clinico-pathologic correlation: the alabama age-related maculopathy grading system (alarmgs)

C.A. Curcio, 20030513, ALARMGS Tutorial

Clinico-pathologic Correlation:The Alabama Age-Related

Maculopathy Grading System (ALARMGS)

Christine A.Curcio, Ph.D.Department of Ophthalmology

University of Alabama at Birmingham

C.A. Curcio, 20030513, ALARMGS Tutorial

References

• Curcio CA, Medeiros NE, Millican CL: The Alabama Age-related Macular Degeneration Grading System for donor eyes. Invest Ophthalmol Vis Sci 1998, 39:1085-1096 (ALARMGS)

• Curcio CA, Millican CL: Basal linear deposit and large drusen are specific for early age-related maculopathy. Arch Ophthalmol 1999, 117:329-339 (Basal Deposits)

C.A. Curcio, 20030513, ALARMGS Tutorial

Introduction

• Macula: Topography and Layers• Bruch’s Membrane

C.A. Curcio, 20030513, ALARMGS Tutorial

Macula: Topography & Layers

PhRPE BrM ChC

PhotoreceptorsRetinal pigment epithelium

Bruch’s membraneChoriocapillaris

Cones Rods

Anatomical and epidemiologic macula:6 mm (21°) diameterSmall, cone-dominated foveaLarge, rod-dominated parafovea

C.A. Curcio, 20030513, ALARMGS Tutorial

Bruch’s Membrane:A Specialized Vascular Intima

• Intima (inner wall of large arteries)– Located between 2 diffusion barriers– Thickens throughout adulthood in response to

stress of blood flow– Collagen, elastin, proteoglycans

• Bruch’s membrane (a flat vessel wall)– Located between 2 diffusion barriers– Thickens (3X) throughout adulthood– Choroidal blood flow is 8-fold higher in macula

than periphery– Collagen, elastin, proteoglycans

ChC

RPE

L

3 EL

5 ChC-BL

2 ICL1 RPE-BL

4 OCL

C.A. Curcio, 20030513, ALARMGS Tutorial

Methods

• Photography• Grading

C.A. Curcio, 20030513, ALARMGS Tutorial

ALARMGS: Finding ARM Eyes

Eyes from 60-90 donors/ yr, < 4 hrs post-mortem Contact donor families/ eye doctorsDetailed gross and histopathologic exam

Curcio et al., 1998, IOVS 39: 1085

Post-mortem fundus Histopathologic evaluation Pre-mortem fundus

ALABAMAEYE BANK

C.A. Curcio, 20030513, ALARMGS Tutorial

Stereo dissecting scope

C.A. Curcio, 20030513, ALARMGS Tutorial

Normal Eye

Fovea -- all conesFovea -- all conesParafovea -- cones & rodsParafovea -- cones & rods

87 yr old man

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WARMGS & ALARMGS

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ALARMGS Study Design

C.A. Curcio, 20030513, ALARMGS Tutorial

34 eyes examined for fundus appearance and histopathology

• 26 human donors & 8 orbital exenteration patients

• <3.5 hr. from death/enucleation to preservative

• all > 50 years of age

• excluded diabetes, high myopia, non-ARM macular chorioretinal pathology

C.A. Curcio, 20030513, ALARMGS Tutorial

Clinical Information: Summary

ALARMGS eyes Felloweye age Sex OE LED (mo) VAcc Lens Phot/FA Significant macular history Hx A

1 OD 60 M x 0.0 20/30 2 x/- drusen, mild AMD Y2 OS 63 F 9.7 20/25+1 2 x/- dry AMD Y Y3 OS 64 M n.a. n.a. n.a. no visual complaint as per family Y4 OD 74 M 23.1 20/40- 3 x/- drusen and/or pigment changes Y Y5 OS 74 M 18.7 20/20 2 x/x dry AMD, drusen, pigment clumping Y N6 OD 74 M x 0.0 20/50 3 x/- prob MD, pigment clump, no drusen Y7 OS 75 M x 0.6 20/60ph40 2 drusen Y8 OS 80 M x 0.3 20/40-1 0 x/- few drusen, areas RPE atrophy Y9 OD 83 F 7.0 20/60 0 giant drusen, ARMD Y Y

10 OD 90 F n.a. n.a. n.a. n.a. Y

C.A. Curcio, 20030513, ALARMGS Tutorial

Histopathology Grades

Lesion 0 1 2 3 4

Total basal deposits none patchy thin continous thick continuous n.a.

