Glaucoma is a chronic disease in ophthalmology, affecting 3% of the Belgian population. The most important risk-factor of glaucoma is an elevated intraocular pressure. Objective outcomes such as visual field and optic nerve defects only give limited information about the real impact of glaucoma and its treatment on a patients daily life. Therefore the patients perspective or so-called patient reported outcomes (PRO s) are essential for evaluating treatment efficacy, clinical outcomes, and disease impact. Due to the treatment complexity, its lifelong character and the presumable effect of nonadherence on disease outcomes, nonadherence should be considered as a very important PRO for patients with glaucoma. Yet, the PRO and adherence literature in glaucoma is characterized by content-and methodology related shortcomings. To fill these gaps, we first performed a systematic review on glaucoma specific PRO s and rated them on their quality (chapter 2). Second, a prospective study was conducted to explore the dynamics of eye drop nonadherence and its theory based predictors (chapter 3). Third, we investigated selected system factors in relation to nonadherence in a multi-center study (chapter 4). Fourth, we developed and validated instruments to assess two important theoretical drivers of nonadherence, i.e. barriers (chapter 5) and eye drop administration skills (chapter 6). Patient reported outcomes (PRO s) in glaucomaOf the 25 PRO-tools retrieved from literature, most were quality of life measures, with most being poorly developed and not validated according to the current methodological standards. A conceptual definition/framework and patient input were often lacking, which is mandatory for the guidance of the item generation process and further psychometric testing. Second, the selection of items in the final instrument and dimensionality was seldom tested using appropriate statistical techniques, while this is needed to derive subsequent valid (sub) scale scores. Third, the widely applied one size fits all rating scale is outdated, meaning that rating scales should be statistically justified with ranges that might vary across items and within 1 instrument. Finally, researchers should first provide strong evidence with respect to the instrument s content validity, before starting further validation based on predefined hypotheses. Unfortunately, most tools did not meet these requirements, indicating a need for well developed and validated PRO instruments for use in glaucoma populations. Future directions in PRO-research should be: 1) improving existing instruments using Rasch-analysis, 2) developing and validating new PRO s using modern validation techniques and 3) creating glaucoma specific item banks per patient reported outcome content (e.g. quality of life, side effects, adherence) integrating calibrated scales adapted to the patients ability.Nonadherence to eye drop treatmentIn our prospective study the prevalence of eye drop nonadherence was 52% at baseline and 68.4% after follow-up. Repeated measurements allowed us to detect 4 medication behavior dynamics, i.e. stable adherence, persistent nonadherence, increasing and decreasing adherence, learning us that 25% of the patients altered their behavior over time. Most of the patients reported more problems with timing- (i.e. about 40-47%) compared to taking nonadherence (or instilling eye drops) (i.e. about 30%)). Future studies hence should prospectively monitor adherence over time. Due to possible effects of timing deviations on the effectiveness of eye drops, attention should not only be given to instilling eye drops (i.e. taking adherence), but also to keeping regular intervals between doses (i.e. timing adherence). At patient-level, the number of reported barriers was the single significant predictor of eye drop nonadherence. Other factors such as knowledge, eye drop administration skills, and intention do not seem to play a major role in predicting medication adherence based on the Integrated Model of Behavioral Prediction we used to operationalize our risk factors of interest. Hence, assessing barriers and subsequently developing adherence-enhancing interventions are necessary to prevent adherence. Unfortunately, the glaucoma literature did not provide a well developed and validated tool to assess these barriers. We therefore developed a 13-item instrument focusing on barriers to eye drop adherence. The median number of reported barriers by glaucoma patients was 2 barriers (range 2-10), with the most frequently reported barriers being I had difficulties with getting an eye drop into my eye , something interfered with my daily routine (e.g. vacation) and I forgot to administer my eye drops . Given that barriers are highly individually determined, tailored interventions are mandatory. Besides risk-factors at the patient level, policy guidelines recommend that factors at the healthcare provider and healthcare system are worthwhile to be looked at. In our cross-sectional, multicenter study, using multilevel analyses, we found that, on top of known determinants at the patient level, patients with a lower frequency of follow-up (< every 3 months) are at higher risk for nonadherence, compared to patients visiting their ophthalmologist less frequently. This study also revealed that ophthalmologists cannot accurately detect nonadherence, given that the sensitivity of their adherence-assessment against self-report was only 3%. This indicates the need for training of ophthalmologists in adherence measurement. Not only is the high prevalence of eye drop nonadherence a concern, yet patients also seemed to possess poor eye drop administration skills. These findings were congruent with previous results, yet our study was the first to assess these skills using a standardized observation tool (EYEDO) we developed based on the state of the art eye drop administration technique based on the Fraunfelder method and American Academy of Ophthalmology guidelines. By using an objective observation scale, problems inherent to self-report (i.e. social desirability) are eliminated. When usingthe EyeDO in a sample of 133 patients with glaucoma, the most problematic skills were: 1) forming a conjunctival pocket (20.5%), 2) directing the bottle properly above the eye (60.6%) and 3) compressing the lachrymal duct for 1 to 3 minutes (85.6%). ConclusionGlaucoma demands many self management tasks of patients, which should be supported by the health care team. Based on our results, patients are preferably seen at least every 3 months during their life-long follow-up. Moreover, there is a need to educate and train both patients and professionals in adherence and eye drop administration skills. An advanced practice nurse can play a crucial role in bridging the gap between research and clinical practice. Not only can she support the team by giving evidence based education and training, but can also strengthen patients self management skills. More specifically, an advanced practice nurse can assess adherence and barriers to adherence regularly throughout long-term follow-up and offer patient-tailored interventions to overcome these barriers. Yet, these interventions have to be tested on their efficacy and effectiveness in future studies.status: publishe