Vitreo-Retinal-Choroidal Disease Review (Anatomy & Testing)

Dr. Yacoub (Disease III)

characteristics of vitreous

• 80% of the total volume of the eye

• 4g and 4ml in volume

• composed of a matrix of type II collagen fibrils, hyaluronic acid, proteoglycans, glycoproteins, H2O

• hyaluronic acid + collagen fibrils = gel-like consistency and transparency of vitreous

4 functions of vitreous

1. acts as shock absorber

2. maintains connection of neurosensory retina to RPE

3. stores and transfers nutrients to lens and retina

4. transmits and refracts light which helps focus light on retina

strongest vitreous attachment to weakest

strongest

1. vitreous base which is at ora serrata

2. optic nerve (vitreous inserts into glial peripapillary ring)

3. ILM in macula region

4. ILM over the retinal vasculature

5. ILM elsewhere

weakest

*posterior hyaloid face of vitreous attaches to the following from strongest to weakest

order of vitreous degeneration

synchysis → syneresis → PVD

define synchysis

liquefaction of the vitreous due to breakdown of hyaluronic acid

• collagen fibrils disorganize and aggregate in clumps → floaters

• water separates from collagen and forms pockets of water called lacunae

• myopia, ocular inflammation, ocular trauma, retinal vascular disease, aphakia, and vitreous hemorrhage can accelerate snchysis

factors that accelerate synchysis of vitreous

• myopia

• ocular inflammation

• ocular trauma

• retinal vascular disease

• aphakia

• vitreous hemorrhage

define syneresis

enlarging/coalescing lacunae → increase in weight of water centrally and anteriorly → disorganization of collagen fibrils → pulls/contracts vitreous → vitreous collapses and shrinks (syneresis)

define posterior vitreous detachment (PVD)

contraction and shrinkage of vitreous → leakage of fluid thru breaks/thins in cortex → loss of attachment of retina and ON called PVD

about ___% of patients over age 65 develop a PVD

65%

stages of PVD

1. separation of posterior hyaloid face from perifovea with continued attachment to the fovea

2. complete separation of posterior hyaloid face from macula (including fovea)

3. extensive separation from retina with continued attachment to ON

4. complete PVD, no more adhesion to ON except vitreous base

what will the posterior hyaloid face of vitreous still be attached to during stage 4 of PVD?

vitreous base

if you see a ___, you can assume the pt had a PVD

weiss ring

if the retina is transparent, what gives the retina its reddish color?

the color seen is due to the combo of the retinal pigment epithelium, choroid, and choroidal vasculature

the retina is thickest in the ____ and thins out as the retina goes further out in periphery

macular region

the ora serrata is considered the ____ limit of the neural retina

anterior limit

• the retina extends from optic dish in both directions up until the ora serrata

the edge of the temporal optic disc is about ___ away from the fovea

3.7 mm away from fovea

majority of rods are found in ____ and cones are found in ____

rods → peripheral retina

cones → posterior pole

the short ciliary nerves arises from the ____ and long ciliary nerves arises from the ____

short ciliary nerves → ciliary ganglion

long ciliary nerves → nasocilliary branch of CN V1

the SCN transmits _____ and LCN transmits ____

SCN → sensory (nasocilliary br of CN V1), sympathetic, and parasympathetic (CN III and VII)

LCN → sensory (nasocilliary br of CN V1), sympathetic info to → conj, cornea, CB, dilator muscle in iris

layers of retina from inner to outer

inner (vitreous)

1. ILM

2. RNFL

3. GCL

4. IPL

5. INL

6. OPL (aka Henle fiber layer)

7. ONL

8. ELM

9. photoreceptor layer

   1. myoid zone, ellipsoid zone, outer segments of PR

   2. interdigitation zone (IDZ) between PR and RPE

10. RPE

    bruch membrane

outer (choroid)

T/F: Bruch’s membrane has strong adhesion to RPE and RPE has weak adhesion to photoreceptor layer

true

why does the macula normally have a granular appearance?

within individual RPE cells, there’s unequal distribution of pigment → macula looks granular

• most apparent at macula since RPE cells are most dense at the macula

RPE cells are interlocked tightly by ___ and ____ which forms the outer blood-retina layer

zonula occludens (tight jxn) and zonula adherens (anchoring jxn)

what allows for the electrical coupling and low-resistance channel for flow of ions, metabolites, and nutrients from the choroid into the retina?

desmosomes and gap junctions are present throughout the RPE

the ____ surface of RPE cell is closest to Bruch’s membrane

basal surface

what are the reasons for RPE and photoreceptor attachment if there’s subretinal space there?

