Spectral-domain Optical Coherence Tomography Volume Scans Research Articles

The Double Layer Sign Is Highly Predictive of Progression to Exudation in Age-Related Macular Degeneration

The presences of a double layer sign (DLS) and a shallow irregular retinal pigment epithelium (RPE) elevation (SIRE) were investigated using spectral domain-OCT (SD-OCT) imaging to determine their ability to predict progression to exudative macular neovascularization (eMNV) in the unaffected fellow eyes (study eye) of participants with age-related macular degeneration (AMD) with newly diagnosed unilateral eMNV. Retrospective, reanalysis of SD-OCT scans of study eyes from the Early Detection of Neovascular AMD (EDNA) study with 3 years follow-up (FU). The EDNA study repository of SD-OCT scans was assessed for inclusion. Cases with incomplete data sets, low quality scans, or exhibiting other pathology were excluded, which resulted in 459 eligible cases. Spectral domain-OCT volume scans of study eyes were graded for irregular elevation of the RPE (IE), with length, and height measurements made on the most affected B-scan. Eyes with heterogeneous reflectivity within the IE were classified as exhibiting the DLS. Eyes with DLS where the length of separation between RPE and Bruch's membrane was ≥ 1000 μm in length and < 100 μm in height were subclassified as SIRE. Hazard of progression to eMNV for DLS and SIRE. Of the 459 eyes, 268 had IE, of which 101 were DLS-like and 51 also fulfilled criteria for SIRE. Over the 3 years FU period, 104 (23%) eyes progressed to eMNV. After an FU of 18 months, a significantly higher proportion of study eyes (P < 0.001) with IE, DLS, and SIRE developed eMNV compared with those without these features (IE: 17% vs. no IE 6.3%; DLS: 23% vs. no DLS 9.9%; SIRE: 22% vs. no SIRE 11%). In the adjusted Cox regression models, a significantly greater hazard of progression (P < 0.001) was associated with the presence of IE (adjusted hazard ratio [HR], 3.01; 95% confidence interval [CI], 1.88-4.82), DLS (adjusted HR, 3.41; 95% CI, 2.26-5.14), or SIRE (adjusted HR, 2.83; 95% CI, 1.68-4.75). The DLS is a highly sensitive predictor of progression to eMNV, and the use of SIRE does not improve predictability. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Monitoring Lesion Area Progression in Stargardt Disease: A Comparison of En Face Optical Coherence Tomography and Fundus Autofluorescence.

To compare longitudinal changes in en face spectral domain-optical coherence tomography (SD-OCT) measurements of ellipsoid zone (EZ) and retinal pigment epithelium (RPE) loss to changes in the hypoautofluorescent and hyperautofluorescent (AF) areas detected with short-wavelength (SW)-AF in ABCA4-associated retinopathy. SD-OCT volume scans were obtained from 20 patients (20 eyes) over 2.6 ± 1.2 years (range 1-5 years). The EZ, and RPE/Bruch's membrane boundaries were segmented, and en face slab images generated. SubRPE and EZ slab images were used to measure areas of atrophic RPE and EZ loss. These were compared to longitudinal measurements of the hypo- and abnormal AF (hypoAF and surrounding hyperAF) areas. At baseline, the en face area of EZ loss was significantly larger than the subRPE atrophic area, and the abnormal AF area was significantly larger than the hypoAF area. The median rate of EZ loss was significantly greater than the rate of increase in the subRPE atrophic area (1.2 mm2/yr compared to 0.5 mm2/yr). The median rate of increase in the abnormal AF area was significantly greater than the increase in the hypoAF area (1.6 mm2/yr compared to 0.6 mm2/yr). En face SD-OCT can be used to quantify changes in RPE atrophy and photoreceptor integrity. It can be a complementary or alternative technique to SW-AF with the advantage of monitoring EZ loss. The SW-AF results emphasize the importance of measuring changes in the hypo- and abnormal AF areas. The findings are relevant to the selection of outcome measures for monitoring ABCA4-associated retinopathy.

Probabilistic Forecasting of Anti-VEGF Treatment Frequency in Neovascular Age-Related Macular Degeneration.

