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IMPORTANCE: Preterm infants are at risk for poor visual acuity (VA) outcomes, even without retinal problems on ophthalmoscopy. Infant retinal microanatomy may provide insight as to potential causes. OBJECTIVE: To evaluate the association between preterm infant retinal microanatomy and VA at 9 months’ corrected age. DESIGN, SETTING, AND PARTICIPANTS: This prospective observational study took place from November 2016 and December 2019 at a single academic medical center and included preterm infants enrolled in Study of Eye Imaging in Preterm Infants (BabySTEPS). Infants were eligible for enrollment in BabySTEPS if they met criteria for retinopathy of prematurity (ROP) screening, were 35 weeks’ postmenstrual age or older at the time of first OCT imaging, and a parent or guardian provided written informed consent. Of 118 infants enrolled in BabySTEPS, 61 were included in this analysis. Data were analyzed from March to April 2021. EXPOSURES: Bedside optical coherence tomography (OCT) imaging at a mean (SD) 39.85 (0.79) weeks’ postmenstrual age and monocular grating VA measurement at 9 months’ corrected age. MAIN OUTCOMES AND MEASURES: Presence and severity of macular edema and presence of ellipsoid zone at the fovea measured by extracting semiautomated thicknesses of inner nuclear layer, inner retina, and total retina at the foveal center; choroid across foveal 1 mm; and retinal nerve fiber layer (RNFL) across the papillomacular bundle (PMB). Pearson correlation coefficients were calculated and 95% CIs were bootstrapped for the association between retinal layer thicknesses and continuous logMAR VA. Associations were analyzed between retinal microanatomy and normal (3.70 cycles/degree or greater) vs subnormal grating VA at 9 months’ corrected age using logistic regression and with logMAR VA using linear regression, adjusting for birth weight, gestational age, and ROP severity at the time of OCT imaging and accounting for intereye correlation using generalized estimating equations. RESULTS: The mean (SD; range) gestational age of included infants was 27.6 (2.8; 23.0-34.6) weeks, and mean (SD; range) birth weight was 958.2 (293.7; 480-1580) g. In 122 eyes of 61 infants, the correlations between retinal layer thicknesses and logMAR VA were as follows: r, 0.01 (95% CI, −0.07 to −0.27) for inner nuclear layer; r, 0.19 (95% CI, 0.01 to 0.35) for inner retina; r, 0.15 (95% CI, −0.02 to 0.31) for total retina; r, −0.22 (95% CI, −0.38 to −0.03) for choroid; and r, −0.27 (95% CI, −0.45 to 0.10) for RNFL across the PMB. In multivariable analysis, thinner RNFL across the PMB (regression coefficient, −0.05 per 10-μm increase in RNFL thickness; 95% CI, −0.10 to −0.01; P = .046) and prior ROP treatment (regression coefficient, 0.33 for ROP treatment; 95% CI, 0.11 to 0.56; P = .003) were independently associated with poorer 9-month logMAR VA. CONCLUSIONS AND RELEVANCE: In preterm infants, RNFL thinning across the PMB was associated with poorer 9-month VA, independent of birth weight, gestational age, need for ROP treatment, and macular microanatomy. Evaluation of RNFL thickness using OCT may help identify preterm infants at risk for poor vision outcomes.

IMPORTANCE: Early diagnosis of plus disease is critical in the management of retinopathy of prematurity (ROP). However, there is substantial interexpert disagreement in the diagnosis of plus disease based on vascular changes alone. Information derived from optical coherence tomography (OCT) may help characterize the severity of vascular and structural abnormalities in ROP. OBJECTIVE: To describe integrated visualization of 3-dimensional (3-D) data from investigational swept-source OCT optimized to delineate retinal vascular and microanatomical features in eyes with and without ROP. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional, observational report of OCT was captured in the prospective Study of Eye Imaging in Preterm Infants (BabySTEPS) designed in July 2016 at the Duke Health Intensive Care Nursery. Between December 2018 and August 2019, 2 preterm infants born at 24 and 30 weeks’ gestation were enrolled, underwent ROP screening, and were imaged at those screening visits. Data at 36 weeks’ postmenstrual age were analyzed via this visualization developed between September 2020 and May 2021. MAIN OUTCOMES AND MEASURES: Superimposed en face retinal vascular shadow view (RVSV) montages and thickness maps were used along with OCT B-scans to evaluate retinal vasculature and cross-section in eyes with and without ROP. RESULTS: In the right eyes of 2 infants, 3-D data were integrated and visualized from investigational bedside OCT imaging at the posterior pole. In the infant who developed type 1 ROP, RVSV-OCT confirmed presence of dilated and tortuous posterior pole vessels, shunting, and incomplete perifoveal vascular development, resulting in a temporal notch of avascular retina in zone 1. The thickness map revealed irregular pockets of thickening and thinning, and integrated visualization outlined the demarcation between thicker vascularized retina and thinner avascular fovea and presence of extraretinal neovascularization overlying elevated vessels in the superior arcades. In the infant without ROP (stage 0), RVSV-OCT revealed no abnormal vascular findings at the posterior pole. The integrated visualization showed a dome-shaped retinal thickening at the fovea, which was confirmed as macular edema. CONCLUSIONS AND RELEVANCE: In 2 preterm infants in BabySTEPS, 3-D visualization of OCT findings during the ongoing ROP disease process demonstrated supplemental information about the retinal vasculature and microanatomy that can be useful to clinicians. These additional details provided by OCT could be integrated into future ROP screening methods with artificial intelligence–based analytics.

