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Biomedical subjects

P R Healey

Publications and source records attributed to P R Healey.

15 recordsLinked to original sources

Meta-analysis of randomised controlled trials comparing latanoprost with brimonidine in the treatment of open-angle glaucoma, ocular hypertension or normal-tension glaucoma.

AIM: To compare the efficacy and tolerability of latanoprost versus brimonidine in the treatment of open-angle glaucoma, ocular hypertension or normal-tension glaucoma. METHOD: Systematic review of randomised controlled trials comparing latanoprost and brimondine, identified by searches including Medline, Embase and Cochrane Controlled Trials Register. Two reviewers independently assessed trials for eligibility and quality and extracted data. Data were synthesised (random effects model) and expressed as the absolute mean intraocular pressure (IOP) reduction difference from baseline to end point for efficacy and relative risk for adverse events. Subgroup analysis and regression were used to explore heterogeneity according to patient characteristics, trial design and quality. RESULTS: 15 publications reporting on 14 trials (1784 participants) were included for meta-analysis. IOP reduction favoured latanoprost (weighted mean difference (WMD) = 1.10 mm Hg (95% confidence interval (CI) 0.57 to 1.63)). Significant heterogeneity was present (chi(2)(13) = 38.29, p = 0.001, I(2) = 66.0%). Subgroup analysis showed greater WMD for studies where data were analysed from end points >6 months duration, cross-over design, open-angle glaucoma or ocular hypertension and monotherapy. Multiple regression showed no significant association of WMD with trial duration (t(9) = 1.92, p = 0.09), trial design (t(9) = 1.79, p = 0.11), trial quality (t(9) = -0.46, p = 0.66), or monotherapy or adjunctive therapy (t(9) = -2.14, p = 0.06). Fatigue was less commonly associated with latanoprost (RR = 0.27, 95% CI 0.08 to 0.88). Publication bias was not evident on visual inspection of a funnel plot. CONCLUSION: Latanoprost is more effective than brimonidine as monotherapy in lowering IOP. Brimonidine is associated with a higher rate of fatigue.

Administration, Topical↗

Trypan blue identifies antimetabolite treatment area in trabeculectomy.

AIM: Colourless solutions of mitomycin C (MMC) and 5-fluorouracil (5-FU) are widely used during trabeculectomy to inhibit postoperative scarring. The poor visibility of these agents on the eye has several drawbacks including the inability to accurately assess the area of treatment. This study examined the utility of using trypan blue dye to colour antimetabolites used during trabeculectomy and the effect of trypan blue on antimetabolite cytotoxicity in vitro. METHODS: For in vitro experiments, MMC (0.4 mg/ml) and 5-FU (25 mg/ml) were reconstituted with or without trypan blue. A lactate dehydrogenase release assay was used to measure drug induced cell death and viable cell number 7 days after treatment. For clinical assessment, trypan blue 0.1% was added to MMC and 5-FU to final concentrations of between 0.01% and 0.05%. The mixture was applied to Tenon's capsule and sclera via pre-wet or into dry 5x8 mm sponges (MMC and 5-FU) for 3 minutes or by direct subconjunctival injection after completion of surgery (5-FU). Twenty two consecutive patients undergoing trabeculectomy either with or without trypan blue were followed for 2 years postoperatively. RESULTS: The addition of 0.05% trypan blue to MMC or 5-FU did not alter MMC induced cell death or the number of viable fibroblast in vitro. In vivo, trypan blue clearly delineated the antimetabolite treatment area and facilitated control of excess antimetabolite at the wound margins as well as sponge removal. With direct subconjunctival injection, total staining area varied for a given volume with location of the needle tip. Any leakage from the injection site could be easily seen. No adverse effects attributable to trypan blue were found in 2 years of follow up. CONCLUSIONS: Trypan blue permits delineation of antimetabolite/tissue interactions without affecting cytoxicity for the assays investigated. Trypan blue can be used to visualise antimetabolite soaked sponges, estimate treatment area, and show areas of unintended tissue contact during trabeculectomy. The addition of trypan blue to antimetabolites has potential benefits in clinical, research, and teaching aspects of ocular surgery and therapy.