1. IOP

2. osmotic pressure

3. vitreous

4. apical microvilli of RPE

5. interphotoreceptor matrix (IPM) - GAGS and proteins make matrix ‘sticky’

   1. keeps photoreceptor up against RPE

the potential space between RPE and PR is absent along the ___ and ____ which means that the retina is strongly attached in these areas

absent along the peripapillary ring around optic disc and ora serrata

functions of RPE

1. absorb scattered light (improve optical quality, decrease photo-oxidative stress)

2. control of fluid, nutrients, waste products

3. visual pigment (rhodopsin)

4. key for visual cycle

5. synthesis of signaling molecules (VEGF, TGF, PEDG, PDGF)

6. phagocytosis of photoreceptor waste

7. involved in regeneration and repair

8. stores vit A

9. synthesizes IPM

10. acts as the outer-blood retina barrier esp due to tight junctions found in the RPE

what is the interdigitation zone (IDZ)?

area where apices of RPE cells encase part of the cone outer segments as well as the rod outer segments

• visible in post pole

• part of subretinal space

define verhoeff membrane?

anatomical structure that surrounds the apical portion of the RPE composed of the tight junctions between RPE cells

• found in the interdigitation zone (IDZ)

there are about ____ total rods in retina and ____ total cones

120 million rods

6 million cones

T/F: no rods are found at the foveola, only cones

true

rod density is greatest concentrically ____ from the foveola

4.5 mm or 15 degrees from foveola

T/F: some photoreceptors are found at optic nerve

false - NO pr at optic nerve (blind spot)

characteristics of rods

• 40-60 microns

• 1 type of rod

• rods tend to be longer and thinner than cones

• rod outer segments are longer

• rod spherules connect with bp cells, horizontal cells, and other rod spherules and cone pedicles

• more active in dim (scotopic)

• senses contrast, brightness, motion

characteristics of cones

• 40-50 microns long

• cone outer segments shorter and may not reach RPE

  • microvilli from apical RPE reach and surround cone outer segments

  • exception: at the macula, cone outer segments have similar shape to rods

• bright conditions (photopic)

• cone pedicles connect with bp cells, horizontal cells, other rod spherules, cone pedicles

• senses fine resolution, spatial resolution, color

which layer of retina acts as a metabolic barrier and prevents passage of large molecules and stabilizes the transducing portion of photoreceptors?

external limiting membrane (ELM)

ONL is thickest at ____ and thinnest at ____

thickest at foveola and fovea (50 microns thick)

thinnest just temporal to the optic nerve (22 microns)

rank the thickness of ONL in the retina photo from thickest to thinnest

thickest 4, 1, 3, 2 thinnest

the synaptic junction between the photoreceptors and 2nd order neurons which include the bp cells and horizontal cells is called ____

outer plexiform layer (OPL)

in the fovea and esp at the foveola, there are no ____ because cone pedicles are displaced laterally (called the Henle layer)

no synaptic terminals bc cone pedicles are displaced laterally

the middle limiting membrane is composed of

desmosome-like attachments called synaptic densities that are found within the branching, interwoven bp dendrites and horizontal cells

in what layers can part of a photoreceptor be found in?

IDZ to OPL

what cells are found in the inner nuclear layer (INL)?

contains cell bodies of horizontal cells, bp cells, amacrine cells, interplexiform neurons, muller cells, displaced ganglion cells

what synapses occur in the inner plexiform layer (IPL)?

connections between axons of bp cells and dendrites of ganglion cells

• synapses with amacrine cells

• synapses between 2nd order and 3rd order neurons of the visual pathway

• this layer disappears at the foveola

function of plexiform layers

prevent spread of fluid to other layers

• IPL is stronger > than OPL

each ganglion cell is separated by

glial process of each muller cell

convergence of rods vs. cones

rods (75,000) → bp cells (500) → amacrine cells (250) → ganglion cells (1)

