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

C.A. Curcio, , ALARMGS Tutorial Introduction Macula: Topography and Layers Bruch’s Membrane

C.A. Curcio, , ALARMGS Tutorial Macula: Topography & Layers Ph RPE BrM ChC Photoreceptors Retinal pigment epithelium Bruch’s membrane Choriocapillaris ConesRods Anatomical and epidemiologic macula: 6 mm (21°) diameter Small, cone-dominated fovea Large, rod-dominated parafovea

C.A. Curcio, , 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 ICL 1 RPE-BL 4 OCL

C.A. Curcio, , ALARMGS Tutorial Methods Photography Grading

C.A. Curcio, , ALARMGS Tutorial ALARMGS: Finding ARM Eyes Eyes from donors/ yr, < 4 hrs post-mortem Contact donor families/ eye doctors Detailed gross and histopathologic exam Curcio et al., 1998, IOVS 39: 1085 Post-mortem fundusHistopathologic evaluationPre-mortem fundus ALABAMA EYE BANK

C.A. Curcio, , ALARMGS Tutorial Stereo dissecting scope

C.A. Curcio, , ALARMGS Tutorial Normal Eye Fovea -- all cones Parafovea -- cones & rods 87 yr old man

C.A. Curcio, , ALARMGS Tutorial WARMGS & ALARMGS

C.A. Curcio, , ALARMGS Tutorial ALARMGS Study Design

C.A. Curcio, , 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, , ALARMGS Tutorial Clinical Information: Summary

C.A. Curcio, , ALARMGS Tutorial Histopathology Grades

C.A. Curcio, , 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, , 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, , ALARMGS Tutorial Review of Cases

C.A. Curcio, , ALARMGS Tutorial Eyes with Drusen Case 1 Case 3 Case 4 Case 5 Case 2 Case 9

C.A. Curcio, , ALARMGS Tutorial Case 1 60 yr old man LED <1 mo, 20/30 “drusen, mild AMD”

C.A. Curcio, , ALARMGS Tutorial Case 3 64 yr old man No visual complaint as per family

C.A. Curcio, , ALARMGS Tutorial Case 4 74 yr old man LED 23.7 mo, 20/40- “dry ARM and pigment changes”

C.A. Curcio, , ALARMGS Tutorial Case 5 74 yr old man LED 18.7 mo, 20/20 “drusen, RPE clumping”

C.A. Curcio, , ALARMGS Tutorial Case 5

C.A. Curcio, , ALARMGS Tutorial Case 7 75 yr old man LED 0.6 mo, 20/60 “drusen”

C.A. Curcio, , ALARMGS Tutorial Case 2 63 yr old woman LED 9.7 mo, 20/25+1 Fundus photo 22 yr before death

C.A. Curcio, , ALARMGS Tutorial Case 2

C.A. Curcio, , ALARMGS Tutorial Case 9 83 yr old woman LED 7.0 mo, 20/60 “giant drusen”

C.A. Curcio, , ALARMGS Tutorial Case 9 83 yr old woman LED 7.0 mo, 20/60 RPE detachment

C.A. Curcio, , ALARMGS Tutorial Eyes with Pigmentary Change Case 10 Case 8 Case 6

C.A. Curcio, , ALARMGS Tutorial Case yr old woman RPE clumping Thick deposits

C.A. Curcio, , ALARMGS Tutorial Case 10

C.A. Curcio, , ALARMGS Tutorial Case 8 75 yr old man LED 0.3 mo, 20/40 “drusen, RPE atrophy”

C.A. Curcio, , ALARMGS Tutorial Case 8

C.A. Curcio, , ALARMGS Tutorial Case 6: Pattern Dystrophy

C.A. Curcio, , ALARMGS Tutorial 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, , ALARMGS Tutorial RPE Changes in ARM (2) 1 - Nonuniform size & pigment 2 - Clumping, heaping 3 - Anterior migration 4 - Atrophy

C.A. Curcio, , ALARMGS Tutorial RPE changes in ARM (3) Stage-specific increase in vimentin- immunoreactivity Anti-Vimentin Bright field Autofluorescence Guidry C, Medeiros NE, Curcio CA. IOVS 2002, 43: