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Comparison between histopathologic findings and indocyanine green angiographic findings in Lewis rats with experimental autoimmune uveoretinitis.

PURPOSE: Recently, indocyanine green angiography (IA) was used to examine chorioretinal circulation in posterior uveitis in humans, and abnormal IA findings were reported. However, choroidal pathologic examination in conjunction with these abnormal IA findings has rarely been done. Experimental autoimmune uveoretinitis (EAU) is a model for posterior uveitis in humans. The purpose of this study was to correlate abnormal IA findings in Lewis rats with EAU with pathologic findings. METHODS: Eleven male Lewis rats were immunized with bovine S-antigen in complete Freund's adjuvant with Bordetella pertussis. After immunization, IA was performed by using a scanning laser ophthalmoscope. Eyes with abnormal IA findings were enucleated and examined histopathologically. RESULTS: Demonstrated leakage from retinal vessels at the initial stage of disease; a decrease of background fluorescence and of the number of moderate and large vessels of the choroid, and leakage from choroidal vessels at the progressive stage; and hypofluorescent areas at the late stage. Histopathologic examination at the initial, progressive, and late stages revealed inflammation of the inner layers of the retina, a large number of inflammatory cells in the thickened retina and choroid, and impaired choroidal capillaries, respectively. CONCLUSION: Since a correlation between pathologic findings and IA findings was demonstrated in Lewis rats with EAU, IA may be useful for evaluating the severity of uveitis in humans.

Animals↗

[Ocular involvement in rheumatoid arthritis].

The authors evaluated ocular involvement in 23 patients affected by rheumatoid arthritis (RA) according to ARA criteria. Slit-lamp biomicroscopic examination showed signs of keratoconjunctivitis sicca in one patient (4%), while a positive bilateral Schirmer test was found in six subjects (26%). Fluorescein angiography, carried out in 11 of the 23 RA patients, showed retinal vasculitis in 18% of the patients examined, even if no clinical and ophthalmoscopic signs of retinal vessel inflammation were present. The authors suggest that fluorescein angiography should be performed in patients affected by particularly active RA, with recent onset of the disease (< 12 months), high titres of classical IgM rheumatoid factor and raised concentrations of circulating immune complexes. The study confirmed moreover the uncommon ocular toxicity related to the drugs frequently employed in RA treatment (antimalarials, gold salts, glucocorticoids). Indeed, only one case (4%) of posterior subcapsular cataract clearly related to steroid therapy was found.

Adult↗

Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of a single treatment in a phase 1 and 2 study.

OBJECTIVE: To evaluate the safety and short-term visual and fluorescein angiographic effects of a single photodynamic therapy treatment with verteporfin with the use of different dosage regimens in patients with choroidal neovascularization (CNV) from age-related macular degeneration. DESIGN: Nonrandomized, multicenter, open-label, clinical trial using 5 dosage regimens. SETTING: Four ophthalmic centers in North America and Europe providing retinal care. PARTICIPANTS: Patients with subfoveal CNV caused by age-related macular degeneration. METHODS: Standardized protocol refraction, visual acuity testing, ophthalmic examination, color photographs, and fluorescein angiograms were used to evaluate the effects of a single treatment of photodynamic therapy with verteporfin. Follow-up was planned through 3 months in 97 patients and for less than 3 months in 31 other patients. RESULTS: The mean visual acuity change (and range of change) from baseline at the follow-up examination at week 12 after a single treatment with regimens 1 through 5 was -0.2 (-3 to +2), -0.9 (-9 to +5), -1.6 (-9 to +2), +0.4 (-8 to +7), and +0.1 (-8 to +9) lines, respectively. Only the highest light dose (150 J/cm2) in regimens 2 and 3, which produced angiographic nonperfusion of neurosensory retinal vessels, caused marked vision loss. Some cessation of fluorescein leakage from CNV was achieved without loss of vision when the light dose used was less than 150 J/cm2. Systemic adverse events were rare. Cessation of fluorescein leakage from CNV was noted in all regimens by 1 week after photodynamic therapy. Fluorescein leakage from at least a portion of the CNV reappeared by 4 to 12 weeks after treatment in almost all cases. Progression of classic CNV beyond the area of CNV identified before treatment was noted in 42 (51%) of the 83 eyes with classic CNV followed up for 3 months after a single treatment. Eyes in which the area of any CNV leakage at 12 weeks was less than at baseline had a significantly better visual acuity outcome (+0.8 line) than eyes in which CNV leakage progressed (-0.8 line). CONCLUSIONS: Photodynamic therapy with verteporfin achieved short-term cessation of fluorescein leakage from CNV without loss of vision or growth of classic CNV in some patients with age-related macular degeneration. Except for nonperfusion of neurosensory retinal vessels at a light dose of 150 J/cm2, no other adverse events were of concern. Randomized clinical trials to investigate whether this new modality can preserve vision in patients with CNV secondary to age-related macular degeneration are justified.

