Flemming Møller

Purpose: To investigate changes in choroidal and retinal thickness before and during myopia control treatment with orthokeratology lenses (OKL) in myopic children. Methods: This was a sub‐study of CONTROL and CONTROL2 studies. The present study was a 2‐year, prospective, single‐group interventional study consisting of a 6‐month pre‐treatment observation period followed by 18‐month OKL treatment. Choroidal and retinal thicknesses were measured using a 3D macula scan with swept‐source optical coherence tomography. All thickness measures were corrected for magnification using the Imagenet6 software. Axial length was measured using Lenstar LS900 and corrected for change in central corneal thickness. Data were collected at three pre‐treatment visits and seven post‐treatment visits (from Day 3 up to 18 months). Results: The 20 study participants had a mean age of 11.2 ± 1.9 years, median cycloplegic spherical equivalent refractive error of −2.58 diopters (range − 4.75 to −1.00) and mean axial length of 24.56 ± 0.63 mm. During the pre‐treatment period, there was a statistically significant decrease in retinal thickness of −1.44 μm ( p = 0.038, SE 0.70, 95% CI –2.82 to −0.08), but a significant increase was seen after initiation of OKL treatment. Thickness peaked at 2.54 μm ( p < 0.001, SE 0.72, 95% CI 1.13 to 3.95) at the 6‐month follow‐up. We observed a tendency for the choroidal thickness to decrease during the pre‐treatment period (−5.96 μm, p = 0.12, SE 3.78, 95% CI –13.37 to 1.46) and then a statistically significant increase after treatment initiation with a peak of 11.95 μm after 1 month of treatment ( p = 0.003, SE 4.08, 95% CI 3.94 to 19.96). Short‐term change in choroidal thickness after treatment initiation did not correlate with change in overall eye length defined as subfoveal choroidal thickness plus axial length adjusted for post‐treatment change in central corneal thickness. For each individual participant, the choroidal thickness and retinal thickness were highly positively correlated at each visit throughout the study ( p < 0.001, 95% CI 0.69 to 2.09, linear mixed model). Conclusion: Treatment with OKL increased both retinal and choroidal thickness in myopic children. Short‐term change in choroidal thickness was not a predictor for growth of the overall eye length. Further studies of the presumed structural changes in the choroid and the retina are warranted.

To determine the effectiveness of various interventions in reducing myopia progression in children. Literature databases were searched on December 2, 2023: PubMed, Embase, the Cochrane Central, Web of Science Core Collection, BIOSIS Previews, Current Contents Connect, Data Citation Index, Derwent Innovations Index, KCI‐Korean Journal Database, Preprint Citation Index, ProQuest™ Dissertations and Theses Citation Index and SciELO Citation Index. PRISMA guidelines and the Cochrane Handbook recommendations were followed. All unique interventions were analyzed individually in order to generate clinically applicable results. The main outcome was axial length progression. Secondary outcomes were incident corneal infiltrates, photophobia, development of an allergic response towards the intervention, visual acuity at near and distance and drop‐out from allocated intervention/control. We identified 74 RCTs involving 12 154 participants aged 6–18 years. Network meta‐analysis compared axial length after 1 year between 45 interventions and placebo or single‐vision spectacles. The most effective interventions reported in weighted mean difference and 95% confidence interval were low‐level red‐light (−0.33 mm (−0.40, −0.25)), ortho‐K with 5 mm treatment zone (−0.32 mm (−0.41, −0.24)), ortho‐K with aspheric base curve (−0.29 mm (−0.37, −0.22)), atropine 1.0% (−0.28 mm (−0.30, −0.26)), combined atropine 0.01% and ortho‐K (−0.24 mm (−0.37, −0.11)), spectacles with highly aspherical lenslets (−0.23 mm (−0.26, −0.19)), ortho‐K with increased compression factor (−0.23 mm (−0.28, −0.17), atropine 0.05% (−0.21 mm (−0.30, −0.13)) and defocus incorporated multiple segments spectacles (−0.21 mm (−0.27, −0.15)). Photophobia and reduced near‐visual acuity were reported for atropine, and lower adherence to treatment was found for atropine at 1.0%. There was no significant association between any interventions and corneal infiltrates or allergic reactions. Over 70% of the studies were conducted in Asian populations. This systematic review and network meta‐analysis highlights the efficacy of various interventions, including orthokeratology lenses, atropine, highly aspherical lenslets and defocus incorporated multiple segments spectacles in slowing axial elongation in children. Low‐level red‐light therapy also slowed axial length progression, but further research is needed to assess the potential side effects. Future studies should include diverse populations and standardized methodologies to enhance the applicability and comparability of results.

