Optical Coherence Tomography Angiography of Optic Disc and Macula Vessel Density in Glaucoma and Healthy Eyes.

AIM: To study the microvascular density of the macular and optic nerve head in healthy and glaucoma subjects using optical coherence tomography angiography. METHODOLOGY: We performed a cross-sectional cohort study on healthy subjects and patients with glaucoma. The AngioVue Enhanced Microvascular Imaging System was used to capture the optic nerve head and macula images during one visit. En face segment images of the macular and optic disc were studied in layers. Microvascular density of the optic nerve head and macula were quantified by the number of pixels measured by a novel in-house developed software. Areas under the receiver operating characteristic curves (AUROC) were used to determine the accuracy of differentiating between glaucoma and healthy subjects. RESULTS: A total of 24 (32 eyes) glaucoma subjects (57.5±9.5-y old) and 29 (58 eyes) age-matched controls (51.17±13.5-y old) were recruited. Optic disc and macula scans were performed showing a greater mean vessel density (VD) in healthy compared with glaucoma subjects. The control group had higher VD than the glaucoma group at the en face segmented layers of the optic disc (optic nerve head: 0.209±0.05 vs. 0.110±0.048, P<0.001; vitreoretinal interface: 0.086±0.045 vs. 0.052±0.034, P=0.001; radial peripapillary capillary: 0.146±0.040 vs. 0.053±0.036, P<0.001; and choroid: 0.228±0.074 vs. 0.165±0.062, P<0.001). Similarly, the VD at the macula was also greater in controls than glaucoma patients (superficial retina capillary plexus: 0.115±0.016 vs. 0.088±0.027, P<0.001; deep retina capillary plexus: 0.233±0.027 vs. 0.136±0.073, P<0.001; outer retinal capillary plexus: 0.190±0.057 vs. 0.136±0.105, P=0.036; and choriocapillaris: 0.225±0.053 vs. 0.153±0.068, P<0.001. The AUROC was highest for optic disc radial peripapillary capillary (0.96), followed by nerve head (0.92) and optic disc choroid (0.76). At the macula, the AUROC was highest for deep retina (0.86), followed by choroid (0.84), superficial retina (0.81), and outer retina (0.72). CONCLUSIONS: Microvascular density of the optic disc and macula in glaucoma patients was reduced compared with healthy controls. VD of both optic disc and macula had a high diagnostic ability in differentiating healthy and glaucoma eyes.

Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma.

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

A Cytomegalovirus Retinitis Screening Program: Evaluation of Enrollment Criteria for HIV Patients in Singapore.

PURPOSE: Identification of optimal enrollment criteria for a CMVR screening program suitable for a resource-limited environment. METHODS: A prospective audit was performed on newly diagnosed HIV patients referred for CMVR screening with any of the following four criteria: (1) visual symptoms, (2) low CD4(+) counts (<50 cells/µL), (3) AIDS-defining illnesses (ADI), and/or (4) opportunistic infections (OI). Odds ratios for each of the demographic factors and enrollment criteria were calculated. Sensitivities, specificities, and workload reduction for the various combinations were determined. RESULTS: A total of 348 screening visits for 176 HIV patients were performed. While individually only ADI was statistically significant for increased CMVR risk, the combination of CD4(+) counts <50 cells/µL with either ADI or visual symptoms or all 3 criteria were also statistically significant. Two enrollment criteria, ADI and ADI with CD4(+) <50 cells/µL, demonstrated good sensitivities, specificities, and workload reduction. CONCLUSION: We propose ADI and possibly CD4(+) counts <50 cells/µL as enrollment criteria for CMVR screening.

ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Telemedicine screening for cytomegalovirus retinitis using digital fundus photography.

