Ching-Lin Ho

Genome-wide association analyses identify three 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 including 1,854 PACG cases and 9,608 controls across 5 sample collections in Asia. Replication experiments were conducted in 1,917 PACG cases and 8,943 controls collected from a further 6 sample collections. We report significant associations at three new loci: rs11024102 in PLEKHA7 (per-allele odds ratio (OR) = 1.22; P = 5.33 × 10−12), rs3753841 in COL11A1 (per-allele OR = 1.20; P = 9.22 × 10−10) and rs1015213 located between PCMTD1 and ST18 on chromosome 8q (per-allele OR = 1.50; P = 3.29 × 10−9). Our findings, accumulated across these independent worldwide collections, suggest possible mechanisms explaining the pathogenesis of PACG.

Novel anterior-chamber angle measurements by high-definition optical coherence tomography using the Schwalbe line as the landmark

Objective To propose the Schwalbe line (SL) as a new anatomical landmark, independent of the scleral spur (SS) location, for assessing anterior chamber angle (ACA) width quantitatively with high-definition optical coherence tomography (HD-OCT). Methods Study subjects underwent dark-room gonioscopy and HD-OCT in one randomly selected eye. The authors developed a computer-aided program to define two new quantitative parameters for assessing ACA width: Schwalbe line-angle opening distance (SL-AOD) measured at the SL, and Schwalbe line-trabecular–iris space area (SL-TISA) measured 500 μm from the SL. The associations between SL parameters, SS parameters and gonioscopic grading were evaluated. Results Seventy-three (47 females, 26 males) subjects were recruited, the majority of whom were Chinese (89%). The authors excluded 29 images (19.9%) owing to poor image quality, leaving 117 HD-OCT images (65 nasal, 52 temporal) for analysis. SL and SS could be identified in 95% and 85% of quadrants respectively (p=0.035). SL-AOD and SL-TISA were significantly correlated with SS parameters (all r≥0.85) and gonioscopic grading (all r≥0.69). In eyes with closed angles (n=36), SL parameters showed strong correlations with gonioscopic grading (r ranged from 0.43 to 0.44). Conclusions Novel angle parameters, based on SL as a landmark, may be useful to quantify ACA width and to assess for risk of angle closure.

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.

Postoperative Complications After Glaucoma Surgery for Primary Angle-Closure Glaucoma vs Primary Open-Angle Glaucoma

OBJECTIVES To investigate the incidence of postoperative complications arising in the first year after trabeculectomy and combined phacotrabeculectomy in eyes with primary angle-closure glaucoma (PACG) vs those with primary open-angle glaucoma (POAG). METHODS This was a retrospective study of all glaucoma operations done at a Singapore hospital from January 9, 2001, to December 30, 2004. The types of glaucoma surgery included trabeculectomy and phacotrabeculectomy, all with mitomycin C or fluorouracil. The incidences of postoperative complications and reoperations were analyzed. For those who underwent bilateral or repeated operations, only the first operated eye of each subject was included. RESULTS A total of 446 subjects with PACG (112 who underwent trabeculectomy and 334 who underwent phacotrabeculectomy) and 816 subjects with POAG (208 who underwent trabeculectomy and 608 who underwent phacotrabeculectomy) were analyzed. Postoperative complications occurred in 65 of 1262 eyes (5.2%) overall, with 27 eyes (8.4%) in the trabeculectomy group (PACG: 8.0%; 95% confidence interval [CI], 4.3%-14.6%; POAG: 8.7%; 95% CI, 5.5%-13.3%; P > .99) and 38 eyes (4.0%) in the phacotrabeculectomy group (PACG: 5.1%; 95% CI, 3.2%-8.0%; POAG: 3.5%; 95% CI, 2.3%-5.2%; P = .31). The rate of complications was significantly higher in the trabeculectomy group than the phacotrabeculectomy group overall (P = .003), but there was no significant difference between the POAG and PACG groups overall (POAG: 4.8%; 95% CI, 3.5%-6.5%; PACG: 5.8%; 95% CI, 4.0%-8.4%; P = .53). The commonest complication found was hypotony with overfiltration (23 cases [1.8%]), followed by bleb leak (11 cases [0.9%]). There was no significant difference in incidence of reoperations between POAG (2.7%; 95% CI, 1.8%-4.1%) and PACG (4.0%; 95% CI, 2.6%-6.3%) (P = .27). CONCLUSION The incidences of postoperative complications and reoperations in the first year after glaucoma surgery were similar for PACG and POAG.

