Inner-retinal changes in AMD: Evidence, mechanisms, and future perspectives.

Area of Science:

• Ophthalmology
• Neuroscience
• Pathogenesis of Age-related Macular Degeneration (AMD)

Background:

• Traditionally, Age-related Macular Degeneration (AMD) was viewed as an outer-retina and choroid disorder.
• Emerging evidence highlights significant inner-retinal involvement from early stages of AMD.
• This challenges the established understanding of AMD pathogenesis.

Purpose of the Study:

• To review clinical and experimental evidence of inner-retinal changes in AMD.
• To explore how these changes impact disease understanding and management.
• To reframe AMD as a multi-layer neurovascular disease.

Main Methods:

• Synthesis of clinical and experimental data on inner-retinal alterations in AMD.
• Utilisation of advanced imaging like optical coherence tomography (OCT) and OCT angiography (OCTA).
• Inclusion of high-resolution histology findings.

Main Results:

• Identified inner-retinal changes include layer-specific thinning, microvascular rarefaction, impaired neurovascular coupling, and reactive gliosis.
• These changes are prevalent in early AMD and can precede or parallel outer-retinal degeneration.
• Inner-retinal pathology contributes to visual dysfunction not solely explained by photoreceptor loss.

Conclusions:

• Inner- and outer-retinal pathologies interact bidirectionally, supporting a neurodegenerative model.
• Inner-retinal integrity is crucial for AMD pathogenesis, influencing vulnerability.
• Recognizing inner-retinal involvement offers potential for earlier diagnosis, monitoring, and novel therapeutics.