Aged↗

Open-angle glaucoma and systemic thyroid disease in an older population: The Blue Mountains Eye Study.

PURPOSE: To assess whether thyroid disease is independently associated with open-angle glaucoma (OAG), using history of thyroid disease and current thyroxine use. METHODS: The Blue Mountains Eye Study examined 3654 persons, aged 49-97 years. Interviewers collected self-reported history of diagnosis and treatment for thyroid disease. Eye examinations included applanation tonometry, stereoscopic optic disc photography and automated perimetry. OAG was diagnosed from the presence of matching typical glaucomatous field changes and optic disc cupping, independent of intraocular pressure. Associations between thyroid disease (history and treatment) and OAG were assessed in a multivariate model. RESULTS: Of 324 participants (8.9%) reporting history of thyroid disease, 147 (4.0%) were currently using thyroxine. Although we could not accurately categorize the thyroid disorder for all cases, current use of thyroxine suggests a prior hypothyroid state. All thyroid disease subgroups affected women more frequently than men, P=0.001. OAG was diagnosed in 108 subjects (3.0%) and was more frequent in those reporting past thyroid disease (4.6 vs 2.8%). This relationship was not statistically significant after adjusting for potential confounders, multivariate odds ratio (OR) 1.6; 95% confidence interval (95% CI) 0.9-2.9. OAG was significantly more frequent, however, in subjects reporting current thyroxine use (6.8 vs 2.8%), multivariate OR 2.1; 95% CI 1.0-4.4, or history of thyroid surgery (6.5 vs 2.8%), multivariate OR 2.5; 95% CI 1.0-6.2. CONCLUSIONS: This population-based study suggests that thyroid disease, indicated by current thyroxine use or past thyroid surgery, could be independently related to OAG.

Age Distribution↗

The effect of optic disc diameter on vertical cup to disc ratio percentiles in a population based cohort: the Blue Mountains Eye Study.

OBJECTIVE: The 97.5th percentile for vertical cup to disc ratio (VCDR) has been proposed as a useful tool to assist in the diagnosis of glaucoma in population studies. Previous reports of VCDR percentiles have either not been adjusted for disc size or have been calculated by regression analysis from small hospital based cohorts. The authors' aim was to generate VCDR percentiles in a large, population based sample. METHODS: Data were collected from 3654 individuals, aged 49 years or older, living in the Blue Mountains, west of Sydney. Vertical disc diameter and VCDR were determined by planimetry from stereo optic disc photographs. The distribution of VCDR and percentiles (95th, 97.5th, 99th) were calculated. RESULTS: 6678 eyes were included in the analysis. Median cup to disc ratio, 95th, 97.5th, and 99th percentile increased with vertical optic disc diameter in a linear fashion. An increase of 0.2 in median VCDR (0.35 to 0.55) was observed between small (1.1-1.3 mm) and large (1.8-2.0 mm) optic discs. An equivalent increase of 0.2 (0.59 to 0.74) was observed for the 97.5th percentile from small to large discs. CONCLUSION: VCDR percentiles for a "normal" population, adjusted for vertical optic disc diameter are presented. One quarter of all discs fell within the small or large disc categories highlighting the importance for estimating optic disc size. These data may assist in the diagnosis of glaucoma in clinical practice as well as providing a normative database. Sole use of VCDR percentile cut offs in defining glaucoma cases in population surveys requires further validation.

Fundus Oculi↗

Female reproductive factors and open angle glaucoma: the Blue Mountains Eye Study.

