[Show abstract][Hide abstract] ABSTRACT: To analyze changes in refraction and associated biometric changes in atropine- and placebo-treated eyes in the Atropine for Treatment of Myopia study (ATOM1).
A total of 400 myopic children, aged 6 to 12 years, were assigned randomly to receive 1% atropine or a placebo agent in one eye daily for 2 years, after which drops were stopped and children monitored for another year. Cycloplegic autorefraction, A-scan biometry, and automated keratometry were performed at the initial visit, 2 weeks (baseline), and at 4, 8, 12, 16, 20, 24, 30, and 36 months.
A total of 313 children (78.3%) completed the study. In placebo-treated eyes, there was myopic progression of -1.55 diopters (D), between baseline and 36 months, associated with reductions in corneal curvature (K; -0.13 D) and anterior chamber depth (ACD; -0.17 mm) and increases in lens thickness (LT; 0.05 mm), vitreous chamber depth (VCD; 0.65 mm), and axial length (AL; 0.53 mm). Multivariate analysis of change in spherical equivalent demonstrated that the hyperopic shift (0.20 D) noted in atropine-treated eyes between baseline and 4 months, and the myopic rebound (-0.74 D) noted between 24 to 30 months when atropine was stopped, were associated with a reduction and increase in VCD and AL, respectively, after adjusting for age and sex. Changes in K, ACD, and LT were less relevant. Between 4 and 24 months, atropine-treated eyes demonstrated gradual myopic progression (-0.40 D), accompanied by reduction in K (-0.06 D) and ACD (-0.07 mm) and increase in VCD (0.13 mm) and AL (0.06 mm).
Atropine appeared to slow myopia progression mainly by reducing or slowing the growth in VCD, and thereby AL. (ClinicalTrials.gov number, NCT00371124.).
[Show abstract][Hide abstract] ABSTRACT: Treating infections caused by multidrug-resistant Gram-negative pathogens is challenging, and there is concern regarding the toxicity of the most effective antimicrobials for Gram-negative pathogens. We hypothesized that conjugating a fatty acid moiety onto a peptide dimer could maximize the interaction with lipopolysaccharide (LPS) and facilitate the permeabilization of the LPS barrier, thereby improving potency against Gram-negative pathogens. We systematically designed a series of N-lipidated peptide dimers that are active against Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae (CRE). The optimized lipid length was 6-10 carbons. At these lipid lengths, the N-lipidated peptide dimers exhibited strong LPS permeabilization. Compound 23 exhibited synergy with select antibiotics in most of the combinations tested. 23 and 32 also displayed rapid bactericidal activity. Importantly, 23 and 32 were non-hemolytic at 10 mg/mL, with no cellular or in vivo toxicity. These characteristics suggest that these compounds can overcome the limitations of current Gram-negative-targeted antimicrobials such as polymyxin B.
[Show abstract][Hide abstract] ABSTRACT: To describe improvements in visual acuity and contrast sensitivity following Descemet stripping automated endothelial keratoplasty (DSAEK).
We analysed 128 consecutive patients (128 eyes) with Fuchs endothelial dystrophy (FED) and bullous keratopathy (BK) who underwent DSAEK at a single tertiary referral centre from January 2006 to September 2009. Our main outcome measures were best-corrected visual acuity (BCVA) and contrast sensitivity over 24 months follow-up.
Median age was 67 (60-73) years with 55% women (n=70) and majority Chinese (74%, n=94) in our Asian population. There were no significant differences between demographics between the FED (48%, 61 eyes) and BK (52%, 67 eyes) groups. Forward multivariate linear regression adjusted for age, gender, donor graft thickness and diagnosis (FED vs BK) revealed that preoperative visual acuity was the most significant factor associated with visual acuity at 1 year (B=0.032, p=0.03, R(2)=0.122). Visual recovery was longer in eyes with BK, with a significantly better visual acuity in the FED group at 12 months (mean logarithm of the minimum angle of resolution BCVA BK: 0.27±0.1 vs FED: 0.22±0.9; p=0.001), but not significant at 24 months (p=0.154). Contrast sensitivity significantly improved more in the first 6 months in the FED when compared with the BK group (at 3.0, 6.0 and 12.0 cycles per degree, p<0.01).
