Francis T.S. Oen

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.

The Singapore 5-Fluorouracil Trabeculectomy Study: Effects on Intraocular Pressure Control and Disease Progression at 3 Years

PURPOSE To report 3-year results of a randomized, controlled trial comparing the use of a single application of 5-fluorouracil (5-FU) with placebo in trabeculectomy surgery. DESIGN Prospective, randomized, double-blinded treatment trial. PARTICIPANTS Two hundred forty-three Asian patients with primary open-angle or primary angle-closure glaucoma undergoing primary trabeculectomy. METHODS One eye of each patient was randomized to receive either intraoperative 5-FU or normal saline (placebo) during trabeculectomy. MAIN OUTCOME MEASURES Primary outcome measure was the level of intraocular pressure (IOP). Secondary outcomes were progression of visual field loss, rates of adverse events, and interventions after surgery. RESULTS Of the 288 eligible patients, 243 were enrolled and 228 completed 3 years follow-up; 120 patients received 5-FU and 123 received placebo. Trial failure, according to predefined IOP criteria, was lower in the 5-FU group compared with the placebo group, although the difference was only significant with a failure criterion of IOP >17 mmHg (P = 0.0154). There was no significant difference in progression of optic disc and/or visual field loss over 36 months between 5-FU and placebo (relative risk [RR], 0.67; 95% confidence interval [CI], 0.34-1.31; P = 0.239). Uveitis occurred more often in the 5-FU-treated group (14/115 [12%] vs 5/120 [4%]; P = 0.032). CONCLUSIONS This is the first masked, prospective, randomized trial reporting the effect of adjunctive 5-FU in trabeculectomy surgery in an East Asian population. The trial shows that an increased success rate can be achieved for several years after a single intraoperative treatment with 5-FU. We conclude that 5-FU is relatively safe and can be routinely used in low-risk East Asian patients. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any materials discussed in this article.

Confirmation of the presence of uveal effusion in Asian eyes with primary angle closure glaucoma: an ultrasound biomicroscopy study.

OBJECTIVE To confirm the presence of uveal effusion in the eyes of Asian patients with primary angle closure glaucoma (PACG) using ultrasound biomicroscopy (UBM). METHODS In this observational case series, 70 patients with PACG (28 untreated patients with newly diagnosed PACG and 42 patients who had undergone previous laser iridotomy and were being monitored) and 12 patients with acute primary angle closure (APAC) were recruited. Eyes of patients with newly diagnosed PACG and APAC underwent UBM before and after laser iridotomy, whereas eyes of patients with treated PACG underwent UBM at enrollment. Uveal effusion was defined as a clear space between the choroid and sclera and was graded as follows: grade 0, none; grade 1, slitlike; grade 2, bandlike; and grade 3, obvious. RESULTS Overall, uveal effusion was found in 11 of 70 eyes with PACG (15.7%; 95% confidence interval, 8.8%-26.2%) and in 3 of 12 eyes with APAC (25%; 95% confidence interval, 8.0%-53.4%). For patients with newly diagnosed PACG, uveal effusion was found in 4 of 28 eyes (14.2%; 95% confidence interval, 5.1%-32.1%) before laser iridotomy; 2 eyes had effusion after laser iridotomy. When present, the effusion was grade 1 in PACG eyes and grade 2 or 3 in APAC eyes. CONCLUSIONS Uveal effusion was present in a significant proportion of Asian eyes with PACG and APAC, confirming a recent report of this finding.

Intraocular pressure and visual field loss in primary angle closure and primary open angle glaucomas.

Aim: To compare the correlation between visual field loss and the pretreatment intraocular pressure (IOP) in primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG). Methods: In a cross sectional observational study of 74 patients (43 PACG, 31 POAG), pretreatment IOP was measured at presentation, before treatment was initiated. The severity of visual field loss was assessed by AGIS score, mean deviation (MD), pattern standard deviation (PSD), and corrected pattern standard deviation (CPSD). Glaucomatous optic neuropathy was assessed from simultaneous stereo disc photographs. Results: There was a stronger correlation between pretreatment IOP and the extent of visual field loss in PACG subjects than in those with POAG for both MD (PACG: Pearson correlation coefficient (r) = 0.43, p = 0.002; r2 = 0.19), (POAG: r = 0.21, p = 0.13; r2 = 0.04) and AGIS score (PACG: r = 0.41, p = 0.003; r2 = 0.17), (POAG: r = 0.23, p = 0.19; r2 = 0.05 respectively). No such associations were seen for pattern standard deviation (PSD) or corrected pattern standard deviation (CPSD) in either group (p> 0.29). Both horizontal and vertical cup-disc ratio were well correlated with severity of field loss but not with presenting IOP for either diagnosis. Conclusions: This is consistent with the hypothesis of a greater IOP dependence for optic nerve damage in PACG than POAG and, conversely, a greater importance of other, less pressure dependent mechanisms in POAG compared to PACG.

