Beth Edmunds

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.

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.

The National Survey of Trabeculectomy. III. Early and late complications.

Purpose There is a considerable body of literature relating to trabeculectomy, however there are no data representative of the national experience of trabeculectomy in the United Kingdom (UK). The Department of Health funded a national survey of trabeculectomy to establish current practice patterns and the outcome of trabeculectomy in the National Health Service (NHS). In this paper we present the reported complications of first-time trabeculectomy from a nationally representative cohort of patients with chronic open angle glaucoma.Methods Cross-sectional study of consultant ophthalmologists performing trabeculectomy in the NHS. Participants recruited their four most recent consecutive first-time trabeculectomy cases with chronic open angle glaucoma according to study eligibility criteria and data were collected by self-administered questionnaire. Follow-up: one year post-trabeculectomy. Main outcome measures: occurrence of early and late complications.Results Clinical outcome data were available for 1240 (85.3%) of cases. Early complications were reported in 578 (46.6%) cases and late complications in 512 (42.3%) cases. Some cases had more than one complication. The most frequent early complications were hyphaema (n = 304, 24.6%), shallow anterior chamber (n = 296, 23.9%), hypotony (n = 296, 24.3%), wound leak (n = 216, 17.8%) and choroidal detachment (n = 175, 14.1%). The most frequent late complications were cataract (n = 251, 20.2%), visual loss (n = 230, 18.8%) and encapsulated bleb (n = 42, 3.4%). The occurrence of most complications was not associated with a consultant’s specialist interest, level of activity, type of hospital or region. Encapsulated bleb was reported more frequently in a university hospital setting.Conclusions The complication rates reported in this paper represent the national experience of first-time trabeculectomy for open angle glaucoma in the UK. These are similar to previous published studies and highlight in particular, the impact of trabeculectomy on visual acuity in the first year following surgery. This survey provides valid and clinically relevant data on the complications of trabeculectomy for the production of guidelines and standards for audit at regional, local and individual level.

A randomised, prospective study comparing trabeculectomy with viscocanalostomy with adjunctive antimetabolite usage for the management of open angle glaucoma uncontrolled by medical therapy

Aims: To compare trabeculectomy with viscocanalostomy augmented with adjunctive antimetabolite use for the control of intraocular pressure (IOP) in open angle glaucoma (OAG). Methods: 45 patients (50 eyes) with uncontrolled OAG were randomised to either trabeculectomy (25 eyes) or a viscocanalostomy technique (25 eyes). Preoperatively, all eyes were graded in terms of risk factors for drainage failure and were given intraoperative antimetabolites (5-fluorouracil 25 mg/ml (5-FU), mitomycin C (MMC) 0.2 mg/ml and 0.4 mg/ml) according to a standard protocol. Results: There were no significant differences between the groups in age, sex, type of OAG, preoperative medications, risk factors for drainage failure, and preoperative IOP. Mean follow up was 20 months (range 3–24 months). It was 12 months or longer in all eyes, except two lost to follow up at 3 months. At 12 months, complete success (IOP<21 mm Hg without antiglaucoma medications) was seen in 91% of eyes undergoing trabeculectomy, but in only 60% of eyes undergoing viscocanalostomy (p<0.02). Similarly, at the last follow up visit (mean 20 months) complete success was seen in 68% of eyes undergoing trabeculectomy and 34% with viscocanalostomy (p<0.05). In terms of qualified success (IOP<21 mm Hg with or without glaucoma medications) and mean IOP measurements postoperatively there were no difference between the groups, although the mean number of antiglaucomatous medications required postoperatively was less with trabeculectomy (0.39) than viscocanalostomy (1.04) (p<0.05). Needling procedures were more commonly required after trabeculectomy (p<0.02). YAG goniotomy was required in three eyes (13%) after viscocanalostomy. Early transient complications such as anterior chamber shallowing and encysted blebs were more common in the trabeculectomy group (p<0.05). Late postoperative cataract formation was similar between the two groups. Conclusion: In terms of complete success and number of antiglaucomatous medications required postoperatively, IOP control appears to be better with trabeculectomy. Viscocanalostomy is associated with fewer early transient postoperative complications.

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 (Spearmans 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.

National survey of antimetabolite use in glaucoma surgery in the United Kingdom

Aims: To assess the pattern of use of antimetabolites in trabeculectomy surgery by all consultant ophthalmologists in the United Kingdom. Methods: A postal questionnaire of 12 questions regarding antimetabolite use in trabeculectomy surgery was sent to all 749 consultant ophthalmologists in the United Kingdom. The consultants were asked to estimate the number of trabeculectomies they performed per year, how often they used 5-fluorouracil (5-FU) in primary and redo surgery, their usual method of administration of 5-FU, how often they used mitomycin (MMC) in primary and redo surgery, and their usual dosage regimen of MMC. Factors that influenced the decision to use or not use antimetabolites were also assessed. Results: The response rate of consultants returning the questionnaire was 82% (615 out of 749); 87% (533) of these consultants perform trabeculectomy surgery. Of these 533 consultants, 98 (18%) never use an antimetabolite. Most consultants (82%) use antimetabolites, but use them infrequently (only 9% using antimetabolites in more than half their cases). The preferred antimetabolite is 5-FU rather than MMC. Of the 435 consultants performing trabeculectomy surgery and using antimetabolites, 402 (93%) use 5-FU and 179 (41%) use MMC. Various factors influenced the decision to use or not use an antimetabolite, but experience of complications associated with their use was a factor for 34% of consultants. Conclusion: The use of antimetabolites, particularly MMC, in the United Kingdom is much less than in America or Japan, where trabeculectomy with MMC is the surgical procedure preferred by glaucoma specialists.

