Barriers to Medical Treatment of Glaucoma - Drop Resistance and Intolerance in Patients Study (DRIPS)

Barriers to Medical Treatment of Glaucoma - Drop Resistance and Intolerance in Patients Study (DRIPS) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Barriers to Medical Treatment of Glaucoma - Drop Resistance and Intolerance in Patients Study (DRIPS) Natalie Liu, Graham A Lee, Jennifer Fan Gaskin, Simon Skalicky, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7362234/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background: Eye drop noncompliance is a recognised risk factor for glaucoma-related vision loss. This study seeks to quantify the factors driving noncompliance with topical therapy among glaucoma patients. Methods: This was a retrospective observational study of glaucoma patients in both private and public clinics, self-completing a 12-item Drop Resistance and Intolerance of Patients Study (DRIPS) questionnaire, categorised into compliance, adverse effects and accessibility. Results: A total of 448 patients (M:F – 225:223) with glaucoma were included in the study. Stronger compliance was significantly associated with fewer adverse effects (β=0.21, p<0.01) and greater accessibility (β=0.15, p<0.01). A greater number of drops was associated with significantly poorer compliance (β=-0.56, p<0.01) and worse adverse effects (β=-0.91, p=0.02). Greater accessibility was significantly associated with older age (β=0.30, p<0.01) and had a nearly significant association with better visual field MD scores (β=0.42, p=0.08). Age (β=-0.09, p=0.10), length of time on drops (β=0 . 05, p=0.50) and visual field MD score (β=0.21, p=0.18) were not significantly associated with compliance. Conclusion: This study of adult glaucoma patients revealed that a greater number of prescribed glaucoma drops is significantly associated with poorer patient compliance and increased adverse effects, highlighting a critical challenge in glaucoma management. While older age was associated with greater drop accessibility, overall compliance was influenced primarily by the complexity of the medication regimen rather than factors such as age, sex, disease severity, or treatment duration. These findings underscore the need for strategies to simplify treatment regimens and address adverse effects to improve patient adherence and outcomes in glaucoma care. compliance glaucoma eye drops patient experience compliance minimally invasive glaucoma surgery (MIGS) Figures Figure 1 Figure 2 Introduction Medical treatments to reduce intraocular pressure (IOP) aim to slow the progression of vision loss and delay the need for invasive surgical intervention. 1 Topical eye drops are traditionally the first-line treatment option. 2 Despite being non-invasive and relatively inexpensive, many glaucoma patients do not take drops as prescribed. 3 – 9 In Australia, contemporary population-based estimates of compliance with topical prescriptions have been reported to be as low as 37% at 6 months and 30% at 12 months, plummeting further to 20% at 36 months. 5 Even among patients who do fill their prescriptions, between 23% and 90% do not adhere to the recommended frequency of instillation. 8 , 10 , 11 Additionally, electronic eye drop monitoring systems have reported nonadherence rates ranging between 3% and 40%. 3, 12 , 13 Noncompliance has long been established as a risk factor for the progression of glaucoma-related vision loss. 14 15–17 However, limited literature exists in Australia on the factors driving noncompliance in glaucoma patients. The barriers to glaucoma treatment adherence are multifaceted, with one study 18 identifying 71 obstacles that could be classified into situational/environmental factors, medication regimens, patient factors and provider factors. Other studies have highlighted important variables, including lack of health literacy regarding glaucoma, depression/mental health status, lack of faith in the efficacy of the drops, issues with eye drop instillation, forgetfulness, trust/rapport with treating clinicians, and practicality of obtaining medications (timing, location, packaging). 8 , 12 , 19 There is varying evidence surrounding the relationship between patient adherence and demographic factors such as age, sex, cultural background, socioeconomic status and geographical location. 6 , 20 Given the nuances inherent in patient behaviours surrounding treatment compliance, it is important to identify the risk factors for poor adherence. Targets can then be identified for interventions tailored to the appropriate patient demographics. This study aimed to evaluate the factors influencing patient intolerance to glaucoma medication. Methods Design and data collection The Drop Resistance and Intolerance Study (DRIPS) is a 12-item questionnaire that addresses compliance, adverse effects and accessibility, common ophthalmic tests, pre- and intra-consultation factors, and cost values (Fig. 1 ). This instrument, developed by coauthors (GL, GK, JFG, and SS), was designed to be patient friendly to optimise participant engagement and comprehension. The data were quantified via a 100 mm visual analogue scale (VAS), where a score of 0 indicates ‘a big problem’ and 100 indicates ‘no problem’. The questionnaire was designed to be self-administered by the patient and assisted by their accompanying person if needed. The epidemiological data, eye status data and glaucoma management data were obtained by an ophthalmic assistant or a doctor. The combination of items in our study is original and has not been previously investigated; however, the 100 mm VAS-based survey format has been previously used within an Australian cohort of glaucoma patients in a private outpatient context. 21 The study questionnaire was piloted with 20 patients to ensure that the format of the questions was optimised. The test duration for each patient was approximately five minutes on average. Where patients marked with a cross above or below the line, measurements were taken from the closest point from the apex of the tick. The following factors were assessed for their associations with compliance, adverse effects and accessibility: age, sex, number of drops, time on drops, and visual field mean deviation (MD) of the eye. The scores of each question were entered into a database such that each patient had a score for each of the categories. Participant selection This study was conducted on adult patients (aged ≥ 21 years) attending ophthalmologists of the Australian and New Zealand Glaucoma Society DRIPS Collaboration from October 2024 to December 2024. Ethics approval was granted by the University of Queensland Human Research Ethics Committee (Project number 2024/HE001611), abiding by the tenets of the Declaration of Helsinki. Patients were provided with information sheets, and informed consent was obtained before their engagement in the study. Individuals were excluded from the study if they were unable to provide consent, were < 21 years of age, had language or comprehension difficulty, had reduced vision preventing completion of the VAS or had acute ocular pathology. Any patient fulfilling the selection criteria was approached prior to their consultation and invited to participate. Data analysis Descriptive statistics were used to summarise patient demographics, clinical characteristics, and questionnaire responses. Continuous variables are presented as the means with standard deviations (SDs), whereas categorical variables are reported as frequencies and percentages. Variables within the three groups of questions—compliance, adverse effects, and accessibility—were averaged to generate an overall score for each respective group. Associations between overall compliance, adverse effects, and accessibility scores were assessed via multiple linear regression models, with adjustments for potential confounders such as age, sex, number of drops, duration of drop use, and visual field MD scores. Beta coefficients (β) with corresponding p values were reported to indicate the strength and significance of relationships. Missing data were handled via pairwise deletion to maximize the use of available information. Statistical significance was set at p < 0.05, and analyses were performed via SPSS (version 23). Results A total of 448 adult patients with glaucoma were included in the study. The mean age was 67.8 years (SD = 11.1), with ages ranging from 21–91 years. The cohort consisted of 225 (50.2%) women and 223 (49.8%) men. The majority of patients (374 (83.5%)) were seen in private clinics, whereas 68 (15.2%) were seen in public hospital clinics. Most patients were phakic 228 (50.9%) (Table 1 ). The most prevalent type of glaucoma was primary open-angle glaucoma 358 (80.0%). Other types of glaucoma included primary angle closure glaucoma 22 (4.9%), normal tension glaucoma 10 (2.2%) and secondary glaucoma 42 (9.4%), including pseudoexfoliation glaucoma 20 (4.5%). In terms of previous glaucoma procedures, selective laser trabeculoplasty (SLT) was the most common procedure 111 (24.8%), followed by trabeculectomy 18 (4.0%), peripheral iridotomy 13 (2.9%) and minimally invasive glaucoma surgery (MIGS) 15 (3.4%). On average, patients took 2.8 (range 1–14) glaucoma drops per day. The average duration of treatment was 8.0 years, with a range of 1 month to 58 years. Patients were most commonly prescribed single agent regimens 201 (44.9%), the most common being prostaglandin analogues (PGA) 159 (35.5%). Beta blockers (BB) were the second most common single agent 27 (6.0%), followed by carbonic anhydrase inhibitors (CAI) 12 (2.7%). There were 145 (32.4%) patients who were prescribed dual agent regimens; the most common combination was BB and PGA, which was prescribed to 92 (20.5%) patients. Among the patients who used three agents (74 [16.5%], the most common combination was BB, CAI, or PGA (43 [9.6%]). Combinations of four agents were less common 22 (4.9%), and regimens with more than 4 agents were rare 3 (0.7%). Table 3 outlines factors predictive of drop compliance, self-reported adverse effects and accessibility. A stronger compliance score was significantly associated with fewer adverse effects (β = 0.21, p < 0.01) and greater accessibility scores (β = 0.15, p < 0.01) (Table 3 ). The number of drops prescribed was the strongest factor influencing patient behaviour around eye drop compliance. A greater number of drops was associated with significantly poorer compliance (β=-0.59, p < 0.01) and worse adverse effects (β=-0.91, p = 0.02). However, the number of drops did not significantly affect patient accessibility to drops (β=-0.04, p = 0.91). Although age had no direct significant association with compliance (β=-0.09, p = 0.10) or adverse effects reported (β = 0.13, p = 0.13), older patients reported significantly higher accessibility scores (β = 0.30, p < 0.01). A better eye visual field MD score was nearly significantly associated with greater accessibility to eye drops (β = 0.42, p = 0.08); however, it was not significantly associated with compliance (β = 0.21, p = 0.18) or adverse effects (β = 0.12, p = 0.67). Gender was not significantly associated with drop compliance (β=-0.59, p = 0.5), adverse effects reported (β=-1.40, p = 0.46), or accessibility scores (β=-2.1, p = 0.20). Length of time on drops also did not significantly influence compliance (β = 0.05, p = 0.50), adverse effects (β=-0.07, p = 0.61), or accessibility (β=-0.09, p = 0.44). Table 1 Patient characteristics (n = 448) Lens status n (%) Phakic 228 (50.9) Pseudophakic 219 (49.0) Aphakic 1 (0.0) Type of Glaucoma POAG 358 (80.0) PACG 22 (4.9) NTG 10 (2.2) OHT 6 (1.3) Secondary 42 (9.4) -PXF 20 (4.5) -Myopic 5 (1.1) -Steroid Responder 3 (0.7) -Traumatic 3 (0.7) POAG: primary open angle glaucoma; PACG: primary angle closure glaucoma; NTG: normal tension glaucoma; OHT: ocular hypertension; PXF: pseudoexfoliation Table 2 Glaucoma Treatment Type of Procedure n = 448 (%) Nil known 283 (63.2) SLT 111 (24.8) Peripheral Iridotomy 13 (2.9) MIGS 15 (3.4) Xen ® Gel Stent 1 (0.2) PreserFlo MicroShunt ® 3 (0.7) Trabeculectomy 18 (4.0) Tube 6 (1.4) Cyclodiode 3 (0.7) SLT: selective laser trabeculoplasty; MIGS: minimally invasive glaucoma surgery Table 3 Table of associations between overall compliance, adverse effects and accessibility scores (significant associations in bold) Compliance Adverse Effect Accessibility ß p ß p ß p Age -0.09 0.10 0.13 0.13 0.30 < 0.01 Gender -0.59 0.51 -1.4 0.46 -2.1 0.20 Number of drops -0.59 0.01 -0.91 0.02 -0.04 0.91 Time on drops 0.05 0.50 -0.07 0.61 -0.09 0.44 Better eye visual field MD 0.21 0.18 0.12 0.67 0.42 0.08 Adverse Effect 0.21 < 0.01 - - - - Accessibility 0.15 < 0.01 - - - - MD: mean deviation Discussion This study highlights the multiple factors influencing glaucoma patients' compliance with topical therapies, including adverse effects, accessibility, and the number of prescribed drops. Our findings underscore that increased numbers of prescribed drops are strongly associated with poorer compliance and a higher incidence of adverse effects. This aligns with previous literature suggesting that complex regimens may overwhelm patients, reducing adherence. 8 , 22 – 23 In clinical practice, these results emphasise the importance of reducing the number of prescribed drops when possible through combination therapies and the use of other modalities, such as lasers. Side effects such as discomfort, blurring, and redness emerged as central factors influencing compliance. These findings support clinical observations that the cumulative burden of multidrug therapy can contribute to ocular surface toxicity, exacerbating symptoms such as hyperaemia, irritation, and visual disturbances. 24 The tolerability and safety of preservative-free ocular hypotensives are well documented. 25 Given our findings that tolerability is central to long-term treatment success, there is a compelling case for preservative-free options, avoiding side effects and optimising patient comfort. Age was not a significant predictor of compliance itself, although it was significantly associated with better perceived accessibility. The Australian health system of subsidised medications for pensioners offsets cost barriers through the national pharmaceutical benefits scheme. 26 Thus, older patients, who no longer perform regular work and have the time to travel to the pharmacy, can more readily access their medications. Accessibility also showed a near-significant association with better visual field MD scores, suggesting that patients with better accessibility and compliance with their medications have improved glaucoma management. 27 This study indicated that intolerance to glaucoma medications involves a complex interplay of compliance, accessibility, and tolerability, with each contributing to varying degrees (Fig. 2 ). There is a need for targeted interventions, particularly for younger patients and those with more severe disease, to improve access and reduce the drop-related burden. As such, pharmacists and clinicians should be vigilant about potential cost-related barriers and consider whether generic or subsidised medications can improve accessibility. This has further implications for reimbursement criteria, such as MBS item 42705, which pertains to lens extraction and intraocular lens insertion in patients diagnosed with open angle glaucoma who are “not adequately responsive to topical antiglaucoma medications or intolerant of antiglaucoma medication”. Inadequate response or intolerance should be understood as encompassing more than merely unpleasant or unwanted side effects and may involve other factors, such as financial limitations and/or dropping regimens that are ill suited to the patient’s lifestyle. The assessment of a patient’s adherence is a critical factor in glaucoma management, particularly for those on multidrop regimens or those reporting significant adverse effects. One meta-analysis demonstrated that a tailored care approach involving face-to-face assessment of a patient’s medical, functional and psychosocial factors affecting drop instillation and personalised care plans yielded the best glaucoma drop adherence scores. 4 Other strategies, including multimedia patient education, motivational interviewing, and the use of device reminders, e.g., mobile phone apps, may also be beneficial. 4 These considerations are especially relevant for patients who have good compliance but exhibit suboptimal IOP reduction. 28 Previous studies have frequently highlighted patients’ tendency to overestimate their proficiency with drops. 29 – 31 In one mixed-methods study, 85.2% of participants reported not requiring assistance; however, qualitative interviews revealed several remarks regarding “trouble with aim”. 32 Several studies have shown that low motivation and a previous diagnosis of depression are significant predictors of poor adherence to glaucoma treatment. 