Publications by authors named "Akitoshi Yoshida"

178 Publications

Retinal Blood Velocity Waveform Characteristics With Aging and Arterial Stiffening in Hypertensive and Normotensive Subjects.

Transl Vis Sci Technol 2021 Nov;10(13):25

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

Purpose: We aimed to explore the velocity waveform characteristics of the retinal artery associated with age and the cardio-ankle vascular index (CAVI) as a conventional arterial stiffness marker by applying the Doppler optical coherence tomography (DOCT) flowmeter.

Methods: In this cross-sectional study, DOCT flowmeter imaging was performed in 66 participants aged 21 to 83 years (17 men, 49 women) with no history of eye diseases and no systemic diseases, except for hypertension. Retinal blood velocity waveform was analyzed where several parameters in time (upstroke time, T1, T2, T3, and T4) and area under the waveform (area elevation, area declination, A1, A2, A3, and A4) were extracted. Systolic blood pressure-adjusted Pearson's coefficients were calculated to determine the correlations of each parameter with age or CAVI.

Results: Corrected upstroke time (UTc) was the waveform parameter most positively correlated with age (r = 0.497, P < 0.001). Area declination was the waveform parameter most negatively correlated with age (r = -0.682, P < 0.001) and CAVI (r = -0.601, P < 0.001).

Conclusions: We extracted the waveform parameters associated with the risks of arterial stiffening. The velocity waveform analysis of the retinal artery with DOCT flowmeter potentially could become a new method for arterial stiffness identification.

Translational Relevance: DOCT flowmeter could evaluate arterial stiffening in a different way from the conventional method of measuring arterial stiffening using pressure waveform. Because the DOCT flowmeter can easily, quickly, and noninvasively provide a retinal blood velocity waveform, this system could be useful as a routine medical examination for arterial stiffening.
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http://dx.doi.org/10.1167/tvst.10.13.25DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606851PMC
November 2021

Impact of the Pressure-Free Yutori Education Program on Myopia in Japan.

J Clin Med 2021 Sep 17;10(18). Epub 2021 Sep 17.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa 078-8510, Hokkaido, Japan.

This study aimed to investigate the influence of educational pressure on myopia. A less-intense school curriculum was introduced nationally in Japan beginning in 2012 based on a pressure-free education policy. In this retrospective observational study, a total of 1025 Japanese medical students of Asahikawa Medical University underwent measurements of the cycloplegic refractive error and axial length (AL), from 2011 to 2020. The spherical equivalent (SE) and AL were correlated significantly with the fiscal year of births ( = 0.004 and = 0.034, respectively) only during enforcement of the system of high-pressure education. The SE and AL regression rates during the two educational approaches differed significantly ( = 0.004 and = 0.037, respectively). The prevalence of high myopia was correlated significantly ( < 0.001) only during the system of high-pressure education. The regression of the prevalence rate of high myopia during the two education approaches differed significantly ( = 0.010). The progression rates of myopia and increased prevalence of high myopia were observed only during high-pressure education, suggesting that not only ophthalmologists but also educators and the government should work on together to control the progression of myopia.
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http://dx.doi.org/10.3390/jcm10184229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472111PMC
September 2021

Regression of taxane-related cystoid macular edema after topical dorzolamide treatment: two case reports.

J Med Case Rep 2021 Jul 21;15(1):355. Epub 2021 Jul 21.

Department of Ophthalmology, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido, Japan.

Background: Cystoid macular edema is a rare, vision-threatening side effect of the taxane family of anticancer agents. There is no established treatment or standard treatment protocol for taxane-related cystoid macular edema. Here, we report two cases of taxane-related cystoid macular edema that were treated with topical dorzolamide.

Case Presentation: In case 1, a 72-year-old Japanese woman with bilateral geographic choroiditis reported for a follow-up visit with a complaint of blurred vision in both eyes for 2 months after starting nanoparticle albumin-bound paclitaxel chemotherapy for multiple metastases of her breast cancer. Her best-corrected visual acuity had dropped from 1.2 to 0.9 in the right eye and from 1.0 to 0.4 in the left eye. Fundus examination showed no newly active geographic choroiditis lesion, but optical coherence tomography exhibited cystoid macular edema. We suspected taxane-related cystoid macular edema and terminated nanoparticle albumin-bound paclitaxel, and started topical dorzolamide treatment. Cystoid macular edema nearly resolved within 6 weeks in the right eye and within 10 weeks in the left eye after starting topical dorzolamide treatment. The resolution of cystoid macular edema without leaving a chorioretinal scar after discontinuation of paclitaxel confirmed our initial diagnosis of taxane-related cystoid macular edema. A few inconspicuous cystoid spaces persisted at the parafovea for a year after dorzolamide treatment ended, but regressed after restarting dorzolamide treatment without any side effects. Best-corrected visual acuity improved to 1.2 in the right eye and 1.0 in the left eye. In case 2, a 70-year-old Japanese man, who received nanoparticle albumin-bound paclitaxel for pancreatic cancer with multiple metastases, developed bilateral cystoid macular edema. Best-corrected visual acuity was 0.3 bilaterally. Cystoid macular edema resolved within 5 weeks after stopping nanoparticle albumin-bound paclitaxel and starting topical dorzolamide treatment confirming the diagnosis of taxane-related cystoid macular edema. Nine weeks later, best-corrected visual acuity improved to 0.8 in the right eye and 1.0 in the left eye.

Conclusions: Cystoid macular edema in each case resolved within a few months without any side effects using topical dorzolamide and terminating taxane-based chemotherapy. Topical dorzolamide appears to be a safe and effective treatment option for patients with taxane-related cystoid macular edema whose quality of life is threatened by visual disturbances.
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http://dx.doi.org/10.1186/s13256-021-02954-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8293476PMC
July 2021

Effect of insulin treatment on pulsatility ratio and resistance index of the retinal artery in patients with type 2 diabetes.