BACKGROUND: Screening for cytomegalovirus retinitis (CMVR) is important in patients with acquired immune deficiency syndrome and low CD4(+) counts. However, many human immunodeficiency virus (HIV) patients lack access to specialist ophthalmological care. Telemedicine screening is a cost-effective method for screening these patients. We aimed to report the use of composite nine-field digital fundus photography (DFP) images for CMVR screening. We report its sensitivity and specificity in detecting CMVR and the level of agreement with gold-standard binocular indirect ophthalmoscopy. MATERIALS AND METHODS: An audit was performed on our national CMVR screening program that screened all HIV patients referred to the Ophthalmology Department at Tan Tock Seng Hospital, Singapore. All patients underwent retinal screening with DFP. Images were categorized as CMVR-positive, CMVR-negative, suspicious, or unreadable by blinded retinal specialists. Patients subsequently underwent dilated gold-standard indirect ophthalmoscopy by a different retinal specialist. Diagnoses were categorized as CMVR-positive, CMVR-negative, or unreadable. Sensitivity and specificity of retinal findings on DFP and kappa values for level of agreement between the two screening methods were calculated. RESULTS: Three hundred seventy screenings on 188 patients were performed. Twenty-three eyes diagnosed with CMVR on indirect ophthalmoscopy were also identified on DFP (100% sensitivity). A 99.9% specificity was achieved. The fundus photograph of one eye without CMVR was read as CMVR-positive because of an artifact, accounting for a false-positive. Kappa values ranged from 0.739 to 0.987. CONCLUSIONS: DFP is a sensitive and specific method of screening HIV patients for CMVR and has a high level of agreement with indirect ophthalmoscopy.

Trends in registered blindness and its causes over 19 years in Western Australia.

PURPOSE: To estimate the population-based incidence rates of blindness registration and their trends over time in Western Australia. METHODS: A retrospective review was performed on all cases of bilateral blindness registered with the Association for the Blind of Western Australia between 1984 and 2002. The causes and mean age at blindness registration were ascertained and incidence rates of blindness due to various causes were calculated. RESULTS: A total of 3852 blind certificates were examined. From 1984 to 1994, the annual incidence of registered bilateral blindness decreased significantly at an average rate of 9.4% per year (p < 0.0001), but then rose at a mean rate of 4.1% per year (p < 0.0001). ARMD blindness similarly fell by 8.9% per year (p < 0.0001), but then rose after 1994 by 4.5% per year (p < 0.0001). The incidence due to glaucoma decreased at an average rate of 10.3% per year (p < 0.0001) until 1994 and then rose at 7.4% per year at borderline significance (p = 0.025). CONCLUSIONS: There has been a nonlinear decrease in the incidence of registered blindness, in particular glaucoma-related blindness, in Western Australia. Rates of total registered blindness and that due to ARMD fell from 1984 to 1994, but have risen since.

Systemic autonomic function in subjects with primary angle-closure glaucoma: a comparative study of symptomatic and asymptomatic disease presentation.

BACKGROUND: Autonomic dysfunction is thought to be a contributory factor in primary angle-closure glaucoma (PACG) by precipitating pupil block in anatomically predisposed eyes. This study aimed to compare systemic autonomic function between subjects who had suffered a previous episode of acute angle closure (symptomatic PACG), those who had asymptomatic PACG, and age and sex-matched controls. METHODS: Tests for systemic parasympathetic function included the heart-rate response to standing (30:15 ratio), heart-rate variation during deep breathing, and the ratio of the heart rate at phases IV and II of the Valsalva manoeuvre (Valsalva ratio). For assessment of the sympathetic nervous system, blood pressure was recorded supine and then after 2 and 5 min of standing. A modified sweat test, the sympathetic skin response, was recorded on the palm and sole. RESULTS: A total of 30 subjects were examined: eight previous symptomatic PACG, eight asymptomatic PACG and 14 control subjects. The mean ages were similar, and all except one subject were Chinese. None of the subjects had evidence of systemic dysautonomia. There was no significant difference found between the groups for the 30:15 ratio, heart-rate variation during deep respiration and the Valsalva ratio. No significant orthostatic hypotension was detected in subjects with PACG. Abnormal sympathetic skin response was not more common in PACG subjects compared to control subjects. CONCLUSIONS: This study identified no systemic autonomic dysfunction in people with PACG.