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To explore demographics, disease characteristics, and wear habits in cosmetic contact lens (CL)-related corneal infections in Asia.Prospective multicenter cross-sectional study.Cases of CL-related corneal infection presenting over a 12-month period were prospectively identified from 11 centers in 8 countries in Asia. Case demographics, clinical features, microbiology, and compliance characteristics were compared between wearers using CLs for cosmetic purposes and those using CLs for the correction of refractive errors.Six hundred and ninety-four CL wearers with corneal infection presented: 204 cosmetic CL (29.4%) and 490 (70.6%) refractive CL wearers. Cosmetic CL infections comprised 7%-54% of cases across the region. Compared with noncosmetic CL wearers, cosmetic CLs wearers were significantly more likely to be female (90% vs 59%), young (aged25, 68% vs 44%), and to have a shorter period of wear experience. Lenses worn by cosmetic CL wearers were more likely to be hydrogel materials and manufactured with the pigment located on the back surface of the CL. Presenting disease characteristics and visual outcomes were similar in both groups. Causative organisms were similar between the 2 groups; however, there was a higher rate of Acanthamoeba disease (9%) in cosmetic wearers, compared with refractive wearers (1%; P.005).Cosmetic CL infections represent a significant proportion of CL-related infections in Asia. Cosmetic CL users with corneal infections are generally young, female, and wearing hydrogel CLs. Internet supply, quality control, and regulation of the sale of these products provide significant challenges in managing this population of vulnerable wearers.

In 2019, the American Academy of Ophthalmology (AAO) created the Task Force on Myopia in recognition of the substantial global increases in myopia prevalence and its associated complications. The Task Force, led by Richard L. Abbott, MD, and Donald Tan, MD, comprised recognized experts in myopia prevention and treatment, public health experts from around the world, and organization representatives from the American Academy of Family Physicians, American Academy of Optometry, and American Academy of Pediatrics. The Academy's Board of Trustees believes that myopia is a high-priority cause of visual impairment, warranting a timely evaluation and synthesis of the scientific literature and formulation of an action plan to address the issue from different perspectives. This includes education of physicians and other health care providers, patients and their families, schools, and local and national public health agencies; defining health policies to ameliorate patients' access to appropriate therapy and to promote effective public health interventions; and fostering promising avenues of research.

Atropine eye drops prevent the progression of myopia, but their use has not been tested in the Japanese schoolchildren population. Here, we evaluate the efficacy and safety of 0.01% atropine eye drops for myopia control in Japanese children. Multicenter (7 university hospitals), randomized, double-masked, placebo-controlled trial. Participants were 171 Japanese schoolchildren aged 6 to 12 years, with progressive myopia, spherical equivalence (SE) of −1.00 to −6.00 diopters (D), and astigmatism of ≤1.5 D. They were randomized to receive either 0.01% atropine (n=85) or placebo (n=86) eye drops once nightly OU for 24 months. Primary and secondary efficacy endpoints were changes in SE and axial length (AL), respectively, from baseline to month 24. Data from 168 subjects were analyzed. At month 24, compliance was similar in both groups (atropine: 83.3%; placebo: 85.7%). The least squares mean change in SE and AL from baseline were, respectively, −1.26 D (95% confidence interval [CI]: −1.35, −1.17) and 0.63 mm (0.59, 0.67) for atropine and −1.48 D (− 1.57, −1.39) and 0.77 mm (0.73, 0.81) for placebo. Inter-group differences were 0.22 D (95% CI: 0.09, 0.35; P

AimTo 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.MethodsThis 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.ResultsThe 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.ConclusionsEyes 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.

Purpose In recent decades, the medical and surgical treatment of limbal stem cell deficiency (LSCD) has evolved significantly through the incorporation of innovative pharmacological strategies, surgical techniques, bioengineering, and cell therapy. With such a wide variety of options, there is a need to establish a global consensus on the preferred approaches for the medical and surgical treatment of LSCD. Methods An international LSCD Working Group was established by the Cornea Society in 2012 and divided into subcommittees. Four face-to-face meetings, frequent email discussions, and teleconferences were conducted since then to reach agreement on a strategic plan and methods after a comprehensive literature search. A writing group drafted the current study. Results A consensus in the medical and surgical management of LSCD was reached by the Working Group. Optimization of the ocular surface by eyelid and conjunctival reconstruction, antiinflammatory therapy, dry eye and meibomian gland dysfunction treatment, minimization of ocular surface toxicity from medications, topical medications that promote epithelialization, and use of a scleral lens is considered essential before surgical treatment of LSCD. Depending on the laterality, cause, and stage of LSCD, surgical strategies including conjunctival epitheliectomy, amniotic membrane transplantation, transplantation of limbal stem cells using different techniques and sources (allogeneic vs. autologous vs. ex vivo-cultivated), transplantation of oral mucosal epithelium, and keratoprosthesis can be performed as treatment. A stepwise flowchart for use in treatment decision-making was established. Conclusions This global consensus provides an up-to-date and comprehensive framework for the management of LSCD.

Objectives The purpose of this study was to develop a reproducible preclinical Fusarium solani keratitis model, which would allow comparative testing of currently available antifungals (NATACYN [Alcon, Fort Worth, TX], voriconazole 1%, and amphotericin B 0.1%) as well as efficacy testing of new antifungals for translation into clinical practice in the future. Methods The rabbit F. solani keratitis model was developed in New Zealand white rabbits using local and systemic immunosuppression. Infection was introduced by intrastromal injection of F. solani spores into one of the immunosuppressed rabbit eyes while the contralateral eye was a control. Progress of the infection was assessed by the clinical features, histopathology, and viable fungal counts. In this study, the efficacy of currently available antifungals (NATACYN [Alcon], voriconazole 1%, and amphotericin B 0.1%) was compared. Rabbits were randomly divided (n=4 in each group), and the respective antifungal was instilled topically 5 times/day for 7 days. Treatment effects were analyzed by evaluating the anterior segment with the help of slit-lamp, histopathological findings and viable fungal culture at the end of the experiment. Results We report the development of a reproducible and progressive rabbit F. solani keratitis model as shown by the substantial viable fungal counts (3 log CFU), the presence of large patchy lesions and substantial hypopyon in the 12-day model correlated with specific histopathological analysis for fungus (extended F. solani hyphae from midcorneal stroma into the anterior chamber and traverse Descemet membrane with anterior chamber suppurative plaque). Voriconazole 1% and NATACYN revealed significant reduction of the fungal wound area (P=0.02 and 0.021), respectively, while amphotericin B 0.1% exhibited P value of 0.083 compared with their infected nontreated controls. Voriconazole 1% and amphotericin B 0.1% showed significant viable fungal count differences (P=0.004 and 0.01), respectively, whereas P value of NATACYN was 0.337 compared with control infected corneas. Conclusion The reported rabbit fungal keratitis model can be used for screening new antifungals and evaluating currently available antifungals to facilitate better clinical outcomes. Voriconazole 1% showed the best efficacy among the three tested currently available antifungals by showing the significant differences in both wound size and viable fungal count comparisons in our F. solani rabbit keratitis model.

