Geographic atrophy: Etiopathogenesis and current therapies

Area of Science:

• Ophthalmology
• Pathophysiology
• Immunology

Background:

• Geographic atrophy (GA) causes severe visual deficit with unclear etiology.
• A hypothesis suggests oxidative damage triggers chronic inflammation in the Bruch's membrane-RPE-choriocapillaris complex, involving complement pathway overactivation.
• Genetic factors can impair inflammatory response modulation, leading to cell damage and waste accumulation.

Purpose of the Study:

• To elucidate the etiology and pathophysiology of geographic atrophy.
• To investigate the role of oxidative damage and complement system overactivation in GA.
• To identify potential therapeutic targets for slowing GA progression.

Main Methods:

• Analysis of cellular damage and waste accumulation in affected tissues.
• Detection of tomographic findings and autofluorescence signals.
• Review of ongoing investigations into anti-inflammatory and antioxidant therapies.

Main Results:

• Waste accumulation (drusen, pigmentary changes) precedes photoreceptor and RPE atrophy.
• Ischemic processes with decreased choroid flow are associated with GA.
• Tomographic and autofluorescence findings aid in prognosis evaluation.

Conclusions:

• Geographic atrophy pathogenesis involves oxidative stress, inflammation, and complement system dysregulation.
• Early detection through imaging is crucial for individualized prognosis.
• Therapeutic strategies focus on reducing inflammation, oxidative damage, and toxin accumulation to preserve retinal cells.