Evaluating the association of clinical factors and optical coherence tomography retinal imaging with axial length and axial length growth among preterm infants.

PURPOSE: To study the association of clinical factors and optical coherence tomography (OCT) retinal imaging with axial length (AL) and AL growth in preterm infants METHODS: Among a subgroup of infants from the prospective BabySTEPS study who were screened for retinopathy of prematurity (ROP) and had both AL measured and OCT imaging performed, we analyzed data collected prior to 42 weeks postmenstrual age (PMA) and prior to ROP treatment. Using linear mixed effects models, we evaluated associations between AL and AL growth with gestational age (GA), birthweight, PMA, sex, race, multiparity, maximum ROP stage, and OCT features. RESULTS: We included 66 infants (132 eyes), mean GA = 27.6 weeks (SD = 2.3; range: 23.0-34.4) and mean birthweight = 961 g (SD = 269, range: 490-1580). In the final predictive model, longer AL was associated with earlier GA, higher birthweight, later PMA, non-White race, and thicker subfoveal choroid (all p values ≤ 0.01). AL increased linearly up to 42 weeks PMA. There was no difference in AL growth rate by GA, sex, race, multiparity, maximum ROP severity, central foveal thickness, or subfoveal choroidal thickness (all p values > 0.05); but AL growth rate was slower in infants with lower birthweight (p = 0.01). CONCLUSIONS: Among preterm infants, those with earlier GA, higher birthweight, later PMA, non-White race, and thicker subfoveal choroid had the longest AL. AL increased linearly up to 42 weeks PMA and lower birthweight was associated with slower AL growth. These findings may improve the accuracy of measurements taken on preterm infants using imaging techniques affected by AL (e.g., measuring lateral dimensions on OCT). TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02887157 , date of registration: August 25, 2016.

VISUALIZATION FROM INTRAOPERATIVE SWEPT-SOURCE MICROSCOPE-INTEGRATED OPTICAL COHERENCE TOMOGRAPHY IN VITRECTOMY FOR COMPLICATIONS OF PROLIFERATIVE DIABETIC RETINOPATHY.

PURPOSE: To evaluate the use of live volumetric (4D) intraoperative swept-source microscope-integrated optical coherence tomography in vitrectomy for proliferative diabetic retinopathy complications. METHODS: In this prospective study, we analyzed a subgroup of patients with proliferative diabetic retinopathy complications who required vitrectomy and who were imaged by the research swept-source microscope-integrated optical coherence tomography system. In near real time, images were displayed in stereo heads-up display facilitating intraoperative surgeon feedback. Postoperative review included scoring image quality, identifying different diabetic retinopathy-associated pathologies and reviewing the intraoperatively documented surgeon feedback. RESULTS: Twenty eyes were included. Indications for vitrectomy were tractional retinal detachment (16 eyes), combined tractional-rhegmatogenous retinal detachment (2 eyes), and vitreous hemorrhage (2 eyes). Useful, good-quality 2D (B-scans) and 4D images were obtained in 16/20 eyes (80%). In these eyes, multiple diabetic retinopathy complications could be imaged. Swept-source microscope-integrated optical coherence tomography provided surgical guidance, e.g., in identifying dissection planes under fibrovascular membranes, and in determining residual membranes and traction that would benefit from additional peeling. In 4/20 eyes (20%), acceptable images were captured, but they were not useful due to high tractional retinal detachment elevation which was challenging for imaging. CONCLUSION: Swept-source microscope-integrated optical coherence tomography can provide important guidance during surgery for proliferative diabetic retinopathy complications through intraoperative identification of different complications and facilitation of intraoperative decision making.

Poorer neurodevelopmental outcomes associated with cystoid macular edema identified in preterm infants in the intensive care nursery.

