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Biomedical subjects

P T Khaw

Publications and source records attributed to P T Khaw.

At least 19 recordsLinked to original sources

Socioeconomic status, systolic blood pressure and intraocular pressure: the Tanjong Pagar Study.

BACKGROUND: Lower socioeconomic status (SES) is associated with higher morbidity and mortality in many countries. Present evidence suggests that glaucoma has similar risk factors to major chronic diseases such as cardiovascular disease. This study investigates the association between SES and intraocular pressure (IOP), an important risk factor for glaucoma. METHODS: The Tanjong Pagar Study was a population-based cross-sectional survey of Chinese people aged 40-79 years, who were randomly selected from the Singapore electoral register. Of the 2000 people selected, 1717 were considered eligible and 1090 were examined in clinic and included in the present study. IOP was measured using applanation tonometry. SES was assessed using a standardised questionnaire; education and income were used as the main explanatory variables. The effect of systolic blood pressure (SBP) was also examined. RESULTS: Participants with lower levels of education and income had higher mean IOP (both p<0.01). These associations remained after adjusting for age and central corneal thickness, a strong independent predictor. SBP was strongly associated with both SES and IOP (both p<0.01). Adjusting for SBP attenuated the association between SES and IOP. CONCLUSION: Participants with lower education and income have a higher mean IOP. This effect may be mediated, in part, by an association of education and income with SBP. This is the first study to suggest that there is a social gradient in the distribution of the only major modifiable risk factor for glaucoma. Increasing similarities exist between the causation models of chronic diseases and that of glaucoma.

Adult↗

Pointwise linear progression criteria and the detection of visual field change in a glaucoma trial.

BACKGROUND: Current pointwise linear regression (PLR) change criteria for visual field analysis are largely empirical. METHODS: Two independent sets of Humphrey Field Analyzer fields were analysed using PLR. Set i, 56 patients, and set ii, 97 patients, were followed over 16 months. Criteria were tested against set i, and then validated using set ii. Each criterion specified a fixed critical slope of 1 dB/year and with a range of significance from P<0.001 to 0.05. The criteria were varied by altering location number, cluster arrangement, and by requiring points to show change over both 12 and 16 months. True glaucomatous change was differentiated from noise by looking for exclusive progression (EP), the detection of progression without detection of improvement. RESULTS: Set i required 1 point to have a slope of 1 dB/year and P<0.05 labelled 64% progressing and 58% improving, whereas several stricter criteria were capable of detecting EP. Two points in a perimetric nerve fibre bundle (PNFB) cluster gave optimal EP detection, labelling 8.9% progressing in set i and 7.2% progressing in set ii with a cutoff P-value of 0.026 inset i and 0.013 inset ii. CONCLUSION: Lax PLR criteria detect large amounts of change. Validating criteria using two data sets allow selection of better criteria, capable of detecting EP. The criterion involving 2 points changing in a PNFB cluster offers the best option for exclusively detecting progression.

Aged↗

Angle-closure glaucoma in East Asian and European people. Different diseases?

In contrast to the pattern of disease in Europeans, primary angle closure has a higher prevalence and tends to be asymptomatic in East Asians. The higher prevalence is attributed to differences in anterior chamber and angle anatomy. Several studies suggest that central anterior chamber depth is shallower in East Asians than in Europeans, although this is not universally accepted. It is debated whether pupil block is the predominant mechanism of angle closure in Asian people. Meaningful comparison between studies is currently hindered by differences in patient selection, examination technique, and case definition; however, the major scientific deficiency is the paucity of prospective followup data to give an insight into natural history of the disease. This review examines the data on prevalence, risk factors, and mechanism of angle closure. Special consideration is given to limitations of methodology in research to date, with the intention of developing more robust data in future studies.

Anterior Chamber↗

Current prospects for adult stem cell-based therapies in ocular repair and regeneration.

