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Purpose To compare the efficacy of Ex-PRESS implantation (EXP) to trabeculectomy (TLE) with mitomycin C, for maintaining low target intraocular pressure (IOP) in patients with open-angle glaucoma. Methods Patients were randomly assigned to receive EXP or TLE. Surgical success was defined according to three target mean IOP ranges (5 mmHg ≤ IOP ≤ 18 mmHg [criterion A], 5 mmHg ≤ IOP ≤ 15 mmHg [criterion B], and 5 mmHg ≤ IOP ≤ 12 mmHg [criterion C]) representing reductions of at least 20% below baseline on two consecutive follow-up visits 3 months post-surgery, with or without antiglaucoma medication and without further glaucoma surgery. Results A total of 73 patients, including 30 in the EXP group and 43 in the TLE group, were included in the study. The baseline IOP was 20.4 ± 4.9 mmHg in the EXP group and 21.9 ± 7.9 mmHg in the TLE group. There were no significant differences in baseline ocular or demographic characteristics between the two groups. There was no statistical difference in IOP every 6 months. After the 3-year follow-up, success rates were A) 60.0% and 60.2%, B) 45.7% and 58.1%, and C) 31.5% and 40.5% for the EXP and TLE groups, respectively. A greater number of glaucoma medications before surgery was associated with a higher failure rate in the TLE group but not the EXP group. Conclusions Both procedures resulted in similar IOP reductions and success rates for low target IOP. The number of preoperative glaucoma medications was a risk factor for TLE failure.

PurposeTo compare the efficacy of Ex-PRESS implantation to trabeculectomy with mitomycin C, for maintaining low target intraocular pressure (IOP) in patients with open angle glaucoma.Materials and MethodsPatients were randomly assigned to receive Ex-PRESS implantation or trabeculectomy. Patients with IOP ≥ 15 mmHg were included in this study. Surgical success was defined according to three target mean IOP ranges (5 mmHg ≤ IOP ≤18 mmHg [criterion A], 5 mmHg ≤ IOP ≤15 mmHg [criterion B], and 5 mmHg ≤ IOP ≤12 mmHg [criterion C]) representing reductions of at least 20% below baseline on two consecutive follow-up visits 3 months post surgery.ResultsA total of 73 patients, including 30 in the Ex-PRESS implantation group and 43 in the trabeculectomy group, were included in the study. The baseline IOP was 20.4 ± 4.9 mmHg in the Ex-PRESS implantation group and 21.9 ± 7.9 mmHg in the trabeculectomy group. There were no significant differences in baseline ocular or demographic characteristics between the two groups. There was no statistical difference in IOP every 6 months. After the 3-year follow-up, success rates were A) 60.0% and 60.2%, B) 45.7% and 58.1%, and C) 31.5% and 40.5% for the Ex-PRESS implantation and trabeculectomy groups, respectively. A greater number of glaucoma medications before surgery was associated with a higher failure rate in the trabeculectomy group but not the Ex-PRESS implantation group.ConclusionsBoth procedures resulted in similar IOP reductions and success rates for low target IOP. The number of preoperative glaucoma medications was a risk factor for trabeculectomy failure.

PurposeCritical flicker fusion frequency (CFF) is a short but sensitive method for evaluating optic nerve function. We measured CFF in patients with pituitary neuroendocrine tumors (Pit-NETs) to assess its usefulness.MethodsData from 184 patients with nonfunctioning Pit-NETs, who had been treated with transsphenoidal surgery and had no medical history of eye diseases, was used in this retrospective study. Visual acuity decline (VAD) was defined as > 0.10 reduction in logMAR visual acuity and CFF decline (CFD) was defined as CFF value ResultsContact between the optic nerve or chiasma and the tumor was present and absent in 161 and 23 patients, respectively. In patients showing contact, the difference in CFF between the left and right eyes was larger (P = 0.0008), and the optimal cut-off value using the receiver operating characteristic curve was 3 Hz. Therefore, ≥ 3 Hz was considered positive for CFF laterality (CFL), the most prevalent condition. Tumor height was lower in patients with CFL positivity compared to those with VAD or VFD (P ConclusionChanges in CFL permit early detection of Pit-NETs. Our results indicate that CFF laterality can be seen in the early stages of compressive optic neuropathy due to Pit-NET.