• first, second, third, and fourth order neurons

cones (1-5) → bp cells (1-5) → ganglion cells (1)

• first, second, third order neurons

function and types of neuroglial cells

provides structure, support, plays a role in neural tissue reaction to injury and infection

• doesn’t participate in synaptic interactions and electrical signaling

• muller cells, migroglial, astrocytes

muller cells project thick and thin processes in both directions to the ___ and ____

ILM and ELM (with microvilli extending into the sub-retinal space)

why macular edema greater at the foveal region of macula?

bc muller cells at macula are weak, few, and diagonally oriented

functions of muller cells

• structural support to neuronal cell bodies

• prevents mechanical deformation of retina

• control homeostasis by regulating [K+] in retina

• maintain extracellular pH by getting rid of metabolic waste as CO2 and ammonia

• recycles glutamate, glycine, GABA

• metabolizes, synthesizes, stores glycogen (fuels aerobic metabolism in neurons)

• helps maintain inner blood-retina barrier

• helps guide light directly to photoreceptors

which neuroglial cell increases in response to tissue inflammation and injury and phagocytize degenerating retinal neurons?

microglial cells

which neuroglial cells are almost entirely restricted to NFL and some of GCL?

astrocytes

functions of astrocytes

• insulation and support to superficial retinal capillaries and nerve fibers

• maintain inner blood-retina barrier

• controls homeostasis by regulating concentration of [K+] in retina

• metabolizes, synthesizes, stores glycogen

• contributes to ILM

macula is ___ mm in diameter

fovea is ___ mm

foveola is ___ mm

macula = 5.5 mm

fovea = 1.5 mm (1 DD)

foveola = 0.35 mm

why does fovea have a dark appearance w a yellow hue?

• high conc. of lutein and zeaxanthin (both xanthophylls) is found at fovea

  • xanthophylls tend to have a more yellow color

• RPE cells are tallest, most dense/pigmented at fovea

• choroidal capillary bed is thickest at fovea

• macular pigment is located in OPL, muller cells, photoreceptor inner fibers, and rod outer segments

there is more lutein than zeaxanthin in the retina ____ while there’s more zeaxanthin than lutein at the ____

more lutein outside fovea

more zeaxanthin at the fovea

what layers of the retina are found at the foveola?

• RPE/bruch complex

• IDZ

• outer segments of photoreceptors

• ellipsoid zone

• myoid zone

• ELM

• ONL

• henle fiber layer

• ILM

why is there a bump along the ellipsoid zone directly under the umbo?

RPE and IDZ are thicker, longer, and densely packed → pushing up the outer segments of photoreceptors → pushes up ellipsoid zone

• cones are also more densely packed and rod-like in shape

define capillary free zone

includes umbo, foveola, part of the fovea

• lack of retinal blood vessels, which allows light to get to the photoreceptors without obstruction

• choriocapillaris is found in retinal capillary free zone

at the ____, the orientation of retinal elements revert back to vertical orientation and henle fiber layer changes into OPL

perifovea

in the peripheral retina, RPE is continuous with ___ and ILM is continuous with ____

RPE continuous with outer pigmented epithelium of CB

ILM continuous with ILM of CB

T/F: choroidal thickness increases with age

false - it decreases with age

functions of choroid

• vascular supply of outer retina

• thermoregulation (maintain temp of the eye)

• limits uncontrolled reflection of light

• involved in VEGF production

5 layers of the choroid

RPE

• Bruch membrane (basal lamina)

• choriocapillaris (stroma)

• haller layer (stroma)

• sattler layer (stroma)

• suprachoroid (space in bw sclera and choroid)

sclera

in the inner retina, central retinal artery provides vascular supply to the inner retina via ____

in outer retina, choroidal capillary bed provides vascular supply to outer retina via ____

inner retina = perfusion

outer retina = diffusion

• note: OPL has dual blood supply

4 types of retinal capillary plexues

superficial vascular complex (SVC)

• radial peripapillary capillary plexus (RPCP) - NFL

• superficial capillary plexus (SCP) - GCL, IPL

deep vascular complex (DVC)

• intermediate/middle capillary plexus (ICP) - IPL, INL

• deep capillary plexus (DCP) - INL, OPL

which plexuses are present in the peripapillary area? macula? central retina? periphery?

peripapillary → RPCP, SCP, ICP, DCP

macula → SCP, ICP, DCP

central retina → SCP, ICP, DCP

periphery → SCP, DCP

if IOP increases, what happens to the inner retina blood flow?

