Analyses of AREDS2 data on natural history of GA provide representative data on GA evolution and enlargement. GA enlargement, which was influenced by lesion features, was relentless, resulting in rapid central vision loss. The genetic variants associated with faster enlargement were partially distinct from those associated with risk of incident GA. These findings are relevant to further investigations of GA pathogenesis and clinical trial planning.

To assess optical coherence tomography in differentiating optic disc edema (ODE) due to papilledema and other optic neuropathies from optic nerve head drusen (ONHD). Methods: Optical coherence tomographic images from 60 subjects (20 with ODE, 20 with ONHD, and 20 control subjects) were assessed qualitatively and quantitatively. Qualitative criteria for ODE included an elevated optic nerve head with smooth internal contour and subretinal hyporeflective space (SHYPS) with recumbent "lazy V" pattern. Optic nerve head drusen displayed a "lumpybumpy" internal optic nerve contour and a rapid decline in SHYPS thickness. Quantitative comparisons included retinal nerve fiber layer and SHYPS thickness. Results: Optical coherence tomography differentiated ODE from ONHD qualitatively (sensitivity, 63%; speci-ficity, 63%) and quantitatively (sensitivity, 80%; specificity, 90%). Respective differences in mean retinal nerve fiber layer thickness between ODE and ONHD were significant (P Ͻ .002) superiorly (206.8 vs 121.7 µm), nasally (176.3 vs 78.6 µm), inferiorly (247.2 vs 153.8 µm), and temporally (180.0 vs 85.5 µm). Respective differences in mean SHYPS thickness between ODE and ONHD were significant (PϽ .001) at radii of 0.75 mm (512.1 vs 274.4 µm), 1.5 mm (291.4 vs 103.0 µm), and 2.0 mm (145.5 vs 60.7 µm). Conclusion: Optical coherence tomography can differentiate ODE from ONHD, particularly when the nasal retinal nerve fiber layer and SHYPS thickness at the 2.0-mm radius are greater than 86 µm and 127 µm, respectively.

This study replicates the results of previous natural history studies of eyes with DPED including the high rates of progression to late AMD and vision loss (regardless of progression to late AMD). The genetic associations are consistent with genes associated with AMD progression.

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 μL/mL); B) anti-fibrotic treatment (50 μM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading scale, modified McDonald-Shadduck (mMS) scoring system, optical coherence tomography (OCT), corneal histopathology, immunohistochemistry (IHC), and transmission electron microscopy (TEM). The used alkali burn dose to produce corneal fibrosis was well tolerated as no significant difference in mMS scores between control and treatment groups (p=0.89) were detected. The corneas of alkali burned dogs showed significantly greater levels of α-smooth muscle actin, the fibrotic marker, than the controls (p=0.018). Total corneal thickness of all dogs post-burn was significantly greater than baseline OCT images irrespective of treatment (p=0.004); TEM showed that alkali burned corneas had significantly greater minimum and maximum interfibrillar distances than the controls (p=0.026, p=0.018). The tested topical corneal alkali burn dose generated significant opacity and fibrosis in dog corneas without damaging the limbus as evidenced by histopathology, IHC, TEM, and OCT findings, and represents a viable large animal corneal fibrosis in vivo model. Additional in vivo SAHA dosing studies with larger sample size are warranted.