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PubMed2006

C-peptide does not affect ocular blood flow in patients with type 1 diabetes.

OBJECTIVE: The aim of the present study was to investigate the effect of intravenous C-peptide infusion on ocular blood flow in patients with type 1 diabetes under euglycemic conditions. RESEARCH DESIGN AND METHODS: The study was performed in a randomized, placebo-controlled, double-masked, two-way, crossover design in 10 type 1 diabetic patients. C-peptide was intravenously administered at two different dosages (dosage 1: 25 pmol . kg(-1) . min(-1) bolus followed by 5 pmol . kg(-1) . min(-1) continuous infusion; dosage 2: six times higher than dosage 1), each for 60 min. Physiologic saline solution was used as a control for C-peptide on a different study day. On both study days, euglycemic clamps were performed. To assess retinal blood flow, laser Doppler velocimetry (blood flow velocities) and retinal vessel analyzer (vessels diameters) measurements were performed. Laser interferometric measurements of fundus pulsation were used to assess pulsatile choroidal blood flow. Blood velocities in the ophthalmic artery were measured using color Doppler imaging. RESULTS: Eight patients (two female and six male) completed the study according to the protocol and without adverse events. One patient developed an anaphylactic reaction to C-peptide, which resolved without sequelae. The following results originate from the remaining eight subjects. Systemic hemodynamic parameters remained stable during both study days. Infusion of C-peptide did not affect any ocular hemodynamic parameter. CONCLUSIONS: The data of the present study indicate that exogenous C-peptide exerts no effect on ocular hemodynamic parameters in type 1 diabetic patients under euglycemic conditions. The maximum detectable change in these parameters was <25%.

Adult↗

PubMed2003

Early upregulation of kinin B1 receptors in retinal microvessels of the streptozotocin-diabetic rat.

(1) Retinal microvessel responses to kinin B1 and B2 receptor agonists and antagonists were investigated in streptozotocin (STZ)-diabetic rats and age-matched controls. In addition, quantitative in vitro autoradiography was performed on retinas from control and STZ-diabetic rats with radioligands specific for B2 ([125I]HPP-Hoe 140), and B1 receptors ([125I]HPP-[des-Arg10]-Hoe 140). (2) In control rats, the B2 receptor agonist bradykinin (BK, 0.1-50 nm) vasodilated retinal vessels in a concentration and time-dependent manner. This effect was completely blocked by the B2 receptor antagonist Hoe140 (1 microm). In contrast, the B1 receptor agonist des-Arg9-BK (0.1-50 nm) was without effect. (3) Des-Arg9-BK was able to produce a concentration-dependent vasodilatation as early as 4 days after STZ injection, and the effect of 1 nm des-Arg9-BK was inhibited by the B1 receptor antagonist des-Arg10-Hoe140 (1 microm). Low-level B1 receptor binding sites were detected in control rats, but densities were 256% higher in retinas from 4- to 21-day STZ-diabetic rats. (4) In control rats, the vasodilatation in response to 1 nm BK involved neither calcium influx nor nitric oxide (NO) as GdCl3 and l-NAME were without effect. However, the vasodilatation did involve intracellular calcium mobilization as well as products of the cyclooxygenase-2 (COX-2) pathway as 2,5-di-t-butylhydroquinone (BHQ), cADP ribose and l-745 337 inhibited this response. The vasodilatation response was blocked by trans-2-phenyl cyclopropylamine (TPC) demonstrating that prostacyclins mediate this response. (5) In STZ-diabetic rats, the vasodilatation in response to des-Arg9-BK involved both calcium influx and intracellular calcium mobilization from stores both IP3 sensitive and non-IP3 sensitive. Indeed, the effect was blocked by GdCl3, BHQ and cADP ribose. Furthermore, NO production and products of the COX-2 pathway including prostacyclin are involved as the response was inhibited by l-NAME, l-745 377 and TPC. (6) Vasodilatation in response to either 1 nm BK or 1 nm des-Arg9-BK were blocked by NF023 demonstrating that a Go/Gi G-protein transduces both these effects. (7) This is the first report on the retinal circulation which provides evidence for vasodilator B2 receptors and the upregulation of B1 receptors very early following induction of diabetes with STZ rats. These results suggest that kinin receptors may be potential targets for therapeutics to treat retinopathies.

