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Morphology and enzyme activities of the retinal capillaries in streptozotocin-diabetic mice.

Male lean mice belonging to the obese-hyperglycemic strain were made diabetic by intravenous injection of streptozoticin. The retinal capillary bed freed by trypsin digestion was studied with regard to morphology and the activity of some enzymes. There was a significant increase in the ratio between the endothelial and mural cells which was interpreted as indicating mural pericyte disappearance. The activities of adenylate kinase, aspartate-aminotransferase and hydroxyacyl-CoA-dehydrogenase in the retinal vessels of the diabetic animal were significantly higher than in vessels from the control animals. No differences were found in the activities of glucose-6-phosphate dehydrogenase, glutathione reductase and phosphofructokinase between the two animal groups. It is suggested that these results reflect early morphological and metabolic changes of the retinal vessels, preceding the well known clinical picture of diabetic retinopathy.

Animals↗

Feasibility of targeted drug delivery to selective areas of the retina.

A new method was developed to deliver locally a bolus dose of a drug to the retinal vasculature. The targeted delivery system was based on encapsulating the drug in heat-sensitive liposomes, which are injected intravenously and lysed in the retinal vessels by a heat pulse generated by a laser. To test if substances delivered in the vessels could also penetrate into the surrounding tissue, 6-carboxyfluorescein was encapsulated in liposomes and used as a marker for drug penetration. Moderate argon laser pulses were applied to the retinal vessels of Dutch pigmented rabbits to induce breakdown of the blood-retinal barrier (BRB). A suspension of liposomes at a dose of 2 ml/kg body weight, corresponding to a carboxyfluorescein dose of 12 mg/kg, was injected into the ear vein. The dye was released from the liposomes proximal to the damaged portion of the vessel. Fundus fluorescein angiograms were recorded with a video camera and digitized for subsequent image analysis. The penetration of carboxyfluorescein into the retinal tissue was evaluated by comparing the fluorescence intensity of the area around the damaged vessel with that of an adjacent control area. The dye penetration increased with the numbers of laser applications (P less than 0.001). The leakage was localized distally to the released site and was restricted to areas with a disrupted BRB. The mass of carboxyfluorescein that penetrated gradually spread with time. Both veins and arteries could be used for the targeted delivery. These results indicated that this delivery system, which is fully controllable by laser through the pupil, can deliver drugs inside the vasculature and into the retinal tissue wherever the BRB is disrupted.

Animals↗

Differentiation of retinal circulation times by videoangiography.

Videoangiography is capable of identifying the different phases of a fluorescein angiogram exactly in terms if time elapsed. We employ slow-motion television techniques to determine the rate at which fluorescein flows through the retinal vessels. By this means the arterial, capillary and venous circulatory phases can be isolated at will for study. The way for this method is opened by a division of the overall circulation interval of a bolus through the retinal vessel into arterial, early venous and late venous circulation times. In the study described here the normal parameters of these circulatory times were determined for a group of healthy subjects (n = 100).

Blood Flow Velocity↗

Development of clustered fenestrae of chorioretinal vessels in pathologic conditions.

The purpose of this study is to reveal the process for the clustered fenestra-formation in endothelial cells. Such a process was investigated in two experimental models by using scanning electron microscopy. One was photocoagulated sites of the choriocapillaris. The other was abnormal vessels seen in urethane-induced retinopathy. In the photocoagulation experiment, no fenestra was seen at the center of the lesion 5 or 7 days after photocoagulation. However, when the observing regions were moved away from the center, clusters of several fenestrae appeared. Further away from the center, larger clusters of fenestrae were observed. Fenestrae were distributed in regular fashion in each cluster regardless of size of the cluster. Similar clusters of fenestrae were found in urethane-induced retinopathy. Fenestration was found in the retinal vessels which were located near the choroid. However, the clusters of fenestrae decreased in number in such retinal vessels located near the vitreous. Based on those observations, the author suggests a hypothesis regarding acquisition of clustered fenestrae in pathologic conditions.

