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AbstractPurposeMethodsResultsConclusionsTo reveal changes in choroidal thickness, retinal vessel density, and serum HIF-1α and TNF-α levels in obstructive sleep apnea syndrome (OSAS) and their correlation.This prospective case-control study included 118 patients divided into mild-to-moderate OSAS (n = 40), severe OSAS (n = 39), and a control group (n = 39). Choroidal thickness was evaluated with OCT, vessel density with OCTA, AHI index with polysomnography, and serum HIF-1α and TNF-α levels were analyzed using the enzyme-linked immunosorbent assay.The serum HIF-1α values of the participants in the mild-moderate OSAS and severe OSAS groups were [893.25(406.7–2068) and 1027(453–2527), respectively], and were both significantly higher than the control group [(521.5(231.6–2741))] (p < 0.001). Serum TNF-α levels did not differ significantly between the groups (p = 0.051).). Subfoveal choroidal thickness (SFCT) values of the severe OSAS groups were significantly lower than the control group (p < 0.05). The superficial and deep capillary plexus vascular density (SVD and DVD) values of the severe OSAS group were lower than the control group (p < 0.05). Serum HIF-1α and TNF-α levels of all participants were negatively correlated with both their SVD values (p < 0.05, r: –0.220 and p < 0.05, r: –0.252, respectively) and their DVD values (p < 0.001, r: –0.324 and p = 0.001, r: –0.299, respectively).Increased serum levels of inflammatory mediators (HIF-1α ve TNF-α) in OSAS cause a decrease in SFCT, SVD, and DVD, which is an indication of systemic vascular damage. Further research on developing treatment strategies to modulate TNF-α ve HIF-1α may help recede vascular morbidity in OSAS patients. [ABSTRACT FROM AUTHOR]

Patients with cystic fibrosis (CF) are at risk to develop CF related diabetes (CFRD) and subsequently even diabetic neuro- and/or vasculopathy. We sought to determine if there are typical signs of diabetes-related retinal alterations present in CF patients with preserved and impaired glycemic control. During routine annual examination CF patients were offered an additional 7-day period of real time continuous glucose monitoring (rtCGM) and an ophthalmological examination including retinal optical coherence tomography (OCT). Patients were categorized according to the glycemic control, i.e. the results of an oral glucose tolerance test (OGTT) and rtCGM were taken into consideration. OCT data was analyzed by our previously published visual analysis software generating dedicated and spatially resolved deviation maps for visualization and quantification of differences in total retinal thickness and thickness of retinal nerve fiber layer (RNFL) as well as ganglion cell layer (GCL) in comparison to age-matched healthy controls and patients with either type 1 or type 2 diabetes mellitus. Results of the rtCGM and/or OGTT enabled discrimination between patients with normal glycemic control (CFNG; n = 6), with abnormal glycemic control (CFAG; n = 6) and overt CFRD (n = 4). OCT data indicates gradually increasing retinal thinning in all 3 groups, depending on the degree of glucose metabolism disorder compared to healthy controls. At the foveal region total retinal thickness and GCL thickness were significantly thinner in CFRD patients compared to CFNG patients (total retinal thickness: 260.4 µm (239.3–270.8) vs. 275.4 µm (254.3–289.5); GCL: 11.82 µm (11.16–15.25) vs. 17.30 µm (13.95–19.82); each p < 0.05). Although we investigated a rather small number of patients, we obtained evidence that intraretinal neurodegenerative changes occur in each of our subgroups (CFNG, CFAG, CFRD). Beyond this, our results favor the detrimental role of additional diabetes, as the deviations from healthy controls were most pronounced in the CFRD group and are similar to those seen in patients suffering from type 1 or type 2 diabetes. [ABSTRACT FROM AUTHOR]

To develop a highly efficient and fully automated method that measures retinal vessel caliber using digital retinal photographs and evaluate the association between retinal vessel caliber and hypertension. The subjects of this study were from two sources in Beijing, China, a hypertension case-control study from Tongren Hospital (Tongren study) and a community-based atherosclerosis cohort from Peking University First Hospital (Shougang study). Retinal vessel segmentation and arteriovenous classification were achieved simultaneously by a customized deep learning model. Two experienced ophthalmologists evaluated whether retinal vessels were correctly segmented and classified. The ratio of incorrectly segmented and classified retinal vessels was used to measure the accuracy of the model's recognition. Central retinal artery equivalents, central retinal vein equivalents and arteriolar-to-venular diameter ratio were computed to analyze the association between retinal vessel caliber and the risk of hypertension. The association was then compared to that derived from the widely used semi-automated software (Integrative Vessel Analysis). The deep learning model achieved an arterial recognition error rate of 1.26%, a vein recognition error rate of 0.79%, and a total error rate of 1.03%. Central retinal artery equivalents and arteriolar-to-venular diameter ratio measured by both Integrative Vessel Analysis and deep learning methods were inversely associated with the odds of hypertension in both Tongren and Shougang studies. The comparisons of areas under the receiver operating characteristic curves from the proposed deep learning method and Integrative Vessel Analysis were all not significantly different (p >.05). The proposed deep learning method showed a comparable diagnostic value to Integrative Vessel Analysis software. Compared with semi-automatic software, our deep learning model has significant advantage in efficiency and can be applied to population screening and risk evaluation. [ABSTRACT FROM AUTHOR]

Purpose: We employed automated analysis of scanning laser ophthalmoscopy (SLO) to determine if mechanical strains imposed on disc, and retinal and choroidal vessels during horizontal duction in children differ from those of adults. Methods: Thirty-one children aged 11.3 ± 2.7 (standard deviation) years underwent SLO in central gaze, and 35° ab- and adduction. Automated registration with deep learning-based optical flow analysis quantified vessel deformations as horizontal, vertical, shear, and equivalent strains. Choroidal vessel displacements in lightly pigmented fundi, and central disc vessel displacements, were also observed. Results: As in adults, strain in vessels during horizontal duction was greatest at the disc and decreased with distance from it. Strain in the pediatric disc was similar to published values in young adults,1 but in the peripapillary region was greater and propagated significantly more peripherally to at least three disc radii from it. During adduction in children, the nasal disc was compressed and disc vessels distorted, but the temporal half experienced tensile strain, while peripapillary tissues were compressed. The pattern was similar but strains were less in abduction (p <.001). Choroidal vessels were visualized in 24 of the 62 eyes and shifted directionally opposite overlying retinal vessels. Conclusions: Horizontal duction deforms the normal pediatric optic disc, central retinal vessels, peripapillary retina, and choroid, shearing the inner retina over the choroid. These mechanical effects occur at the sites of remodeling of the disc, sclera, and choroid associated with typical adult features that later emerge later, including optic cup enlargement, temporal disc tilting, and peripapillary atrophy. [ABSTRACT FROM AUTHOR]

Our objective was to investigate whether there were differences in the short-term changes of retinal and choroidal microvasculature between amblyopic and non-amblyopic eyes after patch occlusion treatment in patients with monocular amblyopia. Additionally, we aimed to determine if these changes were associated with improvements in clinical parameters. We conducted a retrospective, longitudinal paired-eye case-control study by analyzing the medical records of patients under the age of 12 who had monocular amblyopia and underwent patch occlusion treatment for a duration of 2 to 12 months. Using optical coherence tomography angiography images, we compared the foveal avascular zone width, retinal blood vessel density (VD), choroidal thickness (CT), and choroidal vascularity index (CVI) in amblyopic and non-amblyopic eyes before and after patch occlusion treatment. We analyzed the correlations between the aforementioned parameters and changes in best-corrected visual acuity (BCVA) and stereopsis. Overall, 114 eyes from 57 patients were enrolled. At baseline, parafoveal superficial plexus VD, foveal and parafoveal deep capillary plexus VD (DCPD) were lower by 0.994 ± 3.312% (p =.026), 2.403 ± 8.273% (p =.033), and 2.469 ± 4.095% (p <.001), respectively; CT was thicker by 30.6 ± 90.7 μm (p =.014); and CVI was higher by 1.920 ± 3.432% (p < 001) in the amblyopic eyes than in the non-amblyopic eyes. Following short-term patch occlusion treatment, foveal and parafoveal DCPD increased by 1.264 ± 3.829% (p =.017) and 1.028 ± 3.662% (p =.036), respectively, CT thinned by 15.5 ± 51.5 μm (p =.019), and CVI decreased by 1.296 ± 3.997% (p =.018) in the amblyopic eyes. Following patch occlusion treatment, as the foveal DCPD decreased and CVI increased, the BCVA improved (p =.017 and.035, respectively). Following patch occlusion treatment, increased foveal DCPD and decreased CVI were associated with improved BCVA. [ABSTRACT FROM AUTHOR]

