Multimodal Imaging of Central Retinal Disease Progression in a 2-Year Mean Follow-up of Retinitis Pigmentosa

Abstract

Purpose: To determine the rate of progression and optimal follow-up time in patients with advanced-stage retinitis pigmentosa (RP) comparing the use of fundus autofluorescence imaging and spectral-domain optical coherence tomography.

Design: Retrospective analysis of progression rate.

Methods: Longitudinal imaging follow-up in 71 patients with retinitis pigmentosa was studied using the main outcome measurements of hyperautofluoresent ring horizontal diameter and vertical diameter along with ellipsoid zone line width from spectral-domain optical coherence tomography. Test-retest reliability and the rate of progression were calculated. The interaction between the progression rates was tested for sex, age, mode of inheritance, and baseline measurement size. Symmetry of left and right eye progression rate was also tested.

Results: Significant progression was observed in >75% of patients during the 2-year mean follow-up. The mean annual progression rates of ellipsoid zone line and hyperautofluorescent ring horizontal diameter and vertical diameter were 0.45 degree (4.9%), 0.51 degree (4.1%), and 0.42 degree (4.0%), respectively. The ellipsoid zone line width and hyperautofluorescent ring horizontal diameter and vertical diameter had low test-retest variabilities of 8.9%, 9.5%, and 9.6%, respectively. This study is the first to demonstrate asymmetrical structural progression rate between right and left eye, which was found in 19% of patients. The rate of progression was significantly slower as the disease approached the fovea, supporting the theory that RP progresses in an exponential fashion. No significant interaction between progression rate and patient age, sex, or mode of inheritance was observed.

Conclusions: Fundus autofluorescence and optical coherence tomography detect progression in patients with RP reliably and with strong correlation. These parameters may be useful alongside functional assessments as the outcome measurements for future therapeutic trials. Follow-up at 1-year intervals should be adequate to efficiently detect progression.

Copyright © 2015 Elsevier Inc. All rights reserved.

Figures

Figure 1. Structural measurements of a 13 year old girl with autosomal recessive retinitis pigmentosa (Usher’s Syndrome)

Fundus autofluorescence (AF) images (left panels) and optical coherence tomography (OCT) images (right panels) monitor progression over time. Dashed lines indicate the initial width of the horizontal diameter of the hyperautofluorescent ring in the AF images, and the initial width of the ellipsoid zone line in the OCT images. Progressive constrictions of the horizontal diameter and ellipsoid zone line are shown by the shortening of the solid white lines measuring horizontal diameter and ellipsoid zone line width in the three annual visits.

Figure 2. Correlation of standard-domain optical coherence tomography and fundus autofluorescence measurements in a cohort of 71 patients with retinitis pigmentosa

Scatterplots show AF horizontal ring diameter and SD-OCT ellipsoid zone width (left), AF vertical ring diameter and SD-OCT ellipsoid zone width (center), and AF vertical ring diameter and AF horizontal ring diameter (right).

Figure 3. Structural progression of retinitis pigmentosa over the follow up period

Subjects have been centered to start at the same size to more clearly show the change over time. Changes over time for individual subjects are graphed as grey lines. In each row from left to right, the first panel graphs the raw data of individual subjects. The next 3 panels graph the random slopes from the mixed models. The third panel shows data from subjects with baseline size >3000; the fourth panel shows data from subjects with baseline size ≤3000. A solid line depicts the mean line of declination for the data of each graph.

Figure 3. Structural progression of retinitis pigmentosa over the follow up period

Subjects have been centered to start at the same size to more clearly show the change over time. Changes over time for individual subjects are graphed as grey lines. In each row from left to right, the first panel graphs the raw data of individual subjects. The next 3 panels graph the random slopes from the mixed models. The third panel shows data from subjects with baseline size >3000; the fourth panel shows data from subjects with baseline size ≤3000. A solid line depicts the mean line of declination for the data of each graph.

Figure 3. Structural progression of retinitis pigmentosa over the follow up period

Subjects have been centered to start at the same size to more clearly show the change over time. Changes over time for individual subjects are graphed as grey lines. In each row from left to right, the first panel graphs the raw data of individual subjects. The next 3 panels graph the random slopes from the mixed models. The third panel shows data from subjects with baseline size >3000; the fourth panel shows data from subjects with baseline size ≤3000. A solid line depicts the mean line of declination for the data of each graph.

Figure 4. Asymmetry of structural progression in an 11 year old boy with X-linked retinitis pigmentosa

Dashed lines indicate the initial width of the ellipsoid zone line in the OCT images. Progressive constrictions of the ellipsoid zone line for OS and OD are shown by the shortening of the solid white lines measuring ellipsoid zone line width in the two visits 1.4 years apart. The difference between left and right eye progression using the mean of test and retest ellipsoid zone line measurements was 129.4μm/year. Fundus autofluorescence images of the hyperautofluorescent ring revealed a difference between eyes of 113.6μm/year using horizontal diameter measurements and 224.8μm/year using vertical diameter measurements.

Figure 4. Asymmetry of structural progression in an 11 year old boy with X-linked retinitis pigmentosa

Dashed lines indicate the initial width of the ellipsoid zone line in the OCT images. Progressive constrictions of the ellipsoid zone line for OS and OD are shown by the shortening of the solid white lines measuring ellipsoid zone line width in the two visits 1.4 years apart. The difference between left and right eye progression using the mean of test and retest ellipsoid zone line measurements was 129.4μm/year. Fundus autofluorescence images of the hyperautofluorescent ring revealed a difference between eyes of 113.6μm/year using horizontal diameter measurements and 224.8μm/year using vertical diameter measurements.

Figure 4. Asymmetry of structural progression in an 11 year old boy with X-linked retinitis pigmentosa

Dashed lines indicate the initial width of the ellipsoid zone line in the OCT images. Progressive constrictions of the ellipsoid zone line for OS and OD are shown by the shortening of the solid white lines measuring ellipsoid zone line width in the two visits 1.4 years apart. The difference between left and right eye progression using the mean of test and retest ellipsoid zone line measurements was 129.4μm/year. Fundus autofluorescence images of the hyperautofluorescent ring revealed a difference between eyes of 113.6μm/year using horizontal diameter measurements and 224.8μm/year using vertical diameter measurements.

Figure 4. Asymmetry of structural progression in an 11 year old boy with X-linked retinitis pigmentosa

Dashed lines indicate the initial width of the ellipsoid zone line in the OCT images. Progressive constrictions of the ellipsoid zone line for OS and OD are shown by the shortening of the solid white lines measuring ellipsoid zone line width in the two visits 1.4 years apart. The difference between left and right eye progression using the mean of test and retest ellipsoid zone line measurements was 129.4μm/year. Fundus autofluorescence images of the hyperautofluorescent ring revealed a difference between eyes of 113.6μm/year using horizontal diameter measurements and 224.8μm/year using vertical diameter measurements.