THREE-DIMENSIONAL ANALYSIS OF SUBMACULAR PERFORATING SCLERAL VESSELS BY ENHANCED DEPTH IMAGING OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: To analyze submacular perforating scleral vessels (PSVs) using enhanced depth imaging spectral domain optical coherence tomography (EDI-SDOCT). METHODS: Twenty-two eyes of 11 healthy women were included in this retrospective study. Central EDI-SDOCT scans (3 × 4.5 × 1.9 mm, 13.5 mm scan area) were acquired and postprocessed by denoising, manual sclera segmentation, and PSV investigated by five graders. RESULTS: Mean age was 22.4 ± 6.2 years. Mean refractive error was -0.44 ± 0.8 diopters. Mean axial length was 23.08 ± 0.63 mm. The coefficient of agreement for grading was good. Mean number of submacular PSVs was 0.33 ± 0.2 per mm (range from 0 to 9 per eye). Subfield analysis showed 0.2 ± 0.5 (range 0-2) and 2.1 ± 1.8 (range 0-7) vessels, respectively, for central 1-mm diameter and 3-mm diameter. Quadrant analysis showed 0.7 ± 0.9, 0.5 ± 0.9, 0.3 ± 0.6, and 0.4 ± 0.6 vessels, respectively for superior, inferior, nasal, and temporal quadrants. Total number of PSV showed no significant side difference (median difference 0.5, confidence interval -3.0 to 3.0, P = 0.94) or an influence of axial length (P = 0.16). CONCLUSION: This is the first description of three-dimensional EDI-SDOCT visualization of submacular PSV in healthy eyes. This method allows for in vivo imaging of a critical component of outer retinal perfusion at the posterior pole.

A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

PURPOSE: To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). METHODS: Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. RESULTS: In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 µm(3) (range of 0.209764406 mm(3) /209764405.9 µm(3)to 1.78105544 mm(3) /1781055440 µm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). CONCLUSION: Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

A pilot study to compartmentalize small melanocytic choroidal tumors and choroidal vessels with speckle-noise free 1050 nm swept source optical coherence tomography (OCT choroidal "tumoropsy").

PURPOSE: The purpose was to illustrate small melanocytic choroidal tumors with speckle-noise free swept-source optical coherence tomography (SSOCT). METHODS: Twenty-five small melanocytic choroidal tumors in 24 eyes underwent 1050 nm OCT. All tumors were measured manually with the built-in caliper tool and compared to data derived from a semiautomated algorithm that removed speckle noise but preserved the structure of the tumors from the SSOCT data. RESULTS: The average manual measurements for the horizontal, vertical, and axial diameters were 1535.28 µm (range, 547-2807 µm), 1713.8 µm (range, 574-3921 µm), and 227.28 µm (range, 115-489 µm), respectively. The measured average volumes of the tumors were 835,248,212 µm(3) (range, 48,818,700 to 4,567,401,810 µm(3)) and 228,588,535 µm(3) (range, 22,879,641 to 787,668,886 µm(3)) for caliper measurements, respectively, for the extracted volumes. The average volume variation between the two methods was 66.16 % (range, 46.5 % to 82.75 %). The average ratio between the caliper and extracted volumes was 3.402 (range, 1.346-8.198, SD 1.681), 2.367 (range, 1.346-3.258, SD 0.618), 2.321 (range, 1.346-3.258, SD 0.611), 2.402 (range, 1.518-3.258, SD 0.591), and 1.749 (range, 1.518-1.733, SD 0.239) for all tumors, all tumors with the exclusion of extreme parameters, tumor <3 mm, tumor <2 mm, and tumor <1 mm, respectively. The average ratio (tumor index) between the tumor volume and the choroidal vessel volume was 12.539 (range, 0.489-73.701). CONCLUSION: Speckle-noise free swept-source OCT may be an illustrative OCT imaging technology. OCT may be useful for describing and monitoring small melanocytic choroidal tumors and the choroidal vessels.

Advanced Clinical Imaging and Tissue-based Biomarkers of the Eye for Toxicology Studies in Minipigs.

There is increased interest to use minipigs in ocular toxicology studies due to their anatomical similarities with human eyes and as a substitute for nonhuman primates. This requires adaptation of enhanced optical coherence tomography (OCT) techniques and of ocular relevant immunohistochemistry (IHC) or in situ hybridization (ISH) markers to porcine eyes. In this study, OCT and OCT angiography (AngioOCT) were performed on adult Göttingen minipigs. To increase structural information on retinal and choroidal vasculature, OCT data were speckle denoized and choroidal blood vessels were segmented with threshold filtering. In addition, we established a set of IHC and ISH markers on Davidson's fixed paraffin-embedded minipig eyes: neurofilament-160, neuronal nuclei, calretinin, protein kinase C-α, vimentin, glial fibrillary acidic protein, glutamine synthetase, ionized calcium-binding adaptor molecule-1, rhodopsin, synaptophysin, postsynaptic density protein-95, retinal pigment epithelium (RPE)-specific protein-65, von Willebrand factor, α-smooth muscle actin, desmin, and Ki-67, thus enabling visualization of retinal neuronal and glial cells, photoreceptors, synapses, RPE, blood vessels, myocytes, macrophages, or cell proliferation. Using ISH, transcripts of vascular endothelial growth factor A, angiopoietin-2, and endothelial tyrosine kinase were visualized. This article describes for the first time in minipig eyes speckle noise-free OCT, AngioOCT, and a set of IHC/ISH markers on Davidson's fixed paraffin-embedded tissues and helps to establish the minipig for ocular toxicology and pharmacology studies.

