Oliver Arend

Retinal microcirculation in patients with diabetes mellitus: dynamic and morphological analysis of perifoveal capillary network.

The new scanning laser technique allows one to quantify the retinal microcirculation. A digital image analysing system was used to study capillary blood flow velocities and morphological parameters of perifoveal intercapillary areas and foveal avascular zones in normal and diabetic subjects. Diabetic patients showed a significant reduction in capillary blood cell velocities in comparison with normal subjects. Perifoveal intercapillary areas and foveal avascular zones were significantly increased in all stages of diabetic retinopathy, and both parameters increased with progressing diabetic retinopathy. Significant changes in the perifoveal intercapillary areas were observed between normal subjects and patients with no retinopathy.

Retinal Hemodynamics Using Scanning Laser Ophthalmoscopy and Hemorheology in Chronic Open-angle Glaucoma

PURPOSE Recent studies suggest that elevated intraocular pressure is not the only causative factor for the development of visual field loss and optic nerve damage in glaucomatous eyes. The authors determine whether retinal hemodynamics or blood fluidity are alternated in eyes of patients with open-angle glaucoma compared with those of age- and sex-matched healthy subjects. METHOD High-quality video fluorescein angiograms were obtained from single eyes of 51 patients with chronic open-angle glaucoma. From these angiograms, the arm-retina time, mean dye velocity, and arteriovenous passage time were quantified. The data from patients were compared with those of an age- and sex-matched group of healthy subjects. RESULTS In patients with chronic open-angle glaucoma, an 11% reduction of the mean dye velocity (P < 0.05) and a 41% prolongation of the arteriovenous passage time (P < 0.01) was observed relative to the values obtained among the control subjects. Among hematocrit values, plasma viscosity, and erythrocyte aggregation, only plasma viscosity showed a significant increase (4%; P < 0.01) in patients with chronic open-angle glaucoma. CONCLUSION These results indicate that a pronounced circulatory deficit exists within the retinal vasculature of glaucomatous eyes, which may coexist with, but cannot be fully attributed to, an increase in plasma viscosity.

Retinal Capillary Blood Flow Measurement with a Scanning Laser Ophthalmoscope Preliminary Results

The scanning laser technique in combination with digital image analysis allows direct objective measurement of flow velocities in perimacular capillaries. In addition, the complete macular network of capillaries can be observed. By means of digital frame-to-frame picture analysis of digital recordings, blood flow velocities and morphologic data have been measured. The mean flow velocity in perimacular capillaries observed with the scanning laser ophthalmoscope in healthy subjects (n = 21) amounted to 3.28 +/- 0.45 mm/second. In patients (n = 13) with diabetes mellitus (no or background retinopathy), the mean flow velocity was significantly reduced (2.89 +/- 0.57 mm/seconds) compared with healthy subjects. Morphologic data of the perifoveal capillary bed showed a significant reduction of capillaries in patients with diabetes mellitus when compared with healthy subjects.

Hyperoxia improves contrast sensitivity in early diabetic retinopathy.

AIM: The cause of vascular and visual pathology in diabetic retinopathy remains unknown. If retinal hypoxia plays a role, then early in the course of diabetes 100% oxygen breathing should normalise both contrast sensitivity and retinal blood flow. METHODS: This hypothesis was tested in 12 diabetic patients with minimal retinopathy who, none the less, exhibited reduced contrast sensitivity (p = 0.003 versus 12 age and sex-matched controls) and prolonged retinal arteriovenous dye transit (p = 0.0001 versus controls). RESULTS: Isocapnic hyperoxia failed to alter contrast sensitivity in controls, while it significantly improved contrast sensitivity in patients (at 12 cpd; p = 0.042) to levels indistinguishable from normal. Individual improvement in contrast sensitivity correlated positively with the severity of the initial defect (r = +0.84, p = 0.0008). Hyperoxia also had haemodynamic effects; it slowed retinal arteriovenous passage of fluorescein dye in controls, but did not further slow this transit time in patients. CONCLUSIONS: These results demonstrate the reversibility of early contrast sensitivity deficits in diabetes mellitus, and support the hypothesis that factors linked to tissue hypoxia initiate both visual and vascular dysfunction in diabetic retinopathy.

