Novel Contact Lens Design for Myopia Control

Title: Myopia control with novel central and peripheral plus contact lenses and extended depth of focus contact lenses: 2 year results from a randomised clinical trial

Authors: Padmaja Sankaridurg (1) (2), Ravi Bakaraju (1) (2), Thomas Naduvilath (1) (2), Xiang Cheng (3), Rebecca Weng (1), Daniel Tilia (1), Pauline Xu (1), Wayne Li (1), Fabian Condrad (1), Earl Smith 3rd (4), Klaus Ehrmann (1) (2) 

1. Brien Holden Vision Institute, Sydney, Australia
2. School of Optometry and Vision Science, University of New South Wales, Sydney, Australia 
3. State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Centre, Sun Yet Sen University, Guangzhou, China
4. College of Optometry, University of Houston, Houston, USA

Date: June 2019

Reference:  Ophthal Phys Optics. 2019 [Link to open access paper]

The biological processes resulting in myopia are not well understood; however, there is evidence for the role of visual feedback in the emmetropisation process.¹ Studies in animal models demonstrated the importance of the peripheral retina in refractive error development and the instrumental role that peripheral hyperopia plays in axial elongation.² Consequently, a number of lens designs aim to induce myopic defocus and have been demonstrated to reduce axial length elongation. 

The authors of this study conducted a 2-year double blinded, randomised control trial that evaluated the efficacy of two novel contact lenses as a means of myopia control. The first design (lens I and II) aimed to reduce hyperopic defocus and induce myopic defocus across a large portion of the retina. The second design (lens III and IV) featured an extended depth of focus, that incorporated higher order aberrations to modulate retinal image quality. This technology is utilised in a number of commercial contact lenses, including the novel Seed 1-Day Pure EDOF lens.³

The study demonstrates that both lens designs slow myopic progression. The EDOF design potentially induces a superior treatment effect; however, further investigations are required to explore this further.

The novel contact lenses developed by the authors are effective in reducing myopia progression in comparison to single vision lenses 

• At 2 years, the mean rate of myopia progression for design 2 (lenses III and IV) was statistically significantly reduced in comparison to the control group  
  • Control lens SE: -1.15D (-0.99; -1.30)
  • Lens III SE: -0.78D (-0.62; -0.94)                    (32% reduction)
  • Lens IV SE: -0.85D (-0.85; -1.00)                    (26% reduction)
• At 2 years, a statistically significant reduction in axial elongation was observed for all lens types 
  • Control lens AL: 0.60mm (0.53; 0.66)
  • Lens I AL: 0.41mm (0.34; 0.48)                       (32% reduction)
  • Lens II AL: 0.46mm (0.39; 0.53)                      (23% reduction)
  • Lens III AL: 0.45mm (0.38; 0.52)                     (25% reduction)
  • Lens IV AL: 0.43mm (0.36; 0.50)                     (28% reduction)
• Importantly, the outcome measures (both SE and AL) obtained with the four treatment contact lenses were not significantly different to each other (p>0.05)
• In summary, at 2 years both lens designs (lenses I-IV) significantly reduced progression of axial elongation while only EDOF design (lens III and IV) significantly reduced myopic progression (SE)

Increased compliance of lens wear increases treatment effect

• 2 year reduction in SE and AL increased in children who wore contact lenses with increased compliance (6 days/week)
  • Average reduction in SE of test lenses with increased compliance: -0.76D (33%)
  • Average reduction in AL of test lenses with increased compliance: 0.38mm (34%)
• This indicates that the wear time of lenses is important, and treatment effect is reduced if patients wear contact lenses <6 days per week (ie cease contact lens wear for the weekend). 

Treatment efficacy is greatest in first 6 months of lens wear

• For both SE and AL, the authors noted a significant lens by time interaction, with the rate of change between the control and test group significant for only the first 6 months of the study
• Consequently, the treatment effect is greatest in the first 6 months of commencing lens wear, a phenomenon that has been reported previously and Eye care practitioners should remain aware of.⁴

Subjects did not report a subjective reduction in quality of vision with any lens 

• Ratings of subjective quality of vision were generally high, and there was no statistically significant difference between lenses (p>0.005)
• However, all test lenses (excluding lens II high contract) statistically significantly reduced monocular high and low contrast VA 
• This reduction in contrast VA evidently did not affect the subjective quality of subjects vision
• This allows Eye care practitioners to advise patients that their quality of vision will not decrease wearing this design of lens 

The study was subject to high rates of discontinuation and subject drop out 

• In the first month 129/508 children (25.4%) dropped out, and an additional 89 (23.5%) children dropped out over the duration of 2 years 
  • This is attributed to discomfort and concern regarding safety of contact lenses 
  • This may have been avoided by fitting children with contact lenses for a trial period prior to enrolment, however this would affect randomisation and bias with treatment 
  • This prohibited authors from undertaking an intention to treat analysis 

Lens centration for test lenses I and II (design 1) is important and may affect the refractive error measurements taken through the lenses. This potentially limits the accuracy of measurements taken and conclusions made regarding this lens type.

The results are based on group means and the study design features individuals being randomised to a particular group. This makes it difficult to explore if certain individuals or eyes derived a greater or lesser treatment effect

• It is likely there are other factors (lens and patient related) that may influence efficacy, including pupil size, decentration, refractive error profile at both centre and periphery and fit of lens 
• Further research required to determine if efficacy can be optimised for each individual eye

These results are obtained on Chinese children living in China. Results may be differ in other ethnicities and environments. In order to be applicable in Australia, further research should be conducted in our population. Additionally, further research is required into the effect of wear lens wear compliance on efficacy. The authors provided SE and AL for all test lenses averaged when worn with increased compliance. It would have been desirable for the authors to provide results specific for each lens type in order to gain further insight into this effect, as well as average wear time per day.

