Yuko Miwa

Relationship between Functional and Structural Changes in Diabetic Vessels in Optical Coherence Tomography Angiography

The decorrelation signals in optical coherence tomography angiography (OCTA) are derived from the flow of erythrocytes and concomitantly delineate the retinal vasculature. We compared the structural and functional characteristics of vascular lesions visualized in fluorescein angiography (FA), OCTA, and en-face OCT images in 53 eyes (28 patients) with diabetic retinopathy (DR). The foveal avascular zone (FAZ) areas in OCTA images in the superficial layer almost corresponded to those in FA images. The FAZ areas in the en-face OCT images in the superficial layer were smaller than those in the FA images and correlated with each other, which agreed with the finding that en-face OCT images often delineated the vascular structure in the nonperfused areas in FA images. Microaneurysms appeared as fusiform, saccular, or coiled capillaries in OCTA images and ringed, round, or oval hyperreflective lesions in en-face OCT images. OCTA and en-face OCT images detected 41.0 ± 16.1% and 40.1 ± 18.6%, respectively, of microaneurysms in FA images, although both depicted only 13.9 ± 16.4%. The number of microaneurysms in FA images was correlated with that in OCTA and en-face OCT images. Comparisons of these modalities showed the associations and dissociations between blood flow and vascular structures, which improves the understanding of the pathogenesis of DR.

Evaluation Of Macular Ischemia In Eyes With Branch Retinal Vein Occlusion: An Optical Coherence Tomography Angiography Study

Purpose: To quantitatively assess macular morphology and perfusion status using optical coherence tomography, and optical coherence tomography angiography in eyes with branch retinal vein occlusion when macular edema has completely resolved, and to investigate the impact on visual function. Methods: Thirty consecutive eyes with branch retinal vein occlusion–macular edema that resolved after treatment with intravitreal ranibizumab injections were included. Macular sensitivity was measured by microperimetry; defect length of foveal ellipsoid zone band was measured using optical coherence tomography; foveal avascular zone and parafoveal nonperfusion areas (NPA) were measured by optical coherence tomography angiography. Results: The logarithm of minimum angle of resolution visual acuity was significantly associated with the defect length of the foveal ellipsoid zone band (P = 0.005), the parafoveal NPA in the superficial capillary plexus (P = 0.007), and the parafoveal NPA in the deep capillary plexus (P = 0.006). Macular sensitivity correlated with parafoveal thickness on the affected side (P = 0.034), the defect length of the foveal ellipsoid zone band (P = 0.048), parafoveal NPA in the superficial capillary plexus (P = 0.008), and parafoveal NPA in the deep capillary plexus (P = 0.012). Multivariate analysis where the only significant parameters in the univariate analyses were used as the independent variables showed that parafoveal NPA was most significantly associated with the logarithm of minimum angle of resolution visual acuity (&bgr; = 0.500, P = 0.005) and macular sensitivity (&bgr; = −0.480, P = 0.007). Conclusion: In eyes with branch retinal vein occlusion–macular edema resolved by intravitreal ranibizumab treatments, visual function was strongly associated with parafoveal NPA size.

Ranibizumab For Macular Edema After Branch Retinal Vein Occlusion: One Initial Injection Versus Three Monthly Injections

Purpose: To compare the 12-month-efficacy of 1 initial intravitreal ranibizumab injection (IVR) followed by pro re nata (PRN) dosing with that of three initial monthly IVR followed by PRN dosing in patients with macular edema (ME) after branch retinal vein occlusion. Design: Prospective, interventional study. Methods: Of 81 eyes, 42 received 1 initial IVR injection (1+PRN group) and 39 eyes received 3 monthly IVRs (3+PRN). Pro re nata injections were performed when fovea exudative changes were evident. Results: At Month 12, the visual acuity (VA) changes from baseline were −0.245 ± 0.227 and −0.287 ± 0.222, in the 1+PRN and 3+PRN groups, respectively; there were no significant difference between groups (P = 0.728). The stratified analysis showed that patients with better VA (baseline VA >20/40) had similar significant improvement in VA at Month 12 (P < 0.001) to that of those with poorer VA (⩽20/40). Better VA at Month 12 was significantly associated with younger age, better baseline VA, and thinner baseline central foveal thickness (P = 0.003, < 0.001, and < 0.001, respectively). Mean total number of IVR injections in the 1+PRN and 3+PRN groups were 3.8 ± 1.8 and 4.6 ± 1.4, respectively (P = 0.060). In both groups, shorter durations to the first PRN injection were associated with greater total PRN injection number (1+PRN, P = 0.006; 3+PRN; group, P < 0.001). Conclusion: In IVR treatment for ME after branch retinal vein occlusion, 1+PRN and 3+PRN regimens achieved similar 12-month functional outcomes. Patients with shorter durations to initial PRN injection may require more PRN treatments.

