Jodhbir S Mehta

Publications (95)266.31 Total impact

• Article: Optimization of human corneal endothelial cell culture: density dependency of successful cultures in vitro.

  Gary Sl Peh, Kah-Peng Toh, Heng-Pei Ang, Xin-Yi Seah, Benjamin L George, Jodhbir S Mehta
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Global shortage of donor corneas greatly restricts the numbers of corneal transplantations performed yearly. Limited ex vivo expansion of primary human corneal endothelial cells is possible, and a considerable clinical interest exists for development of tissue-engineered constructs using cultivated corneal endothelial cells. The objective of this study was to investigate the density-dependent growth of human corneal endothelial cells isolated from paired donor corneas and to elucidate an optimal seeding density for their extended expansion in vitro whilst maintaining their unique cellular morphology. RESULTS: Established primary human corneal endothelial cells were propagated to the second passage (P2) before they were utilized for this study. Confluent P2 cells were dissociated and seeded at four seeding densities: 2,500 cells per cm2 ('LOW'); 5,000 cells per cm2 ('MID'); 10,000 cells per cm2 ('HIGH'); and 20,000 cells per cm2 ('HIGHx2'), and subsequently analyzed for their propensity to proliferate. They were also subjected to morphometric analyses comparing cell sizes, coefficient of variance, as well as cell circularity when each culture became confluent. At the two lower densities, proliferation rates were higher than cells seeded at higher densities, though not statistically significant. However, corneal endothelial cells seeded at lower densities were significantly larger in size, heterogeneous in shape and less circular (fibroblastic-like), and remained hypertrophic after one month in culture. Comparatively, cells seeded at higher densities were significantly homogeneous, compact and circular at confluence. Potentially, at an optimal seeding density of 10,000 cells per cm2, it is possible to obtain between 10 million to 25 million cells at the third passage. More importantly, these expanded human corneal endothelial cells retained their unique cellular morphology. CONCLUSIONS: Our results demonstrated a density dependency in the culture of primary human corneal endothelial cells. Sub-optimal seeding density results in a decrease in cell saturation density, as well as a loss in their proliferative potential. As such, we propose a seeding density of not less than 10,000 cells per cm2 for regular passage of primary human corneal endothelial cells.
  BMC Research Notes 05/2013; 6(1):176.
• Article: Outcomes of Corneal Transplantation for Irreversible Corneal Decompensation Secondary to Corneal Endotheliitis in Asian Eyes.

  Marcus Ang, Chelvin C A Sng, Soon-Phaik Chee, Donald T H Tan, Jodhbir S Mehta
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  ABSTRACT: PURPOSE: To describe outcomes of corneal transplantation for irreversible corneal decompensation from corneal endotheliitis in Asian eyes. DESIGN: Retrospective, observational case series. METHODS: We reviewed consecutive patients with corneal endotheliitis (32 eyes of 31 subjects) who underwent keratoplasty (January 1, 2008-December 1, 2009). All eyes had preoperative aqueous polymerase chain reaction (PCR) analysis for viruses, including cytomegalovirus (CMV). CMV-positive patients were treated preoperatively with topical corticosteroids and anti-CMV treatment (oral valganciclovir 900 mg twice daily, topical ganciclovir 0.15% 5 applications per day, for 6 weeks) with complete resolution of ocular inflammation, and quiescence for at least 6 months before corneal transplantation. Our main outcome measure was recurrence of endotheliitis within 1 year after corneal transplantation. RESULTS: Five eyes were CMV positive; the remaining 27 eyes were negative for all viruses on PCR analysis. CMV-positive patients had a higher rate of recurrence of endotheliitis within 1 year after corneal transplantation, compared with CMV-negative eyes (60% vs 7.4%, P = .01). The CMV-positive eyes had recurrent endotheliitis at a median of 10 months (range 3-11 months) after corneal transplantation. After successful anti-CMV treatment, all 5 CMV-positive eyes then continued to have clear grafts for a median duration of 21 months (range 13-44 months). CONCLUSION: Our study suggests that Asian patients with corneal endotheliitis may benefit from preoperative aqueous PCR analysis before corneal transplantation. Such patients were more likely to have a recurrence of endothelial inflammation if they were CMV positive preoperatively, despite successful anti-CMV treatment before surgery.
  American journal of ophthalmology 04/2013; · 3.83 Impact Factor
• Article: The Effect of Amniotic Membrane De-epithelialization Method on its Biological Properties and Ability to Promote Limbal Epithelial Cell Culture.