The national survey of trabeculectomy. I. Sample and methods

Purpose The National Survey of Trabeculectomy was designed to evaluate current practices of glaucoma surgery in the United Kingdom and to determine the success and complication rates of trabeculectomy on a national basis. This paper reports the survey methods, levels of consultant activity, waiting times, indications for surgery and the demographic and clinical characteristics of the patient sample.Methods Consultant ophthalmologists performing trabeculectomy in the United Kingdom were studied. Four consecutive patients undergoing trabeculectomy under each consultant prior to 18 June 1996 were retrospectively sampled. Patients were followed prospectively and evaluated 6 and 12 months after surgery. Data were collected by self-administered postal questionnaires. To determine the effects of selection and reporting bias a validation study of 14 randomly selected units was also conducted.Results Three hundred and eighty-two consultants recruited 1454 eligible patients for analysis. The mean age of patients was 69.2 years (standard deviation 10.9) and 51.7% were male. The underlying diagnosis was primary open angle glaucoma in 89.2%, pseudoexfoliation glaucoma in 5.4%, normal tension glaucoma in 3.8% and pigmentary glaucoma in 1.6%. There was advanced visual field damage in 50.5% of the cohort by the time of listing. The main indications for surgery were failure of medication to control intraocular pressure in 57.1%, progressive visual field loss in 26.5% and progressive optic disc damage in 4.8%. Primary surgery was undertaken in 4.8% of patients. In 80% trabeculectomy was performed within 3 months of listing. However, almost a third of consultants considered individual patients waiting time too long. Validation studies confirmed that systematic bias did not operate in the selection of patients for the survey or in the reporting of outcomes.Conclusion The findings of this survey are representative of current practices of trabeculectomy by consultants throughout the United Kingdom and show considerable variation in practice. Failure to control intraocular pressure with topical medications was the main indication for surgery. Advanced glaucomatous visual field damage was present at the time of surgery in half the sample. Though most patients were operated on within 3 months of listing, almost a third of consultants considered the wait unacceptably long.

Causes of visual impairment and common eye problems in Northwest American Indians and Alaska Natives.

OBJECTIVES Little information exists regarding the causes of visual impairment and the most common eye problems in American Indians/Alaska Natives. METHODS We randomly sampled American Indians/Alaska Natives older than 40 years from 3 tribes within the Northwest region. RESULTS We found a higher prevalence of visual impairment and normal-tension glaucoma, as well as a lower prevalence of ocular hypertension, in American Indians/Alaska Natives compared with previous results in other racial/ethnic groups. CONCLUSIONS American Indians/Alaska Natives have a need for vision correction. Future interventions in American Indians/Alaska Natives should include providing spectacles for refractive error, detecting glaucoma, and preventing visual impairment from age-related maculopathy and cataracts.

Central corneal thickness in Northwestern American Indians/Alaskan Natives and comparison with White and African-American persons.

PURPOSE To determine the demographic factors associated with central corneal thickness (CCT) in Northwestern American Indians/Alaskan Natives (AI/ANs) and to compare these CCT measurements with those of White and African-American persons. DESIGN Cross-sectional comparative, observational study. METHODS We performed ultrasonic pachymetry (DGH-500 Pachette; DGH Technologies, Exton, Pennsylvania, USA) on a random sample of AI/AN subjects from three randomly selected AI/AN tribes in the Northwest United States (n = 429). Pachymetry also was performed on a convenience sample of White (n = 46) and African-American (n = 33) persons. Our main outcome measure was the average of right and left eye CCT. RESULTS Average AI/AN CCT was 554.8 +/- 33.9 microm. AI/AN CCT was found to be thicker than that of African Americans (528.5 +/- 33.2 microm) but similar to that of White persons (551.9 +/- 28.3 microm). CCT was greater in AI/AN females than in AI/AN males (557.6 +/- 33.3 microm vs 550.1 +/- 34.5 microm; P = .03). We found no difference in CCT based on percent AI/AN heritage, age, and keratometry readings. We found no significant differences in mean CCT between AI/ANs with glaucoma (556.2 microm) and those who did not have glaucoma (556.6 microm). CONCLUSIONS CCT measurements for the Northwest AI/AN population are similar to those of White persons but thicker than those of African-American persons. Although glaucoma is common in AI/ANs, we did not find an association with thin CCT. We need future studies to explore the risk factors for glaucoma in AI/ANs.