Anne J. Lee

Prevalence and associations of dry eye syndrome in an older population: the Blue Mountains Eye Study

This report describes the prevalence of self‐reported dry eye syndrome and associations with systemic and ocular factors in an older Australian population. Participants of the Extension Blue Mountains Eye Study, aged 50 or older (mean age 60.8 years, n = 1174) completed a comprehensive eye examination and dry eye questionnaire. At least one dry eye symptom was reported by 57.5% of participants, with 16.6% reporting moderate to severe symptoms, more frequent in women (age‐adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1−2.2). Three or more symptoms were reported by 15.3% of participants, also more frequent in women (age‐adjusted OR 1.7, CI 1.2−2.4). No age‐related trends or significant ocular associations were observed. After adjusting for age and sex, systemic factors significantly associated with dry eye syndrome included history of arthritis, asthma, gout, use of corticosteroids, antidepressants and hormone replacement therapy. In this older population, dry eye syndrome was common and has associations with female gender and systemic diseases.

Open-angle glaucoma and systemic hypertension: the blue mountains eye study.

Purpose:To assess whether systemic hypertension is associated with open-angle glaucoma (OAG) in an older population. Patients and Methods: The Blue Mountains Eye Study examined 3654 subjects aged 49 to 97 years. Hypertension was diagnosed from history in treated subjects or from systolic blood pressure (BP) ≥160 mm Hg or diastolic BP ≥95 mm Hg. OAG was diagnosed from congruous glaucomatous optic disc rim thinning and visual field loss, without reference to intraocular pressure (IOP) level. Ocular hypertension (OH) was defined when IOP was > 21 mm Hg in either eye, among persons without OAG. Results:Hypertension was present in 45.7% of subjects, OAG in 3.0%, and OH in 5.2%. Hypertension was significantly associated with OAG, after adjustment for OAG risk factors including IOP, odds ratio (OR) 1.56, 95% confidence interval (CI) 1.01–2.40. This relation was strongest in subjects with poorly controlled treated hypertension (OAG prevalence 5.4%), compared with normotensive subjects (OAG prevalence 1.9%), independent of IOP (OR 1.88, CI 1.09–3.25). The population attributable risk for hypertension (20.4%) was higher than for other identified OAG risk factors. The prevalence of OH was 8.1% in subjects with poorly controlled treated hypertension (OR 1.81, CI 1.20–2.73) and 8.2% in untreated hypertension (OR 1.96, CI 1.31–2.95), compared with 4.2% in normotensive subjects. Conclusions:Hypertension, particularly if poorly controlled, appears related to a modest, increased risk of OAG, independent of the effect of BP on IOP and other glaucoma risk factors. However, we could not exclude nocturnal hypotensive episodes among treated subjects. Hypertension was also associated with OH, a relationship that could in part reflect the influence of BP on IOP.

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.

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 ⩾22 mm Hg. Results: A significantly increased OAG risk with later (>13 years) compared with earlier (⩽12 years) age of menarche was found, odds ratio (OR) = 2.0; 95% confidence interval (CI) 1.0 to 3.9, p for trend = 0.01, after adjustment for multiple confounders. Non-significant increased odds for OAG were found for early natural menopause (<45 years) compared with the reference group (⩾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.

Retinal vessel caliber is associated with the 10-year incidence of glaucoma: the Blue Mountains Eye Study.

