Myopia control with diffusion optics spectacle lenses: 4 year results

Paper title: Control of myopia using diffusion optics spectacle lenses: 4-year results of a multicentre randomised controlled, efficacy and safety study (CYPRESS)

Authors: Laughton, Deborah (1); Hill, Jennifer S (1); McParland, Marcella (1); Tasso, Vanessa (1); Woods, Jill (2); Zhu, Xiaoying (3); Young, Graeme (4); Craven, Ruth (4) Hunt, Chris (4); Neitz, Jay (5); Neitz, Maureen (5); Chalberg, Thomas W (1); Jones, Deborah (2); Wolffsohn, James S (6)

1. SightGlass Vision Inc, Dallas, Texas, USA
2. Centre for Ocular Research and Education, School of Optometry and Vision Science, University of Waterloo, Waterloo, Ontario, Canada
3. College of Optometry, The State University of New York (SUNY), Albany, New York, USA
4. Visioncare Research Limited, Farnham, UK
5. University of Washington, Seattle, Washington, USA
6. College of Health and Life Sciences, Aston University, Birmingham, UK

Date: Oct 2024

References: Laughton D, Hill JS, McParland M, Tasso V, Woods J, Zhu X, Young G, Craven R, Hunt C, Neitz J, Neitz M, Chalberg TW, Jones D, Wolffsohn JS. Control of myopia using diffusion optics spectacle lenses: 4-year results of a multicentre randomised controlled, efficacy and safety study (CYPRESS). BMJ Open Ophthalmol. 2024 Oct 9;9(1): e001790

[Link to open access paper]

The CYPRESS study Part 1 (July 2018 to March 2022) was a 3-yr trial which investigated the safety and long-term efficacy of 2 spectacle lens designs. 

The test lenses used Diffusion Optics Technology (DOT), incorporating translucent microscopic diffusers designed to create wide-angle light scatter and reduce retinal contrast. Test 1 lens (DOT 0.2) had 0.365mm spacing of the diffusers, Test 2 (DOT 0.4) used 0.240mm spacing to create higher density and both had a central 5mm aperture.

1. In Part 1 of the CYPRESS Study, Children (n = 256) aged between 6 and 10yrs with myopia of -0.75 to -4.50D randomly received either Test 1 or Test 2 lens or the single vision control and wore at least 10hrs per day. The measured myopia control effect (difference between Test and control) over one year was 0.40D (74%) and 0.15mm (50%) for Test 1, with Test 2 showing lesser results of 0.32D (59%) and 0.10mm (33%).¹ Test 2 lens had a denser optical pattern and suffered more drop-out, along with lower wearing time compliance.
2. The two-year and three-year data (n=200) did not show an additional treatment effect, with the timing of the COVID-19 pandemic and stay-at-home orders cited as impacting the results, with 76% of children reporting an increase in digital device time when not in usual full-time, in-person schooling. Despite this, the 1 year treatment effect was maintained, and safety and tolerance of lens wear was high, with no lens-related adverse events. The Test 1 lens had significantly better efficacy results.
3. A significant percentage of children removed their lenses for near vision activities. For those who did not, their efficacy was enhanced at 0.52D and 0.21mm at two years, even with the impact of COVID-19 lockdowns.
4. In the fourth year, Test 1 wearers (n = 35) and single vision control wearers (n = 42) continued with their original lens type. Test 2 wearers (n = 21) swapped to wear Test 1 lenses. Mean wearing times exceeded 13 hours per day in all groups. The myopia control effect over 4 years was 0.52D (32%) and 0.20mm (22%), including years 2 and 3 where no effect was seen. Year 4 accrued 25% of the total myopia control effect (0.13D and 0.05mm) while year 1 accounted for 75% (0.40D and 0.15mm). Safety and tolerance were again high, and acuity was no different between DOT lens and single vision control groups (better than 6/6 or 20/20).
   
