Kenji Sogawa

Optical Coherence Tomography Angiography in Diabetic Retinopathy: A Prospective Pilot Study.

PURPOSE To evaluate how optical coherence tomography (OCT) angiography depicts clinical fundus findings in patients with diabetic retinopathy (DR). DESIGN Prospective study evaluating imaging technology. METHODS Forty-seven eyes of 25 patients with DR were scanned using a high-speed 840-nm-wavelength spectral-domain optical coherence tomography instrument (RTVue XR Avanti; Optovue, Inc, Fremont, California, USA). Blood flow was detected using the split-spectrum amplitude-decorrelation angiography algorithm. Fluorescein angiography (FA) images were also obtained in all eyes and the ability to visualize microaneurysms, retinal nonperfused areas, and neovascularization was compared with that of the en face OCT angiograms. RESULTS In 42 eyes, microaneurysms detected by FA near the macula appeared as focally dilated saccular or fusiform capillaries on OCT angiograms of the superficial and/or deep capillary plexus. Retinal nonperfused areas visualized by FA appeared as lesions with no or sparse capillaries on OCT angiograms. Area measurement of retinal nonperfusion near the macula in 7 eyes revealed a difference between the extent of nonperfused areas in superficial and deep plexuses. In 4 eyes, the vascular structures of neovascularization at the optic disc were clearly visualized on OCT angiograms. Decreases and re-increases of flow in new vessels were quantified in an eye treated with anti-vascular endothelial growth factor. CONCLUSIONS OCT angiography can clearly visualize microaneurysms and retinal nonperfused areas and enables closer observation of each layer of the retinal capillaries. Quantitative information on new vessels can also be obtained. OCT angiography may be clinically useful to evaluate the microvascular status and therapeutic effect of treatments for DR.

Relationship Between Choroidal Thickness and Choroidal Circulation in Healthy Young Subjects

PURPOSE To investigate the relationship between the choroidal thickness and choroidal blood flow in healthy young subjects. DESIGN Retrospective, cross-sectional study. METHODS We examined 25 eyes of 25 healthy young Japanese subjects. The subfoveal choroidal thickness was measured by enhanced depth imaging optical coherence tomography (EDI-OCT). The total choroidal blood flow and subfoveal choroidal blood flow were evaluated by pulsatile ocular blood flow using Langham OBF computerized tonometry and the choroidal blood flow using laser Doppler flowmetry. The refractive error, intraocular pressure, and axial length were also measured. RESULTS The mean refractive error was -3.4 ± 3.1 diopters, mean intraocular pressure 15.3 ± 1.7 mm Hg, and axial length 25.4 ± 2.0 mm. The subfoveal choroidal thickness was correlated positively (r = 0.785, P < .01) with the refractive error and negatively (r = -0.735, P < .001) with the axial length. No significant correlation was found between the subfoveal choroidal thickness and the pulsatile ocular blood flow or choroidal blood flow. CONCLUSION Our results suggested that there were no significant correlations between the subfoveal choroidal thickness and the total choroidal blood flow and the subfoveal choroidal blood flow in healthy young subjects; however, decreased subfoveal choroidal thickness was associated with decreased refractive error and axial length.

Impaired retinal circulation in patients with type 2 diabetes mellitus: retinal laser Doppler velocimetry study.

PURPOSE To evaluate the differences in retinal circulation in eyes of patients with type 2 diabetes with no or early-stage diabetic retinopathy compared with control eyes. METHODS Seventy-five nondiabetic eyes and 194 eyes with type 2 diabetes mellitus were evaluated. The type 2 diabetic eyes were classified into two groups: 139 eyes (139 patients) without diabetic retinopathy (NDR) and 55 eyes (55 patients) with mild nonproliferative diabetic retinopathy (NPDR). The retinal circulatory parameters were measured with laser Doppler velocimetry, and the factors that affect retinal hemodynamics were determined in a cross-sectional population of patients with type 2 diabetes. RESULTS The group-averaged blood velocity (V) and retinal blood flow (RBF) in the NDR and mild NPDR groups were significantly (P < 0.01) lower than in the non-DM group. The diameter and wall shear rate were also significantly (P < 0.05) lower in the NDR group than in the nondiabetic control eyes. Multiple regression analysis showed that the RBF was independently and negatively correlated with serum low-density lipoprotein and creatinine. HbA1c was significantly (P < 0.05) higher in participants in the lowest RBF quartile than in the highest quartiles. CONCLUSIONS The results indicate that the RBF may decrease in patients with type 2 diabetes without retinopathy and in those with mild retinopathy.