Aged↗

Coats-like lesions in Usher syndrome type II.

BACKGROUND: An unusual case of Usher syndrome type II associated with bilateral Coats-like exudative retinopathy is described. METHODS: A 14-year-old boy with congenital sensorineural deafness and normal vestibular functions presented with a recent history of night blindness. He was followed for 3 years with fundus photography, intravenous fluorescein angiography, electroretinography and audiometric testings. His parents refused any form of treatment. RESULTS: Fundoscopy showed bilateral retinitis pigmentosa and a single focus of subretinal exudation and overlying telangiectatic retinal vessels inferotemporal to the vascular arcade in the right eye. He had bilateral mild macular edema. A year later, a similar lesion developed inferotemporally in the left fundus. Electroretinography responses, particularly the rod-mediated signals, were significantly reduced. Audiometric studies documented hearing loss in high frequencies. His visual acuity declined from 20/40 to 20/80 RE and from 20/80 to 20/100 LE during follow-up. No new lesions developed. CONCLUSIONS: Coats-type exudative lesions may develop in patients with Usher syndrome type II. Although left untreated, only a minimal increase in exudation occurred over 3 years.

Adolescent↗

Correlations between electroretinography, morphology and function in retinitis pigmentosa.

In a retrospective study, data from 116 patients suffering from different forms of retinitis pigmentosa were analysed, and 15 categories comprising altogether 34 symptoms or clinical signs were tabulated from each patient's record. The 15 categories evaluated were: visual acuity, visual field diameter, ring or central scotoma, nyctalopia, susceptibility to glare, refraction, cataract, electroretinography, colour of the optic disc, bone-spicule pigmentation of the retina, retinal vessel diameters, tapetoretinal reflex, sex, heredity, and age. Correlations between the tabulated 34 subcategories or symptoms were calculated. The results of a factorial analysis of the data showed a high number of highly significant correlations between the different categories. It seemed possible to discriminate between two groups of categories, with the members of each group being closely correlated but correlations with members of the other group being much smaller, if not nonexistent. We tentatively associated the first group with the functional state of the central retina and the second group with the state of the peripheral retina.

Adolescent↗

The ocular manifestations in Fabry's disease.

We present the ocular manifestations in a series of 37 hemizygous male and 25 heterozygous female patients with Fabry's disease. The ocular findings typically do not impair vision, but are unique and diagnostic. Whorl-like corneal deposits were seen in almost all patients and were more severe in the heterozygotes. The lens showed cream-colored anterior capsular deposits, sometimes in striking "propeller" distribution, in one third of the hemizygotes, and in none of the heterozygotes. A faint but unique posterior capsular opacity with a branching radial pattern was seen in 37% of the hemizygotes and 14% of the heterozygotes. Conjunctival vessel aneurysmal dilations and retinal vessel tortuosity were both more frequent and severe in the hemizygotes. Severe visual loss occurred in two hemizygotes as a result of unilateral total central artery occlusions.

Adolescent↗

Ophthalmodynamometric assessment of the central retinal vein collapse pressure in eyes with retinal vein stasis or occlusion.