The purpose of this article is to provide a framework for general ophthalmologists in Singapore to manage dry eye. This framework considers the evidence in the literature as well as recommendations from expert panels such as the Tear Film & Ocular Surface Society Dry Eye Workshop II and the Asia Cornea Society Workgroup. This article covers the assessment of patient medical history and ask triage questions to identify local and systemic causes of dry eye disease (DED), excluding other possible causes, as well as the risk factors for DED and ocular surface inflammation. Evaluation of clinical signs to establish the diagnosis of DED and differentiation from other causes of irritable, red eyes are described. Tests for understanding the underlying disease processes and severity of DED are also presented. Management of dry eye should involve patient education and engagement. Information about the natural history and chronic nature of DED should be provided to improve long-term management of the disease and enhance compliance. Aggravating factors should be removed or lessened. We provide a guide to determine the most appropriate treatment (or combination of treatments) based on the severity and cause(s) of the disease, as well as the patient's needs and preferences. The aim of the management is to relieve ocular discomfort and prevent worsening of symptoms and signs, as well as to optimize visual function and minimize structural ocular damage. We also discuss the systematic follow-up and assessment of treatment response, as well as monitoring side effects of treatment, bearing in mind continuous support and reassurance to patients.

Highly myopic Singaporean children progress rapidly by adolescence to their adult spherical equivalent, with early onset and baseline myopia associated with pathologic findings of thinner choroid and tessellated fundus in young adulthood.

Background There is limited information regarding Descemet stripping automated endothelial keratoplasty (DSAEK) for endothelial failure secondary to cytomegalovirus (CMV) endotheliitis. Treatment is difficult with high recurrence rates. We describe a case when systemic valganciclovir therapy is directed by aqueous CMV-DNA levels, leading to good graft survival. Findings A 59-year-old male with bilateral CMV endotheliitis despite antiviral therapy developed endothelial failure and underwent DSAEK. Prior to surgery, aqueous polymerase chain reaction (PCR) for CMV was repeatedly performed, where CMV-positive episodes were treated with systemic valganciclovir. Monthly aqueous analysis was performed until CMV-DNA was undetectable before DSAEK was performed. Post-operative prophylactic systemic valganciclovir treatment was instituted and switched to topical valganciclovir treatment when aqueous samples were negative for CMV. Conclusion Targeted aqueous sampling for CMV-DNA perioperatively guides antiviral therapy and ensures adequacy of treatment, minimising the duration of systemic valganciclovir therapy to reduce adverse effects of long-term treatment.

PurposeTo describe a surgical approach that involves anterior segment reconstruction with CustomFlex Artificial Iris (CAI; HumanOptics, Erlangen, Germany) followed by Descemet membrane endothelial keratoplasty (DMEK) in complex eyes with corneal decompensation.MethodsRestrospective case series of eyes that underwent anterior segment restoration involving (1) synechiolysis of peripheral anterior synechiae and excision of iris remnants, (2) securing a well-fixated posterior chamber intraocular lens and (3) suture-fixated or capsular bag placement of CAI. All eyes then underwent DMEK using a pull-through technique with the DMEK EndoGlide (Network Medical Products, Ripon, UK). Main outcomes were successful anterior segment restoration and corneal clarity with central corneal thickness (CCT).ResultsFive eyes of five patients (median age 61 years, range 27–69 years; 60% female) underwent anterior segment reconstruction with CAI implantation (4 suture-fixated), followed by successful DMEK surgery (median 2 months later, range 1–5 months). There were no major intraoperative complications or primary graft failure, with one peripheral graft detachment that underwent a successful re-bubble at 1 week. All eyes had stable CAI implants and DMEK grafts remained clear at last follow-up with reduction in mean central corneal thickness (preoperative: 658±86 µm vs postoperative: 470±33 µm, p=0.005).ConclusionThis pilot study highlights a feasible approach of initial anterior segment reconstruction with CAI implantation, prior to DMEK, in eyes with significant anterior segment abnormalities such as iris damage or extensive peripheral anterior synechiae and corneal decompensation.

PURPOSE Endothelial failure and immunological graft rejection remain long-term complications leading to late graft failure in penetrating keratoplasty (PK). Deep anterior lamellar keratoplasty (DALK) has emerged as a viable alternative that enables preservation of the host's endothelial cells to eliminate risks of endothelial rejection and failure. The aim of this study was to compare long-term graft survival between PK and DALK. DESIGN Retrospective clinical cohort study. METHODS All consecutive primary grafts of DALKs (n = 362) and PKs (n = 307) performed for optical indications in a tertiary eye center from the ongoing, prospective Singapore Corneal Transplant Study. Ten-year graft survival outcomes were compared. Cases in which endothelial pathologies were diagnosed were excluded, as DALK was not performed for such cases. Main outcome measurements were mean graft survival rate. RESULTS The survival rate for PK was 94.4%, 80.4%, and 72.0% at 1, 5, and 10 years, respectively; and 95.8%, 93.9%, and 93.9% at 1, 5, and 10 years, respectively, for DALK (P = .001). Patients who underwent PK developed more complications of glaucoma (29.3% vs. 11.6%, respectively; P < .001), allograft rejection (16.6% vs. 1.7%, respectively; P < .001), epithelial problems (10.4% vs. 5.5%, respectively; P = .018), and nonimmunological failure (7.8% vs. 1.9%, respectively; P < .001), compared to DALK. Rates of graft failure attributable to rejection (36.7% vs. 5.9%, respectively; P = .015) and endothelial failure (36.7% vs. 5.9%, respectively; P = .015) were lower in DALK. CONCLUSIONS The 10-year graft survival for primary DALK was superior to that for PK for corneal pathologies with functional endothelium. Primary DALK resulted in fewer post-operative complications and lower rates of graft rejection and failure. This study strengthens the case in favor of performing DALK over PK when possible.

Myopia is an emerging public health issue with potentially significant economic and social impact, especially in East Asia. However, many uncertainties about myopia and its clinical management remain. The International Myopia Summit workgroup was convened by the Singapore Eye Research Institute, the WHO Regional Office for the Western Pacific and the International Agency for the Prevention of Blindness in 2019. The aim of this workgroup was to summarise available evidence, identify gaps or unmet needs and provide consensus on future directions for clinical research in myopia. In this review, among the many ‘controversies in myopia’ discussed, we highlight three main areas of consensus. First, development of interventions for the prevention of axial elongation and pathologic myopia is needed, which may require a multifaceted approach targeting the Bruch’s membrane, choroid and/or sclera. Second, clinical myopia management requires co-operation between optometrists and ophthalmologists to provide patients with holistic care and a tailored approach that balances risks and benefits of treatment by using optical and pharmacological interventions. Third, current diagnostic technologies to detect myopic complications may be improved through collaboration between clinicians, researchers and industry. There is an unmet need to develop new imaging modalities for both structural and functional analyses and to establish normative databases for myopic eyes. In conclusion, the workgroup’s call to action advocated for a paradigm shift towards a collaborative approach in the holistic clinical management of myopia.

