Identification of Missense Extracellular Matrix Gene Variants in a Large Glaucoma Pedigree and Investigation of the N700S Thrombospondin-1 Variant in Normal and Glaucomatous Trabecular Meshwork Cells.

PURPOSE: Primary open-angle glaucoma (POAG) is a complex heterogeneous disease. While several POAG genes have been identified, a high proportion of estimated heritability remains unexplained. Elevated intraocular pressure (IOP) is a leading POAG risk factor and dysfunctional extracellular matrix (ECM) in the trabecular meshwork (TM) contributes to elevated IOP. In this study, we sought to identify missense variants in ECM genes that correlate with ocular hypertensive POAG. METHODS: Whole-genome sequencing was used to identify genetic variants in five members of a large POAG family (n = 68) with elevated IOP. The remaining family members were screened by Sanger sequencing. Unrelated normal (NTM) and glaucomatous (GTM) cells were sequenced for the identified variants. The ECM protein levels were determined by Western immunoblotting and confocal and electron microscopy investigated ECM ultrastructural organization. RESULTS: Three ECM gene variants were significantly associated with POAG or elevated IOP in a large POAG pedigree. These included rs2228262 (N700S; thrombospondin-1 (THBS1, TSP1)), rs112913396 (D563 G; collagen type VI, alpha 3 (COL6A3)) and rs34759087 (E987K; laminin subunit beta 2 (LAMB2)). Screening of unrelated TM cells (n = 27) showed higher prevalence of the THBS1 variant but not the LAMB2 variant, in GTM cells (39%) than NTM cells (11%). The rare COL6A3 variant was not detected. TSP1 protein was upregulated and COL6A3 was down-regulated in TM cells with N700S subject to mechanical stretch, an in vitro method that mimics elevated IOP. Immunofluorescence showed increased TSP1 immunostaining in cell strains with N700S compared to wild-type TM cells. Ultrastructural studies showed ECM disorganization and altered collagen type VI distribution in GTM versus NTM cells. CONCLUSIONS: Our results suggest that missense variants in ECM genes may not cause catastrophic changes to the TM, but over many years, subtle changes in ECM may accumulate and cause structural disorganization of the outflow resistance leading to elevated IOP in POAG patients.

Study of Optimal Perimetric Testing In Children (OPTIC): developing consensus and setting research priorities for perimetry in the management of children with glaucoma.

BACKGROUND: Perimetry is important in the management of children with glaucoma, but there is limited evidence-based guidance on its use. We report an expert consensus-based study to update guidance and identify areas requiring further research. METHODS: Experts were invited to participate in a modified Delphi consensus process. Panel selection was based on clinical experience of managing children with glaucoma and UK-based training to minimise diversity of view due to healthcare setting. Questionnaires were delivered electronically, and analysed to establish 'agreement'. Divergence of opinions was investigated and resolved where possible through further iterations. RESULTS: 7/9 experts invited agreed to participate. Consensus (≥5/7 (71%) in agreement) was achieved for 21/26 (80.8%) items in 2 rounds, generating recommendations to start perimetry from approximately 7 years of age (IQR: 6.75-7.25), and use qualitative methods in conjunction with automated reliability indices to assess test quality. There was a lack of agreement about defining progressive visual field (VF) loss and methods for implementing perimetry longitudinally. Panel members highlighted the importance of informing decisions based upon individual circumstances-from gauging maturity/capability when selecting tests and interpreting outcomes, to accounting for specific clinical features (e.g. poor IOP control and/or suspected progressive VF loss) when making decisions about frequency of testing. CONCLUSIONS: There is commonality of expert views in relation to implementing perimetry and interpreting test quality in the management of children with glaucoma. However, there remains a lack of agreement about defining progressive VF loss, and utilising perimetry over an individuals' lifetime, highlighting the need for further research.

Optical coherence tomographic angiography study of perfusion recovery after surgical lowering of intraocular pressure.

