Flavonoids and glaucoma: revisiting therapies from the past

Abstract

Flavonoids are a large family of phytonutrient compounds found in various plants (berries, tea, citrus fruits) as well as in chocolate and red wine. More than 5000 flavonoid compounds are currently known, grouped into five main categories (flavonols, flavan-3-ols, flavones, flavanones, and anthocyanidins). Flavonoids constitute 25 % of the Ginkgo biloba extract (GBE), processed from the leaves of one of the oldest living tree species, a Bliving fossil^, having survived since the Permian more than 250 million years ago. TheGinkgo biloba tree, which is found in the wild only in China, has been used for its therapeutic effects for more than 5000 years, both in China and worldwide. Today, the tree is cultivated across the world, and continues to be offered as alternative treatments for ailments associated with aging, such as neurodegenerative disorders, cognitive decline, vascular insufficiency and glaucoma, often with controversial results.Gingko biloba is the most common (50 %) herbal supplement used by elderly patients, often as an over-the-counter compound [1]. Due to their perceived antioxidant, anti-inflammatory and neuroprotective benefits, various flavonoids (and in particular GBE) have been proposed for the treatment of non-pressuredependent risk factors associated with glaucoma [2]. This interest has been propelled by the fact that classic glaucoma treatments, based on reduction of the intraocular pressure (IOP), may not always prevent glaucoma progression. This may be particularly true in patients with progressive primary open-angle glaucoma (POAG) despite IOP normalization, or in POAG patients with the normal-tension glaucoma (NTG) subtype. The use of flavonoids in glaucoma has been supported bymany in vitro and in vivo studies, suggesting their active role in neuroprotection, reduction of mitochondrial oxidative stress and improvement of ocular blood flow [3]. Since impaired ocular blood flow can be more pronounced in NTG than in POAG, or in progressive versus stable forms of POAG, it has been suggested that GBE—and more generally, flavonoids—could represent a promising adjuvant therapy in these two settings [4]. The high safety profile of flavonoids also contributes to its current popularity and its large over-thecounter consumption [5]. Despite numerous attempts to evaluate the efficacy of flavonoids and GBE in the treatment of glaucoma, only a few randomized comparative studies have been published so far, with conflicting results [6, 7]. Many of these studies have individually suggested a beneficial role in glaucoma, especially in NTG, but the small number of included patients and the heterogeneity of the study design make it difficult to draw a firm conclusion. In the current issue of Graefe’s Archive for Clinical and Experimental Ophthalmology, Patel et al. evaluate the efficacy of flavonoids in glaucoma and ocular hypertension, performing a review and a meta-analysis of the currently published data, including only randomized controlled trials [8]. The number of included studies was surprisingly small: among the initially 16,840 screened articles, only six trials encompassing a total of 214 participants could be included, based on the inclusion criteria. Despite a rigorous effort to avoid risks of bias at each step of the study, the authors chose to include patient populations with a large variety of conditions (ocular hypertension, POAG, NTG, chronic angle* Tin Aung aung.tin@snec.com.sg