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Retinopathy of prematurity in the intensive care nursery.

Retinopathy of prematurity (retrolental fibroplasia) is once again a problem of major concern to neonatalogists and ophthalmologists. Infants of low birth weight and gestational age seem to be most at risk. The clinical course of the disease is reviewed and a classification, simplistic in its approach, is presented. The discovery of retinopathy of prematurity in an infant should stimulate the ophthalmologist to follow the course of the disease very carefully. Preliminary experience may indicate that intervention on behalf of the infant is possible.

Gestational Age↗
PubMed1976

Retinopathy of prematurity and retinal detachment.

A group of 39 patients with retinopathy of prematurity or retrolental fibroplasia have been evaluated. Nine of these were prematures at the time of their examination and showed severe bilateral disease. One eye in each patient was treated with the other eye serving as a control using either Xenon photocoagulation or cryocoagulation. It will take many years to observe the effect of this form of therapy but initial changes suggest alterations in the amount of retinal traction and in the appearance of blood vessels at the posterior pole in some of the treated patients. Thirty older patients have been assessed and of these, 18 eyes developed retinal detachments. Of the 16 operated upon, 87% had successful scleral buckling surgery. Three additional patients had similar retinal findings to retrolental fibroplasia but no history of prematurity or oxygen therapy. These patients were not included in this study. Retinopathy of prematurity is much less common now that it was 2 decades ago, but still represents a significant cause of ocular morbidity and blindness.

Adolescent↗
PubMed1979

Anterior segment abnormalities in cicatricial retinopathy of prematurity.

Abnormalities that occur in the anterior segments of patients with retinopathy of prematurity have been studied in 72 eyes of 36 patients. The anterior chamber depth, the placido disc image on the cornea, the distortion of polarized light by corneal stress, and keratometry readings were recorded. There was a highly significant correlation between anterior chamber depth, retinopathy of prematurity, and keratometry readings (p less than .001). These findings emphasize the importance of careful follow-up examinations of the anterior segment in retinopathy of prematurity because cataracts, band keratopathy, acute hydrops, and angle-closure glaucoma can progressively occur as complications.

Adolescent↗
PubMed2026

Rates, Timing, and Predictors of Retreatment Across Risk-Cohorts in Retinopathy of Prematurity: Intravitreal Bevacizumab Injection Versus Laser.

OBJECTIVE: To characterize rates, timing, and predictors of retinopathy of prematurity (ROP) retreatment among infants treated with primary laser or intravitreal bevacizumab injection. DESIGN: Retrospective consecutive, comparative clinical study. PARTICIPANTS: Infants who underwent initial treatment for treatment-warranted ROP (TW-ROP) with either intravitreal bevacizumab or laser photocoagulation between 2017 and 2023. METHODS: Patients were stratified into two treatment groups: primary laser group vs primary bevacizumab group. MAIN OUTCOME MEASURES: Retreatment within the first 3 months (0-90 days) was assessed and classified as early (&#x2264;30 days) or late (31-90 days). RESULTS: Two hundred and thirty eight eyes of 122 infants were treated for ROP; of those, 181 (76.1%) eyes of 93 (76.2%) patients were included. There were 116 (64.1%) eyes in the bevacizumab group, and 65 (35.9%) eyes in the laser group. Thirty-three (18.2%) eyes-all micro- or nano-premature (<27 weeks GA and/or <800 grams)-required retreatment for TW-ROP. Sixteen (8.8%) required early retreatment at a median postmenstrual age (PMA) of 40.4 weeks (IQR, 38.44-43.3). There were differences in the proportion of early retreated infants (21.5% for laser vs 1.7% for injection, P < .001). Seventeen (9.4%) eyes required late retreatment. The median PMA at late retreatment was 45.6 weeks (IQR, 43.7-47.4). Infants in the bevacizumab group had lower odds of retreatment within three months than those with laser (OR, 0.23; 95% CI, 0.06-0.82). Similarly, patients in the bevacizumab group had lower odds of requiring early retreatment compared to those with laser (OR, 0.08; 95% CI, 0.04-0.18). Within eyes with retreatment, infants in the bevacizumab group had a later PMA at retreatment than those in the laser group (B = 6.81; 95% CI: 4.68-8.93). AROP was associated with earlier PMA at retreatment (B = -7.72; 95% CI, -9.36 to -6.10). CONCLUSION: In this study, early retreatment was low (8.8%), with most eyes initially treated with laser (21.5%) rather than bevacizumab (1.7%). Aggressive ROP was associated with earlier retreatment, highlighting its role as a marker of more severe disease. Compared to laser, bevacizumab was associated with lower overall and early retreatment, and delayed need for additional intervention when necessary. All retreatments occurred in micro- or nano-premature infants, suggesting that medium-to-low risk infants may require less strict post-treatment monitoring.