  Ting Zhang, Gary Hin-Fai Yam, Andri K Riau, Rebekah Poh, John C Allen, Gary S Peh, Roger W Beuerman, Donald T Tan, Jodhbir S Mehta
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  ABSTRACT: PURPOSE: To characterize the de-epithelialized human amniotic membrane (HAM) and compare cell attachment and proliferation efficiencies. METHODS: HAM was de-epithelialized by 20% ethanol (AHAM), 1.2 U/ml Dispase (DHAM), 0.02% EDTA (EHAM), 0.25% trypsin-EDTA (THAM) and 5M urea (UHAM), respectively, followed by gentle scrapping with #15 blade. Surface topology, extracellular matrix (ECM) and growth factor content were characterized and compared to intact HAM by electron microscopies (EM), atomic force microscopy (AFM), immunohistochemistry and western blotting. Primary human limbal epithelial cells (LEC) attachment and proliferation efficiencies were assayed. Statistical significance was calculated by SPSS and Fisher's Least Significant Difference test. RESULTS: EHAM, THAM and UHAM had intact basal lamina and smooth basement membrane surface shown under transmission and scanning EM and AFM. Cell remnants stayed on AHAM. Disrupted basement membrane and stroma was found in DHAM. Immunostaining intensity quantification and hierarchical clustering revealed that ECM composition of EHAM and UHAM resembled to intact HAM. In contrast, DHAM and THAM had drastic loss of ECM and growth factor content. LEC attachment efficiency at 24 hours post-seeding was the highest in EHAM (51% as on conventional culture surface), followed by UHAM and AHAM. However, cell proliferation indices at day 10 of culture were similar among different HAM substrates, suggesting repair of ECM and basement membrane by growing epithelial cells. CONCLUSION: Urea denudation preserved the basement membrane integrity, ECM and growth factor composition, and had higher cell attachment and proliferation efficiencies. With its short processing time, urea treatment offers a novel alternative for HAM de-epithelialization.
  Investigative ophthalmology & visual science 04/2013; · 3.43 Impact Factor
• Article: Comparison of Four Different VisuMax Circle Patterns for Flap Creation After Small Incision Lenticule Extraction.

  Andri K Riau, Heng P Ang, Nyein C Lwin, Shyam S Chaurasia, Donald T Tan, Jodhbir S Mehta
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  ABSTRACT: To compare four different Circle patterns for flap creation after small incision lenticule extraction (SMILE). SMILE was performed on six rabbits. Twenty-eight days after the initial procedure, corneal flaps were created using Circle patterns. Rabbits were divided into four groups (patterns A, B, C, and D). Pattern A creates a circular side cut to meet the cap cut within the clearance zone (outside of the optical zone). Patterns B, C, and D create a lamellar ring posterior, anterior, and at the same depth, respectively, to the cap to meet the cap cut in the clearance zone with the help of a junction cut. Difficulty of flap lift was graded from 1 (easiest) to 5 (most difficult). The bed quality was assessed by scanning electron microscopy. Flaps created by patterns A and D were the easiest to lift (grade 2). The resulting flap bed was smooth and undisrupted. However, pattern A resulted in a reduced re-treatment area. Flaps created by pattern B were the most difficult to lift (grade 4). The stromal dissection was difficult in an attempt to ascertain the original optical zone from the lamellar ring, placed posterior. Flaps produced by pattern C were easy to lift, with minor intrastromal resistance experienced during the lifting process (grade 3). The transition between the lamellar ring and cap cut was hardly discernible in pattern C-treated corneas. Pattern D, a lamellar ring adjacent to the cap cut, was the most optimal to be used for flap creation in cases of SMILE re-treatment.[J Refract Surg. 2013;29(4):236-244.].
  Journal of refractive surgery (Thorofare, N.J.: 1995) 04/2013; 29(4):236-44. · 2.54 Impact Factor
• Source

  Available from: Andrea Petznick

  Article: Comparison of corneal sensitivity, tear function and corneal staining following laser in situ keratomileusis with two femtosecond laser platforms

  Andrea Petznick, Annabel Chew, Reece C Hall, Cordelia ML Chan, Mohamad Rosman, Donald Tan, Louis Tong, Jodhbir S Mehta
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  ABSTRACT: Purpose: To evaluate longitudinal changes in corneal sensitivity, tear function, and corneal staining in patients who underwent laser in situ keratomileusis (LASIK) using two different femtosecond lasers. Methods: In a prospective, randomized clinical trial, contralateral eyes of 45 patients underwent flap creation by either VisuMax or IntraLase™ femtosecond laser. Corneal sensitivity, tear break up time (TBUT), Schirmer’s test, and corneal fluorescein staining were assessed preoperatively and at 1 week, 1 month, and 3 months postoperatively. Results: There were no statistical differences in any clinical outcome measure between the two femtosecond lasers (P . 0.05), although there was a trend towards slightly lower reductions for corneal sensitivity and TBUT in VisuMax-operated eyes. Overall, corneal sensitivity was significantly reduced at 1 week (P , 0.05), 1 month (P , 0 .001), and 3 months (P , 0.001) postoperatively. A significantly greater reduction of corneal sensitivity was noted in eyes with a myopic spherical equivalent of −6.00 diopters (D) to −11.25 D as compared with eyes that had a relatively lower level of myopia of less than −6.00 D (P , 0.001). TBUT and Schirmer’s test values were significantly diminished at 1 week postoperatively (P , 0.04). Overall, corneal staining was significantly increased at 1 week postoperatively (P , 0.001). The level of myopia did not significantly affect postoperative changes in TBUT, Schirmer’s test values, or corneal staining (P . 0.05). Conclusion: This study showed that changes in corneal sensitivity, tear function, and corneal staining were statistically similar in LASIK using VisuMax and IntraLase femtosecond lasers for flap creation. However, the trend towards faster recovery of corneal sensitivity and TBUT observed in VisuMax-operated eyes may be attributable to improved technical specifications. http://www.dovepress.com/comparison-of-corneal-sensitivity-tear-function-and-corneal-staining-f-peer-reviewed-article-OPTH
  Clinical Ophthalmology 03/2013; 7:591-598.
• Article: Optimization of Subconjunctival Biodegradable Microfilms for Sustained Drug Delivery to the Anterior Segment in a Small Animal Model.

  Yu-Chi Liu, Yan Peng, Nyein Chan Lwin, Tina T Wong, Subbu S Venkatraman, Jodhbir S Mehta
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  ABSTRACT: PURPOSE: To evaluate a biodegradable, sustained-release, prednisolone acetate (PA)-loaded poly [d,l-lactide-co-ε-caprolactone] (PLC) drug delivery system on its biocompatibility, feasibility and release characteristics both in vitro and in vivo. METHODS: Blank and 40% PA-loaded PLC microfilms with a diameter of 2 mm were fabricated and the degradation and drug release profiles of the microfilms were characterized both in vitro and in vivo. The microfilms were implanted into the subconjunctival space of Lewis rats (n=48). All the eyes were clinically assessed using slit lamp biomicroscopy and graded with Hackett-McDonald ocular scoring system and anterior segment optical coherence tomography. Histological and immunohistochemical analysis were performed comparing blank and PA-loaded microfilm groups. PA concentrations in the aqueous humor were determined by high-performance liquid chromatography (HPLC). RESULTS: Subconjunctivally-implanted PLC microfilms were able to deliver PA in a sustained manner over 3 months, with a steady rate of 0.002 mg/day in vivo. Eyes with either blank or PA-loaded implanted microfilms showed a very minimal inflammatory response at the insertion sites and mild degree of collagen encapsulation around the microfilms, with significantly less CD11c cells at 2 and 4 weeks (P = 0.001 and P = 0.002) and collagen formation at 2 weeks (P = 0.001) in PA-loaded microfilm group. Anterior chamber PA levels were achieved, with concentrations at 76.7±5.9, 70.3±2.3 and 42.7±4.1 ng/ml at 2, 4 and 12 weeks, respectively. CONCLUSIONS: PA-loaded PLC microfilms display good biocompatibility, feasibility and desirable sustained drug release profiles, and have the potential to exhibit anti-fibrotic and anti-inflammatory effects. This device is applicable to use in small animal models of anterior segment inflammation.
  Investigative ophthalmology & visual science 03/2013; · 3.43 Impact Factor
• Article: Descemet Stripping Automated Endothelial Keratoplasty in Complex Eyes: Results With a Donor Insertion Device.

  Wei-Boon Khor, Kelvin Y Teo, Jodhbir S Mehta, Donald T-H Tan
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  ABSTRACT: PURPOSE:: Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with complex anterior segment pathology or previous intraocular surgery is at risk of surgical complications and graft failure. We evaluated the use of the EndoGlide donor insertion device for DSAEK in these complex cases. METHODS:: This was a retrospective interventional series of 45 consecutive eyes with endothelial dysfunction and higher risk ocular comorbidities that underwent DSAEK with the EndoGlide. We included eyes with aphakia, glaucoma surgery, prior vitrectomy, anterior chamber intraocular lenses, failed cornea grafts, and primary angle closure glaucoma. Demographic and clinical details, intraoperative and postoperative complications, and postoperative graft clarity, and endothelial cell density (ECD) loss were documented. RESULTS:: The average age was 62 years (range, 16-88 years), and the majority were Chinese (n = 28). The commonest risk factors identified were previous trabeculectomy (n = 13) and failed penetrating keratoplasty (n = 12). Preoperative donor ECD averaged 2790 ± 230 cells per square millimeter and modal graft diameter was 9.0 mm (range, 7.75-9.75 mm). One eye (2.2%) had primary graft failure, and 3 eyes (6.7%) had graft dislocation. Another 3 eyes suffered late graft failure within the first year and 2 were in eyes with an anterior chamber intraocular lenses. At 6 months, the mean ECD was 2363 + 242 cells/mm and the mean ECD loss was 17.9% (n = 16). By 12 months, the mean ECD was 2098 + 462 cells/mm and the mean ECD loss was 27.0% (n = 20). CONCLUSIONS:: Donor insertion with this device can help address inherent intraoperative challenges and minimize endothelial cell damage during DSAEK in complex cases.
  Cornea 02/2013; · 1.73 Impact Factor
• Article: In vivo biocompatibility of two PEG/PAA interpenetrating polymer networks as corneal inlays following deep stromal pocket implantation.

  Xiao Wei Tan, Laura Hartman, Kim Peng Tan, Rebekah Poh, David Myung, Luo Luo Zheng, Dale Waters, Jaan Noolandi, Roger W Beuerman, Curtis W Frank, Christopher N Ta, Donald Th Tan, Jodhbir S Mehta
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  ABSTRACT: This study compared the effects of implanting two interpenetrating polymer networks (IPNs) into rabbit corneas. The first (Implant 1) was based on PEG-diacrylate, the second (Implant 2) was based on PEG-diacrylamide. There were inserted into deep stromal pockets created using a manual surgical technique for either 3 or 6 months. The implanted corneas were compared with normal and sham-operated corneas through slit lamp observation, anterior segment optical coherence tomography, in vivo confocal scanning and histological examination. Corneas with Implant 1 (based on PEG-diacrylate) developed diffuse haze, ulcers and opacities within 3 months, while corneas with Implant 2 (based on PEG-diacrylamide) remained clear at 6 months. They also exhibited normal numbers of epithelial cell layers, without any immune cell infiltration, inflammation, oedema or neovascularisation at post-operative 6 month. Morphological studies showed transient epithelial layer thinning over the hydrogel inserted area and elevated keratocyte activity at 3 months; however, the epithelium thickness and keratocyte morphology were improved at 6 months. Implant 2 exhibited superior in vivo biocompatibility and higher optical clarity than Implant 1. PEG-diacrylamide-based IPN hydrogel is therefore a potential candidate for corneal inlays to correct refractive error.
  Journal of Materials Science Materials in Medicine 01/2013; · 2.32 Impact Factor
• Article: Deep anterior lamellar keratoplasty: surgical techniques, challenges, and management of intraoperative complications.

  Marcus Ang, Karim Mohamed-Noriega, Jodhbir S Mehta, Donald Tan
  International ophthalmology clinics 01/2013; 53(2):47-58.
• Source

  Available from: Andrea Petznick

  Article: Comparison of corneal sensitivity, tear function and corneal staining following laser in situ keratomileusis with two femtosecond laser platforms.

  Andrea Petznick, Annabel Chew, Reece C Hall, Cordelia Ml Chan, Mohamad Rosman, Donald Tan, Louis Tong, Jodhbir S Mehta
  [show abstract] [hide abstract]
  ABSTRACT: To evaluate longitudinal changes in corneal sensitivity, tear function, and corneal staining in patients who underwent laser in situ keratomileusis (LASIK) using two different femtosecond lasers. In a prospective, randomized clinical trial, contralateral eyes of 45 patients underwent flap creation by either VisuMax or IntraLase™ femtosecond laser. Corneal sensitivity, tear break up time (TBUT), Schirmer's test, and corneal fluorescein staining were assessed preoperatively and at 1 week, 1 month, and 3 months postoperatively. There were no statistical differences in any clinical outcome measure between the two femtosecond lasers (P > 0.05), although there was a trend towards slightly lower reductions for corneal sensitivity and TBUT in VisuMax-operated eyes. Overall, corneal sensitivity was significantly reduced at 1 week (P < 0.05), 1 month (P < 0 .001), and 3 months (P < 0.001) postoperatively. A significantly greater reduction of corneal sensitivity was noted in eyes with a myopic spherical equivalent of -6.00 diopters (D) to -11.25 D as compared with eyes that had a relatively lower level of myopia of less than -6.00 D (P < 0.001). TBUT and Schirmer's test values were significantly diminished at 1 week postoperatively (P < 0.04). Overall, corneal staining was significantly increased at 1 week postoperatively (P < 0.001). The level of myopia did not significantly affect postoperative changes in TBUT, Schirmer's test values, or corneal staining (P > 0.05). This study showed that changes in corneal sensitivity, tear function, and corneal staining were statistically similar in LASIK using VisuMax and IntraLase femtosecond lasers for flap creation. However, the trend towards faster recovery of corneal sensitivity and TBUT observed in VisuMax-operated eyes may be attributable to improved technical specifications.
  Clinical ophthalmology (Auckland, N.Z.) 01/2013; 7:591-8.
• Article: Cost-Effectiveness of Descemet's Stripping Endothelial Keratoplasty versus Penetrating Keratoplasty.

  Saideep Bose, Marcus Ang, Jodhbir S Mehta, Donald T Tan, Eric Finkelstein
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  ABSTRACT: PURPOSE: Selective endothelial transplantation in the form of Descemet's stripping endothelial keratoplasty (DSEK) is rapidly replacing traditional full-thickness penetrating keratoplasty (PK) for endothelial disease. An incremental cost-effectiveness analysis was performed to determine whether the benefits of DSEK are worth the additional costs. DESIGN: Retrospective cohort study. PARTICIPANTS: Patients at the Singapore National Eye Center, a tertiary eye center in Singapore, with Fuchs' dystrophy or bullous keratopathy who underwent either PK or DSEK. INTERVENTION: Patients underwent either PK (n = 171) or DSEK (n = 93) from January 2001 through December 2007. Data were collected from inpatient and outpatient notes corresponding to the time immediately before the procedure to up to 3 years after. MAIN OUTCOME MEASURES: Improvements in best spectacle-corrected visual acuity were used to calculate the increase in quality-adjusted life years (QALYs) 3 years after the procedure. This was combined with hospital charges (a proxy for costs) to determine incremental cost-effectiveness ratios (ICERs) comparing PK with no intervention and DSEK with PK. RESULTS: Three-year charges for DSEK and PK were $7476 and $7236, respectively. The regression-adjusted improvement in visual acuity for PK relative to no intervention was -0.613 logarithm of the minimum angle of resolution (logMAR) units (P<0.001), and for DSEK relative to PK, it was -0.199 logMAR units (P = 0.045). The regression-adjusted marginal gain in utility for PK relative to no intervention was 0.128 QALYs (P<0.001) and for DSEK relative to PK was 0.046 QALYs (P = 0.031). This resulted in ICERs of $56 409 per QALY for PK relative to no intervention and $5209 per QALY for the more expensive DSEK relative to PK. CONCLUSIONS: If the goal is to maximize societal health gains given fixed resources, DSEK should be the preferred strategy. For a fixed budget, it is possible to achieve greater QALY gains by providing DSEK to as many patients as possible (and nothing to others), rather than providing PK. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
  Ophthalmology 11/2012; · 5.45 Impact Factor
• Article: Intraocular lens as a drug delivery reservoir.

  Yu-Chi Liu, Tina T Wong, Jodhbir S Mehta
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  ABSTRACT: PURPOSE OF REVIEW: To describe the development and use of intraocular lenses (IOLs) as drug delivery systems and to review the current literature on their application and efficacy. RECENT FINDINGS: Many drugs have been loaded onto IOLs by coating or by attachment in a separate reservoir. With incorporation of polymeric materials either as a coating or by attachment as a separate reservoir, it is possible to achieve a sustained and controlled release of drugs. Experimental evidence in animal models has shown that IOL drug delivery systems are effective in the prevention and treatment of inflammation, infection and posterior capsule opacification after cataract surgery. SUMMARY: The use of IOLs as drug delivery reservoirs appears to show great promise. Although excellent results with therapeutic potential have been reported in experimental animal studies, further studies are needed to reach clinical use.
  Current opinion in ophthalmology 10/2012; · 2.49 Impact Factor
• Article: Refractive lenticule extraction flap and stromal bed morphology assessment with anterior segment optical coherence tomography.

  Eugene Tay, Xiang Li, Cordelia Chan, Donald T Tan, Jodhbir S Mehta
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  ABSTRACT: To evaluate the flap and stromal bed after refractive lenticule extraction using optical coherence tomography (OCT). Singapore National Eye Centre, Singapore. Longitudinal case series. Horizontal scans (RTVue) were taken preoperatively and after refractive lenticule extraction. Two procedures were performed: femtosecond lenticule extraction and small-incision femtosecond lenticule extraction. Flap and bed thicknesses were measured at the center (0.0 mm) and 1.5 mm and 3.0 mm to either side. At 1 week, the mean flap at 0.0 mm was borderline thicker (P=.056) and at +3.0 mm significantly thicker after femtosecond lenticule extraction than after small-incision femtosecond lenticule extraction (P=.003). The mean bed at 0.0 mm was thinner after femtosecond lenticule extraction (P=.03). The flap at -3.0 mm showed thinning between 1 week and 3 months after small-incision femtosecond lenticule extraction (P=.018). The flap at +3.0 mm thinned between 1 week and 1 month after femtosecond lenticule extraction (P=.009). After femtosecond lenticule extraction, there were increases in bed (P=.027) and total corneal (P=.013) thicknesses at 0.0 mm between 1 week and 3 months, remaining stable thereafter (3 months: P=.842 and P=.508, respectively). The mean spherical equivalent decreased and the uncorrected acuity improved after both procedures (P<.001), with stabilization of both variables at 3 months. A significant difference in stromal bed thickness between femtosecond lenticule extraction and small-incision femtosecond lenticule extraction was detectable by AS-OCT 1 week postoperatively.
  Journal of cataract and refractive surgery 09/2012; 38(9):1544-51. · 2.75 Impact Factor
• Article: Reproducibility and age-related changes of ocular parametric measurements in rabbits.

  Andri K Riau, Neil Ys Tan, Romesh I Angunawela, Hla M Htoon, Shyam S Chaurasia, Jodhbir S Mehta
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  ABSTRACT: BACKGROUND: The rabbit is a common animal model for ophthalmic research, especially corneal research. Ocular structures grow rapidly during the early stages of life. It is unclear when the rabbit cornea becomes mature and stabilized. We investigated the changes of keratometry, refractive state and central corneal thickness (CCT) with age. In addition, we studied the intra- and inter-observer reproducibility of anterior chamber depth (ACD) and anterior chamber width (ACW) measurements in rabbits using anterior segment-optical coherence tomography (AS-OCT). RESULTS: The growth of New Zealand White rabbits (n = 16) were monitored from age 1 to 12 months old. Corneal keratometric and refractive values were obtained using an autorefractor/keratometer, and CCT was measured using an AS-OCT. Keratometry and CCT changed rapidly from 1 to 7 months and appeared to be stabilizing after 8 months. The reduction of corneal curvature was approximately 1.36 diopter (D)/month from age 1 to 7 months, but the change decelerated to 0.30 D/month from age 8 to 12 months. An increase of 10 mum/month in CCT was observed from age 1 to 7 months, but the gain was reduced to less than 1 mum/month from age 8 to 12 months. There was a hyperopic shift over the span of 12 months, albeit the increase in spherical equivalent was slow and gradual. Rabbits of random age were then selected for 2 repeated ACD and ACW measurements by 2 independent and masked observers. Bland-Altman plots revealed a good agreement of ACD and ACW measurements inter- and intra-observer and the ranges of 95% limit of agreement were acceptable from a clinical perspective. CONCLUSIONS: Corneal keratometry, spherical equivalent refraction and CCT changed significantly during the first few months of life of rabbits. Young rabbits have been used in a large number of eye research studies. In certain settings, the ocular parametric changes are an important aspect to note as they may alter the findings made in a rabbit experimental model. In this study, we have also demonstrated for the first time a good between observer reproducibility of measurements of ocular parameters in an animal model by using an AS-OCT.
  BMC Veterinary Research 08/2012; 8(1):138. · 2.00 Impact Factor
• Article: Endothelial Cell Loss and Graft Survival after Descemet's Stripping Automated Endothelial Keratoplasty and Penetrating Keratoplasty.

  Marcus Ang, Jodhbir S Mehta, Fiona Lim, Saideep Bose, Hla Myint Htoon, Donald Tan
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  ABSTRACT: PURPOSE: We sought to compare endothelial cell (EC) loss and graft survival after Descemet's stripping automated endothelial keratoplasty (DSAEK) and conventional penetrating keratoplasty (PK) in Asian eyes. DESIGN: Retrospective, nested, cohort study. PARTICIPANTS: Consecutive patients who underwent DSAEK or PK with Fuchs' endothelial dystrophy or pseudophakic and aphakic bullous keratopathy (BK) at a single tertiary center from April 1, 2006, to April 1, 2008. METHODS: Clinical data, and donor and recipient characteristics were recorded from our prospective cohort from the Singapore Corneal Transplant Study. MAIN OUTCOME MEASURES: Percent EC loss and graft survival up to 3 years. RESULTS: There were no differences in baseline characteristics of patients comparing DSAEK and PK; there were more patients with BK (n = 141, 68.4%) than Fuchs' dystrophy. Percent EC loss was lower in DSAEK compared with PK at 1 (30±22% vs 37±25%; P = 0.045), 2 (36±23% vs 45±33%; P = 0.018), and 3 years (39±24% vs 47±28%; P = 0.022) postoperatively. Graft survival was comparable (log-rank P = 0.671) between DSAEK and PK at 1 (94% vs 90%), 2 (88% vs 85%), and 3 years (87% vs 85%). CONCLUSIONS: Compared with PK, DSAEK resulted in lower EC loss with comparable cumulative graft survival rates for up to 3 years in patients with Fuchs' dystrophy and BK. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
  Ophthalmology 08/2012; · 5.45 Impact Factor
• Article: Effect of different femtosecond laser-firing patterns on collagen disruption during refractive lenticule extraction.

