Use of vitamin A and fish oils for retinitis pigmentosa

What is the aim of this review?
The aim of this Cochrane Review was to determine whether vitamin A and fish oils work in delaying the continued worsening of vision in people with an inherited condition of the eyes that causes loss of vision (retinitis pigmentosa) and whether these treatments are safe.

Key messages
We are uncertain whether giving vitamin A or fish oil, or both to people with retinitis pigmentosa delays the continued worsening of vision, as the certainty of the evidence was very low. More research is needed, in particular information about whether vitamin A and/or fish oil with or without other vitamin supplements may affect clinical outcomes.

What was studied in the review?
Retinitis pigmentosa is a group of inherited eye disorders that cause a gradual, yet progressive, loss of vision. People with this eye disorder have difficulty seeing in low-light conditions, problems with vision out of the corner of the eye, and in most cases, gradually become visually impaired. Vitamin A or fish oils, or both have been proposed as having possible benefit in helping delay the progression of vision loss in this group of people.

What are the main results of the review?
We found four studies that were conducted in the USA and Canada, including a total of 944 participants between the ages of 4 and 55 years. The participants were given vitamin A or fish oil, or both because of their inherited eye disorder and were followed for four years. People who were given vitamin A or fish oil, or both, were compared with those who were not given vitamin A or fish oil. Participants in the vitamin A and/or fish oil group were given different doses of vitamin A or fish oil for differing lengths of time. Participants in the no-vitamin A and/or fish oil group were given pills that did not include vitamin A or fish oil (placebo pills); other treatments thought to prevent progression of vision loss such as multivitamins with or without traces of vitamin A; or no treatment at all.

The review shows that whether vitamin A or fish oil, or both, makes any difference in delaying the progression of visual loss is uncertain.

How up-to-date is this review?
We searched for studies that had been published up to 7 February 2020.

Authors' conclusions: 

Based on the results of four studies, it is uncertain if there is a benefit of treatment with vitamin A or DHA, or both for people with RP. Future trials should also take into account the changes observed in ERG amplitudes and other outcome measures from trials included in this review.

Read the full abstract...
Background: 

Retinitis pigmentosa (RP) comprises a group of hereditary eye diseases characterized by progressive degeneration of retinal photoreceptors. It results in severe visual loss that may lead to blindness. Symptoms may become manifest during childhood or adulthood which include poor night vision (nyctalopia) and constriction of peripheral vision (visual field loss). Visual field loss is progressive and affects central vision later in the disease course. The worldwide prevalence of RP is approximately 1 in 4000, with 100,000 individuals affected in the USA. At this time, there is no proven therapy for RP.

Objectives: 

The objective of this review was to synthesize the best available evidence regarding the effectiveness and safety of vitamin A and fish oils (docosahexaenoic acid (DHA)) in preventing the progression of RP.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL), which contains the Cochrane Eyes and Vision Trials Register (2020, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP); and OpenGrey. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 7 February 2020.

Selection criteria: 

We included randomized controlled trials that enrolled participants of any age diagnosed with any degree of severity or type of RP, and evaluated the effectiveness of vitamin A, fish oils (DHA), or both compared to placebo, vitamins (other than vitamin A), or no therapy, as a treatment for RP. We excluded cluster-randomized trials and cross-over trials.

Data collection and analysis: 

We prespecified the following outcomes: mean change from baseline visual field, mean change from baseline electroretinogram (ERG) amplitudes, and anatomic changes as measured by optical coherence tomography (OCT), at one-year follow-up, and mean change in visual acuity, at five-year follow-up. Two review authors independently extracted data and evaluated risk of bias for all included trials. We also contacted study investigators for further information when necessary.

Main results: 

In addition to three trials from the previous version of this review, we included a total of four trials with 944 participants aged 4 to 55 years. Two trials included only participants with X-linked RP and the other two included participants with RP of all forms of genetic predisposition. Two trials evaluated the effect of DHA alone; one trial evaluated vitamin A alone; and one trial evaluated DHA and vitamin A versus vitamin A alone. Two trials recruited participants from the USA, and the other two recruited from the USA and Canada. All trials were at low risk of bias for most domains. We did not perform meta-analysis due to clinical heterogeneity.

Four trials assessed visual field sensitivity. Investigators found no evidence of a difference in mean values between the groups. However, one trial found that the annual rate of change of visual field sensitivity over four years favored the DHA group in foveal (−0.02 ± 0.55 (standard error (SE)) dB versus −0.47 ± 0.03 dB, P = 0.039), macular (−0.42 ± 0.05 dB versus −0.85 ± 0.03 dB, P = 0.031), peripheral (−0.39 ± 0.02 versus −0.86 ± 0.02 dB, P < 0.001), and total visual field sensitivity (−0.39 ± 0.02 versus −0.86 ± 0.02 dB, P < 0.001). The certainty of the evidence was very low.

The four trials evaluated visual acuity (LogMAR scale) at a follow-up of four to six years. In one trial (208 participants), investigators found no evidence of a difference between the two groups, as both groups lost 0.7 letters of the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity per year. In another trial (41 participants), DHA showed no evidence of effect on visual acuity (mean difference −0.01 logMAR units (95% confidence interval −0.14 to 0.12; one letter difference between the two groups; very low-certainty evidence). In the third trial (60 participants), annual change in mean number of letters correct was −0.8 (DHA) and 1.4 letters (placebo), with no evidence of between-group difference. In the fourth trial (572 participants), which evaluated (vitamin A + vitamin E trace) compared with (vitamin A trace + vitamin E trace), decline in ETDRS visual acuity was 1.1 versus 0.9 letters per year, respectively.

All four trials reported electroretinography (ERG). Investigators of two trials found no evidence of a difference between the DHA and placebo group in yearly rates of change in 31 Hz cone ERG amplitude (mean ± SE) (−0.028 ± 0.001 log μV versus −0.022 ± 0.002 log μV; P = 0.30); rod ERG amplitude (mean ± SE) (−0.010 ± 0.001 log μV versus −0.023 ± 0.001 log μV; P = 0.27); and maximal ERG amplitude (mean ± SE) (−0.042 ± 0.001 log μV versus −0.036 ± 0.001 log μV; P = 0.65). In another trial, a slight difference (6.1% versus 7.1%) in decline of ERG per year favored vitamin A (P = 0.01). The certainty of the evidence was very low.

One trial (51 participants) that assessed optical coherence tomography found no evidence of a difference in ellipsoid zone constriction (P = 0.87) over two years, with very low-certainty evidence. The other three trials did not report this outcome.

Only one trial reported adverse events, which found that 27/60 participants experienced 42 treatment-related emergent adverse events (22 in DHA group, 20 in placebo group). The certainty of evidence was very low. The rest of the trials reported no adverse events, and no study reported any evidence of benefit of vitamin supplementation on the progression of visual acuity loss.

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