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Johnson Choon-Hwai Tan, Wee-Jin HengNational Healthcare Group Eye Institute, Tan Tock Seng Hospital, SingaporeBackground: The purpose of this report is to describe the initial outcomes of femtosecond laser-assisted penetrating keratoplasty.Methods: This retrospective surgical case series consisted of 10 eyes from 10 patients undergoing penetrating keratoplasty at a tertiary center. Femtosecond laser was used to perform a zig-square incision on the donor cornea with matched dimensions on the recipient cornea. Outcomes measured included: unaided visual acuity and best spectacle-corrected visual acuity preoperatively and at one, 3, 6, and 12 months postoperatively; manifest refractive and topographic astigmatism at 3, 6, and 12 months postoperatively; and endothelial cell density loss, calculated at the end of the one-year follow-up period.Results: At one-year follow-up, there was an improvement in unaided visual acuity from a mean preoperative logMAR of 1.67 to 0.44, and best spectacle-corrected visual acuity from a mean preoperative logMAR of 1.33 to 0.13. By postoperative month 3, mean manifest refractive and topographic astigmatism was 2.31 ± 1.41 D and 2.59 ± 1.57 D, respectively. The mean reduction in endothelial cell density was 20.7% after one year of follow-up.Conclusion: Femtosecond laser-assisted penetrating keratoplasty provided a good visual outcome and early visual rehabilitation due to precise graft-host alignment and reduced astigmatism in the early postoperative months.Keywords: penetrating keratoplasty, femtosecond laser-assisted keratoplasty

Purpose: To examine the associations between higher order aberrations (HOAs), visual performance, demographics, and ocular characteristics in a young Asian population with high myopia., Methods: This was a retrospective review of military pre-enlistees conducted between March 2014 to September 2018. Visual acuity and contrast sensitivity were tested under photopic, mesopic and simulated night conditions. Ocular, corneal and internal HOAs were measured with a Hartmann-Shack wavefront aberrometer (KR-1W, Topcon Co., Tokyo, Japan)., Results: 522 eyes of 263 consecutive subjects with severe high myopia (defined as spherical equivalent refraction [SER] ≤ -10.00D) in at least one eye, and high myopia (SER ≤ -6.00D) in the fellow eye, [mean (SD) SER -11.85 (2.03D)] were analysed. The mean (SD) age of subjects was 18.5 (1.6) years. Chinese eyes had significantly greater internal total HOA root-mean-square (RMS) compared to Malay eyes [mean difference (SD) 0.0246 (0.007) μm, p < 0.001). More negative SER was associated with greater ocular total HOA (p = 0.038), primary coma (p = 0.003) and tetrafoil (p = 0.025) RMS, as well as more positive ocular (p = 0.003) and internal primary spherical aberration (p = 0.009). Greater ocular total HOAs was associated with reduced visual acuity in simulated night conditions and low contrast, decreased contrast sensitivity under mesopic and simulated night conditions (all p < 0.05)., Conclusions: Greater HOAs were associated with Chinese ethnicity and more negative SER in a young Asian population with high myopia. Greater HOAs were associated with poorer visual performance in low luminance and reduced contrast conditions., Competing Interests: No conflicting relationship exists for any author., (© 2023 The Authors.)

Abstract: 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., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Asia-Pacific Academy of Ophthalmology. Published by Wolters Kluwer Health, Inc. on behalf of the Asia-Pacific Academy of Ophthalmology.)

Objectives: This comparative study aimed to determine if total keratometry (TK) from IOLMaster 700 could be applied to conventional formulas to perform IOL power calculation in eyes with previous myopic laser refractive surgery, and to evaluate their accuracy with known post-laser refractive surgery formulas., Methods: Sixty-four eyes of 49 patients with previous myopic laser refractive surgery were evaluated 1 month after cataract surgery. A comparison of the prediction error was made between no clinical history post-laser refractive surgery formulas (Barrett True-K, Haigis-L, Shammas-PL) and conventional formulas (EVO, Haigis, Hoffer Q, Holladay I, and SRK/T) using TK values obtained with the optical biometer IOLMaster 700 (Carl Zeiss Meditec), as well as Barrett True-K with TK., Results: The mean prediction error was statistically different from zero for Barrett True-K, Barrett True-K with TK, Haigis-L, Shammas-PL, and Holladay I with TK. The mean absolute error (MAE) was 0.424, 0.671, 0.638, 0.439, 0.408, 0.424, 0.479, 0.647, and 0.524, and median absolute error (MedAE) was 0.388, 0.586, 0.605, 0.298, 0.294, 0.324, 0.333, 0.438, and 0.377 for Barrett True-K, Haigis-L, Shammas-PL, Barrett True-K TK, EVO with TK, Haigis with TK, Hoffer Q with TK, Holladay I with TK, and SRK/T with TK, respectively. EVO TK followed by Barrett True-K TK and Haigis TK achieved the highest percentages of patients with absolute prediction error within 0.50 and 1.00 D (68.75%, 92.19%, and 64.06%, 92.19%, respectively) CONCLUSIONS: Formulas combined with TK achieve similar or better results compared to existing no-history post-myopic laser refractive surgery formulas.

An experimental study to measure the heat profile of the phacoemulsification (phaco) tip using standard continuous phaco and hyperpulse phaco with and without waveform power modulation in the Millennium Microsurgical System with Custom Control Software (CCS). The phaco tip was imaged in air using a thermal camera. The highest temperature was measured 15 s after application of phaco power. Continuous, hyperpulse and waveform power modulations of the Millennium Microsurgical System were used with different power settings (20, 50 and 100 %) and duty cycles (40, 60 and 90 %), with the irrigation turned on and off. Using continuous phaco with the irrigation on, the phaco tip temperature remains <28.0 °C. With irrigation off, the temperature is higher compared to irrigation on but still remains <45.0 °C. Comparing the temperatures for all three power modulations when irrigation is on, at each phaco power and duty cycle setting, the temperature of the phaco tip is highest with continuous phaco, followed by hyperpulse with rise time 1, then hyperpulse with rise time 2. When irrigation is off, the highest temperatures are recorded using the hyperpulse with rise time 2, followed by continuous phaco, then hyperpulse with rise time 1. Hyperpulse and waveform modulations reduce heat generation compared to the continuous mode when irrigation is turned on. Lower duty cycles and lower ultrasound power produce less heat at the phaco tip.

Objective: Although registered nurses frequently perform triaging in many emergency departments (EDs), little is known regarding the agreement between nurses and doctors in triaging dyspneic patients. The aim of our study was to compare the effectiveness of trained ED nurses with doctors in the evaluation of dyspneic patients at triage using the SimMan 3G simulator., Methods: We compared eight nurses who underwent a structured training/accreditation program with eight doctors. Two assessors evaluated them through seven common and/or important cardiorespiratory simulated scenarios. Each scenario had an evaluation instrument that scored participants on triage assessment and management. Each nurse was also surveyed over a six-point Likert scale (0-5) on their confidence in triaging dyspneic patients after the study. Data was analyzed using descriptive statistics with statistical significance set at p<0.05., Data/results: There were no statistically significant differences between the mean assessment or management scores across all scenarios between doctors versus nurses (p ranging from 0.070 to 0.798). Six nurses felt they could evaluate ED dyspneic patients alone (score of 4) and the remainder with supervision (score of 2-3)., Conclusion: Trained ED nurses; when compared to doctors; could triage and evaluate dyspneic patients effectively on a simulator., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Nurses are usually the first caregivers for cardiac arrest patients in an in-hospital environment, and subsequently partner with doctors in the further resuscitation of patients. The skills of basic life support are crucial for their practice. The Advanced Cardiac Life Support programme is traditionally geared toward training of medical staff in advanced resuscitation skills. The need for a bridging course that focuses on the knowledge and skills required by nurses to become effective members of the resuscitation team has resulted in the creation of the Life Support Course for Nurses (LSCN) in Singapore. The components of the LSCN programme have evolved over the years, taking into consideration the modifications to resuscitation guidelines. The LSCN programme is gradually including a larger proportion of nurses in the emergency and critical care environments as well as those in the general ward.

