Role of nitric oxide in regulation of retinal blood flow during hypercapnia in cats

PURPOSE: To investigate whether nitric oxide (NO) contributes to the regulation of retinal circulation during hypercapnia in cats. METHODS: NG-nitro-L-arginine-methylester (L-NAME; n=8), a NOS inhibitor; NG-nitro-D-arginine-methylester (D-NAME; n=6), the inactive isomer; or phosphate-buffered saline (PBS; n=8) was injected intravitreously into the cat's eye. A selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI; n=6), was injected intraperitoneally. Hypercapnia was induced for 10 minutes by inhalation of 5% carbon dioxide with 21% oxygen and 74% nitrogen. The vessel diameter and blood velocity were measured simultaneously in large retinal arterioles in cats by laser Doppler velocimetry and the retinal blood flow (RBF) calculated. Retinal vascular resistance (RVR) was also estimated. RESULTS: In the PBS group, the vessel diameter (9.5% +/- 2.7%, P<0.05), blood velocity (15.6% +/- 4.4%, P<0.05), and RBF (37.2% +/- 3.7%, P<0.05) increased, and the RVR decreased (-26.0% +/- 2.7%, P<0.05) during hypercapnia. In the L-NAME group, those changes were greatly suppressed in response to hypercapnia. D-NAME was inactive with regard to RBF during hypercapnia. The RBF responses to hypercapnia after the 7-NI injection were significantly attenuated compared with those before 7-NI injection (P<0.05). CONCLUSIONS: These results indicate that NO contributes to the increase in RBF during hypercapnia. Furthermore, the NO synthesized by the action of nNOS may participate in regulation of RBF during hypercapnia.     

Retinal artery response to acute systemic blood pressure increase during cold pressor test in humans

PURPOSE: The purpose of this study was to investigate the response of the retinal arteriole to an acute increase in systemic blood pressure (BP). METHODS: Sixteen healthy volunteers underwent a 5-minute cold pressor test (CPT) on the left hand. Retinal blood flow (RBF) was determined using a laser Doppler velocimetry system that enables simultaneous measurements of blood velocity and vessel diameter in a retinal artery every 30 seconds for the duration of the CPT. The mean arterial BP (MABP) was measured every 30 seconds during the test. RESULTS: The MABP immediately increased and reached the maximum level (from 85.1 +/- 2.7 to 103.7 +/- 5.0 mm Hg; P < 0.01) 1.5 +/- 0.2 minutes after the CPT began. The peak increase in velocity (from 30.6 +/- 1.3 to 46.1 +/- 2.1 mm/sec; P < 0.01) occurred at 1.6 +/- 0.2 minutes, resulting in an increase in RBF (from 10.1 +/- 1.0 to 14.3 +/- 1.4 microL/min; P < 0.01). The peak decrease in diameter (115.8 +/- 5.0 to 105.1 +/- 5.0 microm; P < 0.01) occurred at 2.9 +/- 0.3 minutes and the RBF returned to the baseline value. The increases in MABP significantly correlated with the decreases in diameter (r = -0.674, P = 0.0059). CONCLUSIONS: The CPT caused an acute increase in MABP that was associated with a transient increase in RBF and blood velocity, followed by constriction of the retinal arterioles and return of RBF to baseline. The results suggest that constriction of the retinal arterioles plays an important role in the maintenance of RBF in response to an acute increase in systemic BP.     

Retinal circulatory changes associated with interferon-induced retinopathy in patients with hepatitis C