12 , 33 , 34 This study has limitations that should be acknowledged. Patients with language barriers were excluded, which may limit the applicability of our findings to non-English-speaking populations. Noncompliance patterns and challenges may differ across culturally and linguistically diverse groups, highlighting the need for further studies to address this gap. Additionally, the study did not collect data on socioeconomic factors such as education level, income, and occupation, which are known to influence adherence. The retrospective observational design of this study introduces bias, particularly in self-reported measures such as the DRIPS questionnaire. Self-reported data are inherently subject to recall and social desirability biases. Furthermore, the cohort was predominantly recruited from private clinics in an urban setting, which does not represent the challenges faced by public hospital patients or those in rural and underserved areas. Future research is needed to provide a more comprehensive understanding of the barriers faced by these different patient demographics. In conclusion, this study provides valuable insights into the factors influencing compliance with glaucoma treatment. Compliance is unaffected by age or the severity of visual field loss, suggesting that barriers are driven more by treatment factors. Reducing the burden of eye drop treatment through combination therapies or novel drug delivery systems may improve both patient adherence and patient outcomes. There is a need for tailored treatment approaches that address individual patient challenges. Clinicians should consider the burden of treatment regimens and prioritise strategies to increase adherence through patient education, cost-effective options, and accessible medication delivery. ANZGS Study Collaboration: Anne Brooks, Chris Chesney, Grant Raymond, Audrey Murugesan, George Kong, Greg Horowitz, Ahmed Hussan, Carman Oakley, Jonathon Ng, Angela Jennings, Katherine Masselos, Alex Tan, Hema Karthik, Dina el Sayed, Chi Man Lam, Sudha Cugati, Fiona Chan, Joan Cosgrove, Siew Then, Neville Lai Kwon, Sophia Leikin, Sarya Saks, Kiran Sindhu, Zanne Harvey, Brian Ang, Chunnie Ch’ng, Adrian Koay, Jonathan Moodie, Christine Tangas. Nathan Neilsen, Graham Lee, Leon Wicks, Brad Horsburgh Declarations Conflict of Interest: The authors declare that there are no conflicts of interest. Funding Sources: None Ethics approval and consent to participate : Ethics approval was granted by the University of Queensland Human Research Ethics Committee (Project number 2024/HE001611), abiding by the tenets of the Declaration of Helsinki. Patients were provided with information sheets, and informed consent was obtained before their engagement in the study. Consent for publication : No individual person’s data Availability of data and materials : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests : The authors declare that they have no competing interests Funding : Nil Authors' contributions : NL undertook data collection and curation and wrote the original draft of the manuscript; GL developed the initial concept, designed the methodology, undertook data collection and curation and wrote the original draft of the manuscript; JFG, SS developed the initial concept, designed the methodology, undertook data collection and curation and wrote the original draft of the manuscript; GK developed the initial concept, designed the methodology, undertook data collection and curation, performed statistical analysis and wrote the original draft of the manuscript. All authors read and approved the final manuscript Acknowledgements : We would like to acknowledge Ethan Lee BSc for his role in the coding and data entry of the proformas. References The International Council of Ophthalmology. ICO Guidelines for glaucoma eye care, 2016 [Available from: http://www.icoph.org/downloads/ICOGlaucomaGuidelines.pdf. National Institute for Health and Care Excellence. Glaucoma: diagnosis and management [Internet]. [London] 2017 [updated 26 Jan 2022; cited 2024 28 May]. Available from: https://www.nice.org.uk/guidance/ng81/. Reardon G, Kotak S, Schwartz GF. Objective assessment of compliance and persistence among patients treated for glaucoma and ocular hypertension: A systematic review. Patient Preference and Adherence. 2011;5:441-63. Ha A, Jang M, Shim SR, Kim CY, Chang IB, Kim YK. Interventions for Glaucoma Medication Adherence Improvement: A Network Meta-analysis of Randomized Controlled Trials. Ophthalmology. 2022;129(11):1294-304. Daniels B, Healey P, Bruno C, Kaan I, Zoega H. Medicine treatment of glaucoma in Australia 2012-2019: prevalence, incidence and persistence. BMJ Open Ophthalmol. 2021;6(1):e000921. Curtis C, Lo E, Ooi L, Bennett L, Long J. Factors affecting compliance with eye drop therapy for glaucoma in a multicultural outpatient setting. Contemporary Nurse. 2009;31(2):121-8. McClelland JF, Bodle L, Little J-A. Investigation of medication adherence and reasons for poor adherence in patients on long-term glaucoma treatment regimes. Patient Preference and Adherence. 2019;13(null):431-9. Spencer SKR, Shulruf B, McPherson ZE, Zhang H, Lee MB, Francis IC, et al. Factors Affecting Adherence to Topical Glaucoma Therapy: A Quantitative and Qualitative Pilot Study Analysis in Sydney, Australia. Ophthalmology Glaucoma. 2019;2(2):86-93 Spencer SKR, Shulruf B, McPherson ZE, Zhang H, Lee MB, Francis IC, et al. Factors Affecting Adherence to Topical Glaucoma Therapy: A Quantitative and Qualitative Pilot Study Analysis in Sydney, Australia. Ophthalmology Glaucoma. 2019;2(2):86-93. Olthoff CM, Hoevenaars JG, van den Borne BW, Webers CA, Schouten JS. Prevalence and determinants of non-adherence to topical hypotensive treatment in Dutch glaucoma patients. Graefes Arch Clin Exp Ophthalmol. 2009;247(2):235-43. Lu VH, Goldberg I, Lu CY. Use of glaucoma medications: state of the science and directions for observational research. Am J Ophthalmol. 2010;150(4):569-74 e9. Boland MV, Chang DS, Frazier T, Plyler R, Friedman DS. Electronic Monitoring to Assess Adherence With Once-Daily Glaucoma Medications and Risk Factors for Nonadherence: The Automated Dosing Reminder Study. JAMA Ophthalmology. 2014;132(7):838-44. Okeke CO, Quigley HA, Jampel HD, Ying GS, Plyler RJ, Jiang Y, et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology. 2009;116(2):191-9. Sleath B, Blalock S, Covert D, Stone JL, Skinner AC, Muir K, et al. The relationship between glaucoma medication adherence, eye drop technique, and visual field defect severity. Ophthalmology. 2011;118(12):2398-402. Bloch S, Rosenthal AR, Friedman L, Caldarolla P. Patient compliance in glaucoma. Br J Ophthalmol. 1977;61(8):531-4. Zimmerman TJ, Zalta AH. Facilitating patient compliance in glaucoma therapy. Surv Ophthalmol. 1983;28 Suppl:252-8. Urquhart J. Pharmacoeconomic Consequences of Variable Patient Compliance With Prescribed Drug Regimens. PharmacoEconomics. 1999;15(3):217-28. Tsai JC, McClure CA, Ramos SE, Schlundt DG, Pichert JW. Compliance Barriers in Glaucoma: A Systematic Classification. Journal of Glaucoma. 2003;12(5). Lacey J, Cate H, Broadway DC. Barriers to adherence with glaucoma medications: a qualitative research study. Eye (Lond). 2009;23(4):924-32. Acuff K, Wu J-H, Varkhedi V, Baxter SL. Social determinants of health and health disparities in glaucoma: A review. Clinical & Experimental Ophthalmology. 2024;52(3):276-93. Lu SJ, Girgis S, Shah P, Lee GA. Patient Experience and Barriers to the Visual Field Test for Glaucoma. J Glaucoma. 2024 Nov 1;33(11):835-840. Robin AL, Covert D. Does Adjunctive Glaucoma Therapy Affect Adherence to the Initial Primary Therapy? Ophthalmology. 2005;112(5):863-8. Claxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clinical Therapeutics. 2001;23(8):1296-310. Stalmans I, Lemij H, Clarke J, Baudouin C. Signs and Symptoms of Ocular Surface Disease: The Reasons for Patient Dissatisfaction with Glaucoma Treatments. Clin Ophthalmol. 2020;14:3675-80. Konstas AG, Labbé A, Katsanos A, Meier-Gibbons F, Irkec M, Boboridis KG, et al. The treatment of glaucoma using topical preservative-free agents: an evaluation of safety and tolerability. Expert Opin Drug Saf. 2021;20(4):453-66. McRae I, van Gool K, Hall J, Yen L, Wright M. Failure to access prescribed pharmaceuticals by older patients with chronic conditions. Australian Health Review. 2020;44(2):270-6. Robin A, Grover DS. Compliance and adherence in glaucoma management. Indian Journal of Ophthalmology. 2011;59(Suppl1). Hahn SR. Patient-Centered Communication to Assess and Enhance Patient Adherence to Glaucoma Medication. Ophthalmology. 2009;116(11):S37-S42. Okeke CO, Quigley HA, Jampel HD, Ying G-s, Plyler RJ, Jiang Y, et al. Adherence with Topical Glaucoma Medication Monitored Electronically: The Travatan Dosing Aid Study. Ophthalmology. 2009;116(2):191-9. Chang DS, Friedman DS, Frazier T, Plyler R, Boland MV. Development and Validation of a Predictive Model for Nonadherence with Once-Daily Glaucoma Medications. Ophthalmology. 2013;120(7):1396-402. Cate H, Bhattacharya D, Clark A, Holland R, Broadway DC. Patterns of adherence behaviour for patients with glaucoma. Eye. 2013;27(4):545-53. McClelland JF, Bodle L, Little JA. Investigation of medication adherence and reasons for poor adherence in patients on long-term glaucoma treatment regimes. Patient Prefer Adherence. 