Oral Ibuprofen is Associated With Reduced Likelihood of Early Bleb Failure After Trabeculectomy in High-Risk Glaucoma Patients.

PRCIS: Individuals prescribed ibuprofen after trabeculectomy have better postoperative intraocular pressure (IOP) control and a higher chance of bleb survival despite being at a higher risk of scarring. PURPOSE: To investigate the effects of early adjunctive oral ibuprofen treatment on IOP and bleb failure in eyes at high risk of scarring. METHODS: In these retrospective analyses, 288 eyes of 273 patients (mean ± SD age: 68.56 ± 10.47 y; 32.60% females) with primary glaucoma who underwent trabeculectomy/phacotrabeculectomy at the Singapore National Eye Centre between April 2020 and April 2021 with a follow-up duration ≥1 year were included. Of these, 77 (26.7%) eyes deemed to be at high risk of scarring were administered oral ibuprofen ≥3 months postoperatively (mean ± SD ibuprofen administration duration: 4.08 ± 2.28 wk). Participant's IOPs at baseline and at postoperative weeks 1, 2-3; and months 1, 2, 3, 6, and 12 were recorded. Bleb failure was defined as 2 consecutive IOP readings of >21, >18, and >15 mm Hg, and/or requiring remedial postoperative laser or surgery. RESULTS: The ibuprofen group experienced significantly greater postoperative IOP reductions at week 1 [mean difference, 95%CI: -2.89 (-5.22, -0.56) mm Hg] and month 1 [-2.29 (-4.53, -0.05) mm Hg]; and substantially lower odds of bleb failure at the >18 mm Hg [odds ratio, 95% CI: 0.39 (0.20-0.79)] and >15 mm Hg [0.52 (0.29-0.94)] thresholds, compared with the non-ibuprofen group. No differences in adverse ocular hypotony events were observed. CONCLUSION: Early adjunctive oral ibuprofen administered to individuals at high risk of posttrabeculectomy scarring is associated with greater IOP reductions and reduced likelihood of bleb failure. Our results suggest that oral nonsteroidal anti-inflammatory drugs may be a safe way of improving trabeculectomy survival in high-risk eyes.

Bidirectional association between glaucoma and chronic kidney disease: A systematic review and meta-analysis.

Background: Glaucoma and chronic kidney disease (CKD) are prevalent and debilitating conditions, with common pathogenic pathways like oxidative stress and fluid dysregulation. We evaluated if there is a bidirectional association between them, as previous studies have yielded conflicting results. Methods: In this systematic review and meta-analysis, we searched PubMed, Embase and Cochrane Library from inception until 15 June 2021, including full-length English articles published in peer-reviewed journals reporting on glaucoma and CKD as either exposure or outcome, among participants aged ≥18 years. We pooled overall summary estimates of odds ratios using random-effect meta-analysis and conducted subgroup meta-analyses and univariate meta regression. We assessed risk of bias using the Newcastle-Ottawa Scale (NOS) and quality of evidence using the GRADE framework. Our article is PROSPERO-registered and adherent to both PRISMA and MOOSE guidelines. This review is registered with PROSPERO (CRD42021262846). Findings: We identified 14 articles comprising of 3 retrospective cohort studies and 12 cross-sectional studies from 2,428 records, including 1,978,254 participants. Risk of bias was low to moderate. Participants with CKD at baseline had higher pooled odds of glaucoma (odds ratio[OR]=1.18, 95% confidence interval[CI]=1.04-1.33, I2=66%, N=12) compared to participants without CKD. The association remained significant in subgroups of longitudinal studies, participants with diabetes, East Asian studies and primary open-angle glaucoma. In the reverse direction, participants with glaucoma at baseline had over three-fold higher odds of incident CKD compared to participants without glaucoma after 10-15 years of follow-up in longitudinal studies (OR=3.67, 95% CI=2.16-6.24, I2=75%, N=2). All studies adjusted for age and sex, while most studies adjusted for comorbidities such as diabetes and hypertension. Meta-regression identified ethnicity (East Asians vs Non-East Asians) as a significant effect moderator. Associations were robust to trim-and-fill adjustment for publication bias, single-study influence and cumulative meta-analyses. Interpretation: Our meta-analysis suggests a bidirectional relationship between glaucoma and CKD, particularly among East Asians. Further studies are required to elucidate underlying mechanisms and account for differential association by ethnicity. Funding: Ching-Yu Cheng is supported by Clinician Scientist Award (NMRC/CSA-SI/0012/2017) of the Singapore Ministry of Health's National Medical Research Council.

