Donald T H Tan

Duke-NUS Graduate Medical School Singapore, Tumasik, Singapore

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Publications (228)808.27 Total impact

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    ABSTRACT: The intent of this review is to comprehensively appraise the state of the art with regard to Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), with particular attention to the ocular surface complications and their management. SJS and TEN represent two ends of a spectrum of immune-mediated, dermatobullous disease, characterized in the acute phase by a febrile illness followed by skin and mucous membrane necrosis and detachment. The widespread keratinocyte death seen in SJS/TEN is rapid and irreversible, and even with early and aggressive intervention, morbidity is severe and mortality not uncommon. We have divided this review into two parts. The purpose of Part I is to summarize the epidemiology and immunopathogenesis of SJS/TEN and discuss systemic therapy and its possible benefits. We hope this review will help the ophthalmologist better understand the mechanisms of disease in SJS/TEN, and by extension, better care for patients with this complex and often debilitating disease.
    11/2015; DOI:10.1016/j.jtos.2015.10.002
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    ABSTRACT: Cataract surgery is the most common surgical procedure and femtosecond laser assisted cataract surgery (FLACS) has gained increased popularity. FLACS requires the application of a suction device to stabilize the laser head and focus the laser beam accurately. This may cause a significant escalation in intra-ocular pressure (IOP), which poses potential risks for patients undergoing cataract surgery. In this study we aimed to assess the effect of the Ziemer LDV Z8 femtosecond cataract machine on IOP. We demonstrated through a porcine model that IOP was significantly higher with a flat interface but could be abrogated by reducing surgical compression and vacuum. Pressure was lower with a liquid interface, and further altering angulation of the laser arm could reduce the IOP to 36 mmHg. A pilot series in patients showed comparable pressure rises with the porcine model (30 mmHg). These strategies may improve the safety profile in patients vulnerable to high pressure when employing FLACS with the Ziemer LDV Z8.
    Scientific Reports 10/2015; 5:14742. DOI:10.1038/srep14742 · 5.58 Impact Factor
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    ABSTRACT: PURPOSE. Synthetic keratoprostheses are required for visual rehabilitation in patients with endstage corneal blindness. This study aimed to assess the biocompatibility of graphene material and its potential as a novel synthetic keratoprosthesis skirt material for corneal tissue engineering. METHODS. Human corneal stromal fibroblasts were cultured on material surfaces including pristine graphene film, graphene foam, pristine titanium (Ti) discs, and tissue culture plastic surface (TCPS). Cell attachment was assayed by immunostaining of paxillin and vinculin. Cell viability and proliferation were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and Click iT 5-ethynyl-2′-deoxyuridine (EdU) assays. The growth of fibroblasts on three-dimensional graphene foam was examined by scanning electron microscopy, and cytokine release was analyzed by enzyme-linked immunosorbent assay. Graphene films were implanted into rabbit corneal stromal pockets and examined by slit-lamp biomicroscopy, anterior segment optical coherence tomography, in vivo confocal microscopy, and histology. RESULTS. Pristine graphene demonstrated good biocompatibility with human stromal fibroblasts in terms of cell adhesion, viability, and proliferation. Cells on graphene films showed higher number than on TCPS control. Cells grown on graphene had 10% more proliferation than on Ti. The expression levels of IL-6 and IL-8 were reduced when cells were seeded on graphene foam as compared to Ti and graphene film. Implantation of graphene film into rabbit stroma (n = 6) did not show any signs of infection, neovascularization, or inflammation. CONCLUSIONS. Graphene displayed excellent short-term biocompatibility with corneal cells and tissue. This demonstrates that graphene can be developed as a tissue engineering material for use in cornea. © 2015 The Association for Research in Vision and Ophthalmology, Inc.
    Investigative ophthalmology & visual science 10/2015; 56(11):6605-6611. DOI:10.1167/iovs.15-17306 · 3.40 Impact Factor
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    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.
    Journal of Medicinal Chemistry 07/2015; 58(16). DOI:10.1021/acs.jmedchem.5b00628 · 5.45 Impact Factor
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    ABSTRACT: To evaluate and compare changes in contrast sensitivity and ocular higher-order aberrations (HOAs) after femtosecond lenticule extraction (FLEx) and pseudo small-incision lenticule extraction (SMILE). Singapore National Eye Centre, Singapore. Retrospective case series. Patients had femtosecond lenticule extraction (Group 1) or pseudo small-incision lenticule extraction (Group 2) between March 2010 and December 2011. The main outcome measures were manifest refraction, HOAs, and contrast sensitivity 1, 3, 6, and 12 months postoperatively. Fifty-two consecutive patients (102 eyes) were recruited, 21 patients (42 eyes) in Group 1 and the 31 patients (60 eyes) in Group 2. The uncorrected and corrected distance visual acuities were significantly better in Group 2 than in Group 1 at 12 months (P = .032). There was no significant increase in 3rd- or 4th-order aberrations at 1 year and no significant difference between the 2 groups preoperatively or postoperatively. At 1 year, there was a significant increase in mesopic contrast sensitivity in Group 2 at 1.5 cycles per degree (cpd) (P = .008) that was not found in Group 1, and photopic contrast sensitivity at 6.0 cpd was higher in Group 2 (P = .027). These results indicate that refractive lenticule extraction is safe and effective with no significant induction of HOAs or deterioration in contrast sensitivity at 1 year. Induction of HOAs was not significantly different between both variants of refractive lenticule extraction. However, there was significant improvement in photopic contrast sensitivity after pseudo small-incision lenticule extraction, which persisted through 1 year. No author has a financial or proprietary interest in any material or method mentioned. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.
    Journal of Cataract and Refractive Surgery 03/2015; 41(3):623-34. DOI:10.1016/j.jcrs.2014.07.032 · 2.72 Impact Factor
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    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.
    Journal of Medicinal Chemistry 12/2014; 58(2). DOI:10.1021/jm501285x · 5.45 Impact Factor
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    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. Methods: 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. Results: 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. Conclusions: 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.
    Investigative Ophthalmology &amp Visual Science 10/2014; 55(11). DOI:10.1167/iovs.14-15390 · 3.40 Impact Factor
  • D.T. Tan · D. Koh · S. Oo · X. Zhang · E. Thia · G. Yeo ·

    Ultrasound in Obstetrics and Gynecology 09/2014; 44(S1):185-185. DOI:10.1002/uog.14000 · 3.85 Impact Factor
  • Jin Rong Low · Arundhati Anshu · Anna Cheng Sim Tan · Hla Myint Htoon · Donald Tiang Hwee Tan ·
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    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
  • Luxia Chen · Rui Hua Wei · Donald T H Tan · Roger W Beuerman · Wenbo Li · Shaozhen Zhao ·
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    ABSTRACT: To determine whether changes in cornea nerve growth factor (NGF) protein and gene expression correlate with corneal nerve regeneration after LASIK in rhesus monkeys. Ten rhesus monkeys underwent randomly assigned LASIK procedures to correct -8.0 diopters of myopia in both eyes and two additional monkeys (with no surgery) served as controls. The central corneas of the experimental animals were excised 3 and 7 days and 1, 3, and 6 months after the surgery. Nerve regeneration, NGF mRNA, and protein expression were analyzed by gold chloride staining, real-time polymerase chain reaction, and enzyme-linked immune sorbent assay analysis, respectively. Compared to controls, the LASIK-treated animals had a significantly diminished nerve plexus in the sub-basal region of the cornea at all times after the surgery (P < .001). NGF protein levels decreased significantly on days 3 and 7 after LASIK (P < .001), but returned to control levels 1 month later. NGF mRNA levels increased 5.4-fold on day 3 after the surgery (P < .001), then reduced to two-fold (P < .05) above control levels on day 7 and were back to normal at 3 months and beyond. After LASIK, the changes of early NGF protein and NGF mRNA levels correlated with the density of the corneal nerve plexuses. The results showed that the LASIK procedure in non-human primates was associated with changes in NGF protein and mRNA levels in the cornea. Such changes may be related to the initiation of nerve regeneration and the final recovery of nerve plexuses in the cornea. [J Refract Surg. 2014;30(2):134-139.].
    Journal of refractive surgery (Thorofare, N.J.: 1995) 02/2014; 30(2):134-9. DOI:10.3928/1081597X-20140120-10 · 3.47 Impact Factor
  • Reece C Hall · Mohamad Rosman · Cordelia Chan · Donald T.H. Tan · Jodhbir S Mehta ·
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    ABSTRACT: To describe the subjective experience of patients and surgeons during laser in situ keratomileusis (LASIK) using the Intralase 60 kHz or the Visumax 500 kHz femtosecond laser. Singapore National Eye Centre, Singapore. Prospective randomized clinical study. In myopic patients, LASIK was performed with the corneal flap created using the 60 kHz laser in 1 eye and the 500 kHz laser in the contralateral eye. Postoperatively, patients completed a standardized validated questionnaire about their subjective intraoperative experiences (eg, light perception, pain, fear). Surgeons reported their intraoperative experiences and preferences. Loss of light perception occurred in 50.0% of 60 kHz laser cases and 0% of 500 kHz laser cases during docking and in 63.0% and 0% of cases, respectively, during laser flap creation (P < .0001). The mean pain score with the 60 kHz laser was significantly higher during docking (P < .0001) but not during laser flap cutting (P = .006). Subconjunctival hemorrhage occurred in 67.4% of eyes with the 60 kHz laser and in 2.2% of eyes with the 500 kHz laser (P < .0001). The 500 kHz laser was preferred by 78.3% of patients, while 21.7% preferred the 60 kHz laser (P < .0001). The surgeons preferred the 60 kHz laser in 50.0% of cases and the 500 kHz laser in 8.7% (P < .0001); 41.3% had no preference. Patients preferred surgery with the 500 kHz laser with no loss of light perception, less pain, less fear, and less subconjunctival hemorrhage. Surgeons preferred the 60 kHz laser. No author has a financial or proprietary interest in any material or method mentioned.
    Journal of Cataract and Refractive Surgery 01/2014; 40(3). DOI:10.1016/j.jcrs.2013.08.056 · 2.72 Impact Factor
  • Annabel C.Y. Chew · Jodhbir S. Mehta · Donald T H Tan ·
