Post Seg Final

4 phases of FA

1. Pre-arterial: choroidal flush (20-30 sec after injection)

2. Arterial: arteries fill, veins still dark

3. Arteriovenous: capillaries and smaller arteries/veins

4. Venous: laminar flow (rapid flow of plasma along BV walls)

why is macula dark in FA?

• Foveal avascular zone: 400-500 microns large, no inner retinal BVs

• More columnar RPE cells, increased conc of lipofuscin, xanthophyll, melanin, etc

What causes hypofluorescence in FA?

• Vascular filling defect → no fluorescein (eg CRVO/CRAO)

• View is blocked (even though fluorescein is present, eg subhyaloid heme blocks view of normal BVs)

What causes hyperfluorescence in FA?

• Window defect: RPE is missing so choroid is visible

• Leakage: fuzzy borders, gets larger in size

• Staining: gradual increase in fluorescein persisting in late stage, size stays the same

• Pooling: cavity fills brightly with dye over time, size stays the same

Characteristics of leakage in FA

• Edges become increasingly blurry/fuzzy in late phase

• Any fluorescein that remains 10-15 minutes after BVs are empty

• Either caused by: break in RPE into subretinal space/inner retina OR out of inner retinal BVs or retinal NV into the vitreous

• Petalloid pattern around macula = CME

• Inner BRB breaks down → leakage into inner retina/vitreous

• Caused by retinal vascular diseases: DR, CRVO/BRVO

• Subretinal leakage = CNVM

• Outer BRB breaks down → leakage into subretinal space/neurosensory retina

What is autofluorescence in FA?

• Fluorescence in the absence of fluorescein dye

• Commonly caused by ONH drusen, astrocytic hamartomas

Advantages of ICG angiography compared to FA

• Indocyanine green absorbs/emits in IR range → not blocked by normal eye pigments

• Best for imaging choroidal circulation, esp thru overlying heme/pigment/fluid

• Eg: PED, occult CNVM, central serous

How FAF works?

• Fundus autofluorescence: using natural fluorescence of lipofuscin to check RPE/cell health

• Large amts of lipofuscin indicates RPE/cell death

• Might see hypoautofluorescence areas (RPE atrophy) surrounded by hyperautofluorescence (lipofuscin accumulation)

List inner retinal layers, outer retinal layers, predominant layers of foveola, and significance of OPL

• Inner retina: ILM, NFL, GC, IPL, INL

• Outer retina: OPL, ONL, ELM, PRs, RPE

• Foveola (RPE OI): RPE, PRs, ELM, ONL, ILM

• OPL: hydrophobic barrier to fluid movement, separates inner and outer retina, mostly perfused by choroid (outer retina)

Which retinal/OCT layers have BV plexi? Which are avascular?

• Retinal layers w/ BV plexi: RNFL, GC, INL

• OCT layers: RNFL, GC/IPL, INL

  • IPL contains vertically oriented BVs that connect GC and INL (not plexi)

• Avascular (all others): OPL, ONL, ELM, PRs, RPE

Regarding problems with retinal vasculature, what does leakage lead to, and what does ischemia lead to?

• Leakage (eg DR/BRVO) → extracellular edema: cysts, schisis, cavities, separation of layers

• Ischemia (eg BRAO) → intracellular edema: swelling of cells within inner retina (layer edges look less distinct)

3 most common reasons for decreased vision in recent onset RVO? Tx options?

edema (anti-VEGF, laser), ischemia (no Tx, monitor for NVG), preretinal hemorrhage (wait for hemorrhage to clear → vitrectomy)

Difference between RD, PED, and foveal schisis (which retinal layers separating?)

• RD: PRs and RPE

  • Either tractional (non-rhegmatogenous) or non-tractional (rhegmatogenous, fluid entering)

• PED: RPE and Bruch’s membrane

  • drusen, CNVM, serous exudates, blood

• Foveal schisis: ONL and OPL

What happens when blood flow is significantly reduced?

• Occlusion

• If blood flow is restricted enough → causes increased pressure in veins and leakage

• Causes decreased oxygen supply → ischemia

What is the critical window for retinal ischemia to be reversible?

• Within 4.5 hours

• past critical window → cell death/necrosis occurs which is irreversible!!

Are retinal arterial occlusions a medical emergency? What are the two categories of RAOs?

• ALL NEW RAOs within 30 days are considered medical emergency

• Goal is to prevent ischemic stroke and death (not to save dead cells, it’s too late for that..)

