Glaucoma, which is the result of the progressive deterioration of the optic nerve, is the second leading cause of blindness.1 For patients with glaucoma, additional eye complications are frequent, including dry eyes2 or ocular surface disease (OSD).3 Both OSD and dry eyes are similar, and researchers have used the broader term OSD4,5 rather than dry eyes to describe the various signs and symptoms involved in the condition. Both terms generally meet the pragmatic approach to diagnosis proposed by the International Dry Eye Workshop. In their report, diagnosis was based on validated questionnaires, presence of at least 1 of 3 symptoms and at least 1 of 2 signs, tear breakup time (TBUT), and Shirmer tear evaluations, or a combination of these criteria.6
However, slight differences in definitions limit comparisons between studies. Dry eyes are defined both by signs (tear film increased osmolarity and ocular surface inflammation) and symptoms (discomfort, visual disturbance, and tear film instability).7 Although the etiology of dry eyes is divided between aqueous deficient and evaporative categories, some overlap related to differentiation and interaction between the mechanisms exists.8
Ocular surface disease is defined as signs of inadequate tear quantity and quality along with ocular surface integrity disruption and symptoms of burning, discomfort, and vision fluctuations.9,10 Specific criteria have varied between researchers, and there is no single algorithm that is widely used to identify OSD.3
The prevalence of these conditions depends upon the definition used. In various epidemiological and clinic-based studies conducted in the glaucoma populations, reported prevalence was 35% to 65% based on signs, 27% to 59% based on symptoms, and 11% to 52% based on a combination of signs and symptoms.2,4,11–13 These higher prevalence rates in patients with glaucoma may be a direct result of the disease because there is growing evidence that glaucoma may result in altered basal tear production rate or dysfunction of the autonomous nervous system.2,14 In addition, glaucoma treatments may result in higher prevalence rates because topical intraocular pressure (IOP)–lowering medications may contain preservatives that contribute to dry eyes.2,4,14 The most frequently used preservative in topical ophthalmic preparations is benzalkonium chloride (BAK), which also has well-established in vitro and ex vivo toxic epithelial effects. Benzalkonium chloride can damage the corneal and conjunctival epithelium, eventually leading to cell necrosis.15–18 Moreover, this direct cellular toxicity of BAK on the ocular surface further increases the risk of dry eye, particularly for patients older than 40 years who are already at risk for age-related dry eye.12 Thus, patients with glaucoma are at a higher risk for developing OSD.2,4 Other risk factors besides increasing age2,19,20 and topical ophthalmic medications include environmental conditions, occupational factors, nutritional factors, hormonal status, contact lens usage, and refractive surgery.2,7,8,21,22
Dry eye is associated with high economic burden23,24 and US$13,404 for first year costs. For those with glaucoma, the additional disease-related costs of dry eyes/OSD would result in an even greater burden. In the US population, Yu et al25 reported costs based on dry eye severity with US$13,364 for mild, $13,340 for moderate, and $19,435 for severe.
Although studies have been conducted in patients with glaucoma worldwide, there have been few studies that have looked at the Australian population. Within the Australian general population older than 40 years of age, dry eye prevalence ranged from 1.5% to 16.8%26 based on signs with moderate to severe symptoms ranging from 6% to 16%.26,27 Risk factors within the Australian population include female sex, certain systemic diseases, and select systemic medications.27 Two recent studies looked at OSD in the glaucoma population.28,29 In an Australian glaucoma population of 300 patients (100 controls), Ghosh et al28 recently reported prevalence rates of 70.3% for patients with 2 or more signs of OSD, compared with 33% of non–glaucoma ophthalmology patients. In addition, there was significant difference between the 2 groups for patients with 1 or more signs of OSD (86% of patients with glaucoma vs 69% of non–glaucoma ophthalmology patients). In a quality of life study of 101 patients with glaucoma, 48% were diagnosed with OSD using the OSD index questionnaire, and a higher proportion of OSD was associated with increasing glaucoma severity.29
The current study is based on the data set used by Ghosh et al5 and extends their work to encompass the selection of an operational criterion for OSD diagnosis using signs and symptoms. In addition, this secondary research estimated the potential economic burden of OSD in the Australian population of patients with glaucoma.
