While myopia management is gaining prominence worldwide, it’s nevertheless still new enough to leave many important questions unanswered at present. The top interventions—multifocal contact lenses, orthokeratology and atropine eye drops—have each demonstrated efficacy, but protocols to guide clinical application are often lacking. 

Researchers have sought clarity on how to balance efficacy with side-effect profile when selecting the appropriate concentration of atropine at least since 2006, when the ATOM1 study was published. While the pharmacological intervention has been studied primarily in Asia, generally with favorable results, a new U.S.-based clinical trial published in JAMA Ophthalmology failed to replicate the slowing of myopia progression seen in studies of East Asian kids.

An OD-MD group of researchers from the Pediatric Eye Disease Investigator Group tested atropine 0.01% against placebo for slowing myopia in U.S. children. Kids aged 5 to 12 years old across 12 different community- and institution-based practices were included. Refractive error ranged from low to moderate bilateral myopia (-1 D to -6 D). The primary outcome of the study was both-eye mean change in spherical equivalent refractive error (SER), from baseline to 24 months. Other outcomes were spherical equivalent change from baseline out to 30 months (the last six months not receiving treatment) and axial length change at both time points. 

A total of 187 children were included in the study (mean age 10 years), with 67 percent receiving atropine and 33 percent receiving the placebo. Follow-up at 24 months was completed by 95 percent of the atropine group and 94 percent of the placebo group. At 30 months, the atropine group displayed a 94-percent follow-up rate and placebo group a 92-percent rate. 

The adjusted mean change in SER at the 24-month primary outcome visit was -0.82 D in the atropine group and -0.8 D in the placebo group. At 30 months—that is, six months after cessation of treatment—adjusted difference in mean SER change from baseline was
-0.04 D. Adjusted mean changes in axial length from baseline to 24 months was 0.44 mm for the atropine group and 0.45 mm for placebo recipients, and mean axial elongation from baseline to 30 months was +0.009 mm. 

Based on the similar numbers between groups, the study authors concluded in their paper that “these results do not support the nightly use of low-dose atropine 0.01% eye drops to slow myopia progression in U.S. children.”¹

In terms of how this may affect clinicians in their practice, study co-author Michael X. Repka, MD, of Johns Hopkins, says, “They’ll reevaluate the concentration they’re using. There was already some push to use a stronger concentration because of the Hong Kong study, so this may move the group. Even if they were having success with 0.01% they might use 0.05% now. I don’t think it’ll dissuade development. I think there’s still a lot of interest.”

As Dr. Repka says, this study’s results are different from five clinical trials conducted in East and South Asian populations with similar age and refractive error eligibility criteria. In 2012, the ATOM2 trial saw differences in SER myopia progression but not axial elongation over two years; however, there was no placebo control group, which reduced certainty of evidence. More recently, the 2019 LAMP study saw reduction in myopia progression and axial length elongation over one year, but higher atropine concentrations were found more effective than lower ones. Another study saw myopia progression reduction after two years and another after one year, while yet another saw reduction in mean SER progression after one year; all studies used 0.01% atropine. 

This contrasts with one two-year clinical trial conducted in Western Australia, which didn’t find significant myopia progression difference when compared with placebo. That study also had similar age and refractive error eligibility criteria to the present research appearing in JAMA Ophthalmology. 

Elucidated by the authors and expanded upon by an invited commentary also published by JAMA Ophthalmology,² one potential reason for this observed difference is that low-concentration atropine may work better for Asian children than other racial or ethnic populations, particularly those of Caucasian origin. Since atropine binds to melanin, the commentary authors noted that the darker irises typical of Asian subjects may have resultant slower release and longer active drug time, which may yield higher effectivity in Asian children. 

Dr. Repka also notes that Asian subjects show a faster progression of myopia, which may have an effect. “I think a more likely factor is they progress more, so there’s more room for slowing down the effect,” he says. “There’s more room for slowing the growth of myopia in the ages placed in the study.”

Another possibility noted by the commentary is that studies longer than one year frequently don’t report additional accrual of treatment effect, so longer trials are less likely to report significant effects, like the present study, when compared with the mostly one-year trials of Asian children. 

Finally, the commentators explain age may play a role, since myopia progression slows with age, and studies conducted on Caucasian children have included subjects up to 16 years old, while the Asian studies maxed out at age 12 in three out of four conducted. 

“Age does play a role,” Dr. Repka avers. “You want to do the treatment in the children that will get the most benefit, so you want it during the time they have the greatest progression.” No one’s yet determined that age, yet, however. “That’s the tough part,” Dr. Repka continues, “we don’t have a lot of longitudinal history data on that.”

