Violet Light for Treatment of Myopia
Phase: NA
Conditions: Myopia, Phototherapy
Sponsor: Children's Hospital Medical Center, Cincinnati

 
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Violet Light for the Treatment of Myopia 
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July 2, 2023 
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Principal Investigator: Melissa Rice, OD 
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Sub-Investigators: Richard Lang, PhD, Veeral Shah, MD, PhD, Kelsey 
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Carriere, OD, Katherine Hogan, OD, Kelsey Mach, OD, Kelly Hayden, OD, 
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Virginia Utz, MD, Anne Slavotinek, MD 
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Table of Contents 
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1. Background and Summary 
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1.1 Epidemiology and Disease Burden 
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1.2 Current Treatments 
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1.3 Myopia and Violet Light 
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1.4 Role of Genetics in Myopia 
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1.5 Bios SkyView Lamps 
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1.6 Impact of UV Blocking Lenses 
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1.7 Study Design 
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1.7 (A) Study Groups 
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1.7 (B) Designating Dawn and Dusk 
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1.7 (C) Onset HOBO Occupancy Sensor (UX90-005M) 
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1.7 (D) DNA Storage via Saliva 
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1.8 Study Objective 
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1.9 Timing of Intervention and Outcome for Proposed Study 
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2. Considerations 
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2.1 Risks 
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2.2 Risk of Examination Procedures 
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2.3 Risk Assessment 
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2.4 Reporting of Adverse Events 
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2.5 Study Costs 
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3. Study Outline 
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4. Enrollment 
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4.1 Eligibility Assessment 
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4.2 Inclusion Criteria 
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4.3 Exclusion Criteria 
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4.4 Sample Size 
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4.5 Historical Information 
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4.6 Survey to Determine Lighting Schedule 
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4.7 Testing at the Enrollment Visit 
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4.8 Refractive Correction 
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5. Randomization 
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5.1 Randomization Process 
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6. Equipment Pickup Visit 
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6.1 Prescription Glasses 
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6.2 Study Lamp 
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6.3 HOBO Sensor 
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6.4 Automated Wall Plug-In 
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6.5 Testing Not Completed at Enrollment 
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7. Follow-Up 
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7.1 REDCap Daily Surveys 
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7.2 Telephone Calls 
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7.3 Follow-Up Visits: 6-Month and 12-Month 
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7.4 Management of Refractive Error 
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7.5 Non-Randomized Treatment Other than Refractive Correction 
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7.6 General Considerations 
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8. Miscellaneous Considerations 
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8.1 Participant Withdrawals 
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8.2 Discontinuation of Study 
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8.3 Payment to Participants 
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8.4 Costs Covered by the Study 
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8.5 Costs Not Covered by the Study 
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9. Data Storage and Analysis 
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9.1 Analysis 
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9.2 Decision Guideline 
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9.3 Data Safety Monitoring Plan 
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9.4 Source Documents and Case Report Forms 
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9.5 Changes to Protocol 
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10. References 
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1. Background and Summary 
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1.1 Epidemiology and Disease Burden 
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Myopia (shortsightedness) is the most common eye condition in the world and is only increasing in 
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prevalence, with studies predicting 4.7 billion afflicted by 2050.1 This increase in prevalence is 
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particularly notable in East Asia, but myopia is increasing in the US as well: a study done with a 
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contemporary American cohort in Southern California found that 41.9% of the cohort, aged 5-19 years 
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old, were myopic.2,3 Although visual impairment caused by myopia is generally correctable (via glasses, 
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contact lenses, etc.), uncorrected refractive error costs $202 billion annually in global GDP.2,3 High 
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myopia is associated with increased risks of glaucoma, cataracts, and retinal detachment.4–6 
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1.2 Current Treatments 
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Slowing the progression of myopia has been attempted through a range of treatments with varying 
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degrees of success. Among the most promising have been soft bifocal contact lenses, orthokeratology, 
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and antimuscarinic agents (pirenzepine, atropine, etc.).7,8 However, these treatments are not without 
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side effects: atropine can cause side effects such as photophobia, and orthokeratology carries the risk of 
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microbial keratosis.9 In addition, compliance with contact lens wear can be poor.10 
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1.3 Myopia and Violet Light 
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An abundance of studies have shown that outdoors exposure is protective against myopia onset.11–16 
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Meta-analysis indicates that one additional hour spent outdoors per week translated to a 2% reduced 
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odds of developing myopia.14 Some studies have also shown that outdoor exposure can reduce myopic 
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progression.14,16 The mechanism for this is yet unclear, but it has been theorized that violet light may be 
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key to this protective effect.17 Due to overzealous UV protection, violet wavelengths have been rendered 
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nearly absent from modern life despite being part of the visible spectrum: windows have very low 
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transmittance for wavelengths below 400 nm, indoor lighting does not incorporate violet, and UV 
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blocking glasses and contact lenses are abundant.17 
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Previous studies by Torii et al. indicated that violet light is protective against myopia progression in 
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humans. A retrospective study compared patients wearing non-violet transmitting eyeglasses, partially 
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violet-blocking contact lenses, and violet light transmitting contact lenses, and found that patients 
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wearing violet light transmitting contact lenses had a significantly decreased amount of myopia 
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progression as measured by axial length elongation.17 Additionally, violet light was shown to influence 