A randomised crossover study comparing bimatoprost and latanoprost in subjects with primary angle closure glaucoma

Background/aims: To compare the intraocular pressure (IOP) lowering efficacy and side effects of latanoprost 0.005% and bimatoprost 0.03% in subjects with chronic primary angle closure glaucoma (PACG). Methods: This was an observer-masked randomised crossover study of 60 PACG subjects who received either latanoprost or bimatoprost for 6 weeks, after which they were crossed over to the other medication for another 6 weeks. The IOP-reducing effect of the medications was assessed by the reduction in IOP after 6 weeks of treatment compared with baseline. Results: Fifty-four subjects (80 eyes) completed the study. Latanoprost reduced IOP (mean (SD)) by 8.4 (3.8) mm Hg and bimatoprost by 8.9 (3.9) mm Hg from a baseline of 25.2 (3.6) mm Hg and 25.2 (3.6) mm Hg respectively (p = 0.23). Adverse events were mild in both groups; however there were twice as many reports of an adverse event in the bimatoprost group (81%) compared with the latanoprost group (40%, p<0.01). Ocular irritation was the most frequently reported adverse event in both groups; 22 subjects (37.9%) treated with bimatoprost experienced ocular hyperaemia as compared with 13 subjects (22.4%) treated with latanoprost (p = 0.11). Conclusions: Bimatoprost once daily was similarly effective in reducing IOP compared with latanoprost once daily in subjects with chronic PACG. Both drugs were well tolerated with mild ocular adverse events.

Argon Laser Peripheral Iridoplasty for Primary Angle-Closure Glaucoma: A Randomized Controlled Trial

PURPOSE To determine the effectiveness of argon laser peripheral iridoplasty (ALPI) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG). DESIGN Randomized controlled trial. PARTICIPANTS Eighty PAC or PACG subjects who underwent laser iridotomy (LI) and had at least 180° of persistent appositional angle closure and intraocular pressure (IOP) of more than 21 mmHg were enrolled. METHODS Subjects were randomized to receive either 360° ALPI (Visulas 532s; Carl Zeiss Meditec, Jena, Germany) or medical therapy (Travoprost 0.004%; Alcon-Couvreur, Puurs, Antwerp, Belgium). Repeat ALPI was performed if the IOP reduction was less than 20% from baseline along with inadequate angle widening at the month 1 or month 3 visit. Intraocular pressure was controlled with systematic addition of medications when required. MAIN OUTCOME MEASURES The primary outcome measure was success rates after ALPI at 1 year. Complete success was defined as an IOP of 21 mmHg or less without medication, and qualified success was defined as an IOP of 21 mmHg or less with medication. Failure was defined as an IOP more than 21 mmHg despite additional medications or requiring glaucoma surgery. RESULTS Forty subjects (51 eyes) were randomized to ALPI and 40 subjects (55 eyes) were randomized to medical therapy. Complete success (IOP ≤21 mmHg without medication) was achieved in 35.0% eyes of the ALPI group compared with 85.0% of eyes in the prostaglandin analog (PGA) group (P < 0.001), and qualified success (IOP ≤21 mmHg with medication) was achieved in 35.0% and 7.5%, respectively (P = 0.003). The IOP decreased by 4.9 mmHg (95% confidence interval [CI], 3.5-6.3 mmHg) in the ALPI group (P < 0.001) and by 6.1 mmHg (95% CI, 5.1-7.1 mmHg) in the medication group (P < 0.001). A failure rate of 30.0% was noted in the ALPI group compared with 7.5% in the medication group (P = 0.01). No treatment-related complications were recorded in either group. CONCLUSIONS After 1 year, ALPI was associated with higher failure rates and lower IOP reduction compared with PGA therapy in eyes with persistent appositional angle closure and raised IOP after LI.

