Successful treatment of retinopathy of prematurity in oculocutaneous albinism with OCA2 variants: a case report and review of literature.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of autosomal recessive hereditary disorders that affect melanin biosynthesis, resulting in abnormalities in hair, skin, and eyes. Retinopathy of prematurity (ROP) is a proliferative retinopathy mainly observed in premature infants with low birth weight and early gestational age, but it can also affect full-term infants or children with normal weight, particularly in developing countries. The coexistence of ROP and OCA is rare. There is limited documentation regarding treatment approaches, with few studies reporting positive outcomes with laser treatment due to the absence of melanin pigment. This study discusses the treatment challenges in a female infant diagnosed with ROP and OCA, and underscores the importance of genetic analysis in guiding therapeutic decisions for this rare comorbid condition. CASE PRESENTATION: The study presents a case of ROP occurring concurrently with OCA. Genetic testing revealed two variants, c.727C > T (p.R243C) and c.1832 T > C (p.L611P), in the OCA2 gene, inherited from the patient's mother and father, respectively. The identified mutations were consistent with a diagnosis of OCA2, classified as a subtype of OCA. The patient initially received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection, followed by laser photocoagulation therapy for a recurrent event. A favorable outcome was observed during the 2-month follow-up period. CONCLUSIONS: The co-occurrence of ROP and OCA is a rare phenomenon, and this is the first recorded case in the Chinese population. The current case supports the use of laser as the primary treatment modality for ROP in OCA2 patients with partial pigmentation impairment. Furthermore, genetic analysis can aid in predicting the effectiveness of laser photocoagulation in this patient population.

Macular Curvature in Adults Born Preterm With and Without ROP: Results from the Gutenberg Prematurity Eye Study.

Purpose: This study investigated the effects of prematurity and retinopathy of prematurity (ROP) as well as the associations of the ocular geometry with macular curvature in adults. Methods: The Gutenberg Prematurity Eye Study is a retrospective cohort study of preterm and full-term participants aged 18 to 52 years with a prospective ophthalmologic examination. The main outcome measure was the macular curvature in the central foveal optical coherence tomography (OCT) scan and its associations with gestational age (GA), birth weight and birth weight percentile, ROP occurrence, ROP treatment, and other perinatal factors were evaluated in univariable and multivariable linear regression analyses. Furthermore, a second model assessed the association of ocular geometry with macular curvature. Results: In the present study, 550 eyes of 284 adults born preterm and 277 eyes of 139 adults born full-term were examined (aged = 28.7 ± 8.7 years, 240 female subjects). In multivariable analyses for perinatal parameters, ROP treatment (B = -52.44, P = 0.023) and maternal smoking during pregnancy (B = 26.41, P = 0.019) showed an association with macular curvature. Regarding ocular geometric parameters, posterior segment length (B = 9.07, P < 0.001) and subfoveal choroidal thickness (B = -0.26, P < 0.001) were associated with macular curvature, central corneal thickness, anterior chamber depth, lens thickness, and foveal retinal thickness were not associated. Conclusions: Adults treated for ROP had relatively more negative curvature values compared to the full-term group, indicating a macular protrusion toward the vitreous cave. A thicker subfoveal choroidal thickness was associated with a flatter macular curvature, whereas a longer posterior segment length was associated with a steeper macular curvature indicating the characteristics of the myopic elongation of the eye.

Visual impairment burden in retinopathy of prematurity: trends, inequalities, and improvement gaps.

Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment, and the increase in number and survival of premature infants may inflate its burden globally. We aimed to comprehensively assess the trends and inequalities in the burden of ROP-related visual impairment and to identify improvement gaps to facilitate appropriate actions in neonatal care systems. We obtained ROP data from the Global Burden of Disease 2019 study. We employed joinpoint regression analysis to assess the trends of the burden of ROP-related visual impairment, measured by age-standardised prevalence rates, health equity analysis methods to evaluate cross-country burden inequalities, and data envelopment and stochastic frontier analyses to identify improvement gaps based on the development status, i.e., sociodemographic index (SDI). Between 1990 and 2019, the age-standardised prevalence rates of ROP-related visual impairment significantly increased worldwide (average annual percentage change: 0.23 [95% confidence interval, 0.21-0.26] among males and 0.26 [0.25-0.27] among females), primarily in developed regions. Although significant SDI-related cross-country inequalities were identified, these reduced over time (slope index of inequality: -57.74 [-66.22 to -49.25] in 1990 to -29.68 [-38.39 to -20.97] in 2019; health concentration index: -0.11 [-0.13 to -0.09] in 1990 to -0.07 [-0.09 to -0.06] in 2019). Notably, some less-developed countries exhibited superior performance despite limited resources, whereas others with a higher SDI delivered lagging performance.  Conclusion: The global burden of ROP-related visual impairment has steadily increased between 1990 and 2019, with disproportionate burden concentration among less-developed countries, requiring appropriate preventive and intervention measures. What is Known: • Retinopathy of prematurity (ROP) is an important cause of avoidable childhood visual impairment. • The prevalence of ROP is anticipated to increase due to the growing number of extremely premature infants. What is New: • The prevalence of ROP-related visual impairment has increased worldwide, primarily in developed regions, with declining but persisting cross-country inequalities. • The increasing burden of ROP-related visual impairment should be considered as part of global and national health agendas, requiring interventions with proven efficacy.

Ophthalmic sequelae of prematurity in late childhood and adulthood: A review.

Advances in the care of premature infants have resulted in unprecedented rates of survival of these infants into adulthood, including those born at very low gestational ages. Ophthalmologists have historically followed premature infants to assess for the presence of and potential need for treatment of retinopathy of prematurity. However, a growing body of literature suggests that the ophthalmic consequences of prematurity extended beyond retinopathy of prematurity and that ophthalmic sequelae of prematurity can endure through adulthood even among formerly preterm adults who were never diagnosed with retinopathy of prematurity. These abnormalities can include a range of both anterior segment and posterior segment sequelae, including higher rates of corneal aberrations, ocular hypertension, strabismus, foveal anomalies, and retinal tears and detachments. This review aims to summarise this literature, underscoring the importance of lifelong examinations and regular monitoring for these complications among adults who were born prematurely.

Outcomes of Modified Limbal Lensectomy-Vitrectomy in Stages 4B and 5 Retinopathy of Prematurity with Extended Retrolental Fibroplasia.

PURPOSE: To report on the anatomical and functional outcomes of a modified limbal lensectomy-vitrectomy (LV) approach for stages 4B and 5 retinopathy of prematurity (ROP) as defined in the International Classification of Retinopathy of Prematurity, 3rd Edition (ICROP 3). DESIGN: Retrospective, monocentric, consecutive case series. PATIENTS: Infants with ROP that underwent limbal LV for diffuse retrolental fibroplasia. METHODS: Clinical charts and Retcam photographs were reviewed. Surgical approach consisted of a limbal LV through peripheral iridectomies with centripetal dissection of the preretinal fibrosis. MAIN OUTCOME MEASURES: Anatomical success and visual function at last follow-up were evaluated. Multivariate logistic regression was used to explore potential prognostic factors affecting the anatomical outcome. RESULTS: A total of 128 eyes of 81 patients with a mean gestational age of 28.7 ± 3.0 weeks and a mean birthweight of 1244 ± 429 g were included. Eighteen eyes (14.1%) had a stage 4B, 24 (18.8%) a stage 5B, and 86 a stage 5C (67.2%) ROP. Mean age at surgery was 57.4 ± 36.3 weeks and mean postoperative follow-up was 22.7 ± 20.4 months. Only 5 eyes (3.9%) had prior peripheral retinal ablation. Macular reattachment was achieved in 74 eyes (57.8%). Controlling for other baseline factors, a stage 5C (versus stage 4B, odds ratio [OR] = 6.9 [1.5-32.1], P = 0.01 and versus stage 5B, OR = 7.4 [1.5-37.1], P = 0.02), the presence of vascular activity (OR = 6.4 [2.3-18.1], P < 0.001), and the presence of Schlieren sign (OR = 13.0 [2.1-82.2], P = 0.006) were associated with a failure of macular reattachment. Visual acuity was assessed in 92 eyes (71.9%), among which 59 eyes (64.1%) had light perception or better. CONCLUSIONS: Modified limbal LV resulted in macular reattachment in more than half of eyes with ROP-related retinal detachment and diffuse retrolental fibrosis. A stage 5C based on ICROP 3, the presence of vascular activity, and a Schlieren sign were significantly associated with a failure of macular reattachment. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Corneal refractive error and astigmatism in patients aged 6 to 18 years with a history of retinopathy of prematurity and birth weight of <1500 g.

