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Vestibular schwannomas (VSs), also called acoustic neuromas, are benign intracranial neoplasms of the vestibulocochlear (VIII) cranial nerve. Management options include “wait-and-scan,” stereotactic radiosurgery and surgical resection. Due to the proximity of the VIII nerve to the facial (VII) nerve in the cerebello-pontine angle, the VII nerve is particularly vulnerable to the effects of surgical resection. This can result in poor eye closure, lagophthalmos and resultant corneal exposure post VS resection. Additionally, compression from the tumor or resection can cause trigeminal (V) nerve damage and a desensate cornea. The combination of an exposed and desensate cornea puts the eye at risk of serious ocular complications including persistent epithelial defects, corneal ulceration, corneal vascularization, corneal melting and potential perforation. The abducens (VI) nerve can be affected by a large intracranial VS causing raised intracranial pressure (a false localizing sign) or as a result of damage to the VI nerve at the time of resection. Other types of neurogenic strabismus are rare and typically transient. Contralaterally beating nystagmus as a consequence of vestibular dysfunction is common post-operatively. This generally settles to pre-operative levels as central compensation occurs. Ipsilaterally beating nystagmus post-operatively should prompt investigation for post-operative cerebrovascular complications. Papilledema (and subsequent optic atrophy) can occur as a result of a large VS causing raised intracranial pressure. Where papilledema follows surgical resection of a VS, it can indicate that cerebral venous sinus thrombosis has occurred. Poor visual function following VS resection can result as a combination of all these potential complications and is more likely with larger tumors.

The purpose of the study was to perform a post hoc analysis to explore the effect of baseline anatomic characteristics identified on OCT on best-corrected visual acuity (BCVA) responses to risuteganib from the completed phase II study in subjects with dry age-related macular degeneration (AMD).Post hoc analysis of a randomized, double-masked, placebo-controlled, phase II study.Eyes with intermediate dry AMD with BCVA between 20/40 and 20/200. Patients with concurrent vision-influencing or macula-obscuring ocular pathologies were excluded.Patients were randomized to receive a 1-mg intravitreal risuteganib injection or a sham injection at baseline. A second 1-mg intravitreal injection of risuteganib was given at week 16 to those in the treatment arm. Two independent, masked reading centers evaluated the baseline anatomic characteristics on OCT to explore features associated with positive responses to risuteganib.Treatment response was defined as a gain of ≥ 8 letters in BCVA from baseline to week 28 in the treatment arm, compared with baseline to week 12 in the sham group. Anatomic parameters, measured by retinal segmentation platforms, including measures of retinal thickness were compared between the responders and nonresponders to risuteganib.Thirty-nine patients completed the study and underwent analysis. In the treatment arm, 48% of eyes demonstrated treatment responses, compared with 7% in the sham group. In the quantitative anatomic assessment, enhanced ellipsoid integrity, greater outer retinal thickness, and decreased geographic atrophy were associated with increased BCVA gains to risuteganib.This post hoc analysis demonstrated that baseline OCT features may help determine the likelihood of a functional response to risuteganib. The characterization of higher-order OCT features may provide important information regarding biomarkers for treatment response and could facilitate optimized clinical trial enrollment and enrichment.

Background/aimsTo quantify retinal cavitation size over time in macular telangiectasia type 2 (MacTel) and to correlate changes with visual acuity and area of ellipsoid zone loss.MethodsOptical coherence tomography (OCT) macula volume scans from sham eyes included in a prospective, phase II clinical trial of human ciliary neutrophic factor for MacTel at baseline, 1 year and 2 years of follow-up were analysed. Cavitations were segmented by two independent readers. Total cavitation volume was compared with area of ellipsoid zone loss and best-corrected visual acuity (BCVA).ResultsFifty-one eyes from 51 unique patients (mean age 62 years, range 45–79 years) were included. Intraclass correlation between readers for cavitation volume was excellent (>0.99). Average cavitation volume was 0.0109 mm3, 0.0113 mm3and 0.0124 mm3at baseline, 1 year and 2 years, respectively. The average rate of cavitation volume change was +0.0039 mm3/year. 10 eyes (20%) had a significant change in cavitation volume during the study (3 decreased, 7 increased). Eyes with increased cavitation volume had worse BCVA compared with eyes with no change/decreased cavitation volume (71.5 vs 76.1 ETDRS letters, respectively). Cavitation volume was negatively correlated to BCVA (r=−0.37) but not to area of ellipsoid zone loss. Cavitation volume was negatively predictive of BCVA in both univariate and multivariate mixed-effects modelling with ellipsoid zone loss.ConclusionsRetinal cavitations and their rate of change in MacTel can be reliably quantified using OCT. Cavitations are negatively correlated with visual acuity and may be a useful OCT-based biomarker for disease progression and visual function in MacTel.

ObjectiveMedial eyelid tumours may result in the loss of the proximal lacrimal system during staged excision and delayed reconstruction, to achieve tumour margin clearance. The remnant canaliculus was marsupialised during reconstruction. The aim was to understand how many patients experienced symptomatic epiphora as a consequence of this.Methods and analysisA retrospective study including patients over a 15-year period with medial eyelid tumours, where the proximal lacrimal system was sacrificed to achieve tumour margin clearance. Included were all who had marsupialisation of the remnant distal stump as part of their delayed reconstruction. All who had pre-existing epiphora were excluded. The primary objective was the rate of epiphora following the procedure. A systematic literature review of postoperative epiphora occurring in patients with lid tumours requiring lacrimal system injury/sacrifice during tumour excision.ResultsThere were 22 eyes (22 patients). All were basal cell carcinomas except for 1 (4.5%) tarsal conjunctival squamous cell carcinoma. All cases involved the lower lid. There were two (9.1%) patients who developed epiphora. One patient underwent a superior three-snip punctoplasty, botulinum toxin to the lacrimal gland and conjunctivodacryocystorhinostomy with Lester Jones tube insertion. The other patient was not overly troubled and did not require further treatment. The literature review showed the median postoperative rate of epiphora in these patients was 12.5% (range 0%–100%).ConclusionMarsupialisation of the remnant canaliculus during delayed reconstruction is a straightforward and effective surgical option, which may help prevent postreconstruction epiphora when the proximal lacrimal system is sacrificed for tumour margin clearance.Trial registration number10391.

Background/objectives To evaluate the outcomes of orbital evisceration with primary implant placement in acutely infected/inflamed eyes, using implant exposure/extrusion as a surrogate of success. To contextualise this with previously published literature. Subjects/methods A retrospective case series of all patients with acutely infected/inflamed eyes undergoing urgent orbital evisceration with primary implants, at a British tertiary centre between January 2006 and August 2018. A systematic literature review of orbital eviscerations with primary implant placement in acute endophthalmitis/infection and recent trauma. Results Twenty-six eyes were eviscerated in the context of acute infection/inflammation. Twenty-four eyes had primary orbital implants. Indications for evisceration included endophthalmitis (18/26, 69%), microbial keratitis with corneal perforation (4/26, 15%), non-infectious corneal perforation (3/26, 12%), and recent trauma (1/26, 4.8%). The implants used were acrylic (15/24, 63%), MEDPOR (5/24, 21%), and silicone (4/24, 17%). The follow-up period was 15 months to 14 years. Implant exposure occurred in two (8.3%), managed with implant exchange and scleral reformation in one, and implant removal with dermis fat grafting in the other. One patient (4.2%) had conjunctival wound dehiscence with spontaneous healing. Six (25%) required further surgery for minor complications as follows: conjunctival prolapse, upper lid ptosis with slight sulcus loss, lower lid entropion with shortened fornix, and lower lid ectropion. The systematic literature review showed that the mean rate of orbital implant exposure/extrusion in this subset of patients was 7.8% (95% CI: 2.7%, 12.9%, SD 8.0%), range 0-27%. Conclusions In acutely infected/inflamed eyes, the implant exposure/extrusion rate following orbital evisceration with primary implant placement is acceptable.

