Long-term outcomes of visual motor integration and motor development children with retinopathy of prematurity.

Premature infants have a risk of neurodevelopmental deficits. Little is known, however, about how retinopathy of prematurity (ROP) affects visual motor integration (VMI), which is necessary for both fine motor skills and further school abilities. Due to the systemic escape of bevacizumab in the treatment of ROP, concerns regarding the long-term neurodevelopmental effect of the drug have arisen. The aim is to evaluate VMI and motor development long-term outcomes after intravitreal bevacizumab (IVB) injection and laser treatment for ROP. Two groups of premature children were included: Bevacizumab group - 16 premature children who received IVB treatment and laser group - 23 premature children who underwent laser photocoagulation treatment in this single center cross-sectional study. At 2-6 years of age, VMI (Beery-Buktenica Developmental Test), motor development (Peabody Developmental Motor Scales-2), visual acuity, and refractive status were assessed. The incidence of abnormal visual function was significantly higher in bevacizumab group than in laser group (p = 0.022). The incidence of abnormal VMI skill was significantly higher in bevacizumab group than in laser group (p = 0.024). Incidences of abnormal gross, fine, and total motor skills were significantly higher in bevacizumab group compared to laser group (p < 0.05). Premature children who received bevacizumab for ROP demonstrated significantly lower VMI and motor development features than those with laser treatment at preschool age. Although our results suggest the relevance of bevacizumab injection in impaired VMI and motor development outcomes, general level of sickness rather than treatment might be the cause of delayed motor development.

Causes of functional low vision in a Brazilian rehabilitation service.

There is limited information on functional low vision (FLV) in Latin America, especially in individuals under 50 years of age. In the present study, we retrospectively evaluated the medical records of 1393 consecutive subjects seen at a Brazilian tertiary rehabilitation service, from February 2009 to June 2016. We collected sociodemographic, clinical data, and information on optical aids and spectacle prescription. Subjects were divided into three age groups: 0 to 14 years old (children), 15 to 49 years old (young adults), and 50 years or older (older adults). The main etiologies leading to FLV in children were cerebral visual impairment (27.9%), ocular toxoplasmosis (8.2%), and retinopathy of prematurity (7.8%). In young adults, retinitis pigmentosa (7.4%) and cone/rod dystrophy (6.5%) were the most frequent, while in older adults, age-related macular degeneration (25.3%) and diabetic retinopathy (18.0%) were the leading causes. Our results indicate that preventable diseases are important causes of FLV in children in the area, and proper prenatal care could reduce their burden. The increasing life expectancy in Latin America and the diabetes epidemic are likely to increase the demand for affordable, people-centered rehabilitation centers, and their integration into health services should be planned accordingly.

Functional Ophthalmic Factors Associated With Extreme Prematurity in Young Adults.