IOP increases → perfusion decreases due to constriction of arteries and arterioles → which dilate to keep homeostasis and maintain perfusion

• in glaucoma, the arteries/arterioles can only autoregulate so much, ultimately arteries/arterioles will constrict → decrease in perfusion

what happens to inner retinal blood flow if arterial pressure increases?

increase in arterial pressure → increase in perfusion → arteries/arterioles constrict to decrease perfusion and maintain homeostasis

• retinal capillaries are dependent on autoregulation and perfusion that occurs in retinal arteries/arterioles

• in HTN, arteries/arterioles can no longer autoregulate → retinal capillary damage

____ supplies the posterior choroid

____ supplies the anterior choroid

ophthalmic artery → short posterior ciliary arteries → posterior choroid → outer retina

ophthalmic artery → long posterior ciliary arteries → anterior choroid → CB and iris

haller vs. sattler layer vs. choriocapillaris

haller layer (outer choroid) = made up of large (“arteries”) non-fenestrated vessels

sattler layer (inner choroid) = made up of smaller (“arterioles”) non-fenestrated vessels

choriocapillaris (innermost choroid) = smaller (“capillaries”) fenestrated vessels directly up against Bruch membrane

since choroidal vessels aren’t able to autoregulate like retinal vasculature, it’s more dependent on ____

perfusion pressure

if you see a lesion on 78D lens, multiply by ____ to get the actl lesion size in mm. 90D? 60D?

78D → 1.2x

90D → 1.33x

60D → 1x

• whatever you see on SL, that’s the measurement. no conversion

benefits of scleral depression

useful in detection, evaluation, differentiation of peripheral retinal anomalies, degenerations, holes, tears, detachments

• ID retinal breaks/tears

• enhances contrast between intact retina and retinal break

• better visualize sub-retinal fluid as it moves around w scleral depression

indications for scleral depression

• symptoms of flashes/floaters

• hx of trauma

• high myopia

• aphakia

• evidence of retinal break

• vitreous hemorrhage

• preretinal hemorrhage

• pigment floating in vitreous (Shafer sign)

• suspected pars planitis

• RD

on optos, the red free filter is for looking at the ____ and the green free filter is used for looking at the ____

red free → retina

green free → choroid

why does the retina normally have a slight glow on FAF?

25% of RPE cell is composed of lipofuscin

• lipofuscin: when photoreceptors shed their outer sesgments, RPE ingests it thru phagocytosis which are then stored in liposomes → lipofuscin

• loss of RPE cells = decrease in autofluorescence

why does the ON and blood vessels show up as dark on FAF normally?

the ON and blood vessels don’t have RPE and thus, no lipofuscin

why does the fovea show up as dark normally?

due to the high concentration of light-absorbing xanthophyll pigment (blocks any underlying lipofuscin)

define iso-autofluorescence

normally expected autofluorescence (AF)

increase in autofluorescence (AF) shows up as ____ than normal

decrease in AF shows up as ____ than normal on FAF

increase in AF = brighter than normal

decrease in AF = darker than normal

purpose of fluorescein angiography (FA)

highlights ON, retina, choroidal circulation (although indocyanine green chorioangiography or ICG images choroidal circulation better)

• useful in detection of subclinical retinal/choroidal/ON changes secondary to vascular conditions

• aids in treatment decisions

• guides retinal laser therapy

how does fluorescein travel/flow after injection in FA?

internal carotid artery → ophthalmic artery → central retinal artery → retina

internal carotid artery → ophthalmic artery → short posterior ciliary arteries → choroid + cilioretinal artery → artery

phases of a fluorescein angiography (FA)

choroidal flush → arterial phase → arteriovenous or laminar venous phase → complete venous phase → late phase

describe the choroidal flush phase of FA (1)

occurs 10 sec after injection

• filling of the choroid is patchy hyperfluorescent (choroidal flush)