• RAOs are either arteritic (5%, GCA or hypercoagulability), or nonarteritic (95%, embolic)

Classic sx and risk factors of GCA

• Sx: jaw claudication, fever, scalp tenderness, malaise, weight loss

• Risk factors: white woman >50 yo

Dx tools for GCA, and why is GCA considered a medical emergency? Tx?

• Gold standard dx: temporal artery biopsy — also ESR, CRP, platelet count

• Medical emergency bc other eye is affected in 50% of patients

• If pt doesn’t have a visible embolus → must consider GCA or an arteritic RAO

• Tx: high dose IV and oral steroids → purpose is to reduce risk of bilateral vision loss (too late to save vision in affected eye)

Why are non-arteritic RAOs a medical emergency?

• Embolic based, usually lodged where lumen size decreases suddenly

• Emergency bc increased risk for concurrent ischemic stroke → need to refer to primary stroke center for neuro/embolic workup

Difference b/w embolus, plaque, thrombus

• Embolus: any particle/mass traveling thru blood (Hollenhorst plaque, platelet, calcific)

• Plaque: buildup on BV wall → narrow lumen

• Thrombus: sudden blood clot forms inside vein/artery

• CRAO

• Retinal whitening caused by intracellular edema/ischemia in the inner retina

• Outer retinal layers and choroid look normal

1. Blot hemes: subretinal/subhyaloid

2. Flame heme: RNFL

3. Dot heme: OPL (capillaries leaking)

4. Subsensory: sheeting, in PRs/RPE (DNVM, will not obscure retinal BVs)

What are RVOs caused by?

• NOT caused by emboli → NOT medical emergency

• Caused by thrombus (compression of artery against vein due to shared common adventitial sheath)

• Thrombus caused by Virchow’s triad:

  • 1. Endo damage

  • 2. Blood stasis

  • 3. Hypercoagulable state

Difference b/w ischemic and non-ischemic CRVOs

• Ischemic CRVO (30%):

  • 1. 10 DA of capillary nonperfusion

  • 2. VA worse than 20/200

  • 3. (+) APD

  • 4. Hemes: numerous, large and dark color

  • more likely to develop sequelae (NVG)

• Non-ischemic CRVO (70%):

  • 1. VA better than 20/200

  • 2. (-) APD

  • 3. Hemes: smaller/fewer

How does pressure in BVs change with RVO vs RAO?

• RVO: pressure within A/V crossing increases from obstruction → causes leakage

• RAO: pressure within vein decreases from lack of blood flow, while pressure in arteries increases next to occlusion (no hemes bc arteries can handle pressure increase)

Ocular sequelae/long-term management of RAOs

• BRAO: RNV and anterior NV is rare

• CRAO: RNV is rare, anterior NV occurs 15%

Ocular sequelae/long-term management of RVOs

• BRVO: RNV 8%, anterior NV rare, CME 5%

• CRVO: RNV 9%, anterior NV 35% in ischemic, 10% in non-ischemic, CME 76%

Gold standard in treatment of retinal/anterior NV

• PRP (panretinal photocoagulation) → killing retina stops VEGF release

• Anti-VEGF is adjunctive therapy with only temporary effect

Risk factors of AMD

• Age: >50 vs >80 triples risk of development

• FHx: 50% AMD risk if (+) FHx

• Smoking: 2-3x increased risk

• Diet: high fat, low omega-3s, vitamins, carotenoids

• HTN

• Lack of exercise

Where does drusen accumulate and what sizes are there?

• B/w RPE and Bruch’s membrane, represent sites of focal inflammation (RPE atrophy)

• Sizes based on size of CRV (diam 125 um)

• Large drusen >125 um

• Intermediate drusen b/w 63-125 um

• Small drusen < 63 um

Hard/nodular drusen characteristics

• <63 um (small)

• Sharp margins, uniform color density

• Found in central and peripheral retina

• Normal with age

Soft drusen characteristics

• >125 um (large)

• Soft/fuzzy margins, white center w/ yellow edges

• Only in posterior pole, assoc with pigmentary changes

• OCT or FA can see if any fluid buildup

Cuticular/basal laminar drusen

• Found in large numbers → cause starry sky in FA, window defect w/ staining

• Can appear like soft drusen when they coalesce, but NOT assoc w/ pigmentary changes