PURPOSE: To evaluate the association between cystoid macular edema (CME) observed in very preterm infants and developmental outcomes at 18 to 24 months corrected age. DESIGN: Cohort study. PARTICIPANTS: Infants born at or less than 1500 g or at or less than 30 weeks postmenstrual age who underwent screening for retinopathy of prematurity (ROP) in an intensive care nursery. METHODS: Bedside handheld spectral-domain optical coherence tomography (SD OCT; Envisu, Bioptigen, Inc, Research Triangle Park, NC) imaging was obtained from preterm infants who were being screened for ROP and graded for presence of CME, central foveal thickness (CFT), inner nuclear layer thickness, and foveal-to-parafoveal thickness ratio. At 18 to 24 months corrected age, the children were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition. MAIN OUTCOME MEASURES: Scores on the Bayley cognitive, language, and motor subscales. RESULTS: Among 77 children with SD OCT imaging, 53 were evaluated with the Bayley Scales. Compared with children who did not have CME as infants (n=22), the mean score for children who had CME (n=31) was 7.3 points (95% confidence interval [CI], -15.5 to 0.9; P=0.08) lower on the cognitive subscale, 14.1 points (95% CI, -22.7 to -5.5; P=0.002) lower for the language subscale, and 11.5 points (95% CI, -21.6 to -1.3; P=0.03) lower for the motor subscale. Differences were maintained after adjusting for gestational age and birth weight. Severity of CME, as assessed by foveal-to-parafoveal thickness ratio, within the CME group correlated with poorer cognitive (R2=0.16, P=0.03) and motor (R2=0.15, P=0.03) development. CONCLUSIONS: Cystoid macular edema observed on SD OCT in very preterm infants screened for ROP is associated with poorer language and motor skills at 18 to 24 months corrected age. Evaluation of the retina with SD-OCT may serve as an indicator of neurodevelopmental health for very preterm infants in the intensive care nursery.

FUNCTIONAL OUTCOMES OF YOUNG INFANTS WITH AND WITHOUT MACULAR EDEMA.

PURPOSE: The authors relate posterior segment microanatomy from perinatal spectral domain optical coherence tomography to visual acuity, brain abnormalities, and neurodevelopment. METHODS: Thirteen infants (11 preterm and 2 term birth), imaged in the nursery with portable spectral domain optical coherence tomography, had visual acuity and sensorimotor testing at age 9 months to 15 months (grating acuity) or 4 years to 5 years (optotype), and medical records reviewed for brain magnetic resonance imaging reports and Bayley scales testing at age 18 months to 24 months. RESULTS: Eight children with age-appropriate macular microanatomy without edema on perinatal spectral domain optical coherence tomography had optimal (≥ 20/40) or within normal limits (grating acuity) visual acuity. Five children with perinatal macular edema had suboptimal visual acuity (in 9/10 eyes) and sensorimotor deficits, magnetic resonance imaging abnormalities, or poor neurodevelopment. Macular edema persisted in 1 infant through 9-month corrected age. CONCLUSION: Maturation of the visual system and evolution of retinal anomalies can be monitored with posterior segment spectral domain optical coherence tomography. Retinal microanatomy observed in infancy might relate to subsequent vision and other central nervous system events, but additional studies are needed to determine the range of normal microanatomy in infants and how this relates to vision and neurodevelopment.

Longitudinal Choroidal Development in Preterm Infants.