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high adult myopia: patients who received non violet light transmitting phakic intraocular lens 
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implantations were significantly more myopic than patients who received violet light transmitting 
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implantations.18 
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Animal studies indicate that the light-sensitive protein OPN5 may be key in violet-light mediated 
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suppression of myopia. OPN5 has previously been shown to regulate light-dependent vascular 
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development in the murine eye via suppression of vitreal dopamine, which simultaneously increased 
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retinal dopamine.19 This is significant because retinal dopamine has been widely hypothesized to 
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antagonize myopia development.20,21 Violet light has been shown to reduce axial length elongation in 
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chicks as well as stimulate a higher long-term retinal dopamine level than blue, red, or white light.17,21 
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Most recently, OPN5 has been shown to be necessary for violet-light mediated suppression of lens 
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defocus-induced myopia in mice. Violet light delivered for 3 hours in the evening (pre-dusk) protected 
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mice from lens defocus-induced myopia, an effect that was shown to be both time and wavelength 
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dependent – but did not protect OPN5 conditional null mice.22 
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1.4 Role of Genetics in Myopia 
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Large-scale genetic studies have been performed in myopia and have implicated the important role of 
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genetic factors. Through molecular techniques, such as linkage analysis, association studies, and 
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sequencing analysis, many of the genes associated with myopia have been identified.23 Furthermore, the 
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prevalence of myopia increases significantly with the number of myopic parents; the associated 
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development risk rates are 7.6% for no myopic parents, 14.9% for one myopic parent, and 43.6% for two 
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myopic parents.24 The evidence is conclusive of a genetic contribution to myopia beyond environmental 
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factors, and exploring the genetic component of patients with myopia is critical in better understanding 
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the disease. 
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1.5 Bios SkyView Lamps 
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In order to effectively deliver violet light, the BIOS SkyView lamp will be used. BIOS lighting uses 
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patented circadian lighting technology to produce the highest melanopic to photopic lux ratio for a given 
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color temperature, translating to better equivalent melanopic lux for a lower correlated color 
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temperature than other LEDs.25 The BIOS SkyView lamps are equipped with wavelength-specific LEDs, 
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able to provide a full profile of violet light (385 nm) for the purpose of this study.26 The SkyView lamps 
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have been approved by CCHMC for research use (assessment ID: 109744). The Aooshine bedside lamps, 
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which will act as the control light source, have also been approved by CCHMC for research use 
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(assessment ID: 133975). 
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1.6 Impact of UV Blocking Lenses 
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UV blocking glasses are ubiquitous in modern society. Pediatric patients are commonly prescribed 
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polycarbonate eyeglasses due to their innate UV-blocking capabilities and shatter resistance.25 However, 
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polycarbonate also attenuates the violet wavelengths that could potentially be crucial to myopia 
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control.17,18,22 UV-blocking glasses, which typically seek to block wavelengths below 400 nm in an 
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overabundance of caution, result in the elimination of much of the violet spectrum (380 nm to 450 nm), 
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and could potentially be a contributing factor to the myopia epidemic. 
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4.9 Study Design 
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A) Study Groups: 
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To assess the effects of violet light and potential contribution from UV-blocking glasses, three study 
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groups will be established: 
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1. A group (n = 24) will use the BIOS SkyView lamp with violet LEDs enabled for at least one hour 
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during dawn and at least one hour during dusk. The group will wear CR-39 (UV-transmitting). 
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2. A group (n = 24) will use the BIOS SkyView lamp with violet LEDs enabled for at least one hour 
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during dawn and at least one hour during dusk. The group will wear polycarbonate (UV-blocking) 
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glasses for the duration of the study. 
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3. A group (n = 24) will use the Aooshine lamp without any violet LEDs enabled for at least one 
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hour during dawn and at least one hour during dusk. The group will wear CR-39 (UV-
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transmitting). 
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The study lamp (BIOS or Aooshine) should be the sole source of artificial illumination in participant 
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rooms for the duration of lamp exposure, and throughout the study, exposure to natural light during 
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designated dawn and dusk times should be minimized. Light is a noninvasive source of therapy, and as 
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such, tracking the actual exposure to the lamps and compliance to the study design can be difficult. 
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Therefore, the HOBO Occupancy Sensor (UX90-005), which measures movements of heat emitted by 
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people in motion via passive infrared technology, will be paired with each BIOS lamp. 
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B) Designating Dawn and Dusk 
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The best times for the SkyView and Aooshine lamps to undergo the dawn and dusk transition will be 
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chosen individually per participant based on their anticipated daily schedule to maximize effectiveness. 
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Each participant will be given a survey prior to enrollment so that research staff can determine the 
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optimal times on an individual basis. 
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The one-hour timeframe is chosen to be consistent with known biological responses and the length of 
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the natural dawn/dusk transition. The SkyView/Aooshine lamp will automatically turn on at dawn and 
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automatically turn off after dusk. Both dawn and dusk are chosen because while dusk exposure was 
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protective in the murine myopia model, this effect may be present at dawn in diurnal mammals.22 
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C) Onset HOBO Occupancy Sensor (UX90-005M) 
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As light is a noninvasive form of treatment, assessing the amount of ‘light’ received is difficult to 
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quantify in measuring the efficacy of violet light in slowing the progression of myopia. The Onset HOBO 
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Occupancy Sensor uses infrared technology to measure fluctuations of temperature within a 5-meter 
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radius. The temperature fluctuation readings are logged as numerical data which can then be 