OBJECTIVE: To report our ability to capture, grade reliably and analyze bedside macular optical coherence tomography (OCT) images from preterm infants and relate OCT findings to biological factors and retinopathy of prematurity (ROP) status at a single time window in the STudy of Eye imaging in Preterm infantS (BabySTEPS). DESIGN: Prospective observational study PARTICIPANTS: Preterm infants eligible for ROP screening, with parental consent for research and a 36±1 weeks postmenstrual age (PMA) visit. METHODS: We imaged both eyes of preterm infants with an investigational non-contact, handheld swept-source OCT at the time of clinical ROP examinations. Macular OCT features and layer thicknesses for untreated eyes of infants at 36±1 weeks PMA were compared to demographic data and clinical ROP examination performed by experts. Statistical analyses accounted for the use of both eyes of infants. MAIN OUTCOME MEASURES: Macular OCT features and layer thicknesses, gender, race/ethnicity, gestational age, birth weight, ROP stage, and plus disease. RESULTS: We captured macular OCT from 169 eyes (one eye excluded for prior ROP treatment) at 36±1 weeks PMA. The quality of OCT volumes was excellent in 33 eyes (19%), acceptable in 112 (67%), poor in 24 (14%) and unusable in 0 (0%). Macular edema was present in 60% of eyes and bilateral in 82% of infants with edema. At the fovea, retinal thickness and inner nuclear layer (INL) thickness increased with edema severity: 183±36μm and 51±27μm in mild edema (16% of eyes), 308±57μm and 163±53μm in moderate (25%) and 460±76μm and 280±83μm in severe (12%), respectively. With an increase in ROP stage from 0 to 2, the mean (standard deviation) retinal thickness at fovea increased from 227(124) to 297(99)μm, p

To describe the foveal avascular zone (FAZ) and vessel density (VD) in the superficial and deep capillary plexus in children with a history of prematurity on optical coherence tomography angiography (OCTA) and their correlation with gestational age (GA) and birth weight (BW). We enrolled 81 preterm- and eight term-born children in this prospective observational study. The Optovue RTVue AVANTI (Optovue Inc., Fremont, CA) was used to procure the OCTA images. The 3 × 3 mm scan protocol centered on the fovea and the central 1 mm of the grid along with the FAZ of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) was acquired. The mean SCP-VD was comparable between the preterms and term controls (p = 0.315) in the central fovea (1-mm grid). However, the SCP-VD of the 3-mm grid was lower in the preterms born without ROP, with type 1 ROP, and with type 2 ROP (47.61, 47.90, and 48.82 respectively) compared to that in the term group (51.38; p = 0.031). The FAZ in the SCP (p = 0.003) and DCP (p = 0.003) was significantly smaller in the preterms compared to that in the controls. Based on the GA sub-analysis, the FAZ was significantly smaller in the SCP and DCP of preterms born 31 weeks GA (p < 0.000, p < 0.035, respectively). Based on the BW, the difference between the FAZ in the SCP (p = 0.002) and DCP (p = 0.003) was significant. There was no association between the visual acuity and FAZ. Optical coherence tomography angiography findings in this study show an altered foveal morphology and vascularity in preterms with and without ROP.

To assess retinal nerve fiber layer (RNFL) thickness in preterm infants.Prospective observational study.We imaged 83 awake infants (159 eyes) at 36 ± 1 weeks postmenstrual age (defined as the time elapsed between the first day of the last maternal menstrual period and the time at imaging) using a handheld optical coherence tomography (OCT) system at the bedside. Blinded graders semi-automatically segmented RNFL in the papillomacular bundle (-15 to +15° relative to the fovea-optic nerve axis). We correlated RNFL thickness and 7 characteristics of interest (sex, race, ethnicity, gestational age, birth weight, stage of retinopathy at prematurity, and presence of pre-plus or plus disease) via univariable and multivariable regressions.RNFL was 3.4 μm thicker in the right eyes than in the left eyes (P.001). Among 7 characteristics, birth weight was the only independent predictor of RNFL thickness (P.001). A 250-g increase in birth weight was associated with 5.2 μm (95% confidence interval: 3.3-7.0) increase in RNFL thickness. Compared with very preterm infants, extremely preterm infants had thinner RNFL (58.0 ± 10.7 μm vs 63.4 ± 10.7 μm, P = .03), but the statistical significance disappeared after adjustment for birth weight (P = .25). RNFL thickness was 11.2 μm thinner in extremely low birth weight infants than in very low birth weight infants (55.5 ± 8.3 μm vs. 66.7 ± 10.2 μm; P.001). The difference remained statistically significant after adjustment for gestational age.Birth weight is a significant independent predictor of RNFL thickness near birth, implying that the retinal ganglion cells reserve is affected by intrauterine processes that affect birth weight.

Background/AimsThe optic nerve development during the critical postnatal weeks of preterm infants is unclear. We aimed to investigate the change of retinal nerve fibre layer (RNFL) in preterm infants.MethodsWe used an investigational handheld optical coherence tomography (OCT) system to serially image awake preterm infants between 30 and 60 weeks postmenstrual age (PMA) at the bedside. We assessed RNFL thickness in the papillomacular bundle and nasal macular ganglion cell layer+inner plexiform layer (GCL+IPL) thickness. We applied a segmented mixed model to analyse the change in the thickness of RNFL and GCL+IPL as a function of PMA.ResultsFrom 631 OCT imaging sessions of 101 infants (201 eyes), RNFL thickness followed a biphasic model between 30 and 60 weeks, with an estimated transition at 37.8 weeks PMA (95% CI: 37.0 to 38.6). RNFL thickness increased at 1.8 μm/week (95% CI: 1.6 to 2.1) before 37.8 weeks and decreased at −0.3 μm/week (95% CI: −0.5 to −0.2) afterwards. GCL+IPL thickness followed a similar biphasic model, in which the thickness increased at 2.9 μm/week (95% CI: 2.5 to 3.2) before 39.5 weeks PMA (95% CI: 38.8 to 40.1) and then decreased at −0.8 μm/week (95% CI: −0.9 to −0.6).ConclusionWe demonstrate the feasibility of monitoring RNFL and GCL+IPL thickness from OCT during the postnatal weeks of preterm infants. Thicknesses follow a biphasic model with a transition age at 37.8 and 39.5 weeks PMA, respectively. These findings may shed light on optic nerve development in preterm infants and assist future study designs.