PURPOSE: To evaluate the effect of interferon (IFN) therapy on retinal microcirculation. METHODS: Thirty-six patients with chronic hepatitis C who were treated with high-dose IFN were included in this prospective study. The changes in vessel diameter and blood velocity were measured, and the retinal blood flow (RBF) and wall shear rate (WSR) were calculated in the retinal arteries before and 2, 4, 8, 16, and 24 weeks after IFN therapy by using laser Doppler velocimetry. RESULTS: Retinal blood velocity, RBF, and WSR significantly (P < 0.0001) increased in all patients, as early as 2 weeks after IFN therapy. The increase in RBF was independently correlated with a decrease in the red blood cell count. In 22 (61%) of the 36 patients asymptomatic retinopathy developed during treatment. In patients with retinopathy, the blood velocity and WSR increased, but the vessel diameter did not change, whereas the vessel diameter increased but the blood velocity and WSR did not change in patients without retinopathy 2 weeks after IFN therapy. Multiple logistic regression analysis showed that patient age and the change in WSR at week 2 were risk factors for the development of IFN-induced retinopathy. CONCLUSIONS: RBF increases in association with IFN therapy in patients with chronic hepatitis C. In addition, the increased WSR in patients with retinopathy indicates that retinal vascular endothelial dysfunction may be associated with IFN-induced retinopathy, because wall shear stress should be constant under physiologic conditions.     

Inhaled carbon monoxide increases retinal and choroidal blood flow in healthy humans

PURPOSE: It has been hypothesized that carbon monoxide (CO) acts as an important vascular paracrine factor and plays a role in blood flow regulation in several tissues. The present study investigated the effect of inhaled CO on retinal and choroidal blood flow. METHODS: Fifteen healthy male volunteers were studied in a randomized, double-masked, placebo-controlled design with washout periods of at least 1 week between study days. CO in a dose of 500 ppm or placebo (synthetic air without CO) was inhaled for 60 minutes. Ocular hemodynamics were measured at baseline and at 30 and 60 minutes after start of inhalation. Retinal vessel diameters were measured with a retinal vessel analyzer. RBC velocity was assessed using bidirectional laser Doppler velocimetry. Retinal blood flow was calculated based on retinal vessel diameters and RBC velocity. Fundus pulsation amplitude (FPA) was measured using laser interferometry, and submacular choroidal blood flow using laser Doppler flowmetry. RESULTS: Breathing of CO significantly increased carboxyhemoglobine, from 1.2 +/- 0.5% to 8.5 +/- 0.9% and 9.4 +/- 0.6% at the two time points, respectively (P < 0.01). The diameter of retinal arteries increased by +3.5 +/- 3.8% and +4.2 +/- 3.9% (P < 0.01) in response to CO inhalation. In retinal veins, CO also induced an increase in diameter of +4.3 +/- 3.0% and +4.8 +/- 5.0%, respectively (P < 0.01). By contrast, placebo did not influence retinal vessel diameter. RBC velocity tended to increase during CO inhalation (+8 +/- 22%), but this effect did not reach the level of significance (P = 0.1). Calculated retinal blood flow increased significantly by +12 +/- 5% (P < 0.02). FPA increased after breathing CO by +20 +/- 20% and +26 +/- 21% at the two time points, respectively (P < 0.01). Subfoveal choroidal blood flow increased by +14 +/- 9% and +15 +/- 9% during breathing of CO (P < 0.01). CONCLUSIONS: This experiment demonstrated that retinal and choroidal blood flow increase during inhalation of CO. Whether this increase is caused by tissue hypoxia or a yet unknown mechanism has to be clarified.     

Relationship between the parameters of retinal circulation measured by laser Doppler velocimetry and a marker of early systemic atherosclerosis

PURPOSE: To examine the relation between intima-media thickness (IMT) in the common carotid artery, which is generally recognized as a marker of early atherosclerosis, and retinal circulatory parameters. METHODS: The vessel diameter and blood velocity of retinal arterioles were measured with laser Doppler velocimetry (LDV) in 33 patients with coronary artery disease (CAD), because they were thought to have general atherosclerosis. The retinal blood flow (RBF) and wall shear rate (WSR), an index of wall shear stress in retinal vessels, were calculated from the two parameters. The carotid IMT was evaluated with B-mode ultrasonography. RESULTS: The patients were divided into two groups: those with an IMT >0.70 mm and those with an IMT < or =0.70 mm. The blood velocity, WSR, and upstroke time in the retinal arterioles were significantly higher in the group with an IMT >0.70 mm compared with the group with an IMT < or =0.70 mm. There were no significant differences in vessel diameter and RBF between the groups. Positive correlations were found between the carotid IMT and blood velocity (r = 0.51, P = 0.002) and WSR (r = 0.60, P = 0.0001). Multiple regression analysis showed that the retinal WSR and blood velocity correlated independently with the IMT in patients with CAD. CONCLUSIONS: The present findings from this pilot study suggest that the retinal circulatory parameters measured by LDV may be associated with systemic atherosclerosis. These results support recent studies showing an association between retinal microvascular changes and cardiovascular disease.     