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retrospectively collected to then measure exposure to light during the duration of the study. 
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D)  DNA Storage via Saliva 
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In addition to exploring the efficacy of violet light exposure in treating myopia, the effects of genetic 
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factors will be assessed from DNA extraction for research purposes only. In recent years, alongside the 
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advent of more sophisticated molecular techniques such as linkage analysis, association studies, and 
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sequencing analysis, many of the genes associated with myopia have been identified.23 Prevalence of 
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myopia has proven to be significantly linked to genetics24, and if conclusive findings are made from this 
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study, further analysis of DNA collected from saliva could provide valuable information for posterity. 
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Participants will be asked to spit 2-3 mL of saliva into a self-collection container provided by the study. A 
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slight dryness in the mouth may occur; this will be a one-time collection. Collected saliva samples are for 
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DNA extraction for the DNA to be banked for future, unspecified use. All future research accessing the 
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samples or genetic datasets would be IRB approved and reviewed by the study team on a case-by-case 
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basis.  
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Participants will be informed that they are donating genetic material, and the most likely outcome is that 
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they will receive no further information regarding those samples.  
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1.8 Study Objective 
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The purpose of this short-term, pilot, randomized trial is to investigate the efficacy of violet light 
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exposure through the BIOS SkyView Lamps at dawn and dusk versus non-violet light exposure through 
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Aooshine Bedside Lamps in slowing the progression of myopia in school aged children as an alternative 
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to current clinical treatments to determine whether to proceed to a full-scale longer-term randomized 
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trial. This decision will be based primarily on assessing responses to light exposure by comparing 
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treatment groups on the following outcomes: 
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Axial length elongation 
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Spherical refractive error 
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Quality of life 
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The proportion of participants reporting adverse effects 
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The proportion of participants reporting >75% light exposure compliance 
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1.9 Timing of Intervention and Outcome for Proposed Study 
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To evaluate the response to violet light exposure for at least one hour at dawn and at least one hour at 
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dusk compared to non-violet light exposure for at least one hour at dawn and at least one hour at dusk, 
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this pilot randomized clinical trial (RCT) is proposed. If a reasonable initial response without significant 
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adverse effects is found, a subsequent full-scale RCT would further evaluate the effectiveness of violet 
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light exposure via the SkyView lamp for myopia treatment. We will define success as violet light 
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exposure intervention demonstrating at least 80% non-inferiority compared to the control group. 
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2. Considerations 
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2.1 Risks 
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Safety testing of both the BIOS SkyView lamp and the Aooshine Bedside Lamp was completed via 
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Underwriter Laboratories. (Document: QOVZ.E516890). Both the SkyView lamp (assessment ID: 109744) 
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and the Aooshine Bedisde Lamp (assessment ID: 133975) have both been approved for IRB study use by 
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CCHMC. 
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There is a risk associated with wearing CR-39 lenses, as they are not as impact resistant as polycarbonate 
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(mechanical strength class S vs F, respectively). Parents and participants will be educated on the risk via 
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the consent form and encouraged to either remove eyeglasses or wear different eyeglasses for activities 
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where there is a strong risk of impact to eyeglass lenses (i.e. sports). If participants are assigned to study 
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group 2 (CR-39 lenses throughout the day), parents and participants will be reminded verbally of this risk 
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using the language present in the consent form. 
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2.2 Risk of Examination Procedures 
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The procedures in this study are part of daily eye care practice in the United States and pose no known 
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risks. 
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2.3 Risk Assessment 
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It is the investigator’s opinion that the protocol’s level of risk falls under DHHS 46.404, which is research 
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not involving greater than minimal risk. 
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2.4 Reporting of Adverse Events 
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There are no expected long-term adverse events associated with violet light exposure. The investigator 
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will abide by CCHMC IRB reporting requirements. 
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2.5 Study Costs 
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This study will be funded internally through CCHMC RIP grant. The department of ophthalmology will be 
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the final dispenser of funds.  
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The subject or his/her insurance provider will be responsible for the costs that are considered standard 
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of care. Because the treatment used in the study is not standard of care, the Enrollment/Randomization, 
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Equipment Pickupand 2 Follow-Up visits will be paid for by the study. The cost of the SkyView/Aooshine 
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lamp will also be paid for by the study. For subjects who wear prescription lenses and are assigned to a 
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group that requires CR-39 or polycarbonate lenses to be worn, the study will provide spectacles and 
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lenses from Zenni Optical not to exceed $80 subject to the following:  
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If the patient/parent desires more expensive frames, they will be responsible for costs that 
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exceed $80. 
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Lens add-ons and upgrades are at study participant’s own expense (e.g., transition lenses, 
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premium polycarbonate lenses). 
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3. Study Outline 
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*Only required if not able to complete at Enrollment/Randomization Visit. 
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** Testing may occur at a separate testing visit if testing equipment is unavailable at the 12-Month Visit. This must 
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occur ± 2 weeks of the 12- Month Visit. 
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4. Enrollment 
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4.1 Eligibility Assessment 
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Enrollment/Randomization
Visit 2: Equipment Recieval
