Clement C.Y. Tham

Genome-wide association analyses identify multiple loci associated with central corneal thickness and keratoconus

Central corneal thickness (CCT) is associated with eye conditions including keratoconus and glaucoma. We performed a meta-analysis on >20,000 individuals in European and Asian populations that identified 16 new loci associated with CCT at genome-wide significance (P < 5 × 10−8). We further showed that 2 CCT-associated loci, FOXO1 and FNDC3B, conferred relatively large risks for keratoconus in 2 cohorts with 874 cases and 6,085 controls (rs2721051 near FOXO1 had odds ratio (OR) = 1.62, 95% confidence interval (CI) = 1.4–1.88, P = 2.7 × 10−10, and rs4894535 in FNDC3B had OR = 1.47, 95% CI = 1.29–1.68, P = 4.9 × 10−9). FNDC3B was also associated with primary open-angle glaucoma (P = 5.6 × 10−4; tested in 3 cohorts with 2,979 cases and 7,399 controls). Further analyses implicate the collagen and extracellular matrix pathways in the regulation of CCT.

Phacoemulsification versus combined phacotrabeculectomy in medically uncontrolled chronic angle closure glaucoma with cataracts.

OBJECTIVE To compare phacoemulsification alone versus combined phacotrabeculectomy in medically uncontrolled chronic angle closure glaucoma (CACG) with coexisting cataract. DESIGN Prospective randomized clinical trial. PARTICIPANTS Fifty-one medically uncontrolled CACG eyes with coexisting cataract of 51 patients. INTERVENTION Recruited patients were randomized into group 1 (phacoemulsification alone) or group 2 (combined phacotrabeculectomy with adjunctive mitomycin C). Postoperatively, patients were reviewed every 3 months for 2 years. MAIN OUTCOME MEASURES Intraocular pressure (IOP) and requirement for topical glaucoma drugs. RESULTS Twenty-seven CACG eyes were randomized into group 1, and 24 CACG eyes were randomized into group 2. Combined phacotrabeculectomy resulted in lower mean postoperative IOP than phacoemulsification alone at 3 months (14.0 vs. 17.0 mmHg, P = 0.01), 15 months (13.2 vs. 15.4 mmHg, P = 0.02), and 18 months (13.6 vs. 15.9 mmHg, P = 0.01). Combined phacotrabeculectomy resulted in 1.25 fewer topical glaucoma drugs (P<0.001) in the 24-month postoperative period, compared with phacoemulsification alone. Combined surgery was associated with more postoperative complications (P<0.001) and more progression of optic neuropathy (P = 0.03), compared with phacoemulsification alone. CONCLUSIONS Combined phacotrabeculectomy with adjunctive mitomycin C is more effective than phacoemulsification alone in controlling IOP in medically uncontrolled CACG eyes with coexisting cataract. Combined phacotrabeculectomy is associated with more postoperative complications.

The clinical outcomes of cataract extraction by phacoemulsification in eyes with primary angle-closure glaucoma (PACG) and co-existing cataract: a prospective case series.

Purpose:To evaluate the clinical outcomes of minimally invasive cataract extraction by phacoemulsification, with primary intraocular lens implantation, in eyes with primary angle-closure glaucoma (PACG) and co-existing cataract. Materials and Methods:Consecutive primary angle-closure glaucoma patients with co-existing visually significant cataract were invited to participate in this prospective study. After obtaining informed consent, cataract extraction by phacoemulsification through a clear corneal incision was performed under topical anesthesia. Foldable intraocular lenses were implanted in the same setting. These patients were then followed up for a minimum of 1 year. Outcome measures included intraocular pressure (IOP), requirement for glaucoma drugs, and visual acuity. Results:Twenty-one primary angle-closure glaucoma eyes of 21 patients were recruited. Mean age (± SD) was 73.7 ± 8.1 years (range, 60-87 years). There were 12 female patients and 9 male patients, with 13 right eyes and 8 left eyes. Nine eyes (42.9%) had history of acute primary angle closure. Mean follow-up duration was 20.7 ± 3.6 months (range, 13-26 months). Intraocular pressure was decreased from a mean preoperative level of 19.7 ± 6.1 mm Hg (range, 11 mm Hg-40 mm Hg) to 15.5 ± 3.9 mm Hg (range, 9 mm Hg-26 mm Hg) at final follow-up (P = 0.022) (paired t test). The number of glaucoma eye drops required was decreased from a mean preoperative level of 1.91 ± 0.77 (range, 1-3) to 0.52 ± 0.87 (range, 0-3) at final follow-up (P < 0.001) (paired t test). In 10 eyes (47.6%), visual acuity improved significantly after surgery. In 9 eyes (42.9%), visual acuity remained the same. In 2 eyes (9.5%), visual acuity deteriorated significantly after surgery. Mean cup-to-disc ratio was 0.6 ± 0.2 (range, 0.3-0.9) preoperatively, and 0.7 ± 0.2 (range, 0.3-0.9) postoperatively (P = 0.047) (paired t test). Conclusions:In primary angle-closure glaucoma patients with co-existing cataract, cataract extraction alone (by phacoemulsification) can significantly reduce both intraocular pressure and the requirement for glaucoma drugs.