Role of nitric oxide in mediating retinal blood flow regulation in cats.

The role of nitric oxide (NO) was evaluated in mediating control of retinal blood flow in the anesthetized cat. This was done under resting conditions and as a function of decreases in perfusion pressure. The retinal blood flow was calculated by measuring blood velocity with laser Doppler velocimetry (LDV) and retinal blood vessel diameter with image analysis. Graded decreases in perfusion pressure were obtained by increasing intraocular pressure (IOP). Following intravenous administration of 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor, the arterial blood pressure increased under resting conditions by 34+/-3% (n = 7), the blood vessel diameter decreased by 18+/-2%, and retinal blood flow significantly declined by 27+/-6% (n = 6). Irrespective of the presence or absence of L-NAME (30 mg/kg), stepwise reductions in perfusion pressure that reached a level that was 35% of the baseline value had no significant effect on retinal blood flow. These results suggest that, under resting conditions, retinal blood flow decreases in response to a putative fall in NO levels. However, NO does not appear to be involved in mediating the autoregulatory response to a decrease in perfusion pressure.     

Noninvasive evaluation of wall shear stress on retinal microcirculation in humans

PURPOSE: To evaluate wall shear stress (WSS) on retinal microcirculation noninvasively. METHODS: Retinal vessel diameter (D) and mean centerline blood velocity (V(max, mean)) were measured in the retinal arterioles and venules at first- and second-order branches in 13 subjects using laser Doppler velocimetry (LDV). Retinal blood flow (RBF) and wall shear rate (WSR) were calculated using these two parameters. Blood viscosity at the calculated shear rate was also measured using a cone-plate viscometer. WSS was calculated as the product of the WSR and the blood viscosity. RESULTS: In the first-order branches, the averaged D, V(max, mean), RBF, and WSR(mean) were 108 +/- 13 microm, 41 +/- 10 mm/s, 11 +/- 4 microL/min, and 1539 +/- 383 s(-1) in the arterioles and 147 +/- 13 microm, 23 +/- 3 mm/s, 12 +/- 4 microL/min, and 632 +/- 73 s(-1) in the venules, respectively. The apparent blood viscosities at the measured shear rates were 3.5 +/- 0.3 centipoise (cP) in the arterioles and 3.8 +/- 0.4 cP in the venules. Therefore, the averaged WSS was 54 +/- 13 dyne/cm2 in the arterioles and 24 +/- 4 dyne/cm2 in the venules. The WSS in the second-order arterioles was significantly lower than that in the first-order branches (P = 0.002), but the WSS in the first-order venules was similar to that in the second-order venules. CONCLUSIONS: The authors demonstrated that the WSS in the retinal vessels could be evaluated noninvasively in humans using LDV and cone-plate viscometry. This system may be useful for further clinical investigation of the role of shear stress in the pathogenesis of various retinal disorders.     