PURPOSE: 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). METHODS: 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). RESULTS: 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 absence of sub-foveal photoreceptor development and sub-foveal fluid. CONCLUSIONS: Bedside handheld OCT imaging within the first two 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.

BACKGROUND: The application of three-dimensional (3D) visualization techniques to evaluate the earliest visible onset of abnormal retinal vascular development in preterm infants with retinopathy of prematurity (ROP), using bedside non-contact optical coherence tomography (OCT) imaging to characterize morphology and sequential structural changes of abnormal extraretinal neovascularization. METHODS: Thirty-one preterm infants undergoing routine ROP screening with written informed consent for research imaging were enrolled in this prospective observational study. We imaged the macula and temporal periphery of preterm infants using a handheld OCT system (Envisu 2300 or handheld swept-source research system). The scans obtained were segmented and using enhanced ray casting were converted to 3D volumes to which color filter were applied. RESULTS: Using colorized 3D visualization, we defined extraretinal neovascular structures as buds, bridging networks and placoid lesions. We could longitudinally follow progression and regression of extraretinal neovascularization in stage 3 ROP after treatment in one infant over 12 weeks and document the appearance of early buds, and formation of florid neovascularization. From stage 2 to 3 ROP, we observed progression from sessile buds to a complex plaque that corresponded to stage 3 ROP on clinical examination. We demonstrated regression of neovascular complexes to small pre-retinal tufts after treatment with anti-VEGF. CONCLUSIONS: The extension of OCT processing to include surface flattening and colorization that further improved structural analysis rendered better understanding of extraretinal tissue. Our ability to image similar areas in the same infant over multiple visits enabled us to study the evolution of these structural components and follow pathological vascular events longitudinally in development and regression after treatment. These methods can be applied to further study which are likely contribute to our understanding of the pathophysiology of neovascularization in ROP.

Background/aimsNeonatal insults from systemic diseases have been implicated in the pathway of impaired neurodevelopment in preterm infants. We aimed to investigate the associations between systemic health factors and retinal nerve fibre layer (RNFL) thickness in preterm infants.MethodsWe prospectively enrolled infants and imaged both eyes at 36±1 weeks postmenstrual age (PMA) using a hand-held optical coherence tomography system at the bedside in the Duke intensive care nurseries. We evaluated associations between RNFL thickness and 29 systemic health factors using univariable and multivariable regression models.Results83 infants with RNFL thickness measures were included in this study. Based on the multivariable model, RNFL thickness was positively associated with infant weight at imaging and was negatively associated with sepsis/necrotising enterocolitis (NEC). RNFL thickness was 10.4 µm (95% CI −15.9 to −4.9) lower in infants with than without sepsis/NEC in the univariable analysis (pConclusionsLow infant weight and sepsis/NEC were independently associated with thinner RNFL in preterm infants at 36 weeks PMA. To our knowledge, this study is the first to suggest that sepsis/NEC may affect retinal neurodevelopment. Future longitudinal studies are needed to investigate this relationship further.

Human foveal development is a complex process that can be altered by retinopathy of prematurity (ROP). Establishing a baseline of normal foveal development is paramount before understanding the impact caused by prematurity and ROP. It is important to recognize ROP as a neurovascular disease that impacts vascular development, neuronal development, and the complex interplay between them.

To describe the foveal avascular zone (FAZ) and vessel density (VD) in the superficial and deep capillary plexus in children with a history of prematurity on optical coherence tomography angiography (OCTA) and their correlation with gestational age (GA) and birth weight (BW).We enrolled 81 preterm- and eight term-born children in this prospective observational study. The Optovue RTVue AVANTI (Optovue Inc., Fremont, CA) was used to procure the OCTA images. The 3 × 3 mm scan protocol centered on the fovea and the central 1 mm of the grid along with the FAZ of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) was acquired.The mean SCP-VD was comparable between the preterms and term controls (p = 0.315) in the central fovea (1-mm grid). However, the SCP-VD of the 3-mm grid was lower in the preterms born without ROP, with type 1 ROP, and with type 2 ROP (47.61, 47.90, and 48.82 respectively) compared to that in the term group (51.38; p = 0.031). The FAZ in the SCP (p = 0.003) and DCP (p = 0.003) was significantly smaller in the preterms compared to that in the controls. Based on the GA sub-analysis, the FAZ was significantly smaller in the SCP and DCP of preterms born31 weeks and31 weeks GA (p0.000, p0.035, respectively). Based on the BW, the difference between the FAZ in the SCP (p = 0.002) and DCP (p = 0.003) was significant. There was no association between the visual acuity and FAZ.Optical coherence tomography angiography findings in this study show an altered foveal morphology and vascularity in preterms with and without ROP.

