Long-term effect of using hard contact lenses on corneal endothelial cell density and morphology in ophthalmologically healthy individuals in Japan – Scientific Reports

We examined the density and morphology of corneal endothelial cells in more than 8000 eyes in patients using HCL for an extended period of more than 14 years. Using multivariate analysis, we demonstrated that the duration of usage is not related to ECD but is related to CV and 6A. HCL usage leads to corneal hypoxia, which in turn leads to lactate accumulation, increased CO₂ concentration, and changes in the pH of the cells^21,22. These homeostatic changes in cellular environment result in morphological changes, polymorphism (decreased in 6A), and polymegathism (increased CV). Previous reports showed that polymegathism occurred after long-term usage of HCL^19,20. Furthermore, mechanical stimulation of the corneal surface while using a contact lens reportedly leads to the release of inflammatory mediators in tear samples²³. Moreover, ultraviolet (UV) radiation can affect the corneal endothelium²⁴. Therefore, the protective effect of HCL against UV might be related to this phenomenon. However, our retrospective data did not include the types of HCL and did not consider whether they had UV protection. Detailed elucidation of the effect of HCL on the corneal endothelium is required, and future analysis and comparison should be performed for basic research.

In this study, changes were observed in the corneal endothelial cell morphology, whereas ECD did not change. It has been reported that ECD does not change with contact lens usage and the results of this study are consistent with those of previous reports^25,26. Since the present study included individuals who had used HCL for extended periods, it was necessary to consider age-related changes in the endothelium. While univariate analysis showed that ECD had changed, multivariate analysis considering the effect of age demonstrated that the number of years of HCL usage had no direct effect on ECD. ECD gradually decreases with aging in both young and older adults¹⁷. Although corneal endothelial cell morphology also changes with age, even after accounting for these changes in the statistical analysis, long-term use of HCL is related to 6A and CV of the endothelium. Unlike the medium-term perspective, this study examined cases of long-term use with an average of more than 14 years, and also included cases in which HCL had been used for more than 40 years; therefore, these conclusions can be considered to be reliable.

HCL is commonly classified into PMMA and RGP lenses. PMMA lenses, which have low oxygen permeability, reportedly result in contact-lens-induced lactate accumulation, changes in pH, CO₂ elevation, and polymegathism²¹. The RGP lens was developed to improve gas permeability (high Dk value), and it induced fewer morphological changes in the corneal endothelium, but morphological changes were still observed^27,28. The effect of the lens type on the condition of the corneal endothelial cells may differ. In this study, we considered the Dk value of 60 as a threshold value. Our results showed that ECD decrease per one-year of HCL usage was -5.42 cells/mm² and -5.05 cells/mm² in the low- and high-Dk groups, respectively. This change, which includes age-related changes, was not high considering the normal age-related range for Japanese patients¹⁷. Changes in CV tended to be lower in the high-Dk group than in the low-Dk group (0.21% vs. 0.088%). Although HCL made of PMMA are not widely prescribed now, there are still patients who have been using the same familiar lenses for a long time. Therefore, the effect of these lenses on the cornea cannot be ignored. It is important to fully understand the changes in morphological characteristics as well as the ECD, and frequent follow-up is necessary, especially in cases where corneal endothelial cells are damaged by ocular trauma, surgical intervention, or other disorders.

Endothelial morphological abnormalities are thought to be caused by changes in the physiological environment, such as cellular hypoxia of the corneal endothelium and systemic diseases, such as diabetes^29,30. This environmental stress induces changes in the CV and 6A, leading to a decrease in ECD. However, our multivariate analysis showed that contact lens use was not significantly associated with ECD, but with endothelial morphology. A previous study showed the same results as ours, and their multiple regression analysis showed that contact lens use was not significantly related to ECD, but to endothelial morphology (CV), but this report was based on a small number of patients, and hard or soft lenses and the type of contact lens was not classified³¹. One reason why ECD is not affected by the duration of HCL usage is the cellular ability of the corneal endothelium to recover from such environmental stresses. Corneal endothelial cells have the ability to recover when the stress is removed or reduced³²; HCL users typically do not use lenses throughout the day and remove them at night. This recovery period explains why ECD is not affected, and morphological changes only occur with HCL use. Clinically, it is important to observe the corneal state even after discontinuation of HCL usage.

In our current study, multivariate analysis revealed that male sex was significantly related to the ECD and CV in eyes with HCL. We previously reported that CV in ophthalmologically healthy males was lower than that in females in a Japanese population¹⁷. Although endocrine disorders, such as acromegaly, are related to ECD³³, the relation of the state of corneal endothelium and sex difference is not fully analyzed and the issue is still controversial; therefore, a further comparative clinical study was required.

One limitation of this study is that the type of lens used by each patient was not available since many patients who had worn HCL for decades did not know the exact type of lens they used or how long they had been using them. However, interviews for the duration of usage were reviewed retrospectively and it was possible to perform a sub-analysis. Secondly, it was difficult to accurately calculate the total time of HCL use in this study, because it was not possible to determine the duration of HCL usage per day. Furthermore, this study was conducted at a single hospital, and we did not evaluate the degree of myopia and did not include a control group. To overcome this limitation, future studies should prospectively evaluate longitudinal data on the corneal endothelium in multiple settings.

In conclusion, long-term use of HCL causes morphological changes in the corneal endothelium, although it does not affect ECD. Clinical ophthalmologists should regularly monitor the morphological changes of the corneal endothelium as well as various complications of HCL.