Randomized Trial of Early Phacoemulsification versus Peripheral Iridotomy to Prevent Intraocular Pressure Rise after Acute Primary Angle Closure

PURPOSE To compare the efficacy of early phacoemulsification versus laser peripheral iridotomy (LPI) in the prevention of intraocular pressure (IOP) rise in patients after acute primary angle closure (APAC). DESIGN Prospective randomized controlled trial. PARTICIPANTS Sixty-two eyes of 62 Chinese subjects, with 31 eyes in each arm. METHODS Subjects were randomized to receive either early phacoemulsification or LPI after aborting APAC by medications. Patients were followed up on day 1; week 1; and months 1, 3, 6, 12, and 18. Predictors for IOP rise were studied. MAIN OUTCOME MEASURES Prevalence of IOP rise above 21 mmHg (primary) and number of glaucoma medications, IOP, and Shaffer gonioscopy grading (secondary). RESULTS Prevalences of IOP rise for the LPI group were 16.1%, 32.3%, 41.9%, and 46.7% for the follow-ups at 3, 6, 12, and 18 months, respectively. There was only one eye (3.2%) in the phacoemulsification group that had IOP rise at all follow-up time points (P<0.0001). Treatment by LPI was associated with significantly increased hazard of IOP rise (hazard ratio [HR], 14.9; 95% confidence interval [CI], 1.9-114.2; P = 0.009). In addition, a maximum IOP at presentation > 55 mmHg was associated with IOP rise (HR, 4.1; 95% CI, 1.3-13.0; P = 0.017). At 18 months, the mean number of medications required to maintain IOP <or= 21 mmHg was significantly higher in the LPI group (0.90+/-1.14) than in the phacoemulsification group (0.03+/-0.18, P<0.0001). Mean IOP for phacoemulsification group (12.6+/-1.9 mmHg) was consistently lower than that of the LPI group (15.0+/-3.4 mmHg, P = 0.009). Mean Shaffer grading for the phacoemulsification group (2.10+/-0.76) was consistently greater than that of the LPI group (0.73+/-0.64, P<0.0001). CONCLUSION Early phacoemulsification appeared to be more effective in preventing IOP rise than LPI in patients after abortion of APAC. High presenting IOP of >55 mmHg is an added risk factor for subsequent IOP rise. For patients with coexisting cataract and presenting IOP of >55 mmHg, early phacoemulsification can be considered as a definitive treatment to prevent IOP rise.

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.

Five‐year follow up of selective laser trabeculoplasty in Chinese eyes

Purpose: To study the effectiveness and safety of selective laser trabeculoplasty (SLT) on primary open‐angle glaucoma and ocular hypertension in Chinese eyes.

Common variants near ABCA1 and in PMM2 are associated with primary open-angle glaucoma

We performed a genome-wide association study for primary open-angle glaucoma (POAG) in 1,007 cases with high-pressure glaucoma (HPG) and 1,009 controls from southern China. We observed genome-wide significant association at multiple SNPs near ABCA1 at 9q31.1 (rs2487032; P = 1.66 × 10−8) and suggestive evidence of association in PMM2 at 16p13.2 (rs3785176; P = 3.18 × 10−6). We replicated these findings in a set of 525 HPG cases and 912 controls from Singapore and a further set of 1,374 POAG cases and 4,053 controls from China. We observed genome-wide significant association with more than one SNP at the two loci (P = 2.79 × 10−19 for rs2487032 representing ABCA1 and P = 5.77 × 10−10 for rs3785176 representing PMM2). Both ABCA1 and PMM2 are expressed in the trabecular meshwork, optic nerve and other ocular tissues. In addition, ABCA1 is highly expressed in the ganglion cell layer of the retina, a finding consistent with it having a role in the development of glaucoma.

