**4. Does carotenoid vitamin therapy only help intermediate stage AMD?**

The AREDS trials showed that supplementation with carotenoid vitamin therapy prevented progression from intermediate to advanced stages of AMD. Further, the AREDS-2 trial [1] showed that the carotenoid supplementation with lutein and zeaxanthin indeed favored treatment, particularly in those that had low serum levels at baseline. It's a fair question to ask if the carotenoid vitamin therapy does benefit other stages of AMD? An equally important question is what other benefits can be seen in individuals with dry-AMD with carotenoid vitamin therapy? These are big questions, and it would be ideal if there were additional large-scale trials like AREDS that give us all the answers for early diagnosis, prognostic, and new treatments when they become available. This aspiration may be in part impractical for all scientific questions and when such large trials are not available doctors will need to evaluate all tiers of evidence available to derive clinical guidelines for disease states. Numerous reports have shown clinical benefits, by raising the levels of xanthophylls in the retina through dietary supplementation, thus, adjunctive carotenoid vitamin therapy may offer enhanced neuroprotection by augmenting MPOD and subsequently preventing further injury [16, 17]. Higher levels of MPOD are thought to preserve retinal tissue, specifically, the layers containing photoreceptors in the fovea, through two primary mechanisms: (1) serving as an innate optical filter against blue light; and (2) as protective antioxidants, by neutralizing free radicals and reducing consequent oxidative injury [16, 17]. In a recent systematic review of carotenoids in the management of AMD showed that there are at least 20 epidemiological studies and 35 randomized controlled trials that have evaluated this topic [17]. These studies evaluated various facets of the topic: supplementation and increase in serum carotenoids, MPOD, and changes in visual function. Whereas improvements in BCVA were seen in six out of eighteen (6/18) trials, remarkable benefits in contrast sensitivity were demonstrated in ten out of fifteen (10/15) randomized controlled trials [17]. Improvements were also seen in glare disability, photostress recovery time, and improvements in multifocal electroretinogram results [17]. Thus, it was concluded that consistent evidence from large-scale epidemiology studies, and several randomized clinical trials, substantiate the synergic neuroprotective benefits afforded by carotenoid vitamin therapy in eyes with any stage of AMD [17]. It is important to note that these visual benefits may be decreased in late-stage AMD compared to early or intermediate stage AMD [17, 18]. A dose-response relationship with stronger effect and greater serum carotenoids and MPOD levels is seen with supplementation of a greater dose of carotenoids [19]. In a recent RCT [20] we found that six-month supplementation with a greater amount of ocular carotenoids (28mg) and omega 3 supplement (675 DHA and 230 EPA), when compared to AREDS-2 formulation soft-gels (12 mg) not only provided greater serum carotenoid levels but also led to significant improvements in measured contrast sensitivity in individuals at risk of AMD. Indicating that quicker and greater visual benefits can be seen if a larger dose of ocular xanthophylls is supplemented to patients. There are numerous questions that remain to be answered for example do potent antioxidants like astaxanthin reach retinal layers? Are there any synergistic effects of these carotenoids? Scientists have answered a lot of questions and a lot more remain.

Roughly one in eight individuals aged 60 or greater is suffering from AMD; it is fair to say that it deserves our special attention. It was long believed that in the chronic disease of dry-AMD not much occurs or is needed until much later in disease state; we can confidently say, that is not true. With the advancement in clinical testing like Rabin Cone Contrast testing, we can detect this disease easily and along

#### *Recent Advances and New Perspectives in Managing Macular Degeneration*

with devices that can measure MPOD we can better manage the disease and monitor its progression. The objective technology of Macular Pigment Reflectometry to measure MPOD, and individual carotenoid optical density shows promise in personalized medicine. Also, there is sufficient data from various RCTs to recommend carotenoid vitamin supplement at all stages of AMD, which may prevent its progression but definitely provides an improvement in vision, and who does not like an improved vision!
