Optic Disc Vascular Density in Normal-Tension Glaucoma Eyes with or without Branch Retinal Vessel Occlusion

We analyzed the vascular densities (VDs) of the optic disc areas in eyes with normal-tension glaucoma (NTG) according to their branch retinal vessel occlusion (BRVO) status. The VDs of the optic discs and peripapillary areas of 68 NTG patients with BRVO (BRVO group; BRVO eyes and fellow eyes) and 37 patients with NTG alone (control eyes) were measured on angiographic images obtained via swept-source optical coherence tomography angiography. VDs were compared among groups and correlations were assessed. The VD of the optic disc large vessel was the highest in BRVO eyes, followed by the fellow eyes and controls (all P < 0.05). Conversely, small and medium vessel VD was in the opposite order (all P < 0.05). Large vessel VD was negatively correlated with small and medium vessel VD (r = −0.697, P < 0.001). Peripapillary VD was lower in the BRVO eyes than in the control and fellow eyes (P < 0.001 and P = 0.861, respectively). In conclusion, significant changes in the distribution of VDs for optic disc larger vessel and small and medium vessels were observed in both eyes of NTG patients with BRVO, compared to NTG patients without BRVO.

Optic Disc Vascular Density in Normal-Tension Glaucoma Eyes with or without Branch Retinal Vessel Occlusion

We analyzed the vascular densities (VDs) of the optic disc areas in eyes with normal-tension glaucoma (NTG) according to branch retinal vessel occlusion (BRVO) status. The VDs of the optic discs and peripapillary areas of 68 patients with NTG + BRVO (eyes with BRVO and fellow eyes with NTG alone) and 37 patients with NTG alone (controls) were measured on binarized angiographic images obtained via swept-source optical coherence tomography angiography. Disc VDs were subdivided into large vessel and small vessel VDs. VD measurements were compared among groups and correlations were assessed. The small vessel and large vessel VDs of the optic disc and peripapillary area differed significantly among eyes in the control, NTG alone, and NTG + BRVO groups (all P < 0.001). More optic disc VDs were significantly larger and fewer were significantly smaller in eyes with BRVO, compared to fellow eyes and control eyes. Large optic disc VD was negatively correlated with small optic disc VD (r = -0.697, P < 0.001). Peripapillary VD was lower in eyes with BRVO than in control eyes, but not in fellow eyes (P < 0.001 and P = 0.975, respectively). In conclusion, significant disc and peripapillary VD changes were observed in eyes with BRVO. However, larger optic disc VD and smaller VD were observed in fellow eyes with NTG alone, but not in control eyes, suggesting that larger optic disc VD may contribute to NTG development in patients with BRVO.

Ocular Phenotype of Mice with Impaired Fibrillin-1 Function on Hypercholesterolemic Apolipoprotein E-Deficient Background

Aim: Transgenic mice with an elastic fiber mutation (C1039G+/-) in the fibrillin-1 gene and apolipoprotein E deficiency express vulnerable atherosclerotic plaque formation in the aorta and coronary and carotid arteries. The fibrillin-1 gene mutation alone leads to impaired fibrillin-1 function common to Marfan syndrome. The aim was to study for the first time the potential effects of atherosclerosis and vulnerable plaques in mouse eye and spontaneous retinal vessel occlusions in these mice.Methods: Apolipoprotein E-deficient and fibrillin-1 mutated mice (ApoE-/-/Fbn1C1039G+/-) were used for the study. ApoE-/- littermates served as controls. Optical coherence tomography and fluorescein angiography were used to study the retina and retinal vessels before and after the 12-week high-fat diet. Series of staining were performed to study morphology, apoptosis, glial fibrillary acidic protein activation, collagen formation, inflammatory cell infiltration and drusen formation.Results: No pathological changes were found in hypercholesterolemic ApoE-/-/Fbn1C1039G+/- mice in imaging studies nor in the histological stainings. There was neither abnormality in the retinal morphology nor any detectable biomarkers.Conclusion: ApoE-/-/Fbn1C1039G+/- mice did not present the ocular signs of Marfan syndrome.12-week high-fat diet is not sufficient to induce retinal vessel occlusion on 20 to 23 weeks old mice. This indicates that the mechanistic background of retinal vessel occlusion is more complex.