  • bc choriocapillaris is fenestrated and fluorescein freely leaks out

  • patchy due to various pigment levels in RPE so variable blockage of choroidal flush

• cilioretinal artery + areas of retina perfused by cilioretinal artery will fill in this stage

describe arterial phase of FA (2)

occurs 1-3 seconds following choroidal flush stage

• arteries/arterioles fill with fluorescein

• veins remain dark

describe the arteriovenous or laminar venous phase of FA (3)

occurs 1-2 seconds following arterial phase

• fluorescein spreads to capillaries and to postcapillary venules/veins

  • only the walls of venules/veins fluoesce while lumen remains dark

    • due to high density of erythrocytes in central lumen of venules/veins that prevent dye from filling centrally at first

describe the complete venous phase of FA (4)

occurs 1-2 seconds following arterial after arteriovenous or laminar venous phase

• best stage to see perifoveal capillary network and foveal avascular zone

maximum vasculature fluorescence typically occurs at ___ after injection (best contrast between areas of hyperfluorescence and hypofluorescence)

25-30 seconds

• after 30-45 sec, dye begins the recirculate and brightness starts to diminish as it makes a first pass thru kidneys

• at 30 min, fluorescein is usually gone

describe late phase of FA (5)

5 min mark after injection and lasts until 20 min after injection

• normal arterioles/arteries and venules/veins will almost be empty of fluorescein

• any retinal leakage becomes more apparent

• margins of ON remain hyperfluorescent (due to staining) as dye adheres to peripapillary choroidal plexus which supplies the prelaminar area of ON

• staining of sclera or Bruch membrane may be seen

why is the macula (esp at fovea and foveola) normally darker on FA?

• RPE cells are larger with more melanin in foveal region

• high conc. of xanthophyll pigment in foveal region

• xanthophyll pigment absorbs excitatory light from the camera

• no retinal vasculature and retinal capillaries in this area (FAZ)

reasons for hypofluorescence?

hypofluorescence: reduction or absence of normal fluorescence (darkness)

• blockage: obscuration of normal brightness due to overlying material

  • ex: intraretinal hemorrhages, preretinal hemorrhages, exudates, CWS, choroidal nevus, CHRPE without lacunae

• filling defect: occurs due to reduced perfusion

  • ex: CRAO, retinal capillary dropout, choroidal non-perfusion, optic atrophy

blockage vs. filling defect

both cause hypofluorescence

• blockage: obscuration of normal brightness due to overlying material

  • ex: intraretinal hemorrhages, preretinal hemorrhages, exudates, CWS, choroidal nevus, CHRPE without lacunae

• filling defect: occurs due to reduced perfusion

  • ex: CRAO, retinal capillary dropout, choroidal non-perfusion, optic atrophy

reasons for hyperfluorescence

hyperfluorescence: increase in normal fluorescence (bright)

• window defect: defect in RPE

• leakage: occurs in extracellular space

• staining: fluorescein binds to tissue/accumulates within

• pooling: leakage that occurs in confined or potential space

define window defect (hyperfluorescence) in FA

defect in RPE allows transillumination of choroidal flush

• initially bright before arteries fill (most noticeable in choroidal flush stage)

• stays the same size and brightness until late stage where it starts to lose its brightness

• margins always distinct

• ex: RPE window defects, geographic atrophy, CHRPE with lacunae

describe leakage (hyperfluorescence) in FA

leakage occurring in extracellular space

• hyperfluorescence that appears early and progressively enlarges and gets brighter with less distinct margins as time goes on

• see leakage well at 5 min mark

• ex: mac edema, retinal neo, choroidal neovascular membrane

• subfoveal, juxtafoveal, extrafoveal leakage

subfoveal vs. juxtafoveal vs. extrafoveal leakage in FA

subfoveal: under the fovea

juxtafoveal: leaking <200 microns from foveal center

extrafoveal: leaking ≥200 microns from foveal center

describe staining (hyperfluorescence) in FA

occurs when fluorescein binds with tissue or accumulates within tissue

• hyperfluorescence gradually gets brighter (not as bright as leakage) in later stages but stays about the same size

• typically seen after 2 min

• ex: drusen, fibrotic tissue