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Purpose: To describe the long-term outcomes of phacotrabeculectomy from a tertiary glaucoma service in Singapore., Design: Retrospective case series., Methods: Seven hundred ninety-six eyes of 698 patients who underwent phacotrabeculectomy surgery at the Singapore National Eye Centre between 2005 and 2007 with a minimum follow-up of three years were included. The primary outcome measure was intraocular pressure (IOP). Secondary outcomes included best-corrected visual acuity (BCVA), number of glaucoma medications, and surgical complications., Results: The mean age was 69.5 years, 51 % were male, and 86 % were Chinese. Most eyes had primary glaucoma (90.6 %). The mean follow-up duration was 9.4 years. The overall success rate at three years was 97 % if surgical success was defined as IOP ≤ 21 mm Hg, 92 % if IOP ≤ 18 mm Hg, 66 % if IOP ≤ 15 mm Hg. By Kaplan-Meier survival analysis over 13 years, the cumulative success rate fell from 98.1 % to 89.1 % if IOP ≤ 21 mm Hg, 98.1-76.9 % if IOP ≤ 18 mm Hg, 98-50.3 % if IOP ≤ 15 mm Hg. The postoperative IOP improved significantly at all time points (P < 0.05) and 72 % had at least 20 % IOP reduction. There was a slight improvement in postoperative BCVA (P < 0.05). The mean number of glaucoma medications was reduced postoperatively (P < 0.001). There were no significant risk factors for surgical failure., Conclusions: Phacotrabeculectomy was found to be safe, resulting in clinically significant IOP lowering for 13 years with reduced dependency on glaucoma medications and improved BCVA., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Virtual glaucoma clinics can help increase health care capacity, easing the disease burden of glaucoma. This study assesses the safety, rate of glaucoma progression, time efficiency, and cost-savings of our expanded Glaucoma Observation Clinic (GLOC) at the Singapore National Eye Centre over 3 years., Methods: All patients seen at GLOC between July 2018 and June 2021 were included. Visual acuity, intraocular pressure, and visual fields or optic nerve head imaging were recorded, followed by a virtual review of the data by an ophthalmologist. An objective review of the management of 100 patients was conducted by 2 senior consultants independently as a safety audit. Patient outcomes including the rate of instability (due to worsening of clinical parameters necessitating a conventional clinic visit), glaucoma progression, the consultation review time efficiency, and cost-savings of GLOC were measured., Results: Of 3458 patients, 16% had glaucoma, and the others had risk factors for glaucoma. The safety audit demonstrated a 95% interobserver agreement. The rate of instability was 14.6%, of which true progression was observed in 3.12%. The time taken for a glaucoma specialist to review a GLOC patient was 5.75±0.75 minutes compared with 13.7±2.3 minutes in a conventional clinic. The per capita manpower cost per GLOC patient per visit was $36.77 compared with $65.62 in the conventional clinic. This translates to a cost-saving of $280.65 over the lifetime of a hypothetical patient., Conclusions: Our expanded virtual glaucoma clinic is a safe, time-efficient, and cost-effective model with low rates of glaucoma progression, which could allow for significant health care capacity expansion., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2023 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Purpose: To assess the implementation outcomes of a new asynchronous virtual clinic, the Glaucoma Observation Clinic (GLOC), at the Singapore National Eye Center, in monitoring patients at low risk for glaucoma progression., Methods: Patients with low risk of glaucoma progression were followed up at GLOC. Visual acuity, intraocular pressure, and visual field testing or optic nerve head imaging were assessed by nurses and technicians, with virtual review of data by an ophthalmologist separately. The implementation outcomes were defined as patient satisfaction, assessed by a nurse-administered questionnaire; the rate of referrals back to the glaucoma outpatient department; the patients' journey time (minutes); the time taken for the specialist review (minutes), and the per capita manpower cost compared with current glaucoma outpatient model., Results: A total of 377 patients were included, with the majority being glaucoma disc suspects (n = 250, 66.4%) and primary angle closure suspects (n = 54, 14.3%). Most patients (more than 90%) reported being satisfied, and only 7.7% (n = 29) were referred back to the specialist outpatient glaucoma clinic due to possible glaucoma progression. Compared with the glaucoma