We investigated the time and location of retinal perfusion recovery after surgical intraocular pressure (IOP) lowering in glaucoma by using optical coherent tomography angiography (OCTA). Seventeen patients were analyzed. The 4.5 × 4.5-mm OCTA scans centered on the disc were performed preoperatively and postoperatively at 6 weeks, 3 months, and 6 months. The peripapillary retinal nerve fiber layer (NFL) thickness, NFL plexus capillary density (NFLP-CD) and visual field (VF) were measured overall and in 8 corresponding sectors. The low-perfusion area (LPA) was used to assess the cumulative area where local NFLP-CD was significantly below normal. At 6 months, the average IOP decreased 5.3 mmHg (P = 0.004), LPA decreased by 15% (P = 0.005), and NFLP-CD improved by 12% (P < 0.001). The NFL thickness and VF mean deviation didn't change significantly at any time point. Among the sectors with significant preoperative NFLP-CD loss, the recovery at 6 months was greatest in sectors with minimal preoperative NFL thinning (P < 0.001). In conclusion, surgical IOP lowering may improve NFLP capillary perfusion after 6 months. The perfusion recovery tended to occur in areas with minimal NFL thinning at baseline. OCTA parameters may have potential usefulness as pharmacodynamic biomarkers for glaucoma therapy.

Measuring Glaucomatous Focal Perfusion Loss in the Peripapillary Retina Using OCT Angiography.

PURPOSE: To measure low perfusion areas (LPAs) and focal perfusion loss (FPL) in the peripapillary retina using OCT angiography (OCTA) in glaucoma. DESIGN: Prospective, observational study. PARTICIPANTS: A total of 47 patients with primary open-angle glaucoma (POAG) and 36 normal participants were analyzed. METHODS: One eye of each subject was scanned using an AngioVue (Optovue, Fremont, CA) 4.5-mm OCTA scan centered on the disc. En face nerve fiber layer (NFL) plexus angiogram was generated. With the use of custom software, a capillary density map was obtained by computing the fraction of area occupied by flow pixels after low-pass filtering by local averaging 21×21 pixels. The low-perfusion map is defined by local capillary density below 0.5 percentile over a contiguous area above 98.5 percentile of the normal reference population. The LPA parameter is the cumulative area, and the FPL is the percent capillary density loss (relative to normal mean) integrated over the LPA. MAIN OUTCOME MEASURES: Peripapillary retinal LPA and FPL. RESULTS: Among patients with POAG, 3 had preperimetric glaucoma and 44 had perimetric glaucoma, with visual field (VF) mean deviation (MD) of -5.14±4.25 decibels (dB). The LPA was 3.40±2.29 mm2 in those with POAG and 0.11±0.18 mm2 in normal subjects (P < 0.001). The FPL was 21.8%±17.0% in those with POAG and 0.3%±0.7% in normal subjects (P < 0.001). The diagnostic accuracy as measured by the area under the receiver operating curve was 0.965 for both LPA and FPL, with a sensitivity of 93.7% at 95% specificity. The repeatability as measured by intraclass correlation coefficient was 0.977 for LPA and 0.958 for FPL. The FPL had excellent correlation with VF MD (Spearman's rho = -0.843), which was significantly (P = 0.008) better than the correlation between NFL thickness and VF MD (rho = 0.760). The hemispheric difference correlation between FPL and VF (Spearman's rho = 0.770) was significantly (P < 0.001) higher than the hemispheric difference correlation between LPA and VF (rho = 0.595). CONCLUSIONS: The low-perfusion map and LPA and FPL parameters are able to assess the location and severity of focal glaucoma damage with good agreement with VF.

Trabeculotomy Ab Interno With the Trab360 Device for Childhood Glaucomas.

