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.

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.

Aqueous shunts with mitomycin C versus aqueous shunts alone for glaucoma.

BACKGROUND: Glaucoma affects more than 70 million people worldwide, with about 10% being bilaterally blind, making it the leading cause of irreversible blindness globally. In patients with advanced glaucoma or those who have failed medical treatment without achieving adequate intraocular pressure (IOP) control, trabeculectomy (glaucoma filtration surgery where an ostium is created into the anterior chamber from underneath a partial thickness scleral flap to allow for aqueous flow out of the anterior chamber intointo the subconjunctival space forming a filtering bleb) and aqueous shunt surgery for more complex and refractory cases remain the mainstay therapies. Proliferation of fibrous tissue around an implanted aqueous shunt may block the diffusion of aqueous humour. Mitomycin C (MMC) is one of two commonly used adjunct antifibrotic agents used during aqueous shunt surgery to prevent proliferation of fibrous tissue. However, the effectiveness and safety of the use of intraoperative MMC during aqueous shunt surgery has not been established. OBJECTIVES: To evaluate the effectiveness and safety of MMC versus no MMC used during aqueous shunt surgery for reducing IOP in primary and secondary glaucoma. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 13 February 2018. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which one group of participants received MMC during aqueous shunt surgery and another group did not. We did not exclude studies based on outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed titles and abstracts from the literature searches. We obtained full-text reports of potentially relevant studies and assessed them for inclusion. Two review authors independently extracted data related to study characteristics, risk of bias, and outcomes. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included five RCTs, with a total of 333 eyes with glaucoma randomized, and identified two ongoing trials. All included trials examined the effect of MMC versus no MMC when used during aqueous shunt surgery for glaucoma. The trials included participants with different types of uncontrolled glaucoma. One study was conducted in China, one in Saudi Arabia, two in the USA, and one study was a multicenter study conducted in Brazil, Canada, Scotland, and USA. We assessed all trials as having overall unclear risk of bias due to incomplete reporting of study methods and outcomes; two of the five trials were reported only as conference abstracts.None of the included trials reported mean decrease from baseline in IOP; however, all five trials reported mean IOP at 12 months post-surgery. At 12 months, the effect of MMC on mean IOP compared with no MMC was unclear based on a meta-analysis of trials (mean difference -0.12 mmHg, 95% CI -2.16 to 2.41; low-certainty evidence). Two trial did not report sufficient information to include in meta-analysis, but reported that mean IOP was lower in the MMC group compared with the no MMC group at 12 months.None of the included trials reported mean change from baseline in visual acuity; however, one trial reported lower mean LogMAR values (better vision) in the MMC group than in the no MMC group at 12 months post-surgery. None of the included studies reported the proportion of participants with stable best-corrected visual acuity. Three trials reported that loss of vision was not significantly different between groups (no data available for meta-analysis).None of the included studies reported the proportion of participants with a postoperative hypertensive phase, which is defined as IOP > 21 mmHg within 3 months after surgery. Two trials reported adverse events (choroidal effusion, corneal edema, flat anterior chamber, and retinal detachment); however, due to small numbers of events and sample sizes, no clear difference between MMC and placebo groups was observed. AUTHORS' CONCLUSIONS: We found insufficient evidence in this review to suggest MMC provides any postoperative benefit for glaucoma patients who undergo aqueous shunt surgery. Data across all five included trials were sparse and the reporting of study methods required to assess bias was inadequate. Future RCTs of this intervention should report methods in sufficient detail to permit assessment of potential bias and estimate target sample sizes based on clinically meaningful effect sizes.

Bulk changes in posterior scleral collagen microstructure in human high myopia.

Purpose: We aimed to characterize any bulk changes in posterior scleral collagen fibril bundle architecture in human eyes with high myopia. Methods: Wide-angle X-ray scattering (WAXS) was employed to map collagen orientation at 0.5 mm × 0.5 mm spatial intervals across the posterior sclera of seven non-myopic human eyes and three eyes with high myopia (>6D of refractive error). At each sampled point, WAXS provided thickness-averaged measures of the angular distribution of preferentially aligned collagen fibrils within the tissue plane and the anisotropic proportion (the ratio of preferentially aligned to total collagen scatter). Results: Non-myopic specimens featured well-conserved microstructural features, including strong uniaxial collagen alignment along the extraocular muscle insertion sites of the mid-posterior sclera and a highly anisotropic annulus of collagen circumscribing the nerve head in the peripapillary sclera. All three myopic specimens exhibited notable alterations in the peripapillary sclera, including a partial loss of circumferential collagen alignment and a redistribution of the normally observed regional pattern of collagen anisotropic proportion. Linear mixed-model analysis indicated that the mean fiber angle deviation from the circumferential orientation in the peripapillary sclera of highly myopic eyes (23.9° ± 18.2) was statistically significantly higher than that of controls (17.9° ± 12.0; p<0.05). Conclusions: Bulk alterations in the normal posterior scleral collagen microstructure occur in human eyes with high myopia. These changes could reflect remodeling of the posterior sclera during axial lengthening and/or a mechanical adaption to tissue stresses induced by fluid pressure or eye movements that may be exacerbated in enlarged eyes.