• Start in Bruch’s → accumulate b/w Bruch’s and RPE

• Strongly associated w/ advanced AMD

Characteristics of calcified drusen

• Considered end-stage drusen, since all drusen likely contain calcium

• Strongly associated w/ advanced AMD

Characteristics of reticular pseudodrusen

• Located in subsensory space, b/w PRs and RPE

• Can coalesce into ribbons → can cause PIL to go away

• White arrows here is pseudodrusen

Definition of geographic atrophy and its cause

• Large area of RPE atrophy → leads to progressive loss of inner retina

• Caused by chronic inflammation: overactive complement system → RPE, PRs, choriocapillaris loss first

Definition of advanced dry AMD

Geographic atrophy of the foveola

• Dry AMD makes up 90% of AMD cases

Definition of wet AMD

• Any presence of CNVM = wet AMD

• AMD is the most common cause of CNVM

• wet AMD makes up 10% of AMD cases, but accounts for 90% of vision loss

Type 1 vs Type 2 CNVM

• Type 1 CNVM = occult CNVM (most common)

  • B/w RPE and Bruch’s membrane → double layer sign on OCT

• Type 2 CNVM = classic CNVM

  • Above RPE (subsensory)

Type 3 CNVM characteristics

• Retinal NV that connects retinal and choroidal circulation

• Starts in inner retina and moves posterior towards choroid

What is a disciform scar?

• Endstage wet AMD, when retinal tissue is replaced w/ scarring and fibrosis

• CNVM can still bleed/leak

4 stages of AMD

• Category 1: no AMD

  • few small or no drusen

• Category 2: early AMD

  • many small drusen or few medium-sized drusen, in one or both eyes

• Category 3: intermediate AMD

  • many medium sized drusen or one large drusen, in one or both eyes

• Category 4: advanced AMD

  • breakdown of any retinal cells or supportive tissue (dry) OR abnormal BVs under retina (wet) - see photo

Risk assessment to quantify risk of advanced AMD in the next five years, what qualifies as 0.5, 1 and 2 points?

• In one eye:

  • Advanced AMD OR wet AMD: 2 points

  • Pigmentary changes: 1 point (includes GA)

  • Large drusen: 1 point

  • Intermediate drusen w/ no large: 0.5 point

• 2 points: 12% risk of adv AMD

• 3 points: 25%

• 4 points: 50%

Difference b/w AREDS and AREDS2

• AREDS2 does NOT have beta-carotene (increases lung cancer risk in smokers)

• AREDS2 has lutein + zeaxanthin added (tendency to be beneficial after 10 years)

• AREDS2 has decreased risk of developing adv AMD by 25% in intermediate or advanced AMD

• AREDS2 has NO BENEFIT For EARLY AMD

Clinical findings of CNVM

• Hemes and fluid: subretinal or sub-RPE

• Hard exudates

• Gray membrane

• Subretinal fibrosis

What is an RPE rip?

• Consequence of anti-VEGF injections

• Common with PED

• If choroidal vessels are clear, and there is shadowing in adjacent area → indicates RPE is bunched up after getting displaced

How does a PVD and ERM affect anti-VEGF injection treatments?

• PVD can have positive effect on injections (may need fewer)

• ERM can have negative effect (may need more injections)

Angioid streaks and systemic associations

• Abnormal Bruch’s membrane → can cause crack-like breaks

• Assoc with pseudoxanthoma elasticum, Paget’s dz, Ehlers-Danlos

POHS: presumed ocular histoplasmosis syndrome

• Caused by histoplasmosis fungus found in Ohio and Mississippi river valleys

• Triad: atrophic chorioretinal punched out scars, PPA, no vitritis

• Asymptomatic unless CNVM forms

3 symptoms of late/end-stage CNVM

• Scotoma

• Hallucinations (Charles Bonnet syndrome)

• Floaters due to breakthru vitreous heme

2 criteria for a “subclinical” RD

• 1 DD of retinal detachment from the edge of the break

• No more than 2DD posterior to the equator

  • subclinical means BIO is required to see it, cannot be detected by VF

What two types of vitreoretinal tufts are associated with RD?

• Zonular: retinal projection of lens zonules

• Cystic: fibroglial projection into vitreous (assoc with cystic degeneration)

Why do retinal breaks look more red when indented?

• Light path from BIO hits more pigment, and is silhouetted against the RPE

• Light has to take a longer pathway thru the choroid

What causes lattice, and which side of lattice is more prone to tearing?

