Donald Tan

Corneal replacement using a synthetic hydrogel cornea, AlphaCor: device, preliminary outcomes and complications.

AbstractPurpose Clinical assessment of outcome of corneal replacement with a synthetic cornea, AlphaCor™, in patients considered at too high risk for conventional penetrating keratoplasty with donor tissue to be successful, but excluding indications such as end-stage dry eye that might be suited to traditional prosthokeratoplasty.Methods All patients in the multicentre clinical trial were managed according to an approved protocol, with Ethics Committee approval in each centre. Preoperative visual acuity ranged from perception of light (PL) to 6/60 (20/200). Implantation was by means of an intralamellar technique, with a conjunctival flap in most cases. Tissues anterior to the optic were removed as a secondary procedure.Results Up to 30 November 2001, 40 AlphaCor™ devices had been implanted in 38 patients, of mean age 60 years. Follow-up ranged from 0.5 months to 3 years. There had been one extrusion (2.5%) and four cases (10%) where a device had been removed due to melt-related complications. All five of these cases received a donor corneal graft after the device was removed, with these grafts remaining anatomically satisfactory and epithelialised to date. Corneal melts in AlphaCor™ recipients were found to be strongly associated with a history of ocular herpes simplex infection. Two further devices (5%) were removed owing to reduced optic clarity after presumed drug-related deposition, and have been successfully replaced with second devices. Mean preoperative best-corrected visual acuity was hand movements. Visual acuities after surgery ranged from PL to 6/6−2 (20/20−2).Conclusions Early results suggest that the AlphaCor™, previously known as the Chirila keratoprosthesis (Chirila KPro), has a low incidence of the complications traditionally associated with keratoprostheses and can be effective in restoring vision in patients considered untreatable by conventional corneal transplantation. Importantly, the device can be replaced with a donor graft in the event of development of a significant complication. A history of ocular herpes simplex is a contraindication to AlphaCor™ implantation. Ongoing monitoring of clinical outcomes in all patients will allow the indications for AlphaCor™, as opposed to donor grafts, to be determined.

Phospholipase D in the human ocular surface and in pterygium.

Background:Post-exposure prophylaxis (PEP) is currently recommended after certain high-risk exposures, and pre-exposure prophylaxis (PrEP) is undergoing evaluation in clinical trials. Media reports have suggested substantial levels of community PrEP use despite its unproven effectiveness. Methods:We conducted a cross-sectional survey of 1819 HIV-uninfected gay/bisexual men in California to assess PEP and PrEP awareness and use. Results:Overall, 47% reported PEP awareness and 4% ever used PEP. Men who were older than 25 years of age (odds ratio [OR] = 2.2, 95% confidence interval [CI]: 1.5 to 3.1), were white (OR = 2.2, 95% CI: 1.6 to 3.0), had an annual income >

