Retinal Blood Vessel Positional Shifts and Glaucoma Progression Nathan M. Radcliffe, MD,1 Scott D. Smith, MD, MPH,2 Zeba A. Syed, BA,3 Sung Chul Park, MD,4 Joshua R. Ehrlich, MD,1 Carlos Gustavo De Moraes, MD,4,5 Jeffrey M. Liebmann, MD,4,5 Robert Ritch, MD4,6 Purpose: To determine the characteristics and significance of retinal blood vessel (RBV) positional shifts over time in a cohort of patients with progressive glaucoma. Design: Retrospective cohort study. Participants: Baseline and serial stereophotographs from 1 eye of 125 patients with open-angle glaucoma with 8 reliable Swedish interactive threshold algorithm standard visual fields (VFs) were included. On the basis of global rates of threshold sensitivity change, patients with glaucoma were divided into groups of minimal (0.6, or intereye asymmetry >0.2 in the absence of other retinal or neurologic abnormality that could explain these findings).
Determination of Visual Field Progression Reliable VF tests had 1/2 disc
diameter away from the scleral ring, whether or not in conjunction with optic nerve head blood vessel shifts. The graders were instructed to identify shifts in the contour or position of RBVs in comparison with the underlying choroidal vasculature or in relation to adjacent retinal features (e.g., fovea and other retinal vessels) to distinguish focal RBV shift (involving only part of the vessel) from global RBV shift (involving the entire vessel) associated with image parallax. The graders were reminded that image parallax is a global image transform and cannot, for example, distort a small region of one RBV in relation to another. The graders also were asked to differentiate focal RBV positional shift from isolated RBV caliber expansion or contraction (without blood vessel displacement) seen with arteriovenous pulsation.19 Arteriovenous pulsation may alter the diameter of arteries or veins but should not cause translational RBV shifts in which both sides of an RBV move in the same direction. Specific instructional examples of image parallax and cardiac cycle/arteriovenous pulsation were provided for reference before grading. After independently assessing all photographic sets for RBV shifts, graders I and II (still masked to all clinical data) jointly reviewed cases in which they had disagreed regarding RBV shift to reach a consensus.
Determination of False-Positive Blood Vessel Movement To determine the false-positive rate of RBV shift detection generated by camera or patient shift (image parallax) or by cardiac cycle,19 a group of 33 patients with glaucoma who had 2 distinct sets of photographs taken on the same day (assuming progression does not happen in such a short interval) were randomized into the photographic set. Assessments of RBV shifts by the graders in these same-day photographic sets were considered to be falsepositives.
Determination of Structural Progression A second set of 2 graders (III and IV) evaluating for optic nerve head progression were masked to the study design and independently evaluated the photographic sets for neuroretinal rim loss,14 PPA progression,16 and presence or absence of DH.15 To ensure high specificity, eyes were considered to have neuroretinal rim loss, PPA progression, or DH only when both graders independently agreed on their presence.
Statistical Analyses Eyes with and without RBV shift were compared with regard to their rate of VF progression (pointwise linear regression analysis) and conventional signs of structural progression (neuroretinal rim loss, PPA progression, and DH) using the Fisher exact test. The kappa statistic was used to calculate agreement between graders III and IV. Logistic models were constructed to evaluate RBV shift as a function of rates of VF progression and conventional signs of structural progression. Covariates were entered in the final multivariable model if their univariable association with RBV shift was significant at P 0.20. Statistical analyses were performed using Stata/IC 11.0 (StataCorp LP, College Station, TX). All statistical tests were 2-sided with a 0.05 level of significance.