Clinical operational considerations and responses to lockdown and reopening in the Covid-19 pandemic: experience of a tertiary ophthalmology centre in Singapore.

BACKGROUND: Much has been written on infection control and clinical measures for ophthalmic institutions and departments to cope with the COVID-19 pandemic. However, few articles have detailed implementation plans to manage lockdowns and subsequent re-openings. In this article, specific operational responses and their outcomes in a large tertiary ophthalmology centre are described. METHOD: Through a concerted effort led by a dedicated task force, the Singapore National Eye Centre (SNEC) planned and executed an operational transformation to respond to the restrictions imposed on healthcare delivery during a national lock down. A carefully calibrated re-starting of services was carried out with the subsequent phased reopening of the country, taking into consideration unique constraints faced at that time. Strategies for operating in the new normal environment were also developed. RESULTS: Outpatient attendances were safely and expediently reduced by 70% (8749 vs. 29,311) and 82% (5164 vs. 29,342) in April and May 2020, respectively, compared to the corresponding months in 2019. A correspondingly large reduction in surgical load was also achieved through a similar triaging and prioritization system. Through optimizing the center's use of space and time, as well as expanding on new models of care, a return to pre-pandemic patient load was achieved 3 months into the phased reopening of the country, and subsequently exceeded in the following months. CONCLUSION: The lessons gleaned from SNEC's experience may be useful for institutions currently facing the same challenges, and for future responses to COVID-19 resurgences or other pandemics.

Utilisation of poor-quality optical coherence tomography scans: adjustment algorithm from the Singapore Epidemiology of Eye Diseases (SEED) study.

PURPOSE: To evaluate the effect of signal strength (SS) on optical coherence tomography (OCT) parameters, and devise an algorithm to adjust the effect, when acceptable SS cannot be obtained. METHODS: 5085 individuals (9582 eyes), aged ≥40 years from the Singapore Epidemiology of Eye Diseases population-based study were included. Everyone underwent a standardised ocular examination and imaging with Cirrus HD-OCT. Effect of SS was evaluated using multiple structural breaks linear mixed-effect models. Expected change for increment in SS between 4 and 10 for individual parameter was calculated. Subsequently we devised and evaluated an algorithm to adjust OCT parameters to higher SS. RESULTS: Average retinal nerve fibre layer (RNFL) thickness showed shift of 4.11 µm from SS of 5 to 6. Above 6, it increased by 1.72 and 3.35 µm to 7 and 8; and by 1.09 µm (per unit increase) above 8 SS. Average ganglion cell-inner plexiform layer (GCIPL) thickness shifted 5.15 µm from SS of 5 to 6. Above 6, increased by 0.94 µm from 7 to 8; and by 0.16 µm (per unit increase) above 8 SS. When compared with reference in an independent test set, the algorithm produced less systemic bias. Algorithm-adjusted average RNFL was 0.549 µm thinner than the reference, while the unadjusted one was 2.841 µm thinner (p<0.001). Algorithm-adjusted and unadjusted average GCIPL was 1.102 µm and 2.228 µm thinner (p<0.001). CONCLUSIONS: OCT parameters can be adjusted for poor SS using an algorithm. This can potentially assist in diagnosis and monitoring of glaucoma when scans with acceptable SS cannot be acquired from patients in clinics.

The Effect of Medical Lowering of Intraocular Pressure on Peripapillary and Macular Blood Flow as Measured by Optical Coherence Tomography Angiography in Treatment-naive Eyes.

