Progression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity Study: Findings at 4 to 6 years of age

doi:10.1016/j.jaapos.2012.10.025

Journal of American Association for Pediatric Ophthalmology and Strabismus

Volume 17, Issue 2, April 2013, Pages 124-128

https://doi.org/10.1016/j.jaapos.2012.10.025 Get rights and content

Purpose

To report the prevalence of myopia and high myopia in children <6 years of age born preterm with birth weights <1251 g who developed high-risk prethreshold retinopathy of prematurity and who participated in the Early Treatment for Retinopathy of Prematurity trial.

Methods

Surviving children from the cohort of 401 participants who had developed high-risk prethreshold ROP in one or both eyes underwent cycloplegic retinoscopy at 6 and 9 months corrected age and yearly between 2 and 6 years postnatal age. Eyes were randomized to receive treatment at high-risk prethreshold ROP or conventional management with treatment only if threshold ROP developed. Myopia (spherical equivalent ≥0.25 D) or high myopia (≥5.00 D) in eyes at 4-, 5-, and 6-year examinations was reported.

Results

At ages 4, 5, and 6 years, there was no difference in the percentage of eyes with myopia (range, 64.8%-69.9%) and eyes with high myopia (range, 35.3%-39.4%) between earlier treated and conventionally managed eyes.

Conclusions

Approximately two-thirds of eyes with high-risk prethreshold ROP during the neonatal period are likely to be myopic into the preschool and early school years. In addition, the increase in the proportion of eyes with high myopia that had been observed in both earlier-treated and conventionally managed eyes between ages 6 months and 3 years does not continue between ages 3 and 6 years.

Section snippets

Subjects and Methods

A total of 401 infants with birth weights <1251 g were enrolled in the ETROP randomized trial between October 1, 2000, and September 30, 2002, at 26 participating centers in the United States.² Study protocols were approved by the review boards of all participating institutions and complied with all guidelines of the US Health Insurance Portability and Accountability Act. Informed consent was obtained from parents or guardians of all participants before they were enrolled in the randomized

Prevalence of Myopia and High Myopia

Table 1 presents the percentage of ET and CM eyes with myopia and high myopia at ages 4, 5, and 6 years of age. In both the ET and CM groups, >60% of eyes had a myopic spherical equivalent of ≥0.25 D, and more than a third of the eyes had ≥5.00 D of myopia. The right two columns of the table further divide the group of CM eyes into CM eyes that progressed to threshold severity and were treated and those CM eyes that regressed without treatment. More than three-quarters of CM eyes that were

Discussion

The results of the ETROP study at 6 years of age indicated that earlier treated eyes with high-risk prethreshold ROP were not statistically different in terms of visual function when compared with the group of eyes that were conventionally managed (ie, eyes with high-risk prethreshold ROP that were treated only if they progressed to threshold ROP).⁹ However, in 2003, based on the Teller acuity results, the study showed a benefit in favor of early treatment. The ETROP investigators developed a

Acknowledgments

The members of the ETROP Cooperative Group gratefully acknowledge the contributions of Velma Dobson, PhD, whose untimely death in 2010 deprived the ROP community of a valued colleague and friend.