PURPOSE: To report outcomes and complications of trabeculotomy ab interno using the Trab360 device (Trab360; Sight Sciences, Menlo Park, California, USA) in eyes with childhood glaucomas. DESIGN: Multicenter retrospective interventional case series. METHODS: Eyes with childhood glaucomas that underwent Trab360 with at least 3 months follow-up were evaluated. Postoperative intraocular pressure (IOP) less than or equal to 24 mm Hg with or without medications and no additional surgery defined success. RESULTS: Forty-six eyes of 41 patients were included. Median age at surgery was 12 months (range 1-325 months, mean 71 months); 54% prior to 20 months. A total of 48% were right eyes; 48% were male. Mean treatment was 290°. Median follow-up was 14.5 months (range 6-34 months, mean 16.2 months). Median preoperative IOP was 30 mm Hg (range 18-49 mm Hg, mean 30.9 mm Hg); median postoperative IOP was 18 mm Hg (range 5-40 mm Hg, mean 20.3 mm Hg]. Median number of preoperative glaucoma medications was 2.5 (range 0-5, mean 2.6); median number postoperatively was 1 (range 0-4, mean 1.6). Success was achieved in 67.4% (95% CI: 51.9%-80.0%) of eyes. Among 40 eyes for which Trab360 was the first glaucoma surgery, success rate was 70% (95% CI 53.3%-82.9%). Success was achieved in 81% (95% CI 57.4%-93.7%) of primary congenital glaucoma (PCG) eyes. Among 18 PCG eyes for which Trab360 was the first glaucoma surgery, success rate was 83.3% (95% CI 57.7%-95.6%). Two eyes (4.3%) suffered cyclodialysis. There were no other significant complications. CONCLUSIONS: Trab360 success resembles literature on other angle surgeries for childhood glaucomas. Good surgical technique and caution in high-risk angles is imperative to avoid cyclodialysis. Our study is limited by the imperfections inherent in any retrospective analysis. Single-incision ab interno trabeculotomy with the Trab360 device is effective and safe for treating childhood glaucomas, especially PCG.

Sectorwise Visual Field Simulation Using Optical Coherence Tomographic Angiography Nerve Fiber Layer Plexus Measurements in Glaucoma.

PURPOSE: To simulate 24-2 visual field (VF) using optical coherence tomographic angiography (OCTA) for glaucoma evaluation. DESIGN: Cross-sectional study. METHODS: One eye each of 39 glaucoma and 31 age-matched normal participants was scanned using 4.5-mm OCTA scans centered on the disc. The peripapillary retinal nerve fiber layer plexus capillary density (NFLP-CD, %area) was measured. The NFLP-CD and 24-2 VF maps were divided into 8 corresponding sectors using an extension of Garway-Heath scheme. RESULTS: Sector NFLP-CD was transformed to a logarithmic dB scale and converted to sector simulated VF deviation maps. Comparing simulated and actual 24-2 VF maps, the worst sector was in the same or adjacent location in the same hemisphere 97% of the time. VF mean deviation (VF-MD) was simulated by NFLP mean deviation (NFLP-MD). The differences between NFLP-MD and VF-MD in early, moderate, and severe glaucoma stages were -0.9 ± 2.0, 0.9 ± 2.9, and 5.8 ± 3.2 dB. NFLP-MD had better (P = .015) between-visit reproducibility (0.63 dB pooled standard deviation) than VF-MD (1.03 dB). NFLP-MD had a significantly higher sensitivity than VF-MD (P < .001) and overall NFL thickness (P = .031). CONCLUSIONS: OCTA-based simulated VF agreed well with actual 24-2 VF in terms of both the location and severity of glaucoma damage, with the exception of severe glaucoma in which the simulation tended to underestimate severity. The NFLP-MD had better reproducibility than actual VF-MD and holds promise for improving glaucoma monitoring. The NFLP-MD had better diagnostic accuracy than both VF-MD and overall NFL thickness and may be useful for early glaucoma diagnosis.

Endogenous hypercortisolism inducing reversible ocular hypertension.