AlphaCor : Clinical outcomes

100,000 (OR = 2.0, 95% CI: 1.2 to 3.4), self-identified as gay/homosexual (OR = 2.4, 95% CI: 1.4 to 4.3), and had unprotected anal sex (OR = 1.8, 95% CI: 1.3 to 2.3) or sex under the influence of a drug (OR = 2.0, 95% CI: 1.5 to 2.7) were more likely to be aware of PEP, whereas speed users (OR = 0.6, 95% CI: 0.4 to 0.9) were less likely to be aware of PEP. Only 16% reported PrEP awareness, and <1% ever used PrEP. Unprotected anal sex (OR = 1.6, 95% CI: 1.1 to 2.3) and sex under the influence of a drug (OR = 1.5, 95% CI: 1.0 to 2.2) were associated with PrEP awareness. Conclusions:PEP awareness and use were modest and PrEP use was rare among gay/bisexual men in California. Although PrEP is not currently recommended, community education on the availability of PEP is suggested.PURPOSE Pterygium is a fibro-vascular disease of unknown etiology characterized by proliferation and advancement of tissue onto the cornea. Phospholipase Ds (PLDs) are members of an important class of enzymes involved in inflammation and differentiation. In cultured corneal epithelial cells, these enzymes play a role in wound healing, and in other contexts, they suppress apoptosis and increase cell motility. We aimed to study the presence of PLD subtypes in native ocular surface tissue and pterygium. METHODS This study involved paired control or uninvolved conjunctival and pterygium tissues from 6 patients. Reverse transcription semiquantitative and quantitative polymerase chain reactions were performed to assess transcript levels for PLD1-5 in normal conjunctiva and pterygium tissue. Immunofluorescent staining by using antibodies against PLD1/2 was used to study the expression and tissue distribution. Western blots were performed for protein detection and to confirm the specificity of the antibodies used. RESULTS PLD1, 2, 3, and 4 transcripts were detected in normal conjunctiva tissue, and types 2, 3, and 4 were upregulated in pterygium. Immunofluorescent staining showed the presence of phospholipase-D1/2 in normal cornea, conjunctival, and pterygial epithelia. In normal cornea and conjunctival epithelia, the expression was mainly localized to the nuclei of the basal and suprabasal epithelial cells, whereas in pterygium, this expression was limited to the cytoplasm and peri-plasma membrane regions. Western blot confirmed the presence of PLD1/2 in proteins extracted from pterygium and conjunctiva tissue. CONCLUSIONS PLD subtypes are present in human ocular surface epithelium. PLD may be involved in pterygium pathogenesis.

Clinical and microbial spectrum of fungal keratitis in Singapore: a 5-year retrospective study

Purpose: To study the outcomes of AlphaCor implantation. Methods: The AlphaCor artificial cornea is indicated for corneal blindness not treatable by donor grafting. Prospective preoperative and follow-up data were collected. Data were evaluated using SPSS for statistical analysis of outcomes, trends, and associations. Results: This report includes data returned through February 28, 2006, for all 322 devices implanted, with mean follow-up in situ of 15.5 months and a maximum of 7.4 years. The probability of AlphaCor retention at 6 months and 1 and 2 years for protocol cases was 92%, 80%, and 62%, respectively, and off-label cases were at higher risk (P = 0.010), as were cases not prescribed medroxyprogesterone (MPG; P = 0.001). Currently, the most common complications were stromal melting, fibrous reclosure of the posterior lamellar opening, and white intraoptic deposits, with incidences in 2005 of 11.4%, 5.1%, and 2.6%, respectively. MPG seems to protect against melts, and eyes with a history of herpetic keratitis were not at increased risk. A history of glaucoma or the presence of tubes did not affect device retention. Complications culminated in loss of an eye in 1.3%. Mean preoperative visual acuity (VA) was hand movements. The VA achieved postoperatively (light perception to 20/20) was affected by previous pathology and postoperative course, with a mean improvement of 2 lines. Conclusion: AlphaCor provides a treatment option where a donor tissue graft would not succeed in severe corneal conditions, while being reversible to a donor graft in the event of complications for anatomic integrity. Surgical technique and adjunctive therapies are evolving with experience. Continued data collection is important for a fuller understanding of AlphaCors role.

Intraocular pressure associations with refractive error and axial length in children

Background: The epidemiology of fungal keratitis varies geographically, but commonly occurs in warm, tropical climates. To determine the microbial and clinical characteristics of this disease in Singapore, we conducted a5-year hospital-based retrospective study. Methods: A retrospective reviewo f culture-positive fungal keratitis at the Singapore National Eye Center and Singapore General Hospital, from January 1991 to December 1995. Results: Twenty-nine consecutive cases of culture-positive fungal keratitis were seen over the study period. The mean age of the cases was 41 years and 23 were males. Amongst the varied occupations, 9 were construction workers. The most common cultured organisms were Fusarium sp. (52%) and Aspergillus flavus (17%). More than half had a history of ocular trauma prior to the development of keratitis, while a quarter had antecedent topical corticosteroid therapy. In contrast, only 2 patients were contact-lens wearers. Despite medical therapy, 10 patients eventually required therapeutic penetrating keratoplasties; of these, 6 were caused by Fusarium species. Conclusion: Fusarium is the commonest cultured organism in fungal keratitis in Singapore and is associated with significant ocular morbidity.