PLoS One 2021 20;16(7):e0254980. Epub 2021 Jul 20.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

This study aimed to evaluate whether long-term insulin treatment is associated with abnormalities in retinal circulation in type 2 diabetic patients. We evaluated 19 eyes of nondiabetic individuals and 68 eyes of type 2 diabetic patients. The eyes of diabetic patients were classified into two groups according to the presence or absence of long-term insulin therapy. We used a Doppler optical coherence tomography flowmeter to measure diameter, velocity, and blood flow in the major temporal retinal artery. The pulsatility ratio (PR) and resistance index (RI), indices of vascular rigidity, were calculated from the blood velocity profile. PR and RI were significantly elevated in type 2 diabetic patients compared with nondiabetic subjects (P < 0.05). In type 2 diabetes patients, PR and RI were significantly higher in patients receiving long-term insulin treatment than in those without (P < 0.01). There was a significant difference in velocity (P < 0.05), but not diameter and blood flow, between nondiabetic subjects and type 2 diabetes patients. No significant difference in diameter, velocity, or blood flow was observed between the groups with and without long-term insulin treatment. Long-term insulin treatment can affect PR and RI, which might be associated with vascular rigidity of the retinal artery in patients with type 2 diabetes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254980PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291657PMC
November 2021

Macular Microvasculature and Associated Retinal Layer Thickness in Pediatric Amblyopia: Magnification-Corrected Analyses.

Invest Ophthalmol Vis Sci 2021 03;62(3):39

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

Purpose: The purpose of this study was to characterize macular microvasculature and structural retinal layers using magnification-corrected optical coherence tomography angiography (OCTA) images in children with amblyopia.

Methods: This prospective cross-sectional study included 22 children with unilateral amblyopia (4-11 years of age) receiving spectral-domain OCTA. Vessel densities in foveal and parafoveal regions of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were measured in amblyopic and fellow eyes using a customized image analysis program correcting the scale of retinal image with axial length. Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) were used to measure mean thickness values of 10 intra-retinal layers rescaled for image size correction.

Results: Foveal and parafoveal vessel densities in amblyopic eyes were lower than that of the fellow eyes in the SCP (fovea: P = 0.006 and parafovea: P = 0.003) and the DCP (P = 0.024 and P = 0.025, respectively). Amblyopic eyes had significantly smaller foveal avascular zone (FAZ) area than fellow eyes (P < 0.001). There were significant differences in retinal layer thickness between paired eyes, particularly in the inner retina in both foveal and parafoveal regions; retinal nerve fiber layer (RNFL) (P = 0.024 and P = 0.095, respectively), ganglion cell layer (P < 0.001 and P = 0.008), inner plexiform layer (IPL; P = 0.12 and P = 0.037), inner nuclear layer (P = 0.005 and P = 0.005), and outer plexiform layer (OPL; P = 0.02 and P = 0.057), except in the foveal IPL, the parafoveal RNFL, and OPL.

Conclusions: Unilateral amblyopic eyes demonstrate reduced macular vessel density and thicker inner retinal layers compared with fellow eyes even after correcting for image magnification. Changes in macular microvasculature and structural layers may offer valuable insights in the development of amblyopia.
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http://dx.doi.org/10.1167/iovs.62.3.39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010361PMC
March 2021

Identification of risk factors for retinal vascular events in a population-based cross-sectional study in Rumoi, Japan.

Sci Rep 2021 03 18;11(1):6340. Epub 2021 Mar 18.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.

We conducted a population-based, cross-sectional study in Japan to identify risk factors for retinal vascular events separately by gender. Forty years or older participants were recruited. Fundus photographs were taken, and lifestyle and health characteristics were determined through a questionnaire and physical examinations. We compared the group of those who had retinal vascular events and those who did not. A total of 1689 participants (964 men) were deemed eligible for the study and retinal vascular events were seen in 59 subjects (3.7% of the men, 3.2% of the women). Self-reported diabetes mellitus was significantly associated with the vascular events in each gender [odds ratio (OR) = 6.97, 6.19 (men, women); 95% confidence interval (CI) 3.02-15.9, 2.25-17.0; p < 0.001]. Higher systolic blood pressure (OR = 1.03; 95% CI 1.01-1.04; p = 0.006) and lower frequency of meat consumption (OR = 0.73; 95% CI 0.54-0.99; p = 0.04) were independently associated with the vascular events in men. In women, while vascular events were associated with self-reported hypertension (OR = 2.64; 95% CI 1.03-6.74; p = 0.04), no association was seen with systolic blood pressure. Women with hypertension may need extra care, not only for blood pressure.
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http://dx.doi.org/10.1038/s41598-021-85655-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973805PMC
March 2021

Association of Rare CYP39A1 Variants With Exfoliation Syndrome Involving the Anterior Chamber of the Eye.

JAMA 2021 02;325(8):753-764

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

Importance: Exfoliation syndrome is a systemic disorder characterized by progressive accumulation of abnormal fibrillar protein aggregates manifesting clinically in the anterior chamber of the eye. This disorder is the most commonly known cause of glaucoma and a major cause of irreversible blindness.

Objective: To determine if exfoliation syndrome is associated with rare, protein-changing variants predicted to impair protein function.

Design, Setting, And Participants: A 2-stage, case-control, whole-exome sequencing association study with a discovery cohort and 2 independently ascertained validation cohorts. Study participants from 14 countries were enrolled between February 1999 and December 2019. The date of last clinical follow-up was December 2019. Affected individuals had exfoliation material on anterior segment structures of at least 1 eye as visualized by slit lamp examination. Unaffected individuals had no signs of exfoliation syndrome.

Exposures: Rare, coding-sequence genetic variants predicted to be damaging by bioinformatic algorithms trained to recognize alterations that impair protein function.

Main Outcomes And Measures: The primary outcome was the presence of exfoliation syndrome. Exome-wide significance for detected variants was defined as P < 2.5 × 10-6. The secondary outcomes included biochemical enzymatic assays and gene expression analyses.

Results: The discovery cohort included 4028 participants with exfoliation syndrome (median age, 78 years [interquartile range, 73-83 years]; 2377 [59.0%] women) and 5638 participants without exfoliation syndrome (median age, 72 years [interquartile range, 65-78 years]; 3159 [56.0%] women). In the discovery cohort, persons with exfoliation syndrome, compared with those without exfoliation syndrome, were significantly more likely to carry damaging CYP39A1 variants (1.3% vs 0.30%, respectively; odds ratio, 3.55 [95% CI, 2.07-6.10]; P = 6.1 × 10-7). This outcome was validated in 2 independent cohorts. The first validation cohort included 2337 individuals with exfoliation syndrome (median age, 74 years; 1132 women; n = 1934 with demographic data) and 2813 individuals without exfoliation syndrome (median age, 72 years; 1287 women; n = 2421 with demographic data). The second validation cohort included 1663 individuals with exfoliation syndrome (median age, 75 years; 587 women; n = 1064 with demographic data) and 3962 individuals without exfoliation syndrome (median age, 74 years; 951 women; n = 1555 with demographic data). Of the individuals from both validation cohorts, 5.2% with exfoliation syndrome carried CYP39A1 damaging alleles vs 3.1% without exfoliation syndrome (odds ratio, 1.82 [95% CI, 1.47-2.26]; P < .001). Biochemical assays classified 34 of 42 damaging CYP39A1 alleles as functionally deficient (median reduction in enzymatic activity compared with wild-type CYP39A1, 94.4% [interquartile range, 78.7%-98.2%] for the 34 deficient variants). CYP39A1 transcript expression was 47% lower (95% CI, 30%-64% lower; P < .001) in ciliary body tissues from individuals with exfoliation syndrome compared with individuals without exfoliation syndrome.

