Myopia of Prematurity
Myopia of prematurity (MOP) is a form of refractive error related to alterations in the development of the anterior segment, rather than axial length, that occur in individuals born prematurely. It is a distinct entity from pathologic or school-age myopia. MOP is closely linked to retinopathy of prematurity (ROP) and its treatment, although there is evidence that premature individuals are at risk for myopic refractive error even in the absence of ROP.
Efforts to describe the role ROP has in MOP have led to a number of proposed names to distinguish whether myopia developed solely from prematurity (i.e. true “myopia of prematurity”) or as a sequela of ROP with treatment (myopia of retinopathy of prematurity) or without treatment (“myopia of spontaneously regressed ROP”). These terms are not universally accepted, however, and many publications do not differentiate between them.
There is no specific ICD code for myopia of prematurity. Depending on the context, codes for retinopathy of prematurity (ICD-9: 362.20; and ICD-10: H35.109), progressive high myopia (ICD-9: 360.21), degenerative myopia (ICD-10: H44.20), or simply myopia (ICD 9: 367.1; and ICD-10: H52.13) may be appropriate. Likewise, there is no specific MeSH identifier for MoP.
Early studies on infants with ROP led to the observation that premature infants with and without ROP were predisposed to myopic refractive error, but the prevalence of myopia was much higher in infants with ROP. In 1981, Fledelius observed “‘Myopia of prematurity’ is almost obligatory in cases of incomplete cicatricial retrolental fibroplasia” 3. (The term “retrolental fibroplasia” is a historic name for stage 5 ROP.)
The Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) trial (study start date:1986) included a natural history subgroup which helped to conclusively demonstrate the reality of MOP. This and subsequent trials, including the Early Treatment of Retinopathy of Prematurity (ET-ROP) trial (study start date: 2001) and the Bevacizumab Eliminates the Angiogenic Threat of Retinopathy of Prematurity (BEAT-ROP) trial (study start date: 2008) provided key information about MOP and the effects of ROP treatment (cryotherapy, laser photocoagulation, and intravitreal bevacizumab) on its development.
In the natural history population of the CRYO-ROP trial there was an overall prevalence of myopia (< -0.25 D) of 21% among all subjects at 1 year, but the prevalence of myopia at the same time point among the subgroup with severe ROP was 80%. Likewise, the overall prevalence of high myopia (< -5.0 D) was 3.9% at one year among all participants but was ~43% among those with severe ROP. Each 100g decrease in birth weight correlated with a 10% increase in the prevalence of myopia. In the ET-ROP study, which enrolled participants with pre-threshold ROP, the prevalence of myopia and high myopia was ~65% and ~35% respectively.
MOP prevalence appears to vary with treatment. Laser photocoagulation results in lower incidence of MOP than cryotherapy ablation. The BEAT-ROP study compared outcomes following laser photocoagulation or intravitreal bevacizumab (IVB) and demonstrated a lower prevalence of myopia in those treated with IVB. The prevalence of myopia at 2.5 years in individuals with zone 1 ROP was 79% in the laser group and 43% in the IVB group. The prevalence of high myopia was 50% in the laser group and 22% in the IVB group. Prevalence of myopia and high myopia was lower among subjects with zone 2 ROP., The study also found a positive correlation between the degree of myopia (in diopters) and the number of laser shots used: -0.14D/100 laser shots.
Longitudinal studies of the development of MOP indicate that the degree of myopia is not static from birth, but in fact develops over time, with the most rapid changes occuring during the first year of life. In one prospective observational study, refractive change over time followed a bi-linear pattern in infants who required panretinal photocoagulation with the most rapid changes in refractive error occurring during the first year of life; conversely, refractive changes followed a steady linear pattern in infants with severe ROP that spontaneously regressed without treatment.
The defining pathophysiologic feature of MOP (with and without associated ROP) is abnormal development of the anterior segment. Eyes with MOP exhibit increased corneal curvature, thick lenses, and shallow anterior chambers. In contrast to pathologic myopia, where increased axial length is a hallmark, eyes with MOP characteristically have shorter axial lengths relative to their dioptric value.
The exact mechanism whereby prematurity and ROP lead to the characteristic anterior segment aberrations of MOP is not known. Observations about the timing of MOP development and the improved refractive outcomes of laser over cryotherapy and IVB over laser have led some to suggest that MOP development reflects a mechanical restriction of ocular growth. Other theories include bone deficiency, retinal dysfunction, and temperature interactions.
