Liu Y, Baniasadi N, Ratanawongphaibul K, Chen TC. Effect of partial posterior vitreous detachment on spectral-domain optical coherence tomography retinal nerve fibre layer thickness measurements. Br J Ophthalmol 2020;104(11):1524-1527.Abstract
BACKGROUND/AIMS: To assess the effect of partial posterior vitreous detachment (pPVD) on spectral-domain optical coherence tomography (OCT) peripapillary retinal nerve fibre layer thickness (RNFL) measurements. METHODS: Spectral-domain OCT RNFL thickness measurements were obtained from 684 consecutive patients who were seen in the Massachusetts Eye and Ear Glaucoma Service. Of these patients, we compared RNFL thickness measurements between 101 eyes of 101 glaucoma suspects who met inclusion criteria (55 eyes with and 46 eyes without pPVD). RESULTS: Among all 684 patients, 253 (37%) had pPVD in at least one eye. Among a subset of 101 eyes of 101 glaucoma suspects, average RNFL thickness was greater in eyes with compared to eyes without pPVD (p=0.02). Measurements were significantly greater in the inferior (p=0.004) and superior quadrants (p=0.008), but not in the nasal (p=0.10) and temporal quadrants (p=0.25). The difference in average RNFL thickness remained significant (p=0.05) even when corrected for expected age-related decline in RNFL thickness. CONCLUSION: Over a third of patients were found on peripapillary spectral-domain OCT to have a pPVD, which was associated with greater RNFL thickness measurements. Judicious clinical interpretation of this finding on spectral-domain OCT RNFL thickness scans should be factored into the assessment of glaucoma suspects.
Liu Y, Simavli H, Que CJ, Rizzo JL, Tsikata E, Maurer R, Chen TC. Patient characteristics associated with artifacts in Spectralis optical coherence tomography imaging of the retinal nerve fiber layer in glaucoma. Am J Ophthalmol 2015;159(3):565-76.e2.Abstract

PURPOSE: To determine patient factors and eye conditions associated with artifacts in Spectralis optical coherence tomography (OCT) retinal nerve fiber layer (RNFL) scans. DESIGN: Retrospective cross-sectional study. METHODS: The prevalence of 12 artifact types were described in this review of 2313 eye scans from 1188 patients who underwent a complete eye examination with Spectralis OCT scanning during the period of September 2009 to July 2013. The generalized estimating equations model was used to analyze associations between increased artifact prevalence and 10 patient characteristics, which included age, sex, race, visual acuity, refractive error, astigmatism, cataract status, glaucoma staging, visual field reliability, and glaucoma diagnosis. RESULTS: A total of 1070 or 46.3% of the 2313 eye scans had at least 1 artifact. Decentration error was the most common artifact (27.8%), followed by posterior vitreous detachment artifacts (14.4%). Visual acuity of less than 20/40 (P < .0001), presence of moderate to severe cataracts (P < .0001), advanced stage of glaucoma (P < .0001), and a diagnosis of open-angle glaucoma (P = .0003) were associated with increased prevalence of artifacts. CONCLUSIONS: Clinicians should first assess scans for artifacts before making therapeutic decisions based on RNFL thickness measurements.

Liu WW, McClurkin M, Tsikata E, Hui P-C, Elze T, Celebi ARC, Khoueir Z, Lee R, Shieh E, Simavli H, Que C, Guo R, de Boer J, Chen TC. Three-dimensional Neuroretinal Rim Thickness and Visual Fields in Glaucoma: A Broken-stick Model. J Glaucoma 2020;29(10):952-963.Abstract
PRECIS: In open-angle glaucoma, when neuroretinal rim tissue measured by volumetric optical coherence tomography (OCT) scans is below a third of the normal value, visual field (VF) damage becomes detectable. PURPOSE: To determine the amount of neuroretinal rim tissue thickness below which VF damage becomes detectable. METHODS: In a retrospective cross-sectional study, 1 eye per subject (of 57 healthy and 100 open-angle glaucoma patients) at an academic institution had eye examinations, VF testing, spectral-domain OCT retinal nerve fiber layer (RNFL) thickness measurements, and optic nerve volumetric scans. Using custom algorithms, the minimum distance band (MDB) neuroretinal rim thickness was calculated from optic nerve scans. "Broken-stick" regression was performed for estimating both the MDB and RNFL thickness tipping-point thresholds, below which were associated with initial VF defects in the decibel scale. The slopes for the structure-function relationship above and below the thresholds were computed. Smoothing curves of the MDB and RNFL thickness covariates were evaluated to examine the consistency of the independently identified tipping-point pairs. RESULTS: Plots of VF total deviation against MDB thickness revealed plateaus of VF total deviation unrelated to MDB thickness. Below the thresholds, VF total deviation decreased with MDB thickness, with the associated slopes significantly greater than those above the thresholds (P<0.014). Below 31% of global MDB thickness, and 36.8% and 43.6% of superior and inferior MDB thickness, VF damage becomes detectable. The MDB and RNFL tipping points were in good accordance with the correlation of the MDB and RNFL thickness covariates. CONCLUSIONS: When neuroretinal rim tissue, characterized by MDB thickness in OCT, is below a third of the normal value, VF damage in the decibel scale becomes detectable.
