A6 Diabetic Retinopathy: Retinal Vascular Damage

Topic

Retinal capillaries—the smallest blood vessels supplying the retina from within the retinal tissue itself, rather than from the underlying choroid—are surrounded by pericytes. These are contractile cells that support the wall of each retinal capillary and help regulate blood flow through it. When a person experiences chronic hyperglycemia—persistently high blood glucose levels over an extended period—this condition selectively damages the pericytes surrounding the retinal capillaries. Consequently, capillaries that lose their pericytes are left with weakened walls, lacking the structural support they previously provided.

A retinal capillary with a wall weakened by the loss of pericytes fails to maintain tight junctions between the cells forming that wall; through these compromised junctions, fluid and proteins begin to leak into the surrounding retinal tissue. This increased tendency for a capillary to allow its contents to escape is known as increased vascular permeability. The more retinal capillaries that lose their pericytes due to chronic hyperglycemia, the greater the overall increase in vascular permeability, leading to more fluid accumulation in the retinal tissue surrounding those capillaries.

In addition to becoming more permeable, some retinal capillaries damaged by chronic hyperglycemia eventually become completely obstructed. They cease supplying blood to the area of ​​the retina that depended on them—a lack of blood supply known as retinal ischemia. The ischemic retina releases vascular endothelial growth factor—the same chemical signal that drives new blood vessel growth in age-related macular degeneration; however, in this context, the signal prompts still-functional retinal capillaries (rather than choroidal vessels) to form new blood vessels that grow across the retinal surface and into the vitreous, the clear gel filling the eye's interior. This growth is known as retinal neovascularization.

The increased vascular permeability and retinal neovascularization caused by chronic hyperglycemia lead to distinct clinical problems. When fluid leaking due to increased vascular permeability accumulates specifically in the macula, the condition is called diabetic macular edema; it impairs central vision in much the same way that edema surrounding the macula does in age-related macular degeneration. Conversely, when the new blood vessels associated with retinal neovascularization continue to grow into the vitreous, their fragile walls may rupture and bleed into the vitreous, or they may pull along fibrous tissue that exerts traction on the retina, detaching it from the eye wall; this more advanced stage, characterized by extensive retinal neovascularization, is known as proliferative retinopathy.

Since both increased vascular permeability and retinal neovascularization stem from the damage chronic hyperglycemia inflicts on retinal capillary pericytes, glycemic control—maintaining blood glucose within a normal range—addresses the root cause and slows the damage to additional pericytes. When diabetic macular edema or proliferative retinopathy is already present, laser photocoagulation deliberately destroys the ischemic peripheral retina to reduce the release of vascular endothelial growth factor, thereby halting the stimulus driving retinal neovascularization; intravitreal anti-VEGF injections directly block that same vascular endothelial growth factor—much like in age-related macular degeneration—to reduce diabetic macular edema and curb retinal neovascularization; and in more advanced stages, characterized by vitreous hemorrhage or retinal traction, vitrectomy surgically removes the affected vitreous and relieves that traction.

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