Interventions for the management of CMV-associated anterior segment inflammation.

BACKGROUND: Cytomegalovirus (CMV) is a virus that usually affects people with reduced immunity. In recent years, this virus has been thought to cause repeated inflammation in the eye, in otherwise healthy people. This form of inflammation can cause damage to the cornea (the outer layer of the eye) or to the optic nerve by causing secondary glaucoma, or to both, leading to visual loss. OBJECTIVES: Our primary objective was to assess the effects of drug therapies for the treatment of CMV-associated anterior segment inflammation.Our secondary objective was to determine the optimal dose and duration of treatment with respect to recurrence and adverse effects. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2017, Issue 2), MEDLINE Ovid (1946 to 21 March 2017), Embase Ovid (1947 to 21 March 2017), the ISRCTN registry (www.isrctn.com/editAdvancedSearch); searched 21 March 2017, ClinicalTrials.gov (www.clinicaltrials.gov); searched 21 March 2017, and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 21 March 2017. We did not use any date or language restrictions in the electronic searches for trials. Two review authors independently reviewed the titles and abstracts. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) on the management of CMV-associated anterior segment inflammation. DATA COLLECTION AND ANALYSIS: We planned to have two review authors independently extract data from reports of included studies and analyse data based on methods expected by Cochrane. MAIN RESULTS: We did not identify any RCTs that met our inclusion criteria. AUTHORS' CONCLUSIONS: There is currently no good-quality evidence on the management of CMV-associated anterior segment inflammation. Ideally, a well-designed RCT is needed to evaluate the effectiveness of different anti-CMV medications as well as the optimal dose and duration.

Argon Laser Peripheral Iridoplasty for Primary Angle-Closure Glaucoma: A Randomized Controlled Trial.

PURPOSE: To determine the effectiveness of argon laser peripheral iridoplasty (ALPI) in primary angle closure (PAC) and primary angle-closure glaucoma (PACG). DESIGN: Randomized controlled trial. PARTICIPANTS: Eighty PAC or PACG subjects who underwent laser iridotomy (LI) and had at least 180° of persistent appositional angle closure and intraocular pressure (IOP) of more than 21 mmHg were enrolled. METHODS: Subjects were randomized to receive either 360° ALPI (Visulas 532s; Carl Zeiss Meditec, Jena, Germany) or medical therapy (Travoprost 0.004%; Alcon-Couvreur, Puurs, Antwerp, Belgium). Repeat ALPI was performed if the IOP reduction was less than 20% from baseline along with inadequate angle widening at the month 1 or month 3 visit. Intraocular pressure was controlled with systematic addition of medications when required. MAIN OUTCOME MEASURES: The primary outcome measure was success rates after ALPI at 1 year. Complete success was defined as an IOP of 21 mmHg or less without medication, and qualified success was defined as an IOP of 21 mmHg or less with medication. Failure was defined as an IOP more than 21 mmHg despite additional medications or requiring glaucoma surgery. RESULTS: Forty subjects (51 eyes) were randomized to ALPI and 40 subjects (55 eyes) were randomized to medical therapy. Complete success (IOP ≤21 mmHg without medication) was achieved in 35.0% eyes of the ALPI group compared with 85.0% of eyes in the prostaglandin analog (PGA) group (P < 0.001), and qualified success (IOP ≤21 mmHg with medication) was achieved in 35.0% and 7.5%, respectively (P = 0.003). The IOP decreased by 4.9 mmHg (95% confidence interval [CI], 3.5-6.3 mmHg) in the ALPI group (P < 0.001) and by 6.1 mmHg (95% CI, 5.1-7.1 mmHg) in the medication group (P < 0.001). A failure rate of 30.0% was noted in the ALPI group compared with 7.5% in the medication group (P = 0.01). No treatment-related complications were recorded in either group. CONCLUSIONS: After 1 year, ALPI was associated with higher failure rates and lower IOP reduction compared with PGA therapy in eyes with persistent appositional angle closure and raised IOP after LI.