Liu Y, Rhee DJ. Acute bilateral angle closure. JAMA Ophthalmol 2013;131(9):1231-2.
Liu Y, Jassim F, Braaf B, Khoueir Z, Poon LY-C, Ben-David GS, Papadogeorgou G, Tsikata E, Simavli H, Que C, Lee R, Shieh E, Vakoc BJ, Bouma BE, de Boer JF, Chen TC. Diagnostic Capability of 3D Peripapillary Retinal Volume for Glaucoma Using Optical Coherence Tomography Customized Software. J Glaucoma 2019;28(8):708-717.Abstract
PRéCIS:: The diagnostic capability of peripapillary retinal volume is similar to peripapillary retinal nerve fiber layer thickness for diagnosing glaucoma, but with fewer artifacts. PURPOSE: To compare the diagnostic capability of 3-dimensional peripapillary retinal volume (RV) versus 2-dimensional peripapillary retinal nerve fiber layer (RNFL) thickness for open-angle glaucoma. PATIENTS AND METHODS: A retrospective cross-sectional analysis was conducted. A total of 180 subjects (113 open-angle glaucoma, 67 normal participants) had spectral domain optical coherence tomography volume scans and RNFL thickness measurements. Peripapillary RV values were calculated using a custom-designed program with 4 circumpapillary annuli (CA): CA1 had circle diameters of 2.5 and 3.5 mm; CA2, 3 and 4 mm; CA3, 3.5 and 4.5 mm; and CA4, 4 and 5 mm. Area under the receiver operating characteristic curves were calculated for global, quadrant, and octant regions for RV (CA1 to CA4) and RNFL thickness. Pair-wise comparisons were conducted. Artifacts rates were determined. RESULTS: Mean age was 62.7±15.4 years, and 47.8% (86/180) were male. Among RV measurements, best diagnostic performances were for the smallest 2 annuli for inferior RV (CA1: 0.964, CA2: 0.955). Of the 4 annuli, CA1 had the highest diagnostic performance. Of specific regions, the inferior RV quadrant had the highest performance across CA1 to CA4. Peripapillary RV had similar diagnostic capability compared with RNFL thickness (P>0.05). The artifact rate per B-scan for RV was 6.0%, which was significantly lower compared with 2-dimensional RNFL thickness in the same patient population (32.2%, P<0.0001). CONCLUSIONS: The diagnostic capability of RV is similar to RNFL thickness for perimetric open-angle glaucoma, but RV had fewer artifacts compared with RNFL thickness.
Liu WW, Werner A, Chen TC. Repair of Tube Erosion by Modifying the Tube Extender. J Glaucoma 2020;29(7):604-606.Abstract
We describe here a case report of a novel technique for tube erosion repair, which modifies and utilizes the commercially available tube extender (Model TE). The modification of the tube extender makes the commercially available tube extender more compact and is useful in cases where conjunctival mobility and space are limited. This debulking of the tube extender may reduce the risk of future tube exposure and dellen formation.
