Neeru Sarin

Optimizing Hand-held Spectral Domain Optical Coherence Tomography Imaging for Neonates, Infants, and Children

PURPOSE To describe age-related considerations and methods to improve hand-held spectral domain optical coherence tomography (HH-SD OCT) imaging of eyes of neonates, infants, and children. METHODS Based on calculated optical parameters for neonatal and infant eyes, individualized SD OCT scan parameters were developed for improved imaging in pediatric eyes. Forty-two subjects from 31 weeks postmenstrual age to 1.5 years were imaged with a portable HH-SD OCT system. Images were analyzed for quality, field of scan, magnification, and potential clinical utility. RESULTS The axial length of the premature infant eye increases rapidly in a linear pattern during the neonatal period and slows progressively with age. Refractive error shifts from mild myopia in neonates to mild hyperopia in infants. These factors affect magnification and field of view of optical diagnostic tools applied to the infant eye. When SD OCT parameters were corrected based on age-related optical parameters, SD OCT image quality improved in young infants. The field of scan and ease of operation also improved, and the optic nerve, fovea, and posterior pole were successfully imaged in 74% and 87% of individual eye imaging sessions in the intensive care nursery and clinic, respectively. No adverse events were reported. CONCLUSIONS SD OCT in young children and neonates should be customized for the unique optical parameters of the infant eye. This customization, not only improves image quality, but also allows control of the density of the optical sampling directed onto the retina.

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.

Abnormal Foveal Morphology in Ocular Albinism Imaged With Spectral-Domain Optical Coherence Tomography

OBJECTIVES To evaluate the spectrum of foveal architecture in pediatric albinism and to assess the utility of spectral-domain optical coherence tomography (OCT) in ocular imaging of children with nystagmus. METHODS Spectral-domain OCT imaging was performed on study subjects in 3 groups: subjects with ocular albinism (OA) or suspected OA with foveal hypoplasia, with nystagmus, and with or without iris transillumination; a subject with oculocutaneous albinism and Hermansky-Pudlak syndrome; and control subjects. Dense volumetric scans of each fovea were captured using standard and handheld spectral-domain OCT devices. Images were postprocessed and scored for the presence and configuration of each retinal layer across the fovea. RESULTS High-quality spectral-domain OCT images obtained from each subject revealed a range of abnormalities in subjects with OA or suspected OA and the subject with oculocutaneous albinism and Hermansky-Pudlak syndrome: persistence of an abnormal, highly reflective band across the fovea, multiple inner retinal layers normally absent at the center of the fovea, and loss of the normally thickened photoreceptor nuclear layer at the fovea when compared with that in control subjects. The optic nerve was elevated in multiple eyes of subjects with OA or suspected OA and the subject with oculocutaneous albinism and Hermansky-Pudlak syndrome. CONCLUSIONS A spectrum of foveal morphological abnormalities is seen in subjects with OA or suspected OA, which in some cases contrasted with previous studies using time-domain OCT. These OCT findings clarify the morphology of foveal hypoplasia seen clinically. This imaging modality may be useful in evaluating children.

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.

Analysis of Pars Plana Vitrectomy for Optic Pit-Related Maculopathy With Intraoperative Optical Coherence Tomography A Possible Connection With the Vitreous Cavity

Optimal management of optic pit-related maculopathy remains to be determined. The fluid source for the maculopathy also remains controversial. In this article, we present a unique surgical technique for internal drainage of the intraretinal fluid and describe the intraoperative use of spectral-domain optical coherence tomography to assist in the surgical management of this condition. Pars plana vitrectomy was performed with elevation of the posterior hyaloid. Following an air-fluid exchange, aspiration over the optic nerve pit was performed. Following aspiration, intraoperative spectral-domain optical coherence tomography demonstrated collapse of the retinoschisis, strongly suggesting a connection between the vitreous cavity and the intraretinal fluid.

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.

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.

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.

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.

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%).