Size of largest druse < 66 µm 63-125 µm ≥ 125 µm n.a. n.a.

Number of drusen none 1 to 3 > 3 n.a. n.a.

RPE morphology uniform nonuniform heaped or sloughed anterior migration atrophy

Detachment none RPE retina n.a. n.a.

Choroidal neovascularization none present n.a. n.a. n.a.

Photoreceptor outer segments normal shortened missing n.a. n.a.

Photoreceptor inner segments normal broadened missing n.a. n.a.

n.a. = not applicable

C.A. Curcio, 20030513, ALARMGS Tutorial

Early ARM: histopathology

• No changes of late ARM

AND

• EITHER 1 large druse (>125 microns)

• OR severe RPE change (heaping, migration, atrophy) with at least one druse or continuous

basal deposits.

C.A. Curcio, 20030513, ALARMGS Tutorial

Early ARM: post-mortem fundus appearance

No changes of late ARM AND

EITHER one large druse (> 125 microns) OR RPE hyperpigmentation >500 microns diameter

C.A. Curcio, 20030513, ALARMGS Tutorial

Review of Cases

C.A. Curcio, 20030513, ALARMGS Tutorial

Eyes with Drusen

• Case 1

• Case 3

• Case 4

• Case 5

• Case 2

• Case 9

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 1

• 60 yr old man

• LED <1 mo, 20/30

• “drusen, mild AMD”

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 3

• 64 yr old man

• No visual complaint as per family

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 4• 74 yr old man

• LED 23.7 mo, 20/40-

• “dry ARM and pigment changes”

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 5• 74 yr old man

• LED 18.7 mo, 20/20

• “drusen, RPE clumping”

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 5

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 7

• 75 yr old man

• LED 0.6 mo, 20/60

• “drusen”

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 2

• 63 yr old woman

• LED 9.7 mo, 20/25+1

• Fundus photo 22 yr before death

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 2

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 9• 83 yr old woman

• LED 7.0 mo, 20/60

• “giant drusen”

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 9

• 83 yr old woman

• LED 7.0 mo, 20/60

• RPE detachment

C.A. Curcio, 20030513, ALARMGS Tutorial

Eyes with Pigmentary Change

• Case 10

• Case 8

• Case 6

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 10

90 yr old womanRPE clumpingThick deposits

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 10

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 8

• 75 yr old man

• LED 0.3 mo, 20/40

• “drusen, RPE atrophy”

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 8

C.A. Curcio, 20030513, ALARMGS Tutorial

Case 6: Pattern Dystrophy

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RPE Changes in ARM (1)• Early ARM

– Focal hyperpigmentation– Hypopigmentation (non-geographic atrophy)

• Late (geographic atrophy): 3 processes– Primary pigmentary change– Drusen regression– Resolution of CNV or detachment

• Risk due to hyperpigmentation = drusen

C.A. Curcio, 20030513, ALARMGS Tutorial

RPE Changes in ARM (2)

1 - Nonuniform size & pigment2 - Clumping, heaping3 - Anterior migration4 - Atrophy

C.A. Curcio, 20030513, ALARMGS Tutorial

RPE changes in ARM (3)

• Stage-specific increase in vimentin-immunoreactivity

Anti-VimentinAnti-Vimentin

Bright fieldBright field

AutofluorescenceGuidry C, Medeiros NE, Curcio CA.

IOVS 2002, 43:267-273.