Retinal Immaturity Research Articles

Maternal and Neonatal risk factors in retinopathy of prematurity: A study from coastal city in south India

Preterm babies often suffer from various systemic illnesses and struggle for survival in the neonatal intensive care unit (NICU). These preterm babies are at risk of developing ROP which is a potentially blinding condition. The presence of predisposing maternal and neonatal factors contributes for the development of ROP. Determining the association of risk factors with the development of ROP is essential in improving the screening and management of ROP. To determine maternal, neonatal risk factors and influence of retinal immaturity at first screening for development of ROP. Prospective, observational study conducted at a level of 3 PICU & department of ophthalmology. All the preterm infants with gestational age ≤ 37 weeks admitted in NICU were first screened by 2 to 3 weeks of chronological age and followed up till the completion of retinal vascularization and regression of ROP following treatment. The zone of retinal vascularization at first screening and various maternal and neonatal risk factors were noted. Out of 166 babies screened, 18.67% progressed to ROP. Of the 36 babies with immature retina 58% developed ROP, while 7.7% neonates with mature retina developed ROP. Gestational age, birth weight, retina immaturity, respiratory distress syndrome and anaemia of prematurity were statistically significant for ROP.Statistical analysis: Descriptive statistics was used to identify the association of risk factors with the development of ROP. Each risk factor was analyzed by univariate & multivariate logistic regression. Low birth weight, low gestational age, immature retina and neonatal risk factors have a significant influence on the development of ROP. Low birth weight, low gestational age and retinal immaturity are important risk factors for Retinopathy of prematurity.

Evaluation of the Effect of Different Treatment Management on Refractive Outcomes in Severe Retinopathy of Prematurity.

Objectives:The purpose of the study was to evaluate the effect of different treatment modalities on refractive outcomes in patients treated with severe retinopathy of prematurity (ROP).Methods:The records of children who were treated for severe ROP in our clinic between January 2015 and August 2018 were retrospectively reviewed. The children who were treated were analyzed in three subgroups as intravitreal bevacizumab (IVB), laser photocoagulation (LPC), and IVB + LPC. Spherical equivalent (SEQ), spherical and cylindrical power measurements of the cases were recorded in diopters (D). SE ≤−0.25D was accepted as myopia and SE of more than 1 D between two eyes was accepted as anisometropia.Results:A total of 160 eyes of 80 participants were eligible for inclusion: 38 eyes in the IVB group, 24 eyes in the LPC group, 16 eyes in the IVB + LPC group, 44 eyes in the spontaneously regressed group, and 38 eyes in the full-term children. Although the mean spherical power and SEQ in the IVB group were lower than in the LPC group (p=0.019 and 0.013, respectively), there was no significant difference between the IVB group and the IVB + LPC group (p=0.541 and 0.804, respectively). In terms of mean cylindrical power and prevalence of myopia and anisometropia, there was no significant difference between the treatment groups (p>0.05).Conclusion:Although spherical power and SEQ can change according to the ROP treatment management, there is no difference in terms of the cylindrical power, prevalence of myopia, and anisometropia. The most important risk factor for myopia and anisometropia in premature children may be ROP severity and retinal immaturity.

Optical coherence tomography angiography in children with spontaneously regressed retinopathy of prematurity.

To assess optical coherence tomography angiography (OCTA) parameters in children born preterm who developed spontaneously regressed retinopathy of prematurity (sr-ROP, group 1), or had no ROP (PreT, group 2), compared with term-born age-matched controls (group 3). Cross-sectional comparative case series. Children aged 6-8 years had a complete ocular examination and OCT and OCTA imaging (Optovue RTVue AVANTI instrument). Foveal avascular zone (FAZ) area, FAZ perimetry, and vascular density in three slabs were measured automatically, and foveal depth was measured manually by two graders. Groups 1, 2, and 3 (26, 32, and 34 eyes respectively) did not differ in age or gender, but differed in gestational age and birth weight. Both inner retinal thickness and foveal depth differed significantly between group 1 and 2, as did vascular density in the superficial and deep vascular plexus. VA, FAZ area, and perimetry were distinct in all three groups. VA correlated positively with FAZ area and foveal depth, negatively with vascular density. OCTA parameters reveal microvascular changes that distinguish eyes with sr-ROP from premature eyes without ROP, as does visual acuity. It is not possible to infer if the cause is the presence of retinopathy or the different severity of retinal immaturity.

Subclinical Retinal versus Brain Findings in Infants with Hypoxic Ischemic Encephalopathy.