Recent advances in stem cell biology have led to the exploration of stem cell-based therapies to treat a wide range of human diseases. In the ophthalmic field, much hope has been placed on the potential use of these cells to restore sight, particularly in those conditions in which other established treatments have failed and in which visual function has been irreversibly damaged by disease or injury. At present, there are many limitations for the immediate use of embryonic stem cells to treat ocular disease, and as more evidence emerges that adult stem cells are present in the adult human eye, it is clear that these cells may have advantages to develop into feasible therapeutic treatments without the problems associated with embryonic research and immune rejection. Here we discuss the current prospects for the application of various adult ocular stem cells to human therapies for restoration of vision.

Adult↗

A review of trabeculectomy in East Asian people--the influence of race.

Glaucoma is the leading cause of irreversible blindness worldwide. East Asians account for approximately half of all glaucoma sufferers. It is likely that trabeculectomy will be needed for many of these people as the intraocular pressure is to be maintained at a satisfactorily low level. The eyes of East Asian people differ in some aspects from those of other races. This review describes the natural history of the eye after trabeculectomy in East Asians.

Asian People↗

Spontaneous inferior subconjunctival haemorrhages in association with circumferential drainage blebs.

AIM: To describe an association of spontaneous inferior subconjunctival haemorrhages in eyes with circumferential drainage blebs following trabeculectomy. METHODS: Observational case series. Patients with multiple episodes of spontaneous inferior subconjunctival haemorrhage following trabeculectomy (with or without antimetabolite) and circumferential blebs are presented. All patients described had multiple episodes. A possible mechanism is discussed. RESULTS: The number of spontaneous haemorrhages ranged from two to more than 10. All individual haemorrhages resolved spontaneously without adverse sequelae CONCLUSIONS: A new clinical presentation of inferior subconjunctival haemorrhage in association with circumferential blebs is described.

Aged↗

Matrix metalloproteinase distribution during early corneal wound healing.

AIM: To compare matrix metalloproteinase (MMP) localisation in anterior keratectomy (AK) and lamellar keratectomy (LK) wounds. METHODS: Wounds were produced in one eye of 24 rabbits. The AK wounds were made to approximately 120 microm in depth and then allowed to re-epithelialise. The LK wounds were of similar depth, but the anterior stroma and epithelium were replaced after a second deeper keratectomy had been performed. Immunohistochemistry was used to localise the MMP-1, -2, -3, and -9 at intervals from 4 h to 14 days following surgery. The contralateral eyes acted as controls. RESULTS: After an AK wound MMP-1 was present at the leading edge of migrating epithelium after 18 h, while MMP-2 and -9 were localised behind the advancing epithelial edge. The presence of these enzymes rapidly fell to low levels after epithelial closure. There was only faint MMP-3 localisation between days 3 and 7. After an LK wound, MMP-1, -3, and -9 were not detected in the stromal interface, but MMP-2 was present at all time points. CONCLUSIONS: This study suggests that after an AK wound, MMP-1 is a key mediator of epithelial migration, while MMP-2 and -9, and to a lesser extent MMP-3, may participate in the remodelling of corneal stroma and the reformation of epithelial basement membrane. In contrast, an LK wound results in a much lower stimulus for MMP activation. The action of MMP-2 in stromal repair is thus partly independent of epithelial injury.

Animals↗

Injury to the eye.

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Burns, Chemical↗

Effect of cataract extraction and intraocular lens implantation on nerve fibre layer thickness measurements by scanning laser polarimeter (GDx) in glaucoma patients.

