Tatyana I. Metelitsina

Foveolar Choroidal Circulation and Choroidal Neovascularization in Age-Related Macular Degeneration

PURPOSE To investigate in a longitudinal study whether foveolar choroidal blood flow changes are associated with the development of choroidal neovascularization (CNV) in AMD. METHODS Relative foveolar choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) were assessed in 135 patients with AMD, at baseline and then annually with laser Doppler flowmetry. All study eyes had visual acuity of 20/40 or better and no CNV at the time of enrollment. Comparison of foveolar choroidal circulatory measurements at baseline and their change before the development of CNV was made between eyes that had CNV and those that did not. RESULTS CNV developed in 28 eyes during the study. Baseline average foveolar ChBVol and ChBFlow in these eyes were 24% (P < 0.0001) and 20% (P = 0.0007) lower than that observed in the 165 eyes in which CNV did not develop. In the eyes with CNV, foveolar ChBVol and ChBFlow decreased by 9.6% and 11.5% before the formation of CNV, whereas in the eyes that did not, they increased by 6.7% (P = 0.006) and 2.8% (P = 0.004), respectively. Eyes with lower baseline foveolar ChBFlow were more likely (risk ratio = 3.47, 95% CI: 1.24-8.70) to show visual loss of three or more lines than were eyes with a higher baseline ChBFlow (P = 0.005). CONCLUSIONS The development of CNV and visual loss are associated with lower choroidal circulatory parameters at baseline. In addition, the results suggest that decreases in the foveolar choroidal circulation precede the development of CNV in AMD and may play some role in its development.

Association of Risk Factors for Choroidal Neovascularization in Age-Related Macular Degeneration With Decreased Foveolar Choroidal Circulation

PURPOSE To investigate the relationship between known risk factors for age-related macular degeneration (AMD) progression and foveolar choroidal circulation in eyes with nonexudative AMD. DESIGN Cross-sectional study of nonexudative AMD. METHODS Laser Doppler flowmetry measurements of relative choroidal blood velocity, choroidal blood volume (ChBVol), and choroidal blood flow (ChBFlow) were obtained in the center of the fovea of 273 study eyes of 204 AMD patients investigated at the Scheie Eye Institute, University of Pennsylvania Medical School. All study eyes had visual acuity of 20/40 or better, good fixation, no other intraocular pathologic features, and no evidence of choroidal neovascularization. RPE hypertrophy was determined from color fundus photographs by trained masked graders at the Scheie Image Reading Center. Correlation analysis and multivariate linear regression analysis with adjustments for significant covariates were carried out. RESULTS A significant inverse correlation was observed between age and ChBFlow (r = -0.36; P < .0001), and ChBVol (r = -0.28; P < .0001), but not for choroidal blood velocity. A significant inverse correlation was observed between spherical equivalent and ChBFlow (r = -0.21; P = .006) and ChBVol (r = -0.14; P = .04), but not for choroidal blood velocity. ChBFlow and ChBVol were significantly lower in patients with a history of hypertension (P < or = .003) and in eyes with retinal pigment epithelium hypertrophy (P < or = .04), respectively. CONCLUSIONS All the above-described risk factors for AMD development and progression are associated with decreased choroidal circulatory parameters, suggesting that decreases in choroidal circulatory parameters may be involved in the development of AMD.

The Association Between Drusen Extent and Foveolar Choroidal Blood Flow in Age-Related Macular Degeneration

Purpose: To investigate the relationship between drusen extent and foveolar choroidal blood flow in nonexudative age-related macular degeneration. Methods: Total drusen area, average druse area, and total drusen number were determined using a computer program developed to quantify the extent of manually outlined drusen from fundus photographs of 157 patients (239 eyes) with nonexudative age-related macular degeneration. Laser Doppler flowmetry was used to assess relative choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) in the center of the fovea. Results: We found a significant inverse relationship between total drusen area and ChBVol or ChBFlow. For every 1-mm2 increase in total drusen area, ChBVol decreased by 0.0061 arbitrary units (P = 0.03) and ChBFlow decreased by 0.23 arbitrary units (P = 0.049). Average druse area was also significantly inversely related to ChBVol and ChBFlow. For every 0.01-mm2 increase in average druse area, the ChBVol decreased by 0.0149 arbitrary units (P = 0.001) and the ChBFlow decreased by 0.4951 arbitrary units (P = 0.003). Adjustment for age weakened the significance, although it remained strong for average druse area versus ChBFlow (P = 0.017) and ChBVol (P = 0.004). The computer-aided quantification of drusen used in this study showed high intra- and intergrader agreement. Conclusion: In patients with nonexudative age-related macular degeneration, there is an association between increased drusen extent and decreased ChBVol and ChBFlow. This suggests the presence of ischemia and possibly the reason why patients with high-risk drusen are prone to advanced disease.