Premature infants and especially those with severe ROP should be monitored vigilantly for development of myopia with correction with spectacles as clinically indicated. Such infants may also be at risk for other refractive complications such as astigmatism and anisometropia. Monitoring for amblyopia secondary to high myopia, anisometropia, or strabismus is also prudent. Laser treatment could be more efficacious in treating ROP than anti-VEGF. However, laser treatment seems to increase myopia and cause more eye complications.
Anti-VEGF-treated preterm children develop a significantly less myopic and astigmatic refractive error compared with laser-treated children; furthermore, high myopia is less prevalent. Although significantly less myopic than laser-treated children even across age, spherical equivalent development of most anti-VEGF-treated children is still relatively abnormal compared with the normal full-term children.
- Fielder AR, Quinn GE. Myopia of prematurity: nature, nurture, or disease? Br J Ophthalmol 1997;81:2–3.
- Fledelius HC. Pre-term delivery and the growth of the eye An oculometric study of eye size around term-time. Acta Ophthalmol 1992;70:10–15.
- Fledelius HC. Myopia of Prematurity — Changes During Adolescence. Ultrasonography in Ophthalmology 1981:217–223. Available at: http://dx.doi.org/10.1007/978-94-009-8659-6_30.
- Nissenkorn I, Yassur Y, Mashkowski D, et al. Myopia in premature babies with and without retinopathy of prematurity. Br J Ophthalmol 1983;67:170–173.
- Geloneck MM, Chuang AZ, Clark WL, et al. Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial. JAMA Ophthalmol 2014;132:1327–1333.
- Scharf J, Zonis S, Zeltzer M. Refraction in premature babies: a prospective study. J Pediatr Ophthalmol Strabismus 1978;15:48–50.
- Quinn GE, Dobson V, Repka MX, et al. Development of Myopia in Infants with Birth Weights Less than 1251 Grams. Ophthalmology 1992;99:329–340.
- Quinn GE, Dobson V, Davitt BV, et al. Progression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity Study: Findings at 4 to 6 years of age. Journal of American Association for Pediatric Ophthalmology and Strabismus 2013;17:124–128. Available at: http://dx.doi.org/10.1016/j.jaapos.2012.10.025.
- Quinn GE, Dobson V, Kivlin J, et al. Prevalence of myopia between 3 months and 5 12 years in preterm infants with and without retinopathy of prematurity. Ophthalmology 1998;105:1292–1300.
- Wang J, Ren X, Shen L, et al. Development of refractive error in individual children with regressed retinopathy of prematurity. Invest Ophthalmol Vis Sci 2013;54:6018–6024.
- Garcia-Valenzuela E, Kaufman LM. High myopia associated with retinopathy of prematurity is primarily lenticular. J AAPOS 2005;9:121–128.
- Fang Y, Yokoi T, Nagaoka N, et al. Progression of Myopic Maculopathy during 18-Year Follow-up. Ophthalmology 2018;125:863–877.
- Pohlandt F. Hypothesis: myopia of prematurity is caused by postnatal bone mineral deficiency. Eur J Pediatr 1994;153:234–236.
- Lue CL, Hansen RM, Reisner DS, et al. The course of myopia in children with mild retinopathy of prematurity. Vision Res 1995;35:1329–1335.
- Fielder AR, Levene MI, Russell-Eggitt IM, Weale RA. Temperature—a factor in ocular development? Developmental Medicine & Child Neurology 1986;28:279–284.
- Yang C-S, Wang A-G, Sung C-S, et al. Long-term visual outcomes of laser-treated threshold retinopathy of prematurity: a study of refractive status at 7 years. Eye 2010;24:14–20. Available at: http://dx.doi.org/10.1038/eye.2009.63.
- Li Z, Zhang Y, Liao Y, Zeng R, Zeng P, Lan Y. Comparison of efficacy between anti-vascular endothelial growth factor (VEGF) and laser treatment in Type-1 and threshold retinopathy of prematurity (ROP). BMC Ophthalmol. 2018 Jan 30;18(1):19. doi: 10.1186/s12886-018-0685-6. PMID: 29378530; PMCID: PMC5789737.
- : Tan Q-Q, Christiansen SP, Wang J (2019) Development of refractive error in children treated for retinopathy of prematurity with anti-vascular endothelial growth factor (anti-VEGF) agents: A meta-analysis and systematic review. PLoS ONE 14(12): e0225643. https://doi.org/10.1371/journal. pone.0225643