AIMS: To determine whether endogenous oestrogen exposures are associated with open angle glaucoma (OAG). METHODS: The Blue Mountains Eye Study examined 2072 women aged 49-97 years during 1992-4. Questions about female reproductive factors included age at menarche and menopause, parity, and use of hormone replacement therapy. Applanation tonometry, visual field tests, and stereo-optic disc photographs were performed. OAG was diagnosed when glaucomatous visual fields matched optic disc changes. Ocular hypertension (OH) was defined in the absence of glaucoma, but with intraocular pressure >or=22 mm Hg. RESULTS: A significantly increased OAG risk with later (>13 years) compared with earlier ( or=50 years), adjusted OR = 1.7; CI: 0.7 to 3.8, and for shorter duration of endogenous oestrogen exposure (<30 years), adjusted OR = 1.8; CI: 0.6 to 5.3. Increasing parity was associated with an increased risk of OAG (p = 0.03) and decreased risk of OH (p = 0.03). CONCLUSION: The modest associations found in relation to late menarche and increased parity do not allow the exclusion of a possible role for endogenous female hormones in the pathogenesis of OAG.

Age Factors↗

Optic disk size in open-angle glaucoma: the Blue Mountains Eye Study.

PURPOSE: To compare optic disk size in eyes of subjects classified as normal with the eyes of subjects with open-angle glaucoma, ocular hypertension, or pseudoexfoliation syndrome in an older population-based sample. METHODS: The Blue Mountains Eye Study examined 3,654 subjects. Vertical disk diameter was measured from stereoscopic disk photographs, and we used spherical equivalent refraction to correct for magnification. Analyses used all eyes in a general estimating equation model. RESULTS: Mean disk diameter was 1.556 mm in glaucomatous eyes, significantly different (P <.05) than normal eyes (1.506 mm) and eyes with ocular hypertension (1.494 mm) or pseudoexfoliation (1.501 mm). CONCLUSIONS: Patients with glaucoma have slightly larger optic disks than nonglaucomatous subjects.

Exfoliation Syndrome↗

Asymmetry in optic disc parameters: the Blue Mountains Eye Study.

PURPOSE: To examine asymmetry in vertical optic disc parameters among subjects classified as normal, as having ocular hypertension (OH), and as having open-angle glaucoma (OAG) in a population-based sample. METHODS: The Blue Mountains Eye Study examined 3654 people aged 49 to 97 years, including 2929 normal subjects, 118 with OH, and 79 with OAG in the groups of interest for the asymmetry study. Optic disc parameters were measured in a masked manner from stereo optic disc photographs. RESULTS: Vertical disc diameter asymmetry (the absolute value of left minus right disc diameters) was similar among normal, OH, and OAG groups (median, 0.07-0.08 mm). Vertical cup- disc ratio asymmetry was higher in patients with OAG (median, 0.11) than in normal subjects (median, 0.06; P < 0.0001) and in those with OH (median, 0.05; P < 0.0001) but was similar between normal subjects and patients with OH (P = 0.17). A cup- disc ratio asymmetry of 0.2 or more was found in 24% of patients with OAG, compared with 1% of patients with OH and 6% of normal subjects. Corresponding rates for cup- disc ratio asymmetry of 0.3 or more in these three groups were 10%, 0%, and 1%, respectively. Using multiple linear regression, cup-disc ratio asymmetry was associated with disc diameter asymmetry and intraocular pressure asymmetry. However, these two factors explained only 3% of the variability of cup- disc ratio asymmetry and 20% of cup diameter asymmetry. CONCLUSIONS: Despite differences between the OAG group and either the OH or normal groups, asymmetry alone was not useful in identifying patients with OAG. At all levels of asymmetry, subjects were more likely to be classified as normal than with OH or OAG.

Aged↗

Optic disc hemorrhages in a population with and without signs of glaucoma.

