Docosahexaenoic Acid Slows Visual Field Progression in X-Linked Retinitis Pigmentosa: Ancillary Outcomes of the DHAX Trial

Abstract

Purpose: Docosahexaenoic acid (DHA) was supplemented in a single-site, placebo-controlled, randomized clinical trial designed to slow vision loss associated with X-linked retinitis pigmentosa (XLRP); the DHAX Trial. We previously reported no significant differences between supplemented and placebo groups in intent-to-treat analysis of primary ERG outcomes. Assessed herein are hypothesis-generating measures of ancillary visual function outcomes in participants fully adhering to trial protocol.

Methods: Male participants with XLRP (range, 7-31 years) received 30 mg DHA/kg/d (n = 29) or placebo (n = 22) for 4 years. Visual outcomes were measured annually and red blood cell (RBC) DHA determined every 6 months.

Results: Oral DHA supplementation increased mean RBC-DHA levels by 4-fold (P < 0.0001) over placebo. No group differences in progression were found for visual acuity (P = 0.11), shape discrimination (P = 0.18), or fundus appearance (P = 0.70). Optical coherence tomography (OCT) became available during year 2 of the trial; no group differences were seen in ellipsoid zone constriction (P = 0.87) over 2 years. Yearly rates of progression were reduced for dark-adapted thresholds (P = 0.06) and visual field sensitivity for foveal, macular, peripheral, total, and ellipsoid zone regions by DHA supplementation (P = 0.039, P = 0.031, P < 0.0001, P < 0.0001, and P = 0.033). Rates of visual field sensitivity decline were dependent on RBC-DHA (P = 0.046 to <0.0001).

Conclusions: Supplementation of DHA significantly elevated blood DHA levels and reduced the rate of progression in final dark-adapted thresholds and visual field sensitivity. From the relationship between RBC-DHA and the rate of field sensitivity loss, we can extrapolate that an RBC-DHA level of 17% could minimize the decline in field sensitivity. (ClinicalTrials.gov number, NCT00100230.)

Figures

Figure 1

Fundus image scoring. Representative images of scoring grades comparing fundus appearance progression from trial year 0 to year 4. A score of 0 = no identifiable change; 1 = minimal change; 2 = moderate change including new pigmentation and/or further vessel attenuation; and 3 = severe progression with multiple new deposits of pigmentation.

Figure 2

Ellipsoid zone anatomic and EZ transitional visual field sensitivity. Identified by semiautomated segmentation of retinal frequency-domain OCT from participant G101 (segmentation lines not shown) is the dense layer of outer photoreceptor segments termed the EZ which lies between the hyperreflective ISe and the hyperreflective RPE band. The anatomic EZ width was defined by the nasal and temporal points where the outer segment layer has declined to zero (▴) at trial year 2 (A) and year 4 (B). By superimposing the visual fields over the segmented scans, two nasal visual field locations just inside the EZ edge were selected for each patient for evaluation of EZ transitional visual field sensitivity (V).

Figure 3

Docosahexaenoic acid in red blood cells (RBCs) of per protocol participants as a function of time. Values for %RBC-DHA at each 6-month time point are depicted for placebo (blue lines) and DHA-supplemented individuals (gray lines). Mean values for the placebo (▴···▴) and DHA (▪ — ▪) groups were significantly different at each time point between 0.5 and 4 years; P

Figure 4

Yearly change in tVFS as a function of time on intervention in the per protocol cohort. Values are the mean ±SE decibels (dB) for each trial year of participants receiving placebo (▴···▴) or DHA (▪ — ▪) supplement. Placebo and DHA group means were significantly different at year 1 (P = 0.016); year 2 (P = 0.005); year 3 (P = 0.018); and year 4 (P

Figure 5

Association of RBC-DHA and 4-year loss of tVFS. Values are mean RBC-DHA (in total percent of fatty acids) for each per protocol participant between year 0.5 and year 4 compared with loss of tVFS (in dB) from year 0 to year 4 for placebo (▴) and DHA (▪) groups. The dashed line represents a Pearson regression (r = −0.55, P