P0.05). These findings support early localized IPL alterations in correlation with progressing visual field defects in glaucomatous eyes. Considering the experimental data, glaucoma-related increase in IPL thickness/density might reflect dendritic remodeling, mitochondrial redistribution, and glial responses for synapse maintenance, but decreased IPL thickness/density might correspond to dendrite atrophy. The bridging of experimental data with clinical findings encourages further research along the translational path.

To evaluate visual outcomes and complications after Descemet stripping automated endothelial keratoplasty (DSAEK) in patients with previous glaucoma surgery.A retrospective chart review was conducted of 129 procedures in 102 eyes of 96 patients who underwent DSAEK and previous glaucoma surgery at New York Eye and Ear Infirmary of Mt Sinai. The mean length of follow-up was 29.1 ± 25.5 months. Patients with postoperative follow-up duration of less than 3 months were excluded from analysis. Intraoperative and postoperative complications, postoperative course, and visual outcomes were analyzed.Graft dislocation occurred in 46 eyes (35.7%) and 38 eyes required repeat injection of air in the anterior chamber. Primary graft failure occurred in 3 eyes (2.3%), early graft failure in 20 eyes (15.5%), and secondary graft failure developed in 29 eyes (22.5%). There was a statistically significant increase in secondary graft failure in patients with previous aqueous shunt implantation compared with eyes with previous trabeculectomy (P = 0.03). Escalation of glaucoma therapy was needed medically in 25 eyes (24.5%), and 8 eyes (7.8%) required additional surgical intervention.There is a significant incidence of graft dislocation and graft failure after DSAEK in eyes with previous glaucoma surgery. In particular, aqueous shunt surgery compared with trabeculectomy may decrease long-term graft survival, and close follow-up is warranted.

Recent advances in glaucoma diagnosis focus on diagnosing the disease in early stages. Despite the importance of such efforts, a meaningful proportion of patients present in advanced stages. The cost for treatment and monitoring of advanced glaucoma often exceeds that with earlier disease, not to mention the significant effect of visual impairment on quality of life. Moreover, structural and functional tests used to monitor changes encounter technical limitations in advanced cases that can delay detection of true progression. New technologies and methods to analyze longitudinal data may prove helpful for monitoring patients with advanced glaucoma and reduce the burdens of the disease.

Purpose To investigate the differences in the frequency of optic disc hemorrhage (DH) and prevalence of beta-zone parapapillary atrophy (βPPA) between individuals of African descent (AD) and European descent (ED). Design Prospective, multicenter, observational cohort. Participants A total of 1950 eyes of 1172 participants of the African Descent and Glaucoma Evaluation Study (ADAGES). Methods Stereoscopic disc photographs of subjects with and without glaucomatous optic neuropathy (GON) followed during the first 13 years of the ADAGES underwent masked review searching for DH and βPPA. A total of 928 eyes (non-GON, 581; GON, 347) of 551 AD patients (non-GON, 334; GON, 217) and 1022 eyes (non-GON, 568; GON, 454) of 611 ED patients (non-GON, 334; GON, 277) were included. We compared the number of eyes with detected DH at any time during follow-up and eyes with βPPA between the AD and ED groups. The analyses were then adjusted for clinical parameters using multivariable logistic regression. Main Outcome Measures Differences in frequency of DH and prevalence of βPPA. Results A total of 9395 stereoscopic disc photographs were reviewed. More ED eyes experience DH than AD eyes (49/1022 [4.8%] vs. 10/928 eyes [1.1%], respectively; P P P P = 0.008). Conclusions Subjects of ED are at higher risk for developing DH compared with AD subjects, whereas AD subjects have greater prevalence of βPPA. These findings suggest that there are structural differences within the optic nerve complex between these groups. Further research is needed to determine whether racial differences in the frequency of DH and prevalence of βPPA affect the likelihood of glaucomatous progression.

Purpose To compare the diurnal intraocular pressure (IOP)-lowering effect of latanoprostene bunod (LBN) ophthalmic solution 0.024% every evening (qpm) with timolol maleate 0.5% twice daily (BID) in subjects with open-angle glaucoma (OAG) or ocular hypertension (OHT). Design Phase 3, randomized, controlled, multicenter, double-masked, parallel-group clinical study. Participants Subjects aged ≥18 years with a diagnosis of OAG or OHT in 1 or both eyes. Methods Subjects were randomized (2:1) to a 3-month regimen of LBN 0.024% qpm or timolol 0.5% 1 drop BID. Intraocular pressure was measured at 8 am, 12 pm, and 4 pm of each postrandomization visit (week 2, week 6, and month 3). Adverse events were recorded throughout the study. Main Outcome Measures The primary efficacy end point was IOP in the study eye measured at each of the 9 assessment time points. Secondary efficacy end points included the proportion of subjects with IOP ≤18 mmHg consistently at all 9 time points and the proportion of subjects with IOP reduction ≥25% consistently at all 9 time points. Results Of 420 subjects randomized, 387 completed the study (LBN 0.024%, n = 264; timolol 0.5%, n = 123). At all 9 time points, the mean IOP in the study eye was significantly lower in the LBN 0.024% group than in the timolol 0.5% group ( P ≤ 0.002). At all 9 time points, the percentage of subjects with mean IOP ≤18 mmHg and the percentage with IOP reduction ≥25% were significantly higher in the LBN 0.024% group versus the timolol 0.5% group (mean IOP ≤18 mmHg: 22.9% vs. 11.3%, P = 0.005; IOP reduction ≥25%: 34.9% vs. 19.5%, P = 0.001). Adverse events were similar in both treatment groups. Conclusions In this phase 3 study, LBN 0.024% qpm demonstrated significantly greater IOP lowering than timolol 0.5% BID throughout the day over 3 months of treatment. Latanoprostene bunod 0.024% was effective and safe in these adults with OAG or OHT.

Purpose To investigate the efficacy of the Amsler grid test in detecting central visual field (VF) defects in glaucoma. Design Prospective, cross-sectional study. Participants Patients with glaucoma with reliable Humphrey 10-2 Swedish Interactive Threshold Algorithm standard VF on the date of enrollment or within the previous 3 months. Methods Amsler grid tests were performed for each eye and were considered "abnormal" if there was any perceived scotoma with missing or blurry grid lines within the central 10 degrees ("Amsler grid scotoma"). An abnormal 10-2 VF was defined as ≥3 adjacent points at P 0.01 with at least 1 point at P 0.005 in the same hemifield on the pattern deviation plot. Sensitivity, specificity, and positive and negative predictive values of the Amsler grid scotoma area were calculated with the 10-2 VF as the clinical reference standard. Among eyes with an abnormal 10-2 VF, regression analyses were performed between the Amsler grid scotoma area and the 10-2 VF parameters (mean deviation [MD], scotoma extent [number of test points with P 0.01 in total deviation map] and scotoma mean depth [mean sensitivity of test points with P 0.01 in total deviation map]). Main Outcome Measures Sensitivity, specificity, and positive and negative predictive values of the Amsler grid scotoma area. Results A total of 106 eyes (53 patients) were included (mean ± standard deviation age, 24-2 MD and 10-2 MD = 66±12 years, −9.61±8.64 decibels [dB] and −9.75±9.00 dB, respectively). Sensitivity, specificity, and positive and negative predictive values of the Amsler grid test were 68%, 92%, 97%, and 46%, respectively. Sensitivity was 40% in eyes with 10-2 MD better than −6 dB, 58% in eyes with 10-2 MD between −12 and −6 dB, and 92% in eyes with 10-2 MD worse than −12 dB. The area under the receiver operating characteristic curve of the Amsler grid scotoma area was 0.810 (95% confidence interval, 0.723–0.880, P 0.001). The Amsler grid scotoma area had the strongest relationship with 10-2 MD (quadratic R 2 =0.681), followed by 10-2 scotoma extent (quadratic R 2 =0.611) and 10-2 scotoma mean depth (quadratic R 2 =0.299) (all P 0.001). Conclusions The Amsler grid can be used to screen for moderate to severe central vision loss from glaucoma.