Purpose: To characterize changes in subfoveal choroidal thickness in preterm infants from 30 to 60 weeks' postmenstrual age (PMA). Design: The prospective, observational Study of Eye Imaging in Preterm infantS (BabySTEPS) enrolled infants eligible for retinopathy of prematurity screening per the American Association of Pediatrics guidelines. Subjects: Infants imaged with an investigational, handheld OCT at ≥ 4 distinct imaging sessions between 30 to 60 weeks' PMA as part of BabySTEPS. Methods: Average choroidal thickness across the central subfoveal 1 mm in each eye at each time point was measured using custom segmentation software, and errors were manually corrected by a trained grader. We prospectively collected birth history data. A segmented mixed model was used to analyze the change in choroidal thickness as a function of PMA, birth weight, and gestational age (GA). Main Outcome Measures: Characterization of normative subfoveal choroidal thickness values and choroidal growth rate between 30 to 60 weeks' PMA. Results: We included 592 imaging sessions of 79 preterm infants (152 eyes). Mean (± standard deviation) GA was 27.5 ± 2.5 weeks. Mean choroidal thickness was 141.4 ± 34.5 µm at 30 weeks, 272.2 ± 83.9 µm at 38 weeks, and 306.2 ± 77.4 µm between 56 and 60 weeks. Between 30 and 60 weeks' PMA, choroidal growth followed a biphasic model, with a linear growth rate of 14.8 µm per week (95% confidence interval [CI], 13.6-16.0) from 30 until 38.4 weeks, then cessation of growth, with a growth rate of 0.3 µm per week (95% CI, -1.1 to 1.6) from 38.4 to 60 weeks. Infants with extremely low birth weight (ELBW; < 1000 g) and extremely preterm (GA < 28 weeks) infants had significantly slower initial growth rates compared with very low and low birth weight and very preterm and preterm infants (ELBW 13.0 vs. 21.0 µm per week; P < 0.0001 and extremely preterm 13.2 vs. 18.0 µm per week; P = 0.003). Conclusions: Preterm infant choroidal thickness experiences rapid linear growth from 30 to 38 weeks' PMA, at which time growth nearly stops. These foundational measurements and identification of the impact of extremes of low birth weight and prematurity on choroidal development will be essential as researchers begin to understand the role of choroidal development in ocular and retinal health in human infants. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Spectral-domain optical coherence tomography characteristics of intermediate age-related macular degeneration.

PURPOSE: Describe qualitative spectral-domain optical coherence tomography (SD-OCT) characteristics of eyes classified as intermediate age-related macular degeneration (nonadvanced AMD) from Age-Related Eye Disease Study 2 (AREDS2) color fundus photography (CFP) grading. DESIGN: Prospective cross-sectional study. PARTICIPANTS: We included 345 AREDS2 participants from 4 study centers and 122 control participants who lack CFP features of intermediate AMD. METHODS: Both eyes were imaged with SD-OCT and CFP. The SD-OCT macular volume scans were graded for the presence of 5 retinal, 5 subretinal, and 4 drusen characteristics. In all, 314 AREDS2 participants with ≥1 category-3 AMD eye and all controls each had 1 eye entered into SD-OCT analysis, with 63 eyes regraded to test reproducibility. MAIN OUTCOME MEASURES: We assessed SD-OCT characteristics at baseline. RESULTS: In 98% of AMD eyes, SD-OCT grading of all characteristics was successful, detecting drusen in 99.7%, retinal pigment epithelium (RPE) atrophy/absence in 22.9%, subfoveal geographic atrophy in 2.5%, and fluid in or under the retina in 25.5%. Twenty-eight percent of AMD eyes had characteristics of possible advanced AMD on SD-OCT. Two percent of control eyes had drusen on SD-OCT. Vision loss was not correlated with foveal drusen alone, but with foveal drusen that were associated with other foveal pathology and with overlying focal hyperreflectivity. Focal hyperreflectivity over drusen, drusen cores, and hyper- or hyporeflectivity of drusen were also associated with RPE atrophy. CONCLUSIONS: Macular pathologies in AMD can be qualitatively and reproducibly evaluated with SD-OCT, identifying pathologic features that are associated with vision loss, RPE atrophy, and even possibly the presence of advanced AMD not apparent on CFP. Qualitative and detailed SD-OCT analysis can contribute to the anatomic characterization of AMD in clinical studies of vision loss and disease progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Biphasic change in retinal nerve fibre layer thickness from 30 to 60 weeks postmenstrual age in preterm infants.

BACKGROUND/AIMS: The 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. METHODS: We 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. RESULTS: From 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). CONCLUSION: We 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.

Associations between systemic health and retinal nerve fibre layer thickness in preterm infants at 36 weeks postmenstrual age.