In macula-wide analyses, spectral-domain (SD) optical coherence tomography (OCT) features including drusen volume, hyperreflective foci, and OCT-reflective drusen substructures independently predict geographic atrophy (GA) onset secondary to age-related macular degeneration (AMD). We sought to identify SD OCT features in the location of new GA before its onset.Retrospective study.Age-Related Eye Disease Study 2 Ancillary SD OCT Study participants.We analyzed longitudinally captured SD OCT images and color photographs from 488 eyes of 488 participants with intermediate AMD at baseline. Sixty-two eyes with sufficient image quality demonstrated new-onset GA on color photographs during study years 2 through 7. The area of new-onset GA and one size-matched control region in the same eye were segmented separately, and corresponding spatial volumes on registered SD OCT images at the GA incident year and at 2, 3, and 4 years previously were defined. Differences in SD OCT features between paired precursor regions were evaluated through matched-pairs analyses.Localized SD OCT features 2 years before GA onset.Compared with paired control regions, GA precursor regions at 2, 3, and 4 years before (n = 54, 33, and 25, respectively) showed greater drusen volume (P = 0.01, P = 0.003, and P = 0.003, respectively). At 2 and 3 years before GA onset, they were associated with the presence of hypertransmission (P0.001 and P = 0.03, respectively), hyperreflective foci (P0.001 and P = 0.045, respectively), OCT-reflective drusen substructures (P = 0.004 and P = 0.03, respectively), and loss or disruption of the photoreceptor zone, ellipsoid zone, and retinal pigment epithelium (RPE, P0.001 and P = 0.005-0.045, respectively). At 4 years before GA onset, precursor regions were associated with photoreceptor zone thinning (P = 0.007) and interdigitation zone loss (P = 0.045).Evolution to GA is heralded by early local photoreceptor changes and drusen accumulation, detectable 4 years before GA onset. These precede other anatomic heralds such as RPE changes and drusen substructure emergence detectable 1 to 2 years before GA. This study thus identified earlier end points for GA as potential therapeutic targets in clinical trials.

To demonstrate the anatomical development of the human macula using handheld spectral domain optical coherence tomography (SD-OCT) during the first 5 years of life. This study is a cross-sectional, observational case series. Thirty-five normal eyes of 35 full-term/late preterm infants and children under 5 years of age were included. Handheld SD-OCT was used to image the macula of each eye. The data were analyzed using the Duke OCT Retinal Analysis Program v17 software. Retinal thickness maps were generated for the total retinal thickness (TRT), the inner retinal layers thickness (IRL), and the photoreceptor layer thickness (PRL). Based on the early treatment diabetic retinopathy study macular map, average thickness measurements were taken at 4 circles centered on the fovea (diameter): the foveal center (0.5 mm), sector 1 (S1) (1 mm), sector 2 (S2) (3 mm), sector 3 (S3) (6 mm). The median age at participation was 24 months (range 5–52 months). The TRT increased throughout the first 5 years of life, and this increase was statistically significant at the foveal center and S1 (p = 0.01, p = 0.016, respectively). The IRL did not show any significant change in thickness from birth and throughout the first 5 years of life. The PRL thickness showed thickening in the first 24 months of age at the foveal center and S1 which was statistically significant at S1 (p = 0.066, p = 0.016, respectively). Interestingly, this PRL thickness increase plateaus beyond 24 months of age. The photoreceptors inner segment/outer segment (IS/OS) band was identified as a distinct layer in all our subjects. Our findings conform with the literature that the anatomical development of the macular IRL completes before 5 months of age and hence before the PRL. We also identify 24 months of age as an important developmental milestone for photoreceptors development in the human macula.

OBJECTIVES/GOALS: The goal of this study is to evaluate and optimize the characterization of cystoid macular edema (CME) using an investigational swept source (SS)-OCT system. Our knowledge of CME in preterm infants is limited; optimizing its characterization is a critical step in understanding its impact on vision. METHODS/STUDY POPULATION: In this IRB-approved protocol, 118 preterm infants were imaged in the Duke intensive care nursery (ICN) with a novel lightweight, hand-held, high-speed, SS-OCT system following routine clinical eye exams. SS-OCT images were deidentified, automatically segmented using custom software (DOCTRAP), measured for several retinal layer thicknesses, and reviewed by masked expert graders for the presence and severity of CME. Reliability of SS-OCT measures will be assessed, and the association between CME status and retinal layer thicknesses will be calculated using logistic regression modeling. RESULTS/ANTICIPATED RESULTS: The prevalence of CME overall and by severity will be calculated. The distribution of several retinal layer thicknesses will be reported and compared by infant CME status and, when edema is present, by CME severity. Reproducibility and repeatability will be reported for objective variables, and intra-grader and inter-grader agreement will be reported for subjective variables. Multivariate logistic regression coefficients and odds ratios will be calculated for each retinal layer thickness variable. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will use a novel SS-OCT system to identify retinal thickness measures that may be objective markers of CME status. This will refine the characterization of CME and provide a framework for correlating CME with functional outcomes like visual acuity. CONFLICT OF INTEREST DESCRIPTION: SC and CT have unlicensed patents on relevant technologies. CT receives royalties from Alcon and Hemosonics and consultation fees from EMMES.

Purpose To test whether ganglion cell layer (GCL) and inner plexiform layer (IPL) topography is altered in albinism. Methods Optical coherence tomography scans were analyzed in 30 participants with albinism and 25 control participants. Horizontal and vertical line scans were acquired at the fovea, then strip registered and averaged. The Duke Optical Coherence Tomography Retinal Analysis Program was used to automatically segment the combined GCL and IPL and total retinal thickness, followed by program-assisted manual segmentation of the boundary between the GCL and IPL. Layer thickness and area under the curve (AUC) were calculated within 2.5 mm of the fovea. Nasal-temporal and superior-inferior asymmetry were calculated as an AUC ratio in each quadrant. Results GCL and IPL topography varied between participants. The summed AUC in all quadrants was similar between groups for both the GCL (P = 0.84) and IPL (P = 0.08). Both groups showed nasal-temporal asymmetry in the GCL, but only participants with albinism had nasal-temporal asymmetry in the IPL. Nasal-temporal asymmetry was greater in albinism for both the GCL (P < 0.0001) and the IPL (P = 0.0006). The GCL usually comprised a greater percentage of the combined GCL and IPL in controls than in albinism. Conclusions The GCL and IPL have greater structural variability than previously reported. GCL and IPL topography are significantly altered in albinism, which suggests differences in the spatial distribution of retinal ganglion cells. This finding provides insight into foveal development and structure-function relationships in foveal hypoplasia.