Purpose To test the hypothesis that a 24-hour recording of intraocular pressure (IOP)-related measurements derived from a contact lens sensor (CLS) correlates to the rate of visual field progression in treated glaucomatous eyes. Design Prospective, cross-sectional study. Participants Forty treated glaucomatous patients with 8 or more 24-2 visual field tests. Methods Twenty-four–hour recording with a CLS that provides IOP-related measurements. Main Outcome Measures Rates of visual field mean deviation (MD) change before and at the time of CLS recording and CLS parameters, namely number of large peaks, mean peak ratio, wake-to-sleep slope, amplitude and area under the cosine curve, and variability from the mean. Results When comparing the rate of MD change before and at the time of CLS recording of all patients, the average slope was −0.05 dB/year faster in the beginning compared with the end ( P = 0.087), suggesting a deceleration of progression by the time of CLS recording. The number of long peaks and the mean peak ratio when patients were awake were the best predictors of faster progression. The combination of CLS parameters provided better measures of goodness of fit than Goldmann IOP parameters (mean, peak, and fluctuation) in the same period. Conclusions Intraocular pressure-related parameters obtained with 24-hour recording with a CLS were associated with the rate of visual field progression in treated glaucomatous eyes. This technology may be useful in detecting eyes at higher risk of glaucoma progression while receiving treatment.

PurposeTo compare race-related differences in estimated rate of change of Bruch's membrane opening-minimum rim width (BMO-MRW) and circumpapillary retinal nerve fiber layer thickness (RNFLT) in healthy, glaucoma suspect, and glaucoma eyes of individuals of European (ED) and African descent (AD).DesignProspective cohort study.MethodsThis study investigated rate of change of BMO-MRW and RNFLT in 124 healthy, 227 glaucoma suspect, and 177 glaucoma eyes followed for approximately 3 years and tested with optical coherence tomography every 6months. Suspect eyes had a history of untreated intraocular pressure (IOP) ≥ 22mm Hg or suspicion of glaucoma by optic disc photograph assessment without repeatable abnormal standard automated perimetry (SAP) results. Glaucoma eyes had repeatable abnormal SAP results (GHT ONL or PSD ≤ 5%). Mixed-effects models were used to estimate the rate of change after controlling for age, mean follow-up IOP, central corneal thickness, axial length, and BMO area.ResultsA race-related difference in rate of change of global BMO-MRW but not average RNFLT in suspect eyes was observed. Rate of change of BMO-MRW was-1.82μm/year and-2.20μm/year in ED and AD suspect eyes, respectively (P= .03). Rate of change of RNFLT was-0.64μm/year and-0.75μm/year in ED and AD suspect eyes, respectively (P= .75). No race-related differences in change rate were found in healthy or glaucoma eyes.ConclusionRace is an important consideration when assessing structural change, particularly minimum rim width, in glaucoma suspect eyes. Differences in rate of structural change may help explain racial disparities in glaucoma susceptibility.

PURPOSE To compare the effects of laser iridotomy (LI) and pilocarpine on iridocorneal angle and anterior chamber structure in anatomically narrow angles (ANAs). MATERIALS AND METHODS Temporal LI was performed 90 minutes after 2% pilocarpine administration in patients with occludable ANA. Swept-source optical coherence tomography B-scans of the anterior segment were obtained at baseline, 60 minutes after 2% pilocarpine administration, and 1 week after LI. Angle-opening distance (AOD), trabecular-iris surface area (TISA), and angle recess area (ARA) were measured at the temporal, superior, nasal, and inferior quadrants. Anterior chamber depth (ACD) and lens vault (LV) were also measured. AOD, TISA, ARA, ACD, and LV were compared among 3 time points: at baseline, 60 minutes after 2% pilocarpine administration, and 1 week after LI. RESULTS Twenty-four eyes (24 patients; mean age, 55 y) were included. In all 4 quadrants and globally, AOD, TISA, and ARA increased from baseline after pilocarpine and after LI (all P

PURPOSE:To evaluate whether automated assessment of beta zone parapapillary atrophy (βPPA) area can differentiate between glaucomatous and healthy eyes of varying axial lengths (AL). DESIGN:Cross-sectional study. METHODS:βPPA was automatically identified in glaucoma and healthy eyes with enhanced-depth imaging optical coherence tomography (OCT) optic nerve head (ONH) radial B-scans. Associations with AL and the presence of glaucoma were assessed. Manually delineated βPPA on individual OCT ONH B-scans of 35 eyes from the Diagnostic Innovations in Glaucoma Study served to validate the automated method. RESULTS:One hundred fifty-three glaucoma eyes (mean ± standard deviation) (visual field mean deviation, -5.0 ± 6.4 dB and mean AL, 25.1 ± 1.1mm) and 73 healthy eyes (visual field mean deviation, 0.1 ± 1.4 dB and mean AL, 24.1 ± 1.1mm) were included. In multivariable analysis, larger βPPA area was significantly associated with a diagnosis of glaucoma after controlling for age, central corneal thickness, and AL. Moreover, in multivariable analysis, the odds of having glaucoma were doubled for each 0.2mm2 larger βPPA area. The age- and AL-adjusted area under the receiver operating characteristic curve (95% confidence interval) of βPPA area for differentiating between glaucoma and healthy eyes was 0.75 (0.68-0.81). Agreement for the location of the Bruch membrane opening and the location of retinal pigment epithelium tips was stronger between the automated technique and each individual observer than it was between the 2 observers. CONCLUSIONS:Larger βPPA area, as determined by automated OCT assessment, is significantly associated with a diagnosis of glaucoma, even after adjusting for age and AL, and may aid in differentiating healthy from glaucomatous eyes.