BACKGROUND/AIMS: Neonatal 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. METHODS: We 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. RESULTS: 83 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 (p<0.001). This difference remained statistically significant after adjustment for confounding variables in various combinations (birth weight, birthweight percentile, gestational age, infant weight at imaging and growth velocity). A 250 g increase in infant weight at imaging was associated with a 3.1 µm (95% CI 2.1 to 4.2) increase in RNFL thickness in the univariable analysis (p<0.001). CONCLUSIONS: Low 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.

Association Between Retinal Microanatomy in Preterm Infants and 9-Month Visual Acuity.

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.

Dynamics of human foveal development after premature birth.

PURPOSE: To determine the dynamic morphologic development of the human fovea in vivo using portable spectral domain-optical coherence tomography (SD-OCT). DESIGN: Prospective, observational case series. PARTICIPANTS: Thirty-one prematurely born neonates, 9 children, and 9 adults. METHODS: Sixty-two neonates were enrolled in this study. After examination for retinopathy of prematurity (ROP), SD-OCT imaging was performed at the bedside in nonsedated infants aged 31 to 41 weeks postmenstrual age (PMA) (= gestational age in weeks + chronologic age) and at outpatient follow-up ophthalmic examinations. Thirty-one neonates met eligibility criteria. Nine children and nine adults without ocular pathology served as control groups. Semiautomatic retinal layer segmentation was performed. Central foveal thickness, foveal to parafoveal (FP) ratio (central foveal thickness divided by thickness 1000 µm from the foveal center), and 3-dimensional thickness maps were analyzed. MAIN OUTCOME MEASURES: In vivo determination of foveal morphology, layer segmentation, analysis of subcellular changes, and spatiotemporal layer shifting. RESULTS: In contrast with the adult fovea, several signs of immaturity were observed in the neonates: a shallow foveal pit, persistence of inner retinal layers (IRLs), and a thin photoreceptor layer (PRL) that was thinnest at the foveal center. Three-dimensional mapping showed displacement of retinal layers out of the foveal center as the fovea matured and the progressive formation of the inner/outer segment band in the opposite direction. The FP-IRL ratios decreased as IRL migrated before term and minimally after that, whereas FP-PRL ratios increased as PRL subcellular elements formed closer to term and into childhood. A surprising finding was the presence of cystoid macular edema in 58% of premature neonates that appeared to affect inner foveal maturation. CONCLUSIONS: This study provides the first view into the development of living cellular layers of the human retina and of subcellular specialization at the fovea in premature infant eyes using portable SD-OCT. Our work establishes a framework of the timeline of human foveal development, allowing us to identify unexpected retinal abnormalities that may provide new keys to disease activity and a method for mapping foveal structures from infancy to adulthood that may be integral in future studies of vision and visual cortex development. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Recovery of the neurosensory retina after macular translocation surgery is independent of preoperative macular sensitivity in neovascular age-related macular degeneration.

PURPOSE: To directly assess the recovery of the retina overlying choroidal neovascularization in neovascular age-related macular degeneration and to understand the relationship between macular sensitivity and visual functional measures and retinal structural alterations as predictive factors for outcome among eyes undergoing macular translocation surgery (MT360). METHODS: In a prospective, consecutive case series of 55 patients with subfoveal choroidal neovascularization undergoing MT360, we explored the relationship between macular sensitivity on the Nidek microperimeter-1 with pathologic features on optical coherence tomography and with distance and near visual acuity, reading speed, contrast sensitivity, color vision, and National Eye Institute Visual Function Questionnaire-25 composite quality-of-life (QOL) score, both before and at 1 year after MT360. RESULTS: On average, there was improvement in all measures of visual function, macular sensitivity, and QOL after MT360. Preoperative median retinal sensitivity score did not predict postoperative measures of visual function, macular sensitivity, and vision-related QOL. Correlation between preoperative median retinal sensitivity score and preoperative measures of visual function and vision-related QOL was generally poor, excepting modest correlation for contrast sensitivity and color vision. However, correlation between postoperative median retinal sensitivity score and postoperative measures of visual function and vision-related QOL was uniformly modest, and change in median retinal sensitivity score correlated modestly with change in most measures of visual function and QOL. Among optical coherence tomography morphologic features, preoperative retinal pigment epithelium elevation predicted reduced postoperative contrast sensitivity (P = 0.04), while preoperative epiretinal membrane or vitreomacular traction predicted increased postoperative contrast sensitivity (P = 0.05). Preoperative cystoid macular edema, subretinal fluid, and subretinal lesion were associated with decreased median retinal sensitivity score (P values ≤0.03). CONCLUSION: The authors' findings demonstrate the resilience and recovery of poorly functioning retina in neovascular age-related macular degeneration but fail to demonstrate a role for macular sensitivity as measured by Nidek microperimeter-1 in identifying irreversibly damaged retina that would not benefit from MT360.