BackgroundTo assess the outcomes of laser-assisted in situ keratomileusis (LASIK) performed for the treatment of myopia in terms of safety, efficacy and predictability in an 18-year clinical audit.MethodIn this single-centre, prospective, non-randomised study, preoperative and postoperative refractions, uncorrected (UCVA), best-corrected Snellen visual acuity (BCVA) and complications of all eyes undergoing myopic LASIK were recorded. Safety, efficacy, refractive predictability, treatment trends, retreatment rates and complication rates were evaluated.ResultsBetween 1998 and 2015, 53 731 eyes of 27312 patients underwent myopic LASIK. Patients’ median age was 31.6 years (mean, 32.6±7.3 years); there were 9703 males (35.5%). Patients were predominantly ethnic Chinese (87.4%). Mean follow-up time was 78±75.6 days (median, 86 days). Overall efficacy index was 0.91 with >99% of eyes achieving UCVA of ≥20/40 and >70% achieving 20/20 since 2010. 95.43% of eyes had no loss of vision postoperatively and 4.2% and 0.37% lost 1 and ≥2 lines BCVA, respectively. From 2010 the safety index has been >1.05. More than 94.0% of eyes achieved within ±1.0 D of target refraction and at least 70% achieved within ±0.50 D of target from 2010 onwards. Retreatment rate was 2.55% and after retreatment 98.4% of eyes achieved ≥20/40 UCVA and 63.5% achieved ≥20/20 UCVA. The overall complication rate is 0.98%, and since 2010, the annual complication rate has been ConclusionsMyopic LASIK performed in Asian eyes is safe and effective with high refractive predictability in a comprehensive LASIK programme with appropriate clinical audit.

IMPORTANCE To describe long-term outcomes of hemi-automated lamellar keratoplasty (HALK). BACKGROUND HALK is a hybrid anterior lamellar keratoplasty technique for corneas with anterior to mid-stromal scars and topographical irregularities. DESIGN Prospective interventional case series. PARTICIPANTS Thirty-five eyes of 35 consecutive patients undergoing HALK at a single tertiary referral centre from 2007 to 2016. METHODS Patients were followed up for a mean period of 61.4 ± 29.2 months. MAIN OUTCOME MEASURE Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), spherical equivalent (SE) and cylinder, endothelial cell density (ECD), central corneal thickness (CCT), graft survival and complications were analysed. RESULTS The most common indications for HALK were scars because of contact lens associated infectious keratitis (29%), unknown origin (26%) or corneal dystrophies (14%). Five patients had a previous keratoplasty (n = 4; deep anterior lamellar keratoplasty, n = 1). Two HALKs failed at 22 and 32 months follow-up. No graft rejections occurred. UCVA improved from 0.91 ± 0.31 to 0.58 ± 0.35 and BSCVA from 0.66 ± 0.30 to 0.21 ± 0.20 logMAR (P

Author(s): Ung, Lawson; Acharya, Nisha R; Agarwal, Tushar; Alfonso, Eduardo C; Bagga, Bhupesh; Bispo, Paulo Jm; Burton, Matthew J; Dart, John Kg; Doan, Thuy; Fleiszig, Suzanne Mj; Garg, Prashant; Gilmore, Michael S; Gritz, David C; Hazlett, Linda D; Iovieno, Alfonso; Jhanji, Vishal; Kempen, John H; Lee, Cecilia S; Lietman, Thomas M; Margolis, Todd P; McLeod, Stephen D; Mehta, Jod S; Miller, Darlene; Pearlman, Eric; Prajna, Lalitha; Prajna, N Venkatesh; Seitzman, Gerami D; Shanbhag, Swapna S; Sharma, Namrata; Sharma, Savitri; Srinivasan, Muthiah; Stapleton, Fiona; Tan, Donald Th; Tandon, Radhika; Taylor, Hugh R; Tu, Elmer Y; Tuli, Sonal S; Vajpayee, Rasik B; Van Gelder, Russell N; Watson, Stephanie L; Zegans, Michael E; Chodosh, James

The manufacture of mechanically strong and biocompatible titania (TiO2 ) materials is of vital importance for their application as corneal implant skirts. This study was aimed at optimizing the selection of raw powder and sintering conditions for TiO2 ceramics. TiO2 compacts were synthesized from five raw powders, denoted as Altair, Inframat, Alfa, Materion, and Amperit, respectively, by spark plasma sintering using different sintering parameters. The XRD and Raman results confirmed that the anatase TiO2 phase in the Inframat powder had converted completely to rutile TiO2 phase after sintering at 900°C and above. The nanoindentation results indicated that among the five types of TiO2 samples sintered at 1100°C, the Inframat pellets possessed the highest Young's modulus and hardness. Additionally, when Materion samples were employed to study the effects of SPS parameters, a higher sintering temperature in the range of 1100-1300°C decreased the mechanical properties of sintered pellets probably due to the generation of more structural defects. Culture of human corneal stromal fibroblasts on the sintered sample surfaces showed that comparably high cell viability and proliferation were observed on all TiO2 samples except Amperit compared to positive control. Furthermore, cells cultured on Inframat TiO2 sintered in the temperature range of 900-1300°C exhibited viability and formation of focal adhesion complex similar to those on control, and those prepared at 1100°C had significantly higher cell proliferation indices than control. In conclusion, Inframat TiO2 consolidated at 1100°C by SPS was the best formulation for the preparation of mechanically strong and biocompatible Keratoprosthesis skirt. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3502-3513, 2017.

A new series of semisynthetic flavone-based small molecules mimicking antimicrobial peptides has been designed from natural icaritin to combat drug-resistant Gram-positive bacterial infections. Compound 6 containing two arginine residues exhibited excellent antibacterial activity against Gram-positive bacteria, including MRSA, and very low toxicity to mammalian cells, resulting in a high selectivity of more than 511, comparable to that of several membrane-active antibiotics in clinical trials. Our data show for the first time that icaritin derivatives effectively kill bacteria. Meanwhile, this is the first study deploying a biomimicking strategy to design potent flavone-based membrane targeting antimicrobials. 6 showed rapid bactericidal activity by disrupting the bacterial membrane and can circumvent the development of bacterial resistance. Importantly, 6 was highly efficacious in a mouse model of corneal infection caused by MRSA and Staphylococcus aureus.

This is the first report of the design of a new series of symmetric xanthone derivatives that mimic antimicrobial peptides using a total synthesis approach. This novel design is advantageous because of its low cost, synthetic simplicity and versatility, and easy tuning of amphiphilicity by controlling the incorporated cationic and hydrophobic moieties. Two water-soluble optimized compounds, 6 and 18, showed potent activities against Gram-positive bacteria, including MRSA and VRE (MICs = 0.78-6.25 μg/mL) with a rapid bactericidal effect, low toxicity, and no emergence of drug resistance. Both compounds demonstrated enhanced membrane selectivity that was higher than those of most membrane-active antimicrobials in clinical trials or previous reports. The compounds appear to kill bacteria by disrupting their membranes. Significantly, 6 was effective in vivo using a mouse model of corneal infection. These results provide compelling evidence that these compounds have therapeutic potential as novel antimicrobials for multidrug-resistant Gram-positive infections.

AimTo evaluate the outcomes and complications of hybrid Descemet membrane endothelial keratoplasty (H-DMEK) using a Descemet stripping automated endothelial keratoplasty (DSAEK) pull-through donor inserter and donor stroma as carrier.MethodsThis was a retrospective interventional case series of eyes with bullous keratopathy (BK) and Fuchs endothelial corneal dystrophy (FECD), which underwent H-DMEK, performed using a bimanual pull-through technique using DSAEK-prepared donor stroma as carrier and the EndoGlide Ultrathin DSAEK donor insertion device. Complex cases with tube shunts, trabeculectomy, aphakia, aniridia, previous vitrectomy, keratoplasty or combined with intraocular lens exchange, were also included. The outcome measures were intraoperative and postoperative complications, best corrected visual acuity (BCVA) and endothelial cell loss after surgery.ResultsOf the 85 eyes from 79 patients, 43.5% (n=37) had BK, 28.2% (n=24) had FECD while 24.7% (n=21) had failed grafts. DMEK was performed in 37 complex eyes (43.5%). Four eyes (4.7%) required rebubbling for graft detachment and two cases of graft failure were observed. A BCVA of 20/25 or better was attained in 44.7% and 57.1% of eyes without pre-existing ocular pathology at 6 and 12 months, respectively. The overall endothelial cell loss was 32.2%±20.5% at 6 months, which improved from 37.2%±20.9% to 24.2%±17.5%, comparing the first 40 and last 45 cases (p=0.012).ConclusionHybrid DMEK offers a controlled ‘pull-through’ technique of donor insertion in the ‘endothelium-in’ configuration, which may be useful especially in complicated eyes. More studies are needed to confirm the long-term endothelial cell loss and graft survival associated with this technique.