To detect retinal features and abnormalities on optical coherence tomography (OCT) without pupil dilation and relate these to brain injury in infants with a clinical diagnosis of hypoxic ischemic encephalopathy (HIE). Under an institutional review board-approved protocol, we imaged eight infants without pharmacologic mydriasis, using handheld, non-contact spectral-domain (Leica Microsystems, IL) or investigational swept-source OCT at the bedside in an intensive care nursery, after birth (depending on primary clinical care team permission based on health status) and weekly until discharge. The newborn infant with HIE is neurologically unstable; therefore, pharmacologic mydriasis and stimulation with visible light for retinal examination are usually avoided. We analyzed images for retinal pathologies, central foveal thickness, and retinal nerve fiber layer (RNFL) thickness at the papillomacular bundle and compared them to historical controls and published normative data, HIE clinical assessment, and abnormalities on brain magnetic resonance imaging (MRI). On OCT, three of eight infants had bilateral multiple small macular and perimacular cystoid spaces; two of these three infants also had pronounced retinal ganglion cell layer thinning and severe brain injury on MRI and the third had bilateral paracentral acute middle maculopathy and mild brain injury on MRI. Other findings in HIE infant eyes included abnormally thin fovea and thin RNFL and markers of retinal immaturity such as the absence of sub-foveal photoreceptor development and sub-foveal fluid. Bedside handheld OCT imaging within the first 2 weeks of life revealed retinal injury in infants with HIE-related brain injury. Future studies may determine the relationship between acute/subacute retinal abnormalities and brain injury severity and neurodevelopmental outcomes in HIE.

Retinal immaturity at first screening and retinopathy of prematurity: Image-based validation of 1202 eyes of premature infants to predict disease progression.

Purpose:To use the extent of retinal immaturity at the first visit to predict progression to any stage and treatment-requiring retinopathy of prematurity (ROP).Methods:Retrospective, multicenter, nonrandomized, observational, clinical, validation study. In all, 601 Asian Indian preterm infants born < 2000 g and/or < 34 weeks of gestation completing ROP screening with RetCam images taken during each visit were included. A total of 1202 eyes of these infants were classified into three groups based on the retinal immaturity at the first screening visit into “mild” (Group 1), vessels reaching the posterior boundary of zone 3; “moderate” (Group 2), vessels entering zone 2 anterior; and “severe” (Group 3), vessels in zone 1 or zone 2 posterior. RetCam images at each subsequent visit were evaluated and the proportion of eyes that progressed to Type 1 or Type 2 ROP was correlated with the degree of retinal immaturity.Results:Of the 958 eyes in Group 1, 200 eyes in Group 2, and 44 eyes in Group 3, any stage ROP developed in 15% of eyes in Group 1, 46.5% of eyes in Group 2, and 100% of eyes in Group 3 (P < 0.001). Sixteen of 128 eyes (12.5%), 12 of 72 (16.6%), and 28 of 44 of eyes (63.6%) in Groups 1, 2, and 3, respectively, required treatment (P < 0.001).Conclusion:Retinal immaturity at first screening visit predicts Type 1 and Type 2 ROP. “Severe” immaturity is more likely to progress to “treatment-requiring” disease. This could be a useful tool for prognostication, counseling, and scheduling follow-up.

Commentary: Retinal immaturity at first screening and retinopathy of prematurity: Image-based validation of 1202 eyes of premature infants to predict disease progression.

Commentary: Retinal immaturity at first screening and retinopathy of prematurity: Image-based validation of 1202 eyes of premature infants to predict disease progression.

High-Resolution Spectral Domain Optical Coherence Tomography Images of Alström Syndrome

Alström syndrome is a multisystemic disorder characterized by cone-rod dystrophy, hearing loss, obesity, insulin resistance and hyperinsulinemia, type 2 diabetes mellitus, dilated cardiomyopathy, and progressive hepatic and renal dysfunction. The cone-rod retinal dystrophy usually develops within a few weeks after birth. The authors examined a young boy with Alström syndrome by means of microperimetry and spectral domain optical coherence tomography (OCT). Instead of the typical alterations observed in cone-rod dystrophies, the characteristics of the central foveal tissue suggest signs of retinal immaturity, with only a single layer of short, thick cones and rods and immature short outer segments. High-speed and high-resolution spectral domain OCT allowed a detailed analysis of retinal layers in a young patient with Alström syndrome for the first time.

Visual acuity correlates with severity of retinopathy of prematurity in untreated infants weighing 750 g or less at birth.

Visual acuity was assessed in 72 patients who weighed 750 g or less at birth, had intact visual pathways as confirmed with computed tomography or magnetic resonance imaging, and had at least one eye evaluated for cicatricial sequelae after active, untreated retinopathy of prematurity without macular detachment (stage 4a or better). Visual acuities were obtained for 137 untreated, sighted eyes. Severity parameters for retinopathy of prematurity (stage of retinopathy of prematurity, refraction [in spherical equivalents], macular ectopia [in disc diameters], and vessel traction [in 30 degrees sectors]) was were significant predictors of visual acuity (P less than .0001) based on results of linear regression and stepwise regression analyses; however, parameters of retinal immaturity (birth weight, gestational age, and zone of retinopathy of prematurity) were not significant predictors of visual acuity. Visual acuity of the study eyes was good (median, 20/30; geometric mean, 20/33.58), with no statistical differences between eyes evaluated on last examination with linear Allen figures and those evaluated with linear Snellen test types.