Purpose To compare the repeatability and reproducibility of axial and lateral retinal measurements using handheld optical coherence tomography (OCT) systems and a tabletop OCT system. Methods Graders measured central foveal thickness (CFT), optic nerve-to-fovea distance (OFD), and retinal nerve fiber layer (RNFL) thickness on OCT scans of the right eye of 10 healthy adults. Three OCT systems were used: handheld Leica Envisu, investigational handheld swept-source OCT (UC3), and Heidelberg Spectralis tabletop system. All eyes were imaged five times with each OCT system by each of two imagers. A components of variance analysis provided estimates of repeatability (variation due to random error) and reproducibility (variation due to imager, grader, and random error) expressed as standard deviation and (coefficient of variation %). Results Repeatability of CFT (µm) for Envisu, UC3, and Spectralis was 5.9 (2.6%), 6.9 (2.9%), and 4.7 (2.1%), and the reproducibility was 6.1 (2.7%), 7.3 (3.1%), and 4.7 (2.1%), respectively. The repeatability of OFD (mm) was 0.13 (2.9%), 0.10 (2.3%), and 0.07 (1.6%), and the reproducibility was 0.13 (3.0%), 0.10 (2.3%), and 0.07 (1.6%,) respectively. The repeatability for RNFL thickness (µm) for Envisu, UC3, and Spectralis was 4.3 (7.8%), 2.7 (5.4%), and 2.9 (4.9%), and the reproducibility was 4.5 (8.3%), 2.9 (5.8%), and 2.9 (4.9%), respectively. Conclusions All three OCT systems had good repeatability and reproducibility with coefficients of variation of less than 3.5% for CFT and OFD measurements, and less than 8.5% for RNFL thickness. Translational relevance Our findings inform the repeatability and reproducibility of retinal axial and lateral measurements on handheld OCT and are useful for both clinical research and patient care.

Macular images of infants with early-onset edema (occurring at or before 33 weeks' postmenstrual age [PMA]) and infants with late-onset edema (at or after 36 weeks' PMA) were compared. At first appearance, early-onset edema has a more severe morphology, with foveal bulging and elongated cystoid spaces than late-onset edema, which presents as small cystoid spaces outside the foveal center. Morphological variations may be an indicator of the underlying cause of edema in preterm infants. The presence of mostly parafoveal small cystoid spaces in the late-onset edema group may be suggestive of an association with neurological injury.

Monitoring pupil size and response has been an important component of neurologic evaluation in both adult and pediatric populations. Undilated handheld optical coherence tomography (OCT) is an alternative method to evaluate the retina and the optic nerve in infants, with a relative contraindication to pharmacologic pupil dilation. This imaging approach is useful for repeated assessments to monitor changes in response to treatment and provides a platform to study the ocular manifestations of neurologic diseases.

To analyze rubella retinopathy qualitatively and quantitatively in children diagnosed with congenital rubella syndrome (CRS) using a handheld spectral-domain (SD) OCT device.Prospective, cross-sectional, nonrandomized, comparative observational study in a tertiary eye care center in south India.Cases comprised 24 eyes of 13 children diagnosed with CRS based on seropositivity with rubella retinopathy. Controls comprised 26 eyes of 13 age-matched healthy children with normal retina.All participants underwent retinal imaging with RetCam fundus photography (Natus Medical Inc, Pleasanton, CA) and handheld SD OCT (Bioptigen, Inc., Durham, NC). The SD OCT images of both cases and controls were segmented. Retinal and choroid thickness parameters were computed.Qualitative and quantitative changes were observed in SD OCT images of rubella retinopathy compared with those from controls.Characteristic salt-and-pepper appearance was observed on fundus photography in children with rubella compared with the healthy children. The appearance of fovea and retinal features such as foveal dip, external limiting membrane, inner segment-outer segment boundary, outer segment-retinal pigment epithelium boundary, and retinal pigment epithelium were significantly different (P0.05) in eyes with rubella retinopathy compared with healthy eyes Furthermore, eyes with rubella retinopathy exhibited significantly reduced central foveal thickness (P = 0.025), subfoveal outer retinal thickness (P = 0.01), and subfoveal choroid thickness (P = 0.007) compared with healthy eyes.Distinct qualitative and quantitative differences were observed in the SD OCT images of eyes with rubella retinopathy compared with those from healthy eyes.

Purpose Bedside examination of premature infants at risk for retinopathy of prematurity (ROP) is performed predominantly with ophthalmoscopic en face viewing of the retina. Although postmortem retinal microstructures have been studied at the vascular–avascular junction, a critical location for pathogenesis of ROP, to date this has not been possible in vivo. Herein we present bedside, nonsedated in vivo cross-sectional imaging and analysis of retinal microstructures at the vascular–avascular junction in infants with ROP using handheld spectral-domain (SD) OCT. Design Prospective observational study. Participants Eleven preterm infants whose parents or guardians gave consent for research imaging during ROP screening examinations. Methods We imaged the vascular–avascular junction in the temporal retina using an SD OCT system (Envisu; Bioptigen, Inc., Research Triangle Park, NC) in 18 eyes from 11 preterm infants with zone I or II and stage 0 through 4 ROP. B-scan and en face images were analyzed and compared with historical light micrographs. Main Outcome Measures Spectral-domain OCT morphologic features at the vascular–avascular junction. Results Multiple bedside SD OCT findings at the vascular–avascular junction were comparable with historic light micrographs. Thickened inner retinal ridge structure in stage 2 ROP was comparable with thickened vanguard and rear guard cells visible on micrographs; vascular tufts on the posterior retinal surface in stage 2 ROP, broad arcs of neovascularization above the retina in stage 3 ROP, and splitting of inner retinal layers into clefts on either side of neovascularization mimicked findings on historic light micrographs. A unique finding was thickening of the avascular inner retinal band adjacent to neovascularization. On SD OCT imaging over several weeks, neovascularization and retinal clefts diminished after intravitreal bevacizumab therapy. Conclusions Retinal morphologic features at the vascular–avascular junction imaged with handheld SD OCT are consistent with known histopathologic features and provide the advantage of monitoring change in vivo over time. These unique findings provide new insights into preterm retinal neurovascular development in ROP.