Liu Y, Garrett ME, Yaspan BL, Bailey JC, Loomis SJ, Brilliant M, Budenz DL, Christen WG, Fingert JH, Gaasterland D, Gaasterland T, Kang JH, Lee RK, Lichter P, Moroi SE, Realini A, Richards JE, Schuman JS, Scott WK, Singh K, Sit AJ, Vollrath D, Weinreb R, Wollstein G, Zack DJ, Zhang K, Pericak-Vance MA, Haines JL, Pasquale LR, Wiggs JL, Allingham RR, Ashley-Koch AE, Hauser MA. DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma. Invest Ophthalmol Vis Sci 2014;55(12):8251-8.Abstract

PURPOSE: We examined the role of DNA copy number variants (CNVs) of known glaucoma genes in relation to primary open angle glaucoma (POAG). METHODS: Our study included DNA samples from two studies (NEIGHBOR and GLAUGEN). All the samples were genotyped with the Illumina Human660W_Quad_v1 BeadChip. After removing non-blood-derived and amplified DNA samples, we applied quality control steps based on the mean Log R Ratio and the mean B allele frequency. Subsequently, data from 3057 DNA samples (1599 cases and 1458 controls) were analyzed with PennCNV software. We defined CNVs as those ≥5 kilobases (kb) in size and interrogated by ≥5 consecutive probes. We further limited our investigation to CNVs in known POAG-related genes, including CDKN2B-AS1, TMCO1, SIX1/SIX6, CAV1/CAV2, the LRP12-ZFPM2 region, GAS7, ATOH7, FNDC3B, CYP1B1, MYOC, OPTN, WDR36, SRBD1, TBK1, and GALC. RESULTS: Genomic duplications of CDKN2B-AS1 and TMCO1 were each found in a single case. Two cases carried duplications in the GAS7 region. Genomic deletions of SIX6 and ATOH7 were each identified in one case. One case carried a TBK1 deletion and another case carried a TBK1 duplication. No controls had duplications or deletions in these six genes. A single control had a duplication in the MYOC region. Deletions of GALC were observed in five cases and two controls. CONCLUSIONS: The CNV analysis of a large set of cases and controls revealed the presence of rare CNVs in known POAG susceptibility genes. Our data suggest that these rare CNVs may contribute to POAG pathogenesis and merit functional evaluation.

Loomis SJ, Kang JH, Weinreb RN, Yaspan BL, Cooke Bailey JN, Gaasterland D, Gaasterland T, Lee RK, Lichter PR, Budenz DL, Liu Y, Realini T, Friedman DS, McCarty CA, Moroi SE, Olson L, Schuman JS, Singh K, Vollrath D, Wollstein G, Zack DJ, Brilliant M, Sit AJ, Christen WG, Fingert J, Kraft P, Zhang K, Allingham RR, Pericak-Vance MA, Richards JE, Hauser MA, Haines JL, Pasquale LR, Wiggs JL. Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss. Ophthalmology 2014;121(2):508-16.Abstract
PURPOSE: The CAV1/CAV2 (caveolin 1 and caveolin 2) genomic region previously was associated with primary open-angle glaucoma (POAG), although replication among independent studies has been variable. The aim of this study was to assess the association between CAV1/CAV2 single nucleotide polymorphisms (SNPs) and POAG in a large case-control dataset and to explore associations by gender and pattern of visual field (VF) loss further. DESIGN: Case-control study. PARTICIPANTS: We analyzed 2 large POAG data sets: the Glaucoma Genes and Environment (GLAUGEN) study (976 cases, 1140 controls) and the National Eye Institute Glaucoma Human Genetics Collaboration (NEIGHBOR) consortium (2132 cases, 2290 controls). METHODS: We studied the association between 70 SNPs located within the CAV1/CAV2 genomic region in the GLAUGEN and NEIGHBOR studies, both genotyped on the Illumina Human 660WQuadv1C BeadChip array and imputed with the Markov Chain Haplotyping algorithm using the HapMap 3 reference panel. We used logistic regression models of POAG in the overall population and separated by gender, as well as by POAG subtypes defined by type of VF defect (peripheral or paracentral). Results from GLAUGEN and NEIGHBOR were meta-analyzed, and a Bonferroni-corrected significance level of 7.7 × 10(-4) was used to account for multiple comparisons. MAIN OUTCOME MEASURES: Overall POAG, overall POAG by gender, and POAG subtypes defined by pattern of early VF loss. RESULTS: We found significant associations between 10 CAV1/CAV2 SNPs and POAG (top SNP, rs4236601; pooled P = 2.61 × 10(-7)). Of these, 9 were significant only in women (top SNP, rs4236601; pooled P = 1.59 × 10(-5)). Five of the 10 CAV1/CAV2 SNPs were associated with POAG with early paracentral VF (top SNP, rs17588172; pooled P = 1.07 × 10(-4)), and none of the 10 were associated with POAG with peripheral VF loss only or POAG among men. CONCLUSIONS: CAV1/CAV2 SNPs were associated significantly with POAG overall, particularly among women. Furthermore, we found an association between CAV1/CAV2 SNPs and POAG with paracentral VF defects. These data support a role for caveolin 1, caveolin 2, or both in POAG and suggest that the caveolins particularly may affect POAG pathogenesis in women and in patients with early paracentral VF defects.