Treatment of non-age-related macular degeneration submacular diseases with macular translocation surgery.

PURPOSE: To evaluate the use of macular translocation surgery 360 in blinding submacular diseases other than age-related macular degeneration. METHODS: A retrospective, consecutive case review was performed of subjects treated with macular translocation surgery 360 for a submacular disease other than age-related macular degeneration. Primary outcome was change in visual acuity. Clinical data were collected and analyzed, including demographics, visual acuity, imaging features, surgery details, and complications. RESULTS: The review identified 16 subjects who had undergone macular translocation surgery 360 from 1996 to 2009 for submacular diseases other than age-related macular degeneration. These diseases included Best disease (n = 2), angioid streaks (n = 1), pathologic myopia (n = 3), punctate inner choroidopathy (n = 2), presumed ocular histoplasmosis syndrome (n = 3), central serous chorioretinopathy (n = 1), adult-onset vitelliform macular dystrophy (n = 3), and North Carolina macular dystrophy (n = 1). Mean preop visual acuity was 20/135 (range, 20/50-20/500). A ≤ 3-line acuity loss was seen in 13 of 16 (81%) subjects. Mean postop visual acuity was 20/110 (range, 20/40-20/1,000). The most common postop complications included epiretinal membrane (50%), cystoid macular edema (31%), residual diplopia (25%), retinal detachment (13%), and recurrent choroidal neovascularization (13%). Mean follow-up was 28 months (range, 4-61 months). CONCLUSION: Macular translocation surgery 360 may be considered in subjects with progressive bilateral vision loss from various conditions other than age-related macular degeneration. Although a significant number of complications occurred, a large percentage of subjects gained >3 lines of visual acuity (38%) and achieved a final visual acuity of ≥ 20/50 (31%).

Macular features from spectral-domain optical coherence tomography as an adjunct to indirect ophthalmoscopy in retinopathy of prematurity.

PURPOSE: To compare vitreoretinal pathology imaged with portable handheld spectral-domain optical coherence tomography (SD-OCT) to conventional indirect ophthalmoscopic examination in neonates undergoing screening for retinopathy of prematurity. METHODS: Spectral-domain optical coherence tomography images were collected from 76 eyes of 38 neonates during 118 routine retinopathy of prematurity examinations. Imaging sessions in the Neonatal Intensive Care Unit were performed immediately after the subjects underwent a standard ophthalmic examination with indirect ophthalmoscopic by a pediatric ophthalmologist. Masked certified SD-OCT graders evaluated scans for preretinal and retinal findings including material in the vitreous, epiretinal membrane, intraretinal cystoid structures and deposits, optic nerve and vascular features, and severity and location of retinopathy of prematurity. The frequency of detection of these features by clinical examination and evaluation of SD-OCT images was compared to determine potential clinical advantages for each modality. RESULTS: Portable SD-OCT imaging characterized macular features of retinal cystoid structures in 39% of examinations and epiretinal membrane in 32% of examinations. Neither feature was visualized by indirect ophthalmoscopy in any cases. The clinician using indirect ophthalmoscopy detected stage of retinopathy of prematurity and the presence or absence of Plus or pre-Plus disease. These were not visualized with SD-OCT. CONCLUSION: Spectral-domain optical coherence tomography provides new information about the premature infant retina that is of unknown importance relative to visual development and acuity. As used in this study, SD-OCT does not replace indirect ophthalmoscopy for evaluation of retinopathy of prematurity.

