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Clinico-pathologic Correlation: The Alabama Age-Related Maculopathy Grading System (ALARMGS)

Clinico-pathologic Correlation: The Alabama Age-Related Maculopathy Grading System (ALARMGS). Christine A.Curcio, Ph.D. Department of Ophthalmology University of Alabama at Birmingham. References.

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Clinico-pathologic Correlation: The Alabama Age-Related Maculopathy Grading System (ALARMGS)

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  1. 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. 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. Introduction • Macula: Topography and Layers • Bruch’s Membrane

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

  5. L RPE 1 RPE-BL 2 ICL 3 EL 4 OCL ChC 5 ChC-BL 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

  6. Methods • Photography • Grading

  7. ALABAMA EYE BANK ALARMGS: Finding ARM Eyes Pre-mortem fundus Post-mortem fundus Histopathologic evaluation • 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

  8. Stereo dissecting scope

  9. Normal Eye 87 yr old man Parafovea -- cones & rods Fovea -- all cones

  10. WARMGS & ALARMGS

  11. ALARMGS Study Design

  12. 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. Clinical Information: Summary

  14. Histopathology Grades

  15. 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. Early ARM: post-mortem fundus appearance No changesof late ARM AND EITHER one large druse (> 125 microns) OR RPE hyperpigmentation >500 microns diameter

  17. Review of Cases

  18. Eyes with Drusen • Case 1 • Case 3 • Case 4 • Case 5 • Case 2 • Case 9

  19. Case 1 • 60 yr old man • LED <1 mo, 20/30 • “drusen, mild AMD”

  20. Case 3 • 64 yr old man • No visual complaint as per family

  21. Case 4 • 74 yr old man • LED 23.7 mo, 20/40- • “dry ARM and pigment changes”

  22. Case 5 • 74 yr old man • LED 18.7 mo, 20/20 • “drusen, RPE clumping”

  23. Case 5

  24. Case 7 • 75 yr old man • LED 0.6 mo, 20/60 • “drusen”

  25. Case 2 • 63 yr old woman • LED 9.7 mo, 20/25+1 • Fundus photo 22 yr before death

  26. Case 2

  27. Case 9 • 83 yr old woman • LED 7.0 mo, 20/60 • “giant drusen”

  28. Case 9 • 83 yr old woman • LED 7.0 mo, 20/60 • RPE detachment

  29. Eyes with Pigmentary Change • Case 10 • Case 8 • Case 6

  30. Case 10 90 yr old woman RPE clumping Thick deposits

  31. Case 10

  32. Case 8 • 75 yr old man • LED 0.3 mo, 20/40 • “drusen, RPE atrophy”

  33. Case 8

  34. Case 6: Pattern Dystrophy

  35. 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. RPE Changes in ARM (2) 1 - Nonuniform size & pigment 2 - Clumping, heaping 3 - Anterior migration 4 - Atrophy

  37. Anti-Vimentin Autofluorescence Bright field RPE changes in ARM (3) • Stage-specific increase in vimentin-immunoreactivity Guidry C, Medeiros NE, Curcio CA. IOVS 2002, 43:267-273.

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