Holding back the tears: is there a role for marsupialisation?

OBJECTIVE: Medial 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 ANALYSIS: A 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. RESULTS: There 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%). CONCLUSION: Marsupialisation 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 NUMBER: 10391.

Impact of Baseline Quantitative OCT Features on Response to Risuteganib for the Treatment of Dry Age-Related Macular Degeneration: The Importance of Outer Retinal Integrity.

OBJECTIVE: 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). DESIGN: Post hoc analysis of a randomized, double-masked, placebo-controlled, phase II study. SUBJECTS: 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. METHODS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Neuro-Ophthalmic Complications of Vestibular Schwannoma Resection: Current Perspectives.

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.

Depth-Resolved Visualization of Perifoveal Retinal Vasculature in Preterm Infants Using Handheld Optical Coherence Tomography Angiography.

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.

To implant or not to implant: emergency orbital eviscerations with primary orbital implants.

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.

Local Anatomic Precursors to New-Onset Geographic Atrophy in Age-Related Macular Degeneration as Defined on OCT.

PURPOSE: 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. DESIGN: Retrospective study. PARTICIPANTS: Age-Related Eye Disease Study 2 Ancillary SD OCT Study participants. METHODS: 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. MAIN OUTCOME MEASURES: Localized SD OCT features 2 years before GA onset. RESULTS: 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 (P < 0.001 and P = 0.03, respectively), hyperreflective foci (P < 0.001 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, P < 0.001 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). CONCLUSIONS: 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.

Retinal cavitations in macular telangiectasia type 2 (MacTel): longitudinal structure-function correlations.

BACKGROUND/AIMS: To 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. METHODS: Optical 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). RESULTS: Fifty-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 mm3 and 0.0124 mm3 at 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. CONCLUSIONS: Retinal 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.

Auto-Processed Retinal Vessel Shadow View Images From Bedside Optical Coherence Tomography to Evaluate Plus Disease in Retinopathy of Prematurity.

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.

Assessing Ganglion Cell Layer Topography in Human Albinism Using Optical Coherence Tomography.

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.

Distribution of OCT Features within Areas of Macular Atrophy or Scar after 2 Years of Anti-VEGF Treatment for Neovascular AMD in CATT.

PURPOSE: Macular atrophy and scar increase in prevalence during treatment for neovascular age-related macular degeneration and are associated with poor visual acuity. We sought to identify the distribution of spectral-domain OCT (SD-OCT)-determined features and subretinal lesion thicknesses at sites of macular scar or atrophy after 2 years of treatment in the Comparison of Age-Related Macular Degeneration Treatments Trials (CATT). DESIGN: Cross-sectional analysis. PARTICIPANTS: CATT participants with SD-OCT, color photographic (CP) and fluorescein angiogram (FA; 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 the following: geographic atrophy (GA, n = 25), non-GA (NGA, n = 44), fibrotic scar (FS, n = 26), or non-FS (NFS, n = 7). The CP/FA components were delineated by CP/FA readers; SD-OCT 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: SD-OCT 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% of NGA, 24% of NFS, and 46% of FS (P < 0.001). (2) Photoreceptor layer thinning covered 85% of GA, 42% of NGA, 33% of NFS, and 59% of FS (P < 0.001). (3) Subretinal lesion features covered 31% of GA, 42% of NGA, 85% of NFS, and 92% of FS (P < 0.001). Mean thickness of the subretinal lesion complex (measured in microns ± standard deviation) differed among GA (48±25 µm), NGA (61±35 µm), NFS (83±17 µm), and FS (151±74 µm) (P < 0.001). In eyes with GA, the thickness was greater in areas with residual lesion (51.4±27 µm) than in those without (27.2±9 µm). CONCLUSIONS: Retinal pigment epithelium atrophy and photoreceptor layer thinning are common not only in areas of macular atrophy but also in areas of FS. Photoreceptor loss extends beyond the areas of clinically apparent atrophy and FS. Subretinal lesion components were common in areas of scar, but they were also present in nearly one-third or more of areas of macular atrophy.

Demonstration of anatomical development of the human macula within the first 5 years of life using handheld OCT.

PURPOSE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Linking OCT, Angiographic, and Photographic Lesion Components in Neovascular Age-Related Macular Degeneration.

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.

Platform-Independent Cirrus and Spectralis Thickness Measurements in Eyes with Diabetic Macular Edema Using Fully Automated Software.

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.

Optical Coherence Tomography Reflective Drusen Substructures Predict Progression to Geographic Atrophy in Age-related Macular Degeneration.

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 < 0.001), (2) development of preatrophic changes at year 2 (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.

Validation of Macular Choroidal Thickness Measurements from Automated SD-OCT Image Segmentation.

PURPOSE: 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. METHODS: 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)). RESULTS: 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). CONCLUSIONS: 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.

Drusen Volume and Retinal Pigment Epithelium Abnormal Thinning Volume Predict 2-Year Progression of Age-Related Macular Degeneration.

PURPOSE: 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). DESIGN: Prospective, observational study. PARTICIPANTS: 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. METHODS: 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. MAIN OUTCOME MEASURES: 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). RESULTS: 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); P < 0.001), 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); P < 0.001). 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 (P < 0.001), noncentral GA (P < 0.001), and progression to central GA (P < 0.001). 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; P < 0.001). In non-AMD eyes, all volumes were significantly lower than AMD eyes and showed no significant 2-year change. CONCLUSIONS: 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.

Kernel regression based segmentation of optical coherence tomography images with diabetic macular edema.

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.

Retinal atrophy in eyes with resolved papilledema detected by optical coherence tomography.

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 Frisén 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.

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.