The impact of cataract surgery on quality of life.

Aim: To assess whether intraocular pressure (IOP) is associated with refractive error or axial length in children. Methods: Of subjects from the Singapore Cohort Study of the Risk Factors for Myopia (SCORM), 636 Chinese children aged 9–11 years from two elementary schools underwent non-contact tonometry, cycloplegic autorefraction, and A-scan biometry during 2001. For analyses, refractive error was categorised into four groups; hypermetropia (spherical equivalent refraction (SE) ⩾+1.0D), emmetropia (−0.5D<SE<+1.0D), low myopia (−3.0D<SE⩽−0.5D) and high myopia (SE⩽−3.0D). Results: Of the 636 children examined, 50.6% were male. The mean IOP was 16.6 (SD 2.7) mm Hg. There were no significant IOP differences between low (mean IOP = 16.4 (2.8) mm Hg) or high myopes (16.7 (2.5) mm Hg) and emmetropes (16.7 (2.9) mm Hg), p = 0.57. IOP was not correlated with spherical equivalent refraction (Spearman correlation, r = 0.009) or axial length (r = 0.030). In regression analyses adjusting for diastolic blood pressure, neither spherical equivalent (regression coefficient = 0.014) nor axial length (regression coefficient = 0.027) were significantly associated with IOP. Conclusion: These findings do not support an association between IOP and refractive error or axial length in children. This questions postulated roles of IOP in the pathogenesis of myopia.

Prevalence rates and epidemiological risk factors for astigmatism in Singapore school children.

Purpose of review This review summarizes the recent literature of the impact of cataract surgery from the patients perspective, with a focus on second-generation patient reported outcome (PRO) measures that used Rasch analysis to explore their data. Recent findings Irrespective of the instrument utilized, the overriding conclusion is that cataract surgery unequivocally improves vision-specific functioning and several aspects of vision-specific quality of life. The benefit of cataract surgery, however, on generic health is less clear, due to limited vision-related items. Evidence suggests that cataract surgery also improves visual functioning in comorbid eye disease, especially in the early stages. Similarly, second eye cataract surgery appears to improve visual ability beyond that achieved with first eye surgery. Recently, there has been a shift toward second-generation, Rasch-validated PROs to assess cataract surgery outcomes and large gains in visual function have been demonstrated. Importantly, measurement precision is dramatically improved compared with the original first-generation instruments. Summary Cataract surgery-induced improvements in visual acuity are translated by considerable gains in real life activities, emotional and social life components. The utilization of second-generation instruments and modern psychometric methods, however, appears to be the best current strategy to optimize the impact of cataract surgery on health-related quality of life.

The relation between birth size and the results of refractive error and biometry measurements in children

Purpose. This study examined the prevalence rate of astigmatism and its epidemiological risk factors in Singapore school children. Methods. In a study of school children aged 7 to 9 years old in two schools in Singapore in 1999, a detailed questionnaire was administered to parents regarding reading or close-work habits, past history of close-work, family history, and socioeconomic factors. Cycloplegic refraction was performed five times in each eye. Defining astigmatism as worse than or equal to 0.5, 0.75, and 1 D cylinder in the right eye, the prevalence of astigmatism was calculated. Results. The study population consisted of 1028 children. The prevalence rate of astigmatism (worse than or equal to 1 D cylinder) was 19.2% (95% confidence interval, 16.8 to 21.6). This was not different between genders, ethnic groups, or age (p > 0.05). With-the-rule astigmatism was more common than against-the-rule astigmatism. The prevalence of astigmatism and myopia was 9.8% (95% confidence interval, 8.0 to 11.6). A high AC/A ratio was associated (p = 0.003) with astigmatism, even after exclusion of myopic children. On vectorial analysis, J0 and J45 were associated with the number of hours of playing video games, whereas J45 was also associated with computer use. Only J45 was associated to male gender, a high AC/A ratio, and a family history of myopia. Conclusions. The prevalence rate of astigmatism (≥1 D) was 19%. Playing video games and computer use may be associated with astigmatism severity, although the presence of astigmatism (≥1 D) was not associated with any nearwork factors. A family history of myopia was associated with oblique astigmatism severity. A high AC/A ratio is associated with astigmatism, and this requires further investigation.

