Development and Validation of Performance-Based Assessment of Daily Living Tasks in Age-Related Macular Degeneration.

Purpose: To establish the reliability and validity of five performance-based activities of daily living task tests (ADLTT), to correlate structure to function, to evaluate the impact of visual impairment (VI) on age-related macular degeneration (AMD), and to develop new outcome measures. Methods: A multidisciplinary team developed five ADLTTs: (1) reading test (RT); (2) facial expression (FE) recognition; (3) item search (IS) task; (4) money counting (MC) task; and (5) making a drink (MD), tested with binocular and monocular vision. ADLTTs were tested for known-group (i.e., difference between AMD group and controls) and convergent (i.e., correlation to other measures of visual function), validity metrics, and test-retest reliability in 36 patients with VI (visual acuity (logMAR VA > 0.4) in at least one eye caused by AMD versus 36 healthy controls without VI. Results: Compared to controls, AMD patients had a slower reading speed (-77.41 words/min; P < 0.001); took longer to complete MC using monocular worse eye and binocular vision (15.13 seconds and 4.06 seconds longer compared to controls, respectively; P < 0.001); and MD using monocular worse eye vision (9.37 sec; P = 0.033), demonstrating known-group validity. Only RT and MC demonstrated convergent validity, showing correlations with VA, contrast sensitivity, and microperimetry testing. Moderate to good test-retest reliability was observed for MC and MD (interclass correlation coefficient = 0.55 and 0.77; P < 0.001) using monocular worse eye vision. Conclusions: Real-world ADL functioning associated with VI-related AMD can be assessed with our validated ADLTTs, particularly MC and MD. Translational Relevance: This study validates visual function outcome measures that are developed for use in future clinical practice and clinical trials.

Factors influencing myopia stabilisation in young myopic adult Singaporeans.

PURPOSE: To evaluate factors influencing stabilisation of myopia in the Singapore Cohort of Risk factors for Myopia. METHODS: We evaluated the longitudinal natural history of 424 myopic participants from 1999 to 2022. The outcome was the change in myopia from the adolescence follow-up visit (aged 12-19 years) to the adulthood follow-up visit (aged 26-33 years). Association of predictive factors, including baseline spherical error, gender, ethnicity, parental myopia, time outdoor, near work and age at adolescence, was examined with the dichotomous outcome of adult myopia progression (≤ -1.00 dioptres (D) over 10 years) using multiple logistic regression and progression in linear regression models. RESULTS: For the primary outcome, the mean rate of progression of the outcome was found to be -0.04±0.09 D per year from the adolescent to the adulthood follow-up visits. 82.3% (95% CI 78.3% to 85.8%) had myopia stabilisation, with progression of less than 1.00 D over 10 years while 61.3% (95% CI 56.5% to 66.0%) of the subjects had progression of less than 0.50 D. In logistic regression models, both male gender (p=0.035) and non-Chinese ethnicity (p=0.032) were more likely to achieve myopia stabilisation while in linear multivariate regression models, males had a significantly slower degree of myopia progression (p=0.021). CONCLUSION: 5 in 6 Singaporean young adults had myopia stabilisation. Male gender is 2 times and non-Chinese ethnicities are 2.5 times more likely to achieve myopia stabilisation. However, a proportion of myopes continue to exhibit a clinically significant degree of progression in adulthood.

Early Visibility of Cellular Aggregates and Changes in Central Corneal Thickness as Predictors of Successful Corneal Endothelial Cell Injection Therapy.

(1) Background: Cell injection therapy is an emerging treatment for bullous keratopathy (BK). Anterior segment optical coherence tomography (AS-OCT) imaging allows the high-resolution assessment of the anterior chamber. Our study aimed to investigate the predictive value of the visibility of cellular aggregates for corneal deturgescence in an animal model of bullous keratopathy. (2) Methods: Cell injections of corneal endothelial cells were performed in 45 eyes in a rabbit model of BK. AS-OCT imaging and central corneal thickness (CCT) measurement were performed at baseline and on day 1, day 4, day 7 and day 14 following cell injection. A logistic regression was modelled to predict successful corneal deturgescence and its failure with cell aggregate visibility and CCT. Receiver-operating characteristic (ROC) curves were plotted, and areas under the curve (AUC) calculated for each time point in these models. (3) Results: Cellular aggregates were identified on days 1, 4, 7 and 14 in 86.7%, 39.5%, 20.0% and 4.4% of eyes, respectively. The positive predictive value of cellular aggregate visibility for successful corneal deturgescence was 71.8%, 64.7%, 66.7% and 100.0% at each time point, respectively. Using logistic regression modelling, the visibility of cellular aggregates on day 1 appeared to increase the likelihood of successful corneal deturgescence, but this did not reach statistical significance. An increase in pachymetry, however, resulted in a small but statistically significant decreased likelihood of success, with an odds ratio of 0.996 for days 1 (95% CI 0.993-1.000), 2 (95% CI 0.993-0.999) and 14 (95% CI 0.994-0.998) and an odds ratio of 0.994 (95% CI 0.991-0.998) for day 7. The ROC curves were plotted, and the AUC values were 0.72 (95% CI 0.55-0.89), 0.80 (95% CI 0. 62-0.98), 0.86 (95% CI 0.71-1.00) and 0.90 (95% CI 0.80-0.99) for days 1, 4, 7 and 14, respectively. (4) Conclusions: Logistic regression modelling of cell aggregate visibility and CCT was predictive of successful corneal endothelial cell injection therapy.

