1. 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

2. 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)

3. C.A. Curcio, 20030513, ALARMGS Tutorial Introduction Macula: Topography and Layers Bruch’s Membrane

4. C.A. Curcio, 20030513, 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

5. 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 ICL 1 RPE-BL 4 OCL

6. C.A. Curcio, 20030513, ALARMGS Tutorial Methods Photography Grading

7. C.A. Curcio, 20030513, ALARMGS Tutorial ALARMGS: Finding ARM Eyes Eyes from 60-90 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

8. C.A. Curcio, 20030513, ALARMGS Tutorial Stereo dissecting scope

9. C.A. Curcio, 20030513, ALARMGS Tutorial Normal Eye Fovea -- all cones Parafovea -- cones & rods 87 yr old man

10. C.A. Curcio, 20030513, ALARMGS Tutorial WARMGS & ALARMGS

11. C.A. Curcio, 20030513, ALARMGS Tutorial ALARMGS Study Design

12. 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

13. C.A. Curcio, 20030513, ALARMGS Tutorial Clinical Information: Summary

14. C.A. Curcio, 20030513, ALARMGS Tutorial Histopathology Grades

15. 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.

16. 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

17. C.A. Curcio, 20030513, ALARMGS Tutorial Review of Cases

18. C.A. Curcio, 20030513, ALARMGS Tutorial Eyes with Drusen Case 1 Case 3 Case 4 Case 5 Case 2 Case 9

19. C.A. Curcio, 20030513, ALARMGS Tutorial Case 1 60 yr old man LED <1 mo, 20/30 “drusen, mild AMD”

20. C.A. Curcio, 20030513, ALARMGS Tutorial Case 3 64 yr old man No visual complaint as per family

21. C.A. Curcio, 20030513, ALARMGS Tutorial Case 4 74 yr old man LED 23.7 mo, 20/40- “dry ARM and pigment changes”

22. C.A. Curcio, 20030513, ALARMGS Tutorial Case 5 74 yr old man LED 18.7 mo, 20/20 “drusen, RPE clumping”

23. C.A. Curcio, 20030513, ALARMGS Tutorial Case 5

24. C.A. Curcio, 20030513, ALARMGS Tutorial Case 7 75 yr old man LED 0.6 mo, 20/60 “drusen”

25. 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

26. C.A. Curcio, 20030513, ALARMGS Tutorial Case 2

27. C.A. Curcio, 20030513, ALARMGS Tutorial Case 9 83 yr old woman LED 7.0 mo, 20/60 “giant drusen”

28. C.A. Curcio, 20030513, ALARMGS Tutorial Case 9 83 yr old woman LED 7.0 mo, 20/60 RPE detachment

29. C.A. Curcio, 20030513, ALARMGS Tutorial Eyes with Pigmentary Change Case 10 Case 8 Case 6

30. C.A. Curcio, 20030513, ALARMGS Tutorial Case 10 90 yr old woman RPE clumping Thick deposits

31. C.A. Curcio, 20030513, ALARMGS Tutorial Case 10

32. C.A. Curcio, 20030513, ALARMGS Tutorial Case 8 75 yr old man LED 0.3 mo, 20/40 “drusen, RPE atrophy”

33. C.A. Curcio, 20030513, ALARMGS Tutorial Case 8

34. C.A. Curcio, 20030513, ALARMGS Tutorial Case 6: Pattern Dystrophy

35. C.A. Curcio, 20030513, 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

36. C.A. Curcio, 20030513, ALARMGS Tutorial RPE Changes in ARM (2) 1 - Nonuniform size & pigment 2 - Clumping, heaping 3 - Anterior migration 4 - Atrophy

37. C.A. Curcio, 20030513, 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, 43:267-273.