MATERIALS AND METHODS
Population and Data Collection
The study population and the data collection (including the questionnaire used and the tests used for the ocular surface assessment) have been previously described in the primary article5 and summarized below. Australian patients attending the Royal Victorian Eye and Ear Hospital, Melbourne, Australia, were eligible to participate in this cross-sectional, case-comparison study. Patients with glaucoma (n = 300 patients from the tertiary referral glaucoma clinic) who were all receiving BAK-containing topical IOP-lowering treatments were compared with patients (n = 100 control patients) attending a comprehensive ophthalmology clinic in the same hospital for the diagnoses of cataract and vision correction and who were not on topical IOP-lowering medication. Eligible patients were identified based on a review of their medical records at the time of their appointment. The study protocol and informed consent were approved by the Human Research Ethics Committee of the Royal Victorian Eye and Ear Hospital, Victoria, Australia.5 Informed consent was obtained before any study-related procedures. The study adhered to the tenets of the Declaration of Helsinki.30
The data collection included an initial assessment of individual OSD clinical signs and symptoms (Figs. 1A, B and 2A, B).5 Clinical signs of OSD included the following: poor tear quantity using the Schirmer test, poor tear quality as evaluated by TBUT, dysfunction of the Meibomian gland measured by secretion characteristics and grade, corneal surface involvement determined as fluorescein staining, and conjunctival surface involvement determined as fluorescein staining. Patient-reported symptoms were measured by a 5-point frequency (none, infrequent, sometimes, often, or always) and included the following: dryness, gritty or sandy feeling, burning feeling, sticky, crusting on eyelashes, watery or teary, or redness. These tests have been previously described,5 whereas the symptoms were the same 7 symptoms used by Lin et al.31
Ocular Surface Disease Prevalence in Australian Patients
Ocular surface disease prevalence in patients with glaucoma was based on the signs and symptoms presented in the primary article.5 The individual signs and symptoms were combined using different cutoff values for signs and symptom thresholds. Two OSD definitions were evaluated: mild OSD and significant OSD (which encompassed both moderate and severe levels of disease severity). More stringent cutoff values for the signs of OSD were used to define significant OSD than to define mild OSD (Table 1). Similarly, the symptom response threshold for significant (moderate/severe) OSD used frequency categories of “often” or “always,” whereas mild OSD used “sometimes,” “often,” or “always” frequency response categories.
For each classification combination, statistical comparisons were made between the patients with glaucoma and the control groups using χ2 tests (P <0.05 was considered significant). Analysis was conducted using the Statistical Analysis System (SAS) version 9.2 (SAS Institute, Inc, Cary, NC).
Ocular Surface Disease Economic Burden and Cost Estimates
To estimate OSD resource use and related costs, the literature was searched. The authors (C.C., J.C.) consulted on the applicability to the Australian environment, and these resources and costs were then extrapolated and customized to the Australian reality. The authors (C.C., J.C.) considered the US practice similar to Australia because both are Western developed nations with similar incidence of dry eyes, health care attitudes, and training of prescribing eye care professionals and/or pharmacists. The burden of illness was estimated from both the health care system (direct costs) and societal (indirect costs) perspectives. Microsoft Excel 2003 (Microsoft, Redmond, WA) was used to run the economic analysis.
Australian sources were used for treatment options, medication unit pricing, and consultation fees.32,33 Market share information for treatments was purchased from Intercontinental Marketing Services (IMS; St Leonards, New South Wales, Australia).
Currently, there are no Australian data estimating the nutritional supplement use, tear replacements and ocular lubricants, or punctal occlusion (plugs). The proportion of resource use by OSD severity was based on the estimates presented by Yu et al25 in the US population. Products or procedures not widely available in Australia were not included in the analysis. Corticosteroid or tetracycline antibiotic drops23,25 and tarsorrhaphy21,23 have been used in other regions, but their use in Australia is not well known. In addition, gold lid weights and botulinum toxin are used in Europe21 but are rarely used in Australia.