Importance Twenty-four–hour intraocular pressure (IOP) patterns may provide more information regarding rates of visual field progression than office-hour measurements. However, little is known about the added value of 24-hour monitoring when stratifying glaucoma risk based on rates of progression. Objective To test the hypothesis that 24-hour IOP-related patterns recorded with a contact lens sensor (CLS) correlate with prior rates of visual field progression. Design, Setting, and Participants A multicenter, retrospective cohort study was conducted at 50 ophthalmology care centers in 13 countries. Participants included 445 patients (445 eyes) with treated, manifest open-angle glaucoma. The study was conducted from November 8, 1999, to September 17, 2016. Interventions Twenty-four–hour recordings of IOP-related patterns were prospectively collected with a CLS system. Retrospective visual field data of patients who underwent at least 3 prior reliable visual field tests were examined. Main Outcomes and Measures Association between CLS variables and rates of visual field mean deviation (MD) change. Results Of the 445 patients included, 238 (53.5%) were women and 394 (88.5%) were white. The mean (SD) age and MD values at the time of CLS recording were 68.9 (11.2) years and −9.0 (7.0) dB. The mean rate of MD change was −0.46 (0.5) dB/y in 5.2 (3) years of follow-up. After adjusting for baseline MD severity, age, and treatment, the following CLS variables were associated with fast visual field progression: mean peak ratio while awake (β = −0.021; 95% CI, −0.04 to −0.003), number of long peaks during sleep (β = 0.036; 95% CI, 0.005 to 0.067), night bursts ocular pulse frequency SD (β = 0.027; 95% CI, 0.004 to 0.051), and night bursts ocular pulse amplitude SD (β = 19.739; 95% CI, 1.333 to 38.145). Regression models including CLS variables had better fit than Goldmann IOP when testing the association with rates of progression. Conclusions and Relevance Results of this study indicate that 24-hour CLS recordings may be associated with prior rates of visual field progression of glaucoma. This association appears to be better than Goldmann mean IOP measured multiple times during office hours. Therefore, the CLS may be useful to assess the risk of future functional loss, even in situations when insufficient historical visual field information is available.

Purpose:To quantify the influence of ocular and demographic factors on central laminar depth (LD) in healthy participants. Methods:A total of 362 normal subjects underwent optical coherence tomography (OCT) enhanced depth imaging of the optic nerve head (ONH) with a 24 radial B-scan pattern aligned to the fovea-to-Bruch's membrane opening (BMO) axis. BMO, anterior lamina, anterior scleral canal opening (ASCO), Bruch's membrane (BM), and the peripapillary scleral surface were manually segmented. The extent of laminar segmentation was quantified within 72 ASCO subsectors. Central LD was quantified relative to four reference planes: BMO, ASCO, BM, and scleral. The effects of age, sex, ethnicity, IOP, BMO area, ASCO area, and axial length on LD were assessed. Results:Laminar visibility was most consistent within the central ASCO (median 89%, range, 69%-95%). LDBMO and LDBM were significantly shallower in eyes with greater age, BMO area, and axial length and in females. LDASCO was shallower in eyes with greater ASCO area and axial length and in European and Hispanic descent compared to African descent eyes. LDSclera behaved similarly, but was not associated with axial length. BMO and ASCO area were not different between African descent and European descent eyes. Conclusions:Central LD was deeper in African descent eyes and influenced least by age, axial length, and sex, but more by ASCO area, when measured relative to the ASCO and sclera. However, the magnitude of these effects for all four reference planes was small, and their clinical importance in the detection of glaucoma and its progression remains to be determined.

PurposeCentral visual field (VF) damage in glaucoma patients can significantly hinder daily activities. The present study investigates whether the presence of localized baseline damage to the central 10 degrees of the VF is predictive of faster global mean deviation (MD) progression.DesignProspective cohort study.MethodsEyes from the multicenter African Descent and Glaucoma Evaluation Study (ADAGES) with established glaucoma and VF loss and a minimum of 5 24-2 VFs were eligible. Baseline central 24-2 damage was defined as any of the 12 central-most points with total deviation (TD) values at P < 0.5% on 2 consecutive examinations. Progression was determined using trend-based and event-based criteria: (1) rates of MD change significantly faster than zero and (2) >-5 dB MD loss over the entire follow-up.ResultsA total of 827 eyes of 584 patients were studied. Mean rate of MD change of the entire sample was-0.15 dB/year (95% CI:-0.19 to-0.12, P&nbsp

PURPOSE: To describe the study protocol and baseline characteristics of the “African Descent and Glaucoma Evaluation Study (ADAGES) III: Contribution of Genotype to Glaucoma phenotype in African Americans”. DESIGN: Cross-sectional, case-control study PARTICIPANTS: There were 3266 glaucoma patients and controls without glaucoma of African or European descent recruited from five 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 subjects 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 controls are 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 controls and 227 ED controls. AD POAG patients and controls were significantly younger (both 67.4 years) than ED POAG patients and controls (73.4 and 70.2 years, respectively). After adjusting for age, AD POAG patients had different phenotypic characteristics compared to ED POAG patients, including higher intraocular pressure, worse visual acuity and visual field mean deviation, and thinner corneas (all p

To evaluate the effectiveness and safety of oral memantine as a potential neuroprotective agent in open-angle glaucoma (OAG) at risk for progression.Two randomized, double-masked, placebo-controlled, parallel-group, multicenter, 48-month studies identically designed, initiated 1 year apart, and completed in 2006. Protocol amendments included a 1-year extension (first study) and change in primary endpoint and analysis (second study).Patients (2298 total) with bilateral OAG; glaucomatous optic disc damage and visual field loss in 1 eye; glaucomatous optic disc damage and/or visual field loss in the contralateral eye (at screening), topically treated or untreated intraocular pressure (IOP) of 21 mmHg or less (at baseline); and at risk of glaucomatous progression (per prespecified criteria).Patients were randomized 3:2:2 to receive memantine 20 mg, memantine 10 mg, or placebo tablets daily. Glaucomatous progression was assessed in the intent-to-treat population by full-threshold standard automated perimetry (SAP), frequency doubling technology (FDT), and stereoscopic optic disc photographs, standardized by quality control assessment at centralized reading centers. Safety evaluations included adverse events (AEs), best-corrected visual acuity, biomicroscopy, IOP, and ophthalmoscopy. Efficacy data from each study were analyzed per protocol. Pooled analyses of efficacy and safety data were also performed.The predefined primary efficacy measure was glaucomatous visual field progression, as measured by SAP. Additional efficacy measures included glaucomatous progression of visual field (FDT) and optic nerve damage (stereoscopic optic disc photographs).The proportion of patients who completed the studies was similar among groups (80%-83%). Compared with placebo, daily treatment with memantine 10 mg or 20 mg for 48 months did not delay glaucomatous progression significantly in the individual studies and pooled analyses. The pooled risk reduction ratio (95% confidence interval) assessed by SAP was -0.13 (-0.40, 0.09) and -0.17 (-0.46, 0.07) for memantine 10 mg and 20 mg, respectively. Results were similar per FDT and stereoscopic optic disc photographs. The most common AEs leading to treatment discontinuations were dizziness, headache, fatigue, and nausea.With technologies available when the studies were conducted, daily treatment with memantine over 48 months was not shown to prevent glaucomatous progression in this patient population.

