The Food and Drug Administration (FDA) recently brought together representatives from optometry and ophthalmology to discuss regulatory review of contact lenses and future medical devices to control the progression of myopia, primarily in children.
Silver Spring, MD-The Food and Drug Administration (FDA) recently brought together representatives from optometry and ophthalmology to discuss regulatory review of contact lenses and future medical devices to control the progression of myopia, primarily in children.
The workshop addressed selection criteria for trial participants, key safety and effectiveness outcomes, and other design features that could impact clinical trial design and outcomes for myopia control devices.
“This conversation among optometry, ophthalmology, and the FDA will hopefully enable companies to educate parents about the benefits of myopia control, which can lead to better care for our nearsighted patients and fewer complications,” says Jeffrey J. Walline, OD, PhD, associate dean for research at The Ohio State University (OSU). Dr. Walline represented the American Academy of Optometry at the workshop.
Participating organizations included:
• American Academy of Optometry
• American Optometric Association
• American Academy of Ophthalmology
• American Society of Cataract and Refractive Surgeons
• Contact Lens Association of Ophthalmologists
• American Association for Pediatric Ophthalmology and Strabismus
“We would all like to use myopia control products with an FDA-approved label for myopia control that come with study data that tell us what we should tell patients to set expectations,” says Donald O. Mutti, OD, PhD, E.F. Wildermuth Professorship at The Ohio State University. “It was so important for optometry and ophthalmology to be there at the table together to give our input on what those studies should look like.”
Myopia isn’t usually considered a disease, but Chris Quinn, OD, president-elect of the American Optometric Association, agrees that myopia fits the definition.
“We need science to support the care of the future and this workshop hopefully laid the groundwork for developing real evidence for preventing the progression of myopia in the U.S. and worldwide,” he says. Dr. Quinn represented the American Optometric Association at the workshop.
Representatives from the six participating organizations formed panels for discussion. Panelists and workshop attendees were tasked with providing discussion around questions pertaining to future study design and outcomes.
• Eligibility for future clinical trial participants
• What type of control group to include
• What and how to measure as primary effectiveness endpoints
• Acceptable rate of microbial keratitis as an adverse event
• How to use patient-reported outcomes
Trial participant eligibility
Panelists agreed that eligibility criteria for participants should include:
• Range for refractive errors of -1.00 D to -4.00 D
• Refraction determined by cycloplegic autorefraction (open field of view where possible) using tropicamide; spherical equivalent acceptable as long as astigmatism is <1.00 D
• Maximum of 1.50 D of astigmatism allowed
• Maximum of 1.50 D of anisometropia allowed
• Age range of participants should be 7 to 12 years
• Myopia progression should not affect eligibility
• Participants should have no prior atropine or bifocal contact lens wear
• Ethnicity of participants should reflect that of the U.S. population
Panelists agreed that a single vision soft contact lens group is the most appropriate control group to evaluate effectiveness of a myopia control device.
Per the panel, both axial elongation and refractive error change should be primary effectiveness endpoints; however, axial elongation has preference.
Related: Myopia and public health
Panelists did not come to consensus on clinically meaningful differences for primary endpoints among and within study arms. In general, the device should show results that slow ≈50 percent of myopia progression and a difference between treatment arms >0.75 D over three years, with 30 percent of the study group affected to be clinically significant. The eventual product label must state the percentage of patients affected.
Panelists had no consensus on secondary endpoints.
Most panelists agreed that the patient should use the device for a minimum of three years to determine primary effectiveness outcome, although some panelists preferred two years. In addition, the patient should abstain from device usage to ensure stability of refractive outcome for six months to one year. After device abstention, rebound effect should be assessed at six months to one year.
Microbial keratitis adverse event acceptability
Panelists agreed that the acceptable rate of microbial keratitis should be no greater than current rates for contact lenses: 4/10,000 eyes for daily wear and 18/10,000 eyes for overnight wear.1,2
Methods to improve clinical trial patient enrollment and retention include:
• Examining past studies to learn why patients drop out
• Free comprehensive eye care and free products
• Social media
• Enlisting help from other care providers
• Helping parents with logistics such as transportation or child care
• Public records requests at local schools
• Sports club membership lists
Better engage parents, children, and potential advocacy groups to help trials yield informative results with:
• Social media
• Focus groups with parents
• Understanding resistance to studies
• Local leaders engaged in communities
• Local providers as sub-investigators
Myopia in the U.S. and around the world
In 1983, about 25 percent of Americans were myopic.3 However, that number was revised up to about 33 percent in 2009.4
Myopia is increasing in the U.S., says Dr. Mutti, but he’s not so sure there’s an epidemic in the U.S.
Asia, however, is another story.
“Asian-Americans seem to have the fastest progression rates and reach the highest levels of myopia,” he says. “African-Americans have the slowest progression rates and the lowest levels of myopia.”
A 2003 study by Kleinstein et al showed prevalence of refractive error as a function of ethnicity in 2,523 children aged five to 17 years. Some 9.2 percent of participating children were myopic, and the ethnic breakdown was as follows:5
Asian: 91 percent
Hispanic: 61 percent
White: 46 percent
African-American: 35 percent
Geographic variations in myopia are primarily due to differing environmental exposures, says Prof. Ian Morgan, PhD, visiting fellow at Australian National University College of Medicine, Biology, and Environment.
“In Nepal, children who don’t go to school don’t become myopic,” he says. “In China, the trigger point was the end of the Cultural Revolution when children were put back in school.”
