Table > 1500 g. Both lower birth

Table 8 Summary of longitudinal cohort of refractive
outcomes in preterm infants with or without retinopathy of prematurity (ROP)

Age at examination

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Authors

n

%  Myopia or SE

Mean GA, BBW

6, 9 month; 2, 3 year

The ETROP study11

317

ET: 55.5%, 64.8%, 70.5%, 71.3%
CM: 61.4%, 70.7%, 71.5%, 71.6%

<1251 g 6 months: 3, 6 year Choi et al.39 65 No ROP: +0.22, +0.11, +0.27D ROP but no cicatricial ROP:   -2.37, -3.55, -3.54D Cicatricial ROP grade II:          -5.16, -5.13, -4.19D   <28 week, <1250 g 1, 2, 3 year Theng et al.40 113 ROP: 33.3%, 33.3%, 25% No ROP: 7%, 3.4%, 3.8% <34 week, <1500 g Birth, term, 6months, 1, 4 year Saunders et al.41 59 No ROP: +0.47, +0.87, +2.07, +1.86, +1.64D Full term: +3.47, +3.47, +2.36, +1.11D, n/a 1720 g   3470 g 6 months, 10-12 years O'connor et al.42, 43 572 ROP stage 1, 2, 3 & no ROP:  -1.18, +0.71, +0.85, +1.07 D <1700 g 6, 30 months Hsieh et al.16 109 Threshold ROP: -0.72, -1.21 D Regressed ROP: +0.35, +0.38 D No ROP: +0.78, +0.35 Full term: +1.62, +0.72   928 g 1171 g   1541 g 3177g Baseline, after 3 months Our study 80 Laser treated ROP: -0.9, -0.1 (62.5%, 40%) Regressed ROP: -0.6, 0.8 (37.5%, 7.5%) 835-2000 g 800-1940 g     The various studies like Lo CY et al44, Morrison et al45, Ricci et al46, Chen TC47 et al, O'Connor et al42,43 in case of Type II ROP report less percentage of myopia and low MSE as compare to laser treated ROP  as also observed in our study.            In our study astigmatism was comparable in both the groups. Astigmatism has been known to be associated with ROP.12, 20, 28 Most of the premature infants develop astigmatism, and children with advanced ROP tend to have more astigmatism.28 Holmstrom et al48 reported that 52 % of premature infants with birth weight < 1500 g developed astigmatism at 6 months corrected age and 18% had high astigmatism (>2D). Our study showed
comparable findings but only 5% eyes in both the groups have high astigmatism
probably could be explained on basis as our study also included preterm infants
with birth weight > 1500 g. Both lower birth weight and presence of ROP were
significantly associated with higher incidence of astigmatism. Yang et al26
reported that compared with age-matched controls, the laser-treated threshold
ROP eyes had significantly higher prevalence and severity of astigmatism at 9
years of age. Davitt et al12, in longitudinal of ETROP, reported
that nearly 43% of their laser-treated premature (<1251 g) infants, either early treated or conventional laser management, developed astigmatism. Kent et al and Laws et al have also reported increasing astigmatism with increasing stage of ROP.49,50       In normal development, most growth of the eye takes place in the first year of life; Axial length increases, the cornea and lens flatten after birth. There is no evidence of an association between increasing axial length and either prematurity or severity of ROP in historical data. In fact Mcloone et al27 reported that mean axial length appears to be shorter in sub-threshold and threshold eyes compared to those with no ROP, indicating that myopia in these infants is non axial in nature. In our study, mean axial length (mm) at baseline was 15.9  ± 0.8 in group A (range 15-18.4) and was 16.1 ± 0.5 in group B (range 15.3-17.1). Though the mean axial length was slightly smaller in group A the difference was not statistically significant difference between the two (p value 0.138). Mean axial length (mm) at the end of three months was 17.7 ± 1.1 (range 15.6-19.9) in group A and 18.1 ± 1in group B (range 16.6-20.7) and there is no statistically significant difference between the two (p value 0.204). So we can say, in our study myopia is non axial in nature as reported by Connolly et al17, Mcloone et al27, Kaur et al28, Zhu et al51 etc except in 2 eyes having high myopia. So axial length contributes to the development of high myopia.        