Purpose To discuss guidelines and ethical considerations associated with the development and prescription of treatments intended for myopia control (MC). Methods Critical review of published papers and guidance documents was undertaken, with a view to carefully considering the ethical standards associated with the investigation, development, registration, marketing, prescription, and use of MC treatments. Results The roles and responsibilities of regulatory bodies, manufacturers, academics, eye care practitioners, and patients in the use of MC treatments are explored. Particular attention is given to the ethical considerations for deciding whether to implement a MC strategy and how to implement this within a clinical trial or practice setting. Finally, the responsibilities in marketing, support, and education required to transfer required knowledge and skills to eye care practitioners and academics are discussed. Conclusions Undertaking MC treatment in minors creates an ethical challenge for a wide variety of stakeholders. Regulatory bodies, manufacturers, academics, and clinicians all share an ethical responsibility to ensure that the products used for MC are safe and efficacious and that patients understand the benefits and potential risks of such products. This International Myopia Institute report highlights these ethical challenges and provides stakeholders with recommendations and guidelines in the development, financial support, prescribing, and advertising of such treatments.

An artificial cornea or keratoprosthesis requires high mechanical strength, good biocompatibility, and sufficient wear and corrosion resistance to withstand the hostile environment. We report a reduced graphene oxide-reinforced titania-based composite for this application. Graphene oxide nanoparticles (GO) and liquid crystalline graphene oxide (LCGO) were the graphene precursors and mixed with titanium dioxide (TiO2) powder. The composites reinforced with reduced GO or LCGO were produced through spark plasma sintering (SPS). The mechanical properties (Young's modulus and hardness), wear behaviour and corrosion resistance were studied using nanoindentation, anoidic polarization, long-term corrosion assay in artificial tear fluid and tribology assay in corroboration with atomic force microscopy and scanning electron microscopy. Biocompatibility was assessed by human corneal stromal cell attachment, survival and proliferation, and DNA damages. Sintered composites were implanted into rabbit corneas to assess for in vivo stability and host tissue responses. We showed that reduced graphene/TiO2 hybrids were safe and biocompatible. In particular, the 1% reduced LCGO/TiO2 (1rLCGO/TiO2) composite was mechanically strong, chemically stable, and showed better wear and corrosion resistance than pure titania and other combinations of graphene-reinforced titania. Hence the 1rLCGO/ TiO2 bioceramics can be a potential skirt biomaterial for keratoprosthesis to treat end-stage corneal blindness. STATEMENT OF SIGNIFICANCE: The osteo-odonto-keratoprosthesis (OOKP) is an artificial cornea procedure used to restore vision in end-stage corneal diseases, however it is contraindicated in young subjects, patients with advanced imflammatory diseases and posterior segment complications. Hence, there is a need of an improved keratoprosthesisskirt material with high mechanical and chemical stability, wear resistance and tissue integration ability. Our study characterized a reduced graphene oxide-reinforced titania-based biomaterial, which demonstrated strong mechanical strength, wear and corrosion resistance, and was safe and biocompatible to human corneal stromal cells. In vivo implantation to rabbit corneas did not cause any immune and inflammation outcomes. In conclusion, this invention is a potential keratoprosthesis skirt biomaterial to withstand the hostile environment in treating end-stage corneal blindness.

An artificial cornea or keratoprosthesis requires high mechanical strength, good biocompatibility, and sufficient wear and corrosion resistance to withstand the hostile environment. We report a novel reduced graphene oxide-reinforced titania-based composite for this application. Graphene oxide nanoparticles (GO) and liquid crystalline graphene oxide (LCGO) were the graphene precursors and mixed with titanium dioxide (TiO2) powder. The composites reinforced with reduced GO or LCGO were produced through spark plasma sintering (SPS). The mechanical properties (Young's modulus and hardness), wear behaviour and corrosion resistance were studied using nanoindentation, anoidic polarization, long-term corrosion assay in artificial tear fluid and tribology assay in corroboration with atomic force microscopy, scanning and transmission electron microscopies. Biocompatibility was assessed by human corneal stromal cell attachment, survival and proliferation, and DNA damages. Sintered composites were implanted into rabbit corneas to assess for in vivo stability and host tissue responses. We showed that reduced graphene/TiO2 hybrids were safe and biocompatible. In particular, the 1% reduced LCGO/TiO2 (1rLCGO/TiO2) composite was mechanically strong, chemically stable, and showed better wear and corrosion resistance than pure titania and other combinations of graphene-reinforced titania. Hence the novel 1rLCGO/ TiO2 bioceramics can be a potential skirt biomaterial for keratoprosthesis to treat end-stage corneal blindness.

To compare the long-term graft survival outcomes and complications of patients who underwent Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK), and penetrating keratoplasty (PK) for Fuchs endothelial corneal dystrophy (FECD) and bullous keratopathy (BK).Retrospective comparative cohort study.Patients with FECD and BK who underwent DMEK (121 eyes), DSAEK (423 eyes), or PK (405 eyes) from the prospective cohort from the Singapore Corneal Transplant Registry were included. A Kaplan-Meier survival analysis was conducted to compare the survival probabilities of the 3 groups. The main outcome measure was graft survival.The DMEK group had the best overall cumulative graft survival of 97.4%, compared to DSAEK (78.4%) and PK (54.6%) (P.001). In eyes with FECD, the DMEK group had the best graft survival of 98.7% compared to DSAEK (96.2%) and PK (73.5%) (P = .009). The graft survival in eyes with BK was poorer overall; however, the DMEK group still had the best graft survival of 94.7%, compared to DSAEK (65.1%) and PK (47.0%, P = .001). Eyes that underwent DMEK had the lowest rate of graft rejection (1.7% vs DSAEK 5.0% vs PK 14.1%, P.001) and postoperative elevation of intraocular pressure (11.6% vs DSAEK 23.6% vs PK 22.5%, P = .015).Patients who underwent DMEK for FECD and BK had better graft survival compared to DSAEK and PK. Eyes that underwent DMEK also had a significantly lower rate of graft rejection and elevated intraocular pressure compared to DSAEK and PK for the same indications.