Purpose To establish methods to visualize depth-resolved perifoveal retinal vasculature in preterm infants using handheld optical coherence tomography angiography (OCT-A). Methods In this exploratory study, eyes of preterm infants were imaged using an investigational noncontact, handheld swept-source OCT-A device as part of the prospective BabySTEPS infant retinal imaging study. We selected high-quality OCT-A volumes at two developmental stages for analysis. Customized MATLAB scripts were used to segment retinal layers, test offset parameters, and generate depth-resolved OCT-A slabs. The superficial (SCP), intermediate (ICP), and deep (DCP) capillary plexuses were visualized and qualitatively assessed by three image graders. Results Six eyes from six preterm infants were included in this analysis. A three-layered perifoveal retinal vasculature was successfully visualized in all three eyes (three infants) in the 40 weeks postmenstrual age (PMA) group (one of three eyes with treated type 1 retinopathy of prematurity [ROP]). No obvious ICP or DCP was found in good-quality scans of the three eyes (three infants) in the 35 weeks PMA group (three of three eyes developed type 1 ROP). Conclusions Custom segmentation parameters are useful to visualize perifoveal retinal vasculature in preterm infants. At term age, a three-layered capillary structure is visible in most eyes, while prior to detectable flow within the ICP and DCP, the perifoveal vasculature may be better visualized in two layers. Translational relevance Development of segmentation parameters for depth-resolved OCT-A of perifoveal retinal vasculature in preterm infants facilitates the study of human retinal vascular development and vascular pathologies of ROP.

Purpose To describe the creation of en face retinal vessel shadow view (RVSV) optical coherence tomography (OCT) images and assess the feasibility of using these for evaluating vascular disease in preterm infants at risk for retinopathy of prematurity (ROP). Methods In this exploratory study, we selected images from eyes with a range of ROP vascular disease, prospectively acquired from preterm infants using an investigational, noncontact, handheld, bedside swept-source OCT. We autosegmented OCT volumes using custom infant-specific software, extracted RVSV-OCT images from volumetric data bracketed around the retinal pigment epithelium, and automontaged the resulting RVSV-OCT images. Three masked ophthalmologists graded the RVSV-OCT montages as plus, pre-plus, or neither and ranked them by relative vascular disease severity. Results We selected images from 17 imaging sessions (7 plus, 4 pre-plus, 6 neither on clinical examination). On review, 15/17 (88%) RVSV-OCT montages were gradable for plus, pre-plus, or neither and all 17 montages were rankable for relative severity. Intergrader agreement for plus, pre-plus, or neither grading was good (κ, 0.67; 95% confidence interval, 0.42-0.86) and for relative severity ranking was excellent (intraclass correlation coefficient, 0.98; 95% confidence interval, 0.96-0.99). Conclusions Our novel automatic processing method can create RVSV-OCT montages optimized for retinal vessel visualization for ROP screening. Although our data support the feasibility of using RVSV-OCT montages for ranking relative vascular disease severity, there is room for improved OCT image capture and processing methods in preterm infants screened for ROP. Translational relevance Creation and grading of RVSV-OCT images could eventually be integrated into an alternative method for ROP screening.

PURPOSE: Macular atrophy and scar increase in prevalence during treatment for neovascular age-related macular degeneration (AMD) and are associated with poor visual acuity. We sought to identify the distribution of spectral domain optical coherence tomography (SDOCT)-determined features and subretinal lesion thicknesses at sites of macular scar or atrophy after two years of treatment in the Comparison of AMD Treatments Trials (CATT). DESIGN: Cross-sectional analysis PARTICIPANTS: CATT participants with SDOCT, color photograph and fluorescein angiogram (CP/FA) images at Year 2. METHODS: Sixty-eight study eyes at Year 2 in CATT, were selected based on image quality and CP/FA-determined predominant presence of: geographic atrophy (GA, n=25), non-GA (NGA, n=44), fibrotic scar (FS, n=26) or non-FS (NFS, n=7). CP/FA components were delineated by CP/FA readers; SDOCT morphologic features and thicknesses were delineated by OCT readers. Using custom software and graphic user interfaces, images were registered, overlaying features and components per pixel; differences were analyzed across groups. MAIN OUTCOME MEASURES: OCT features, CP/FA components, and retinal and subretinal lesion thicknesses at each pixel of regional overlays. RESULTS: SDOCT assessment of registered areas of pathology revealed the following: 1) retinal pigment epithelium atrophy (with or without residual lesion material) covered 75% of pixels designated as GA, 22% as NGA, 24% of NFS and 46% of FS (p

In this chapter, the authors examine some of the advantages and challenges of applying the super-resolution framework to applications in medical imaging. They describe super-resolution and its applications from the medical imaging community’s point of view. The authors describe the general super-resolution framework and provide a brief review of the different super-resolution algorithms. They focus on X-ray and Optical Coherence Tomography (OCT) image enhancement, similar strategies can be exploited for enhancing the quality of some other volumetric medical imaging devices such as ultrasound. Commonly, the lateral, axial, and azimuthal resolution of many imaging systems, including OCT, are associated with the illumination source characteristics, the optical path, and other physical characteristics. The invention of the charge coupled device created a new era of imaging wherein optical images could be efficiently captured by an array of solid-state detectors and stored as digital information.

Objective To define quantitative indicators for the presence of intermediate age-related macular degeneration (AMD) via spectral-domain optical coherence tomography (SD-OCT) imaging of older adults. Design Evaluation of diagnostic test and technology. Participants and Controls One eye from 115 elderly subjects without AMD and 269 subjects with intermediate AMD from the Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study. Methods We semiautomatically delineated the retinal pigment epithelium (RPE) and RPE drusen complex (RPEDC, the axial distance from the apex of the drusen and RPE layer to Bruch's membrane) and total retina (TR, the axial distance between the inner limiting and Bruch's membranes) boundaries. We registered and averaged the thickness maps from control subjects to generate a map of "normal" non-AMD thickness. We considered RPEDC thicknesses larger or smaller than 3 standard deviations from the mean as abnormal, indicating drusen or geographic atrophy (GA), respectively. We measured TR volumes, RPEDC volumes, and abnormal RPEDC thickening and thinning volumes for each subject. By using different combinations of these 4 disease indicators, we designed 5 automated classifiers for the presence of AMD on the basis of the generalized linear model regression framework. We trained and evaluated the performance of these classifiers using the leave-one-out method. Main Outcome Measures The range and topographic distribution of the RPEDC and TR thicknesses in a 5-mm diameter cylinder centered at the fovea. Results The most efficient method for separating AMD and control eyes required all 4 disease indicators. The area under the curve (AUC) of the receiver operating characteristic (ROC) for this classifier was >0.99. Overall neurosensory retinal thickening in eyes with AMD versus control eyes in our study contrasts with previous smaller studies. Conclusions We identified and validated efficient biometrics to distinguish AMD from normal eyes by analyzing the topographic distribution of normal and abnormal RPEDC thicknesses across a large atlas of eyes. We created an online atlas to share the 38 400 SD-OCT images in this study, their corresponding segmentations, and quantitative measurements.

BACKGROUND AND OBJECTIVE: To enhance understanding of ethnically diverse normal newborn retinal morphology, the authors report spectral-domain optical coherence tomography (SD-OCT) macular findings in healthy Hispanic newborns. PATIENTS AND METHODS: In this IRB-approved prospective, observational case series, 20 full-term Hispanic newborns had dilated retinal examinations and imaging by hand-held SD-OCT without sedation at the Duke Birthing Center. RESULTS: Of 20 newborns imaged (35% male; median gestational age: 39 weeks; range: 36 to 40 weeks), two (10%) had bilateral subfoveal fluid, including one case of bilateral double subretinal fluid pockets. Three eyes of two infants (10%) had retinal macular cystoid structures (one enlarged at 1.5 months, with resolution by 3 months). These SD-OCT findings were not visible by indirect ophthalmoscopy. CONCLUSION: Some Hispanic newborns have sub-retinal fluid or macular cystoid structures on SD-OCT. This study expands our understanding of findings seen by SD-OCT in healthy full-term newborns of various races. [ Ophthalmic Surg Lasers Imaging Retina . 2013;44:448–454.]