PurposeTo probabilistically forecast needed anti-vascular endothelial growth factor (anti-VEGF) treatment frequency using volumetric spectral domain–optical coherence tomography (SD-OCT) biomarkers in neovascular age-related macular degeneration from real-world settings.MethodsSD-OCT volume scans were segmented with a custom deep-learning-based analysis pipeline. Retinal thickness and reflectivity values were extracted for the central and the four inner Early Treatment Diabetic Retinopathy Study (ETDRS) subfields for six retinal layers (inner retina, outer nuclear layer, inner segments [IS], outer segments [OS], retinal pigment epithelium-drusen complex [RPEDC] and the choroid). Machine-learning models were probed to predict the anti-VEGF treatment frequency within the next 12 months. Probabilistic forecasting was performed using natural gradient boosting (NGBoost), which outputs a full probability distribution. The mean absolute error (MAE) between the predicted versus actual anti-VEGF treatment frequency was the primary outcome measure.ResultsIn a total of 138 visits of 99 eyes with neovascular AMD (96 patients) from two clinical centers, the prediction of future anti-VEGF treatment frequency was observed with an accuracy (MAE [95% confidence interval]) of 2.60 injections/year [2.25–2.96] (R2 = 0.390) using random forest regression and 2.66 injections/year [2.31–3.01] (R2 = 0.094) using NGBoost, respectively. Prediction intervals were well calibrated and reflected the true uncertainty of NGBoost-based predictions. Standard deviation of RPEDC-thickness in the central ETDRS-subfield constituted an important predictor across models.ConclusionsThe proposed, fully automated pipeline enables probabilistic forecasting of future anti-VEGF treatment frequency in real-world settings.Translational RelevancePrediction of a probability distribution allows the physician to inspect the underlying uncertainty. Predictive uncertainty estimates are essential to highlight cases where human-inspection and/or reversion to a fallback alternative is warranted.

EXPLORING PHOTORECEPTOR REFLECTIVITY THROUGH MULTIMODAL IMAGING OF OUTER RETINAL TUBULATION IN ADVANCED AGE-RELATED MACULAR DEGENERATION.

To investigate the microscopic structure of outer retinal tubulation (ORT) and optical properties of cone photoreceptors in vivo, we studied ORT appearance by multimodal imaging, including spectral domain optical coherence tomography (SD-OCT) and adaptive optics scanning laser ophthalmoscopy. Four eyes of four subjects with advanced age-related macular degeneration underwent color fundus photography, infrared reflectance imaging, SD-OCT, and adaptive optics scanning laser ophthalmoscopy with a high-resolution research instrument. Outer retinal tubulation was identified in closely spaced (11 μm) SD-OCT volume scans. Outer retinal tubulation in cross-sectional and en face SD-OCT was a hyporeflective area representing a lumen surrounded by a hyperreflective border consisting of cone photoreceptor mitochondria and external limiting membrane, per previous histology. In contrast, ORT by adaptive optics scanning laser ophthalmoscopy was a hyporeflective structure of the same shape as in en face SD-OCT but lacking visualizable cone photoreceptors. Lack of ORT cone reflectivity by adaptive optics scanning laser ophthalmoscopy indicates that cones have lost their normal directionality and waveguiding property due to loss of outer segments and subsequent retinal remodeling. Reflective ORT cones by SD-OCT, in contrast, may depend partly on mitochondria as light scatterers within inner segments of these degenerating cells, a phenomenon enhanced by coherent imaging. Multimodal imaging of ORT provides insight into cone degeneration and reflectivity sources in optical coherence tomography.

Near-infrared autofluorescence: its relationship to short-wavelength autofluorescence and optical coherence tomography in recessive stargardt disease.

We compared hypoautofluorescent (hypoAF) areas detected with near-infrared (NIR-AF) and short-wavelength autofluorescence (SW-AF) in patients with recessive Stargardt disease (STGD1) to retinal structure using spectral domain optical coherence tomography (SD-OCT). The SD-OCT volume scans, and SW-AF and NIR-AF images were obtained from 15 eyes of 15 patients with STGD1 and registered to each other. Thickness maps of the total retina, receptor-plus layer (R+, from distal border of the RPE to outer plexiform/inner nuclear layer boundary), and outer segment-plus layer (OS+, from distal border of the RPE to ellipsoid zone [EZ] band) were created from SD-OCT scans. These were compared qualitatively and quantitatively to the hypoAF areas in SW-AF and NIR-AF images. All eyes showed a hypoAF area in the central macula and loss of the EZ band in SD-OCT scans. The hypoAF area was larger in NIR than SW-AF images and it exceeded the area of EZ band loss for 12 eyes. The thickness maps showed progressive thinning towards the central macula, with the OS+ layer showing the most extensive and severe thinning. The central hypoAF areas on NIR corresponded to the OS+ thinned areas, while the hypoAF areas on SW-AF corresponded to the R+ thinned areas. Since the larger hypoAF area on NIR-AF exceeded the region of EZ band loss, and corresponded to the OS+ thinned area, RPE cell loss occurred before photoreceptor cell loss. The NIR-AF imaging may be an effective tool for following progression and predicting loss of photoreceptors in STGD1.