Polymorphic markers of the G1639A form of VKORC1 involved in the development of retinal vessel occlusion

Background. Retinal vessel occlusion (RVO) is an eye disease that leads to decreased visual acuity, ultimately resulting in blindness. RVO is observed in 1%–2% of individuals older than 40 years. The etiology of RVO remains unclear. However, the most widely recognized risk factors include age, hypertension, hyperlipidemia, atherosclerosis, cardiovascular diseases, and diabetes. The number of patients with RVO among the young population has increased in recent years, and owing to this increased incidence, more attention is paid to genetic factors. Polymorphisms in the genes encoding proteins involved in the vitamin K cycle are one of these genetic factors that might influence RVO. According to literature, the G1639A polymorphism in the vitamin K epoxide reductase complex subunit 1 (VKORC1) is a possible risk factor for RVO. The purpose of the study. To estimate the association between carriers of the G1639A form of VKORC1 and the development of venous RVO (VRVO) and arterial RVO (ARVO). Materials and methods. The study included 126 patients aged between 40 and 80 years, with a mean age of 61.5 years. Genotyping for the presence of the G1639A polymorphism of VKORC1 was performed using polymerase chain reaction (PCR). Statistical analysis was performed using the program Instat. Results. The GG genotype was found to be significantly more frequently in patients with VRVOthan in those without pathology of retinal vessels (42.6 vs 32%, p = 0.0449). The GG genotype was observed at a higher frequency in patients with ARVO than in those without pathology of retinal vessels (60 versus 32%, p = 0.0925). However, having the AA form of G1639A was significantly less frequent in patients with VRVO compared with those without vascular pathology of the retina (9.8 vs 28%, p = 0.0238, RR 2.015, 95% confidence interval 1.011–4.16). The AA genotype was observed at a lower frequency in patients with ARVO than the control group (6.7 vs 28%, p = 0.1593). Conclusions. Our study demonstrates that having the GG form of the G1639A polymorphism of VKORC1 is associated with the development of VRVO and possibly ARVO. However, having the AA form of this polymorphism is associated with a lower risk of developing VRVO and may also be associated with a lower risk of developing ARVO.

Ischemia-induced spreading depolarization in the retina

Cortical spreading depolarization is a metabolically costly phenomenon that affects the brain in both health and disease. Following severe stroke, subarachnoid hemorrhage, or traumatic brain injury, cortical spreading depolarization exacerbates tissue damage and enlarges infarct volumes. It is not known, however, whether spreading depolarization also occurs in the retina in vivo. We report now that spreading depolarization episodes are generated in the in vivo rat retina following retinal vessel occlusion produced by photothrombosis. The properties of retinal spreading depolarization are similar to those of cortical spreading depolarization. Retinal spreading depolarization waves propagate at a velocity of 3.0 ± 0.1 mm/min and are associated with a negative shift in direct current potential, a transient cessation of neuronal spiking, arteriole constriction, and a decrease in tissue O2 tension. The frequency of retinal spreading depolarization generation in vivo is reduced by administration of the NMDA antagonist MK-801 and the 5-HT(1D) agonist sumatriptan. Branch retinal vein occlusion is a leading cause of vision loss from vascular disease. Our results suggest that retinal spreading depolarization could contribute to retinal damage in acute retinal ischemia and demonstrate that pharmacological agents can reduce retinal spreading depolarization frequency after retinal vessel occlusion. Blocking retinal spreading depolarization generation may represent a therapeutic strategy for preserving vision in branch retinal vein occlusion patients.