D: Macular Disease 1 - Week 1 Flashcards by Alexander Bowden

What 2 main processes are involved in AMD development?

RPE changes

Bruchs membrane/choriocapillaris changes

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Explain how lipofuscin accumulates in RPE cells

Pr OS phagocytosis by RPE cells (for the visual cycle) results in O2 free-radical formation, which damages RPE cells over time. These damaged components of the RPE cells cannot be degraded (e.g. by RPE autophagy) and are called “lipofuscin”

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How does lipofuscin formation in RPE cells differ from formation in most other cells in the body?

RPE: forms as a result of Pr OS phagocytosis

Other cells: form as a result of own internal autophagy

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How can we visualise RPE lipofuscin? What is the major lipofuscin component contributing to this?

Lipofuscin is the major source of FAF (Fundus Auto-Fluorescence). This fluorescence mainly comes from A2E.

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What does Hyper- and Hypo- fluorescence in FAF imaging represent?

Hyperfluorescence = Excess lipofuscin
Hypofluorescence = RPE cells are dead (no lipofuscin) = Geographic atrophy (well demarcated region of loss)

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How do small and intermediate drusen appear in FAF?

Small drusen - may remain undetected.
Intermediate drusen - central hypo- fluorescence with annulus of hyper-fluorescence [likely b/c of central RPE atrophy surrounded by abnormal RPE]

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How do large soft drusen appear in FAF?

hyper-fluorescence

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Does FAF generally detect early CNVM? What about CFP?

For both: No, not early. Later on yes.

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How does A2E/lipofuscin interact with the RPE?

Interferes with RPE cell function, leading to apoptosis and subsequent GA (geographic atrophy)

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What does the accumulation of lipofuscin ultimately result in?

Lipofuscin vesicles which coalesce to give BlamD (basal laminar deposits) which are shed by the RPE to form BLinD (Basal linear deposits) or sub-retinal drusenoid deposits (Druplets)

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How is drusen formed?

When druplets coalesce

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What are the two types of drusen and which one is more serious?

Reticular drusen (located above RPE) - more serious
(classic) drusen (located below RPE).

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What is reticular drusen also known as?

Sub-retinal Drusenoid Deposits (SDD)

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What happens to the bruchs membrane with age? (2) How does this affect bm interaction with the RPE?

Gets thicker and more complex
Takes up more cholesterol (develops chol. plaques)

Results in reduced exchange of RPE cells with the choriocapillaris. Which reduces VEGF exchange.

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What is factor H (CFH)?

CFH = Complement Factor H. It is the major soluble inhibitor of complement, preventing complement activation and thus reducing positive feedback/inflammation

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How does the presence of factor H affect the process of AMD development? (2)

Factor H +ve: promotes RPE apoptosis and leads to Dry AMD

Factor H -ve: increased inflammation from complement and leads to Wet AMD.

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List 9 risk factors for AMD

RPE disruption
Age
Smoking
Fellow Eye
Genotype
Diet
Blue eyes
Caucasian?
Female?

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What genotypes are risk factors for AMD?

Increased incidence of AMD in patients with a family history
CFH mutation (Y402H  + other variants)
Apo-E variants

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Name 2 dietary nutrients/compounds that affect risk of AMD

Carotenoids - protection

Saturated fat - promotes progression

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What are the clinical stages of AMD? What percentage of AMD cases are dry/wet?

Druplets and drusen
RPE stress: pigment irregularities (hyper/hypo-fluorescent)
3a. Dry atrophic (85% of cases)
3b. Wet exudative (15% of cases)

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What does the inflammatory overlay in wet AMD promote? (3) What is the end histopathological result expected over time?

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CNVM
Leakage of blood/fluid from CNVM
Serous RPE detachment

Over time results in a fibrovascular scar ‘disciform degeneration’ (RHS)

With what 4 criteria can we classify AMD based on appearance?

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Drusen size (large or small)
Presence of pigment abnormality (hypo/hyper/disrupted)
Fellow eye status
Other modifying factors

From what distance within the fovea are drusen judged as for AMD?

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2 disc diopters

What are the sizes of small (druplet), intermediate, and large drusen?