outpatient clinic, the average journey time in GLOC was 50% less (59.3 mins vs 132 mins), the average time for a specialist review was 3 times faster (5.8 mins vs 19.5 mins), and the per capita manpower cost of GLOC was halved ($20.07 vs $39.78)., Conclusions: GLOC is a time-efficient, cost-saving, and sustainable model of care for managing patients with low risk of glaucoma progression. It was well received by patients and freed up the conventional clinic to treat patients with complex needs., Competing Interests: The authors have no funding or conflicts of interest to declare., (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Purpose: To investigate whether newly identified genetic loci for primary angle-closure glaucoma (PACG) are associated with early stage angle-closure disease defined as primary angle closure suspect (PACS)., Design: Case-control study., Participants: A total of 1397 PACS patients and 943 controls of Chinese ethnicity from Singapore and 604 PACS patients and 287 controls of Indian ethnicity., Methods: The 8 PACG single nucleotide polymorphisms (SNPs; rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 son chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) were genotyped by Taqman assays. The association between SNP genotypes and PACS status was measured using logistic regression. A P value of 0.006 was set to account for the testing of 8 genetic loci using a Bonferroni correction. A meta-analysis was conducted to calculate the overall P value and accompanying per-allele odds ratios for each SNP analyzed., Main Outcome Measures: Association of PACG loci with PACS status., Results: The PACS patients were significantly older in both cohorts (Chinese, P < 0.001; Indian, P = 0.002), and there were also more women (P < 0.001, both Chinese and Indian cohorts). In the Chinese cohort, significant evidence of association was noted at 3 SNPs: rs1015213 [A] in PCMTD1-ST18 (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.36-4.11; P = 0.002), rs3816415 [A] in EPDR1 (OR, 1.49; 95% CI, 1.19-1.85; P < 0.001), and rs3739821 [G] in DPM2-FAM102A (OR, 1.40; 95% CI, 1.18-1.65; P < 0.001). Only PCMTD1-ST-18 was replicated modestly in the Indian population (P = 0.056). Meta-analysis showed significant evidence of association for PCMTD1-ST-18 (OR, 1.55; 95% CI, 1.18-2.04; P = 0.002) and DPM2-FAM102A (OR, 1.27; 95% CI, 1.12-1.45; P = 0.0002)., Conclusions: In this study, 2 of 8 PACG-associated loci were associated significantly with PACS status, the earliest stage in the angle-closure glaucoma disease course. The association of these PACG loci with PACS status suggests that these loci may confer susceptibility to a narrow angle configuration., (Copyright © 2018 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the acceptance and preferences rates of 3 sustained drug delivery systems in glaucoma patients., Materials and Methods: A cross-sectional study involving 250 Chinese patients recruited from outpatient glaucoma clinics in Singapore using an interviewer-administered survey. Beliefs toward medicines, eye drops, illness perception, medication adherence, and health literacy were assessed using validated questionnaires. After receiving standard information on the 3 sustained drug delivery systems, that is, subconjunctival, intracameral, and punctal routes; each route's acceptance and attitudes were determined., Results: The subconjunctival (acceptance: 61.6%, n=154), intracameral (acceptance: 57.2%, n=143), and punctal (acceptance: 63.2%, n=158) routes were willing to be accepted by the majority of the interviewed patients. Among those, 78.6%, 79.1%, and 78.5% were willing to pay an equal or higher cost compared with their current eye drops for the subconjunctival, intracameral, and punctal plug routes, respectively. Independent factors associated with the acceptance for subconjunctival, intracameral, and punctal plug routes included: male sex (P=0.007, 0.014, 0.046, respectively), patients not on health care subsidies (P=0.022, 0.002, 0.016, respectively), and bilateral glaucoma disease (P=0.003, 0.013, 0.004, respectively). A total of 120 (48.0%) patients ranked punctal plug placement as the preferred route for sustained drug delivery followed by subconjunctival (n=76, 30.4%) and intracameral (n=54, 21.6%) routes., Conclusions: Sustained drug delivery for the medical treatment of glaucoma is an acceptable alternative to daily eye drop administration by most Singaporean Chinese individuals in this study. Male patients, nonsubsidized patients, and those with bilateral glaucoma were independently associated with preference of these 3 alternative routes of administration to traditional glaucoma drops.