6-Month Visit
12- Month Visit
Day ≤0
Week 4 ± 2 weeks
6 Months ± 2 weeks
12 Months ± 2 weeks
Informed Consent
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Demographics
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Medical History
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X
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Standard Refraction
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X
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Cycloplegic Autorefraction
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Distance Visual Acuity Testing
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Binocular Near Visual Acuity
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X
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Monocular Amplitude of Accomodation
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Axial Length Measurement
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OCTA
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Prescribe Refractive Correction If Needed
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Randomization
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Receive Lamp
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Receive Glasses
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Receive HOBO Sensor
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Receive Automated Wall Plug-In
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HOBO Sensor Data Collection
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A child is considered for the study after undergoing a routine eye examination (as part of standard care) 
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where myopia is identified, and the child appears to meet the eligibility criteria for enrollment.  The 
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study will be discussed with the child’s guardian(s).  Guardians who express an interest in the study will 
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be given a copy of the informed consent form to read. Written informed consent must be obtained from 
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the guardians prior to performing any study-specific procedures that are not part of routine care. 
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Participants aged 5 to <13 years with myopia who meet all eligibility criteria will be enrolled in the study. 
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Up to 72 participants will be enrolled and randomized in the study. 
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4.2 Inclusion Criteria 
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Diagnosis of myopia (ICD-10-CM Diagnosis Code H52.13)  
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Refractive error meeting the following by cycloplegic autorefraction: 
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Myopia -1.00D to -6.00D spherical equivalent (SE) in both eyes  
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Astigmatism <= 1.50D in both eyes  
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Anisometropia < 1.00D SE 
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Complete eye exam with cycloplegic refraction within the past 12 months  
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5 to < 13 years of age 
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Parent understands the protocol and is willing to accept randomization to 380 nm light or control. 
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Parent has a phone (or access to phone) and is willing to be contacted by Investigator’s site staff. 
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Relocation outside of the area of CCHMC site within the next 12 months is not anticipated. 
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4.3 Exclusion Criteria 
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Current or previous myopia treatment with atropine, pirenzepine or other antimuscarinic agent. 
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Current or previous use of bifocals, progressive-addition lenses, or multi-focal contact lenses. 
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Current or previous use of orthoK, rigid gas permeable, or other contact lenses being used to reduce 
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myopia progression. 
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Current or prior history of manifest strabismus, amblyopia, or nystagmus.  
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Abnormality of cornea, lens, central retina, iris, or ciliary body.  
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Prior eyelid, strabismus, intraocular, or refractive surgery.  
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Down syndrome or cerebral palsy. 
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4.4 Sample Size 
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Up to 72 participants will be enrolled in this study. Up to 24 will be enrolled into the three experimental 
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groups:  
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Violet light experimental group with polycarbonate glasses 
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Violet light experimental group with CR-39 glasses 
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Non-violet control group with CR-39 glasses. 
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4.5 Historical Information 
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Historical information elicited will include the following: date of birth, sex, race, ethnicity, current 
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refractive correction, iris color (brown or not brown), parental history of myopia (0, 1, or 2 parents), 
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current medication use, history of and current medical conditions, and myopia treatment history. 
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4.6 Survey to Determine Lighting Schedule 
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To determine suitable dawn and dusk times for each participant, participants will be asked when they 
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typically wake up, eat dinner, and sleep. Additionally, participants will be asked to detail their typical 
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evening schedule and any activities that may negatively affect compliance. 
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4.7 Testing at the Enrollment/Randomization Visit 
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Testing at the enrollment/randomization visit will include the following: 
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1. Standard Refraction 
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The investigator may use his/her standard refraction technique (with or without cycloplegia) at any 
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time during the visit to ensure that the participant meets eligibility criteria with respect to refractive 
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correction as described in section 2.5. 
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2. Cycloplegic Autorefraction 
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Combination Drops (tropicamide 1%, cyclopentolate 1%, phenylephrine 2.5%) – one drop twice to 
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each eye with 5 minutes between drops. The use of proparacaine prior to the cycloplegic drops is at 
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investigator discretion. For each eye, three autorefraction measurements will be taken. For each 
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measurement, the autorefractor will yield a final reading (either an individual reading or the 
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mean/median of several individual readings, depending on the autorefractor) consisting of sphere, 
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cylinder, and axis (see manual of procedures). Each final reading will be converted to a spherical 
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equivalent refractive error (SER) and the mean of the 3 SER values for each eye will be used for 
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confirming eligibility. A specific autorefractor model is not required for the study; however, each 
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participant should have their autorefraction assessed using the same instrument during the entire 
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study. The cycloplegic autorefraction should occur at 30 minutes ± 5 minutes from the time the 
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second drop was instilled. If eyes are not sufficiently dilated/cyclopleged and/or if the 
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dilation/cycloplegia has worn off before all cycloplegic procedures have been performed, another 
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drop may be administered, followed by an additional 30-minute wait before testing. The use of 
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proparacaine prior to this cycloplegic drop is at investigator discretion. 
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3. Axial Length Measurement and Additional Biometry 
