Overnight orthokeratology is a technique for correcting myopia and is more recently proposed for the prevention of myopic progression. It is potentially an alternative to laser in situ keratomileusis and may be offered to parents whose children are not candidates for refractive surgery and who are searching for an intervention that may lessen or ameliorate developing myopia. In this issue of the Journal , Koffler and Sears present a comprehensive review of overnight orthokeratology. Clinical and theoretical issues remain, however, and this editorial will attempt to add perspective.
Overnight orthokeratology works to correct myopia by flattening the cornea through a mechanism of central epithelial thinning. The corneal periphery becomes thicker, thereby enhancing the peripheral corneal curvature. Good vision is possible by 1 week, stabilizing by 1 month. Treatment effects appear to be transient unless retainer lenses are worn every 1-2 nights to maintain the flattening effect. Overnight orthokeratology clearly alters the structural integrity of the epithelium. Following overnight orthokeratology, the central epithelium displays significant changes in the shape and size of apical cells. These cells may lose the normal microprojections (plicae) that are absent in deeper layers. Animal models demonstrate increased adhesion of pseudomonas to surface cells, accompanied by thinning and reduced turnover of the epithelial complement. These factors, plus the compressive lens effect, may render the cornea more susceptible to microbial invasion. Nieto-Bona and associates demonstrated that stromal keratocyte density is maintained and there are no endothelial cell density changes after 1 month to 1 year, but at 1 year polymegethism increased significantly and did not recover to baseline.
The Food and Drug Administration (FDA) granted approval to 2 overnight orthokeratology lenses in 2002. Paragon (Grand Rapids, Michigan, USA) was approved for −6.00 spherical and −1.75 cylindrical correction. Euclid Systems (Bausch and Lomb, Rochester, New York, USA) was approved for −5.00 and −1.50, respectively. The Paragon premarket study included 218 subjects (and only 12 adolescents). The FDA Advisory Panel recommended approval for patients aged 18 years and older unless further safety data for younger eyes became available. No adolescents were studied in the Euclid Systems cohort. No cases of serious microbial keratitis were reported, but 1 infiltrate was treated. There were no cases of permanent vision loss. The FDA did not endorse the Advisory Panel recommendations and granted overnight orthokeratology approval without age restriction, stating there were no additional safety issues for adolescents as long as the lenses were used according to the approved labeling and were fit only by trained practitioners. Overall, 11% of the premarket study cohort comprised adolescents aged 12-17 years old. However the market for adolescents may be much larger. A recent survey of overnight orthokeratology indicates fits represent 28% of all contact lenses prescribed to minors.
The quality of vision in overnight orthokeratology has been extensively studied. Spherical aberration is induced from the continued application of rigid lenses. The normal prolate shape becomes oblate. Mesopic contrast sensitivity deteriorates significantly and higher-order aberrations are induced. Higher-order aberration and contrast sensitivity show recovery to pretreatment levels 1 week after discontinuing the lenses. Likewise, refractive correction and uncorrected visual acuity show resolution to baseline at 1 week, with continued improvement at 1 month. Thus overnight orthokeratology appears to be reversible.
A second proposed, but unapproved, use of overnight orthokeratology is in preventing myopic progression. Published studies include young early-school-age children. Many studies regarding myopic progression have been published, some of which are not randomized or prospective, introducing the potential for observer bias. Many are plagued by design flaws, unbalanced data sets and subject retention (a 20%-30% dropout rate), small sample groups (20-30 subjects), and short-duration follow-up (0.5-2.0 years). Various ages have been studied (usually 6-to-12-year-olds), but occasionally older teens have been included. The effect or length of a “washout” period has not been established, and most studies were not conducted with a “cross-over” design. A previous literature review indicated level II or III evidence studies to support the safety and efficacy of overnight orthokeratology. There are still no class I (well-designed, well-conducted randomized) clinical trials as evidentiary support. In order to address design flaws, a prospective randomized clinical trial would need to include very young children (preschool-/early-school-aged) followed into their teens or twenties.
The mechanistic theory for overnight orthokeratology myopic prevention is described as “peripheral hyperopic defocus.” The normal prolate shape, flatter peripherally, can be a signal to the peripheral retina to control eye growth, at least in experimental animal models. This controversial theory has been questioned in at least 2 studies of American and Asian schoolchildren. These studies suggest that axial elongation is unrelated to average peripheral refraction. Whether peripheral hyperopia is a cause or consequence (concomitant) of axial myopia is unclear. This lack of a strong causal relationship suggests “questionable therapeutic value” for any optical or pharmacologic intervention, including overnight orthokeratology. Further unresolved questions remain. What is the optimum treatment duration to slow progression? Will any slowing of axial elongation be maintained upon cessation of overnight orthokeratology? If these interventions are discontinued, do eyes naturally “catch up”? In summary, no studies definitively answer the questions: what is the optimum age to initiate therapy, at what age is myopic progression the greatest, and does this progression attenuate as children age?
Ultimately, the risk of microbial keratitis (MK) remains the major concern as children and adolescents are disproportionately represented (>50%) in the treatment populations. Reported MK case series show that Acanthamoeba and Pseudomonas are highly represented, with significant potential for visual loss. The exact incidence of MK in overnight orthokeratology is unknown, and many cases probably go unreported. The FDA 522 Post-market Surveillance Studies Program is now in effect, requiring manufacturers to study the rate of MK in minors. In reviewing the historic and more recent MK case reports, Schein pointed out the following concerns: (1) most infections are severe and central, caused by aggressive organisms such as gram-negative rods or Acanthamoeba ; (2) most cases occurred in children or adolescents; and (3) the infections were associated with multiple brands of rigid gas-permeable (RGP) lenses, and occurred in different countries. Recently, Bullimore conducted a practitioner survey of 1317 overnight orthokeratology patients (677 children). MK occurred in 2 children; 6 of 8 infiltrative keratitis events also occurred in children. The estimated MK incidence was 7.7/10 000 (overall) and 13.9/10 000 (children). This compares to daily-wear RGP MK incidence of 1.2/10 000 and extended wear soft lenses (13.3-19.5/10 000).
In the absence of any other data, it would appear that myopic intervention with overnight orthokeratology must be constant. To achieve and maintain an effect, practitioners must continue the regular application of overnight orthokeratology lenses in overnight fashion, thus maintaining the ongoing risk of infection. The large numbers of children and adolescents with MK previously and recently reported “necessitate the highest level of vigilance.”
Educated patients (and parents) are key components in managing risk. Ethical and knowledgeable practitioners, exercising prudence and forbearance, are the driving forces as we strive to enhance safety in this developing technology.