Effect of systemic hypertension on foveolar choroidal blood flow in age related macular degeneration

Aim: To investigate the effect of systemic hypertension (SH) on the foveolar choroidal circulation in patients with age related macular degeneration (AMD). Methods: This study included 163 study eyes with early AMD characteristics of 124 AMD patients. Study eyes had visual acuity of 20/40 or better, drusen ⩾63 µm, and/or RPE hypertrophy. 56 of the AMD patients had a history of SH and 47 of these patients were receiving antihypertensive medications. Laser Doppler flowmetry (Oculix) was used to assess relative choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) in the centre of the fovea of the study eyes. Differences in the mean haemodynamic parameters between groups of eyes were assessed using analysis of variance (ANOVA) and a test of linear trend, with adjustment for the correlation between eyes of the same patient. Results: AMD patients with SH showed decreased ChBFlow in comparison with those without SH (ANOVA, p = 0.02). This association was maintained after adjustments for multiple factors (p = 0.04). Conclusions: AMD patients with SH have lower ChBFlow than those without SH. This decrease in choroidal blood circulation may help explain the mechanism by which systemic hypertension may contribute to the progression of AMD and the development of choroidal neovascularisation.

Effect of sildenafil citrate (Viagra) on retinal blood vessel diameter

PURPOSE The present investigation was conducted to evaluate the effect of sildenafil citrate (Viagra, Pfizer Inc., New York, NY) on retinal blood vessel diameter. DESIGN Double-blind randomized, placebo-controlled, cross-over study. METHODS Fifteen healthy male volunteers (mean age 39 years) received 100-mg doses of sildenafil or matching placebo on 2 separate days. Monochromatic fundus photography was obtained in one eye, and brachial artery blood pressure and intraocular pressure were measured at baseline, 1 hour, and 5 hours after dosing. The diameters of two major temporal veins and one artery were measured in a masked fashion from digitized photographic negatives. RESULTS In comparison with placebo, no statistically significant change in average venous diameter was observed for the superior (analysis of variance [ANOVA], P =.97), inferior retinal temporal vein (ANOVA, P =.73), or the retinal temporal artery (ANOVA, P =.89) after sildenafil treatment. In comparison to placebo, there was no significant difference in the percentage change from baseline in venous or arterial diameter at 1 or 5 hours after sildenafil. The power to detect a 6.5% change in retinal vascular diameter following sildenafil was approximately 80% (P =.05). CONCLUSIONS These data suggest that at the maximum therapeutic dose used clinically (100 mg), sildenafil does not have a significant effect on retinal vascular caliber.

Effect of niacin on the choroidal circulation of patients with age related macular degeneration

Aim: To investigate the effects of niacin on choroidal blood flow in age related macular degeneration (AMD). Methods: 12 AMD patients with bilateral drusen and visual acuity of 20/40 or better in the study eye received a single oral dose of niacin (six subjects received 500 mg and six received 250 mg) or matching placebo on two separate occasions. Laser Doppler flowmetry was used to assess relative choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow) in the foveola of the study eye at baseline, 30, and 90 minutes after dosing. Results: In comparison with placebo, a statistically significant 24% increase in ChBVol was observed 30 minutes after niacin administration (ANOVA, p = 0.01). In comparison with placebo, a significant decrease in ChBVel of 23% was observed in the 500 mg group (p = 0.04) and no significant change in ChBVel was seen in the 250 mg group at 30 minutes. No significant changes in ChBFlow were detected at 30 or 90 minutes. Also, there were no statistically significant changes in ChBVol or ChBVel at 90 minutes. Conclusion: In comparison with placebo, a significant 24% increase in ChBVol was observed 30 minutes after niacin administration. Owing to simultaneous decrease in ChBVel, however, no significant change in ChBFlow was detected.