   

Theaw results demonstrate that modulating retinal contrast is effective for slowing myopia progression in children aged from 6 to 10 years at commencement, through to 14 years at last follow-up. COVID-19 restrictions negatively impacted treatment efficacy throughout years 2 and 3 of the study period, reinforcing findings from other studies which also reported reduced performance during that time.^2-4 However, DOT lenses still demonstrated robust efficacy compared to single vision lenses over 4yrs, with the majority of the treatment effect achieved within the 1^st year of wear. 

• This reinforces the importance of considering a child’s environment, behaviour and lifestyle regardless of receiving myopia control treatment, in order to maximise the benefits.
• The enhanced treatment effect found at two years for those who wore their lenses for all near vision activities is in line with results in highly aspherical lenslet spectacles, highlighting the importance of full-time wear. 
• This is the first myopia control spectacle data including age groups down to 6 years, with highly aspherical lenslet and defocus incorporated multiple segment (DIMS) lens data including participants from age 8. Data on effective treatments for younger children is important due to their rapid physiological (and myopic) eye growth.
  
  

1. This study included mostly white (approximately 75%) North American children aged from 6yrs old and results may not be directly applicable to other ethnicities with behavioural and genetic differences. An ongoing study is evaluating the efficacy of DOT lens design in a Chinese cohort.
2. In the Stage 1 report of this trial, the authors discussed Test 1 lens efficacy in the context of expected physiological growth for younger children up to age 10yrs.^5,6 Due to naturally faster AL progression rates in younger children, they concluded that although large differences were seen between Test 1 group and the control group, the overall treatment effect was similar to that of the older group and normal physiological growth made it difficult to accurately assess efficacy in younger children.
3. It was not possible to assess the existence of a dose-dependent association between retinal contrast modulation and slowed progression due to a smaller sample size and greater non-compliance in wearers of the Test 2 lens (denser optical profile). Further research ensuring compliance in a larger cohort may discover a dose-dependent relationship.

Limitations of this study include self-reported wearing compliance, which may not accurately reflect spectacle wear when restricted to indoors during COVID-19, and needing to exclude results from some late follow-up visits, meaning efficacy may be under-estimated.

Title: Control of myopia using diffusion optics spectacle lenses: 4-year results of a multicentre randomised controlled, efficacy and safety study (CYPRESS)

Authors: Deborah Laughton, Jennifer S Hill, Marcella McParland, Vanessa Tasso, Jill Woods, Xiaoying Zhu, Graeme Young, Ruth Craven, Chris Hunt, Jay Neitz, Maureen Neitz, Thomas W Chalberg, Deborah Jones, James S Wolffsohn

Purpose: To evaluate the myopia control efficacy of Diffusion Optics Technology (DOT) spectacle lenses in children over a 4-year treatment period.

Methods: CYPRESS Part 1 (NCT03623074) was a 3-year multicentre, randomised, controlled, double-masked trial comparing two investigational spectacle lens DOT designs (Test 1, Test 2) and standard single vision Control lenses in 256 North American children aged 6-10 years. Children completing Part 1 (n=200) were invited to enrol in CYPRESS Part 2 (NCT04947735) for an additional 1-year period. In Part 2, Test 1 (n=35) and Control groups (n=42) continued with their original lens assignment and the Test 2 group (n=21) were crossed over to Test 1 (DOT 0.2) lenses. The co-primary endpoints were change from baseline in axial length (AL) and cycloplegic spherical equivalent refraction (cSER).

Results: Test 1 spectacle lenses demonstrated superiority to the Control in both co-primary endpoints: with a difference between means (Test 1-Control) of -0.13 mm for AL (p=0.018) and 0.33 D for cSER (p=0.008) in Part 1 and -0.05 mm for AL (p=0.038) and 0.13 D for cSER (p=0.043) in Part 2. Comparing treatment effects in Part 1 and 2 suggests that COVID-19 public health restrictions negatively impacted treatment efficacy in study years 2 and 3.

Conclusions: DOT 0.2 spectacle lenses are safe and effective at reducing myopia progression, with additional benefit evident in year 4 of wear. These results support the hypothesis that a mild reduction in retinal contrast can slow myopia progression in young children. The unprecedented disruption in participant schooling and lifestyle during the COVID-19 pandemic may have depressed treatment efficacy in Part 1.

[Link to open access paper]