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Axial length will be measured 3 times in each eye using optical biometry (e.g., IOLMaster, LENSTAR). 
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The following will also be measured 3 times in each eye using optical biometry (e.g., IOLMaster, 
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LENSTAR) at the same time as axial length. 
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• 
Mean corneal radius (mm to 100th) 
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• 
Anterior chamber depth (mm to 100th) 
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• 
Lens thickness, if available (mm to 100th) 
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A specific instrument is not required for the study; however, each participant should have axial 
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length and additional biometry assessments made using the same instrument during the entire 
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study. 
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If the Enrollment Visit occurs at a time or location that the IOLMaster or LENSTAR is unavailable, the 
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Axial length measurement may be completed at the Equipment Pickup Visit. 
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4. Optical Coherence Tomography Angiography (OCTA) 
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OCTA will be utilized to image retinal vasculature. 3 x 3 mm OCT angiograms will be obtained for 
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each eye. 
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 OCTA will be performed using the Heidelberg HRA2 Spectralis device (Heidelberg Engineering, 
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Germany). Using a standardized scanning protocol of 15 degree field of view, 4.4 × 2.9-mm X by Y 
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dimension on the retina, 256 B-scans (12 µm between B-scans), a Z-dimension of 1.9 mm (496 pixels 
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approximated to 3.87 µm/pixel), and automatic real-time tracking (ART) of 5; patients will be imaged 
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with macular area OCTA images of superficial vascular complex, deep vascular complex, 
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choriocapillaris and choroid, centered at the fovea. 
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If the Enrollment Visit occurs at a time or location that the Heidelberg HRA2 Spectralis Device is 
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unavailable, the OCTA may be completed at the Equipment Pickup Visit. 
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4.8 Refractive Correction 
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To be eligible for randomization, the participant must be wearing refractive correction in each eye 
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(single vision eyeglasses or soft, daily wear single vision contact lenses with any necessary 
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adjustment for contact lens rotation and vertex distance) that meets the following criteria:  
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1. Myopia (by spherical equivalent) in both eyes must be corrected to within ±0.50 D the 
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investigator’s cycloplegic measurement of refractive error.  
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2. Cylinder power in both eyes must be within ±0.50 D of the investigator’s standard refraction 
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technique, which can be based on a cycloplegic or non-cycloplegic refraction. 
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3. Cylinder axis for both eyes must be within ±5 degrees of the axis found on the investigator’s 
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standard refraction when cylinder power is >= 1.00 D or within ±15 degrees when the cylinder 
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power is < 1.00 D. 
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Measurement of refractive error for assessing the above criteria may be performed as an over 
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refraction or without refractive correction. If the participant meets all eligibility criteria, but their 
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current correction does not meet the requirements for randomization, then new refractive 
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correction (or a change in refractive correction) can be prescribed to meet the requirements. A new 
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(or change) in refractive correction can also be prescribed if the investigator elects to change a 
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smaller amount of refractive error, but the resulting prescription must meet the criteria above. The 
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prescribed correction can be single vision eyeglasses or contact lenses. Single vision lenses will be 
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paid for by the study; contact lenses will be at the participants’ own expense. A pair of eyeglasses is 
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recommended for all participants and may be ordered through Zenni by the study team. 
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5. Randomization 
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5.1 Randomization Process 
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Participants eligible for randomization will be randomly assigned in a 1:1:1 distribution respectively to: 
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 
Violet light experimental group (BIOS SkyView Lamp) with polycarbonate glasses 
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 
Violet light experimental group (BIOS SkyView Lamp) with CR-39 glasses  
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 
Non-violet control group (Aooshine Bedside Lamp) with CR-39 glasses 
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The investigator will construct a separate Master Randomization List using a permuted block design 
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stratified by the treatment group.  A participant is considered randomized when REDCap randomization 
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process is completed. 
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The participant, parents, testers, and investigators will be masked to treatment group. If the need arises, 
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the investigator may become unmasked after discussion of a specific case with the study team in 
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response to any adverse events. The study coordinator will remain unmasked to the treatment group in 
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order to facilitate the type of equipment and lenses the participant will need. 
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6. Equipment Pickup Visit 
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6.1 Prescription Glasses 
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Participants will come back for their Equipment Pickup Visit once the study team has received the 
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glasses shipment from Zenni. These lenses must be used in conjunction with the lamp, therefore must be 
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picked up alongside the lamp. 
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6.2 Study Lamp 
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Participants will receive their lamp at this visit. Patients were randomized at the 
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enrollment/randomization visit and are prepared to receive their respective lamp. The study coordinator 
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will instruct the participant and guardian on the use and setup of the lamp. The HOBO sensor will be 
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attached to the lamp, and participants and guardians will be instructed on how to remove the sensor 
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from the lamp to bring to follow-up visits. 
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6.3 HOBO Sensor 
408 
Participants will receive the HOBO sensor attached to their lamp. The sensor will be removable to bring 
409 
to follow-up visits. Participants and guardians will be instructed how to remove the sensor properly, and 
410 
how to put it back on the lamp.  
411 
6.4 Automated Wall Plug-In 
412 
Participants will receive an outlet timer that will be set to the times the parent or guardian has specified 
413 
to be their on (dawn) and off (dusk) times. It will be during these times that the child will be asked to be 
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in the room with the light on for at least one hour at dawn and one hour at dusk. This will allow the lamp 
415 
to turn on and off automatically during the designated times. 
416 
6.5 Testing Not Completed at Enrollment 
417 
Participants that were unable to complete testing at the enrollment visit due to unavailability of 
418 
equipment may have this testing performed at this visit. 
419 
 
