This prospective study in patients undergoing trabecular micro-bypass implantation (iStent or iStent inject) contributes some of the first data specifically analyzing the effect of a MIGS device on ocular surface health in patients with glaucoma. Three months after iStent or iStent inject implantation with cataract surgery, clinically and statistically significant improvements were observed in nearly all ocular surface parameters, including OSDI, corneal/conjunctival staining, and tear break-up time. The patient-level significance of these changes is that patients’ average OSDI severity improved from severe to mild, mean corneal staining decreased more than threefold, and eyes on average remained lubricated approximately 50% longer before break-up of tears, respectively. Conjunctival hyperemia also decreased, although this did not reach statistical significance (preoperative score was already in the Trace range).
In nearly all OSD studies, a central challenge is that patient symptoms (as measured by OSDI) do not necessarily match clinical signs (as measured by Oxford, Efron, FTBUT). However, the improvement of each measurement over time for a given patient is meaningful even if there is imperfect correlation between the various tests. By collecting such OSD data alongside traditional glaucoma outcomes (i.e., IOP, medications), this study may aid surgeons and patients in understanding the ocular surface effects of iStent and iStent inject implantation. Any observed effects may be expected to apply specifically to iStent and iStent inject devices, given they are the smallest available trabecular meshwork implants and have a longstanding evidence base showing favorable safety and minimal tissue disruption and inflammation. The same ocular surface benefits may not necessarily be transferrable to larger more invasive devices and procedures that could cause hyperemia and/or inflammatory cascades counteracting ocular surface improvements. Thus, any positive ocular surface effects may become part of the benefit-risk consideration of various medical and surgical treatment options for glaucoma.
Of the four OSD parameters measured in this study, the most dramatic improvements were observed in patients’ OSDI scores. Given the preeminence of this test in OSD clinical studies [32, 35], and its widespread utilization in clinical practice, these improvements are especially promising. It also deserves mention that by 3 months postoperatively, significant improvements were observed in both subjective symptoms (e.g., OSDI) and clinical signs (e.g., FTBUT and Oxford staining). In other words, clinically detectable changes were apparent to the eye care provider, but patients also felt a tangible improvement in their symptoms (and conceivably in their quality of life). A similar correspondence between subjective and objective findings was demonstrated in a recent study by Agnifili et al. , which showed OSDI scores to be directly correlated to the tear meniscus height and area measured by anterior segment optical coherence tomography (AS-OCT). The findings of both the present study and that of Agnifili et al. are notable given that in many OSD studies, symptoms do not necessarily correlate with objective measures .
Likely the primary factor contributing to these ocular surface improvements after iStent or iStent inject implantation is the significant reduction in medications, which themselves are known to promote or worsen OSD (6–9). The negative ocular surface effects of medications are widely documented. For example, Baudouin et al. demonstrated that longer duration of exposure to glaucoma medication(s) resulted in significant increases in ocular surface inflammatory markers such as immunoglobulin E (IgE) and class II human leukocyte antigen-D related antigen (HLA-DR) . The same investigators also showed increased inflammatory markers with multiple topical glaucoma medications as compared to monotherapy . Similarly, Rossi et al. demonstrated a clear relationship between dry eye disease and number of glaucoma medications, with dry eye present in 11% of eyes on one eyedrop compared to 39% and 43% of eyes on two and three drops, respectively . Fechtner et al. also reported incrementally higher OSDI scores in patients using more glaucoma medications, with mean OSDI scores of 12.9, 16.7, and 19.4 in eyes on one, two, and three glaucoma medications, respectively . Alongside such studies correlating medications with ocular surface disease, the medication reductions consistently observed after stent implantation also are well known and widely documented [16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31]. Thus, it stands to reason that stent implantation would result in ocular surface improvement. However, to our knowledge, the present study contributes some of the first data on changes in ocular surface disease measurements before and after stent implantation.
Besides ocular surface benefits, reducing medication burden also can positively impact patient adherence. Suboptimal medication adherence is widely acknowledged to be a key limitation of topical glaucoma treatments, with an estimated 50% of patients not using medications as prescribed . This is particularly relevant for the approximately 40–50% of glaucoma patients who are on multiple medications, as adherence is known to drop dramatically when more than 1 medication is prescribed [10, 11]. Reducing exposure to medications and preservatives also can preserve conjunctival health, thereby reducing the risk of failure of future subconjunctival glaucoma surgery [12, 13].
Although the study’s focus was on the impact of iStent or iStent inject surgery on ocular surface parameters and medication burden, the significant IOP reductions achieved also deserve mention. Even as medications were reduced 2.5-fold, mean IOP was reduced by nearly 3 mmHg. This reduction is especially noteworthy given the cohort’s relatively low preoperative mean IOP (17.4 mmHg) and the well-known observation of smaller IOP reductions with lower preoperative IOP .
This study is not without limitations. There was no control group of cataract surgery alone or fellow-eye control. As is frequently done in single-arm clinical studies, patients’ preoperative measurements served as their own control, although we acknowledge that this does not replace a true control group. The sample size was modest, as this was a pilot study, so future studies may include greater numbers of participants or sites. Another possible direction for future research could be to examine whether intracameral or preservative-free postoperative medications could have a different effect compared to topical medications containing preservatives. As is common in OSD studies, there was inconsistent correlation between patients’ symptoms (i.e., OSDI score) and objective clinical tests (i.e., Efron, Oxford, FTBUT). However, given that the tests were completed by the same clinicians in the same patients over time, the preoperative versus postoperative comparison is still meaningful. The study was unmasked, leaving open the possibility of bias in clinicians’ observations and patients’ perception of their own symptoms. Study follow-up extended up to 3 months, and longer-term data may be needed to detect chronic changes in corneal and conjunctival health after stent surgery.
Limitations notwithstanding, this study contributes useful evidence on a topic currently lacking in the MIGS literature. Ocular surface health plays a central role in patient adherence, quality of life, and outcomes of future conjunctival surgery in patients with glaucoma. Implantation of iStent or iStent inject with cataract surgery produced significant improvements in ocular surface health, alongside significant reductions in IOP and medications. Thus, ocular surface improvement may be an additional postoperative benefit for doctors and patients to consider as they are evaluating glaucoma treatment options.