PURPOSE: To assess the influence of visually significant cataract on the measurement of nerve fibre layer thickness by scanning laser polarimetry (GDx) in glaucoma patients undergoing phacoemulsification cataract extraction. METHOD AND SUBJECTS: All subjects with primary glaucoma participating in a prospective trial of glaucoma surgery who subsequently underwent cataract extraction were eligible. A single trained observer using the GDx nerve fibre layer analyser (LDT) performed pre- and post-operative measurements of nerve fibre layer thickness (NFLT). NFLT parameters, best-corrected LogMAR visual acuity, and automated visual fields were assessed before and after phacoemulsification cataract extraction with implantation of an acrylic intraocular lens. RESULTS: A total of 49 subjects were assessed: 22 (45%) had POAG and 29 (55%) PACG; all were Asian (36 (73%) were Chinese), with mean age 67.1 (+/-7.6 SD) and mean 'LOCS III' lens opacity grading 11.4 (+/-3.1 SD). Visual acuity significantly improved (mean LogMAR 0.5 vs 0.15, P<0.0001). Corrected pattern standard deviation (6.1 vs 6.4, P=0.2) and mean deviation (-17.7 dB vs -17.0 P=0.91) were little changed after cataract removal. Pseudo-phakic measurements of NFLT were significantly different from pre-op values. Measures of absolute thickness (including the average thickness, ellipse, ellipse average, superior and inferior averages, superior integral) were significantly greater than preoperative values (all P<0.01), whereas ratios and measures of symmetry (symmetry, superior/nasal) were unchanged (all P>0.1) and 'the number' was smaller (P=0.04). Differences in measured NFLT were most strongly correlated with posterior subcapsular cataract (average thickness, P=0.01). CONCLUSIONS: Removal of cataract resulted in greater absolute measurements of NFLT but ratio values were unchanged. Scanning laser polarimetry measurements can change significantly after cataract extraction. New baseline measurements may be required.

Aged↗

Interocular asymmetry of visual field defects in primary open angle glaucoma and primary angle-closure glaucoma.

AIM: To compare the interocular asymmetry in visual field loss of patients with primary open-angle (POAG) and primary angle-closure glaucoma (PACG). METHODS: Subjects entering a prospective, randomised, controlled trial of intraoperative 5-fluorouracil in glaucoma surgery in Singapore were included. Preoperative visual field testing was performed using automated white-on-white perimetry (24-2 test pattern, threshold program, Mk II, Model 750, Zeiss-Humphrey, San Leandro, CA, USA). A minimum of two tests were required with mean deviation within 2 dB on two tests, fixation losses <20%, false positives <33%, and false negatives <33%. The second field was scored using AGIS II criteria and the 'mean asymmetry score' defined as the mean difference between eyes for both AGIS scores and global indices. RESULTS: In 230 subjects assessed (128 POAG, 102 PACG), mean interocular asymmetry of visual field loss was greater for the PACG group. The mean AGIS asymmetry scores for total (PACG=9.21+/-6.87 vs POAG=6.48+/-5.58, P=0.001), superior (PACG=4.31+/-3.39 vs POAG=3.35+/-3.13, P=0.035), and inferior (PACG=4.43+/-3.31 vs POAG=2.64+/-2.77, P<0.0001) areas and mean deviation (MD) asymmetry scores (PACG=6.89+/-13.22 vs POAG=1.66+/-16.97, P=0.012) were all significantly different. Interocular correlation of visual field loss for POAG was significant; total AGIS, r=0.27 (P=0.003), superior field AGIS, r=0.24 (P=0.008), inferior field AGIS, r=0.34 (P=0.0001), and MD, r=0.27 (P=0.003). In PACG, there was no significant correlation between eyes; total AGIS, r=-0.02 (P=0.85), superior field AGIS, r=-0.02 (P=0.82), inferior field AGIS, r=-0.17 (P=0.87), and MD, r=0.015 (P=0.89). CONCLUSION: There was a greater asymmetry of visual field loss between eyes, as measured by AGIS scores and MD, in PACG than that in POAG.

Aged↗

A pilot study of a system for grading of drainage blebs after glaucoma surgery.