Objective: To report the 8-year outcomes of Asian subjects who underwent trabeculectomy augmented by intraoperative 5-fluorouracil (5-FU) or placebo., Design: Retrospective review of a randomized controlled trial., Participants: Subjects with primary open-angle or angle-closure glaucoma., Methods: Study subjects were prospectively followed up for 3 years. After the last subject recruited had completed 8 years of follow-up, the charts of all subjects were reviewed to capture data from the year 3 visit onward. Kaplan-Meier survival function with Cox regression was performed to identify risk factors associated with trabeculectomy failure at 8 years., Main Outcome Measures: The primary outcome was trabeculectomy failure defined as intraocular pressure (IOP) >21 or <6 mmHg on 2 consecutive occasions after the first 6 weeks after surgery, repeat glaucoma surgery, or loss of light perception. Further end points were defined at IOP levels >17 and >14 mmHg. Secondary outcomes included IOP at 8 years and number of glaucoma medications. Complete success was defined using IOP end points ≤ 21, ≤ 17, or ≤ 14 mmHg at 8 years without medications., Results: Of the 243 enrolled subjects, 170 (70.0%) completed 8 years follow-up, 86 in the 5-FU and 84 in the placebo group. There was no significant difference in failure rates at 8 years for the failure definitions of IOP >21 mmHg (11.6% of the 5-FU group vs. 16.7% of the placebo group; P = 1.00), IOP >17 mmHg (23.3% of the 5-FU group vs. 31% of the placebo group; P = 0.78), and IOP >14 mmHg (46.5% of the 5-FU group vs. 58.3% of the placebo group; P = 0.37). Mean IOP at 8 years was 13.7 mmHg in the 5-FU versus 14.4 mmHg in the placebo group (P = 0.24). Mean number of medications was 0.65 drops in the 5-FU versus 0.93 drops in the placebo group (P = 0.06). Complete success with IOP ≤ 21 mmHg at 8 years was achieved in 48 subjects (55.8%) in the 5-FU and 33 subjects (39.3%) in the placebo group (P = 0.09). Absence of bleb microcysts at 1 year, preoperative IOP, and number of bleb needlings performed within the first year were significantly associated with failure., Conclusions: There was no significant difference in IOP between the 5-FU and the placebo group at 8 years., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To evaluate the impact of bilateral primary glaucoma on glaucoma-specific functioning in Asians., Methods: Patients with bilateral primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG) aged 40 years or above of Chinese ethnicity in Singapore were recruited. All underwent a comprehensive clinical assessment of glaucoma. Glaucoma was diagnosed with a standard criteria including optic disc abnormality and visual field defect. The Glaucoma Quality of Life-15, a glaucoma-specific questionnaire, was used to evaluate the impact of glaucoma, and Rasch analysis was used to validate the Glaucoma Quality of Life-15., Results: A total of 192 patients (mean±SD age, 65.73±17.6 y and 65.1% male) were recruited, of which 56.2% (n=108) and 43.8% (n=84) had POAG and PACG, respectively. Fifty-four (28.1%), 85 (44.3%), and 53 (27.6%) had bilateral mild glaucoma, mild glaucoma in 1 eye and moderate/severe glaucoma in the other, and bilateral moderate/severe glaucoma, respectively. In multivariate analyses, compared with patients with mild glaucoma in both eyes, those with (a) mild glaucoma in 1 eye and moderate/severe in other; and (b) moderate/severe glaucoma in both eyes, reported significantly poorer functioning (β-coefficient=-8.20; confidence interval, -14.36 to -2.04; P<0.05) and (β=-21.05; confidence interval, -28.06 to -14.04; P<0.05), respectively. A similar independent association was found for POAG and PACG. These associations were also considered to be clinically significant while comparing bilateral mild glaucoma with bilateral moderate/severe glaucoma. We however, found no significant difference for functioning and severity of glaucoma between PACG and POAG patients (P<0.05)., Conclusions: Bilateral glaucoma is worse than the mild form in any eye and is significantly associated with poor glaucoma-specific functioning in this Singaporean Chinese sample. These data emphasize the need for strategies to identify patients early and prevent deterioration beyond the mild form of the condition.