Humans↗
PubMed2026

Assessment of Methodological Bias in Studies Reporting Racial Differences in Retinopathy of Prematurity in the United States.

PURPOSE: To assess methodological biases in studies reporting racial and ethnic differences in retinopathy of prematurity (ROP). METHODS: Systematic review of peer-reviewed studies published between 2014 and 2024 that reported on ROP outcome measures by race, ethnicity, or social determinants of health (SDOH). Three reviewers independently assessed each observation for selection and collider bias using definitions derived from perinatal epidemiology literature. Findings were also compared using a structured comparative synthesis between studies with and without identified methodological bias. RESULTS: A structured PubMed search identified 78 articles; 13&#x2009;met inclusion criteria, with one study contributing two distinct analytical approaches, yielding 14 total observations. Survivorship bias was identified in 6 of 14 observations (42.9%), primarily due to the exclusion of infants who died prior to ROP screening. Potential collider bias was most common, found in 9 of 14 observations (64.3%), and was introduced through adjustment or stratification by gestational age and/or birthweight. Three studies did not exhibit either assessed biases. Among studies with identified bias, 8 of 10 observations reported lower ROP risk among Black versus White infants, whereas 3 of 4 observations without identified bias reported higher ROP risk or incidence among Black infants. CONCLUSION: Methodological biases in ROP studies investigating race or ethnicity are prevalent. Adjustment for gestational age or birthweight may introduce spurious race-ROP associations and contribute to paradoxical findings. Further exploration of the impact of SDOH on disease outcomes may reduce the misattribution of race as a biological risk factor and improve the interpretation of ROP disparities.

Collider bias↗
PubMed2026

Proteomic Profile in Retinopathy of Prematurity: A Secondary Analysis of the Mega Donna Mega Randomized Clinical Trial.

IMPORTANCE: Identifying early proteomic profiles in infants who develop severe retinopathy of prematurity (ROP) may reveal targets for preventive interventions to reduce retinal vessel loss and the subsequent risk of severe ROP. OBJECTIVE: To assess early longitudinal profiles of blood protein levels in preterm infants with or without severe ROP and the effect of arachidonic acid (AA) and docosahexaenoic acid (DHA) supplementation. DESIGN, SETTING, AND PARTICIPANTS: This was an exploratory, post hoc analysis of serum proteome profiles in preterm infants in the double-masked Mega Donna Mega (MDM) randomized clinical trial using targeted Olink Proximity Extension Assay proteomics covering 538 analytes. The setting was 3 university hospitals in Sweden and included extremely preterm infants born before 28 weeks of gestational age (GA), from 2016 to 2019. Data were analyzed from January to March 2025. EXPOSURES: All infants received standard nutrition; additionally, half received enteral lipid supplementation with AA/DHA (100/50 mg/kg per day) from birth to term equivalent age. MAIN OUTCOMES AND MEASURES: Longitudinal protein profiles during the first month of life were examined using mixed models for repeated measures, adjusted for GA, study center, and AA/DHA supplementation, and tested for the interaction between severe ROP (stage &#x2265;3 and/or treated) and postnatal age. RESULTS: A total of 177 extremely preterm infants (mean [SD] GA, 25.6 [1.4] weeks; 100 male [56.5%]) were included, of whom 50 (28.2%) developed severe ROP. Of 538 longitudinal analyzed proteins, 109 protein profiles in the first month of life associated with severe ROP, proteins related to immune response, apoptotic processes, blood coagulation, and lipid metabolism. The most pronounced association with severe ROP was a fast rise in fibroblast growth factor 21 (FGF-21; &#x3b2;&#x2009;=&#x2009;0.68; 95% CI,&#x2009;0.39-0.97; Q =.002) and tissue plasminogen activator (tPA; &#x3b2;&#x2009;=&#x2009;0.21; 95% CI,&#x2009;0.13-0.29; Q <.001) during the first postnatal days. The increase in serum FGF-21 level in the first week of life was associated with lower GA, lower birth weight, low enteral energy intake, and more days receiving mechanical ventilation. No association was observed between AA/DHA supplementation and the proteome. CONCLUSIONS AND RELEVANCE: In this post hoc exploratory analysis of data from the MDM randomized clinical trial, a fast rise in FGF-21 levels, a metabolic stress-induced hormone, during the first postnatal days was strongly associated with the development of severe ROP in extremely preterm infants. These findings suggest that early interventions improving bioenergetic status may help prevent severe ROP. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03201588.

