In our daily practice, the diagnosis of dry eye syndrome is based on the results of Schirmer's test, BUT, ocular surface staining test with fluorescein and the presence of ocular irritation symptoms. [17] In glaucoma patients, tear dysfunction is mainly attributed to chronic administration of preservative-containing glaucoma medications. It is well recognized that moderate dry eye can develop with age. The rate of age-related dry eye disease has been found to be 15% in patients of similar age group without glaucoma. [18] Considering the effect of patient age on tear film, we included only patients and individuals with similar age and gender distribution in our study.
Antiglaucomatous therapy-induced OSD is largely due to preservatives rather than the active molecule. [7–9] Benzalkonium chloride (BAK) is the most commonly accused preservative. BAK causes disruption of tear film stability, goblet cell loss, conjunctival squamous metaplasia, apoptosis, corneal epithelial barrier disruption and corneal nerve damage. [10–16]
Trabeculectomy is a widely used surgical treatment to control intraocular pressure in glaucoma patients who cannot be controlled with medical therapy. Previously, MMC was only used as an adjunctive treatment for failed trabeculectomy or complicated cases. Currently, MMC is used for primary trabeculectomy in both adults and children. In our study, all glaucoma patients underwent trabeculectomy with MMC. Kim et al. suggested that there may be long-term damage to the bleb conjunctival epithelium after trabeculectomy with MMC. [19] In the following years, Amar et al. showed by immunofluorescence staining on impression cytology samples taken from the bleb area that blebs without antimetabolites had only scattered inflammatory cells, but blebs with MMC had many dendritiform inflammatory cells. [20] Baiocchi et al. found that the inflammatory reaction after trabeculectomy surgery using MMC was more pronounced than the surgical procedure associated with the Xen 45 Gel Stent. [21] Mitomycin C increases the success rate of trabeculectomy but may cause toxic effects on the conjunctiva. Different studies have shown that trabeculectomy efficiently lowers intraocular pressure by providing better control of the 24-hour mean pressure, but it can extensively alter the ocular surface anatomy, causing a persistent clinical or subclinical inflammatory process. [22, 23]
When the tear function tests of the patient group and the control group were compared, it was observed that there was a significant decrease in BUT and Schirmer II test values in both patient groups. Schirmer II test results were similar in the trabeculectomy group and the drop group (p = 0.701) Although the BUT was shorter in the drop group, there was no statistically significant difference with the trabeculectomy group (p = 0.270). These results suggest that antiglaucomatous drugs and trabeculectomy with MMC may affect both the mucin and aqueous layers of the tear at a similar rate, resulting in OSD. At the same time, the presence of bleb may also disrupt the uniform distribution of tears on the cornea, leading to worsening of tear function test results.
When corneal and conjunctival fluorescein staining results were compared between the patient group and the control group, a significant increase in Oxford grading scores was observed in the patient groups. Similar findings are available in studies in which topical medications containing BAK are mostly used in treatment. Superficial punctate keratitis has been reported in 50% of patients treated with three drugs per day. [24–27] This result shows that ocular surface chronic cell damage can occur in both treatment groups.
When the conjunctival impression cytology samples of the patient group and the control group were compared according to the Nelson staging system, deterioration in the morphologic structure of conjunctival epithelial cells and a significant decrease in the density of goblet cells were observed in the patient groups compared to the control group. Contrary to our expectation, Nelson staging results were more severe in the trabeculectomy group, but there was no statistically significant difference between the drop group (p = 0.401). This result may be attributed to the fact that trabeculectomy patients receive multidrug therapy for many years in the preoperative period and the negative effect of MMC and filtration bleb on conjunctival epithelium and goblet cells. [7–9, 19] We also found that the results of conjunctival impression cytology improved with increasing time after trabeculectomy, although not statistically significant.
In eyes undergoing trabeculectomy surgery, these results may be due to the chronic effect of BAK on ocular surface due to long-term topical antiglaucomatous treatments received in the preoperative period, or to the extensive alteration of the ocular surface anatomy by postoperative bleb, or to the effect of MMC used to improve surgical success on conjunctival epithelium and goblet cells, or to all three effects. The number of individuals included in the patient group may also have affected our results. Results may differ in larger patient groups. In addition, there were no data on the tear function and degree of ocular surface discomfort of patients before trabeculectomy surgery. Therefore, studies that follow patients from the initial diagnosis will be useful in detecting ocular surface changes during the treatment process.
The frequency of ocular surface disease increases over time in glaucoma patients. When selecting medication, it should be kept in mind that the treatment will be long-term; treatment should be started with a single drug as much as possible and preservative-free alternatives should be considered.
In conclusion, trabeculectomy surgery with MMC and topical medications in glaucoma patients caused similar severity of SCI in our patient group. After trabeculectomy surgery with MMC, OSD findings tend to improve with longer follow-up, although not statistically significant. Therefore, in terms of OSD in glaucoma patients, there is no superiority between drug and trabeculectomy with MMC in the early period. However, trabeculectomy with MMC may become more advantageous in the following years with the elimination of drug use.