Aims: To determine the analgesic effect of supplemental intracameral lidocaine 1% during phacoemulsification under topical anaesthesia, and to assess the risk factors associated with pain., Methods: In a double-masked, randomised, clinical trial, 506 patients undergoing phacoemulsification under topical anaesthesia were randomised to receive a supplemental intracameral injection of either 0.5 cc of 1% lidocaine (277 patients, 54.7%) or balanced salt solution (BSS) (229 patients, 45.3%). Patients were interviewed by a trained interviewer using a standardised questionnaire. The main outcome measure was intraoperative pain, scored on a visual analogue scale of 0-10. Logistic regression was performed to assess ORs., Results: 125 of 277 patients (45.1%) experienced pain in the lidocaine group, compared with 123 of 229 patients (53.7%) in the BSS group. The proportion of patients who experienced pain was significantly lower in the intracameral lidocaine group compared with the BSS group (multivariate OR 0.68, 95% CI 0.47 to 0.97; p=0.034). The median pain score (range) was 0.0 for intracameral lidocaine group compared with 1.0 for BSS group (p=0.039). Pain was more common in females (54.3% vs 43.6%; OR 1.56), non-Chinese (62.3% vs 46.9%; OR 2.13) and those who had previous cataract surgery to the fellow eye (55.3% vs 44.7%; OR 1.61)., Conclusion: The use of 0.5 cc of 1% intracameral lidocaine during phacoemulsification under topical anaesthesia significantly reduces pain experienced by patients. Risk factors for pain include females, non-Chinese and previous cataract surgery.

Introduction: While non-contrast computed tomography (CT) of the brain can be used to rapidly identify patients with altered mental status (AMS) in the emergency department (ED), with an acute intracranial bleed or infarct, a wide variation in its use exists. The aim of this pilot study was to identify the clinical predictors of an abnormal CT result in ED patients with AMS., Methods: We conducted a retrospective study of patients aged 15 years and older presenting with undifferentiated AMS in a busy urban ED over one year. Data collected included demographical, clinical, laboratory and radiological features. The primary outcome of interest was the presence of an abnormal CT result defined as an acute infarct or intracranial bleed. Secondary outcomes were clinical predictors of an abnormal CT result. The data was analysed using descriptive statistics. Logistic regression was used to identify clinical predictors of an abnormal CT result. Odds ratios (ORs) were reported with 95 percent confidence intervals (CIs)., Results: 578 patients were recruited, of which 284 (49.1 percent) were males. 327 (56.6 percent) patients underwent CT of the brain. 128 scans (39.1 percent) were abnormal. Logistic regression revealed seven clinical features that were associated with an abnormal CT result. They were mean age greater than or equal to 73 years (OR 1.03; 95 percent CI 1.015-1.045), drowsiness or unresponsiveness (OR 1.73; 95 percent CI 0.17-17.72), previous cerebrovascular accident (OR 2.03; 95 percent CI 0.82-5.02), previous epilepsy (OR 1.63; 95 percent CI 0.63-4.19), tachycardia [greater than 120/min] (OR 1.16; 95 percent CI 0.38-3.54), bradycardia [less than 60/min] (OR 1.35; 95 percent CI 0.19-9.59) and exposure to drugs (OR 1.90; 95 percent CI 0.58-6.26)., Conclusion: We identified seven clinical predictors of an abnormal CT result in AMS patients. Future research in prospective studies is needed to validate these findings.

Purpose: To describe an outbreak of Acanthamoeba keratitis (AK) cases among contact lens wearers., Design: Retrospective cohort study., Methods: Patients with AK were included. Relevant demographic and clinical data were obtained from case records, and patients were interviewed using a standardized questionnaire. Contact lens practices, including type of contact lens and solution used, were noted. In addition, clinical features at presentation, management, and clinical outcomes were recorded., Results: Forty-two patients (affecting 43 eyes) treated between 2000 and 2007 were included. Diagnosis was made by microbiologic culture in 35 cases and by microbiologic and histologic analysis in 2 cases, whereas the remainder were diagnosed based on clinical features and response to treatment. There was a gradual increase in cases since 2005, with a sharp increase in 2007, when 8 local patients were treated. Of 30 patients where contact lens solution data were available, 18 reported using a Complete brand Multipurpose solution (Advanced Medical Optics, Santa Ana, California, USA) before the infection. Among resident cases treated since February 2006, 7 (63%) of 11 patients used a Complete brand solution. Suboptimal hygiene practices were found in all patients interviewed. Fifteen patients required corneal grafting, with 11 undergoing therapeutic deep lamellar keratoplasty (DLK), 2 undergoing optical penetrating keratoplasty (PK), 1 undergoing optical DLK, and 1 undergoing therapeutic PK. The remainder were treated successfully medically with combination antiamebic therapy. The average duration of therapy was 116.2 days (range, 15 to 283 days). Of patients with radial keratoneuritis with or without epithelial disease, 83.3% achieved final vision of 20/40 or better, whereas this was achieved in 41.7% of those with ring infiltrate. Twenty-five percent of patients with ring infiltrate had final visual acuity of counting fingers or worse, whereas no patient with keratoneuritis and epithelial disease had final vision worse than counting fingers., Conclusions: There was an increase in the number of contact lens users with AK seen in the major eye departments of Singapore. Most of our patients also reported using a Complete brand Multipurpose solution before infection, and this parallels a similar outbreak in the United States. Increasing severity of infection was associated with worse visual outcome.

Somatic mutations in epidermal growth factor receptor (EGFR) tyrosine kinase domain, particularly deletions in exon 19 and point mutation in exon 21, are associated with clinical outcome in patients with lung adenocarcinoma, suggesting that EGFR mutation would have an important role in clinical decision making. DNA was extracted from the excised specimens of 60 lung adenocarcinoma patients with phenol-chloroform and ethanol precipitation. Exon 19 and 21 were amplified by PCR, and direct sequenced from both sense and antisense directions. EGFR somatic mutations were present in 13 of 60 patients (21.67%), including seven cases of in-frame deletion in exon 19 around codon 746 and six cases of amino acid substitution in exon 21. Exon 21 mutation is more frequent in adenocarcinomas with bronchi-alveolar component than exon 19 deletions. Mutations were more prevalent in well-differentiated adenocarcinomas (9/27, 33.33%) than in moderate to poor-differentiated adenocarcinomas (4/33, 12.12%) (P < 0.05). Adenocarcinomas with bronchi-alveolar components had higher mutation frequency (8/22,36. 36%) than those without bronchi-alveolar components (5/38, 13.16%) (P < 0.05). In this study, female patients had more mutation rate than male patients. This trend was also observed in the patients with pathologic stage I-II compared with stage III-IV, but neither of them was statistically significant. Patients with cisplatin-based adjuvant chemotherapy had no significantly prolonged survival compared with single radical resection. But patients with EGFR mutation had relative longer survival. In conclusion, our study suggest that EGFR mutations may be a valuable prognostic factor for disease free survival of surgically treated lung adenocarcinoma patients independently from adjuvant chemotherapy.