The prevalence of myopia has markedly increased in East and Southeast Asia, and pathologic consequences of myopia, including myopic maculopathy and high myopia-associated optic neuropathy, are now some of the most common causes of irreversible blindness. Hence, strategies are warranted to reduce the prevalence of myopia and the progression to high myopia because this is the main modifiable risk factor for pathologic myopia. On the basis of published population-based and interventional studies, an important strategy to reduce the development of myopia is encouraging schoolchildren to spend more time outdoors. As compared with other measures, spending more time outdoors is the safest strategy and aligns with other existing health initiatives, such as obesity prevention, by promoting a healthier lifestyle for children and adolescents. Useful clinical measures to reduce or slow the progression of myopia include the daily application of low-dose atropine eye drops, in concentrations ranging between 0.01% and 0.05%, despite the side effects of a slightly reduced amplitude of accommodation, slight mydriasis, and risk of an allergic reaction; multifocal spectacle design; contact lenses that have power profiles that produce peripheral myopic defocus; and orthokeratology using corneal gas-permeable contact lenses that are designed to flatten the central cornea, leading to midperipheral steeping and peripheral myopic defocus, during overnight wear to eliminate daytime myopia. The risk-to-benefit ratio needs to be weighed up for the individual on the basis of their age, health, and lifestyle. The measures listed above are not mutually exclusive and are beginning to be examined in combination. peerReviewed

Purpose The purpose of this study was to evaluate the association of childhood progression of spherical equivalent (SE) with high myopia (HM) in teenagers in the Singapore Cohort of Risk factors for Myopia (SCORM). Methods We included 928 SCORM children followed over a mean follow-up of 6.9 ± 1.0 years from baseline (6–11 years old) until their teenage years (12–19 years old). Cycloplegic autorefraction and axial length (AL) measurements were performed yearly. The outcomes in teenagers were HM (SE ≤ −5 diopter [D)], AL ≥ 25 mm, SE and AL. Three-year SE and AL progression in childhood and baseline SE and AL with outcomes were evaluated using multivariable logistic or linear regression models, with predictive performance of risk factors assessed using the area under the curve (AUC). Results At the last visit, 9.8% of teenagers developed HM and 22.7% developed AL ≥ 25 mm. In multivariate regression analyses, every −0.3 D/year increase in 3-year SE progression and every 0.2 mm/year increase in 3-year AL progression were associated with a −1.14 D greater teenage SE and 0.52 mm greater teenage AL (P values < 0.001). The AUC (95% confidence interval [CI]) of a combination of 3-year SE progression and baseline SE for teenage HM was 0.97 (95% CI = 0.95 – 0.98). The AUC of 3-year AL progression and baseline AL for teenage AL ≥ 25 mm was 0.91 (95% CI = 0.89 – 0.94). Conclusions Three-year myopia progression in childhood combined with baseline SE or AL were good predictors of teenage HM. Clinicians may use this combination of factors to guide timing of interventions, potentially reducing the risk of HM later in life.

Purpose To investigate the association between 1-year myopia progression and subsequent 2-year myopia progression among myopic children in the Singapore Cohort Study of the Risk Factors for Myopia. Methods This retrospective analysis included 618 myopic children (329 male), 7 to 9 years of age (mean age, 8.0 ± 0.8) at baseline with at least two annual follow-up visits. Cycloplegic autorefraction was performed at every visit. Receiver operating characteristic (ROC) curves from multiple logistic regressions were derived for future fast 2-year myopia progression. Results Children with slow progression during the first year (slower than –0.50 diopter [D]/y) had the slowest mean subsequent 2-year myopia progression (–0.41 ± 0.33 D/y), whereas children with fast progression (faster than –1.25 D/y) in year 1 had the fastest mean subsequent 2-year myopia progression (–0.82 ± 0.30 D/y) (P for trend < 0.001). Year 1 myopia progression had the highest area under the curve (AUC) for predicting fast subsequent 2-year myopia progression (AUC = 0.77; 95% confidence interval [CI], 0.73–0.80) compared to baseline spherical equivalent (AUC = 0.70; 95% CI, 0.66–0.74) or age of myopia onset (AUC = 0.66; 95% CI, 0.61–0.70) after adjusting for confounders. Age at baseline alone had an AUC of 0.65 (95% CI, 0.61–0.69). Conclusions One-year myopia progression and age at baseline were associated with subsequent 2-year myopia progression in children 7 to 9 years of age. Translational Relevance Myopia progression and age at baseline may be considered by eye care practitioners as two of several factors that may be associated with future myopia progression in children.

Purpose To evaluate a novel technique of Descemet membrane endothelial keratoplasty (DMEK) donor insertion using the EndoGlide pull-through device. Design Prospective, interventional cases series. Methods We performed DMEK using the EndoGlide technique with a protoype donor carrier device (Descemet Mat, or D-Mat) in 30 patients by a single surgeon (including learning curve). Clinical data and donor and recipient characteristics were tracked from our prospective Singapore Corneal Transplant Registry. Main outcome measures were intraoperative complications and the incidence of postoperative graft detachment and primary graft failures within 3 months from surgery. Results In our preliminary study of 30 eyes in 30 patients (73% female, mean age 64.5 ± 8.3 years), we observed 3 cases (10%) of partial donor detachment requiring rebubbling and 1 (3%) primary donor failure. Twenty of 30 eyes (66.7%) achieved ≥20/25 3-month best spectacle-corrected visual acuity. Six-month endothelial cell loss reduced from 65% ± 13% to 48% ± 11% ( P = .02) comparing the first and last 15 cases. With the exception of 1 case with excessive fibrin formation, we did not experience any further intraoperative complications related to donor tissue insertion, incomplete tissue unfolding, donor tissue malposition, or incorrect orientation. Conclusion Our study suggests that the described technique allows for donor control and insertion in the correct orientation with the endothelium facing down. Further studies are required to confirm if this DMEK donor insertion technique can lead to reduced endothelial cell loss and better graft survival.

Purpose To report the incidence and risk factors of elevated IOP following deep anterior lamellar keratoplasty (DALK). Design A retrospective case series. Methods A retrospective study investigating the 5-year incidence of raised IOP following DALK cases performed from 2004 to 2008 in a tertiary center. Patients with less than 6 months of follow-up were excluded. Elevated IOP was defined as IOP >21 mm Hg. Results An episode of elevated IOP occurred in 36.1% of cases (44/122 cases), 11.4% (n = 5) occurring within the first week. The average duration of raised IOP was 48.9 (SD: 65.5) days. Causes included pupil block from air, swollen grafts, and corticosteroid response. Surgical intervention to lower IOP was required in 3 cases (6.8%). In multivariate analyses, the use of Olopatadine 0.1% or cyclosporine eye drops before DALK (OR = 14.51, 95% CI = 1.43–147.23) and use of topical prednisolone acetate 1% compared with dexamethasone 0.1% post DALK (OR = 4.79, 95% CI = 0.73–31.52) were associated with higher rates of elevated IOP post DALK. At 5 years post DALK, 3 of 71 cases (4.48%) developed de novo glaucomatous field defects, and 1 case with pre-existing glaucoma had progression of glaucomatous field defect. Conclusions DALK was associated with a significant incidence of transiently elevated IOP postoperatively, but had a low incidence of de novo glaucoma at 5 years in our study. Risk factors for raised IOP post DALK included the use of topical prednisolone acetate 1% compared with dexamethasone 0.1%, and the use of Olopatadine 0.1% or any concentration of cyclosporine eye drops prior to DALK.