Results A total of 158 image sets (125 longitudinal and 33 controls) with a mean follow-up of 6.51.6 years were analyzed. Demographic information for the 125 patients with open-angle glaucoma included in this study is summarized in Table 1. On the basis of global rates of VF threshold sensitivity change, patients were divided into tertiles
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Ophthalmology Volume 121, Number 4, April 2014 Table 1. Demographic Features of 125 Patients with Minimal, Moderate, or Fast Visual Field Progression Variables/Rate of Progression
Minimal Progression (N[33)
Moderate Progression (N[59)
Fast Progression (N[33)
Total (N[125)
Age (yrs) Female sex Mean IOP (mmHg) Baseline mean deviation (dB) Duration of follow-up (yrs) Global rate of progression (dB/yr)
61.712.1 13 15.02.3 6.94.7 6.01.6 0.210.19
63.511.3 22 14.83.3 6.74.4 6.81.4 0.300.21
64.211.4 13 15.82.4 5.94.3 6.21.8 1.040.53
63.211.5 48 15.12.9 6.54.4 6.51.6 0.360.56
P Value* 0.575 0.971 0.242 0.475 0.046y
Determination of Visual Field Progression Reliable VF tests had 1/2 disc
diameter away from the scleral ring, whether or not in conjunction with optic nerve head blood vessel shifts. The graders were instructed to identify shifts in the contour or position of RBVs in comparison with the underlying choroidal vasculature or in relation to adjacent retinal features (e.g., fovea and other retinal vessels) to distinguish focal RBV shift (involving only part of the vessel) from global RBV shift (involving the entire vessel) associated with image parallax. The graders were reminded that image parallax is a global image transform and cannot, for example, distort a small region of one RBV in relation to another. The graders also were asked to differentiate focal RBV positional shift from isolated RBV caliber expansion or contraction (without blood vessel displacement) seen with arteriovenous pulsation.19 Arteriovenous pulsation may alter the diameter of arteries or veins but should not cause translational RBV shifts in which both sides of an RBV move in the same direction. Specific instructional examples of image parallax and cardiac cycle/arteriovenous pulsation were provided for reference before grading. After independently assessing all photographic sets for RBV shifts, graders I and II (still masked to all clinical data) jointly reviewed cases in which they had disagreed regarding RBV shift to reach a consensus.
Determination of False-Positive Blood Vessel Movement To determine the false-positive rate of RBV shift detection generated by camera or patient shift (image parallax) or by cardiac cycle,19 a group of 33 patients with glaucoma who had 2 distinct sets of photographs taken on the same day (assuming progression does not happen in such a short interval) were randomized into the photographic set. Assessments of RBV shifts by the graders in these same-day photographic sets were considered to be falsepositives.
Determination of Structural Progression A second set of 2 graders (III and IV) evaluating for optic nerve head progression were masked to the study design and independently evaluated the photographic sets for neuroretinal rim loss,14 PPA progression,16 and presence or absence of DH.15 To ensure high specificity, eyes were considered to have neuroretinal rim loss, PPA progression, or DH only when both graders independently agreed on their presence.
Statistical Analyses Eyes with and without RBV shift were compared with regard to their rate of VF progression (pointwise linear regression analysis) and conventional signs of structural progression (neuroretinal rim loss, PPA progression, and DH) using the Fisher exact test. The kappa statistic was used to calculate agreement between graders III and IV. Logistic models were constructed to evaluate RBV shift as a function of rates of VF progression and conventional signs of structural progression. Covariates were entered in the final multivariable model if their univariable association with RBV shift was significant at P 0.20. Statistical analyses were performed using Stata/IC 11.0 (StataCorp LP, College Station, TX). All statistical tests were 2-sided with a 0.05 level of significance.
Results A total of 158 image sets (125 longitudinal and 33 controls) with a mean follow-up of 6.51.6 years were analyzed. Demographic information for the 125 patients with open-angle glaucoma included in this study is summarized in Table 1. On the basis of global rates of VF threshold sensitivity change, patients were divided into tertiles
843
Ophthalmology Volume 121, Number 4, April 2014 Table 1. Demographic Features of 125 Patients with Minimal, Moderate, or Fast Visual Field Progression Variables/Rate of Progression
Minimal Progression (N[33)
Moderate Progression (N[59)
Fast Progression (N[33)
Total (N[125)
Age (yrs) Female sex Mean IOP (mmHg) Baseline mean deviation (dB) Duration of follow-up (yrs) Global rate of progression (dB/yr)
61.712.1 13 15.02.3 6.94.7 6.01.6 0.210.19
63.511.3 22 14.83.3 6.74.4 6.81.4 0.300.21
64.211.4 13 15.82.4 5.94.3 6.21.8 1.040.53
63.211.5 48 15.12.9 6.54.4 6.51.6 0.360.56
P Value* 0.575 0.971 0.242 0.475 0.046y