To compare the Retina-based Microvascular Health Assessment System (RMHAS) with Integrative Vessel Analysis (IVAN) for retinal vessel caliber measurement. Eligible fundus photographs from the Lingtou Eye Cohort Study were obtained alongside their corresponding participant data. Vascular diameter was automatically measured using IVAN and RMHAS software, and intersoftware variations were assessed by intra-class correlation coefficients (ICC), and 95% confidence intervals (CIs). Scatterplots and Bland–Altman plots assessed the agreement between programs, and a Pearson's correlation test assessed the strength of associations between systemic variables and retinal calibers. An algorithm was proposed to convert measurements between software for interchangeability. ICCs between IVAN and RMHAS were moderate for CRAE and AVR (ICC; 95%CI)(0.62; 0.60 to 0.63 and 0.42; 0.40 to 0.44 respectively) and excellent for CRVE (0.76; 0.75 to 0.77). When comparing retinal vascular calibre measurements between tools, mean differences (MD, 95% confidence intervals) in CRAE, CRVE, and AVR were 22.34 (–7.29 to 51.97 µm),–7.01 (–37.68 to 23.67 µm), and 0.12 (–0.02 to 0.26 µm), respectively. The correlation of systemic parameters with CRAE/CRVE was poor and the correlation of CRAE with age, sex, systolic blood pressure, and CRVE with age, sex, and serum glucose were significantly different between IVAN and RMHAS (p < 0.05). CRAE and AVR correlated moderately between retinal measurement software systems while CRVE correlated well. Further studies confirming this agreeability and interchangeability in large-scale datasets are needed before softwares are deemed comparable in clinical practice. [ABSTRACT FROM AUTHOR]

This study monitored the dynamic changes in retinal vascular width and the AVR in full-term neonates within 1–10 days of birth. It was conducted at hospitals in the Anhui province from October 2020 to March 2022. A total of 700 full-term, healthy infants were chosen randomly within 10 days of birth, and the Star Pupil Medical Cloud Data System (XBDS) was used to collect fundus images. Infants within 6 days of birth were grouped into groups one to six, while those within the 7th to 10th days were grouped into group seven. The fundus photographs were imported into Image-Pro-Plus (IPP) software. The optic disc diameter was measured. The retinal artery and vein's diameter was measured at a distance between 0.5- and 1.0-disc diameter from the optic disc's margin. The AVR was also calculated. Finally, each group's retinal vessel diameters and AVR were compared separately to show their dynamic changes. There were differences in the retinal artery diameter between groups one and two, three and four, four and five, and five and six. For retinal vein diameter, there were differences between groups one and two and groups six and seven. There were also differences in the AVR between all groups. In addition, there was a significant positive correlation between the small retinal artery and vein diameters. The retinal artery and vein diameters and AVR in neonates change dynamically during the first 10 days of life. The AVR undergoes the most dramatic change daily and is considerably smaller than the AVR in adults. Hence, this study found that the external environment undergoes significant changes following birth that affect the microcirculation. Then, the retinal central vascular system undergoes similar emergency and adaptive alterations. [ABSTRACT FROM AUTHOR]

Retinal vessels reflect alterations related to hypertension and arteriosclerosis in the physical status. Previously, we had reported a deep-learning algorithm for automatically detecting retinal vessels and measuring the total retinal vascular area in fundus photographs (VAFP). Herein, we investigated the relationship between VAFP and brachial–ankle pulse wave velocity (baPWV), which is the gold standard for arterial stiffness assessment in clinical practice. Retinal photographs (n = 696) obtained from 372 individuals who visited the Keijinkai Maruyama Clinic for regular health checkups were used to analyze VAFP. Additionally, the baPWV was measured for each patient. Automatic retinal-vessel segmentation was performed using our deep-learning algorithm, and the total arteriolar area (AA) and total venular area (VA) were measured. Correlations between baPWV and several parameters, including AA and VA, were assessed. The baPWV was negatively correlated with AA (R = –0.40, n = 696, P < 2.2e-16) and VA (R = –0.36, n = 696, P < 2.2e-16). Independent variables (AA, sex, age, and systolic blood pressure) selected using the stepwise method showed a significant correlation with baPWV. The estimated baPWV, calculated using a regression equation with variables including AA, showed a better correlation with the measured baPWV (R = 0.70, n = 696, P < 2.2e-16) than the estimated value without AA (R = 0.68, n = 696, P < 2.2e-16). AA and VA were significantly correlated with baPWV. Moreover, baPWV estimated using AA correlated well with the actual baPWV. VAFP may serve as an alternative biomarker for evaluating systemic arterial stiffness. [ABSTRACT FROM AUTHOR]

Susac's syndrome (ScS) is a rare, potentially life-threatening auto-immune disease. Ophthalmic imaging can depict characteristic branch retinal arteriolar occlusions (BRAO) and arterial wall hyperfluorescences that form one of the three diagnostic pillars of this condition. We aim to demonstrate that ophthalmological ultrawide-field (UWF) imaging allows for a qualitative and quantitative assessment in ScS, with application in diagnostics, monitoring of treatment response, and titration of therapy. In seven ScS patients (♀:♂ = 2:5), with a median age of 36 years, range 18 to 57 years, serial ultrawide-field fluoresceine angiography (UWF-FA) studies were performed, with adjunctive wide-field optical coherence tomography angiography analyses (WF-OCTA) in five patients. Mean follow-up was 12.5 months, range 1 to 46 months. In all seven patients, BRAO and arterial wall hyperfluorescences were present in UWF-FA and calculated as a quantitative score of disease activity in fluorescein angiography (DA-FA) during follow-up visits. Treatment response was accessible in follow-up imaging as partial reperfusion of retinal vessels, resolution of arterial wall hyperfluorescences and consequently, in reduction of DA-FA score. While qualitative analysis of WF-OCTA provided further information about retinal micro-perfusion, quantitative analysis did not demonstrate a vectored treatment response as it was accessible in FA. DA-FA score, as a comprehensive disease activity parameter in ScS has potential to facilitate optimal communication between subspecialties and thereby treatment success. [ABSTRACT FROM AUTHOR]

Purpose/Aim of this study: Retinal vessel caliber is an independent risk marker of cardiovascular disease risk. However, variable mechanical delays in capturing retinal photographs and cardiac cycle-induced retinal vascular changes have been shown to reduce the accuracy of retinal vessel caliber measurements, but this has only ever been investigated in healthy subjects. This cross-sectional study is the first study to investigate this issue in type 2 diabetes. The aim of this study was to determine whether ECG-gating retinal photographs reduce the variability in retinal arteriolar and venular caliber measurements in controls and type 2 diabetes. Materials and Methods: Fifteen controls and 15 patients with type 2 diabetes were arbitrarily recruited from Westmead Hospital, Sydney, Australia. A mydriatic fundoscope connected to our novel ECG synchronization unit captured 10 ECG-gated (at the QRS) and 10 ungated digital retinal photographs of the left eye in a randomized fashion, blinded to study participants. Two independent reviewers used an in-house semi-automated software to grade single cross-sectional vessel diameters across photographs, between 900 and 1800 microns from the optic disc edge. The coefficient of variation compared caliber variability between retinal arterioles and venules. Results: Our ECG synchronization unit reported the smallest time delay (33.1 ± 48.4 ms) in image capture known in the literature. All 30 participants demonstrated a higher reduction in retinal arteriolar (ungated: 1.02, 95%CI 0.88–1.17% vs ECG-gated: 0.39, 95%CI 0.29–0.49%, p <.0001) than venular (ungated 0.62, 95%CI 0.53–0.73% vs ECG-gated: 0.26, 95%CI 0.19–0.35%, p <.0001) coefficient of variation by ECG-gating photographs. Intra-observer repeatability and inter-observer reproducibility analysis reported high interclass correlation coefficients ranging from 0.80 to 0.86 and 0.80 to 0.93 respectively. Conclusion: ECG-gating photographs at the QRS are recommended for retinal vessel caliber analysis in controls and patients with type 2 diabetes as they refine measurements. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the retinal blood vessel parameters and the foveal avascular zone (FAZ) area using optical coherence tomography angiography (OCTA) in patients with acromegaly in comparison with healthy controls. A total of 45 patients with acromegaly and 45 healthy controls were included in this study. In all patients, the vessel density (VD) of the deep and superficial macular vascular networks and the foveal avascular zone (FAZ) were measured using OCTA. The correlation of insulin-like growth factor 1 (IGF-1) level and disease duration with deep macular VD and FAZ values was analyzed. All parameters were registered. Results were assessed and compared between the two groups. Deep macular plexus VD values were lower in patients with acromegaly compared to the control group. No significant differences in VD values in the superficial segment, except for that in the inferior parafovea (P =.01) were found between the two groups. Furthermore, patients with acromegaly showed enlargement in the superficial (P =.30) and deep FAZ areas (P <.001). IGF-1 level and disease duration showed a significant negative correlation with the deep whole image (R = −0.216, P =.041, R = −0.339, P =.001, respectively), deep parafovea (R = −0.271, P =.01; R = −0.372, P <.001, respectively), deep parafovea superior hemi (R = −0.342, P =.001; R = −0.350, P =.001, respectively), deep parafovea temporal (R = −0.224, P =.034; R = −0.234, P =.026, respectively), deep parafovea nasal (R = −0.320, P =.002; R = −0.361, P <.001, respectively), and deep parafovea superior VD values (R = −0.293, P =.005; R = −0.307, P =.003, respectively) and a significant positive correlation with the deep FAZ area values (R = 0.244, P =.02; R = 0.329, P =.002, respectively). VD values in the deep macular capillary plexus were lower in patients with acromegaly, and the superficial and deep FAZ area enlarged. Patients with acromegaly may have an increased risk of developing ocular vascular complications. OCTA can be used to evaluate retinal blood VD in patients with acromegaly. [ABSTRACT FROM AUTHOR]

