Postnatal growth and metabolic blood biomarkers in preterm infants developing reversible retinopathy of prematurity

Purpose To investigate predictive potential of growth and metabolic blood biomarkers in the development of milder, reversible retinopathy of prematurity (ROP) stages. Methods Biomarkers were obtained from blood samples collected every second postnatal week in a prospective, longitudinal cohort study including 108 infants born with a gestational age (GA) &lt;32 weeks in four hospitals in the Capital Region of Denmark, 2018-2019. ROP diagnoses were obtained from the electronic medical record system together with demographic, clinical and laboratory data. Measurement of glucose was summarised as mean and SD for every postnatal week and growth was summarised as increment in weight, head circumference (biparietal diameter) and length every postnatal week. The predictive potential of each biomarker and each marker of growth in turn were evaluated in univariate receiver operating characteristics curve analyses and in multivariate analyses including GA and small for gestational age (SGA) as known predictors. Results The strongest isolated postnatal predictor of ROP was weight gain at the second postnatal week with an area under the curve (AUC) of 0.80 (95% CI: 0.70 to 0.89). However, it only added insignificantly to the AUC (0.85; 95% CI: 0.76 to 0.93, adj. p=0.89) compared with GA and SGA alone (AUC=0.80, 95% CI: 0.70 to 0.90). Mean glucose in PNA weeks 1-4, glycaemic variability as measured by glucose SD weeks 1-3 PNA, and concentrations of adiponectin/glucose (mean) ratio were also associated with ROP diagnosis (AUCs ranging from 0.679 to 0.77) but did also not contribute significantly to the AUC compared with GA and SGA alone. Conclusions Postnatal growth and metabolic blood biomarkers were significantly associated with milder, reversible ROP, but none of these gave prediction over and above GA and SGA. Due to the small sample sizes, potential predictors could only be investigated in univariate analyses. Larger studies are needed to fully explore the predictive potential of all the biomarkers.</p

Evaluation of a Deep Learning-Derived Quantitative Retinopathy of Prematurity Severity Scale

Purpose To evaluate the clinical usefulness of a quantitative deep learning-derived vascular severity score for retinopathy of prematurity (ROP) by assessing its correlation with clinical ROP diagnosis and by measuring clinician agreement in applying a novel scale. Design Analysis of existing database of posterior pole fundus images and corresponding ophthalmoscopic examinations using 2 methods of assigning a quantitative scale to vascular severity. Participants Images were from clinical examinations of patients in the Imaging and Informatics in ROP Consortium. Four ophthalmologists and 1 study coordinator evaluated vascular severity on a scale from 1 to 9. Methods A quantitative vascular severity score (1–9) was applied to each image using a deep learning algorithm. A database of 499 images was developed for assessment of interobserver agreement. Main Outcome Measures Distribution of deep learning-derived vascular severity scores with the clinical assessment of zone (I, II, or III), stage (0, 1, 2, or 3), and extent (6 clock hours) of stage 3 evaluated using multivariate linear regression and weighted κ values and Pearson correlation coefficients for interobserver agreement on a 1-to-9 vascular severity scale. Results For deep learning analysis, a total of 6344 clinical examinations were analyzed. A higher deep learning-derived vascular severity score was associated with more posterior disease, higher disease stage, and higher extent of stage 3 disease (P < 0.001 for all). For a given ROP stage, the vascular severity score was higher in zone I than zones II or III (P < 0.001). Multivariate regression found zone, stage, and extent all were associated independently with the severity score (P < 0.001 for all). For interobserver agreement, the mean ± standard deviation weighted κ value was 0.67 ± 0.06, and the Pearson correlation coefficient ± standard deviation was 0.88 ± 0.04 on the use of a 1-to-9 vascular severity scale. Conclusions A vascular severity scale for ROP seems feasible for clinical adoption; corresponds with zone, stage, extent of stage 3, and plus disease; and facilitates the use of objective technology such as deep learning to improve the consistency of ROP diagnosis

The usefulness of the Retinomax autorefractor for childhood screening validated against a Danish preterm cohort examined at the age of 4 years

BACKGROUND AND PURPOSE: Refractometers have gained a foothold in childhood screening for ophthalmic disorders. Given the results of an ophthalmic follow-up of an extremely preterm Danish cohort, the results of the Retinomax autorefractor were further evaluated. MATERIALS AND METHODS: A nationwide cohort of infants born before gestational age 28 weeks (n=178) and 56 term controls were examined at the age of 4 years. Refraction was given as the cycloplegic Retinomax value. For this study, we analysed the equipment's confidence value on the printout and equipment-induced myopization (as the difference between refraction measured before and after topical cyclopentholate 1%), both items hypothetical with a view to having identified factual ophthalmic deviations. RESULTS: Thirty-two of 42 eyes with visual acuity ≤0.4 had high Retinomax confidence values (8–9); the Retinomax values were also high in 10 of 12 children with strabismus and lack of stereopsis. Low values (1–6) were recorded in 11 single eyes, 5 of which were normal (false positives). Three children already known to have low vision were unable to cooperate. The overall mean value for equipment-induced myopization was 1.9 D (range, 0–6.87 D). Myopization showed no correlation with visual acuity and corneal curvature, and a weak positive correlation with refractive value disappeared when the myopic outliers were excluded. CONCLUSIONS: The hand-held Retinomax seemed to be reliable for assessing refraction in 4-year-old children, provided a cycloplegic agent is applied; if used alone, the Retinomax would have missed several cases of ophthalmic deviation during screening. Equipment-induced myopization was not indicative