Lowry EA, Hou J, Hennein L, Chang RT, Lin S, Keenan J, Wang SK, Ianchulev S, Pasquale LR, Han Y. Comparison of Peristat Online Perimetry with the Humphrey Perimetry in a Clinic-Based Setting. Transl Vis Sci Technol 2016;5(4):4.Abstract

PURPOSE: We determined the receiver operating characteristic (ROC) curves for Peristat online perimetry at detecting varying degrees of glaucoma and the correlation between Peristat online perimetry and Humphrey visual field. METHODS: A prospective, comparative study of Peristat online perimetry (an achromatic static computer threshold testing program) and Humphrey visual field (HVF) 24-2 SITA standard testing was performed by 63 glaucoma patients and 30 healthy controls in random order. The number of total adjacent abnormal test points were identified for each test, and compared with Spearman correlation. Receive operating characteristic curves were generated for Peristat online perimetry detection of mild and moderate-severe glaucoma patients using contrast sensitivity thresholds of -16.7, -21.7, and -26.7 dB. RESULTS: The area under the ROC curve for glaucoma detection ranged from 0.77 to 0.81 for mild disease (mean deviation [MD], >-6 dB on HVF) and 0.85 to 0.87 for moderate to severe disease (MD, <-6 dB on HVF) depending on contrast threshold. Peristat online perimetry and Humphrey visual field abnormal points were highly correlated with Spearman rank correlations ranging from 0.55 to 0.77 (all P < 0.001). CONCLUSIONS: Peristat online perimetry exhibits a reasonable ROC curve without specialized equipment and exhibited significant correlation with the conventional 24° Humphrey visual field test. TRANSLATIONAL RELEVANCE: Low cost widely available internet-based visual fields may complement traditional office-based visual field testing.

Lu SY, Rong SS, Wu Z, Huang C, Matsushita K, Ng TK, Leung CKS, Kawashima R, Usui S, Tam POS, Tsujikawa M, Young AL, Zhang M, Wiggs JL, Nishida K, Tham CC, Pang CP, Chen LJ. Association of the CAV1-CAV2 locus with normal-tension glaucoma in Chinese and Japanese. Clin Exp Ophthalmol 2020;48(5):658-665.Abstract
BACKGROUND: The CAV1-CAV2 locus has been associated with primary open-angle glaucoma (POAG) and intraocular pressure. However, its association with normal-tension glaucoma (NTG) was inconclusive. Therefore, we evaluated this association in Chinese and Japanese. METHODS: Two single-nucleotide polymorphisms (SNPs, rs4236601 and rs1052990) from previous genome-wide association studies of POAG were genotyped in a total of 2220 study subjects: a Hong Kong Chinese cohort of 537 NTG patients and 490 controls, a Shantou Chinese cohort of 102 NTG and 731 controls and an Osaka Japanese cohort of 153 NTG and 207 controls. Subgroup analysis by gender was conducted. Outcomes from different cohorts were combined using meta-analysis. RESULTS: SNP rs4236601 was significantly associated with NTG in the two Chinese cohorts (P = .0019, OR = 4.55, I = 0). In contrast, rs4236601 was monomorphic in the Osaka cohort. The association of rs1052990 was insignificant in a meta-analysis combining Chinese and Japanese cohorts (P = .81, OR = 1.05; I = 64%), and the OR tended towards opposite directions between Chinese (OR = 1.26) and Japanese (OR = 0.69). Gender-specific effects of the SNPs were not statistically significant in the logistic regression or Breslow-day tests of ORs (P > .05), although rs4236601 was significant in males (P = .0068; OR = 10.30) but not in females (P = .14; OR = 2.65) in the meta-analysis of Chinese subjects. CONCLUSIONS: In this study, we confirmed the association of rs4236601 at the CAV1-CAV2 locus with NTG in Chinese. SNP rs4236601 is monomorphic, and rs1052990 tends towards a different direction in the Japanese cohort. Further studies are warranted to verify the ethnic difference and gender-specific effects of this locus.