OBJECTIVE: This study aimed to determine the prevalence and associations of optic disc hemorrhage in a well-defined older Australian population. DESIGN: The study design was a population-based, cross-sectional study. PARTICIPANTS: A total of 3654 persons 49 years of age or older, representing 88% of permanent residents from an area west of Sydney, participated in the study. MAIN OUTCOME MEASURES: Participants underwent a detailed eye examination. The diagnosis of optic disc hemorrhage was made from masked photographic grading; disc hemorrhages were subclassified as flame or blot in shape. Open-angle glaucoma was diagnosed from matching visual field loss and optic disc rim thinning. RESULTS: The overall prevalence of disc hemorrhage in either or both eyes was 1.4%. Disc hemorrhage prevalence was higher in women (odds radios [OR], 1.9; confidence interval [CI], 1.0-3.5) and increased with age (OR, 2.2 per decade; CI, 1.7-2.8 per decade). The overall prevalence in subjects with open-angle glaucoma was 13.8% (8% in high-pressure glaucoma and 25% in low-pressure glaucoma) and 1.5% in subjects with ocular hypertension. Disc hemorrhages were associated with increasing intraocular pressure (OR, 1.7 per 5 mmHg; CI, 1.3-2.3 per 5 mmHg), pseudoexfoliation (OR, 3.5; CI, 1.1-11.8), diabetes (OR, 2.9; CI, 1.4-6.3), and increasing systolic blood pressure (OR, 1.1 per 10 mmHg; CI, 1.0-1.3) after adjusting for age and gender. Among subjects without open-angle glaucoma, disc hemorrhages were more frequent in eyes with larger vertical cup-disc ratios and in subjects with a history of typical migraine headache (OR, 2.2; CI, 1.1-4.6). No associations were found among subjects with a history of vascular events, smoking, regular aspirin use, or myopia. CONCLUSIONS: Disc hemorrhage prevalence in this population is higher than that in the two previous population-based reports. Although the strong association of disc hemorrhage with open-angle glaucoma was confirmed (particularly low-pressure glaucoma), most disc hemorrhages (70%) were found in participants without definite signs of glaucoma.

Age Distribution↗

Open-angle glaucoma and diabetes: the Blue Mountains eye study, Australia.

PURPOSE: The authors explore the relationship between diabetes and open-angle glaucoma in a defined older Australian population. METHODS: Three thousand six hundred fifty-four people 49 to 96 years of age, living west of Sydney, underwent a detailed eye examination. This included automated perimetry, stereo optic disc photographs, and applanation tonometry; in addition, fasting plasma glucose levels were ascertained. Glaucoma was diagnosed if matching visual field and optic disc cupping were present, without reference to intraocular pressure (IOP) level. Ocular hypertension (OH) was diagnosed if IOP in either eye was > or = 22 mm and glaucomatous disc and visual field changes were absent. RESULTS: Glaucoma prevalence was increased in people with diabetes, diagnosed from history or elevated fasting plasma glucose level (5.5%), compared with those without diabetes (2.8%; age-gender adjusted odds ratio [OR] 2.12, 95% confidence intervals [CI] 1.18-3.79). Ocular hypertension was also more common in people with diabetes (6.7%), compared with those without diabetes (3.5%; OR 1.86, CI 1.09-3.20). Diabetes was present in 13.0% of people with glaucoma, compared with 6.9% of those without glaucoma. This increase was highest for previously diagnosed glaucoma cases (16.7%; OR 2.82, CI 1.35-5.87). However, in 67% of such cases, glaucoma was diagnosed before the diabetes. For those not receiving glaucoma treatment, IOP was consistently slightly higher in people with diabetes, with the age-gender adjusted mean IOP 0.6 mm higher. CONCLUSIONS: The significant and consistent association between diabetes and glaucoma found in our study, which appeared independent of the effect of diabetes on IOP, suggests that there is a real association between these two diseases.

Aged↗

Relationship between cup-disc ratio and optic disc diameter: the Blue Mountains Eye Study.

PURPOSE: To determine the effects of optic disc size on vertical cup-disc ratio in subjects free of glaucoma and other optic nerve disease. METHODS: Data were collected from 3654 people, 49 years of age of older, living in the Blue Mountains, west of Sydney (NSW, Australia). Examinations performed included subjective refraction and Zeiss colour stereo optic disc photographs. Eye and camera magnification effects were corrected. RESULTS: Mean vertical disc diameter was 1.51 mm (95% confidence interval (CI) 1.504-1.516 mm) and the mean vertical cup-disc ratio was 0.43 (95% CI 0.425-0.435). Both parameters were distributed unimodally. The cup-disc ratio was strongly associated with disc diameter. Controlling for other variables, cup-disc ratio increased 0.270 (95% CI 0.250-0.290) per mm increase in disc diameter. CONCLUSIONS: Vertical optic disc diameter and cup-disc ratio are distributed near normally in older Australians. Optic discs with larger vertical diameters have considerably greater vertical cup-disc ratios.