PRCIS: Reduction of intraocular pressure (IOP) by latanoprost in treatment-naive eyes is significantly correlated to an increase in vessel density (VD) at the optic nerve head (ONH). PURPOSE: To evaluate the effect of topical latanoprost on ocular microvasculature using optical coherence tomography angiography (OCTA). PATIENTS AND METHODS: In this prospective case-control study, 26 eyes from 18 treatment-naive subjects in whom prostaglandin analogue (PGA) latanoprost 0.005% was initiated were included as cases. In 10 out of the 18 subjects, medication was initiated in only 1 eye; their contralateral untreated eyes were used as controls. OCTA (AngioVue, Optovue Inc., Fremont, CA) was performed at baseline and ≥3 weeks after commencing treatment. Main outcome measures were change in flow area and VD at the ONH, radial peripapillary capillaries (RPC), and macula. Comparison between the 2 visits was performed using a linear mixed model adjusted for intereye correlation and mean ocular perfusion pressure. RESULTS: IOP decreased by 26.1%±11.3% (P<0.001) in the cases and 0.18%±12.2% (P=0.63) in controls. Significant correlations between change in IOP and change in ONH VD (correlation coefficient [r]=-0.42, P=0.04), and between change in IOP and change in RPC VD (r=-0.48, P=0.02) were observed in the cases, whereas none were observed in the controls. When multiple testing was considered, no significant changes in flow area and VD were observed in cases and controls. CONCLUSIONS: The reduction of IOP by a PGA in treatment-naive eyes was significantly correlated to the increase in ONH VD and RPC VD. This may indicate a mechanism by which IOP reduction modulates the risk of glaucoma progression by improving ocular microperfusion.

Evaluation of Primary Angle-Closure Glaucoma Susceptibility Loci for Estimating Angle Closure Disease Severity.

PURPOSE: To investigate whether recently identified genetic loci for primary angle-closure glaucoma (PACG) are associated with disease severity. DESIGN: Case-control study. PARTICIPANTS: Eight hundred four PACG patients and 943 control participants of Chinese ethnicity from Singapore. METHODS: The 8 PACG-associated single nucleotide polymorphisms (SNPs; rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 on chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) identified from genome-wide association studies were tested for association with disease severity using logistic regression adjusted for age and gender. A P value of 0.006 was set as significant after Bonferroni correction for testing of 8 loci. We also calculated the weighted genetic risk score (GRS) weighted by the estimated individual SNP effect size on PACG calculated as logarithm of the odds ratio (OR). Disease severity was based on the visual field mean deviation (MD) and classified as early to moderate (MD, >-12 dB) and severe (MD, <-20 dB). MAIN OUTCOME MEASURES: Association of PACG loci with severe disease. RESULTS: Of the 804 PACG patients, genotyping data were available for 768 individuals and included 436 with mild-to-moderate PACG and 206 with severe PACG. The PACG patients were significantly older (mean age, 64.3 ± 9.1 years vs. 56.4 ± 8.9 years; P < 0.001) and there were proportionately more women compared with control participants (58.4% vs. 49.0%; P < 0.001). Of the 8 loci investigated, we observed significant evidence of association with severe PACG at 1 SNP, namely rs3816415 in EPDR1 (OR, 2.03; 95% confidence interval [CI], 1.49-2.78; P = 1 × 10-5). A higher-weighted GRS was associated significantly with severe PACG, with an OR of 3.11 (95% CI, 1.95-4.96) comparing the lowest quartile with the highest quartile. CONCLUSIONS: Our results show that EPDR1 is associated significantly with severe PACG, suggesting that it may predispose patients to more aggressive disease development. Individuals with PACG with a higher GRS were associated with a higher risk of severe PACG.

Integration of Genetic and Biometric Risk Factors for Detection of Primary Angle Closure Glaucoma.

