Abstract
Purpose :
The pathogenesis of keratoconus (KCN) remains poorly understood. There is increasing evidence for the presence of subclinical inflammation in KCN. Thrombospondin-1 (TSP1) is a secreted multifunctional matricellular protein that plays a role in immune modulation. Matrix metalloproteinases 9 and 3 (MMP9 and MMP3) have previously been found to be dysregulated in KCN. We assessed whether TSP1, MMP9 and MMP3 levels were altered in tears of KCN patients, and could potentially serve as biomarkers of KCN disease state.
Methods :
This research was conducted with approval from the Boston University Medical Campus Institutional Review Board. Subjects with KCN and age-matched controls without KCN were recruited from the Ophthalmology Clinic at Boston Medical Center, Boston, MA. TSP1, MMP9 and MMP3 levels were measured using microbead immunoassay analysis from tear samples collected from each eye. Wilcoxon test was used to compare TSP1 levels between KCN vs non-KCN eyes, and Student’s t-test to compare TSP1 between progressive and non-progressive KCN, as well as between patients with and without a history of atopy. Since multiple samples in each group had undetectable levels of MMPs, MMP9 and MMP3 presence in KCN and non-KCN tears was compared using Chi-squared tests.
Results :
We collected tears from 102 eyes of 53 KCN patients, and 96 eyes of 51 control patients. TSP1 was significantly elevated in KCN tears (p=0.03). The KCN group had a smaller proportion of samples with detectable MMP9 (p=0.0004). There was no significant difference in number of eyes with detectable MMP3. TSP1 levels between KCN eyes with (n=22) and without (n=44) progression within an 18 month period were not significantly different (p=0.84). Interestingly, although TSP1 was not higher in subjects with atopic disease overall (p=0.12), nor within our control group (p=0.37), we found that within our KCN group, TSP1 was significantly higher in KCN patients with atopic disease (n=24) vs without (n=78) (p=0.03).
Conclusions :
TSP1 was significantly increased in the tears in our KCN population. We also found that fewer KCN eyes expressed detectable levels of MMP9, and that MMP3 detectability was not significantly different in KCN. Further, among our KCN patients, those with atopic disease had higher tear TSP1 than those without, while this relationship with atopy was not seen in controls. Tear film TSP1 could potentially serve as a biomarker in KCN, but validation is needed.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.