Initial Management of Acute Primary Angle Closure: A Randomized Trial Comparing Phacoemulsification with Laser Peripheral Iridotomy

PURPOSE To compare the 2-year efficacy of phacoemulsification and intraocular lens implant (phaco/IOL) with laser peripheral iridotomy (LPI) in the early management of acute primary angle closure (APAC) and coexisting cataract. DESIGN Randomized, controlled trial. PARTICIPANTS We included 37 subjects presenting with APAC who had responded to medical treatment such that intraocular pressure (IOP) was ≤30 mmHg within 24 hours, and had cataract with visual acuity of ≤6/15. MAIN OUTCOME MEASURES The primary outcome measure was failure of IOP control defined as IOP between 22 to 24 mmHg on 2 occasions (readings taken within 1 month of each other) or IOP ≥25 mmHg on 1 occasion, either occurring after week 3. Secondary outcome measures were complications, degree of angle opening, amount of peripheral anterior synechiae, visual acuity, and corneal endothelial cell count (CECC). METHODS Subjects were randomized to receive either LPI or phaco/IOL in the affected eye within 1 week of presentation and were examined at fixed intervals over 24 months. Patients underwent a standardized examination that included Goldmann applanation tonometry, gonioscopy, and CECC measurements. Logistic regression was used to estimate the effect of treatment on failure of IOP control. Time to failure was evaluated using the Kaplan-Meier technique and Cox regression was used to estimate the relative risk of failure. RESULTS There were 18 patients randomized to LPI and 19 to phaco/IOL. The average age of subjects was 66.0±9.0 years and mean IOP after medical treatment was 14.5±6.9 mmHg. The 2-year cumulative survival was 61.1% and 89.5% for the LPI and phaco/IOL groups, respectively (P = 0.034). There was no change in CECC for either group from baseline to month 6. There was 1 postoperative complication in the phaco/IOL group compared with 4 in the LPI group (P = 0.180). CONCLUSIONS Performed within 1 week in patients with APAC and coexisting cataract, phaco/IOL resulted in lower rate of IOP failure at 2 years compared with LPI.

Original articleInitial Management of Acute Primary Angle Closure: A Randomized Trial Comparing Phacoemulsification with Laser Peripheral Iridotomy

PURPOSE To compare the 2-year efficacy of phacoemulsification and intraocular lens implant (phaco/IOL) with laser peripheral iridotomy (LPI) in the early management of acute primary angle closure (APAC) and coexisting cataract. DESIGN Randomized, controlled trial. PARTICIPANTS We included 37 subjects presenting with APAC who had responded to medical treatment such that intraocular pressure (IOP) was ≤30 mmHg within 24 hours, and had cataract with visual acuity of ≤6/15. MAIN OUTCOME MEASURES The primary outcome measure was failure of IOP control defined as IOP between 22 to 24 mmHg on 2 occasions (readings taken within 1 month of each other) or IOP ≥25 mmHg on 1 occasion, either occurring after week 3. Secondary outcome measures were complications, degree of angle opening, amount of peripheral anterior synechiae, visual acuity, and corneal endothelial cell count (CECC). METHODS Subjects were randomized to receive either LPI or phaco/IOL in the affected eye within 1 week of presentation and were examined at fixed intervals over 24 months. Patients underwent a standardized examination that included Goldmann applanation tonometry, gonioscopy, and CECC measurements. Logistic regression was used to estimate the effect of treatment on failure of IOP control. Time to failure was evaluated using the Kaplan-Meier technique and Cox regression was used to estimate the relative risk of failure. RESULTS There were 18 patients randomized to LPI and 19 to phaco/IOL. The average age of subjects was 66.0±9.0 years and mean IOP after medical treatment was 14.5±6.9 mmHg. The 2-year cumulative survival was 61.1% and 89.5% for the LPI and phaco/IOL groups, respectively (P = 0.034). There was no change in CECC for either group from baseline to month 6. There was 1 postoperative complication in the phaco/IOL group compared with 4 in the LPI group (P = 0.180). CONCLUSIONS Performed within 1 week in patients with APAC and coexisting cataract, phaco/IOL resulted in lower rate of IOP failure at 2 years compared with LPI.

Utility values in Singapore Chinese adults with primary open-angle and primary angle-closure glaucoma.