Short-Term Effects of Topical Tafluprost on Retinal Blood Flow in Cats

PURPOSE The aim of this study was to determine the short-term effects of topical tafluprost, a novel prostaglandin F(2) derivative, on feline retinal circulation. METHODS Seventeen (17) adult cats were anesthetized with enflurane and mechanically ventilated. One (1) drop of tafluprost (0.0015%; n = 8), latanoprost (0.005%; n = 5), or control vehicle (n = 4) was instilled in 1 eye and the fellow eye was untreated. We measured the intraocular pressure (IOP), vessel diameter, and blood velocity simultaneously for 120 min in the large retinal arterioles and calculated the retinal blood flow (RBF) with a laser Doppler velocimetry system. RESULTS Tafluprost 0.0015% significantly increased RBF (maximum change, 42.8 +/- 4.2% [mean +/- standard error of the mean; P < 0.01) and blood velocity (maximum change, 24.1 +/- 3.3%; P < 0.01) for 120 min after instillation; there was no significant change in vessel diameter. Latanoprost 0.005% significantly increased RBF (maximum change, 31.7 +/- 3.4%; P < 0.05); there was no significant change in vessel diameter and blood velocity. There were no significant differences in the IOP reduction among the three groups. CONCLUSIONS We observed, for the first time, that topical tafluprost significantly increased RBF in cats, suggesting that dual-action tafluprost may be a beneficial antiglaucomatous agent for reducing IOP and increasing RBF.

Idiopathic Full-Thickness Macular Holes and the Vitreomacular Interface: A High-Resolution Spectral-Domain Optical Coherence Tomography Study

PURPOSE To analyze the vitreomacular interface in idiopathic full-thickness macular holes (MHs) using spectral-domain optical coherence tomography. DESIGN Prospective cross-sectional case series. METHODS Ninety-one eyes of 86 consecutive patients with a MH were examined by spectral-domain optical coherence tomography. The vitreomacular interface was assessed and the presence or absence of an operculum was analyzed. RESULTS Fifty-two eyes had a stage 2 MH, 12 eyes a stage 3 MH, and 27 eyes a stage 4 MH. No posterior hyaloid membrane was detected in any eyes with a stage 4 MH. In 35 (54.7%) of the 64 eyes with an MH without a complete posterior vitreous detachment (PVD), we saw a perifoveal PVD with vitreofoveal adhesion and partial dehiscence of the raised inner retina with an outer retinal separation in the MHs. In 24 (37.5%) of the 64 eyes without a complete PVD, an operculum, which is a hyperreflective structure of the foveal retina, was in front of the MH. The posterior hyaloid membrane was separated completely but adhered to the optic disc. In 2 (3.1%) of the 64 eyes without a complete PVD, the posterior hyaloid membrane was separated from the macula without an operculum. In 3 (4.7%) of the 64 eyes without a complete PVD, vitreofoveal adhesion on both edges of the hole was connected to the taut posterior hyaloid membrane without an operculum. CONCLUSIONS The vitreomacular interface had 4 configurations in MHs without a complete PVD. Approximately 55% of cases with an open roof in the eyes without a complete PVD may be at risk for progression to operculum formation (loss of retinal tissue).