To compare 5-year graft survival after Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) in Asian eyes.Prospective, nested, cohort study.Consecutive patients who underwent DSAEK (423 eyes) or PK (405 eyes) for Fuchs' endothelial dystrophy (FED) or bullous keratopathy (BK).Clinical data and donor and recipient characteristics were recorded from our prospective cohort from the Singapore Corneal Transplant Registry. All surgeries were performed by the corneal surgeons at our center, which included cases performed or partially performed by corneal fellows in training under direct supervision.Five-year cumulative graft survival.Overall mean age was 67.8±9.8 years, and 50.1% of patients were men. There were no significant differences in age (P = 0.261) or gender (P = 0.78) between PK and DSAEK groups in our predominantly Chinese (76.6%) Asian cohort, with more BK compared with FED (68.1% vs. 31.9%; P 0.001). Overall 5-year graft survival was superior for DSAEK compared with PK (79.4% vs. 66.5%; P0.001, log-rank test). Median 5-year percent endothelial cell density loss was significantly greater in PK compared with DSAEK (60.9% vs. 48.7%; P = 0.007). Cox regression analysis revealed that BK was a significant factor associated with graft failure (hazard ratio [HR], 3.30; 95% confidence interval [CI], 2.05-5.33; P0.001), and PK was more likely to fail compared with endothelial keratoplasty (HR, 1.61; 95% CI, 1.08-2.41; P = 0.02) adjusting for confounders such as recipient age, gender, and donor factors. Five-year cumulative incidence of complications such as graft rejection (P 0.001), epitheliopathy (P0.001), suture-related corneal infections (P0.001), and wound dehiscence (P = 0.002) were greater in the PK group compared with the DSAEK group.In Asian eyes from the same study cohort with standardized surgical and postoperative regimes, 5-year graft survival was superior for DSAEK compared with PK in eyes with FED and BK.

Purpose To investigate the effect of age of myopia onset on the severity of myopia later in life among myopic children. Methods In this prospective study, school children aged 7–9 years from the Singapore Cohort Of the Risk factors for Myopia (SCORM) were followed up till 11 years (n = 928). Age of myopia onset was defined either through questionnaire at baseline (age 7–9 years) or subsequent annual follow-up visits. Age of onset of myopia was a surrogate indicator of duration of myopia progression till age 11 years. Cycloplegic refraction and axial length were measured at every annual eye examination. High myopia was defined as spherical equivalent of ≤−5.0 D. A questionnaire determined the other risk factors. Results In multivariable regression models, younger age of myopia onset (per year decrease) or longer duration of myopia progression was associated with high myopia (odds ratio (OR) = 2.86; 95% CI: 2.39 to 3.43), more myopic spherical equivalent (regression coefficient (β) = −0.86 D; 95% CI: −0.93 to −0.80) and longer axial length (β = 0.28 mm; 95% CI: 0.24 to 0.32) at aged 11 years, after adjusting for gender, race, school, books per week and parental myopia. In Receiver Operating Curve (ROC) analyses, age of myopia onset alone predicted high myopia by 85% (area under the curve = 0.85), while the addition of other factors including gender, race, school, books per week and parental myopia only marginally improved this prediction (area under the curve = 0.87). Conclusions Age of myopia onset or duration of myopia progression was the most important predictor of high myopia in later childhood in myopic children. Future trials to retard the progression of myopia to high myopia could focus on children with younger age of myopia onset or with longer duration of myopia progression.

Our purpose is to comprehensively review the state of the art with regard to Stevens- Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to improving the management of associated ocular surface complications. SJS and TEN are two ends of a spectrum of immune-mediated disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. Part I of this review focused on the systemic aspects of SJS/TEN and was published in the January 2016 issue of this journal. The purpose of Part II is to summarize the ocular manifestations and their management through all phases of SJS/TEN, from acute to chronic. We hope this effort will assist ophthalmologists in their management of SJS/TEN, so that patients with this complex and debilitating disease receive the best possible care and experience the most optimal outcomes in their vision and quality of life.

Purpose: To compare the safety and efficacy of different concentrations of atropine eyedrops in controlling myopia progression over 5 years. Design: Randomized, double-masked clinical trial. Participants: A total of 400 children originally randomized to receive atropine 0.5%, 0.1%, or 0.01% once daily in both eyes in a 2:2:1 ratio. Methods: Children received atropine for 24 months (phase 1), after which medication was stopped for 12 months (phase 2). Children who had myopia progression (≥−0.50 diopters [D] in at least 1 eye) during phase 2 were restarted on atropine 0.01% for a further 24 months (phase 3). Main Outcome Measures: Change in spherical equivalent and axial length over 5 years. Results: There was a dose-related response in phase 1 with a greater effect in higher doses, but an inverse dose-related increase in myopia during phase 2 (washout), resulting in atropine 0.01% being most effective in reducing myopia progression at 3 years. Some 24%, 59%, and 68% of children originally in the atropine 0.01%, 0.1%, and 0.5% groups, respectively, who progressed in phase 2 were restarted on atropine 0.01%. Younger children and those with greater myopic progression in year 1 were more likely to require re-treatment. The lower myopia progression in the 0.01% group persisted during phase 3, with overall myopia progression and change in axial elongation at the end of 5 years being lowest in this group (−1.38±0.98 D; 0.75±0.48 mm) compared with the 0.1% (−1.83±1.16 D, P = 0.003; 0.85±0.53 mm, P = 0.144) and 0.5% (−1.98±1.10 D, P < 0.001; 0.87±0.49 mm, P = 0.075) groups. Atropine 0.01% also caused minimal pupil dilation (0.8 mm), minimal loss of accommodation (2–3 D), and no near visual loss compared with higher doses. Conclusions: Over 5 years, atropine 0.01% eyedrops were more effective in slowing myopia progression with less visual side effects compared with higher doses of atropine. NMRC (Natl Medical Research Council, S’pore)

Efforts to reduce myopia progression in childhood are driven by the increasing incidence of high myopia and its attendant health risks. Interventional approaches to reduce myopia progression in childhood have included the use of spectacles, contact lens, and pharmacological methods, of which the latter appear to be most promising. We review the use of topical atropine eye drops in the retardation of myopia progression in children and discuss the efficacy and safety profiles when used at different concentrations (1.0%, 0.5%, 0.1%, and 0.01%). Topical atropine reduces myopia progression and axial elongation in children in a dose-related manner, but a rebound phenomenon occurs with higher doses. Its use has been shown to be safe, but higher doses cause pupil dilation, loss of accommodation and near vision. Atropine 0.01% has the best therapeutic index, with clinically insignificant amounts of pupil dilation, near vision, and accommodation loss but remains as effective as higher doses.

We recently reported the bioinspired synthesis of a highly potent nonpeptidic xanthone, 2c (AM-0016), with potent antibacterial activity against MRSA. Herein, we report a thorough structure-activity relationship (SAR) analysis of a series of nonpeptidic amphiphilic xanthone derivatives in an attempt to identify more potent compounds with lower hemolytic activity and greater membrane selectivity. Forty-six amphiphilic xanthone derivatives were analyzed in this study and structurally classified into four groups based on spacer length, cationic moieties, lipophilic chains, and triarm functionalization. We evaluated and explored the effects of the structures on their membrane-targeting properties. The SAR analysis successfully identified 3a with potent MICs (1.56-3.125 μ/mL) and lower hemolytic activity (80.2 μg/mL for 3a versus 19.7 μg/mL for 2c). Compound 3a displayed a membrane selectivity of 25.7-50.4. Thus, 3a with improved HC50 value and promising selectivity could be used as a lead compound for further structural optimization for the treatment of MRSA infection.

