Ocular drug delivery systems: glaucoma patient perceptions from a German university hospital eye clinic

The only currently effective treatment for chronic open-angle glaucoma (COAG) consists of lowering intraocular pressure (IOP) with individual target pressures varying for each patient [1‐3]. Initial therapy usually consists of topical medication and/or selective laser trabeculoplasty (SLT) [4]. Poor adherence to IOP-lowering topical medication can lead to visual field progression and deterioration of glaucoma in a significant number of cases [5]. The majority of glaucoma patients do not take their medications as prescribed and adherence in glaucoma patients is even lower when compared to other chronic conditions [6, 7]. A recent cost-utility analysis showed that patients non-adherent to glaucoma drops developed unilateral blindness years earlier than those engaged in their treatments[8].

Ocular drug delivery devices (ODD) offer a potential solution to the problem of poor adherence with regard to self-administration of topical glaucoma medications [9]. These devices include contact lenses (CLs) [10, 11], punctal plugs (PPs) [12], subconjunctival implants [13], intracameral implants [14], and drug-emitting stents[15], each delivering ocular anti-glaucomatous medications over varying time frames. Two previous studies from Singapore demonstrated high acceptance for subconjunctival implants as eye-drops replacement, with patients even willing to accept higher costs for such treatments [16, 17]. Our study was performed to evaluate patients’ beliefs towards glaucoma adherence and illness perception and their acceptance towards ODD within a busy German university hospital glaucoma clinic. To our knowledge, this is the first ever survey on ODD involving patients from continental Europe.

Of 206 eligible patients, 152 (73.8%) were willing to participate in the study and 102 (49.5%) successfully completed the questionnaire. Forty-four patients (43.1%) were male. The majority of patients (94, 92.2%) had public, subsidized insurance. Twenty-five patients (24.5%) stated they lived alone at home, and 89 patients (87.3%) self-administered their eye-drops. The mean time that patients needed to get to our eye clinic was 1.13 h. All 102 patients were using IOP-lowering drops, with 46 (45.1%) confirming having had side-effects from them at some point. We asked patients to rank the degree of side-effects on a scale from zero to ten (see Appendix). The mean degree of side-effects was 2.44/10. Side-effects included dry eye symptoms (18.6%), red eye (10.8%), visual deterioration (9.8%), pain (2.0%), and others (7.8%), amongst which headaches. Table 1 describes further patient characteristics.

In terms of patient beliefs regarding their glaucoma medication (Table 2), the majority felt that their health depended on their eye-drops (79.4%) and that eye-drops “protected them” (90.2%).

Some patients stated that their life was disrupted by eye-drops (35.3%) and that they were worried about eye-drop intake (41.2%). Patients in our study felt that medicines in general help people live better lives (87.3%) with benefits outweighing their risks (89.2%). Nevertheless, nearly half (47.1%) stated that they believe doctors would prescribe fewer medications if they had more time for their patients.

With regard to the BIPQ (Table 3), patients felt that glaucoma had a moderate impact on their lives (mean value 4.83/10 scale). The majority believed that their glaucoma would continue forever (9.07 mean value). Patients said they were rather concerned about their glaucoma (7.16 mean value) and moderately affected emotionally (4.12 mean value).

As to medication adherence (Table 4), the majority stated that they applied their eye-drops regularly, with 63 patients (61.8%) ng so 90–99% of the time and 31 patients (30.4%) 70–89% of the time. The majority reported that they either never (31.4%) or seldomly (50%) forgot their eye-drops whilst fewer patients stated that this was sometimes (9.8%) or always (2.9%) the case. Thirty-seven patients (36.3%) felt stressed by the use of their glaucoma medication.

Non-adherence to topical glaucoma medications can lead to disease progression with concomitant irreversible visual field loss. As clinicians, it is essential to keep this problem in mind and to remember that patients may feel disturbed or worried by their medication use. It is easy for us to assume that we know better than our patients and that perhaps other options such as ODD may be deemed ineffective, too invasive, or simply too expensive. The first thing that our survey demonstrates is a clear majority (62%) of patients favoring an ODD over the use of eye drops.

