PGA is the most widely used first-line therapeutic medication for POAG due to its highest effectiveness in decreasing IOP and reducing circadian IOP fluctuations, as well as its convenient dosing and tolerable side effects. However, PGA was found to have some other effects, such as decreasing the thickness of central cornea. Our results showed CCT declined under treatment of PGA over time, which was in accordance with previous studies[21, 22], implying a possible time cumulative effect of PGA on cornea tissue. The mechanisms of CCT reduction are possibly due to the MMPs up-regulation and extracellular matrix degradation stimulated by PGA in the cornea[8, 9, 23].
The cornea is considered to have both viscous and elastic properties. Studies conducted on the ORA showed that IOP decreased and CH increased significantly after topical PGA treatment[24, 25]. Increased CH indicates an increased corneal viscoelastic response. IOP is a significant influencing factor of corneal deformation[1, 27] and should always be taken into account when analyzing corneal biomechanics. Hence, to better elucidate the corneal biomechanical changes with long-term treatment of PGA and to avoid the influences of IOP sudden decrease on it, baseline Corvis ST measurements, namely those before initiation of PGA treatment, were not analyzed.
In this study, we showed that DA, AT1 and AV1 changed with statistical significances under PGA therapy over time. Since the results were adjusted for age, gender, axial length, corneal curvature, IOP and CCT, it suggested long-term use of PGA might influence the corneal biomechanics directly. Our observation was consistent with an previous observational study, which found CH increased significantly after 6 months treatment of PGA on newly diagnosed POAG patients measured by ORA, and this increase was only significantly correlated with basal IOP but not with the drug induced IOP reduction, suggesting PGA could have a direct effect on cornea biomechanical properties.
A more deformable cornea is characterized by reaching the first applanation faster (with shorter AT1 and greater AV1), the second applanation slower (with longer AT2 and lower AV2) and the highest concavity with greater DA. In our study, although not all of the biomechanical parameters reached statistical significances, DA (β=-0.0015), AV1 (β=-0.0004) and AT2 (β=-0.0059) decreased and AT1 (β = 0.0089) increased as PGA treatment time extended after adjusting for potential confounding factors. Based on the meanings of the parameters, our results indicated a less deformable cornea as PGA treatment prolonged.
Our observations were supported by a few previous studies as follows. Hussnain et al observed a significant decrease in CH among medication, laser or surgery treated POAG patients in a retrospective study. They hypothesized that CH decreased over time in POAG patients even though increased in a short term with therapies to reduce IOP. However, the percentages and types of medical treatment were not mentioned in their publication. Another recent prospective study conducted by Meda et al showed that POAG patients with long-term PGA therapy for at least 1 year had significantly lower CH values than those whose PGA were discontinued, which indicated that long-term use of PGA might cause CH decrease.
Pathogenesis differences between NTG and HTG have been investigated by many studies. Factors other than IOP probably contribute more to the onset and development of NTG. Interestingly, we found there were statistically significant differences in corneal biomechanical parameters under PGA treatment between NTG and HTG groups. After adjusting for age, gender, axial length, corneal curvature, IOP and CCT, AT1 was shorter and AV1 was greater in NTG than in HTG, which means that corneas in NTG tend to be more deformable compared to those in HTG with the extension of PGA treatment. It probably could partially explain the relatively slower progression of NTG than HTG[29, 30].
The limitation of our study is that the patient profile may not necessarily represent the whole population data because of our clinic-based design. Another one is that the patients had variant follow-up times and different intervals between visits.
To our knowledge, this is the first prospective study investigating the long-term changes of corneal biomechanical properties with chronic use of PGA measured by Corvis ST. Our study indicated that long-term treatment of PGA might make cornea less deformable. It should be taken into consideration when analyzing corneal biomechanics in patients with PGA treatment. We speculate the corneal extracellular matrix remodeling may be involved, although the underlying mechanisms remain unknown. It would be interesting for further studies to validate these changes at a molecular level.