Drusen and migrating retinal pigment epithelium have been associated with hyperreflective foci (HF) detected by spectral-domain optical coherence tomography (SD-OCT). This study sought to quantify the change in intraretinal HF distribution and its correlation with age-related macular degeneration (AMD) disease progression.Prospective observational study from the multicenter Age-Related Eye Disease Study 2 (AREDS2) Ancillary SD-OCT Study.Patients (n=299) with 1 enrolled eye with intermediate AMD and baseline SD-OCT, followed by SD-OCT imaging at 1-year and 2-year visits.The number and location of HF were scored in SD-OCT scans of all 299 eyes. The change in transverse (horizontal) and axial (vertical) distribution of HF in the macula were evaluated with pairwise signed-rank tests. Two-year inner retinal HF migration was determined by the change in HF-weighted axial distribution (AxD) score calculated for each eye. The correlation of HF with SD-OCT features of AMD progression was evaluated with logistic regression analysis.The mean change in number of HF, transverse and axial distribution of HF in the macula, and AxD per eye.In 299 study eyes, the 2-year increase in the number of HF (P0.001) and the AxD (P0.001) per eye represented longitudinal proliferation and shift to inner retinal layers, respectively. Eyes with geographic atrophy (GA) at 2 years were correlated with the presence of baseline HF (P0.001; odds ratio [OR], 4.72; 95% confidence interval [CI], 2.43-9.80), greater number of baseline HF (P0.001; OR, 1.61 per HF; 95% CI, 1.32-2.00), and greater baseline AxD (P0.001; OR, 1.58 per AxD point; 95% CI, 1.29-1.95).Proliferation and inner retinal migration of SD-OCT HF occurred during follow-up in eyes with intermediate AMD. These characteristics were associated with greater incidence of GA at year 2; therefore, SD-OCT HF proliferation and migration may serve as biomarkers for AMD progression.Proprietary or commercial disclosure may be found after the references.

Purpose To develop methods to make precise comparisons of specific retinal features between and within spectral-domain (SD) OCT images, color fundus photography (CFP) images, and fluorescein angiography (FA) images in eyes treated with anti–vascular endothelial growth factor (VEGF) agents for neovascular age-related macular degeneration (nAMD). Design Retrospective study. Participants Patients with good study-eye images at the 104-week visit in the Comparison of Age-Related Macular Degeneration Treatments Trials. Methods Graders reviewed CFP and FA images and delineated areas of fibrotic or nonfibrotic scar and geographic atrophy (GA) or non-GA. Other graders reviewed SD-OCT images and delineated retinal and subretinal lesion characteristics. Using newly developed custom software and graphic user interfaces, the presence and thickness of each feature at each pixel on the en face view was determined. Main Outcome Measures Spectral-domain OCT findings versus CFP and FA lesion components from regional overlays. Results Per-eye distribution and thickness of SD-OCT features within CFP- and FA-established areas of scar and atrophy can be determined precisely, can be displayed in multiple formats, and can be extracted into pixel-specific data sets. These methods enable statistical analysis of imaging results within eyes and across eyes of different patients. For example, photoreceptor loss, subretinal lesion material, and thicknesses of photoreceptor layer and subretinal material across those SD-OCT features can be related precisely to CFP and FA regions of scar or atrophy. Conclusions Methods to integrate qualitative and quantitative retinal and subretinal changes to coincide with photographic and angiographic designations of the nAMD lesion areas and sequelae are integral for accurate assessments of posttreatment retinal morphologic features. These may lead to better understanding of disease progression and improved treatment strategies.

Appearance of geographic atrophy (GA) on color photography (CP) is preceded by specific features on spectral-domain optical coherence tomography (SD OCT). We aimed to build SD OCT-based risk assessment models for 5-year new onset of GA and central GA on CP.Prospective, longitudinal study.Age-Related Eye Disease Study 2 Ancillary SD OCT study participants with age-related macular degeneration (AMD) with bilateral large drusen or noncentral GA and at least 1 eye without advanced disease (n = 317).For 1 eye per participant, qualitative and quantitative SD OCT variables were derived from standardized grading and semiautomated segmentation, respectively, at baseline. Up to 7 years later, annual outcomes were extracted and analyzed to fit multivariate logistic regression models and build a risk calculator.New onset of CP-visible GA and central GA.Over a follow-up median of 4.0 years and among 292 AMD eyes (without advanced disease at baseline) with complete outcome data, 46 (15.8%) developed central GA. Among 265 eyes without any GA on baseline CP, 70 (26.4%) developed CP-visible GA. Final multivariate models were adjusted for age. In the model for GA, the independent predicting SD OCT factors (P0.001-0.03) were: hyperreflective foci and retinal pigment epithelium (RPE) layer atrophy or absence, followed by choroid thickness in absence of subretinal drusenoid deposits, photoreceptor outer segment loss, RPE drusen complex volume, and RPE drusen complex abnormal thinning volume. For central GA, the factors (P0.001) were RPE drusen complex abnormal thinning volume, intraretinal fluid or cystoid spaces, hyperreflective foci, and RPE layer atrophy or absence. The models yielded a calculator that computes the probabilities of CP-visible, new-onset GA and central GA after 1 to 5 years.For AMD eyes with large drusen and no advanced disease, we built a novel risk assessment model-based on age and SD OCT segmentation, drusen characteristics, and retinal pathology-for progression to CP-visible GA over up to 5 years. This calculator may simplify SD OCT grading and with future validation has a promising role as a clinical prognostic tool.

Spectral domain optical coherence tomography (SD-OCT) imaging permits in vivo visualization of the choroid with micron-level resolution over wide areas and is of interest for studies of ocular growth and myopia control. We evaluated the speed, repeatability, and accuracy of a new image segmentation method to quantify choroid thickness compared to manual segmentation.Two macular volumetric scans (25 × 30°) were taken from 30 eyes of 30 young adult subjects in two sessions, 1 hour apart. A single rater manually delineated choroid thickness as the distance between Bruch's membrane and sclera across three B-scans (foveal, inferior, and superior-most scan locations). Manual segmentation was compared to an automated method based on graph theory, dynamic programming, and wavelet-based texture analysis. Segmentation performance comparisons included processing speed, choroid thickness measurements across the foveal horizontal midline, and measurement repeatability (95% limits of agreement (LoA)).Subjects were healthy young adults (n = 30; 24 ± 2 years; mean ± SD; 63% female) with spherical equivalent refractive error of -3.46 ± 2.69D (range: +2.62 to -8.50D). Manual segmentation took 200 times longer than automated segmentation (780 vs. 4 seconds). Mean choroid thickness at the foveal center was 263 ± 24 μm (manual) and 259 ± 23 μm (automated), and this difference was not significant (p = 0.10). Regional segmentation errors across the foveal horizontal midline (±15°) were ≤9 μm (median) except for nasal-most regions closest to the nasal peripapillary margin-15 degrees (19 μm) and 12 degrees (16 μm) from the foveal center. Repeatability of choroidal thickness measurements had similar repeatability between segmentation methods (manual LoA: ±15 μm; automated LoA: ±14 μm).Automated segmentation of SD-OCT data by graph theory and dynamic programming is a fast, accurate, and reliable method to delineate the choroid. This approach will facilitate longitudinal studies evaluating changes in choroid thickness in response to novel optical corrections and in ocular disease.

This paper presents a generalized framework for segmenting closed-contour anatomical and pathological features using graph theory and dynamic programming (GTDP). More specifically, the GTDP method previously developed for quantifying retinal and corneal layer thicknesses is extended to segment objects such as cells and cysts. The presented technique relies on a transform that maps closed-contour features in the Cartesian domain into lines in the quasi-polar domain. The features of interest are then segmented as layers via GTDP. Application of this method to segment closed-contour features in several ophthalmic image types is shown. Quantitative validation experiments for retinal pigmented epithelium cell segmentation in confocal fluorescence microscopy images attests to the accuracy of the presented technique.