PURPOSE: To investigate corneal refractive power (CR) and astigmatism (AS) in 6- to 18-year-old children with a history of retinopathy of prematurity (ROP) and birth weight of <1500 g who either did or did not undergo retinal photocoagulation (PC). STUDY DESIGN: Retrospective study. METHODS: We examined 143 eyes of 77 children in 2021. The children were divided into three groups for evaluation of CR and AS: those with a birth weight of ≥2500 g (normal birth weight [NBW] group, 13 eyes) as controls, those with spontaneously resolved ROP (sr-ROP group, 27 eyes), and those who underwent PC for treatment of ROP (PC-ROP group, 103 eyes). Swept-source anterior segment optical coherence tomography was used to analyze the cornea. RESULTS: The median CR in the NBW, sr-ROP, and PC-ROP groups was 42.2 (41.3, 42.8) diopters (D), 44.5 (43.2, 45.5) D, and 45.2 (43.8, 46.6) D, respectively. The median AS in the NBW, sr-ROP, and PC-ROP groups was 1.2 (1.0, 1.5) D, 1.1 (0.8, 1.6) D, and 2.1 (1.4, 2.7) D. In the PC-ROP group, the with-the-rule astigmatic axis was 97%. In all three groups, a strong positive correlation was found between the mean anterior and posterior CR (NBW: r=0.795, sr-ROP: r=0.842, PC-ROP: r=0.890) and AS (NBW: r=0.883, sr-ROP: r=0.841, PC-ROP: r=0.860). CONCLUSION: CR was significantly higher in the sr-ROP (p=0.013) and PC-ROP (p<0.001) groups than in the NBW group. The PC-ROP group had significantly more AS than the sr-ROP group. There was a strong correlation between the anterior and posterior CR and AS.

Successful management of iatrogenic tear in vitrectomy for retinopathy of prematurity-related retinal detachment: a case report / Tratamento bem-sucedido de rotura iatrogênica em vitrectomia para descolamento de retina por retinopatia da prematuridade: relato de caso

ABSTRACT Retinal detachment related to retinopathy of prematurity is a surgical challenge, and vitrectomy can directly release transvitreal traction resulting from fibrous proliferation. The presence of iatrogenic breaks is a poor prognostic factor and has been considered a dismal prognosis. We report a case of premature female baby that underwent a 3-port 23-Gauge pars plana vitrectomy for stage 4A retinopathy of prematurity, with intraoperative progressive rhegmatogenous detachment complication. Lensectomy, extensive membrane dissection and vitreous shaving, followed by a posterior retinotomy, fluid air exchange, extensive peripheral photocoagulation and C3F8 15% injection were performed. Successful anatomical result was obtained.