To investigate independent risk factors for contact lens-related microbial keratitis in Singapore and estimate their impact on disease load. Cases were contact lens wearers presenting to Singapore National Eye Centre with microbial keratitis between 2008 and 2010. Community contact lens wearers were recruited as controls. All wearers completed a previously validated questionnaire describing contact lens wear history, hygiene and compliance habits, and demographics. Risk factors significant in univariate analysis (P

Purpose To report the incidence and outcomes of intraoperative Descemet membrane (DM) perforations during deep anterior lamellar keratoplasty (DALK). Design Retrospective, consecutive, interventional case series. Methods A retrospective audit of all DALK cases performed from 2004 to 2015 in a tertiary center, with and without intraoperative DM perforations. We excluded cases with preexisting corneal perforations before surgery. Results There were a total of 540 eyes, of which 101 (18.7%) had intraoperative DM perforations. These included 79 eyes (78.2%) with microperforations and 15 eyes (14.9%) with macroperforation. The most common steps at which DM perforation occurred intraoperatively were during deep lamellar dissection (32 cases; 31.7%), air injection (27 cases; 26.7%), and suturing (21 cases; 20.8%). Management of the DM perforations included a combination of intracameral air tamponade (49 cases; 48.5%), stromal patching (10 cases; 9.9%), fibrin glue (8 cases; 7.9%), and suturing of the defect (1 case; 1.1%). There were 2 eyes (2/540; 0.37%) that were converted to penetrating keratoplasty (PK). There were no significant differences in the postoperative unaided or best-corrected visual acuity, or in the numbers of patients with postoperative graft failure, graft rejection, or subsequent surgery at postoperative years 1 and 3. Conclusions DALK cases with DM perforations intraoperatively are often able to be managed without conversion to PK. Cases with DM perforations intraoperatively have equivalent visual acuity outcomes compared to those without DM perforations, and did not have any increased risk of graft failure, rejection, or subsequent surgery at postoperative years 1 and 3.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size = −0.045 mm, P = 8.17×10−9). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06–1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45×10−9; 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions., Author Summary The anterior chamber is the space within the eye which is bound by the cornea, and the anterior surfaces of the iris and lens. Anterior chamber depth (ACD) is the distance measured along the eye's optical axis, from the cornea to the lens surface. ACD is an important risk factor for primary angle closure glaucoma (PACG), a major cause of irreversible blindness worldwide, and in particular, individuals of Asian ethnicity. In order to identify the genes that underlie PACG susceptibility, we conducted a two-staged study. We first conducted a large scale genetic study on a total of 5,308 population-based individuals of Asian descent to identify the genetic variants that influence ACD. This was followed by testing for associations between the identified genetic variant and PACG in another independent collection of 4,276 PACG cases and 18,801 controls. We found that a genetic variant within ABCC5 was associated with an increased risk of having PACG. Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants that influence the anterior chamber dimensions of the eye.

Aims: To describe the long-term outcomes of deep anterior lamellar keratoplasty (DALK) performed after Descemet stripping automated endothelial keratoplasty (DSAEK) in cases of infection and residual stromal opacity. Methods: Ten eyes of nine consecutive patients undergoing DALK after DSAEK at a single tertiary referral center (SNEC) from 2011 to 2016 were analyzed for best spectacle-corrected visual acuity (BSCVA), refraction, spherical equivalent (SE) and cylinder, as well as graft diameters, survival, and complications. Results: The mean pre-DSAEK BSCVA was 1.73 ± 0.76 LogMAR. At a mean follow-up of 9.8 ± 7.1 months, visual acuity had improved significantly (p = 0.028) to 1.09 ± 0.55 LogMAR after DSAEK. DALK was performed at 10.3 ± 7.2 months after DSAEK because of residual stromal scarring in nine and a corneal infection in one case. At the last follow-up visit (19.4 ± 13.9 months) after DALK, BSCVA had improved to 0.38 ± 0.6 LogMAR, significantly better than after DSAEK alone (p = 0.015) and before DSAEK (p = 0.018). Spherical equivalent (− 4.8 ± 3.5 D) and cylinder (− 2.5 ± 2.0 D) did not show significant changes compared to after DSAEK (SE p = 0.17; cylinder p = 0.19) or 3 months after DALK (SE p = 0.17; cylinder p = 0.46). One endothelial graft failed 3 months after DALK. Kaplan-Meier estimated average survival for all cases was 45.3 (95% CI 36.6–54.0) months. The cumulative survival probability for the entire cohort was 90% at 1, 2, and 4 years of follow-up. Conclusions: DALK surgery after DSAEK can improve vision in cases of residual host scarring and treat host corneal infection, while avoiding open-sky surgery and sparing a healthy endothelial graft.

Purpose To compare vision-related quality of life (VRQoL) scores and clinical outcomes between small-incision lenticule extraction and laser in situ keratomileusis (LASIK). Setting Singapore National Eye Centre, Singapore. Design Prospective study. Methods Patients had small-incision lenticule extraction using the Visumax 500 kHz femtosecond laser; or LASIK excimer ablation with the Wavelight Allegretto 400 Hz laser. Primary outcomes were 3-month predictability, efficacy, and safety. Secondary outcomes were intraoperative experience, visual symptoms, and VRQoL (validated Quality of Life Impact of Refractive Correction [QIRC] questionnaire) in 25 a subgroup of patients in each group. Following Rasch analysis, "Functional" and "Emotional," QIRC dimensions were analysed separately. Results At 3 months, predictability (82.5% versus 85.3%, ±0.5 diopters attempted correction, P =.453), safety index (1.13 ± 0.19 [SD] versus 1.07 ± 0.16, P = .158), and efficacy index (0.91 ± 0.21 versus 0.97 ± 0.19; P = .002) were found when comparing small-incision lenticule extraction (172 eyes) and LASIK (matched 688 eyes). Intraoperative experience between groups was not statistically different; visual fluctuations ( P = .020) and episodes of visual blurring ( P = .008) were greater after small-incision lenticule extraction than after LASIK at 1 month but not at 3 months. There was no difference in "functional" (66.7 ± 15.7 versus 55.3 ± 22.2, P = .064) and "emotional" (42.7 ± 23.2 versus 37.9 ± 23.8, P = .394) QIRC dimensions between the 2 groups (25 patients in each group) at 3 months. Conclusion The study, 3-month predictability, safety, and VRQL scores were not statistically different between small-incision lenticule extraction and LASIK. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.

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 nonhemolytic 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.

Purpose To describe improvements in visual acuity and contrast sensitivity following Descemet stripping automated endothelial keratoplasty (DSAEK). Methods 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. Results 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 Conclusions 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.

Purpose To investigate variables associated with myopic progression despite treatment in the Atropine in the Treatment of Myopia Study. Design Retrospective cohort study. Methods Two hundred of 400 children were randomized to receive atropine 1% in 1 eye only in this institutional study. Children were followed up with cycloplegic autorefraction every 4 months over 2 years. Children whose myopia progressed by more than 0.5 diopter (D) in the atropine-treated eye at 1 year were classified as being progressors. Results Among the 182 children still in the study at 1 year, 22 (12.1%) were classified as progressors. Univariate analysis suggested these children tended to be younger (8.5 ± 1.4 years vs 9.3 ± 1.5 years; P = .023), to have higher myopic spherical equivalent (SE) at baseline (−3.6 ± 1.3 D vs −2.8 ± 1.4 D; P = .015), and to have 2 myopic parents (77.3% vs 48.1%; P = .012). In nonprogressors, the myopia progression at 1 year was less in the atropine-treated eyes compared with the untreated fellow eye (+0.16 ± 0.37 D vs −0.73 ± 0.48 D; P P = .363). Regression analysis showed that the risk of being a progressor was 40% lower with each year of increased age, 43% lower for every 1.0 D less in myopia at baseline, and 59% lower for every 1.0 D less in myopic change in the untreated eyes over the first year. Conclusions Doctors and parents need to be aware that there is a small group of children (younger, with higher myopia, and greater tendency of myopic progression) who may still progress while receiving atropine treatment.