Nitric oxide production by isolated human and porcine ciliary processes

Background: In the kidney, the trachea, and the colon, nitric oxide (NO) can modulate transepithelial fluid transport. This study investigates whether isolated human and porcine ciliary processes produce NO.Methods: Porcine ciliary processes and iris were used either fresh or thawed after storage at –70°C. Post-mortem (8–12 h) human ciliary processes were used thawed after storage at –70°C. NO was measured by placing a nafion-coated polymeric porphyrinic microsensor (differential pulse voltammetry) on the surface of the tissue. Measurements were conducted in the absence or in the presence of the NO formation inhibitor N ^G-nitro-l-arginine methyl ester (L-NAME; 0.2 mM, 1 mM) or its biologically inactive d-enantiomer N ^G-nitro-d-arginine methyl ester (D-NAME; 1 mM).  Results: NO concentrations in porcine ciliary processes (1.27±0.25 μM) were higher (P=0.001) than those in the iris (0.00±0.02 μM) and were significantly (P<0.001) decreased by L-NAME (fresh specimen). From thawed porcine ciliary processes, NO concentrations measured (1.85±0.47 μM) were not significantly different (P=0.16) from those measured in fresh specimen and were also reduced (P <0.001) by L-NAME, but not by D-NAME. In human ciliary processes, NO concentrations measured (0.08±0.11 μM) were somehow lower but were again decreased (P<0.001) by L-NAME (thawed specimen).  Conclusion: Reflecting the biological activity of a nitric oxide synthase, isolated human and porcine ciliary processes produce NO. Received: 11 May 1999 Revised: 20 September 1999 Accepted: 13 October 1999     

Effect of aging on retinal circulation in normotensive healthy subjects

Although it is important to investigate the effects of normal aging on the ocular circulation, few studies have examined the effects of aging on the retinal microcirculation in healthy subjects. The purpose of this study was to evaluate the effects of aging on the retinal microcirculation in healthy men. Forty-five healthy men were divided into three groups based on age (young, middle-aged, elderly). We measured vessel diameter and blood velocity and calculated the retinal blood flow (RBF) and wall shear rate (WSR) in the retinal arteries. We performed pulse wave analysis obtained from the retinal blood velocity measurements. We also divided the subjects into two groups based on the presence or absence of prehypertension defined as 120–139/80–89 mmHg. No significant differences in vessel diameter, blood velocity, RBF, and WSR were seen among the groups. Pulse wave analysis showed significant increases in upstroke time (UT) in elderly men compared with young men (P < 0.05). Multiple regression analysis showed that the UT was correlated with age in all subjects. A significant difference was seen only in the UT between subjects with and without prehypertension. The UT calculated from the retinal blood velocity profile is associated significantly with aging, suggesting that measurement of the UT may detect the changes in the retinal and the systemic vessels with increasing age. The UT is the only parameter that increased significantly in subjects with prehypertension compared with those without prehypertension, suggesting that the UT may indicate the effects of prehypertension on the retinal arterioles.     

Effect of nos inhibition on retinal arterial and capillary circulation in early arterial hypertension

BACKGROUND: Arterial hypertension is involved in the pathogenesis of end organ damage by influencing the ability of the vascular endothelium to produce nitric oxide (NO). This study analyzes changes of retinal and systemic NO-dependent circulation parameters by inhibiting nitric oxide synthase (NOS) in both hypertensive and normotensive individuals. METHODS: In a double-blind crossover trial, 19 hypertensive patients (H, age 28.2 +/- 0.9 years) and 19 normotensive controls (N, age 26.9 +/- 0.9 years) were randomized treated either with candesartan or placebo. Both retinal capillary flow (RCF) and mean blood flow velocity of the central retinal artery (VCRA) were registered before and after NOS inhibition with N-monomethyl-L-arginine (L-NMMA, 3 mg/kg). In a subpopulation mean arterial pressure (MAP), cardiac output (CO), and the total peripheral resistance (TPR) were determined simultaneously. RESULTS: Changes from baseline: In normotensive and hypertensive subjects infusion of L-NMMA led to an increase of MAP (N, +13.3 +/- 1.8%, P < 0.01; H, +14.3 +/- 2.4%, P < 0.01) and TPR (N, +36.9 +/- 3.8%, P < 0.01; H, +45.0 +/- 4.5%, P < 0.01), and to a decrease of CO (N, -21.1 +/- 1.5%, P < 0.01; H, -24.6 +/- 2.3%, P < 0.01). The L-NMMA effect on VCRA and RCF differed between controls and hypertensives. VCRA changed by + 17.3 +/- 6.2% (P < 0.05) and RCF by -7.3 +/- 3.0% (P < 0.05) in controls. In hypertensive subjects corresponding results were + 9.5 +/- 5.2% (P = NS) and + 2.7 +/- 3.8% (P = NS), respectively. The decrease of RCF due to L-NMMA was reduced in hypertension as compared to controls (P < 0.05). The calculated cross-sectional area of CRA was reduced by -58.7% in controls and increased by + 31.1% in hypertensive subjects. There was no significant correlation between the flow in the systemic and retinal circulation. CONCLUSION: Only normotensives L-NMMA induces an acceleration of VCRA due to a probable vasoconstriction of the central retinal artery and despite of a reduced RCF. Already in early hypertension the NOS-dependent vascular tone in retinal arteries and capillaries is impaired. The regulation of the retinal capillary flow appeared to be independent from systemic circulation.     