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    ABSTRACT: The purpose of this study was to provide an update of significant cornea literature published in the past 1 year. This was a literature review. The authors conducted a 1-year English-language literature search on PubMed, from January 1, 2012, to December 31, 2012, using the following terms: corneal transplantation, anterior lamellar keratoplasty, penetrating keratoplasty, endothelial keratoplasty, Descemet stripping automated endothelial keratoplasty, Descemet membrane endothelial keratoplasty, Descemet membrane endothelial transfer, ocular surface epithelial transplantation, limbal epithelial transplantation, cultivated oral mucosal epithelial transplantation, keratoprosthesis, infectious keratitis, cross-linking, keratoconus, corneal neovascularization, corneal imaging, optical coherence tomography, Pentacam Scheimpflug imaging, and in vivo confocal microscopy. This review includes original articles and review articles that contain significant updates and novel aspects in the field of cornea from the following journals: American Journal of Ophthalmology, British Journal of Ophthalmology, Ophthalmology, Investigative Ophthalmology and Visual Science, and Cornea. Letters to the editor, unpublished work, manuscripts not in English, and abstracts were not included. This review highlights significant literature that is applicable to the practicing ophthalmologist.
    11/2013; 2(6):401-413. DOI:10.1097/APO.0000000000000022
  • Laurence S Lim · Chong Lye Ang · Edmund Wong · Doric W.K. Wong · Donald T.H. Tan ·
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    ABSTRACT: To describe the indications for and approaches to vitreoretinal surgery in patients with osteo-odonto-keratoprosthesis (OOKP). Retrospective case series. This was a retrospective review of all patients who had undergone OOKP surgery between 2003 and 2012 at our center. OOKP procedures were performed for severe ocular surface disease according to the indications and techniques described in the patient demographics of the Rome-Vienna Protocol. Indications for retinal surgery, surgical outcomes, and intraoperative and postoperative complications were documented. Operative techniques were reviewed from the surgical records, and any subsequent surgeries were also recorded. Thirty-six patients underwent OOKP, and retinal surgery was indicated in 13 (36%). The indications for and approaches to surgery were retinal detachment repair using an Eckardt temporary keratoprosthesis; assessment of retina and optic nerve health prior to OOKP surgery, using either a temporary keratoprosthesis or an endoscope; endoscopic cyclophotocoagulation for intractable glaucoma; endoscopic trimming of a retroprosthetic membrane; or vitrectomy for endophthalmitis with visualization through the OOKP optic using the binocular indirect viewing system. In all cases, retinal surgical aims were achieved with a single procedure. Postoperative vitreous hemorrhage occurred in 16 patients (44%), but all resolved spontaneously. OOKPs represent the last hope for restoration of vision in severe ocular surface disease, and the retinal surgeon is frequently called upon in the assessment and management of these patients. Temporary keratoprostheses and endoscopic vitrectomies are valuable surgical tools in these challenging cases, improving functional outcomes without compromising OOKP success.
    American Journal of Ophthalmology 10/2013; 157(2). DOI:10.1016/j.ajo.2013.08.033 · 3.87 Impact Factor
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    ABSTRACT: To describe the use of high-resolution anterior segment optical coherence tomography (AS-OCT) during deep anterior lamellar keratoplasty (DALK). Prospective case series. At the Singapore National Eye Centre we performed sequential intraoperative AS-OCT scans using iVue 100-2 (Optovue, Fremont, CA, USA) during various DALK techniques. In case 1 (corneal scarring) the OCT images helped to guide manual dissection, showed the depth of the needle track before air injection, and identified the location of a small bubble when the big bubble failed. In cases 2 (macular dystrophy) and 3 (lattice), viscodissection was undertaken, but in case 2 the OCT showed the viscoelastic trapped intrastromally, compared to case 3, in which the viscobubble dissection was successful. In case 4 (irregular corneal thinning and scarring), AS-OCT enabled accurate decision on initial trephination and guided dissection. In case 5 (keratoconus), the OCT showed the achieved big-bubble and detached Descemet membrane. Case 6 was a repeat DALK; the OCT guided the manual dissection of the residual stroma underlying the failed graft. In case 7, the OCT showed an intrastromal retention of fluid that was not detectable by the operating microscope due to diffuse scarring following alkaline injury. The OCT helped to assess the location of the Descemet membrane and guided the manual dissection. Intraoperative high-definition AS-OCT obtained good-quality images of the cornea during DALK and proved useful in various cases of DALK to help the surgeon decide on a number of surgical steps.
    American Journal of Ophthalmology 10/2013; 157(2). DOI:10.1016/j.ajo.2013.10.001 · 3.87 Impact Factor
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    S. Oo · D. Tan · X. Zhang · V. Gurumurthy · P. Mahavadi · S. Yeo ·