PURPOSE: The purpose of this study was to investigate whether the addition of primary angle closure glaucoma (PACG)-associated genetic loci allows improved detection of PACG, compared to anterior segment parameters measured by imaging. DESIGN: Case-control study. METHODS: Genotype data of the 8 PACG single-nucleotide polymorphisms (SNPs) (rs11024102 at PLEKHA7, rs3753841 at COL11A1, rs1015213 located between PCMTD1 and ST18 on Chromosome 8q, rs3816415 at EPDR1, rs1258267 at CHAT, rs736893 at GLIS3, rs7494379 at FERMT2, and rs3739821 mapping in between DPM2 and FAM102A) were available. Customized software was used to measure anterior segment optical coherence tomography (ASOCT) parameters, namely, anterior chamber depth, width, and area (ACD, ACW, and ACA) and lens vault (LV). Statistical analysis for positive predictive values was modeled using the receiver operating characteristic curve (AUC). Statistical significance comparing predictive power of the different parameters was calculated using permutation. RESULTS: A total of 388 PACG subjects and 751 controls with both ASOCT and genetic data were available for analysis. Anterior segment parameters including ACD, ACA, and LV had excellent predictive value (AUCs >0.94), except ACW (AUC=0.65), for identifying PACG. The inclusion of genetic risk alleles (either singly or as a composite genetic risk score for 8 genomewide association study SNPs) to ACD only provided a +0.50% improvement in reclassifying PACG cases and controls over and above the discriminatory value of ACD. This +0.50% improvement was not statistically significant (P > .05). CONCLUSIONS: Although significant on their own, the incorporation of genetic data in the context of anterior segment imaging parameters like ACD provided only a marginal improvement of PACG detection.

Characteristics of the Corneal Endothelium Across the Primary Angle Closure Disease Spectrum.

Purpose: To evaluate the corneal endothelial characteristics across the primary angle closure (PAC) disease spectrum amongst patients diagnosed as PAC suspects (PACS), PAC, PAC glaucoma (PACG), and previous acute PAC (APAC). Methods: We analyzed a total of 529 subjects (51 PACS, 170 PAC, 234 PACG, and 74 with previous APAC). All subjects had undergone laser peripheral iridotomy prior to study recruitment. Corneal endothelial parameters were measured using a noncontact specular microscope and the following parameters were obtained: mean central endothelial cell density (ECD; cells/mm2), coefficient of variation (CV) in cell area, and percentage of hexagonal cells. Results: The mean age of the subjects was 65.1 ± 8.2 years, and 55.2% were females. The mean central ECD was 2582.0 ± 472.8 cells/mm2 in PACS, 2566.0 ± 408.3 cells/mm2 in PAC, 2523.8 ± 406.8 cells/mm2 in PACG, and 2504.0 ± 558.1 cells/mm2 in APAC, with no significant differences in ECD across the subgroups (P = 0.61). The CV was lowest in PACS (34.38 ± 6.05 µm2/cell), and highest in APAC (37.61 ± 7.98 µm2/cell), but the differences were not significant (P = 0.07). Likewise, the percentage of hexagonality was not significantly different between the groups. A subgroup analysis on the eyes with previous APAC with their fellow eye also showed no significant differences in the corneal endothelial characteristics. Conclusions: The corneal ECD and morphological characteristics such as CV and hexagonality are not significantly different across the PAC disease spectrum. This may reflect the lack of a sustained and/or dramatic IOP insult and/or an insignificant deleterious effect from medications, age, and chronicity on corneal endothelial parameters.

Evaluation of Primary Angle-Closure Glaucoma Susceptibility Loci in Patients with Early Stages of Angle-Closure Disease.

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.

Structural Measurements for Monitoring Change in Glaucoma: Comparing Retinal Nerve Fiber Layer Thickness With Minimum Rim Width and Area.