Purpose To investigate the relationship between previous disc hemorrhage (DH) and subsequent rates of retinal nerve fiber layer (RNFL) thinning. Design Longitudinal, observational cohort study. Participants Twenty-eight patients with glaucoma and patients with suspected glaucoma who had a history of DH in 1 eye (unilateral DH), but not in the fellow eye, enrolled in the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study were included. Methods All subjects underwent annual optic disc photography and semiannual spectral-domain OCT RNFL thickness measurements. Multivariable linear mixed-effects models were used to investigate the relationship between the presence of previous DH and RNFL thinning rates while adjusting for potential confounding factors, such as race, age, mean intraocular pressure (IOP), baseline disease severity, and central corneal thickness (CCT). The relationship between the timing of DH and the rates of RNFL thinning also was investigated in eyes with a history of DH. Main Outcome Measures Rates of global and local RNFL thinning. Results Previous DH was significantly associated with faster RNFL thinning rates globally (−0.39 μm/year faster, P = 0.010), in DH quadrants (−0.77 μm/year faster, P = 0.012), and non-DH quadrants (−0.49 μm/year faster, P = 0.038) after adjustment for race, mean IOP, baseline age, baseline standard automated perimetry mean deviation, and CCT. Higher IOP was also significantly associated with faster thinning rates globally (−0.07 μm/year faster per 1 mmHg higher, P = 0.047) and in DH quadrants (−0.10 μm/year faster per 1 mmHg higher, P = 0.044). In eyes with a history of DH, the time elapsed from the latest DH episode to the first OCT examination was not significantly associated with the rate of RNFL thinning. Conclusions A history of DH is an independent risk factor for faster rates of RNFL thinning in non-DH quadrants and in DH quadrants; this risk is present even in eyes that exhibited DH several years earlier.

Precis:In this retrospective case series of 85 eyes, 31.8% developed graft failure and graft survival was 50% at 3 years. The presence of an aqueous shunt has a significantly adverse effect on long-term graft survival.Purpose:To report visual outcomes and complications of Descemet stripping endothel

Primary open angle glaucoma (POAG) is the most common type of glaucoma, and is responsible for approximately 90% of glaucoma cases in North America. POAG is characterized by an asymptomatic onset, where patients do not present with symptoms until significant visual loss occurs in late stages of the disease. Importantly, while glaucoma is associated with several risk factors that contribute to damage and disease progression, intraocular pressure (IOP) is the only proven modifiable risk factor at this time. Treatments for POAG include use of pharmacologic and surgical interventions. As of this writing, available pharmacologic options reduce IOP through reduction of aqueous humor production or by facilitating aqueous humor drainage through the uveoscleral outflow pathway (the unconventional pathway). Although cholinergic agonists (eg, pilocarpine) indirectly targets aqueous humor draining through the trabecular meshwork/Schlemm's canal (the conventional outflow pathway), cholinergic agonists are not frequently used, and as of this writing, no agents are currently available that target both the conventional and unconventional outflow pathways. Therapies in late-stage development include trabodenoson, netardsudil, and latanoprostene bunod.

Purpose Glaucoma-related molecular biomarkers can improve clinical testing to diagnose the disease early, predict its prognosis, and monitor treatment responses. Based on the evidence of increased oxidative stress in glaucomatous tissues, this study analyzed oxidative stress-related biomarker candidates in blood and aqueous humor samples with or without glaucoma. Methods The blood and aqueous humor samples collected from carefully selected groups of 96 patients with glaucoma and 64 healthy subjects without glaucoma were included in the study. The samples were analyzed for protein carbonyls and advanced glycation end products (AGEs) through ELISA-based quantification assays. To allow proper comparisons, the Goldmann-Witmer coefficient that reflects the ratio of aqueous humor to blood values corrected to total protein concentration in individual samples was calculated. Results Blood and aqueous humor levels of protein carbonyls and AGEs were found significantly higher in glaucomatous samples compared with age-matched nonglaucomatous controls (P < 0.001). The glaucoma-related increase in protein carbonyls and AGEs was more prominent in aqueous humor samples than blood samples (2.6-fold versus 1.9-fold for protein carbonyls, and 3.1-fold versus 1.9-fold for AGEs; P < 0.001). Comparison of the Goldmann-Witmer coefficients indicated greater values for protein carbonyls (1.37 ± 0.3 vs. 3.07 ± 0.8) and AGEs (1.2 ± 0.3 vs. 3.2 ± 1.1) in the glaucoma group (P < 0.001). Conclusions Findings of this study encourage further validation studies of oxidative stress-related biomarkers in glaucoma. Analysis of protein carbonyls and AGEs in longitudinal studies of larger and heterogeneous patient cohorts should better assess the value of these promising candidates as molecular biomarkers of glaucoma for clinical predictions.

Purpose The purpose of this study is to test the hypothesis that the relationship between baseline visual field damage and the rate of progression depends upon the use of logarithmic (dB) versus linear (1/Lambert) scale. Methods A total of 60 eyes (60 patients) with treated, established glaucoma and at least 5 reliable 24-2 visual fields were included. Baseline visual field mean deviation (MD) in dB was transformed to 1/Lambert using standard equation. Mixed effects linear regression was used to calculate the slopes (MD rates of progression over time) with linear and nonlinear scales. We tested the relationship between baseline MD and MD slopes for each scale of measure. Results In dB scale, worse baseline visual field loss was associated with faster MD slopes (P=0.037), whereas the opposite effect was seen in 1/Lambert (P=0.001). For a similar rate of progression in dB/y, eyes with mild visual field damage lost more linear sensitivity over a given period of time than those with more severe baseline damage. Conclusions There is a significant relationship between baseline visual field severity and rates of MD progression, although the direction of this association depends on the scale sensitivity is measured. The definition of fast versus slow visual field progression should be revised and take into account that sensitivity in linear scales show a better correlation with structural loss than when conventionally measured in nonlinear scale.

Importance Little is known about the association between structural macular damage and self-reported visual function of people with glaucoma. Objective To determine the association between vision-related quality of life among patients with primary open-angle glaucoma with structural macular retinal ganglion cell plus inner plexiform layer (RGC+IPL) loss identified by spectral-domain optical coherence tomography (SD-OCT) machine-generated deviation maps and thickness measurements. Design, Setting, and Participants This cross-sectional prospective study was conducted from March 1, 2014, to March 30, 2015, at the Department of Ophthalmology at Columbia University Medical Center. The participants were 107 patients who were enrolled in the study and represented the entire range of glaucomatous damage. All 214 eyes of the 107 participants underwent 10-2 visual field tests and SD-OCT scans, and all participants completed the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). They also received ophthalmologic examination, including medical history review, best-corrected visual acuity, slitlamp biomicroscopy, intraocular pressure measurement, gonioscopy, dilated ophthalmoscopy, and standard automated perimetry. Macular RGC+IPL loss was determined by diffuse or focal patterns on SD-OCT–generated deviation maps (probability map that compared patients with aged-matched normative database) and thickness measurements. Main Outcomes and Measures Regression analyses to assess the association of NEI VFQ-25 scores (score range: 41.9-99.5; higher scores indicate better functioning) with patterns of RGC+IPL loss and with RGC+IPL thickness measurements. Results Of the 107 patients, 48 (45%) were men and the mean (SD) age was 65 (11) years. The self-reported race/ethnicity of participants consisted of 45 (46%) black, 47 (48%) white, and 6 (6%) “other” individuals. In the univariable analyses, patients with diffuse macular RGC+IPL loss had mean composite Rasch-calibrated NEI VFQ-25 scores that were 6.15 points lower than the scores of patients with focal damage (β = −6.15; 95% CI, −11.7 to −0.59; P = .03). The effect remained significant even after controlling for mean RGC+IPL thickness (β = −7.64; 95% CI, −14.2 to −1.03; P = .02). Conclusions and Relevance Characteristic patterns of glaucoma-related macular RGC+IPL loss appeared to be more important predictors of vision-related quality of life than thickness measures, with diffuse RGC+IPL loss as an indicator for diminished vision-related quality of life.