Conclusions And Relevance: In this whole-exome sequencing case-control study, presence of exfoliation syndrome was significantly associated with carriage of functionally deficient CYP39A1 sequence variants. Further research is needed to understand the clinical implications of these findings.
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http://dx.doi.org/10.1001/jama.2021.0507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903258PMC
February 2021

A comparison of laparoscopic procedures performed by novice medical students using 8K ultra-high-definition/two-dimensional and 2K high-definition/three-dimensional monitors.

Surg Today 2021 Aug 9;51(8):1397-1403. Epub 2021 Jan 9.

Division of Gastrointestinal Surgery, Department of Surgery, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, 078-8510, Japan.

Purpose: 8K Ultra-high-definition (UHD) imaging has been developed in accordance with the progression of imaging technologies. We evaluated laparoscopic procedures performed by novice medical students using 2K/two-dimensional (2D), 2K/three-dimensional (3D) and 8K/2D monitors, with a particular focus on depth perception.

Methods: Nine medical students were enrolled. They performed two tasks using 2K/2D, 2K/3D and 8K/2D monitors. In Task 1, they were asked to grasp three metal rods with forceps using each hand. In Task 2, they were asked to grasp a metal rod with forceps held in the right hand, pass the metal rod through a metal ring and transfer it to their left hand.

Results: In Task 1, when performed with the dominant hand, the procedures performed using 2K/3D took a significantly shorter time than those performed using 8K/2D (P = 0.04). However, there was no significant difference among the three groups in the time required for procedures performed by the non-dominant hand. In Task 2, the procedure time with 2K/2D was significantly longer than that with 2K/3D or 8K/2D (P = 0.02).

Conclusion: 2K/3D showed superior utility to 8K/2D for performing forceps procedures using the dominant hand. However, when the movement of both hands was coordinated ("bi-hand coordination"), the laparoscopic procedures were performed almost as deftly with 8K/2D and 2K/3D.
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http://dx.doi.org/10.1007/s00595-020-02215-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286219PMC
August 2021

Effect of Rho Kinase Inhibitor Ripasudil (K-115) on Isolated Porcine Retinal Arterioles.

J Ocul Pharmacol Ther 2021 03 22;37(2):104-111. Epub 2020 Dec 22.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

To investigate the vasorelaxation effect of ripasudil (K-115), a novel Rho-associated coiled-coil-containing protein kinase (ROCK) inhibitor, on isolated retinal arterioles. We determined whether the actions of ripasudil on the retinal microvascular diameter were dependent on the endothelium and/or potassium channels in the smooth muscle, with the goals of uncovering the signaling mechanisms required for this vasomotor activity and inhibiting the action of endothelin-1 (ET-1). In this study, we isolated porcine retinal arterioles, which were cannulated and pressurized without flow. We recorded diametric changes using videomicroscopic techniques. In a dose-dependent (10 nM-30 μM) manner, retinal arterioles were relaxed in response to ripasudil [maximum % resting diameter, 160.3% ± 7.7% (mean ± standard error of the mean)]. The ripasudil-induced vasorelaxation was unaffected by endothelium removal, using nonselective potassium channel blocker tetraethylammonium, Ca-activated large-conductance potassium channel blocker iberiotoxin, voltage-gated potassium channel blocker 4-AP, ATP-sensitive potassium channel blocker glibenclamide, and inward rectifier potassium channel blocker BaCl. Ripasudil prevented ET-1-caused vasoconstriction of the retinal arterioles regardless of the presence of endothelium to a similar extent. The ROCK inhibitor ripasudil elicits endothelium-independent relaxation and inhibits the action of ET-1 on the retinal arterioles. Determining the relaxation properties of ripasudil on the retinal microvasculature will likely support the development of potential therapies for glaucoma.
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http://dx.doi.org/10.1089/jop.2020.0082DOI Listing
March 2021

Effect of Background Brightness on Preferred Retinal Loci in Patients With Macular Disease.

Transl Vis Sci Technol 2020 10 28;9(11):32. Epub 2020 Oct 28.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

Purpose: To evaluate the effect of background brightness on the preferred retinal locus (PRL) in patients with macular disease.

Methods: The study included 27 eyes (27 patients) with macular disease. Microperimetry (MP) was performed to evaluate the PRL and retinal sensitivity (RS) at 10 cd/m. A prototypical device was used to evaluate the PRL at 650 cd/m. Patients were divided into two groups: central fixation (CF) and eccentric fixation (EF).

Results: The PRLs under different brightness levels differed significantly ( < 0.001) in 15 of 27 eyes (two of 13 eyes in the CF group and 13 of 14 eyes in the EF group). The best-corrected visual acuities (BCVAs) in eyes with different PRLs were significantly worse ( = 0.019) than in eyes with one PRL, although the foveal RS did not differ significantly. In patients with BCVAs over 0.1, the PRLs differed in four of 13 eyes in the CF group and in three of four eyes in the EF group ( > 0.05); in patients with BCVAs of 0.1 or lower, the PRLs differed in one of four eyes and 10 of 10 eyes, respectively ( = 0.011).

Conclusions: In patients with macular disease, PRLs can change depending on the surrounding brightness. It may be beneficial to evaluate PRLs under brighter background conditions (e.g., in ambient light) when performing visual rehabilitation for these patients.

Translational Relevance: This study provides important information for visual rehabilitation of patients with macular disease.
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http://dx.doi.org/10.1167/tvst.9.11.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594603PMC
October 2020

Effect of illumination on reading performance in Japanese patients with age-related macular degeneration.