Role of Nitric Oxide in Regulation of Retinal Blood Flow in Response to Hyperoxia in Cats

PURPOSE To investigate whether nitric oxide (NO) regulates retinal circulation during and after induction of hyperoxia in cats. METHODS Hyperoxia was induced for 10 minutes with 100% oxygen. The vessel diameter and blood velocity were measured simultaneously in second-order retinal arterioles by laser Doppler velocimetry; the retinal blood flow (RBF) and wall shear rate (WSR) were calculated during and after hyperoxia. PBS, L-NAME, D-NAME, BQ-123, BQ-788, and 7-nitroindazole (7-NI) were administered before induction of hyperoxia. RESULTS In the PBS group, vessel diameter, blood velocity, and RBF decreased during hyperoxia and returned to baseline within 10 minutes after hyperoxia ended. WSR decreased transiently and then returned to baseline by the delayed constriction of retinal arterioles during hyperoxia. In the l-NAME and BQ-788 groups, the decreases in RBF during hyperoxia did not differ from those in the PBS group. However, the recovery of RBF after hyperoxia ended was attenuated significantly until 20 minutes after hyperoxia ended in both groups compared with the PBS group (P < 0.05). In the BQ-123 group, the intravitreous injection of BQ-123 caused less reduction of blood velocity and RBF during hyperoxia compared with that in the PBS group, whereas the RBF immediately returned to baseline after hyperoxia. D-NAME and 7-NI did not affect RBF in response to hyperoxia. CONCLUSIONS The current results indicate that NO contributes to RBF recovery after hyperoxia, probably through the action of endothelial NOS via the ETB receptor in the vascular endothelium of the retinal arterioles, suggesting that the RBF response to hyperoxia may be used to evaluate the endothelial function of the retinal arterioles.

Acute hyperglycemia-induced endothelial dysfunction in retinal arterioles in cats.

PURPOSE To investigate the effects of acute hyperglycemia on retinal microcirculation and endothelial function in cats and removal of superoxide to prevent retinal endothelial dysfunction from hyperglycemia. METHODS Hyperglycemia was induced by intravenous injection of 25% glucose to maintain the plasma glucose concentration at 30 mM. Laser Doppler velocimetry was used to measure the vessel diameter (D) and blood velocity (V) simultaneously and calculated retinal blood flow (RBF) in second-order retinal arterioles in cats. Intravitreous, endothelial-dependent vasodilator bradykinin (BK) and endothelium-independent vasodilator sodium nitroprusside (SNP) were administered into the vitreous cavity to evaluate endothelial function in the retinal arterioles. To control osmolality, 25% mannitol was administered the same way. Systemic hyperoxia was induced to noninvasively examine endothelial function during hyperglycemia. To determine the effect of the superoxide on the hyperglycemia-induced changes in the retinal circulation, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL) was administered in drinking water for 14 days before the experiment. RESULTS The D, V, and RBF increased with acute hyperglycemia and mannitol compared with baseline. BK-induced increases in D, V, and RBF significantly declined, whereas SNP-induced increases were unattenuated during acute hyperglycemia. Return of the decreased RBF to baseline after cessation of systemic hyperoxia was significantly (P < 0.05) inhibited by acute hyperglycemia. TEMPOL significantly (P < 0.05) prevented a decrease in the BK-induced increase in RBF during hyperglycemia. CONCLUSIONS The results suggest that acute hyperglycemia increases RBF via increased osmolality and may cause retinal endothelial dysfunction partially via increased oxidative stress. Systemic hyperoxia can be used to noninvasively evaluate retinal endothelial function during hyperglycemia.

Retinal arteriolar responses to acute severe elevation in systemic blood pressure in cats: role of endothelium-derived factors.