For tear replacements and ocular lubricants, the proportion of resource use by OSD severity estimates were 67.6% for mild, 81.3% for moderate, and 86% for severe.25 For other preserved and nonpreserved tear replacements, the daily cost of the detailed brands was averaged.34 According to Yu et al,25 1 drop has a volume of 0.05 mL, and the average number of daily drops was 5.7 per day. The formula for calculating the yearly cost of ocular lubricants was the following: mean price of each drop of ocular lubricant treatment × the average number of daily drops for a dry eye population × 365 days. Systane PF market share of 2.4% was split equally between the 2 formulations. Tear replacements were assumed to be used equally for both eyes.
For nutritional supplements, the resource use estimates were 60.2% for mild, 63.3% for moderate, and 71.5% for severe.25 In the case of 2 nutritional supplements,35,36 market share was assumed 50-50, and pricing was from the product Web site. Daily fish oil dose was 2 capsules per day.35 Daily recommended flaxseed oil dose was, for adults, at 1 to 2 capsules, 3 times a day, for a total of 4.5 capsules per day.36 For punctal occlusion (plugs), the resource use estimates were 24.3% for mild, 12.8% for moderate, and 15.5% for severe.25 Regarding the punctal occlusion (plugs), this would be performed as an outpatient procedure in the ophthalmologist’s office and there would be a consultation plus the physician fee for the procedure plus the cost of the device. For plug insertion, the Australian Medical Association (AMA) recommendation was considered, and 2011 estimates were used.33
Overall, frequency use of physicians was based on estimates from Yu et al.25 Generally, physicians may reassess every 6 months and may suggest another method or treatment if the condition is still a problem. For ophthalmologist visits, the frequency was 1.1 visits per year for mild, 1.14 visits for moderate, and 1.85 for severe; for optometrist visits, the frequency was 0.9 visits per year for mild, 0.9 visits for moderate, and 1.7 for severe.25 To account for differences in usage by severity of dry eye,25 it also has been assumed that half of the patients were followed up by the ophthalmologist, and half, by optometrist. One visit every 6 months to either the ophthalmologist or the optometrist was assumed. The fees of the AMA guidelines for fair and equitable reimbursement for 2011 were used.33
For indirect costs, the working week for fulltime employees was 40 hours,37 and the average weekly fulltime earning was AU$1004.10 to yield a gross hourly rate of AU$25.10.38 The net hourly rate was calculated as AU$16.00 based on general taxation withholding estimates for 2011.38,39 In a US population, Yu et al25 used the Work Productivity and Activity Impairment questionnaire to estimate indirect costs for the United States. Affected performance was reported as 37.9% for mild severity, 39.5% for moderate, and 53.4% for severe diagnosis, whereas the percentage of lost work days per year (assuming a 40-hour work week) were 8.4% for mild severity, 3.7% for moderate severity, and 14.2% for severe.25 Because the glaucoma population is typically older than the general population, the US estimates25 were adjusted for the Australian population of patients with glaucoma. Assuming a retirement age of 65 years, 36.4% of patients were working individuals, and 63.6% were retired.40
The cost impact of OSD on the Australian society used the number of individuals with glaucoma, as reported by the Australia Institute of Health and Welfare; a total of 137,000 patients with glaucoma were estimated in Australia in the 2005 report.40 Physician costs assumed that most physicians charge above the rebate amount (Medicare benefit); costs were calculated as cost to government (representing the rebate amount) and the gap cost that is cost to the patient.33,41 The economic burden was calculated using the updated OSD definitions derived from the calculation of OSD prevalence in patients with glaucoma and point estimates of direct and indirect costs derived from the average use of resources.
Ocular Surface Disease Prevalence in Australia
In our analysis, significant OSD was experienced by 39% of patients with glaucoma (Table 2), and prevalence was significantly higher OSD in patients with glaucoma compared with the control group (18%, P < 0.0001). Of note, there were significant differences between the glaucoma and control groups when the criterion for OSD used 2 signs or more with 2 or more symptoms (P = 0.0049, data not shown). These descriptors are consistent with published literature2,4,12,27,42 and resulted in the definition of significant OSD as the presence of 2 or more signs plus 1 or more symptoms reported “often” or “always.”