Jpn J Ophthalmol 2020 Nov 5;64(6):597-604. Epub 2020 Sep 5.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

Purpose: Several studies of Western patients with age-related macular degeneration (AMD) have investigated reading performance that improved at high levels of illumination; however, the relation between reading performance and macular function has not been evaluated in detail in Japan. The goals of this study were to evaluate the effect of different levels of illumination on reading performance in Japanese patients with AMD and determine the factors, such as macular function, that affect these results.

Study Design: Cross-sectional study.

Methods: We prospectively included 39 patients with bilateral AMD or maculopathy. We evaluated reading performance; reading acuity (RA), critical print size (CPS), and maximal reading speed (MRS) using charts with Japanese sentences based on the MNREAD-J in 500-7500 lx. Patients were classified into two groups based on the presence of a central scotoma (CS) or no CS (NCS) diagnosed by microperimetry.

Results: The RA improved significantly in 500-7500 lx in both groups (NCS, p = 0.001; CS, p = 0.046). The RA improvement differed significantly (2000 lx, p = 0.021; 5,000 lx; p = 0.021; 7500 lx, p = 0.047) between 500 lx and other illumination levels only in the NCS group and then plateaued over 2000 lx. The CPS and MRS did not improve significantly at any illumination level.

Conclusions: These results suggest that the difference in macular function was related to improvement in the RA with increased illumination in Japanese patients with AMD.
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http://dx.doi.org/10.1007/s10384-020-00769-6DOI Listing
November 2020

Deterioration of Retinal Blood Flow Parameters in Branch Retinal Vein Occlusion Measured by Doppler Optical Coherence Tomography Flowmeter.

J Clin Med 2020 Jun 13;9(6). Epub 2020 Jun 13.

Department of Ophthalmology, School of Medicine, Asahikawa Medical University, Asahikawa 078-8510, Japan.

Background: Doppler optical coherence tomography (DOCT) flowmeter can be used to measure retinal blood flow (RBF) parameters, including vessel diameter, blood velocity, and the absolute value of RBF within 2.0 s. We investigated the RBF parameters in eyes with branch retinal vein occlusion (BRVO) using a DOCT flowmeter.

Methods: Seventeen patients with unilateral BRVO were enrolled. All subjects underwent comprehensive ophthalmologic examinations. The RBF parameters were assessed from three veins, i.e., (1) an occluded vein, (2) a non-occluded vein in the BRVO eyes, and (3) an equivalent (superior or inferior) vein in the fellow eye (non-affected vein), using prototype DOCT flowmeter (Topcon, Tokyo, Japan). Moreover, the correlation between RBF parameters and the best corrected visual acuity (BCVA) was examined. We investigated the correlation between (1) the RBF parameters and the time from the initial visit, (2) the RBF parameters and the time from the last injection, and (3) the RBF parameters and the number of anti-vascular endothelial growth factor injections (VEGF).

Results: The diameter of the occluded vein (95.9 ± 24.7 µm) was smaller than that of the non-occluded vein (127.9 ± 23.7 µm) and that of the healthy veins (116.4 ± 13.9 µm). The RBF was lower in the occluded veins (4.7 ± 3.7 µL/min) than that in the non-occluded veins (10.3 ± 5.1 µL/min; < 0.01) and in the fellow eyes (8.6 ± 4.0 µL/min; = 0.013). In contrast, the blood velocity was not significantly different among the three types of veins. BCVA was correlated with the diameter of the occluded vein (ρ = 0.711, = 0.001) but not with the RBF and blood velocity. The time from the initial visit, the time from the last injection, and the total number of anti-VEGF injections were not associated with any RBF parameters on the occluded vein.

Conclusions: The RBF was significantly lower in the occluded veins than that in the other veins, and the diameter of the occluded vein was significantly smaller than that of the other veins in patients with BRVO. However, neither the time from the initial visit, nor the time from the last injection, nor the number of anti-VEGF injections were correlated with the RBF parameters on the occluded vein.
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http://dx.doi.org/10.3390/jcm9061847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356189PMC
June 2020

Association Between Alterations of the Choriocapillaris Microcirculation and Visual Function and Cone Photoreceptors in Patients With Diabetes.

Invest Ophthalmol Vis Sci 2020 06;61(6)

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Purpose: The purpose of this study was to investigate the association between the choriocapillaris microcirculation and the visual function and cone photoreceptor structure in patients with diabetes.

Methods: Thirteen control subjects and 26 patients with type 2 diabetes were recruited. The patients with diabetes were divided into three groups based on the grade of diabetic retinopathy (DR). The retinal sensitivity (RS) was evaluated using microperimetry. Cone photoreceptor mosaics were imaged using an adaptive optics retinal camera, and the cone heterogeneity packing index (HPi) was calculated. Optical coherence tomography angiography (OCTA) images of the choriocapillaris were obtained using spectral-domain OCTA, and the area of flow deficit (FD) was evaluated. All parameters were evaluated in the foveal and parafoveal areas.

Results: The study included four patients with diabetes without retinopathy, 12 patients with nonproliferative diabetic retinopathy (NPDR), and 10 patients with proliferative diabetic retinopathy (PDR). The foveal and parafoveal FDs were correlated significantly (fovea, r = -0.58; P = 0.046 and r = -0.82; P = 0.003; parafovea, r = -0.59; P = 0.044 and r = -0.72; and P = 0.019, respectively) with the RS in patients with NPDR and PDR, but not in control and no diabetic retinopathy (NDR) groups. There were no differences in the foveal HPi among the groups.

Conclusions: Impaired choriocapillaris microcirculation is associated with impaired visual function but not cone photoreceptor integrity in eyes with DR.
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http://dx.doi.org/10.1167/iovs.61.6.1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7415292PMC
June 2020

Circumpapillary collateral vessel development in iatrogenic central retinal artery occlusion observed using OCT angiography.

Am J Ophthalmol Case Rep 2020 Sep 11;19:100740. Epub 2020 May 11.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

Purpose: It has been reported that peripapillary loops develop after central retinal artery occlusion (CRAO). Although cilioretinal anastomoses have been shown by fluorescein angiography (FA) and indocyanine green angiography, these examinations cannot confirm the structural continuity between the retinal arteries and the posterior ciliary arteries. In the current report, we followed a patient with iatrogenic CRAO in which circumpapillary collaterals formed and assessed the connection between these two vascular systems using optical coherence tomography angiography (OCTA).