Lye-Barthel M, Sun D, Jakobs TC. Morphology of astrocytes in a glaucomatous optic nerve. Invest Ophthalmol Vis Sci 2013;54(2):909-17.Abstract
PURPOSE: To establish the morphologic changes of astrocytes in the glial lamina of glaucomatous mice. METHODS: A strain of mice that expresses GFP in individual astrocytes (hGFAPpr-GFP) was crossed into the DBA/2J strain that develops glaucoma. In the resulting strain (D2.hGFAPpr-GFP) we assessed the severity of glaucoma by staining the retina for neurofilaments and counting the neurons of the retinal ganglion cell layer. We observed the morphology of astrocytes in the glial lamina of the optic nerves. RESULTS: D2.hGFAPpr-GFP mice developed glaucoma in an age-dependent manner. Astrocytes in the glial lamina showed morphologic changes that correlated with the severity of glaucoma. The cells showed thickening of processes from 1.3 ± 0.28 μm in nondiseased animals to 1.71 ± 0.46 μm in eyes with moderate glaucoma and 2.1 ± 0.42 μm in those with severe glaucoma. Their spatial coverage, as determined by their convex polygon area, was reduced in eyes with severe glaucoma. The astrocytes in severely glaucomatous optic nerves also showed simplification of their processes. In 6-month-old mice with no obvious signs of degeneration in the retina, we found astrocytes with appendages growing out of primary astrocyte processes into the axon bundles. This localized hypertrophy of processes was never observed in the hGFAPpr-GFP strain. CONCLUSIONS: Confirming results after optic nerve crush, astrocytes in glaucomatous optic nerves had thickened and simplified processes, and reduced spatial coverage. We also found evidence of localized sprouting of new processes in early stages of the disease, before detectable changes in ganglion cell number.
Marando CM, Mansouri K, Kahook MY, Seibold LK. Tolerability and Functionality of a Wireless 24-Hour Ocular Telemetry Sensor in African American Glaucoma Patients. J Glaucoma 2019;28(2):119-124.Abstract
PURPOSE: The purpose of the study was to evaluate the tolerability and functionality of a wireless ocular telemetry sensor in African American patients with glaucoma. MATERIALS AND METHODS: In this prospective, observational cohort study, 20 African American patients with primary open angle glaucoma (POAG) were evaluated at the University of Colorado Eye Center. Before lens placement, patients recorded ocular comfort and underwent a baseline eye exam. Following the exam, patients were fitted with a SENSIMED Triggerfish contact lens sensor and data recording device. Patients were sent home and instructed to record their activities in a journal and return in 24 hours. Repeat exams were performed at various time points in clinic before and after lens removal. RESULTS: All 20 patients retained the lens for the 24-hour study period. The patient reported comfort was excellent, with a nadir of mean recorded comfort of 7.05/10. Significant clinical changes were noted in lid/conjunctival erythema, BCVA, refraction, and pachymetry over the course of lens wear. The majority of these changes were improved or resolved by 1 hour after lens removal. Voltage output was significantly greater nocturnally than diurnally (184.79 mV and 71.48 mV, respectively; P<0.0001). There was no significant change in signal variability or slope over the entire duration of the sleep/wake period based on sleep. CONCLUSIONS: The wireless ocular sensor is well tolerated over a 24-hour period in African American patients with POAG despite transient changes in visual acuity and conjunctival erythema. Clinically usable 24-hour profiles were generated for all patients, with voltage output increasing significantly during periods of sleep.
Margeta MA, Lad EM, Proia AD. CD163+ macrophages infiltrate axon bundles of postmortem optic nerves with glaucoma. Graefes Arch Clin Exp Ophthalmol 2018;256(12):2449-2456.Abstract
PURPOSE: Prior research in animal models has shown that macrophages and microglia play an important role in pathogenesis of glaucoma, but the phenotype and distribution of macrophages in human glaucomatous tissue have not been sufficiently characterized. METHODS: We analyzed H&E, CD68-, and CD163-immunostained slides from 25 formaldehyde-fixed, paraffin-embedded autopsy eyes: 12 control eyes and 13 eyes with glaucoma. The diagnosis of glaucoma was made based on a history of glaucoma as reported in the medical record and histological changes characteristic of glaucoma. Glaucoma cases and controls were matched in terms of age, sex, and race. RESULTS: Qualitative analysis of the conventional outflow pathway and the optic nerve revealed that all eyes contained CD163+ cells but a negligible number of CD68+ cells. CD163+ macrophages infiltrated the trabecular meshwork and surrounded Schlemm's canal of normal eyes and eyes with glaucoma, but the pattern was variable and qualitatively similar between groups. In optic nerves of control eyes, CD163+ macrophages were present at low levels and restricted to septa between axon bundles. In glaucomatous optic nerves, the number of CD163+ cells was increased both qualitatively and quantitatively (glaucoma 5.1 ± 0.6 CD163+ cells/mm, control 2.5 ± 0.3 CD163+ cells/mm, p < 0.001), with CD163+ cells infiltrating axon bundles in cases of both mild and severe diseases. CONCLUSIONS: The increase in CD163+ cell number in eyes with mild and severe glaucoma is the first demonstration of macrophage infiltration in glaucomatous human optic nerves. This finding supports a role for macrophages in glaucoma pathogenesis and progression.