Predictors of myopic macular degeneration in a 12-year longitudinal study of Singapore adults with myopia.

PURPOSE: To investigate the predictive factors for myopic macular degeneration (MMD) and progression in adults with myopia. METHODS: We examined 828 Malay and Indian adults (1579 myopic eyes) with myopia (spherical equivalent (SE) ≤-0.5 dioptres) at baseline who participated in both baseline and 12-year follow-up visits of the Singapore Malay Eye Study and the Singapore Indian Eye Study. Eye examinations, including subjective refraction and axial length (AL) measurements, were performed. MMD was graded from fundus photographs following the Meta-Analysis for Pathologic Myopia classification. The predictive factors for MMD development and progression were assessed in adults without and with MMD at baseline, respectively as risk ratios (RR) using multivariable modified Poisson regression models. The receiver operating characteristic curve was used to visualise the performance of the predictive models for the development of MMD, with performance quantified by the area under the curve (AUC). RESULTS: The 12-year cumulative MMD incidence was 10.3% (95% CI 8.9% to 12.0%) among 1504 myopic eyes without MMD at baseline. Tessellated fundus was a major predictor of MMD (RR=2.50, p<0.001), among other factors including age, worse SE and longer AL (all p<0.001). The AUC for prediction of MMD development was found to be 0.78 (95% CI 0.76 to 0.80) for tessellated fundus and increased significantly to an AUC of 0.86 (95% CI 0.84 to 0.88) with the combination of tessellated fundus with age, race, gender and SE (p<0.001). Older age (p=0.02), worse SE (p<0.001) and longer AL (p<0.001) were found to be predictors of MMD progression. CONCLUSIONS: In adults with myopia without MMD, tessellated fundus, age, SE and AL had good predictive value for incident MMD. In adults with MMD, 1 in 10 eyes experienced progression over the same period. Older age, more severe myopia and longer AL were independent risk factors for progression.

Should Aquaporin-4 Antibody Test Be Performed in all Patients With Isolated Optic Neuritis?

BACKGROUND: Optic neuritis (ON) may be the initial manifestation of neuromyelitis optica spectrum disorder (NMOSD). Aquaporin-4 antibody (AQP4 Ab) is used to diagnose NMOSD. This has implications on prognosis and is important for optimal management. We aim to evaluate if clinical features can distinguish AQP4 Ab seropositive and seronegative ON patients. METHODS: We reviewed patients with first episode of isolated ON from Tan Tock Seng Hospital and Singapore National Eye Centre who tested for AQP4 Ab from 2008 to 2017. Demographic and clinical data were compared between seropositive and seronegative patients. RESULTS: Among 106 patients (120 eyes) with first episode of isolated ON, 23 (26 eyes; 22%) were AQP4 Ab positive and 83 (94 eyes; 78%) were AQP4 Ab negative. At presentation, AQP4 Ab positive patients had older mean onset age (47.9 ± 13.6 vs 36.8 ± 12.6 years, P < 0.001), worse nadir VA (OR 1.714; 95% CI, 1.36 to 2.16; P < 0.001), less optic disc swelling (OR 5.04; 95% CI, 1.682 to 15.073; p = 0.004), and higher proportions of concomitant anti-Ro antibody (17% vs 4%, p = 0.038) and anti-La antibody (17% vs 1%, p = 0.008). More AQP4 Ab positive patients received steroid-sparing immunosuppressants (74% vs 19%, p < 0.001) and plasma exchange (13% vs 0%, p = 0.009). AQP4 Ab positive patients had worse mean logMAR VA (visual acuity) at 12 months (0.70 ± 0.3 vs 0.29 ± 0.5, p = 0.051) and 36 months (0.37±0.4 vs 0.14 ± 0.2, p = 0.048) follow-up. CONCLUSION: Other than older onset age and retrobulbar optic neuritis, clinical features are non-discriminatory for NMOSD. We propose a low threshold for AQP4 Ab serology testing in inflammatory ON patients, particularly in high NMOSD prevalence populations, to minimize diagnostic and treatment delays.

