It has been established that the quality of vision, surgical outcome, and quality of life of individuals is highly dependent on the health of the ocular surface. The complexity of the ocular surface is maintained by a delicate homeostasis; therefore, any destabilization in this balance can have serious structural and functional consequences . Among the various risk factors for the development of OSD, there is robust scientific and empirical evidence to suggest there is a risk associated with the long-term use of ocular hypotensive medications, especially those containing chemical preservatives . In fact, the prevalence of OSD among individuals with glaucoma can be as high as between 48% and 75% [38–40]. Remarkably, evidence has demonstrated that the use of antiglaucoma drugs preserved with benzalkonium chloride can cause as much as twice the risk of ocular surface abnormalities . In the current study, involving a Latino population, 2634 out of 5158 cases (51.06%) under topical antiglaucoma treatment showed some signs of OSD. Those individuals with more severe cases were older and had been using more antiglaucoma medications, and for a longer time, compared with individuals with mild OSD.
To expand on the ethnicity factor, some studies have indicated that ethnicity is a major determinant of being predisposed to developing OSD or dry eye disease (DED). For instance, it has been recognized that there is a greater proclivity to develop DED among individuals of Asian ethnicity than among individuals of Caucasian ethnicity [41,42]. However, there is scarce information regarding the development of OSD or DED in people of Latin American ethnicity, in particular from the Mexican population, which constituted the sample analyzed in our study. Of the research that has been conducted, Graue-Hernandez et al  identified a DED prevalence of 41.1% among a sample of 1508 adults in the central region of Mexico. Garza-Leon et al  found an unusually high prevalence (70.4%) of DED among a university population in northern Mexico, where being of the female sex, smoking, and the use of eye drops represented risk factors. Additionally, Martinez and colleagues  found that in an eye care center in Mexico City, of 338 consecutive first-time adult patients, 43% had OSDI scores classified as severe. Rodriguez-Garcia et al  noted that, in Mexico´s two largest cities, more than 70% of 2725 patients had a positive fluorescein test and the presence of DED. They also identified Sjogren’s syndrome and glaucoma as being important risk factors for significant damage to the ocular surface. More specifically, in the context of OSD in Mexican patients with glaucoma, Orozco-Garcia et al  found a global prevalence of 51.07%; this increased almost exponentially from 17.9% in patients < 40 years of age to > 70% in patients aged more than 70 years. In another preliminary report about Mexican patients with glaucoma, by Giorgi-Sandoval and colleagues , it was reported that 76.7% (336/438) of patients receiving treatment to reduce IOP were classified as mild to severe (OSDI scores), and then 40% were classified as severe. They also showed a correlation between the severity of symptoms, the number of ocular hypotensive medications being taken, and the duration of antiglaucoma treatment. The studies outlined contribute to the literature focused on OSD among the Latino population.
In terms of treatment, it is crucial to mention that the TFOS DEWS II (Tear Film and Ocular Surface Society’s Dry Eye Workshop II)  reviewed contemporary options for the treatment and management of DED, which included anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations, and complementary therapies. It has been established that tear replacement using artificial tears (tear substitutes) is the traditional treatment for OSD, especially when there is a DED component. Tear substitutes, in a variety of formulations, such as drops, gels, ointments, and lubricants, can prevent ocular complications by reducing evaporation and stabilizing the tear film (50). Pucker and colleagues  evaluated the effect of over-the-counter (OTC) tear substitutes by conducting a system review of 43 randomized controlled clinical trials that compared artificial tear formulations with no treatment or placebo. In this review, the authors reported that the overall quality of the evidence was low and, although artificial tears could be effective in treating DED, there was a need for more extensive research to support any conclusions regarding the effectiveness of specific formulations. It is important to note that preservative-free hyaluronate, which was used as the main tear substitute in our study, becomes widely distributed at the ocular surface and the anterior segment, therefore binding to ocular surface cells and contributing to the repair of tissues [52–57]. There is a wide range of commercial products available that contain hyaluronate, and scientific research has demonstrated that these treatments can improve the symptoms of DED .
With regard to treatment for OSD in patients who are using antiglaucoma drugs, it is essential to identify the intensity of the inflammatory process at the ocular surface and to determine whether the use of anti-inflammatory agents could inactivate some of the cascade of events that often result in OSD symptoms. Despite the existing variety of topical steroids used to slow the inflammatory process , certain treatments are preferred due to their efficacious and safe results on the ocular surface, such as loteprednol, fluorometholone, and prednisolone [59–61], all of which were used in this study. We found that fluorometholone and loteprednol were the most commonly chosen topical steroids in both treatment groups (T + and T-) due to the empirical and scientific evidence showing their usefulness in the management of the most intense cases of OSD [28,49,59–61]. Nevertheless, the use of steroids should be personalized to each individual patient, using a careful and meticulous approach to seek the best risk/benefit balance for them. No relevant structural side-effects or IOP loss of control were found in the current study (data not shown) as a result of the short-term use of topical steroids.
In other therapeutic approaches, as has been demonstrated in both clinical and experimental studies [31–35], trehalose participates in the promotion of the survival of cells and tissues exposed to desiccation stress. This suggests that trehalose could facilitate better clinical outcomes in a potentially synergistic way with hyaluronate and topical steroids. Thus, trehalose can be considered an appropriate complement to traditional treatment regimens to help mitigate the harmful effect of antiglaucoma agents containing chemical preservatives and other concomitant conditions that can damage the ocular surface.
It is important to point out that the current study had some limitations, in that it was retrospective in nature and lacked randomization. Nevertheless, the abundant information in the medical records and the sample size are advantages that should be taken into consideration.
Finally, it is essential to emphasize that due to the adverse effects that OSD can have on the visual function and quality of life of patients using ocular hypotensive drugs [16,21–23], the involvement of ocular surface experts and the performance of early glaucoma surgery should be kept in mind, particularly in young people or those with a greater predisposition toward the development of the more advanced stages of OSD. Furthermore, the findings obtained from the current study strongly suggest that a reduction in ocular discomfort and an improvement in the signs of surface damage in patients with glaucoma who developed OSD due to ocular hypotensive agents can be attributed to the use of a multiple therapeutic regimen. It is important to emphasize that a regimen including a preservative-free artificial tears solution based on hyaluronate, steroid drops, and topical trehalose treatment as well as an indication of preservative-free ocular hypotensive agents can be appropriate to treat moderate to severe cases of OSD associated with the use of preserved topical glaucoma treatment.