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Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial
2024, eClinicalMedicine
Concerns remain over the long-term safety of vascular endothelial growth factor (VEGF) inhibitors to treat retinopathy of prematurity (ROP). RAINBOW is an open label randomised trial comparing intravitreal ranibizumab (in 0.2 mg and 0.1 mg doses) with laser therapy in very low birthweight infants (<1500 g) with ROP.
Of 201 infants completing RAINBOW, 180 were enrolled in the RAINBOW Extension Study. At 5 years, children underwent ophthalmic, development and health assessments. The primary outcome was visual acuity in the better-seeing eye. The study is registered with ClinicalTrial.gov, NCT02640664.
Between 16-6-2016 and 21-4-2022, 156 children (87%) were evaluated at 5 years. Of 32 children with no acuity test result, 25 had a preferential looking test, for 4 children investigators reported low vision for each eye, and in 3 further children no vision measurement was obtained. 124 children completed the acuity assessment, the least square mean (95% CI) letter score in the better seeing eye was similar in the three trial arms—66.8 (62.9–70.7) following ranibizumab 0.2 mg, 64.6 (60.6–68.5) following ranibizumab 0.1 mg and 62.1 (57.8–66.4) following laser therapy; differences in means: ranibizumab 0.2 mg v laser: 4.7 (95% CI: −1.1, 10.5); 0.1 mg v laser: 2.5 (−3.4, 8.3); 0.2 mg v 0.1 mg: 2.2 (−3.3, 7.8). High myopia (worse than −5 dioptres) in at least one eye occurred in 4/52 (8%) children following ranibizumab 0.2 mg, 8/55 (15%) following ranibizumab 0.1 mg and 11/45 (24%) following laser therapy (0.2 mg versus laser: odds ratio: 3.99 (1.16–13.72)). Ocular and systemic secondary outcomes and adverse events were distributed similarly in each trial arm.
5-year outcomes confirm the findings of the original RAINBOW trial and a planned interim analysis at 2 years, including a reduced frequency of high myopia following ranibizumab treatment. No effects of treatment on non-ocular outcomes were detected.
Novartis Pharma AG.
Structural and refractive outcomes of intravitreal ranibizumab followed by laser photocoagulation for type 1 retinopathy of prematurity
2022, Journal of AAPOS
To evaluate refractive and structural outcomes for patients treated for retinopathy of prematurity (ROP) with the anti–vascular endothelial growth factor (anti-VEGF) agent ranibizumab and “delayed laser,” defined as any laser photocoagulation treatment administered at least 2 weeks and <1 year after the initial anti-VEGF injection.
The medical records of infants with type 1 ROP treated between 2015 and 2020 with intravitreal 0.25 mg ranibizumab followed by delayed laser photocoagulation, with a minimum of 6 months’ follow-up, were reviewed retrospectively. Refractive and structural outcomes were extracted from the record.
A total of 68 eyes of 34 neonates were included, with median gestational age of 24 weeks and birthweight of 657 g. Patients were aged 0.9 to 4.4 years at last follow-up; mean follow-up interval was 2.7 ± 1.02 years. There was no progression to stage 4 or 5 following treatment during the study period. At 2 years’ follow-up (mean age, 2.41 ± 0.23 years), median spherical equivalent (SE) was −0.13 D (IQR, 4.20 D). At most recent examination (mean age, 2.70 ± 1.02 years), the most common ocular findings included strabismus (32%), optic atrophy (24%), amblyopia (21%), high myopia (7%), and nystagmus (4%).
In our small cohort, neonates with type 1 ROP treated with intravitreal ranibizumab and delayed laser demonstrated good structural outcomes, with no progression to retinal detachment. We found lower rates of high myopia compared with previous reports of laser photocoagulation monotherapy.
Refractive outcomes following unilateral laser treatment for type 1 retinopathy of prematurity
2022, Journal of AAPOS
To compare refractive outcomes of infants with type 1 retinopathy of prematurity (ROP) in whom one eye was treated with laser and the fellow eye spontaneously regressed.
The medical records of infants who underwent IVB and laser treatment for type 1 ROP or aggressive posterior-ROP between January 2016 and December 2019 were retrospectively evaluated. Infants in whom ROP in the fellow eye regressed and for whom refractive data was available in the record were included in the study. Refractive outcomes of unilaterally treated infants were assessed.