Observation: Iatrogenic CRAO developed in the left eye of a 30-year-old woman during preoperative embolization of a convexity meningioma. FA and OCTA showed complete impairment of the retinal circulation. Two weeks after this event, OCTA images showed flow in the retinal vessels and the beginning of collateral vessel development on the optic disc margin. Six months later, OCTA images showed that these circumpapillary collaterals connected branches of the retinal arteries with the vessels supplying the optic disc, which originate from the posterior ciliary arteries.

Conclusion And Importance: OCTA aided our understanding of the three-dimensional configuration of the circumpapillary collaterals that developed after iatrogenic CRAO, which included anastomosis of the retinal and posterior ciliary artery systems. OCTA is useful for noninvasively monitoring the status of retinal circulatory dynamics after iatrogenic CRAO.
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http://dx.doi.org/10.1016/j.ajoc.2020.100740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256303PMC
September 2020

Role of Arginase in Selective Impairment of Endothelium-Dependent Nitric Oxide Synthase-Mediated Dilation of Retinal Arterioles during Early Diabetes.

Invest Ophthalmol Vis Sci 2020 05;61(5):36

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Purpose: Retinal vasomotor activity can be regulated by two major endothelial enzymes, nitric oxide synthase (NOS) and cyclooxygenase (COX). The vascular arginase also consumes a NOS substrate and thus impedes NOS-mediated vasodilation. Diabetes mellitus exhibits vascular complications in the retina with elevated oxidative stress and compromised NOS-mediated vasodilation. However, the underlying molecular mechanisms remain unclear, and the effect of diabetes on COX-mediated vasodilation is unknown. Herein, we examined the relative impact of diabetes on retinal arteriolar dilations to COX and NOS activation and the roles of arginase and superoxide in diabetes-induced vasomotor dysfunction.

Methods: Retinal arterioles were isolated from streptozocin-induced diabetic pigs (2 weeks of hyperglycemia, 433 ± 27 mg/dL) or age-matched control pigs (97 ± 4 mg/dL). The vasodilations to bradykinin (NOS activator) and histamine (NOS/COX activator) were examined in vitro.

Results: Retinal arteriolar dilations to histamine and bradykinin were significantly reduced after 2 weeks of diabetes. The NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME) attenuated the dilations of control vessels, but not diabetic vessels, to histamine. In the presence of L-NAME and COX inhibitor indomethacin, histamine-induced dilations of control and diabetic vessels were reduced similarly. Treatment of diabetic vessels with arginase inhibitor nor-NOHA, but not superoxide dismutase mimetic TEMPOL, preserved both histamine- and bradykinin-induced dilations in an L-NAME-sensitive manner.

Conclusions: Arginase, rather than superoxide, impairs endothelium-dependent NOS-mediated dilation of retinal arterioles during diabetes, whereas vasodilation mediated by COX remains intact. Blockade of vascular arginase may improve endothelial function of retinal arterioles during early onset of diabetes.
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http://dx.doi.org/10.1167/iovs.61.5.36DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405695PMC
May 2020

Retinal blood flow reduction in normal-tension glaucoma with single-hemifield damage by Doppler optical coherence tomography.

Br J Ophthalmol 2021 01 26;105(1):124-130. Epub 2020 Mar 26.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.

Aims: To evaluate the associations between retinal blood flow (RBF) and optical coherence tomography (OCT) structural measurements in normal-tension glaucoma (NTG) eyes with single-hemifield visual field (VF) damage by the Doppler OCT.

Methods: The Doppler OCT was used to measure temporal artery (TA) RBF and temporal vein (TV) RBF. Retinal nerve fibre layer thickness (RNFLT) was measured by spectral-domain OCT.

Results: Forty-three consecutive eyes of 43 patients with NTG with VF defect confined to a single hemifield and 24 eyes of 24 age-matched healthy subjects were studied. TA and TV RBF and RNFLT were reduced in the damaged hemisphere compared with the normal hemisphere (mean (SD), 3.61 (1.68) vs 5.86 (2.59) µL/min, p<0.001; 5.61 (2.51) vs 6.94 (2.83) µL/min, p=0.010; 69.0 (19.7) vs 99.7 (22.8) µm, p<0.001). Those values in the normal hemisphere of NTG eyes also decreased compared with the healthy hemisphere of the healthy eyes (8.40 (3.36) µL/min, p<0.001; 9.28 (4.47) µL/min, p<0.002; 122.8 (20.2) µm, p<0.001). Multivariate model showed that normal and damaged hemispheres and RNFLT were associated with RBF reduction. In addition, the RBF in the normal hemisphere was lower than that in the healthy hemisphere even after adjusting for RNFLT.

Conclusion: In NTG eyes with single-hemifield damage, the RBF was significantly reduced in the damaged hemisphere compared with the normal one. The RBF decreased in the normal and damaged hemispheres of NTG eyes compared with the healthy hemisphere independent from RNFLT.
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http://dx.doi.org/10.1136/bjophthalmol-2019-315616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7529938PMC
January 2021

A Proposed Classification of Intraretinal Microvascular Abnormalities in Diabetic Retinopathy Following Panretinal Photocoagulation.

Invest Ophthalmol Vis Sci 2020 03;61(3):34

,.

Purpose: To investigate the characteristics of intraretinal microvascular abnormalities (IRMAs) before and after panretinal photocoagulation (PRP) for diabetic retinopathy (DR) by using optical coherence tomography angiography (OCTA).

Methods: Forty-six eyes of 29 patients with DR were included (26 eyes with severe nonproliferative diabetic retinopathy [SNPDR] and 20 eyes with proliferative diabetic retinopathy [PDR]). En face OCTA images of IRMAs in a 6 × 6-mm area were acquired by using Cirrus 5000 with AngioPlex. The morphological changes in IRMAs were evaluated before and after PRP. The changes in the IRMAs were divided into five subtypes: unchanged; tuft regression; reperfusion; mixed (combined tuft regression/reperfusion); and worsening (new appearance of tuft).

Results: Unchanged IRMAs were identified in 15 SNPDR eyes and 2 PDR eyes; all neovascularization (NV) had regressed after PRP. Tufts were more frequently observed in the PDR eyes (15/20, 75%) than in the SNPDR eyes (8/26, 31%) (P = 0.003), and two tufts tended to exceed the inner limiting membrane, which showed progression to NV before PRP. The reperfusion phenomenon was observed in 7/26 SNPDR eyes and 4/20 PDR eyes, including the mixed type, and showed two vascular patterns: abnormal (dilated, tortuous, and twisted) and normal vessels. The worsening type was observed in 1/26 SNPDR eye and 2/20 PDR eyes.