The effect of pregnancy on retinal hemodynamics in diabetic versus nondiabetic mothers

PURPOSE: To investigate retinal circulatory changes that occur during the third trimester of pregnancy in diabetic patients and control subjects. METHODS: Bidirectional laser Doppler velocimetry and monochromatic fundus photography were used to assess the retinal circulation in seven pregnant diabetic patients and 13 age-matched pregnant control subjects. Retinal venous diameter (D), maximum erythrocyte velocity (Vmax), and retinal volumetric blood flow rate (Q) were measured in one eye of each subject during the third trimester of pregnancy (DPREG, VmaxPREG, and QPREG, respectively). These measurements were repeated during the postpartum period for both diabetic patients (11+/-7 weeks postpartum) and control subjects (16+/-6 weeks postpartum; P = .203; DPOST, VmaxPOST, and QPOST). RESULTS: In control subjects, DPREG was significantly reduced by -4.5%+/-4.4% (mean percent difference +/-1 standard deviation; paired t test, P =.006) relative to DPOST. In diabetic women, DPREG was also significantly reduced by -8.1%+/-3.2% compared with DPOST (P = .001), a change that was significantly larger than that seen in control subjects (unpaired t test; P = .035). Compared with QPOS T, QPREG was reduced by -7.1%+/-14.2% (P = .123), in control subjects. In diabe tic women, QPREG was significantly decreased by -18.4%+/-9.3% compared with QPOST (P = .012). This reduction in QPREG was significantly greater in diabetic patients than in nondiabetic control subjects (unpaired t test, P = .040). No significant differences between VmaxPREG and VmaxPOST were observed in either diabetic patients (-3.1%+/-12.9%; P =.400) or control subjects (+1.9%+/-14.4%; P = .787). CONCLUSIONS: Retinal venous diameter is decreased during the third trimester of pregnancy in both diabetic and nondiabetic mothers. This decrease is significantly larger in diabetic than in nondiabetic mothers. In addition, we observed a reduction in retinal volumetric blood flow in diabetic patients during pregnancy that was significantly larger than that present in nondiabetic women. This fall in retinal volumetric blood flow in diabetic patients may exacerbate retinal ischemia and hypoxia and thus may be associated with the progression of diabetic retinopathy.     

Effect of panretinal photocoagulation on retinal blood flow in proliferative diabetic retinopathy

The effect of panretinal photocoagulation (PRP) on retinal volumetric blood flow rate and its regulatory response to hyperoxia was investigated in a main temporal vein of 15 eyes with proliferative diabetic retinopathy, using bi-directional laser Doppler velocimetry and monochromatic fundus photography. At an average of 4 +/- 2 months after the beginning of PRP, retinal venous diameter decreased from an average of 174 +/- 20 micron to 162 +/- 19 micron (P less than 0.01), red blood cell velocity decreased from 1.3 +/- 0.4 cm/sec to 1.1 +/- 0.4 cm/sec (P less than 0.01), and blood flow decreased from 11.5 +/- 3.8 microliter/min to 8.4 +/- 3.3 microliter/min (P less than 0.001). The regulatory response to hyperoxia, characterized by the percentage decrease in retinal blood flow during 100% oxygen breathing, improved from 20 +/- 15% prior to treatment to 45 +/- 12% following treatment (P less than 0.001). The decrease in retinal blood flow is most likely due to a decrease in viable retinal tissue and an improvement in retinal oxygenation following PRP. The increase in the regulatory response to 100% O2 breathing following PRP may also result from such an improved retinal oxygenation.     