This report aims at expanding the current knowledge of retinal microanatomy in children with incontinentia pigmenti using hand-held spectral domain optical coherence tomography (SDOCT).We reviewed OCT scans from 7 children (4 weeks-13 years) obtained either in the clinic or during an examination under anesthesia. The scans were analyzed for anatomical changes in the outer and inner retina, by certified graders. Medical records were assessed for systemic findings.We observed abnormal retinal findings unilaterally in three children. We found inner and outer retinal thinning temporally in two participants. This thinning was present prior to and persisted after treatment. One child showed a distorted foveal contour and significant retinal thickening secondary to dense epiretinal membrane and vitreomacular traction. All other children had normal retinae.Hand-held SDOCT imaging of the retina has brought to light additional retinal structural defects that were not previously reported or visualized via routine clinical ophthalmic examination including retinal photography. Despite a normal foveal structure and visual acuity, we identified inner and outer retinal thinning on SDOCT which may benefit from future functional assessment such as visual field testing.

Background/purpose Using handheld spectral domain optical coherence tomography (SDOCT) imaging to investigate in vivo microanatomic retinal changes and their progression over time in young children with juvenile X-linked retinoschisis (XLRS). Methods This retrospective analysis was of handheld SD OCT images obtained under a prospective research protocol in children who had established XLRS diagnosis based on genetic testing or clinical history. Three OCT graders performed standardized qualitative and quantitative assessment of retinal volume scans, which were divided into foveal, parafoveal, and extrafoveal regions. Visual acuity data were obtained when possible. Results Spectral domain OCT images were available of both eyes in 8 pediatric patients with ages 7 months to 10 years. The schisis cavities involved inner nuclear layer in over 90% (15/16) of eyes in all 3 regions. Retinal nerve fiber and ganglion cell layer involvement was present only in the extrafoveal region in 63% (10/16) eyes and outer nuclear and plexiform layer in few others. In 7 children followed over 2 months to 15 months, the location of schisis remained consistent. Central foveal thickness decreased from the baseline to final available visit in 4/6 eyes. Ellipsoid zone disruption seemed to accompany lower visual acuity in 1/4 eyes. Conclusion Early in life, the SD OCT findings in XLRS demonstrate differences in schisis location in fovea-parafoveal versus extrafoveal region, possible association between poor visual acuity and degree of ellipsoid zone disruption and decrease in central foveal thickness over time in this group. Furthermore, they illustrates that the pattern of XLRS in adults is already present in very young children, and unlike in older children and adults, those presenting with earlier disease may have a more aggressive course. Further studies in this early age group may provide more insights into treatment and prevention of progressive visual impairment in children with XLRS.

Purpose: Trisomy 21, also known as Down syndrome (DS), is the most common trisomy worldwide. Although ocular associations have been reported, retinal anatomy and pathology remain uninvestigated. We evaluate the role of spectral domain optical coherence tomography (SD-OCT) in analyzing foveal morphology of children with DS. Methods: Nineteen consecutive DS children and eight controls were enrolled under a cross-sectional study in an institutional practice. All subjects underwent SD-OCT imaging on a hand-held device. The morphology and thickness of central fovea, inner retinal layers, outer retina, and photoreceptor layers were measured and compared with age-group sub-analysis. Results: Mean age of the cases was 24 months (3–78 months). All cases and controls had a normal fundus on ophthalmoscopy and foveal thickness was comparable (p = 0.718). Inner retinal fusion was complete in the foveal center in only three eyes (15.8%) of cases compared to all eyes (100%) of controls (p < 0.001). The outer plexiform layer was normal in 10 eyes of cases (52.6%) compared to all eyes (100%) of the controls. Only 10 eyes of DS (52.6%) had a normal external limiting membrane, compared to all eyes of controls (100%, p = 0.01). The interdigitation zone (outer segment) was normal in one (5.3%) case compared to eight (67%) controls (p = 0.001). On subgroup analysis, in older cohorts, cases had a greater proportion of abnormal layers compared to controls. Visual acuity was found to be lower in cases when compared to controls, although not significant (p = 0.19). Conclusion: DS babies have abnormal foveal morphology and persistence of inner retinal layers. This may assist our understanding of their visual development.

Purpose To explore vitreoretinal pathologies and their longitudinal changes visible on handheld optical coherence tomography (OCT) of young children with familial exudative vitreoretinopathy. Methods The authors retrospectively analyzed handheld OCT images for vitreoretinal interface and retinal abnormalities and optic nerve head (ONH) elevation. Results From 26 eyes of 16 children (mean age 32 months) with familial exudative vitreoretinopathy, 10 had ONH dragging on photographs, and in these, handheld OCT revealed temporal and anterior retinal displacement, prominent vitreopapillary adhesion or traction, and retinal nerve fiber layer thickening at ONH margins with adjacent retinal elevation. Despite a nearly normal photographic appearance, handheld OCT revealed ONH elevation with vitreopapillary traction (6/16 eyes), ONH edema (1/16 eye), and retinal vascular protrusion (5/16 eyes). Handheld OCT-visualized vitreous abnormalities (18/26 eyes) were more prevalent at higher stages of disease. Handheld OCT-visualized elevation of ONH and the retina worsened over time in nine eyes and improved in 5/6 eyes after vitrectomy. Conclusion Handheld OCT can detect early ONH, retinal, and vitreous changes in eyes with familial exudative vitreoretinopathy. Contraction of strongly adherent vitreous in young patients with familial exudative vitreoretinopathy appears to cause characteristic ONH dragging and tractional complications without partial posterior vitreous detachment. Vitreopapillary dragging may be visible only on OCT and may progress in the absence of obvious retinal change on conventional examination.