AimIn patients who underwent multiple intraocular surgeries, we evaluated determinants of decreased corneal endothelial cell density (CECD) after sulcus placement following Ahmed and Baerveldt drainage device surgery.MethodsWe retrospectively reviewed consecutive patients with glaucoma who underwent sulcus placement with an Ahmed glaucoma valve or a Baerveldt glaucoma implant. We compared presurgical and postsurgical CECD and risk factors for decreased CECD.ResultsWe examined 41 eyes of 41 patients. Postsurgical CECD measurements were assessed 2.0±1.0 times during a median follow-up period of 28 months. The mean intraocular pressure (IOP) decreased from 28.4±11.6 mmHg to 12.2±5.3 mmHg 24 months after the operation. At 24 months, CECD decreased 14.6±5.4% after considering the variability in the number and time points of CECD determinations. History of prior surgery and higher preoperative IOP were significantly associated with a trend for a time-dependent decrease in CECD.ConclusionsRisk factors for decreased CECD after sulcus placement during Ahmed and Baerveldt drainage device surgery included the number of previous intraocular surgeries and higher presurgical IOP.

PRECIS Corvis ST Tonometry and Ocular Response Analyzer (ORA) measurements were conducted in primary open-angle glaucoma and normative subjects. Many parameters were significantly correlated, however, the strengths were weak to moderate. PURPOSE Reichert ORA parameters are derived from pressure information following the application of air-jet, whereas detailed structural observation can be made using the Corneal Visualization Scheimpflug Technology instrument (CST). The purpose of the study was to investigate the association between CST measurements and ORA measured corneal hysteresis (CH). METHODS Measurements of CST, ORA, axial length, average corneal curvature, central corneal thickness (CCT) and intraocular pressure with Goldmann applanation tonometry were carried out in 104 eyes of 104 patients with primary open-angle glaucoma and 35 eyes from normative subjects. The association between CST and ORA parameters was assessed using linear regression analysis, with model selection based on the second order bias corrected Akaike Information Criterion index. RESULTS Deformation amplitude ratio (corneal softness, R=-0.51), SP A1 (corneal stiffness, R=0.41), and Inverse Radius (integrated area under the curve of the inverse concave radius, R=-0.44) were significantly correlated with CH (P

Carriers of functionally deficient mutations in the CYP39A1 gene have been recently reported to have a 2-fold increased risk of exfoliation syndrome (XFS). The aim of this study was to evaluate the risk of blindness and related clinical phenotypes of XFS patients carrying the loss-of-function CYP39A1 G204E mutation in comparison with XFS patients without any CYP39A1 mutation.Retrospective case study.A total of 35 patients diagnosed with XFS carrying the CYP39A1 G204E mutation and 150 XFS patients without any CYP39A1 mutation who were randomly selected from the Japanese XFS cohort.Two-sided Fisher exact test with an alpha level0.05 was used to estimate the significance of the calculated odds ratio (OR) for all categorical measures. Comparisons between groups of subjects were performed using linear mixed effect models with group as random effect and taking possible dependence between eyes within a subject into account.Primary analysis compared the incidence of blindness (defined as visual acuity [VA]0.05 decimal), prevalence of exfoliation glaucoma (XFG), history of glaucoma surgery, and indices of glaucoma severity such as visual field (VF) mean deviation (MD), intraocular pressure (IOP), and vertical cup-disc ratio (CDR) between CYP39A1 G204E carriers and those without any CYP39A1 mutation.The overall risk for blindness was significantly higher in XFS patients carrying the CYP39A1 G204E variant (10/35 [28.6%]) compared with XFS patients without any CYP39A1 mutations (8/150 [5.4%]; odds ratio [OR], 7.1; 95% confidence interval [CI], 2.7-20.2]; P0.001). A higher proportion of XFS patients with the CYP39A1 G204E mutation (23/35 [65.7%]) had evidence of XFG in at least 1 eye compared with the comparison group (41/150 [27.3%]; OR, 5.1; 95% CI, 2.4-11.4]; P0.0001). Significantly higher peak IOP, larger vertical CDR, and worse VF MD were also found in CYP39A1 G204E variant carriers (P0.001). Additionally, patients with the CYP39A1 G204E mutation (18/35 [51.4%]) required more laser or glaucoma surgical interventions compared with those without any CYP39A1 mutation (32/150 [21.3%], P0.001).Patients with XFS carrying the CYP39A1 G204E mutation had significantly increased risk of blindness, higher occurrence of XFG, and more severe glaucoma compared with patients with XFS without any CYP39A1 mutation.