About 60 years ago, 10 to 20 percent of the Chinese population was myopic; in 2015 up to 90 percent of teens and young adults were myopic. In Seoul, South Korea, that number jumped to 97 percent of 19-year-old men.6
Related: Fitting ortho-k contact lenses
Time spent outdoors reduces a child’s risk of myopia onset, according to Dr. Mutti, as compared to those not spending time outdoors, regardless of whether the child has myopic parents. This is contrary to the concept that near work affects the prevalence of myopia.7,8
However, once a child becomes myopic, time outdoors does not affect his rate of progression.9
According to Prof. Morgan, the development of myopia is driven by environmental exposures associated with schooling, such as near work and limited time outdoors. This is not obvious in Western countries where many years of schooling from preschool on is the general rule.
In China, the government is trying to eliminate homework in primary schools,” he says. “There is huge parent backlash.”
Contact lenses and myopia control
Myopia control devices have focused on contact lenses, including orthokeratology (ortho-k). Atropine and progressive addition spectacle lenses (PALs) have also been used.
It is difficult to find the prevalence of contact lens use in children.
Robin L. Chalmers, OD, FAAO, FBCLA, independent trial consultant in Atlanta, says that from 2005 through 2009, new contact lens fits comprised about 14 percent of teens and three percent of children. About 28 percent of those contact lens wearers were fit with ortho-k lenses.10
She reports that among pediatric emergency department visits for medical device-associated adverse events, contact lenses accounted for the most visits at 23 percent.11
“It’s hard to tell if this represents a high risk,” she says. “It does say that emergency departments need to be prepared.”
The Contact Lens Assessment in Youth (CLAY) study12 aimed to determine if children and adolescents were at higher risk of adverse events that interrupted lens wear and if so, at what age did the risk abate.
“Very few kids younger than age 8 had lens wear interrupter events,” she says. “There was a peak in 18-25 years group. Younger wearers had fewer inflammatory events.”
Dr. Chalmers identified risk factors to control in ongoing contact lens studies: overnight contact lens wear, reusable vs. daily disposable lenses, and lens and lens case care.
“Compared with reusable lenses, daily disposable lenses reduce the risk by 12.5 times of having an inflammatory event,” she says. “To minimize risk with children, daily disposables from the start is a good idea. That way the child never learns to misuse them.”
Gaps in knowledge today, according to Dr. Chalmers, include no proper studies of microbial keratitis in children with soft contact lenses, especially daily disposables and the effect of proper retraining on long-term compliance.
The most serious complication with contact lens wear is infectious keratitis, says Jodhbir Mehta, MD.
1.Schein OD, Glynn RJ, Poggio EC, Seddon JM, Kenyon KR. The relative risk of ulcerative keratitis among users of daily-wear and extended-wear soft contact lenses. A case-control study. Microbial Keratitis Study Group. N Engl J Med. 1989 Sep 21;321(12):773-8.
2. Schein OD, McNally JJ, Katz J, Chalmers RL, Tielsch JM, Alfonso E, Bullimore M, O’Day D, Shovlin J. The incidence of microbial keratitis among wearers of a 30-day silicone hydrogel extended-wear contact lens. Ophthalmology. 2005 Dec;112(12):2172-9.
3. Vitale S, Sperduto RD, Ferris FL 3rd. Increased prevalence of myopia in the United States between 1971-1972 and 1999-2004. Arch Ophthalmol. 2009 Dec;127(12):1632-9.
4. Sperduto RD, Seigel D, Roberts J, Rowland M. Prevalence of myopia in the United States.
Arch Ophthalmol. 1983 Mar;101(3):405-7.
5. Kleinstein RN, Jones LA, Hullett S, Kwon S, Lee RJ, Friedman NE, Manny RE, Mutti DO, Yu JA, Zadnik K; Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error Study Group. Refractive error and ethnicity in children. Arch Ophthalmol. 2003 Aug;121(8):1141-7.
6. Dolgin E. The myopia boom. Nature. 2015 Mar 19;519(7543):276-8.
7. Jones LA, Sinnott LT, Mutti DO, Mitchell GL, Moeschberger ML, Zadnik K. Parental history of myopia, sports and outdoor activities, and future myopia. Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3524-32.
8. Zadnik K, Sinnott LT, Cotter SA, Jones-Jordan LA, Kleinstein RN, Manny RE, Twelker JD, Mutti DO; Collaborative Longitudinal Evaluation of Ethnicity and Refractive Error (CLEERE) Study Group. Prediction of Juvenile-Onset Myopia. JAMA Ophthalmol. 2015 Jun;133(6):683-9
9. Jones-Jordan LA, Sinnott LT, Cotter SA, Kleinstein RN, Manny RE, Mutti DO, Twelker JD, Zadnik K; CLEERE Study Group. Time outdoors, visual activity, and myopia progression in juvenile-onset myopes. Invest Ophthalmol Vis Sci. 2012 Oct 1;53(11):7169-75.
10. Morgan PB, Efron N, Woods CA; International Contact Lens Prescribing Survey Consortium. An international survey of contact lens prescribing for presbyopia. Clin Exp Optom. 2011 Jan;94(1):87-92.
11. Wang C, Hefflin B, Cope JU, Gross TP, Ritchie MB, Qi Y, Chu J. Emergency department visits for medical device-associated adverse events among children. Pediatrics. 2010 Aug;126(2):247-59.
12. Chalmers RL, Wagner H, Mitchell GL, Lam DY, Kinoshita BT, Jansen ME, Richdale K, Sorbara L, McMahon TT. Age and other risk factors for corneal infiltrative and inflammatory events in young soft contact lens wearers from the Contact Lens Assessment in Youth (CLAY) study. Invest Ophthalmol Vis Sci. 2011 Aug 24;52(9):6690-6.