Our study suggests that while there was significant improvement in contrast sensitivity and visual acuity after DSAEK, poor preoperative visual acuity was associated with an inferior visual outcome and the time to recovery was longer in eyes with BK.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
The British journal of ophthalmology 07/2015; DOI:10.1136/bjophthalmol-2015-306975 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Descemet membrane endothelial keratoplasty (DMEK) allows for selective replacement of damaged endothelial cells, using only donor Descemet's membrane with endothelium. However, early adoption by corneal surgeons has been limited (illustrated by graft registry reports: 0.7% all corneal transplants in the USA; 0.4% in Australia for 2011) due to challenges in donor preparation and surgical technique. Recently, innovative donor preparation techniques may improve availability of pre-stripped DMEK donors from eye banks. The refinement of donor insertion and manipulation techniques has also improved outcomes and reduced graft detachment rates-still, the most common postoperative complication following DMEK. Randomised studies are needed to compare clinical practices and surgeon preferences, such as intraoperative use of long-acting gas, early versus late intervention of graft detachments and postoperative steroid management. A review of current literature reveals that most publications to date are reports from similar study cohorts by surgeons who pioneered and advocate this technique. Thus, more long-term clinical studies in other tertiary centres are required in order to confirm if the purported advantages of DMEK such as improved visual outcomes and reduced graft rejection are replicable among most corneal surgeons.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
The British journal of ophthalmology 05/2015; DOI:10.1136/bjophthalmol-2015-306837 · 2.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The global shortage of donor corneas has garnered extensive interest in the development of graft alternatives suitable for endothelial keratoplasty using cultivated primary human corneal endothelial cells (CECs). We have recently described a dual media approach for the propagation of human CECs. In this work, we characterize the effects of a Rho-kinase inhibitor Y-27632 on the cultivation of CECs propagated using the dual media culture system. Seventy donor corneas deemed unsuitable for transplantation were procured for this study. We assessed the use of Y-27632 for its effect at each stage of the cell culture process, specifically for cell attachment, cell proliferation, and during both regular passaging and cryopreservation. Lastly, comparison of donor-matched CEC-cultures expanded with or without Y-27632 was also performed. Our results showed that Y-27632 significantly improved the attachment and proliferation of primary CECs. A non-significant pro-survival effect was detected during regular cellular passage when CECs were pre-treated with Y-27632, an effect that became more evident during cryopreservation. Our study showed that the inclusion of Y-27632 was beneficial for the propagation of primary CECs expanded via the dual media approach, and was able to increase overall cell yield by between 1.96 to 3.36 fold.
[Show abstract][Hide abstract] ABSTRACT: Antibiotic resistance is a critical global health care crisis requiring urgent action to develop more effective antibiotics. Utilizing the hydrophobic scaffold of xanthone, we identified three components that mimicked the action of an antimicrobial cationic peptide to produce membrane-targeting antimicrobials. Compounds 5c and 6, which contain a hydrophobic xanthone core, lipophilic chains and cationic amino acids, displayed very promising antimicrobial activity against multidrug-resistant Gram-positive bacteria, including MRSA and VRE, rapid time-kill, avoidance of antibiotic resistance and low toxicity. The bacterial membrane selectivity of these molecules was comparable to that of several membrane-targeting antibiotics in clinical trials. 5c and 6 were effective in a mouse model of corneal infection by S. aureus and MRSA. Evidence is presented indicating that 5c and 6 target the negatively charged bacterial membrane via a combination of electrostatic and hydrophobic interactions. These results suggest that 5c and 6 have significant promise for combating life-threatening infections.
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To test the association between the CTG18.1 trinucleotide repeat expansion of TCF4 gene and Fuchs' endothelial corneal dystrophy (FECD) in a Chinese population.
The trinucleotide repeat polymorphism CTG18.1 was genotyped using short tandem repeat and triplet repeat primed polymerase chain reaction assays in 57 Chinese subjects with FECD and 121 controls. Statistical association of the expanded CTG18.1 allele and 18 single nucleotide polymorphisms (SNPs) across TCF4 with FECD was evaluated. To investigate the linkage disequilibrium structure of the TCF4 region, haplotype analysis was performed on our study subjects and compared with genotyping data of 97 Han Chinese and 85 Caucasians in the 1000 Genomes Project.