Conclusions: OCTA enabled classification of IRMA into more detailed types. The unchanged and reperfusion types suggested that IRMAs had aspects of remodeling. However, IRMAs with tufts were observed in 75% of the PDR eyes, and the tufts had aspects of NV.
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http://dx.doi.org/10.1167/iovs.61.3.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7401423PMC
March 2020

Longitudinal Changes in Retinal Blood Flow in a Feline Retinal Vein Occlusion Model as Measured by Doppler Optical Coherence Tomography and Optical Coherence Tomography Angiography.

Invest Ophthalmol Vis Sci 2020 02;61(2):34

,.

Purpose: We aimed to observe longitudinal changes in retinal blood flow (RBF) and structural transformations in capillaries using Doppler optical coherence tomography (DOCT) and optical coherence tomography angiography (OCTA) in a feline retinal blood occlusion (RVO) model.

Methods: RVO was induced by argon green laser photocoagulation (PC) in six eyes of six cats. RBF was measured at a first-order retinal artery and vein by a DOCT flowmeter, and structural changes in the capillaries around the occluded vessels (12 × 12 and 3 × 3 mm) were assessed by OCTA before (at baseline); immediately after PC; and on days 1, 4, 7, and 14 thereafter. Systemic and ocular parameters were monitored during the observation period.

Results: There were no significant differences in any systemic or ocular parameters before and after PC. Arterial RBF increased significantly on day 1 (160.6 ± 8.6% vs. baseline, P < 0.001) and decreased below baseline after day 1 through 14. Venous RBF decreased immediately after PC (17.4 ± 9.6% vs. baseline, P = 0.001) and then gradually increased afterwards, but did not return to baseline. OCTA showed dilatation of retinal venules immediately after PC to day 1. Collateral vessels began to form on day 4, had matured by day 7, and were pruned on day 14, which formed as mature as normal retinal venule diameters.

Conclusions: With increasing arterial RBF within 1 day after inducing RVO, venules gradually expanded to form collateral vessels, suggesting that collateral vessels originate from existing capillary networks, not neovascularization.
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http://dx.doi.org/10.1167/iovs.61.2.34DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326600PMC
February 2020

Retinal Nonperfusion Relationship to Arteries or Veins Observed on Widefield Optical Coherence Tomography Angiography in Diabetic Retinopathy.

Invest Ophthalmol Vis Sci 2019 10;60(13):4310-4318

New England Eye Center, Tufts Medical Center, Boston, Massachusetts, United States.

Purpose: To evaluate whether retinal capillary nonperfusion is found predominantly adjacent to arteries or veins in eyes with diabetic retinopathy (DR).

Methods: Sixty-three eyes from 44 patients with proliferative DR (PDR) or non-PDR (NPDR) were included. Images (12 × 12-mm) foveal-centered optical coherence tomography (OCT) angiography (OCTA) images were taken using the Zeiss Plex Elite 9000. In 37 eyes, widefield montages with five fixation points were also obtained. A semiautomatic algorithm that detects nonperfusion in full-retina OCT slabs was developed, and the percentages of capillary nonperfusion within the total image area were calculated. Retinal arteries and veins were manually traced. Based on the shortest distance, nonperfusion pixels were labeled as either arterial-side or venous-side. Arterial-adjacent and venous-adjacent nonperfusion and the A/V ratio (arterial-adjacent nonperfusion divided by venous-adjacent nonperfusion) were quantified.

Results: Twenty-two eyes with moderate NPDR, 16 eyes with severe NPDR, and 25 eyes with PDR were scanned. Total nonperfusion area in PDR (median: 8.93%) was greater than in moderate NPDR (3.49%, P < 0.01). Arterial-adjacent nonperfusion was greater than venous-adjacent nonperfusion for all stages of DR (P < 0.001). The median A/V ratios were 1.93 in moderate NPDR, 1.84 in severe NPDR, and 1.78 in PDR. The A/V ratio was negatively correlated with the total nonperfusion area (r = -0.600, P < 0.0001). The results from the widefield montages showed similar patterns.

Conclusions: OCTA images with arteries and veins traced allowed us to estimate the nonperfusion distribution. In DR, smaller nonperfusion tends to be arterial-adjacent, while larger nonperfusion tends toward veins.
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http://dx.doi.org/10.1167/iovs.19-26653DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6996665PMC
October 2019

A Case of Progressive Diabetic Retinopathy Related to Pregnancy Followed on Optical Coherence Tomography Angiography.

Ophthalmic Surg Lasers Imaging Retina 2019 06;50(6):393-397

A 27-year-old woman with type 2 diabetes mellitus had mild diabetic retinopathy (DR) during the early gestation period. Optical coherence tomography angiography (OCTA) showed microaneurysms and small capillary nonperfusion with little change until before delivery. The patient later developed pregnancy-induced hypertension, which continued after delivery, and the DR worsened markedly. OCTA showed onset and recovery of paracentral acute middle maculopathy. Macular edema (ME) also developed, and OCTA showed irregular dilation in the radial peripapillary capillaries. After starting antihypertensive therapy, the capillary dilation and ME decreased. OCTA enables close follow-up of DR related to pregnancy during the perinatal period. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:393-397.].
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http://dx.doi.org/10.3928/23258160-20190605-09DOI Listing
June 2019

Retinal Arteriole Pulse Waveform Analysis Using a Fully-Automated Doppler Optical Coherence Tomography Flowmeter: a Pilot Study.

Transl Vis Sci Technol 2019 May 6;8(3):13. Epub 2019 May 6.

Research and Development Division, Topcon Corporation, Tokyo, Japan.

Purpose: To evaluate the repeatability and reproducibility of the measurement of retinal arteriole pulse waveforms using a novel fully-automated Doppler optical coherence tomography (DOCT) flowmeter in healthy subjects.

Methods: Twenty eyes of 20 healthy subjects were included to test the intrasession repeatability of pulse waveform analysis. DOCT measurements were performed based on a newly developed instantaneous Doppler angle measurement method. Upstroke time (UT), which is the time from the minimum to the maximum retinal blood velocity, and the resistance index (RI) of the retinal arteriole pulse waveform were measured. Coefficients of variation (CVs) and intraclass correlation coefficients (ICCs) were calculated. Interdevice reproducibility between two instruments was assessed in five eyes of five subjects.

