Is ‘Standard’ of care enough? AMD through the lens of Fundus Autofluorescence

6 11 2012

In optometric practice, the AMD demographic is rising as the baby-boomers balloon the aging population. AMD being the complex condition it is requires a comprehensive evaluation of all factors involved from the patient’s family and medical history all the way to the metabolic functioning of the basal layer of RPE cells. Ophthalmological evaluation in addition to visual functioning has been the gold standard of care until the emergence of in vivo dissection techniques offered by optical coherence tomography. OCT has opened the doorway to allowing primary care providers with the ability to decipher the need for tertiary intervention. In the vast majority of AMD patients that fall into the dry category, management of these patients can be scrutinized down to a metabolic level. Current understanding of the disease as an inflammatory condition has opened a new realm of pharmaceutical development that targets inflammatory precursors to prevent further degradation. The ENVISION CLARITY trial, for example, involves a vision cycle modulator (VCM) called acu-4429 which inhibits the disproportionate accumulation of A2-E in the post-mitotic RPE .  In pursuit of new therapies for diseases like AMD, the landscape of eye care is changing below our feet.

A 'normal' digital fundus image

A ‘normal’ digital fundus image

Fundus Autofluorescence of the same eye

Fundus Autofluorescence of the same eye revealing moderate AMD

… when the common denominator dictates what practitioners should and should not do, this actually reduces the standard of care to, arguably, a lower calibre of care

Dry AMD or non-exudative AMD has been reported to make up some 85-90% of AMD, the remainder being comprised of the exudative form. In recent years, research has pointed to disregulation of local inflammatory factors as the main contributor to AMD. AMD is known as a polygenic disease giving each individual multiple sequences to increase the risk of developing the condition.

Considering the inflammatory role of the disease, the metabolism of the RPE becomes an important indicator of local tissue health; specifically the accumulation of lipofuscin as a by-product of the RPE. Fundus autoflurescence (FAF) can therefore demonstrate the concentration and distribution of associated lipofuscin which correlates to the condition of the RPE in AMD patients . A dark area or hypofluoresced area demarks atrophic RPE as the major fluorophore is absent in this area. Hypo areas may also be a result of overlying haemorrhagic changes, increased melanotic tissue and the presence of subretinal fluid.

Hypo and hyperfluoresced areas in FAF can migrate from one to the next, depending on the local state of the tissue. Pigment epithelial and neurosensory detachment and areas with extracellular fluid accumulation associated with exudative lesions can be observed in FAF as increased or decreased signal. Fluid accumulation under pigment epithelium detachment, extracellular deposition of material under the RPE (drusen), and fluid originated from CNV can occur with increased, normal or decreased FAF intensity . It is always important to rely on multiple modalities of imaging to correlate FAF findings.

Once the advanced state of the disease is confirmed, a risk assessment results in the need for intervention. AREDS, a widely accepted study, looked at the natural history of AMD and also studied the modified risk of a specific pharmacological dose of nutritional supplements on the progression to advanced forms of AMD. The findings suggested that a combination dose of zinc, copper, Vitamin C, E and beta-carotene resulted in a risk reduction of 25% of disease progression and a 19% risk reduction of moderate vision loss (defined by ETDRS) over 5 years.

AREDS 2, which will be completed by 2013 was undertaken to extend the risk reduction protocol to include omega 3 (DHA and EPA) in addition to lutein and zeathanthin . Also, the question of whether beta-carotene should be included is being assessed as studies have shown that beta-carotene used with vitamin E in smokers has statistically significant risk of developing lung cancer. Although results haven’t been released, pharmaceutical companies have released versions of these supplements consistent with AREDS 2 to include both the omega-3 and lutein and zeathanthin (10mg lutein/2mg zeaxanthin and 350mg DHA/650mg EPA).

The availability of technologies like FAF will make them integral components of primary eye care. New therapeutics will only be as effective as the technology quantifying its efficacy by means of measuring the metabolic state of the retina.  Current discussions in all clinical practices revolve around standards of care and how clinicians can rise to that standard. One question that arises:  is a standard enough?  Is common ground the best way to drive health care decisions? Establishing a standard requires common agreement of the majority of a spectrum of clinicians based on current evidence and available tools. However in this scenario when the common denominator dictates what practitioners should and should not do, this actually reduces the standard of care to, arguably, a lower calibre of care. Individual standards give the practitioner the opportunity to think outside the box and truly reach a higher calibre of care.

Dr. Richard Maharaj OD, FAAO




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