Current AMD research impacts clinical practice
During the COVID slowdown, researchers seem to have sped up publishing breakthrough research on age-related macular degeneration. Much of this can be applied to real-life optometric practice.
Healthy lifestyle affects visual impairment
Investigators at University of Massachusetts Medical School and Harvard Medical School recently conducted a longitudinal analysis among 5,421 eyes with nonadvanced AMD at baseline in 2,976 participants in the Age-Related Eye Disease Study (AREDS) (Seddon et al., AREDS Research Group).
The study, which was published in the December 2020 issue of Retina, noted that during a mean follow-up of 9.3 years, 948 eyes progressed to advanced AMD, 487 eyes progressed to geographic atrophy (GA), and 495 progressed to neovascular disease (NV) (some eyes had both endpoints). Remarkably, the researchers found that in addition to rare variants in the complement pathway and a common risk allele in ARMS2/HTRA1, smoking and higher BMI can lead to as much as 11.5 additional years of disease and treatment burden. As such, the authors conclude that closer adherence to healthy lifestyles could reduce years of visual impairment.
These study results indicate that optometrists should be more involved in AMD care throughout the disease continuum because injection therapy is not the only sight-saving intervention.
DA useful in AMD management
A systematic literature review of studies published between January 2006 and January 2020 found overwhelming evidence of an association between impaired dark adaptation (DA) and AMD (Higgins et al.).
To be eligible for inclusion in this 2021 review, studies had to be published in the English language in a peer-reviewed journal, include participants with AMD of any stage and include a dynamic measurement of rod and/or cone DA. Forty-eight studies were eligible for inclusion, 20 of which used the AdaptDx (MacuLogix) and assessed rod-intercept time (RIT).
The authors concluded that assessment of DA, which has been reported as a diagnostic indicator of AMD (Jackson et al. 2014 Invest Ophthalmol Vis Sci, Jackson et al. 2008) is a promising measure of visual function. Furthermore, because DA also has been shown to progressively increase with increasing severity of AMD, it may be used as a biomarker for disease progression as well (Jackson et al. 2014 Optom Vis Sci., Dimitrov et al., Owsley et al. 2017).
To that end, DA currently is being examined as a biomarker in a large multicenter longitudinal study aiming to find better ways to detect AMD progression (Thompson et al.). Extensive peer-reviewed evidence reveals that DA is a useful tool for diagnosing AMD and monitoring progression over time.
Oxidative stress may drive AMD
A 2021 cross-sectional study by researchers at Harvard Medical School analyzed the association between plasma metabolite levels and DA in AMD (Mendez et al.).
The study included patients with early (n=13), intermediate (n=31) and late (n=9) AMD as well as control subjects (n=18) older than 50 years with no vitreoretinal disease. Associations between DA and metabolite levels were tested, adjusting for age, gender, BMI, smoking, race, AMD stage and AREDS formulation supplementation.
Describing the motivation for the investigation, the authors note that although visual acuity (VA) is considered the gold-standard outcome in AMD, patients usually do not present with vision loss until late in the disease process (Laíns et al. 2017).
Impaired DA has been shown to occur early on AMD disease progression (Owsley et al. 2016 Ophthalmology, Owsley et al. 2001), even in the setting of normal visual acuity (Laíns et al. 2018) and it can differentiate between patients with and without AMD across all severity stages of the disease (Laíns et al. 2017, Owsley et al. 2016 Curr Eye Res, Owsley et al. 2007, Jackson et al. 2014 Invest Ophthalmol Vis. Sci.). Because of this, the researchers chose it as the outcome measure in this novel metabolome study that can help pave the way for a better understanding of AMD pathogenesis and address the substantial unmet need for new AMD treatments.
To that end, this study contributed meaningful insights, as it further confirms that oxidative stress and mitochondrial dysfunction may play an important role in driving AMD and visual impairment.
The study results indicate that when managing patients with early- through intermediate-stage AMD, optometrists should consider the impacts of oxidative stress in AMD pathogenesis and progression and consider strategies to combat it.
AMD is the leading cause of irreversible legal blindness, affecting one in eight adults age 60 and older (Klein et al.). As primary care providers, optometrists are uniquely positioned to intervene in meaningful ways, particularly now that methods of early detection are widely accepted and approaches to earlier intervention are likewise gaining widespread attention.
References:
Age-Related Eye Disease Study Research Group. Arch Ophthalmol. 2001;doi:10.1001/archopht.119.10.1417.
Dimitrov PN, et al. Invest Ophthalmol Vis Sci. 2012;doi:10.1167/iovs.11-8958.
Higgins BE, et al. Ophthalmol Ther. 2021;doi:10.1007/s40123-020-00323-0.
Jackson GR, et al. Invest Ophthalmol Vis Sci. 2014;doi:10.1167/iovs.13-13745.
Jackson GR, et al. J Ocul Biol Dis Inform. 2008;doi:10.1007/s12177-008-9002-6.
Jackson GR, et al. Optom Vis Sci. 2014;doi:10.1097/OPX.0000000000000247.
Klein R, et al. Arch Ophthalmol. 2011;doi:10.1001/archophthalmol.2010.318.
Laíns I, et al. Am J Ophthalmol. 2018,doi:10.1016/j.ajo.2018.03.035.
Laíns I, et al. Ophthalmology. 2017;doi:10.1016/j.ophtha.2017.03.061.
Mendez KM, et al. Metabolites. 2021;doi:10.3390/metabo11030183.
Owsley C, et al. Curr Eye Res. 2016;doi:10.3109/02713683.2015.1011282.
Owsley C, et al. Ophthalmology. 2001,doi:10.1016/s0161-6420(01)00580-2.
Owsley C, et al. Ophthalmology. 2007;doi:10.1016/j.ophtha.2006.12.023.
Owsley C, et al. Ophthalmology. 2016;doi:10.1016/j.ophtha.2015.09.041.
Owsley C, et al. Trans Vis Sci Technol. 2017;doi:10.1167/tvst.6.3.15.
Seddon JM, et al. Invest Ophthalmol Vis Sci. 2020;doi:10.1167/iovs.61.14.32.
Thompson AC, et al. Invest Ophthalmol Vis Sci. 2018;doi:10.1167/iovs.17-22528.
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