Uncorrected refractive error in Singapore teenagers

Aim: To study the prevalence rate of uncorrected refractive error and associated risk factors among Singapore schoolchildren aged 12–16 years (grade 7). Methods: A cross sectional study of 628 participants (participation rate 99.8%) was conducted in two schools. An interviewer led questionnaire asking about sociodemographic variables and risk factors was administered. Refractive errors were measured using a table mounted autorefractor. Participants with habitual visual acuity (VA) of 0.2 logMAR or worse underwent subjective refraction. Uncorrected refractive error was defined as improvement of at least 0.2 logMAR in best corrected visual acuity after subjective refraction. Results: The prevalence rate of uncorrected refractive error was 22.3% (95% confidence interval (CI) 19.0% to 25.5%). The multivariate adjusted odds ratio of uncorrected refractive error in students with the lowest academic ability was 2.24 (95% CI 1.34 to 3.73). Increasing time interval since the last visit to an eye care provider increased the risk of uncorrected refractive error (trend p = 0.001). Conclusion: Uncorrected refractive error was a significant problem among Singapore students aged 12–16 years (grade 7). Uncorrected refractive error was more common among students with low academic ability or those who had not visited an eye care provider for a long time.

Severe vernal keratoconjunctivitis requiring trabeculectomy with mitomycin C for corticosteroid-induced glaucoma.

Background:  To describe clinical features of severe vernal keratoconjunctivitis with steroid response in Asian children and risk factors for glaucoma filtration surgery.

Efficacy and safety of a systematic switch from latanoprost to travoprost in patients with glaucoma.

PurposeTo assess the efficacy and safety of systematically switching a large number of hospital-based glaucoma patients from latanoprost to travoprost therapy. Materials and MethodsIn this prospective observational study, patients on latanoprost were systematically switched to travoprost without washout and followed-up for 12 weeks. The main outcome measures were control of intraocular pressure (IOP), rate of switching back, and tolerability. IOP was measured at baseline (while on latanoprost), and at weeks 6 and 12 after switching to travoprost. Adverse effects were assessed and conjunctival hyperemia was graded using a standardized scale. ResultsNinety-three consecutive patients (mean age 63.3±12.1 y) were enrolled. Nine patients were lost to follow-up. Four patients (4.3%) were switched back to latanoprost after 6 weeks due to travoprost intolerance. There was no significant difference between mean IOP at baseline [16.4±3.4 mm Hg, 95% confidence interval (CI) 15.6-17.2] and that at week 6 (15.9±4.2 mm Hg, 95% CI 14.9-16.8) (P=0.2) and week 12 (16.4±5.7 mm Hg, 95% CI 15.1-17.7) (P=0.99). There was no significant difference in the mean hyperemia score at week 12 compared with baseline (P=0.09). The majority of patients (86.9%) felt that both medications were comparable in terms of degree of comfort; 5 felt that travoprost caused more redness. ConclusionsIn this study, when glaucoma patients were systematically switched from latanoprost to travoprost, the efficacy and safety of the 2 medications were found to be comparable. A high switch rate (95.2%) was achieved with average hyperemia scores being comparable.

Updates on the Surgical Management of Pediatric Glaucoma.

AbstractChildhood glaucoma is known to be one of the most challenging conditions to manage. Surgical management is more complicated than in adults because of differences in anatomy from adults along with variations in anatomy caused by congenital and developmental anomalies, wide-ranging pathogenetic mechanisms, a more aggressive healing response, and a less predictable postoperative course. Challenges in postoperative examination and management in less cooperative children and the longer life expectancies preempting the need for future surgeries and reinterventions are also contributing factors. Angle surgery is usually the first-line treatment in the surgical management of primary congenital glaucoma because it has a relatively good success rate with a low complication rate. After failed angle surgery or in cases of secondary pediatric glaucoma, options such as trabeculectomy, glaucoma drainage devices, or cyclodestructive procedures can be considered, depending on several factors such as the type of glaucoma, age of the patient, and the severity and prognosis of the disease. Various combinations of these techniques have also been studied, in particular combined trabeculotomy-trabeculectomy, which has been shown to be successful in patients with moderate-to-advanced disease. Newer nonpenetrating techniques, such as viscocanalostomy and deep sclerectomy, have been reported in some studies with variable results. Further studies are needed to evaluate these newer surgical techniques, including the use of modern minimally invasive glaucoma surgeries, in this special and diverse group of young patients.