Phacoemulsification versus Trabeculectomy in Medically Uncontrolled Chronic Angle-Closure Glaucoma without Cataract

OBJECTIVE To compare phacoemulsification versus trabeculectomy with adjunctive mitomycin C in medically uncontrolled chronic angle-closure glaucoma (CACG) without cataract. DESIGN Prospective, randomized clinical trial. PARTICIPANTS Fifty medically uncontrolled CACG eyes without cataract of 50 patients. INTERVENTION Patients were randomized into undergoing either phacoemulsification or trabeculectomy with adjunctive mitomycin C. After surgery, patients were followed up every 3 months for 2 years. MAIN OUTCOME MEASURES Intraocular pressure (IOP) and requirement for glaucoma drugs. RESULTS Twenty-six CACG eyes were randomized to receive phacoemulsification, and 24 eyes underwent trabeculectomy with mitomycin C. Phacoemulsification and trabeculectomy resulted in significant and comparable IOP reduction at 24 months after surgery (reduction of 8.4 mmHg or 34% for phacoemulsification vs. 8.9 mmHg or 36% for trabeculectomy; P=0.76). Over first 24 months, trabeculectomy-treated eyes required on average 1.1 fewer drugs than phacoemulsification-treated eyes (P<0.001). However, trabeculectomy was associated with significantly more surgical complications than phacoemulsification (46% vs. 4%; P=0.001). Eight (33%) of 24 trabeculectomy eyes demonstrated cataract during follow-up. CONCLUSIONS Both phacoemulsification and trabeculectomy are effective in reducing IOP in medically uncontrolled CACG eyes without cataract. Trabeculectomy is more effective than phacoemulsification in reducing dependence on glaucoma drugs, but is associated with more complications. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Efficacy and safety of immediate anterior chamber paracentesis in the treatment of acute primary angle-closure glaucoma: a pilot study.

OBJECTIVE To study the safety and effectiveness of immediate anterior chamber paracentesis, combined with antiglaucomatous medications, in the intraocular pressure control and relief of symptoms of acute primary angle-closure glaucoma (PACG). DESIGN Prospective noncomparative case series. PARTICIPANTS Eight consecutive patients with their first attack of acute PACG, with intraocular pressure > or =50 mmHg, were recruited into the study. INTERVENTION On presentation, each patient received topical pilocarpine (4%) and timolol (0.5%), immediate anterior chamber paracentesis, and systemic acetazolamide and mannitol as primary treatment. The intraocular pressures at 15 and 30 minutes, and then at 1, 2, 3, 12, and 24 hours, were documented by applanation tonometry. MAIN OUTCOME MEASURES Symptoms, visual acuity, intraocular pressure, corneal edema, angle status on gonioscopy, pupillary size, and reaction. RESULTS Ten eyes of eight patients seen with acute PACG were recruited. The mean intraocular pressure was reduced from 66.6 +/- 9.1 mmHg to 15.1 +/- 3.5 mmHg immediately after paracentesis, and then to 17.1 +/- 7.0 mmHg at 15 minutes, 21.7 +/- 10.2 mmHg at 30 minutes, 22.7 +/- 11.0 mmHg at 1 hour, and 20.1 +/- 14.6 mmHg at 2 hours after paracentesis. The mean intraocular pressure was less than 21 mmHg at 2 hours and beyond. There was instant symptomatic relief for all patients. No complications from the paracentesis were encountered. CONCLUSIONS From this preliminary study, immediate paracentesis seems to be safe and effective in controlling the intraocular pressure and eliminating symptoms in acute PACG.

Efficacy and safety of the Ahmed glaucoma valve implant in Chinese eyes with complicated glaucoma

AIMS To evaluate the efficacy and safety of the Ahmed glaucoma valve implant in Chinese eyes with complicated glaucomas. METHODS This retrospective study reviewed the final intraocular pressure, visual outcome, and incidence of complications in all patients with the Ahmed glaucoma valve implant performed at the Prince of Wales Hospital, Hong Kong, between June 1996 and November 1998. RESULTS A total of 65 eyes from 60 patients were treated with the Ahmed glaucoma implant. At a mean follow up (SD, median) of 21.8 (9.2, 28.0) months (range 6–37 months), the mean intraocular pressure was reduced from 37.0 (SD 12.1) mm Hg before the implant surgery to 16.1 (12.4) mm Hg at the last follow up after surgery. The success rate of intraocular pressure control of <22 mm Hg was achieved in 73.8% of operated eyes. Transient postoperative hypotony with shallow anterior chamber occurred in 10.8% of cases. The most common postoperative complication was the formation of encapsulated bleb (24.6%). CONCLUSIONS The Ahmed glaucoma valve implant appears to be effective and relatively safe for treating complicated glaucomas in Chinese eyes. The success rate is comparable with those reported in non-Asian eyes. Formation of postoperative encapsulated bleb is, however, more commonly encountered.