PURPOSE: Minimum rim width (MRW) and area (MRA) have been introduced as anatomically defensible measures of neuroretinal rim tissue observable using spectral-domain optical coherence tomography (SDOCT). They have been reported to change earlier than retinal nerve fiber layer thickness (RNFLT) in glaucoma. This study sought to determine which is better to distinguish subsequent change from variability, using the previously described longitudinal signal-to-noise ratio (LSNR). METHODS: Data from 157 eyes of 157 participants with high-risk ocular hypertension or non-end-stage glaucoma (mean deviation [MD] from -22 to +3 dB) were used. Participants were tested approximately every 6 months for at least six visits. For each eye, MRW, MRA, and RNFLT were regressed linearly against time. Longitudinal signal-to-noise ratio for each eye was defined as the rate of change over time (signal) divided by the standard deviation of residuals from this trend (noise). These were compared between parameters using a Wilcoxon signed rank test. RESULTS: The median LSNRs were -0.58y⁻¹ for RNFLT (bootstrapped 95% confidence interval -0.69 to -0.48y⁻¹); -0.44y⁻¹ (-0.59 to -0.32y⁻¹) for MRW; and -0.23y⁻¹ (-0.32 to -0.08y⁻¹) for MRA. Longitudinal signal-to-noise ratios were significantly more negative for RNFLT than for MRW (P = 0.025) or for MRA (P < 0.001). CONCLUSIONS: Retinal nerve fiber layer thickness measured by SDOCT had a better LSNR than MRW or MRA. Although MRW and MRA may be more sensitive for early detection of glaucomatous damage, these data suggest that RNFLT may be preferable for monitoring change.

Bleb needling outcomes for failed trabeculectomy blebs in Asian eyes: a 2-year follow up.

AIM: To describe the outcomes of bleb needling in primary glaucoma in an Asian tertiary eye centre over a 2y period. To compare the success rates between primary angle-closure glaucoma (PACG) and primary open angle glaucoma (POAG). Lastly, to identify factors associated with success of bleb needling. METHODS: This was a retrospective review of 227 patients who underwent bleb needling between June 2009 and June 2011 in Singapore National Eye Centre. The 5-fluorouracil (5-FU) augmented bleb needling was performed either at the slit lamp or in the operating theatre. Repeat bleb needlings were performed as necessary. Complete success was defined as maintenance of intraocular pressure (IOP) ≥6 mm Hg and ≤21 mm Hg, in the absence of further surgery or use of antiglaucoma medication. Qualified success met the above criteria with or without use of antiglaucoma medications. RESULTS: One hundred and seventy-five eyes completed the two-year follow up. Sixty-nine percent of participants had POAG and 31% had PACG. The mean interval between filtering surgery and bleb needling was 299.9±616.4d for POAG and 167.1±272.2d for PACG. Mean needling attempts were 1.9±1.4 and 2±1.6 for POAG and PACG respectively. In general, there was a statistically significant reduction of IOP ranging from 21.9% to 26.8% from month 1 through to month 24. The complete success rates at month 6 were 70.0% for POAG and 65.7% for PACG. At month 12, this decreased to 62.2% for POAG and PACG and at month 24, 57.9% for POAG and 63.0% for PACG respectively. The qualified success rates at month 6 for POAG and PACG were 23.8% and 29.9% respectively, 32.2% and 29.2% at month 12, and 34.7% and 29.6% at month 24. The success rates between POAG and PACG were not significantly different (P>0.05 for complete and qualified success at months 6, 12 and 24). An increased number of needlings and higher pre-needling IOP were associated with failure. CONCLUSION: The 5-FU augmented bleb needling within one year of trabeculectomy in Asian eyes can provide clinically significant IOP lowering of more than 20% for 2y. POAG and PACG had similar complete success rates (58% and 63% respectively). Factors associated with greater risk of procedure failure included increased number of needlings and higher pre-needling IOP. Asian eyes have a greater propensity for scarring but bleb needling, if performed in a timely manner can rescue bleb function.

Ocular hypertension: an approach to assessment and management.

Ocular hypertension is a common and important problem seen by eye care providers. This review presents a practical approach to individuals with ocular hypertension. It describes the common functional and structural investigations used in evaluation, as well as the advantages and disadvantages of each test. This review also discusses several landmark studies on ocular hypertension and provides a practical guide to the management of this problem.

Myopia, axial length, and age-related cataract: the Singapore Malay eye study.