Importance: Children born preterm (<37 weeks' gestation) have a higher risk of visual impairment and ocular morbidities compared peers born at full term. However, the long-term ocular sequelae in adulthood for those born extremely preterm (EP), who have the highest risk of neonatal retinopathy, are unknown. Objective: To evaluate visual function and ocular morbidity in young adults born EP compared with controls born full term. Design, Setting, and Participants: This prospective cohort study of a geographically based birth cohort in the UK and Ireland born from March 1 through December 31, 1995, included 128 participants aged 19 years (born at 22-25 weeks' gestation) and 65 age-matched controls born at full term. Statistical analysis was performed from March 1, 2020, to November 26, 2021. Exposures: Participants underwent eye examinations as part of a comprehensive outcome evaluation. Main Outcomes and Measures: Best-corrected visual acuity, refractive status, contrast sensitivity, color vision, prevalence of strabismus and nystagmus, and patient-reported visual function, measured using the Health Utilities Index Mark 3. Results: The study comprised 128 participants (256 eyes; 68 female participants [53%]; mean [SD] age, 19.3 [0.5] years) and 65 age-matched controls born at full term (130 eyes; 40 female participants [62%]; mean [SD] age, 19.2 [0.5] years). Compared with control eyes, the mean (SD) best-corrected visual acuity among eyes in the EP group was significantly worse (monocular vision: -0.06 [0.14] logMAR in the control group vs 0.14 [0.38] logMAR in the EP group; P < .001; binocular vision: -0.14 [0.15] logMAR in the control group vs 0.06 [0.37] logMAR in the EP group; P < .001). Participants in the EP group had a significantly higher prevalence of strabismus (36% [46 of 127] vs 0%; P < .001), abnormal ocular motility (15% [19 of 125] vs 0%; P < .001), and nystagmus (13% [16 of 127] vs 0%; P < .001) than the control group. No significant differences between participants in the EP group and controls were observed for refractive error, contrast sensitivity, color vision, or patient-reported visual function. Among the participants in the EP group, 48% of eyes (120 of 250) had no retinopathy of prematurity (ROP), 39% (98 of 250) had ROP not requiring neonatal treatment, and 13% (32 of 250) received cryotherapy or laser ablation for ROP. Within the EP group, there was no significant difference in binocular visual function parameters, prevalence of ocular morbidity, and patient-reported visual function by neonatal ROP status. Conclusions and Relevance: Extreme prematurity is associated with an increased prevalence of visual and ocular deficits in young adulthood; this study suggests that, for individuals born EP, visual and ocular deficits appear to be partially independent of ROP status in the neonatal period but reports similar overall visual function.

Ranibizumab in retinopathy of prematurity - one-year follow-up of ophthalmic outcomes and two-year follow-up of neurodevelopmental outcomes from the CARE-ROP study.

PURPOSE: The primary endpoint results from the comparing alternative ranibizumab dosages for safety and efficacy in retinopathy of prematurity (CARE-ROP) core study identified ranibizumab as an effective treatment to control acute retinopathy of prematurity (ROP). This study reports the 1- and 2-year follow-up data focusing on long-term functional outcomes and safety. METHODS: The CARE-ROP trial compared 0.12 mg versus 0.20 mg ranibizumab in 20 infants with ROP in a multicentric, prospective, randomized, double-blind, controlled study design. Sixteen patients entered the follow-up period. An ophthalmologic assessment at one year postbaseline was acquired from all 16 patients and a neurodevelopmental assessment at two years postbaseline was acquired from 15 patients. RESULTS: Fifteen of 16 infants were able to fixate and follow moving objects at one year postbaseline treatment. One child progressed to stage 5 ROP bilaterally between the end of the core study and the 1-year follow-up (first seen at PMA 75 weeks). Mean spherical equivalents were -1.9 diopters (D) and -0.75 D in the 0.12 mg and the 0.20 mg treatment arms. Strabismus was present in seven and nystagmus in five out of 16 infants. Mental development scores were within normal limits in six out of ten patients with available data. No statistically significant difference was observed between the two treatment arms. CONCLUSION: Neurodevelopmental and functional ocular outcomes 1 and 2 years after treatment with ranibizumab are reassuring regarding long-term safety. Late reactivation of ROP, however, represents a challenge during the follow-up phase and it is of utmost importance that regular follow-ups are maintained.

Seeing stars: Development and function of retinal astrocytes.

Throughout the central nervous system, astrocytes adopt precisely ordered spatial arrangements of their somata and arbors, which facilitate their many important functions. Astrocyte pattern formation is particularly important in the retina, where astrocytes serve as a template that dictates the pattern of developing retinal vasculature. Thus, if astrocyte patterning is disturbed, there are severe consequences for retinal angiogenesis and ultimately for vision - as seen in diseases such as retinopathy of prematurity. Here we discuss key steps in development of the retinal astrocyte population. We describe how fundamental developmental forces - their birth, migration, proliferation, and death - sculpt astrocytes into a template that guides angiogenesis. We further address the radical changes in the cellular and molecular composition of the astrocyte network that occur upon completion of angiogenesis, paving the way for their adult functions in support of retinal ganglion cell axons. Understanding development of retinal astrocytes may elucidate pattern formation mechanisms that are deployed broadly by other axon-associated astrocyte populations.

