STUDY MOTIVATION Glaucomas are eye diseases in which intraocular pressure damages the optic nerve Glaucoma often has no symptoms other than progressive permanent vision loss There is no cure, but early diagnosis and treatment can manage the disease progression Current diagnosis protocols involve specialized tests and careful examination of the eye Hypothesis Some glaucomas are caused by vascular deterioration and associated with capillary abnormalities Very early, non-invasive and simple diagnosis may be made by microscopic examination nailfold capilaries http://www.allaboutvision.com/conditions/glaucoma.htm https://www.dreamstime.com/stock-illustration-hand-blood-vessels-medical-accurate-illustration-image56648127 http://www.rheumaknowledgy.com/nailfold-capillaroscopy/

Nailfold Capillary Abnormalities in Exfoliation Syndrome Clara C. Cousins1 Courtney Bovee2, Angela Turalba2, Lucy Shen2, Stacey Brauner2, Scott Greenstein2, Ai Ren2, Jay Wang2, Janey L. Wiggs2, Paul Knepper3, Jae H. Kang3, Louis R. Pasquale2,4 1Harvard College, 2Massachusetts Eye and Ear Infirmary, Boston MA; 3Northwestern University Feinberg School of Medicine, Chicago IL; 4Brigham & Women’s Hospital, and Harvard Medical School, Boston MA STUDY PURPOSE To investigate nailfold capillary morphological abnormalities in exfoliation syndrome and glaucoma (XFS/XFG) compared to primary open-angle glaucoma (POAG) and controls through nailfold videomicroscopy STUDY POPULATION 80 POAG, 51 XFS/XFG, 67 controls from MEEI age 40-80 Controls: IOP < 22 mmHg OU, CDR ≤ 0.6 OU POAG diagnosis with visual field loss on reliable perimetry XFS/XFG exfoliation material on slit lamp exam http://optiliamedical.eu/capillaroscopy-menu/overview/

ASSESSMENT OF NAILFOLD CAPILLARY MORPHOLOGY ABNORMALITIES Hemorrhage Avascular Zones Tortuosity via Rating Score “low” = 0 “mild” = 1 “moderate” = 2 “severe” = 3 Waviness Tortuosity via Limb Crossing Control XFG Yellow tracing confirms no crossing points in the control, but 3 crossing points in XFG Straight vascular segment Traced path of vessel

DISCUSSION AND CONCLUSIONS STATISTICAL ANALYSES Multivariable logistic regression analysis on severity of microvascular abnormalities in controls, POAG, and XFS/XFG † Adjusted for age, sex, race, mean arterial pressure, diabetes, arthritis, use of blood thinner, body mass index, smoking, cancer, family history of glaucoma, Microvascular features (% distribution) Multivariable adjusted† odds ratios (95% CI) for POAG v Controls Multivariable adjusted† odds ratios (95% CI) for XFS/XFG v Controls Multivariable adjusted‡ odds ratios (95% CI) for XFS/XFG v POAG Hemorrhages per 100 capillaries 0 (44) 1.0 (ref) >0 and <1 (25) 3.6 (1.4, 9.1) 0.6 (0.2, 2.3) 0.2 (0.1, 0.8) ≥1 (30) 6.0 (2.2, 16) 11 (2.7, 47) 0.6 (0.2, 1.8) P-trend 0.01 <0.0001 0.72 Avascular zones ≥ 200 μm per 100 capillaries 0 (47) >0 and <0.5 (15) 6.3 (2.0, 20) 11.8 (2.1, 65) 1.2 (0.3, 5.0) ≥0.5 (38) 10.4 (3.5, 31) 48 (9.6, 241) 2.6 (0.9, 7.7) <.0001 0.08 Microvascular features (% distribution) Multivariable adjusted† odds ratios (95% CI) for POAG v Controls Multivariable adjusted† odds ratios (95% CI) for XFS/XFG v Controls Multivariable adjusted‡ odds ratios (95% CI) for XFS/XFG v POAG Tortuosity score <1.0 (46) 1.0 (ref) ≥1.0 and <1.5 (26) 5.1 (2.0, 13) 9.7 (2.1, 45) 1.3 (0.4, 4.2) ≥1.5 (28) 2.7 (1.0, 7.7) 21 (5.3, 82) 3.9 (1.2, 12) P-trend 0.01 <.0001 0.02 Capillary limb crossing points per 100 μm segment per 20 capillaries <0.5 (34) ≥0.5 and <1.0 (31) 4.8 (2.0, 12) 4.6 (0.7, 30) 0.8 (0.2, 3.5) ≥1.0 (35) 6.2 (2.2, 18) 259 (25, 2719) 8.1 (2.0, 34) Waviness ratio per 20 capillaries <1.2 (38) ≥1.2 and <1.4 (43) 14 (5.1, 36) 165 (13, 2086) 1.8 (0.5, 6.9) ≥1.4 (19) 4.6 (1.0, 21) 646 (41, 10242) 20 (3.8, 106) DISCUSSION AND CONCLUSIONS XFS/XFG exhibit more severe nailfold capillary tortuosity compared to POAG and controls while POAG exhibits more severe tortuosity compared to controls. XFS/XFG show more avascular zones compared to controls while XFS/XFG show borderline more avascular zones compared to POAG. XFS/XFG and POAG both contain more nailfold hemorrhages compared to controls. Three different measures for tortuosity yield consistent findings Multivariable model decreases effect of confounding by systemic conditions