PURPOSE: To describe the associations of myopia and axial length (AL) with age-related cataract in an Asian population in Singapore. METHODS: A population-based cross-sectional study that examined 3280 (78.7% response) adults of Malay ethnicity aged 40 to 80 years. Refractive error was determined by subjective refraction and AL was measured using the Zeiss IOL-Master. Digital slit lamp and retroillumination lens photographs were taken and graded for age-related nuclear, cortical, and posterior subcapsular (PSC) cataract following the Wisconsin system. RESULTS: After excluding eyes with prior refractive or cataract surgery, 5474 eyes with gradable lens photographs were analyzed. In multivariate analyses adjusting for age, sex, body mass index, systolic blood pressure, glycosylated hemoglobin, smoking status, and education, myopia (spherical equivalent less than -0.5 diopter [D]) was associated with an increased prevalence of nuclear (OR: 4.99, 95% CI: 3.72­6.69) and PSC cataract (OR: 1.34, 95% CI: 1.30-1.39) but not with cortical cataract (OR: 0.85, 95% CI: 0.68-1.08) compared with emmetropia. Per-millimeter increase in AL was not associated with any of the three cataract subtypes. When myopia was defined as spherical equivalent of less than -5.0 D to -6.0 D, the OR of myopia for PSC cataract increased dramatically. CONCLUSIONS: Our study shows that myopia, but not AL, was associated with nuclear cataract, supporting the concept of index myopia with aging. Myopia, especially high myopia, may predispose to PSC cataract formation. Clinically, ophthalmologists should be aware that risk of PSC cataract appears to vary by refractive status.

Conventional and emerging treatments in the management of acute primary angle closure.

The management of acute primary angle closure is directed at lowering the intraocular pressure and relieving pupil block. Conventional treatment involves the use of medical treatment and laser peripheral iridotomy, respectively, as a means for achieving these aims. Newer therapeutic strategies have been described that are potentially useful adjuncts or alternatives to conventional treatment. Emerging strategies that lower intraocular pressure include anterior chamber paracentesis, as well as laser procedures such as iridoplasty and pupilloplasty. A possible alternative to relieving pupil block is lens extraction, and may be combined with adjunctive measures such as goniosynechiolysis and viscogoniosynechiolysis. Trabeculectomy has a limited role in the acute setting. This review paper reviews the current evidence regarding conventional and newer treatment modalities for acute primary angle closure.

Outcomes of trabeculectomy after descemet stripping automated endothelial keratoplasty: a comparison with penetrating keratoplasty.

PURPOSE: To compare the outcomes of trabeculectomy surgery after Descemet stripping automated endothelial keratoplasty (DSAEK) to penetrating keratoplasty (PK). DESIGN: Retrospective case-control study. METHODS: Patients within an institutional setting who underwent trabeculectomy with mitomycin C (MMC) for uncontrolled elevated intraocular pressure (IOP) after corneal graft surgery were included. Patients with pre-existing glaucoma were excluded. Twenty patients with trabeculectomy after DSAEK and 41 patients with trabeculectomy after PK were analyzed. The main outcome measure was IOP control at 12 months. Secondary outcome measures were postoperative interventions including reinstatement of IOP-lowering medications, bleb needling with 5-fluorouracil (5FU) or further glaucoma surgery, and the incidence of complications related to trabeculectomy and/or corneal graft surgery. RESULTS: There was no difference in pre-trabeculectomy IOP between DSAEK vs PK group (35.5 ± 10.1 vs 32.9 ± 8.9, P = .31). At 12 months after trabeculectomy, mean IOP in the DSAEK group was lower compared to the PK controls (10.6 ± 3.2 vs 14.6 ± 8.5, P = .04). The proportion of patients who achieved an IOP less than 12 mm Hg was significantly higher in the DSAEK group (80.0% vs 48.6%, P = .03). The proportions of eyes that required intervention after trabeculectomy were comparable between the 2 groups (DSAEK vs PK, all interventions: 20.0% vs 39.5%, P = .15; IOP-lowering medications required: 15.0% vs 39.5%, P = .08; needling with 5FU: 20.0% vs 23.7%, P > .99; further glaucoma surgery: 0% vs 13.2%, P = .15). Corneal graft failure arising after trabeculectomy was seen in 10.0% of DSAEK cases and in 10.5% of PK controls (P = 1.0). CONCLUSION: Compared to trabeculectomy after PK, trabeculectomy after DSAEK achieved lower mean IOP at 12 months, and a larger proportion of DSAEK patients achieved an IOP of less than 12 mm Hg. There was no difference in the need for intervention after trabeculectomy, or incidence of other complications. Trabeculectomy is an effective surgical procedure for the management of postgraft ocular hypertension in DSAEK patients, and DSAEK may have an advantage in terms of success of trabeculectomy surgery over PK.