Purpose Structural and compositional heterogeneity within drusen comprising lipids, carbohydrates, and proteins have been previously described. We sought to detect and define phenotypic patterns of drusen heterogeneity in the form of optical coherence tomography–reflective drusen substructures (ODS) and examine their associations with age-related macular degeneration (AMD)–related features and AMD progression. Design Retrospective analysis in a prospective study. Participants Patients with intermediate AMD (n = 349) enrolled in the multicenter Age-Related Eye Disease Study 2 (AREDS2) ancillary spectral-domain optical coherence tomography (SD OCT) study. Methods Baseline SD OCT scans of 1 eye per patient were analyzed for the presence of ODS. Cross-sectional and longitudinal associations of ODS presence with AMD-related features visible on SD OCT and color photographs, including drusen volume, geographic atrophy (GA), and preatrophic features, were evaluated for the entire macular region. Similar associations were also made locally within a 0.5-mm-diameter region around individual ODS and corresponding control region without ODS in the same eye. Main Outcome Measures Preatrophy SD OCT changes and GA, central GA, and choroidal neovascularization (CNV) from color photographs. Results Four phenotypic subtypes of ODS were defined: low reflective cores, high reflective cores, conical debris, and split drusen. Among the 349 participants, there were 307 eligible eyes and 74 (24%) had at least 1 ODS. The ODS at baseline were associated with (1) greater macular drusen volume at baseline ( P P = 0.001–0.01), and (3) development of macular GA ( P = 0.005) and preatrophic changes at year 3 ( P = 0.002–0.008), but not development of CNV. The ODS at baseline in a local region were associated with (1) presence of preatrophy changes at baseline ( P = 0.02–0.03) and (2) development of preatrophy changes at years 2 and 3 within the region ( P = 0.008–0.05). Conclusions Optical coherence tomography–reflective drusen substructures are optical coherence tomography–based biomarkers of progression to GA, but not to CNV, in eyes with intermediate AMD. Optical coherence tomography–reflective drusen substructures may be a clinical entity helpful in monitoring AMD progression and informing mechanisms in GA pathogenesis.

BACKGROUND To apply automated spectral domain optical coherence tomography (SD-OCT) segmentation to eyes with resolving papilledema. METHODS Ninety-four patients with idiopathic intracranial hypertension seen at the Duke Eye Center neuro-ophthalmology clinic between November 2010 and October 2011 were reviewed. Excluded were eyes with papilledema with Frisen grade >2, other optic neuropathies or retinopathies, and those that did not have SD-OCT imaging. The remaining 43 patients were split into 2 groups: non-atrophic papilledema and atrophic papilledema. Automated SD-OCT segmentation was performed on patients with non-atrophic papilledema and age-matched controls for each of the 9 regions of the Early Treatment Diabetic Retinopathy Study map. Bonferroni correction was used for multiple comparisons. All SD-OCT scans were reviewed for retinal structural abnormalities. RESULTS Total macular thickness was significantly thinner within the fovea and inner macular ring in non-atrophic papilledema vs control eyes (266 vs 276 μm, P = 0.04; 333 vs 344 μm P < 0.01, n = 26 non-atrophic papilledema, 30 controls). SD-OCT demonstrated thinning within the fovea, inner macular ring, and outer macular ring of the outer plexiform layer plus nuclear layer in non-atrophic papilledema vs control (124 vs 131 μm, P < 0.01; 112 vs 118 μm, P = 0.03; 95 vs 100 μm, P = 0.03). Retinal structural changes were seen in 21/33 eyes with atrophic papilledema vs none of the eyes with non-atrophic papilledema or controls. CONCLUSIONS SD-OCT shows qualitative and quantitative changes in the macula of eyes with resolved papilledema.

We present a fully automatic algorithm to identify fluid-filled regions and seven retinal layers on spectral domain optical coherence tomography images of eyes with diabetic macular edema (DME). To achieve this, we developed a kernel regression (KR)-based classification method to estimate fluid and retinal layer positions. We then used these classification estimates as a guide to more accurately segment the retinal layer boundaries using our previously described graph theory and dynamic programming (GTDP) framework. We validated our algorithm on 110 B-scans from ten patients with severe DME pathology, showing an overall mean Dice coefficient of 0.78 when comparing our KR + GTDP algorithm to an expert grader. This is comparable to the inter-observer Dice coefficient of 0.79. The entire data set is available online, including our automatic and manual segmentation results. To the best of our knowledge, this is the first validated, fully-automated, seven-layer and fluid segmentation method which has been applied to real-world images containing severe DME.

PurposeTo determine the effect of anti-vascular endothelial growth factor (VEGF) therapy on choroidal thickness in eyes with diabetic macular edema (DME).DesignA retrospective, cohort analysis of 59 eyes from 59 patients with DME without prior anti-VEGF therapy.MethodsChoroidal thickness was measured using semiautomated segmentation of enhanced depth imaging optical coherence tomography images at 0.5-mm intervals from 2.5 mm nasal to 2.5 mm temporal to the fovea. Changes in choroidal thickness with and without anti-VEGF treatment over 6 months were compared. Best-corrected visual acuity and central foveal thickness were analyzed to evaluate the association of choroidal thickness with functional and anatomic outcomes.ResultsOf the 59 eyes with DME, 26 eyes were observed without treatment, whereas 33 underwent intravitreal anti-VEGF therapy (mean number of injections, 2.73) over 6 months. In untreated eyes, there was no significant change in best-corrected visual acuity (P = .098), central foveal thickness (P = .472), or choroidal thickness at all measurements along the macula (P = .057 at the fovea). In eyes treated with anti-VEGF injections, choroidal thickness decreased significantly at the fovea (246.6 to 224.8 μm; P < .001) and at 0.5 mm nasal (240.9 to 221.9 μm; P = .002) and 0.5 mm temporal (249.3 to 224.8 μm; P = .011) to the fovea. The decrease in subfoveal choroidal thickness after anti-VEGF treatment was not associated with the cumulative number of anti-VEGF injections (R(2) = 0.031; P = .327) or to changes in best-corrected visual acuity (R(2) = 0.017; P = .470) or central foveal thickness (R(2) = 0.040; P = .263).ConclusionsCentral choroidal thickness decreases after anti-VEGF therapy for DME after 6 months, but may not be associated with functional or anatomic outcomes in eyes with DME.

Purpose The goal was to assess effects of IOP and pilocarpine-induced ciliary muscle contraction on conventional outflow pathway tissues in living anesthetized mice. Methods Intraocular pressure was controlled by intracameral cannulation of mouse eyes while imaging using spectral-domain optical coherence tomography (SD-OCT). Time-lapse sagittal SD-OCT sections through Schlemm's canal (SC) were acquired while changing IOP stepwise between 10 and 45 mm Hg. After topical application of 1% pilocarpine, the series of IOP steps and imaging were repeated. Effects of pilocarpine on IOP and outflow facility in living mice were verified by rebound tonometry and flow measurements at three different IOPs, respectively. In vivo OCT images were compared with eyes analyzed by standard histology. Results In living mice imaged by SD-OCT, the lumen of SC progressively collapsed with increasing IOP, reaching near complete closure at 20 mm Hg. Schlemm's canal collapse was reversible, with the lumen opening within minutes after returning IOP from 45 to 10 mm Hg. Pilocarpine-induced ciliary muscle contraction changed SC lumen area by 131.6% ± 21.0% compared with untreated controls at 10 mm Hg, opened the trabecular meshwork, and prevented complete collapse of the SC lumen at higher pressures. Similar results were observed by standard histology. Pilocarpine increased outflow facility 4-fold (P = 0.02) and lowered IOP (16.46 ± 2.23 vs. 11.08 ± 2.28 mm Hg, P = 0.03). Conclusions Spectral-domain OCT was effective at visualizing changes in SC lumen in living mice. Results with pilocarpine are consistent with the concept that a primary role for the ciliary muscle is to prevent collapse of SC.