Purpose: To assess the agreement between Line 3–5 raster scan mode and circular scan mode for measuring retinal vessel diameter, and to analyze the influence of scanning distance on retinal vessel diameter and agreement. Methods: 79 healthy participants (79 eyes) were scanned with two modes. The scanning distance was defined as the distance from the center of the optic disc to the intersection of the blood vessel and the scan line on the raster image. The large superior temporal vessel was measured, with the distance between vascular wall hyperreflectivities measured to obtain vessel diameters. The degree of agreement between the line 3–5 raster scan and circular scan modes, and the effect of scanning distance on agreement and vascular diameter were assessed. Results: There was good agreement between line 3 subgroup and the circular scan for measuring venous and arterial diameter (venous: intraclass correlation coefficients (ICCs) = 0.87, p <.001; arterial: ICCs = 0.84, p <.001). Unexpectedly, diameters from the fourth raster scan were only comparable to the circular scan in measuring venous diameter (ICCs = 0.86, p <.001), despite the same scanning distance between the fourth raster line and circular scan. Vessels with a scanning distance between 1400 μm – 1799 μm showed good agreement with the circular scan (venous and arterial: all ICCs ≥ 0.84, p <.001). In addition, venous diameter and arterial diameter decreased with increasing distance from the optic disc center, with venous and arterial diameter decreasing by 0.02 μm/μm (p <.001) and 0.007 μm/μm (p =.02), respectively. Conclusion: Arterial and venous diameter measured by the circular mode was comparable to only one scan line and two scan lines of the raster scan mode, respectively. Our study identified a difference between the two scan modes, with the difference not fully attributable to differences in scanning distance. Prospective studies reporting vascular diameter as a primary outcome should report the scan mode used. [ABSTRACT FROM AUTHOR]

Purpose: To assess the correlation between the choriocapillaris (CC) on optical coherence tomography (OCT) angiography and the inner choroid (IC) on structural OCT. Methods: In this prospective, cross-sectional, observational, pilot study, consecutive healthy subjects were imaged with a 6x6mm macular scan using OCTA PlexElite. Angiographic images of the CC were isolated using 10 μm-thick slab starting 21 μm posterior to the automatically segmented retinal pigment epithelium (RPE) band centerline. The structural en face OCT images of the IC were isolated using five 10 μm-thick slabs starting 11 to 51 μm posterior to the automatically segmented RPE band centerline. Retinal vessels masking was obtained by two methods: automated OCTA superficial vessel slab and automated structural OCT outer retina to CC (ORCC) slab. The en face OCT images were binarized for computation of the stromal index (SI). The flow deficits (FD) of the angiographic CC were correlated with the SI of the structural en face OCTs of the IC. Results: Twenty eyes of 20 subjects were enrolled. The strongest correlation was observed between the CC FD and the inner choroid SI of the 31–41 slab (IC SI31-41) using the ORCC mask (R = 0.603, p =.005). Similar results were observed when the analysis was repeated when using IC SI31-41 values obtained with the superficial vessels mask (R = 0.561, p =.01). Conclusions: The angiographic CC FD was significantly correlated with the structural inner choroidal stromal index. These findings suggest that there may be an opportunity to use structural OCT data to analyze the CC, which may allow longitudinal assessment from historical structural OCT datasets. [ABSTRACT FROM AUTHOR]

To determine vessel changes in retinochoroid with optical coherence tomographic angiography (OCT angiography) and spectral-domain OCT (SD-OCT) of patients with central serous chorioretinopathy (CSC) after half-dose photodynamic therapy (hd-PDT). A prospective observational study of 62 eyes of 58 patients undergoing hd-PDT was followed for 3 months. Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed at baseline; best-corrected visual acuity (BCVA), fundus photography, OCT angiography and SD-OCT were performed at baseline, 1-month, and 3-month follow-up visits. The mean vessel density of inner retina (VDIR) layer was 50.72 ± 3.17 at baseline, then decreased to 48.97 ± 4.34 at 1-month follow-up (p <.001), and partially recovered to 49.00 ± 4.28 at 3-month follow-up (p <.001); the mean area of foveal avascular zone (FAZ) was 0.303 ± 0.107 mm2 at baseline, and then increased to 0.339 ± 0.121 mm2 and 0.342 ± 0.125 mm2 at 1-month and 3-month follow-up after hd-PDT (p <.001, p <.001). The mean diameters of choroidal big vessels (DCV) were 309.66 ± 72.24 microns at baseline, then decreased to 300.13 ± 69.38 microns at 1-month and 293.39 ± 69.92 microns at 3-month after treatment (p <.001, p <.001). Currently common applied hd-PDT for patients with CSC has significantly impact on both retinal and choroidal vessels. The retinal capillary flow decreased, therefore optimizing PDT parameters for treating CSC may still be necessary in the future. [ABSTRACT FROM AUTHOR]

Using optical coherence tomography angiography (OCT-A) to compare the retinal micro vessel alteration between obstructive sleep apnea (OSA) children and normal subjects. One hundred-thirty-two eyes (132 participants) were recruited in this study. The average age of OSA group (66 eyes) and healthy control group (66 eyes) were 6.23 ± 1.73 and 6.76 ± 1.89 years, respectively. The retinal vascular network density indices and the fovea avascular zone (FAZ) size were analyzed by OCT-A. All of the OCT-A parafoveal vessel indices, including the vascular diameter (VD), vascular area density (VAD), vascular skeleton density (VSD), and vessel perimeter index (VPI) in the macular superficial/deep capillary plexus (SCP/DCP) as well as the FAZ in the DCP, were significantly lower in the OSA group than in the control group (p <.05). The four parafoveal quadrants indices (temporal, superior, nasal, and inferior) of VD and VAD in both the two layer were significantly lower in the OSA group than in control group (p <.05). However, the differences of VSD and VPI indices in the SCP/DCP did not show statistical significant changes. The intermittent hypoxia in children with OSA might influence the retinal capillary vascular supply. We speculate that the indices of the quadrants are lower in OSA children compared with those in healthy controls, which may be due to the change of the retinal metabolic demands. OCT-A is an ideal method to evaluate the retinal alterations in pediatric OSA. OCT-A: optical coherence tomography angiography; OSA: obstructive sleep apnea; FAZ: fovea avascular zone; VD: vascular diameter; VAD: vascular area density; VSD: vascular skeleton density; VPI: vessel perimeter index; SCP/DCP: superficial/deep capillary plexus; BCVA: best corrected visual acuity; SE: spherical equivalent; AL: ocular axial length; T: temporal; N: nasal; (S): superior; (I): inferior; (SD): standard deviation [ABSTRACT FROM AUTHOR]

Background: The purpose of this pilot study was to investigate the differences in neurovascular coupling between Caucasian patients with normal tension glaucoma (NTG) and healthy subjects (HS) with laser speckle flowgraphy (LSFG). Methods: Measurement of optic nerve head blood flow was performed with LSFG. The mean blur rate of the whole optic nerve head (MA), of the big retinal vessels (MV) and of the microvasculature (MT) was analysed during continuous flicker light stimulation for four minutes. Results: We included 12 eyes from 12 Caucasian patients with a diagnosis of normal tension glaucoma and 12 eyes from 12 age- and sex-matched healthy individuals. MA, MV and MT all increased significantly in both groups during the observation period with no difference between the groups. Conclusion: Neurovascular coupling is detectable in NTG patients. Flicker light stimulation leads to a comparable increase in ocular blood flow in glaucoma patients and healthy individuals. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether invivo optical imaging methods and histology can detect comparable vascular and neuronal damage in the retina due to the effects of progressive chronic hypertension on the retinal vasculature and neurons using the spontaneously hypertensive rat (SHR) model at young and old ages. Methods: Male SHR and normotensive Wistar Kyoto (WKY) rats were studied at 10 and 40 weeks of age (n = 6 each group). Arterial blood pressure was measured with a tail-cuff. Under anesthesia, fundus photography was used to measure retinal arterial diameters and optical coherence tomography was used to measure retinal layer thicknesses. Histology was then used to measure microvascular and cell density in different retinal layers. Results: Blood pressure was significantly higher in SHR than WKY in both age groups (p <.05). Fundus images showed no gross abnormalities, hemorrhage, or stenosis in all groups. Retinal vessels, however, appeared more tortuous in SHR compared to WKY at both ages. Retinal vessel diameters in SHR were significantly narrower than in WKY at both age groups (p <.05). Microvascular densities at 10 weeks were not significantly different (p >.05) but were markedly reduced in SHR at 40 weeks compared to WKY (p <.05). The outer nuclear layer thickness of SHR was significantly thinner than that of WKY at both ages (p <.05), consistent with histological cell density measurements (p <.05). The ganglion cell layer and inner nuclear layer thicknesses were not significantly different between SHR and WKY (p >.05), consistent with the corresponding histological cell density measurements (p >.05). Conclusion: In vivo optical imaging showed that systemic hypertension progressively reduces retinal arterial diameter and thicknesses of the outer retina in spontaneously hypertensive rats, with consistent vascular and neuronal findings from histology. [ABSTRACT FROM AUTHOR]