Importance Recent evidence supports the presence of macular damage (within 8° of the central field) to retinal ganglion cells and associated central visual field (VF) defects in glaucoma, even in early stages. Despite this, to our knowledge, the association of 10-2 VF damage with vision-related quality of life (QOL) has not been well studied. Objective To determine the association between QOL and visual function as measured by 24-2 and 10-2 VFs in patients with primary open-angle glaucoma and to test the hypothesis that patients with vision-related QOL disproportionate to their 24-2 VF status may exhibit 10-2 damage overlooked by the 24-2 test. Design, Setting, and Participants In this cross-sectional analysis of observational cohort study data taken from a tertiary care specialty practice, 113 patients with glaucoma with the entire range of 24-2 VF damage completed the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Data were collected from May 2014 to January 2015 and were analyzed from March 2016 to May 2016. Interventions Standardized binocular 24-2 and 10-2 VF sensitivities were calculated for each patient. Main Outcomes and Measures Association of binocular 24-2 and 10-2 VF sensitivity with Rasch-calibrated NEI VFQ-25 scores. Detection of outliers was based on Cook distance of the regression of binocular 24-2 and NEI VFQ-25 score. Outlier association with QOL was then assessed using a linear regression model, with binocular 10-2 VF sensitivity as the independent variable. Results Of the 113 patients, the mean (SD) age was 70.1 (10.9) years, and 51 (45.1%) were male and 71 (62.8%) were white. The composite NEI VFQ-25 score was associated with both binocular 24-2 (β = 1.95; 95% CI, 0.47-3.43; P = .01) and 10-2 (β = 2.57; 95% CI, 1.12-4.01; P = .001) sensitivities, but the 10-2 VF univariable model showed an almost 2-fold better fit to the data ( R 2 = 9.2% vs 4.9%). However, the binocular 10-2 sensitivities of 24-2 outliers had the strongest association with the composite NEI VFQ-25 scores (β = 2.78; 95% CI, 0.84-4.72; P = .006.) and the best fit to the data ( R 2 = 18.2%.) Conclusions and Relevance The 10-2 VF model showed a stronger association with NEI VFQ-25 score than the 24-2 VF model. Patients with disproportionately low quality of vision relative to patients with 24-2 VF damage may have damage on the central field missed by the 24-2 grid. Future prospective testing, including additional dimensions of quality of life, is indicated.

A mouse model of glaucoma implicates mitochondrial dysfunction resulting from a deficit in retinal nicotinamide adenine dinucleotide — together with elevated intraocular pressure — as causing susceptibility to glaucoma.

Purpose To investigate the prevalence of visual field defects in glaucomatous eyes, glaucoma suspects, and ocular hypertensives with 24-2 and 10-2 visual fields. Design Prospective, cross-sectional study. Participants Patients with or suspected glaucoma tested with 24-2 and 10-2. Patients were classified into 3 groups on the basis of the presence of glaucomatous optic neuropathy (GON) and 24-2 visual field abnormalities: early glaucoma (GON and abnormal visual field, mean deviation >−6 decibels [dB]), glaucoma suspects (GON and normal visual field), and ocular hypertensives (normal disc, normal visual field, and intraocular pressure >22 mmHg). For the classification of visual field abnormalities, 24-2 and 10-2 tests performed on the same visit were analyzed. Main Outcome Measures Comparison of the prevalence of abnormal 24-2 versus 10-2 visual field results based on cluster criteria in each diagnostic group. Results A total of 775 eyes (497 patients) were evaluated. A total of 364 eyes had early glaucoma, 303 eyes were glaucoma suspects, and 108 eyes were ocular hypertensives. In the glaucoma group, 16 of the 26 eyes (61.5%) classified as normal based on cluster criteria on 24-2 tests were classified as abnormal on 10-2 visual fields. In eyes with suspected glaucoma, 79 of the 200 eyes (39.5%) classified as normal on the 24-2 test were classified as abnormal on 10-2 visual fields. In ocular hypertensive eyes, 28 of the 79 eyes (35.4%) classified as normal on the 24-2 were classified as abnormal on the 10-2. Patients of African descent were more likely to have an abnormal 10-2 result (67.3 vs. 56.8%, P = 0.009). Conclusions Central visual field damage seen on the 10-2 test is often missed with the 24-2 strategy in all groups. This finding has implications for the diagnosis of glaucoma and classification of severity.

PurposeTo investigate longitudinal temporal and spatial associations between disc hemorrhage (DH) and rates of local retinal nerve fiber layer (RNFL) thinning before and after DHs.DesignLongitudinal, observational cohort study.ParticipantsForty eyes of 37 participants (23 with glaucoma and 17 with suspect glaucoma at baseline) with DH episodes during follow-up from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study.MethodsAll subjects underwent optic disc photography annually and spectral-domain optical coherence tomography (OCT) RNFL thickness measurements every 6 months. The rates of RNFL thinning were calculated using multivariate linear mixed-effects models before and after DH.Main outcome measuresRates of global and local RNFL thinning.ResultsThirty-six eyes of 33 participants with inferior or superior DHs were analyzed. The rates of RNFL thinning were significantly faster in DH quadrants than in non-DH quadrants after DH (-2.25 and-0.69 μm/year; P < 0.001). In the 18 eyes with intensified treatment after DH, the mean rate of RNFL thinning significantly slowed after treatment compared with before treatment in the non-DH quadrants (-2.89 and-0.31 μm/year; P < 0.001), but not in the DH quadrants (-2.64 and-2.12 μm/year; P= 0.19). In 18 eyes with unchanged treatment, the rate of RNFL thinning in the DH quadrant was faster after DH than before DH (P= 0.008). Moreover, compared with eyes without a treatment change, intensification of glaucoma treatment after DH significantly reduced the global, non-DH quadrants, and DH quadrant rates of RNFL thinning after DH compared with before DH (global, P= 0.004; non-DH quadrant, P < 0.001; DH quadrant, P= 0.005). In the multiple linear regression analysis, treatment intensification (β, 1.007; P= 0.005), visual field mean deviation (β, 0.066; P= 0.049), and difference in intraocular pressure before and after DH (β,-0.176; P= 0.034) were associated significantly with the difference of global RNFL slope values before and after DH.ConclusionsAlthough the rate of RNFL thinning worsened in a DH quadrant after DH, glaucoma treatment intensification may have a beneficial effect in reducing this rate of thinning.

