Cone dysfunction in ARR3-mutation-associated early-onset high myopia: an electrophysiological study

Abstract

Abstract Background Myopia-26, a Mendelian form of early-onset high-myopia caused by mutations in the X-chromosomal ARR3 gene and predominantly affecting females, curiously, may provide an alternative route of investigation to unveil retinal mechanisms underlying pathological eye growth. We conducted a case-control cross-sectional prospective electrophysiological study in genetically characterized Myopia-26 patients (ARR3 heterozygous mutants) compared with high myopes harboring intact ARR3 alleles. Results Participants were 24 females: 10 healthy controls (E-CTRL, mean age = 31.5 ± 8.8 years) and 14 high myopes (HM; mean age = 27.0 ± 13.1 years) divided in two groups: seven without (M-CTRL) and seven with (MYP-26) genetic alteration in the ARR3 gene. The clinical evaluation included complete eye screening and ISCEV full field ERGs recorded from both eyes under mydriasis. Spherical equivalent was comparable (mean=-9.55 ± 2.46 and − 10.25 ± 3.22 for M-CTRL and MYP-26, respectively) and BCVA was significantly different between M-CTRL (full BCVA) and MYP-26 (mean = 0.406 ± 0.253). E-CTRL and M-CTRL showed similar light-adapted flash and flicker ERG amplitudes; however, the prior values were reduced by cca. 35% (a- and b-waves alike), the latter by cca. 55% in the MYP-26 group (F(2,47) > 21.821, p < 0.005). The presence of myopia slightly reduced dark-adapted a-wave amplitudes (~ 20%), but this was not specific for ARR3 mutations (M-CTRL vs MYP-26, p = 0.999). Conclusions The cone dysfunction observed in MYP-26 patients is not the consequence of HM, i.e. elongation of the eye, it rather plays a role in the pathogenesis of Myopia-26. Further studies may reveal retinal mechanisms connecting cone dysfunction to eye growth in Myopia-26 patients.