Clinical relevance of reduced decorrelation signals in the diabetic inner choroid on optical coherence tomography angiography

Diabetes induces lesions of the retinal and choroidal capillaries, which promote the pathogenesis of diabetic retinopathy (DR). The decorrelation signals in optical coherence tomography angiography (OCTA) represent the blood flow and vascular structure, and three-dimensional OCTA images enable individual capillary layers to be evaluated separately. The current study documented that en-face OCTA images revealed spots of flow void in the choriocapillaris layer in eyes with DR. Quantitative investigation demonstrated that non-flow areas within the central subfield (CSF) increased in eyes with more severe DR grades. The non-flow areas in the choriocapillaris layer were also associated with poorer visual acuity (VA) in all 108 eyes. A modest correlation was noted between the areas of flow void and poorer VA in 69 eyes without DME, whereas the non-flow areas were not related to VA or to CSF thickness measured by OCT in 39 eyes with DME. In 12 eyes with ischemic maculopathy, the choriocapillaris layer beneath the disrupted ellipsoid zone of the photoreceptor (EZ) had greater areas of flow void than did the area beneath an intact EZ. These data suggested that disrupted choroidal circulation has clinical relevance and contributes to the pathogenesis of DR.

Characterization of Inner Retinal Spots With Inverted Reflectivity on En Face Optical Coherence Tomography in Diabetic Retinopathy.

PURPOSE The purpose of this study was to characterize inner retinal spots with inverted reflectivity on en face images of swept-source optical coherence tomography (SS-OCT) in diabetic retinopathy (DR). METHODS We retrospectively reviewed seventy-five eyes of 75 patients with DR (15 eyes with individual grades of DR severity). We obtained three-dimensional images (6 × 6 mm) centered on the fovea, followed by the generation of en face images. We investigated the morphologic characteristics of spots with inverted reflectivity, which had lower reflectivity than the surrounding areas in the nerve fiber layer (NFL) and higher reflectivity in the ganglion cell layer (GCL). RESULTS Thirty-seven of 45 eyes (82.2%) with moderate nonproliferative diabetic retinopathy (NPDR) or more severe grades were accompanied with well-defined spots with inverted reflectivity, whereas 30 eyes with no apparent retinopathy or mild NPDR had no such lesions. These spots had various shapes in the NFL and GCL on en face OCT images; the mean area was 0.126 ± 0.052 mm2 at the NFL level. In all 75 eyes, 153 of 184 spots (83.2%) were localized in the NFL and GCL, whereas 31 spots (16.8%) extended to retinal layers deeper than the GCL. One-hundred sixty-nine spots (91.8%) were not visible on color fundus photographs, and 15 spots (8.2%) were accompanied by whitish-yellow lesions in the corresponding areas. In 45 eyes for which fluorescein angiography images were obtained, mild hypofluorescence was seen in 156 spots (84.8%) and focal nonperfused areas in 17 spots (9.2%). CONCLUSIONS En face images of SS-OCT showed spots with inverted reflectivity in the NFL and GCL in DR.

Relation between macular morphology and treatment frequency during twelve months with ranibizumab for diabetic macular edema

Purpose To investigate whether baseline optical coherence tomography (OCT) parameters can predict the treatment frequency of intravitreal ranibizumab (IVR) injections during the first year in patients with diabetic macular edema (DME) treated with pro re nata (PRN) IVR injections. Methods We retrospectively reviewed 68 eyes of 63 patients with center-involved DME who received IVR injections for 12 months or longer according to three monthly IVR injections followed by the PRN dosing. We measured the mean retinal thicknesses in the individual subfields of the Early Treatment Diabetic Retinopathy Study grid and evaluated the qualitative and quantitative parameters on OCT sectional images. We investigated the relationship between these OCT parameters at baseline and the number of IVR injections during the 12-month follow-up. Results Three loading doses were administered to 10 eyes; four to seven annualized IVR injections were administered to 34 eyes. The number of eyes that received IVR injections decreased gradually until month 6 and was almost constant from months 7 to 11. No relationships were seen between the treatment frequency and baseline systemic factors and the ophthalmic examination findings. Univariate analyses showed that the number of IVR injections during the first year was associated with the mean retinal thickness in the individual subfields and the transverse length of the disrupted external limiting membrane (ELM) and ellipsoid zone of the photoreceptors. Multivariate analysis showed a significant association with the thickness in the inferior subfield alone. The treatment frequency during the 12-month follow-up was not correlated with improved visual acuity but was associated with the decrease in the central subfield thickness and disrupted ELM. Conclusion The retinal thickness in the inferior subfield predicts the treatment frequency during the first year in eyes with DME treated with PRN IVR injections.

Restoration of foveal photoreceptors after intravitreal ranibizumab injections for diabetic macular edema.