Inter-device size variation of small choroidal nevi measured using stereographic projection ultra-widefield imaging and optical coherence tomography.

PURPOSE: Our purpose was to compare the tumor sizes of small choroidal nevi using ultra-widefield imaging (UWF) and different optical coherence tomography systems. METHODS: Thirteen choroidal nevi were measured using automatic and manual segmentation techniques, including enhanced depth imaging spectral-domain optical coherence tomography (EDI-SDOCT) and 1050 nm swept source OCT (SSOCT), to compare to measurements obtained using the Optos projection ultra-widefield fundus (UWF) imaging technique. Segmentation artifacts were evaluated for all 13 cases, alongside an additional 12 choroidal nevi, using SSOCT. RESULTS: In tumor eyes, segmentation artifacts for the choroid-sclera interface were found in 42 % of SSOCT scans. EDI-SDOCT can underestimate tumor dimensions and differs up to -8.41 % compared to UWF imaging and by 1.25 % compared to SSOCT cases. The horizontal length of the nevi showed an average difference between EDI-SDOCT and SSOCT of ± 9.38 %. Measured markers showed an average difference in length of ± 12.51 %. The average tumor thickness showed a difference of ± 11.47 %. Comparisons between EDI-SDOCT/UWF, SSOCT/EDI-SDOCT, and marker EDI-SDOCT/SSOCT showed significant mean differences of -122 µm (CI: -212 to -31 µm, p = 0.013), 134 µm (CI: 65-203 µm, p = 0.0012), and -193 µm (CI: -345 to -41 µm, p = 0.017), whereas SSOCT/UWF showed no significant difference with a measurement of 13 µm (CI: -69-95 µm, p = 0.74). CONCLUSIONS: Automatic segmentation of nevi requires much caution, because a choroidal tumor can trigger many artifacts. It would be beneficial to monitor choroidal nevi using the same type of OCT technology, because a tumor is displayed differently.

Ultra-Short-Term Reproducibility of Speckle-Noise Freed Fluid and Tissue Compartmentalization of the Choroid Analyzed by Standard OCT.

PURPOSE: We measured reproducibility of speckle-noise freed fluid and tissue compartmentalization of the choroid (choroidal angiography and tissue characterization). METHODS: This study included 26 eyes of 13 healthy females: 13 were used for repeated measurements and 13 were used for side comparison. A semiautomated algorithm removed speckle-noise with structure preservation. RESULTS: Intraclass correlation (ICC), with respect to reproducibility of the method, showed an ICC for choroidal fluid inner space analysis (FISA) of 95.15% (90.01-98.24). The ICC of tissue inner space analysis (TISA) was 99.75% (99.47-99.91). The total choroid ratio (TCR), calculated from volumes of tissue to vessels, showed an ICC of 88.84% (78.28-95.82). Comparison of eyes (left to right) showed a difference for FISA of 0.033 (95% confidence interval [CI] -0.0018-0.0680, P = 0.063), TISA -0.118 (CI -0.2373-0.0023, P = 0.055), and TCR -0.590 (CI -0.9047 to -0.2754, P = 0.004). The ICC for FISA and TISA showed a trend in the difference comparing left and right eyes; however, TCR showed a significant difference between the eyes in the measured area (P < 0.001). Mean overall FISA was 0.58 mm3 (range, 0.25-0.98 mm3, SD = 0.14). Mean TISA was 3.45 mm3 (range, 2.38-5.0 mm3, SD 0.072). Mean TCR was 6.13 (overall range, 3.93-10.2, SD = 1.34). CONCLUSIONS: Differences in choroidal layers between subjects were found mainly due to alterations in choroidal tissue. Reproducibility of speckle-noise freed choroidal angiography appeared excellent. TRANSLATIONAL RELEVANCE: Speckle noise is a granular "noise" that appears in a wide range of medical imaging methods as ultrasonography, magnetic resonance, computer tomography, or optical coherence tomography (OCT). Findings from basic science about speckle noise were translated into a novel, medical image postprocessing application that can separate signal from speckle noise with structure preservation with high reproducibility and enhance medical imaging.