Axial length measurement (see 4.7.3) 
420 
 
OCTA (see 4.7.4) 
421 
7. Follow-Up 
422 
7.1 REDCap Daily Surveys 
423 
Each day, the parent or guardian of the participant will receive a survey via email with two questions as 
424 
to what times the lamp was used during the dawn hours and dusk hours that day. Parents and guardians 
425 
will be reminded of the importance of this survey during telephone calls and follow-up visits.  
426 
This survey will serve as a second point of compliance data to compare to the data received from the 
427 
HOBO sensor. 
428 
7.2 Telephone Calls 
429 
Telephone calls will be made by the study coordinators to the participants and guardians at 2 weeks (+ 3 
430 
days), 3 months (+ 1 month), and 9 months (+ 1 month) post Equipment Pickup visit.  
431 
Coordinators will contact parents to confirm that the BIOS SkyView/Aooshine lamp is working properly, 
432 
encourage compliance, and question the parent as to whether the child is experiencing any issues with 
433 
treatment. 
434 
Additionally, these calls will help maintain direct contact with the parents of the participants, develop 
435 
and maintain rapport with the family, and assist with scheduling of study visits if needed. 
436 
7.3 Follow-Up Visits: 6-Month and 12-Month 
437 
The following will be performed at Follow-Up Visits and recorded in the Follow-Up Visit CRF via Redcap. 
438 
- 
Medical History 
439 
o Includes questioning about the occurrence of adverse effects of treatment. Concomitant 
440 
medications will be recorded, as well as current eyeglasses or contact lenses correction. 
441 
- 
Compliance Assessment (HOBO sensor data collection) 
442 
o App data will be reviewed and assessments of compliance will be recorded on the 
443 
Follow-up Examination Form. 
444 
- 
Standard Refraction 
445 
o The investigator may use their standard refraction technique (with or without 
446 
cycloplegia) at any time during the visit to ensure that refractive correction meets study 
447 
criteria at each visit. 
448 
- 
Cycloplegic Autorefraction 
449 
o See 4.7.2 
450 

 
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- 
Binocular Near Visual Acuity 
451 
o Binocular near visual acuity is measured with participant wearing current refractive 
452 
correction prior to administration of cycloplegia. 
453 
- 
Distance Visual Acuity  
454 
o Monocular distance visual acuity tested at the start of the exam without cycloplegia in 
455 
current correction.  
456 
o Measurement of best corrected visual acuity in each eye by a study certified visual 
457 
acuity tester using the E-ETDRS testing protocol.  
458 
o If the vision is more than one line (>= 5 letters) worse than baseline, retest using trial 
459 
frames or phoropter with the most recent subjective refraction. 
460 
- 
Monocular Amplitude of Accommodation 
461 
o Measured in their current correction without cycloplegia with a study-specified and 
462 
provided accommodation near-point rule.  
463 
o Axial Length Measurement (12-Month Only) 
464 
o See 4.7.3 
465 
- 
OCTA- Performed (12-Month Only) 
466 
o See 4.7.4 
467 
7.4 Management of Refractive Error 
468 
Spectacle correction must be updated whenever the investigator’s standard refraction technique reveals 
469 
a change in refractive error. A change in refractive error is defined as any of the following amounts: 
470 
 
A difference of >0.75D sphere  
471 
 
A difference of >0.75D cylinder  
472 
 
A difference of >0.50D in SE anisometropia  
473 
 
A difference in axis of 6 degrees or more when the cylinder is ≥1.00D.  
474 
Whether to update the correction for smaller differences in refraction is at investigator discretion. 
475 
updated, the refractive correction must meet the requirements described in section 4.7. 
476 
7.5 Non-Randomized Treatment Other than Refractive Correction 
477 
Non-randomized treatment for myopia other than changes in refractive error as described above is not 
478 
permitted during the study. The investigator must call the principal investigator to discuss the case and 
479 
obtain approval for an exception prior to initiating non-randomized treatment (including OrthoK, rigid 
480 
gas permeable, and other contact lenses being prescribed for myopia management). 
481 
7.6 General Considerations 
482 
The study is being conducted in compliance with the policies described in the study policies document, 
483 
with the ethical principles that have their origin in the Declaration of Helsinki, with the protocol 
484 
described herein, and with the standards of Good Clinical Practice. 
485 
Data will be directly collected in electronic CRFs, which will be considered the source data. 
486 
A risk-based monitoring approach will be followed, consistent with the FDA “Guidance for Industry 
487 
Oversight of Clinical Investigations – a Risk-Based Approach to Monitoring” (August 2013). 
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8. Miscellaneous Considerations 
489 
8.1 Participant Withdrawals 
490 
Parents may withdraw their child from the study at any time. If the parents indicate that they want to 
491 
withdraw their child from the study, the investigator should attempt to speak with the parents personally 
492 
to determine the reason. If their interest is in transferring the child’s care to another eye care provider, 
493 
every effort should be made to comply with this and at the same time, try to keep the participant in the 
494 
study under the new provider’s care. 
495 
8.2 Discontinuation of Study 
496 
The study may be discontinued by the study team prior to the pre-planned completion of enrollment 
497 
and follow-up for all participants.   
498 
8.3 Payment to Participants 
499 
The parent/guardian of each participant will be compensated $50 by ClinCard upon completion of the 
500 
Enrollment/Randomization Visit, Equipment Pickup Visit, 6-Month Visit, and 12-Month Visits, for a 
501 
maximum of $250. 
502 
8.4 Costs Covered by the Study 
503 
The study will pay for the office visits that are part of the study (Enrollment/Randomization Visit, 
504 
Equipment Pickup Visit, 6-Month Visit, and 12-Month Visit).  
505 
The study will pay for the following: 
506 
• 
BIOS SkyView/Aooshine lamp will be provided to each participant at no cost. 
507 
• 
Eyeglasses will be ordered at enrollment (if needed).   
508 
• 
Frames and Lenses will be ordered by the study team from Zenni. 
509 
• 
Lens changes will be provided at 6 months if a change is required, and the lenses will be ordered 
510 
by the study team through Zenni.    
511 
8.5 Costs Not Covered by the Study 
512 
The study will not pay for eyeglasses obtained elsewhere (the study pays for glasses if needed through 
513 
Zenni only).  The study will not pay for contact lenses.   
514 
9. Data Storage and Analysis 
515 
9.1 Analysis 
516 
Primary Analyses 
517 
The primary analysis will be an experimental vs control group comparison of change from baseline to 12 
518 
months in spherical equivalent refractive error (SER), as measured using cycloplegic autorefraction. At 
519 
baseline and all follow-up visits, the mean of the three readings from autorefraction in each eye will be 
520 
calculated and then the mean of both eyes for each participant will be used for the analysis. If fewer 
521 
than 3 readings are available in each eye, the mean of available readings will be used for each eye to 
522 
obtain the mean of both eyes for each participant.      
523 