Marra KV, Wagley S, Omar A, Kinoshita T, Kovacs KD, Silva P, Kuperwaser MC, Arroyo JG. Case-matched comparison of vitrectomy, peripheral retinal endolaser, and endocyclophotocoagulation versus standard care in neovascular glaucoma. Retina 2015;35(6):1072-83.Abstract

PURPOSE: To evaluate the efficacy of combination pars plana vitrectomy, endoscopic peripheral panretinal photocoagulation, and endocyclophotocoagulation (ECP) as compared with standard care in patients with neovascular glaucoma. METHODS: This age-matched case-controlled retrospective series of 54 eyes compared the clinical outcomes between a consecutive series of combination pars plana vitrectomy/panretinal photocoagulation/ECP (n = 27) versus the current standard of care (n = 27) for patients with neovascular glaucoma. "Standard" treatments for patients with neovascular glaucoma include panretinal photocoagulation, intravitreal bevacizumab, filtration surgery, pars plana vitrectomy, and Ahmed valve placement. RESULTS: After 1 year, mean intraocular pressure reduced from 40.7 ± 12.40 mmHg preoperatively to 12.3 ± 4.84 mmHg (P < 0.001) in the ECP group and from 34.7 ± 12.38 mmHg to 23.2 ± 12.34 mmHg in the control group (P = 0.002). Compared with controls, the mean drop in intraocular pressure in the ECP group was significantly greater at all postoperative visits. Logarithm of the minimal angle of resolution visual acuity outcomes were similar in both groups. There were 2 cases (7.4%) of postoperative phthisis bulbi in each group. CONCLUSION: Endoscopic pars plana vitrectomy, panretinal photocoagulation, and ECP seem to control intraocular pressure to a greater extent than standard glaucoma treatments in patients with neovascular glaucoma. In this aged-matched comparative case series, there was no significant difference between the two treatments' effects on visual acuity.

Mayro EL, Wang M, Elze T, Pasquale LR. The impact of artificial intelligence in the diagnosis and management of glaucoma. Eye (Lond) 2020;34(1):1-11.Abstract
Deep learning (DL) is a subset of artificial intelligence (AI), which uses multilayer neural networks modelled after the mammalian visual cortex capable of synthesizing images in ways that will transform the field of glaucoma. Autonomous DL algorithms are capable of maximizing information embedded in digital fundus photographs and ocular coherence tomographs to outperform ophthalmologists in disease detection. Other unsupervised algorithms such as principal component analysis (axis learning) and archetypal analysis (corner learning) facilitate visual field interpretation and show great promise to detect functional glaucoma progression and differentiate it from non-glaucomatous changes when compared with conventional software packages. Forecasting tools such as the Kalman filter may revolutionize glaucoma management by accounting for a host of factors to set target intraocular pressure goals that preserve vision. Activation maps generated from DL algorithms that process glaucoma data have the potential to efficiently direct our attention to critical data elements embedded in high throughput data and enhance our understanding of the glaucomatous process. It is hoped that AI will realize more accurate assessment of the copious data encountered in glaucoma management, improving our understanding of the disease, preserving vision, and serving to enhance the deep bonds that patients develop with their treating physicians.