Animals↗

PubMed2000

[Effect of dark adaptation on retinal blood flow].

PURPOSE: Laser Doppler measurements performed immediately after the transition from dark adaptation (DA) to light led to the hypothesis that retinal blood flow, Fret, is increased during DA, but the use of visible lasers had prevented measurements during DA. Our aim was to test this hypothesis by measuring Fret during and after DA. MATERIAL AND METHODS: Fret in retinal vessels at the optic disk surface was recorded quasi-continuously in one eye of 6 normal subjects (age 27 to 60 years) using a laser Doppler flowmeter in the near-infrared (810 nm). Measurements were performed during light (baseline), various periods of DA and again during light. DA lasted between 2 and 32 min. RESULTS: Average Fret for the 6 subjects did not change significantly (-2.7 +/- 8% sd, p > 0.05) during the various periods of DA, as determined from linear regressions of the flux versus time. Following the transition from DA to light, there was, in most cases, a rapid transient increase of the flux, which reached an average value of 37 +/- 10% above the pre-transition value and peaked at 30-60 sec after the transition. CONCLUSIONS: These results do not support the hypothesis that Fret in normal volunteers is increased during DA. Rather, they strongly suggest that the transient increase in flux observed after DA is induced by the transition from dark to light (FNSRS #3200-043157 et CNR, It. #95.01715.CT04).

Adaptation, Ocular↗

PubMedDate not supplied

[Color Doppler echography study of ocular blood flow velocity in patients with proliferative diabetic retinopathy after performance of retinal pan-photocoagulation: 2 years' follow-up].

PURPOSE: Color Doppler imaging allows for simultaneous two-dimensional anatomical imaging and Doppler measurement of blood flow velocity. Because hemodynamic changes have been seen in diabetic patients after photocoagulation by other techniques, the authors compared 25 eyes with proliferative diabetic retinopathy before, 6 months, 1 year, and 2 years after panretinal photocoagulation with a matched control group of 30 healthy volunteers. METHODS: The ophthalmic artery, short posterior ciliary artery, central retinal vessels and vortex veins of all patients were examined, and the systolic, diastolic and mean arterial velocities were measured. Panretinal photocoagulation was performed with these parameters: 800-1000 spots, 0.1s, 500 micron argon laser. RESULTS: Student's t test revealed that the perfusion velocity was significantly lower in diabetic patients than in normals (Vsystolic in the ophthalmic artery: 31.7 (6.7) cm/s vs 36.6 (7.0) cm/s, respectively, P = 0.03). After treatment, blood flow velocities were significantly lower than before photocoagulation (Vsystolic in the ophthalmic artery: 6 months after treatment 26.9 (7.2) cm/s, P = 0.018 and 1 year after photocoagulation 25.5 (7.0) cm/s, P = 0.009; and 2 years after photocoagulation, 25.7 (6.8) cm/s, P = 0.01). No statistically significant differences were found between 6 months, 1 year, and 2 years after panretinal photocoagulation. No significant correlations were found between age and blood velocities in diabetics and healthy volunteers. CONCLUSIONS: Eyes with proliferative diabetic retinopathy showed lower ocular perfusion velocities than normals. Photocoagulation resulted in a reduction in ocular blood flow velocities; these values did not change during 2 years of follow-up.

Adult↗

PubMed2000

Angiography of fluoresceinated anti-vascular endothelial growth factor antibody and dextrans in experimental choroidal neovascularization.