Animals↗

Immunostaining of heat shock proteins in the retina and optic nerve head of normal and glaucomatous eyes.

PURPOSE: To examine immunostaining of 60-kd and 27-kd heat shock proteins (HSP 60 and HSP 27), which are known to increase cell survival in response to stress, in glaucomatous retina and optic nerve head. METHODS: Six postmortem eyes from patients with primary open-angle glaucoma, 6 eyes from patients with normal-pressure glaucoma, and 6 eyes from age-matched normal subjects were studied by immunohistochemistry. The sections of the retina and optic nerve head were examined after immunostaining with antibodies to HSP 60 and HSP 27. RESULTS: The intensity of the immunostaining and the number of labeled cells for heat shock proteins (HSPs) were greater in retina sections from glaucomatous eyes than in sections from normal eyes from age-matched donors. Retinal immunostaining of HSP 60 was prominent in the retinal ganglion cells and photoreceptors, whereas immunostaining of HSP 27 was prominent in the nerve fiber layer and ganglion cells as well as in the retinal vessels. In addition, retinal immunostaining of these HSPs exhibited regional and cellular differences. Optic nerve heads of glaucomatous eyes exhibited increased immunostaining of HSP 27, but not HSP 60, which was mostly associated with astroglial cells in the lamina cribrosa. CONCLUSION: The increased immunostaining of HSP 60 and HSP 27 in the glaucomatous eyes may reflect a role of these proteins as a cellular defense mechanism in response to stress or injury in glaucoma. CLINICAL RELEVANCE: These findings suggest that immunoregulation is an important component of glaucomatous optic neuropathy.

Aged↗

[The myogenic response of retinal arterioles in diabetic retinopathy].

OBJECTIVES: The retinal vessel analyzer (RVA) offers the unique opportunity for noninvasive online measurements of the "Bayliss effect." In the presented study this myogenic response is used to test vessel contractility of retinal arterioles in different stages of diabetic retinopathy (DR). METHODS: Forty patients with diabetes were exposed to a standardized rise in blood pressure. The myogenic response of a retinal arteriole was measured by continuous use of the RVA during this time. The subjects were divided into four groups (each n=10) according to different stages of DR. Group I: no DR, group II: mild/moderate DR, group III: moderate/severe nonproliferative DR with laser treatment, and group IV: proliferative DR with laser treatment. RESULTS: A similar blood pressure rise was achieved in all subjects. In response to this BP rise, group I demonstrated a vasoconstriction of -7.6% (+/-4.1). In group II -0.85% (+/-4.3) and in group III a mild vasodilation of +0.44% (+/-5.9) was found. Group IV presented a vasodilatation of +3.2% (+/-5.9). CONCLUSION: According to the progression of the morphological changes in diabetic retinopathy a functional deficit in the autoregulation of retinal arterioles can be measured with the RVA.

Blood Pressure↗

Maculo-papillary branch retinal artery occlusions following the Wada test.

BACKGROUND: The Wada test induces short-term anesthesia of one hemisphere by injection of sodium amytal into an internal carotid artery. It is an important presurgical diagnostic tool in epileptic patients. PATIENT: A 22-year-old man with idiopathic epilepsy noticed a shadow in the central visual field of his right eye immediately following a Wada test of the right hemisphere. RESULTS: The patient presented with an occlusion of two small branch retinal arteries and corresponding defects in his visual field. Fluorescence angiography revealed small dense hyperfluorescent spots within the occluded retinal vessels. CONCLUSION: Branch retinal artery occlusions are a possible complication of the Wada test, possibly induced by undissolved contrast medium or sodium amytal.

Adult↗

Cancer-associated retinopathy associated with invasive thymoma.