To investigate associations between Corvis ST-measured corneal biomechanical parameters and glaucomatous optic nerve head (ONH) morphology. In total, 118 eyes of 70 patients with open-angle glaucoma were examined in this retrospective cross-sectional study. We measured Heidelberg retina tomograph and Corvis ST values in all eyes. We used the linear mixed model in four sectors (temporal superior, TS; temporal inferior, TI; nasal superior, NS; and nasal inferior, NI) to detect associations between six ONH-related parameters and 14 Corvis ST–related parameters, controlling for age, intraocular pressure, axial length, and central corneal thickness. We calculated the ONH temporal and nasal sector vertical asymmetries (TS-TI and NS-NI asymmetries) and identified the optimal linear mixed models to describe them using model selection with the second-order bias corrected Akaike Information Criterion. The Corvis ST A2 velocity was negatively associated with the rim volume in the NS sector (p

To validate a deep residual learning algorithm to diagnose glaucoma from fundus photography using different fundus cameras at different institutes.Cross-sectional study.A training dataset consisted of 1364 color fundus photographs with glaucomatous indications and 1768 color fundus photographs without glaucomatous features. Two testing datasets consisted of (1) 95 images of 95 glaucomatous eyes and 110 images of 110 normative eyes, and (2) 93 images of 93 glaucomatous eyes and 78 images of 78 normative eyes.A deep learning algorithm known as Residual Network (ResNet) was used to diagnose glaucoma using a training dataset. The 2 testing datasets were obtained using different fundus cameras (different manufacturers) across multiple institutes. The size of the training data was artificially increased by adding minor alterations to the original data, known as "image augmentation." Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AROC).Area under the receiver operating characteristic curve.When image augmentation was not used, the AROC was 94.8% (90.3-96.8) in the first testing dataset and 99.7% (99.4-100.0) in the second dataset. These AROC values were significantly (P0.05) smaller without augmentation (87.7% [82.8-92.6] in the first testing dataset and 94.5% [91.3-97.6] in the second testing dataset).The previously developed deep residual learning algorithm achieved high diagnostic performance with different fundus cameras across multiple institutes, in particular when image augmentation was used.

To compare surgical outcomes between patients who underwent Baerveldt glaucoma implantation versus trabeculectomy (TLE) for the treatment of neovascular glaucoma. We performed a prospective, randomized, controlled clinical trial at Hiroshima University and Tsukazaki Hospital, Japan. Patients were randomized to Baerveldt glaucoma implantation (23 patients) or TLE (27 patients). The primary outcome measure was the rate of intraocular-pressure control. Secondary outcome measures included complications and interventions. We defined “failure” as intraocular pressure ≥ 22 mmHg or

Purpose: To investigate the association between macular inner retinal layer thickness and macula visual field (VF) mean deviation as measured by the Humphrey Field Analyzer (HFA) or macular function as measured by focal macular electroretinograms (ERGs) in patients with glaucoma.Methods: The participants in this cross-sectional study were 71 patients with glaucoma and 10 healthy controls. Macular inner retinal layer thickness and function were measured in all participants using optical coherence tomography (OCT) and HFA or focal macular ERGs, respectively. Macular OCT images were segmented into the macular retinal nerve fiber layer (mRNFL), macular ganglion cell layer/inner plexiform layer (GCL/IPL), and ganglion cell complex (GCC). Spearman correlation analysis was used to assess the relationship between macular inner retinal layer thickness and function.Results: Focal macular ERGs were composed of a negative wave (N1), a positive wave (P1), and a slow negative wave (N2). The N2 response density was significantly reduced in eyes with glaucoma, and was significantly associated with the thickness of the mRNFL (R = 0.317), GCL/IPL (R = 0.372), or GCC (R = 0.367). The observed structure–function relationship was also significantly correlated with the HFA VF mean deviation for each thickness [mRNFL (R = 0.728), GCL/IPL (R = 0.603), or GCC (R = 0.754)].Conclusions: Although a significant correlation was found between the N2 response density and the thickness of the macular inner layer, the observed structure–function relationship with the mean deviation of the HFA VF was higher than that of the N2 response density.