PURPOSE: To develop and evaluate a novel bleb grading scheme for clinical and photographic evaluation. METHOD: A system for grading bleb photographs using widely applicable parameters was designed, and reference color photographs printed. A prospective masked agreement study was undertaken comparing slit lamp examination with mono and stereo photographs; 36 eyes of 28 patients with previous glaucoma surgery were graded according to defined parameters on a 1 to 10 scale clinically at the slit lamp by four ophthalmologists and two optometrists. Standardized stereo and mono photographs of the blebs were taken on the same day. The photographs were graded at least one week later in a masked fashion by the same observers, with grading of mono and stereo photographs also separated by one week. Analysis was performed to determine the variability and agreement between slit lamp results and photographic results, and to identify the presence of systematic bias. RESULTS: High levels of agreement were found between slit lamp and both stereo and mono photographs for vascularity indices, bleb wall thickness, and bleb elevation. Lower levels of agreement were found for the relative components of demarcated versus diffuse areas of the bleb, and for the total width of the bleb. The interquartile range for the median difference between slit lamp and photograph grading was -1.0 to 1.0 for all criteria except diffuse component (-2.0 to 2.0), and the median difference for all scores was 0.0. The median interobserver difference for all criteria was 0.0; the quartile range for all scores was between -0.5 and 1.0 except for diffuse component and width assessments whose quartiles fell in the -1.75 to 1.0 range. Examiners agreed with photographic grading within +/- 1 in more than 80% of gradings for vascularity and bleb height, within +/- 1 in more than 75% of gradings for bleb wall thickness, within +/- 2 in 61% of bleb width assessments, and +/- 2 in 59% of diffuse component. CONCLUSION: This bleb grading system is reproducible clinically and photographically. High levels of agreement between scores for photographs versus slit lamp examination were found for most categories, with good interobserver agreement for both photograph and slit lamp grading. Further refinement of scoring and reference photographs is required for optimization, especially for grading of bleb morphology.

Drainage↗

T lymphocyte mediated lysis of mitomycin C treated Tenon's capsule fibroblasts.

AIMS: To evaluate the effect of T cell co-culture on mitomycin C treated and untreated Tenon's capsule fibroblasts. METHODS: IL-2 dependent allogeneic T cells were incubated over a monolayer of mitomycin C treated or control fibroblasts. Fibroblast numbers were evaluated by direct counts using phase contrast microscopy. To determine whether T cell mediated lysis was a consequence of MHC mismatch, co-culture experiments were repeated with autologous T cells. The effect of Fas receptor blockade was established by co-incubation with a Fas blocking (M3) antibody. RESULTS: T cell co-culture resulted in a dramatic reduction in fibroblast survival compared to mitomycin C treatment alone (p = 0.032). T cell killing required fibroblast/lymphocyte cell to cell contact and was observed in both allogeneic and autologous co-culture experiments. Fas blocking antibodies did not significantly inhibit T cell killing (p = 0.39). CONCLUSION: T cells augment mitomycin C treated fibroblast death in vitro. Similar mechanisms may contribute to the cytotoxic effect of mitomycin C in vivo and account for the largely hypocellular drainage blebs that are observed clinically.

Antibiotics, Antineoplastic↗

Defining "occludable" angles in population surveys: drainage angle width, peripheral anterior synechiae, and glaucomatous optic neuropathy in east Asian people.

BACKGROUND: /aim: A current consensus in epidemiological studies of primary angle closure (PAC) is to diagnose the condition only if the posterior (usually pigmented) trabecular meshwork is seen for less than 90 degrees of the angle circumference, termed an "occludable angle." The authors sought to assess the validity of this epidemiological classification by exploring the relation between drainage angle width, peripheral anterior synechiae (PAS) and glaucomatous optic neuropathy (GON). METHODS: 918 Mongolians and 995 Chinese Singaporeans, both groups aged 40 years and older were examined in two population based surveys. Gonioscopic angle width was graded in five categories (0 = closed to 4 = wide open) according the scheme described by Shaffer. Cases with secondary PAS were excluded. RESULTS: The rate of PAS was between 0.3% and 1.7% in people with wide angles (grades 3 and 4). In those with grade 2 angles, PAS were seen in between 8% of eyes. In eyes with grade 1 angles, the rate rose to 17% in Chinese Singaporeans, and 31% in Mongolians. The odds of PAS were higher in people with narrower angles. However, there was a greater absolute number of people with PAS whose drainage angles were classified as "not occludable" than those classified "occludable." CONCLUSIONS: The traditional view that primary angle closure becomes a significant possibility in drainage angles of < or = grade 2 (approximately 20 degrees ) is valid in east Asians. The definition of an "occludable" angle examined here excludes many people with PAS. This probably serves to underemphasise the role of PAC in population surveys of glaucoma prevalence in Asian people.

Adult↗

The effects of single doses of beta radiation on the wound healing behaviour of human Tenon's capsule fibroblasts.