As expected, there were significantly fewer patients with glaucoma without OSD compared with the control (9% vs 20%, P = 0.005; Table 2). Of note, all patients with glaucoma were receiving BAK-containing topical glaucoma treatments.
In this study population, mild OSD (Table 2) was experienced by 52.0% of patients with glaucoma and 62.0% of the control group; there were no significant differences in prevalence between the glaucoma and control groups. The criterion used for mild OSD presented in Table 1 included the following: the presence of 1 or more signs (including Schirmers ≤10 mm, TBUT ≤10 seconds, or any conjunctival or corneal staining) and the presence of 1 or more symptoms (which occur sometimes, often, or always) and not meeting the definition for significant OSD.
Resource Use and Cost of Ocular Surface Disease in Australia
The management of dry eye includes the direct cost estimates found in supplemental tables 1 and 2, http://links.lww.com/APJO/A38 and http://links.lww.com/APJO/A39, and the results for the economic burden for 1 year are presented in Table 3. Because the prevalence of patients with glaucoma with mild OSD was not significantly different from patients in the general population, the mild group was not included in this cost analysis. Thus, only the significant OSD category was used to calculate the economic burden of OSD associated with glaucoma; of note, this category included both patients with moderate and those with severe OSD.
For patients with significant OSD (Table 3), patient cost that included tear replacements or ocular lubricants, nutritional supplements, and punctal occlusion was estimated at AU$764.04, whereas associated health management (eg, consultation and procedure fees, cost of plugs) costs per patient per year were estimated at AU$297.21. Thus, total direct costs were estimated at AU$1061.25 for patients diagnosed with significant OSD. Total indirect costs associated with reduced productivity or absenteeism were estimated at AU$14,078.40 for patients diagnosed with significant OSD. After adjustments for working/retired patients, the mean total cost (direct and indirect) was estimated at AU$6185.79 worth of resources per year for a patient diagnosed with significant OSD.
Based on the Australia Institute of Health and Welfare report that there were 137,000 patients with glaucoma receiving treatment living in Australia,40 we estimated that there were approximately 53,430 individuals with significant OSD and glaucoma in Australia (Table 3). This included 19,449 working and an additional 33,981 individuals considered retired. Thus, the total direct costs associated with significant OSD in patients with glaucoma was estimated at $56,702,578.50, and the estimated total cost (both direct and indirect) to the Australian society for 1 year of treating patients with glaucoma with significant OSD was approximately AU$330.5 million.
The prevalence of significant OSD is significantly higher in patients with glaucoma (39%) compared with the general Australian population (18%). Similar to our analysis, the literature also reports higher rates of OSD in patients with glaucoma compared with patients without glaucoma.5,29,42 Because of the patients with glaucoma receiving treatment with BAK-containing topical treatments and the glaucoma being a condition associated with an age older than 40 years, a greater prevalence of OSD among the patients with glaucoma was expected when compared with the control group.2,4,28,29
In addition, the prevalence of OSD in the glaucoma population varies based on the definition used.4,5 Because the literature showed that there is no clear-cut defining/diagnosing algorithm for OSD, we defined significant OSD (encompassing both moderate and severe OSD) as the presence of 2 or more signs that used more stringent cutoff values (Schirmers ≤ 5 mm, TBUT ≤ 5 seconds, or any conjunctival/corneal staining) and 1 or more symptoms reported as “often” or “always.” Our rate of 39% for significant OSD was lower than the 48% rate reported by Skalicky et al29 that used a smaller Australian glaucoma population and a criterion of OSD index of greater than 12/100. Our rate of significant OSD also was lower than the combined 46% rate reported by Yu et al25 for patients who used professional eye care (40% for those who did not seek professional care). These researchers used the criteria of either OSD index of greater than 12/100 or previous OSD diagnosis to stratify patients by OSD severity (54%–60% mild, 31%–34% moderate, and% 9–12% severe).25 Of note, Ghosh et al (2012) reported higher rates (70%–86%) when they defined significant OSD using only 2 or more signs.28 Compared with other US glaucoma populations, our rate of 39% was higher than a survey using diagnosis codes and/or medication (16.5%)42 or a study of symptom responses and number of IOP-lowering drops taken per day (15%–26%).12 Our rates were also similar to a third study that used survey questions of symptoms or tests of signs (severe OSD, 27%–65%). This later study combined mild and moderate OSD, so comparisons with our rates are limited.4