To examine myopia control efficacy of novel contact lenses that (1) reduced both central and peripheral defocus, and (2) provided extended depth of focus (EDOF) with better global retinal image quality for locations on, and anterior to, the retina and degraded for locations posterior to the retina. 

This study is a prospective, parallel arm, double blinded trial that randomised (initially) 508 Chinese children aged between 8-13 years into 1 of 5 groups. Groups detailed listed below, with an image detailing lens design: 

• Control Group: Single vision contact lens (n: start =102, end=50)
• Design 1:Aimed to reduce hyperopic defocus and induce myopic defocus across a large portion of retina. Contains incorporated relative plus in a stepped manner, commencing at 1.5mm cord and with maximum power at 3.00mm. Also incorporates a stepped, relative positive power centrally (up to 1.00mm semi-chord) of up to +1.00D
  • Lens I: Maximum +2.50D at 3.00mm (n: start =103, end=47)
  • Lens II: Maximum +1.50D at 3.00mm (n: start =101, end=45)
• Design 2:EDOF lens that incorporates higher order aberrations to improve retinal image quality in locations on and anterior to the retina, and degrades image quality posterior to the retina. The refractive profile across the optic zone was non-monotonic and aperiodic across the optic zone.
  • Lens III: EDOF of up to +1.75D (n: start = 98, end= 45)
  • Lens IV: EDOF of up to +1.25D (n: start = 104, end=47)

Children were evaluated as candidates then fit with contact lenses, then followed up at 1 and 3 months. High and low contrast VA was assessed. Cycloplegic autorefraction (Shin-Nippon SRW 500) and axial length (Lenstar 900) was measured at 6 month intervals. At each visit, children completed a questionnaire on subjective assessment of vision, comfort and compliance.

Table 1: Results (Spherical Equivalent D, and Axial Length mm) at 24 months. Note bolded values indicate a statistically significant result.

As discussed above, at 24 months, all test contact lenses resulted in a statistically significant reduction in axial length, while lenses III and IV (design 2) reduced myopic progression (spherical equivalence). Importantly, there was no statistically significant result between lenses. 

Effect of Discontinuation

Interestingly, the authors reported a statistically significant difference in progression between subjects that discontinued/were lost to follow up in comparison to those in the study (p<0.001); however, from the paper it is unclear how lost to follow up comparisons were calculated.

This study demonstrated that significant reductions in myopic progression can be obtained with the use of novel contact lenses aimed at reducing peripheral and central defocus, and those of EDOF design. The study indicated that EDOF lenses may be more effective in reducing myopia progression, however no statistically significant result was obtained and further research required to investigate this further. 

Title: Myopia control with novel central and peripheral plus contact lenses and extended depth of focus contact lenses: 2 year results from a randomised clinical trial

Authors: Sankaridurg P, Bakaraju R, Naduvilath T, Chen X, Weng R, Tilia D, Xu P, Li W, Conrad F, Smith E, Ehrmann K.

Purpose: We aimed to determine myopia control efficacy with novel contact lenses (CL) that (1) reduced both central and peripheral defocus, and (2) provided extended depth of focus with better global retinal image quality for points on, and anterior to, the retina and degraded for points posterior to the retina.

Methods: Children (n = 508, 8-13 years) with cycloplegic spherical equivalent (SE) −0.75 to −3.50D were enrolled in a prospective, double blind trial and randomised to one of five groups: (1) single vision, silicone hydrogel (SH) CL; (2) two groups wearing SH CL that imposed myopic defocus across peripheral and central retina (test CL I and II; +1.00D centrally and +2.50 and +1.50 for CL I and II at 3 mm semi‐chord respectively); and (3) two groups wearing extended depth of focus (EDOF) hydrogel CL incorporating higher order aberrations to modulate retinal image quality (test CL III and IV; extended depth of focus of up to +1.75D and +2.50D respectively). Cycloplegic autorefraction and axial length (AL) measurements were conducted at six monthly intervals. Compliance to lens wear was assessed with a diary and collected at each visit. Additionally, subjective responses to various aspects of lens wear were assessed. The trial commenced in February 2014 and was terminated in January 2017 due to site closure. Myopia progression over time between groups was compared using linear mixed models and where needed post hoc analysis with Bonferroni corrections conducted

Results: Myopia progressed with control CL −1.12 ± 0.51D/0.58 ± 0.27 mm for SE/AL at 24 months. In comparison, all test CL had reduced progression with SE/AL ranging from −0.78D to −0.87D/0.41-0.46 mm at 24 months (AL: p < 0.05 for all test CL; SE p < 0.05 for test CL III and IV) and represented a reduction in axial length elongation of about 22% to 32% and reduction in spherical equivalent of 24% to 32%. With test CL, a greater slowing ranging from 26% to 43% was observed in compliant wearers (≥6 days per week; Control CL: −0.64D/0.30 mm and −1.14D/0.58 mm vs test CL: −0.42D to −0.47D/0.12-0.18 mm and −0.70 to −0.81D/0.19-0.25 mm at 12 and 24 months respectively).

Conclusion: Contact lenses that either imposed myopic defocus at the retina or modulated retinal image quality resulted in a slower progression of myopia with greater efficacy seen in compliant wearers. Importantly, there was no difference in the myopia control provided by either of these strategies.