RESUMO O descolamento de retina relacionado à retinopatia da prematuridade é um desafio cirúrgico, e a vitrectomia é um procedimento capaz de romper diretamente a tração vitreorretiniana resultante da proliferação fibrosa. A presença de roturas iatrogênicas é um fator prognóstico ruim e tem sido considerada como prognóstico sombrio. Relatamos um caso de bebê prematuro do sexo feminino que foi submetido à vitrectomia via pars plana (23 Gauge; três incisões), para retinopatia da prematuridade estágio 4A, complicada por descolamento regmatogênico progressivo intraoperatório. Foram realizadas lensectomia, dissecção extensa da membrana e aspiração vítrea, seguidas de retinotomia posterior, troca fluido-ar, fotocoagulação periférica extensa e injeção de C3F8 a 15%. O resultado anatômico bem-sucedido foi obtido.

Limited Hyperoxia-Induced Proliferative Retinopathy (LHIPR) as a Model of Retinal Fibrosis, Angiogenesis, and Inflammation.

The progression to fibrosis and traction in retinopathy of prematurity (ROP) and other ischemic retinopathies remains an important clinical and surgical challenge, necessitating a comprehensive understanding of its pathogenesis. Fibrosis is an unbalanced deposition of extracellular matrix components responsible for scar tissue formation with consequent tissue and organ impairment. Together with retinal traction, it is among the main causes of retinal detachment and vision loss. We capitalize on the Limited Hyperoxia Induced Retinopathy (LHIPR) model, as it reflects the more advanced pathological phenotypes seen in ROP and other ischemic retinopathies. To model LHIPR, we exposed wild-type C57Bl/6J mouse pups to 65% oxygen from P0 to P7. Then, the pups were returned to room air to recover until later endpoints. We performed histological and molecular analysis to evaluate fibrosis progression, angiogenesis, and inflammation at several time points, from 1.5 months to 9 months. In addition, we performed in vivo retinal imaging by optical coherence tomography (OCT) or OCT Angiography (OCTA) to follow the fibrovascular progression in vivo. Although the retinal morphology was relatively preserved, we found a progressive increase in preretinal fibrogenesis over time, up to 9 months of age. We also detected blood vessels in the preretinal space as well as an active inflammatory process, altogether mimicking advanced preretinal fibrovascular disease in humans.

Surgical outcomes in aggressive retinopathy of prematurity (AROP)-related retinal detachments.

Introduction: Aggressive retinopathy of prematurity (AROP) is a severe and progressive variant of retinopathy of prematurity (ROP) rapidly forming fibrous tissue extending from the disc toward the posterior lens surface progressing to Stage 5 disease without traversing the classical course that includes Stages 1 to 3. Since AROP behaves differently from type 1 ROP, this study was undertaken to evaluate the surgical outcome of AROP-related detachments. Methods: Retrospective analysis of data from electronic medical records of babies diagnosed with AROP-related detachments who underwent micro-incision vitrectomy surgery (MIVS) was included. The demographic data, details of primary intervention (laser and/or intravitreal bevacizumab), and surgery were noted. In a subset of patients, surgical intervention was planned early at the onset of fibrovascular tissue. Results: 43 eyes of 26 babies with median birth weight 1175 g and median gestational age of 29 weeks were analyzed. 42/43 eyes underwent primary intervention in form of laser and/or anti-VEGF injection before surgery. 41.8%, 25.5%, and 32.5% eyes progressed to stages 4A, 4B, and 5, respectively, requiring surgical intervention. 66% eyes underwent lensectomy and vitrectomy (LV), and 44% eyes underwent lens sparring vitrectomy (LSV). 58% eyes had attached macula. 44% eyes that had a relatively less vascular diseases had better anatomical outcome (P = 0.019). At final follow-up, 53.4% eyes followed or at least had light fixation, and 77.7% eyes undergoing LSV fixated and/or followed light compared to 33% for LV (P = 0.04). Conclusion: Challenges in AROP include rapid progression to advanced stages of ROP requiring close monitoring and multiple interventions. Surgeries for AROP have a favorable anatomical and functional outcome in 58% and 53%, respectively. Eyes undergoing lens sparing vitrectomy had better visual outcomes.