Objective: To investigate P2Y purinergic receptor activated PI-3K/Akt signaling pathway in the regulation of growth and invasion of prostate cancer in vitro., Methods: Western blot was used to detect phosphorylation of Akt (a downstream target molecule of PI-3K) by P2Y receptor agonist in 1E8 cells (a highly metastatic subclone derived from PC-3 prostatic cancer cell line). Cell counts, flow cytometry, Matrigel invasion assay, wound healing assay and gelatin zymography were used to detect changes of biological behaviors of 1E8 cells after P2Y receptor activation., Results: AMP-PNP, one non-hydrolysis ATP analogue and P2Y receptor agonist, induced significant phosphorylation of Akt in a time- and dose-dependent manner in IE8 cells. LY294002, a specific inhibitor of PI-3K, effectively blocked Akt phosphorylation induced by AMP-PNP. Continuous exposure to AMP-PNP induced significant growth inhibition of 1E8 cells (inhibition rate at 50.2% at the 8th day), and this inhibition was mainly due to an arrest at S phase of the cell cycle (the S phase fraction of AMP-PNP treated cells was 22.3% higher than that of the control). Application of LY294002 did not reverse the growth inhibition effect of AMP-PNP. Matrigel invasion assay showed that AMP-PNP stimulation increased invasive ability of 1E8 cells, and this effect was effectively blocked by LY294002. No significant changes in the activation of MMP-2 and MMP-9 were detected by gelatin zymography, although wound healing assay showed 21.2% increase in cell migration after AMP-PNP treatment., Conclusions: PI-3K/Akt signaling pathway participates in P2Y receptor-stimulated prostate cancer invasion by enhancing cell motility, rather than up-regulating MMP-2 and MMP-9 activities. PI-3K signaling pathway plays an important role in prostate cancer proliferation, but is not involved in P2Y receptor mediated growth inhibition.

Background: To describe the acute and late ocular manifestations and complications in toxic epidermal necrosis (TEN) and Stevens-Johnson syndrome (SJS), and identify predictors for development of late complications., Methods: Cases of TEN and SJS during a 9-year period were included. Patients with ocular involvement were reviewed for acute ocular complications. Patients with a minimum 6 months follow-up were reviewed for late complications. Records were reviewed for their demographics, etiology, and severity of ocular involvement., Results: There were 117 patients with a mean age of 52.2 +/- 18.6 years. Eighty-one of these (69%) had acute ocular involvement. This was mild in 40%, moderate in 25% and severe in 4%. Adverse drug reactions were the predominant cause. Patients with thrombocytopenia had more severe acute ocular involvement. Forty-four patients had a minimum 6 months of follow-up and half developed late complications. Severe dry eyes and trichiatic lashes were the commonest late complications. Patients treated with topical antibiotic were more likely to have late complications, particularly dry eyes. There was no difference in the severity of acute eye involvement or late complications when SJS and TEN patients were compared. The severity of the acute ocular disease and abnormal laboratory tests were not found to be the significant risk factors of late complications., Conclusions: Ocular involvement is common in SJS and TEN and can be severe and blinding. The severity of acute ocular complications does not predict late complications. The diagnosis of TEN does not imply a more severe ocular involvement or increased frequency of late ocular complications compared with SJS. Care should be taken even in mild cases. Appropriate intervention during acute ocular disease may prevent late complications.

Objective: To study the role of Mycobacterium tuberculosis in the pathogenesis of sarcoidosis., Methods: Archival material of 22 patients with a histologic diagnosis of sarcoidosis were retrieved. Real-time fluorescent polymerase chain reaction (PCR) was used to detect DNA fragments of the complex-specific insertion sequence IS6110 of Mycobacterium tuberculosis in formalin-fixed and paraffin-embedded biopsy samples., Results: Among the 22 samples studied, Mycobacterium tuberculosis DNA was detected in 11 cases. The sequence of PCR amplified IS6110 DNA fragments completely matched with the related sequence in Mycobacterium tuberculosis gene., Conclusions: Mycobacterium tuberculosis DNA is identified in a certain proportion of patients with a clinicopathologic diagnosis of sarcoidosis. Mycobacterium tuberculosis may be an important etiologic agent, at least in some of these patients.

Introduction: The aim of the study was to compare the visual performance of LASIK eyes measured using high-contrast logMAR letter charts under bright (photopic) and dim (mesopic) conditions., Materials and Methods: A total of 46 subjects (35 +/- 8 years of age) undergoing LASIK procedures were recruited for the study. The best spectacle-corrected visual acuity (BSCVA) of each subject was measured using the high-contrast ETDRS logMAR chart under photopic and mesopic conditions at 3 visits: preoperative (Pre), 1 month postoperative (Post1) and 3 months postoperative (Post3). The differences in logMAR scores for the right eyes only were analysed for the Pre-Post1 (n = 46), Pre-Post3 (n = 18) and Post1-Post3 (n = 16) comparisons., Results: The logMAR scores of subjects were worse at the 1-month postoperative visit than preoperatively, and improvement in visual performance was seen at the 3-month postoperative visit. These changes in visual performance became more evident under mesopic conditions. The means and standard errors of the differences in logMAR scores for the Pre-Post3 (0.097 +/- 0.020) were slightly larger than those of the Pre-Post1 (-0.067 +/- 0.019) and Post1-Post3 (0.031 +/- 0.012) comparisons. Under mesopic conditions, the visual performance of the subjects was statistically significant for the 3 comparisons, but not under photopic conditions., Conclusion: High-contrast logMAR chart performed under mesopic conditions has the potential to replace visual acuity measured under photopic conditions in providing more reliable representation of postoperative visual outcomes of LASIK eyes. Eye doctors should consider performing this vision test routinely to gauge the success of LASIK surgery.

Introduction: To report the sequential changes in corneal topography and astigmatism following limited macular translocation. CLINICAL PICTURE AND TREATMENT: A 45-year-old-man who underwent limited macular translocation for idiopathic subfoveal choroidal neovascularisation in the right eye was evaluated by corneal topography and manifest refraction preoperatively and serially for 1 year postoperatively., Outcome: An increase in astigmatism with corneal steepening along meridians corresponding to the area of chorioscleral infolding was observed and this persisted for 1 year after surgery. Vector-analysed astigmatic change showed significant surgically induced astigmatism of 2.18 dioptres (D) X 52.9 degrees, 2.17 D X 57.8 degrees and 2.56 D X 59.1 degrees at 2, 5 and 12 months after surgery respectively., Conclusion: Surgically induced corneal changes are evident after limited macular translocation and may remain up to 1 year after surgery.

Context: Fungal keratitis is a potentially blinding condition that is rarely seen with contact lens wear., Objective: To describe a nationwide outbreak of fungal keratitis caused by Fusarium species among contact lens wearers in Singapore., Design, Setting, and Patients: Nationwide, hospital-based case series. All cases of fungal keratitis among contact lens wearers in all ophthalmology departments in Singapore were reviewed along with the charts of all contact lens wearers with culture-proven fungal keratitis from March 2005 through May 2006. A standardized telephone interview was conducted to obtain additional clinical information., Main Outcome Measure: Diagnosis of Fusarium keratitis associated with contact lens wear., Results: During the study period, 66 patients (68 affected eyes) were diagnosed with Fusarium keratitis associated with contact lens wear; the estimated annual national incidence is 2.35 cases per 10,000 contact lens wearers (95% confidence interval, 0.62-7.22). Patients ranged in age from 13 to 44 years (mean [SD], 27.1 [8.4] years), of which 32 (48.5%) were men. The vast majority (65 patients; 98.5%) wore soft, disposable contact lenses; 62 patients (93.9%) reported using 1 brand of contact lens cleaning solution (ReNu, Bausch & Lomb, Rochester, NY), including 42 patients (63.6%) who recalled using ReNu with MoistureLoc. Most patients (81.8%) reported poor contact lens hygiene practices, including overnight use of daily wear contact lenses (19.7%), and use of contact lenses past the replacement date (43.9%). The final best-corrected visual acuity ranged from 20/20 to 20/80. Five patients (5 eyes; 7.4%) required emergency therapeutic or tectonic corneal transplantation., Conclusions: A new and evolving epidemic of Fusarium keratitis associated with contact lens wear was found in Singapore. Physicians and eye care practitioners worldwide need to be aware of the likelihood of similar outbreaks emerging among contact lens wearers.