"Endothelium-Out" and "Endothelium-In" Descemet Membrane Endothelial Keratoplasty (DMEK) Graft Insertion Techniques: A Systematic Review With Meta-Analysis.

Background: We evaluated the visual outcomes and complications of "endothelium-out" and "endothelium-in" Descemet membrane endothelial keratoplasty (DMEK) graft insertion techniques. Materials and Methods: Electronic searches were conducted in CENTRAL, Cochrane databases, PubMed, EMBASE, ClinicalTrials.gov. Study designs included clinical trials, comparative observational studies, and large case series (≥25 eyes). PRISMA guidelines were used for abstracting data and synthesis. Random-effects models were employed for meta-analyses. Results: 21,323 eyes (95 studies) were included. Eighty-six studies reported on "endothelium-out" techniques; eight studies reported on "endothelium-in" techniques. One study compared "endothelium-out" to "endothelium-in" techniques. Eighteen "endothelium-out" studies reported that 42.5-85% of eyes achieved best-corrected visual acuity (BCVA) ≥20/25 at 6 months; pooled proportion of eyes achieving BCVA ≥20/25 at 6 months was 58.7% (95% CI 49.4-67.7%,15 studies). Three "endothelium-in" studies reported that 44.7-87.5% of eyes achieved BCVA of ≥20/25 at 6 months; pooled proportion of eyes achieving BCVA ≥20/25 at 6 months was 62.4% (95% CI 33.9-86.9%). Pooled mean endothelial cell loss was lower in the "endothelium-in" studies (28.1 ± 1.3%, 7 studies) compared to "endothelium-out" studies (36.3 ± 6.9%,10 studies) at 6 months (p = 0.018). Graft re-bubbling rates were higher in the "endothelium-out" studies (26.2%, 95% CI 21.9-30.9%, 74 studies) compared to "endothelium-in" studies (16.5%, 95% CI 8.5-26.4%, 6 studies), although statistical significance was not reached (p = 0.440). Primary graft failure rates were comparable between the two groups (p = 0.552). Quality of evidence was considered low and significant heterogeneity existed amongst the studies. Conclusion: Reported rates of endothelial cell loss were lower in "endothelium-in" DMEK studies at 6 months compared to "endothelium-out" studies. Outcomes of "endothelium-in" techniques were otherwise comparable to those reported in "endothelium-out" studies. Given the technical challenges encountered in "endothelium-out" procedures, surgeons may consider "endothelium-in" techniques designed for easier intra-operative DMEK graft unfolding. "Endothelium-in" studies evaluating outcomes at longer time points are required before conclusive comparisons between the two techniques can be drawn.

Using Sterile Flocked Swabs as an Alternative Method for Rodent Health Monitoring.

Routine health monitoring is an integral part of managing SPF rodent colonies. In recent years, rack-level environmental sampling has been introduced as an adjunct method or replacement for exposure of sentinel rodents to soiled bedding. However, rack-level environmental monitoring is not compatible with rodent housing systems that have cage-level filtration. The current study investigated whether exposure of sterile flocked swabs to soiled bedding can be an alternative sampling method for routine health monitoring in mice, thus replacing the use of sentinels in soiled-bedding cages. Flocked swabs were placed in cages containing pooled samples of soiled bedding but no mice; swabs remained there for 90 d, with weekly agitation and biweekly swabbing of the cage floor to mimic the agitation of soiled bedding by sentinel mice and facilitate the collection of dust particles. Fecal samples were collected from both colony and sentinel mice. For environmental samples, exhaust debris was collected from the rack plenum, and dust samples were collected from the exhaust hose. All samples were collected on days 88 through 91 and were tested for multiple pathogens by using real-time PCR assays. To determine the diagnostic agreement of flocked swab sampling with the other methods, we used κ statistics to compare the test results from flocked swabs with those from sentinel feces, exhaust debris, and colony animal feces; we found excellent agreement between the colony feces and the flocked swab methods. The sterile flocked swab method detected all enzootic pathogens in the colonies tested. Results from flocked swab samples had the least agreement with sentinel feces, which also failed to detect the presence of fur mites. This study supports the use of sterile flocked swabs as alternative to using sentinel mice, thus conforming to the guiding principles of replacement and reduction in the use of animals for routine colony health monitoring.