PURPOSE: To report a case of cancer-associated retinopathy associated with invasive thymoma. DESIGN: Interventional case report. METHOD: A 41-year-old Japanese woman was observed between February 1998 and May 2001. Ophthalmologic examinations and systemic examinations were performed. The patient received treatment including corticosteroid pulse therapy, plasmapheresis, and thymectomy. RESULTS: The patient developed progressive visual dysfunction including bilateral visual acuity loss, concentric contraction of visual fields, and color vision loss. In both eyes, retinal vessel attenuation and retinal pigment epithelium degeneration were observed with fundus ophthalmoscopy and fluorescein angiography. Response in electroretinogram was reduced, suggesting both rod and cone dysfunction. Autoantibody against 23-kD cancer-associated retinopathy (CAR) antigen (antirecoverin antibody) was detected in the patient's serum. A mediastinal tumor that was histopathologically diagnosed as invasive thymoma was detected and was surgically resected. During more than 3 years of follow-up, no other malignancy was detected despite extensive systemic evaluation. The patient also suffered from subclinical myasthenia gravis. Although temporary improvement of visual function was observed after treatment with steroid pulse therapy and plasmapheresis' light perception of each eye was lost in the end. CONCLUSIONS: The patient was diagnosed as having CAR. Invasive thymoma was considered to be the causative tumor because there had been no evidence that suggested other systemic malignancy during more than 3 years of follow-up.

Adult↗

[Hemodynamic findings in patients with retinitis pigmentosa].

The hemodynamic status of 26 patients with retinitis pigmentosa was examined using video fluorescein angiography. The hemorheological parameters hematocrit, plasma viscosity, erythrocyte aggregation and erythrocyte rigidity were determined. The results were compared to a matched pairs-group. Video angiography showed for retinitis pigmentosa patients a normal arm-retina time and a significant increase of the arteriovenous passage time. The rheological parameters for both groups were within the reference range. Interestingly the hemodynamic disturbance of microcirculation could be demonstrated already in early stages with no ophthalmoscopic symptoms and no atrophy of retinal vessels detectable at the time. The results indicate that disturbance of the retinal hemodynamics in early stages of retinitis pigmentosa may play a role in the pathogenesis of the disease.

Adolescent↗

High altitude stress and retinal hemorrhage: relation to vascular headache mechanisms.

Retinal hemorrhage occurred in 36% of 39 subjects exposed to altitudes at or above 14,200 feet. In subjects with a history of vascular headaches at sea level, there was a higher incidence of and more severe altitude headache, as well as a higher incidence of retinal hemorrhage than among those previously headache-free. In subjects without altitude headache, none had retinal hemorrhage. In subjects with altitude headache, 42% had retinal hemorrhage. A progressive rise in the incidence of retinal hemorrhage was correlated with progressively greater intensity of altitude headache. Factors that intensified the rate or degree of exposure, including rapid ascent and strenuous exertion, appeared to increase the likelihood of hemorrhage. An optimal balance between acclimatization and subsequent altitude stress appeared to prevent retinal hemorrhage. Increased retinal blood flow, retinal vessel engorgement, increased retinal vein and prevenous capillary pressure, and possibly decreased intraocular pressure may contribute to the pathogenesis of retinal hemorrhage.

Acclimatization↗

Relationship between carotid artery stiffness and retinal arteriolar narrowing in healthy middle-aged persons.