Results: The mean UT was 130.3 ms (range, 110.1-152.1 ms), and the mean RI was 0.66 (range, 0.51-0.82). The respective ICCs of UT and the RI for the intrasession repeatability of assessment were 0.87 and 0.78. The respective CVs of UT and the RI were 6.6 ± 3.3% and 4.7 ± 2.1%. Regarding interdevice reproducibility, there were no significant differences between the measurements derived from the instruments ( > 0.05).

Conclusions: Pulse waveform measurement in retinal arterioles using a fully-automated DOCT flowmeter exhibited good repeatability and interdevice reproducibility.

Translational Relevance: The above-described improved DOCT flowmeter system provides reasonably repeatable measurements of retinal arteriole pulse waveforms, potentially facilitating systemic-circulation abnormality monitoring. The examination of the circulation with the novel device can be potentially useful for evaluating systemic circulation.
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http://dx.doi.org/10.1167/tvst.8.3.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6504205PMC
May 2019

Effect of ripasudil on diabetic macular edema.

Sci Rep 2019 03 6;9(1):3703. Epub 2019 Mar 6.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

The current study aimed to address whether ripasudil, a Rho-associated coiled-coil containing protein kinase (ROCK) inhibitor developed to treat glaucoma and ocular hypertension (OH), improves diabetic macular edema (DME) since it is known that ROCK upregulates vascular endothelial growth factor. We retrospectively investigated the foveal thickness (FT) measured by spectral-domain optical coherence tomography, visual acuity (VA), and intraocular pressure (IOP) in 12 eyes with DME that received ripasudil treatment for primary open-angle glaucoma or OH and compared them with 14 eyes that received no treatment. One month after ripasudil therapy, the mean FT decreased significantly from 439 ± 72 µm to 395 ± 62 µm (P = 0.003); this change was significantly different from that in the controls, in which the mean FT increased by 1 ± 39 µm (P = 0.01). Ripasudil also caused a significant decrease in IOP from 17.3 ± 5.2 mmHg to 14.6 ± 4.0 mmHg (P = 0.02); this change was significantly greater than that in the controls, in which IOP changed by 0.0 ± 1.6 mmHg (P < 0.008). There was no significant difference in the VA changes between groups. Our results suggested that ripasudil may have positive effects on both IOP and DME.
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http://dx.doi.org/10.1038/s41598-019-40194-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403390PMC
March 2019

Retinal blood flow reduction after panretinal photocoagulation in Type 2 diabetes mellitus: Doppler optical coherence tomography flowmeter pilot study.

PLoS One 2018 8;13(11):e0207288. Epub 2018 Nov 8.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

To use a Doppler optical coherence tomography (DOCT) flowmeter to investigate segmental retinal blood flow (RBF) and sum of the segmental RBFs (SRBF) changes after panretinal photocoagulation (PRP) was used to treat type 2 diabetes mellitus with severe diabetic retinopathy (DR). Data from five patients with proliferative DR (PDR) (mean age 51.9 ± 10.5 years) was analyzed. The vessel diameter (D), average velocity (V), and retinal blood flow (RBF) in veins were measured using a DOCT flowmeter before and four weeks after PRP. Segmental RBF from inferotemporal (IT), superotemporal (ST), inferonasal (IN), and superonasal (SN) veins were measured, and SRBF was defined as the sum of these measurements. All data were analyzed by Wilcoxson test. After PRP, there were statistically significant decreases in the every segmental D, V, RBF (P<0.03) and SRBF (P = 0.002). The other parameters showed no statistically significant differences (P>0.05). The DOCT flowmeter has the potential to be a clinically useful tool to noninvasively evaluate the changes in retinal circulation during PRP in patients with PDR.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0207288PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6224130PMC
April 2019

Asian age-related macular degeneration: from basic science research perspective.

Eye (Lond) 2019 01 12;33(1):34-49. Epub 2018 Oct 12.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.

In Asian populations, polypoidal choroidal vasculopathy (PCV), a distinct phenotype of neovascular age-related macular degeneration (AMD), is more prevalent than Caucasians. Recently, there has been significant focus on how PCV differs from typical AMD. Although typical AMD and PCV share a variety of mechanisms by which abnormal angiogenic process occurs at the retinochoroidal interface, PCV has different clinical characteristics such as aneurysm-like dilation at the terminal of choroidal neovascular membranes, less frequent drusen and inner choroidal degeneration due to the thickened choroid. Recent studies support an important role for inflammation, angiogenesis molecules and lipid metabolism in the pathogenesis of neovascular AMD. Furthermore, although less attention has been paid to the role of the choroid in AMD, accumulating evidence suggests that the choriocapillaris and choroid also play a pivotal role in drusenogenesis, typical AMD and PCV. This review discusses the basic pathogenic mechanisms of AMD and explores the difference between typical AMD and PCV.
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http://dx.doi.org/10.1038/s41433-018-0225-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6328602PMC
January 2019

A low meat diet increases the risk of open-angle glaucoma in women-The results of population-based, cross-sectional study in Japan.

PLoS One 2018 2;13(10):e0204955. Epub 2018 Oct 2.

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Hokkaido, Japan.

Background: Studies identifying modifiable lifestyle risk factors related to open-angle glaucoma (OAG) are limited, especially from Asian countries. This study aimed to identify lifestyle risk factors for OAG in a Japanese population.

Methods And Findings: This population-based, cross-sectional study recruited Japanese participants aged 40 years or older from January 2013 to March 2015. We took fundus photographs for OAG screening, determined lifestyle and health characteristics through a questionnaire and performed physical examinations. The participants who had suspect findings in the fundus photographs were sent for a detailed ophthalmic examination to diagnose OAG. Lifestyle and heath characteristics were statistically compared between the OAG and non-OAG participants. A total of 1583 participants were included in the study, of which 42 had OAG and 1541 did not have OAG. The number of days per week that the female participants consumed meat (mean±SD; OAG: 1.7±1.2 days, non-OAG: 2.7±1.5 days) was negatively associated with OAG (OR = 0.61; 95% CI: 0.43-0.88; p = 0.007). Higher intraocular pressure was positively associated with OAG in men (OR = 1.20; 95% CI: 1.05-1.38, p = 0.009). No significant difference between participants with and without OAG was observed for a range of other lifestyle factors and health criteria including self-report of diabetes, number of family living together, body mass index, blood pressure, pulse rate, coffee drinking, tea drinking, alcohol drinking, number of fruits consumed per day and days of fish consumption per week.