  Andri K Riau, Romesh I Angunawela, Shyam S Chaurasia, Donald T Tan, Jodhbir S Mehta
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  ABSTRACT: To evaluate the changes in corneal collagen architecture subjected to different laser-firing patterns during refractive lenticule extraction. Singapore Eye Research Institute, Singapore. Experimental study. Refractive lenticule extraction was performed in rabbits without lenticule removal. Rabbits were divided into 4 groups that had incisions in the following firing patterns: (A) from periphery in (lenticule's posterior surface) and from center out (lenticule's anterior surface); (B) from center out and from center out; (C) from periphery in and from periphery in; and (D) from center out and from periphery in. The corneas were collected 18 hours postoperatively and were subjected to immunofluorescent staining of fibronectin, CD11b, and collagen type I. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Refractive lenticule extraction-treated corneas showed no significant difference in fibronectin and CD11b expression. Similar expression patterns of collagen type I were observed in corneas that had femtosecond firing patterns A, B, and C; however, a discontinuous and relatively more intense staining pattern along the anterior plane of the lenticule was detected in corneas treated with pattern D. The TEM also showed a more disrupted collagen arrangement along the anterior incision site in pattern D-treated corneas. Differential laser firing patterns during refractive lenticule extraction resulted in different levels of collagen derangement along the anterior plane of the lenticule, with pattern D showing the most disrupted surface. Such disruption in the collagen architecture might affect postoperative visual recovery and refractive outcomes. No author has a financial or proprietary interest in any material or method mentioned.
  Journal of cataract and refractive surgery 08/2012; 38(8):1467-75. · 2.75 Impact Factor
• Article: Reproducibility of Corneal Graft Thickness measurements with COLGATE in patients who have undergone DSAEK (Descemet Stripping Automated Endothelial Keratoplasty).

  Melissa Hy Wong, Annabel Chew, Hla M Htoon, Beng H Lee, Jun Cheng, Jiang Liu, Donald T Tan, Jodhbir S Mehta
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  ABSTRACT: The CorneaL GrAft Thickness Evaluation (COLGATE) system was recently developed to facilitate the evaluation of corneal graft thickness from OCT images. Graft thickness measurement can be a surrogate indicator for detecting graft failure or success. The purpose of this study was to determine the reproducibility of the COLGATE system in measuring DSAEK graft area between two observers. This was a prospective case series in which 50 anterior segment OCT images of patients who had undergone DSAEK in either eye were analysed. Two observers (MW, AC) independently obtained the image analysis for the graft area using both semi automated and automated method. One week later, each observer repeated the analysis for the same set of images. Bland-Altman analysis was performed to analyze inter and intra observer agreement. There was strong intraobserver correlation between the 2 semi automated readings obtained by both observers. (r = 0.936 and r = 0.962). Intraobserver ICC for observer 1 was 0.936 (95% CI 0.890 to 0.963) and 0.967 (95% CI 0.942 to 0.981) for observer 2. Likewise, there was also strong interobserver correlation (r = 0.913 and r = 0.969). The interobserver ICC for the first measurements was 0.911 (95% CI 0.849 to 0.949) and 0.968 (95% CI 0.945 to 0.982) for the second. There was statistical difference between the automatic and the semi automated readings for both observers (p = 0.006, p = 0.003). The automatic readings gave consistently higher values than the semi automated readings especially in thin grafts. The analysis from the COLGATE programme can be reproducible between different observers. Care must be taken when interpreting the automated analysis as they tend to over estimate measurements.
  BMC Medical Imaging 08/2012; 12:25. · 1.09 Impact Factor
• Article: Dual functionalization of titanium with vascular endothelial growth factor and β-defensin analog for potential application in keratoprosthesis.

