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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.

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.

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.

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.

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.

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.

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.