White dots as a novel marker of diabetic retinopathy severity in ultrawide field imaging

Purpose: To characterize white dots in diabetic retinopathy (DR) and their association with disease severity using ultra-wide-field scanning laser ophthalmoscopy. Methods: We randomly selected 125 eyes of 77 patients (25 eyes from individual categories of the international classification of DR severity) for which ultrawide field photographs were obtained. We characterized white dots, which were delineated by higher signal levels on green but not red laser images, and evaluated the relationship between the number of white dots and the international severity scale of DR. Results: Most white dots were located in nonperfused areas, and the number of total white dots was significantly correlated to that of dots in nonperfused areas. White dots corresponded to microaneurysms around the boundary between nonperfused areas and perfused areas or unknown lesions in nonperfused areas. Eyes with DR had significantly more white dots than those with no apparent retinopathy. The numbers of white dots in moderate nonproliferative diabetic retinopathy (NPDR) or more severe grades were significantly higher than in mild NPDR. The area under the receiver operating characteristics curve (AROC) analyses demonstrated that the number of white dots had the significance in the diagnosis of DR (0.908-0.986) and moderate NPDR or more severe grades (0.888-0.974). Conclusions: These data suggest the clinical relevance of white dots seen on ultrawide field images in the diagnosis of the severity of DR

SDF-1/CXCR4は網膜血管新生において血管先導端細胞とマイクログリアの活性化に寄与する

京都大学0048新制・課程博士博士(医学)甲第15604号医博第3489号新制||医||983(附属図書館)28131京都大学大学院医学研究科外科系専攻(主査)教授 伊藤 壽一, 教授 戸井 雅和, 教授 長澤 丘司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDA

Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy,”

Citation: Arichika S, Uji A, Murakami T, et al. Retinal hemorheologic characterization of early-stage diabetic retinopathy using adaptive optics scanning laser ophthalmoscopy. Invest Ophthalmol Vis Sci. 2014;55:8513-8522. DOI:10.1167/ iovs.14-15121 PURPOSE. Adaptive optics scanning laser ophthalmoscopy (AO-SLO) is a noninvasive technique that allows for the direct monitoring of erythrocyte aggregates in retinal capillaries. We analyzed the retinal hemorheologic characteristics in normal subjects, diabetic patients without diabetic retinopathy (NDR), and diabetic patients with nonproliferative diabetic retinopathy (NPDR), using spatiotemporal (ST) blood flow images to visualize blood corpuscle trajectory. METHODS. AO-SLO images of the parafoveal capillary network were acquired for three groups: 20 healthy volunteers, 17 diabetic patients with NDR (8 type 1 and 9 type 2 patients), and 10 diabetic patients with NPDR (4 type 1 and 6 type 2). The erythrocyte aggregate velocity assigned to a relative cardiac cycle and the elongation rate of the erythrocyte aggregate were calculated. RESULTS. Careful observation revealed that flow velocity fluctuations were found with higher frequency in diabetic patients than in normal subjects. The total average velocities were 1.26 6 0.22 mm/s in the normal group, 1.31 6 0.21 mm/s in the NDR group, and 1.63 6 0.35 mm/s in the NPDR group. The average velocities of the NPDR group were higher than those in the normal (P ¼ 0.001) and NDR (P ¼ 0.009) groups. The average elongation rates of the 3 groups were 0.67 6 0.20, 0.39 6 0.19, and 0.33 6 0.11, respectively. Elongation rate differed significantly between the normal and NDR (P ¼ 0.003) groups as well as the normal and NPDR (P ¼ 0.001) groups. CONCLUSIONS. AO-SLO can be used to detect retinal hemorheologic changes in the early stages of diabetic retinopathy

Differentiation of the white dots from the dot-like artifacts on ultrawide field imaging.

<p>(A, B) Raw images of two sequential green-channel images. (C, D) The Find Edges function of the ImageJ software is applied to the images. (E) The co-localization highlighter function of the ImageJ plugin is then applied. (F, G) The magnified images of the left and right squares in panel E, respectively. (F) The twin dots (green and red) correspond to the white dots. (G) Dot-like artifacts are co-localized completely.</p

White dots are seen in the perfused or nonperfused areas in diabetic retinopathy.

<p>White dots are delineated rarely in the typical perfused areas (A-E) and mainly in the typical nonperfused areas (F-J). Some white dots correspond to microaneurysms in the areas at the border between the typical perfused areas and nonperfused areas (K-O). (A, F, K) Fluorescein angiography and (B, G, L) its magnified image. (C, H, M) Pseudocolor, (D, I, N) green-channel, and (E, J, O) red-channel ultrawide field scanning laser ophthalmoscopy images corresponding to the magnified FA images (B, G, L), respectively. Arrowheads = white dots.</p

Different appearances of white dots and typical hard exudates in diabetic retinopathy.

<p>(A) color fundus photograph shows yellow and metallic hard exudates and white dots (rectangular area). (B, C) Pseudocolor and green-channel ultrawide field scanning laser ophthalmoscopy images. (D) The red-channel image shows that hard exudates and not white dots are accompanied by higher signal intensity. (E) The margin of the hard exudates is delineated clearly with the Find Edges function of the ImageJ software compared to that of the white dots. (F) A merged image comprised of the panels C (gray) and E (red). Oval areas = hard exudates; arrowheads = white dots.</p

Clinical significance of white dots in the diagnosis of diabetic retinopathy severity.

<p>(A) The number of white dots (box plot) in individual grades of the international severity scale of diabetic retinopathy. *, <i>P</i><0.001 vs. no apparent retinopathy. (B) The receiver operating characteristic (ROC) curve for diabetic retinopathy (DR) diagnosis of the total number of white dots or red spots discriminating 125 eyes of diabetic patients from 25 nondiabetic control subjects. The ROC curve for DR severity diagnoses (mild nonproliferative diabetic retinopathy [NPDR] or more severe [C], moderate NPDR or more severe [D], severe NPDR or more severe [E], and proliferative diabetic retinopathy [PDR] [F]) of the total number of white dots or red spots in 125 eyes of diabetic patients. AROC = the area under the receiver operating characteristic curve. black line = ROC curve of white dots; gray line = ROC curve of red spots.</p

A white dot in the typical nonperfused area in diabetic retinopathy.

<p>A white dot seen in a color fundus photograph (A), pseudocolor image (B), green-channel (C), and red-channel (D) on ultrawide field scanning laser ophthalmoscopy images is seen in the typical nonperfused areas on fluorescein angiography image (E). (B-E) The magnified images corresponding to the black rectangle in panel A. (F) Optical coherence tomography image dissecting along the arrow in panel B shows a lesion with high reflectivity in the inner retinal layers. Arrowheads = white dots.</p

Systemic characteristics of control subjects and diabetic patients.

<p>Systemic characteristics of control subjects and diabetic patients.</p