The idea of exploring patients’ perspectives on ODD is not completely new. In 2015, Chan et al. performed a survey in a Singaporean glaucoma population, looking at subconjunctival, intracameral and PP routes as ODD[21]. The majority of interviewed patients accepted at least one of the three alternatives; PPs being the preferred route in this cohort whilst “effectiveness” was the most important factor determining the actual choice. Due to the further development and broader selection of ODD, we included five different choices: CLs, PPs, subconjunctival implants, AC injections and drug-emitting stents, based on the literature and studies performed to evaluate these different ODD types. We included a brief description of these various options, including specific availability, evidence, and potential side-effects, in order to enable informed patient responses [22‐28]. Compared to Chan et al., we incorporated similar (albeit not exactly the same) question strategies. However, a main difference is that patients in Singapore “co-pay” for their health care system, whereby costs for citizens with lower socioeconomic standing are subsidized. In Germany, a compulsory health insurance exists, with patients usually subsidized without additional costs, with an option to purchase additional private insurance if desired.

The BMQ outcomes in our study showed that the majority of patients felt that their eye-drops protected them (90.2%) and that their health depended on them (79.4%), depicting a positive perception of glaucoma medications in most patients. On answering the BIPQ, patients highly rated the questions about whether their treatment could help their condition and if they understood their disease, underlining their understanding of glaucoma and the fact that treatment reduces progression. Chan et al. had similar findings stating that patients felt their medication delivered a positive benefit. This understanding is of course essential for patients with a chronic disease such as glaucoma and can influence their adherence behaviors. On the other hand, a considerable proportion of patients interviewed were worried or felt disrupted by eye-drop intake (41.2%, 35.3%), rating their concern about glaucoma at 7.15. This shows that although most patients know that eye-drops are necessary to protect their health, many of them worry about drop intake, whilst also being concerned about their disease. Nearly half of responders believed that doctors would prescribe fewer medications if they had more time, denoting the potential perception that drops are prescribed to appease patients and facilitate patient turnover in busy clinics. As clinicians we should therefore invest in time explaining why medication is prescribed and in ways of highlighting the importance of adherence to self-administered therapy. We specifically included the MMAS-8 questionnaire to obtain real-world data on the latter with a considerable number stating that they sometimes forget their eyedrops (39.2%), forget them when not at home (23.5%), or feel stressed by their medication (36.3%). This confirms the long-known fact that glaucoma patients’ eye-drop adherence is sub-optimal, particularly as effectiveness relies on regular administration [29]. As a consequence, clinicians may often get a false idea of actual IOP values or medication effectiveness, either because of seemingly controlled IOP (in those who only medicate on the day of an appointment) or high IOP (for those missing drop administration).

ODD will almost certainly evolve, becoming more available and popular over time [30]. However, most of our patients had not heard of any ODD alternatives to eye-drops (see Table 5) despite the survey being conducted within a large university hospital, known to be an active investigator and implementer of new devices. People who only have access to local ambulatory health care might be even less aware of such alternatives. Our patients’ paucity of knowledge on ODD may also reflect limited awareness amongst ophthalmologists. Many clinicians would probably commence or maintain topical IOP-lowering therapy despite known side-effects, possibly as they are still considered the least invasive option. The advent of SLT, including trials promoting it as first line therapy [31], has not really dented the large proportion of glaucoma patients still treated with eye-drops. Whereas many clinicians may not have heard of the various ODD available, others might just consider them more invasive in comparison to drops or SLT. It is thus our duty as glaucoma specialists to inform both patients and colleagues on any available or forthcoming ODD modalities so that they can weigh the benefits and risks for each individual patient.