2019;13:431-9. Skalicky S, Goldberg I. Depression and Quality of Life in Patients With Glaucoma: A Cross-sectional Analysis Using the Geriatric Depression Scale-15, Assessment of Function Related to Vision, and the Glaucoma Quality of Life-15. Journal of Glaucoma. 2008;17(7). Lim MC, Watnik MR, Imson KR, Porter SM, Granier AM. Adherence to Glaucoma Medication: The Effect of Interventions and Association With Personality Type. Journal of Glaucoma. 2013;22(6). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviewers agreed at journal 24 Sep, 2025 Reviewers invited by journal 23 Sep, 2025 Editor assigned by journal 16 Sep, 2025 Editor invited by journal 01 Sep, 2025 Submission checks completed at journal 30 Aug, 2025 First submitted to journal 30 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7362234","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":524496264,"identity":"629bb431-fdf9-4694-89a8-4c1af6830ab5","order_by":0,"name":"Natalie Liu","email":"","orcid":"","institution":"University of Queensland","correspondingAuthor":false,"prefix":"","firstName":"Natalie","middleName":"","lastName":"Liu","suffix":""},{"id":524496265,"identity":"2c7bebf1-f16a-44d7-b5e7-0573f04b9b90","order_by":1,"name":"Graham A Lee","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAw0lEQVRIiWNgGAWjYFAC5gYGBgMbMFOCSC2MQC0FaSRr+XCYBC3yDoyNDz4YnE/sO8B88DYPg11iAyEthgcYmw1nGNxOnHmALdmahyGZCC0NjG3SPEAtGw7wmEnzMDATpaX99x+Dc0At/N+AWuoJa5FnYGxjZjA4ALKFDajlMGEtBsyMzZI9BsnGMw+zGVvOMThuTNiW9uaDH378sZPtO9788MabimpZwrYchrHADANC6kG2wA09QITqUTAKRsEoGJkAANwHO+7fxgWKAAAAAElFTkSuQmCC","orcid":"","institution":"University of Queensland","correspondingAuthor":true,"prefix":"","firstName":"Graham","middleName":"A","lastName":"Lee","suffix":""},{"id":524496267,"identity":"f966175b-0819-45a1-824d-32d52f4e6aa7","order_by":2,"name":"Jennifer Fan Gaskin","email":"","orcid":"","institution":"Royal Victorian Eye \u0026 Ear Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jennifer","middleName":"Fan","lastName":"Gaskin","suffix":""},{"id":524496269,"identity":"77f46816-c1ea-43d9-bbda-b1cf180ecbd8","order_by":3,"name":"Simon Skalicky","email":"","orcid":"","institution":"Royal Victorian Eye \u0026 Ear Hospital","correspondingAuthor":false,"prefix":"","firstName":"Simon","middleName":"","lastName":"Skalicky","suffix":""},{"id":524496271,"identity":"0014df61-871f-41e8-9d0a-77599a2a57a4","order_by":4,"name":"George Kong","email":"","orcid":"","institution":"Royal Victorian Eye \u0026 Ear Hospital","correspondingAuthor":false,"prefix":"","firstName":"George","middleName":"","lastName":"Kong","suffix":""}],"badges":[],"createdAt":"2025-08-13 07:53:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7362234/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7362234/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":92843806,"identity":"0468c525-28a2-49ac-b2fc-5feda6e80833","added_by":"auto","created_at":"2025-10-06 09:19:37","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":650257,"visible":true,"origin":"","legend":"","description":"","filename":"DRIPS6i.docx","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/15430d77713530429cca8232.docx"},{"id":92843810,"identity":"c0076a4c-8c20-40c3-96f6-2ab50245e511","added_by":"auto","created_at":"2025-10-06 09:19:37","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":7369,"visible":true,"origin":"","legend":"","description":"","filename":"71dbaddc3bd8456d81a627f1149bba74.json","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/29dc0f313f09b712d20c2dde.json"},{"id":92847104,"identity":"d5b38819-fe37-4dba-8ad1-dce2a29cb968","added_by":"auto","created_at":"2025-10-06 09:43:37","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":86825,"visible":true,"origin":"","legend":"","description":"","filename":"71dbaddc3bd8456d81a627f1149bba741enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/654e036c1789ddf06655c391.xml"},{"id":92845862,"identity":"23754d21-9f96-4974-a469-63f6deb3ae50","added_by":"auto","created_at":"2025-10-06 09:35:37","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":743255,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/b292f08922b24b0e9942574a.jpeg"},{"id":92845496,"identity":"be501570-e976-4356-b425-3cb4d1f9f841","added_by":"auto","created_at":"2025-10-06 09:27:37","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1074,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/aecd84455737d0615fffa6dd.jpeg"},{"id":92843815,"identity":"64c9434b-2a1b-42f0-8db5-b2284f0ca5e2","added_by":"auto","created_at":"2025-10-06 09:19:37","extension":"jpeg","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":347561,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/fe2ce7431be3f30c3ebdfed7.jpeg"},{"id":92843813,"identity":"3d0720c2-1415-44bd-9ac2-23cc571f6b87","added_by":"auto","created_at":"2025-10-06 09:19:37","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":182675,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/eed9c89b0f3a21fa73dbd85c.png"},{"id":92843805,"identity":"63363419-89f2-401e-8c1c-bf4c2da6af4c","added_by":"auto","created_at":"2025-10-06 09:19:37","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":935,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/93317df22ab4f3dc78e17cbc.png"},{"id":92843814,"identity":"53d6189a-a879-4d80-b081-7c754a67dfb8","added_by":"auto","created_at":"2025-10-06 09:19:37","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":68058,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/d9200edff7e2ed67d5e71053.png"},{"id":92843816,"identity":"8444324b-e241-4ab7-9bc8-dfa7674eeed0","added_by":"auto","created_at":"2025-10-06 09:19:37","extension":"xml","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":84239,"visible":true,"origin":"","legend":"","description":"","filename":"71dbaddc3bd8456d81a627f1149bba741structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/485230b2b7cf45147a31e177.xml"},{"id":92843817,"identity":"a6ab622e-fae3-4757-aa97-ffd490fa4148","added_by":"auto","created_at":"2025-10-06 09:19:38","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":93281,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/7ae6658a7779317ab44e6783.html"},{"id":92845497,"identity":"3064c36e-68d1-4fc9-a77e-0e0fb0df1358","added_by":"auto","created_at":"2025-10-06 09:27:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":269449,"visible":true,"origin":"","legend":"\u003cp\u003eDrop Resistance and Intolerance of Patients Study (DRIPS) Questionnaire with avisual analogue scale (mm)\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/f24acbb4f26431b8e8642739.png"},{"id":92845861,"identity":"218d6edb-5e3f-4273-b3ea-85ac5c420a12","added_by":"auto","created_at":"2025-10-06 09:35:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":114096,"visible":true,"origin":"","legend":"\u003cp\u003ePatient compliance and influencing factors\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/f0a0241be5c9eb01b65276a6.png"},{"id":92847105,"identity":"bd999a5f-7f19-4bc1-90d2-77ea726c49b3","added_by":"auto","created_at":"2025-10-06 09:43:42","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":760527,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7362234/v1/269be18f-4965-4187-98da-2044ba9b98c2.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Barriers to Medical Treatment of Glaucoma - Drop Resistance and Intolerance in Patients Study (DRIPS)","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMedical treatments to reduce intraocular pressure (IOP) aim to slow the progression of vision loss and delay the need for invasive surgical intervention.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Topical eye drops are traditionally the first-line treatment option.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e Despite being non-invasive and relatively inexpensive, many glaucoma patients do not take drops as prescribed.\u003csup\u003e\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e In Australia, contemporary population-based estimates of compliance with topical prescriptions have been reported to be as low as 37% at 6 months and 30% at 12 months, plummeting further to 20% at 36 months.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e Even among patients who do fill their prescriptions, between 23% and 90% do not adhere to the recommended frequency of instillation.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e Additionally, electronic eye drop monitoring systems have reported nonadherence rates ranging between 3% and 40%.\u003csup\u003e3, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eNoncompliance has long been established as a risk factor for the progression of glaucoma-related vision loss.