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Many factors contribute to geographic atrophy development
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WAILEA, Hawaii — Risk factors for geographic atrophy development and progression are well known but the precise causal mechanism is not.
“The ultimate answer may only become apparent when an effective drug is developed that, in turn, implicates a mechanism,” Daniel F. Martin, MD, said at Retina 2018, adding that subclinical choroidal neovascularization may play a role.
Many cell types are involved in the pathophysiology of geographic atrophy, he said, coupled with the combination of biological and genetic risk factors, such as higher body mass index and smoking history.
“The real problem is that we don’t have an animal model to help us sort this out,” he said.
Over the years a variety of pathways have been implicated as mechanisms: oxidative stress, excessive accumulation of lipofuscin, chronic inflammation, malfunction of the complement system, loss of vascular perfusion and now the presence of subclinical CNV.
The cause is likely multifactorial, according to Martin.
“What’s clear to me is that the critical pathway that should be targeted is not scientifically proven,” he said and suggested that the pathophysiology of geographic atrophy may ultimately only be determined by finding an effective drug and working backward.
Even though data implicate the complement system in the pathogenesis of AMD, it does not necessarily mean that complement dysfunction contributes primarily to geographic atrophy, he said.
“There’s no hard evidence that says it’s complement that’s responsible for that,” he said.
Regarding CNV, Martin said that many eyes harbor occult subclinical CNV and that nonexudative CNV has been identified in as many as 20% of eyes with intermediate dry AMD on OCT angiography, suggesting an “intriguing” possible role for subclinical CNV in development of geographic atrophy. – by Patricia Nale, ELS
Reference:
Martin DF. Geographic atrophy: What causes it? Presented at: Retina 2018; Jan. 14-19, 2018; Wailea, Hawaii.
Disclosure: Martin reports no relevant financial disclosures.