Impairment of endothelium-dependent vasodilator function of retinal blood vessels in adult rats with a history of retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a proliferative retinal vascular disease, initiated by delayed retinal vascular growth after premature birth. In the majority of cases, ROP resolves spontaneously; however, a history of ROP may increase the risk of long-term visual problems. In this study, we evaluated the endothelial function of retinal blood vessels in adult rats with a history of ROP. ROP was induced in rats by subcutaneous injection of a vascular endothelial growth factor receptor tyrosine kinase inhibitor (KRN633) on postnatal day (P) 7 and P8. On P56, vasodilator responses to acetylcholine, GSK1016790A (an activator of transient receptor potential vanilloid 4 channels), NOR3 (a nitric oxide [NO] donor), and salbutamol (a ß2-adrenoceptor agonist) were assessed. Compared to age-matched controls, retinal vasodilator responses to acetylcholine and GSK1016790A were attenuated in P56 rats with a history of ROP. No attenuation of acetylcholine-induced retinal vasodilator response was observed under inhibition of NO synthase. Retinal vasodilator responses to NOR3 and salbutamol were unaffected. These results suggest that the production of and/or release of NO is impaired in retinal blood vessels in adult rats with a history of ROP. A history of ROP might increase the risk of impaired retinal circulation in adulthood.

Severe retinopathy of prematurity is associated with early post-natal low platelet count.

Pathophysiology of retinopathy of prematurity (ROP) still presents a gap. Lately blood tests parameters of premature infants have been measured at different times of ROP, attempting to detect correlations with ROP development and progression. So far, very early post-natal biomarkers, predictive of ROP outcome, have not been detected. Our purpose is to evaluate, in the earliest post birth blood sample, the correlation between routinely dosed blood parameters and ROP outcome. 563 preterm babies, screened according to ROP guidelines, were included and classified in conformity with ET-ROP study in "Group 1" (ROP needing treatment), "Group 2" (ROP spontaneously regressed) and "noROP" group (never developed ROP). The earliest (within an hour after delivery) blood test parameters routinely dosed in each preterm infant were collected. Platelet count was decreased in Group 1 versus noROP group (p = 0.0416) and in Group 2 versus noROP group (p = 0.1093). The difference of thrombocytopenic infants among groups was statistically significant (p = 0.0071). CRP was higher in noROP versus all ROPs (p = 0.0331). First post-natal blood sample revealed a significant thrombocytopenia in ROP needing treatment, suggesting a role of platelets in the pathophysiology and progression of ROP, possibly considering it as a predictive parameter of ROP evolution.

Role of LASERS in stage 4A retinopathy of prematurity (ROP).

To study the anatomical success rate of light amplification by stimulated emission of radiation (LASERS) as first line of management in stage 4A retinopathy of prematurity (ROP). Observational, prospective case series of 14 eyes of 7 babies (males: 3, females: 4) with stage 4A ROP who underwent LASERS for stage 4A between January 2018 and July 2019. Gestation age (GA), birth weight (BW), and post-menstrual age (PMA) at which laser was done were noted in all cases. A number of clock hours of detachment at the time of presentation were noted in all babies. All babies were followed up up to 6 months after laser for any recurrence. Success was defined as complete regression of disease without the need of any other modality of treatment like anti-vascular endothelial growth factor (anti-VEGF) or pars plana vitrectomy. A total of 92.85% (13/14) showed complete regression of disease. One eye progressed to stage 4B ROP warranting lens-sparing vitrectomy (LSV). LASERS is an effective method of management without any need of anti-VEGF or surgical intervention even in babies with stage 4A ROP.

ANATOMICAL AND VISUAL OUTCOMES IN STAGE 5 RETINOPATHY OF PREMATURITY WITH MICROINCISION VITRECTOMY SURGERY.