Endothelial keratoplasty with anterior chamber intraocular lens versus secondary posterior chamber intraocular lens.

AIM: To describe the long-term outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) with an anterior chamber intraocular lens (ACIOL) compared to secondary posterior chamber (PC) IOL. METHODS: This was a retrospective comparative cohort study. The clinical data of 82 eyes from 82 consecutive patients with pseudophakic (PBK) or aphakic bullous keratopathy (ABK) who either underwent DSAEK with retained or secondary ACIOL (n=23) or DSAEK with IOL exchange and/or secondary PCIOL (retropupillary iris-claw IOL, n=25; intrascleral-fixated IOL, n=29; or sulcus IOL, n=5) were analysed. The main outcome measures were graft survival and complications up to 5 years. RESULTS: The graft survival in the secondary PCIOL group was superior than the ACIOL group over 5 years (year 1, 100.0% vs 100.0%; year 3, 94.7% vs 75.0%; year 5, 91.1% vs 60.6%, p=0.022). The presence of an ACIOL was a significant risk factor associated with graft failure (HR, 4.801; 95% CI, 1.406 to 16.396, p=0.012) compared to a secondary PCIOL. There was no significant difference in the rate of graft detachment and elevated intraocular pressure between the groups. There were five cases (9.3%) of IOL subluxation or dislocation in the retropupillary iris-claw and intrascleral-fixated IOL groups. CONCLUSIONS: Eyes that underwent DSAEK with ACIOL in situ had poorer long-term graft survival compared with those with secondary PCIOL. Intraocular lens exchange was not associated with a higher complication rate. In ABK or PBK eyes with ACIOL, we recommend performing IOL exchange and/or secondary PCIOL implantation combined with endothelial keratoplasty.

Peripapillary sclera exhibits a v-shaped configuration that is more pronounced in glaucoma eyes.

AIMS: To compare the shape of the anterior surface of the peripapillary sclera (PPS) between glaucoma and healthy subjects. METHODS: 88 primary open angle glaucoma (POAG), 98 primary angle closure glaucoma (PACG) and 372 age-matched and gender-matched healthy controls were recruited in this study. The optic nerve head of one randomly selected eye of each subject was imaged with spectral domain optical coherence tomography. The shape of the PPS was measured through an angle defined between a line parallel to the nasal anterior PPS boundary and one parallel to the temporal side. A negative value indicated that the PPS followed an inverted v-shaped configuration (peak pointing towards the vitreous), whereas a positive value indicated that it followed a v-shaped configuration. RESULTS: The mean PPS angle in normal controls (4.56±5.99°) was significantly smaller than that in POAG (6.60±6.37°, p=0.011) and PACG (7.90±6.87°, p<0.001). The v-shaped PPS was significantly associated with older age (ß=1.79, p<0.001), poorer best-corrected visual acuity (ß=3.31, p=0.047), central corneal thickness (ß=-0.28, p=0.001), peripapillary choroidal thickness (ß=-0.21, p<0.001) and presence of POAG (ß=1.94, p<0.009) and PACG (ß=2.96, p<0.001). The v-shaped configuration of the PPS significantly increased by 1.46° (p=0.001) in healthy controls for every 10-year increase in age, but not in glaucoma groups. CONCLUSIONS: The v-shaped configuration of the PPS was more pronounced in glaucoma eyes than in healthy eyes. This posterior bowing of the PPS may have an impact on the biomechanical environment of the optic nerve head.

Visual field defects and myopic macular degeneration in Singapore adults with high myopia.

