Abstract
Purpose :
High refractive error in infancy is a risk factor for strabismus and amblyopia. We recently derived a polygenic score (PGS) quantifying an individual’s genetic susceptibility to spherical equivalent refractive error (SER). The PGS explains 15-19% of the variance in SER in adults of European ancestry. We tested the hypothesis that the PGS can identify those at risk of strabismus and amblyopia.
Methods :
Avon Longitudinal Study of Parents and Children (ALSPAC) participants aged 7 years-old were examined by an orthoptist. Habitual visual acuity (hVA) and pinhole habitual visual acuity (pVA) were measured for each eye (ETDRS chart at 4 meters). Strabismus was detected by cover test. SER was estimated by non-cycloplegic autorefraction (average for the two eyes). Amblyopia was defined as a 2-line difference in logMAR VA (better of hVA and pVA in each eye). A PGS was calculated for each child based on 770,000 genetic variants distributed across the genome. Firth logistic regression analyses were performed in 6,104 participants of European ancestry, for the outcomes: esotropia, exotropia and amblyopia.
Results :
A one standard deviation increase in the PGS was associated with an odds ratio (OR)=1.45 (95% confidence interval 1.18 to 1.78; P=0.0004) increased risk of esotropia; OR=0.67 (0.48 to 0.94; P=0.02) reduced risk of esotropia and an OR=1.39 (1.09 to 1.79; P=0.009) increased risk of amblyopia. However, the highest and lowest deciles of the PGS showed limited enrichment of affected individuals, compared to the extreme deciles of SER (Figure).
Conclusions :
A state-of-the-art PGS for refractive error was only weakly predictive of esotropia, exotropia and amblyopia. A PGS with much greater accuracy would be required to achieve clinical utility.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.