Purpose: To investigate patients’ perception of glaucomatous VF loss and its association with glaucoma severity using the Amsler grid test. Methods: In this prospective cross-sectional study, glaucoma patients with abnormal 10–2 Humphrey Swedish Interactive Threshold Algorithm-standard VF tests were enrolled consecutively. All patients underwent a black-on-white Amsler grid test for each eligible eye. They were asked to outline any perceived scotomas (areas with abnormal grid lines) on the grid and then describe verbally their perception of the scotomas. Examiners asked patients to clarify their descriptions. All descriptions used by patients were recorded in their own words, which were then sorted into descriptor categories according to similar themes. The number of descriptor categories was counted for each eye. 10–2 VF mean deviation (MD) was compared among eyes that reported different number of descriptor categories. The mean 10–2 VF MD values were compared among different descriptor categories. Results: Fifty glaucoma patients (88 eyes) were included. Patients used a total of 44 different descriptors for their scotomas. Patients’ descriptors were classified into categories that incorporated similar themes, resulting in 4 overarching descriptor categories: Missing/White, Blurry/Gray, Black, and Not Aware. Fifty-two eyes reported one descriptor category and 19 eyes reported two descriptor categories (mean number of descriptor categories = 1.27±0.45). Eyes that reported two descriptor categories had worse VF MD than those that reported one (-17.86±10.31 dB vs. -12.08±7.53 dB; p = 0.012). When eyes were organized according to its combination of descriptor categories, each eye naturally sorted into one of the following 5 groups, in frequency order: Missing/White (27 eyes; 31%), Blurry/Gray (21 eyes; 24%), combined Missing/White and Blurry/Gray (19 eyes; 21%), Not Aware (17 eyes; 19%), and Black (4 eyes; 5%). The mean 10–2 VF MD severity order was Black (-21.18±10.59 dB), combined Missing/White and Blurry/Gray (-17.86±10.31 dB), Missing/White (-11.92±6.76 dB), Blurry/Gray (-10.55±7.03 dB), and Not Aware (-3.91±4.05 dB) (p

PURPOSE To characterize the in vivo effect of selective laser trabeculoplasty (SLT) on the Schlemm canal (SC) in eyes with primary open-angle glaucoma (POAG). MATERIALS AND METHODS Eighty-one serial horizontal enhanced depth imaging optical coherence tomograph B-scans (interval between B-scans, ∼35 μm) of the nasal corneoscleral limbus were obtained before and 4 weeks after SLT. Fifty B-scans in the overlapping regions before and after SLT were selected for analysis based on the structures of aqueous and blood vessels as landmarks. The SC cross-sectional area (CSA) was measured in each selected B-scan and averaged to generate the mean SC CSA of the eye. SC volume in the overlapping region was calculated using commercially available 3-dimensional reconstruction software. The mean SC CSA and SC volume were compared between pre-SLT and post-SLT B-scans. Correlation analysis was performed between SC CSA changes and intraocular pressure (IOP) changes. RESULTS Thirteen POAG eyes (13 patients) were included for analysis (mean age, 68.2±9.2 y). After SLT, the mean IOP was reduced from 19.8±7.6 to 14.4±3.8 mm Hg (P=0.003); the mean SC CSA increased by 8%, from 2478±550 to 2682±598 μm (P=0.029); and the mean SC volume increased from 4,304,592±954,777 to 4,658,250±1,039,956 μm (P=0.029). Increase in SC CSA had a significant positive correlation with IOP reduction after SLT (P=0.023, R=0.622). CONCLUSIONS SLT expands SC in POAG patients and even more so with greater IOP reduction after SLT. Post-SLT expansion of SC may be due to increased trabecular aqueous outflow, IOP decrease, or structural changes in trabecular meshwork resulting from SLT.

Objective The objective of this prospective, longitudinal study of patients with normal-tension glaucoma (NTG) was to determine whether patients with nocturnal hypotension are at greater risk for visual field (VF) loss over 12 months than those without nocturnal hypotension. Design Prospective, longitudinal study. Participants Consecutive patients with NTG with at least 5 prior VF tests were screened for eligibility. Methods The baseline evaluation assessed demographic and clinical characteristics, covering systemic comorbid conditions, including systemic hypertension. All oral and ophthalmologic medications were recorded. A complete ophthalmological examination was performed at baseline and follow-up. Patients had their blood pressure (BP) monitored every 30 minutes for 48 hours with an ambulatory recording device at baseline and 6 and 12 months. Main Outcome Measures The primary outcome was based on the global rates of VF progression by linear regression of the mean VF threshold sensitivity over time (decibels/year). Results Eighty-five patients with NTG (166 eyes; mean age, 65 years; 67% were women) were included. Of the 85 patients, 29% had progressed in the 5 VFs collected before study enrollment. The nocturnal mean arterial pressure (MAP) was compared with the daytime MAP. Multivariate analysis showed that the total time that sleep MAP was 10 mmHg below the daytime MAP was a significant predictor of subsequent VF progression ( P Conclusions Cumulative nocturnal hypotension predicted VF loss in this cohort. Our data suggest that the duration and magnitude of decrease in nocturnal blood pressure below the daytime MAP, especially pressures that are 10 mmHg lower than daytime MAP, predict progression of NTG. Low nocturnal blood pressure, whether occurring spontaneously or as a result of medications, may lead to worsening of VF defects.

To evaluate the association between focal, structural defects of the lamina cribrosa (LC) and glaucomatous visual field (VF) progression.Retrospective, observational study.A total of 169 patients with glaucoma (169 eyes) with a range of glaucomatous damage.Serial horizontal and vertical enhanced-depth imaging optical coherence tomography (EDI OCT) B-scans of the optic nerve head were obtained from patients with glaucoma with 5 or more prior Humphrey 24-2 VFs (Carl Zeiss Meditec, Inc, Dublin, CA). The EDI OCT scans were reviewed for the presence of focal LC defects (laminar holes or disinsertions with a diameter100 μm). The VF progression was defined as having ≥ 2 significantly progressing test points (with a slope calculated using pointwise linear regression [PLR], worse than -1.0 dB/year at P0.01). Age, intraocular pressure (IOP), baseline VF mean deviation (MD), disc hemorrhage, and central corneal thickness (CCT) were recorded.The relationship between focal LC defects and the rate and risk of VF progression.Mean age and VF MD at the time of EDI OCT were 69 ± 12 years and -11.49 ± 6.87 dB, respectively. Sixty eyes (36%) progressed according to PLR criteria. Progression was more common in eyes with, rather than without, focal LC defects (38/81 eyes [47%] vs. 22/88 eyes [25%], P = 0.003). Among the evaluated parameters, the presence of focal LC defects, disc hemorrhage, higher mean follow-up IOP, greater number of VFs, and longer follow-up period were significantly associated with VF progression in the multivariable analyses (odds ratios, 2.90, 4.66, 1.22, 1.25, and 1.27, respectively; P = 0.010, P = 0.002, P = 0.002, P0.001, and P0.001, respectively). The mean global progression rate was significantly faster in the group with focal LC defect than in the group with no focal LC defect (-0.54 ± 0.99 dB/year vs. -0.28 ± 0.52 dB/year; P = 0.031). Among the 60 progressing eyes, despite no significant difference in the mean number of progressing VF points per eye (6.7 ± 7.0 vs. 6.5 ± 4.4; P = 0.899), the mean localized progression rate was significantly faster in the eyes with focal LC defects than in the eyes with no focal LC defects (-2.85 ± 1.85 dB/year vs. -1.75 ± 0.56 dB/year; P = 0.009).Focal LC defects are strongly associated with glaucomatous VF progression, and eyes with focal LC defects tend to progress faster than those without.