Objective: To investigate the status of c-kit and PDGFRA mutations of GIST in a the large sample of Chinese patients., Method: One hundred and sixty-five cases were evaluated for the presence of c-kit and PDGFRA mutations. Exon 9, 11, 13, 17 of c-kit and exon 12, 18 of PDGFRA were analyzed by PCR amplification and direct sequencing., Results: Immunohistochemical demonstrations of KIT (CD117) were seen in 94% of the cases (155/165). Overall, c-kit mutations were identified in 76.1% (118/155) of CD117 positive cases: 67.1% (104/155) involving exon 11, 7.1% (11/155) involving exon 9, 1.3% (2/155) involving exon 13 and 0.6% (1/155) involving exon 17. The c-kit exon 11 mutations were mostly heterogeneous and clustered in the classic "hot spot" at the 5' end of the exon, including in-frame deletion and point mutation. The second "hot spots" were internal tandem duplications (ITD) at the 3' end of the exon, which were associated with female patient, older age, stomach location and low mitotic counts. The exon 9 mutations correlated with a distinct subset of GISTs involving the small bowel of young male patients. A new point mutation of L641P was identified in exon 13. PDGFRA mutations were present in 50% (5/10) of CD117-negative GISTs, all involving exon 18 with the majority of mutations being D842V. One novel in-frame deletion of IMHD mutation at codon 843 - 846 with S847T was identified. GISTs with PDGFRA mutations were often larger tumors arising from the omentum/mesentery of young male patients with high risk of aggressive behavior., Conclusions: The vast majority of GISTs in this study harbored c-kit and PDGFRA mutations, there were non-random relations between the gene mutation patterns and the locations of GISTs. It appears that Chinese GIST patients have some unique mutation patterns. It is necessary to evaluate the gene mutations status of GISTs to guide target therapy.

Purpose: To compare acute ocular complications of toxic epidermal necrolysis (TEN) following treatment with high-dose human intravenous immunoglobulin (IVIG) with a historical cohort not treated with IVIG., Methods: Retrospective, historically controlled study. In all, 10 consecutive patients with TEN (treatment cohort) presenting between 1 July 2001 and 30 June 2002. Totally, 18 consecutive patients with TEN (historical cohort). SettingTan Tock Seng Hospital, Singapore. The treatment cohort received high-dose IVIG (2 g/kg body weight over 2 days). Patients' records were retrospectively reviewed for their demographic characteristics, causative drug, treatment, ocular involvement (if any, as assessed by an ophthamologist), and its severity. The historical cohort comprised patients coded with a diagnosis of TEN (ICD Code 695.1) between 1 July 1995 and 30 June 2001., Results: Nine (90%) of 10 patients treated with IVIG had ocular involvement. Phenytoin was the implicated drug in three (37.5%) patients. Of the nine patients, 1 died of septic shock. Of the eight survivors, IVIG was initiated immediately upon onset of TEN as all the patients were hospitalized by the time of onset of an exanthema. Acute ocular complications were mild in two (25%) (lid oedema or mild conjunctival injection), moderate in four (50%) (pseudomembranes) and severe in two (25%) (nonhealing epithelial defect with visual loss and symblepharon). In total, 10 (55.6%) of 18 patients in the historical cohort with TEN had acute ocular involvement. Two patients died. Ocular involvement in survivors was mild in five (62.5%) cases and moderate in three (37.5%), with no severe cases., Conclusions: IVIG did not appear to reduce the severity of visually significant ocular complications. Larger studies are needed to confirm this finding.

Aim: To assess the knowledge and willingness of Singapore adults towards corneal donation., Methods: The study population consists of a cluster random sample of the population living in Bedok North (an area in the eastern part of Singapore). The study population comprised residents aged 21-65 years living in 675 randomly sampled housing units. The participation rate was 65.9% (544/825). All participants were interviewed face to face with a questionnaire formulated according to the modified Horton and Horton model. Knowledge, values, attitudes, and spiritual beliefs of participants were assessed to evaluate their willingness to donate their corneas., Results: 67.0% of participants were willing to donate their corneas. Ethnicity (Chinese) and religion (Christians, Hindus, or those with no religion) were associated with increased willingness to donate corneas. Greater knowledge and increased altruistic values were also associated with increased willingness to donate corneas., Conclusion: A proportion of participants were willing to donate their corneas. Awareness of corneal donation is high but specific knowledge should be further increased among adults.

Objective: To investigate the effects of protein tyrosine phosphatase-SHP2 and dual-specificity MAPK phosphatase-MKP5 on the activation of MAPKs and cell invasion induced by P2Y purinergic receptor in human prostate cancer cell lines with different metastatic potentials., Methods: The wide type (-wt) SHP2, mutant type (-cs) SHP2 and wide type (-wt) MKP5 cDNA expression vectors were constructed and stably transfected into 1E8 cells (highly metastatic) and/or 2B4 cells (non-metastatic). The tyrosine phosphorylation of SHP2 was examined by immunoprecipitation. The activation of ERK1/2 and p38 induced by P2Y receptor agonist ATP was analyzed by Western blot with phospho-specific antibodies against the dually phosphorylated, active forms of ERK1/2 and p38. The in-vitro invasive ability through Matrigel was measured by boyden-chamber assay., Results: ATP induced significant SHP2 phosphorylation, which was stronger and lasted longer in 1E8 than in 2B4. SHP2-wt enhanced the ERK1/2 activation induced by ATP in 2B4 cells, while SHP2-cs delayed and decreased this effect in 1E8 cells. Both SHP2-wt and SHP2-cs had no obvious influence on p38 activation. ATP stimulated cell invasion of both 1E8 and 2B4, while transfection of SHP2-wt into 2B4 cells further increased the invasive-stimulating ability of ATP (18.7% increase compared with ATP treatment alone). Transfection of SHP2-cs into 1E8 cells, however, antagonized the invasive-stimulating ability of ATP (40.9% decrease compared with ATP treated group). Up-regulation of MKP5-wt inhibited phosphorylation of p38 by ATP and reduced cell invasion stimulated by ATP (22.4% and 28.7% decrease compared with ATP treated group of 1E8 and 2B4, respectively)., Conclusions: Both SHP2 and MKP5 play some roles in P2Y receptor-mediated activation of MEK/ERK, p38 signaling pathways and prostate cancer invasion. SHP2 positively regulates ERK activation and prostate cancer invasion, whereas MKP5 inhibits the invasion by suppressing p38 activation.

Hypoxia-inducible factor (HIF) is critical in the modulation of tumour angiogenesis in response to hypoxia. In the present study, the mechanisms underlying basic fibroblast growth factor (bFGF)-induced activation of HIF-1 and the subsequent release of vascular endothelial growth factor (VEGF) in a human breast cancer cell line (T47D) under normoxic conditions were explored. The data show that HIF-1alpha expression is induced by bFGF in a dose- and time-dependent fashion, while increased HIF-1alpha protein expression and transactivity of HIF-1 are due to the phosphorylation of Akt by bFGF, as indicated by application of the phosphatidylinositol 3-kinase (PI-3K) inhibitor LY294002. The data also show that the MEK1 (mitogen-activated protein kinase kinase-1)/ERK (extracellular signal-regulated kinase) pathway is only involved in bFGF-induced transactivity of HIF-1, but not HIF-1alpha expression, indicating roles for both the PI-3K/Akt and the MEK1/ERK pathways in bFGF activity. In addition, the translation inhibitor cycloheximide confirmed that bFGF-induced HIF-1alpha protein expression was due to de novo protein synthesis. In contrast, p38 was not required for the expression of HIF-1alpha or HIF-1 transactivity, although significant phosphorylation of p38 was observed after bFGF treatment. Treatment of the cells with bFGF increased the amount of VEGF release, and this could be suppressed by either PD98059 or LY294002, suggesting the presence of a HIF-1alpha-dependent pathway for bFGF-induced VEGF production. In conclusion, the PI-3K/Akt and MEK1/ERK pathways, in a potentially independent and co-operative fashion, can modulate HIF-1 activation by bFGF. Further studies will pinpoint whether HIF-1 is the transcriptional factor responsible for the increased VEGF production following bFGF treatment of breast tumour cells.