McLaurin E, Cavet ME, Gomes PJ, Ciolino JB. Brimonidine Ophthalmic Solution 0.025% for Reduction of Ocular Redness: A Randomized Clinical Trial. Optom Vis Sci 2018;95(3):264-271.Abstract
SIGNIFICANCE: The α2-adrenergic receptor agonist brimonidine has been reported to induce conjunctival blanching in cataract, strabismus, laser refractive, and filtration procedures. Clinicians are often faced with red eyes with no apparent underlying pathology. Low-dose brimonidine reduced ocular redness in such subjects with efficacy maintained over 1 month and negligible rebound redness. PURPOSE: The aim of this study was to evaluate the safety and efficacy of brimonidine tartrate ophthalmic solution 0.025% for the treatment of ocular redness. METHODS: In this single-center, double-masked, phase 3 clinical trial, adult subjects with baseline redness of more than 1 unit in both eyes (0- to 4-unit scale) were randomized 2:1 to brimonidine 0.025% or vehicle. A single dose was administered in-office (day 1); thereafter subjects instilled treatment four times a day for 4 weeks, with clinic visits on days 15, 29, and 36 (7 days post-treatment). Efficacy end points included investigator-evaluated redness 5 to 240 minutes post-instillation on day 1 (primary); investigator-evaluated change from baseline 1, 360, and 480 minutes post-instillation on day 1, and 1 and 5 minutes post-instillation on days 15 and 29; total clearance of redness, and subject-assessed redness. Safety/tolerability measures included adverse events, rebound redness, and drop comfort. RESULTS: Sixty subjects were randomized (n = 40 brimonidine, n = 20 vehicle). Investigator-assessed redness was lower with brimonidine versus vehicle over the 5- to 240-minute post-instillation period (mean [SE], 0.62 [0.076] vs. 1.49 [0.108]; P < .0001) and at each time point within that period (P < .0001). At 1, 360, and 480 minutes post-instillation, respectively, the mean differences (95% confidence interval) between treatments were -0.73 (-1.05 to -0.41), -0.57 (-0.84 to -0.29), and -0.39 (-0.67 to -0.10), respectively. No tachyphylaxis was evident with brimonidine on days 15 and 29, and minimal rebound redness was observed following discontinuation. Adverse events were infrequent, and brimonidine was rated as very comfortable. CONCLUSIONS: Brimonidine 0.025% appeared safe and effective for reduction of ocular redness, with an 8-hour duration of action, no evidence of tachyphylaxis, and negligible rebound redness.
Mihailovic A, Varadaraj V, Ramulu PY, Friedman DS. Evaluating Goldmann Applanation Tonometry Intraocular Pressure Measurement Agreement Between Ophthalmic Technicians and Physicians. Am J Ophthalmol 2020;219:170-176.Abstract
PURPOSE: To examine IOP measurement disagreement between technicians and physicians and the impact of an educational intervention on the short and long-term disagreement in IOP measurement using Goldmann applanation tonometry. DESIGN: Prospective study designed to enhance measurement reliability. SETTING: A glaucoma clinic at a university hospital. StudyPopulation: 6 technicians and 2 physicians. INTERVENTION: An educational intervention was implemented for the technicians to improve IOP measurement agreement with physicians. MainOutcomeMeasures: Frequency of IOP measurement disagreement between physicians and technicians, defined as a difference in IOP of >2 or >3 mm Hg and assessed at baseline and immediately and 6 months postintervention. RESULTS: IOP was evaluated for a total of 529 eyes (physician measured mean IOP = 16.4 mm Hg [SD = 5.9]), 30 per technician-physician pair for each data collection period: baseline, immediately postintervention and 6 months postintervention. At baseline, physicians disagreed 17% and 7% of the time when measuring IOP using >2 and >3 mm Hg to define disagreement, respectively, whereas the average disagreement between technicians and physicians was 25% and 13%. Disagreement was greater at IOPs greater than 20 mm Hg. No significant changes were noted in the frequency of disagreement between technicians and physicians immediately or 6 months postintervention. CONCLUSIONS: Two physicians measuring the same patient in the same room disagreed by >2 mm Hg in 17% of patients' eyes, and this amount of disagreement was even higher when comparing physicians to certified technicians. An educational intervention did not improve agreement in IOP measurements between technicians and physicians. This highlights an important limitation of Goldmann tonometry.
Mihlstin M, Juzych MS, Kromrei HT, Hwang FS, Yin J. Resident Compliance With the American Academy of Ophthalmology Preferred Practice Patterns for Primary Open-Angle Glaucoma Suspect. J Glaucoma 2016;25(12):963-967.Abstract

PURPOSE: To study resident compliance with the American Academy of Ophthalmology (AAO) Preferred Practice Patterns (PPPs) for primary open-angle glaucoma suspect (POAGS) in a resident ophthalmology clinic. PATIENTS AND METHODS: Two hundred charts were selected for analysis of adult patients with the International Classification of Diseases diagnosis code for POAGS during their initial visit between November 2, 2010 and May 6, 2014 at the Kresge Eye Institute resident clinic. Electronic medical records of clinic visits for POAGS patients were evaluated for documentation and compliance with 17 elements of AAO PPPs. RESULTS: The overall mean compliance was 73.8% for all charts (n=200), 74.4% for first-year residents (n=53), 74.5% for second-year residents (n=38), and 73.3% for third-year residents (n=109). Documentation rates were high (>90%) for 9 elements, which included most elements of physical examination and history. Documentation of ocular history, central corneal thickness, gonioscopy, optic nerve head and retinal nerve fiber layer analysis, and visual field ranged from 40% to 80%. Documentation was lowest for patient education elements which ranged from 0% to 10%. Compliance was not significantly different (P>0.05) between residents or between different resident years for any element. CONCLUSIONS: Residents' compliance was high for most elements of the PPPs for POAGS. We identified elements with poor compliance especially regarding patient education. Adherence to AAO PPPs can be a helpful method of assessing resident performance.