Effects of Milrinone on Neonates after Patent Ductus Arteriosus Ligation: A Retrospective Nationwide Database Study.

INTRODUCTION: Milrinone is administered after patent ductus arteriosus (PDA) ligation to prevent and treat postoperative hemodynamic instability (i.e., postligation cardiac syndrome). We aimed to explore the effectiveness of milrinone on in-hospital outcomes in infants who underwent PDA ligation using a nationwide inpatient database in Japan. METHODS: Using the Japanese Diagnosis Procedure Combination database, we identified patients who received milrinone after PDA ligation (n = 428) in neonatal intensive care units between July 2010 and March 2021 and those who did not (n = 3,392). We conducted a 1:4 propensity score-matched analysis with adjustment for background characteristics (e.g., gestational age, birth weight, comorbidities, preoperative treatments, and hospital background) to compare morbidities (bronchopulmonary dysplasia, intraventricular hemorrhage, necrotizing enterocolitis, and retinopathy of prematurity), mortality, total hospitalization costs, and other outcomes. For sensitivity analysis, we performed an overlap propensity score-weighted analysis. RESULTS: In-hospital morbidity, bronchopulmonary dysplasia, intraventricular hemorrhage, and necrotizing enterocolitis occurred in 58%, 48%, 9.5%, and 7.1% of patients, respectively; the in-hospital mortality was 5.4%. After 1:4 propensity score matching, no significant difference was observed regarding mortality (7.1 vs. 5.7%), in-hospital morbidity (55 vs. 50%), bronchopulmonary dysplasia (44 vs. 41%), intraventricular hemorrhage (7.8 vs. 9.1%), necrotizing enterocolitis (8.5 vs. 8.9%), retinopathy of prematurity (21 vs. 22%), or total hospitalization costs (median: approximately 86,000 vs. 82,000 US dollars) between milrinone users (n = 425) and nonusers (n = 1,698). Sensitivity analyses yielded consistent results. CONCLUSIONS: Milrinone use after PDA ligation was not associated with improved in-hospital outcomes, such as mortality and morbidity.

Strabismus in Retinopathy of Prematurity: Risk Factors and the Effect of Macular Ectopia.

Objectives: This study aimed to examine factors associated with strabismus in patients with retinopathy of prematurity (ROP) and the relationship between strabismus and macular ectopia. Materials and Methods: Patients with ROP were divided into three groups: Group 1, patients with spontaneous regression (n=45); Group 2, patients who received laser treatment (n=70); and Group 3, patients who underwent surgical treatment (n=91). Rates of anisometropia, amblyopia, nystagmus, macular ectopia, and retinal pathologies were evaluated and their impacts on strabismus development were determined. Disc-to-fovea distance (DFD) was measured from color fundus photographs and the correlation of macular ectopia with severity of strabismus was evaluated. Results: A total of 206 patients were included. Rates of anisometropia, amblyopia, nystagmus, macular ectopia, retinal pathologies causing vision loss, and strabismus were higher in Group 3 (p=0.0001) and correlated with higher stages of ROP (p=0.0001). Macular ectopia (p=0.005), retinal pathologies (p=0.005), and amblyopia (p=0.012) had the strongest impact on strabismus development in ROP patients. DFD and strabismus severity were not significantly correlated (p=0.364). Mean visual acuity (VA) was significantly higher in orthophoric patients compared to those with esotropia and exotropia (p=0.027). Esotropic patients had lower VA compared to patients with exotropia, but this finding was not statistically significant (p=0.729). Conclusion: Presence of macular ectopia, retinal pathologies, and amblyopia were the most strongly correlated risk factors for strabismus development in ROP patients. DFD was not associated with severity of strabismus. Exotropia was mostly related to higher DFD and a possible relationship between esotropia and lower VA was observed.

The Development of Retinal Function and Refractive Error in Children With Retinopathy of Prematurity.