BACKGROUND AND PURPOSE: Both carotid atherosclerosis and cerebral arteriolosclerosis are associated with stroke. However, the relationship between carotid atherosclerosis and cerebral arteriolosclerosis is unknown. We examined the association between carotid artery stiffness, a marker of early atherosclerosis, and retinal arteriolar narrowing, a marker of arteriolosclerosis, in healthy middle-aged people. METHODS: This population-based, cross-sectional study involved 8031 men and women 45 to 64 years of age. Carotid arterial stiffness was estimated from high-resolution ultrasonic echo tracking of the left common carotid artery and was defined as adjusted arterial diameter change (AADC, micro, adjusted for diastolic blood pressure, pulse pressure and pulse pressure squared, and diastolic arterial diameter and height, with smaller AADC reflecting greater arterial stiffness). Generalized retinal arteriolar narrowing was estimated from measurements of diameters of retinal vessels from digitized retinal photographs and summarized as the arteriole-to-venule ratio (AVR, with smaller AVR indicating greater retinal arteriolar narrowing). RESULTS: After controlling for age, sex, ethnicity, hypertension, diabetes, and cigarette smoking, decreasing AADC was associated with decreasing AVR. The mean AADCs, comparing the lowest and highest quartiles of AVR, were 394 (SE, 4) and 409 (SE, 4) micro, respectively (P<0.01). The pattern of the graded association between carotid arterial stiffness and generalized retinal arteriolar narrowing was similar among persons with and without hypertension. CONCLUSIONS: Greater stiffness of the carotid arteries is related to generalized narrowing of the retinal arterioles independent of blood pressure and other vascular factors. This supports a relationship between macrovascular and microvascular disease processes important in stroke pathogenesis.

Arterioles↗

A case of normal tension glaucoma associated with Buerger's disease.

Open angle glaucoma, a slowly progressive optic atrophy, is clinically characterized by visual field defects corresponding to excavation of the optic disc, called glaucomatous cupping. Open angle glaucoma is further divided into primary open angle glaucoma caused by elevated intraocular pressure (higher than the normal limit of 21 mmHg), and normal tension glaucoma, in which intraocular pressure is in the normal range. Here we report a case of normal tension glaucoma associated with Buerger's disease, also known as thromboangiitis obliterans, which causes systemic blood flow disturbance. A 66-year-old man suffering from Buerger's disease for 10 years was diagnosed as having branch retinal artery occlusion in his left eye. He was referred to our clinic due to progressive visual field disturbance in that eye. Ophthalmologic examinations revealed occlusion in the infero-temporal retinal artery in the left eye, and glaucomatous cupping, normal intraocular pressure, retinal vessel tortuosity and retinal arteriosclerosis in both eyes. Visual field examination revealed decreased retinal sensitivities in the areas within the visual field arches above and below fixation from the blind spot to the median raphe, corresponding to the arcuate retinal nerve fibers comprising the Bjerrum areas and the area corresponding to the retinal artery occlusion. Buerger's disease is characterized by the development of segmental thrombotic occlusions and vasospasm of the medium and small arteries. Our case suggests that the blood flow disturbance due to arteriosclerosis, thrombotic occlusions and vasospasm associated with Buerger's disease might affect the ophthalmic circulation system, thereby contributing to the etiology of normal tension glaucoma.

Aged↗

[Laser coagulation and cryocoagulation in the treatment of isolated retinal angiitis].

Isolated retinal vasculitis (IRV) is a form of retinal vasculitis without other inflammations of the eye or systemic vasculitis. Occlusion of retinal vessels without subsequent retinal ischemia and neovascularization is one of the main problems in the management of such patients. Laser photocoagulation seems to be a method to control this problem. Argon laser photocoagulation was used in the treatment of 34 IRV patients (56 eyes) (29 men and 15 women aged 25-41 years, mean age 32.9 +/- 5.2 years). A total of 168 sessions were carried out. Regression of neovascularization was achieved in 29 of 44 eyes (79.5%). Additional cryotherapy had to be performed in 15 eyes, good results were attained in 9 eyes (60%). Patients treated with prednisolone in a daily dose of 10-20 mg during laser coagulation had IRV recurrences more rarely than those treated with lower doses (5 mg) (0-6.7% vs. 50%, p < 0.0013), those treated with metipred-depot for 7-14 days (0-6.7% vs. 53.8-66.6%, p < 0.0023), or untreated ones (0-6.7% vs. 73.9%, p < 0.0000).

Adult↗

Pathology of macular lesions from subnanosecond pulses of visible laser energy.

