Antioxidant Saffron and Central Retinal Function in ABCA4-Related Stargardt Macular Dystrophy

Marco Piccardi, Antonello Fadda, Francesco Martelli, Dario Marangoni, Adriano Magli, Angelo M Minnella, Matteo Bertelli, Stefano Di Marco, Silvia Bisti, Benedetto Falsini, Marco Piccardi, Antonello Fadda, Francesco Martelli, Dario Marangoni, Adriano Magli, Angelo M Minnella, Matteo Bertelli, Stefano Di Marco, Silvia Bisti, Benedetto Falsini

Abstract

Retinal oxidative damage, associated with an ATP-binding cassette, sub-family A, member 4, also known as ABCA4 gene mutation, has been implicated as a major underlying mechanism for Stargardt disease/fundus flavimaculatus (STG/FF). Recent findings indicate that saffron carotenoid constituents crocins and crocetin may counteract retinal oxidative damage, inflammation and protect retinal cells from apoptosis. This pilot study aimed to evaluate central retinal function following saffron supplementation in STG/FF patients carrying ABCA4 mutations.

Methods: in a randomized, double-blind, placebo-controlled study (clinicaltrials.gov: NCT01278277), 31 patients with ABCA4-related STG/FF and a visual acuity >0.25 were randomly assigned to assume oral saffron (20 mg) or placebo over a six month period and then reverted to P or S for a further six month period. Full ophthalmic examinations, as well as central 18° focal electroretinogram (fERG) recordings, were performed at baseline and after six months of either saffron or placebo. The fERG fundamental harmonic component was isolated by Fourier analysis. Main outcome measures were fERG amplitude (in µV) and phase (in degrees). The secondary outcome measure was visual acuity.

Results: supplement was well tolerated by all patients throughout follow-up. After saffron, fERG amplitude was unchanged; after placebo, amplitude tended to decrease from baseline (mean change: -0.18 log µV, p < 0.05). Reverting the treatments, amplitude did not change significantly. fERG phase and visual acuity were unchanged throughout follow-up.

Conclusions: short-term saffron supplementation was well tolerated and had no detrimental effects on the electroretinographic responses of the central retina and visual acuity. The current findings warrant further long-term clinical trials to assess the efficacy of saffron supplementation in slowing down the progression of central retinal dysfunction in ABCA4-related STG/FF.

Keywords: ABCA4 gene mutation; antioxidants; focal electroretinogram; neuroprotection; personalized medicine; photoreceptors; retinal function; saffron.

Conflict of interest statement

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. A patent “Compositions based on saffron for the prevention and/or treatment of degenerative eye disorders” covering the topic of this manuscript has been filed on 20 March 2015 (W02015/145316) and is owned by Hortus Novus Srl. S.B. is one of the inventors of the patent. S.B. holds a nonremunerative relationship with Hortus Novus Srl.

Figures

Figure 1
Figure 1
Box plots the fERG amplitude values recorded at baseline and after six months of S (Treatment) or P (Placebo) supplementation, following the cross-over study design. The symbol and line in the middle of the box indicate the mean and the median, the box lower and upper boundaries the 25th and 75th percentiles, and the lower and upper whiskers the 5th and 95th percentiles, respectively.
Figure 2
Figure 2
(A) Box plot showing the difference from baseline fERG Log amplitude recorded at the end of the first six-month study period in patients assuming S (Treatment) and those assuming P (Placebo). (B.) The same changes recorded in A shown as a scatter of data points. The diagonal line in the plot indicates equivalence. It can be noted that in seven out of 17 patients assuming P, fERG amplitude losses were substantially larger compared to those recorded in the 14 patients assuming S.

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