Objective: To explore whether ERK1/2 and p38 pathways mediate P2Y receptor-induced prostate cancer invasion., Methods: The two subclones from the PC-3 human prostate carcinoma cell line: 1E8 (highly metastatic) and 2B4 (non-metastatic), were cultured and transfected with the plasmid pcDNA3-KA-MEK1 containing the dominant negative mutant of MEK1 (KA-MEK1) and wild type MKP-5 (a dual-specificity phosphatase of p38). P2Y receptor-activated ERK1/2 and p38 kinases were detected using phospho-specific antibodies directed against the dually phosphorylated active forms of these kinases by Western blotting. P2Y receptor agonists ATP and P2Y receptor antagonist suramin were used respectively to observe their effects on the activity of ERK1/2. The roles ERK1/2 and p38 pathways play in P2Y receptor-induced in vitro invasion were detected by in vitro invasion assay. The cells were pre-treated with ATP, SB203580, a p38 inhibitor, and PD98059, a blocker of ERK1/2 pathway, respectively., Results: ATP activated ERK1/2 and p38 kinase time-dependently. Suramin significantly inhibited the activation of ERK1/2 and p38 kinase by ATP. ATP stimulated prostate cancer cell invasion. The stimulated cancer cell invasion was significantly inhibited by pretreatment of the cells with PD98059 or SB203580. Transfected of 1E8 cells with KA-MEK1 or up-regulation of MKP-5 both, while inhibiting phosphorylation of ERK1/2 or p38, significantly reduced the invasion of prostate cancer cells in vitro., Conclusion: P2Y receptor-induced prostate cancer cell invasion is mainly regulated through ERK1/2 and p38 pathways.

The G protein-coupled P2Y purinoceptors have wide physiological functions, but their role(s) in tumor progression remain unclear. Here, we report that stimulation of P2Y receptors enhances prostate cancer cell invasion in two human prostate carcinoma cell lines, which is mediated by ERK1/2 and p38 signaling pathways. P2Y agonists stimulated prostate cancer cell invasion, and increased the activities of ERK1/2 and p38 protein kinases. The stimulated cancer cell invasion was inhibited by the presence of MEK1 inhibitor PD98059 or p38 inhibitor SB203580. Expression of dominant-negative mutant of MEK1 (KA-MEK1), or up-regulation of MKP-5 (a dual-specificity phosphatase of p38), both reduced the invasion of cultured prostate cancer cells. These results suggest that P2Y receptors and their down-stream ERK1/2 and p38 protein kinases are important regulators promoting prostate cancer invasion.

Objective: To explore the mechanism of basic fibroblast growth factor (bFGF)-mediated hypoxia inducible factor (HIF-1) activation and the down-stream signaling pathways involved., Methods: Human breast cancer cells of the line T47D were cultured and lysed to extract the total protein in the supernatant. The amounts of extracellular signal kinase 1/2 (ERK1/2), Akt, p38, and beta-tubulin were measured. T47D cells were inoculated into a 24-well plate, co-transfected with luciferase vector OB-HRE containing HIF-1 functional sequence (HRE) and pRL-SV40 (as inner marker), pretreated with SU5402, inhibitor of FGFR1, SB203580, inhibitors of PI-3K, PD98059, inhibitors of MEK1, or LY294002, inhibitors of p38, treated with basic fibroblast growth factor (bFGF), and then lysed. The amounts of ERK1/2, Akt, p38, and beta-tubulin were measured. Western blotting was used to detect the HIF-1alpha level in total protein. Dual luciferase assay was used to analyze the transactivity of HIF-1. The firefly/renilla luciferase ratio was measured to access the transcription activity of HIF-1. Western blotting was used to detect the expression of HIF-1alpha protein and phosphorylated Akt, ERK1/2 and p38 in whole cell extract., Results: After the addition of bFGF Western blotting showed that the and phosphorylation of Akt, ERK1/2 and p38 in the T47D cells were increased time- and dose-dependent manner, and dual luciferase assay showed that the fluorescent intensity was increased, signifying the increase of expression of HIF-1alpha protein. Ten minutes after the addition of CHX the expression of HIF-1alpha protein began to be decreased and ceased 90 minutes after. SU5402 remarkably dose-dependently blocked the bFGF-induced phosphorylation of ERK1/2, Akt and p38. 15 micromol/L LY294002 completely blocked the bFGF-induced phosphorylation of Akt. 5 micromol/L PD98059 blocked 80% of the bFGF-induced phosphorylation of ERK1/2. 10 approximately 20 micromol/L SB203580 basically blocked the bFGF-induced phosphorylation of p38. SU5402 and LY294002 100% inhibited the bFGF-induced expression of HIF-1alpha protein. However, PD98059 and SB203580 did not significantly influence the expression of HIF-1alpha protein induced by bFGF. Luciferase assay showed that SU5402 and PD98059 inhibited the bFGF-induced transcription activity of HIF-1 by 94.8% and 81.7% respectively. LY294002 not only completely inhibited the bFGF-induced transcription activity of HIF-1 but also inhibited the basic transcription of HIF-1, and SB203580 did not significantly influence the transcription activity of HIF-1., Conclusion: bFGF activates HIF-1 via the PI-3K/Akt and MEK1/ERK pathways that co-operatively and differentially regulate this process with PI-3K/Akt pathway playing a more important role.

Background & Objective: Metastasis is one of the most important factors in determining the prognosis of lung cancer patients. However, it is difficult to determine single cancer cell in lymph nodes by routine methods. This study was designed to investigate a sensitive method for detecting lymph node micrometastases in human lung carcinomas., Methods: Mutation detection for p53 gene (exon 5-8) was performed in 39 cases of primary lung carcinomas and 110 corresponding lymph nodes (LNS) by PCR-TGGE method. Serial sectioning was performed to confirm micrometastases in some of these samples., Results: p53 mutations were found in 23 of 39 cases with primary lung cancer. Forty LNSs showed p53 mutation in 67 corresponding LNSs. They were located at the same exon as their primary tumors. Only twenty-six LNSs were detected metastases by routine histopathology. Forty-three LNSs from sixteen cases of primary tumor without p53 mutation and ten LNSs from the patients without tumor disease did not have any p53 mutations. By PCR-TGGE assay p53 gene mutations were determined in fourteen LNSs without histopathological evidence of metastasis. Micrometastases were found in four of the serially sectioned cases., Conclusion: Mutation detection for p53 gene (exon 5-8) showed lymph node micrometastases in patients with lung carcinoma. It may be used as a complement for the routine histopathology.