PURPOSE: To report anatomical and visual outcomes and potential prognostic factors with microincision vitrectomy surgery in Stage 5 retinopathy of prematurity. METHODS: The medical records of premature babies who underwent microincision vitrectomy surgery for Stage 5 retinopathy of prematurity using 23G, 25G, or 27G instrumentation and had a minimum follow-up of 6 weeks were, retrospectively, analyzed. Primary outcome measures were anatomical success at last follow-up defined as retinal attachment at the posterior pole and visual outcomes. Potential risk factors and complications influencing anatomical outcomes were also analyzed. RESULTS: One hundred seventy eyes of 115 infants underwent lensectomy and vitrectomy with microincision vitrectomy surgery. After a mean follow-up of 30.59 ± 33.24 weeks, anatomical success was achieved in 56 eyes (33.7%) of 166 eyes that had a minimum follow-up of 6 weeks. Occurrence of vitreous hemorrhage was more with 23 gauge (62.27%) as compared to 25 gauge (37.73%) (P = 0.024). With increase in age with each week, the probability of achieving anatomical success was found to be significantly more (odds ratio 1.030; confidence interval = 1.010-1.060; P = 0.008). Presence of anterior segment pathology was associated with poor anatomical outcomes (odds ratio 2.480; confidence interval = 1.190-5.160; P = 0.010). Seventeen children with attached retina had a follow-up of 14 months-5 years, of which ambulatory vision was recorded in five eyes and the ability to identify objects close to face in 12 eyes. CONCLUSION: Although surgery for Stage 5 retinopathy of prematurity is challenging, anatomical success can be seen in one-third of cases with microincision vitrectomy surgery. Visual prognosis may be limited but still beneficial.

Foveal thickness, foveal microvasculature, and refractive error in children with asymmetric involvement of retinopathy of prematurity.

OBJECTIVE: To evaluate foveal thickness, foveal microvasculature, and refractive error in children with asymmetric involvement of retinopathy of prematurity who had laser treatment in one eye and spontaneously regressed retinopathy of prematurity in the fellow eye. METHODS: Totally, 17 children (34 eyes) with a history of asymmetric course of acute Zone II retinopathy of prematurity were assessed. Data on best-corrected visual acuity, refractive status, axial length, anterior chamber depth, and optical coherence tomography angiography findings were analyzed between treated and non-treated fellow eyes. RESULTS: Treated eyes were more myopic than non-treated eyes (mean, -0.09 ± 1.86 diopters vs mean, 0.07 ± 0.98 diopters, p = 0.026). Compared to non-treated eyes, treated eyes had shallower anterior chamber depth (mean, 3.27 ± 0.24 mm vs mean, 3.55 ± 0.19 mm, p = 0.02). No significant difference was observed regarding optical coherence tomography angiography parameters between two eyes of the children. The mean central foveal thickness was found to be higher in treated eyes than in non-treated eyes (297.46 ± 22.03 vs 275.55 ± 18.45, p = 0.009). Higher number of laser spots were associated with decreased parafoveal superficial capillary plexus vessel density (r = -0.56, p = 0.02) and increased central foveal thickness (r = 0.62, p = 0.008). CONCLUSION: Our results revealed no difference in optical coherence tomography angiography parameters between laser-treated and non-treated eyes in children with asymmetric involvement of Zone II retinopathy of prematurity except for a higher central foveal thickness in laser-treated eyes. Treated eyes were more myopic than the non-treated eyes. Number of laser applications during treatment had an impact on parafoveal superficial capillary plexus vessel density.

Efficacy of Aflibercept Treatment and Its Effect on the Retinal Perfusion in the Oxygen-Induced Retinopathy Mouse Model of Retinopathy of Prematurity.

