A look at what other optometrists say about this myopia treatment

Low-dose atropine (LDA) eye drops have been increasingly prescribed by both optometrists and ophthalmologists as a convenient way to control and delay of the onset of myopia.

Currently, there is no clinical guidelines for the use of LDA for myopia management, but the efficacy and safety of various concentrations for long-term use are a research focus in the field of clinical myopia.

Below, I review the latest clinical findings on the use of LDA, the response from optometrists about those results, what variables still need to be researched, and my own thoughts on its use.

Latest LDA findings

In June this year, the three year safety and efficacy outcomes of a manufacture-sponsored trial (CHAMP) were published. This randomized placebo-controlled, parallel-group (0.01% and 0.02%) Phase 3 trial involved 573 participants in the safety set and 489 participants in the modified intention-to-treat set. As expected, the safety outcome from preservative-free atropine formulation in both concentrations was superior with no serious adverse events associated with atropine use. The primary efficacy outcome was evaluated using responder analysis, in which the proportion of eyes that progressed less than 0.50 D in normalized spherical equivalent refraction over 36 months were compared with placebo-controlled group.¹

In July this year, the Pediatric Eye Disease Investigator Group (PEDIG) published a National Eye Institute-funded randomized clinical trial of children ages 5 to 12, who had myopia from -1D to -6D in a diverse ethnicity distribution. The study concluded that the nightly use of 0.01% had no effect in retarding myopia or axial elongation.²

This past February, the two-year LAMP2 trial, which enrolled over 400 nonmyopic children ages 4 to 9 to investigate the efficacy of LDA on reducing myopia incidence, reported a dose-dependent effect of atropine on lowering myopia incidence. In that study, 0.05% atropine was found to be effective at lowering myopia incidence and reducing myopic shift.³

Optometrist response

The outcomes from both trials have garnered widespread attention and enthusiastic discussions, both within the profession and in consumer society. Many practitioners felt that the conclusions from the trials did not fully echo their real-world clinical experiences, especially in the cases where 0.01% atropine was combined with other optical modalities, such as orthokeratology, multifocal scleral contact lenses, or novel spectacles, for which the potential synergistic effect in the combination treatment has been reported in multiple studies.^4-6

Nonetheless, the PEDIG and LAMP2 trials provided important perspective to reevaluate the effectiveness of ultra-low concentration atropine for preventive application, as well as standalone treatment for myopia control.

Variables needing research

It is worth noting that despite the converging evidence demonstrating the dose-dependent efficacy of LDA, some factors have not been fully explored, such as the predictive indicators of LDA responders and ethnicity-dependent differences. Additionally, the common but important factors influencing the absorption of topical LDA have largely been overlooked. More specifically, the productive absorption (the bioavailability of the active ingredient at the site of action) from topical instillation, despite being the most convenient choice of the route of administration, is subject to many variables, such as:

• Conjunctival hyperemia, which takes away LDA from the ocular surface, and hence reduces productive absorption.
• Chronic ocular allergy, in which case the protein composition in tear film is significantly higher, subsequently affecting the percentage of unbound atropine molecules available for distribution.
• Corneal epithelial permeability, which is significantly higher in contact lens wearers, hence facilitating the absorption of atropine.
• Iris pigmentation, which serves as a critical drug depot for atropine, potentially affecting its pharmacokinetic profile as in the case for all other cycloplegic agents.

Considering the highly diluted concentration, the proposed posterior location as the site of action for myopia control, and the topical route of administration of LDA, all of which contribute to the individual variability in the absorption of LDA and its efficacy for myopia control, further clinical studies are necessary to explore the possibility of surrogate markers for LDA absorption at the target site. This research could improve understanding of the sources of variability in treatment efficacy.

My thoughts

Taking into account the convenience of LDA drops and its ability to retard abnormal axial elongation, practitioners should not be discouraged by the lack of unified research evidence or expert opinions regarding the dosing regimen of LDA for the long-term management of myopia. With evidence supporting the use of higher concentrations, such as 0.05% at the initiation of the treatment, practitioners should be mindful about its potential impact on the tolerability and compliance to the regimen, which can be different in real world than trial settings.

Additionally, the potential for rebound is also dose dependent. The frequency and severity of rebound progression in higher concentrations has not been thoroughly tested in clinical trials beyond the first 24 to 36 months of therapy.

Finally, in the cases of combining atropine with optical treatments, the dose-dependent effect has not been fully established and caution is necessary in starting with higher concentrations of 0.05% and above, due to its significant role on potentiating the negative visual impacts such as halo, glare, ghosting, and sensitivity to light from optical modalities. OM

References:

References1. Zadnik, K., et al., Efficacy and Safety of 0.01% and 0.02% Atropine for the Treatment of Pediatric Myopia Progression Over 3 Years: A Randomized Clinical Trial. JAMA Ophthalmol, 2023.

2. Repka, M.X., et al., Low-Dose 0.01% Atropine Eye Drops vs Placebo for Myopia Control: A Randomized Clinical Trial. JAMA Ophthalmology, 2023. 141(8): p. 756-765.

3. Yam, J.C., et al., Effect of Low-Concentration Atropine Eyedrops vs Placebo on Myopia Incidence in Children: The LAMP2 Randomized Clinical Trial. JAMA, 2023. 329(6): p. 472-481.

4. Tsai, H.R., et al., Efficacy of atropine, orthokeratology, and combined atropine with orthokeratology for childhood myopia: A systematic review and network meta-analysis. J Formos Med Assoc, 2022. 121(12): p. 2490-2500.

5. Nucci, P., et al., A comparison of myopia control in European children and adolescents with defocus incorporated multiple segments (DIMS) spectacles, atropine, and combined DIMS/atropine. PLoS One, 2023. 18(2): p. e0281816.

6. Erdinest, N., et al., Myopia control utilizing low-dose atropine as an isolated therapy or in combination with other optical measures: A retrospective cohort study. Taiwan J Ophthalmol, 2023. 13(2): p. 231-237.

DR. LIU is an associate professor at Herbert Wertheim School of Optometry & Vision Science, University of California Berkeley. She is also the founder of the Myopia Control Clinic, UC Berkeley Eye Center. She received her bachelor’s degree of Clinical Medicine from Peking University, her OD from Pacific University, and her PhD and MPH from UC Berkeley. She is a world-recognized clinical researcher in myopia. Dr. Liu is a consultant for Coopervision and Essilor China.