PURPOSE: To describe the clinical findings of two patients with reversible ocular hypertension secondary to endogenous hypercortisolism. DESIGN: Retrospective, observational case series. SUBJECTS: A 65-year-old man (patient 1) and a 21-year-old woman (patient 2) were both found to have Cushing's syndrome after presentation to our clinic with elevated intraocular pressures (IOP). METHODS: Clinical histories, ophthalmic examinations including IOP measurements, optical coherence tomography of the retinal nerve fiber layer, visual field testing, magnetic resonance imaging and computerized tomography of two patients were reviewed between 2007 and 2019. OBSERVATIONS: Patient 1 demonstrated elevated IOP (maximum 26 mmHg OD and 22 mmHg OS) and bilateral disc edema. Following diagnosis of Cushing's syndrome, the patient underwent two pituitary resections and bilateral adrenalectomy, with subsequent resolution of his hypercortisolism and ocular hypertension (OHT). Patient 2 presented with blurred vision and found to have OHT (maximum 32 mmHg OU). Following diagnosis of Cushing's disease and two resections of her adrenocorticotropic hormone (ACTH) producing pituitary adenoma, her IOPs normalized. Both patients maintained normal IOPs after resolution of their endogenous hypercortisolism and discontinuation of topical IOP-lowering medication. CONCLUSIONS AND IMPORTANCE: Ocular hypertension induced by endogenous hypercortisolism is, in some cases, fully reversible following normalization of cortisol levels. These findings suggest that the physiologic changes to the trabecular meshwork induced by endogenous hypercortisolism may be fully reversible.

Electron Beam Irradiated Corneal Versus Gamma-Irradiated Scleral Patch Graft Erosion Rates in Glaucoma Drainage Device Surgery.

INTRODUCTION: Patch graft erosion and implant exposure is a known complication of glaucoma drainage device (GDD) surgery. Recently, electron beam (e-beam) irradiated corneal tissue ha s become available; however, limited data exist on the rates of erosion for e-beam irradiated corneal grafts compared to traditional scleral grafts after GDD surgery. METHODS: This retrospective study examines the records of 253 eyes from 225 adult subjects who underwent GDD surgery with either e-beam irradiated corneal or scleral grafts at the Casey Eye Institute by five surgeons between April 22, 2014 and October 11, 2017. Surgical procedures and the occurrence of graft erosion were determined using billing codes and verified by manual review of electronic health records. RESULTS: The average age at the time of surgery was 61.3 ± 17.5 years (n = 200) and 60.8 ± 16.8 years (n = 53) for the e-beam irradiated cornea and sclera groups, respectively. The average follow-up time post-surgery was 416 ± 345 days and 495 ± 343 days for the e-beam irradiated cornea and sclera groups, respectively. There were no statistically significant differences in sex, age, follow-up time, and glaucoma diagnosis between the groups; however, the e-beam irradiated cornea group was statistically more likely to have an Ahmed implant as compared to the sclera group. No erosion events were noted in either group. CONCLUSION: e-Beam irradiated corneal grafts were used 3.8 times more frequently relative to scleral grafts, yet there were no cases of graft erosion in either group during the follow-up period.

Projection-Resolved Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma.

PURPOSE: To detect plexus-specific peripapillary retinal perfusion defects in glaucoma, using projection-resolved optical coherence tomography angiography (PR-OCTA). DESIGN: Prospective cross-sectional study. METHODS: One eye each of 45 perimetric glaucoma participants and 37 age-matched normal participants were scanned using 4.5-mm OCTA scans centered on the disc. The PR-OCTA algorithm removed flow projection artifacts in OCT angiograms. Five en face OCTA slabs were analyzed: nerve fiber layer plexus (NFLP), ganglion cell layer plexus (GCLP), superficial vascular complex (SVC [NFLP + GCLP]), deep vascular complex (DVC), and all plexi combined. Peripapillary retinal capillary density (CD) and vessel density (VD) were calculated using a reflectance-compensated algorithm. RESULTS: Focal capillary dropout could be visualized more clearly in the NFLP than in the other slabs. The NFLP, SVC, and all-plexus CD in the glaucoma group were significantly lower (P < 0.001) than in the normal group, but no significant differences in GCLP-CD and DVC-CD appeared between the 2 groups. Both NFLP-CD and SVC-CD had excellent diagnostic accuracy, as measured by the area under the receiver operating characteristic curve (AROC = 0.981 and 0.976), correlation with visual field mean deviation (Pearson r = 0.819 and 0.831), and repeatability (intraclass correlation coefficients = 0.947 and 0.942). Performances of NFLP-VD and SVC-VD were similar to the corresponding CD parameters. CONCLUSIONS: In this glaucoma group, reduction in perfusion was more pronounced in superficial layers of the peripapillary retina (NFLP and SVC) than in the deeper layers. Reflectance-compensated CD and VD parameters for both NFLP and SVC could be useful in the clinical management of glaucoma.