Compared with OSD in the general population, our rates would be expected to be higher in this glaucoma population.25–27 Furthermore, our rates were higher compared with those of Australian studies evaluating dry eye in the general population26,27; however, both studies used different definitions of dry eyes. Similar to our study, the Melbourne study used both a patient-ranked severity scale and clinical signs,26 whereas the second study used only patient-ranked symptoms as a severity scale.27 In the US study evaluating dry eyes in the general population, self-reported severity of symptoms was also used to define moderate to severe dry eye.25
Of note, a definition for mild OSD was proposed based on our analysis and includes the following: the presence of 1 or more signs (including Schirmers ≤ 10 mm, TBUT ≤ 10 seconds, or any conjunctival or corneal staining), the presences of 1 or more symptoms (which occur sometimes, often, or always), and not meeting the definition for significant OSD. In our study, 52% of the patients with glaucoma and 62% of the control patients had mild OSD. In the Australian Blue Mountain Eye Study, almost 58% reported at least 1 symptom in the general Australian population.27 These results are similar to ours in both the glaucoma and general population.
In our study, the direct costs were estimated at AU$1,061.25 for treating patients with significant OSD. By comparison, the results in Yu et al25 showed decreased costs for treating moderate dry eye disease (AU$747) and slightly higher costs for treating severe OSD (AU$1228). Similarly, for indirect costs, our estimate of AU$14,078.40 was between the Yu et al25 values for moderate (AU$12,181) and severe (AU$17,607) for dry eye disease. Although indirect costs, represented by loss of work time (absenteeism) and productivity loss (present), were high in our study, these patient-related costs are often overlooked by clinicians in a busy clinic setting.
Furthermore, our total cost (direct and indirect) of AU$6185.79 per patient for significant OSD was lower than the dry eye disease costs for moderate (AU$12,928, adjusted from US$13,340) and severe (AU$18,835, adjusted from US$19,435) reported by Yu et al25 in the general population. This was expected because the glaucoma population has a higher proportion of older and retired individuals than a general population; hence, the indirect costs (time lost from work because of absenteeism and loss of productivity) were lower. For significant OSD, the total cost to Australian society was estimated as approximately AU$330.5 million. This is based on 137,000 patients diagnosed with glaucoma in Australia. However, the Australian Institute of Health and Welfare noted that approximately half of the population may not be aware of having glaucoma.40
Of note, mild OSD costs, which were not included in the overall Australian burden estimates, were similar in prevalence to the control population, and this suggests that overall economic burden for OSD would be similar for the 2 populations. This result may also be due to underdiagnosis of glaucoma as proposed by the Australian Institute of Health and Welfare.40 However, in our study, control subjects were also attending the eye clinic for nonglaucoma diagnosis and underdiagnosis of glaucoma were less likely to occur with these additional evaluations. The presence of more than 50% of both populations with mild OSD may be due to other environmental (including medications) or occupational influences that were not classified in our study. Of note, mild OSD total direct (AU$985.58) and indirect (AU$12,723.20) costs per year per patient were also adjusted to account for the older glaucoma population; after adjustments for older working (AU$13,708.78) and retired individuals (AU$985.58), the average total costs was AU$5616.82. As expected in a glaucoma population, this estimate was also lower compared with the AU$12,951 (adjusted from US$13,364) reported by Yu et al25 in a general population. Furthermore, based on a prevalence rate of 52%, mild OSD would add an additional AU$400.1 million to the estimated disease burden of significant OSD, whether they had glaucoma or not.
