Myopia of Prematurity (MOP) is a form of refractive error that occurs in preterm infants. Unlike pathological myopia or school myopia, which are primarily caused by elongation of the axial length, MOP is an independent disease concept resulting from developmental changes in the anterior segment (cornea, lens, anterior chamber).
MOP is closely associated with retinopathy of prematurity (ROP) and its treatment, but the risk of myopic refractive error is also recognized in preterm infants who do not develop ROP. There is no specific ICD code or MeSH identifier for MOP; depending on the context, codes such as ROP (ICD-10: H35.109), degenerative myopia (H44.20), or myopia (H52.13) are used.
To explain the role of ROP in MOP, the following terms have been proposed:
However, these terms are not universally accepted and are not distinguished in many publications.
Early studies of infants with ROP observed that preterm infants, regardless of ROP status, tend to develop myopic refractive errors. In 1981, Fledelius reported that “myopia of prematurity” is almost inevitable in incomplete cicatricial retrolental fibroplasia.
Major clinical trials that contributed to the understanding of MOP are listed below.
Myopia prevalence in major clinical trials is shown below.
| Study | Population | Myopia Prevalence | High Myopia Prevalence |
|---|---|---|---|
| CRYO-ROP (overall) | At 1 year | 21% | 3.9% |
| CRYO-ROP (severe ROP) | At 1 year of age | 80% | Approximately 43% |
| ET-ROP | Prethreshold ROP | Approximately 65% | Approximately 35% |
In the CRYO-ROP study, a correlation was found: for every 100 g decrease in birth weight, the prevalence of myopia increased by 10%.
In the BEAT-ROP study, significant differences in mean spherical equivalent at 2.5 years were observed between the IVB group and the laser group. For Zone I ROP, the IVB group was -1.51 D and the laser group was -8.44 D (P < .001); for Zone II ROP, the IVB group was -0.58 D and the laser group was -5.83 D (P < .001). The incidence of high myopia (≥ -8.00 D) was 3.8% in Zone I and 1.7% in Zone II for the IVB group, compared to 51.4% and 36.4% respectively for the laser group.
In Japan, ROP develops in 86.1% of extremely low birth weight infants (birth weight < 1000 g), and the treatment rate is reported to be 41%. Given the high prevalence of ROP, the potential number of cases of MOP is also estimated to be substantial.
Ordinary pathological myopia is primarily caused by excessive elongation of the axial length, but in myopia of prematurity, the axial length is rather short relative to the refractive error. The main causes are developmental abnormalities of the anterior segment, such as steepening of the corneal curvature, thickening of the lens, and shallowing of the anterior chamber. The underlying mechanism is fundamentally different. For details, see the section on [“Pathophysiology”] (#6-病態生理学詳細な発症機序).
The main subjective symptom of MOP is decreased distance vision due to myopia. In infancy, symptoms are difficult to perceive, and it is often first detected through refraction testing. When astigmatism or anisometropia is present, more complex visual dysfunction occurs.
Characteristic findings of MOP are structural changes in the anterior segment. Comparison with pathological myopia is clinically important.
Myopia of Prematurity
Increased corneal curvature: The cornea is steeper than in full-term infants.
Lens thickening: The lens is thicker and has increased refractive power.
Shallow anterior chamber: Anterior chamber depth is decreased.
Relatively short axial length: Axial length is rather short relative to the refractive value.
Pathological Myopia
Excessive elongation of axial length: May exceed 26 mm.
Normal to flat corneal curvature: The cornea does not steepen.
Normal lens thickness: Lens abnormality is not the main cause.
Normal anterior chamber depth: Shallow anterior chamber is not characteristic.
The degree of myopia in MOP is not fixed from birth and progresses over time.
In a 17-year long-term study of threshold ROP treated with laser, all eyes evaluated at age 17 were myopic (mean spherical equivalent -6.35 D, range -1.25 to -12.38 D), and 43% of eyes had high myopia (< -6.0 D). Compared to full-term control eyes, these eyes had significantly more astigmatism, flatter horizontal corneal curvature, shallower anterior chamber depth, thicker lens, and shorter axial length. Myopia and astigmatism were reported to continue progressing until adolescence.
The main risk factors involved in the development of MOP are listed below.
It varies significantly. In the BEAT-ROP study, the mean spherical equivalent at 2.5 years of age for Zone I ROP was -1.51 D in the IVB group and -8.44 D in the laser group, showing a marked difference. The incidence of high myopia (≥ -8.00 D) was 3.8% in the IVB group versus 51.4% in the laser group. However, even children who received anti-VEGF therapy still have abnormal refractive development compared to full-term infants.
The basis for diagnosing MOP is the measurement of spherical equivalent by cycloplegic refraction. In infants, retinoscopy under cycloplegia with atropine or cyclopentolate is standard to eliminate the influence of accommodation.
Biometry using A-scan ultrasound or IOLMaster is useful for evaluating anterior segment structures.
In Japan, ROP screening is indicated for infants born at less than 34 weeks gestation or with a birth weight of 1,800 g or less. Cases requiring high-concentration oxygen therapy or mechanical ventilation are subject to fundus examination regardless of these criteria. The recommended timing for the first examination is from a corrected age of 29 weeks for infants born before 26 weeks gestation, and at 2-3 weeks after birth for those born at 26 weeks or later.