\u003csup\u003e14 15\u0026ndash;17\u003c/sup\u003eHowever, limited literature exists in Australia on the factors driving noncompliance in glaucoma patients. The barriers to glaucoma treatment adherence are multifaceted, with one study\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e identifying 71 obstacles that could be classified into situational/environmental factors, medication regimens, patient factors and provider factors. Other studies have highlighted important variables, including lack of health literacy regarding glaucoma, depression/mental health status, lack of faith in the efficacy of the drops, issues with eye drop instillation, forgetfulness, trust/rapport with treating clinicians, and practicality of obtaining medications (timing, location, packaging).\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e There is varying evidence surrounding the relationship between patient adherence and demographic factors such as age, sex, cultural background, socioeconomic status and geographical location.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eGiven the nuances inherent in patient behaviours surrounding treatment compliance, it is important to identify the risk factors for poor adherence. Targets can then be identified for interventions tailored to the appropriate patient demographics. This study aimed to evaluate the factors influencing patient intolerance to glaucoma medication.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eDesign and data collection\u003c/p\u003e\u003cp\u003eThe Drop Resistance and Intolerance Study (DRIPS) is a 12-item questionnaire that addresses compliance, adverse effects and accessibility, common ophthalmic tests, pre- and intra-consultation factors, and cost values (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This instrument, developed by coauthors (GL, GK, JFG, and SS), was designed to be patient friendly to optimise participant engagement and comprehension. The data were quantified via a 100 mm visual analogue scale (VAS), where a score of 0 indicates \u0026lsquo;a big problem\u0026rsquo; and 100 indicates \u0026lsquo;no problem\u0026rsquo;. The questionnaire was designed to be self-administered by the patient and assisted by their accompanying person if needed. The epidemiological data, eye status data and glaucoma management data were obtained by an ophthalmic assistant or a doctor. The combination of items in our study is original and has not been previously investigated; however, the 100 mm VAS-based survey format has been previously used within an Australian cohort of glaucoma patients in a private outpatient context.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e The study questionnaire was piloted with 20 patients to ensure that the format of the questions was optimised. The test duration for each patient was approximately five minutes on average. Where patients marked with a cross above or below the line, measurements were taken from the closest point from the apex of the tick. The following factors were assessed for their associations with compliance, adverse effects and accessibility: age, sex, number of drops, time on drops, and visual field mean deviation (MD) of the eye.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe scores of each question were entered into a database such that each patient had a score for each of the categories.\u003c/p\u003e\u003cp\u003eParticipant selection\u003c/p\u003e\u003cp\u003eThis study was conducted on adult patients (aged\u0026thinsp;\u0026ge;\u0026thinsp;21 years) attending ophthalmologists of the Australian and New Zealand Glaucoma Society DRIPS Collaboration from October 2024 to December 2024. Ethics approval was granted by the University of Queensland Human Research Ethics Committee (Project number 2024/HE001611), abiding by the tenets of the Declaration of Helsinki. Patients were provided with information sheets, and informed consent was obtained before their engagement in the study. Individuals were excluded from the study if they were unable to provide consent, were \u0026lt;\u0026thinsp;21 years of age, had language or comprehension difficulty, had reduced vision preventing completion of the VAS or had acute ocular pathology. Any patient fulfilling the selection criteria was approached prior to their consultation and invited to participate.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData analysis\u003c/h2\u003e\u003cp\u003eDescriptive statistics were used to summarise patient demographics, clinical characteristics, and questionnaire responses. Continuous variables are presented as the means with standard deviations (SDs), whereas categorical variables are reported as frequencies and percentages. Variables within the three groups of questions\u0026mdash;compliance, adverse effects, and accessibility\u0026mdash;were averaged to generate an overall score for each respective group. Associations between overall compliance, adverse effects, and accessibility scores were assessed via multiple linear regression models, with adjustments for potential confounders such as age, sex, number of drops, duration of drop use, and visual field MD scores. Beta coefficients (β) with corresponding p values were reported to indicate the strength and significance of relationships. Missing data were handled via pairwise deletion to maximize the use of available information. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05, and analyses were performed via SPSS (version 23).\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 448 adult patients with glaucoma were included in the study. The mean age was 67.8 years (SD\u0026thinsp;=\u0026thinsp;11.1), with ages ranging from 21\u0026ndash;91 years. The cohort consisted of 225 (50.2%) women and 223 (49.8%) men. The majority of patients (374 (83.5%)) were seen in private clinics, whereas 68 (15.2%) were seen in public hospital clinics.\u003c/p\u003e\u003cp\u003eMost patients were phakic 228 (50.9%) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The most prevalent type of glaucoma was primary open-angle glaucoma 358 (80.0%). Other types of glaucoma included primary angle closure glaucoma 22 (4.9%), normal tension glaucoma 10 (2.2%) and secondary glaucoma 42 (9.4%), including pseudoexfoliation glaucoma 20 (4.5%). In terms of previous glaucoma procedures, selective laser trabeculoplasty (SLT) was the most common procedure 111 (24.8%), followed by trabeculectomy 18 (4.0%), peripheral iridotomy 13 (2.9%) and minimally invasive glaucoma surgery (MIGS) 15 (3.4%).\u003c/p\u003e\u003cp\u003eOn average, patients took 2.8 (range 1\u0026ndash;14) glaucoma drops per day. The average duration of treatment was 8.0 years, with a range of 1 month to 58 years. Patients were most commonly prescribed single agent regimens 201 (44.9%), the most common being prostaglandin analogues (PGA) 159 (35.5%). Beta blockers (BB) were the second most common single agent 27 (6.0%), followed by carbonic anhydrase inhibitors (CAI) 12 (2.7%). There were 145 (32.4%) patients who were prescribed dual agent regimens; the most common combination was BB and PGA, which was prescribed to 92 (20.5%) patients. Among the patients who used three agents (74 [16.5%], the most common combination was BB, CAI, or PGA (43 [9.6%]). Combinations of four agents were less common 22 (4.9%), and regimens with more than 4 agents were rare 3 (0.7%).\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e outlines factors predictive of drop compliance, self-reported adverse effects and accessibility. A stronger compliance score was significantly associated with fewer adverse effects (β\u0026thinsp;=\u0026thinsp;0.21, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and greater accessibility scores (β\u0026thinsp;=\u0026thinsp;0.15, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The number of drops prescribed was the strongest factor influencing patient behaviour around eye drop compliance. A greater number of drops was associated with significantly poorer compliance (β=-0.59, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and worse adverse effects (β=-0.91, p\u0026thinsp;=\u0026thinsp;0.02). However, the number of drops did not significantly affect patient accessibility to drops (β=-0.04, p\u0026thinsp;=\u0026thinsp;0.91). Although age had no direct significant association with compliance (β=-0.09, p\u0026thinsp;=\u0026thinsp;0.10) or adverse effects reported (β\u0026thinsp;=\u0026thinsp;0.13, p\u0026thinsp;=\u0026thinsp;0.13), older patients reported significantly higher accessibility scores (β\u0026thinsp;=\u0026thinsp;0.30, p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). A better eye visual field MD score was nearly significantly associated with greater accessibility to eye drops (β\u0026thinsp;=\u0026thinsp;0.42, p\u0026thinsp;=\u0026thinsp;0.08); however, it was not significantly associated with compliance (β\u0026thinsp;=\u0026thinsp;0.21, p\u0026thinsp;=\u0026thinsp;0.18) or adverse effects (β\u0026thinsp;=\u0026thinsp;0.12, p\u0026thinsp;=\u0026thinsp;0.67). Gender was not significantly associated with drop compliance (β=-0.59, p\u0026thinsp;=\u0026thinsp;0.5), adverse effects reported (β=-1.40, p\u0026thinsp;=\u0026thinsp;0.46), or accessibility scores (β=-2.1, p\u0026thinsp;=\u0026thinsp;0.20). Length of time on drops also did not significantly influence compliance (β\u0026thinsp;=\u0026thinsp;0.05, p\u0026thinsp;=\u0026thinsp;0.50), adverse effects (β=-0.07, p\u0026thinsp;=\u0026thinsp;0.61), or accessibility (β=-0.09, p\u0026thinsp;=\u0026thinsp;0.44).