There have been 2 OSD studies in the Australian general population26,27 and 3 studies in the Australian glaucoma population; there were no studies identified in the literature that evaluated the impact of dry eyes or OSD on Australian patient quality of life. However, there were studies that evaluated QoL in populations with similar demographics to the Australian population.12,43–48 The literature showed that the impact of dry eye on QoL is mainly symptom driven.43 Thus, QoL measures provide patient-reported data that cannot be obtained through objective measures. These become extremely valuable in assisting clinicians in the assessment of dry eye severity and its management,44 especially with the documented lack of concordance between patient-reported symptoms of dry eye and commonly used diagnostic tests or physician-assessed severity.46–48 In the case of patients with glaucoma, patients who had 3 drops of glaucoma medication daily had lower QoL, based on the OSD index; however, the number of drops taken per day did not correspond to OSD severity.12 To confirm QoL results in the Australian population, additional studies are needed.
Direct estimation of the burden of treating OSD in the Australian system was limited by connectivity between records and records maintained in multiple and disparate sources. Thus, extrapolation techniques were used to estimating the burden for Australian care. In the future, additional studies that allow connectivity between the various sources of records would allow confirmation of the estimates presented in our study.
There were several limitations. The criteria used in survey data collection were not standardized. Our symptom questionnaire was previously used in the Shihpai Eye Study31 and used a 5-point Likert response scale that was similar to the OSD index scale.28 Ocular surface disease definitions vary across studies, and we were not able to separate severe and moderate OSD based on the symptoms reported in the questionnaire.5,31 Because signs and symptoms may not be aligned across various studies, between-trial comparisons are limited. Patients selected for this prevalence study were from a tertiary referral clinic mostly on polypharmacy and therefore likely to have higher rates of OSD than the general community of patients with glaucoma. Furthermore, the high rate in the control patients may be because these patients were also from a comprehensive eye clinic, which includes patients with various eye conditions.
The literature search for resource utilization and cost was not a systematic review. Actual utilization data was not collected, and therefore, point estimates were based on available published information and clinical inputs from the authors. Although the authors used the article by Yu 25 because of similarities between the US population and their practice, the US data may not reflect the same resource use in Australia. The hospital-based cohort may not reflect patients treated in a nonhospital setting.
The economic burden point estimates relied on the prevalence analyses of our population, and the total costs of OSD to society might be overestimated. Economic burden estimates were based on extrapolation because of limited connectivity between patient records in Australia.
The wide use of standard OSD definition across studies will allow comparison of results and improved determination of the OSD prevalence. In this Australian cross-sectional, hospital clinic-based population, the prevalence of significant (moderate and severe) OSD in patients with glaucoma was 39% and was significantly higher than in the control group. Mild OSD was identified in 52% of the patients with glaucoma in our study, and this was not significantly different from the control group. These relatively high rates of OSD in our study population may be related to the increased risk of OSD associated with the use of BAK-containing therapies by the patients of a comprehensive eye clinic. The economic burden of significant OSD was estimated at approximately AU$330.5 million. This is the first step at understanding the economic impact of OSD in the Australian glaucoma population. Additional studies to estimate actual direct/indirect costs of OSD in the Australian population are being considered, and modeling studies that use simulated or observational data would provide additional use and costs estimates. Within this context, additional studies to evaluate quality of life are needed.
The authors thank the following OptumInsight employees: Laura Oberthur Johnson, PhD (United States), for her contribution in preparing the first draft and final revision of this article, and Margaret Hux (Burlington, Ontario, Canada) for providing assistance with the conduct of the study.
1. Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol
. 2006; 90: 262–267.
2. Erb C, Gast U, Schremmer D. German register for glaucoma patients with dry eye. I. Basic outcome with respect to dry eye. Graefes Arch Clin Exp Ophthalmol
. 2008; 246: 1593–1601.
3. Pflugfelder SC, Baudouin C. Challenges in the clinical measurement of ocular surface disease in glaucoma patients. Clin Ophthalmol
. 2011; 5: 1575–1583.
4. Leung EW, Medeiros FA, Weinreb RN. Prevalence of ocular surface disease in glaucoma patients. J Glaucoma
. 2008; 17: 350–355.
5. Ghosh S, O’Hare F, Lamoureux E, et al.. Prevalence of signs and symptoms of ocular surface disease in individuals with and without glaucoma. Clin Experiment Ophthalmol
. 2012; 40: 675–681.