Purpose: To investigate changes in peripapillary retinal vessel density after acute intraocular pressure (IOP) elevation caused by laser peripheral iridotomy (LPI) in primary angle-closure suspects (PACS) by optical coherence tomography angiography (OCTA). Materials and Methods: Ninety-seven participants with PACS were included in this cross-sectional observational study. OCTA and IOP measurement were performed at baseline and 1 h after LPI. PACS eyes were further divided into three groups according to IOP increase 1 h after LPI (group 1 = IOP elevation <5 mmHg, 42eyes; group 2 = IOP elevation ≥5 mmHg and <10 mmHg, 34 eyes; group 3 = IOP elevation ≥10 mmHg, 21eyes). The changes of vessel density in radial peripapillary capillary (RPC) and entire retina were compared among groups. Results: When all eyes were included, the vessel density of RPC and entire retina 1 h after LPI were significantly decreased compared to the baseline (RPC: 64.5 ± 7.9 vs.67.8 ± 6.8, P <.001; retina: 86.3 ± 4.6 vs.88.3 ± 3.8, P <.001). There were significant differences among the three groups in the RPC and retinal vessel density at 1 h after LPI (RPC: 67.4 ± 7.3 vs. 63.2 ± 7.6 vs. 60.9 ± 7.5, P =.003; retinal: 87.7 ± 4.0 vs. 85.8 ± 4.5 vs. 84.3 ± 5.2, P =.015). In group 2 with an increased IOP from 5 mmHg to 10 mmHg, the reduction of vessel density in the RPC was more significant than that of the entire retina (RPC vs. retina: 7.1 ± 10.0% vs. 3.0 ± 4.4%, P =.006). Conclusions: LPI-induced IOP spikes resulted in a decrease in retina vessel density with PACS eyes by OCTA. The reduction of RPC vessel density was more significant than that of the entire retina in the subgroup of IOP increase from 5 to 10 mmHg. This suggests that vessel density in RPC was more sensitive to IOP increase than that of the entire retina in the peripapillary area. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the short-term influence of uncomplicated phacoemulsification on fundus structure and vasculature change. Methods: A total of 51 eyes from 51 patients with mild-to-moderate cataracts were included. Retinal vessel density, perfusion density, and layer thickness in both macular and peripapillary areas were scanned by OCT at baseline and at 1 day, 1 week, and 1 month after cataract surgery. Cumulative dissipated energy (CDE), U/S total time (USTT) and total aspiration time (TAT) were recorded as parameters of surgical injury to analyze the surgical influence on fundus change. Results: There was a significant increase up in retinal vasculature parameters in both macular and optic nerve area after the surgery. The retinal layer thickness had pronounced increase from 1 week after the surgery (all p <.05, repeated-measures analysis of variance). Retinal nerve fiber layer (RNFL) thickness and ganglion cell layer (GCL) thickness increased more rapidly than other layers. There was a positive correlation between CDE and vasculature changes from 1 week to 1 month (Vessel density in macular to CDE: standardized β = 0.448, p =.005; Perfusion density in peripapillary area to CDE: standardized β = 0.382, p =.015). Conclusions: Retinal vasculature and layer thickness increased in short-term follow-up after cataract surgery. Whether these changes would persist over a longer period needs to be verified. [ABSTRACT FROM AUTHOR]

Purpose: Retinopathy of prematurity (ROP) is characterized by morphological abnormalities in retinal blood vessels, but how an episode of ROP affects vascular function remains to be fully elucidated. The purpose of the present study was to assess the distribution of pericyte/smooth muscle in retinal blood vessels and retinal vasodilator responses in a rat model of ROP. Methods: ROP was induced in rats by the subcutaneous injection of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor KRN633 (10 mg/kg) on postnatal day (P) 7 and P8. The distribution of pericyte/smooth muscle in retinal blood vessels was examined on P14 and P35 by immunohistochemistry. Retinal vasodilator responses were assessed on P35 by measuring the diameter of retinal arterioles in fundus images. Results: In retinas of KRN633-treated (ROP) rats, progressive angiogenesis, tortuous arteries, enlarged veins, and enhanced expression of α-smooth muscle actin in pericytes on capillaries and veins were observed on P14. These abnormalities in retinal vasculature showed a tendency to normalize by P35. Vasodilation of retinal arterioles induced by acetylcholine, an endothelium-dependent vasodilator, was smaller in P35 ROP rats than age-matched controls, whereas retinal vasodilator responses to the nitric oxide (NO) donor NOR3 were unaltered. Conclusions: Phenotypic changes in pericytes occur in the ROP model rats and endothelium-dependent vasodilatory mechanisms in retinal blood vessels are impaired. The impaired vasodilator function may contribute to the progression and pathogenesis of ROP. [ABSTRACT FROM AUTHOR]

Objective: Recent studies have shown that atrial fibrillation (AF) is more prevalent in patients with retinal vessel occlusion and may be associated with both central retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO). However, there is no systematic review and meta-analysis to confirm this finding. Methods: We searched the databases of MEDLINE and EMBASE from inception to January 2019. Included studies were published cohort, case-control or cross-sectional studies, and randomized control trials reporting the prevalence of AF in patients with CRAO or CRVO. Data from each study were combined using the random-effects model. Results: Eleven studies were included in our meta-analysis, involving a total population of 12,305 subjects with retinal vessel occlusion. The prevalence of AF ranged from 4.1% to 21.4% (pooled prevalence = 11.5%, 95% CI: 7.0–16.1, I2 = 96.3%). Five studies reported a control group of patients without retinal vessel occlusion. We found that AF is significantly associated with retinal vessel occlusion (pooled OR = 2.24, 95% CI:2.07–2.43, I2 = 0.0%). Conclusion: Our study showed that AF is significantly associated with retinal vessel occlusion. Further studies are needed to fully elucidate the exact mechanism linking AF with CRAO and CRVO. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to measure retinal vessel diameter using spectral domain optical coherence tomography (SD-OCT), and to compare patients with unilateral pseudoexfoliation syndrome (PEX) with controls. Materials and Methods: 40 patients with pseudoexfoliation material (40+) eyes and (40−) eyes and 32 healthy controls was included study. Observation of pseudoexfoliative material on the anterior lens capsule or pupillar margin in one or both eyes was set as the diagnostic criteria for PEX. The diameter of superior temporal vein, inferior temporal vein; superior temporal artery and inferior temporal artery were measured by SD-OCT device. Results: when PEX (+) eyes were compared with PEX (−) eyes, a significant decrease was noted in vertical diameter of the arteries, as in the superior nasal artery. In PEX (+) patients the diameter of vascular structures was significantly decreased. Conclusion: We report a relationship between PEX and retinal vessel diameter. Vascular narrowing in the contralateral eye was also seen. Thus detection of this narrowing in the non-PEX eye vessels might be important for diagnosis and prevention of early glaucoma. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the multimodality imaging features of retinal cavernous hemangiomas (RCHs). Materials and methods: The clinical data of three patients with RCH were reviewed and the imaging findings were analyzed. Results: The color photographs of the fundus showed bead-like vesicles in the retina. Some vesicles showed plasma erythrocyte separation – with plasma on the top and erythrocytes at the bottom – which was consistently detected as high spontaneous fluorescence on fundus fluorescence angiography. Other vesicles were surrounded by thick walls and fibrous tissue, showing high spontaneous fluorescence, although they did not show any changes on fluorescence angiography. Optical coherence tomography (OCT) could not discriminate the different characteristics of the vesicles, but could clearly discriminate the appearance of the vesicles and their location on the retina, as well as other structural features. Conclusions: Fundus color photography, fundus fluorescein angiography, and OCT can aid in acquiring a better understanding of the structural features of cavernous hemangioma and its relationship with retinal vessels. [ABSTRACT FROM AUTHOR]

Introduction: The evaluation of retinal vessels and the retinal blood flow is important for ocular diseases. We introduce a spectral domain optical coherence tomography (SD-OCT) based method for facilitating a retinal blood vessel analysis using the scattering properties of retinal vessels. The intensity of the distal shadow of vessels caused by the scattered signal is measured, correlated with the pulsatile ocular blood flow (POBF), and its repeatability is analyzed. Methods: About 20 eyes of 20 healthy, young participants (mean age 23.15 years, standard deviation 2.3 years) were included in the analysis. Participants underwent ophthalmic diagnostics including three repeated SD-OCT examinations and measurement of POBF. The vessel shadow intensity analysis is based on peripapillary SD-OCT scans and automatically analyses the intensity of the distal vessel shadow compared to its surroundings. Results: The distal shadow of arteries in SD-OCT scans correlated with the POBF (r = 0.647, p = 0.002). Furthermore, the shadow intensity correlated with the established morphological arterio-venous ratio. The evaluation of repeatability was performed using the interclass correlation coefficient (ICC), showing good repeatability for individual vessels (ICC = 0.825) and arteries (ICC = 0.820). Conclusions: In summary, we indicate that the scattering properties of retinal vessels in SD-OCT images might correlate with the vessel morphology and for retinal arteries with the retinal blood flow volume as well. Further studies are needed to establish this method's sensitivity and specificity in participants with retinal and cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Purpose: Dual wavelength retinal oximetry allows the quantification of oxygen saturation in the larger retinal vessels. However, the technique might be refined further by identifying factors that are responsible for the different oxygen saturations in first order arterioles from the same eye shortly after their branching from the central retinal artery. The purpose of the present study is to investigate whether these factors involve rheological characteristics in the studied vessels. Materials and Methods: In fourty healthy persons the oxygen saturation was measured by dual wavelength oximetry and the blood flow by Doppler OCT in the upper and lower temporal and nasal arterioles and venules shortly after their branching from the central retinal artery and vein. The relationship of the measured oxygen saturations with age, vessel diameter, and blood linear velocity were assessed. Results: The measured oxygen saturations were (mean± SD) 97.8% ± 6.4% in the arterioles and 60.2% ± 8.8% in the venules. For both the arterioles and the venules the measured oxygen saturation (Sm) correlated significantly with the linear velocity (v) of the blood in mm/s (Sm = 101.6-0.28*v, p < 0.0001 for arterioles and Sm = 64.5-0.38*v, p = 0.002 for venules). After correction for the variation in linear velocity, the differences in saturation between first order branches from both arterioles and venules were significantly reduced and the standard deviation of the oxygen saturations were reduced to less than one third. Conclusions: Measurements of oxygen saturation in larger retinal arterioles and venules using dual wavelength oximetry can be improved by correcting for the influence of the linear velocity of the blood. [ABSTRACT FROM AUTHOR]