Nearly half of our patients felt that costs would be irrelevant (47.1%) in the context of ODD preference. However, we must consider that many glaucoma patients may actually not afford the additional expense. A cross-sectional study in the USA showed more cost-related non-adherence amongst glaucoma patients compared to participants without glaucoma, underlining the importance of cost considerations and their impact on therapy adherence [32]. Our surveyed patients stated that they were willing to pay from between €20 and €20,000 extra for an ODD, evidencing a huge variance between additional funding patients may have beyond health insurance cover. The majority of our interviewed patients (92.2%) had subsidized insurance with most on a monthly income of €0–€2000 (29.4%) and €2001–€5000 (40.2%) with additional treatment costs implying they would have to draw on significant savings. Clearly there is a discrepancy between people’s wishes and what they could really afford. The mainstay for ODD development has been the drive to remove patient adherence issues. Ironically, the inhibiting cost may become a determinant factor against this becoming an effective strategy.

When considering an ODD intervention, it is important to evaluate which ODD would best suit an individual patient. If each treatment was equally effective, the majority would prefer CLs (40.2%) followed by stents (25.5%) and PPs (22.5%). A possible explanation for this selection would be that CLs are commonly used or known by many people in the context of refractive error correction. Furthermore, CLs can be inserted independently and outside a clinic setting. PPs also showed a high acceptance overall, although this was less popular compared to the CLs option. This might be explained by the fact that PPs need to be administered by the eye specialist. Moreover, patients would not be too familiar with this way of administration compared to CLs. In comparison to the three other ODD options in our questionnaire, PPs and CLs may have been preferred as they do not involve needles, sharp objects or higher degrees of invasiveness. Although stents were the second preferred option, 30.4% of patients stated they would reconsider their decision if the intervention was performed in the operating room. When comparing the three “more invasive” procedures, stents seemed to be more widely accepted than subconjunctival or AC implants. This could be attributed to the fact that far more patients (22.5%) had already heard of a “stent” option whilst less than 10% had heard of the other alternatives, and therefore more comfortable with a more familiar type of procedure. When asked whether preference would shift to a more invasive option should this be more effective or longer lasting, our patients replied affirmatively, with the majority preferring a stent in this scenario.

Our study has various limitations. Firstly, it is a single-center study with limits to extrapolating the results to a wider regional, national or global population. Furthermore, 102 patients represent a relatively small number of participants, so that a certain selection bias may be present. The latter is also the case in terms of which patients might be more inclined to accept the invitation of participating in such a survey. An international, multicenter study, which we currently have underway, reflecting different patient characteristics and larger numbers, would be more able to discern differences between various centers and countries. We also did not gather visual field data on the patients surveyed and therefore could not classify them into actual severity types. However, we did not recruit patients with known advanced disease or those having undergone previous glaucoma surgery. Another limitation of such a survey is the limited knowledge related to ODD in this case. We tried addressing this by including different descriptions of the various ODD to offer patients a basic foundation on which to base answers. Although these descriptions were completely objective, a certain bias may always be present, and the images and wording used may in themselves introduce this.

Moreover, the majority of our patients had not heard of ODD prior to participating in the questionnaire. This can lead to a certain selection bias depending on how ODD were explained to the patients. In order to counteract this problem, we handed out patient information sheets before starting the questionnaire which introduced ODD in general to our patients to give them information. The different ODD were then explained in detail within the questionnaire with images showing the different ODD and our trained interviewers were available for questions. We attempted to keep descriptions, images (see Appendix) and explanations as objective and realistic as possible in order to not affect patients’ decisions and opinions towards certain ODD. Our trained interviewers were told to not influence patients and state an opinion of their own. However, a remaining bias or influence could have still been present.

In conclusion, this survey strongly confirms that many patients are non-adherent to topical glaucoma medications and feel worried and negatively influenced by their drop treatment and disease. The study also shows that there is a potentially high acceptance towards the possibility of ODD as alternatives to drop treatment, with PPs, CLs, and drug-emitting stents being the most popular in our patient cohort. Our patients reported having little knowledge on ODD, highlighting the need for better information on these options for both patients and clinicians. Patients with sub-optimal adherence to glaucoma topical medications may benefit from the option of an ODD, with the choice of which being made individually for every patient after thorough discussion and consideration of the risks and benefits of each modality.