OBJECTIVE: To determine if anti-vascular endothelial growth factor antibody and a range of dextrans with varying diffusion radii and molecular weights are permeable through experimental choroidal neovascularization (CNV). METHODS: Choroidal neovascularization was induced in 10 cynomolgus monkey retinas by means of argon laser injury. Digital fundus fluorescein angiograms were performed with fluorescein sodium, fluoresceinated IgG antibodies (anti-vascular endothelial growth factor and a control antibody), and fluoresceinated dextrans with molecular weights of 4, 20, 40, 70 and 150 kd. The 40- and 70-kd dextrans straddle the effective diffusion radius of IgG. For each reagent, early and late angiograms were performed in a standardized fashion, with follow-up images obtained to monitor residual fluorescence. RESULTS: Perfusion of retinal vessels and choroidal vasculature was seen with all reagents. Fluorescein and 4- and 20-kd dextran leaked rapidly from the CNV within the first minute. Angiography with the use of 40-kd dextran and fluoresceinated antibody, either anti-vascular endothelial growth factor or control IgG, showed fluorescence within the CNV that increased during the first 1 to 5 hours, with mild leakage from the CNV. By 24 hours, fluorescence in the CNV was minimal, although in some cases persistent fluorescence in the surrounding tissue was evident up to 2 weeks. The 70-kd dextran showed fluorescence within the CNV and leakage in 1 of 3 eyes. The 150-kd dextran showed fluorescence within the CNV but did not demonstrate leakage. CONCLUSIONS: Fluoresceinated antibodies and dextran with smaller effective diffusion radii showed CNV perfusion and leakage. Dextrans with larger effective diffusion radii (70 kd and 150 kd) perfused into CNV but did not show leakage consistently. CLINICAL RELEVANCE: Determining the permeablity of antibodies and molecules of similar size through CNV can help ascertain the feasibility of using intravenously administered antibodies against angiogenic growth factors as a future treatment for choroidal neovascularization.

Animals↗

PubMed2002

Is the nasal optic disc sector important for morphometric glaucoma diagnosis?

BACKGROUND/AIM: Since the central retinal vessel trunk usually located in the nasal optic disc sector can render difficult the delineation of the neuroretinal rim and optic disc, the aim of this study was to evaluate whether the nasal region of the optic nerve head is important, or can be left out, for the morphometric glaucoma diagnosis. METHODS: The clinical observational study included 1337 patients with primary or secondary open angle glaucoma and 649 normal subjects. The glaucoma group was divided into 1187 patients with glaucomatous visual field defects ("perimetric glaucoma"), and into 150 patients with optic nerve head changes and normal visual fields ("preperimetric glaucoma"). Colour stereo optic disc photographs were morphometrically evaluated. RESULTS: Highest diagnostic power for the separation between the normal group and the perimetric glaucoma group, and for the differentiation between the normal group and the preperimetric glaucoma group, had the sum of inferotemporal rim area plus superotemporal rim area, the sum of inferotemporal rim area plus superotemporal rim area plus temporal rim area, and the inferotemporal rim area as single parameter. The lowest diagnostic precision had the nasal rim area as single parameter or in combination with rim measurements in other disc sectors. CONCLUSION: Excluding the nasal optic disc sector does not markedly decrease the diagnostic power of morphometric optic disc analysis in glaucoma diagnosis. It may have importance for an automated computerised morphometric detection of glaucomatous optic nerve damage.

Adult↗

PubMed2000

Acquired tumors arising from congenital hypertrophy of the retinal pigment epithelium.

BACKGROUND: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is widely recognized to be a flat, stationary condition. Although it can show minimal increase in diameter, it has not been known to spawn nodular tumor that is evident ophthalmoscopically. OBJECTIVES: To report 5 cases of CHRPE that gave rise to an elevated lesion and to describe the clinical features of these unusual nodules. METHODS: Retrospective medical record review. RESULTS: Of 5 patients with a nodular lesion arising from CHRPE, there were 4 women and 1 man, 4 whites and 1 black. Three patients were followed up for typical CHRPE for longer than 10 years before the tumor developed; 2 patients were recognized to have CHRPE and the elevated tumor concurrently. Visual acuity was decreased in 3 patients, mainly due to cystoid macular edema. The tumor was located between the equator and ora serrata in all 5 patients. There was no predilection for quadrant of the fundus. The flat part of the lesion was black and had visible lacunae in all 5 patients. The CHRPE ranged in basal diameter from 3 x 3 mm to 13 x 11 mm. The size of the elevated lesion ranged from 2 x 2 x 2 mm to 8 x 8 x 4 mm. The nodular component in all cases was supplied and drained by slightly prominent, nontortuous retinal blood vessels. Yellow retinal exudation occurred adjacent to the nodule in all 5 patients and 1 patient developed a secondary retinal detachment. Two tumors that showed progressive enlargement, increasing exudation, and progressive visual loss were treated with iodine 125-labeled plaque brachytherapy, resulting in deceased tumor size but no improvement in the visual acuity. CONCLUSIONS: Congenital hypertrophy of the retinal pigment epithelium can spawn a nodular growth that slowly enlarges, attains a retinal blood supply, and causes exudative retinopathy and chronic cystoid macular edema. Although no histopathologic evidence is yet available, we believe that the tumor probably represents either an acquired adenoma or a reactive proliferation of the retinal pigment epithelium. The best treatment of these lesions is not yet established.

