BTX-A has been used to treat HFS and BEB since the 1980s.[19] It is a safe and effective treatment that relieves the symptoms of BEB and HFS in 66–100% of cases [20, 21].
The results of studies showing the relationship between dry eye and BTX-A treatment are contradictory. Although evaluation times are different, at the time when the effect of BTX-A is maximum, the TBUT and Schirmer test results are different between studies. While a study reported an increase in TBUT and Schirmer test [4], Kocabeyoglu et al. reported an increase in TBUT, no change in Schirmer test [22], others have shown an increase in TBUT and decrease in Schirmer test [9, 23]. The most likely cause of these different results is the differences in injection sites and dosages.
BTX-A injection into the lacrimal gland reduces aqueous tear secretion so it is used in the treatment of epiphora. Conversely, BTX-A injection to the lower medial canthal region is used in dry eye treatment. It decreases the blinking rate, reduces the action of the lacrimal pump and increases tear retention due to paralysis of the orbicularis muscle [24, 25].
Lu et al. showed that inflammation related cytokines, like TNF-α, IL-6 and IL-1ß, are higher in patients with BEB and DED compared to patients with only DED. The authors concluded that blinking in BEB patients leads to micro abrasive effects in the conjunctiva and increases inflammation [5]. Ho et al. showed that lipid tear thickness is significantly increased, without any change in meibomian gland dropout, when compared to baseline at the first month of BTX-A treatment. They concluded that this effect is due to paralysis of the lacrimal pump and the retention of tears on the ocular surface [26].
According to the TFOS DEWS II report, tear film thickness (TFT) is one of the dry eye sub-classification methods, and the tear film is composed of two layers; the muco-aqueous gel layer underneath, and an overlying lipid layer [27]. OCT measures the height, area and curvature of the upper and lower menisci and, although these parameters don’t show the central tear film, the lower tear meniscus height shows the muco-aqueous tear volume [12, 28, 29]. In this study, after BTX-A treatment, TMH and TMD were significantly increased and OSDI scores, which evaluate the patients’ symptoms, decreased significantly. TMH and TMD correlate well with dry eye symptoms [30]. Gunes et al. and Lu et al. also reported a significant decrease in OSDI scores after BTX-A injections in BEB and HFS patients [5, 9]. Despite the improvement in OSDI scores, there were no significant changes in TBUT, Schirmer I or CFSS. This finding can be related to the increase in inflammatory mediators on the ocular surface and can be explained by the poor correlation between dry eye symptoms and signs including via the Schirmer test and ocular staining, as reported previously [31].
In the present study, TMH and TMA increased significantly after BTX-A injection. In a recent study, Park et al. evaluated lacrimal drainage and TMH in BEB patients and showed an increase in TMH and tear clearance time after BTX-A treatment [4]. The results of these studies suggest that BTX-A related paralysis of the orbicularis muscle leads to a decrease in nasolacrimal outflow and tear retention.
Eyelid pressure is an important cause of corneal astigmatism. Previous studies have reported corneal topographic changes after ptosis, blepharoplasty and gold-weight implant surgery [32, 33]. Gunes et al. evaluated corneal topographic changes after BTX-A treatment in HFS and BEB patients and reported a significant decrease in astigmatism [9]. Similarly, Osaki et al. reported that steep keratometry and astigmatism decreased significantly at 2 months and 3 months after treatment in HFS patients [34]. While the decrement in steep K, mean K and astigmatism values was statistically significant 3 weeks after BTX-A injections, the change between the baseline and 3rd week measurements (0.2 D for the steep K and 0.1 D for the mean K) was very close to the repeatability limits of Pentacam [35].
In the present study, the changes in anterior corneal aberrations after BTX-A treatment were also investigated. Previous studies have shown that abnormalities in the tear film and an increase in the interblink interval increase corneal and total aberrations and effect visual quality [36–39]. Isshiki et al. evaluated total ocular aberration and reported a significant decrease in HOA in BEB patients after relieving spasms [16]. Yakibu et al. reported a significant decrease in total hRMS and SA after treatment in BEB and HFS patients [17]. This is the first study to evaluate anterior corneal aberrations after BTX-A injections in patients with BEB and HFS. Although hRMS and tRMS decreased after treatment, the results were not significant). The difference between these results may be explained by the difference in the measured aberrations, that is, ocular versus corneal. An improvement in tear functions and decreased blinking rate can change the quality of light transmitted to intraocular structures which causes an improvement in corneal and other ocular aberrations.
There are some limitations of this study. Firstly, the number of participants is low and, secondly, all patients included in the study had undergone long-term BTX-A treatment. As the effect of BTX-A can last for up to 6 months, the previous BTX-A effect may not be completely over at the time participants were enrolled for the study. Finally, the Schirmer test was completed first so this might have affected the CFSS results.
In conclusion, BTX-A injection increases tear meniscus and decrease symptoms related to dry eye disease in BEB and HFS patients. It decrease astigmatism and keratometry values but it does not cause a significant change in corneal aberrations.