PURPOSE To examine associations between quantitatively measured retinal vessel caliber and the 10-year incidence of primary open-angle glaucoma (OAG). DESIGN Population-based cohort study. PARTICIPANTS The Blue Mountains Eye Study examined 3654 persons at baseline and 2461 persons at either 5 years, 10 years, or both times. After excluding 44 subjects with OAG at baseline, 2417 participants at risk of OAG at the 5- or 10-year examinations were included. METHODS Retinal vessel calibers of baseline retinal photographs were measured using a computer-based program and summarized as central retinal artery and vein equivalents (CRAE, CRVE). Incident OAG was defined as the development of typical glaucomatous visual field loss combined with matching optic disc rim thinning and an enlarged cup-to-disc (C:D) ratio of >0.7 or C:D asymmetry between the 2 eyes (≥0.3) at either the 5- or 10-year examination. Generalized estimating equation models were used to account for correlation between eyes while adjusting for glaucoma risk characteristics including intraocular pressure (IOP) or ocular perfusion pressure (OPP). MAIN OUTCOME MEASURES We assessed the 10-year incidence of OAG. RESULTS There were 82 persons (104 eyes) who developed incident OAG over the 10-year follow-up. After adjusting for age, sex, family history of glaucoma, smoking, diabetes, hypertension, hypercholesterolemia, body mass index, spherical equivalent refraction, and C:D ratio, narrower CRAE was associated with higher risk of incident OAG (adjusted odds ratio [OR], 1.77; 95% confidence interval [CI], 1.12-2.79, per standard deviation decrease in CRAE). This association persisted after further adjustment for IOP (adjusted OR, 1.87; 95% CI, 1.14-3.05) or OPP (adjusted OR, 1.76; 95% CI, 1.11-2.78), and remained significant when analyses were confined to eyes with IOP<20 mmHg and C:D ratio<0.6 at baseline. There were no independent associations between CRVE and incident OAG. CONCLUSIONS Retinal arteriolar narrowing, quantitatively measured from retinal photographs, was associated with long-term risk of OAG. These data support the concept that early vascular changes are involved in the pathogenesis of OAG and suggest that computer-based measurements of retinal vessel caliber may be useful to identify people with an increased risk of developing the clinical stage of glaucoma. FINANCIAL DISCLOSURE(S) The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Does smoking affect intraocular pressure? Findings from the Blue Mountains Eye Study.

PurposeTo assess the relationship between smoking and intraocular pressure. Materials and MethodsThe Blue Mountains Eye Study examined 3654 residents aged 49 years and older in an area west of Sydney, Australia from 1992 to 1994. A trained interviewer collected a detailed history of smoking. Intraocular pressure was measured using Goldmann applanation tonometry; as the correlation between right and left eyes was very high, only right-eye data are presented. Participants using glaucoma medications or who had evidence of previous cataract surgery were excluded. ResultsCurrent smokers (15.8% of participants) had slightly higher mean intraocular pressures (16.34 mm Hg) than nonsmokers (16.04 mm Hg). Intraocular pressure (in the right eye) was significantly associated with current smoking, after adjusting for age and sex (P = 0.03). This association remained unchanged after simultaneous adjustment for other variables associated with intraocular pressure, including blood pressure, diabetes, myopia, glaucoma, family history, and pseudoexfoliation (P = 0.02). ConclusionsThis study identified a modest cross-sectional positive association between current smoking and intraocular pressure.

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

AbstractPurpose 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 vs2.8%). 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 vs2.8%), multivariate OR 2.1; 95% CI 1.0–4.4, or history of thyroid surgery (6.5 vs2.8%), 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.

Emerging drugs for ocular hypertension

Introduction: Glaucoma is a prevalent ocular disease with characteristic optic disc and visual field changes. Globally, it is the second most common cause of visual disability, and the most common cause of irreversible and preventable blindness. Ocular hypertension (OH) occurs where intraocular pressure elevation occurs in the absence of glaucomatous disc and visual field changes. OH is a strong risk factor for glaucoma. Ocular hypotensive medications are the mainstay of glaucoma and OH treatment, and their use modifies the course of the disease by preventing onset and progression of damage. Areas covered: Prostaglandin analogs, β-blockers, α-agonists, carbonic anhydrase inhibitors and parasympathomimetics are available in our glaucoma armamentarium and are reviewed. Novel agents have evolved as our understanding of the complex mechanisms involved in aqueous humor production and obstacles to aqueous outflow increases. Potential future candidates appear to act on enhancing trabecular meshwork outflow: the Rho-kinase inhibitors, ion-channel modulators and chelating agents. Further work is needed on other promising agents: serotonergics, melatonins, cannabinoids, adenosine agonists, components of the actomyosin system, nucleotide analogs and gene silencing. Methods to improve side effect profiles or efficacy of currently available therapies are also being developed. As glaucoma treatment adherence is poor, novel drug delivery methods might address this challenge. Expert opinion: Although there are good intraocular pressure-lowering medications available, novel mechanisms and drug delivery modes may provide more effective glaucoma control in future.