Longitudinal Analysis of Reticular Drusen Associated with Age-Related Macular Degeneration Using Combined Confocal Scanning Laser Ophthalmoscopy and Spectral-Domain Optical Coherence Tomography Imaging

Purpose: To evaluate longitudinal variations of reticular drusen (RDR) in age-related macular degeneration using confocal scanning laser ophthalmoscopy (cSLO), near-infrared reflectance (NIR) and spectral-domain optical coherence tomography (SD-OCT) imaging. Methods: Eighteen eyes of 12 patients with RDR (median observational time 5 months, range 3-10) were included. Changes over time in the en face cSLO NIR images, the identical SD-OCT B scan (simple approach) and the dense SD-OCT volume scans (11 µm between B scans, detailed approach) for 5 preselected RDR lesions were analysed, respectively. Results: Nineteen of 90 (21%) lesions were no longer detectable at the follow-up examination with the simple SD-OCT approach (increase 7/decrease 48/unchanged 15/not gradable 1). By contrast, no disappearance of single lesions was noted for both cSLO (3/8/61/18) and detailed SD-OCT image analysis (67/22/1/0). Within the dense SD-OCT volume scan, a median change of individual lesion height of 10 µm/year was determined. Conclusions: The findings indicate a recordable progression of RDR lesions in lateral and vertical dimensions. Using dense SD-OCT volume scans, individual RDR lesion progression can be quantified and may be applied in future longitudinal studies.

Multiple layer segmentation and analysis in three-dimensional spectral-domain optical coherence tomography volume scans

Spectral-domain optical coherence tomography (SD-OCT) is a three-dimensional imaging technique that allows direct visualization of retinal morphology and architecture. The various retinal layers may be affected differentially by various diseases. An automated graph search algorithm is developed to sequentially segment 11 retinal surfaces in SD-OCT volumes using a three-stage approach. In stage 1, the four most easily discernible and/or distinct surfaces are identified in four-times-downsampled images and are used as a priori information to limit the graph search for the other surfaces in stage 2. Eleven surfaces were then detected in two-times-downsampled images in stage 2, and refined in the original images in stage 3 using the graph search integrating the estimated morphological shape models. Twenty macular SD-OCT volume scans from 20 normal subjects are used in this initial study. The overall mean and absolute mean differences in border positions between the automated and manual segmentation for the 11 surfaces are -0.20 ± 0.53 voxels (-0.76 ± 2.06 μm) and 0.82 ± 0.64 voxels (3.19 ± 2.46 μm), respectively. Intensity/reflectivity and thickness properties in various retinal layers are also investigated. This investigation in normal subjects may provide a comparative reference for subsequent adaptations in eyes with diseases.

Functional and morphological changes in diabetic macular edema over the course of anti-vascular endothelial growth factor treatment

To evaluate macular morphology and function in diabetic macular edema (DME) over the course of intravitreal anti-vascular endothelial growth factor (VEGF) treatment with Ranibizumab. A consecutive series of 39 study eyes with centre-involving DME were included in this study. In all subjects, best-corrected visual acuity (BCVA) according ETDRS protocol, fluorescein angiography (FA), microperimetric macular sensitivity (MP) and Spectral Domain optical coherence tomography (SD-OCT) cross-sectional scans were obtained before treatment and after 3 monthly applied intravitreal Ranibizumab injections. Six different morphological qualities [IS/OS layer integrity, outer nuclear layer (ONL) cysts, ONL cyst size, inner nuclear layer (INL) cysts, blocking phenomenon and subretinal fluid] were graded of each cross-sectional OCT scan before and over the course of treatment by two experienced graders. Correlation analyses between functional and morphological parameters were obtained. Mean BCVA increased from 26 ± 14 to 33 ± 13 letters after 3 consecutive monthly applied Ranibizumab injections (p < 0.001). Central retinal thickness (CRT) decreased from 504 ± 144 to 387 ± 122 μm (p < 0.001). Over the course of treatment, IS/OS continuity improved (index: 0.56 ± 0.52 to 0.43 ± 0.49, Z = -1.415, p = 0.157), ONL cyst prevalence and size decreased significantly (index: 0.61 ± 0.44 to 0.56 ± 0.35, Z = -3.41, p = 0.001 and 1.75 ± 0.88 to 1.17 ± 1.05, Z = -4.02, p < 0.001), INL cyst prevalence decreased (index: 0.35 ± 0.52 to 0.28 ± 0.52, Z = -1.60, p = 0.109), blocking phenomenon did not change significantly (index: 00.12 ± 0.16 to 0.13 ± 0.15, Z = -0.45, p = 0.656) and subretinal fluid almost disappeared (index: 0.10 ± 0.24 vs. 0.00 ± 0.01, Z = -2.56, p = 0.011). Correlation analyses revealed highest significant correlations between ONL cyst prevalence and their size and CRT as well as BCVA and MP before treatment and over the course of treatment. ONL cysts and their size as morphological parameters correlate with retinal function measured with BCVA and microperimetry before and over the course of anti-VEGF therapy with Ranibizumab in patients with DME.