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).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.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.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.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.

Purpose To determine whether a novel automatic segmentation program, the Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can be applied to spectral-domain optical coherence tomography (SD-OCT) images obtained from different commercially available SD-OCT in eyes with diabetic macular edema (DME). Methods A novel segmentation framework was used to segment the retina, inner retinal pigment epithelium, and Bruch's membrane on images from eyes with DME acquired by one of two SD-OCT systems, Spectralis or Cirrus high definition (HD)-OCT. Thickness data obtained by the DOCTRAP software were compared with those produced by Spectralis and Cirrus. Measurement agreement and its dependence were assessed using intraclass correlation (ICC). Results A total of 40 SD-OCT scans from 20 subjects for each machine were included in the analysis. Spectralis: the mean thickness in the 1-mm central area determined by DOCTRAP and Spectralis was 463.8 ± 107.5 μm and 467.0 ± 108.1 μm, respectively (ICC, 0.999). There was also a high level agreement in surrounding areas (out to 3 mm). Cirrus: the mean thickness in the 1-mm central area was 440.8 ± 183.4 μm and 442.7 ± 182.4 μm by DOCTRAP and Cirrus, respectively (ICC, 0.999). The thickness agreement in surrounding areas (out to 3 mm) was more variable due to Cirrus segmentation errors in one subject (ICC, 0.734-0.999). After manual correction of the errors, there was a high level of thickness agreement in surrounding areas (ICC, 0.997-1.000). Conclusions The DOCTRAP may be useful to compare retinal thicknesses in eyes with DME across OCT platforms.

Purpose We determine whether the automated segmentation software, Duke Optical Coherence Tomography Retinal Analysis Program (DOCTRAP), can measure, in a platform-independent manner, retinal thickness on Cirrus and Spectralis spectral domain optical coherence tomography (SD-OCT) images in eyes with diabetic macular edema (DME) under treatment in a clinical trial. Methods Automatic segmentation software was used to segment the internal limiting membrane (ILM), inner retinal pigment epithelium (RPE), and Bruch's membrane (BM) in SD-OCT images acquired by Cirrus and Spectralis commercial systems, from the same eye, on the same day during a clinical interventional DME trial. Mean retinal thickness differences were compared across commercial and DOCTRAP platforms using intraclass correlation (ICC) and Bland-Altman plots. Results The mean 1 mm central subfield thickness difference (standard error [SE]) comparing segmentation of Spectralis images with DOCTRAP versus HEYEX was 0.7 (0.3) μm (0.2 pixels). The corresponding values comparing segmentation of Cirrus images with DOCTRAP versus Cirrus software was 2.2 (0.7) μm. The mean 1 mm central subfield thickness difference (SE) comparing segmentation of Cirrus and Spectralis scan pairs with DOCTRAP using BM as the outer retinal boundary was -2.3 (0.9) μm compared to 2.8 (0.9) μm with inner RPE as the outer boundary. Conclusions DOCTRAP segmentation of Cirrus and Spectralis images produces validated thickness measurements that are very similar to each other, and very similar to the values generated by the corresponding commercial software in eyes with treated DME. Translational relevance This software enables automatic total retinal thickness measurements across two OCT platforms, a process that is impractical to perform manually.

Geometrical analysis of the photoreceptor mosaic can reveal subclinical ocular pathologies. In this paper, we describe a fully automatic algorithm to identify and segment photoreceptors in adaptive optics ophthalmoscope images of the photoreceptor mosaic. This method is an extension of our previously described closed contour segmentation framework based on graph theory and dynamic programming (GTDP). We validated the performance of the proposed algorithm by comparing it to the state-of-the-art technique on a large data set consisting of over 200,000 cones and posted the results online. We found that the GTDP method achieved a higher detection rate, decreasing the cone miss rate by over a factor of five.

Purpose To correlate human foveal development visualized by spectral-domain optical coherence tomography (SDOCT) with histologic specimens. Design Retrospective, observational case series. Methods Morphology and layer thickness of retinal SDOCT images from 1 eye each of 22 premature infants, 30 term infants, 16 children, and 1 adult without macular disease were compared to light microscopic histology from comparable ages. Results SDOCT images correlate with major histologic findings at all time points. With both methods, preterm infants demonstrate a shallow foveal pit indenting inner retinal layers (IRL) and short, undeveloped foveal photoreceptors. At term, further IRL displacement forms the pit and peripheral photoreceptors lengthen; the elongation of inner and outer segments (IS and OS, histology) separates the IS band from retinal pigment epithelium. Foveal IS and OS are shorter than peripheral for weeks after birth (both methods). By 13 months, foveal cone cell bodies stack >6 deep, Henle fiber layer (HFL) thickens, and IS/OS length equals peripheral; on SDOCT, foveal outer nuclear layer (which includes HFL) and IS/OS thickens. At 13 to 16 years, the fovea is fully developed with a full complement of SDOCT bands; cone cell bodies >10 deep have thin, elongated, and tightly packed IS/OS. Conclusions We define anatomic correlates to SDOCT images from normal prenatal and postnatal human fovea. OCT bands typical of photoreceptors of the adult fovea are absent near birth because of the immaturity of foveal cones, develop by 24 months, and mature into childhood. This validates the source of SDOCT signal and provides a framework to assess foveal development and disease.

Objective To investigate whether the severity of cystoid macular edema (CME) in neonates who were 31 to 36 weeks' postmenstrual age, as viewed by spectral-domain optical coherence tomography (SD-OCT) imaging, predicts the severity of retinopathy of prematurity (ROP) or is related to systemic health. Design Of 62 prematurely born neonates in a prospective institutional review board–approved study, 42 met the following inclusion criteria: at least 1 SD-OCT imaging session prior to 37 weeks' postmenstrual age and prior to ROP laser treatment, if a laser treatment was performed, and an ophthalmic ROP examination at or after 41 weeks' postmenstrual age, evidence of complete retinal vascularization in zone III, or documentation through telephone report of such information after transfer of care. Measures of CME severity, including central foveal thickness, retinal layer thicknesses, and foveal-to-parafoveal thickness ratio in 1 eye per subject, were compared with ROP outcomes: laser treatment, maximum plus disease, and maximum ROP stage. Systemic health factors were also correlated. Results Cystoid macular edema was present in 50% of neonates. Multiple elongated cystoid structures within the inner nuclear layer were most common. The presence of CME was not associated with ROP outcomes. The central foveal thickness, the thickness of the inner retinal layers, and the foveal-to-parafoveal thickness ratio were higher in eyes that required laser treatment or that developed plus disease or ROP stage 3. Cystoid macular edema was not clearly associated with systemic factors. Conclusions Cystoid macular edema is common in premature infants screened for ROP before 37 weeks' postmenstrual age, with the most common SD-OCT phenotype of a bulging fovea from multiple elongated cystoid spaces. Detection of CME is not associated with ROP severity; however, tomographic thickness measurements could potentially predict a higher risk of requiring laser treatment or developing plus disease or ROP stage 3. Systemic health factors are probably not related to the development of CME.