Purpose: Clinical trials have demonstrated that retinal blood flow deficiencies are present in patients with open-angle glaucoma (OAG). We introduce a method for facilitating retinal vessel analysis: The intensity of the distal shadow of vessels in optical coherence tomography (OCT) caused by the scattered signal is analyzed, compared between healthy subjects and OAG patients and correlated with OCT angiography (OCT-A) flow density. Patients and Methods: We recruited 80 patients with diagnosed OAG (mean age 63.4 ± 13.2 years) and 80 healthy age-matched control subjects for comparison, and 20 patients for the correlation with OCT-A flow density. Patients received perimetry, peripapillary OCT measurements, and selected patients OCT-A of the papillary area. The vessel shadow intensity (VSI) is based on peripapillary OCT scans: the intensity of the distal vessel shadow was automatically compared to its surroundings, separated by arteries and veins. Flow density of the OCT-A scan was calculated by binarization and quantification of the pixel density. Results: The VSI for arteries was in OAG patients with 7.52 ± 2.62 [%] significantly lower compared to healthy subjects (9.03 ± 3.38 [%], p = 0.0029). In veins, the VSI was as well significantly lower for OAG patients (14.9 ± 3.59 [%]) compared to healthy subjects (17.46 ± 4.45 [%], p < 0.0001). Furthermore, in OAG patients there was a significant correlation of mean deviation of the visual field results with the veins’ VSI (p = 0.0006; r = −0,454). There was no significant correlation of scattering properties with OCT-A flow density (p > 0.05). Conclusions: We conclude that the OCT-based analysis of the scattering properties of retinal vessels differs significantly between patients with OAG and healthy subjects. Furthermore, changes in the scattering properties of veins correlated with the stage of the disease in terms of visual field deficits. These properties might complement existing measurements of ocular blood flow including OCT-A flow density. [ABSTRACT FROM AUTHOR]

Purposes: To investigate the therapeutic potential of YC-1 for experimental central retinal vein occlusion (CRVO) of rhesus monkey. Methods: Six adult rhesus monkeys were recruited in this study. Laser-induced CRVO was established in both eyes of all subjects. Intravitreal injection of YC-1 90 μl (200 μM with 0.01% dimethyl sulfoxide (DMSO) as vehicle) was administrated in right eye and 0.01% DMSO 90 μl in left eye respectively at 1 week after CRVO established. All eyes underwent routine examination at 1 day, 1 week, 2 week, and 1 month after intravitreal injection of YC-1 or DMSO. Meanwhile, vitreous fluid was collected at each time points to analyze concentration of VEGF, HIF-1α, IL-6, IL-8, and MCP-1 mediators by CBA or ELASA method. Results: The experimental CRVO was successfully established in six rhesus monkeys. As expected, the thickness of macular edema significantly decreased at 1 week and 2 weeks after YC-1 injection compared with that of DMSO injection. Subsequently, the central macular thickness in all eyes was recovered to the initial levels at 1 month after photocoagulation. Intraocular pressure (IOP) was not significantly different between two groups during all follow up. Meanwhile, the concentration of IL-6, IL-8, VEGF, and HIF-1α in vitreous fluid significantly decreased after YC-1 injection compared with that of DMSO injection, MCP-1 was not significantly different between both groups. Conclusions: Intravitreal injection of YC-1 significantly alleviated macular edema compared with that of DMSO control group. Meanwhile, both inflammatory factors and angiogenesis-related factors expression were inhibited in vitreous by YC-1 injection. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate macular ganglion cell complex (GCC) thickness and peripapillary retinal nerve fiber layer (RNFL) thickness in patients treated with SSRIs. Methods: The present study included 62 eyes of 31 patients who were using SSRIs and 60 eyes of 30 healthy, age- and gender-matched control subjects. All patients underwent a full ophthalmological examination in which macular thickness, GCC thickness, and peripapillary RNFL thickness were measured using optical coherence tomography (OCT). The Mann-Whitney U test was used to compare the patients’ group with the age- and gender-matched control group. Pearson correlation analyses were also performed to assess the relationships between macular thickness, GCC thickness, RNFL thickness, and the duration of SSRI usage. Results: The mean duration of SSRI usage was 29.96 ± 27.19 (range 6-120) months. The foveal thickness was 253.48 ± 22.77µm in the patients’ group and 266.60 ± 20.64 µm in the control group; the difference between the groups was statistically significant. In addition, the perifoveal GCC thickness in the inferonasal and inferotemporal quadrant were significantly smaller thinner in the patient group (Mann-Whitney U test, p = 0.021and p = 0.013, respectively). Conclusions: Our results suggest a relation between SSRIs and decreased retinal GCC thickness and RNFL thickness. Future long-term prospective studies should elucidate the actual effect of SSRIs on GCC and RNFL thickness. [ABSTRACT FROM AUTHOR]

Purpose: To assess changes in retinal vascular caliber in response to short-term use of nepafenac eye drops in patients with mild diabetic macular edema. Materials and methods: Thirty-four patients with previously untreated bilateral mild diabetic macular edema were included in this prospective study. For each participant, one eye was randomly assigned to nepafenac treatment (0.1%, three times/day) and the other eye was left untreated throughout the study. Using digital fundus photographs, retinal vascular calibers were calculated and compared in treated and untreated eyes at the baseline, week 1, and week 6. Results: Baseline vessel diameters did not differ in treated and fellow eyes (p > 0.05). Over the 6 weeks of the study, significant vasoconstriction of the retinal arteriolar caliber was observed at weeks 1 (p < 0.05) and 6 (p < 0.05), while an unchanged retinal venular caliber was noted between the treated and untreated eyes (p > 0.44). Significant macular thickness difference was only observed at week 6 (p = 0.002). Conclusions: Topical nepafenac has a significant narrowing effect on the retinal arteriolar diameter and a significant reductive effect on central macular thickness in eyes with mild diabetic retinopathy. [ABSTRACT FROM PUBLISHER]

Purpose: Hypertension (HT) strongly affects the vascular endothelium, resulting in chronic inflammatory disease. Dynamic vessel analysis (DVA) is a modern methodological approach to analyze vascular function in the retinal microcirculation. The aim of this study was to examine whether a defective retinal vessels response is associated with HT-induced endothelial dysfunction. Materials and Methods: Retinal vessel reactions to flicker stimulation were examined by DVA in both eyes of 37 hypertensive and 41 healthy control subjects. Plasma concentrations of C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha (TNFɑ) were measured using the enzyme-linked immunosorbent assay. Results: Both arterial and vein responses to flicker stimulation were significantly decreased in patients with HT compared with the healthy controls (dilatation of the arteries was lower in the HT group by, on average, 1.31,p = 0.001 and dilatation of the veins was lower in the HT group by, on average, 1.32,p = 0.002) after independent adjustment for age, sex, body mass index, and pressure values. In the hypertensive group, there was a negative correlation between the arterial response to flicker stimulation and the plasma CRP concentration (Spearman’s Rank-order Coefficient (Rs) = −0.29,p = 0.07). Similarly, the plasma TNFα concentrations negatively correlated with the arterial response to flicker stimulation (Rs = −0.39,p = 0.02). Conclusions: Our results indicate that DVA directly reflects the actual metabolic status of the retinal endothelium. DVA might be used as an early noninvasive screening tool to detect vascular dysregulation and pan-endothelial dysfunction in patients with HT. [ABSTRACT FROM PUBLISHER]

Purpose: Disturbances in retinal blood flow are a prominent feature of vision threatening retinal diseases. The regulation of tone in retinal resistance vessels involves the perivascular retinal tissue, but it is unknown to what extent neurons or glial cells contribute to the effect. Therefore, the purpose of the present study was to study the contribution of neurons in the perivascular retina to vascular tone during activation of voltage-gated sodium channels with veratridine and electrical field stimulation (EFS). Methods: Porcine retinal arterioles with and without perivascular tissue were mounted in an isometric myograph system for studying the effects of the voltage-gated sodium channel opener veratridine and EFS on retinal vascular tone. Results: Veratridine induced concentration-dependent relaxation of retinal arterioles which was more pronounced in arterioles with preserved perivascular retinal tissue than in isolated vessels. In the presence of this tissue, veratridine-induced relaxation was inhibited by the voltage-gated sodium channel blocker tetrodotoxin and the nitric oxide synthase inhibitor, Nω-Nitro-L-arginine methyl ester (L-NAME), but was unaffected by the inhibition of the cyclo-oxygenase inbitior ibuprofen and by blocking of adenosine receptors with 8-(p-Sulfophenyl)theophylline hydrate (8-PSPT). Electrical field stimulation induced no changes in retinal vascular tone. Conclusions: Sodium channels of neuronal origin are likely to be involved in the regulation of retinal vascular tone. The lack of effect of EFS on retinal vascular tone may be due to the lack of autonomic nerves in the retina. [ABSTRACT FROM PUBLISHER]