Effect of hypertension on foveolar choroidal haemodynamics

Aims: To assess the effect of systemic hypertension on the choroidal circulation in subjects with a normal eye examination. Methods: Laser Doppler flowmetry was used to determine relative choroidal blood velocity (Chvel), volume (Chvol), and flow (Chflow) in the centre of the fovea. Measurements were obtained in 15 eyes of 15 subjects with systemic hypertension. The mean average duration of hypertension was 11 (SD 6) years. Findings obtained in these patients were compared with those of 15 eyes of 15 age matched healthy controls. All subjects had normal eye examinations. Results: No significant differences in Chvel, Chvol, and Chflow, were found between the subjects with and without systemic hypertension despite a 17% higher perfusion pressure (PP) in patients with hypertension. No significant correlation was found between mean arterial pressure or PP and the choroidal circulatory parameters. It was estimated that there is a 90% power to detect a 35% difference in Chflow between the two groups. Conclusion: Systemic hypertension does not seem to have a large effect on the choroidal circulation in hypertensive patients that are controlled by antihypertensive therapy. Further studies are needed to elucidate whether systemic hypertension has an effect on the choroidal circulation in patients with ocular diseases.

Effect of laser treatment for dry age related macular degeneration on foveolar choroidal haemodynamics

Aim: Previous studies have suggested that laser photocoagulation therapy is associated with the resolution of drusen in some age related macular degeneration (AMD) patients. The main aim of the study was to determine whether low intensity laser treatment applied according to the Complications of AMD Prevention Trial (CAPT) protocol produces changes in the choroidal circulation that may help explain the mechanism leading to the resolution of drusen material. Methods: This ancillary study included 30 CAPT patients with bilateral drusen that were treated and followed at the University of Pennsylvania. Laser Doppler flowmetry was used to measure relative choroidal blood velocity (Chvel), volume (Chvol), and flow (Chflow) in the centre of the fovea. Measurements were obtained through a dilated pupil in both eyes of each patient at the initial CAPT visit before laser treatment was applied in one eye. Measurements were repeated in both eyes of each subject three months later. Analysis of laser Doppler measurements was performed in a masked fashion. Results: In comparison to baseline, no significant differences in Chvel, Chvol, or Chflow were observed three months following the application of low intensity laser according to the CAPT protocol in the untreated and treated eyes. In comparison to the untreated eyes, no significant differences were detected in the treated eyes. Based on the variability of flow measurements in the untreated eyes, the authors estimated an 85% power to detect a 15% change in relative blood flow. Conclusions: The results suggest that large alterations in choroidal blood flow do not occur at three months after low intensity laser therapy following the CAPT protocol.

Effect of isometric exercise on choroidal blood flow in patients with age-related macular degeneration

Aim We compared the regulatory responses induced by isometric exercise in control subjects and patients with age-related macular degeneration (AMD) to investigate choroidal vascular regulation in AMD. Methods Seventeen eyes of 17 patients with dry AMD in the study eye and 19 eyes of 19 controls were included in this study. Both groups were well matched for age, race and sex. Brachial artery blood pressure determinations and laser Doppler flowmetry (Oculix) measurements of relative foveolar choroidal blood velocity, volume and flow were obtained in the study eye of each subject during 30 s of baseline, and then during 3 min of isometric exercise consisting of squeezing a handgrip in each hand. Similar measurements were then also obtained during the 2 min following the cessation of exercise. Using non-paired, two-tailed t test, changes in circulatory parameters during exercise and following the end of exercise were compared between AMD patients and control subjects. The slope for the relationship between circulatory changes and perfusion pressure changes was calculated and compared between patients with AMD and controls using linear regression analysis. Analysis of data was performed in a masked fashion. Results There were no statistically significant differences between the changes in choriodal blood velocity, volume and flow observed in control subjects and patients with AMD during the isometric exercise phase and after exercise. Conclusions Our results suggest that the response of the choroidal circulation to this type of isometric exercise resulting in a moderate increase in blood pressure does not seem to be affected by AMD.

Effect of Niacin on Retinal Vascular Diameter in Patients with Age-Related Macular Degeneration

Purpose: Niacin is a B vitamin well-known for causing vasodilation and flushing. The purpose of this study was to investigate its effect on the retinal vasculature of patients with age-related macular degeneration (AMD). Methods: Twelve patients with AMD were enrolled in a double-blind, randomized, placebo-controlled, crossover trial. Fundus photographs of the posterior pole were taken at baseline, 30 min, and 90 min after a single dose of niacin or placebo. The protocol was repeated after a washout period using the alternate study drug. The diameters of two veins and one artery on each image were measured. Results: An analysis of variance for repeated measures comparing the effects of niacin with those of placebo demonstrated a significant increase in the inferior temporal retinal artery diameter (p = 0.01), with a 5.3 ± 7.7% increase at 30 min (p = 0.05) and 5.8 ± 5.0% increase at 90 min (p = 0.003). No significant changes were observed in the temporal retinal veins. Conclusions: Our results suggest that niacin produces vasodilatation of retinal arterioles. Further studies are needed to ascertain whether niacin treatment may be beneficial in retinal ischemic diseases.