Distinct iris gene expression profiles of primary angle closure glaucoma and primary open angle glaucoma and their interaction with ocular biometric parameters.

BACKGROUND: This study aimed to evaluate differences in iris gene expression profiles between primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG) and their interaction with biometric characteristics. DESIGN: Prospective study. PARTICIPANTS: Thirty-five subjects with PACG and thirty-three subjects with POAG who required trabeculectomy were enrolled at the Singapore National Eye Centre, Singapore. METHODS: Iris specimens, obtained by iridectomy, were analysed by real-time polymerase chain reaction for expression of type I collagen, vascular endothelial growth factor (VEGF)-A, -B and -C, as well as VEGF receptors (VEGFRs) 1 and 2. Anterior segment optical coherence tomography (ASOCT) imaging for biometric parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV) and lens vault (LV), was also performed pre-operatively. MAIN OUTCOME MEASURES: Relative mRNA levels between PACG and POAG irises, biometric measurements, discriminant analyses using genes and biometric parameters. RESULTS: COL1A1, VEGFB, VEGFC and VEGFR2 mRNA expression was higher in PACG compared to POAG irises. LV, ACD and ACV were significantly different between the two subgroups. Discriminant analyses based on gene expression, biometric parameters or a combination of both gene expression and biometrics (LV and ACV), correctly classified 94.1%, 85.3% and 94.1% of the original PACG and POAG cases, respectively. The discriminant function combining genes and biometrics demonstrated the highest accuracy in cross-validated classification of the two glaucoma subtypes. CONCLUSIONS: Distinct iris gene expression supports the pathophysiological differences that exist between PACG and POAG. Biometric parameters can combine with iris gene expression to more accurately define PACG from POAG.

Sectoral variations of iridocorneal angle width and iris volume in Chinese Singaporeans: a swept-source optical coherence tomography study.

PURPOSE: To assess variations in the iridocorneal angle width and iris volume in Chinese subjects using swept-source optical coherence tomography (SS-OCT). METHODS: Consecutive subjects, aged 40-80 years, with no previous ophthalmic problems were recruited from a population-based study of Chinese Singaporeans. All subjects underwent 360° SS-OCT (SS-1000 CASIA, Tomey Corporation, Nagoya, Japan) angle imaging and gonioscopy in one randomly selected eye in the dark. For each eye, 16 frames (11.25° apart) were selected for analysis from 128 cross-sectional images, and measurements of the trabecular iris space area 750 µm from the scleral spur (TISA750) and iris volume were made for each image. The measurements from four consecutive frames were further averaged as a sector of 45°. Sector-wise angle width and quadrant-wise iris volume were analyzed. RESULTS: Two hundred and twelve subjects (90 with closed-angles) were examined. The majority of the subjects were female (70.7 %) with mean age 61 (±8.9) years. The TISA750 (mm(2)) of superior [0.101 (0.09)], inferior [0.105 (0.09)], superior-nasal [0.111 (0.09)] and superior-temporal [0.117 (0.09)] sectors were smaller compared with other sectors (P < 0.05). The nasal iris volume (mm(3)) was the smallest compared with other quadrants for the entire cohort [nasal 8.18 (1.2) < inferior 9.13 (1.3) < temporal 9.16 (1.2) < superior 9.33 (1.3), P < 0.001], as well as for open- and closed-angle groups. CONCLUSIONS: The irido-corneal angle was narrower in the superior, inferior, superior-nasal and superior-temporal sectors compared with other sectors. Iris volume in the nasal quadrant was the smallest compared with the other quadrants.

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.

Differential expression of the Slc4 bicarbonate transporter family in murine corneal endothelium and cell culture.

