High-risk MMP9 genotype is associated with worse long-term change in PED width in treated eyes with neovascular AMD.

Abstract

Purpose : The MMP9 locus is specifically associated with neovascular AMD (nvAMD); however, the impact of this genotype on long term outcomes of eyes treated with intravitreal injections (IVI) is unknown. This retrospective study aims to determine whether eyes getting IVIs for nvAMD with high-risk compared to low-risk MMP9 genotype had changes in retinal pigment epithelial detachment (PED) measurements during treatment.

Methods : Patients undergoing nvAMD treatment at the University of Iowa were genotyped for the rs4810482 SNP and divided into two groups: those homozygous for the low-risk (CC) and those with the high-risk alleles (TT) for MMP9. Individuals with heterozygosity, history of vitrectomy, poor OCT visualization or conditions that could mimic nvAMD, such as central serous chorioretinopathy, diabetic retinopathy and venous occlusions, were excluded. The Heidelberg Heyex platform was used for manual OCT evaluation, measuring maximum PED diameter and height at baseline and employing the "progression" mode for subsequent analyses. Measurements were performed at the first and fourth IVI, at the two-year treatment mark, and the last visit. Linear mixed effects model was used for statistical evaluation, with a significance threshold set at p=0.05.

Results : 41 patients were genotyped, the 11 eyes (8 patients) classified as CC and the 20 eyes (12) as TT were included for analysis. There were no statistical differences between the groups regarding age, sex or BCVA at baseline. The median (25%/75%) follow-up time was 8.6 (7.66/12.18) years in TT and 8.57 (5.05/13.47) in CC; after the 2-year mark median was 7.86 (6.41/10.34) years for TT and 9.56 (5.28/11.35) for CC. At final visit, TT showed an increase in PED width, the mean change compared to baseline was -236.4µm for CC vs 782µm for TT (p=0.016); -144.8µm vs 628.6µm compared to the fourth IVI (p=0.023); -285.1µm vs 788.3µm compared to the two-year mark (p=0.048). No statistical differences were observed in PED height.

Conclusions : Patients with high-risk MMP9 genotype may experience a widening of PED over time. Further investigations are warranted to elucidate the consequences and underlying reasons for these findings, especially concerning the potential association with fibrosis development and neovascular membrane enlargement.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.

 

Change in PED width at final visit, compared to baseline, fourth shot and at the two-year treatment mark.