 In light of these possibilities, the study authors believe that “future studies of pharmacologic myopia control in U.S. children should consider increased atropine concentrations, new pharmaceuticals, objective measures of treatment adherence, alternative eye-drop delivery systems and schedules as well as evaluating the impact of environmental and genetic factors and optical interventions on myopia control treatment.”¹

The authors of the commentary feel similarly and point out that “stronger concentrations of atropine should be considered for first-line treatment of myopia progression, especially when considering eye growth outcomes in white children.”²

Along those lines, Dr. Repka says their next study should look at a diffrent concentration. “We’re trying to gauge interest to see if our group will spend the resources to do that study,” he says, “but I think it needs to be done. We’d try a 0.05% dose, which hasn’t been studied in the West. There’s a reasonable signal of beneficial effect of that dose in the publications.”

^{1. Repka MX, Weise KK, Chandler DL, et al. Low-dose 0.01 atropine eye drops vs. placebo for myopic control: a randomized clinical trial. JAMA Ophthalmol. July 13, 2023. [Epub ahead of print].} 

^{2. Walline JJ, Berntsen DA. Atropine, 0.01%, or myopia control. JAMA Ophthalmol. July 13, 2023. [Epub ahead of print].} 

Risk of Detachment after Cataract Surgery 

With the rate of cataract surgery increasing comes an increase in postop complications, such as rhegmatogenous retinal detachment (RRD). In a new study, Swedish researchers analyzed preoperative visual acuity to see if they could discern the risk of RRD after cataract surgery.¹ They concluded that there must be strong indications of need for IOL implantation in those with a high risk of retinal detachment, and the patient must be given adequate information on the risk-benefit trade-offs. Many could get by adequately with spectacle correction, for instance, they argued.

Preoperative visual acuity in nearly 60,000 patients undergoing cataract surgery between during 2015 and 2017 was analyzed (n=58,624), with data retrieved from the Swedish National Cataract Register. This was then cross-referenced with patients undergoing surgery for retinal detachment at the Skåne University Hospital in Lund from 2015 to 2020. The main outcome was the risk-benefit ratio of measuring preoperative visual acuity before cataract surgery and the risk of RRD.

Groups were divided into the following: those aged 60 and younger, those aged 60 and younger with axial length over 25 mm and males aged 60 and younger with axial length over 25 mm.

In a previous study, the same group identified pseudophakic patients with a high risk of long-term complications such as RRD, especially men under the age of 60 with axial length exceeding 25 mm who had almost 10-percent risk within five years. These patients should be thoroughly informed of the risks associated with cataract surgery, and the indications for cataract surgery should be strong.

In the group of patients under 60 years with an axial length over 25 mm with a 6.4-percent risk of RRD in less than five years, more than 15 percent saw 0.8 or better. “The risk-benefit ratio is subjective to each patient, but in our opinion, these patients could have avoided cataract surgery and obtained the same improvement in vision with better spectacles,” the authors noted in the present study.

Between the group being small and the considerable variation in the visual acuity within the group, the authors noted it’s important to inform patients with relative good visual acuity that new spectacles may be an alternative to cataract surgery.

Also, in the same group more than 55 percent saw better than 0.5 logMAR, which used to be the indications in several regions for surgery, based on a 2010 study from Spain that found cataract surgery was usually deemed inappropriate in patients whose visual function wasn’t impaired or only slightly impaired. In this new study, the patients with RRD had similar visual acuity in the operated eye as the whole study group, but there was a large difference in the fellow eye, where the RRD patients had better visual function.

“This indicates that cataract surgery isn’t necessary for many who have a risk for RRD as their binocular vision is still adequate,” the authors noted in their paper.

Many of the patients probably underwent cataract surgery on the eye with poorer vision, and then later on the better eye, especially in the case of myopic patients to avoid anisometropia. “Postoperative refraction must be considered when choosing the intraocular lens for the first eye to avoid putting them at risk for RRD with cataract surgery on the fellow eye,” the authors noted.

Although there are few complications during surgery and shortly after, based on these findings, the authors concluded that a greater awareness of the long-term risk of RRD is required in high-risk patients before cataract surgery.

“We illustrate in this study that many times the visual acuity for these patients is surprisingly good preoperative of cataract surgery where perhaps the best option for the patient is to wait with the surgery,” the authors concluded. “We hope that in the future there will be an individual risk assessment for each patient to consider before doing the surgery.” 

^{1. Thylefors J, Jakobsson G, Zetterberg M, Sheikh R. Visual acuity prior to cataract surgery and risk of retinal detachment-A population-based study. Clin Ophthalmol. 2023;2023:17:1975-80.}