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.

Corneal transplantation is the only treatment available to restore vision for individuals with blindness due to corneal endothelial dysfunction. However, severe shortage of available donor corneas remains a global challenge. Functional regulatory compliant tissue-engineered corneal endothelial graft substitute can alleviate this reliance on cadaveric corneal graft material. Here, isolated primary human corneal endothelial cells (CEnCs) propagated using a dual media approach refined towards regulatory compliance showed expression of markers indicative of the human corneal endothelium, and can be tissue-engineered onto thin corneal stromal carriers. Both cellular function and clinical adaptability was demonstrated in a pre-clinical rabbit model of bullous keratopathy using a tissue-engineered endothelial keratoplasty (TE-EK) approach, adapted from routine endothelial keratoplasty procedure for corneal transplantation in human patients. Cornea thickness of rabbits receiving TE-EK graft gradually reduced over the first two weeks, and completely recovered to a thickness of approximately 400 µm by the third week of transplantation, whereas corneas of control rabbits remained significantly thicker over 1,000 µm (p

Objective: The aim was to compare the visual, refractive, topographic and biomechanical outcomes in patients with progressive keratoconus treated with either conventional or accelerated crosslinking at one year follow up. Methods: It is a prospective, non-randomised interventional study of 76 patients who underwent conventional (CXL; 3mW/cm2 for 30 minutes) or accelerated cross linking (KXL; 30mW/cm2 for 4 minutes) for progressive keratoconus. Baseline and postoperative visual acuity, manifest refraction, corneal topography, pachymetry, endothelial cell density and biomechanical parameters of corneal hysteresis and corneal resistance factor were evaluated and compared. Results: The 2 groups were comparable in terms of uncorrected and best corrected visual acuity and spherical equivalent. Both groups showed no significant increase in K1, K2 and Kmean from baseline at 12 months. There was also no difference between the CXL and KXL group for postoperative corneal topography as well as central and minimal pachymetry up to 12 months. There was a significant increase in both corneal hysteresis (0.62mm Hg, P=0.04) and corneal resistance factor (0.91mm Hg, P=0.003) in the KXL group at 12 months but not in the CXL group. There was no significant endothelial cell loss throughout follow up in both the groups. Conclusion: We have established comparability of the 2 protocols in stabilizing the progression of keratoconus. Our findings also suggested an added biomechanical advantage of accelerated crosslinking at 1 year follow up.

To compare 5-year visual acuity and refraction outcome in Descemet stripping automated endothelial keratoplasty (DSAEK) and penetrating keratoplasty (PK) for Fuchs endothelial dystrophy (FED) or bullous keratopathy (BK) in Asian eyes.Prospective interventional case series.We analyzed 828 consecutive cases of DSAEK (423) or PK (405) for FED and BK from the Singapore Cornea Transplant Registry performed from 1991 to 2011. Our main outcome measures were best spectacle-corrected visual acuity (BSCVA) with astigmatism (cylinder) and spherical equivalent (SE) over 5 years of follow-up.Mean age was 67.5 ± 11.5 years (50.1% male, 49.9% female) and majority was Chinese (76.6%, n = 634) in our multiracial Asian population. DSAEK eyes had significantly better BSCVA (P.001-.037) with lower SE (P.001-.017) and cylinder (P.001), independent of surgical indication, compared to PK over 5 years. DSAEK was superior to PK over 5 years (P.001-.026) in FED, but only over 3 years in BK (P.001-.031). DSAEK in FED eyes had significantly better BSCVA compared to BK eyes (P = .006 at 4-year follow-up). DSAEKs with preoperative BSCVA1.3 logMAR had significantly better visual outcomes than cases with ≥ 1.3 logMAR (P.001-.042). PKs had significantly higher postoperative refractive correction than DSAEKs, with no significant influence of the surgery indication.In our study cohort, DSAEK provided significantly better long-term BSCVA and lower astigmatism than PK over 5 years of follow-up. Visual outcomes of DSAEK for FED were better than BK. In some analyses for years 1-3, analysis of covariance adjustment indicated that this DSAEK-associated better long-term BSCVA was independent of better preoperative vision in DSAEK eyes.

Efforts to reduce the progression of myopia in childhood are on the rise, due to an increasing incidence of myopia worldwide and its associated sight-threatening complications. Interventions are aimed at reducing myopia in childhood and include environmental considerations, spectacles, contact lenses, and pharmacological agents. We reviewed recent literature with interventions aimed at reducing myopia progression in children and found that a number of interventions were significant in reducing the progression of myopia. Of these interventions, atropine showed the largest dose-related effect on myopia progression control. Although higher doses are associated with side effects of pupil dilatation, loss of accommodation, near vision blur, and rebound phenomenon, low-dose atropine has also been shown to provide effective myopia control with minimal side effects and rebound. To a lesser degree, bifocal soft contact lenses have also been shown to be effective in reducing the progression of myopia, though compliance is an issue. Similarly, orthokeratology lenses have also been shown to be effective in reducing axial length elongation and myopia progression, though long-term data on its rebound effects are unavailable.

Peripheral melting disorders require surgical intervention when medical treatment is insufficient and there is continual tissue destruction and the impending risk of perforation. The previous chapter (Chap. 6) discussed the indications and timing of surgical intervention in active peripheral ulcerative keratitis, as well as the principles and concepts of surgery, which is both tectonic and therapeutic. The chapter also dealt with the optically acceptable end-result and also addressed the reduction of ectasia and irregular astigmatism associated with the primary melting condition. Our surgical procedure of choice, which is also aimed at limiting surgery to diseased areas and avoiding unnecessary replacement of healthy adjacent corneal tissue, and endothelial replacement, takes the form of peripheral, lamellar “C”-shaped patch grafts. Peripheral lamellar “C”-shaped grafts can effectively restore tectonic integrity, while maintaining a reasonable corneal contour to enhance visual acuity. This chapter details the exacting and detailed surgical techniques to perform lamellar “C”-shaped patch grafts in peripheral ulcerative keratitis which has failed to respond to conventional medical and adjunctive therapies.

Peripheral Ulcerative Keratitis (PUK) resulting from a myriad of conditions is extremely challenging to manage. Patients have to be co-managed with internal physicians and care has to be individualized. Management aims to firstly establish the diagnosis and underlying cause of the PUK, and to commence both local and systemic therapies when appropriate. The role of the Ophthalmologist is to manage the primary disease, monitor for complications and intervene surgically if necessary. With advancements in surgical techniques and better knowledge of the disease, earlier interventions have a role in curbing the disease process and reducing morbidity. Surgical interventions are not only useful in the active, progressive phase of the disease when conservative measures fail, but also play an important role in visual rehabilitation of the patient. This chapter aims to explore the various available surgical approaches to management of PUK, principles of surgical management and our technique of choice in management of these complex cases. We will illustrate with two case examples, the use of tectonic, C-shaped lamellar corneal grafts, and the appropriate postoperative management of the patient.

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. Financial Disclosure No author has a financial or proprietary interest in any material or method mentioned.