Murphy RM, Bakir B, O'Brien C, Wiggs JL, Pasquale LR. Drug-induced Bilateral Secondary Angle-Closure Glaucoma: A Literature Synthesis. J Glaucoma 2016;25(2):e99-e105.Abstract

PURPOSE: We performed a literature synthesis to identify the full spectrum of compounds implicated in drug-induced, bilateral secondary angle-closure glaucoma (2° ACG). METHODS: Systematic PubMed literature review identified relevant bilateral 2° ACG case reports. We evaluated these reports with both the Naranjo adverse drug reaction probability scale to assess the causality of reported drug reactions and a 2° ACG scale scoring system we developed to determine the likelihood that the event represented bilateral 2° ACG. Two independent graders performed these analyses and their scores were averaged for interpretation. The Naranjo scale ranges from -4 to +13 and the drug reaction was considered definite if the score was ≥9, probable if 5 to 8, possible if 1 to 4, and doubtful if ≤0. The 2° ACG score ranges from 0 to 7. We considered a 2° ACG score of ≥4 as evidence of significant likelihood that the drug reaction represented bilateral 2° ACG. RESULTS: No drug had a definite Naranjo score, but the following drug entities had probable Naranjo scores and 2° ACG scores ≥4: acetazolamide, "anorexiant mix," bupropion, cabergoline, "ecstasy," escitalopram, flavoxate, flucloxacillin, hydrochlorothiazide, hydrochlorothiazide/triamterene, mefenamic acid, methazolamide, oseltamivir, topiramate, topiramate/bactrim, and venlafaxine. Root chemical analysis revealed that sulfur-containing and non-sulfur-containing compounds contributed to bilateral 2° ACG. CONCLUSIONS: Several compound preparations were implicated in drug-induced bilateral 2° ACG. Treating physicians should be aware that some forms of recreational drug use, which the patient may not admit to, could contribute to this vision-threatening side effect.

Newman-Casey PA, Talwar N, Nan B, Musch DC, Pasquale LR, Stein JD. The potential association between postmenopausal hormone use and primary open-angle glaucoma. JAMA Ophthalmol 2014;132(3):298-303.Abstract
IMPORTANCE: Retinal ganglion cells are known to express estrogen receptors and prior studies have suggested an association between postmenopausal hormone (PMH) use and decreased intraocular pressure, suggesting that PMH use may decrease the risk for primary open-angle glaucoma (POAG). OBJECTIVE: To determine whether the use of 3 different classes of PMH affects the risk for POAG. DESIGN, SETTING, AND PARTICIPANTS: Retrospective longitudinal cohort analysis of claims data from women 50 years or older enrolled in a US managed-care plan for at least 4 years in which enrollees had at least 2 visits to an eye care provider during the period 2001 through 2009. EXPOSURE: Postmenopausal hormone medications containing estrogen only, estrogen + progesterone, and estrogen + androgen, as captured from outpatient pharmacy claims over a 4-year period. MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) for developing incident POAG. RESULTS: Of 152,163 eligible enrollees, 2925 (1.9%) developed POAG. After adjustment for confounding factors, each additional month of use of PMH containing estrogen only was associated with a 0.4% reduced risk for POAG (HR, 0.996 [95% CI, 0.993-0.999]; P = .02). The risk for POAG did not differ with each additional month of use of estrogen + progesterone (HR, 0.994 [95% CI, 0.987-1.001]; P = .08) or estrogen + androgen (HR, 0.999 [95% CI, 0.988-1.011]; P = .89). CONCLUSIONS AND RELEVANCE: Use of PMH preparations containing estrogen may help reduce the risk for POAG. If prospective studies confirm the findings of this analysis, novel treatments for this sight-threatening condition may follow.