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePatient characteristics (n\u0026thinsp;=\u0026thinsp;448)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLens status\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhakic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e228 (50.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePseudophakic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e219 (49.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAphakic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (0.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eType of Glaucoma\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePOAG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e358 (80.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePACG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22 (4.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNTG\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10 (2.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOHT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (1.3)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSecondary\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e42 (9.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e-PXF\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20 (4.5)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e-Myopic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5 (1.1)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e-Steroid Responder\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (0.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e-Traumatic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (0.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003ePOAG: primary open angle glaucoma; PACG: primary angle closure glaucoma; NTG: normal tension glaucoma; OHT: ocular hypertension; PXF: pseudoexfoliation\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eGlaucoma Treatment\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"2\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eType of Procedure\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;448 (%)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNil known\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e283 (63.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSLT\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e111 (24.8)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePeripheral Iridotomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13 (2.9)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMIGS\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15 (3.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eXen\u003csup\u003e\u0026reg;\u003c/sup\u003e Gel Stent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1 (0.2)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePreserFlo MicroShunt\u003csup\u003e\u0026reg;\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (0.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTrabeculectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18 (4.0)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTube\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e6 (1.4)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCyclodiode\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (0.7)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"2\"\u003eSLT: selective laser trabeculoplasty; MIGS: minimally invasive glaucoma surgery\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTable of associations between overall compliance, adverse effects and accessibility scores (significant associations in bold)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eCompliance\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eAdverse Effect\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eAccessibility\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026szlig;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026szlig;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026szlig;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u003cb\u003e0.30\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e-0.59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.51\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNumber of drops\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e-0.59\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e-0.91\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cb\u003e0.02\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime on drops\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.44\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBetter eye visual field MD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse Effect\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.21\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAccessibility\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u003cb\u003e0.15\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cb\u003e\u0026lt;\u0026thinsp;0.01\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e-\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eMD: mean deviation\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study highlights the multiple factors influencing glaucoma patients' compliance with topical therapies, including adverse effects, accessibility, and the number of prescribed drops. Our findings underscore that increased numbers of prescribed drops are strongly associated with poorer compliance and a higher incidence of adverse effects. This aligns with previous literature suggesting that complex regimens may overwhelm patients, reducing adherence.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e In clinical practice, these results emphasise the importance of reducing the number of prescribed drops when possible through combination therapies and the use of other modalities, such as lasers.\u003c/p\u003e\u003cp\u003eSide effects such as discomfort, blurring, and redness emerged as central factors influencing compliance. These findings support clinical observations that the cumulative burden of multidrug therapy can contribute to ocular surface toxicity, exacerbating symptoms such as hyperaemia, irritation, and visual disturbances.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e The tolerability and safety of preservative-free ocular hypotensives are well documented.\u003csup\u003e\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Given our findings that tolerability is central to long-term treatment success, there is a compelling case for preservative-free options, avoiding side effects and optimising patient comfort.\u003c/p\u003e\u003cp\u003eAge was not a significant predictor of compliance itself, although it was significantly associated with better perceived accessibility. The Australian health system of subsidised medications for pensioners offsets cost barriers through the national pharmaceutical benefits scheme.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Thus, older patients, who no longer perform regular work and have the time to travel to the pharmacy, can more readily access their medications. Accessibility also showed a near-significant association with better visual field MD scores, suggesting that patients with better accessibility and compliance with their medications have improved glaucoma management.