Retinal Blood Supply and RPE Structure

• Two arteries supply blood to the retina: choriocapillaries and the central retinal artery.
• Choriocapillaries supply blood to the outer layers of the retina from short posterior ciliary arteries.
• The central retinal artery provides blood to the inner layers of the retina.
• The superficial plexus is in the NFL, and the deep plexus is in the INL.
• The outer retinal barrier prevents blood or fluid from the choriocapillaries from entering, between Bruch's membrane and RPE with tight junctions.
• The inner retinal barrier is formed by endothelial cells of the vessel walls, with tight junctions to prevent leakage of blood or fluid.

RPE structure

• The RPE is a single layer.
• The cells have an outer non-pigmented basal element with a nucleus.
• They contain an inner pigmented apical section containing melanosomes, which are more concentrated in the foveal area to absorb more photons.
• The cell base is in contact with Bruch's membrane.
• In the posterior pole and fovea, RPE cells are taller, thinner, and more regular with more melanosomes compared to the periphery.

RPE functions

• The RPE and zonula occludens, which are tight junctions, make up the outer blood-retinal barrier.
• Zonula occludens prevent leakage from Bruch's membrane and choriocapillaries between RPE cells.
• Phagocytosis and lysosomal degradation of outer segments of photoreceptors.
• RPE cells conduct phagocytosis of waste products because of phototransduction.
• Waste products accumulate, forming lipofuscin when disrupted.
• The outer blood-retinal barrier is maintained to transport metabolites and metabolic waste products.
• RPE cells store, metabolize, and transport vitamin A for the visual cycle, aquiring it from choriocapillaries for photoreceptors to enable phototransduction using 11-cis-retinal.
• The RPE is dense to absorb light.

Bruch's membrane structure

• Bruch's membrane separates the RPE from the choriocapillaries.
• It is a barrier that prevents leakage from the choroid to the RPE, and contains tight junctions that make up the outer-retina blood barrier.
• It is composed of 5 elastic collagen layers.
• If it breaks, vessels move into the outer and inner retinal layers, and is linked to ARMD and geographic atrophy.
• Its integrity is important in suppressing choroidal neovascularization (CNV).

Bruch's membrane function

• The RPE uses Bruch's membrane as a transportation route for waste metabolic products out of the retina.
• Changes in it are involved in the pathogenesis of macular disorders.

Anatomical landmarks

• Macula: 5-6 mm diameter, central 10-15 degrees visual field, yellow from xanthophyll, carotenoid pigments lutein and zeaxanthin (higher concentration), than in periphery
• Fovea: depression center, 1.5 mm diameter
• Foveola: center of fovea, 0.35 mm diameter, thinnest part of retina, cones, muller cells, no bipolar cells

Foveal avascular zone (FAZ)

• The foveal avascular zone has no retinal blood vessels but is surrounded by a network of capillaries.
• Umbo: depression in the center of the foveola, foveal reflex (no FR is an early sign of a problem)

Tests to perform

• Visual acuities
• Contrast sensitivity
• Amsler grid
• Fundus biomicroscopy
• Post pole evaluation
• Peripheral evaluation
• Fluorescein angiography (FA)
• Indocyanine green (IG) – choroidal circulation
• Optical Coherence Tomography (OCT)
• Fundus Autofluorescence (FAF) –RPE function (loss of autofluorescence)

Macular edema

• Usually results from pathologic hyperpermeability of retinal blood vessels
• Increased vascular permeability results in extravasation of fluid, proteins, and macromolecules into the retinal interstitium
• Contributes to vascular leakage through leucocyte adherence to vessel walls (leukostasis) and is mediated by inflammatory like microphages
• Molecules that may induce the retinal vascular hyperpermeability include extravasation, prostaglandins (PGD) and leukotrienes, protein kinase C, nitric oxide and various cytokines like vascular endothelial growth factor, and Tumor necrosis factor-alpha, Insulin-like growth factor-1, and Interleukins

Protein kinase C

• Important involvement in macular ischemic cascade process
• Also increases in ischemic diseases in retina, associated to oxidative stress like DR, RP, ARMD

Vascular endothelial growth factor (VEGF)

• There are 2 endothelial growth factors in the RPE: PEGF & VEGF.
• PEGF maintains equilibrium and prevents the increase in quantity of VEGF because VEGF enhances the production of new vessels

Macular disease symptoms

• Blurred vision: difficulty w/ close work
• Scotoma: obstruction of central vision
• Metamorphopsia: distortion of images
• Micropsia: decrease in image size, spreading apart foveal cones
• Macropsia: increase in image size, crowding together foveal cones
• Difficulty related to dark adaptation: poor vision in dim light

Outer retinal blood barrier

• Barrier formed by RPE zonula occludens junctions
• Regulates movement of solutes and nutrients from choroid to subretinal space
• Fenestrated capillaries allow fluorescein get into the Bruch's membrane, reaching the RPE blocked by tight junctions

Inner retinal blood barrier

• Barrier form by tight junction between retinal capillary endothelial cells
• Fluorescein can't pass through the wall of endothelial cells

Fluorescein angiogram (FA)

• Photographic surveillance of the passage of fluorescein through the retinal and choroidal circulations
• Administered by IV injection
• It enters through the ophthalmic artery, passing through the short posterior ciliary artery to reach the choroidal circulation.
• Choroidal circulation fills ~1 second before retinal circulation (9-15 sec after injection)
• FAZ: NO vessels
• Normal FA showing patchy choroidal filling with cilioretinal artery filling (choroidal), arterial phase with choroid and retinal arteries filling, arteriovenous phase with complete arterial/early laminar venous flow, early venous phase with marked laminar venous flow, mid-venous phase showing almost complete venous filling, and late recirculation phase.
• Blockage of choroidal fluorescence by xanthophyll pigment and melanin in the RPE

Hyperfluorescence

• A window defect occurs with atrophy/absence of the RPE such as in ARMD, macular hole, RPE tears, unmasking normal choroidal fluorescence, and very early hyperfluorescence due to dry age-related macular degeneration.
• Pooling occurs in the anatomical space from breakdown of outer blood retinal barrier in the RPE tight junctions or CSR in the subretinal space.

Leakage

• Early hyperfluorescence
• Increase in area and intensity
• From breakdown of the inner BBB
• Dysfunction or loss of endothelial tight junctions
• Seen in Proliferative diabetic retinopathy or CRVO, CME or Papilledema.

Hypofluorescence

• Masking retinal fluorescence by preretinal lesions such as blood (subhyaloid or pre-retinal hemorrhage)
• Masking of background choroidal fluorescence from Intraretinal hemorrhages, dense exudates: sub-RPE blood or lesions: Increase density of RPE (hypertrophy)
• Filling defects because of vascular occlusion

Indocyanine Green Angiography

• Used to evaluate choroidal vascularization and for delineating the choroidal vasculature (masking by the RPE)
• Penetrates ocular pigments like xanthophyll/Melanin
• Used for Polypoidal choroidal vasculopathy and Exudative ARMD and Retinal angiomas and Chronic CSC and Posterior uveitis and Choroidal tumors and Breaks in Bruch membrane

Fundus hyperautofluorescence

• Uses an enhanced fundus camera
• Permits visualization of accumulated lipofuscin in the RPE
• Demonstrates expense macular disease
• Useful in ARMD

Cystoid macular edema

• Leakage in inner layers of the retina; cysts that appear also

CSCR

• Showing smokestack or blot of ink and demarcation of the detachment