• Vitreous liquefaction over lesion and vitreoretinal adhesion at margins of lattice

• Posterior side will tear more than anterior, due to direction of vitreous traction

• The border farther from the ora (closer to posterior pole) → more potential for traction

Crater vs atrophic hole

• Crater: more moth-eaten, not distinct borders, RPE is not fully present

• Atrophic hole: all 9 retinal layers completely missing → looking directly at the RPE

Differentiate b/w recent and chronic RDs

• Recent RD: corrugations, edematous retina, bleeding from sheared BVs

• Chronic RD: bullous, clear, no bleeding

• Pavingstone degeneration: multiple round punched out RPE areas

• Choroidal BVs visible since RPE is thinner/missing

• Common with increasing age

• Benign, commonly seen bilateral

• Atrophic retinal hole: break in retina not assoc w/ vitreoretinal traction

• Low risk for RD (higher if fluid assoc with hole

• Vitreoretinal tuft: location of strong vitreoretinal adhesion

• Can result in retinal tears/holes during PVD → rhegmatogenous RD

Meridional fold

• Radially oriented fold of the retina at the ora, assoc w/ oral bays

• Sometimes can have retinal break at posterior border

• White and slightly elevated

When to follow up for an acute asymptomatic PVD without retinal tear/detachment

• If no vitreous heme/retinal break → 1 month f/u

• If small vitreous heme w/ good view of fundus → 1-2 week f/u

• If vitreous heme w/ poor fundus view → B-scan w/ extremely close monitoring

What occurs in a rhegmatogenous retinal detachment

• Full thickness hole or tear in the retina → vitreous seeps in → retina detaches from RPE

• If lattice with holes → can cause chronic RD with pigment line demarcating

• Retinal dialysis: caused by ocular trauma

• Avulsion of vitreous base, when retina is pulled off ora

• 8-15% risk of RD (progresses slowly)

• Giant retinal tear: > 3 clock hours

• Can have a rolled edge bc the RD is so large

• Likely caused by trauma

• Fresh rhegmatogenous RD

• Convex configuation, with an opaque corrugated appearance

• Also loss of underlying choroidal pattern

• Chronid RC: retinal thinning due to atrophy

• Can be confused for retinoschisis

• Subretinal demarcation lines caused by RPE proliferation at the junction of flat/detached retina

• Peripheral retinoschisis: split b/w INL and OPL from viscous fluid accumulation in OPL

• Most non-progressive and rarely become RRD

• Smooth and dome-shaped with beaten metal appearance, and white flecks on surface

WWOP

• Scalloped edges

• Found in 30% of normal eyes, younger patients

• Unknown cause: could be abnormal reflex or vitreous traction

• No correlation with RD/breaks

• Dark without pressure

• Flat, brown fundus lesion with well-defined margins in peripheral retina

• Can be posterior to WWOP, can look like retinal tear

• Choroidal detachment: dome-shaped elevation

• Usually caused by hypotony → serum or blood accumulates b/w choroid and scleral

• Ora seen w/o depression

Pathophysiology of cotton wool spots

• Occlusion of precapillary arterial flow

• Focal ischemia stops anterograde and retrograde axoplasmic flow → causes RNL swelling locally

Pathophysiology of microaneurysms in DR

• From capillary nonperfusion → causes pericyte loss and degen of basement membrane → capillary wall bulges and outpouching forms

• Becomes hyalinized over time → leakage can occur around it

Pathophysiology of flame hemes

• Nonperfusion of post-arteriolar capillary bed, following NFL contour

• If flame hemes only: likely vascular occlusion or HTN

• DR is usually a combo of flame and dot hemes/MAs

Pathophysiology of intraretinal hemes (dot/blot hemorrhage)

• In INL/OPL (deep retinal capillary bed)

• indicates deep retinal edema, and a sign of venous stasis

Pathophysiology of hard exudates

• Exudates come from compromised deep retinal capillaries

• Blood lipids and macrophages will migrate to edge of edema (circling the wagon)

• Hard exudates in FAZ indicate severe edema

Pathophysiology of venous beading

• Localized venous dilation that indicates severe nonperfusion

• Strictures: when venous walls get so thick that blood flow is blocked

Pathophysiology of IRMA (intraretinal microvascular abnormalities)

• Larger area of nonperfusion → existing capillaries dilate and endo cells proliferate