A hierarchical approach to learn from visual field data was adopted to identify glaucomatous visual field defect patterns and to detect glaucomatous progression. The analysis pipeline included three stages, namely, clustering, glaucoma boundary limit detection, and glaucoma progression detection testing. First, cross-sectional visual field tests collected from each subject were clustered using a mixture of Gaussians and model parameters were estimated using expectation maximization. The visual field clusters were further estimated to recognize glaucomatous visual field defect patterns by decomposing each cluster into several axes. The glaucoma visual field defect patterns along each axis then were identified. To derive a definition of progression, the longitudinal visual fields of stable glaucoma eyes on the abnormal cluster axes were projected and the slope was approximated using linear regression (LR) to determine the confidence limit of each axis. For glaucoma progression detection, the longitudinal visual fields of each eye on the abnormal cluster axes were projected and the slope was approximated by LR. Progression was assigned if the progression rate was greater than the boundary limit of the stable eyes; otherwise, stability was assumed. The proposed method was compared to a recently developed progression detection method and to clinically available glaucoma progression detection software. The clinical accuracy of the proposed pipeline was as good as or better than the currently available methods. © 1964-2012 IEEE.

Purpose To test different visual field progression criteria using trend analysis in a glaucoma population followed with long sequences of 10-2 tests as a first attempt to understand and document rates of progression in the central field. Design Retrospective cohort study. Participants We included 146 eyes of 146 patients with established glaucoma. Methods Pointwise linear regression analysis using the methods of ordinary least squares was performed on the 68 test locations of the 10-2 visual field sequences. Threshold sensitivities at each test location were plotted as the dependent variable against follow-up time as the independent variable. Statistically significant progression or improvement of a visual field test point was defined if its regression slope measured ≤−1.0 dB/year or ≥+1.0 dB/year, respectively, at P Main Outcome Measures The performance of different visual field progression criteria to detect fast rates of mean deviation (MD) change. Results Median baseline 10-2 MD value was −12.0 dB (interquartile range [IQR], −6.7 to −17.8 dB), and the median rate of 10-2 MD change over time was −0.38 dB/year (IQR, −0.07 to −0.77 dB/year). The highest PIR was obtained with the progression criterion requiring at least 3 test points located in the same LCA-derived 10-2 visual field sector progressing faster than −1.0 dB/year at P Conclusions This is the first study to investigate progression criteria for 10-2 visual fields using rates of change and to test their performance and validity. These findings may be useful to improve the monitoring of patients with glaucoma at different levels of functional loss and to develop new perimetric algorithms that scrutinize specific visual field locations for a more accurate detection of progression.

Purpose: To investigate the longitudinal variability of glaucoma risk calculation in ocular hypertensive (OHT) subjects. Methods: We reviewed the charts of untreated OHT patients followed in a glaucoma referral practice for a minimum of 60 months. Clinical variables collected at baseline and during follow-up included age, central corneal thickness (CCT), intraocular pressure (IOP), vertical cup-to-disc ratio (VCDR), and visual field pattern standard deviation (VFPSD). These were used to calculate the 5-year risk of conversion to primary open-angle glaucoma (POAG) at each followup visit using the Ocular Hypertension Treatment Study and European Glaucoma Prevention Study calculator (http://ohts.wustl.edu/ risk/calculator.html). We also calculated the risk of POAG conversion based on the fluctuation of measured variables over time assuming the worst case scenarios (final age, highest PSD, lowest CCT, highest IOP, and highest VCDR) and best case scenarios (baseline age, lowest PSD, highest CCT, lowest IOP, and lowest VCDR) for each patient. Risk probabilities (%) were plotted against follow-up time to generate slopes of risk change over time. Results: We included 27 untreated OHT patients (54 eyes) followed for a mean of 98.3 ± 18.5 months. Seven individuals (25.9%) converted to POAG during follow-up. The mean 5-year risk of conversion for all patients in the study group ranged from 2.9% to 52.3% during follow-up. The mean slope of risk change over time was 0.37 ± 0.81% increase/y. The mean slope for patients who reached a POAG endpoint was significantly greater than for those who did not (1.3 ± 0.78 vs. 0.042 ± 0.52%/y, P < 0.01). In each patient, the mean risk of POAG conversion increased almost 10fold when comparing the best case scenario with the worst case scenario (5.0% vs. 45.7%, P < 0.01). Conclusions: The estimated 5-year risk of conversion to POAG among untreated OHT patients varies significantly during follow-up, with a trend toward increasing over time. Within the same individual, the estimated risk can vary almost 10-fold based on the variability of IOP, CCT, VCDR, and VFPSD. Therefore, a single risk calculation measurement may not be sufficient for accurate risk assessment, informed decision-making by patients, and physician treatment recommendations.

PurposeTo evaluate the validity of using progressive loss of neuroretinal rim area as a surrogate end point for the development of visual field loss in glaucoma.DesignProspective, observational cohort study.ParticipantsThe study group included 492 eyes of 328 patients classified with suspected glaucoma at the baseline visit. These eyes had an average of 7.4±2.8 confocal scanning laser ophthalmoscopy (CSLO) images during a mean follow-up time of 6.6±1.6 years.MethodsRim area measurements were acquired with CSLO during follow-up. The visual field end point was considered the development of 3 consecutive abnormal visual fields on standard automated perimetry. Strong predictive ability and large proportion of treatment effect (PTE) explained are requisites for a suitable surrogate end point. A joint longitudinal survival model was used to evaluate the ability of rates of rim area loss in predicting visual field development, adjusting for confounding variables (baseline age, race, and corneal thickness and follow-up measurements of intraocular pressure [IOP] and pattern standard deviation). The PTE was calculated by comparing the effect of IOP on the risk of development of visual field loss when incorporating rim area loss in the same model with the effect of IOP in the model excluding rim area measurements.Main outcome measuresPredictive strength was measured by survival-adapted R(2) and PTE.ResultsSixty-two of 492 eyes (13%) developed visual field loss during follow-up. The mean rate of rim area change in eyes that developed visual field loss was-0.011 mm(2)/year versus-0.003 mm(2)/year in eyes that did not (P