Purpose: Our aim was to evaluate the alterations of subfoveal choroidal thickness (SFCT), photoreceptor layer thickness (PRT), and retinal vessel diameter in the dark and light adaptation. Methods: Twenty-four eyes of 24 healthy volunteers (12 males, 12 females) were included in this cross-sectional and observational study. The SFCT, PRT, retinal arteriole, and venule caliber measurements were performed with spectral domain optical coherence tomography in the dark (0.0 cd/m2) and under light (80 cd/m2) adapted conditions. Results: The mean age of the participants was 30.4 ± 4.4 years (range: 22–42). The SFCT increased statistically significantly in dark adaptation (p < 0.001), then returned to baseline values following light adaptation. The PRT, retinal arteriole, and venule caliber measurements were similar in the dark and light (p > 0.05). Conclusions: While SFCT increased, PRT, and retinal vessel diameter did not change following transition from light to dark. [ABSTRACT FROM AUTHOR]

Purpose: Although Arg-Gly-Asp (RGD) motif-containing disintegrins are associated with integrin inhibition and the activation of various biological processes, little is known about the role of RGD motif-containing disintegrin in vascular development and remodeling. We therefore investigated the role of RGD-containing disintegrin in vascular remodeling in oxygen-induced retinopathy (OIR) mouse model. Materials and methods: EGT022, an RGD-containing disintegrin originated from human a disintegrin and metalloproteinase 15 (ADAM15), was used to investigate the role of the disintegrin in vascular development in OIR mouse model. To analyze the functional effects of EGT022 on retinal vascular development, the immunohistochemistry on mouse retinas after fluorescein isothiocyanate (FITC) perfusion was conducted and the vessel integrity was examined using modified Mile’s permeability assay. Results: EGT022 was able to reduce overall retinopathy scores by 75%, indicating its efficacy in retinal microvessel maturation stimulation. Pericyte coverage was greatly stimulated by EGT022 treatment in OIR mouse model. EGT022 was also effective to significantly improve blood vessel integrity. Conclusions:RGD-containing disintegrin EGT022 stimulated vascular maturation in OIR mouse model. Experimental results suggest that EGT022 is useful for treatments to improve ischemia in nonproliferative diabetic retinopathy (NPDR), the early stage of diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Purpose/Aim: To investigate the association between retinal vascular tortuosity and traditional- and vascular-related risk factors in persons with diabetes. Methods: We recruited 224 diabetic patients. Retinal vascular tortuosity was measured from fundus photographs. Association of tortuosity with the following factors was assessed after adjusting for significant co-factors: diabetes duration, HbA1c, systolic blood pressure (SBP), cholesterol and body mass index (BMI), flicker-light induced retinal vasodilatation, and markers of endothelial function and inflammation (skin microvacular responses to acetylcholine iontophoresis, soluble e-selectin, inter-cellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelin-1, total nitrite, C-reactive protein). Results: Adjusting for age and gender, longer diabetes duration was associated with more tortuous retinal arterioles (mean difference in arteriolar tortuosity 5.85 × 10−5, 95% Confidence Interval 1.44–10.3 × 10−5;p = 0.016; ≤10 versus >10 years duration). Reduced flicker-light induced retinal vasodilatation was associated with tortuous arterioles and venules (mean difference in arteriolar tortuosity 5.62 × 10−5, 4.50–6.72 × 10−5;p < 0.001 and in venules 5.94 × 10−5, 3.33–8.55 × 10−5;p < 0.001; comparing highest versus lowest tertile of flicker-light vasodilatation). These associations remained after adjusting for co-factors. Diabetes duration explained about 36% and flicker-light vasodilatation 25% of the variation in retinal arteriolar tortuosity. No associations were found between retinal arteriolar or venular tortuosity and HBA1c, SBP, cholesterol, BMI and serum markers of endothelial function. Conclusions: Increased retinal arteriolar tortuosity was related to longer diabetes duration and reduced flicker-light induced vasodilatory response, suggesting that retinal vascular tortuosity in adults with diabetes may be influenced by multiple diabetes-related physio-pathological changes. [ABSTRACT FROM PUBLISHER]

Purpose: To determine whether lactoferrin, specifically endogenous mouse lactoferrin and exogenous intraperitoneal lactoferrin treatment, plays a role in reducing the chorioretinal damage in the laser-induced model of choroidal neovascularization. Materials and methods: Four 532-nm argon laser spots were placed between the retinal vessels of each eye. At Day 7, Fluorescein Angiography was performed to grade the lesions. The mice were perfused with fluorescein-labeled tomato lectin and sacrificed. The retinal pigment epithelium-choroid-sclera complex was flat-mounted and analyzed with a confocal microscope to measure the volume of the lesions. The effect of endogenous lactoferrin was studied by comparing lactoferrin knockout and wild-type (WT) mice. The effect of exogenous lactoferrin treatment was studied by comparing lactoferrin knockout and WT mice treated with lactoferrin for seven days to their respective controls. Results: Lactoferrin knockout mice demonstrated 47% larger lesion volumes than WT mice (p < 0.001). Intraperitoneal treatment with Lactoferrin reduced the lesion volume in Lactoferrin knockout mice by 26% (p < 0.04). Regarding the fluorescein angiography, lesions indicating the greatest damage (grade 2B) occurred more frequently in control lactoferrin knockout mice compared with control WT mice (16% versus 5%). Intraperitoneal treatment with Lactoferrin reduced the grade 2B lesions from16% to 2% in Lactoferrin knockout mice. Conclusion: The endogenous lactoferrin present in WT mice appears to reduce the choroidal neovascularization in the laser-induced choroidal neovascularization model in mice. Treatment with exogenous lactoferrin is capable of reducing the choroidal neovascularization in lactoferrin knockout mice but does not add a significant protective effect to WT. [ABSTRACT FROM PUBLISHER]

Purpose: Inhibition of cyclooxygenase (COX) and nitric oxide synthesis (NOS) has previously been shown to modify hypoxia-induced relaxation of retinal arterioles in vitro. The purpose of the present study was to investigate whether these findings can be reproduced in vivo. Methods: Twenty healthy persons aged 20-55 years were examined. Using the dynamic vessels analyzer (DVA), the resting diameter and diameter changes during isometric exercise and flicker stimulation were studied before and during breathing of a hypoxic gas mixture. The examinations were carried out before and during intravenous infusion of the NOS-inhibitor l-NMMA, and were repeated on a second study day after topical administration of the COX-inhibitor diclofenac. Results: The resting diameter of retinal arterioles increased significantly during hypoxia and decreased significantly during l-NMMA infusion ( p < 0.0001) which compensated for changes in the blood pressure. During hypoxia and l-NMMA infusion together contraction of retinal arterioles could not compensate for the increased blood pressure as assessed by a gain factor significantly lower than one ( p = 0.002). The arteriolar contraction induced by isometric exercise was significantly reduced by diclofenac and flicker-induced dilatation of retinal arterioles was increased during l-NMMA infusion ( p < 0.0001). Conclusion: Diameter changes of retinal vessels during acute hypoxia in vivo are modified by inhibiting NO and prostaglandin synthesis. The evidence points to possible new targets of intervention on the diameter regulation of retinal arterioles in diseases where retinal hypoxia is part of the disease pathogenesis. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies have shown that injury to the retinal vasculature, including capillary degeneration, occurs following N-methyl- d-aspartate (NMDA)-induced neuronal cell loss, but it is unclear whether there are age-dependent differences in the severity of vascular damage. The purpose of the present study was to determine age-related changes in retinal capillary degeneration in NMDA-induced retinal damage rat model. Materials and Methods: A single intravitreal injection of NMDA (200 nmol/eye) was performed in 1-, 2-, 3-, 7- and 15-week-old male Sprague-Dawley rats. Seven days after NMDA injection, damage to retinal neurons and blood vessels were assessed by measuring the number of cells in the ganglion cell layer and the length of empty basement membrane sleeves, left behind by regressing endothelial cells, respectively. Results: At all ages examined, the NMDA-induced neurotoxicity exhibited similar levels of ganglion cell death. However, the degeneration of capillaries in NMDA-treated retina was severe during the early stages of retinal vascular development, and the degree of capillary degeneration decreased with age. Conclusion: The degree of retinal capillary degeneration in NMDA-induced retinal damage rat model decreases in an age-dependent manner. Retinal capillaries may be resistant to retinal neuronal damage in young adults. [ABSTRACT FROM AUTHOR]