IMPORTANCE: Binocular indirect ophthalmoscopy (BIO) examination for retinopathy of prematurity (ROP) is a well-known cause of repeated preterm infant stress. OBJECTIVE: To compare stress during investigational optical coherence tomography (OCT) imaging to that during BIO for ROP. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study examined infants at the bedside in the intensive care nursery. Consecutive preterm infants enrolled in Study of Eye Imaging in Preterm Infants (BabySTEPS) who had any research OCT imaging as part of the study. Patients were recruited from June to November 2019, and analysis began April 2020. MAIN OUTCOMES AND MEASURES: Infant stress was measured using modified components of a neonatal pain assessment tool before (baseline) and during OCT imaging and BIO examination of each eye. RESULTS: For 71 eye examinations of 16 infants (mean [SD] gestational age, 27 [3] weeks; birth weight, 869 [277] g), change from baseline to each eye examination was lower during OCT imaging than during BIO and the difference between OCT imaging and BIO at each eye examination was significant for the following: infant cry score (first eye examination: mean [SD], 0.03 [0.3] vs 1.68 [1.2]; −1.65 [95% CI, −1.91 to −1.39]; second eye examination: mean [SD], 0.1 [0.3] vs 1.97 [1.2]; −1.87 [95% CI, −2.19 to −1.54]), facial expression (first eye: 3 [4%] vs 59 [83%]; −79% [95% CI, −87% to −72%]; second eye: 4 [6%] vs 61 [88%]; −83% [95% CI, −89% to −76%]), and heart rate (first eye: mean [SD], −7 [16] vs 13 [18]; −20 [95% CI, −26 to −14]); second eye: mean [SD], −3 [18] vs 20 [20] beats per minute; −23 [95% CI, −29 to −18]) (P

Purpose The purpose of this study was to evaluate the contrast threshold in Asian Indian preterm infants with and without retinopathy of prematurity (ROP) using Newborn Contrast Cards measured during the first ROP screening and to correlate with final outcome and visual acuity at 3 months of corrected age. Methods Preterm infants born ≤ 2000 grams birth weight (BW) and/or ≤ 34 weeks gestational age (GA) undergoing ROP screening were enrolled prospectively. Visual acuity was recorded using Teller Acuity Cards. Contrast threshold was measured with Newborn Contrast Cards at first screening visit and at the end of ROP screening at 40 weeks of postmenstrual age or older. Results Of the 173 study infants, 134 (77.5%) did not have any stage of ROP. Of the remaining 39 (22.5%), 34 (87%) had type 2 ROP and 5 (13%) had type 1 ROP requiring treatment. The mean contrast threshold at the first visit of the no ROP type 1 and type 2 groups was 0.36 ± 0.07, 0.65 ± 0.19, and 0.46 ± 0.09, respectively (P < 0.001). Contrast threshold had a significant correlation with BW (R = −0.291, P = < 0.001) and gestational age (R = −0.47, P = < 0.001). The contrast threshold at the first visit correlated with visual acuity measured at 3 months of corrected age in logMAR (R = 0.36, P = 0.01). Other than BW and GA, no other systemic risk factors correlated with contrast threshold measured at the first screening visit. Conclusions Newborn Contrast Cards are a viable tool to test contrast threshold in preterm infants. The association between contrast threshold and ROP, and its correlation with visual acuity, suggest that contrast threshold measurement may help predict the clinical vision outcome among prematurely born infants. Translational Relevance Contrast threshold measurement may prove to be a useful tool in the estimation of visual potential in preterm infants.

Purpose Children with a history of prematurity often have poorly developed foveae but when during development foveal differences arise. We hypothesize that the course of foveal development is altered from the time of preterm birth. Methods Eyes of 102 preterm infants undergoing retinopathy of prematurity screening examinations in the STudy of Eye imaging in Premature infantS (BabySTEPS) (NCT02887157) were serially imaged between 30 and 42 weeks postmenstrual age (PMA) using handheld optical coherence tomography systems. Total retinal thickness, inner retinal layer (IRL) thickness, and outer retinal layer (ORL) thickness were measured at the foveal center and parafovea. Foveal put depth, IRL thickness, and ORL thickness were compared between infants born at different gestational ages using mixed effects models. Results Foveal pit depth and IRL thickness were inversely related to gestational age; on average, the most premature infants had the thickest IRL and shallowest pits at all PMAs. Differences were evident by 30 weeks PMA and persisted through 42 weeks PMA. The foveal pits of the most premature infants did not progressively deepen, and the IRLs did not continue to thin with increasing chronological age. Conclusions Foveation in extremely preterm infants is arrested from the earliest observed ages and fails to progress through term equivalent age. The developmental displacement of the IRL from the foveal center into the parafovea does not occur normally after preterm birth. These observations suggest that foveal hypoplasia seen in children with history of prematurity is due to disturbances in foveal development that manifest within weeks of birth.

Current-generation software for rendering volumetric OCT data sets based on ray casting results in volume visualizations with indistinct tissue features and sub-optimal depth perception. Recent developments in hand-held and microscope-integrated intrasurgical OCT designed for real-time volumetric imaging motivate development of rendering algorithms which are both visually appealing and fast enough to support real time rendering, potentially from multiple viewpoints for stereoscopic visualization. We report on an enhanced, real time, integrated volumetric rendering pipeline which incorporates high performance volumetric median and Gaussian filtering, boundary and feature enhancement, depth encoding, and lighting into a ray casting volume rendering model. We demonstrate this improved model implemented on graphics processing unit (GPU) hardware for real-time volumetric rendering of OCT data during tissue phantom and live human surgical imaging. We show that this rendering produces enhanced 3D visualizations of pathology and intraoperative maneuvers compared to standard ray casting.