Visual acuity outcomes after deep anterior lamellar keratoplasty: a case-control study

Aim: To examine the association of birth parameters with biometry and refraction in Singapore Chinese schoolchildren. Methods: Chinese children aged 7–9 years (n = 1413) from three schools in Singapore were recruited. Birth parameter information on birth weight, head circumference, length at birth, and gestational age were obtained from standard hospital records. Cycloplegic autorefraction, keratometry and biometry measures (axial length, vitreous chamber depth, lens thickness, and anterior chamber depth) were obtained. Results: Across the normal birthweight range (2.0–4.9 kg), children with birth weights ⩾4.0 kg had longer axial lengths (adjusted mean 23.65 mm versus 23.16 mm), compared with children with birth weights <2.5 kg, after controlling for age, sex, school, height, parental myopia, and gestational age. For every 1 cm increment in head circumference at birth, the axial length was longer by 0.05 mm. For every 1 cm increment in birth length, the axial length was longer by 0.02 mm in multivariate analysis. Additional week increases in gestational age till 46 weeks resulted in axial lengths that were longer by 0.04 mm, controlling for age, sex, school, parental myopia, and height. Children with larger birth weights, head circumferences, birth lengths, or gestational ages had deeper vitreous chambers and larger corneal curvature radii; however, there were no significant associations with refraction. Conclusions: Children who were born heavier, had larger head sizes or lengths at birth, or who were born more mature had longer axial lengths, and deeper vitreous chambers; but there were no differences in refraction at ages 7–9 years, possibly because of the observed compensatory flattening of the cornea.

AlphaCor™ cases : comparative outcomes

Aim To compare visual outcomes between deep anterior lamellar keratoplasty (DALK) and penetrating keratoplasty (PK). Secondarily to compare refractive outcomes, complications and graft survival between the three cohorts. Methods Retrospective case-control study evaluating visual acuity outcomes (VA) following DALK with complete Descemets baring (DALKa) (modified Anwar big bubble technique—51 eyes), pre-descemetic anterior lamellar keratoplasty (DALKm) (manual technique—52 eyes) and PK (103 eyes) with mean follow-up of 13.6, 19.3 and 18.6 months, respectively. Results The common indications for surgery were corneal scars (36.4%), keratoconus (28.6%) and corneal dystrophies (13.6%). A best-corrected VA of 6/7.5 or better was achieved in 19.4% (PK), 21.6% (DALKm) and 38.5% (DALKa) of cases (p=0.02), and eyes that underwent DALKa had significantly better visual outcomes than PK (p=0.03). Complications following PK were glaucoma (15%), endothelial rejection (12%) and epithelial problems (11%); in the lamellar group, glaucoma (9%), epithelial problems (5%) and Descemets detachment (3%) were more common. The 2-year estimated probability of graft survival was 90% for PK, 98% for DALKm and 100.0% for DALKa (p=0.35). Conclusions Lamellar keratoplasty with complete baring of the Descemets membrane (DALKa) gave significantly better visual outcomes compared to PK or pre-descemetic ALK and should be the preferred from of corneal replacement in corneal disorders with healthy endothelium.