• Comes before retinal NV

Pathophysiology of superficial retinal NV

• Severe nonperfusion over large area = large hypoxia

• VEGF causes new BVs to grow + fibrous proliferation

• This causes traction on the retina

When to consider PRP treatment vs vitrectomy

• Consider PRP with severe NPDR, low risk PDR

• Must tx with PRP if high risk PDR

• If active/severe PDR: tx with vitrectomy

Mild, mod, severe, and very severe NPDR requirements

• Mild: 1+ MAs or intraretinal hemorrhage

• Moderate: b/w mild and severe

• Severe (one of following): 4 quadrants of MAs, 2 quadrants of venous beading, or 1 quadrant of IRMA

• Very severe: 2+ of above conditions

Requirements for high risk PDR

• NVD >1/3 DA

• NVD with assoc preretinal/vitreous hemes

• NVE >1/2 DA with assoc preretinal/vitreous hemes

Requirements for clinically significant DME

• Retinal thickening within 500 um of FAZ

• Hard exudates within 500 um of FAZ w/ retinal thickening

• Retinal thickening area >1DD within 1DD of FAZ

Features of CRAO

• Sudden painless monoc vision loss (20/200 to CF, + APD)

• ± amaurosis fugax

• Cherry red spot, boxcarring (segmenting blood column), delayed arterial filling and AV transit time in FA

• Even if retinal circulation is restored, vision loss is irreversible

What changes does CRAO cause to an ERG?

• CRAO causes reduction of B wave

• A wave: outer retina (PRs)

• B wave: inner retina

Features of ophthalmic artery obstruction

• VA: usually HM or NLP

• No cherry red spot (bc choroidal blood flow also blocked)

• causes pigmentary disturbance after few weeks

• ERG results: reduced/absent A and B wave

Treatment for CRVO

• Goal is to stabilize BRB and decrease vascular permeability

• Anti-VEGF and steroids (to decrease inflammation)

Which ocular disease is most commonly associated with CRVO?

• Glaucoma most assoc w/ CRVO

• Advanced glc increases risk of CRVO 5-7x

Optociliary shunt vessels

• Collateral vessels connecting choroid and retinal vasculature

• Most common in RVOs (but also chronic papilledema, GLC, and ON meningioma)

Features of hemi-retinal vein occlusion (HRVO)

• Variant of CRVO with 2 quadrants (superior or inferior half of retina)

• Caused by anatomic variation of ONH (veins draining each half are merging posterior to lamina cribrosa)

• Behaves like CRVO (more than branch)

Features of ocular ischemic syndrome

• Severe carotid artery stenosis/occlusion

• Causes ischemic ocular pain, mid-peripheral retinal hemorrhages, vision loss

• More common elderly men>women

• High risk anterior seg NV

Features and side effects of PRP (panretinal photocoagulation)

• Tx for ischemic retina: to kill retinal cells and reduce VEGF load and oxygen demand (NOT cauterizing BVs)

• Side effects: macular edema, exudative RD, choroidal effusion, VF defects, night vision issues

What is laser creep

• When scar created by focal laser expands over time

• Can cause delayed vision loss, in first 3 months of surgery or years later

Solar retinopathy (photochemical mechanism of damage)

• Causes color change on fundus due to damaged PRs that contain carotenoids

• RPE usually no damaged

Mechanical mechanism of damage (eg laser pointer injury)

• Both RPE and PRs are damaged (stronger choroidal signal)

• Light energy deposits faster than mechanical relaxation

Hydroxychloroquine/plaquenil is used as which treatment, MOA and dosage

• Plaquenil treats malaria or autoimmune disorders (RA, lupus)

• Helps reduce inflammation and swelling, reduce WBCs, blocks platelet aggregation/adhesion

• Dosage 200-400 mg per day

How does plaquenil affect the retina

• Affects metabolism of retinal cells

• Toxic to RPE → reduces phagocytosis of PRs → PR loss → futher RPE degeneration

Risk factors for plaquenil toxicity

• Medication dosage

  • > 1000 g (cumulative)

  • > 200-400 mg per day

  • > 5 mg/kg daily (rare to develop toxicity below 6.5 mg/kg)

• Medication duration: > 5-7 years

Monitoring guidelines for plaquenil

• 10-2 for non-Asian pts, 24-2 for Asian pts

• After 5 years: annual screening with HVF, FAF, mfERG, SD-OCT

• mfERG extremely sensitive to early HCQ toxicity (when changes are still reversible)

• SD-OCT sees structural changes: ONL thickness, PIL, COST → RPE loss

• FAF sees early parafoveal hyperautofluorescence (from increased lipofuscin) → becomes hypoautofluorescence due to RPE cell death