Objective: To determine the role of extracellular signal-regulated kinase (ERK1/2) and p38 cascades in P2Y receptor-evoked effects on prostatic cancer cells., Methods: Highly metastatic prostatic cancer cells 1E8 were transfected with dominant-negative MAPK kinase 1 (KA-MEK1). The activation of ERK1/2 was determined by Western blot technique. The role of ERK1/2 and p38 cascades in P2Y receptor-evoked effects on in vitro growth, colony formation and in vitro invasion was detected by cell count, soft agar colony formation assay and in vitro invasion assay. The effect of ATP on apoptosis was detected by flow cytometry., Results: ERK1/2 activity in 1E8-KA-MEK1 transfectants was significantly suppressed by dominant-negative MEK1 transfection. After culture of 6 days, 1E8-KA-MEK1 transfectants exhibited a growth inhibition of 71% as compared with 1E8-pcDNA3 control. Moreover, after continuous treatment with 100 micro mol/L ATP for 6 days, the growth of 1E8-KA-MEK1 transfectants was further inhibited by an additional 17.2%. Pretreatment with 10 micro mol/L p38 inhibitor SB203580 antagonized the effect of ATP-induced additional growth inhibition, suggesting that ERK1/2 and p38 pathways play an important role in ATP-induced growth inhibition. In soft agar assay, 1E8-KA-MEK1 transfectants formed smaller colonies and exhibited a 75% decrease in colony formation (as compared with control). Further treatment with ATP or SB203580 plus ATP did not show significant effect on colony formation of 1E8-KA-MEK1 cells, implying a potential role of ERK1/2, instead of p38, in P2Y receptor-mediated inhibitory effect on colony formation. In in vitro invasion assay, 1E8-KA-MEK1 cells showed a 41% decrease in passing through matrigel-coated membranes, as compared with control. Treatment with ATP could restore their invasive ability, and this effect by ATP could be blocked by pretreatment with SB203580, indicating the involvement of both ERK1/2 and p38 pathways in invasive ability of prostatic cancer cells., Conclusions: The effects of ATP on in vitro growth, invasion and colony formation of prostatic cancer cells depend on the status of P2Y receptor activation by different treatment protocols. Continuous activation of P2Y receptor results in growth inhibition and transient activation of P2Y receptor stimulates in vitro invasion of prostatic cancer cells. Both ERK1/2 and p38 pathways are responsible for these effects; but only the ERK1/2 pathway is involved in regulation of colony formation of prostatic cancer cells.

Objective: To investigate the effects of mitogen-activated protein kinase phosphatase-5 (MKP5) on the biological behaviors of cell and the activation of mitogen-activated protein kinase (MAPK) induced by P2Y purinergic receptor agonist ATP in the prostate cancer cell line 1E8., Methods: 1E8 cells were cultured. The recombinant plasmid pcDL-SRalpha296-MKP5 containing the human wild type MKP5 cDNA and blank vector pcDL-SRalpha were co-transfected with pcDNA3 vector plasmid into the 1E8 cells respectively to get strong expression clones. RT-PCR was used to detect the expression of MKP5 mRNA. ATP, MEK inhibitor PD 98059, and p38 inhibitor SB 203580 were added into the culture. Then the total protein was extracted, SDS-PAGE and Western blotting were used to detect the activation of p38 and ERK1/2 induced by ATP with phosphospecific antibodies directed against the dually phosphorylated, active forms of p38 and ERK1/2. The in vitro growth curve was drawn, soft agar colony formation test was made, and Matrigel membrane-penetrating experiment was made to test the invasion ability of 1E8 cells., Results: The activity of p38 and that of ERK1/2 of the 1E8 cells untreated by ATP were almost undetected. ATP time-dependently stimulated the activities of ERK1/2 and p38 kinases, inhibited the in vitro growth and colony formation on soft agar, and promoted the in vitro invasion of 1E8 cells. MKP5-transfection effectively inhibited the p38 activity induced by ATP and blocked the effects by ATP stimulation on 1E8 cells. The activity of p38 kinase was significantly decreased both in the control and MKP5 transfected cells that were pretreated with SB203580 and then with ATP with an inhibition rates of 83.14% and 58.00% (P < 0.001 and P = 0.003). The growth of cells transfected with MKP5 was significantly inhibited (P < 0.001) and further inhibited by addition of ATP. The inhibition of growth of MKP5-transfected cells by ATP could be partially reversed by pretreatment of PD98059 (P < 0.05). The number of cells transfected with MKP5 that penetrated the membrane was significantly less than that of the control cells (P = 0.000 9). ATP increased the penetrating ability of different cells (all P < 0.01), and this action was partially inhibited by MKP5 transfection and addition of SB203580 (P < 0.001), but not by the addition of PD98059. ATP treatment decreased the colony formation on soft agar of different cells, especially of the MKP5 transfected cells (P < 0.001). Such action was partially reversed by SB203580 and PD98059., Conclusion: The p38 and ERK1/2 pathways exert different effects on the in vitro growth, invasion and colony formation of 1E8 prostate cancer cells related to ATP. The p38 pathway may be more important in the invasive capability of 1E8 cells. MKP5 plays an important role in the regulation of p38 action.

Objective: To develop a newly real-time RT-polymerase chain reaction assay for severe acute respiratory syndrome (SARS) related coronavirus in human whole blood., Methods: A pair of primers and a probe (molecular beacon) had been designed that were specific for the recognition of a highly conservative region between 15 301 and 15 480 of the SARS-related coronavirus polymerase gene sequences obtained from GenBank (G130027616)., Results: In the real-time RT-PCR assay, the extent of SARS related coronavirus amplification was measured in terms of the increase in fluorescence during the amplification process. The 145 bp fragment of PCR product was further confirmed by conventional PCR assay and proved by DNA sequencing to be identical to the target sequence to which the probe was hybridized., Conclusion: This assay has a broad application for clinical diagnosis and surveillance investigation.

Objective: To detect the mutations of Krit-1 gene that cause familial cerebral cavernous malformation (CCM) in the Han ethnic origin., Methods: The subjects were hospitalized in the Department of Neurosurgery, Tiantan Hospital affiliated to Capital University of Medical Sciences. Two families (A and B) and 8 apparently sporadic individuals affected with CCM were screened for mutations of Krit-1 gene. Members of the family CCM have a wide range in age of onset with seizures, headaches and skin lesions. The gene was screened by PCR amplification of 16 exons and mutation was detected by direct sequencing., Results: In family A samples, analysis of the Krit-1 gene revealed a new point mutation in exon 14 [a heterozygous C to G transition at nucleotide 1 289 (counting from the start codon or nt 2 308 counting from the first nt of the mRNA, aligned according to Gene Bank AF388384)] which predicts the substitution of a premature termination codon for Serine at codon 430 (S430X), belonging a nonsense point mutation. No mutation was identified in one of family A members as well as in any of the sporadic individuals with the exception of a single nucleotide polymorphism., Conclusions: Report the first family in the Han with CCM having a novel mutation in the CCM1 gene on the continent of Asia. The newly identified mutation creates a premature termination codon and is predicted to produce a truncated Krev1 interaction-trapped 1 protein, KRIT1. This result allows efficient presymptomatic molecular diagnosis.

Purpose: To describe the clinic-pathological analysis of the visually significant opacification of the Cirrus International Hydroflex foldable hydrophilic acrylic intraocular lens (IOL) (model SC600-2, Medical Developmental Research Inc., Clearwater, Florida) and to highlight that this IOL is the same model as the Acryflex SC600-2 IOL, by the same manufacturer., Methods: Retrospective review of five eyes of four patients with opacification of their Cirrus International Hydroflex foldable hydrophilic acrylic IOLs (model SC600-2) after uncomplicated phacoemulsification and IOL implantation. Two IOLs were explanted from two patients 14 to 24 months after initial implantation. Each explanted lens was divided into equal halves, one half for scanning electron microscopy (SEM) study and the other half for transmission electron microscopy (TEM) examination. SEM and TEM samples were also subjected to energy dispersive X-ray analysis (EDX)., Results: The IOL opacification was detected 14 to 24 months after uncomplicated phacoemulsification and IOL implantation. EDX analysis showed that the crystals contained calcium and phosphorus, presumably calcium phosphate., Conclusions: The Cirrus International Hydroflex foldable hydrophilic acrylic IOL (model SC600-2) is associated with opacification, that appeared worse centrally than peripherally. This is the same model as the Acryflex SC600-2 IOL, made by the same manufacturer. The opacification consists of calcium and phosphate.