A total of 283 cases were reviewed: of these, 17 experienced spontaneous regression in the fellow eye and were included. All unilateral laser-treated eyes had type 1 ROP in zone Ⅱ. The median age at treatment was 40 weeks’ postmenstrual age (IQR, 39-41). The mean spherical equivalent at the last examination was 2.1 ± 2.5 D in treated eyes and 2.50 ± 1.4 D in nontreated eyes, at a mean age of 25.0 ± 9.1 months (P = 0.378). Of the 7 infants who underwent fluorescein angiography, the median of the ratio of the length of the temporal retinal vascularization to the optic disk–to-fovea distance was 3.71 (3.22-3.79) in treated and 4.28 (3.90-4.49) in untreated eyes, at a median age of 18 months (P = 0.018).
In laser-treated eyes with peripheral zone Ⅱ ROP and with advanced treatment age, we did not observe a significant myopic change compared to the fellow untreated eye.
Real-World Visual Outcomes of Laser and Anti-VEGF Treatments for Retinopathy of Prematurity
2022, American Journal of Ophthalmology
Citation Excerpt :
Our group previously used anterior segment optical coherence tomography (OCT) to demonstrate that myopia after laser treatment is due to arrested anterior segment development as opposed to axial myopia seen in nonpreterm, school-aged children.19 Other studies have implicated more posterior location of ROP disease as a risk factor for myopia, finding zone I disease was associated with higher rates of myopia.20 In addition, studies have found that laser directed more posteriorly (eg, zone I or II treatment) is a risk factor for myopia.21
To characterize visual outcomes in children screened for retinopathy of prematurity (ROP).
Retrospective, interventional case series.
Patients who received ROP screening examinations at UCLA Medical Centers and were followed with outpatient eye examinations at Stein Eye Institute and/or Doheny Eye Institute (Los Angeles, California) were included. Data were collected on birth characteristics, worst type of ROP, and ROP treatment. Adverse visual outcomes included myopia, strabismus, amblyopia, macular dragging, and optic atrophy. Snellen visual acuity was reported for children 4 years and older.
A total of 175 infants (350 eyes) were included for analysis (mean gestational age = 28.2 weeks and birth weight = 1059 g) from a screening population of 539 infants (1078 eyes, 32.4% follow-up) over a 9-year period. Fifteen eyes received primary anti–vascular endothelial growth factor (anti-VEGF) therapy, whereas 59 eyes received primary laser therapy. Primary anti-VEGF therapy, as compared with primary laser treatment, was associated with a decreased incidence of amblyopia (adjusted odds ratio [aOR] = 0.6-0.86, P < .0001) after controlling for gestational age and birth weight. The rates of optic atrophy (P = .79), strabismus (P = .98), and myopia (P = .93) were not different between anti-VEGF and laser treatment groups. Infants receiving anti-VEGF therapy had more posterior disease than laser-treated infants (P = .041). Infants receiving laser therapy were more likely to have severe myopia (aOR = 1.02-1.3, P = .023), amblyopia (aOR = 1.12-1.61, P = .002), and optic atrophy (aOR = 1.01-1.32, P = .045) than infants not treated.
These findings add to the advantages of anti-VEGF treatment compared with primary laser treatment, particularly in posterior ROP.
2-year outcomes of ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW extension study): prospective follow-up of an open label, randomised controlled trial
2021, The Lancet Child and Adolescent Health
Intravitreal injection of vascular endothelial growth factor (VEGF) inhibitors is increasingly used to treat retinopathy of prematurity (ROP) in the absence of evidence about long-term efficacy or safety. In this prespecified interim analysis of the RAINBOW extension study, we aimed to prospectively assess outcomes at age 2 years.
RAINBOW was an open-label, randomised trial that compared intravitreal ranibizumab (at 0·1 mg and 0·2 mg doses) with laser therapy for the treatment of ROP in very low birthweight infants (<1500 g). Families of the 201 infants that completed the RAINBOW core study were approached for consent to enter the extension study, which evaluates treatment outcomes prospectively through to 5 years of age. At age 20–28 months corrected for prematurity, participants had ophthalmic, development, and health assessments. The primary outcome was the absence of structural ocular abnormalities; secondary outcomes included vision-related quality of life (reported by parents using the Children's Visual Function Questionnaire), development (assessed with the Mullen Scales of Early Learning), motor function, and health status. Investigator-determined ocular and non-ocular serious and other adverse events were recorded. This study is registered with ClinicalTrials.gov, NCT02640664.