PURPOSE: To characterize the relative expression levels of all the solute carrier 4 (Slc4) transporter family members (Slc4a1-Slc4a11) in murine corneal endothelium using real-time quantitative (qPCR), to identify further important members besides Slc4a11 and Slc4a4, and to explore how close to the baseline levels the gene expressions remain after cells have been subjected to expansion and culture. METHODS: Descemet's membrane-endothelial layers of 8-10-week-old C57BL6 mice were stripped from corneas and used for both primary cell culture and direct RNA extraction. Total RNA (from uncultured cells as well as cultured cells at passages 2 and 7) was reverse transcribed, and the cDNA was used for real time qPCR using specific primers for all the Slc4 family members. The geNorm method was applied to determine the most stable housekeeping genes and normalization factor, which was calculated from multiple housekeeping genes for more accurate and robust quantification. RESULTS: qPCR analyses revealed that all Slc4 bicarbonate transporter family members were expressed in mouse corneal endothelium. Slc4a11 showed the highest expression, which was approximately three times higher than that of Slc4a4 (3.4±0.3; p=0.004). All Slc4 genes were also expressed in cultured cells, and interestingly, the expression of Slc4a11 in cultured cells was significantly reduced by approximately 20-fold (0.05±0.001; p=0.000001) in early passage and by approximately sevenfold (0.14±0.002; p=0.000002) in late passage cells. CONCLUSIONS: Given the known involvement of SLC4A4 and SLC4A11 in corneal dystrophies, we speculate that the other two highly expressed genes in the uncultured corneal endothelium, SLC4A2 and SLC4A7, are worthy of being considered as potential candidate genes for corneal endothelial diseases. Moreover, as cell culture can affect expression levels of Slc4 genes, caution and careful design of experiments are necessary when undertaking studies of Slc4-mediated ion transport in cultured cells.

The Singapore 5-fluorouracil trial: intraocular pressure outcomes at 8 years.

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.

Efficacy and safety of collagen matrix implants in phacotrabeculectomy and comparison with mitomycin C augmented phacotrabeculectomy at 1 year.

BACKGROUND: To assess the efficacy and safety of collagen matrix implant (Ologen) in phacotrabeculectomy. DESIGN: Prospective, non-randomized, comparative study. PARTICIPANTS: Sixty-six Asian patients. METHODS: Thirty three consecutive patients underwent phacotrabeculectomy with Ologen implant and intraocular lens implantation, and 33 subjects recruited as controls underwent surgery with mitomycin C augmentation. MAIN OUTCOME MEASURES: The primary outcome measure was postoperative intraocular pressure at month 12. Additional postoperative treatments, such as bleb needling, and adverse events were secondary outcomes. RESULTS: The overall percentage reduction in intraocular pressure was 13% (95% confidence interval 6.7-19.2) in the Ologen group and 26% (95% confidence interval 14.8-37.9) in the mitomycin C group (P = 0.05). At 1 year after surgery (after adjusting for baseline differences), intraocular pressure decreased by 4.2 mmHg (95% confidence interval 2.8-5.6 mmHg) and 5.6 mmHg (95% confidence interval 4.2-7.0 mmHg), respectively (P = 0.16). Needling with 5-fluorouracil was required more often in the Ologen group (39% vs. 6%; P = 0.003). There was similar frequency (<10%) of adverse events in both groups, and there were no complications directly related to the Ologen implant. The blebs in the mitomycin C group had greater central area (P = 0.005), maximal area (P = 0.01) and height (P = 0.005), and were less vascular (P = 0.023) than the Ologen blebs. CONCLUSIONS: At 1 year, the overall performance of Ologen in combined phacotrabeculectomy was suboptimal compared with combined surgery with mitomycin C. Eyes in the Ologen group required more frequent bleb needling procedures.

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.

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.

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.

Reproducibility and age-related changes of ocular parametric measurements in rabbits.

BACKGROUND: The rabbit is a common animal model for ophthalmic research, especially corneal research. Ocular structures grow rapidly during the early stages of life. It is unclear when the rabbit cornea becomes mature and stabilized. We investigated the changes of keratometry, refractive state and central corneal thickness (CCT) with age. In addition, we studied the intra- and inter-observer reproducibility of anterior chamber depth (ACD) and anterior chamber width (ACW) measurements in rabbits using anterior segment-optical coherence tomography (AS-OCT). RESULTS: The growth of New Zealand White rabbits (n = 16) were monitored from age 1 to 12 months old. Corneal keratometric and refractive values were obtained using an autorefractor/keratometer, and CCT was measured using an AS-OCT. Keratometry and CCT changed rapidly from 1 to 7 months and appeared to be stabilizing after 8 months. The reduction of corneal curvature was approximately 1.36 diopter (D)/month from age 1 to 7 months, but the change decelerated to 0.30 D/month from age 8 to 12 months. An increase of 10 µm/month in CCT was observed from age 1 to 7 months, but the gain was reduced to less than 1 µm/month from age 8 to 12 months. There was a hyperopic shift over the span of 12 months, albeit the increase in spherical equivalent was slow and gradual. Rabbits of random age were then selected for 2 repeated ACD and ACW measurements by 2 independent and masked observers. Bland-Altman plots revealed a good agreement of ACD and ACW measurements inter- and intra-observer and the ranges of 95% limit of agreement were acceptable from a clinical perspective. CONCLUSIONS: Corneal keratometry, spherical equivalent refraction and CCT changed significantly during the first few months of life of rabbits. Young rabbits have been used in a large number of eye research studies. In certain settings, the ocular parametric changes are an important aspect to note as they may alter the findings made in a rabbit experimental model. In this study, we have also demonstrated for the first time a good between observer reproducibility of measurements of ocular parameters in an animal model by using an AS-OCT.

