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    • br Clinical Importance and Key Message

    2018-10-23


    Clinical Importance and Key Message The Wong et al. study (Wong et al., 2016) is of epidemiological and clinical significance. The prevalence of VI as indexed in those with CKD is 36%, versus 13% among those without CKD. In the former, the odds ratio of VI among individuals without diabetes was 1.11 compared to 1.80 among individuals with diabetes. Moreover, the odds ratio of retinopathy among individuals without diabetes was 1.45 compared with 1.95 among individuals with diabetes. This is unacceptably high risk given that CKD, diabetes and eye diseases are treatable and preventable. Screening for ocular diseases in those with CKD, especially individuals with diabetes, is warranted. More generally, the Wong et al. paper (Wong et al., 2016) tells us that eye is not only the window to the kidney, but also to the brain.
    Disclosure
    Age-related macular degeneration (AMD) is the leading cause of blindness among people over 50years of age in the industrialized world (). A cardinal clinical feature of the disease is extracellular deposition of lipid-rich deposits underneath the retinal pigmented epithelium (RPE) called drusen, which contain high amounts of esterified and unesterified cholesterol (). In AMD, lipid accumulation can also be observed as sub-retinal drusenoid deposits or as thickening of the Bruch\'s membrane, an elastin-rich layer that separates the RPE from the choriocapillaris. Although drusen themselves do not always affect vision, they typically precede advanced AMD, which is associated with vision loss. Advanced AMD occurs in two forms that can co-exist: a) geographic atrophy (GA) associated with loss of RPE protease inhibitor cocktail and b) choroidal neovascularization (CNV) characterized by proliferative, anomalous growth of blood vessels underneath the retina that leads to hemorrhage and fibrosis (). Both GA and CNV ultimately cause vision loss due to photoreceptor cell death. Recent studies demonstrate that lipid deposits in AMD serve as a nidus for disease progression (). There are multiple mechanisms by which drusen and other extracellular lipids get deposited underneath the retina and accelerate disease pathogenesis: i) age-associated impairment of cholesterol homeostasis and reverse cholesterol transport (RCT) by macrophages and RPE, ii) lipid mediated RPE dysfunction and iii) activation of the innate immune response including aberrant macrophage polarization, activation of the complement cascade and accumulation of membrane attack complexes (MAC) around drusen and in the choroid (). Therefore, reducing the lipid burden in AMD without causing RPE atrophy or stimulating CNV is a desirable outcome and merits investigation. Previous interventions such as laser to reduce drusen have not been successful (). In this issue of , Vavvas et al. report anatomic and visual outcomes of a prospectively designed, non-randomized lipid lowering strategy in patients with AMD (). They demonstrate a quantitative reduction in drusen volume in 10 of 23 patients placed on high dose, oral atorvastatin without significant change in visual acuity. Although baseline cholesterol levels of participants were reported, lipid profiling including lipid class and lipoprotein particle size information was not reported. These measurements may have provided key insights into why there was no correlation between drusen reduction and serum lipid response to atorvastatin in this study. Carefully collected baseline lipid metrics will be essential in future studies. This study is very relevant since prior epidemiological studies have reported conflicting results regarding the efficacy of statins in AMD progression (). The report by Vavvas et al. illustrates the complexity of lipid modulation as a therapeutic strategy (). There are several unanswered questions: a) Is the natural history of disease always associated with an increase in drusen volume? A matched control group would be necessary to make definitive conclusions; b) Does an increase in drusen volume correlate with increased risk for developing GA or CNV?; c) Is there an association between a reduction in macular drusen and RPE atrophy as has been previously reported?; d) What is the optimal time and dose of treatment to assess therapeutic response and side effects so that the risk to benefit ratio can be reduced? These questions mandate large, randomized prospective studies. As such, we should exercise caution in interpreting the results of this small, prospective cohort.