Anthropometry↗

The influence of age and intraocular pressure on the optic cup in a normal population.

PURPOSE: To determine the effects of age and intraocular pressure (IOP) on optic cup and neural rim size, and cup-disc ratio in a well defined population free from apparent glaucoma and other optic nerve disease. METHODS: Data were collected on 3654 people, 49 years or older, living in the Blue Mountains, west of Sydney. Examination included subjective refraction and Zeiss colour stereo (Carl Zeiss, Oberkochen, Germany) optic disc photographs. Magnification effects of the eye and camera were corrected. After excluding subjects with optic nerve diseases, data from 6579 normal phakic eyes of 3358 subject (91.9% of those examined) were used. RESULTS: Adjusted for optic disc size and IOP, cup diameter increased 0.01 mm, cup-disc ratio increased 0.01, and neural rim width decreased 0.01 mm for every decade of age increase. Adjusted for age and optic disc size, cup diameter increased 0.01 mm, cup-disc ratio increased 0.04, and neural rim width decreased 0.07 mm for every 10 mmHg increase in IOP. The IOP-related increase in cup-disc ratio amounted to 9.5% of the mean per 10 mmHg, while the age related increase was 1.9% of the mean. CONCLUSIONS: These data support the hypothesis that there is an age-related loss of tissue from the neuroretinal rim. However the mean change between the ages of 50 and 90 years is very small. The association between increasing IOP and smaller neural rim width could suggest a causal relationship. However, it is also plausible that IOP and optic cup size are both determined by other unmeasured factors.

Aged↗

Prevalence of open-angle glaucoma in Australia. The Blue Mountains Eye Study.

PURPOSE: The purpose of this study was to determine the prevalence of open-angle glaucoma and ocular hypertension in an Australian community whose residents are 49 years of age or older. SUBJECTS: There were 3654 persons, representing 82.4% of permanent residents from an area west of Sydney, Australia, who were examined. The population was identified by a door-to-door census of all dwellings and by closely matched findings from the national census. METHODS: All participants received a detailed eye examination, including applanation tonometry, suprathreshold automated perimetry (Humphrey 76-point test), and Zeiss stereoscopic optic disc photography. Glaucoma suspects were asked to return for full threshold fields (Humphrey 30-2 test), gonioscopy, and repeat tonometry. RESULTS: A 5-point hemifield difference on the 76-point test was found in 616 persons (19% of people tested). Humphrey 30-2 tests were performed on 336 glaucoma suspects (9.2% of population), of whom 125 had typical glaucomatous field defects. Two hundred three persons had enlarged or asymmetric cup-disc ratios (> or = 0.7 in 1 or both eyes or a cup-disc ratio difference of > or = 0.3). Open-angle glaucoma was diagnosed when glaucomatous defects on the 30-2 test matched the optic disc changes, without regard to the intraocular pressure level. This congruence was found in 87 participants (2.4%), whereas an additional 21 persons (0.6%) had clinical signs of open-angle glaucoma but incomplete examination findings. Open-angle glaucoma was thus found in 108 persons, a prevalence of 3.0% (95% confidence interval [CI], 2.5-3.6), of whom 49% were diagnosed previously. An exponential rise in prevalence was observed with increasing age. Ocular hypertension, defined as an intraocular pressure in either eye greater than 21 mmHg, without matching disc and field changes, was present in 3.7% of this population (95% CI, 3.1-4.3), but there was no significant age-related increase in prevalence. The prevalence of glaucoma was higher in women after adjusting for age (odds ratio, 1.5; CI, 1.0-2.2). There was no sex difference in the age-adjusted prevalence of ocular hypertension. CONCLUSIONS: These data provide detailed age and sex-specific prevalence rates for open-angle glaucoma and ocular hypertension in an older Australian population.

Age Distribution↗