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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:The5-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.

(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.

Objective: To compare the 3-year incidence of de novo ocular hypertension (OHT) after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK). For DSAEK, to evaluate predictors for OHT and 2-year outcomes after OHT development. Methods: This was a review of the prospective Singapore Corneal Transplant Study at a single tertiary referral center. Consecutive DSAEKs and PKs for Fuchs' endothelial dystrophy (FED) and pseudophakic bullous keratopathy (PBK) in eyes without pre-existing glaucoma were analyzed. OHT incidence after DSAEK and PK were compared using Kaplan-Meier survival analysis, and OHT risk factors identified using Cox proportional regression. OHT was defined: intraocular pressure (IOP) ⩾ 24 mmHg or ⩾ 10 mmHg from baseline. Secondary outcomes 2 years after OHT development in DSAEK were rates of glaucoma medical therapy failure, IOP success, graft failure and rejection, and best-spectacle corrected visual acuity (BSCVA). Results: There were 108 (96.4%) DSAEKs and 216 (96%) PKs. The 1-, 2- and 3-year de novo OHT incidence was not significantly different between DSAEK (36.1%, 47.2%, 47.2%, respectively) and PK (35.7%, 44.9%, 45.8%, respectively; P = 0.914). OHT incidence did not differ in subgroup analyses of multiple clinical variables (P . 0.1). OHT predictors after DSAEK were: fellow eye glaucoma (hazard ratio [HR] 3.20, P = 0.004), age ,60 years (HR 2.41, P = 0.016), concurrent goniosynechiolysis (HR 3.29, P = 0.021), post-graft complications or procedures (HR 2.85, P = 0.006). Two years after OHT onset, 29.7% of DSAEKs failed glaucoma medical therapy requiring trabeculectomy. Complete and qualified IOP success was achieved in 23.5% and 76.5%, respectively. Graft failure developed in 9.8% and graft rejection in 5.9%. At 6 months, 1, and 2 years from OHT onset, 86.3%, 88.3%, and 92.1% achieved BSCVA 20/40, respectively. Conclusion: DSAEK and PK have comparable OHT risks. A significant 30% of DSAEK eyes with OHT require filtration surgery. Effective IOP control and good graft and visual outcomes are achieved with treatment. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract 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.

Abstract 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,

BackgroundWe evaluated the visual outcomes and complications of “endothelium-out” and “endothelium-in” Descemet membrane endothelial keratoplasty (DMEK) graft insertion techniques.Materials and MethodsElectronic 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.Results21,323 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.ConclusionReported 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.

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.