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThis study indicated that intolerance to glaucoma medications involves a complex interplay of compliance, accessibility, and tolerability, with each contributing to varying degrees (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). There is a need for targeted interventions, particularly for younger patients and those with more severe disease, to improve access and reduce the drop-related burden. As such, pharmacists and clinicians should be vigilant about potential cost-related barriers and consider whether generic or subsidised medications can improve accessibility. This has further implications for reimbursement criteria, such as MBS item 42705, which pertains to lens extraction and intraocular lens insertion in patients diagnosed with open angle glaucoma who are \u0026ldquo;not adequately responsive to topical antiglaucoma medications or intolerant of antiglaucoma medication\u0026rdquo;. Inadequate response or intolerance should be understood as encompassing more than merely unpleasant or unwanted side effects and may involve other factors, such as financial limitations and/or dropping regimens that are ill suited to the patient\u0026rsquo;s lifestyle.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe assessment of a patient\u0026rsquo;s adherence is a critical factor in glaucoma management, particularly for those on multidrop regimens or those reporting significant adverse effects. One meta-analysis demonstrated that a tailored care approach involving face-to-face assessment of a patient\u0026rsquo;s medical, functional and psychosocial factors affecting drop instillation and personalised care plans yielded the best glaucoma drop adherence scores.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Other strategies, including multimedia patient education, motivational interviewing, and the use of device reminders, e.g., mobile phone apps, may also be beneficial.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e These considerations are especially relevant for patients who have good compliance but exhibit suboptimal IOP reduction.\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e Previous studies have frequently highlighted patients\u0026rsquo; tendency to overestimate their proficiency with drops.\u003csup\u003e\u003cspan additionalcitationids=\"CR30\" citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e In one mixed-methods study, 85.2% of participants reported not requiring assistance; however, qualitative interviews revealed several remarks regarding \u0026ldquo;trouble with aim\u0026rdquo;.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e Several studies have shown that low motivation and a previous diagnosis of depression are significant predictors of poor adherence to glaucoma treatment.\u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThis study has limitations that should be acknowledged. Patients with language barriers were excluded, which may limit the applicability of our findings to non-English-speaking populations. Noncompliance patterns and challenges may differ across culturally and linguistically diverse groups, highlighting the need for further studies to address this gap. Additionally, the study did not collect data on socioeconomic factors such as education level, income, and occupation, which are known to influence adherence. The retrospective observational design of this study introduces bias, particularly in self-reported measures such as the DRIPS questionnaire. Self-reported data are inherently subject to recall and social desirability biases. Furthermore, the cohort was predominantly recruited from private clinics in an urban setting, which does not represent the challenges faced by public hospital patients or those in rural and underserved areas. Future research is needed to provide a more comprehensive understanding of the barriers faced by these different patient demographics.\u003c/p\u003e\u003cp\u003eIn conclusion, this study provides valuable insights into the factors influencing compliance with glaucoma treatment. Compliance is unaffected by age or the severity of visual field loss, suggesting that barriers are driven more by treatment factors. Reducing the burden of eye drop treatment through combination therapies or novel drug delivery systems may improve both patient adherence and patient outcomes. There is a need for tailored treatment approaches that address individual patient challenges. Clinicians should consider the burden of treatment regimens and prioritise strategies to increase adherence through patient education, cost-effective options, and accessible medication delivery.\u003c/p\u003e\u003cp\u003eANZGS Study Collaboration: Anne Brooks, Chris Chesney, Grant Raymond, Audrey Murugesan, George Kong, Greg Horowitz, Ahmed Hussan, Carman Oakley, Jonathon Ng, Angela Jennings, Katherine Masselos, Alex Tan, Hema Karthik, Dina el Sayed, Chi Man Lam, Sudha Cugati, Fiona Chan, Joan Cosgrove, Siew Then, Neville Lai Kwon, Sophia Leikin, Sarya Saks, Kiran Sindhu, Zanne Harvey, Brian Ang, Chunnie Ch\u0026rsquo;ng, Adrian Koay, Jonathan Moodie, Christine Tangas. Nathan Neilsen, Graham Lee, Leon Wicks, Brad Horsburgh\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflict of Interest: The authors declare that there are no conflicts of interest.\u003c/p\u003e\n\u003cp\u003eFunding Sources: None\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eEthics approval and consent to participate :\u0026nbsp;Ethics approval was granted by the University of Queensland Human Research Ethics Committee (Project number 2024/HE001611), abiding by the tenets of the Declaration of Helsinki. Patients were provided with information sheets, and informed consent was obtained before their engagement in the study.\u003c/li\u003e\n \u003cli\u003eConsent for publication : No individual person’s data\u003c/li\u003e\n \u003cli\u003eAvailability of data and materials : The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u003c/li\u003e\n \u003cli\u003eCompeting interests : The authors declare that they have no competing interests\u003c/li\u003e\n \u003cli\u003eFunding : Nil\u003c/li\u003e\n \u003cli\u003eAuthors' contributions : NL undertook data collection and curation and wrote the original draft of the manuscript; GL developed the initial concept, designed the methodology, undertook data collection and curation and wrote the original draft of the manuscript; JFG, SS developed the initial concept, designed the methodology, undertook data collection and curation and wrote the original draft of the manuscript; GK developed the initial concept, designed the methodology, undertook data collection and curation, performed statistical analysis and wrote the original draft of the manuscript. All authors read and approved the final manuscript\u003c/li\u003e\n \u003cli\u003eAcknowledgements : We would like to acknowledge Ethan Lee BSc for his role in the coding and data entry of the proformas.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eThe International Council of Ophthalmology. ICO Guidelines for glaucoma eye care, 2016 [Available from: http://www.icoph.org/downloads/ICOGlaucomaGuidelines.pdf.\u003c/li\u003e\n \u003cli\u003eNational Institute for Health and Care Excellence. Glaucoma: diagnosis and management [Internet]. [London] 2017 [updated 26 Jan 2022; cited 2024 28 May]. Available from: https://www.nice.org.uk/guidance/ng81/.\u003c/li\u003e\n \u003cli\u003eReardon G, Kotak S, Schwartz GF. Objective assessment of compliance and persistence among patients treated for glaucoma and ocular hypertension: A systematic review. Patient Preference and Adherence. 2011;5:441-63.\u003c/li\u003e\n \u003cli\u003eHa A, Jang M, Shim SR, Kim CY, Chang IB, Kim YK. Interventions for Glaucoma Medication Adherence Improvement: A Network Meta-analysis of Randomized Controlled Trials. Ophthalmology. 2022;129(11):1294-304.\u003c/li\u003e\n \u003cli\u003eDaniels B, Healey P, Bruno C, Kaan I, Zoega H. Medicine treatment of glaucoma in Australia 2012-2019: prevalence, incidence and persistence. BMJ Open Ophthalmol. 2021;6(1):e000921.\u003c/li\u003e\n \u003cli\u003eCurtis C, Lo E, Ooi L, Bennett L, Long J. Factors affecting compliance with eye drop therapy for glaucoma in a multicultural outpatient setting. Contemporary Nurse. 2009;31(2):121-8.\u003c/li\u003e\n \u003cli\u003eMcClelland JF, Bodle L, Little J-A. Investigation of medication adherence and reasons for poor adherence in patients on long-term glaucoma treatment regimes. Patient Preference and Adherence. 2019;13(null):431-9.\u003c/li\u003e\n \u003cli\u003eSpencer SKR, Shulruf B, McPherson ZE, Zhang H, Lee MB, Francis IC, et al. Factors Affecting Adherence to Topical Glaucoma Therapy: A Quantitative and Qualitative Pilot Study Analysis in Sydney, Australia. Ophthalmology Glaucoma. 2019;2(2):86-93\u003c/li\u003e\n \u003cli\u003eSpencer SKR, Shulruf B, McPherson ZE, Zhang H, Lee MB, Francis IC, et al. Factors Affecting Adherence to Topical Glaucoma Therapy: A Quantitative and Qualitative Pilot Study Analysis in Sydney, Australia. Ophthalmology Glaucoma. 2019;2(2):86-93.\u003c/li\u003e\n \u003cli\u003eOlthoff CM, Hoevenaars JG, van den Borne BW, Webers CA, Schouten JS. Prevalence and determinants of non-adherence to topical hypotensive treatment in Dutch glaucoma patients. Graefes Arch Clin Exp Ophthalmol. 