Anti-vascular endothelial growth factor drugs are the first-line treatment for diabetic macular edema (DME), although the mechanism of the visual acuity (VA) improvement remains largely unknown. The association between photoreceptor damage and visual impairment encouraged us to retrospectively investigate the changes in the foveal photoreceptors in the external limiting membrane (ELM) and ellipsoid zone (EZ) on spectral-domain optical coherence tomography (SD-OCT) images in 62 eyes with DME treated with intravitreal ranibizumab (IVR) injections. The transverse lengths of the disrupted EZ and ELM were shortened significantly (P < 0.001 and P = 0.044, respectively) at 12 months. The qualitative investigation also showed restoration of the EZ and ELM lines on SD-OCT images. The EZ at 12 months lengthened in 34 of 38 eyes with discontinuous EZ and was preserved in 16 of 21 eyes with complete EZ at baseline. VA improvement was positively correlated with shortening of the disrupted EZ at 12 months (ρ = 0.463, P < 0.001), whereas the decrease in central subfield thickness was associated with neither VA improvement nor changes in EZ status (ρ = 0.215, P = 0.093 and (ρ = 0.209, P = 0.103, respectively). These data suggested that photoreceptor restoration contributes to VA improvement after pro re nata treatment with IVR injections for DME independent of resolved retinal thickening.

Association between retinal hemorrhagic pattern and macular perfusion status in eyes with acute branch retinal vein occlusion

This prospective study included 63 eyes with acute branch retinal vein occlusion (BRVO) to evaluate the retinal hemorrhagic patterns at the posterior poles and explore their clinical relevance in macular perfusion differentiation. Retinal hemorrhagic patterns and macular perfusion status were evaluated via fundus photography and fluorescein angiography, respectively. Macular perfusion was judged as nonischemic in 30, ischemic in 28, and undeterminable in 5 among the 63 eyes. Predominant hemorrhagic patterns were flame-shaped in 39 (67.2%) and non-flame-shaped in 19 (32.8%) eyes. All 39 eyes with a flame-shaped hemorrhage showed a nonischemic macula. Of the 19 eyes classified as having a non-flame-shaped hemorrhage, 13 (68.4%) had an ischemic macula and 6 (31.6%) had a nonischemic macula (P < 0.001). Parallelism in eyes with a flame-shaped hemorrhage was higher than in those with a non-flame-shaped hemorrhage (P < 0.001), and in those with a nonischemic macula versus those with an ischemic macula (P < 0.001). The area under the curve for parallelism was 0.975 (P < 0.001), suggesting an accurate diagnostic parameter for macular perfusion differentiation. In conclusion, we objectively evaluated retinal hemorrhagic patterns at the posterior pole in BRVO using the parallelism method, which was useful in differentiating macular perfusion status.

Euglena extract suppresses adipocyte-differentiation in human adipose-derived stem cells

Euglena gracilis Z (Euglena) is a unicellular, photosynthesizing, microscopic green alga. It contains several nutrients such as vitamins, minerals, and unsaturated fatty acids. In this study, to verify the potential role of Euglena consumption on human health and obesity, we evaluated the effect of Euglena on human adipose-derived stem cells. We prepared a Euglena extract and evaluated its effect on cell growth and lipid accumulation, and found that cell growth was promoted by the addition of the Euglena extract. Interestingly, intracellular lipid accumulation was inhibited in a concentration-dependent manner. Quantitative real-time PCR analysis and western blotting analysis indicated that the Euglena extract suppressed adipocyte differentiation by inhibiting the gene expression of the master regulators peroxisome proliferator-activated receptor-γ (PPARγ) and one of three CCAAT-enhancer-binding proteins (C/EBPα). Further Oil Red O staining experiments indicated that the Euglena extract inhibited the early stage of adipocyte-differentiation. Consistent with these results, we observed that down-regulation of gene expression was involved in the early stage of adipogenesis represented by the sterol regulatory element binding protein 1 c (SREBP1c), two of three CCAAT-enhancer-binding proteins (C/EBPβ, C/EBPδ), and the cAMP regulatory element-binding protein (CREB). Taken together, these data suggest that Euglena extract is a promising candidate for the development of a new therapeutic treatment for obesity.

Anti-Vascular Endothelial Growth Factor Therapy for Macular Edema following Central Retinal Vein Occlusion: 1 Initial Injection versus 3 Monthly Injections

Purpose: To compare the 12-month efficacy of 1 initial intravitreal injection of an anti-vascular endothelial growth factor (VEGF) agent followed by pro re nata (PRN) dosing with that of 3 initial monthly injections followed by PRN dosing in patients with macular edema (ME) after central retinal vein occlusion (CRVO). Methods: Twenty-nine eyes received 1 initial injection (1+PRN group) and 20 received 3 monthly injections (3+PRN group). Results: At month 12, changes in logMAR visual acuity from baseline were -0.172 ± 0.372 and -0.142 ± 0.317 in the 1+PRN and 3+PRN groups, respectively; the difference was not significant (p = 0.769). The number of anti-VEGF injections administered in the 3+PRN group (5.9 ± 2.1) was significantly greater than that in the 1+PRN group (4.1 ± 2.8; p = 0.022). Conclusion: When used for ME after CRVO, a 1+PRN regimen achieved 12-month outcomes similar to those of a 3+PRN regimen with fewer injections.