A comparative study of betaxolol and dorzolamide effect on ocular circulation in normal-tension glaucoma patients

OBJECTIVE To determine whether dosages of a selective beta-blocking agent (betaxolol) and a topical carbonic anhydrase inhibitor (dorzolamide), sufficient to significantly lower intraocular pressure (IOP), have similar or disparate impact on the retinal and retrobulbar circulation. DESIGN Counterbalanced crossover, with open-label use of medications. PARTICIPANTS Nine persons with normal-tension glaucoma (NTG). INTERVENTION After a 3-week drug washout, NTG patients were studied after 1 month of treatment with either dorzolamide or betaxolol, with determinations of IOP and retinal and retrobulbar hemodynamics. MAIN OUTCOME MEASURES At baseline and after treatment with each drug, retinal arteriovenous passage time was determined by scanning laser ophthalmoscopy after fluorescein dye injection, and flow velocities in the central retinal and ophthalmic arteries were measured with color Doppler ultrasonography imaging. RESULTS Betaxolol and dorzolamide each lowered IOP significantly, with these changes apparent and maximal after 2 weeks (each P < 0.05). In contrast, dorzolamide (but not betaxolol) accelerated arteriovenous passage of fluorescein dye in the inferior temporal quadrant of the retina (P < 0.05). Neither drug affected arteriovenous passage in the superotemporal retina or any aspect of central retinal or ophthalmic artery flow velocity after either 2 or 4 weeks. CONCLUSIONS Although both dorzolamide and betaxolol are effective ocular hypotensive agents and their topical instillation leaves retrobulbar hemodynamics unaltered, dorzolamide alone accelerates inferotemporal retinal dye transit.

Hemodilution therapy in central retinal vein occlusion

Systemic hemorheologic abnormalities may play a part in the pathogenesis of central retinal vein occlusions. A statistically significant elevation of plasma viscosity was found in patients with acute central retinal vein occlusion compared with control patients. Local retinal blood flow parameters including arteriovenous passage time and mean arterial dye bolus velocity were significantly altered in the central retinal vein occlusion patients compared with age-matched controls at baseline examination. We performed a randomized, prospective, single-blind clinical investigation to determine the effect of hemorheological manipulation on the clinical course and retinal blood flow of eyes with central vein occlusion. Hemodilution included plasma expansion with hydroxyethyl-starch, withdrawal of whole blood if the hematocrit was above 42%, and rheologic manipulation with parenteral pentoxifylline. We found a statistically significant improvement in visual acuity at 1 year post-treatment for the treated group compared with the control group (increase of visual acuity of 1.5 lines vs decrease of 1.5 lines). The retinal blood flow parameters were markedly improved soon after the institution of therapy, and this may have contributed to the improvement in visual acuity in the treated group. There was no statistically significant difference between the two groups in the progression to ischemic central vein occlusion.

Measurement of retinal hemodynamics with scanning laser ophthalmoscopy: Reference values and variation

High resolution video fluorescein angiography using scanning laser ophthalmoscopy allows the assessment of retinal macro- and microcirculation. Data on the retinal macrocirculation were obtained from 221 healthy subjects. The data were derived from estimations of the arm-retina time, the arteriovenous passage time and mean arterial dye velocity, characterizing the passage of fluorescein to the eye, the mean arterial plasma velocity, and the arteriovenous passage through the entire vascular bed of one segment. Additionally, the transit of hypofluorescent segments in the capillary macular network were measured in 90 healthy subjects. These parameters provide a wide range of information for understanding the physiology of healthy and diseased eyes. Fundamental for all interpretations is the knowledge of the physiological variations. In the present study the inter- and intraindividual variability of retinal hemodynamics in healthy volunteers were assessed. The interindividual variation was 23.8% for the arm-retina time, 20.7% for the arteriovenous passage time, 23.7% for the mean arterial dye velocity, and 14.2% for the capillary flow velocity; the coefficient for variation, characterizing the intraindividual variation, was 26.6%, 15.6%, 16.7%, and 7.9%, respectively. The knowledge of the inter- and intraindividual variation of retinal blood flow indices allows for a priori power estimations for pathophysiologic and pharmacological studies.