The expanded CTG18.1 allele was associated with FECD (P = 4.7 × 10(-14)), with the odds ratio of each copy of the expanded allele estimated to be 66.5 (95% confidence interval: 12.6-350.1). Five TCF4 SNPs showed association with FECD at a nominal level (P < 5.0 × 10(-2)); however, conditional on the expanded CTG18.1 polymorphism, none of the SNPs showed association with FECD. The only haplotype associated with the disease was the one with the expansion at the CTG18.1 locus.
Transethnic replication of the association between the CTG18.1 repeat expansion in the TCF4 gene and FECD suggests it is a common, causal variant shared in Eurasian populations conferring significant risk for the development of FECD. Our data suggest that the expanded CTG18.1 allele is the main, if not sole, causal variant at this gene locus in the Chinese population.
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To describe the transition and outcomes of 3 refractive lenticule extraction (ReLEx) techniques: femtosecond lenticule extraction (FLEx), small-incision lenticule extraction (SMILE), and pseudo small-incision lenticule extraction. SETTING: Singapore National Eye Center, Singapore. DESIGN: Prospective comparative case series. METHODS: Refractive lenticule extraction was performed between March 1, 2010, and November 1, 2012, using the Visumax 500 kHz femtosecond laser system. The main outcome measures were the refractive efficacy, predictability, and safety over 12 months. RESULTS: The study enrolled 88 eyes. All 3 refractive lenticule extraction techniques yielded good refractive outcomes and stability over 12 months. Three months postoperatively, the mean overall efficacy index of refractive lenticule extraction was 0.89 +/- 0.22 (SD), with 95.5% of eyes attaining an uncorrected distance visual acuity (UDVA) of better than 20/40 and 60.2% of better than 20/20. Of all eyes, 95.5% were within +/-1.00 diopter (D) and 78.4% within +/-0.50 D of the attempted correction. The mean overall safety index was 1.06 +/- 0.17. At 3 months, all small-incision lenticule extraction eyes and 96.7% of pseudo small-incision lenticule extraction eyes had a UDVA of 20/40 or better, while femtosecond lenticule extraction eyes had a lower efficacy index (87.0%). However, efficacy was comparable in all 3 groups by 12 months (mean 0.87 +/- 0.04 [standard error of the mean]; P = 1.00). CONCLUSION: The efficacy, safety, and predictability profiles of the 3 refractive lenticule extraction techniques were good over a 12-month follow-up. (C) 2014 ASCRS and ESCRS
Journal of Cataract and Refractive Surgery 09/2014; 40(9):1415-24. DOI:10.1016/j.jcrs.2013.12.026 · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To analyze graft survival of endothelial keratoplasty (EK) under a previous failed penetrating keratoplasty (PK) compared to repeat PK. DESIGN: Retrospective, comparative case series. METHODS: Analysis involved consecutive patients who underwent either a repeat PK or EK under PK, after failed PK, whose primary surgical indication was pseudophakic bullous keratopathy at a single tertiary center. Clinical data and donor and recipient characteristics were recorded from our prospective cohort from the Singapore Corneal Transplant Study. Main outcome measure was graft survival up to 5 years follow-up. RESULTS: We included a total of 113 eyes that underwent a repeat PK (n = 81) or EK under a failed PK (n = 32). Cumulative graft survival probabilities comparing repeat PK with EK under PK were at 91.9% vs 96.2% (1 year), 82.6% vs 91.6% (2 years), 66.8% vs 86.4% (3 years), and 51.3% vs 86.4% up to 5 years follow-up, respectively (log-rank P value = .013). Multivariate Cox regression analysis was performed, which adjusted for: age, sex, risk factors for graft failure (corneal neovascularization, ocular surface disease, glaucoma, active corneal inflammation, anterior synechiae), donor endothelial cell count, and repeat donor size. Repeat PK was a significant risk factor for graft failure compared to performing an EK under PK (hazard ratio: 10.17; 95% CI 1.10-93.63; P = .041). CONCLUSION: In our study of eyes with bullous keratopathy, endothelial keratoplasty under a previously failed PK provided better graft survival outcomes than repeat PK, adjusting for potential confounders and risk factors for graft failure.