    Ultrasound in Obstetrics and Gynecology 10/2013; 42(s1). DOI:10.1002/uog.12969 · 3.85 Impact Factor
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    D.T. Tan · X. Wei · X. Zhang · S. Oo · W. Fan · K. Tan · K. Kwek · S. Yeo ·

    Ultrasound in Obstetrics and Gynecology 10/2013; 42(s1). DOI:10.1002/uog.13090 · 3.85 Impact Factor
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    ABSTRACT: We investigated an outbreak of 47 probable and 6 confirmed cases of microsporidial keratoconjunctivitis involving participants of an international rugby tournament in Singapore in April 2012.The mode of transmission was eye contact with soil. Vittaforma corneae was identified in 4 of 6 corneal scrapings and in 1 of 12 soil water samples.
    Emerging Infectious Diseases 09/2013; 19(9):1484-6. DOI:10.3201/eid1909,121464 · 6.75 Impact Factor
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    ABSTRACT: Purpose: To establish an animal model of congenital hereditary endothelial dystrophy (CHED) using Slc4a11 knockout (KO) mice and evaluate the abnormalities in the cornea and kidney. Methods: The Slc4a11 KO mouse model was generated by gene deletion. Corneal abnormalities were evaluated using slit-lamp photography, anterior segment optical coherence tomography (AS-OCT), immunohistochemistry, RT-PCR, corneal endothelial cell staining, and electron microscopy. The temporal corneal changes were also monitored. Histological and functional changes of the kidney were also evaluated. Results: Successful knockout of the Slc4a11 gene was confirmed by immunohistochemistry and RT-PCR. Slit-lamp photography and AS-OCT showed progressive corneal edema. Increased corneal endothelial cell size with decreased corneal endothelial cell density was observed with increased age. Scanning electron microscopy also revealed progressive cell swelling and distortion of the hexagonal cell morphology with time. Transmission electron microscopy showed characteristic ultrastructural findings of CHED, including endothelial vacuolization, thickening of the Descemet membrane, disorganization of collagen fibril, deposition of amorphous material, and progression of these changes with age. Decreased urine osmolarity and electrolyte concentrations suggesting abnormality in water resorption were also detected. Conclusions: Our Slc4a11 KO mouse model successfully represents clinical manifestations of human CHED. We were able to show chronological corneal progression for the first time in a knockout mouse model as well as renal abnormalities.
    Investigative ophthalmology & visual science 08/2013; 54(9). DOI:10.1167/iovs.13-12089 · 3.40 Impact Factor
  • Wei-Boon Khor · Sang-Beom Han · Jodhbir S Mehta · Donald T H Tan ·
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    ABSTRACT: To study the clinical outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) with the EndoGlide donor insertion device. Retrospective interventional case series. We included 100 eyes that underwent DSAEK for Fuchs endothelial dystrophy or pseudophakic bullous keratopathy (PBK) at a single institution. Eyes with anterior segment pathology or previous intraocular surgery (except for uncomplicated cataract surgery) were excluded. Preoperative data included visual acuity and donor endothelial cell density by specular microscopy. The main outcome measures were postoperative best spectacle-corrected visual acuity (BSCVA) and endothelial cell loss at 3, 6, and 12 months. There were 59 eyes with Fuchs dystrophy and 41 eyes with PBK. In eyes without vision-limiting pathology, the median postoperative BSCVA was consistently 20/40 (range 20/20-20/400) at 3 months (n = 61 eyes), 6 months (n = 55 eyes), and 12 months (n = 48 eyes). Endothelial cell loss was 13.7% at 3 months (n = 57), 13.5% at 6 months (n = 