AIM: To determine the effects of single doses of beta radiation on the wound healing functions of human Tenon's capsule fibroblasts (hTf). METHODS: hTf were grown in tissue culture and irradiated with beta radiation using a strontium 90 source. The effects of beta radiation on fibroblast migration was studied using microporous transwell membranes. The effects of radiation on fibroblast contraction was investigated using a fibroblast populated collagen gels model. Production of extracellular matrix molecules (collagen I, collagen III, and fibronectin) by monolayers of irradiated fibroblasts was quantified for 14 days following single doses of beta radiation. RESULTS: Growth inhibiting doses of beta radiation did not inhibit fibroblast migration or contraction at any time point. Levels of soluble fibronectin from irradiated populations were significantly reduced after >500 cGy beta radiation. Collagen I and III levels were not reduced after any dose of radiation, and increased following treatment with 1000 cGy beta radiation. CONCLUSIONS: Growth arresting doses of beta radiation have unique effects on the wound healing behaviour of human Tenon's capsule fibroblasts. There was no significant effect on cellular migration or contraction, but ECM production was altered. Fibronectin production was inhibited following higher radiation doses, and collagen I and III production increased after 1000 cGy. The effects of single doses of beta radiation on ocular fibroblast wound healing behaviour are very different from those of 5-fluorouracil and mitomycin C, and these differences may be exploited clinically in the regulation of wound healing after glaucoma filtration surgery.

Beta Particles↗

National survey of antimetabolite use in glaucoma surgery in the United Kingdom.

AIMS: To assess the pattern of use of antimetabolites in trabeculectomy surgery by all consultant ophthalmologists in the United Kingdom. METHODS: A postal questionnaire of 12 questions regarding antimetabolite use in trabeculectomy surgery was sent to all 749 consultant ophthalmologists in the United Kingdom. The consultants were asked to estimate the number of trabeculectomies they performed per year, how often they used 5-fluorouracil (5-FU) in primary and redo surgery, their usual method of administration of 5-FU, how often they used mitomycin (MMC) in primary and redo surgery, and their usual dosage regimen of MMC. Factors that influenced the decision to use or not use antimetabolites were also assessed. RESULTS: The response rate of consultants returning the questionnaire was 82% (615 out of 749); 87% (533) of these consultants perform trabeculectomy surgery. Of these 533 consultants, 98 (18%) never use an antimetabolite. Most consultants (82%) use antimetabolites, but use them infrequently (only 9% using antimetabolites in more than half their cases). The preferred antimetabolite is 5-FU rather than MMC. Of the 435 consultants performing trabeculectomy surgery and using antimetabolites, 402 (93%) use 5-FU and 179 (41%) use MMC. Various factors influenced the decision to use or not use an antimetabolite, but experience of complications associated with their use was a factor for 34% of consultants. CONCLUSION: The use of antimetabolites, particularly MMC, in the United Kingdom is much less than in America or Japan, where trabeculectomy with MMC is the surgical procedure preferred by glaucoma specialists.

Antimetabolites↗

MMP inhibition prevents human lens epithelial cell migration and contraction of the lens capsule.

PURPOSE: The development of posterior capsule contraction following cataract surgery is caused by the activity of residual lens epithelial cells. Matrix metalloproteinases (MMPs) are a group of proteolytic enzymes, which are essential for cell migration and cell mediated contraction following wound healing. The authors investigated whether inhibiting MMP activity can reduce lens epithelial cell migration and as a result, lead to a reduction in cell mediated capsule contraction. METHODS: Human donor lens capsules were cultured and treated with a broad spectrum MMP inhibitor, Ilomastat (GM6001). MMP-2 and MMP-9 production were determined by ELISA. Cell migration onto the posterior capsule and capsule contraction were digitally measured. RESULTS: MMP inhibition significantly reduced lens epithelial cell migration onto the posterior capsule (p<0.05), and a reduction in capsule contraction was observed (p<0.05). CONCLUSIONS: Ilomastat significantly reduced lens epithelial cell migration onto the posterior capsule surface and inhibited capsule contraction. MMP inhibition may have a role in the therapeutic treatment of posterior capsule opacification.

Cataract Extraction↗