Proptosis masquerading as buphthalmos following glaucoma drainage device surgery in a child with congenital glaucoma.

Glaucoma drainage devices are commonly used in the surgical treatment of children with glaucoma. We report a case of unusually large reservoir formation causing proptosis, exposure keratopathy, and motility deficits. This case highlights the importance of B-scan and axial length measurements in differentiating proptosis from buphthalmos in children with glaucoma. Reducing the reservoir improved the proptosis and resolved the motility and exposure issues.

Ex-PRESS Miniature Glaucoma Shunt Versus Ahmed Glaucoma Valve in the Surgical Treatment of Glaucoma in Pseudophakic Patients.

PURPOSE: The aim of this study was to compare the 3-year outcome of Ex-PRESS miniature glaucoma shunt versus Ahmed glaucoma valve in pseudophakic patients. PATIENTS AND METHODS: We retrospectively reviewed the records of patients with a history of clear corneal phacoemulsification alone, or failed trabeculectomy following phacoemulsification, who subsequently underwent Ahmed glaucoma valve (AGV) implantation or Ex-PRESS shunt surgery. The main outcome measure, surgical success, was defined as an intraocular pressure between 5 and 21 mm Hg and a 20% intraocular pressure reduction from baseline (with/without glaucoma medications) without glaucoma reoperation. RESULTS: In total, 92 patients (92 eyes) were included (43 AGV, 49 Ex-PRESS). Overall success at 3 years was 92.7% for AGV and 66.1% for Ex-PRESS (P=0.006). AGV had a higher success rate in patients with prior phacoemulsification and failed trabeculectomy (96% AGV vs. 64.1% Ex-PRESS; P=0.023). There was no difference in success rate for patients with only previous phacoemulsification (87.5% AGV vs. 69.4% Ex-PRESS; P=0.205). Glaucoma reoperation rates were 4.6% and 30.6% in the AGV and Ex-PRESS group, respectively (P=0.001). Both procedures had similar complication rates. CONCLUSIONS: AGV compared with Ex-PRESS shunt, had a higher success rate for secondary surgeries but not primary surgeries, in patients with prior clear corneal phacoemulsification. The AGV surgery also had a lower overall glaucoma reoperation rate.

Ophthalmic imaging in children: current practice patterns and perceived barriers.

Pediatric ophthalmologists were surveyed to determine current practice patterns regarding ophthalmic imaging for children and to identify perceived barriers to the adoption of imaging technologies in their practices. Some form of imaging was available in the majority of practices (94%), but its use varied widely among different clinical scenarios. The two most frequently perceived barriers to performing imaging in children were cooperation and lack of sufficient data supporting ophthalmic imaging in clinical practice.

Projection-Resolved Optical Coherence Tomography Angiography of Macular Retinal Circulation in Glaucoma.