INTRODUCTION: Bevacizumab and ranibizumab, which are anti-vascular endothelial growth factor (VEGF) medications, are used frequently in the treatment for retinopathy of prematurity (ROP) in infants. Aflibercept, or VEGF Trap, has been used anecdotally, but translation and clinical studies are lacking. OBJECTIVE: This study investigates the efficacy of aflibercept at reducing areas of non-perfused retina and studies its effect on normal angiogenesis in the oxygen-induced retinopathy mouse model of ROP. METHODS: C57BL/6 J mice were assigned to room air control (n = 21 eyes) or hyperoxia with 75% oxygen (n = 84 eyes). The hyperoxic mice were assigned to 1 of 3 groups: 0 ng (n = 14 eyes), 100 ng (n = 35 eyes), or 1,000 ng (n = 35 eyes) of intravitreal aflibercept administered on postnatal day 14. Eyes were enucleated at PN17 and PN25 postinjection. Retinas were stained with anti-collagen IV antibody and photographed with microscopy. Areas of perfused and non-perfused retina were quantified using ImageJ software. Statistical comparisons were made using ANOVA with Tukey post hoc comparisons. RESULTS: At PN17, there was no significant difference in the area of non-perfused retina between the hyperoxic control and the 100 and 1,000 ng aflibercept groups. At PN25, the 100 ng (p < 0.05) and 1,000 ng (p = 0.008) treatment groups displayed less non-perfusion compared to hyperoxic controls. At the 1,000 ng dose, there was increased non-perfusion compared to the 100 ng dose (p = 0.02). There was reduced non-perfusion by PN25 compared to PN17 for the 100 ng group (p < 0.05), with no difference in the 1,000 ng group. CONCLUSIONS: The study shows that the area of non-perfused retina decreases effectively with aflibercept at PN25 with 100 ng dosage. With the 1,000 ng dosage, there is an inhibition of the physiologic angiogenesis with a higher area of non-perfused retina.

GLYCEMIC VARIABILITY IS ASSOCIATED WITH TREATMENT REQUIRING RETINOPATHY OF PREMATURITY: A Case-Control Study.

PURPOSE: To assess the association between glycemic variability (GV) and Type 1 retinopathy of prematurity (ROP) in infants with birth weights of less than 1,251 g. METHODS: A case-control study of infants with birth weights of less than 1,251 g who developed Type 1 ROP (n = 20) was conducted. Controls had a less severe ROP or no eye disease and were individually matched for gestational age and birth weight (n = 40). Odds ratios of ROP were calculated based on multiple factors including oxygen exposure, respiratory support, incidence of hyperglycemia, and GV. For glucose measurements, a continuous glucose monitoring system was used. RESULTS: There were no significant differences in gender, antenatal steroid administration, severity of illness, and Apgar score. Univariate analyses suggest increased risk for the development of Type 1 ROP based on incidence of intraventricular hemorrhage Grade 3 or 4 (P = 0.048), duration of oxygen exposure (P = 0.003), incidence of hyperglycemia over 150 mg/dL (P = 0.01), and GV according to significantly higher SD (P = 0.002), coefficient of variation (P = 0.001), and mean amplitude of glucose excursion (P = 0.008). Using a multiple regression model, increased risk of Type 1 ROP was only found to be associated with duration of oxygen exposure and higher GV. CONCLUSION: Our study demonstrates a relationship between GV and the development of severe ROP.

Thyroid Activating Enzyme, Deiodinase II Is Required for Photoreceptor Function in the Mouse Model of Retinopathy of Prematurity.

