What’s on the horizon for myopia management?

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Currently, one-third of children and adolescents worldwide have myopia, with the prevalence expected to dramatically increase by the year 2050.¹ Although our profession has made significant strides in progressing myopia management toward standard of care, optometrists still face challenges implementing myopia management into everyday clinical practice. Parents are often skeptical about what they may perceive as a novel approach to myopia, may have cost concerns, or even be fearful of potential adverse effects that contact lenses or eye drops may have on their child. To make the most impact on our concerted fight against myopia, we need a plethora of options to accommodate each type of patient, refractive error, and budget. This article will highlight the future of myopia management and what options are on the horizon.

Eye drops

Currently, the most widely accepted eye drop for myopia management is atropine, a nonselective muscarinic antagonist. Although the exact mechanism of action is unknown, the leading hypothesis is that atropine targets muscarinic and nonmuscarinic receptors in the retina and sclera, limiting their thinning and ultimately retarding axial elongation.² Clinically, atropine is being used off label, but findings from the LAMP trial have shown 0.05% atropine to be more effective than 0.025% and 0.01% when controlling myopia progression. In addition, all concentrations resulted in minimal adverse effects.³ Despite findings from clinical trials supporting safety and efficacy of atropine, many parents are still leery of using a non–FDA-approved pharmaceutical agent for their child. Thus, there have been significant efforts in our industry to get an FDA-approved formulation to market.

Sydnexis’ SYD-101 is a patented atropine formulation containing a unique ingredient that stabilizes atropine to near physiologic pH. To prevent rapid degradation of atropine, most water-based formulations are dropped below pH 5, which is very acidic and consequently uncomfortable for the user and decreases bioavailability. On the contrary, SYD-101 is specially designed to maximize comfort, stability, and efficacy.⁴ Currently, SYD-101 (0.01% and 0.03% atropine) is in an ongoing phase 3 clinical trial (STAR; NCT03918915) with more than 850 participants enrolled, with an expected completion date in 2025.⁵

Vyluma’s Childhood Atropine for Myopia Progression (CHAMP; NCT03350620) trial tested the efficacy of NVK002, their preservative-free, low-dose atropine formulation (0.01% and 0.02%). CHAMP was a multicenter, international trial that enrolled 576 children with myopia over a 4-year period. Results showed 0.01% atropine was associated with slower myopic progression and axial elongation when compared with placebo. In addition, it exhibited a strong safety profile and no significant rebound effect, proving NVK002 as a potential treatment for childhood myopia.⁶ Currently, Vyluma is in discussion with the FDA to address their questions about Vyluma’s trial and their atropine formulation in hopes of forging a path forward.

Eyenovia’s phase 3 CHAPERONE trial (NCT03942419) tested MicroPine low-dose atropine (0.1% and 0.01%) with their proprietary Optejet dispensing platform. This was a US-based, multicenter trial that evaluated 252 children with myopia over 4 years. The drug was well tolerated by the participants; however, the rate of myopic progression was unfortunately not significantly different between the 2 treatment arms and the placebo arm. Because the study did not meet its primary end point of less than 0.5 D of progression over 3 years, Eyenovia decided to terminate the trial as of November 2024.⁷ However, the company is now more thoroughly reviewing the data and evaluating next possible steps.

iVeena’s IVMED-85 is an experimental topical eye drop containing copper used twice daily to slow myopia progression. Copper is a cofactor for lysyl oxidase (LOX). The proposed mechanism of action is to increase LOX, which is the enzyme that mediates collagen cross-linking in both the sclera and cornea. IVMED-85, theoretically, should increase LOX activity and result in corneal flattening, scleral stiffening, and axial elongation reduction.⁸ In October 2023, iVeena Delivery Systems was awarded a National Eye Institute Phase 1 Small Business Research Grant for IVMED-85. For now, we are currently awaiting further information on their first human clinical trials.⁹

Spectacles

Likely the most anticipated addition to comprehensive myopia management is an FDA-approved spectacle option. Although several lenses are in the pipeline, none are currently available in the US market.