PURPOSE: To detect macular perfusion defects in glaucoma using projection-resolved optical coherence tomography (OCT) angiography. DESIGN: Prospective observation study. PARTICIPANTS: A total of 30 perimetric glaucoma and 30 age-matched normal participants were included. METHODS: One eye of each participant was imaged using 6×6-mm macular OCT angiography (OCTA) scan pattern by 70-kHz 840-nm spectral-domain OCT. Flow signal was calculated by the split-spectrum amplitude-decorrelation angiography algorithm. A projection-resolved OCTA (PR-OCTA) algorithm was used to remove flow projection artifacts. Four en face OCTA slabs were analyzed: the superficial vascular complex (SVC), intermediate capillary plexus (ICP), deep capillary plexus (DCP), and all-plexus retina (SVC + ICP + DCP). The vessel density (VD), defined as the percentage area occupied by flow pixels, was calculated from en face OCTA. A novel algorithm was used to adjust the vessel density to compensate for local variations in OCT signal strength. MAIN OUTCOME MEASURES: Macular retinal VD, ganglion cell complex (GCC) thickness, and visual field (VF) sensitivity. RESULTS: Focal capillary dropout could be visualized in the SVC, but not the ICP and DVP, in glaucomatous eyes. In the glaucoma group, the SVC and all-plexus retinal VD (mean ± standard deviation: 47.2%±7.1% and 73.5%±6.6%) were lower than in the normal group (60.5%±4.0% and 83.2%±4.2%, both P < 0.001, t test). The ICP and DCP VD were not significantly lower in the glaucoma group. Among the overall macular VD parameters, the SVC VD had the best diagnostic accuracy as measured by the area under the receiver operating characteristic curve (AROC). The accuracy was even better when the worse hemisphere (inferior or superior) was used, achieving an AROC of 0.983 and a sensitivity of 96.7% at a specificity of 95%. Among the glaucoma participants, the hemispheric SVC VD values were highly correlated with the corresponding GCC thickness and VF sensitivity (P < 0.003). The reflectance compensation step in VD calculation significantly improved repeatability, normal population variation, and correlation with VF and GCC thickness. CONCLUSIONS: On the basis of PR-OCTA, glaucoma preferentially affects perfusion in the SVC in the macula more than the deeper plexuses. Reflectance-compensated SVC VD measurement by PR-OCTA detected glaucoma with high accuracy and could be useful in the clinical evaluation of glaucoma.

Combined Glaucoma Tube Shunt (Ahmed) and Fluocinolone Acetonide (Retisert™) Implantation Compared to Ahmed Alone in Uveitic Glaucoma.

INTRODUCTION: Glaucoma is a known complication of uveitis, and may require glaucoma tube shunt implantation for intraocular pressure (IOP) control. The success of glaucoma tube shunt implantation in the setting of a local ocular steroid depot in uveitic glaucoma remains unknown. The purpose of this study was to determine whether patients who underwent combined glaucoma tube shunt (Ahmed) and fluocinolone acetonide (Retisert™, Bausch + Lomb, Bridgewater, NJ, USA) implantation have superior outcomes compared to patients with Ahmed implants only in the setting of uveitic glaucoma. METHODS: All participants were studied retrospectively and underwent Ahmed implantation alone or with existing/concurrent Retisert implantation (combined group) at a single academic institution. The main outcome measures were IOP, visual acuity (VA), number of IOP-lowering medications, and adverse events at 6 months after Ahmed implantation. Secondary outcome measures included adverse events and surgical success at 6 months after Ahmed implantation. RESULTS: Mean IOP at 6 months after Ahmed implantation was 15.3 ± 4.8 and 15.1 ± 4.9 mm Hg in the Ahmed only group (n = 17) and the combined group (n = 17), respectively (p = 0.89). The mean number of IOP-lowering medications at 6 months after Ahmed implantation was 1.7 ± 1.0 and 1.8 ± 1.0 in the Ahmed only group and the combined group, respectively (p = 0.86). Mean VA at 6 months after Ahmed implantation was 0.35 ± 0.29 and 0.42 ± 0.33 log mean angle of resolution in the Ahmed only group and the combined group, respectively (p = 0.50). No significant differences in surgical success or adverse events were noted between the two groups. CONCLUSION: At 6 months, no significant differences in mean IOP, mean number of IOP-lowering medications, VA, surgical success, or adverse events were noted between Ahmed implantation alone or combined Ahmed and Retisert implantation in patients with uveitic glaucoma.

Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma.