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Small - <63 microns (<1/4 BV)
Intermediate - 63-125 microns (1/2 BV)
Large - > 125 microns (size of vein @ disc)

``` What stage of AMD are the following deposits classified as? Druplets Intermediate Drusen Large Drusen Reticular Drusen ```

Druplets - normal ageing Intermediate - early AMD Large - intermediate AMD Reticular - high risk modifying factor

How do you score with AREDS?

1. Take CFP (colour fundus photo) 2. Score drusen and pigment within 2DD of foveola (vascular arcades) as: - hyper/hypo or disrupted (>1/4DD) = +1 - Large drusen > 125 microns = +1 Modifiers incl. - Reticular drusen = +1 - Bilateral intermediate drusen = +1 - End stage AMD in fellow eye (wet or dry) = +1 Max score = 4 for any person

How do you manage an AMD patient with AREDS = 0-1? [low risk] (2)

2 yearly reviews: CFP/OCT | Anti-oxidant (AO) for AREDS = 1

How do you manage an AMD patient with AREDS = 2 [medium risk] (2)

1 yearly reviews: CFP/OCT | Home monitor + Anti-oxidant (AO)

How do you manage an AMD patient with AREDS = 3 [high risk] (2)

6 monthly reviews: CFP 1 yr, OCT 6 mth | Home monitor + Anti-oxidant (AO)

How do you manage an AMD patient with AREDS = 4 [very high risk] (2)

3 montly reviews: CFP 1 yr, OCT 3 mth | Home monitor + Anti-oxidant (AO)

For how long in the progression of AMD should you monitor (with OCT and function) until referring?

Until 'nascent'/newly developing GA or 'pre-wet' AMD. Refer when functional loss or OCT change established.

How can a patient monitor AMD weekly at home? (2)

Amsler | Tablet or smart phone

When do anti-oxidants stop being protective against AMD? Do we still use them?

Not protective once score >2. We still use them though.

List 6 components of an AMD workup (6)

Visual function: VA - LC/HC/LLLC; VF-mac DFE: look for foveal/mac swelling, CNVM CFP: colour fundus photo OCT: to identify cases for referral FAF-SLO OCTA for CNVM NB: LLLC = Low luminance low contrast

On what OCT results do we refer AMD cases? (2)

Foveal thickness > 300 microns | Central retinal thickness > 350 microns

List the 5 OCT signs of CNVM

ISe disruption (indicates advanced disease) Sub-retinal fluid (dark bands) Cystic formation within inner retinal layers (dark bubbles) PED (clear internal cf drusen) Increase in foveal thickness >100 microns b/w eyes (or >350 microns)

List the order of development of nascant GA in OCT in 6 steps. How long does this take?

Stages 1-5 develop over 12-15 months. ``` ISe disruption Drusen regression (12th month) Subsidence of OPL and INL Hypo-reflective wedge (15th/18th month) Increased signal below BM Complete loss of OS/RPE ```

What is the normal loss in acuity for a LLLC chart compared to HC (i.e. in healthy patient)?

2-3 lines

List 4 tests that provide a functional assessment of unilateral vision loss in macula disease

Visual acuity (pH, LL, LC, SF filter) RAPD (retina 1+; ON > 2+) Colour vision Amsler grid

Why is the amsler grid not useful in 50% of macula disease patients?

Due to cortical filling

Other than assessing unilateral vision loss, how else can we functionally assess macula disease? (25)

``` Mac perimetry (HFA 10-2) Ipad/iphone + home monitor Dark adaptation (photostress) Maddox rod (watzke sign: better than amsler) mfERG (implicit time delayed with retinal disease) ```

Why do we use 10-2 instead of FDT 24-2 for assessing the macula?

10-2 has the points/spots closer together. Better accuracy.

What interventions can we use for AMD patients (medium + risk, score >1)? (2)

Diet (anti-oxidants) | nanosecond laser

According to AREDS 2, how does anti-oxidant intake affect AMD? (2)

reduces risk for developing wet AMD by 26% | reduces risk for disease progression by 18%

When do we use nanosecond laser on AMD patient? What does it do?

when score >/= 3. | Gives drusen regression, but progression of AMD to dry? especially if reticula drusen (so it stops wet but not dry)

What 2 interventions are/were used for advanced AMD?

``` Photodynamic therapy (PDT. Not used anymore) aVEGF - intravitreal injections (e.g. avastin, lucentis, eyelea) = best option to retain current vision. ```

Are there any interventions for advanced dry AMD?

NO. Low vision aids.

What is RAP?

Retinal angiomatous proliferation. Is when the neovascularisation occurs in the inner retina instead of it's typical location under the RPE

In what percentage of AMD CNVM does it occur as RAP?

20%

Does RAP show cystic formation early with OCT?

yes.

What size of geographic atrophy is clinically significant?

>0.50DD

D: Macular Disease 1 - Week 1 Flashcards

(51 cards)