Essilor’s Stellest lenses employ highly aspherical lenslet target (HALT) technology. The lens consists of 1021 invisible lenslets strategically arranged on 11 rings. This design creates a volume of myopic defocus in the peripheral retina. The clinical trial results reveal the Stellest lenses save 1.75 D of myopia over a 5-year period, providing conclusive evidence in its ability to slow myopia progression.¹⁰ Recently, they became available in several sun tints, with expanded parameters on the horizon for non-US markets.

HOYA’s MiYOSMART lenses use “defocus incorporated multiple segments” technology. The lens consists of a clear 9-mm central optic zone surrounded by several segments of +3.50 D arranged in a honeycomb-like pattern, creating peripheral blur. Findings from the 2-year clinical trial concluded that children wearing the MiYOSMART lenses had 60% less myopia progression when compared with children wearing single-vision lenses.¹¹ This study is ongoing and is the longest running myopia control spectacle lens study to date. MiYOSMART lenses are also available in photochromics and polarized sun tints in 30 countries but are not yet available in the US.

SightGlass Vision lenses use the Diffusion Optics Technology (DOT) design, which consists of a clear, central optic zone surrounded by thousands of light-scattering microdots, which mimic natural light settings. These lenses slow myopia progression by scattering the light before it reaches the retina, which, in turn, interrupts the signal for axial elongation. The 2-year pivotal CYPRESS trial (NCT04947735) results showed 59% reduction in myopia progression for participants wearing the DOT lenses full-time vs those wearing single-vision lenses.¹² In addition, the 4-year data echoed the 2-year data, showing statistically significant slowing of axial elongation and cycloplegic spherical equivalent refraction.¹³ In February 2024, SightGlass received Breakthrough Device designation from the FDA, which is reserved for “highly innovative devices that provide more effective treatment or diagnosis of life-threatening or irreversibly debilitating human disease or conditions.”¹⁴ This allows for more frequent FDA feedback during the premarket review phase along with prioritized submission review.

Contact lenses

Currently, CooperVision’s MiSight 1 Day is the only FDA-approved myopia control option. MiSight is a dual-focus lens consisting of 2 correction zones for the correction of the patient’s refractive error and 2 treatment zones consisting of 2 D of defocus. In findings from their landmark 7-year clinical trial, MiSight slowed myopia progression and axial elongation by an average of 59% and 57%, respectively, in children aged 8 to 12 years at the initiation of treatment. After 6 years, approximately 25% of patients showed minimal to no progression, and after 7 years, there was no rebound effect after lens cessation.^15-17

Visioneering Technologies has an ongoing clinical trial, Progressive Myopia Treatment Evaluation for NaturalVue Multifocal Contact Lens Trial (PROTECT; NCT05159765), evaluating the effectiveness of NaturalVue Multifocal in managing myopia progression in children. NaturalVue Multifocal is a daily, disposable, center-distance, extended depth-of-focus design. The 1-year results are promising, with adjusted outcomes of 89% reduction in myopia progression and 58% reduction in axial elongation when compared with single-vision lens wearers. Further insights into the long-term impacts of this lens design will be revealed in the 2- and 3-year data.¹⁸

Johnson & Johnson Vision’s Abiliti 1-Day Soft Therapeutic Lenses for Myopia Management are silicone hydrogel lenses designed with RingBoost technology. These lenses create a ring of focus that is formed in front of the retina and around the visual axis, theoretically allowing more treatment power to be engineered into the lens design. Their 6-month pilot study comparing ACUVUE OASYS, a dual-focus design on OASYS material, with Abiliti 1-Day resulted in Abiliti 1-Day providing the least amount of axial elongation. More studies are underway as we anticipate more long-term data findings.¹⁹

Novel treatments

Repeated low-level red light (RLRL) therapy has recently gained attention as a potential treatment for myopia progression. The exact mechanism of action is not yet well understood, but the leading hypothesis is that red light can prevent structural changes in both the retina and choroid and reduce scleral hypoxia seen in patients with myopia, both of which could prevent myopia onset and reduce progression.²⁰ RLRL therapy consists of foveal exposure to long-wavelength red light (635-650 nm) for 3 minutes twice daily. Although RLRL appears to be an attractive, simple option for myopia management, serious safety concerns have been raised, including the long-term impacts of red-light exposure. Findings from a recent study found that during the 3-minute sessions, 2 different RLRL devices approached or surpassed their thermal and photochemical maximum permissible exposure, putting the retina at significant risk for irreversible damage.²¹ Findings from this study highlight the urgent need for further research into the particular area of myopia management before implementing into clinical practice.