AIMS: To characterise the association between visual field (VF) defects and myopic macular degeneration (MMD) in highly myopic adults without glaucoma. METHODS: Participants (n=106; 181 eyes) with high myopia (HM; spherical equivalent ≤-5.0 D or axial length (AL) ≥26 mm), after excluding glaucoma and glaucoma suspects, from the Singapore Epidemiology of Eye Diseases-HM study were included in this cross-sectional study. Humphrey VF (central 24-2 threshold), cup-disc ratio (CDR) and intraocular pressure (IOP) measurements were performed. Mean deviation (MD) and pattern SD (PSD), VF defects (normal or abnormal; p<0.05 in ≥3 non-edge contiguous locations) and pattern (eg, generalised sensitivity loss) were analysed. MMD presence was diagnosed from fundus photographs. Generalised estimating equations were used for analysing factors (MD, PSD, VF defects, CDR and IOP) associated with MMD. RESULTS: Mean age was 55.4±9.9 years and 51.9% were women (AL=26.7±1.1 mm). MMD eyes had lower MD (-3.8±2.9 dB vs -1.1±1.4 dB) and higher PSD (2.8±1.7 dB vs 1.7±0.6 dB). A higher percentage of MMD eyes (n=48) had abnormal VF (62.5% vs 28.6%; p<0.001) compared with no MMD (n=133 eyes). VF pattern in MMD eyes was significantly different from eyes without MMD (p=0.001) with greater generalised sensitivity loss (53.3% vs 10.5%) and arcuate defects (16.7% vs 10.5%). In multivariate analyses, MD (OR=1.52) and PSD (OR=1.67) were significantly (p=0.003) associated with MMD, but VF defects were not associated with MMD. CONCLUSION: Highly myopic adults with MMD may have VF loss when compared with highly myopic patients without MMD even in adults without glaucoma.

Hybrid derivative of cathelicidin and human beta defensin-2 against Gram-positive bacteria: A novel approach for the treatment of bacterial keratitis.

Bacterial keratitis (BK) is a major cause of corneal blindness globally. This study aimed to develop a novel class of antimicrobial therapy, based on human-derived hybrid host defense peptides (HyHDPs), for treating BK. HyHDPs were rationally designed through combination of functional amino acids in parent HDPs, including LL-37 and human beta-defensin (HBD)-1 to -3. Minimal inhibitory concentrations (MICs) and time-kill kinetics assay were performed to determine the concentration- and time-dependent antimicrobial activity and cytotoxicity was evaluated against human corneal epithelial cells and erythrocytes. In vivo safety and efficacy of the most promising peptide was examined in the corneal wound healing and Staphylococcus aureus (ATCC SA29213) keratitis murine models, respectively. A second-generation HyHDP (CaD23), based on rational hybridization of the middle residues of LL-37 and C-terminal of HBD-2, was developed and was shown to demonstrate good efficacy against methicillin-sensitive and methicillin-resistant S. aureus [MIC = 12.5-25.0 µg/ml (5.2-10.4 µM)] and S. epidermidis [MIC = 12.5 µg/ml (5.2 µM)], and moderate efficacy against P. aeruginosa [MIC = 25-50 µg/ml (10.4-20.8 µM)]. CaD23 (at 25 µg/ml or 2× MIC) killed all the bacteria within 30 min, which was 8 times faster than amikacin (25 µg/ml or 20× MIC). After 10 consecutive passages, S. aureus (ATCC SA29213) did not develop any antimicrobial resistance (AMR) against CaD23 whereas it developed significant AMR (i.e. a 32-fold increase in MIC) against amikacin, a commonly used treatment for BK. Pre-clinical murine studies showed that CaD23 (0.5 mg/ml) achieved a median reduction of S. aureus bioburden by 94% (or 1.2 log10 CFU/ml) while not impeding corneal epithelial wound healing. In conclusion, rational hybridization of human-derived HDPs has led to generation of a potentially efficacious and safe topical antimicrobial agent for treating Gram-positive BK, with no/minimal risk of developing AMR.

Development and Validation of a Preference-Based Glaucoma Utility Instrument Using Discrete Choice Experiment.