Adenoma↗

PubMed1992

Late ultrastructural changes in the retina of the rat following low-dose X-irradiation.

This study describes ultrastructural changes in the pigmented hooded Lister rat retina, 3-12 months following X-irradiation with single doses of between 200 and 2000 cGy. The extreme radiosensitivity of the photoreceptor cells was underlined by the continued manifestation of fine structural changes and cell death up to 6 months post-radiation in animals receiving doses above 500 cGy. The retinal pigment epithelial (RPE) cells were more radioresistant than photoreceptors and RPE cell loss was only observed at doses of more than 1500 cGy. One year after irradiation with 1500 cGy the retinal vasculature showed capillary occlusion with some evidence of recanalisation. Telangiectasia was observed in the large retinal veins. Although the inner retinal neurones and glial cells showed no evidence of direct radiation damage, the nerve fibre layer adjacent to occluded retinal vessels demonstrated ultrastructural evidence of ischaemic neuropathy and retinal oedema. At doses above 1500 cGy the choriocapillaris showed platelet aggregation and capillary loss.

Animals↗

PubMed2000

Photodynamic therapy of choroidal hemangioma: two case reports.

BACKGROUND: Photocoagulation, cryotherapy and radiotherapy have been used to treat angiomatous lesions. Depending on the location of the angioma, these treatments can cause additional, significant functional damage. Photodynamic therapy (PDT) however, allows a selective occlusion of vascular lesions without damaging adjacent retinal structures. METHODS: Two patients with isolated choroidal hemangiomas involving the posterior pole were treated with PDT. Treatments were performed using a diode laser at 692 nm, a light dose of 100 J/cm2 and 6 mg/m2 body surface area verteporfin (BPD-MA). PDT was applied in two courses in one eye and in four in the other eye at 1-4 months intervals. Patients were followed up for 9-12 months with visual acuity measurements and dilated ophthalmoscopy. Ultrasound, indocyanine green angiographic and fluorescein angiographic images were evaluated at each visit. RESULTS: Tumor heights were 3.3 and 4.6 mm on pretreatment ultrasound. After therapy, patients with isolated choroidal hemangioma showed total regression of the lesion and improved visual acuity due to resorption of retinal edema. Serous retinal detachment and cystoid macular edema resolved. Ultrasound demonstrated a progressive decrease in tumor height after each PDT application, with complete disappearance of the lesion. Retinal vessels were not affected by the treatment, and retinal function recovered in areas with previous tumor involvement. CONCLUSION: PDT allows selective treatment of large intraocular angiomatous lesions. Without optimized parameters, complete regression of choroidal hemangiomas, resolution of secondary complications and improvement of visual acuity were documented.

Adult↗

PubMed2006

Recent developments in optical coherence tomography for imaging the retina.

Optical coherence tomography (OCT) was introduced in ophthalmology a decade ago. Within a few years in vivo imaging of the healthy retina and optic nerve head and of retinal diseases was a fact. In particular the ease with which these images can be acquired considerably changed the diagnostic strategy used by ophthalmologists. The OCT technique currently available in clinical practice is referred to as time-domain OCT, because the depth information of the retina is acquired as a sequence of samples, over time. This can be done either in longitudinal cross-sections perpendicular to, or in the coronal plane parallel to the retinal surface. Only recently, major advances have been made as to image resolution with the introduction of ultrahigh resolution OCT and in imaging speed, signal-to-noise ratio and sensitivity with the introduction of spectral-domain OCT. Functional OCT is the next frontier in OCT imaging. For example, polarization-sensitive OCT uses the birefringent characteristics of the retinal nerve fibre layer to better assess its thickness. Blood flow information from retinal vessels as well as the oxygenation state of retinal tissue can be extracted from the OCT signal. Very promising are the developments in contrast-enhanced molecular optical imaging, for example with the use of scattering tuneable nanoparticles targeted at specific tissue or cell structures. This review will provide an overview of these most recent developments in the field of OCT imaging focussing on applications for the retina.

Humans↗

PubMed1967