Randomized, controlled trial of a sustained delivery formulation of 5-fluorouracil for the treatment of failing blebs.

PURPOSE: To determine the efficacy of a subconjunctival injection of hyaluronic acid (HA) with 5-fluorouracil (5FU) formulation as an adjunct in reviving bleb function by needling. DESIGN: Prospective, randomized, controlled trial. PARTICIPANTS: Fifty patients with previous trabeculectomy and scheduled by the managing physician for a needling intervention. METHODS: One eye of each patient was randomized to receive needling with HA-5FU mixture or needling with subconjunctival injection of 5FU solution alone. MAIN OUTCOME MEASURES: The primary outcome was the percentage of subjects with an intraocular pressure (IOP) <15 mmHg without any medications at 3 months. Secondary outcomes included the need for additional needling procedures and changes in bleb morphology. RESULTS: Forty-nine subjects (25 in the HA-5FU group and 24 in the 5FU group) completed 3 months of follow-up. At baseline, there was no significant difference between the groups in terms of demographic features, subtype of glaucoma, vertical cup-to-disc ratio, or visual field indices. The mean number of glaucoma medications at baseline was higher in the 5FU group (0.8±1.1 [mean ± standard deviation] vs. 0.2±0.6, P = 0.04). An IOP <15 mmHg without medications was reached in 48.0% of subjects in the HA-5FU group and in 33.3% of subjects in the 5FU group (P = 0.2). At 3 months, both groups demonstrated a significant decrease in IOP from baseline (HA-5FU: decrease of 5.9 mmHg [95% confidence interval, 3.4-8.4]; 5FU: decrease of 6.0 mmHg [95% confidence interval, 3.2-8.2]; P<0.001 for both). Intergroup comparisons for IOP change from baseline was not significant (P = 0.9). However, repeat needling was required more frequently in the 5FU group compared with the HA-5FU group (50.0% vs. 12.0%; P = 0.004). There were no significant differences in the number of reported adverse events, bleb vascularity, or morphology between the 2 groups. CONCLUSIONS: Subconjunctival injection of HA-5FU to revive bleb function after bleb needling is as effective as 5FU solution. Fewer repeat needlings were required after treatment with HA-5FU, suggesting that the use of a combined formulation of HA-5FU may improve the overall outcomes of bleb needlings.

Tear cytokine profile in medicated glaucoma patients: effect of monocyte chemoattractant protein 1 on early posttrabeculectomy outcome.

PURPOSE: To determine the tear cytokine profile from medicated glaucoma patients scheduled for trabeculectomy and to establish whether a specifically elevated cytokine level is related to early postoperative scarring. DESIGN: Prospective case-control study. PARTICIPANTS: Sixty-one patients treated with topical antiglaucoma medications and 29 normal subjects with no prior topical treatment were recruited for the study. METHODS: Schirmer strips were used to collect tear samples. A multiplex bead assay was used to quantify the presence of proinflammatory cytokines in the tears. The patients were followed up for 6 months after surgery to determine whether any postoperative intervention to maintain filtering bleb function was required. MAIN OUTCOME MEASURES: The level of cytokines in tear specimens from medicated glaucoma patients was the main outcome measure for the study. The need for postoperative bleb needling within 6 months was a secondary outcome measure. RESULTS: Of the 17 cytokines assayed, only monocyte chemoattractant protein 1 (MCP-1) was elevated significantly in the medicated eyes compared with the unmedicated eyes (P < 0.0004). At 6 months after surgery, 18 (30%) of the 61 eyes required postoperative intervention. A much higher MCP-1 level was detected in these eyes compared with the remaining 43 that did not require intervention (P < 0.0001). The duration of use of topical medication correlated with increasing levels of MCP-1, although the types of glaucoma medication and the number of bottles of medications did not have any significant relationship with the level of MCP-1. CONCLUSIONS: In tears from topically medicated glaucoma eyes in an Asian population, MCP-1 was found to be the predominant cytokine elevated. Eyes with a propensity to scar in the early postoperative period have a significantly raised level of MCP-1. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

C-reactive protein and age-related macular degeneration and cataract: the singapore malay eye study.