Purpose: HM-3, an RGD-modified endostatin-derived polypeptide, is a potent angiogenesis inhibitor synthesized in our laboratory. This study investigated the HM-3 pharmacokinetics of intravitreally administered in mice eyes as an anti-angiogenesis drug for age-related macular degeneration. Materials and methods: A total of 288 C57BL/6J mice were evaluated and divided into four groups. Each mouse in different groups received single bilateral intravitreal injection with HM-3. The concentrations of HM-3 in choroid/sclera, retina and serum were determined by indirect competitive enzyme-linked immunosorbent assay. Results: After intravitreal administration of doses of 0, 10, 20 and 40 μg/eye HM-3, the observed maximum concentration ( Cmax) was 12.98 ± 1.42, 27.87 ± 3.64 and 55.96 ± 11.94 ng/mg, respectively; and the total area under the curve (AUCtot) was 739.23 ± 190.32, 1171.74 ± 528.75 and 1777.71 ± 511.64 h ng/mg; the elimination half-life ( T1/2) in retina was 104.85 ± 36.90, 107.42 ± 35.25 and 101.12 ± 15.82 h; the mean residence time (MRT) was 172.46 ± 63.80, 164.70 ± 52.72 and 181.32 ± 26.01 h, respectively. In choroid/sclera, the Cmax was 5.29 ± 0.34, 6.29 ± 1.87 and 8.14 ± 0.71 ng/mg, respectively; AUCtot was 579.03 ± 56.50, 762.20 ± 201.09 and 720.91 ±243.87 h ng/mg; T1/2 was 54.04 ± 25.99, 59.33 ± 24.46 and 47.10 ± 10.00 h, respectively; MRT was 139.98 ± 23.93, 155.43 ± 17.81 and 136.45 ± 18.17 h, respectively. But in serum, the Cmax was 482.00 ± 38.97, 493.94 ± 97.64 and 1033.10 ± 276.33 ng/ml, respectively; AUCtot was 21128.55 ± 4683.68, 53444.57 ± 16963.99 and 53164.84 ±1535.06 h ng/ml; T1/2 was 48.39 ± 14.89, 47.96 ± 12.97 and 49.98 ± 30.07 h, respectively; MRT was 108.6 ± 47.17, 159.76 ± 18.82 and 125.33 ± 21.41 h, respectively. Conclusions: The pharmacokinetic profiles of intravitreal administration HM-3 provide the basis for the development of reasonable dosing regimens of clinical choroidal neovascularization (CNV) treatment. However, the vitreous and blood retinal barrier might be barriers to drug distribution and diffusion. In addition, fluid flow for the anterior transport and choroidal blood circulation might play important roles for multiple peaking. Carrying out the research into pharmacokinetics of HM-3 provides the information for laying down drug delivery scheme in mice model of CNV. [ABSTRACT FROM AUTHOR]

Purpose: Maturity is a critical factor in the pathogenesis of retinopathy of prematurity (ROP). One widely used method for studying this condition is that of oxygen-induced retinopathy (OIR). The general conditions of an OIR term animal, both at the time of birth and following birth, differ from those of the preterm infant. This, to simulate preterm conditions and to provide a basis for further studies on ROP, we investigated the effect(s) of preterm birth on retinal vascularization using the neonatal rat. Materials and methods: Sprague-Dawley (SD) rats were delivered preterm by caesarean section on the day 19 of gestation. Term pups were used as controls. On the day of birth, preterm and term pups were housed under conditions of room air or cyclic oxygen. Retinas of pups housed in room air on days 4, 7, 10, 14, 18 and 22, as well as pups housed in oxygen on days 14, 18, and 22 were whole-mounted and stained with isolectin-B4. On day 18, cross-sections of the retina were cut and stained with hematoxylin and eosin for the identification of preretinal neovascular tufts. Images of avascular and neovascular areas were compared using light and fluorescence microscopy. Results: Preterm pups had significantly larger avascular retinal areas than term rats on the various postnatal days. After exposure to cyclic oxygen, preterm pups demonstrated significantly larger avascular (days 14 and 18) and neovascular areas (day 18) compared with term rats. On day 22, residual retinopathy of preterm pups was greater than that of term pups. Conclusions'. Preterm birth of rats, which are comparable in their physiology to humans, had negative effects on retinal vascularization. The impaired retinal vascular development and subsequent vasoproliferation resulting from hyperoxia in preterm pups is more severe and enduring. [ABSTRACT FROM AUTHOR]

Purpose: To describe the association between retinal vessel caliber and risk factors for branch retinal vein occlusion (BRVO). Materials and Methods: We included 10,890 participants who underwent a health checkup at Kangbuk Samsung Hospital between January 2006 and December 2006. BRVO was diagnosed from retinal photographs taken for both eyes. Retinal vascular caliber measurements were performed using a computer-assisted program. Risk factors were assessed based on a patient-answered questionnaire and laboratory investigations. Logistic regression analyses were performed to identify potential risk factors for BRVO. Results: The overall prevalence of BRVO was 0.8%. Among all BRVO patients, the mean central retinal artery equivalent (CRAE) was 142.59 µm (±14.63 µm), and the mean central retinal vein equivalent (CRVE) was 203.46 µm (±18.84 µm). The mean CRAE and CRVE of the control eyes were 148.15 µm (± 15.89 µm) and 211.12 µm (±18.54 µm), respectively. There were significant differences in mean CRAE and CRVE between the control group and the BRVO group ( P < 0.05). Arterial hypertension was an important risk factor for BRVO (OR: 1.02 (1.01-1.03). Conclusions: Eyes with BRVO had narrow CRAE and CRVE when compared with age- and gender-matched normal eyes. Generalized attenuation of retinal vessel caliber may be characteristic of eyes with BRVO. Emphasis on blood pressure control is needed for the prevention of BRVO. [ABSTRACT FROM AUTHOR]

Purpose: To study RhoA activation and the effect of the Rho-kinase inhibitor in the development of retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Methods: C57BL/6 mice at postnatal day (P7) were exposed to hyper-oxygen for 5 days and returned to room air for 5 days to induce OIR. RhoA-GTP, an active form of RhoA, in retinas at P12, P13 and P17 was detected. Mice received a single intravitreal injection of Y27632 (5 µM or 50 µM), a Rho-kinase inhibitor, in one eye during the transition from oxygen to room air at P12. Contralateral eyes were used as the control. Fluorescein-conjugated dextran angiography of retinal whole mount was prepared to score features of neovascular retinopathy at P17. The preretinal neovascular nuclei quantification was performed in frozen sections as well to evaluate the neovascularization. Results: The retinal RhoA-GTP in OIR mice significantly increased from 0.24 ± 0.06 at P12 to 0.38 ± 0.12 at P13 ( p < 0.05). The median total retinopathy score of 5.7 was significantly lower in eyes treated with Y27632 than controls ( p < 0.001). Significant improvement was found in the specific categories of vascular tufts ( p < 0.01) and extraretinal neovascularization ( p < 0.05) in treated eyes. Those treated eyes also had a significantly decreased number of neovascular nuclei ( p < 0.01). Conclusions: These results suggest that Rho/Rho-kinase signaling pathways are involved in the early process of hypoxia-induced retinal neovascularization and Y27632 might have therapeutic potential for the treatment of retinal neovascularization. [ABSTRACT FROM AUTHOR]

Purpose: The purpose was to investigate the effect of the superoxide dismutase mimetic tempol on decreases in retinal blood flow that are found in diabetic mice. Materials and Methods: Streptozotocin (STZ) was injected into male C57BL/6 mice to induce hyperglycemia. One week following the STZ injection, subsets of the mice were given drinking water with or without 1 mM tempol for an additional three weeks. At the end of the four-week protocol, microvascular parameters were quantified via intravital microscopy, and included measurements of retinal diameters, red blood cell (RBC) velocities, blood flow rates, and wall shear rates. Results: Diabetes induced ~40--45% decreases in retinal blood flow rate ( p < 0.001) four weeks following injection of STZ. The decrease in blood flow rate occurred with decreases in microvascular diameters (D) and RBC velocities (V). The average percentage decrease in velocity was greater than the percentage decrease in diameter and, therefore, wall shear rates (== 8 V/D) were ~25% lower in the diabetics than in the non-diabetics ( p < 0.05). A three-week administration of tempol in the STZ mice allowed significantly higher blood flow rates than in the untreated STZ mice, with RBC velocities improved by the antioxidant ( p < 0.05 on the venular side). However, tempol provided only moderate (and not statistically significant) improvements in wall shear rates. Conclusions: The antioxidant tempol provides partial improvements in retinal microvascular hemodynamics early in the progression of STZ-induced diabetes in mice. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to investigate immediate changes in the blood retinal barrier (BRB) after the infusion of triolein emulsion. Materials and Methods: Triolein emulsion was infused into the carotid artery of 12 cats to induce experimental fat embolism. The injection of fluorescein dye into the carotid artery followed immediately. Early retinal vascular flow was recorded by a fluorescein angiography (FA) video, and then a FA photograph was obtained up to 30 min after the injection. Leakage of the dye in the choroidal or retinal vessels was evaluated. Results: In the early phase, multifocal non-perfuse areas were noted in all cats due to embolism by triolein emulsion, which was released by blood perfusion in the late phase. Perfusion defects persisted in the retina of five cats and in the choroid of four cats. Leakage of the dye through the retinal vessels was seen in five cats (42%) in the early phase and in nine cats (75%) in the late phase. In the choroid, leakage of the dye was seen in seven cats (58%) in the early phase and in all cats (100%) in the late phase. Conclusions: The inner and outer BRB was opened immediately after infusion of triolein emulsion into the carotid artery. Embolism by triolein emulsion was readily resolved due to the liquid nature of triolein. [ABSTRACT FROM AUTHOR]