Purpose:To evaluate utility values in Chinese glaucoma patients. Patient and Methods:Singapore Chinese residents (n = 213) with primary open-angle glaucoma or primary angle-closure glaucoma were recruited from a single tertiary ophthalmic center. Standard face-to-face interviews were conducted to ask about utility values (time trade-off and standard gamble for both death and blindness). Ocular information, including current visual acuity, intraocular pressure, visual field defect, and cup-disc ratio were also obtained. Results:The mean time trade-off utility value was 0.88 (95% confidence interval 0.85, 0.91), and standard gamble for death and blindness were 0.94 (95% confidence interval 0.93, 0.96) and 0.95 (95% confidence interval 0.93, 0.97), respectively. Only 35.7% of patients were willing to trade time, and 34.3% willing to risk blindness in return for perfect vision. Both primary angle-closure glaucoma and primary open-angle glaucoma patients had similar utility values. After adjusting for age, gender, language spoken, educational level, and diagnosis, patients with better eye visual field PSD > 10 were 2.52 times (95% confidence interval 1.13, 5.61) more willing to trade time. In a multivariate model, the odds ratio of willingness to risk blindness for a complete hypothetical glaucoma cure was 9.88 (95% confidence interval 1.65, 59.23) for patients who had only visited an ophthalmologist 15 years or more ago, and 0.53 (95% confidence interval 0.27, 1.02) for patients who had previous trabeculectomy. Conclusion:Most Chinese glaucoma patients in Singapore are not willing to trade time or risk blindness. Patients with worse visual fields in the better-seeing eye are more willing to trade time; whereas patients who have not seen an ophthalmologist for at least 15 years or who had no history of a previous trabeculectomy are more willing to risk blindness.

Glaucoma management in patients with osteo-odonto-keratoprosthesis (OOKP): the Singapore OOKP Study.

PurposeTo report diagnostic modalities and treatment options for glaucoma in eyes with osteo-odonto keratoprosthesis (OOKP). MethodsEyes that underwent OOKP were evaluated for glaucoma at the time of the first postoperative visit, then at 1 and 3 months after the procedure, and thereafter every 6 months. All eyes underwent stereo-biomicroscopic optic nerve head (ONH) assessment, kinetic (Goldmann perimetry) and automated static visual field testing, ONH photography, Heidelberg retina tomograph, scanning laser polarimetery (GDx), and optical coherence tomography. Treatment of glaucoma was also reviewed. ResultsAverage follow-up period was 19.1 (range: 5 to 31) months. Of the 15 eyes that underwent OOKP, 5 eyes had preexisting glaucoma. None of the other 10 eyes developed glaucoma after OOKP. ONH photography and visual field testing were the most reliable methods to assess status of the disease, whereas Heidelberg retina tomograph and optical coherence tomography could be performed with reasonable reproducibility and quality; GDx imaging was poor. All patients with glaucoma were treated with oral acetazolamide 500 mg twice a day. Transscleral cyclophotocoagulation was performed in 3 eyes at stage 2 of OOKP surgery. Progression of glaucoma was noted in 2 eyes on the basis of optic disc photographs and automated perimetry. ConclusionsVisual field testing and optic disc assessment with optic disc photographs seem to be effective methods to monitor eyes with OOKP for glaucoma. Treatment strategies include oral medications to lower intraocular pressure and cyclophotocoagulation.

Visual acuity after acute primary angle closure and considerations for primary lens extraction

Background/aim: Primary lens extraction has been advocated for acute primary angle closure (APAC), but it is not known if this is warranted in all cases. The aim of this study was to investigate the visual acuity (VA) of APAC eyes shortly after resolution of the acute episode in order to assess the appropriateness of performing such surgery in this condition. Methods: This was a prospective observational case series. As part of a randomised controlled trial comparing phacoemulsification and laser iridotomy, 135 consecutive APAC subjects over a 2 year period underwent subjective refraction and measurement of Snellen VA once the acute episode had resolved with reduction of intraocular pressure (IOP) and improved corneal clarity. Results: Subjects were predominantly Chinese (95.6%) and female (79.3%), with a mean age of 63.6 (SD 9.6) years. When assessed 1.7 (2.7) days after presentation, the majority of APAC cases (50.4%) had good VA (6/12 or better), with more than a quarter of cases having VA of 6/7.5 or better. Poor VA was associated with duration of symptoms (p = 0.04, OR = 4.1, 95% CI 1.1 to 15.7) and time taken to resolution of APAC (p = 0.04, OR = 2.2, 95% CI 1.02 to 4.6), but not with sex (p = 0.31), age (p = 0.26), duration from presentation to measurement of visual acuity (p = 0.53), or presenting IOP (p = 0.73). Conclusion: Within days after APAC, more than half of APAC affected eyes had good VA (6/12 or better). The role of lens extraction in the management of APAC warrants further debate, especially for eyes with good VA.

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.