Anand Vinekar,1 Chaitra Jayadev,1 Siddesh Kumar,2 Shwetha Mangalesh,1,3 Mangat Ram Dogra,4 Noel J Bauer,5 Bhujang Shetty6 1Department of Pediatric Retina, Narayana Nethralaya Eye Hospital, Bangalore, 2Raichur Institute of Medical Sciences, Raichur, Karnataka, India; 3Department of Ophthalmology, Duke University, Durham, NC, USA; 4Advanced Eye Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 5Department of Ophthalmology, Maastricht University of Health Sciences, Maastricht, the Netherlands; 6Department of Ophthalmology, Narayana Nethralaya Postgraduate Institute of Ophthalmology, Bangalore, India Purpose: To report the reduction in the incidence and severity of retinopathy of prematurity (ROP) in rural India over a 4-year period following the introduction of improved neonatal care practices. Methods: The Karnataka Internet Diagnosis of Retinopathy of Prematurity program (KIDROP), is a tele-medicine network that screens for ROP in different zones of Karnataka state in rural India. North Karnataka is the most underdeveloped and remote zone of this program and did not have any ROP screening programs before the intervention of the KIDROP in 2011. Six government and eleven private neonatal centers in this zone were screened weekly. Specific neonatal guidelines for ROP were developed and introduced in these centers. They included awareness about risk factors, oxygen regulation protocols, use of pulse oxymetry, monitoring postnatal weight gain, nutritional best practices, and management of sepsis. The incidence and severity of ROP were compared before the guidelines were introduced (Jan 2011 to Dec 2012) and after the guidelines were introduced (July 2013 to June 2015). Results: During this 4-year period, 4,167 infants were screened over 11,390 imaging sessions. The number of enrolled infants increased from 1,825 to 2,342 between the two periods (P

The authors investigated feasibility of undilated handheld spectral domain optical coherence tomography (SDOCT) retinal imaging in preterm infants and children with neurologic abnormalities.Under an institutional review board-approved protocol, the authors attempted handheld SDOCT imaging of the retina, choroid, and optic nerve in infants and young children without pupil dilation. Scans were analyzed for quality and successful capture of foveal, optic nerve, and retinal structural parameters and abnormalities.The authors obtained images through an undilated pupil of 11 infants/children over 28 eye imaging sessions, 27 at the bedside without sedation, and one under anesthesia. Infants had retinopathy of prematurity (n = 8), hypoxic ischemic encephalopathy (n = 2), or obstructive hydrocephalus (n = 1 child). Pupil sizes ranged from 1.0 mm to 3.5 mm. The authors captured fovea and optic nerve scans in 25/28 eye imaging sessions, with scans of adequate quality to discern prespecified foveal and optic nerve morphology, and of the 25 sessions, the choroidal-scleral junction was visible in all but 6 sessions.Undilated, handheld SDOCT imaging is a potential alternative method to evaluate the retina and optic nerve in patients with relative contraindication to pharmacological pupil dilation. This approach will enable the study of the eye-brain connection and ocular manifestations of neurologic diseases.

Middle-income countries such as India are suffering from the third epidemic of retinopathy of prematurity (ROP). Improved survival and lower infant mortality rates have resulted in an increased number of preterm survivors in rural areas that unfortunately lack ROP specialists. We report our experience of a public-private partnership in rural India of an ongoing telemedicine program Karnataka Internet Assisted Diagnosis of Retinopathy of Prematurity program KIDROP that provides ROP screening by non-physicians. The analysis of 20,214 imaging sessions of 7106 from 36 rural centers in 77 months of activity are presented. The overall incidence of any stage and treatment requiring ROP was 22.39% and 3.57% respectively. We found a higher incidence of severe ROP in private (7.1%) vs government centers (1.7%). Fifty of the 254 babies (19.69%) who underwent treatment were outside the American screening guidelines cut-off. The report compares other "real-world" tele-ROP programs, summarizes the impact, and provides future strategies for outreach ROP screening in middle-income countries.

Purpose Universal eye screening of neonates is currently not standard of care. Early detection of abnormalities could offer prompt management and a reduction in visual morbidity. We report a pilot study using wide-field digital imaging to screen all infants at birth to explore its feasibility as a tool for universal screening. Methods Consecutively enrolled 1021 term infants in a public hospital were imaged within 72 hr of birth using the Retcam shuttle (Clarity MSI, USA). Anterior and dilated posterior segment images were obtained. Infants with abnormal images were examined clinically, and medical or surgical treatment was given when needed, at no cost to the family. Results Of the 1021 healthy full-term newborns, 48 babies had abnormal findings (4.7%). Retinal haemorrhages were the most common (52.1%) abnormality of which 24% were macular. A ‘ridge’ resembling retinopathy of prematurity in both eyes constituted 18.8% of all abnormalities. Nine infants (18.8% of abnormalities and 0.9% overall) had conditions meriting medical or surgical intervention and would have been missed otherwise. Seven of these nine babies (0.7%) needed medical attention with a systemic work-up for conditions such as posterior uveitis with linear perivasculitis, salt and pepper retinopathy or posterior synechia. Two of nine babies (0.2%) required surgical intervention for unilateral cataract and retinoblastoma. Conclusion Universal eye screening of all neonates using wide-field digital imaging is possible and safe. Extrapolating our results to the national scenario, we estimate that 226 950 infants requiring treatment would go undiagnosed annually. Universal infant eye imaging strategies must receive serious national consideration.

