Epilepsy patients treated with vigabatrin exhibit reduced ocular blood flow.

BACKGROUND/AIM: Reduced cerebral blood flow and decreased glucose metabolism have been identified in epilepsy patients receiving vigabatrin. It is likely that such a change may extend to the eye and may be linked to previously reported irreversible visual field defects. The aim of this study was to determine whether patients who have undergone anti-epileptic drug (AED) therapy with vigabatrin have altered ocular haemodynamics. METHODS: The study cohort comprised 11 normal subjects (mean age 42.6 (SD 12.7) years and 17 epilepsy patients, of which 10 were either currently or previously treated with vigabatrin (38.6 (11.7) years) and seven were treated with AEDs excluding vigabatrin (46.0 (9.8) years). The three groups were matched at baseline for pulse rate, diastolic and systolic blood pressure, and intraocular pressure (IOP). At a single visit, the ocular blood flow analyser (OBFA; Paradigm Medical Instruments Inc, UT, USA) was used to measure pulsatile ocular blood flow (POBF) and pulse amplitude (PA) in each eye of all subjects. One way ANCOVA (with age as a covariate) was used to identify differences in POBF and PA between the groups. For the vigabatrin group only, Pearson's product moment correlation coefficient was used to explore potential interactions between ocular blood flow parameters and cumulative vigabatrin dose, duration, and maximum dose. RESULTS: Both the vigabatrin treated epilepsy group and conventionally treated epilepsy group exhibited significantly reduced POBF (p=<0.001, p=0.040) and PA (p=<0.001, p=0.005) compared to normal subjects. Patients treated with vigabatrin exhibited a further reduction in POBF (p=0.046) and PA (p=0.034) compared to conventionally treated epilepsy patients. No significant correlations were found between drug dosage and POBF and PA for the vigabatrin treated epilepsy group. CONCLUSIONS: A significant reduction in POBF and PA is apparent in epilepsy patients treated with AEDs when compared to normal subjects. A further reduction in POBF and PA is apparent between vigabatrin treated and conventionally treated patients. The reduction in ocular perfusion, which is more pronounced in patients previously treated with vigabatrin, may have implications in the impairment of visual function associated with the drug.

Effect of senescence on ocular blood flow in the retina, neuroretinal rim and lamina cribrosa, using scanning laser Doppler flowmetry.

PURPOSE: To determine the effects of age on blood flow measurements obtained using the scanning laser Doppler flowmeter (SLDF). METHOD: Using SLDF (Heidelberg retina flowmeter, Heidelberg Engineering, Germany) three 10 degrees images were taken of the superior temporal retina and three further images of the superior temporal neuroretinal rim in 15 young, healthy subjects (mean age 27.9 years +/- 6.2 years) and 15 mature, healthy subjects (mean age 65.2 years +/- 13.7 years). In addition, measurements were taken of the lamina cribrosa in 12 of the volunteers from each subject group (mean age 27.1 +/- 6.3 years and 64.8 +/- 13.2 years respectively). Using a 10 x 10 pixel measurement frame, blood flow readings were obtained at a predetermined position on the retina, neuroretinal rim and lamina cribrosa. Student's two-tailed unpaired t-tests were used to compare measures of blood flow, volume and velocity between the two subject groups (P < 0.05). In addition, linear regression analysis was used to assess the relationship between age and blood flow, volume and velocity at the retina, neuroretinal rim and lamina cribrosa. RESULTS: Retinal blood volume measured at the retina was significantly lower in the mature compared with the young subject group (P = 0.01). Mature subjects also exhibited reduced blood flow and velocity at the neuroretinal rim (P = 0.01 for both parameters) and lamina cribrosa (P = 0.008 and P = 0.01 respectively). Regression analysis revealed negative trends for all blood flow parameters in each of the anatomical areas with advancing age. Significant negative correlations were obtained for retinal blood volume (r = -0.455, P < 0.05), neuroretinal rim blood velocity (r = -0.359, P < 0.05) and lamina cribrosa blood volume (r = -0.475, P < 0.05). CONCLUSION: Capillary blood flow in the retina, neuroretinal rim and lamina cribrosa decreases with advancing age. This may be of consequence in the progression of chronic ocular diseases such as glaucoma, and should be considered in the longitudinal determination of change in disease monitoring.

Application of a local search strategy improves the detection of blood flow deficits in the neuroretinal rim of glaucoma patients using scanning laser Doppler flowmetry.

BACKGROUND/AIM: Blood flow measures acquired using the scanning laser Doppler flowmeter (SLDF) are known to be highly susceptible to spatial and temporal variations of physiological origin. The purpose of this study was to evaluate a local search strategy intended to overcome these intrinsic variations, thereby improving the detection of blood flow defects resulting from glaucoma. METHODS: The sample consisted of one eye of each of 15 glaucoma patients (aged 69.1 (SD 6.6) years) and 15 normal subjects (aged 65.2 (13.7) years). Three 10 degree images of the superior temporal retina and three images of the superior temporal rim were acquired using the Heidelberg retina flowmeter (HRF). Standard analysis was performed using a 10 x 10 pixel frame. For the search strategy the same frame was located within a 15 x 15 pixel window and manually repositioned in order to identify the highest and lowest local values of blood flow. Student's paired t test was used to identify differences between groups for the two methods (p<0.05). RESULTS: The standard strategy revealed no significant differences in blood flow measures between the subjects at either the retina or neuroretinal rim. With the search strategy there was also no difference in blood flow measures at the retina. At the neuroretinal rim, the search strategy demonstrated that the highest measured blood flow, volume, and velocity values were significantly lower for the glaucoma patients (p = 0.002, 0.02, and 0.002 respectively) while comparison of the lowest flow values showed that glaucoma patients had lower blood flow and velocity only (p = 0.023 and 0.021 respectively). CONCLUSIONS: Glaucoma patients exhibit reduced ocular blood flow at the neuroretinal rim, which seems to affect high velocity flow more profoundly than low velocity flow. When analysing perfusion images a local search strategy is recommend to identify the highest local blood flow values in order to optimise the ability to differentiate between subject groups.

Hypercapnia invokes an acute loss of contrast sensitivity in untreated glaucoma patients.

BACKGROUND/AIM: It is widely accepted that hypercapnia results in increased retinal, choroidal, and retrobulbar blood flow. Reports of a visual response to hypercapnia appear mixed, with normal subjects exhibiting reduced temporal contrast sensitivity in some studies, while glaucoma patients demonstrate mid-peripheral visual field improvements in others. This suggests that under hypercapnic conditions a balance exists between the beneficial effects of improved ocular blood flow and some other factor such as induced metabolic stress; the outcome may be influenced by the disease process. The aim of this study was to evaluate the contrast sensitivity response of untreated glaucoma patients and normal subjects during mild hypercapnia. METHODS: 10 previously untreated glaucoma patients and 10 control subjects were evaluated for contrast sensitivity and intraocular pressure while breathing room air and then again during mild hypercapnia. RESULTS: During room air breathing, compared with normal subjects, glaucoma patients had higher IOP (p = 0.0003) and lower contrast sensitivity at 3 cycles/degree (cpd) (p = 0.001). Mild hypercapnia caused a significant fall in contrast sensitivity at 6, 12, and 18 cpd (p < 0.05), only in the glaucoma group. CONCLUSION: Glaucoma patients with early disease exhibit central vision deficits as shown by contrast sensitivity testing at 3 cpd. Hypercapnia induces further contrast loss through a range of spatial frequencies (6-18 cpd) which may be predictive of further neuronal damage due to glaucoma.