This study was conducted to determine whether there were significant differences in choroidal thickness, contrast, outer choroidal vessel (OCV), and choroidal-scleral junction (CSJ) visualization in inverted versus upright spectral-domain optical coherence tomography (SD-OCT).Images were captured on Bioptigen SD-OCT, Zeiss Cirrus HD-OCT, and Heidelberg Spectralis in 42 eyes of 21 healthy subjects. Average choroidal thickness across a fovea-centered 4-mm segment was determined with MATLAB. Quantitative measures of choroidal contrast were measured and CSJ assessed by applying a score of 0 to 3. OCV was determined by counting choroidal vessels ≥ 200 μm.Mean choroidal thickness was greater in inverted versus upright images captured by Bioptigen (P ≤ 0.003) and Spectralis (P ≤ 0.015). Choroidal thickness varied significantly between the three machines (P0.05). Contrast was higher in inverted versus upright images captured by Bioptigen (P ≤ 0.02) and Spectralis (P0.001), but not in Cirrus (P0.10, both observers). CSJ score was highest in the following: Spectralis inverted = Spectralis EDICirrus uprightBioptigen inverted. Mean OCV was highest in Spectralis inverted mode.The most favorable modes to visualize CSJ and OCV are the Spectralis EDI, Spectralis inverted, Cirrus upright, and Bioptigen inverted. These modes demonstrate the highest outer choroidal contrast and choroidal thickness measurements. Choroidal thickness cannot be compared between machines due to conversion factor differences. Future studies and construction of automated segmentation and detection software should take these benefits and pitfalls into account.

Purpose To report retinal findings for healthy newborn infants imaged with handheld spectral-domain optical coherence tomography (SD OCT). Design Prospective, observational case series. Methods Thirty-nine full-term newborn infants underwent dilated retinal examinations by indirect ophthalmoscopy and retinal imaging by handheld SD OCT, without sedation, at the Duke Birthing Center. Results Of the 39 infants imaged, 44% (17/39) were male. Race and ethnicity composition was 56% white, 38% black, 3% Asian, and 3% Hispanic. Median gestational age was 39 weeks (range, 36 to 41 weeks). Six (15%) of the 39 infants had bilateral subfoveal fluid on SD OCT not seen by indirect ophthalmoscopy. Eight infants (21%) had retinal hemorrhages noted on dilated retinal examination, 1 of which had subretinal fluid on SD OCT. Subretinal fluid was noted on follow-up examination to have resolved on SD OCT 1 to 4 months later. Infants with bilateral subretinal fluid had an older gestational age compared with infants without subretinal fluid (median, 40.4 vs 39.1 weeks, respectively; P = .03) and were more likely to have had mothers with diabetes (2/6 vs 0/33, respectively; P = .02). Vaginal versus Caesarian section delivery was not significantly different between the 2 groups. Conclusions Some healthy full-term infants have bilateral subfoveal fluid not obvious on dilated retinal examination. This fluid resolves within several months. The visual significance of this finding is unknown, but clinicians should be aware that it is common when evaluating newborn infants for retinal pathologic features using SD OCT.

Segmentation of anatomical structures in corneal images is crucial for the diagnosis and study of anterior segment diseases. However, manual segmentation is a time-consuming and subjective process. This paper presents an automatic approach for segmenting corneal layer boundaries in Spectral Domain Optical Coherence Tomography images using graph theory and dynamic programming. Our approach is robust to the low-SNR and different artifact types that can appear in clinical corneal images. We show that our method segments three corneal layer boundaries in normal adult eyes more accurately compared to an expert grader than a second grader—even in the presence of significant imaging outliers.

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. Paticipants 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.

We describe an efficient approach for the automated segmentation of pathological/morphological structures in ophthalmic Spectral Domain Optical Coherence Tomography (SDOCT) images. In this algorithm, image pixels are treated as nodes of a graph with edge weights assigned to associate pairs of pixels. The weights vary according to the distances, brightness differences, and feature variations between pixel pairs. Cuts through the graph with minimum accumulated weights correspond to morphological layer boundaries. This approach has been applied to SDOCT images with encouraging results and thus forms an adaptable framework for the segmentation of many different ophthalmic structures.

Accurate detection-characterization of drusen is an important imaging biomarker of age-related macular degeneration (AMD) progression. We report on the development of an automatic method for detection and segmentation of drusen in retinal images captured via high speed spectral domain coherence tomography (SDOCT) systems. The proposed algorithm takes advantage of a priori knowledge about the retina shape and structure in the AMD and normal eyes. In the first step, the location of the retinal nerve fiber layer (RNFL) is estimated by searching for the locally connected segments with high radiometric vertical gradients appearing in the upper section of the SDOCT scans. The high reflective and locally connected pixels that are spatially located below the RNFL layer are taken as the initial estimate of the retinal pigment epithelium (RPE) layer location. Such rough estimates are smoothed and improved by using a slightly modified implementation of the Xu-Prince gradient vector flow based deformable snake method. Further steps, including a two-pass scan of the image, remove outliers and improve the accuracy of the estimates. Unlike healthy eyes commonly exhibiting a convex RPE shape, the shape of the RPE layer in AMD eyes might include abnormalities due to the presence of drusen. Therefore by enforcing local convexity condition and fitting second or fourth order polynomials to the possibly unhealthy (abnormal) RPE curve, the health (normal) shape of the RPE layer is estimated. The area between the estimated normal and the segmented RPE outlines is marked as possible drusen location. Moreover, fine-tuning steps are incorporated to improve the accuracy of the proposed technique. All methods are implemented in a graphical user interface (GUI) software package based on MATLAB platform. Minor errors in estimating drusen volume can be easily manually corrected using the user-friendly software interface and the program is constantly refined to correct for the repeating errors. This semi-supervised approach significantly reduces the time and resources needed to conduct a large-scale AMD study. The computational complexity of the core automated segmentation technique is attractive as it only takes about 6.5 seconds on a conventional PC to segment, display, and record drusen locations in an image of size (512 × 1000) pixels. Experimental results on segmenting drusen in SDOCT images of different subjects are included, which attest to the effectiveness of the proposed technique.

To analyze the value of novel measures of retinal pigment epithelium-drusen complex (RPEDC) volume to predict 2-year disease progression of intermediate age-related macular degeneration (AMD).Prospective, observational study.Three hundred forty-five AMD and 122 non-AMD participants enrolled in the Age Related Eye Disease Study 2 Ancillary Spectral-Domain (SD) Optical Coherence Tomography (OCT) study.High-density SD OCT macular volumes were obtained at yearly study visits. The RPEDC abnormal thickening (henceforth, OCT drusen) and RPEDC abnormal thinning (RAT) volumes were generated by semiautomated segmentation of total RPEDC within a 5-mm-diameter macular field.Volume change and odds ratio (OR) with 95% confidence intervals (CI) for progression to advanced AMD with choroidal neovascularization (CNV) or central geographic atrophy (GA).Complete volumes were obtained in 265 and 266 AMD eyes and in 115 and 97 control eyes at baseline and at year 2, respectively. In AMD eyes, mean (standard deviation) OCT drusen volume increased from 0.08 mm(3) (0.16 mm(3)) to 0.10 mm(3) (0.23 mm(3); P0.001), and RAT volume increased from 8.3 × 10(-4) mm(3) (20.8 × 10(-4) mm(3)) to 18.4 × 10(-4) mm(3) (46.6 × 10(-4) mm(3); P0.001). Greater baseline OCT drusen volume was associated with 2-year progression to CNV (P = 0.002). Odds of developing CNV increased by 31% for every 0.1-mm(3) increase in baseline OCT drusen volume (OR, 1.31; 95% CI, 1.06-1.63; P = 0.013). Greater baseline RAT volume was associated with significant 2-year increase in RAT volume (P0.001), noncentral GA (P0.001), and progression to central GA (P0.001). Odds of developing central GA increased by 32% for every 0.001-mm(3) increase in baseline RAT volume (OR, 1.32; 95% CI, 1.14-1.53; P0.001). In non-AMD eyes, all volumes were significantly lower than AMD eyes and showed no significant 2-year change.Macular OCT drusen and RAT volumes increased significantly in AMD eyes over 2 years. These quantitative SD OCT biomarkers predict 2-year AMD progression and may serve as useful biomarkers for future clinical trials.