6. Dry Eye Workshop Subcommittee (DEWS). Methodologies to diagnose and monitor dry eye disease: report of the Diagnostic Methodology Subcommittee of the International Dry Eye WorkShop. Ocul Surf
. 2007; 5: 108–152.
7. Dry Eye Workshop Subcommittee (DEWS). The definition and classification of dry eye disease: report of the Definition and Classification Subcommittee of the International Dry Eye Workshop. Ocul Surf
. 2007; 5: 75–92.
8. Perry HD. Dry eye disease: pathophysiology, classification, and diagnosis. Am J Manag Care
. 2008; 14 (Suppl 3): S79–S87.
9. Latkany R. Dry eyes: etiology and management. Curr Opin Ophthalmol
. 2008; 19: 287–291.
10. Lemp MA, Foulks GN. The definition and classification of dry eye disease: report from the Definition and Classification Subcommittee of the Internation Dry Eye Workshop. Ocul Surf
. 2007; 5: 75–92.
11. Fechtner RD, Godfrey DG, Budenz D, et al.. Prevalence of ocular surface complaints in patients with glaucoma using topical intraocular pressure-lowering medications. Cornea
. 2010; 29: 618–621.
12. Rossi G, Tinelli C, Pasinetti G, et al.. Dry eye syndrome-related quality of life in glaucoma patients. Eur J Ophthalmol
. 2009; 19: 572–579.
13. Garcia-Feijoo J, Sampaolesi JR. A multicenter evaluation of ocular surface disease prevalence in patients with glaucoma. Clin Ophthalmol
. 2012; 6: 441–446.
14. Tsai JH, Derby E, Holland EJ, et al.. Incidence and prevalence of glaucoma in severe ocular surface disease. Cornea
. 2006; 25: 530–532.
15. Gasset AR, Ishii Y, Kaufman H, et al.. Cytotoxicity of ophthalmic preservatives. Am J Ophthalmol
. 1974; 78: 98–105.
16. Wilson F. Adverse external effects of topical ophthalmic medications. Surv Ophthalmol
. 1979; 24: 57–88.
17. Burstein N. Corneal cytotoxicity of topically applied drugs, vehicles and preservatives. Surv Ophthalmol
. 1980; 25: 15–30.
18. Burstein N. The effects of topical drugs and preservatives on the tears and corneal epithelium in dry eye. Trans Ophthalmol Soc UK
. 1985; 104: 402–409.
19. Moss SE, Klein R, Klein BE. Prevalence of and risk factors for dry eye syndrome. Arch Ophthalmol
. 2000; 118: 1264–1268.
20. Rudnicka AR, Mt-Isa S, Owen CG, et al.. Variations in primary open-angle glaucoma prevalence by age, gender, and race: a Bayesian meta-analysis. Invest Ophthalmol Vis Sci
. 2006; 47: 4254–4261.
21. Clegg JP, Guest JF, Lehman A, et al.. The annual cost of dry eye syndrome in France, Germany, Italy, Spain, Sweden and the United Kingdom among patients managed by ophthalmologists. Ophthalmic Epidemiol
. 2006; 13: 263–274.
22. Dry Eye Workshop Subcommittee (DEWS). The epidemiology of dry eye disease: report of the Epidemiology Subcommittee of the International Dry Eye WorkShop. Ocul Surf
. 2007; 5: 93–107.
23. Reddy P, Grad O, Rajagopalan K. The economic burden of dry eye: a conceptual framework and preliminary assessment. Cornea
. 2004; 23: 751–761.
24. Pflugfelder SC. Prevalence, burden, and pharmacoeconomics of dry eye disease. Am J Manag Care
. 2008; 14 (Suppl 3): S102–S106.
25. Yu J, Asche CV, Fairchild CJ. The economic burden of dry eye disease in the United States: a decision tree analysis. Cornea
. 2011; 30: 379–387.
26. McCarty CA, Bansal AK, Livingston PM, et al.. The epidemiology of dry eye in Melbourne, Australia. Ophthalmology
. 1998; 105: 1114–1119.