Monitoring for amblyopia due to high myopia, anisometropia, and strabismus is necessary. In children with a history of ROP, regular ophthalmologic follow-up should be continued to avoid missing these complications during the critical period of visual development.
Even in ROP eyes that regressed without treatment, late complications such as lattice degeneration, retinal tears, and retinal detachment have been reported in adulthood 1). Long-term follow-up for retinal complications as well as refractive errors is recommended in preterm infants with a history of ROP.
The basic treatment for MOP is refractive correction with glasses. Prescription should be given at an appropriate time according to clinical indications. If astigmatism or anisometropia is present, correction including these conditions is necessary.
If amblyopia due to high myopia, anisometropia, or strabismus is present, amblyopia treatment such as occlusion therapy or atropine penalization should be performed. Appropriate intervention within the sensitive period of visual development is important.
The choice of ROP treatment significantly affects the development and severity of MOP. A comparison of refractive outcomes by major treatment methods is shown below.
| Treatment | Refractive Outcome |
|---|---|
| Cryotherapy | Highest myopia risk |
| Laser photocoagulation | Better than cryotherapy |
| Anti-VEGF therapy (IVB) | Best |
Laser photocoagulation is effective for treating ROP, but it tends to worsen myopia and cause more ocular complications. Preterm infants who received anti-VEGF therapy have significantly milder myopia and astigmatism and a lower prevalence of high myopia compared to the laser treatment group. However, even in the anti-VEGF therapy group, refractive development still follows an abnormal course compared to full-term infants.
Glasses correction is the basic treatment. MOP is mainly due to excessive refractive power of the anterior segment, and correction with appropriate concave lenses can be expected to improve visual acuity. However, in cases of high myopia, corrected visual acuity may not be sufficient, and attention must also be paid to the complication of amblyopia.
The etiology of MOP is multifactorial, involving changes in corneal curvature, lens characteristics, and ocular elongation. The pathophysiological feature that defines MOP is abnormal development of the anterior segment.
Normal retinal blood vessels develop from near the optic disc at 12–14 weeks of gestation and extend along the retinal surface toward the ora serrata. They reach the periphery around 36–40 weeks of gestation, so in full-term infants, retinal vessels are already complete at birth. In preterm infants, on the other hand, there are avascular areas in the peripheral retina, and exposure to the abrupt environmental change from intrauterine to extrauterine life can cause cessation of normal vascular growth and formation of abnormal new vessels (ROP).
Eyes with MOP show the following characteristics.
In contrast to pathological myopia, which is characterized by axial elongation, myopia in MOP results from excessive refractive power of the anterior segment structures.
Several hypotheses have been proposed regarding the development of MOP.
The basic pathophysiology of ROP involves pathological angiogenesis driven by retinal ischemia. When the immature retina of a preterm infant is exposed to a hyperoxic environment, VEGF and IGF-1 are suppressed, inhibiting normal angiogenesis. Subsequent changes in oxygen environment lead to ischemia, releasing excessive VEGF and inducing pathological angiogenesis.
The exact mechanism is not fully understood, but the main hypotheses are as follows. Anti-VEGF therapy treats ROP without destroying the peripheral retina, thus preserving normal ocular growth signaling. Laser extensively destroys the peripheral retina, potentially disrupting the hyperopic defocus mechanism or causing mechanical restriction of ocular growth. Additionally, improvement in retinal vascular development with anti-VEGF may normalize local growth factors and promote proper anterior segment development.
The BEAT-ROP study is an important study that demonstrated the refractive benefit of anti-VEGF therapy in ROP treatment.
In the BEAT-ROP study, the mean spherical equivalent at 2.5 years of age was -1.51 D in the IVB group and -8.44 D in the laser group for Zone I ROP (P < .001). For Zone II ROP, it was -0.58 D in the IVB group and -5.83 D in the laser group (P < .001). High myopia (≥ -8.00 D) was observed in 3.8% of Zone I and 1.7% of Zone II eyes in the IVB group, compared to 51.4% and 36.4% in the laser group, respectively. A positive correlation between myopic degree and number of laser spots ( -0.14 D per 100 spots) was reported.
In a 17-year long-term study of threshold ROP treated with laser, all eyes evaluated at age 17 were myopic (mean SE -6.35 D), and 43% had high myopia. Compared to full-term controls, they had steeper corneal curvature, shallower anterior chamber depth, thicker lens, and shorter axial length. It was concluded that myopia and astigmatism continue to progress until adolescence.
A cross-sectional study comparing laser photocoagulation group, untreated ROP group, preterm infants without ROP, and full-term infants showed that the laser group had significantly steeper corneal curvature, more myopic spherical equivalent, shorter axial length, and shallower anterior chamber depth compared to full-term infants. Interestingly, the untreated regressed ROP group also showed steeper corneal curvature and shorter axial length compared to full-term infants, suggesting that peripheral retinal immaturity itself may contribute to the development of MOP.
Hamad et al. (2020) reported a multicenter retrospective study of 363 eyes of 186 patients who did not meet ROP treatment criteria in infancy and were untreated 1). Even in untreated regressed ROP eyes, late complications such as lattice degeneration, retinal tears, and retinal detachment were observed in adulthood, emphasizing the importance of long-term ophthalmic follow-up.