 
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The treatment group difference (violet vs. non-violet light) and a 95% confidence interval will be 
524 
calculated based on the model estimates at 12 months.    
525 
Secondary Analyses 
526 
 
Difference in change in axial length at 6 and 12 months between the violet and non-violet light 
527 
group 
528 
 
Compliance will be assessed at each follow up and described as excellent (76%-100%), good 
529 
(51%-75%), fair (26%-50%) or poor (<25%). 
530 
9.2 Decision Guideline 
531 
The data collected in this short-term, pilot randomized clinical trial will primarily be used to determine 
532 
whether to proceed to a full-scale, longer-term randomized trial of violet light vs control non-violet. The 
533 
side effect profiles in the experimental and control groups will also be considered when deciding 
534 
whether to proceed with a full-scale trial.  
535 
The decision guideline for determining whether to proceed to a full-scale randomized trial will be based 
536 
on the primary and secondary outcomes at study conclusion.  
537 
9.3 Data Safety Monitoring Plan 
538 
The participants in this study are patients routinely seen by the investigator or his colleagues as part of 
539 
standard clinical care at CCHMC, Division of Pediatric Ophthalmology. Participants will continue to be 
540 
followed clinically by either the investigator or the referring clinicians in addition to attending the study 
541 
visits. 
542 
During the study, participants are observed closely to detect occurrences of any adverse events or 
543 
complications that may have arisen. At each study visit, the participants and their guardians will be asked 
544 
questions regarding the occurrence of adverse events to determine whether any complications or 
545 
adverse events might have occurred since the previous visit. 
546 
In the case of a suspected adverse event, further testing may be performed, and non-study treatment 
547 
may be initiated to ensure patient safety. 
548 
9.4 Source Documents and Case Report Forms 
549 
Adequate records will be maintained for the study including participant medical records, test reports, 
550 
signed informed consent forms, adverse event reports, and information regarding participant 
551 
discontinuation and reasons for discontinuation. All original source documentation will be stored 
552 
electronically in the password-protected CCHMC shared-drive or in a locked filing cabinet located in the 
553 
investigator’s office or research coordinator’s workspace. 
554 
In accordance with 21 CFR 50, guardians will provide written informed consent for participation in this 
555 
study.   
556 
9.5 Changes to Protocol 
557 
The investigator will notify the IRB of any unanticipated problem requiring a change in the protocol to 
558 
eliminate apparent immediate hazard to a subject per CCHMC Research Policy, R-18. Changes that affect 
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the scientific soundness of the study or the rights, safety, or welfare of human subjects will be submitted 
560 
to the IRB in an amendment prior to implementation.   
561 
 
