Atropine 0.01% combined with orthokeratology over two years

Paper title: Combined 0.01% atropine with orthokeratology in childhood myopia control (AOK) study: A 2-year randomized clinical trial

Authors: Qi Tan (1), Alex LK Ng (2), George PMCheng (3), Victor CP Woo (2), Pauline Cho (1)

1. School of Optometry, The Hong Kong Polytechnic University, Hong Kong, China.
2. Department of Ophthalmology, The University of Hong Kong, Hong Kong, China; Hong Kong Ophthalmic Associates, Hong Kong, China.
3. Hong Kong Laser Eye Centre, Hong Kong, China.

Date: May 2022

Reference: Tan Q, Ng AL, Cheng GP, Woo VC, Cho P. Combined 0.01% atropine with orthokeratology in childhood myopia control (AOK) study: A 2-year randomized clinical trial. Cont Lens Anterior Eye. 2022 May 30:101723.

[Link to open access paper]

Chinese children aged 6 to less than 11 years wore orthokeratology for two years, with half randomized to also receive 0.01% atropine nightly. Axial length was measured at six-monthly intervals. Pupil size and choroidal thickness was also measured to investigate potential mechanisms for different outcomes between the groups.

The children undergoing atropine plus orthokeratology (AOK) treatment showed 0.17mm axial growth over two years, compared to 0.34mm in the OK only group. This represents 50% slower growth, and an average overall growth of less than 0.1mm per year in AOK treated children.

Interestingly, the largest growth difference between the groups occurred in the first six months, with the AOK group showing -0.02 ± 0.10mm growth (mean axial shortening, partly due to choroidal thickening) while the OK group showed 0.07 ± 0.08mm growth. From 6 to 12 months and 18 to 24 months there were no differences in growth rate between the groups. From 12 to 18 months, there was 0.04mm in the AOK versus 0.08mm growth in the OK group. This indicates that most of the treatment effect occurred during the first six months, with these early gains being maintained over the full 24 month treatment duration.

Pupil size increased by around 0.5mm in photopic and mesopic conditions for the AOK children. Amplitude of accommodation was not affected. In the AOK group, 13% of children noted photophobia (reported as "well tolerated  without complaints of causing inconvenience") but none of the OK group did. There were no differences between groups in other symptoms like blurred vision, halo, dry eye or adverse events which were of a low rate and none of which were serious.

Choroidal thickness increased in the AOK group from 1 month, and the difference between AOK and OK groups increased from 10 to 32µm over the study. The authors postulated this as a potential mechanism of the additive efficacy, although an increase in ocular higher-order aberrations due to enlarged pupils is another possible mechanism.

Self-reported compliance with ortho-k wear was 93%, and it was also 93% for atropine eye drops, which was measured by the empty single-use preservative free vials which were brought back to the examiners.

This is the first randomized trial of atropine 0.01% combined with orthokeratology using a preservative free, single use eye drop and measuring pupil size, accommodation and choroidal thickness. This adds to the evidence on combination treatments - this being a gold standard study. The results are in close alignment with one other prospective study, using atropine 0.01% diluted from 1%, which found 0.18mm less axial elongation in the atropine plus ortho-k group over two years,¹ compared to 0.17mm found here.

This previous study found the additive effect was observed only in the first 12 months, and only for 1-3D myopes (not 3-6D myopes, who had slower progression) in children aged 8-12 years.¹ By comparison, the additive effect here was found from 0-6 months and 12-18 month time periods, but not the other six-month periods, in children aged 6 to 11 years with 1-4D of myopia.

This data indicates the ideal patients and treatment duration for combining atropine 0.01% with orthokeratology for additive myopia control efficacy.

1. Why the treatment effect of the combination seems to only be short-term and doesn't continue across the whole 24 month treatment period.
2. Whether stronger atropine concentrations would have a stronger additive efficacy. According to the LAMP Study,  atropine 0.01% appears to have minimal efficacy as a monotherapy. Could atropine 0.025% or 0.05% with ortho-k increase this effect? One retrospective study in 2018 found 0.025% atropine and ortho-k had a similar effect² to these results with 0.01%.
3. Whether combining atropine with other optical treatments has an additive effect; and if not, what makes ortho-k different. It is interesting that a recent study combining atropine 0.01% with Biofinity centre-distance +2.50 Add multifocal contact lenses didn't show an additive effect.³

Title: Combined 0.01% atropine with orthokeratology in childhood myopia control (AOK) study: A 2-year randomized clinical trial

Authors: Qi Tan, Alex LK Ng, George PM Cheng, Victor CP Woo, Pauline Cho

Background: To investigate whether combining 0.01% atropine with orthokeratology (AOK) has a better effect in retarding axial elongation, compared with orthokeratology alone (OK) over two years.

Methods: A total of 96 Chinese children aged six to < 11 years with myopia (1.00 – 4.00 D, inclusive) were randomized into either the AOK or OK group in a 1:1 ratio.

Axial length (the primary outcome), and secondary outcomes (e.g. pupil size and choroidal thickness) were measured at 1-month and at 6-monthly intervals after commencement of treatment.

Results: Both intention-to-treat and per-protocol analyses showed significantly slower axial elongation in the AOK group than OK group over two years (P = 0.008, P < 0.001, respectively). AOK subjects had statistically slower axial elongation (adjusted mean [standard error], 0.17 [0.03] mm vs 0.34 [0.03] mm, P < 0.001), larger increase in mesopic (0.70 [0.09] mm vs 0.31 [0.09] mm, P = 0.003) and photopic pupil size (0.78 [0.07] mm vs 0.23 [0.07] mm, P < 0.001), and greater thickening of the choroid (22.6 [3.5] µm vs −9.0 [3.5] µm, P < 0.001) than OK subjects over two years. Except for a higher incidence of photophobia in the AOK group (P = 0.006), there were no differences in the incidence of any other symptom or adverse events between the two groups. Slower axial elongation was associated with a larger increase in the photopic pupil size and a greater thickening in the choroid in the AOK group.

Conclusions: Slower axial elongation following 2-year AOK treatment may result from increased pupil dilation and a thickening in the choroid observed in the AOK group.

[Link to open access paper]