IMPORTANCE: A glaucoma-specific instrument for estimating utilities across the spectrum of glaucoma severity is currently lacking, hindering the assessment of the cost-effectiveness of glaucoma treatments. OBJECTIVE: To develop and validate the preference-based Glaucoma Utility Instrument (Glau-U) and to ascertain the association between Glau-U utilities and severity of glaucoma and vision impairment. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted in 2 stages at the Singapore National Eye Centre glaucoma clinics. Stage 1 focused on the identification and pretesting of the Glau-U attributes and was carried out between June 2009 and May 2016. Stage 2 involved the development and administration of the discrete choice experiment (DCE) survey and tasks and was conducted between May 7, 2018, and December 11, 2019. Stage 2 participants were English- or Mandarin-speaking Singaporean citizens or permanent residents of Chinese, Malay, or Indian ethnicity who were 40 years or older and had a clinical diagnosis of glaucoma in at least 1 eye. EXPOSURES: Glau-U comprised 6 quality-of-life attributes: activities of daily living, lighting and glare, movement, eye discomfort, other effects of glaucoma, and social and emotional effects. The descriptions or response options for these attributes were no difficulty or never, some difficulty or sometimes, or severe difficulty or often. MAIN OUTCOMES AND MEASURES: Utility weights for Glau-U were developed using a DCE questionnaire, which was interviewer administered to participants. Mixed logit regression determined utility weights for each health state. Glau-U utility weights across better- or worse-eye glaucoma and vision impairment severity were calculated using 1-way analysis of variance. Correlations between Glau-U utilities and better- or worse-eye visual fields and EuroQol 5-Dimension utilities were ascertained to assess convergent and divergent validity. RESULTS: Of the 304 participants (mean [SD] age, 68.3 [8.7] years; 182 men [59.9%]), 281 (92.4%) had no vision impairment in the better eye, 13 (4.3%) had mild impairment, and 10 (3.3%) had moderate to severe vision impairment. Mean (SD) Glau-U utilities decreased as better-eye glaucoma severity increased (none: 0.73 [0.21]; mild: 0.66 [0.21]; moderate: 0.66 [0.20]; severe: 0.60 [0.28]; and advanced or end-stage: 0.22 [0.38]; P < .001), representing reductions of 20.7% to 76.1% in quality-adjusted life-years compared with a health state that included preperimetric glaucoma. Mean (SD) Glau-U utilities also decreased as better-eye vision impairment worsened from 0.67 (0.23) for none to 0.58 (0.32) for mild to 0.46 (0.29) for moderate to severe vision impairment. Glau-U utilities demonstrated moderate correlations with better-eye (r = 0.34; P < .001) and worse-eye (r = 0.33; P < .001) mean deviation scores and low correlations with EuroQol 5-Dimension utilities (r = 0.22; P < .001), supporting convergent and divergent validity. CONCLUSIONS AND RELEVANCE: Use of Glau-U revealed large decrements in utility that were associated with late-stage glaucoma, suggesting that this new instrument may be useful for cost-effectiveness analyses of interventions and informing resource allocation policies for glaucoma and vision loss.

Cosmetic outcome of femtosecond laser-assisted pterygium surgery.

BACKGROUND: To examine the cosmetic outcome of femtosecond laser-assisted pterygium surgery (FLAPS) with conjunctival autograft (CAG) and its potential predictive factors. METHODS: This was a prospective interventional case series (NCT02866968). We included 29 patients (29 eyes) with primary pterygium who underwent FLAPS. Cosmetic outcome was graded by two graders (an ophthalmology resident and an experienced ophthalmologist) using Hirst classification system (1-4 = excellent-poor). Weighted Cohen's kappa analysis was performed to examine the intra- and inter-rater reliability. The relationship between cosmetic outcome and various factors were determined by Spearman's correlation coefficients (r). RESULTS: The preoperative severity of pterygium (Tan grading system) was mild/atrophic (7%), moderate/intermediate (62%), and severe/fleshy (31%). An ultrathin CAG (mean thickness of 74.5 ± 9.8 µm) was fashioned intraoperatively. An excellent cosmetic outcome of FLAPS (median ± IQR) was observed at 3 months (1.0 ± 1.0) and remained similar at 6 months (1.0 ± 0.0) and 12 months (1.0 ± 0.0) postoperatively. At final follow-up, 27 (93%) patients achieved good-to-excellent cosmetic outcome, with 1 (3%) patient having a poor outcome due to incomplete pterygium removal. Weighted kappa analysis of Hirst grading system showed excellent intra-rater (κ = 0.86-0.95) and inter-rater reliability (κ = 0.84-0.88). There was a weak and borderline significant correlation between good cosmetic outcome and reduced postoperative CAG thickness (r = 0.38, P = 0.06) but not with age, gender, preoperative pterygium severity, or intraoperative CAG thickness. CONCLUSIONS: FLAPS can result in an excellent cosmetic outcome, which may be attributed to the beneficial effect of an ultrathin CAG. TRIAL REGISTRATION: ClinicalTrials.gov , NCT02866968 . Registered in July 2016.

Proposal and validation of a new grading system for pterygium (SLIT2).