PURPOSE: Using a new Goldmann contact lens associated ophthalmodynamometric device, it was the purpose of the present study to determine the central retinal vein collapse pressure in eyes with retinal vein occlusions or retinal venous stasis. METHODS: The prospective clinical non-interventional comparative study included 19 patients with central retinal vein occlusion ( n=8), branch retinal vein occlusion (n=4), or retinal venous stasis (n=7) and 42 subjects of a control group. With topical anesthesia, a Goldmann contact lens fitted with a pressure sensor was put onto the cornea. Pressure was exerted on the globe by pressing the contact lens, and the pressure value at the time when the central retinal vein started pulsating was noted. RESULTS: Central retinal vein collapse pressure measured 103.6+/-25.4 arbitrary units (AU) in eyes with central retinal vein occlusion what was significantly higher than in the eyes with retinal venous stasis (58.1+/-37.5 AU; p=0.02) and the eyes with branch retinal vein occlusion (43.8+/-25.5 AU; p=0.004). In the latter two groups, the measurements of the central retinal vein collapse pressure were significantly (p<0.001) higher than the measurements in the eyes of the control group (4.2+/-7.8 AU). CONCLUSION: As measured by a new ophthalmodynamometer with direct biomicroscopic visualization of the central retinal vessels during examination, central retinal vein collapse pressure is significantly higher in eyes with central retinal vein occlusion, followed by eyes with branch retinal vein occlusion, eyes with retinal venous stasis and, finally, normal eyes. These findings may have diagnostic and therapeutic implications.

Adult↗

Breakdown of the blood-retinal barrier induced by activated T cells of nonneural specificity.

The cellular and microvascular responses of JC Lewis rats to an intravenous injection of activated T cells specific for ovalbumin were examined with the retinal whole mount technique. The retina was examined at various times post-injection (pi) with the use of antibodies to the alphabeta T cell receptor (TCR) or to major histocompatibility complex class II (MHC II), the monoclonal antibody ED1, and intravascular tracers. By 12 hours pi, small numbers of TCR(+), ED1(+), and MHC II(+) cells were present within the lumen of retinal vessels, and minor breakdown of the blood-retinal barrier (BRB) and microglial activation were evident. The intensity of these responses had increased by 1 day pi, when small numbers of TCR(+) cells had also undergone extravasation. By 2 to 3 days pi, the numbers of TCR(+), ED1(+), and MHC II(+) cells in the retinal parenchyma had increased, but the BRB breakdown and microglial activation had subsided. Thus, in the absence of target antigen, activated T cells induced limited and transient breakdown of the BRB, microglial activation, and the extravasation of ED1(+), MHC II(+) monocytes. In contrast, the retina of rats that received an intraocular injection of ovalbumin in addition to the intravascular injection of T cells showed massive cellular recruitment and breakdown of the BRB. These results indicate that an increase in the number of activated T cells in the circulation, such as that which occurs during viral or bacterial infection, has the potential to result in transient breakdown of the BRB and a mild local microglial response.

Animals↗

Coats' disease and persistent hyperplastic primary vitreous. Role of MR imaging and CT.

Coats' disease is an idiopathic disorder in which telangiectatic and aneurysmal retinal vessels leak a lipoproteinaceous exudate, with consequent bullous retinal detachment. It is a diagnostic challenge, and CT and MR imaging provide valuable information to differentiate it from other pathologies, particularly from retinoblastoma. Typical, advanced Coats' disease shows on CT a denser substance posterior to the vitreous, which on MR is hyperintense on all pulse sequences. Contrast administration on both CT and MR might give slight linear enhancement at the boundary between vitreous and exudation. Persistent hyperplastic primary vitreous (PHPV) is a unilateral disorder in a microphthalmic eye, seen in full-term infants. PHPV rarely is bilateral in patients with Norrie's disease, Warburg syndrome, or patients with retinal dysplasia. Persistent fetal vasculature leads to fibrosis, resulting in elongation of the ciliary processes, retinal detachment, and spontaneous cataracts. The CT appearance in the disorder is quite variable; however, MR imaging may be superior in demonstrating the enhancing retrolental mass and the elongated ciliary processes.