Corneal curvature is usually steep in newborn infants and steeper in premature infants.28 Mean corneal curvature (D) was 52.5 ± 2.8 (44.8-59.81) in group A and 51.4 ± 2.8 in group B (45.94-57.63) at baseline and was 47.1 ± 2.7 (42.0-52.7) in group A and 47.6 ± 2.5 in group B (41.6-52.8) at the end of three months. Donzis et al52 observed a longitudinal decrease and rapid flattening in corneal curvature in eyes of six premature babies born at 28-34 weeks GA, starting from last few months of gestation and continuing for the first three months of life. Donzis et al reported that the corneal curvature is about 60 D at 28 weeks gestatinal age and about 51 D at term. . In similar way, in our study mean corneal curvature was steeper in both the groups at baseline and there was rapid flattening in corneal curvature in both the groups (more flattening in group A) after 3 months. The mean change in corneal curvature in both groups was significant. Yamamoto et al53 also reported a mean corneal curvature of 50.75D in premature infants compared with 48.06D in term infants, with an increased keratometric power concomitant with an increased severity of ROP. Both the groups had steep corneal curvatures supporting the concept of anterior segment arrest in premature eyes with ROP.        In our study we also measured central corneal thickness, which was comparable in both groups at baseline (p value 0.468) and at three months (p value 0.511). Corneal thickness (u) at baseline was 560.7 ± 62 (range 466-685) in group A and 552.3 ± 37.2 (range 470-665) in group B. Corneal thickness (u) at 3 months was 548.5 ± 44.8 (range 470-665) in group A and 539.9 ± 41.6 (range 450-640) in group B. None of studies in literature discuss about corneal thickness in ROP.       Table 7: Comparison of our biometric outcomes with data from literature Study population Mean age at time of study No. of eyes SE (D) AL  (mm) ACD (mm) Corneal power (D) Lens power (D) Preterm, laser treated, threshold ROP (Connolly et al 2002) 17 Retrospective   9.9 years 20 -4.56 22.89 3.44 46.68 22.80 Preterm, subthreshold ROP (Mcloone et al 2006) 27 Retrospective   11.2 years 9 +1.07 22.47 3.70 44.82 23.50 Preterm, laser treated, threshold ROP (Mcloone et al 2006) 27 Retrospective   11.1 years 16 -2.33 22.81 3.38 45.24 21.80 Preterm, laser treated, ROP (Kaur et al 2017) 28 Retrospective     7.37 years 72 -4.05 20.35 2.95 45.8 NA Preterm, prethreshold ROP (Zhu et al 2017)51 Retrospective   6 years 56 +1.44 22.35 3.05 43.88 NA Our study Laser treated threshold ROP Prospective   35 weeks 48 weeks       40     -0.9, -0.1     15.9,17.7 NA 52.5, 47.1 NA Spontaneously regressed ROP Prospective     37 weeks 50 weeks   40 -0.6, 0.8 16.1,18.1 NA 51.4, 47.6 NA          Many studies reported about shallower ACD and greater lens thickness in laser treated and spontaneously regressed ROP eyes.17,27,28,51 However other biometric determinants (ACD and LT) were not measured in our study which might have better explained exact refractive determinant of myopia. Another limitation of our study is that an ideal control group for this study would consist of infants with threshold ROP randomized to observation without laser treatment. However, in the light of unequivocal benefit of treatment, this is obviously unethical. The comparision of these cohort of infants with preterm infants having no ROP, would have also been beneficial to better explain biometric determinants of myopia. The other major limitation of our study is its small sample size and short follow up.       Our study is kind of pilot study. Future larger prospective studies are required to find out the exact causation of myopia. It is also important to find out long term changes of refractive outcome in these subset of infants and to find out what other environmental factors can be responsible. Low Functional acuity despite minimal refractive error in substantial proportion of infants also reported in some studies which needs further elaboration. Timely intervention and early recognition of refractive errors is therefore important to prevent amblyopia in these infants.