Pathological angiogenesis, as seen in many inflammatory, immune, malignant, and ischemic disorders, remains an immense health burden despite new molecular therapies. It is likely that further therapeutic progress requires a better understanding of neovascular pathophysiology. Surprisingly, even though transmembrane voltage is well known to regulate vascular function, no previous bioelectric analysis of pathological angiogenesis has been reported. Using the perforated-patch technique to measure vascular voltages in human retinal neovascular specimens and rodent models of retinal neovascularization, we discovered that pathological neovessels generate extraordinarily high voltage. Electrophysiological experiments demonstrated that voltage from aberrantly located preretinal neovascular complexes is transmitted into the intraretinal vascular network. With extensive neovascularization, this voltage input is substantial and boosts the membrane potential of intraretinal blood vessels to a suprahyperpolarized level. Coincident with this suprahyperpolarization, the vasomotor response to hypoxia is fundamentally altered. Instead of the compensatory dilation observed in the normal retina, arterioles constrict in response to an oxygen deficiency. This anomalous vasoconstriction, which would potentiate hypoxia, raises the possibility that the bioelectric impact of neovascularization on vascular function is a previously unappreciated pathophysiological mechanism to sustain hypoxia-driven angiogenesis.neovascularization | proliferative retinopathy | retinopathy of prematurity | proliferative diabetic retinopathy | retina T he abnormal growth of blood vessels is a key pathophysiological feature of numerous disorders, including tumorigenesis, arthritis, endometriosis, and retinopathies. Despite substantial progress from studies of patients and animal models, abnormal neovascularization remains a common threat to health and wellbeing. To help address this challenge, we devised a unique experimental approach to better understand neovascular pathophysiology. Because almost nothing is known about the electrogenic profile of neovascular complexes and how these complexes functionally interact with their parent vessels, we focused on the bioelectric features of neovascularization. These gaps in knowledge are surprising, considering that it is well established that the transmembrane voltage of vascular cells (1), as well as electrotonic cell-cell interactions within a vascular network (2-4), play vital roles in regulating blood flow.In this electrophysiological analysis of pathological angiogenesis, we focused on abnormal vasoproliferation in rodent and human retinas. For multiple reasons, the retina is an ideal tissue for this undertaking. First is its clinical importance. Retinal vasoproliferation is the major cause of blindness in prematurely born infants (retinopathy of prematurity) and persons with diabetes (proliferative diabetic retinopathy) and sickle cell disease (sickle cell retinopathy). The hallmark of these disorders is abno...

PurposeTo investigate the relationship between laser speckle flowgraphy (LSFG) and optical coherence tomography angiography (OCTA) measurements of the peripapillary retina and optic nerve head (ONH) in normal eyes and eyes with primary open-angle glaucoma (POAG).Patients and methodsOne eye from each of 46 normal subjects and mild and moderate/advanced POAG patients were included. ONH blood flow acquired by LSFG, circumpapillary vessel density (cpVD, a 250 μm-wide elliptical annulus around the optic disc), and intra-papillary vessel density (ipVD, a 1.5×1.5 mm scan field) acquired by OCTA were measured. Their values were compared among normal controls and patients at each stage of glaucoma using one-way ANOVA, and the correlation between measurements obtained by the two methods was examined by univariate regression analysis.ResultsONH tissue blood flow, tissue mean blur rate (MBR-T), and cpVD in the outer layer of the retina significantly decreased with the progression of glaucoma stage, although the latter showed no significant difference between normal subjects and mild-stage glaucoma patients. MBR-T was significantly correlated with cpVD, but not with ipVD, in the retinal outer layer.ConclusionA correlation was found only between MBR-T and cpVD in the retinal outer layer. A difference in MBR-T, but not in cpVD, was detected between normal controls and mild glaucoma patients.

Purpose: To report a case of rhegmatogenous retinal detachment in the late stage, despite the fact that it had previously been halted after intravitreal injection of an antimicrobial agent against endogenous bacterial endophthalmitis (EBE). Case: This study involved a 62-year-old male who had previously been diagnosed with septicemia due to liver abscess and the detection of Klebsiella pneumoniae in a culture of his liver abscess, and who underwent ophthalmic examination after his conjunctival hyperemia had failed to improve. Visual acuity could not be measured due to his general condition being poor and his declining level of consciousness. Slit lamp examination revealed bilateral iritis and cataracts, and the fundus was invisible due to vitreous opacity. Ultrasonic B-mode examination showed subretinal abscess and exudative retinal detachment, leading to the diagnosis of EBE. Vitreous injections of antibiotics were administered to both of his eyes. His right eye became affected by phthisis bulbi, but the condition in his left eye subsided, leaving a scarred lesion near the macula. However, complete retinal detachment occurred in his left eye approximately 10 months after the vitreous injection. During vitreous surgery, proliferative membrane formation was observed in the posterior pole area, and an irregular retinal break was detected in the scar margin caused by the traction of the proliferative membrane. After vitreous surgery, the retina was reattached under silicone oil. Conclusion: In cases of EBE, even if the inflammation has previously subsided, strict follow-up examinations are necessary, since complications such as rhegmatogenous retinal detachment may occur at a late stage.

Introduction: We report a case of type III uveal effusion syndrome (UES) suspected to be related to pachychoroid spectrum disease. Patient concerns: A 42-year-old man became aware of visual field constriction and deterioration of visual acuity in his right eye. Diagnosis: Upon examination, a bullous non-rhegmatogenous retinal detachment was observed in the inferior 2 quadrants of the right eye fundus, and the subretinal fluid moved with postural changes. The axial length in that eye was 22.36 mm, thus indicating no nanophthalmia. Preoperative indocyanine green angiography revealed dilated choroidal vessels in the posterior pole of the right eye and mild leakage in the late phase. Optical coherence tomography examination revealed choroidal thickening in both eyes. Interventions: For treatment, we first performed sclerotomy, and the intraoperative findings showed no thickening of the sclera. Following surgery, reattachment of the retina was not achieved. Outcomes: Thus, we next performed vitrectomy, which led to successful reattachment of the retina. Lessons: In this case, we theorize that pachychoroid spectrum disease might have been involved in the pathogenesis of type III UES.