Preterm Infant Stress During Handheld Optical Coherence Tomography vs Binocular Indirect Ophthalmoscopy Examination for Retinopathy of Prematurity.

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 < .001 for all). Change in respiratory rate and oxygen saturation did not differ between OCT imaging and BIO. CONCLUSIONS AND RELEVANCE: While the role of OCT alone or in combination with BIO is currently unknown for ROP, these findings suggest that investigational OCT imaging of ROP is less stressful than BIO examination by a trained ophthalmologist.

Systemic Factors Associated with a Thinner Choroid in Preterm Infants.

Purpose: To identify systemic health factors associated with a thinner choroid, which has been hypothesized as a cause of poor visual outcomes in low-birth weight infants. Design: The prospective, observational Study of Eye Imaging in Preterm Infants (BabySTEPS) enrolled infants recommended for retinopathy of prematurity screening based on the American Association of Pediatrics guidelines. Participants: Infants who underwent imaging with investigational handheld OCT at 36 ± 1 weeks' postmenstrual age (PMA) as part of BabySTEPS. Methods: Average choroidal thickness was measured across the central subfoveal 1 mm. We concurrently collected maternal and infant clinical health data. Univariate and multivariate linear regression analyses were performed to evaluate factors associated with choroidal thickness. The left and right eyes showed similar thicknesses, so their average was used for analysis. Main Outcomes Measures: Association between infant health factors and subfoveal choroidal thickness. Results: Subfoveal choroidal thickness was measurable in 82 of 85 infants and 94% of eyes. Mean choroidal thickness was 231 ± 78 µm. In the univariate analysis, a thinner choroid was associated with decreased growth velocity (P < 0.001), lower birth weight (P < 0.001), smaller head circumference (P < 0.001), younger gestational age (P = 0.01), the presence of patent ductus arteriosus (P = 0.05), sepsis or necrotizing enterocolitis (P = 0.03), bronchopulmonary dysplasia (P = 0.03), pulmonary interstitial emphysema (P = 0.002), more days on oxygen support (P < 0.001), and being on oxygen support at 36 weeks (P < 0.001) and at the time of imaging (P < 0.001). In the multivariate analysis, growth velocity (P = 0.002) and oxygen support at the time of OCT imaging (P = 0.004) remained associated with a thinner choroid. Conclusions: A thinner choroid is associated independently with growth velocity and receiving oxygen support at 36 ± 1 weeks PMA. This suggests that choroidal development in preterm infants may be related to growth rate in the first weeks of life and the prolonged use of supplemental oxygen. Longitudinal studies are needed to assess differences in choroidal thickness before 36 weeks PMA and to assess their impact on visual outcomes.

Birth Weight Is a Significant Predictor of Retinal Nerve Fiber Layer Thickness at 36 Weeks Postmenstrual Age in Preterm Infants.

PURPOSE: To assess retinal nerve fiber layer (RNFL) thickness in preterm infants. DESIGN: Prospective observational study. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Morphological characteristics of early- versus late-onset macular edema in preterm infants.

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.

Characterization of Long Working Distance Optical Coherence Tomography for Imaging of Pediatric Retinal Pathology.

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.

Relationship of central choroidal thickness with age-related macular degeneration status.

