Polygenic risk is associated with differential treatment response to SLT and medical therapy in treatment-naive glaucoma

Abstract

Purpose : Lowering intraocular pressure reduces the risk of glaucoma vision loss. First-line therapy is
typically topical medication or selective laser trabeculoplasty (SLT), but treatment response can be
variable. In a retrospective analysis within a prospective longitudinal study, we compared treatment response to initial therapy between high and low PRS individuals treated with either medical therapy ot SLT at clinican discretion.

Methods : Participants were drawn from the PROGRESSA clinical registry of glaucoma suspects with a calculated PRS and
at least one eye that was treatment-naive at baseline (n=1425 eyes of 767 participants). Treatment
initiation was at the clinician's discretion and IOP reduction was measured at the next clinic visit.
Participants with a PRS in the top quintile (high PRS) of population risk were compared to the rest of the cohort.
Treatment success was defined a a 20% reduction in IOP from baseline.

Results : 167 eyes of 117 patients were treatment-naive at baseline and commenced treatment during the study period (medical therapy in 103 eyes and
SLT in 64 eyes). Mean IOP at baseline was 17.2mmHg in the SLT treated group and 17.0mmHg in the medical therapy group (P=0.81).
High PRS individuals had greater IOP reduction when treated with SLT compared to medical therapy (OR 3.7, p=0.046). In indiviudals treated with SLT, those with high PRS experienced greater IOP reduction (OR 3.9. p=0.042). There was a trend for lower PRS individuals to have greater IOP reduction with medical therapy than SLT (OR 2.9, p=0.08).

Conclusions : In treatment naive glaucoma suspects who progressed to require treatment during the study period, individuals with high PRS experienced greater IOP reduction when treated with SLT compared to medical therapy. There was a trend for lower PRS individuals experiencing greater IOP reduction with medical therapy. In this study a higher proportion of individuals were commenced on therapy for normal tension glaucoma than high tension glaucoma, and consequently the magnitude of IOP reduction is lower than in other studies of early glaucoma.

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