Purpose. To describe associations between C-reactive protein (CRP) and age-related macular degeneration (AMD) and cataract in an Asian population. Methods. A population-based, cross-sectional study of 3280 (78.7% response) Malay persons aged 40 to 80 years was conducted in Singapore. Wisconsin grading protocols were used to grade retinal photographs for signs of early and late AMD, and lens photographs were assessed for nuclear, cortical, and posterior subcapsular (PSC) cataract. Venous blood samples were assessed for serum CRP. Results. Of 3100 (94.5%) subjects with gradable fundus photographs, 177 (5.7%) had any AMD, 155 (5.0%) early AMD, and 22 (0.7%) late AMD. No association was found between CRP and AMD. After subjects were stratified by diabetes status, the data showed that higher CRP was associated with any AMD in 2385 persons without diabetes (multivariate-adjusted odds ratio [OR], 1.73; 95% confidence interval [CI], 1.03-2.91, comparing the 4th versus the 1st quartiles of CRP). Cataract was present in 1431 (48.5%) subjects, and 634 (21.5%), 881 (29.9%) and 443 (15.0%) had nuclear, cortical, and PSC cataract, respectively. After multivariate analysis, no association was found between CRP and any cataract (OR, 0.99; 95% CI, 0.73-1.34), nuclear (OR, 0.98; 95% CI, 0.68-1.40), cortical (OR, 0.94; 95% CI, 0.71-1.23), or PSC (OR, 1.12; 95% CI, 0.81-1.55) cataract. Conclusions. In the general population, there were no associations between CRP and AMD or cataract. In persons without diabetes, higher CRP was associated with AMD. These data suggest only a weak link between systemic inflammation and AMD and cataract in Asian people.

Magnetic resonance imaging in acute optic neuritis in Singapore.

INTRODUCTION: The Optic Neuritis Treatment Trial (ONTT) has established that the magnetic resonance imaging (MRI) findings at the time of presentation of optic neuritis (ON) is the strongest indicator of the development of multiple sclerosis (MS). Reports from Singapore as well as other Asian countries have indicated that these abnormalities are less frequently encountered compared to that reported by the ONTT. This paper aims to describe systematically the brain MRI as well as the optic nerve abnormalities in patients after an episode of acute optic neuritis. MATERIALS AND METHODS: Patients who presented with acute optic neuritis were retrieved from our prospective optic neuritis study and their MRI scans were reviewed and graded in accordance with the standardised classification employed in the ONTT. RESULTS: Fifteen of 24 patients had MRI brain and optic nerves performed during the acute episode. In the evaluation of brain abnormalities, 40% were classified as grade 0, 20% grade I, 20% grade II, 6.7% grade III and 13.3% grade IV. Optic nerve abnormalities were observed in 80% of cases. At study entry, 10 patients had idiopathic (monosymptomatic) ON, 3 had multiple sclerosis (MS), one each with infective and autoimmune optic neuritis, respectively. The single patient who developed MS at study completion presented with grade II brain abnormalities at the initial MRI. For those with idiopathic ON, our study revealed a higher percentage of grade 0-I brain changes as well as a lower lesion load compared to the ONTT.Lesion Load and grade was also lower in anterior optic neuritis compared with retrobulbar disease. CONCLUSION: Our study revealed a lower percentage of grade II-IV brain MRI abnormalities as well as less lesion load in idiopathic ON compared to the ONTT. This may be related to the lower prevalence of MS in our predominantly Asian population. As diagnostic tests and understanding of neuromyelitis optica or Devic's disease improves, we may see more patients being diagnosed with this condition, which may also explain our findings. Our data also showed that MRI grade and lesion load in cases of anterior ON was lower than for retrobulbar disease. MRI in ON has an essential role in characterising the disease, evaluating for associated brain lesions, and assessing prognosis in retrobulbar disease but may be less useful in anterior disease.