Purpose: To compare the efficacy of low-dose intravenous methylprednisolone or conservative treatment in the management of traumatic optic neuropathy., Methods: A non-randomized retrospective study of 21 patients (21 eyes) with traumatic optic neuropathy treated between October 95 and November 97 in a tertiary ophthalmology unit. Traumatic optic neuropathy was defined as traumatic visual loss with afferent pupillary defect in the absence of direct injury to the globe or optic nerve. The median follow-up period was one year. Nine patients were treated with 125-250 mg methylprednisolone 6-hourly intravenously for a mean of 3.3 days (range 2-5 days) and 12 patients were treated conservatively. Visual acuity (VA) was measured with a Snellen chart before and after treatment at each follow-up visit. Visual recovery was defined as an improvement of 2 or more Snellen lines one week post-injury or later., Results: The patients' mean age was 37.1 years (range 12-65 years). There were more males (90.5%) than females (9.5%). Traumatic optic neuropathy was in 12 right eyes and 9 left eyes. The cause of injury included traffic accidents (52.4%), falls (28.6%), assault (14.2%) and others (4.8%). The mean interval between the injury and steroid therapy was 3.6 days (range 1-11 days). Visual recovery was observed in 44.4% of eyes treated with methylprednisolone and in 33.3% treated conservatively (p = 0.673, Fisher's exact test)., Conclusions: Intravenous methylprednisolone at the dosage and duration used in this retrospective study did not significantly improve the visual recovery of eyes with traumatic optic neuropathy compared to conservative treatment. However, this small sample may not be sensitive enough to detect a small difference in visual recovery rates, and further studies with larger samples may be warranted.

Purpose: We evaluated the performance of the SoftPerm contact lens (Wesley Jessen) in patients with irregular astigmatism, usually due to keratoconus or after penetrating keratoplasty (PK), who were unable to befitwith, or intolerant of, rigid gas permeable (RGP) contact lenses., Methods: A retrospective study of patients fit with SoftPerm lenses in the Cornea Department at Wills Eye Hospital between March 1985 and March 2000 was performed., Results: Thirty-five cases were reviewed, with follow-up available in 33 cases. Most of the eyes had irregular astigmatism secondary to keratoconus (22/35,62.9%) or PK (10/35,28.6%) and had failed a trial of RGP lenses. The mean logMAR visual acuity with SoftPerm lenses was 0.13+/-0.18 (range -0.12 to 0.6). In 25 cases in which comparison with glasses or RGP lenses was possible, SoftPerm lenses provided better visual acuity than glasses in 17/25 cases (68%) with a mean difference of -0.24 (P = 0.001, paired t-test); visual acuity with SoftPerm lenses was better than RGP visual acuity in 13/25 cases (52%), with a mean difference of -0.06 (P = 0.07, paired t-test). Complications included broken lenses (16/33,48.5%), giant papillary conjunctivitis (GPC) (9/33, 27.3%), and peripheral corneal neovascularization (9/33, 27.3%). The GPC and peripheral corneal neovascularization were often delayed in presentation. The major subjective complaint was discomfort (13/33, 39.4%). At the last follow-up, the SoftPerm lens was still in use in 22/33 cases (66.7%). Discomfort was the most common reason for discontinuation. The mean duration of lens wear was 52.5+/-31.7 months, range 3 to 110 months., Conclusions: The SoftPerm lens can provide satisfactory visual correction in many cases of irregular astigmatism with RGP failure. However, problems such as frequent breakage, GPC, peripheral corneal neovascularization, and discomfort necessitate close follow-up.

Purpose: Pennsylvania Act 102 implemented in March 1995 required all acute care hospitals in Pennsylvania to routinely refer all deaths to the Organ Procurement Organization for determination of suitability for organ/tissue donation. This study analyzed the effect of the law on eye donation., Methods: Retrospective analysis of the total number of referrals and the actual number of eye donations from 62 hospitals in Pennsylvania to the Lions Eye Bank of Delaware Valley was performed for the years 1993 to 1998. Information gathered included donor's age, gender, race, cause of death, referring institution, and result of referral., Results: From 1993 to 1998, the total numbers of referrals were 988, 1,647, 8,101, 21,123, 21,783, and 22,987, and the numbers of donors were 570, 574, 660, 644, 594, and 568, respectively. The increase in the number of donors after implementation of the law was not commensurate with the number of referrals. This was caused by a disproportionate increase in the number of referrals older than 70 years of age (from a mean of 33% to 52%), which exceeded the donor age limit of 69 years, and also to a lower family consent rate (from a mean of 48% to 24%)., Conclusions: Well-designed state legislation with proper implementation greatly increased hospital referrals for eye donation. However, there was only a small increase in the number of eye donors because many of the referrals were beyond the acceptable upper age limit for eye donation. A small increase in the donor age limit would increase the number of eye donations without having to expand the potential donor pool. Education of the public may help to improve the family consent rate.

Purpose: To identify changes in number of contact lens-related corneal ulcers per year and the type of contact lenses involved., Methods: Charts of 299 patients with corneal ulcers seen at the Cornea Service of Wills Eye Hospital from January 1, 1996, to June 30, 1999, were retrospectively reviewed. A corneal ulcer was defined as an infiltrate that was treated at least hourly with topical fortified antibiotics or fluoroquinolones., Results: Of these 299 cases, 37 (12.4%) were related to contact lens use. Contact lens-related ulcers accounted for 10.7% of all corneal ulcers in 1996, 15.3% in 1997, 8.6% in 1998, and 18.2% in the first 6 months of 1999. The contact lenses most commonly associated with ulcers were conventional soft daily-wear contact lenses (33%). There were similar numbers of ulcers associated with extended wear (n = 16) and daily wear (n = 17) of soft contact lenses. In addition, the number of cases associated with conventional (n = 17) and disposable/frequent replacement (n = 16) lenses were similar. Corneal cultures were performed in 15 (40.5%) cases and were positive in 8. There has been a significant decrease in the number of contact lens-related ulcers treated at our institution compared with previous years (1988-1999, p < 0.01)., Conclusions: The number of contact lens-related corneal ulcers in the past 4 years was significantly fewer than previous years at our institution. A similar number of ulcers were associated with conventional and disposable/frequent replacement lenses despite the commercial preponderance of the latter type of lenses.

The authors describe a novel approach for the fixation of enucleated eyes during microsurgical procedures using common household plumbing accessories. The device consists of a ring adaptor with 4 round-ended screws placed horizontally at its sides and a plastic hose connector. The enucleated globe is secured in the center of the ring adaptor by gently tightening the screws. The hose connector supports the posterior pole of the globe and is secured onto a styrofoam board that provides a platform for resting the surgeon's hands. The device proved very satisfactory to residents during the teaching of cataract surgery and trabeculectomy on porcine eyes. Our globe fixation device is simple, inexpensive, effective, and readily available. It may be especially useful in developing countries.

