Control of myopia using diffusion optics spectacle lenses: 12-month results of a randomised controlled, efficacy and safety study (CYPRESS)

Abstract

Background: Mutations in the L/M cone opsin gene array cause abnormally high perceived retinal contrast and the development of myopia. Environmental factors may also lead to high visual contrast and cause myopia. Diffusion optics technology (DOT) lenses are designed to reduce contrast signalling in the retina and slow myopia progression.

Methods: The Control of Myopia Using Peripheral Diffusion Lenses Efficacy and Safety Study (CYPRESS, NCT03623074) is a 36-month, multicentre, randomised, controlled, double-masked trial evaluating two investigational spectacle lenses versus control lenses in myopic children aged 6-10, with a planned interim analysis at 12 months. The primary endpoints are change from baseline in axial length (AL) and spherical equivalent refraction (SER).

Results: 256 children (58% female; mean age at screening, 8.1 years) were dispensed spectacles. Across all groups, baseline averages were AL 24.02 mm (SD±0.77 mm), SER -2.01 D (SD±0.9 D) using manifest refraction, and SER -1.94 D (SD±1.0 D) using cycloplegic autorefraction. At 12 months, mean difference in SER progression for test 1 versus control was -0.40 D (p<0.0001), representing a 74% reduction and -0.32 D for Test 2 (p<0.0001), representing a 59% reduction. The difference in AL progression for test 1 versus control was 0.15 mm (p<0.0001) and test 2 versus control was 0.10 mm (p=0.0018).

Conclusion: 12-month results from this ongoing trial demonstrate the safety and effectiveness of DOT spectacles for reducing myopic progression.

Keywords: Clinical Trial; Treatment other; Vision.

Figure 1

Contrast hypothesis of myopia and development of DOT lens. X-chromosome opsin gene array for a male with high myopia due to the LVAVA haplotype is shown. (A) OPN1LW gene (pink) with LVAVA exon 3 haplotype and OPN1MW gene (green) with MVVVA exon 3 haplotype. The LVAVA haplotype causes exon three to be skipped in pre-mRNA splicing so only about 6% of the mRNA is full length. (B) L (pink) and M (green) cones have dramatically different photopigment OD because of mis-splicing. S cones are blue. (C) Retina signals high contrast even under uniform white light because of OD differences. Activity of L cones (grey) is low, activity of M and S cones (black) is high. We hypothesised that the constitutive contrast signalling due to photopigment OD differences stimulates axial elongation of the eye and causes myopia. (D) The hypothesis led to the development of a novel spectacle lens (DOT lens) that reduces contrast (left lens) compared with a standard of care lens (right). DOT, diffusion optics technology; OD, optical density.

Figure 2

Least squares mean changes (±SE) from baseline for AL (A) and SER (B), mITT population. LS, SR and p values are derived from an ANCOVA model adjusting for age, gender, and baseline AL or SER value. Missing data were handled by the multiple imputation with regression method. The least squares mean changes (±SE) from baseline from the same model with data as observed (ie, no imputation) in AL or SER and was 0.15 (±0.020) mm or −0.14 (±0.052) D for test 1 and 0.19 (±0.023) mm or −0.24 (±0.061) D for test 2 vs 0.30 (±0.018) mm or −0.54 (±0.049) D for the control group. AL, axial length; ANCOVA, analysis of covariance; D, dioptre; LS, least squares; mITT, modified intention-to-treat; SER, spherical equivalent refraction.

Figure 3

Scatterplot of change from baseline in SER at 12 months versus change from baseline in AL for each treatment group. AL, axial length; D, dioptre; SER, spherical equivalent refraction.