562 
 
563 
 
564 
 
565 
10. References 
566 
1. 
Holden, B. A. et al. Global Prevalence of Myopia and High Myopia and Temporal Trends from 
567 
2000 through 2050. Ophthalmology (2016) doi:10.1016/j.ophtha.2016.01.006. 
568 
2. 
Theophanous, C. et al. Myopia prevalence and risk factors in children. Clin. Ophthalmol. (2018) 
569 
doi:10.2147/OPTH.S164641. 
570 
3. 
Foster, P. J. & Jiang, Y. Epidemiology of myopia. Eye (2014) doi:10.1038/eye.2013.280. 
571 
4. 
Praveen, M. R., Vasavada, A. R., Jani, U. D., Trivedi, R. H. & Choudhary, P. K. Prevalence of 
572 
Cataract Type in Relation to Axial Length in Subjects with High Myopia and Emmetropia in an 
573 
Indian Population. Am. J. Ophthalmol. (2008) doi:10.1016/j.ajo.2007.07.043. 
574 
5. 
Mitchell, P., Hourihan, F., Sandbach, J. & Wang, J. J. The relationship between glaucoma and 
575 
myopia: The blue mountains eye study. Ophthalmology (1999) doi:10.1016/S0161-
576 
6420(99)90416-5. 
577 
6. 
Risk factors for idiopathic rhegmatogenous retinal detachment. Am. J. Epidemiol. (1993) 
578 
doi:10.1093/oxfordjournals.aje.a116735. 
579 
7. 
Walline, J. J. Myopia control: A review. Eye and Contact Lens (2016) 
580 
doi:10.1097/ICL.0000000000000207. 
581 
8. 
Walline, J. & Smith, M. Controlling myopia progression in children and adolescents. Adolesc. 
582 
Health. Med. Ther. (2015) doi:10.2147/ahmt.s55834. 
583 
9. 
Leo, S. W. et al. Current approaches to myopia control. Current Opinion in Ophthalmology (2017) 
584 
doi:10.1097/ICU.0000000000000367. 
585 
10. 
Lam, C. S. Y., Tang, W. C., Tse, D. Y. Y., Tang, Y. Y. & To, C. H. Defocus Incorporated Soft Contact 
586 
(DISC) lens slows myopia progression in Hong Kong Chinese schoolchildren: A 2-year randomised 
587 
clinical trial. Br. J. Ophthalmol. (2014) doi:10.1136/bjophthalmol-2013-303914. 
588 
11. 
He, M. et al. Effect of time spent outdoors at school on the development of myopia among 
589 
children in China a randomized clinical trial. JAMA - J. Am. Med. Assoc. (2015) 
590 
doi:10.1001/jama.2015.10803. 
591 
12. 
Wu, P. C., Tsai, C. L., Wu, H. L., Yang, Y. H. & Kuo, H. K. Outdoor activity during class recess 
592 
reduces myopia onset and progression in school children. Ophthalmology (2013) 
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doi:10.1016/j.ophtha.2012.11.009. 
594 
13. 
Rose, K. A. et al. Myopia, lifestyle, and schooling in students of Chinese ethnicity in Singapore and 
595 
Sydney. Arch. Ophthalmol. (2008) doi:10.1001/archopht.126.4.527. 
596 
14. 
Sherwin, J. C. et al. The association between time spent outdoors and myopia in children and 
597 
adolescents: A systematic review and meta-analysis. Ophthalmology (2012) 
598 
doi:10.1016/j.ophtha.2012.04.020. 
599 
15. 
Xiong, S. et al. Time spent in outdoor activities in relation to myopia prevention and control: a 
600 
meta-analysis and systematic review. Acta Ophthalmologica (2017) doi:10.1111/aos.13403. 
601 
16. 
Jin, J. X. et al. Effect of outdoor activity on myopia onset and progression in school-aged children 
602 
in northeast china: The sujiatun eye care study. BMC Ophthalmol. (2015) doi:10.1186/s12886-
603 
015-0052-9. 
604 
17. 
Torii, H. et al. Violet Light Exposure Can Be a Preventive Strategy Against Myopia Progression. 
605 
EBioMedicine (2017) doi:10.1016/j.ebiom.2016.12.007. 
606 
18. 
Torii, H., Ohnuma, K., Kurihara, T., Tsubota, K. & Negishi, K. Violet Light Transmission is Related to 
607 
Myopia Progression in Adult High Myopia. Sci. Rep. (2017) doi:10.1038/s41598-017-09388-7. 
608 
19. 
Nguyen, M. T. T. et al. An opsin 5–dopamine pathway mediates light-dependent vascular 
609 
development in the eye. Nat. Cell Biol. (2019) doi:10.1038/s41556-019-0301-x. 
610 
20. 
Zhou, X., Pardue, M. T., Iuvone, P. M. & Qu, J. Dopamine signaling and myopia development: 
611 
What are the key challenges. Progress in Retinal and Eye Research (2017) 
612 
doi:10.1016/j.preteyeres.2017.06.003. 
613 
21. 
Wang, M., Schaeffel, F., Jiang, B. & Feldkaemper, M. Effects of light of different spectral 
614 
composition on refractive development and retinal dopamine in chicks. Investig. Ophthalmol. Vis. 
615 
Sci. (2018) doi:10.1167/iovs.18-23880. 
616 
22. 
Jiang X, Pardue MT, Mori K, Ikeda S, Torii H, D’Souza S, Lang RA, Kurihara T, Tsubota K. “Violet 
617 
light suppresses lens-induced myopia via neuropsin (OPN5) in mice.” Proc Natl Acad Sci. 2020. (in 
618 
review) 
619 
23. 
Yap M, Wu M, Liu ZM, Lee FL, Wang SH. Role of heredity in the genesis of myopia. Ophthalmic 
620 
Physiol Opt. 1993;13:316–9.  
621 
 
622 
24. 
Ip JM, Huynh SC, Robaei D, Rose KA, Morgan IG, Smith W, Kifley A, Mitchell P. Ethnic Differences 
623 
in the impact of parental myopia: findings from a population-based study of 12-year-old 
624 
Australian children. Invest Ophthalmol Vis Sci. 2007;48:2520–8. 
625 
25. 
BIOS. WELL Building Standard: Circadian Lighting Design. Jan 2020. 
626 
https://bioslighting.com/human/well-building-standard/ 
627 
26. 
BIOS. SkyView Wellness Table Lamp. Jan 2020. https://bioslighting.com/product/SkyView-
628 
wellness-table-lamp/ 
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