Purpose: The purpose of this study is to investigate 3‐year efficacy of orthokeratology lenses (OKL) in controlling axial length progression in myopic Scandinavian children. Through a cross‐over design of the control group to compare the treatment efficacy in younger versus older children, with the latter having higher cycloplegic spherical refractive error (cSEQ) at treatment initiation. Further, the study aimed to evaluate the safety of the treatment.Methods: This was a continuation of the randomized controlled study Clinical study Of Near‐sightedness; TReatment with Orthokeratology Lenses (CONTROL study) in which the follow‐up period of the original intervention group, that received OKL, was extended from 18 months to 36 months. Meanwhile, the original control group was crossed‐over to OKL after the 18‐month follow‐up visit and treated for 18 months. Biometry was measured using Lenstar LS900, and contact lens complications were graded according to Efron Grading Scale for Contact Lens Complications (Efron score). Mixed models were used for statistical analysis.Results: Nineteen subjects in the OKL group and 28 in the control group completed the CONTROL study. Hereof, 17 and 24 subjects from the OKL group and control group, respectively, agreed to participate in the CONTROL2 study. In the OKL continue group, the treatment efficacy did not decline during the 3‐year study period (p‐values for follow‐up visits were all ≥0.82). There was no statistically significant difference between treatment efficacy when OKL treatment was initiated in younger versus older children (p‐value ≥0.14 for all follow‐up visits). Low‐grade corneal staining was seen in several subjects at some point during the study, but here were no treatment‐requiring or sight‐threatening adverse events during the study period.Conclusion: The efficacy of myopia control by OKL was stable during 3 years of treatment. Similar treatment efficacies were found regardless of the age at treatment initiation. No severe adverse events occurred during the study period.

Introduction Our aim in this work was to investigate the macular choroidal thickness (ChT) changes in 6–12-year-old Danish children with myopia during 2 years of low-dose atropine treatment and 1-year wash-out vs. placebo in an investigator-initiated, placebo-controlled, double-blind randomized clinical trial. Methods Ninety-seven participants were randomized to either 0.01% for 2 years, 0.1% loading dose for 6 months followed by 0.01% for 18 months, or placebo, then a 1-year wash-out. The primary outcome was ChT in the sub-foveal and inner and outer superior, nasal, inferior, and temporal sectors. The secondary outcome was axial length (AL). Outcomes were measured at baseline and 6, 12, 24, and 36 months. One-way analysis of variance was used to detect baseline ChT differences between AL-stratified groups (< 24 mm, 24–25 mm, or > 25 mm). To determine the longitudinal changes in ChT and its effect on AL, all eyes were included in linear mixed modeling with individual eyes nested in the study ID as a random effect. Results Longer eyes had significantly thinner ChT in all choroidal sectors (adj-P < 0.01) at baseline. There was no statistically significant change in any ChT sector after 3 years in the placebo group. Sub-foveal and nasal ChT in the 0.1% loading dose and 0.01% group were not significantly different from placebo after 2-year treatment. In the placebo group, a 1-mm increase in AL was significantly associated with a 47-µm thinner nasal ChT after 3 years (95% confidence interval (CI): – 55; – 38, adj-P < 0.001). A 10-µm thicker nasal choroid at baseline was associated with 0.13 mm (95% CI: 0.009; 0.017, adj-P < 0.001) less 3-year axial elongation. Conclusions The ChT in Danish children with myopia remained stable over the 3-year follow-up. A thinner choroid at myopia onset might predispose to increased axial elongation. Treatment with 0.01% atropine did not change the ChT. We speculate that low-dose atropine does not primarily reduce myopia progression via a choroidal mechanism. Trial Registration ClinicalTrials.gov identifier, NCT03911271.

Purpose: To translate and cross‐culturally adapt PREP2 into Danish and to investigate the face validity and reliability of Danish PREP2 through cognitive interviewing, Rasch and reliability analyses. Methods: The Danish PREP2 was translated using a standardized procedure and then pretested following the Three‐Steps‐Interviews (TSTI) process. A total of 15 myopic children aged 7–14 wearing either orthokeratology lenses (ortho‐k) or single‐vision spectacles (SVS) were included in pretesting comprising cognitive interviews and Rasch analysis. Data from cognitive interviewing was analysed thematically according to Collins. Rasch analysis was used to pretest the psychometric properties in terms of person‐ and item‐fit statistics. Reliability was assessed via test–retest using Intra‐class correlation coefficient (ICC) in the CONTROL study population, which consisted of 60 Danish children aged 7–14 years wearing either ortho‐k or SVS. Results: Fifteen children participated in pilot studies comprising of cognitive interviewing and Rasch analysis and 44 out of 60 CONTROL children participated in test–retest reliability analysis. The translation process resulted in a Danish version of PREP2 corroborating the original. Pretesting highlighted issues in the contextualization of items and in marking responses. Thus, we introduced a digital format with help texts. Cognitive interviewing identified issues in the following Collins’ themes: comprehension (understanding of concepts), judgement (ambiguity of items) and response (selecting answers). Rasch analysis indicated that help texts were useful for clarifying context. The ICC was 0.77 (95% CI: 0.66–0.85). Conclusions: The cross‐cultural adaptation of PREP2 was satisfactory and issues were identified and corrected through pretesting. The test–retest reliability showed substantial consistency. The instrument could be validated in a more generalizable setting in future studies. Trial registration: NCT03246464 (CONTROL study).