Purpose: Retinopathy of prematurity (ROP) is a severe complication of premature infants, leading to vision loss when untreated. Presently, the molecular mechanisms underlying ROP are still far from being clearly understood. This study sought to investigate whether thyroid hormone (TH) signaling contributes to the neuropathology of ROP using the mouse model of ROP to evaluate longitudinal photoreceptor function. Methods: Animals were exposed to hyperoxia from P7 to P12 to induce retinopathy, thereafter the animals were returned to room air (normoxia). The thyroid-activating enzyme type 2 deiodinases (Dio2) knockout (KO) mice and the littermate controls that were exposed to hyperoxia or maintained in room air and were then analyzed. The retinal function was evaluated using electroretinograms (ERGs) at three and seven weeks followed by histologic assessments with neuronal markers to detect cellular changes in the retina. Rhodopsin protein levels were measured to validate the results obtained from the immunofluorescence analyses. Results: In the ROP group, the photoreceptor ERG responses are considerably lower both in the control and the Dio2 KO animals at P23 compared to the non-ROP group. In agreement with the ERG responses, loss of Dio2 results in mislocalized cone nuclei, and abnormal rod bipolar cell dendrites extending into the outer nuclear layer. The retinal function is compromised in the adult Dio2 KO animals, although the cellular changes are less severe. Despite the reduction in scotopic a-wave amplitudes, rhodopsin levels are similar in the adult mice, across all genotypes irrespective of exposure to hyperoxia. Conclusions: Using the mouse model of ROP, we show that loss of Dio2 exacerbates the effects of hyperoxia-induced retinal deficits that persist in the adults. Our data suggest that aberrant Dio2/TH signaling is an important factor in the pathophysiology of the visual dysfunction observed in the oxygen-induced retinopathy model of ROP.

Comparison of the Efficiency of the Botulinum Toxin for the Treatment of Esotropia in Children with and without Neurological Disease and/or Prematurity.

OBJECTIVE: To compare the effect of botulinum toxin injection for the management of esotropia in patients with and without neurological disease and/or prematurity. METHODS: A single-center, retrospective, nonrandomized controlled study was performed on botulinum toxin in 87 children divided into two groups: study group of esotropia in 56 children with neurological disease and/or prematurity and, control group of 31 healthy children with infantile esotropia. All patients were followed for at least 24 months after injection. Success was defined as motor alignment with 10Δ of orthotropia after single bilateral botulinum injection. RESULTS: Mean age at treatment was similar in both groups (15.5 vs 14.8 months; p = .555). Mean pretreatment deviation was similar in both groups (50.8Δ vs 50Δ; p = .855). The success rate was better in the control group (61.2% vs 51.7%, p = .265) at 24 months after injection, but the change in the mean angle of deviation was not statistically significant between the groups at 12 and 24 months after injection (p = .264 and p = .547, respectively). Multivariate regression analysis showed that pretreatment angle of deviation and presence of retinopathy of prematurity were significant predictors at 12 months after injection (p = .0001 and p = .004, respectively), while pretreatment angle of deviation was found to be a predictor at 24 months after injection (p = .0001). CONCLUSIONS: Decreased angle of deviation and absence of retinopathy of prematurity were associated with a better result. There was no difference in motor alignment of esotropia in children with and without neurological disease and/or prematurity. In these patients, botulinum injection may be used as an alternative to surgery.

Longitudinal Analysis of Refractive Errors in Premature Children during the First Three Years of Life.

PURPOSE: To examine the longitudinal behavior of refractive errors in both retinopathy of prematurity (ROP) and non-ROP screened premature children during the first three years of life. METHODS: This retrospective cohort included premature children (less than 37 weeks gestational age) born between 10/2011 and 8/2013 with ≥ two cycloplegic refractions. Cycloplegic refractions were converted into power vectors: M (spherical equivalent), J0 [positive for with-the-rule (WTR) and negative for against-the-rule (ATR) astigmatism], and J 45 (oblique astigmatism). Each power vector component was fitted by multilevel mixed-effects linear regression models; the mean change over time was analyzed. RESULTS: Mean J0 was 0.59 (95% CI 0.53-0.66) at six months and 0.29 (95% CI 0.19-0.39) at 18 months; afterward, the change was <0.1 per year. J0 decreased -0.32 (0.64 diopters) over three years. When analyzed in one-year increments, the mean change in J0 and M was lowest at 24 months. M decreased 1.13 diopters over three years. CONCLUSION: WTR astigmatism and spherical equivalent decreased over the first three years of life. WTR astigmatism accounted for the majority of amblyopogenic refractive errors. The change in J0 leveled after 18 months and the lowest rate of change was at 24 months in J0 and M, thus it may be appropriate to screen this high-risk population around 18-24 months.