  Xiao Wei Tan, R Lakshminarayanan, Shou Ping Liu, Eunice Goh, Donald Tan, Roger W Beuerman, Jodhbir S Mehta
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  ABSTRACT: Functionalization of material surfaces can improve their biointegration and bactericidal effect. To expand the biomedical applications of titanium in artificial cornea implantation surgery, titanium alloy substrates were coated with polydopamine and dual bound with recombinant vascular endothelial growth factor (VEGF) and anti-microbial peptide (AMP), SESB2V. Successful chemical binding was assessed with attenuated total reflectance-Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. Coating thickness was assessed by atomic force microscopy. Cellular studies revealed that the functionalized substrates displayed the abilities to enhance primary human corneal fibroblast adhesion, proliferation, and viability. Angiogenesis assay with human mesenchymal stem cells was used to verify the biological functions of immobilized VEGF while bactericidal assay was evaluated for the anti-microbial activities of immobilized SESB2V peptide. We found that the titanium surface that was sequentially functionalized with VEGF and SESB2V had enhanced fibroblast proliferation and anti-microbial properties. The incorporation of such peptides into an artificial cornea implant is important for implant-tissue integration and wound healing. This may improve implant integration and reduce the risk of device infection following artificial cornea implantation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
  Journal of Biomedical Materials Research Part B Applied Biomaterials 07/2012; 100(8):2090-100. · 2.15 Impact Factor
• Article: Correlation of anterior segment optical coherence tomography measurements with graft trephine diameter following descemet stripping automated endothelial keratoplasty.

  Gavin S Tan, Mingguang He, Donald T Tan, Jodhbir S Mehta
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  ABSTRACT: To assess repeatability of the Zhongshan Assessment Program (ZAP) software measurement of Anterior Segment Optical Coherence Tomography (ASOCT) images and correlate with graft trephine diameter following Descemet Stripping Automated Endothelial Keratoplasty (DSAEK) METHODS: Retrospectively evaluated interventional case series. 121 consecutive eyes undergoing DSAEK over a 26 month period underwent ASOCT imaging 1 month after their surgery. ASOCT images were processed using ZAP software which measured the graft and cornea parameters including anterior and posterior graft arc length and cord length, posterior cornea arc length (PCAL) and anterior chamber width. The graft measurements showed good repeatability on ASOCT using ZAP with high intra class coefficient and small variation in the coefficient of variation. On ASOCT, the mean recipient PCAL was 12.99+/-0.69 mm and the anterior chamber width was 11.16+/-0.57 mm. The mean Graft anterior arc length was 9.69+/-0.66 mm and the mean Graft anterior cord length was 8.92+/-2.94 mm. The mean graft posterior arc length was 9.24+/-0.75 mm and the mean graft posterior cord length was 8.15+/-0.57 mm. Graft posterior arc length (rho=0.788, p< 0.001) correlated best with intra-operative graft trephine diameter. The mean ratio of posterior graft arc length to PCAL was 0.712 +/- 0.056. We have validated the repeatability of the ZAP software for DSAEK graft measurements from ASOCT images and shown that the graft arc length parameters calculated from the ASOCT images correlate well with the intra-operative graft trephine diameter. This software may help surgeons determine the optimal DSAEK graft size based on pre-operative ASOCT measurements of the recipient eye.
  BMC Medical Imaging 07/2012; 12:19. · 1.09 Impact Factor
• Article: In vitro effect of a corrosive hostile ocular surface on candidate biomaterials for keratoprosthesis skirt.

  Xiao Wei Tan, Andri Riau, Zhi Long Shi, Anna C S Tan, Koon Gee Neoh, Khiam Aik Khor, Roger W Beuerman, Donald Tan, Jodhbir S Mehta
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  ABSTRACT: Keratoprosthesis (KPro) devices are prone to long-term corrosion and microbiological assault. The authors aimed to compare the inflammatory response and material dissolution properties of two candidate KPro skirt materials, hydroxyapatite (HA) and titania (TiO(2)) in a simulated in vitro cornea inflammation environment. Lipopolysaccharide-stimulated cytokine secretions were evaluated with human corneal fibroblasts on both HA and TiO(2). Material specimens were subjected to electrochemical and long-term incubation test with artificial tear fluid (ATF) of various acidities. Topography and surface roughness of material discs were analysed by scanning electron microscopy and atomic force microscopy. There were less cytokines secreted from human corneal fibroblasts seeded on TiO(2) substrates as compared with HA. TiO(2) was more resistant to the corrosion effect caused by acidic ATF in contrast to HA. Moreover, the elemental composition of TiO(2) was more stable than HA after long-term incubation with ATF. TiO(2) is more resistant to inflammatory degradation and has a higher corrosion resistance as compared with HA, and in this regard may be a suitable material to replace HA as an osteo-odonto-keratoprosthesis skirt. This would reduce resorption rates for KPro surgery.
  The British journal of ophthalmology 07/2012; 96(9):1252-8. · 2.92 Impact Factor