Humans↗
PubMed2025

Retinal hypoxia reversal with PLGA-oxygen nanobubbles.

Pathologies associated with retinal hypoxia, including diabetic retinopathy, central/branch retinal artery occlusion (CRAO/BRAO), central/branch retinal vein occlusion (CRVO/BRVO), retinopathy of prematurity, sickle cell retinopathy, etc., have limited effective therapeutic intervention strategies. To address this shortcoming, herein we propose a biocompatible and biodegradable poly (lactic-co-glycolic acid) shell-based oxygen nanobubbles (PLGA-ONBs) platform, formulated with PLGA, polyvinyl alcohol (PVA), and NaHCO3. The formulation of a novel PLGA-ONBs was proposed, and the synthesis process was optimized with respect to dependent (sonication power, PVA, and NaHCO3 concentrations) and response (hydrodynamic diameter and oxygen capacity) variables. The optimized formulation has a concentration of (13.8 &#xb1; 0.01) &#xd7; 1010 particles per ml with a hydrodynamic diameter of 142.83 &#xb1; 11.46 nm, and oxygen loading capacity of 47.2 &#xb1; 2.4 mg L-1. After 4 weeks of storage, the ONBs were found to have an oxygen concentration of 38.9 &#xb1; 2.9 mg L-1, indicating excellent oxygen retention capability. The PLGA-ONBs tested in vitro in Muller and R28 retinal cell lines demonstrated excellent biocompatibility and potential to mitigate hypoxia. In addition, the PLGA-ONBs treatment on hypoxic cells demonstrated restoration of mRNA expression of three key hypoxic genes (HIF-1&#x3b1;, PAI-1, and VEGF-A) to normoxic states, indicating hypoxia reversal potential. Biosafety of the PLGA-ONBs was demonstrated in a rabbit model, demonstrating promise in clinical translation. The PLGA-ONBs developed exhibited excellent oxygen loading and retention, potential in hypoxia mitigation, and a safety profile that could be a promising route to treating ischemic diseases of the eye.

Polylactic Acid-Polyglycolic Acid Copolymer↗
PubMed1977

[Prematurity and retinal detachment (author's transl)].

Cases of retinal detachment due to retinopathy of prematurity are presented. 1. There are cases of total retinal detachment without a complete retrolental fibroplasia. 2. Very typical are cases with a dragged disc and mascular ectopy due to preretinal strands in the temporal periphery, the symptoms of an earlier retinopathy of prematurity. By traction these temporal alterations can cause a retinal detachment, the distortion of the retinal vessels can heavily increase after surgical reattachment of the retina. 3. There are cases of juvenile myopes without further signs of a retinopathy of prematurity. A retinal detachment may occur, due to round holes.

Humans↗
PubMed1977

The prophylactic treatment of retrolental fibroplasia.

10 premature infants with stage 3 retinopathy of prematurity have had photocoagulation and/or cryocoagulation therapy to one eye and have been followed for a period of 1-6 years. Although the long-term results of this therapy are not known, particularly in the prevention of retinal detachment, early observations suggest that treatment is neither harmful nor particularly beneficial. Macular dragging does not seem to be influenced by treatment. The refractive error, as one would expect, does not appear to be altered by this form of therapy. Marked amelioration of the vascular dilatation and tortuosity at the posterior pole is apparent shortly after treatment. It is stressed that this is a trial project and until more definite beneficial results are obtained, treatment of stage 3 retinopathy should be deferred. Retinal detachments (stage 4) may be quite amenable to a buckling procedure.

Child↗
PubMed1977

[Early ERG-signs of retrolental fibroplasia (author's transl)].

Examinations of retinograms of premature infants by the authors showed a time lag, changes in the wave form and reduction of the bioelectric activity of the retina (which shows itself very early) in association with the first signs of retrolental fibroplasia. In their experience the ERG becomes normal when the fibroplasia stabilizes itself early or when the retinal changes regress. In conclusion it must be stressed that with progression of the fibroplasia and retinal changes the biological activity of the retina also suffers.

Bioelectric Energy Sources↗