IMPORTANCE: Vascular factors may have important roles in the pathophysiology of glaucoma. A practical method for the clinical evaluation of ocular perfusion is needed to improve glaucoma management. OBJECTIVE: To detect peripapillary retinal perfusion in glaucomatous eyes compared with normal eyes using optical coherence tomography (OCT) angiography. DESIGN, SETTING, AND PARTICIPANTS: Prospective observational study performed from July 24, 2013, to April 17, 2014. Participants were recruited and tested at Casey Eye Institute, Oregon Health & Science University. In total, 12 glaucomatous eyes and 12 age-matched normal eyes were analyzed. The optic disc region was imaged twice using a 3 × 3-mm scan by a 70-kHz, 840-nm-wavelength spectral OCT system. The split-spectrum amplitude-decorrelation angiography algorithm was used. Peripapillary flow index was calculated as the mean decorrelation value in the peripapillary region, defined as a 700-µm-wide elliptical annulus around the disc. Peripapillary vessel density was the percentage area occupied by vessels. The data statistical analysis was performed from October 30, 2013, to May 30, 2014. MAIN OUTCOMES AND MEASURES: Variability was assessed by the coefficient of variation. The Mann-Whitney test was used to compare the 2 groups of eyes. Correlations between vascular and visual field variables were assessed by linear regression analysis. RESULTS: In 12 normal eyes, a dense microvascular network around the disc was visible on OCT angiography. In 12 glaucomatous eyes, this network was visibly attenuated globally and focally. In normal eyes, between-visit reproducibilities of peripapillary flow index and peripapillary vessel density were 4.3% and 2.7% of the coefficient of variation, respectively, while the population variabilities of peripapillary flow index and peripapillary vessel density were 8.2% and 3.0% of the coefficient of variation, respectively. Peripapillary flow index and peripapillary vessel density in glaucomatous eyes were lower than those in normal eyes (P < .001 for both). Peripapillary flow index (Pearson r = -0.808) and peripapillary vessel density (Pearson r = -0.835) were highly correlated with visual field pattern standard deviation in glaucomatous eyes (P = .001 for both). The areas under the receiver operating characteristic curve for normal vs glaucomatous eyes were 0.892 for peripapillary flow index and 0.938 for peripapillary vessel density. CONCLUSIONS AND RELEVANCE: Using OCT angiography, reduced peripapillary retinal perfusion in glaucomatous eyes can be visualized as focal defects and quantified as peripapillary flow index and peripapillary vessel density, with high repeatability and reproducibility. Quantitative OCT angiography may have value in future studies to determine its potential usefulness in glaucoma evaluation.

Respiratory complications associated with ketamine anesthesia for ophthalmic procedures following intraocular pressure measurement in children.

BACKGROUND: We compared respiratory complications (RCs) in children who received intramuscular (IM) versus intravenous (IV) or no ketamine for intraocular pressure (IOP) measurement to test our observation that IM ketamine is associated with higher incidence of RCs. MATERIALS AND METHODS: We analyzed 149 eye examinations under anesthesia with ketamine in 27 patients and 263 non-ketamine examinations under anesthesia in 81 patients using a mixed effects logistic regression model. RESULTS: IM KETAMINE WAS STRONGLY ASSOCIATED WITH INCREASED ODDS OF RCS COMPARED TO NO KETAMINE (ODDS RATIO (OR): 20.23, P < 0.0001) and to IV ketamine (OR: 6.78, P = 0.02), as were higher American Society of Anesthesiologists (ASA) classification (OR: 2.60, P = 0.04), and the use of volatile agents (OR: 3.32, P = 0.02). CONCLUSION: Further studies should be conducted to confirm our observation of increased RCs with IM ketamine.

Optical coherence tomography angiography of optic disc perfusion in glaucoma.