2009;247(2):235-43.\u003c/li\u003e\n \u003cli\u003eLu VH, Goldberg I, Lu CY. Use of glaucoma medications: state of the science and directions for observational research. Am J Ophthalmol. 2010;150(4):569-74 e9.\u003c/li\u003e\n \u003cli\u003eBoland MV, Chang DS, Frazier T, Plyler R, Friedman DS. Electronic Monitoring to Assess Adherence With Once-Daily Glaucoma Medications and Risk Factors for Nonadherence: The Automated Dosing Reminder Study. JAMA Ophthalmology. 2014;132(7):838-44.\u003c/li\u003e\n \u003cli\u003eOkeke CO, Quigley HA, Jampel HD, Ying GS, Plyler RJ, Jiang Y, et al. Adherence with topical glaucoma medication monitored electronically the Travatan Dosing Aid study. Ophthalmology. 2009;116(2):191-9.\u003c/li\u003e\n \u003cli\u003eSleath B, Blalock S, Covert D, Stone JL, Skinner AC, Muir K, et al. The relationship between glaucoma medication adherence, eye drop technique, and visual field defect severity. Ophthalmology. 2011;118(12):2398-402.\u003c/li\u003e\n \u003cli\u003eBloch S, Rosenthal AR, Friedman L, Caldarolla P. Patient compliance in glaucoma. Br J Ophthalmol. 1977;61(8):531-4.\u003c/li\u003e\n \u003cli\u003eZimmerman TJ, Zalta AH. Facilitating patient compliance in glaucoma therapy. Surv Ophthalmol. 1983;28 Suppl:252-8.\u003c/li\u003e\n \u003cli\u003eUrquhart J. Pharmacoeconomic Consequences of Variable Patient Compliance With Prescribed Drug Regimens. PharmacoEconomics. 1999;15(3):217-28.\u003c/li\u003e\n \u003cli\u003eTsai JC, McClure CA, Ramos SE, Schlundt DG, Pichert JW. Compliance Barriers in Glaucoma: A Systematic Classification. Journal of Glaucoma. 2003;12(5).\u003c/li\u003e\n \u003cli\u003eLacey J, Cate H, Broadway DC. Barriers to adherence with glaucoma medications: a qualitative research study. Eye (Lond). 2009;23(4):924-32.\u003c/li\u003e\n \u003cli\u003eAcuff K, Wu J-H, Varkhedi V, Baxter SL. Social determinants of health and health disparities in glaucoma: A review. Clinical \u0026amp; Experimental Ophthalmology. 2024;52(3):276-93.\u003c/li\u003e\n \u003cli\u003eLu SJ, Girgis S, Shah P, Lee GA. Patient Experience and Barriers to the Visual Field Test for Glaucoma. J Glaucoma. 2024 Nov 1;33(11):835-840.\u003c/li\u003e\n \u003cli\u003eRobin AL, Covert D. Does Adjunctive Glaucoma Therapy Affect Adherence to the Initial Primary Therapy? Ophthalmology. 2005;112(5):863-8.\u003c/li\u003e\n \u003cli\u003eClaxton AJ, Cramer J, Pierce C. A systematic review of the associations between dose regimens and medication compliance. Clinical Therapeutics. 2001;23(8):1296-310.\u003c/li\u003e\n \u003cli\u003eStalmans I, Lemij H, Clarke J, Baudouin C. Signs and Symptoms of Ocular Surface Disease: The Reasons for Patient Dissatisfaction with Glaucoma Treatments. Clin Ophthalmol. 2020;14:3675-80.\u003c/li\u003e\n \u003cli\u003eKonstas AG, Labb\u0026eacute; A, Katsanos A, Meier-Gibbons F, Irkec M, Boboridis KG, et al. The treatment of glaucoma using topical preservative-free agents: an evaluation of safety and tolerability. Expert Opin Drug Saf. 2021;20(4):453-66.\u003c/li\u003e\n \u003cli\u003eMcRae I, van Gool K, Hall J, Yen L, Wright M. Failure to access prescribed pharmaceuticals by older patients with chronic conditions. Australian Health Review. 2020;44(2):270-6.\u003c/li\u003e\n \u003cli\u003eRobin A, Grover DS. Compliance and adherence in glaucoma management. Indian Journal of Ophthalmology. 2011;59(Suppl1).\u003c/li\u003e\n \u003cli\u003eHahn SR. Patient-Centered Communication to Assess and Enhance Patient Adherence to Glaucoma Medication. Ophthalmology. 2009;116(11):S37-S42.\u003c/li\u003e\n \u003cli\u003eOkeke CO, Quigley HA, Jampel HD, Ying G-s, Plyler RJ, Jiang Y, et al. Adherence with Topical Glaucoma Medication Monitored Electronically: The Travatan Dosing Aid Study. Ophthalmology. 2009;116(2):191-9.\u003c/li\u003e\n \u003cli\u003eChang DS, Friedman DS, Frazier T, Plyler R, Boland MV. Development and Validation of a Predictive Model for Nonadherence with Once-Daily Glaucoma Medications. Ophthalmology. 2013;120(7):1396-402.\u003c/li\u003e\n \u003cli\u003eCate H, Bhattacharya D, Clark A, Holland R, Broadway DC. Patterns of adherence behaviour for patients with glaucoma. Eye. 2013;27(4):545-53.\u003c/li\u003e\n \u003cli\u003eMcClelland JF, Bodle L, Little JA. Investigation of medication adherence and reasons for poor adherence in patients on long-term glaucoma treatment regimes. Patient Prefer Adherence. 2019;13:431-9.\u003c/li\u003e\n \u003cli\u003eSkalicky S, Goldberg I. Depression and Quality of Life in Patients With Glaucoma: A Cross-sectional Analysis Using the Geriatric Depression Scale-15, Assessment of Function Related to Vision, and the Glaucoma Quality of Life-15. Journal of Glaucoma. 2008;17(7).\u003c/li\u003e\n \u003cli\u003eLim MC, Watnik MR, Imson KR, Porter SM, Granier AM. Adherence to Glaucoma Medication: The Effect of Interventions and Association With Personality Type. Journal of Glaucoma. 2013;22(6).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"compliance, glaucoma, eye drops, patient experience, compliance, minimally invasive glaucoma surgery (MIGS)","lastPublishedDoi":"10.21203/rs.3.rs-7362234/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7362234/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Eye drop noncompliance is a recognised risk factor for glaucoma-related vision loss. This study seeks to quantify the factors driving noncompliance with topical therapy among glaucoma patients.\u003c/p\u003e\n\u003cp\u003eMethods: This was a retrospective observational study of glaucoma patients in both private and public clinics, self-completing a 12-item Drop Resistance and Intolerance of Patients Study (DRIPS) questionnaire, categorised into compliance, adverse effects and accessibility.\u003c/p\u003e\n\u003cp\u003eResults: A total of 448 patients (M:F – 225:223) with glaucoma were included in the study. Stronger compliance was significantly associated with fewer adverse effects (β=0.21, p\u0026lt;0.01) and greater accessibility (β=0.15, p\u0026lt;0.01). A greater number of drops was associated with significantly poorer compliance (β=-0.56, p\u0026lt;0.01) and worse adverse effects (β=-0.91, p=0.02). Greater accessibility was significantly associated with older age (β=0.30, p\u0026lt;0.01) and had a nearly significant association with better visual field MD scores (β=0.42, p=0.08). Age (β=-0.09, p=0.10), length of time on drops (β=0\u003cem\u003e.\u003c/em\u003e05, p=0.50) and visual field MD score (β=0.21, p=0.18) were not significantly associated with compliance.\u003c/p\u003e\n\u003cp\u003eConclusion: This study of adult glaucoma patients revealed that a greater number of prescribed glaucoma drops is significantly associated with poorer patient compliance and increased adverse effects, highlighting a critical challenge in glaucoma management. While older age was associated with greater drop accessibility, overall compliance was influenced primarily by the complexity of the medication regimen rather than factors such as age, sex, disease severity, or treatment duration. These findings underscore the need for strategies to simplify treatment regimens and address adverse effects to improve patient adherence and outcomes in glaucoma care.\u003c/p\u003e","manuscriptTitle":"Barriers to Medical Treatment of Glaucoma - Drop Resistance and Intolerance in Patients Study (DRIPS)","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-06 09:19:33","doi":"10.21203/rs.3.rs-7362234/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"58358004789220706760431717811862953753","date":"2025-09-24T06:48:39+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-24T02:46:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-16T18:58:43+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-01T08:43:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-30T10:45:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Ophthalmology","date":"2025-08-30T10:42:18+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-ophthalmology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"boph","sideBox":"Learn more about [BMC Ophthalmology](http://bmcophthalmol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/boph","title":"BMC Ophthalmology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"95a7d733-163f-41e3-8811-0ffc521a51e5","owner":[],"postedDate":"October 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-10-06T09:19:33+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-06 09:19:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7362234","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7362234","identity":"rs-7362234","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}