PURPOSE: To compare choroidal thickness in patients with intermediate or advanced age-related macular degeneration (AMD) and control subjects using enhanced-depth imaging optical coherence tomography (EDI-OCT). DESIGN: Retrospective cross-sectional study of 325 eyes from 164 subjects who underwent EDI-OCT for the Age-Related Eye Disease Study (AREDS) 2 Ancillary Spectral Domain OCT study. METHODS: Choroidal thickness was measured by semi-automated segmentation of EDI-OCT images from 1.5 mm nasal to 1.5 mm temporal to the fovea. Multivariate linear regression was used to evaluate the association of subfoveal choroidal thickness or average choroidal thickness across the central 3-mm segment with systemic and ocular variables. Choroidal thickness measurements were compared between eyes with no AMD (n = 154) (ie, controls), intermediate AMD (n = 109), and advanced AMD (n = 62). RESULTS: Both subfoveal and average choroidal thicknesses were associated with age (P < .001) and refractive error (P < .001), but not other variables tested. Mean average choroidal thickness was significantly reduced in advanced AMD as compared with control eyes (P = .008), with no significant difference between advanced and intermediate AMD eyes (P = .152) or between intermediate AMD and control eyes (P = .098). Choroidal thinning was also noted from 1.5 mm nasal to 1.5 mm temporal to the fovea when comparing advanced AMD with control eyes (P < .05 at all 0.5 mm interval locations). After adjustment for age and refractive error, however, there was no significant difference in subfoveal (P = .675) or average choroidal thickness (P = .746) across all 3 groups. CONCLUSIONS: When adjusted for age and refractive error, central choroidal thickness may not be significantly influenced by AMD status based on AREDS categorization.

Characterization of the choroid-scleral junction and suprachoroidal layer in healthy individuals on enhanced-depth imaging optical coherence tomography.

IMPORTANCE: Accurate measurements of choroidal thickness (CT) using enhanced-depth imaging optical coherence tomography (EDI-OCT) require a well-defined choroid-scleral junction (CSJ), which may appear in some eyes as a hyporeflective band corresponding to the suprachoroidal layer (SCL). OBJECTIVE: To identify factors associated with the presence and thickness of the SCL in healthy participants and determine how different CSJ boundary definitions impact CT measurements. DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of EDI-OCT images obtained prospectively from 74 eyes of 74 controls (mean age, 68.6 years) from the Age-Related Eye Disease Study 2 Ancillary SDOCT Study. MAIN OUTCOMES AND MEASURES: The CSJ appearances were categorized as either having no visible SCL or a hyporeflective band corresponding to the SCL. Ocular parameters associated with the presence and thickness of the SCL were identified. Subfoveal CT was measured using 3 different posterior boundaries: (1) the posterior vessel border (vascular CT [VCT]), (2) inner border of the SCL (stromal CT [StCT]), and (3) inner border of the sclera (total CT [TCT]). Manual segmentation using custom software was used to compare VCT, StCT, and TCT across the macula. RESULTS The SCL was visible in 33 eyes (44.6%). Factors associated with SCL presence and thickness included hyperopic refractive error (R2 = 0.123; P = .045) and increased TCT (R2 = 0.215; P = .004), but not age, visual acuity, intraocular pressure, retinal foveal thickness, VCT, or StCT. In eyes where the SCL was not visible, mean [SD] subfoveal VCT was 222.3 [101.5] µm and StCT and TCT were 240.0 [99.0] µm, with a difference of 17.7 [16.0] µm (P < .001). In eyes where the SCL was visible, mean [SD] subfoveal VCT, StCT, and TCT were 221.9 [83.1] µm, 257.7 [97.3] µm, and 294.1 [104.8] µm, respectively, with the greatest difference of 72.2 [30.4] µm between VCT and TCT (P < .001). All 3 CT measurements were significantly different along all points up to 3.0 mm nasal and temporal to the fovea. CONCLUSIONS AND RELEVANCE: A hyporeflective SCL is visible at the CSJ on EDI-OCT in nearly half of healthy individuals, and its presence correlates with hyperopia. Different posterior boundary definitions may result in significant differences in CT measurements and should be explicitly identified in future choroidal studies and segmentation algorithms.