Reproducibility of Corneal Graft Thickness measurements with COLGATE in patients who have undergone DSAEK (Descemet Stripping Automated Endothelial Keratoplasty).

BACKGROUND: The CorneaL GrAft Thickness Evaluation (COLGATE) system was recently developed to facilitate the evaluation of corneal graft thickness from OCT images. Graft thickness measurement can be a surrogate indicator for detecting graft failure or success. The purpose of this study was to determine the reproducibility of the COLGATE system in measuring DSAEK graft area between two observers. METHODS: This was a prospective case series in which 50 anterior segment OCT images of patients who had undergone DSAEK in either eye were analysed. Two observers (MW, AC) independently obtained the image analysis for the graft area using both semi automated and automated method. One week later, each observer repeated the analysis for the same set of images. Bland-Altman analysis was performed to analyze inter and intra observer agreement. RESULTS: There was strong intraobserver correlation between the 2 semi automated readings obtained by both observers. (r = 0.936 and r = 0.962). Intraobserver ICC for observer 1 was 0.936 (95% CI 0.890 to 0.963) and 0.967 (95% CI 0.942 to 0.981) for observer 2. Likewise, there was also strong interobserver correlation (r = 0.913 and r = 0.969). The interobserver ICC for the first measurements was 0.911 (95% CI 0.849 to 0.949) and 0.968 (95% CI 0.945 to 0.982) for the second. There was statistical difference between the automatic and the semi automated readings for both observers (p = 0.006, p = 0.003). The automatic readings gave consistently higher values than the semi automated readings especially in thin grafts. CONCLUSION: The analysis from the COLGATE programme can be reproducible between different observers. Care must be taken when interpreting the automated analysis as they tend to over estimate measurements.

Pseudophakic rhegmatogenous retinal detachment in a large Asian tertiary eye centre: a cohort study.

BACKGROUND: To determine the incidence and identify risk factors for the development of rhegmatogenous retinal detachment in patients who had cataract surgery at the Singapore National Eye Centre between 2001 and 2003. DESIGN: Retrospective case-control study. PARTICIPANTS: All patients who had cataract surgery between 2001 and 2003 and subsequently retinal detachment surgery in the same eye, between 2001 and June 2008, at Singapore National Eye Centre. METHODS: Review of case records. MAIN OUTCOME MEASURES: Incidence of posterior capsular rupture and retinal detachment. RESULTS: Thirty-nine eyes, out of 24 846 cataract operations performed between 2001 and 2003, developed rhegmatogenous retinal detachment in the follow-up period from 2001 to 2008 (cumulative incidence 0.16%, 95% confidence interval 0.11-0.21%). Of the 508 eyes with posterior capsular rupture during cataract surgery, nine developed retinal detachment (cumulative incidence 1.77%, 95% confidence interval 0.87-3.23%). Men were more likely to develop retinal detachment (P < 0.001). On Kaplan-Meier survival analysis, younger patients had a higher probability of retinal detachment in comparison with older subjects (P < 0.001). Similarly, eyes with posterior capsular rupture during surgery had shorter interval duration to retinal detachment, compared with eyes that did not (P = 0.002). When compared with patients more than 70 years of age, younger patients had significantly higher hazard ratios of retinal detachment (hazard ratio 19.7, 95% confidence interval 3.6-107.3, P < 0.05). CONCLUSION: The incidence of pseudophakic retinal detachment in our institution is low. Posterior capsular rupture during surgery, men and younger age at time of surgery increases the risk of developing retinal detachment, and careful observation for the occurrence of retinal detachment may be warranted in these groups of patients.