Aqueous flare is increased in patients with clinically significant cystoid macular oedema after cataract surgery

BackgroundTo analyse the relationship of clinically significant cystoid macular oedema (CME after phacoemulsification to blood–aqueous barrier breakdown as determined by aqueous flare, visual acuity and retinal thickness in optical coherence...

Point-wise Relationships Between Visual Field Sensitivity and Macular Thickness Determined by Spectral-domain Optical Coherence Tomography

Purpose: To evaluate the point-wise relationships between visual field sensitivity (VFS), as measured by standard automated perimetry (SAP), and macular thickness, as determined by spectral-domain optical coherence tomography (SD-OCT), in patients with glaucoma.Materials and methods: One hundred and six glaucoma subjects (one eye per subject) recruited from an academic institution underwent SAP tests (Humphrey field analyzer, central 24-2 of Swedish Interactive Thresholding Algorithm standard) and SD-OCT volume scans (SPECTRALIS, posterior pole asymmetry analysis). The retinal sensitivities of 16 central test points from the SAP results were recorded. Macular thickness values from 4 square cells in an 8 × 8 posterior pole retinal thickness map were averaged for a mean retinal thickness (MRT) value, which corresponded to the 16 central test points in the SAP. In each 16-point area, linear regression analyses of the VFS and the MRT value were performed.Results: The VFS of each 16 central test point showed a significant relationship with the corresponding MRT values (R2 = 0.133–0.383, all p < 0.001). Central and nasal test points corresponding to an arcuate region revealed a relatively strong correlation in both the superior and inferior hemispheres (R2 = 0.311–0.383 and 0.288–0.345, respectively), but the superior and inferior-temporal points revealed a relatively weaker correlation (R2 = 0.149 and 0.133, respectively).Conclusions: The VFS showed a significant reciprocal relationship with corresponding macular thickness at each test point. However, the level of the relationship varied among different macular sectors, showing the strongest relationship in the arcuate region.

Grading of Age-Related Macular Degeneration: Comparison between Color Fundus Photography, Fluorescein Angiography, and Spectral Domain Optical Coherence Tomography

Purpose. To compare color fundus photography (FP), fluorescein angiography (FA), and spectral domain optical coherence tomography (SDOCT) for the detection of age-related macular degeneration (AMD), choroidal neovascularisation (CNV), and CNV activity. Methods. FPs, FAs, and SDOCT volume scans from 120 eyes of 66 AMD and control patients were randomly collected. Control eyes were required to show no AMD, but other retinal pathology was allowed. The presence of drusen, pigmentary changes, CNV, and signs for CNV activity was independently analyzed for all imaging modalities. Results. AMD was diagnosed based on FP in 75 eyes. SDOCT and FA showed sensitivity (specificity) of 89% (76%) and 92% (82%), respectively. CNV was present on FA in 68 eyes. Sensitivity (specificity) was 78% (100%) for FP and 94% (98%) for SDOCT. CNV activity was detected by SDOCT or FA in 60 eyes with an agreement in 46 eyes. Sensitivity was 88% for SDOCT and 88% for FA. FP showed sensitivity of 38% and specificity of 98%. Conclusions. CNV lesions and activity may be missed by FP alone, but FP may help identifying drusen and pigmentary changes. SDOCT is highly sensitive for the detection of AMD, CNV, and CNV activity; however, it cannot fully replace FA.