Between June 16, 2016, and Jan 22, 2018, 180 infants were enrolled in the RAINBOW extension study, and 153 (85%) were evaluated at 20–28 months of age. No child developed new ocular structural abnormalities. Structural abnormalities were present in one (2%) of 56 infants in the ranibizumab 0·2 mg group, one (2%) of 51 infants in the 0·1 mg group, and four (9%) of 44 infants in the laser therapy group. The odds ratio of no structural abnormality was 5·68 (95% CI 0·60–54·0; p=0·10) for ranibizumab 0·2 mg versus laser therapy, 4·82 (0·52–45·0; p=0·14) for ranibizumab 0·1 mg versus laser therapy, and 1·21 (0·07–20; p=0·90) for ranibizumab 0·2 mg vs 0·1 mg. High myopia (–5 dioptres or worse) was less frequent after 0·2 mg ranibizumab (five [5%] of 110 eyes) than with laser therapy (16 [20%] of 82; odds ratio 0·19, 95% CI 0·05–0·69; p=0·012). Composite vision-related quality of life scores seemed higher among the ranibizumab 0·2 mg group (mean 84, 95% CI 80–88) compared with laser therapy (77, 72–83; p=0·063). Mullen Scales T-scores for visual reception, receptive and expressive language were distributed similarly between the three trial groups and there were similar proportions of infants with motor and hearing problems among treatment groups. The proportion of infants with respiratory symptoms and Z scores of standing height, weight, and head circumference were similarly distributed in the treatment groups. There were no adverse events considered by the investigator to be related to the study intervention.
2-year outcomes following ranibizumab 0·2 mg for the treatment of ROP confirm the ocular outcomes of the original RAINBOW trial and show reduced high myopia, with possibly better vision-related quality of life. This treatment did not appear to affect non-ocular infant development.
Novartis Pharma AG.
Preterm refraction and ocular biometry in children with and without retinopathy of prematurity in the first year of life
2021, Journal of AAPOS
To determine ocular biometric and refractive profiles of premature children at risk of retinopathy of prematurity (ROP), comparing those who did and did not require laser treatment.
In this prospective study, premature infants underwent biometry and refraction with their first ROP examination. Study parameters were assessed again at 3 months, 6 months, and 1 year. The main outcome measures were spherical equivalent, axial length, and keratometry.
A total of 122 infants (243 eyes) were included. At baseline, infants without ROP, those with ROP who never needed treatment, and those who later needed treatment had overall comparable axial length (P = 0.53) and myopia (P = 0.05); the highest severity group had higher corneal steepness and more myopia at baseline. At 1 year, children with laser-treated ROP had the shortest axial lengths, with the least decrease in keratometry, and the greatest increase in myopia (−2.0 D; P = 0.001). Anisometropia, if present initially, persisted through the 1-year examination. Mean refractive error was more myopic in zone 1 disease (P = 0.3) and in aggressive posterior ROP (P = 0.15).
Severe ROP is associated with disruption of emmetropization, and steeper corneas and more myopia at the first ROP examination, before any intervention. In our study cohort, these differences became more marked over the course of 1 year after laser therapy. The myopia in these cases was not axial. Laser therapy did not induce new anisometropia.

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: Supported by cooperative agreements 5U10 EY12471 and 5U10 EY12472 with the National Eye Institute of the National Institutes of Health, U.S Department of Health and Human Services, Bethesda, Maryland.

^∗: A list of the members of the Early Treatment for Retinopathy of Prematurity Cooperative Group is provided as e-Supplement 1, available at jaapos.org.

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Major ArticleProgression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity Study: Findings at 4 to 6 years of age

Purpose

Methods

Results

Conclusions

Section snippets

Subjects and Methods

Prevalence of Myopia and High Myopia

Discussion

Acknowledgments

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Ophthalmology

Major Article
Progression of myopia and high myopia in the Early Treatment for Retinopathy of Prematurity Study: Findings at 4 to 6 years of age