Management outcomes of secondary glaucoma due to retinopathy of prematurity: A 19-year prospective study at a tertiary eye care Institute. The Indian Twin cities ROP Screening (ITCROPS) database report number 8.

PURPOSE: To report the clinical presentation and management outcomes of glaucoma in the "Indian Twin cities retinopathy of prematurity (ROP) Screening database." METHODS: All children with diagnosis of ROP and glaucoma between 1997 and 2016 from a prospective database were included. Glaucoma was classified as open when anterior chamber (AC) was deep, closed when AC was shallow or flat and neovascular when there was extensive iris neovascularization. ROP was classified based on International classification of ROP. RESULTS: The prevalence of secondary glaucoma in our cohort was 1.36% (82 eyes of 6000 children). Eighty-two eyes of 54 children with secondary glaucoma due to ROP where included in this study. The distribution of glaucoma among the ROP stages included, stage V (58.5%), stage 1V (24.3%), stage III (2.4%) and stage II (1.2%) eyes. Median (interquartile range) duration from birth to glaucoma diagnosis was 7.8 (4.2, 24.9) months. Type of glaucoma was angle closure in 39 (47.6%), open angle in 35 (42.7%) and neovascular in 8 (9.8%) eyes. Retinal interventions included vitreoretinal surgery in 59 (72%), retinal laser in 14 (17%) and intravitreal bevacizumab injection in 19 (23.1%) eyes. The mean (±standard deviation) IOP at presentation was 22.6 ±11.8 mm Hg. Glaucoma was managed medically in 66 (76%) and surgically in 16 (19.5%) eyes. The mean follow up for the entire cohort was 1.14±2.24 years. At final visit, 37% eyes with ROP and glaucoma had ambulatory vision with mean IOP of 16.0±8.1 mm Hg and 56 eyes (68.2%) needed glaucoma medications. CONCLUSION: In this large ROP cohort, 1.36% eyes developed secondary glaucoma. Majority of them had stage V or IV ROP and 1/5 of them needed glaucoma surgery. Around 1/3rd of the ROP eyes with glaucoma had ambulatory vision.

A safety review of drugs used for the treatment of retinopathy of prematurity.

INTRODUCTION: Retinopathy of Prematurity (ROP) is a sight-threatening disease representing one of the main disabling diseases affecting premature newborns. Presently, ROP is treated by surgical interventions and drug therapies are limited to the off-label use of a little amount of molecules approved for other pathologies. AREAS COVERED: Many drugs that may potentially be used in treating ROP are recently proposed, in many cases after the demonstration of their effectiveness in preclinical studies. In this review, the authors discuss safety and effectiveness of the main proposed approaches in the pharmacologic treatment of the disease, including approaches based on oxygen therapy and nutritional interventions. EXPERT OPINION: Surgical approaches to ROP are not without side effects. However, most of the proposed pharmacologic interventions can also raise specific concerns. In particular, these approaches follow a curative paradigm and are proposed in patients once the disease has progressed, with an effectiveness that is often smaller than expected. A goal in the treatment of ROP would be moving the paradigm toward a preventive approach that could be potentially effective in treating extremely low birth weight preterm infants before ROP becomes manifest.

Incidence, Long-Term Visual Outcomes, and Mortality in Retinopathy of Prematurity in Korea: A Nationwide Population-Based Study.