American Journal of Ophthalmology 08/2014; 158(6). DOI:10.1016/j.ajo.2014.08.024 · 3.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Endothelial keratoplasty has largely replaced penetrating keratoplasty as the preferred technique to selectively replace diseased corneal endothelium. Descemet’s stripping automated endothelial keratoplasty (DSAEK) is the most common type of endothelial keratoplasty performed worldwide. One of the challenges in DSAEK is the insertion of the donor lenticule into the eye using a method so as to minimize endothelial cell loss. Various techniques have been suggested such as forceps insertion and graft insertion devices. With the trend towards using thinner DSAEK tissue and Descemet membrane endothelial keratoplasty, there are increasing challenges in inserting and manipulating even more delicate tissue. The EndoGlide Ultrathin has several new features that will enable easier insertion of thinner DSAEK tissue. This paper presents the features and surgical technique of the EndoGlide Ultrathin during DSAEK.
Expert Review of Medical Devices 08/2014; 11(6). DOI:10.1586/17434440.2014.947273 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Titanium (Ti) is a promising candidate biomaterial for an artificial corneal skirt. Antimicrobial peptide (AMP) immobilization
may improve the bactericidal effect of the Ti substrate. In this study, we tested the bactericidal efficacy of a functionalized
Ti surface in a rabbit keratitis model. A corneal stromal pocket was created by a femtosecond laser. The Ti films were then
inserted into the pocket, and Staphylococcus aureus or Pseudomonas aeruginosa was inoculated into the pocket above the implant films. The corneas with Ti-AMP implants were compared with the corneas implanted
with unprotected Ti by slit lamp observation and anterior segment optical coherence tomography (AS-OCT). Inflammatory responses
were evaluated by bacterium counting, hematoxylin-eosin staining, and immunostaining. There was a lower incidence and a lesser
extent of infection on rabbit corneas with Ti-AMP implants than on those with unprotected Ti implants. The bactericidal effect
of AMP against S. aureus was comparable to that of postoperative prophylactic antibiotic treatment; hence, SESB2V AMP bound to the Ti implant provided
functional activity in vivo, but its efficacy was greater against S. aureus than against P. aeruginosa. This work suggests that SESB2V AMP can be successfully functionalized in a rabbit keratitis model to prevent perioperative
[Show abstract][Hide abstract] ABSTRACT: PURPOSE: To evaluate the long-term corneal graft survival and risk factors for graft failure in pediatric eyes. DESIGN: Retrospective, interventional consecutive case series. METHODS: Unilateral eyes of 105 patients aged 16 years and below were included from the Singapore Corneal Transplant Study between April 4, 1991 and April 4, 2011. Corneal graft survival was calculated using Kaplan-Meier survival analysis, and survival distributions were compared using log-rank test. RESULTS: Mean recipient age was 8.38 +/- 5.63 years (range 0.18-15.92 years). Mean follow-up time was 34.16 +/- 39.10 months. Main diagnoses were corneal scar (22.9%), limbal dermoid (21.9%), anterior segment dysgenesis (15.2%), and keratoconus (14.3%). Forty-four eyes (41.9%) underwent penetrating keratoplasty (PK), 37 (35.2%) underwent anterior lamellar keratoplasty (ALK), 22 (21.0%) underwent lamellar corneal patch graft, and 2 (1.9%) underwent Descemet stripping automated endothelial keratoplasty (DSAEK). Kaplan-Meier survival rates for PK were 92.8% at 1 year, 88.9% at 2-4 years, and 80.9% at 5-16 years; survival rates for ALK were 88.0% at 1 year and 84.3% at 2-7 years; survival rates for corneal patch graft were 100% at 1-3 years and 90% at 4-10 years; these were not statistically significant (P = .362). Deep corneal vascularization (P = .012), preexisting active inflammation (P = .023), preexisting glaucoma drainage device (P = .023), and preexisting ocular surface disease (P = .037) were associated with reduced graft survival in a univariate analysis. CONCLUSIONS: We report good long-term graft survival following pediatric keratoplasty for various indications. Lamellar keratoplasty, when indicated, should be the procedure of choice in high-risk keratoplasties.
American Journal of Ophthalmology 05/2014; 158(3). DOI:10.1016/j.ajo.2014.05.020 · 3.87 Impact Factor