BACKGROUND/AIMS: To propose and validate a new pterygium grading system based on slit-lamp evaluation. METHODS: This prospective cross-sectional study included 217 patients with pterygium. All patients underwent slit-lamp examination, and slit-lamp photographs were independently graded by two graders twice. A total of eight parameters were evaluated and all parameters were assigned with a score of 1-4 (normal-severe). Intra-rater and inter-rater reliability as determined by weighted Cohen's kappa analysis. RESULTS: A total of 868 independent assessment, based on 217 slit-lamp images, were performed by two graders. For conjunctival assessment, the intra-rater reliability was excellent for body thickness (κ=0.81-0.89) and size at limbus (κ=0.87-0.92), substantial-to-excellent for body vascularity (κ=0.72-0.86), and moderate-to-excellent for body length (κ=0.57-0.81), whereas the inter-rater reliability was excellent for size at limbus (κ=0.86), substantial for body thickness (κ=0.72-0.73) and body vascularity (κ=0.66-0.75), and moderate for body length (κ=0.54-0.57). For corneal assessment, the intra-rater reliability was excellent for all four parameters (κ=0.84-0.90) whereas the inter-rater reliability was excellent for head length (κ=0.86-0.87), substantial-to-excellent for head vascularity (κ=0.78-0.82), substantial for Stocker's line (κ=0.79-0.80) and head thickness (κ=0.67-0.69). The grading system was named SLIT2, which included S tocker's line, S ize at limbus, L ength of head/body, I njection/vascularity of body/head, and T hickness of body/head. CONCLUSION: The proposed SLIT2 grading system, consisting of eight components, may serve as a reliable tool to standardise the reporting of pterygium severity and disease recurrence for clinical and research applications.

Modified manual small incision cataract surgery technique for phacoemulsification-trained surgeons.

PURPOSE: To present the technique and outcomes of a modified manual small incision cataract surgery designed for the phacoemulsification surgeons who are learning to perform manual small incision cataract surgery. METHODS: This was a retrospective, single-centred, comparative study. We included all the patients who underwent the modified manual small incision cataract surgery for visually significant cataract at Singapore National Eye Centre. All surgeries were performed by either a senior phaco-trained surgeon (M.A.) who had performed more than 500 manual small incision cataract surgery or a junior phaco-trained surgeon (D.C.) who had performed around 500 phacoemulsification but never performed any manual small incision cataract surgery. The main modification of this technique lies in the creation of an additional phaco-like main wound at 90° to the scleral tunnel wound, with most surgical steps performed through this additional wound. The outcomes were analysed and compared between the senior and junior surgeons. The main outcome measures were visual outcome and major intraoperative complications such as posterior capsular rupture and zonular dialysis. RESULTS: A total of 132 cases were included; 102 (77.3%) and 30 (22.7%) cases were performed by the senior and junior surgeons, respectively. Pre-operatively, 85.6% eyes had best-corrected visual acuity of counting fingers or worse. Postoperatively, the visual outcome at 1 month was similar between the senior and junior surgeons, with 68.7% eyes achieving a best-corrected visual acuity of ⩾6/12 (p = 0.17). No posterior capsular rupture, zonular dialysis or endophthalmitis was observed during the study period. CONCLUSIONS: This modified technique may serve as a useful transition technique for the phaco-trained surgeons to develop skills in manual small incision cataract surgery, with demonstrable good visual outcome and safety.

Effect of Pharmacological Pupil Dilatation on Angle Configuration in Untreated Primary Angle Closure Suspects: A Swept Source Anterior Segment Optical Coherence Tomography Study.

PRECIS: Angle-closure worsens with pharmacological dilatation in about 50.0% of the subjects diagnosed as primary angle-closure suspects (PACSs). PURPOSE: The purpose of this study was to evaluate the changes in angle configuration with swept-source anterior segment optical coherence tomography before and after pharmacological pupil dilatation in untreated PACSs. PATIENTS AND METHODS: A total of 106 subjects over the age of 50 years and diagnosed as PACSs were included in this cross-sectional cohort study. 360-degree scans of the angles were captured using swept-source optical coherence tomography before and 1 hour after pharmacological dilatation. The angle scans from swept-source optical coherence tomography were analyzed to calculate the iris-trabecular contact (ITC) index. The main outcome measure was to evaluate the change in ITC index after dilatation. Multivariate linear and logistic regression analysis were performed to identify factors influencing change of ITC index and to identify factors associated with increase in ITC index after dilatation. RESULTS: Majority of subjects were Chinese (93.4%) and female (79.2%). The overall mean predilatation ITC index was 45.3% (±23.7) and postdilatation ITC index was 46.05% (±25.9) with a mean change of 0.78% (±16.5; P=0.62). Fifty-three eyes (50.0%) showed an increase in ITC index (angle narrowing) after dilatation. An increase in ITC index was associated with shallower anterior chamber depth (odds ratio: 0.18; 95% confidence interval: 0.04-0.77) and bigger lens vault (odds ratio: 14.31; 95% confidence interval: 1.55-132.34). CONCLUSIONS: Pharmacological pupil dilatation worsened angle closure in 50.0% of subjects with narrow angles. Shallower anterior chamber and bigger lens vault were associated with greater angle narrowing in these subjects.