SDOCT Thickness Measurements of Various Retinal Layers in Patients with Autosomal Dominant Optic Atrophy due toOPA1Mutations

Purpose. To specify thickness values of various retinal layers on macular spectral domain Optical Coherence Tomography (SDOCT) scans in patients with autosomal dominant optic atrophy (ADOA) compared to healthy controls. Methods. SDOCT volume scans of 7 patients with ADOA (OPA-1 mutation) and 14 healthy controls were quantitatively analyzed using manual grading software. Mean thickness values for the ETDRS grid subfields 5–8 were calculated for the spaces neurosensory retina, retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), a combined space of inner plexiform layer/outer plexiform layer/inner nuclear layer (IPL+INL+OPL), and a combined space of outer nuclear layer/photoreceptor layers (ONL+PL). Results. ADOA patients showed statistically significant lower retinal thickness values than controls (P < 0.01). RNFL (P < 0.001) and GCL thicknesses (P < 0.001) were significantly lower in ADOA patients. There was no difference in IPL+INL+OPL and in ONL+PL thickness. Conclusion. Manual subanalysis of macular SDOCT volume scans allowed detailed subanalysis of various retinal layers. Not only RNFL but also GCL thicknesses are reduced in the macular area of ADOA patients whereas subjacent layers are not involved. Together with clinical findings, macular SDOCT helps to identify patients with suspicion for hereditary optic neuropathy before genetic analysis confirms the diagnosis.

Time-Periodic Characteristics in the Morphology of Idiopathic Central Serous Chorioretinopathy Evaluated by Volume Scan Using Spectral-Domain Optical Coherence Tomography

To investigate the time-period characteristics associated with morphologic changes in idiopathic central serous chorioretinopathy (CSC) using volume scans acquired by spectral-domain optical coherence tomography (SD-OCT). Retrospective, observational, cross-sectional case series. Patients underwent visual acuity measurements, fundus examinations, fluorescein angiography, indocyanine green angiography, and SD-OCT volume scans. Patients were classified into 5 categories-acute CSC, early chronic (EC) CSC, late chronic (LC) CSC, sequelae of CSC, or recurrent CSC-according to the chronicity and the recurrence. We investigated the relationship between our classification and the detailed morphologic changes of the retinal pigment epithelium and outer retina that were observed in the SD-OCT images. A total of 76 eyes from 75 patients were included in this study. Serous retinal detachment was relatively higher in acute CSC. Low to flat pigment epithelial detachments (PEDs) were most commonly observed in all stages of CSC, especially in LC CSC, but some semicircular PEDs were occasionally observed in eyes with acute or EC CSC. Retinal dragging with fibrin was most frequently observed in eyes that were in the early stage of acute CSC. A thickened posterior surface of the detached retina was most commonly observed in eyes with acute CSC, whereas a thinned posterior surface of the detached retina was observed in eyes with LC CSC. Hyperreflective dots and subretinal exudates were more commonly observed in eyes with EC and LC CSC than in eyes with acute CSC. In eyes with recurrent CSC, 2 different patterns of SD-OCT findings were observed; these patterns resembled those that were found in either acute CSC or LC CSC. SD-OCT finding patterns in CSC eyes differ according to the chronicity and the recurrence of the disease. Detailed investigation of the retinal pigment epithelium and outer retina using SD-OCT could be useful for estimating the duration of CSC.

Segmentation of spectral domain OCT volume scans of patients with no or minimal diabetic retinopathy

Abstract Purpose A comparison of thickness measurements of segmented spectral domain optical coherence tomography (OCT) derived topographic maps of patients with no or minimal diabetic retinopathy (DR) versus healthy controls. Methods Ninety‐nine patients, 44 with type 1 DM, and 36 with type 2 DM, with no or minimal DR underwent full ophthalmic examination, fundus photography and spectral domain OCT (3D OCT‐1000, Topcon). Following automated segmentation the mean thickness was calculated for 6 layers: 1/ Retinal Nerve Fibre Layer (RNFL), 2/ Ganglioncell layer (GCL) + Inner Plexiform Layer (IPL), 3/ Inner Nuclear Layer, 4/ Outer Plexiform Layer, 5/ Outer Nuclear Layer + Inner Segments (photoreceptor), 6/ Outer Segments (photoreceptor), in the ETDRS defined regions of the macula and compared to 76 age and sex matched healthy controls. Results The total retinal thickness in the diabetic patients was reduced compared to the healthy controls. In the diabetic patients both the mean RNFL and the mean OPL were significantly (p&lt;0.05) thinner. Conclusion The decreased total retinal thickness in diabetic patients with no or minimal retinopathy may be due to a selective loss of thickness in several retinal layers and supports the concept of early DR as a neuro‐degenerative disease.