We report on the development of quantitative, reproducible diagnostic observables for age-related macular degeneration (AMD) based on high speed spectral domain optical coherence tomography (SDOCT). 3D SDOCT volumetric data sets (512 x 1000 x 100 voxels) were collected (5.7 seconds acquisition time) in over 50 patients with age-related macular degeneration and geographic atrophy using a state-of-the-art SDOCT scanner. Commercial and custom software utilities were used for manual and semi-automated segmentation of photoreceptor layer thickness, total drusen volume, and geographic atrophy cross-sectional area. In a preliminary test of reproducibility in segmentation of total drusen volume and geographic atrophy surface area, inter-observer error was less than 5%. Extracted volume and surface area of AMD-related drusen and geographic atrophy, respectively, may serve as useful observables for tracking disease state that were not accessible without the rapid 3D volumetric imaging capability unique to retinal SDOCT.

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).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.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).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.When adjusted for age and refractive error, central choroidal thickness may not be significantly influenced by AMD status based on AREDS categorization.

Purpose To determine whether choroidal imaging is feasible in preterm and term infants using an 840-nm portable spectral domain optical coherence tomography (SD-OCT) system without the use of enhanced-depth imaging techniques and to assess choroidal development by comparing choroidal thickness of preterm infants, term infants, and adults. Methods SD-OCT images were obtained from 86 preterm infants, 59 term infants, and nine adults using a portable SD-OCT system plus nine adults using a tabletop system. An unprocessed image across the macula from one randomly selected eye of each participant was selected for determination of whether the choroidal-scleral junction (CSJ) could be visualized and for measurement of choroidal thickness. Results Subfoveal CSJ was visualized in 96% of young-preterm infants (imaged from 30-36 weeks postmenstrual age [PMA]); 78% of term-aged preterm infants (imaged from 37-42 weeks PMA); 49% of term infants; and 39% of adult subjects. Racial pigmentation did not affect CSJ visibility in young-preterm infants (P = 0.57). Subfoveal choroidal thickness (SFCT) in young-preterm infants, term-aged preterm infants, term infants, and adults was 176 ± 53 μm, 289 ± 92 μm, 329 ± 66 μm, and 258 ± 66 μm, respectively, and these were all statistically significantly different from one another except term-aged preterms to adults. Conclusions Infant choroid can be imaged with a portable SD-OCT system without enhanced depth imaging. Melanin in the RPE and choroid does not hinder outer choroidal imaging in young-preterm infants without advanced retinopathy of prematurity (ROP). In preterm infants, choroidal thickness increased with age but was thinner when compared to term infants suggesting delayed development due to ROP.

Variance processing methods in Fourier domain optical coherence tomography (FD-OCT) have enabled depth-resolved visualization of the capillary beds in the retina due to the development of imaging systems capable of acquiring A-scan data in the 100 kHz regime. However, acquisition of volumetric variance data sets still requires several seconds of acquisition time, even with high speed systems. Movement of the subject during this time span is sufficient to corrupt visualization of the vasculature. We demonstrate a method to eliminate motion artifacts in speckle variance FD-OCT images of the retinal vasculature by creating a composite image from multiple volumes of data acquired sequentially. Slight changes in the orientation of the subject's eye relative to the optical system between acquired volumes may result in non-rigid warping of the image. Thus, we use a B-spline based free form deformation method to automatically register variance images from multiple volumes to obtain a motion-free composite image of the retinal vessels. We extend this technique to automatically mosaic individual vascular images into a widefield image of the retinal vasculature.

i s O i a a ● PURPOSE: To report retinal findings for healthy newborn infants imaged with handheld spectral-domain optical coherence tomography (SD OCT). ● DESIGN: Prospective, observational case series. ● METHODS: Thirty-nine full-term newborn infants underwent dilated retinal examinations by indirect ophthalmoscopy and retinal imaging by handheld SD OCT, without sedation, at the Duke Birthing Center. ● RESULTS: Of the 39 infants imaged, 44% (17/39) were male. Race and ethnicity composition was 56% white, 38% black, 3% Asian, and 3% Hispanic. Median gestational age was 39 weeks (range, 36 to 41 weeks). Six (15%) of the 39 infants had bilateral subfoveal fluid on SD OCT not seen by indirect ophthalmoscopy. Eight infants (21%) had retinal hemorrhages noted on dilated retinal examination, 1 of which had subretinal fluid on SD OCT. Subretinal fluid was noted on follow-up examination to have resolved on SD OCT 1 to 4 months later. Infants with bilateral subretinal fluid had an older gestational age compared with infants without subretinal fluid (median, 40.4 vs 39.1 weeks, respectively; P .03) and were more likely to have had mothers with diabetes (2/6 vs 0/33, respectively; P .02). Vaginal versus Caesarian section delivery was not significantly different between the 2 groups. ● CONCLUSIONS: Some healthy full-term infants have bilateral subfoveal fluid not obvious on dilated retinal examination. This fluid resolves within several months. The visual significance of this finding is unknown, but clinicians should be aware that it is common when evaluating newborn infants for retinal pathologic features using SD OCT. (Am J Ophthalmol 2012;153:167–175. © 2012 by Elsevier Inc. All rights reserved.)

PURPOSE To automatically segment retinal spectral domain optical coherence tomography (SD-OCT) images of eyes with age-related macular degeneration (AMD) and various levels of image quality to advance the study of retinal pigment epithelium (RPE)+drusen complex (RPEDC) volume changes indicative of AMD progression. METHODS A general segmentation framework based on graph theory and dynamic programming was used to segment three retinal boundaries in SD-OCT images of eyes with drusen and geographic atrophy (GA). A validation study for eyes with nonneovascular AMD was conducted, forming subgroups based on scan quality and presence of GA. To test for accuracy, the layer thickness results from two certified graders were compared against automatic segmentation results for 220 B-scans across 20 patients. For reproducibility, automatic layer volumes were compared that were generated from 0° versus 90° scans in five volumes with drusen. RESULTS The mean differences in the measured thicknesses of the total retina and RPEDC layers were 4.2 ± 2.8 and 3.2 ± 2.6 μm for automatic versus manual segmentation. When the 0° and 90° datasets were compared, the mean differences in the calculated total retina and RPEDC volumes were 0.28% ± 0.28% and 1.60% ± 1.57%, respectively. The average segmentation time per image was 1.7 seconds automatically versus 3.5 minutes manually. CONCLUSIONS The automatic algorithm accurately and reproducibly segmented three retinal boundaries in images containing drusen and GA. This automatic approach can reduce time and labor costs and yield objective measurements that potentially reveal quantitative RPE changes in longitudinal clinical AMD studies. (ClinicalTrials.gov number, NCT00734487.).

Segmentation of anatomical and pathological structures in ophthalmic images is crucial for the diagnosis and study of ocular diseases. However, manual segmentation is often a time-consuming and subjective process. This paper presents an automatic approach for segmenting retinal layers in Spectral Domain Optical Coherence Tomography images using graph theory and dynamic programming. Results show that this method accurately segments eight retinal layer boundaries in normal adult eyes more closely to an expert grader as compared to a second expert grader.