Conclusions: A higher weekly consumption of meat appears to be negatively associated with OAG in Japanese women. Increasing the dietary intake of meat can contribute to reducing the risk of developing OAG.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204955PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168154PMC
March 2019

Thrombin-Induced Responses via Protease-Activated Receptor 1 Blocked by the Endothelium on Isolated Porcine Retinal Arterioles.

Curr Eye Res 2018 11 24;43(11):1374-1382. Epub 2018 Jul 24.

a Department of Ophthalmology , Asahikawa Medical University , Asahikawa , Japan.

Purpose: Thrombin, a serine protease, causes organ-specific responses to vessels. However, the mechanism by which thrombin affects the retinal microcirculation remains unclear. We examined the effects of thrombin on the retinal microvasculature and signaling mechanisms.

Methods: Porcine retinal arterioles were isolated, cannulated, and pressurized (55 cmHO) without flow in this in vitro study. Videomicroscopy techniques recorded changes in diameter in the retinal arterioles in response to thrombin at concentrations ranging from 0.001 to 20 mU/ml.

Results: Extraluminal administration of thrombin induced concentration-dependent vascular responses, that is, vasoconstriction at low concentrations less than 5 mU/ml and vasorelaxation with high concentrations greater than 5 mU/ml. However, intraluminal administration of thrombin (5 mU/m) did not constrict the retinal arterioles; in denuded vessels, intraluminal administration constricted the retinal arterioles. Thrombin-induced vasoconstriction was significantly (p < 0.01) suppressed by pretreatment with a protein kinase C (PKC) inhibitor and a protease-activated receptor (PAR)-1 inhibitor but not by PAR-2 and PAR-4 inhibitors or denudation. A rho kinase (ROCK) inhibitor also suppressed thrombin-induced vasoconstriction (5 mU/ml) compared with sodium nitroprusside. Endothelial denudation and pretreatment with an endothelial nitric oxide (NO) synthase inhibitor suppressed vasorelaxation caused by a high concentration of thrombin.

Conclusions: A low concentration of thrombin causes vasoconstriction of smooth muscles via PAR-1, PKC, and ROCK, and a high concentration of thrombin possibly causes vasorelaxation of the retinal arterioles via nitric oxide synthase activation in the endothelium. The vascular endothelium might block signaling of thrombin-induced vasoconstriction in the retinal arterioles when administered intraluminally.
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http://dx.doi.org/10.1080/02713683.2018.1496266DOI Listing
November 2018

Resection and anterior transposition of the inferior oblique muscle for treatment of inferior rectus muscle hypoplasia with esotropia.

Am J Ophthalmol Case Rep 2017 Sep 13;7:70-73. Epub 2017 Jun 13.

Department of Ophthalmology, Asahikawa Medical University, 2-1-1 Midorigaoka, Higashi, Asahikawa, Hokkaido, 078-8510, Japan.

Purpose: To report a case of inferior rectus muscle hypoplasia with esotropia, which was treated successfully by resection and anterior transposition of the inferior oblique muscle.

Observations: A 1-year-old boy presented with esotropia. He had esotropia of 15-30° and intermittent left hypertropia. At the age of 3 years, the alternate prism cover test showed esotropia of 35Δ and left hypertropia of 25Δ. Magnetic resonance imaging of the orbit revealed left inferior rectus muscle dysgenesis. Strabismus surgery was performed and a hypoplastic left inferior rectus muscle was identified. We performed bilateral medial rectus muscle recession, and resection and anterior transposition of the left inferior oblique muscle. Nine months after the surgery, the patient had esotropia of 8Δ and left hypertropia of 6Δ.

Conclusions And Importance: Resection and anterior transposition of the inferior oblique muscle is useful for hypoplasia of the inferior rectus muscle accompanied by horizontal strabismus.
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http://dx.doi.org/10.1016/j.ajoc.2017.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5722129PMC
September 2017

Benzo(e)pyrene Inhibits Endothelium-Dependent NO-Mediated Dilation of Retinal Arterioles via Superoxide Production and Endoplasmic Reticulum Stress.

Invest Ophthalmol Vis Sci 2017 11;58(13):5978-5984

Department of Ophthalmology, Asahikawa Medical University, Asahikawa, Japan.

Purpose: To investigate whether benzo(e)pyrene (B(e)P), a toxicant in cigarette smoke, affects the endothelium-dependent nitric oxide (NO)-induced vasodilation of the retinal arterioles, and whether oxidative stress, distinct protein kinase signaling pathways, and endoplasmic reticulum (ER) stress are associated with the B(e)P-induced effect on the retinal arterioles.

Methods: In this in vitro study, porcine retinal arterioles were isolated, cannulated, and pressurized without flow. These vessels were treated with intraluminal administration of B(e)P or B(e)P plus blockers for 180 minutes. Diametric changes to agonists were recorded by videomicroscopy.

Results: Intraluminal treatment with 100 μM B(e)P for 180 minutes significantly reduced the arteriolar vasodilation caused by the endothelium-dependent NO-mediated agonists bradykinin and A23187 but not that caused by endothelium-independent NO donor sodium nitroprusside. The adverse effects of B(e)P on the vasodilatory action of bradykinin were prevented by the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL), the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) inhibitor apocynin, the c-Jun N-terminal kinase (JNK) inhibitor SP600125, the p38 mitogen-activated protein kinase inhibitor SB203580, genistein, resveratrol (RSV), and the ER stress inhibitor 4-phenylbutyrate (4-PBA). The xanthine oxidase inhibitor allopurinol did not alter the effect of B(e)P on the vasodilatory action induced by bradykinin.

Conclusions: B(e)P decreases the endothelium-dependent NO-induced vasodilation in the retinal arterioles through the production of superoxide from NADPH oxidase, which is linked to JNK and p38 kinase. The results suggested that ER stress is instrumental in B(e)P-induced endothelial dysfunction and that genistein and RSV might preserve endothelial function.
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http://dx.doi.org/10.1167/iovs.17-21925DOI Listing
November 2017

Impaired vascular endothelial function in patients with diabetic macular edema.

Graefes Arch Clin Exp Ophthalmol 2018 Feb 8;256(2):439-440. Epub 2017 Oct 8.

Department of Ophthalmology, Asahikawa Medical University, Midorigaoka Higashi 2-1-1-1, Asahikawa, 078-8510, Japan.

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http://dx.doi.org/10.1007/s00417-017-3803-xDOI Listing
February 2018
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