Purpose: The amplitude of spontaneous retinal venous pulsations (SRVP) is known to be affected by intraocular pressure (IOP), retinal venous pressure, and intracranial pressure (ICP). This study characterized SRVPs adjacent to the disc and quantified changes in the amplitude of these pulsations during IOP manipulation in normal subjects. Methods: The study included 12 subjects (40 ± 15, 4 females, 8 males). Baseline IOP (range 10-25 mmHg) was measured and SRVP recorded using the dynamic retinal vessel analyzer (DVA). IOP was lowered using aproclonidine 0.5% and measured every 15 min, followed by dynamic recording of SRVP. Two subjects were also tested with timolol 0.5%, and three were treated with a placebo drop. Mean amplitude of SRVP was determined within each sample at the same site. Blood pressure and heart rate were tracked continuously. Results: Amplitude of SRVP decreased in all subjects with reduction of IOP with aproclonidine and timolol. Mean SRVP amplitude was 8.5 ± 6 μm at baseline and reduced to 2.5 ± 1.8 μm after 45 min ( p < 0.0001). IOP fell from 14.4 ± 2.6 mmHg to 10.2 ± 2.9 mmHg over the same period ( p < 0.001). Venous diameter, blood pressure, and heart rate did not change significantly from the baseline. Analysis of waveforms showed a slight phase shift only (150 ± 78.5 ms, p = 0.93) between disc veins and adjacent retinal vein. Conclusion: SRVPs in the peripapillary retina have similar waveform characteristics to those at the disc. SRVP amplitudes are reduced by manipulation of IOP downwards with pharmacological intervention. The relationship was consistent in all individuals tested for two classes of drugs and was independent of BP or heart rate changes. [ABSTRACT FROM AUTHOR]

Vascular basement membrane (BM) thickening is a fundamental structural alteration of small blood vessels in diabetes. Over two decades of research has established hyperglycemia as the primary causal factor mediating this alteration. Various high glucose-induced mechanisms have been investigated and excess synthesis of BM components has been identified as a major contributing factor to BM thickening. Although BM thickening has been long hailed as the histological hallmark of diabetic microangiopathy, the consequences of BM thickening on the functionality of target organs of diabetes remain elusive even today. This review presents an overview of our current understanding of the BM structure and function, and focuses on how capillary BM thickening develops, its effect on retinal vascular function, and potential strategies for preventing the development of BM thickening in diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Aim: To assess the influences of imaging variation (different photographic angle) on the measurement of retinal vascular fractal dimension ( Df), using two segmentation methods. Materials and methods: Nonlinear orthogonal projection segmentation (International Retinal Imaging Software-Fractal, termed IRIS-Fractal) and curvature-based segmentation (Singapore Institute Vessel Assessment-Fractal, termed SIVA-Fractal) methods were used to measure Df and were assessed for their reproducibility in detecting retinal vessels of 30 stereoscopic pairs of optic disc color images. Each pair was taken from the same eye with slightly different angles of incidence. Each photograph of the pairs had subtle variations in brightness between areas temporal and nasal to the optic disc. Results: Intragrader reproducibility of Df measurement was similar (intraclass correlation 0.81 and 0.96, respectively) for IRIS-Fractal and SIVA-Fractal. Within-image pair Pearson’s correlation coefficients ( r) of Df measurements were moderate for both methods (0.57 and 0.48, respectively). Conclusions: Both nonlinear orthogonal projection and curvature-based retinal vessel segmentation methods were found to be sensitive to variations in image brightness, resulting from iris shadowing associated with different angle of photographic incidence. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the effects of endostatin on tight junction (TJ) integrity in retinal microvascular endothelial cells (RMECs) in vitro and in vivo. Moreover, it was hypothesized that endostatin-induced occludin upregulation regulated VEGF165-mediated increases in endothelial cell permeability and involved activation of the MAPK signaling cascade. Endostatin is a 20-kDa fragment of collagen XVIII that has been shown to be efficacious in the eye by preventing retinal neovascularization. Endostatin is a specific inhibitor of endothelial cell proliferation, migration, and angiogenesis and has been reported to reverse VEGF-mediated increases in vasopermeability and to promote integrity of the blood-retinal barrier (BRB). In order to determine the mechanism of endostatin action on BRB integrity, we have examined the effects of endostatin on a number of intracellular pathways implicated in endothelial cell physiology. Methods: C57/Bl6 mice were injected with VEGF165 and/or endostatin, and the distribution of occludin staining was determined using retinal flatmounts. Western blot analysis of RMECs treated with VEGF165 and/or endostatin was used to determine changes in occludin expression and p38 MAPK and extracellular regulated kinase (ERK1/ERK2 MAPK) activation, while FD-4 flux across the RMEC monolayer was used to determine changes in paracellular permeability. Results: Endostatin prevented the discontinuous pattern of occludin staining observed at the retinal blood vessels of mice administered an intraocular injection of VEGF165. It was shown that endostatin activated p38 MAPK 5 min after addition to RMECs and continued to do so for approximately 30 min. Endostatin was also shown to activate ERK1/ERK2 5 min after addition and continued to do so, albeit with less potency, up to and including 15 min after addition. Inhibition of p38 MAPK and ERK1/ERK2 prevented endostatin's ability to upregulate levels of occludin expression. Inhibition of these key signaling molecules was shown to prevent endostatin's ability to protect against VEGF165-mediated increases in paracellular permeability in vitro. However, it appears that p38 MAPK may play a more important role in VEGF-mediated permeability, as inhibition of ERK1/ERK2 will not prevent VEGF165-mediated permeability compared with control (untreated) cells or cells treated with both a p38 MAPK inhibitor and VEGF165. Conclusions: Occludin is important for the maintenance of tight junction integrity in vivo. In a p38 MAPK and ERK1/ERK2 dependent manner, endostatin was shown to upregulate the levels of expression of the tight junction protein occludin. Inhibition of these key MAPK components may prevent endostatin's ability to decrease VEGF165-induced paracellular permeability. [ABSTRACT FROM AUTHOR]

Purpose : Niacin is a B vitamin well-known for causing vasodilation and flushing. The purpose of this study was to investigate its effect on the retinal vasculature of patients with age-related macular degeneration (AMD). Methods : Twelve patients with AMD were enrolled in a double-blind, randomized, placebo-controlled, crossover trial. Fundus photographs of the posterior pole were taken at baseline, 30 min, and 90 min after a single dose of niacin or placebo. The protocol was repeated after a washout period using the alternate study drug. The diameters of two veins and one artery on each image were measured. Results : An analysis of variance for repeated measures comparing the effects of niacin with those of placebo demonstrated a significant increase in the inferior temporal retinal artery diameter (p = 0.01), with a 5.3 ± 7.7% increase at 30 min (p = 0.05) and 5.8 ± 5.0% increase at 90 min (p = 0.003). No significant changes were observed in the temporal retinal veins. Conclusions : Our results suggest that niacin produces vasodilatation of retinal arterioles. Further studies are needed to ascertain whether niacin treatment may be beneficial in retinal ischemic diseases. [ABSTRACT FROM AUTHOR]

Purpose : To report an optical imaging system that was developed to measure oxygen tension (pO 2 ) in the chorioretinal vasculatures. The feasibility of the system for the measurement of changes in pO 2 separately in the retinal and choroidal vasculatures was established in rat eyes by varying the fraction of inspired oxygen and inhibiting nitric oxide activity. Methods : Our optical section phosphorescence imaging system was modified to provide quantitative measurements of pO 2 separately in the retinal and choroidal vasculatures. A narrow laser line was projected at an angle on the retina after intravenous injection of an oxygen-sensitive probe (Pd-porphyrin), and phosphorescence emission was imaged. A frequency-domain approach allowed measurements of the phosphorescence lifetime by varying the phase relationship between the modulated excitation laser light and sensitivity of the imaging camera. Chorioretinal pO 2 was measured while varying the fraction of inspired oxygen and during intravenous infusion of N ? -nitro-L-arginine ( N ? -NLA), a nonselective nitric oxide synthase inhibitor. Results : The systemic arterial pO 2 varied according to the fraction of inspired oxygen. The pO 2 in the retinal and choroidal vasculatures increased as the fraction of inspired oxygen was increased. Compared with baseline, choroidal pO 2 decreased during infusion of N ? -NLA, whereas the pO 2 in the retinal vasculatures remained relatively unchanged. The choroidal pO 2 decreased markedly with each incremental increase in N ? -NLA infusion rate, in the range 1–6 mg/min, and there was no additional change in the choroidal pO 2 at N ? -NLA infusion rates above 6 mg/min. Conclusions : An optical method combining pO 2 phosphorescence imaging with chorioretinal optical sectioning was established that can potentially be applied for better understanding of retinal and choroidal oxygen dynamics in physiologic and pathologic states. [ABSTRACT FROM AUTHOR]

Purpose : To describe serotonergic retinopetal axons in monkeys. Methods : Whole macaque and baboon retinas, fixed in 4% paraformaldehyde, were labeled with antisera raised against serotonin (5-HT). Results : Several large-diameter 5–HT-immunoreactive (IR) axons emerged from the optic disk. Most axons ran to the peripheral retina, where they branched extensively. Most terminated in the ganglion cell layer, but a few 5-HT-IR axons terminated in distal inner plexiform or within inner nuclear layer. Some axons branched extensively near the fovea, and a dense plexus of 5-HT-IR axons was also found around the optic disk. Varicose 5-HT-IR axons were also associated with blood vessels, especially in the central retina. Conclusions : Immunoreactive serotonin is present in a distinct population of retinopetal axons in the monkey retina. Receptors for serotonin are present in the primate retinas, and based on physiological studies in other mammals, these retinopetal axons are expected to modulate neuronal activity and regulate blood flow. [ABSTRACT FROM AUTHOR]