Effect of aging on retinal circulation in normotensive healthy subjects

Although it is important to investigate the effects of normal aging on the ocular circulation, few studies have examined the effects of aging on the retinal microcirculation in healthy subjects. The purpose of this study was to evaluate the effects of aging on the retinal microcirculation in healthy men. Forty-five healthy men were divided into three groups based on age (young, middle-aged, elderly). We measured vessel diameter and blood velocity and calculated the retinal blood flow (RBF) and wall shear rate (WSR) in the retinal arteries. We performed pulse wave analysis obtained from the retinal blood velocity measurements. We also divided the subjects into two groups based on the presence or absence of prehypertension defined as 120–139/80–89 mmHg. No significant differences in vessel diameter, blood velocity, RBF, and WSR were seen among the groups. Pulse wave analysis showed significant increases in upstroke time (UT) in elderly men compared with young men (P < 0.05). Multiple regression analysis showed that the UT was correlated with age in all subjects. A significant difference was seen only in the UT between subjects with and without prehypertension. The UT calculated from the retinal blood velocity profile is associated significantly with aging, suggesting that measurement of the UT may detect the changes in the retinal and the systemic vessels with increasing age. The UT is the only parameter that increased significantly in subjects with prehypertension compared with those without prehypertension, suggesting that the UT may indicate the effects of prehypertension on the retinal arterioles.     

Effect of stellate ganglion block on human retinal blood flow

PURPOSE: The effect of stellate ganglion block (SGB) on human retinal blood flow was evaluated. METHODS: We measured the diameter of the retinal artery and vein, and retinal venous flow rate by laser speckle retinal blood flow meter simultaneously in 11 eyes of 11 normal volunteers. RESULTS: The reliable data from 9 eyes of 9 person were used for analysis. SGB did not change the blood pressure, heart rate, retinal arterial diameter, or venous diameter. However SGB increased retinal blood velocity significantly from 9.9 +/- 1.6 (mean +/- standard deviation) mm/s to 11.1 +/- 1.5 mm/s (p < 0.01). Intraocular pressure decreased from 12.3 +/- 2.1 (mean +/- standard deviation)mmHg to 9.4 +/- 2.2 mmHg after SGB (p < 0.01). There was no relationship between the change of ocular perfusion pressure and that of retinal venous blood velocity. CONCLUSION: SGB increased the retinal venous blood velocity without changing the retinal vessel diameter.     

Ocular blood flow and retinal metabolism in abyssinian cats with hereditary retinal degeneration

PURPOSE: To investigate if retinal blood flow decreases with progression of the disease in Abyssinian cats with progressive retinal atrophy (PRA), to examine if the choroidal blood flow was affected by the disease, and to determine the uptake of glucose and formation of lactate in the outer retina. METHODS: Local blood flow in different parts of the eye was determined with radioactive microspheres, in 9 normal cats and in 10 cats at different stages of PRA. Three blood flow determinations were made in each animal, during control conditions, after IV administration of indomethacin and after subsequent administration of N(omega)-nitro-L-arginine (L-NA). Blood samples from a choroidal vein and a femoral artery were collected to determine the retinal formation of lactate and uptake of glucose. RESULTS: In Abyssinian cats with PRA (n = 10), the retinal blood flow was significantly (P < or = 0.01) lower than in normal cats (n = 9) during control conditions, 6.4 +/- 1.7 compared with 14.1 +/- 1.9 g min(-1) x (100 g)(-1). The vascular resistance in the iris and ciliary body was significantly higher in the cats at a late stage of PRA, both compared with normal cats and to cats at an early stage of the disease, whereas the choroidal vascular resistance was not significantly affected. Indomethacin had no effect on ocular blood flows in normal cats, but in cats with PRA, iridal blood flow was more than doubled after indomethacin. The retinal formation of lactate was significantly (P < or = 0.001) lower in cats with PRA than in normal cats, 0.111 +/- 0.035 (n = 8) compared with 0.318 +/- 0.024 (n = 8) micromol x min(-1). The uptake of glucose was not significantly different in cats with PRA. CONCLUSIONS: Retinal blood flow is severely decreased in Abyssinian cats at a late stage of retinal degeneration, whereas the choroidal microcirculation is not significantly affected by the disease. At a late stage of retinal degeneration, vascular resistance in the iris is significantly increased, which at least in part could be caused by cyxlooxygenase products.     

