A Randomized Prospective Trial Comparing Repository Corticotropin Injection and Intravenous Methylprednisolone for Neuroprotection in Acute Optic Neuritis.

BACKGROUND: Repository corticotrophin injection (RCI, Acthar Gel) and intravenous methylprednisolone (IVMP) improve the rate but not the extent of visual recovery following acute optic neuritis. RCI has adrenal-stimulating and melanocortin receptor-stimulating properties that may endow it with unique anti-inflammatory properties relative to IVMP. METHODS: Individuals with acute optic neuritis of less than 2 weeks duration were prospectively enrolled and randomized 1:1 to receive either RCI or IVMP. Peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer thickness (GC + IPL) were serially evaluated by OCT. In addition, patient-reported outcomes (PROs) for changes in fatigue, mood, visual function, depression, and quality of life (QOL) were measured, and high and low contrast visual acuity were recorded. RESULTS: Thirty-seven subjects were enrolled (19 RCI; 18 IVMP); the average time from symptom to treatment was 8.8 days. At 6 months, there was no difference in the primary outcome: loss of average pRNFL thickness in the affected eye (RCI vs IVMP: -13.1 vs -11.7 µm, P = 0.88) 6 months after randomization. Additional outcomes also showed no difference between treatment groups: 6-month attenuation of GC + IPL thickness (RCI vs IVMP: -13.8 vs -12.0 µm, P = 0.58) and frequency of pRNFL swelling at 1 month (RCI vs IVMP: 63% vs 72%, P = 0.73) and 3 months (RCI vs IVMP: 26% vs 31%, P = 0.99). Both treatments resulted in improvement in visual function and PROs. CONCLUSIONS: Treatment of acute optic neuritis with RCI or IVMP produced no clinically meaningful differences in optic nerve structure or visual function.

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 (ChB Vol), and flow (ChBF low) in the center of the fovea. RESULTS: We found a significant inverse relationship between total drusen area and ChB Vol or ChB Flow. For every 1-mm2 increase in total drusen area, ChB Vol decreased by 0.0061 arbitrary units (P = 0.03) and ChBF low decreased by 0.23 arbitrary units (P = 0.049). Average druse area was also significantly inversely related to ChB Vol and ChBF low. For every 0.01-mm2 increase in average druse area, the ChB Vol decreased by 0.0149 arbitrary units (P = 0.001) and the ChB Flow decreased by 0.4951 arbitrary units (P = 0.003). Adjustment for age weakened the significance, although it remained strong for average druse area versus ChB Flow (P = 0.017) and ChB Vol (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 ChB Vol and ChB Flow. This suggests the presence of ischemia and possibly the reason why patients with high-risk drusen are prone to advanced disease.

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 choroidal 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.

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.

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.

Effect of viagra on retinal vein diameter in AMD patients.

The aim of the present study was to investigate the effect of sildenafil citrate (viagra) on retinal venous diameter in patients with age-related macular degeneration (AMD). We investigated 14 male patients in a double-masked, randomized, placebo-controlled, crossover study. In each subject, one eye with typical non-exudative AMD fundus features was studied. Each of the subjects received 100 mg dose of sildenafil or matching placebo on two separate study visits. Monochromatic fundus photographs were obtained in the study eye before dosing and then 30, 90, 180 and 300 min later. Measurements of the diameter of the major retinal veins from digitized negatives were carried out using "Vessel map" static vessel analysis program (IMEDOS GmbH, Weimar, Germany). Statistical analysis of the data comparing the effect of sildenafil and placebo on venous diameters was performed using analysis of variance (ANOVA) for repeated measures. An analysis of variance (ANOVA) comparing the effects of sildenafil citrate and placebo on retinal vein diameters showed a significant interaction between time and treatment (P = 0.03). In comparison to placebo, sildenafil citrate produced a statistically significant vasodilatation of major retinal veins of 4.7% at 90 min (P = 0.004), 5.5% at 180 min (P < 0.0001) and 5.8% at 300 min (P < 0.0001). At 30 min there was a 2.2% difference, which was not statistically significant (P=0.14). Our results suggest that in patients with age-related macular degeneration, sildenafil citrate (viagra) produces a statistically significant vasodilatation of major retinal veins that is similar to what has been reported in normal subjects. Whether this vasodilatation is associated with changes in retinal blood flow needs to be further investigated.

Effect of Viagra on the foveolar choroidal circulation of AMD patients.

To investigate the effects of sildenafil citrate (Viagra) on foveolar choroidal circulation in patients with age related macular degeneration (AMD). Double-blinded, randomized, placebo-controlled, crossover study. Fifteen male AMD patients received a dose of 100 mg of sildenafil or matching placebo on two separate days. Laser Doppler flowmetry was performed to assess relative choroidal blood velocity (ChB(Vel)), volume (ChB(Vol)) and flow (ChB(Flow)) in the study eye prior to administration of the drug at baseline and 30, 90, 180, 300 min after dosing. Best corrected visual acuity (BCVA), contrast sensitivity (CS), mean arterial blood pressure (BPm), heart rate (HR), intraocular pressure (IOP) and ocular perfusion pressure (PP) were determined. In comparison to placebo, sildenafil did not cause any statistically significant changes in mean ChB(Vel) (ANOVA, P=0.12), ChB(Vol) (ANOVA, P=0.24) or ChB(Flow) (ANOVA, P=0.46). There were no statistically significant changes in CS (ANOVA, P=0.59), BCVA (P=0.58), IOP (P=0.81) or HR (P=0.07) throughout the study. Significant decreases in BPm (P=0.006) and PP (P=0.006) were observed at 30 min after sildenafil. Administration of sildenafil citrate didn't cause any statistically significant changes in the foveolar choroidal circulation of AMD patients.

Reduced foveolar choroidal blood flow in eyes with increasing AMD severity.

PURPOSE: In an earlier study, the authors reported that foveolar choroidal blood flow (ChBFlow) decreases in patients with AMD and drusen. To explore further the choroidal circulatory changes in patients with AMD, the relationship between ChBFlow and fundus features associated with increased risk of choroidal neovascularization (CNV) were investigated. METHODS: The study included 26 control eyes of 17 normal subjects and 163 eyes with early AMD characteristics of 123 patients with AMD. The AMD study eyes were divided into three groups according to increasing risk for development of CNV: (1) drusen > or =63 microm, no RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye; (2) drusen > or =63 microm, RPE hyperpigmentary changes in the study eye, and no CNV in the fellow eye; and (3) eyes with CNV in the fellow eye. Laser Doppler flowmetry was used to assess relative foveolar choroidal blood velocity (ChBVel), volume (ChBVol), and flow (ChBFlow). Differences in the mean circulatory parameters were assessed by analysis of variance (ANOVA) and test of linear trend. RESULTS: Mean ChBVel, ChBVol, and ChBFlow decreased with increased risk for CNV (linear trend, P < 0.05). The lowest circulatory parameters were observed in the eyes with the highest risk for CNV development. Trends for ChBVel and ChBFlow were still significant after adjustment for multiple factors. CONCLUSIONS: There is a systematic decrease in choroidal circulatory parameters with an increase in the severity of AMD features associated with risk for the development of CNV, suggesting a role for ischemia in the development of CNV.