Purpose: To report the impact of transient, self-resolving, untreated "macular edema" detected on spectral domain optical coherence tomography in Asian Indian premature infants with retinopathy of prematurity (ROP) on visual acuity (VA) and refraction at 1-year of corrected age. Materials and Methods: Visual acuity and refraction of 11 infants with bilateral macular edema (Group A) was compared with gestational age-matched 16 infants with ROP without edema (Group B) and 17 preterms infants without ROP and without edema (Group C) at 3, 6, 9 and 12 months of corrected age using Teller Acuity Cards and cycloplegic retinoscopy. Sub-group analysis of the previously described pattern A and B macular edema was performed. Results: Visual acuity was lower in infants with macular edema compared with the other two control groups throughout the study period, but statistically significant only at 3 months. Visual improvement in these infants was highest between the 3 rd and 6 th month and plateaued by the end of the 1 st year with acuity comparable to the other two groups. The edema cohort was more hyperopic compared to the other two groups between 3 and 12 months of age. Pattern A edema had worse VA compared to pattern B, although not statistically significant. Conclusion: Macular edema, although transient, caused reduced VA as early as 3 months of corrected age in Asian Indian premature infants weighing

Purpose: The purpose of this study is to estimate the unknown burden of retinopathy of prematurity (ROP) blindness from nine states of India using demographic, incidence and treatment data from an ongoing statewide ROP program in Karnataka called the Karnataka Internet Assisted Diagnosis of ROP (KIDROP) and to calculate the fiscal quantum of preventable blindness in these states. Materials and Methods: The KIDROP model is an ongoing tele-ROP service providing screening and treatment for ROP in Karnataka since 2008. Using this index strategy, an impact assessment in nine other states was constructed, the number of potential blind babies enumerated, the fiscal quantum of blindness prevented in blind person-years (BPYs), and the increase in burden with improving survival and institutional deliveries calculated. Results: The total population in the ten study states is 681.5 million. The eligible babies for ROP screening annually are 467,664. The number of babies admitted to neonatal units is 188,561 of which 160,277 are likely to survive and require screening. Based on KIDROP data, ROP would develop in 35,886 of these infants, and 1281 babies would require treatment annually. The fiscal quantum of BPY saved in these ten states is USD 108.4 million annually, with a further increase of USD 106.8 million with improving infant survival and higher admission rates for delivery. Conclusion: A KIDROP like model can provide ROP screening in low-resource settings, remote centers, and regions with few ROP specialists. Expanding the model to other states with similar demographics can prevent over USD 100 million of blindness burden annually.

Preterm infants with retinopathy of prematurity are at increased risk of poor neurodevelopmental outcomes. Because the neurosensory retina is an extension of the central nervous system, anatomic abnormalities in the anterior visual pathway often relate to system and central nervous system health. We describe optical coherence tomography as a powerful imaging modality that has recently been adapted to the infant population and provides noninvasive, high-resolution, cross-sectional imaging of the infant eye at the bedside. Optical coherence tomography has increased understanding of normal eye development and has identified several potential biomarkers of brain abnormalities and poorer neurodevelopment.

PURPOSE We determined the feasibility of fovea and optic nerve head imaging with a long working distance (LWD) swept source optical coherence tomography (OCT) prototype in adults, teenagers, and young children. METHODS A prototype swept source OCT system with a LWD (defined as distance from the last optical element of the imaging system to the eye) of 350 mm with custom fixation targets was developed to facilitate imaging of children. Imaging was performed in 49 participants from three age groups: 26 adults, 16 children 13 to 18 years old (teenagers), and seven children under 6 years old (young children) under an approved institutional review board protocol. The imaging goal was to acquire high quality scans of the fovea and optic nerve in each eye in the shortest time possible. OCT B-scans and volumes of the fovea and optic nerve head of each eligible eye were captured and graded based on four categories (lateral and axial centration, contrast, and resolution) and on ability to determine presence or absence of pathology. RESULTS LWD-OCT imaging was successful in 88 of 94 eligible eyes, including seven of 10 eyes of young children. Of the successfully acquired OCT images, 83% of B-scan and volumetric images, including 86% from young children, were graded as high-quality scans. Pathology was observed in high-quality OCT images. CONCLUSIONS The prototype LWD-OCT system achieved high quality retinal imaging of adults, teenagers, and some young children with and without pathology with reasonable alignment time. TRANSLATIONAL RELEVANCE The LWD-OCT system can facilitate imaging in children.

INTRODUCTION: Studies have shown that myopic subjects have a two to threefold increased risk of glaucoma compared with that of nonmyopic subjects. The age and sex of an individual with refractive error might also play a major role in altered IOP and thereby added risk factor to develop glaucoma in future. MATERIAL & METHODS: 100 cases (50-myopia and 50hypermetropia) and 100 controls were examined for intraocular pressure using the Goldmann’s Applanation Tonometer, slit lamp mounted. RESULTS: In the 35 to 40 year age group, males with myopia in the right eye, 60% showed higher IOP value ranging between 19 to 20mmHg when compared to control, whereas the males with myopia, in the left eye, did not show higher IOP in any of the age groups. In case of right eyed myopic females of 25 to 30 and 30 to 35 years age groups the mean IOP was found to be higher i.e. 17.7 and 18 respectively. The mean IOP value in right as well as the left eye in hypermetropic males does not show deviation from that of controls of all the age groups, whereas hypermetropic females of the age group of 30 to 35 shows lower mean IOP value as 10.8 and 10.3 Hg mm respectively in the right and the left eye. CONCLUSION: The myopic females of 25-30 years and myopic males of 35-40 years, in the right eye, with higher IOP are prone to develop glaucoma. Further the elevated IOP among the myopics can be used as clue for higher risk of Glaucoma in future.