PURPOSE: To compare optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc perfusion changes in glaucoma. DESIGN: Observational, cross-sectional study. PARTICIPANTS: Twenty-four normal subjects and 11 patients with glaucoma were included. METHODS: One eye of each subject was scanned by a high-speed 1050-nm-wavelength swept-source OCT instrument. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to compute 3-dimensional optic disc angiography. A disc flow index was computed from 4 registered scans. Confocal scanning laser ophthalmoscopy (cSLO) was used to measure disc rim area, and stereo photography was used to evaluate cup/disc (C/D) ratios. Wide-field OCT scans over the discs were used to measure retinal nerve fiber layer (NFL) thickness. MAIN OUTCOME MEASURES: Variability was assessed by coefficient of variation (CV). Diagnostic accuracy was assessed by sensitivity and specificity. Comparisons between glaucoma and normal groups were analyzed by Wilcoxon rank-sum test. Correlations among disc flow index, structural assessments, and visual field (VF) parameters were assessed by linear regression. RESULTS: In normal discs, a dense microvascular network was visible on OCT angiography. This network was visibly attenuated in subjects with glaucoma. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% CV, respectively. The disc flow index was reduced by 25% in the glaucoma group (P = 0.003). Sensitivity and specificity were both 100% using an optimized cutoff. The flow index was highly correlated with VF pattern standard deviation (R(2) = 0.752, P = 0.001). These correlations were significant even after accounting for age, C/D area ratio, NFL, and rim area. CONCLUSIONS: Optical coherence tomography angiography, generated by the new SSADA, repeatably measures optic disc perfusion and may be useful in the evaluation of glaucoma and glaucoma progression.

Variants in ASB10 are associated with open-angle glaucoma.

The molecular events responsible for obstruction of aqueous humor outflow and the loss of retinal ganglion cells in glaucoma, one of the main causes of blindness worldwide, remain poorly understood. We identified a synonymous variant, c.765C>T (Thr255Thr), in ankyrin repeats and suppressor of cytokine signaling box-containing protein 10 (ASB10) in a large family with primary open angle glaucoma (POAG) mapping to the GLC1F locus. This variant affects an exon splice enhancer site and alters mRNA splicing in lymphoblasts of affected family members. Systematic sequence analysis in two POAG patient groups (195 US and 977 German) and their respective controls (85 and 376) lead to the identification of 26 amino acid changes in 70 patients (70 of 1172; 6.0%) compared with 9 in 13 controls (13 of 461; 2.8%; P = 0.008). Molecular modeling suggests that these missense variants change ASB10 net charge or destabilize ankyrin repeats. ASB10 mRNA and protein were found to be strongly expressed in trabecular meshwork, retinal ganglion cells and ciliary body. Silencing of ASB10 transcripts in perfused anterior segment organ culture reduced outflow facility by ∼50% compared with control-infected anterior segments (P = 0.02). In conclusion, genetic and molecular analyses provide evidence for ASB10 as a glaucoma-causing gene.

Comparison of the new perimetric GATE strategy with conventional full-threshold and SITA standard strategies.

PURPOSE: A new, fast-threshold strategy, German Adaptive Thresholding Estimation (GATE/GATE-i), is compared to the full-threshold (FT) staircase and the Swedish Interactive Thresholding Algorithm (SITA) Standard strategies. GATE-i is performed in the initial examination and GATE refers to the results in subsequent examinations. METHODS: Sixty subjects were recruited for participation in the study: 40 with manifest glaucoma, 10 with suspected glaucoma, and 10 with ocular hypertension. The subjects were evaluated by each threshold strategy on two separate sessions within 14 days in a randomized block design. RESULTS: SITA standard, GATE-i, and GATE thresholds were 1.2, 0.6, and 0.0 dB higher than FT. The SITA standard tended to have lower thresholds than those of FT, GATE-i, and GATE for the more positive thresholds, and also in the five seed locations. For FT, GATE-i, GATE, and SITA Standard, the standard deviations of thresholds between sessions were, respectively, 3.9, 4.5, 4.2, and 3.1 dB, test-retest reliabilities (Spearman's rank correlations) were 0.84, 0.76, 0.79, and 0.71, test-retest agreements as measured by the 95% reference interval of differences were -7.69 to 7.69, -8.76 to 9.00, -8.40 to 8.56, and -7.01 to 7.44 dB, and examination durations were 9.0, 5.7, 4.7, and 5.6 minutes. The test duration for SITA Standard increased with increasing glaucomatous loss. CONCLUSIONS: The GATE algorithm achieves thresholds that are similar to those of FT and SITA Standard, with comparable accuracy, test-retest reliability, but with a shorter test duration than FT.