Clinical Drug Experience Knowledgebase

Neurodegeneration of the optic nerve and associated ganglion cell death in glaucoma leads to several well-characterized losses in visual function, most notably progressive peripheral visual field loss. Several recent studies have characterized significant visual function deficits in glaucoma patients that may be more sensitive indicators of disease than classical visual field loss, including compromised contrast sensitivity (CS), increased disability glare (DG) and protracted dark adaptation (DA).

Given the available evidence, it appears that visual function, if assessed carefully, is a reliable indicator of ocular health and/or disease state. It follows that an improvement in visual function would be indicative of an improvement in ocular health. Although improvement of visual function is not typically seen in ocular disease, there is recent evidence to suggest that visual performance and associated progression of ocular disease may actually be modifiable via nutritional strategies and dietary modification in age-related macular degeneration (AMD). Because some of the compromised visual performance experienced in glaucoma is associated with increased ocular inflammation, local anti-inflammatory action may improve visual performance in glaucoma patients. Given their exceptional anti-inflammatory activity and potential for rich deposition in the retina, the macular carotenoids lutein (L), zeaxanthin (Z), and mesozeaxanthin (MZ) may hold promise for this strategy. Indeed, a recent cross-sectional study of the relationship between macular carotenoid level and visual performance in glaucoma patients found that those patients with low levels were significantly more likely to experience problems with glare - and were also more likely to have greater ganglion cell loss.

L and Z are diet-derived, yellow-orange colored carotenoids obtained primarily from leafy-green vegetables. L and Z are not synthesized by the body, and therefore must be obtained via dietary means; those who have diets rich in leafy greens, or supplement with sufficient L and Z tend to maintain and accumulate higher blood and tissue concentrations. One of the conspicuous features of L and Z is their specific accumulation in the macular retina, where they can reach extremely high concentrations - values as high as 1.50 log optical density near the foveal center are not uncommon; it is also not uncommon to see concentrations in the fovea that exceed 10,000 times that seen in the blood. Once deposited in the retina, some of the L is converted to a stereoisomeric form of zeaxanthin, called mesozeaxanthin (MZ). Although rare, MZ has been shown to exist in nature, and indeed in the human food chain - its presence has been recently verified in salmon, trout, and sardine skin, and also trout flesh. Importantly, MZ has been shown to be readily deposited in the retina when taken in supplement form. The accumulation of these three carotenoids in the macula yields a yellowish-orange coloration, classically known to ophthalmologists as the "macula lutea" ("yellow spot"). Today, this collective pigmentation is commonly referred to as macular pigment (MP), with concentrations typically expressed in terms of optical density (MPOD). Xanthophyll carotenoids such as L, Z, and MZ are especially potent antioxidants. Via a process called triplet excitation transfer, L, Z, and MZ can regenerate to repeatedly "quench" the energy of singlet oxygen. This makes them capable of long-term accumulation in target tissues such as the retina, where, in the absence of excessive oxidative or inflammatory stress (e.g. smoking, or systemic disease such as diabetes), they are resistant to turnover, and can provide continuous protection against oxidation and inflammation.

Another critical function of the macular carotenoids involves their optical properties within the eye. Visual discomfort in glare, disability glare, and photostress recovery time are all significantly improved with higher MPOD status. CS has also been found in several laboratories (for both normal and clinical populations) to be related to / enhanced by augmentation of MPOD. Dark adaptation speed, absolute scotopic thresholds, and mesopic contrast sensitivity have also been found to be impacted positively by MPOD.

A high concentration of macular carotenoids (i.e. high MPOD) is therefore advantageous in at least three ways: 1) Protection from oxidation and inflammation, 2) Filtration of potentially actinic high-energy short-wavelength light, and 3) Improvement of visual performance (via pre-receptoral screening of short-wave light and neurophysiological enhancement).

For baseline measures, the proposed study has the potential to determine cross-sectional relationships between MPOD, visual performance, and disease severity in glaucoma. Given the recent data, significant relationships are plausible - and if the investigators determine these kinds of relationships, standard of care for glaucoma patients could be changed to include improved patient education regarding nutrition. Additionally, visual function testing (to include CS, DA, and DG testing) may be instituted for glaucoma suspects and established glaucoma patients. If the investigators are able to show an acute effect of improvement in visual performance, it could lead to larger trials that may yield extremely important data with regard to management of glaucoma. Given the predicted exponential increase in worldwide glaucoma prevalence (76 million in 2020 to 111.8 million in 2040), strategies that may promote good visual function in glaucoma would be hugely significant.