Visual field progression 8 years after trabeculectomy in Asian eyes: results from The Singapore 5-Fluorouracil Study.

BACKGROUND/AIMS: This work aimed to study the effect of long-term intraocular pressure (IOP) fluctuation on visual field (VF) progression 8 years post-trabeculectomy in Asian eyes. METHODS: This was a retrospective analysis of 8-year post-trabeculectomy data from The Singapore 5-Fluorouracil (5-FU) Study. VFs were analysed using Progressor software (Medisoft, Leeds, UK). Outcome measures included mean slope for VF per year, number of progressing points and mean slope for progressing points per year. Multivariate regression analyses were performed adjusting for age, gender, ethnicity, glaucoma type, intraoperative 5-FU, diabetes mellitus, hypertension, best pre-trabeculectomy VF mean deviation, post-trabeculectomy mean IOP, IOP reduction and IOP fluctuation (SD of IOPs at 6-monthly timepoints). RESULTS: 127 (52.3%) subjects completed 8-year follow-up with ≥5 reliable VFs and ≥8 6-monthly IOP measurements. Mean age was 61.8±9.6 years. Post-operatively, mean IOP was 14.2±2.8 mm Hg and mean IOP fluctuation was 2.53±1.20 mm Hg. Higher IOP fluctuation was associated with greater mean slope for field (B=-0.071; p=0.013), number of progressing points (B=0.963; p=0.014) and VF progression as defined by ≥1 progressing point (OR=1.585; p=0.029). There was also a trend towards eyes with higher IOP fluctuation having ≥3 adjacent progressing points in the same hemifield (OR=1.489; p=0.055). Greater mean IOP reduction post-trabeculectomy was associated only with a lower mean slope for progressing points per year (B=-0.026; p=0.028). There was no significant effect of intra-operative 5-FU compared with placebo for all outcome measures. CONCLUSION: In post-trabeculectomy Asian eyes with well-controlled IOP, higher long-term IOP fluctuation may be associated with greater VF progression.

Randomized Clinical Trial Comparing Femtosecond LASIK and Small-Incision Lenticule Extraction.

PURPOSE: To compare femtosecond LASIK with small-incision lenticule extraction (SMILE) for the treatment of myopia and myopic astigmatism. DESIGN: Prospective, randomized, paired-eye, single-masked clinical trial. PARTICIPANTS: Consecutive eligible patients were randomized to undergo SMILE and LASIK in either eye at a single tertiary referral eye center. METHODS: Patients were treated in each eye using the VisuMax (Carl Zeiss Meditec, Jena, Germany) 500-kHz femtosecond laser system. Excimer ablation was subsequently performed using the WaveLight EX500 excimer laser (Alcon Laboratories, Inc, Fort Worth, TX) in the eye for LASIK. MAIN OUTCOME MEASURE: Refractive predictability at 3 months. Secondary outcomes were refractive outcomes, that is, efficacy and safety at 3 and 12 months. RESULTS: We recruited 70 consecutive patients (mean age, 28±5 years; 64% women; all Asian) with no difference in preoperative spherical equivalent (SE) between eyes (-5.3±1.8 diopters [D] vs. -5.2±1.7 D; P = 0.87). At 3 months, 99% of SMILE eyes and 97% of LASIK eyes achieved SE within ±1.0 D of attempted correction (P = 1.0). Small-incision lenticule extraction achieved similar results as LASIK in terms of efficacy index (0.97±0.20 vs. 0.99±0.20; P = 0.56), uncorrected distance visual acuity (UDVA) of 20/40 or better (100% vs. 100%; P = 1.0), and UDVA of 20/20 or better (84% vs. 87%; P = 0.63). Safety index (1.1±0.2 vs. 1.1±0.2; P = 0.57) was similar between SMILE and LASIK eyes at 3 months. At 12 months, SMILE was similar to LASIK in terms of efficacy (85% vs. 83% UDVA ≥20/20; P = 0.81), predictability (99% vs. 99% ±1.0 D of attempted correction SE; P = 1.0), and safety (1.15±0.20 vs. 1.15±0.20; P = 0.93). CONCLUSIONS: The results from this randomized trial suggest that SMILE produced promising refractive outcomes in terms of predictability, efficacy, and safety at 3 and 12 months of follow-up.