A randomized clinical trial using atropine, cyclopentolate, and tropicamide to compare refractive outcome in hypermetropic children with a dark iris; skin pigmentation and crying as significant factors for hypermetropic outcome.

Purpose: To evaluate the refractive outcome and influencing factors following atropine 0.5% eye-drops applied twice daily during 2 ½ days at home and two drops of cyclopentolate 1% (C+C) and one drop of cyclopentolate 1% and one drop of tropicamide 1% (C+T) applied in an outpatient clinic, in hypermetropic children with a dark iris. Methods: Double-blind randomized study including 67 3-6-year-old children receiving C+C in one eye and C+T in the other eye. Two weeks later followed by atropine 0.5% in both eyes. Primary outcome measures were: spherical equivalent (SEQ) following C+C, C+T and atropine, and secondarily SEQ with respect to sex, ethnicity, skin pigmentation (light, medium, dark) and crying. Data on atropine are divided in those with C+C (CC) or C+T (CT) as a first intervention. Results: Mean SEQ±SD for C+C, C+T, atropine-(CC) and atropine-(CT) was +1.74 ± 1.35, +1.77 ± 1.34, +2.15 ± 1.43 and +2.10 ± 1.38 diopter (D). Atropine 0.5% revealed significantly more hypermetropia than C+C and C+T; +0.41 ± 0.43, 95%CI +0.31 to +0.52D and +0.33 ± 0.39, 95%CI +0.24 to +0.34D. No significant difference was present between C+C and C+T; -0.03 ± 0.56, 95%CI -0.16 to +0.11D. Ethnicity and skin-color were strongly associated (r = 0.84, p < .001). Sex was not affecting outcomes (p = .101). Ethnicity was borderline significant (p = .049). Skin-color was a highly significant factor (p = .002). A statistical model combining intervention and skin-color, with light-pigmented subjects receiving atropine-(CC) as reference group (mean SEQ +2.61 ± 1.46D), indicated borderline significantly less hypermetropia in atropine-(CC)-dark: mean decrease (95%CI): -0.81 (-1.66 to +0.05)D and atropine-(CT)-dark -0.87 (-1.70 to -0.03)D, furthermore significantly less hypermetropia in C+C-dark: -1.15 (-1.97 to -0.32)D; C+T-dark: -1.21 (-2.03 to -0.39)D, C+C-medium: -1.02 (-1.81 to -0.24)D and C+T-medium: -0.86 (-1.64 to -0.08)D. Adding crying to the model significantly less hypermetropia was found for subjects crying in all interventions; -0.53 (-0.98 to -0.09)D. Within the interventions, with light-pigmented non-crying subjects as reference group (mean SEQ in atropine, C+C, respectively, C+T: +2.62 ± 1.41, +2.33 ± 1.20 and +2.32 ± 1.20D), showed significantly less hypermetropia in dark-pigmented crying subjects in each individual intervention: atropine -1.10 (-2.01 to -0.19), C+C -1.28 (-2.14 to -0.42) and C+T -1.34 (-2.20 to -0.48)D. For medium pigmented crying subjects this was present in atropine: -0.82 (-1.61 to -0.03)D and C+C: -0.86 (-1.68 to -0.04)D, but not in C+T: -0.58 (-1.25 to +0.09)D. Conclusions: Atropine 0.5% revealed a slight significantly higher hypermetropia. A dark-pigmented skin, especially when crying upon application, resulted in lower hypermetropia in all interventions. C+T provided clinically better results in medium pigmented crying subjects compared to C+C, and equal results compared to atropine 0.5%.