Variability of refixations in infants

In adults, visual fixation is a foveal function in which a single retinal locus of regard (the fovea) is directed to a point of regard in the stimulus. Because of the immaturity of the infant fovea, the question arises as to whether or not infants use a consistent retinal locus of regard to direct fixations. Consistency of refixations of a small eccentric target was quantitatively examined in infants and adults using a television-based corneal reflection eye tracker. The scatter of refixations for most infants extended beyond the boundaries of the 1.5° square target but was not as large as the degree of central retinal immaturity that has been reported for infants. The mean standard deviation of scatter was about 0.8° [ n = 73]. No trend in age (19–388 days) was found. This scatter was greater for infants than for adults instructed to fixate carefully (0.1°). However, uninstructed adults exhibited extensive scatter (0.4°, n = 25), and some showed more scatter than some infants. These results suggest that attentional factors limit the scatter in refixations more than sensory or oculomotor immaturity in the visual system. The implications of these findings for the measurement and calibration of infant looking behavior are discussed.

Light and the developing retina

Retinopathy of prematurity (ROP) has increased in the United States in the past decade. Its resurgence has been attributed to advances in medical care which have increased the survival of infants less than 1000 g. Retinal immaturity and exposure to supplementary oxygen are generally accepted as the principal factors associated with ROP, however precocious exposure of the immature retina to light may also contribute. The preterm infant is routinely exposed for the duration of hospital stay to bright continuous light at levels which produce retinal damage in animals. A recent study has provided evidence implicating light in ROP. Preterm infants for whom the light levels were reduced had a lower incidence of ROP, compared to a similar group of preterms exposed to standard levels of nursery light. Given the problems of a non-randomized design, the results must be considered preliminary; however the findings are substantiated by parallel results in both hospitals studied and by an effect of exposure to light within the treatment group. Speculations regarding the mechanisms of light as a contributor to ROP include: alterations of retinal metabolism, cellular damage by phototoxicity, and the generation of free radicals. Mechanisms of phototoxicity are compatible with theories of oxygen toxicity. Light may not be necessary for ROP to occur, but it may increase the risk.

Retinopathy of prematurity (ROP): Optimal timing of clinical evaluation and standard procedures

The authors present the protocol currently used in their institution for initial and follow-up evaluation of infants at high risk for developing retinopathy of prematurity (ROP). After topical anesthesia and lid speculum insertion, the examination is carried out using an indirect binocular ophthalmoscope with a +20 or +28-diopter lens. Mydriasis is achieved by instilling one drop of 1% tropicamide, followed by one drop of 0.5% tropicamide + 2.5% phenylephrine 15 minutes later and after an additional 15 minute interval, another drop of 1% tropicamide. If mydriasis is insufficient after one hour, one drop of a 0.5% tropicamide-5.0% phenylephrine solution may be instilled. The initial examination is performed between the third and fourth weeks of life. If any areas of retinal immaturity are found, the examination is repeated every other week and, later, every three to four weeks, until vascularization has reached the ora serrata. Should any sign of ROP be present during the first examination, the patient is examined weekly or every other week depending on the severity of clinical findings.

Home Oxygen Administration and Retinopathy of Prematurity: Survey of 1988 Practices

Sir .—Premature infants are subjected to stringent invasive and noninvasive oxygen monitoring in the pursuit of the elusive safe path between hypoxic brain damage on the one hand and increased risks of blindness from retinopathy of prematurity (ROP) on the other. For the majority of infants, this period is relatively short. In some infants, however, chronic lung disease leads to such a prolonged oxygen requirement that home oxygen administration is considered. Hudak et al 1 have recently reported a growth benefit to 30 infants receiving oxygen at home when their pulse oximetry was kept over 95% saturation. They also stressed avoidance of hyperoxia but did not relate this to the degree of retinal immaturity or ROP present in a particular infant. The risk for severe ROP appears to be proportional to the degree of retinal immaturity, ie, the amount of avascular retina. It follows from this understanding that when the

Retinal anomalies in trisomy 18.

The eyes of three patients with trisomy 18, the second most common human autosomal trisomy, were examined histopathologically. In the posterior retina transmission and scanning electron microscopic examinations reveal cytological details characteristic of immature neural retinas. We are able to confirm the report that the posterior retinal pigment epithelium in trisomy 18 has a paucity of mature melanosomes and, in fact, resembles human albino retinal pigment epithelium. The asociation of hypopigmentation and retinal immaturity suggests pigmentation plays a role in the control of the maturation of the neural retina.