The purpose of this study was to investigate the roles of endothelium-derived factors in the retinal arteriolar responses to acute severe elevation in systemic blood pressure (BP) in cats. Acute elevation of mean arterial BP by 60% for 5 min was achieved by inflating a balloon-tipped catheter in the descending aorta. The retinal arteriolar diameter, flow velocity, wall shear rate (WSR) and blood flow (RBF) changes during BP elevation were assessed with laser Doppler velocimetry 2 h after intravitreal injections of nitric oxide (NO) synthase inhibitor l-NAME, cyclooxygenase inhibitor indomethacin, endothelin-1 receptor antagonists (BQ-123 for type A and BQ-788 for type B), or Rho kinase inhibitor fasudil. BP elevation caused a marked increase in retinal arteriolar flow velocity and WSR with slight vasoconstriction, resulting in an increase in RBF. The increases in velocity, WSR and RBF, but not diameter, were correlated with the increase in ocular perfusion pressure. With l-NAME or indomethacin, the increase in RBF upon BP elevation was significantly attenuated due to enhanced retinal arteriolar vasoconstriction. In contrast, BQ-123 and fasudil potentiated the increased RBF. BQ-788 had no effect on arteriolar diameter and hemodynamics. Our data suggest that acute elevation of BP by 60% leads to an increase in RBF due to the release of NO and prostanoids probably through a shear stress-induced vasodilation mechanism. The release of endothelin-1 and Rho kinase activation help to limit RBF augmentation by counteracting the vasodilation. It appears that the retinal endothelium, by releasing vasoactive substances, contributes to RBF regulation during acute severe elevation of systemic blood pressure.

Association Between Diabetic Retinopathy and Flow-Mediated Vasodilation in Type 2 DM

Objective: Retinal endothelial dysfunction is a key in the etiogenesis of diabetic retinopathy (DR), in patients with type 2 diabetes mellitus (DM). Brachial artery flow-mediated vasodilation (FMD) is a marker of endothelial function associated with production of endogenous nitric oxide. Using FMD, we investigated the relationship between macrovascular function and DR. Methods: We studied 74 patients with type 2 DM, including non-DR (NDR) (n = 30); mild nonproliferative DR (NPDR) (n = 16); moderate NPDR (n = 10); severe NPDR (n = 10); and proliferative DR (PDR) (n = 8); and 21 age-matched controls. We measured FMD in each group. Retinal blood flow and pulsatility ratios were measured using laser Doppler velocimetry. Results: FMD decreased significantly in patients with DM compared with healthy control subjects. No significant differences were found in FMD among the NDR, mild NPDR, and moderate NPDR groups. FMD decreased significantly in the severe NPDR and PDR groups compared with the NDR group. FMD was significantly and negatively correlated with duration of DM and pulsatility ratio. Conclusion: Systemic endothelial dysfunction appears to be associated with DR and vascular abnormalities in patients with type 2 DM.

Changes in retinal blood flow in patients with macular edema secondary to branch retinal vein occlusion before and after intravitreal injection of bevacizumab.

Purpose: To investigate the effect of intravitreal bevacizumab (IVB) injections for macular edema secondary to acute branch retinal vein occlusion on the retinal microcirculation. Methods: The study was a prospective, interventional case series. Central macular thickness using spectral-domain optical coherence tomography and retinal blood flow (RBF) in untreated eyes with macular edema secondary to acute branch retinal vein occlusion in occluded (V1) and opposite venules in affected eyes (V2) and the equivalent venules in contralateral eyes (V3), using laser Doppler velocimetry during follow-up and after IVB injection, were measured. Results: In 33 eyes with acute branch retinal vein occlusion of <2 months of duration at the first visit, changes in the retinal microcirculation for 1 month was observed; the macular edema improved spontaneously, and the RBF was unchanged in 15 of 33 eyes, and the RBF increased by 23.3% in 18 eyes with persistent macular edema. Twenty-four eyes received an IVB injection (1.25 mg per 0.05 mL). The RBF did not change significantly during follow-up. In 8 of 24 eyes (33%) with improved macular edema 3 months after the treatment, the average RBF values before injection were significantly higher compared with that of eyes with recurrent edema. Conclusion: One IVB injection might have little effect on the retinal microcirculation in patients with macular edema secondary to acute branch retinal vein occlusion at least 3 months after the injection. However, the increased RBF in the occluded venules before injection might be associated with improved macular edema after the IVB injection.