Stuart Richer, OD, PhD, FAAO
Chief, Optometry Section – Eye Clinic
Dept of Veterans Affairs Medical Center
Associate Professor, Family & Preventive Medicine
Rosalind Franklin University of Medicine & Science
North Chicago, Illinois USA
“Dry” AMD: What’s New?
"Age-Related Macular Degeneration (AMD) is the leading cause of vision loss in aging western societies particularly among the more aged US WWII veterans. Dry AMD constitutes 90% of cases. While some 5.5 million Americans are projected to require emergency high tech management to avoid catastrophic vision loss from neovascular AMD by the year 2050, ten times this number, or some 55 million Americans will develop less severe, but none-the-less visually disabling RPE/photoreceptor atrophy. Beyond poly-genetic abnormalities (i.e. primarily complement 1H and myriad chromosones – 2, 5, 9, 22), we know from AREDS post hoc study data, that clinical cardiovascular associations including obesity, elevated homocysteine & c-reactive protein are related to environmental and nutritional problems common in America. We now know that presence of even a single large drusen doubles the cardiovascular death rate in that patient. Sedentary lifestyles, high intake of simple carbohydrates, saturated & manufactured trans fat, grain fed livestock, minimal consumption of micronutrient rich plant food & anti-inflammatory omega III oils (fish/nuts) - have all been shown to be associated with cardiovascular/ocular disease. High dose statins may be helpful on the one hand in reducing the classic cardiovascular risk factor cholesterol as well as c-reactive protein, yet on the other hand, are likely to deplete mitochondrial COQ10 reserves so crucial for photoreceptor metabolism. Results with statin therapy to date have been mixed and they should be used cautiously in patients where AMD is combined with neurodegenerative disease such as Parkinson’s. Vastly improved 2005 US governmental dietary guidelines, however, (www.mypyramid.gov
) (eating fewer calories, being more active and making wiser food choices) are generating much excitement with respect to public health and offer the best hope in preventing all age related eye diseases.
At our medical center, we have 15 years of experience managing atrophic AMD. We have published 3 major clinical trials (1996, 1999 & 2004) demonstrating that the atrophic form is nutrition responsive. Our 1996 Clinical Results demonstrated stabilization of visual function with multivitamins (without lutein) and were in part later validated by the AREDS National Eye Institute / NEI trial in 2001. Our 1999 two-part study provided a protocol for evaluation of atrophic AMD utilizing the amsler grid, contrast sensitivity function (CSF), Smith Ketterwell Low Luminance Test (SKILL), photo-stress - glare recovery, dietary food analysis and NEI/VFQ14 night vision symptom score. (Richer SP, Chapter 1: Antioxidants and the Eye. In: International Ophthalmology Clinics, Nutrition/CRC Press; Mitchell H. Friedlaender, Editor. Vol.40. Philadelphia: Lippincott Williams & Wilkins; 2000: 1-16). When used in an analogous fashion to a glaucoma workup (i.e. baseline and serial exams), this metric was useful for evaluating visual function in both incipient AMD (AREDS stage I and II retinal disease) as well as more advanced AMD (AREDS III and IV). Case series experimentation with spinach consumption provided a basis for a formal double masked, randomized placebo controlled study with lutein and lutein/antioxidants. Our 2004 study on Lutein (detailed below) is being evaluated by the National Eye Institute (AREDS II 2006–2012), in which I am a clinical investigator. Science from our laboratory and others suggests that the carotenoid lutein, among other nutrients, improves the visual function of most patients with AMD, even if these patients have only early manifestations of the disease not typically detected during standard eye examinations. The impact of such improvements in contrast sensitivity, glare recovery and night vision, and their effect on the sense of well being of the patient, as well as their driving safety have been traditionally underestimated by eye physicians. Whether or not advanced disease can be definitively prevented with lutein remains an unresolved scientific question, requiring a large number of patients studied over many years (AREDS II 2006-2012). Nonetheless, the majority of my male veteran AMD patients report dramatic improvements in their visual function within a few months of increasing either spinach or lutein supplementation especially when cosupplemented with fish. It is useful to frame the discussion with respect to a brief review of the science of AREDS, the emerging science of carotenoids and omega III fatty acids (AREDS II), temporal response (or non-response) to lutein supplemenation (LAST II) and other clinical work of interest: the Luxea and Phototrop® studies. Many basic science studies are underway as well.
In 2001, the US NEI demonstrated that supplementation of AMD patients with a combination of high-dose zinc/copper, beta-carotene, vitamin C, and vitamin E slowed visual loss and progression to advanced AMD, however, atrophic AMD patients did not typically have visual improvement. The NEI results were similar to our 1997 findings using multivitamins/minerals without lutein (JAOA
1997;67,12-49). Shortly thereafter, we placed patients on spinach, and noted short term improvement in visual function in case series experiments. (JAOA
1999;70;24-36). We further determined that photo-stress glare recovery (GR) and contrast sensitivity (CSF) are weak surrogate markers for macular pigment optical density (MPOD) - (ARVO 2001, Richer et al, #3804; ARVO 2002, Pratt et al, #2540) and that high MPOD in female patients with and without a family history of AMD resulted in equal visual function (GR and CSF) in these 2 groups of patients. (ARVO
2002, Pratt et al #2540) The objective of the lutein antioxidant supplementation trial (LAST STUDY–Optometry
2004;75:216-30) was to determine whether nutritional supplementation with the carotenoid lutein (found in spinach) or lutein together with antioxidants, vitamins and minerals, improves visual function and symptoms in atrophic AMD. Methods
The LAST study was aprospective, 12-month, randomized, double-masked, placebo-controlled trial conducted at an urban mid western-Veterans Administration Hospital. Ninety patients with atrophic AMD were referred by ophthalmologists at two Chicago, USA veterans medical facilities. Patients in group 1 received lutein 10 mg (L) , in group 2 a lutein 10 mg / antioxidants / vitamins and minerals broad spectrum supplementation