Clinical utility and differential effects of prostaglandin analogs in the management of raised intraocular pressure and ocular hypertension

Prostaglandin analogs (PGA) are powerful topical ocular hypotensive agents available for the treatment of elevated intraocular pressure (IOP). Latanoprost 0.005% and travoprost 0.004% are prodrugs and analogs of prostaglandin F2α. Bimatoprost 0.03% is regarded as a prostamide, and debate continues as to whether it is a prodrug. The free acids of all 3 PGAs reduce IOP by enhancing uveoscleral and trabecular outflow via direct effects on ciliary muscle relaxation and remodeling of extracellular matrix. The vast majority of clinical trials demonstrate IOP-lowering superiority of latanoprost, bimatoprost and travoprost compared with timolol 0.5%, brimonidine 0.2%, or dorzolamide 2% monotherapy. Bimatoprost appears to be more efficacious in IOP-lowering compared with latanoprost, with weighted mean difference in IOP reduction documented in one meta-analysis of 2.59% to 5.60% from 1- to 6-months study duration. PGAs reduce IOP further when used as adjunctive therapy. Fixed combinations of latanoprost, bimatoprost or travoprost formulated with timolol 0.5% and administered once daily are superior to monotherapy of its constituent parts. PGA have near absence of systemic side effects, although do have other commonly encountered ocular adverse effects. The adverse effects of PGA, and also those found more frequently with bimatoprost use include ocular hyperemia, eyelash growth, and peri-ocular pigmentary changes. Iris pigmentary change is unique to PGA treatment. Once daily administration and near absence of systemic side effects enhances tolerance and compliance. PGAs are often prescribed as first-line treatment for ocular hypertension and open-angle glaucoma.

Bias in self-reported family history and relationship to glaucoma: the Blue Mountains Eye Study.

PURPOSE To examine bias in the relationship between self-reported family history of glaucoma and its relationship to the prevalence of glaucoma and ocular hypertension. METHODS In a cross-sectional population-based study of 3654 Australians aged 49–97, participants were asked whether any first-degree relatives had been diagnosed with glaucoma. Open-angle glaucoma was diagnosed from matching optic disc and typical visual field changes, after gonioscopy. Ocular hypertension (OH) was diagnosed from elevated intraocular pressure (IOP) in subjects without glaucoma. RESULTS Glaucoma was present in 3.0% and ocular hypertension in 5.2% of subjects. A parent or sibling was reported to have glaucoma by 8.6%,including 10.5% of women and 5.9% of men. A positive family history was reported more frequently in parents (6.4%) than siblings (2.6%). Glaucoma was reported more frequently to affect mothers (5.0%) and sisters (1.6%) than fathers (1.5%) and brothers (1.2%). A first-degree family history was given by 15.7% of subjects with glaucoma compared to 8.3% of controls, odds ratio (OR) 3.2 (95% CI 1.8–5.6), after adjusting for glaucoma risk factors, including IOP. The association had a similar magnitude for a family history in parents and siblings. Although recall bias was evident from the finding of increased odds (OR 4.2) among previously diagnosed cases, the relationship with family history also persisted in newly-diagnosed cases (OR 2.4). A slightly stronger relationship was found between OH and glaucoma family history, OR 3.9 (95% CI 2.6–5.7), after adjusting for confounders, but was also strongly influenced by recall bias. CONCLUSION Although a positive family history of glaucoma may help to identify those at risk, it is subject to recall, selection and survival bias as well as community under-diagnosis of glaucoma and will most likely substantially underestimate the genetic influence.