Dopavision’s MyopiaX is an innovative smartphone application that provides noninvasive, nonpharmaceutical treatment to the eye to slow myopia progression. Although children are engaging in fun virtual reality or educational content, the app administers patented blue light to the optic nerve head, activating a network of cells in the retina and increasing dopamine release. Dopamine is a neurotransmitter proven to inhibit axial elongation and myopia progression. Dopavision’s MyopiaX-1 randomized, controlled clinical trial (NCT04967287) is being conducted across 6 European countries with 124 children with myopia and is currently ongoing. The 6-month data released in October 2024 showed promising results of positive clinical effects on myopia progression and no ocular safety events.²² Completion of the MyopiaX-1 trial will provide further insights and allow for future clinical trials and further development of MyopiaX.

NovaSight’s TrackSight, an application capable of running on a laptop, tablet, or smartphone, uses the in-device camera to track eye movements. It is intended to be used by both children and young adults. Although the individual is using the app, reduction in myopia progression is achieved by real-time peripheral blur on their screen. Unlike spectacles, which offer static peripheral blur optics, this app tracks eye movements and creates custom-tailored contrast degradation depending on the location of the eyes. This allows for natural eye movements and uninterrupted on-axis acuity during the user’s experience. NovaSight is currently planning a feasibility trial to evaluate the immediate response on choroidal thickness, which would then be followed by a 12-month pilot study.²³

Conclusions

Because the number of patients with myopia will continue to increase, so should our number of options to help mitigate this worsening issue. As we await the exciting future of myopia management, be diligent about capitalizing on the options we currently have available, both on- and off-label.

References:

1. Liang J, Pu Y, Chen J, et al. Global prevalence, trend and projection of myopia in children and adolescents from 1990 to 2050: a comprehensive systematic review and meta-analysis. Br J Ophthalmol. 2024;bjo-2024-325427. doi:10.1136/bjo-2024-325427

2. Upadhyay A, Beuerman RW. Biological mechanisms of atropine control of myopia. Eye Contact Lens. 2020;46(3):129-135. doi:10.1097/ICL.0000000000000677

3. Yam JC, Zhang XJ, Zhang Y, et al. Three-year clinical trial of Low-Concentration Atropine for Myopia Progression (LAMP) study: continued versus washout: phase 3 report. Ophthalmology. 2022;129(3):308-321. doi:10.1016/j.ophtha.2021.10.002

4. Safe and effective low-dose atropine can be stable and comfortable too. Review of Myopia Management. August 15, 2023. Accessed January 8, 2025. https://reviewofmm.com/sydnexis-low-dose-atropine-formulation-can-be-stable-and-comfortable-too/

5. The safety and efficacy of SYD-101 in children with myopia (STAR). ClinicalTrials.gov. Updated February 15, 2024. Accessed January 8, 2025. https://clinicaltrials.gov/study/NCT03918915

6. Zadnik K, Schulman E, Flitcroft I, et al; CHAMP Trial Group Investigators. 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;141(10):990-999. doi:10.1001/jamaophthalmol.2023.2097

7. Eyenovia provides update on phase 3 CHAPERONE study. News release. Eyenovia. November 15, 2024. Accessed January 8, 2025. https://eyenoviabio.gcs-web.com/news-releases/news-release-details/eyenovia-provides-update-phase-3-chaperone-study

8. Ambati B, Molokhia S. Advancing myopia therapy with IVMED-85. Review of Myopia Management. October 15, 2021. Accessed January 8, 2025. https://reviewofmm.com/advancing-myopia-therapy-with-ivmed-85/