Objective: The aim of this study was to investigate the subjective visual experience of patients during phacoemulsification and intraocular lens (IOL) implantation under topical anesthesia., Design: Postoperative questionnaire survey., Participants: The study cohort consisted of 52 patients with cataracts. There were 18 male (34.6%) and 34 female (65.4%) patients. Their mean (+/- SD) age was 67.5 (+/-10.8) years., Intervention: The patients underwent routine phacoemulsification and IOL implantation under topical anesthesia., Main Outcome Measures: The patients were interviewed on the same day after their operation regarding their visual experience in the operated eye during surgery., Results: All patients (100%) reported that they could see at least some light during the surgery. Some patients reported they could also see one or more colors (50 patients, 96.2%), movements (32 patients, 61.5%), flashes (24 patients, 46.2%), the surgeon's fingers/hands (13 patients, 25%), instruments (12 patients, 23.1%), and/or the surgeon (4 patients, 7.7%). The colors seen included red (24 patients, 46.2%), yellow (23 patients, 44.2%), blue (12 patients, 23.1%), green (7 patients, 13.5%), and orange (6 patients, 11.5%). Eight patients (15.4%) saw the spectrum of colors similar to that of the rainbow. Twenty-four patients (46.2%) reported that the brightness of light changed during the course of the operation. Eight patients (15.4%) found their visual experience frightening. There was no statistically significant association between those who found the visual experience frightening and the sex or age of the patient, a history of cataract operation in the fellow eye, the type of visual sensation experienced, or the presence of coexisting ocular pathology., Conclusion: All patients undergoing phacoemulsification under topical anesthesia experience a variety of visual sensations that may be frightening in a small proportion of patients.

Purpose: To determine the visual outcome and incidence of complications after posterior capsule rupture during phacoemulsification surgery., Methods: Forty-four eyes of 43 patients which sustained posterior capsule rupture or zonulysis during phacoemulsification surgery between April 1993 and May 1996 were retrospectively studied. Eyes With pseudoexfoliation syndrome, traumatic cataract and myopia > 6 dioptres were excluded from the study. The mean postoperative follow-up period was 26 months (range 3 to 47 months)., Results: Forty-one eyes had posterior capsule rupture and 3 eyes had zonulysis. Of these 44 eyes, 41 eyes had vitreous loss and anterior vitrectomy at the time of surgery or subsequently. Excluding 2 eyes with pre-existing conditions that precluded good vision, 36 out of 42 eyes (85.7%) achieved spectacle corrected visual acuity of 6/12 or better post-operatively. Of all 42 eyes, 20 had anterior chamber intraocular lens (ACIOL) implantation while the others had posterior chamber intraocular lens (PCIOL) implantation. For eyes with ACIOL, 17 out of 20 eyes (85.0%) had best corrected visual acuity of 6/12 or better. For eyes with PCIOL, 19 out of 22 eyes (86.4%) had best corrected visual acuity of 6/12 or better., Conclusions: Phacoemulsification surgery, even if complicated by posterior capsule rupture or zonulysis, is compatible with good visual outcome. This is provided prompt attention is paid to the management of complications.

Purpose: To report a rare case of episcleral neurofibroma and discuss the possible differential diagnoses., Methods: Case report of a 36-year-old man who presented with a painless epibulbar mass of the left eye. We describe the clinical and histopathologic features of the tumour and compare it with other tumours which may have a similar clinical presentation., Results: An excisional biopsy of the tumour was performed. Histopathologic examination revealed the tumour to be an isolated episcleral neurofibroma., Conclusion: It is often difficult to clinically differentiate this tumour from other conditions. Because of the slow growth of neurofibromas and its slow risk of malignant transformation, these lesions may be observed periodically for progression. Surgical excision may be performed if the lesion is found to be progressively enlarging in size.

The paper retrospectively reviews the spectrum of ophthalmic manifestations in human immunodeficiency virus (HIV) infection in Singapore between May 1995 and October 1996. One hundred and eighteen patients were examined for ocular abnormalities. Criteria for examination were 1) visual complaints, 2) absolute CD4 count of less than 50 cells/ul, 3) patients with acquired immunodeficiency syndrome-defining illness or 4) any relevant systemic illnesses which may have ocular involvement. Only 25 patients (21.2%) had visual symptoms. Eighteen patients (15.3%) had abnormalities associated with microvasculature. Forty-four patients (37.3%) had opportunistic infection involving the eye of which 37 were that of cytomegalovirus retinitis (CMVR). Seven patients (5.9%) had neuro-ophthalmic disorders. One patient presented with proptosis due to orbital lymphoma. Four patients (3.4%) had episcleritis and 3 patients (2.5%) had symptomatic dry eyes. It is still not known if episcleritis and dry eyes are associated with HIV infection or are coincidental. Fifty-one patients (43.2%) had no ocular pathology and remained so throughout the period of study. Nine patients (7.6%) had more than one pathology. The major cause of visual loss was due to ocular infections, with CMVR being most prevalent. Recognising the ophthalmic signs in HIV patients will facilitate early diagnosis. Prompt treatment of eye involvement can prevent or delay blindness, which is psychologically and functionally important to these patients.

Eight eyes of 8 patients with compound myopic astigmatism were treated with excimer laser photorefractive keratectomy (PRK) using a hand-held ablatable mask in conjunction with the Summit excimer laser. The attempted correction ranged from -1.25 to -400 dioptres (D) of astigmatism and 0 to -8.00 D of myopia. All eyes had attained at least 6 months of postoperative follow-up. Five of the 8 eyes achieved an unaided visual acuity of 6/12 or better. Postoperative refractions ranged from -0.50 to -3.50 D of refractive cylinder and from +0.50 to -3.75 D of spherical error. Decentration of the ablation zone was encountered in 3 eyes due to shifts in patients' fixation. Technical difficulty with the use of the hand-held ablatable mask limited the widespread application of this procedure and it has now been superseded by newer excimer laser systems which can correct astigmatism without having to employ a mask. Despite this, because of the theoretical ability of the mask to correct any form of refractive error, the concept of the mask shape transfer process will remain as a potential alternative in refractive surgery, especially for correction of hyperopia and hyperopic astigmatism.

Contrast sensitivity functions (CSFs) were obtained for 257 emmetropic subjects (514 eyes) and 35 contact lens users (64 eyes) in the Republic of Singapore Air Force using the Vistech Contrast Test System. For the emmetropes, contrast sensitivity tests were carried out with and without plano spectacles (PS). For the myopes, we compared their performances with spectacles, daily-wear soft contact lenses (CLs), and CL plus PS at Snellen visual acuities of 6/6 or better. Paired t-tests showed that there were no significant differences (P > 0.05) when CSFs of the emmetropes were measured with and without PS and when that of the CL users were measured with spectacles, CL and CL plus PS. We therefore conclude that myopic optical correction media do not retard CSF significantly based on the Vistech charts, although they may reduce image size and modify light transmission by being imperfect transparencies. The observed decrease in CSF for myopes even after myopic correction might therefore be related to other factors associated with myopia, such as retinal changes or possibly mild amblyopia.

To conduct a prospective, nonrandomized clinical trial to assess the efficacy, stability and safety of the use of excimer laser photorefractive keratectomy (PRK) to correct myopia of greater than -6.00 diopters (D) in Singapore. Two hundred thirty-three eyes of 176 patients with a mean preoperative spherical equivalent refraction of -8.70 +/- 2.3 D (range, -5.75 D to -18.13 D) underwent PRK with a 193nm ArF excimer laser (ExciMed, Summit) for myopic corrections of between -6.20 D and -11.90 D. The first 66 of 233 eyes that reached at least 1 year of postoperative follow up are reported. One year postoperatively, the mean manifest spherical equivalent refraction was -1.50 D +/- 1.90 D (range -6.25 D to +3.25 D); 34% of eyes were within +/- 1.00 D of attempted correction; uncorrected visual acuity was 20/40 or better in 75% of eyes. No eyes lost two or more Snellen lines of spectacle corrected visual acuity. Central corneal haze was mild in 20% of eyes and moderate in 3% of eyes. Five eyes developed ocular hypertension that subsequently resolved with treatment. Excimer laser PRK is reasonably effective and safe in the treatment of -6.00 D to -12.00 D of myopia. However, it is less accurate than PRK in eyes with low to moderate myopia and is more likely to result in significant corneal haze.