PURPOSE: To demonstrate how current theories regarding ultrashort laser pulse effects may apply to ocular tissue, a prospective clinicopathologic study of macular lesions from ultrashort laser pulses compared the pathologic effects with the clinical and fluorescein angiographic appearance of the laser lesions. METHODS: Ninety-femtosecond, 3-picosecond, and 60-picosecond laser pulses, throughout a range of energies, were delivered to the retina of Macaca mulatta. Clinical examination and fluorescein angiography were performed at 1 hour in all eyes and 24 hours after exposure in selected eyes. Eyes were enucleated at 1 or 24 hours after lesion placement. The structure and extent of retinal lesions were scored for comparison with the clinical findings. RESULTS: Focal retinal pathologic appearance correlated well with a clinically visible lesion observed 24 hours after laser delivery. Retinal lesions were small foci of retinal pigment epithelium (RPE) and retinal disruption, without choriocapillaris involvement. Lesions that contained focal RPE vacuoles or lifting of the RPE also demonstrated leakage, in fluorescein angiographic studies. Suprathreshold laser delivery frequently caused focal columns of retinal injury and intraretinal hemorrhages from retinal vessel bleeding, with no rupture of choroidal blood vessels. CONCLUSIONS: The retinal response to ultrashort laser pulses at moderate energy followed a pattern of focal damage from laser-induced breakdown without significant thermal spread.

Animals↗

[Histopathological findings in cytomegalovirus retinitis].

PURPOSE: We examined eyeballs collected from autopsied acquired immunodeficiency syndrome patients with cytomegalovirus (CMV) retinitis, and analyzed the precise pathogenesis of CMV retinitis. MATERIAL AND METHODS: Eyeballs were fixed with 10% buffered formalin embedded in paraffin. CMV antigens were investigated by histopathological and immunohistochemical analyses. Histopathological findings were compared with funduscopic images. RESULTS: CMV antigens remained in the necrotic area of the retina and many CMV immediate early antigens existed in intact parts of the inner retina showing almost intact structure, and around retinal vessels. CONCLUSIONS: The results suggest that CMV infects the inner retina first via the retinal vessels, although funduscopic examination may appear normal. It extends through the neuronal cells and glial cells horizontally and Muller cells vertically. CMV severely damages the retinal structure.

AIDS-Related Opportunistic Infections↗

Ocular manifestations of Fabry's disease: data from the Fabry Outcome Survey.

BACKGROUND: Fabry's disease is an X-linked lysosomal storage disorder characterised by deficient activity of the enzyme alpha-galactosidase A. AIM: To study eye abnormalities in patients with Fabry's disease in the Fabry Outcome Survey (FOS). METHODS: This is the largest study of ocular manifestations in patients with Fabry's disease. In all, 173 of the 688 patients enrolled in FOS underwent a detailed ophthalmic examination, with a special focus on abnormalities of the cornea, lens, conjunctival and retinal vessels. RESULTS: Cornea verticillata was reported in 76.9% of females and 73.1% of males; vessel tortuosity was observed in 21.9% of females and in 48.7% of males. Fabry cataract was recorded in 9.8% of females and in 23.1% of males. Cornea verticillata was therefore the most frequently reported ophthalmic abnormality in Fabry's disease in both hemizygotic males and heterozygotic females. Tortuous conjunctival and retinal vessels and Fabry cataract were more frequently found in males than in females. Vessel tortuosity was more frequently observed in patients with a higher severity score and greater impairment of renal and cardiac function, suggesting that it may be associated with a more severe disease. The youngest patient with ocular changes was 3 years old. The prevalence of tortuous vessels in males increased with age. CONCLUSION: The presence of cornea verticillata is a useful aid in the diagnosis of Fabry's disease, as it is often present at the time of diagnosis. Vessel tortuosity may have some predictive value for systemic involvement.

Adolescent↗