Effect of arteriovenous sheathotomy on retinal blood flow and macular edema in patients with branch retinal vein occlusion

PURPOSE: To determine the effect of arteriovenous sheathotomy on retinal blood flow (RBF) in eyes with branch retinal vein occlusion (BRVO). DESIGN: Interventional case series. METHODS: Seven eyes of 7 patients with BRVO underwent sheathotomy and were followed for more than 6 months. RESULTS: At 1 week postoperatively, the RBF in the affected vessels was significantly improved from 14.1 +/- 5.7 to 27.3 +/- 11.3 pixel(2)/sec (P < 0.01), and the foveal thickness (FT) was significantly reduced from 536 +/- 84 to 366 +/- 134 microm (P = 0.03). However, the RBF was reduced again to 11.7 +/- 7.7 pixel(2)/sec at 1 month postoperatively, and the FT was increased to 424 +/- 184 microm. CONCLUSIONS: Arteriovenous sheathotomy led to a transient improvement of the RBF and was effective in reducing macular edema. It is not clear whether the transient effect of sheathotomy affects the long-term visual acuity and macular edema.     

L-NAME protects against acute light damage in albino rats,but not against retinal degeneration in P23H and S334ter transgenic rats

Two previous studies have shown that N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of neuronal nitric oxide synthase, protects retinas of albino rats and mice from damaging levels of light. The aims of the present study were two-fold: (1) to confirm the protective effect of L-NAME on wild type albino rats and (2) to determine if L-NAME protects the retinas of transgenic rats with P23H and S334ter rhodopsin mutations. In the first study, albino rats born and raised in 5-10 lux cyclic light were injected intraperitoneally with either L-NAME or its inactive isomer D-NAME 30 min before being placed in bright light (2700 lux) for 24hr. Electroretinograms (ERGs) were recorded before light treatment and 2 days after cessation of exposure, and eyes were enucleated for morphologic evaluation. L-NAME, but not D-NAME provided structural protection of photoreceptor cells from light damage. The functional rescue was not statistically significant between the drug treated groups. In the second study, albino WT, P23H transgenic, and S334ter transgenic rats were born and raised in 400 lux cyclic light. Three week old animals received daily intraperitoneal injections of L-NAME or D-NAME for 4 weeks, and the same drugs were added to their drinking water. At 7 weeks of age, the ERG sensitivity curves and the outer nuclear layer thickness of both transgenic groups were significantly reduced compared to WT controls. However, administration of L-NAME did not protect against retinal degeneration caused by the rhodopsin mutation in either strain of transgenic (P23H and S334ter) rats. Thus, although photoreceptor cell death in light damage and inherited retinal degenerations share a common apoptotic mechanism, there must be significant 'up-stream' differences that allow selective neuroprotection by L-NAME.     