Purpose: We investigated patients' attitudes and perceptions toward a subconjunctival implant as a novel ocular drug delivery method for glaucoma., Methods: We recruited 344 Chinese patients with primary open angle or angle closure glaucoma currently on topical antiglaucoma medication for a minimum of six months from specialist glaucoma clinics. Sociodemographic data, and information about patients' general and ocular health were collected. Beliefs about medicines, glaucoma, eye drops, and self-reported adherence were assessed by trained interviewers using validated questionnaires. A description about the implant was provided and patients subsequently were assessed on their understanding and acceptance., Results: Of the 344 Chinese patients enrolled, 216 (62.8%) would accept the implant as a replacement for their current eye drops. Of those who accepted the implant, 99 (45.8%) were willing to accept it at similar costs, while 40 (18.5%) and 20 (9.3%) patients were willing to pay 1.5 and 2 times the cost of their present medication, respectively. Patients who accepted the implant had more severe glaucoma (P = 0.015) and felt that the implant was more helpful than eye drops (P < 0.001). Beliefs toward medicines, glaucoma, eye drops, self-reported adherence, and sociodemographic factors did not have a significant impact on the patients' decisions., Conclusions: An ocular drug implant would be an acceptable alternative to topical eye drops for subgroups of glaucoma patients.

Purpose: To determine the proinflammatory cytokine profile of aqueous humor from glaucomatous eyes., Methods: Aqueous humor samples were prospectively collected from 38 eyes (26 primary open angle glaucoma [POAG] and 12 primary angle closure glaucoma [PACG] eyes) of 37 medically treated glaucoma patients and 23 cataract subjects recruited in an institutional setting in this case-controlled study. The main outcome measure was to quantify the levels of 29 inflammatory cytokines in the aqueous of glaucoma and cataract subjects using a multiplexed cytokine analysis. Data on patient demographics, duration of glaucoma, preoperative intraocular pressure (IOP) as well as duration of anti-glaucoma therapy were also collected for correlation analysis., Results: Mean duration of glaucoma was 53.8 months (range 1-360 months). Aqueous obtained from the glaucoma patients showed increased concentration of interleukin (IL)-9 (p=0.032), IL-12 (p=0.003), interferon (IFN)-α (p=0.034), IFN-γ (p=0.002), monokine induced by interferon-gamma (MIG or CXCL9) (p=0.006), and IL-10 (p=0.050), compared to the cataract group. The POAG group had higher IL-12 (p=0.011), IFN-γ (p=0.005), and CXCL9 (p=0.047) levels than controls, while the PACG group had higher interleukin-8 (CXCL8) (p=0.015) and CXCL9 (p=0.023) levels than the controls. No significant correlation was observed between aqueous cytokine level and preoperative IOP and duration of glaucoma. Duration of topical Timolol and Alphagan therapy correlated negatively with CXCL8 (r=-0.588, p=0.035), respectively., Conclusions: Primary glaucoma is associated with an aqueous inflammatory response and this is different between POAG and PACG groups. Duration of glaucoma treatment may have an effect on cytokine profile in the aqueous.

Purpose: To describe the distribution of intraocular pressure (IOP) and its cross-sectional relationship to age, systolic blood pressure (sBP), and central corneal thickness (CCT) in an Asian population., Methods: This was a population-based, cross-sectional study of 3280 Malay subjects (78.7% response) aged 40 to 80 years residing in Singapore. The participants had a standardized interview, examination, and ocular imaging at a centralized study clinic. IOP was measured with Goldmann applanation tonometry (GAT) before pupil dilation, CCT measurements were obtained with an ultrasound pachymeters, and sBP was taken with participants seated after 5 minutes of rest with an automatic blood pressure monitor., Results: IOP increased with age to the sixth decade, after which a decrease in IOP was seen with further increase in age, resulting in an inverted U pattern. sBP increased linearly with age whereas CCT decreased linearly with age. In regression models, age, CCT, and sBP were all significant determinants of IOP (P < 0.001 for all three). In younger persons aged 40 to 59 years, both CCT and sBP were positively associated with IOP (P < 0.001 for both), but in older persons of 60 to 80 years, only age and sBP had a positive association with of IOP (P = 0.001 for age, P < 0.001 for sBP)., Conclusions: Age, CCT and sBP are significant determinants of IOP in persons aged 40 to 80 years, with CCT being a more important determinant in younger persons. The opposing effects of age-specific changes in sBP and CCT interact to lead to a relatively flat profile of IOP with age, possibly with a subtle inverted U-shaped relationship.

Objective: To determine the prevalence of tilted and torted optic discs and associated risk factors among Chinese adults in Singapore., Methods: As part of a population-based survey, optic disc stereophotographs of both eyes were obtained, and left eyes were analyzed using imaging software. A tilted optic disc was defined as an index of tilt (ratio of minimum to maximum optic disc diameter) less than 0.75. The angle of tilt was defined as the angle between the maximum and vertical optic disc diameter, and optic discs were graded as torted if the angle of tilt exceeded 15 degrees ., Results: Twenty-six of 739 subjects (3.5%) had tilted optic discs, and 478 (64.7%) had torted optic discs. Myopia was present in 23 of 26 eyes (88.5% [95% confidence interval, 69.9%-97.6%]) with tilted optic discs and in 211 of 661 eyes (31.9% [28.4%-35.6%]) without tilted optic discs (P < .001). On multivariate analysis, myopia (spherical equivalent) was a significant risk factor for tilted optic discs (P < .001). Index of tilt was not associated with corneal astigmatism or with cylindrical refractive error. Seventeen eyes (65.4%) with tilted optic discs had an optic disc morphologic abnormality, but none were glaucomatous., Conclusions: The prevalence of tilted optic discs among this Chinese population was 3.5%. Tilted optic discs were associated with myopia but not with glaucoma.

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.

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.