Aneurysm↗

When and how to do a grid laser for diabetic macular edema.

Macular edema is a common feature of posterior segment diseases. It is an expression of abnormal permeability in either retinal vessels (inner blood-retinal barrier) or in the retinal pigment epithelium (outer blood-retinal barrier). It occurs in either a diffuse pattern where the macula appears generally thickened or, in more severe cases, as cystoid edema with the typical petaloid appearance. Grid laser treatment may be useful to reduce macular edema. Spots of 100-250 micrometers in diameter are applied to the whole posterior pole, one to two groups apart. The foveal avascular zone remains untouched. In patients treated bilaterally, areas temporal and nasal to the macula must be spared to prevent the development of deep scotomas. The mechanism yielding positive results with the grid technique is still debated. Among the most reliable hypotheses are: Proliferation of pigment epithelial cells, followed by and improved efficiency of the outer blood-retinal barrier; proliferation of endothelial cells in retinal capillaries followed by an improved efficiency of the inner blood-retinal barrier; improvement of the retinochoroidal exchanges, and finally, release by coagulative necrosis of a factor able to improve the efficiency of the blood-retinal barriers. Lasers with long wavelengths, such as krypton red and diode, are the most appropriate ones to perform grid treatment.

Blood-Retinal Barrier↗

Age-related normal tolerance intervals for retinal vascular response to systemic autonomic nerve stimulation.

This study establishes the age-adjusted tolerance intervals for retinal vascular responses to sustained handgrip contraction (a test of sympathetic nerve function). Forty adult subjects (mean age: 39.7 +/- 14.1 years, range: 20 to 72 years; 19 males) were included in the final analysis. Mean percentage calibre change in response to sustained handgrip contraction in this population was -5.61% with a significant correlation between subject age and percentage retinal vessel calibre change (p less than 0.001). Mean retinal arteriolar calibre change in response to systemic autonomic stimulation varied significantly with age: between -8.48% at age 20 years and -2.06% at age 70 years with a mean of -5.95% at the mean age of 39.7 years. The standard deviation is 3.04% and the 95% confidence intervals were set between +/-6.17%. This autoregulatory reflex appears to be inversely related to age.

Adult↗

A prospective cohort study of retinal arteriolar narrowing and mortality.

The authors examined the relation of narrowed retinal arteriolar diameters, a marker of hypertensive damage, to mortality in a population-based cohort of 4,926 persons aged 43-84 years living in Wisconsin. A computer-assisted method was used to measure retinal vessel diameters from digitized retinal photographs taken at the baseline examination (1988-1990). These measurements were summarized as the retinal arteriole-to-venule ratio (AVR), with a smaller AVR indicating narrower arterioles compared with venules. Its relation to 10-year mortality was analyzed by using Cox proportional hazards models, adjusting for age, gender, blood pressure, diabetes, and other risk factors. No relation was found between smaller AVR and increased mortality. In relation to the largest AVR quartile, the adjusted relative risks of all-cause mortality were 0.93 for the smallest AVR quartile, 0.71 for the second AVR quartile, and 0.80 for the third AVR quartile. Results were largely similar in analyses of cause-specific mortality (vascular disease and non-vascular-disease mortality) and in subgroups stratified by age, gender, and diabetes and hypertension status. These data contrast with recent studies showing a relation between narrowed retinal arterioles and increased cardiovascular risk, suggesting that further research is needed to understand the systemic associations of retinal microvascular changes.

Adult↗

Congenital retinal arterial loops with spontaneous vitreous hemorrhage.

A young adult demonstrated a spontaneous vitreous hemorrhage in an eye which harbored two retinal arterial loops, with bleeding originating in the area of the larger loop. These congenital vascular anomalies characteristically originate on the optic disk and terminate by anastomosing with or forming a retinal vessel. Although uncommon, congenital retinal arterial loops can no longer be thought innocuous and must be considered when decreased visual acuity occurs.

Adult↗