Purpose: The purpose of this study was to test the hypothesis that retinopathy of prematurity (ROP) prolongs development of rod-mediated thresholds for detection of stimuli at 10 degrees but not 30 degrees eccentricity. In addition, to evaluate the thresholds at each site for an association with visual acuity (VA) and spherical equivalent (SE). Methods: We estimated rod-mediated dark-adapted thresholds (DATs) for the detection of 2 degree diameter, 50 ms, blue (λ < 510 nm) flashes at 10 degrees and 30 degrees eccentric in former preterm subjects (n = 111), stratified by ROP severity: None (n = 32), Mild (n = 66), and Severe (n = 13). We also tested Term-born (n = 28) controls. To determine the age at half-maximal sensitivity (Agehalf) for each group and eccentricity, we fit DATs to logistic growth curves. We obtained VA and SE for Preterm subjects and evaluated the course of threshold development at 10 degrees and 30 degrees for significant association with VA and SE predicted at age 10 years. Results: DAT development at 10 degrees was significantly delayed in ROP (Mild and Severe); ROP did not significantly alter DAT development at 30 degrees. At age 10 years, among Preterm subjects, both VA and SE were significantly associated with group (None,Mild, and Severe). SE was predicted by the course of DAT development at 30 degrees. VA was not associated with the course of DAT development at 10 degrees. Conclusions: At 10 degrees, ROP-whether mild or severe-is associated with significant delays in DAT development, evidence that the late-maturing central retina is vulnerable to ROP. The association of 30 degree threshold and myopia are evidence that more peripheral retina is important to refractive development.

Visual impairment due to retinopathy of prematurity and concomitant disabilities in the Netherlands.

AIM: Determine incidence of visual impairment due to retinopathy of prematurity (ROP) and concomitant disabilities between 2009 and 2018 in the Netherlands and compare data to four former similar studies. Secondly, monitor if infants were missed for ROP-screening since the adoption of stricter, risk factor guided criteria (2013). METHODS: Retrospective inventory on anonymous data of infants diagnosed with ROP from Dutch visual impairment-institutes. Data including: best corrected visual acuity, ROP-treatment and concomitant disabilities: bronchopulmonary dysplasia, behavioral abnormalities, epilepsy, hearing deficit, developmental delay, cerebral palsy and cerebral visual impairment. During the study period, lower age limit for neonatal life support (2010) and higher oxygen saturation targets (2014) were implemented. RESULTS: Records of 53 infants were analyzed. Visual impairment incidence due to ROP was 2.02 per 100.000 live births (2000-2009: 1.84, p = 0.643). Compared to earlier periods (1975-2000), a significant decrease was observed. The incidence of concomitant disabilities remained stable. Mean gestational age (GA) continued to decrease to 26.6 ± 1.9 weeks (2000-2009: 27.4 ± 2.0 weeks, p = 0.047). All patients met the screening inclusion criteria. CONCLUSION: The incidence of visual impairment due to ROP and concomitant disabilities between 2009 and 2018 has not increased, despite lower GA and higher oxygen saturation targets. None of the infants were missed for ROP screening following introduction of more restricted screening inclusion criteria.

[Late sequelae of retinopathy of prematurity in infancy]. / Spätfolgen der Frühgeborenenretinopathie im Kindesalter.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the most frequent causes of severe visual impairment or blindness in childhood and can lead to severe late complications in children even after the initial disease has resolved. PURPOSE: The present study summarizes possible late effects in childhood after treated and untreated ROP. A special focus is on the development of myopia, retinal detachment, as well as neurological and pulmonary development after anti-vascular endothelial growth factor (VEGF) treatment. MATERIAL AND METHODS: This work is based on a selective literature search on late effects in childhood of treated or untreated ROP. RESULTS: Preterm infants have an increased risk of developing high-grade myopia. Interestingly, several studies indicate that the risk of myopia is reduced following anti-VEGF treatment. With anti-VEGF treatment, however, late recurrences after initial response are possible even after several months, making long-term and frequent follow-up examinations essential. Controversy exists regarding the possible negative effects of anti-VEGF treatment on neurological and pulmonary development. After both treated and untreated ROP, rhegmatogenous, tractional or exudative retinal detachment, vitreous hemorrhage, high myopia and strabismus are possible late complications. DISCUSSION: Children with a history of ROP with or without treatment have an increased risk for late ocular sequelae, such as high myopia, retinal detachment, vitreous hemorrhage and strabismus. A seamless transition from ROP screening to pediatric and ophthalmological follow-up care is therefore essential for timely detection and treatment of possible refractive errors, strabismus, or other amblyogenic changes.