Author(s): Christopher, Mark; Nakahara, Kenichi; Bowd, Christopher; Proudfoot, James A; Belghith, Akram; Goldbaum, Michael H; Rezapour, Jasmin; Weinreb, Robert N; Fazio, Massimo A; Girkin, Christopher A; Liebmann, Jeffrey M; De Moraes, Gustavo; Murata, Hiroshi; Tokumo, Kana; Shibata, Naoto; Fujino, Yuri; Matsuura, Masato; Kiuchi, Yoshiaki; Tanito, Masaki; Asaoka, Ryo; Zangwill, Linda M | Abstract: PurposeTo compare performance of independently developed deep learning algorithms for detecting glaucoma from fundus photographs and to evaluate strategies for incorporating new data into models.MethodsTwo fundus photograph datasets from the Diagnostic Innovations in Glaucoma Study/African Descent and Glaucoma Evaluation Study and Matsue Red Cross Hospital were used to independently develop deep learning algorithms for detection of glaucoma at the University of California, San Diego, and the University of Tokyo. We compared three versions of the University of California, San Diego, and University of Tokyo models: original (no retraining), sequential (retraining only on new data), and combined (training on combined data). Independent datasets were used to test the algorithms.ResultsThe original University of California, San Diego and University of Tokyo models performed similarly (area under the receiver operating characteristic curve = 0.96 and 0.97, respectively) for detection of glaucoma in the Matsue Red Cross Hospital dataset, but not the Diagnostic Innovations in Glaucoma Study/African Descent and Glaucoma Evaluation Study data (0.79 and 0.92; P l .001), respectively. Model performance was higher when classifying moderate-to-severe compared with mild disease (area under the receiver operating characteristic curve = 0.98 and 0.91; P l .001), respectively. Models trained with the combined strategy generally had better performance across all datasets than the original strategy.ConclusionsDeep learning glaucoma detection can achieve high accuracy across diverse datasets with appropriate training strategies. Because model performance was influenced by the severity of disease, labeling, training strategies, and population characteristics, reporting accuracy stratified by relevant covariates is important for cross study comparisons.Translational relevanceHigh sensitivity and specificity of deep learning algorithms for moderate-to-severe glaucoma across diverse populations suggest a role for artificial intelligence in the detection of glaucoma in primary care.

AimsCorvis ST (CST) yields biomechanical corrected IOP (bIOP) which is purported to be less dependent on biomechanical properties. In our accompanied paper, it was suggested that the repeatability of bIOP is high. The purpose of the current study was to assess the relationship between intraocular pressure (IOP) measured with CST and central corneal thickness (CCT) and corneal hysteresis (CH), in comparison with IOP measured with Goldmann applanation tonometry (GAT) and the ocular response analyzer (ORA).MethodsA total of 141 eyes from 141 subjects (35 healthy eyes and 106 glaucomatous eyes) underwent IOP measurements with GAT, CST and ORA. The relationships between IOP measurements (ORA-IOPg, ORA-IOPcc, CST-bIOP and GAT IOP) and biomechanical properties (CCT, CH and corneal resistance factor (CRF)) were analysed using the linear regression analysis.ResultsIOPg, IOPcc and GAT IOP were significantly associated with CCT (pConclusionThe bIOP measurement from CST is independent from CCT, but dependent on CH and CRF.

IMPORTANCE Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness. OBJECTIVE To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function. DESIGN, SETTING, AND PARTICIPANTS A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome. EXPOSURES Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function. MAIN OUTCOMES AND MEASURES The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 x 10(-6). The secondary outcomes included biochemical enzymatic assays and gene expression analyses. RESULTS The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 x 10(-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4%[interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome. CONCLUSIONS AND RELEVANCE In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings. National Research Foundation of SingaporeNational Research Foundation, Singapore [NRF-NRFI2018-01]; US National Eye Institute of the National Institutes of Health [R01 EY020928, P30 EY014104, UM1 CA186107, U01 CA167552, EY015473]; Glaucoma Research Foundation of Canada [X052, CIRG17may053]; National Medical Research Council of SingaporeNational Medical Research Council, Singapore The study was funded by grant NRF-NRFI2018-01 from the National Research Foundation of Singapore. Additional support was provided by grants R01 EY020928, P30 EY014104, UM1 CA186107, U01 CA167552, and EY015473 from the US National Eye Institute of the National Institutes of Health, funding from the Glaucoma Research Foundation of Canada, and grants X052 and CIRG17may053 from the National Medical Research Council of Singapore.