Colour Doppler imaging and fluorescein filling defects of the optic disc in normal tension glaucoma

Aim: To investigate the relation between blood flow parameters of the retrobulbar vessels measured by means of colour Doppler imaging (CDI) and fluorescein filling defects of the optic nerve head in patients with normal tension glaucoma (NTG) and control subjects. Methods: 29 patients with NTG and 29 age and sex matched control subjects were included in this study. Blood flow velocities—peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive indices (RI) of the ophthalmic artery (OA), the central retinal artery (CRA), and of the temporal and nasal short posterior ciliary arteries (TPCA, NPCA)—were measured with CDI. Fluorescein angiograms were performed with a scanning laser ophthalmoscope. The extent of absolute fluorescein filling defects of the optic nerve head in relation to the optic nerve head was assessed. Results: The PSV of the OA, the PSV and EDV of the CRA, and of the TPCA and NPCA were significantly reduced in NTG (p<0.05). The RI of the CRA, the TPCA and NPCA were significantly increased in NTG (p<0.01). The optic nerve head fluorescein filling defects were significantly larger in NTG (p<0.01). The filling defects were significantly negatively correlated (p<0.05) with the PSV and EDV of the CRA (PSVCRA: r = −0.41; EDVCRA: r = −0.34), with the PSV and EDV of the NPCA (PSVNPCA: r = −0.34; EDVNPCA: r = −0.38), and with the EDV of the TPCA (r = −0.29). A significant positive correlation (p<0.05) was found with the RI of both PCAs (RINPCA: r = 0.28; RITPCA: r = 0.29). Conclusion: Patients with NTG had reduced blood flow velocities and higher resistive indices in most retrobulbar vessels. Optic nerve head fluorescein filling defects were larger compared to controls. The filling defects were correlated with end diastolic velocities and resistive indices of the PCAs and with blood flow velocities of the CRA. Capillary loss of the optic nerve head may be related to higher downstream resistance and reduced blood flow velocities of the retrobulbar vessels.

Perifoveal microcirculation with non-insulin-dependent diabetes mellitus

Fluorescein angiograms were performed to evaluate perifoveal capillary blood velocities (v), capillary density (perifoveal intercapillary areas: PIA) and the foveal avascular zone (FAZ) by means of the scanning laser technique (SLO-101 Rodenstock). The angiograms were digitally stored and the data quantified off-line with an image analyzing system (IBAS). In the present study 46 patients with non-insulin-dependent diabetes mellitus (NIDDM) were examined and their data compared with that of 31 healthy volunteers. The perifoveal capillary flow velocity of the NIDDM subjects (v = 2.33±0.36 mm/s) was significantly (P <0.01) decreased as compared to healthy subjects (v = 2.86 ±0.41 mm/s). The perifoveal intercapillary areas in the foveal avascular zone were significantly increased in patients with NIDDM (PIA=10029 ± 3402 μm2; FAZ = 0.415 ± 0.272 mm2) as compared with healthy subjects (PIA = 3965 ± 467 μm2; FAZ=0.221 ± 0.071 mm2). These data suggest the possibility that a decrease in perifoveal capillary blood velocities in combination with decreased capillary density (enlarged PIA) and an enlargement of the foveal avascular zone may occur in patients with NIDDM. The determination of these parameters could help in monitoring the progress of diabetic retinopathy and diabetic maculopathy.

Altered retrobulbar vascular reactivity in early diabetic retinopathy

AIM/BACKGROUND In diabetic eye disease the factors leading to compromised circulation and the resulting loss of visual function are poorly understood. Although retinal circulation has been widely investigated, it accounts for only a fraction of total eye blood flow. Blood flow was investigated in the larger vessels feeding the eye in patients with early diabetic retinopathy. METHODS Eleven patients with early diabetes with minimal or no retinopathy and 11 healthy controls were evaluated for retrobulbar blood flow velocity using colour Doppler imaging for the ophthalmic and central retinal arteries. Patients and subjects were tested while breathing room air and again under conditions of isocapnic hyperoxia. RESULTS Hyperoxia induced a significant change in the central retinal artery end diastolic velocity (EDV) (p = 0.008) and resistance index (RI) (p = 0.032) in normal subjects, but not in diabetic patients. Consequently, during hyperoxia, the diabetic patients were significantly higher for EDV (p = 0.006) and significantly lower for RI (p = 0.002) compared with normal controls. Hyperoxia caused no significant change in either group in the ophthalmic artery; nevertheless, under isocapnic hyperoxia conditions the diabetic patients had lower peak systolic velocity (p = 0.05) and lower RI (p = 0.05) than normal subjects. CONCLUSIONS Imposition of isocapnic hyperoxia produces significant differences in the ophthalmic and central retinal artery blood flow velocities in diabetic patients with early disease when compared with normal subjects. These results demonstrate that diabetic patients with minimal or no retinopathy suffer from irregular ocular vascular function in the major vessels feeding the eye.