27. Chia EM, Mitchell P, Rochtchina E, et al.. Prevalence and associations of dry eye syndrome in an older population: the Blue Mountains Eye Study. Clin Experiment Ophthalmol
. 2003; 31: 229–232.
28. Ghosh S, O’Hare F, Lamoureux E, et al.. Prevalence of signs and symptoms of ocular surface disease in individuals treated and not treated with glaucoma medication. Clin Experiment Ophthalmol
. 2012; 40: 675–681.
29. Skalicky SE, Goldberg I, McCluskey P. Ocular surface disease and quality of life in patients with glaucoma. Am J Ophthalmol
. 2012; 153: 1–9 e2.
30. Assembly tWG. WMA Declaration of Helsinki—Ethical Principles for Medical Research Involving Human Subjects
. October 2008 ed. Seoul, Korea: World Medical Association (WMA); 2008.
31. Lin PY, Tsai SY, Chend CY, et al.. Prevalence of dry eye among an elderly Chinese population in Taiwan—the Shihpai Eye Study. Ophthalmology
. 2003; 110: 1096–1101.
32. Asbell PA, Lemp MA Dry Eye Disease: The Clinician’s Guide to Diagnosis and Treatment
. New York: Thieme Medical Publishers, Inc; 2006.
33. Australian Medical Association (AMA). List of medical services and fees: McPherson’s Printing Group; 2010.
34. Michou L, Brown JP. Emerging strategies and therapies for treatment of Paget’s disease of bone. Drug Design Devel Therapy
. 2011; 5: 225–239.
35. Blackmores. Product information—Fish Oil 1000. Blackmores (Australia) Web site. 2011. Available at: http://www.blackmores.com.au/products/fish-oil-1000
. Accessed 15 February 2011.
36. Blackmores. Product Information—Flaxseed Oil. Blackmores (Australia) Web site. 2011. Avaolable at: http://www.blackmores.com.au/products/flaxseed-oil
. Accessed 15 February 2011.
37. Pink B. 2009–10 Year Book Australia
. Canberra, Australia: Australian Bureau of Statistics (ABS); 2010.
38. Australian Bureau of Statistics. 6302.0—Average weekly earnings, Australia, Feb 2011. 2011; Available at: http://abs.gov.au/ausstats/[email protected]/mf/6302.0/
. Accessed 14 June 2011.
39. Australian Taxation Office. Tax Withheld Calculator Home Page. 2011; Available at: http://www.ato.gov.au/scripts/taxcalc/
. Accessed 14 June 2011.
40. Australian Institute of Health and Welfare (AIHW). Vision problems among older australians. 2005;Bulletin no.27(AUS cat. No. AUS 60). Available at: http://www.aihw.gov.au/publications/aus/bulletin27/bulletin27.pdf
. Accessed February 17, 2011.
42. Schmier J, Covert D. Characteristics of respondents with glaucoma and dry eye in a national panel survey. Clin Ophthalmol
. 2009; 3: 645–650.
43. Hirsch JD. Considerations in the pharmacoeconomics of dry eye. Manag Care
. 2003; 12: 33–38.
44. Friedman NJ. Impact of dry eye disease and treatment on quality of life. Curr Opin Ophthalmol
. 2010; 21: 310–316.
45. Miljanovic B, Dana R, Sullivan DA, et al.. Impact of dry eye syndrome on vision-related quality of life. Am J Ophthalmol
. 2007; 143: 409–415.
46. Mizuno Y, Yamada M, Miyake Y. Dry eye survey group of the National Hospital Organization of Japan. Association between clinical diagnostic tests and health-related quality of life surveys in patients with dry eye syndrome. Jpn J Ophthalmol
. 2010; 54: 259–265.
47. Buchholz P, Steeds CS, Stern LS, et al.. Utility assessment to measure the impact of dry eye disease. Ocul Surf
. 2006; 4: 155–161.
48. Schiffman RM, Walt JG, Jacobsen G, et al.. Utility assessment among patients with dry eye disease. Ophthalmology
. 2003; 110: 1412–1419.
I shut my eyes in order to see.
– Paul Gauguin