We investigated the two-year safety and efficacy of 0.1% loading dose and 0.01% low-dose atropine eye drops in Danish children for reduction in myopia progression in an investigator-initiated, placebo-controlled, double-masked, randomized clinical trial. Ninety-seven six- to twelve-year old myopic participants were randomized to 0.1% loading dose for six months and then 0.01% for eighteen months (loading dose group, N = 33), 0.01% for two years (0.01% group, N = 32) or placebo for two years (placebo, N = 32). Axial length (AL) and spherical equivalent refraction (SER) were primary outcomes. Secondary outcomes included adverse events and reactions, choroidal thickness, and other ocular biometrical measures. Outcomes were measured from baseline and at six-month intervals. Individual eyes nested by participant ID were analyzed with linear-mixed model analysis. Data were analyzed with intention-to-treat. Mean AL was 0.08 mm less (95% confidence interval (CI): −0.01; 0.17, p-value = 0.08) in the 0.1% loading dose and 0.10 mm less (95% CI: 0.01; 0.19, p-value = 0.02) in the 0.01% group after two years of treatment compared to placebo. Mean SER progression was 0.12 D (95% CI: −0.10; 0.33) less in the loading dose and 0.26 D (95% CI: 0.04; 0.48) less in the 0.01% groups after two years of treatment compared to placebo (p-value = 0.30 and 0.02, respectively). In total, 17 adverse events were reported in the second-year follow-up, and all were rated as mild. Adjusting for iris color did not affect treatment effect estimates. Intra-ocular pressure increased over two years comparably between all groups but remained within normal limits. Two-year treatment with 0.01% low-dose atropine eye drops is a safe and moderately efficacious intervention in Danish children for reducing myopia progression.

This study aimed to investigate changes in non-cycloplegic ocular biometrics during the initial six months of treatment with a 0.1% atropine loading dose and 0.01% atropine compared with a placebo and analyze their contribution to the treatment effect on cycloplegic spherical equivalent (SE) progression. The study was based on a randomized, double-masked, placebo-controlled, multicenter trial evaluating a 0.1% atropine six-month loading dose and 0.01% atropine in reducing myopic progression in Danish children. The treatment phase was 24 months, and the washout phase was 12 months. Parameters measured included changes in axial length (AL), anterior chamber depth (ACD), lens thickness (LT), vitreous chamber depth (VCD), and choroidal thickness (ChT), while cycloplegic SE and lens power were calculated. Longitudinal changes and contributions to treatment effects were analyzed using constrained linear mixed models and mediation analyses, respectively. After six months, AL was 0.13 mm shorter (95% confidence interval [CI], −0.18 to −0.07 [adjusted p < 0.001]) and 0.06 mm shorter (95% CI, −0.11 to −0.01 [adjusted p = 0.060]) with a 0.1% atropine loading dose and 0.01% atropine, respectively, compared to the placebo group. Similar concentration-dependent changes were found with ACD, LT, VCD, ChT, and cycloplegic SE. Although the treatment effects trended toward concentration-dependent responses, only the treatment effect mediated by AL at three months differed significantly between 0.01% atropine and a 0.1% atropine loading dose (adjusted p = 0.023). Several ocular biometrics, including AL, ACD, and LT, changed dose-dependently during low-dose atropine treatment. Moreover, the treatment effect of atropine on SE progression was mediated by a subset of ocular biometrics, mainly AL, with trends toward concentration dependency and distributional shifts over time.

The effect and safety of low-dose atropine in myopia control have not been studied in randomized, placebo-controlled trials outside Asia. We investigated the efficacy and safety of 0.1% atropine loading dose and 0.01% atropine compared with a placebo in a European population. Investigator-initiated, randomized, double-masked, placebo-controlled, equal-allocation, multicenter study comparing 0.1% atropine loading dose (six months) followed by 0.01% atropine (18 months), 0.01% atropine (24 months), and placebo (24 months). Participants were monitored for a 12-months washout period. Outcome measures were axial length (AL), cycloplegic spherical equivalent (SE), photopic and mesopic pupil size, accommodation amplitude, visual acuity, intraocular pressure (IOP), and adverse reactions and events. We randomized 97 participants (mean [standard deviation] age, 9.4 [1.7] years; 55 girls (57%) and 42 boys (43%)). After six months, AL was 0.13 mm shorter (95% confidence interval [CI], −0.18 to −0.07 [adjusted p < 0.001]) with 0.1% atropine loading dose and 0.06 mm shorter (95% CI, −0.11 to −0.01 [adjusted p = 0.06]) with 0.01% atropine than in the placebo group. We observed similar dose-dependent changes in SE, pupil size, accommodation amplitude, and adverse reactions. No significant differences in visual acuity or IOP were found between groups, and no serious adverse reactions were reported. We found a dose-dependent effect of low-dose atropine in European children without adverse reactions requiring photochromatic or progressive spectacles. Our results are comparable to those observed in East Asia, indicating that results on myopia control with low-dose atropine are generalizable across populations with different racial backgrounds.