**1. Introduction**

Lowering of intraocular pressure (IOP) is the only proven treatment to slow or delay the progression of glaucoma [1–4]. Medical treatment is the most common approach to achieving an individual eye "safe" IOP, followed by monitoring to determine the rate of progression [5]. As glaucoma is chronic optic neuropathy, and patients usually need to take lifelong medications. Therefore, adherence to a treatment regimen is crucial to maintain visual function. The reported rates of nonadherence to topical glaucoma medication vary widely from 16% to 67%, reflecting different methods to identify nonadherence as well as absence of a quantitative standard for measuring adherence to glaucoma medication [6]. Adherence over a longer period has been found to be even lower. Thus, only one-quarter of patients with newly diagnosed glaucoma continued their glaucoma medication after 2 years of follow up in Taiwan [7], whereas only 15% with newly diagnosed glaucoma in another study showed persistently good adherence over 4 years of follow up [8]. For most patients of newly prescribed glaucoma medications, adherence patterns observed in the first year of treatment mirror adherence patterns over the subsequent 3 years [8]. It is recognized that poorer adherence to glaucoma treatment leads to higher IOP, greater fluctuations in

**Citation:** Cvenkel, B.; Kolko, M. Devices and Treatments to Address Low Adherence in Glaucoma Patients: A Narrative Review. *J. Clin. Med.* **2023**, *12*, 151. https://doi.org/ 10.3390/jcm12010151

Academic Editors: Michele Lanza and Luigi Fontana

Received: 7 November 2022 Revised: 5 December 2022 Accepted: 21 December 2022 Published: 24 December 2022

**Copyright:** © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

IOP and consequently progression of glaucoma [9–11]. Glaucoma patients who reported less than 80% adherence to their prescribed medications were significantly more likely to have worse visual field defects [11]. Few studies longitudinally assessed the relationship between medication adherence and visual field progression. A longitudinal study assessing adherence in 35 glaucoma patients reported that patients with a stable visual field had a significantly higher median adherence rate of 85% compared to progressing patients with a median medication adherence of 21% [12]. In another study, patients randomized to the treatment arm of the Collaborative Initial Glaucoma Treatment Study were assessed for medication adherence using telephone interviews scheduled at the same 6-month intervals as clinical visits but on different days and followed up for an average of 7.3 years [13]. Scheduling timing of telephone interviews independently of clinical visit represents a strength of the study as nonadherence is often not admitted in front of the treating physician. Patients who reported never missing a dose of medication over the follow up had an average mean deviation (MD) loss of 0.62 dB over time, consistent with age-related loss, whereas patients missing medication doses at one-third and two-thirds of visits had an average loss of 1.42 and 2.23 dB of MD, respectively [13]. These findings indicate a dose–response relationship between medication adherence and visual field progression. A range of factors affect adherence and persistence, with one study identifying 71 barriers to adherence over four categories: situation factors, medication regimen, individual patient factors and medical provider issues [14]. Patients with poor adherence cited several barriers to medication adherence, which varied between individuals. The most important barriers associated with nonadherence included forgetfulness, low self-efficacy, difficulties with drop instillation and treatment schedule, side effects of medication, lack of motivation, poor education and other specific individual and age differences [15–17]. In addition, certain types of disabilities such as having a limb disability, being in a vegetative state, and having dementia reduce glaucoma medication adherence by up to 17.6% [18]. Therefore, approaches addressing adherence to glaucoma medications need to be multifaceted and individually tailored [19].

The purpose of this narrative review is to discuss strategies that may improve adherence by reducing the side effects of drops, the number of instillations and the number of medications required to control intraocular pressure. These approaches include medical treatments using preservative-free drops, intracameral sustained drug delivery and various drug delivery systems still undergoing clinical trials, smart drug delivery-connected devices as well as selective laser trabeculoplasty and minimally invasive glaucoma surgery.