9. iVeena awarded NEI-SBIR grant for progressive myopia drug candidate IVMED-85. News release. iVeena. October 26, 2023. Accessed January 8, 2025. https://iveenamed.com/news/item/84-iveena-awarded-nei-sbir-grant-for-progressive-myopia-drug-candidate-ivmed-85

10. Li X, Huang Y, Liu C, et al. Myopia control efficacy of spectacle lenses with highly aspherical lenslets: results of a 5-year follow-up study. Presented at: Association for Research in Vision and Ophthalmology Annual Meeting; May 5-9, 2024; Seattle, WA.

11. Lam CSY, Tang WC, Tse DYY, et al. Defocus incorporated multiple segments (DIMS) spectacle lenses slow myopia progression: a 2-year randomised clinical trial. Br J Ophthalmol. 2020;104(3):363-368. doi:10.1136/bjophthalmol-2018-313739

12. Rappon J, Neitz J, Neitz M, Chung C, Chalberg TW. Two-year effectiveness of a novel myopia management spectacle lens with full-time wearers. Invest Ophthalmol Vis Sci. 2022;63(7):408.

13. Chalberg T, Chung C, Young G, et al. Control of myopia using diffusion optics spectacle lenses: efficacy and safety study (CYPRESS) 42-month results. Presented at: Association for Research in Vision and Ophthalmology Annual Meeting; April 27, 2023; New Orleans, LA.

14. Kaiser Maharjan E. FDA grants SightGlass Vision Breakthrough Device designation for DOT spectacle lenses. Optometry Times. February 15, 2024. Accessed January 8, 2025. https://www.optometrytimes.com/view/fda-grants-sightglass-vision-breakthrough-device-designation-for-dot-spectacle-lenses

15. Chamberlain P, Peixoto-de-Matos SC, Logan NS, Ngo C, Jones D, Young G. A 3-year randomized clinical trial of MiSight lenses for myopia control. Optom Vis Sci. 2019;96(8):556-567. doi:10.1097/OPX.0000000000001410

16. Chamberlain P, Logan N, Jones D, Gonzalez-Meijome J, Saw SM, Young G. Clinical evaluation of a dual-focus myopia control 1 day soft contact lens: 6-year results. Presented at: 2020 American Academy of Optometry Annual Meeting; October 7-22, 2020.

17. Chamberlain P, Arumugam B, Arumugam B, et al. Myopia progression on cessation of dual-focus contact lens wear: MiSight 1 day 7-year findings. Optom Vis Sci. 2021;98:210049.

18. PROTECT RCT data update. Visioneering Technologies. Updated September 2024. Accessed January 8, 2025. https://global.vtivision.com/protect-study/

19. Johnson & Johnson Vision announces availability of ACUVUE Abiliti 1-day soft therapeutic lenses for myopia management in Singapore. News release. Johnson & Johnson Vision. December 8, 2022. Accessed January 8, 2025. https://www.jjvision.com/press-release/johnson-johnson-vision-announces-availability-acuvue-abiliti-1-day-soft-lenses

20. He X, Wang J, Zhu Z, et al. Effect of repeated low-level red light on myopia prevention among children in China with premyopia: a randomized clinical trial. JAMA Network Open. 2023;6(4):e239612. doi:10.1001/jamanetworkopen.2023.9612

21. Ostrin LA, Schill AW. Red light instruments for myopia exceed safety limits. Ophthalmic Physiol Opt. 2024;44(2):241-248. doi:10.1111/opo.13272

22. Joy J. Dopavision announces topline results for MyopiaX trial for slowing pediatric myopia progression. Optometry Times. May 29, 2024. Accessed January 8, 2025. https://www.optometrytimes.com/view/dopavision-announces-topline-results-for-myopiax-trial-for-slowing-pediatric-myopia-progression

23. Eye-tracking software for myopia prevention. Review of Myopia Management. July 23, 2024. Accessed January 8, 2025. https://reviewofmm.com/eye-tracking-software-for-myopia-prevention/