Purpose: To evaluate the incidence, visual prognosis, and mortality in retinopathy of prematurity (ROP) in Korea. Methods: We used the National Health Insurance and the Korean Disability Registry database, which covers the entire newborn population in 2006 to 2014 and includes information on all newborns diagnosed with ROP until 2016. Using these databases, we evaluated the incidence, rate of visual impairment (VI), and mortality in patients with ROP according to the birth weight categories and treatment modalities. Results: The ROP incidence per 1000 newborns was 1.99, which broke down into 317.14 in the very low birth weight (VLBW) less than 1500 g population, 25.45 in the 1500 to 2499 g population, and 0.29 in the 2500 g or greater population. When assessed at age 10, the VI rate was 2.2 per 100 person-years, which was highest at 4.5 per 100 person-years in the VLBW population compared with the population in other birth weight categories. Among treated cases, the proportion of VI in patients undergoing laser photocoagulation or cryotherapy was 1.6% (42/2595), which was lower than the 2.9% (2/68) of patients treated with anti-vascular endothelial growth factor injection, and 32.2% (82/255) of patients undergoing vitrectomy or scleral buckling. The mortality rate was 4.8 per 1000 person-years, which was highest in the VLBW population, but similar across treatment modalities. Conclusions: The ROP incidence in Korea was approximately 1 in 500 among all newborns, and 1 in 3 in the VLBW population. As the first nationwide population-based study of long-term visual prognosis in ROP, we report the higher VI rate in ROP than previously determined in other studies. Differences in visual outcomes and comparable mortality risks between treatment modalities require further verification.

Effect and mechanism of the long noncoding RNA MALAT1 on retinal neovascularization in retinopathy of prematurity.

AIMS: The most typical pathological manifestation of retinopathy of prematurity (ROP) is Retinal neovascularization (RNV). Long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to mediate angiogenesis. Our experiment aimed to research the effect and mechanism of the MALAT1 on RNV in ROP. MAIN METHODS: C57 mice was used to establish oxygen-introduced retinopathy (OIR), and divided into control, hyperoxia, hyperoxia control siRNA, and hyperoxia MALAT1 siRNA groups. KEY FINDINGS: It was shown that MALAT1 mRNA was high expressed in the retinas of OIR mice. Further studies revealed that after intravitreal injection of MALAT1 siRNA, the degree of retinopathy was significantly reduced compared with OIR group. In addition, the protein and mRNA expression levels of CCN1, AKT and VEGF were significantly decreased. This was accompanied by a decrease in inflammatory genes including IL-1ß, IL-6, and TNF-α compared with the hyperoxia control siRNA mice. SIGNIFICANCE: The result suggested that MALAT1 may be involved in the process of RNV in ROP and MALAT1 siRNA may be a promising agent for the treatment of ROP by inhibiting RNV.

Early visual and neuro-development in preterm infants with and without retinopathy.

BACKGROUND: Retinopathy of prematurity (ROP) is often associated with visual impairment and multiple developmental disabilities. AIMS: As most of the previous studies include infants with brain lesions, that can determine visual impairment per se, a cohort of low neurological risk preterm infants without ROP and with various degree of severity of ROP was assessed in order to establish visual and neurodevelopmental outcome. STUDY DESIGN: Preterm infants born at <31 weeks gestation, without major brain lesions, underwent visual function assessment at 1 year corrected age and neurodevelopmental assessment at 2 years corrected age. SUBJECTS: One hundred and five infants were included in the study: 42 infants did not develop ROP, 7 reached stage 1 in zone 2 ROP, 37 reached prethreshold (untreated) type 2 ROP. The remaining 19 infants were classified as type 1 ROP. OUTCOME MEASURES: Visual function (including fixing, tracking, visual acuity, visual field, attention at distance and nystagmus) were assessed at 12 months corrected age and Griffiths Scales at 2 years corrected age. RESULTS: The severity of ROP was strongly correlated (p < 0.001) with both visual function at 1 year and neurodevelopment at 2 years. Similarly, the presence of nystagmus was also strongly correlated with visual and neurodevelopmental sequelae. CONCLUSIONS: Infants with no or milder retinopathy showed normal visual function at 1 year and neurodevelopment at 2 years. Infants who underwent treatment more frequently showed abnormal results on several aspects of visual function. Presence of nystagmus appeared to increase the risk for abnormal visual function and neurodevelopmental outcome.