61), and 14.9% at 12 months (n = 53). Primary graft failure occurred in 1 eye, attributable to incorrect use of the insertion device. Two eyes with complete donor dislocation were rebubbled successfully. The most common complication was glaucoma/ocular hypertension in 29 eyes (34.1%) without prior glaucoma and treatment escalation in 6 eyes (40.0%) with prior glaucoma. Of the 78 eyes with 12 months follow-up, 2 (2.6%) developed endothelial rejection, and 1 (1.3%) subsequently failed. The use of this donor insertion device during DSAEK demonstrates good outcomes and potentially low endothelial cell loss at up to 12 months after surgery.
    American Journal of Ophthalmology 07/2013; 156(4). DOI:10.1016/j.ajo.2013.05.012 · 3.87 Impact Factor
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    ABSTRACT: To develop a mouse model of bullous keratoplasty and evaluate the safety and efficacy of cryoinjury-induced corneal endothelial decompensation. Transcorneal freezing was performed on the right eye of each mouse. One cycle of cryoinjury was performed in 18 eyes (group A), and three cycles were performed in 17 eyes (group B). Pachymetry and intraocular pressure (IOP) measurements were done preoperatively, as well as at 1, 3, 7, 14, and 21 days after cryoinjury. At each post-cryoinjury time point, three mice from each group were euthanized, and the corneas underwent histology and electron microscopy. In both groups, significant corneal edema was noted at post-cryoinjury day 1, which was maintained throughout the study period. IOP remained within normal range in group A, but increased significantly with time in group B (p=0.011 at day 1, 0.038 at day 3, 0.026 at day 14, and 0.008 at day 21). In group B, serious complications including hyphema (one case), severe iridocorneal adhesion (15 cases), and total cataract (three cases) were detected, while only mild iridocorneal adhesion (four cases) and cataract (three cases) were noted in group A. Live/dead cell assay, hematoxylin and eosin staining, and scanning electron microscopy revealed successful ablation of corneal endothelial cells and absence of regeneration in both groups. Hematoxylin and eosin staining and terminal deoxynucleotidyl transferase-mediated nick end labeling assay showed that apoptosis was mainly confined to the posterior stroma and endothelium in group A, while severe apoptosis was observed throughout all layers of the cornea in group B. One cycle of cryoinjury was safer than three, while both were equally effective in inducing bullous keratopathy. This cryoinjury mouse model of bullous keratopathy was a consistently reproducible model that can be used for further studies on endothelial cell damage and rescue therapy.
    Molecular vision 06/2013; 19:1222-30. · 1.99 Impact Factor

Publication Stats

7k Citations
808.27 Total Impact Points


  • 2011-2015
    • Duke-NUS Graduate Medical School Singapore
      Tumasik, Singapore
  • 2014
    • Duke University
      Durham, North Carolina, United States
  • 2011-2014
    • KK Women's and Children's Hospital
      • Department of Maternal Fetal Medicine
      Tumasik, Singapore
  • 2006-2014
    • National University of Singapore
      • Department of Ophthalmology
      Tumasik, Singapore
    • Tan Tock Seng Hospital
      Tumasik, Singapore
    • University of Alberta
      • Department of Biochemistry
      Edmonton, Alberta, Canada
  • 2001-2014
    • Singapore Eye Research Institute
      Tumasik, Singapore
  • 1993-2014
    • Singapore National Eye Centre
      Tumasik, Singapore
  • 2012-2013
    • National University Health System
  • 2009
    • Singapore General Hospital
      • Department of Pathology
      Tumasik, Singapore
  • 1995
    • Moorfields Eye Hospital NHS Foundation Trust
      Londinium, England, United Kingdom