Reduced Central Retinal Artery Blood Flow Is Related to Impaired Central Visual Function in Retinitis Pigmentosa Patients

Abstract

Purpose: We evaluated the test-retest repeatability of blood flow velocities in the retrobulbar central retinal artery (CRA) and explored whether reduced blood flow is related to the degree of visual function loss in retinitis pigmentosa (RP) patients with wide range of disease severity.

Materials and methods: We measured CRA peak systolic velocity (PSV) and end diastolic velocity (EDV) to calculate mean flow velocity (MFV) in 18 RP patients using color Doppler imaging with spectral flow Doppler (GE Logiq7 ultrasound) twice in each eye at each of two visits within a month. At each of these two visits, we measured ETDRS visual acuity (VA), quick Contrast Sensitivity Function (qCSF), Goldmann visual fields (GVF), 10-2 Humphrey visual fields (HVF), and dark-adaptation at 5° from fixation with the AdaptDx; multifocal electroretinography (mfERG) was obtained at a single visit.

Results: Mean coefficients of variation for PSV, EDV and MFV were 16.1-19.2% for within-visit measurements and 20.1-22.4% for between-visit measures. Across patients, greater visual function loss assessed with VA (p = 0.04), extinguished versus measurable amplitude in ring 1 for mfERG (p = 0.001), and cone-only versus rod function with the AdaptDx (p = 0.002) were statistically significantly correlated with reduced MFV in the CRA when included a multilevel multivariate regression model along with the qCSF and HVF results, which all together accounted for 47% of the total variance in MFV. GVF log retinal areas (V4e and III4e; p = 0.30 and p = 0.95, respectively) and measurable far peripheral vision during GVF testing (p = 0.66) were not significantly related to MFV.

Conclusions: MFV in the CRA decreased with impaired central vision due to loss of both rod and cone function, had good test-retest repeatability, and may serve as a biomarker outcome to determine the potential physiological basis for improvements in RP clinical trials of therapies with indirect effects on blood flow to the retina.

Keywords: Blood flow; central retinal artery; color Doppler imaging; mean flow velocity; retinitis pigmentosa; visual function.

Figure 1

Bland-Altman graph of the mean test–retest percent difference between-visits plotted against the mean velocities obtained for PSV, EDV and MFV in each eye. The mean differences are shown as solid lines, and the 95% limits of agreement are shown with dashed lines.

Figure 2

Scatterplot of MFV, mean log PSV and mean EDV in the CRA in relation to mean logMAR ETDRS VA in each eye. The drawn lines represent linear regression lines. The R² value and p-value are for the relationship between MFV and VA adjusted for age and gender.

Figure 3

Scatterplot of MFV, mean log PSV, and mean EDV in the CRA in relation to AULCSF for the qCSF test in each eye. The drawn lines represent linear regression lines. The R² value and p-value are for the relationship between MFV and AULCSF for the qCSF test adjusted for age and gender.

Figure 4

Scatterplot of MFV, mean log PSV, and mean EDV in the CRA as an average of both eyes in relation to mean binocular Pelli-Robson log CS. The drawn lines represent linear regression lines. The R² value and p-value are for the relationship between MFV and Pelli-Robson log CS adjusted for age and gender.

Figure 5

Scatterplot of MFV, mean log PSV, and mean EDV in the CRA in relation to 10-2 HVF MD score with the size III test target in each eye. The drawn lines represent linear regression lines. The R² value and p-value are for the relationship between MFV and HVF MD score adjusted for age and gender.

Figure 6

Scatterplot of MFV, mean log PSV, and mean EDV in the CRA in relation to the mean score for the four most central test locations around fixation in the HVF 10-2 test in each eye. The drawn lines represent linear regression lines. The R² value and p-value are for the relationship between MFV and HVF mean score for the four most central test locations adjusted for age and gender.

Figure 7

Box plot of MFV, mean log PSV, and mean EDV in the CRA of each eye according to patients who had or did not have a recordable mfERG for ring 1. The bottom and top of the box are the 25th and 75th percentile (i.e., the upper and lower quartiles, respectively), and the band near the middle of the box is the 50th percentile (i.e., the median). The ends of the whiskers represent the lowest datum within 1.5 times the interquartile range of the lower quartile, and the highest datum still within 1.5 times the interquartile range of the upper quartile. Any data not included between the whiskers are plotted as an outlier indicated by a dot. The R² value and p-value are for the relationship between MFV and recordable mfERG for ring 1 adjusted for age and gender.