Author(s): Girkin, Christopher A; Fazio, Massimo A; Bowd, Christopher; Medeiros, Felipe A; Weinreb, Robert N; Liebmann, Jeffrey M; Proudfoot, James; Zangwill, Linda M; Belghith, Akram | Abstract: PurposeTo determine if variation in anterior lamina cribrosa surface depth (ALCSD) differs between glaucoma patients of African (AD) and European descent (ED).MethodsA total of 178 eyes from 123 glaucoma patients in the African Descent and Glaucoma Evaluation Study (ADAGES) and Diagnostic Innovations in Glaucoma Study (DIGS) were included. ALCSD and choroidal thickness were measured using the San Diego Automated Layer Segmentation Algorithm (SALSA). ALCSD was defined by both Bruch's membrane opening (BMO)-based (ALCSD-BMO) and scleral-based (ALCSD-Scl) reference planes. Racial differences in ALCSD were evaluated using cross-sectional univariate and multivariable models.ResultsA deeper ALCSD-Scl was found in males (52.4 μm, P = 0.0401), AD individuals (78.6 μm, P = 0.0004), younger individuals (-3.1 μm/year, P l 0.0213), and eyes with larger discs (81.0 μm/mm2, P = 0.024), increased visual field loss (mean defect, MD: -6.4 μm/dB [decibel], P = 0.0106), and higher intraocular pressure (IOP: 14.1 μm/mm Hg, P = 0.0256). Significant deepening of ALSCD was observed with increasing IOP and visual field severity only in the AD group. Race modified the relationship between ALCSD-Scl and age (P = 0.0145) with ALCSD-Scl in AD individuals becoming more shallow with increasing age (-3.1 μm/year, P = 0.0213), while there was no significant association in the ED group (2.1 μm/mm Hg, P l 0.2026).ConclusionsThis study demonstrates that a deeper ALCSD, regardless of the ALCSD reference plane used, is associated with more severe glaucoma and higher IOP in the ADAGES cohort, particularly in individuals of AD. These results suggest that characterizing ALCSD morphology and its relationships to IOP, aging, and glaucoma progression may help explain racial differences in disease susceptibility.

Objective To compare the performance of 10-2 versus 24-2 visual fields (VFs) in detecting progression of initial parafoveal scotoma (IPFS) in glaucomatous eyes. Design Retrospective, observational study. Participants Glaucoma patients with the following criteria: (1) an IPFS (≥3 adjacent points with P P Methods Based on threshold map sensitivities, VF progression, defined as having 1 or more significantly progressing point(s) with a slope of sensitivity of less than –1.0 dB/year at P Main Outcome Measures The number of progressing eyes in 10-2 and 24-2 VF analyses. Results Fifty eyes (50 patients) were included (mean age ± standard deviation, 62±9 years). Mean follow-up period (5.7 vs. 5.6 years) and number of VFs (7.6 vs. 7.8) were similar between 10-2 and 24-2 analyses (all P >0.3). Significantly more progressing eyes were detected in 10-2 than in 24-2 analyses (24 vs. 11 eyes; P = 0.007). This difference became greater within the central 10° (24 vs. 4 eyes; P Conclusions The 10-2 VF detects more progressing eyes than the 24-2 VF in glaucoma patients with IPFS, suggesting that closer surveillance of the central VF using testing algorithms with closely spaced grids is warranted in eyes with parafoveal scotomas. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Objective To assess the value of enhanced depth imaging optical coherence tomography (EDI OCT) in diagnosing and evaluating optic nerve head drusen (ONHD) compared with conventional diagnostic methods. Design Prospective, comparative, cross-sectional study. Participants Thirty-four patients with clinically visible or suspected ONHD in either eye based on dilated optic disc examination or optic disc stereophotography and without ocular comorbidity. Methods Spectral-domain OCT of the optic nerve head in both conventional (non-EDI) and EDI modes, ultrasound B-scan, and standard automated perimetry were performed on both eyes of all participants. Main Outcome Measures Detection and findings of ONHD between EDI OCT and conventional diagnostic methods. Results Sixty-eight eyes were clinically classified into 3 groups: 32 eyes with definite ONHD, 25 eyes with suspected ONHD, and 11 normal-appearing fellow eyes. In the definite ONHD group, EDI OCT, non–EDI OCT, and ultrasound B-scan were positive for ONHD in all eyes and visual field (VF) was abnormal in 24 eyes. In the suspected ONHD group, EDI OCT, non–EDI OCT, ultrasound B-scan, and VF were positive in 17, 14, 7, and 3 eyes, respectively; 8 eyes had no evidence of ONHD in any of the tests. In normal-appearing fellow eyes, EDI OCT, non–EDI OCT, ultrasound B-scan, and VF were positive in 3, 1, 1, and 0 eyes, respectively; 4 eyes had no evidence of ONHD in any of the tests. Enhanced depth imaging OCT had a significantly higher ONHD detection rate than ultrasound B-scan in all eyes (52/68 eyes vs. 40/68 eyes; P P P = 0.002). Enhanced depth imaging OCT–detected ONHD appeared as signal-poor regions surrounded by short, hyper-reflective bands or isolated/clustered hyper-reflective bands without a signal-poor core. In non–EDI OCT, posterior surfaces of the ONHD and deep-seated hyper-reflective bands were invisible or less clear than in EDI OCT. Conclusions Enhanced depth imaging OCT detects lesions likely representing ONHD more often and better assesses their shape and structure than conventional tests. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

� PURPOSE: To compare rates of topographic change in ocular hypertensive eyes that develop primary open-angle glaucoma (POAG) compared to eyes that do not, and to identify factors that influence the rate of change. � DESIGN: Longitudinal, randomized clinical trial. � METHODS: Four hundred forty-one participants (832 eyes) in the Confocal Scanning Laser Ophthalmoscopy Ancillary Study to the Ocular Hypertension Treatment Study were included. POAG was defined as repeatable visual field, photography-based optic disc changes, or both. The rate of topographic change in the 52 participants (66 eyes) who developed POAG was compared with that of participants who did not develop POAG using multivariable mixed effects models. � RESULTS: In both univariate and multivariate analyses, the rate of rim area loss was significantly faster in eyes in which POAG developed than in eyes in which it did not (univariate mean, L0.0131 mm 2 /year and L0.0026 mm 2 /year, respectively). The significantly faster rate of rim area loss in black persons found in the univariateanalysisdidnotremainsignificantwhenbaseline disc area was included in the model. In multivariate analyses, the rate of rim area loss and other topographic parameters also was significantly faster in eyes with worse baseline visual field pattern standard deviation and higher intraocular pressure during follow-up. Moreover, a significant rate of rim area loss was detected in eyes in which POAG did not develop (P < .0001). The rate of rim area loss in eyes with an optic disc POAG endpoint was significantly faster than in those with a visual field POAG endpoint. � CONCLUSIONS: The rate of rim area loss is approximately 5 times faster in eyes in which POAG developed compared with eyes in which it did not. These results suggest that measuring the rate of structural change can provide important information for the clinical management of ocular hypertensive patients. Additional follow-up is needed to determine whether the statistically significant change in the eyes in which POAG did not develop represents normal aging or glaucomatous change not detected by conventional methods. (Am J Ophthalmol 2013;155:971‐982. 2013 by Elsevier Inc. All rights reserved.)

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