Level of prematurity as a predictor for the activity of retinopathy of prematurity and strabismus.

Objective: To evaluate the prevalence of strabismus in premature children after the screening for retinopathy of prematurity (ROP) and to determine whether the level of prematurity (birth weight and gestation age) can be used as a predictor for both strabismus development and disease activity. Methods: This is a retrospective study, conducted in the Clinic for Eye Disease, section for Pediatric Ophthalmology of the Clinical Centre University of Sarajevo during the period from December 2013 until January 2017. 126 patients were involved. The inclusion criteria were gestational age ≤ 34 weeks, birthweight ≤ 2000 g and performed screening test for ROP. Patients were divided into three groups: patients without ROP, patients with spontaneous regression and patients with active ROP. Results: 52.4% patients were suffering from strabismus (30.2% esotropia, 22.2% exotropia). All the patients with active ROP had esotropia (60.0%). The average birth weight and gestational age were lower in patients with strabismus (1371.3 ± 58.0 g and 29.7 ± 0.4 weeks respectively). Conclusion: Lower gestational age and birth weight of premature children showed the increased probability of strabismus development especially esotropia. Prematurity level was significantly lower in patients with active ROP compared to the rest of the patients. Abbreviations: ROP = Retinopathy of prematurity, ICROP = International Classification of Retinopathy of prematurity, BCVA = best corrected visual acuity.

Retinopathy of prematurity protection conferred by uteroplacental insufficiency through erythropoietin signaling in an experimental Murine Model.

BACKGROUND: Recent clinical studies suggest that preeclampsia, characterized by uteroplacental insufficiency (UPI) and infant intrauterine growth restriction (IUGR), may be protective against retinopathy of prematurity (ROP) in preterm infants. Experimental models of UPI/IUGR have found an association of erythropoietin (EPO) with less severe oxygen-induced retinopathy (OIR); however, it is unclear if EPO/EPO receptor (EPOR) signaling was involved. We hypothesized that maternal UPI and resultant infant IUGR would protect against features of ROP through EPO/EPOR signaling. METHODS: We compared transgenic mice with hypoactive EPOR signaling (hWtEPOR) to littermate wild-type mice (mWtEpoR) in a novel combined model of IUGR and ROP. Thromboxane A2 (TXA2) was infused into pregnant C57Bl/6J dams to produce UPI/IUGR; postnatal pups and their foster dams were subjected to a murine OIR model. RESULTS: Following hyperoxia, hematocrits were similar between littermate wild-type (mWtEpoR) TXA2/OIR and vehicle/OIR pups. mWtEpoR TXA2/OIR had increased serum EPO, retinal EPO and VEGF, and decreased avascular retinal area (AVA) compared to vehicle/OIR pups. In comparison to the mWtEpoR TXA2/OIR pups, AVA was not reduced in hWtEPOR TXA2/OIR pups. CONCLUSION: Our findings provide biologic evidence that UPI/OIR-induced endogenous EPOR signaling confers protection against hyperoxia-induced vascular damage that may be related to pathophysiology in ROP. IMPACT: Maternal preeclampsia and infant growth restriction confer retinovascular protection against high oxygen-induced damage through endogenous erythropoietin signaling.