Response of retinal vessel diameters to flicker stimulation in patients with early open angle glaucoma

INTRODUCTION: Diffuse luminance flicker increases retinal vessel diameters in animals and humans, indicating the ability of the retina to adapt to different metabolic demands. The current study seeks to clarify whether flicker-induced vasodilatation of retinal vessels is diminished in glaucoma patients. METHODS: Thirty-one patients with early stage glaucoma (washout for antiglaucoma medication) and 31 age- and sex- matched healthy volunteers were included in the study. Retinal vessel diameters were measured continuously with a Retinal Vessel Analyzer. During these measurements three episodes of square wave flicker stimulation periods (16, 32, and 64 secs; 8 Hz) were applied through the illumination pathway of the retinal vessel analyser. RESULTS: Flicker-induced vasodilatation in retinal veins was significantly diminished in glaucoma patients as compared with healthy volunteers (ANOVA, P < 0.01). In healthy volunteers, retinal venous vessel diameters increased by 1.1 +/- 1.8% (16 seconds, P < 0.001), 2.0 +/- 2.6 (32 seconds, P < 0.001), and 2.1 +/- 2.1% (64 seconds, P < 0.001) during flicker stimulation. In glaucoma patients, venous vessel diameters increased by 0.2 +/- 1.7% (16 seconds, P < 0.6), 1.1 +/- 2.1% (32 seconds, P < 0.01), and 0.8 +/- 2.5 (64 seconds, P < 0.09). In retinal arteries, no significant difference in flicker response was noticed between the two groups (ANOVA, P < 0.6). In healthy controls, flicker stimulation increased retinal arterial vessel diameters by 1.0 +/- 2.4% (P < 0.03), 1.6 +/-3.2% (P < 0.004) and 2.4 +/- 2.6% (P < 0.001) during 16, 32, and 64 seconds of flicker, respectively. In glaucoma patients, flickering light changed arterial vessel diameters by 0.3 +/-2.6% (16 seconds, P = 0.4), 1.3 +/-3.1% (32 seconds, P = 0.03), and 1.8 +/- 3.8% (64 seconds, P = 0.005). CONCLUSION: Flicker-induced vasodilatation of retinal veins is significantly diminished in patients with glaucoma compared with healthy volunteers. This indicates that regulation of retinal vascular tone is impaired in patients with early glaucoma, independently of antiglaucoma medication.     

Effect of haemodialysis on retinal circulation in patients with end stage renal disease

AIMS: To investigate the effect of haemodialysis on retinal circulation in patients with end stage renal disease (ESRD). METHOD: Seventeen consecutive patients with ESRD were recruited into the study. The authors simultaneously measured changes in vessel diameter and blood velocity and calculated the retinal blood flow (RBF) in the retinal veins in patients with ESRD before and after haemodialysis using a laser Doppler velocimetry system. In addition, the relations between the changes in systemic and retinal circulatory parameters were examined. RESULTS: There was a group averaged increase in vessel diameter (p = 0.003) after haemodialysis. However, the blood velocity and RBF values obtained after haemodialysis were not significantly different from those before haemodialysis (p = 0.66 and p = 0.63, respectively). The changes in vessel diameter were negatively (r = -0.549, p = 0.02) correlated with the change in MABP, but the changes in blood velocity and RBF were positively correlated with the change in MABP (r = 0.683, p<0.002 and r = 0.589, p<0.01, respectively). The change in RBF was also inversely correlated with the increase in haematocrit (r = -0.693, p<0.002) and the amount of fluid removed (r = -0.597, p<0.01). CONCLUSION: The results indicate that haemodialysis and the associated changes in systemic circulatory parameters may affect the retinal circulation in patients with ESRD.     

Does timolol modify retinal hemodynamics in patients with normal pressure glaucoma?]

In 31 patients with normal-pressure glaucoma, retinal blood flow, diameter of the retinal vessels and velocity were measured with 2-point fluorometry and automatic measurement of the diameters before and after administration of 0.5% timolol over 2 weeks. After timolol therapy the tension was significantly decreased (before therapy: 18.26 +/- 2.50; after therapy: 15.61 +/- 2.56 mm Hg, P < or = 0.01). The arterial and venous diameters and blood flow were nearly unchanged, but a slight increase in the arterial and venous velocity was noted. We conclude that timolol does not significantly influence the retinal hemodynamics in patients with normal-pressure glaucoma.