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The Age-Related Macular Degeneration Complex: Linking Epidemiology and Histopathology Using the Minnesota Grading
Timothy W Olsen1, Alexander R Bottini1, Pia Mendoza1
1Emory Eye Center, Emory University Department of Ophthalmology, Atlanta, Georgia. Presented as the Inaugural Frederick C. Blodi Lecture at the 151st American Ophthalmological Society meeting, May 16, 2015, Newport, Rhode Island.
Purpose:
To describe the histopathologic findings of the four stages of age-related macular degeneration (AMD) as defined by the Age-Related Eye Disease Study (AREDS) using the Minnesota grading system (MGS).
Clinical Relevance:
There are no animal models for AMD. Eye banks enable access to human tissue with AMD. The level of AMD (grades 1 through 4) as defined by AREDS is determined ex vivo using the MGS. The AREDS has the largest collection to date of prospectively gathered data on the natural history of AMD. Since the MGS uses the same clinical criteria as AREDS, the addition of histopathologic findings of graded tissue confirms important pathophysiology at each stage of AMD.
Methods:
Four eye bank eyes were graded according to the MGS. Only the right eyes were dissected for phenotype grading. The fellow (left) eyes were fixed for histopathologic study. The eyes were serially sectioned (7 μm) through the macula. Individual slides were examined, and a two-dimensional reconstruction of the topography of the macula was created for each donor. Selected, unstained slides were used for immunohistochemical staining. In one donor, portions of tissue were obtained for transmission electron microscopic (TEM) processing.
Results:
Donor 1 had a rare hard, nodular druse (MGS1). Donor 2 had intermediate confluent drusen (MGS2). Donor 3 had numerous intermediate drusen (MGS3) in the right eye. Histopathology of the fellow left showed basal laminar deposits (BLamD), soft drusen, and an area of occult choroidal neovascularization underlying the retinal pigment epithelium (RPE) with endothelial cells (CD31-positive). Donor 4 also had MGS 3 along with reticular pseudodrusen (RPD). Histologic and TEM examination demonstrated diffuse BLamD, thickening of Bruch's membrane, hard drusen, and focal nodules underlying the RPE that corresponded to the RPD. EM examination demonstrated both BLamD and electron-dense material located just external to the elastic layer of Bruch's membrane.
Conclusion:
Eye bank eyes graded using the MGS serve as an important link to the phenotypic and epidemiologic data from the AREDS. Thus, the MGS serves as a system to study the histopathology at each stage of AMD to better understand the relevant pathophysiologic changes in disease progression.
Insights
Histopathologic findings of age-related macular degeneration (AMD) were described using the Minnesota grading system (MGS) and linked to Age-Related Eye Disease Study (AREDS) data. This confirms pathophysiology across AMD stages.
Area of Science:
- Ophthalmology
- Pathology
- Histology
Background:
- Age-related macular degeneration (AMD) is a leading cause of vision loss.
- The Age-Related Eye Disease Study (AREDS) established clinical grading criteria for AMD.
- Understanding the histopathologic basis of AMD progression is crucial for developing effective treatments.
Discussion:
- This study describes the histopathologic findings of four stages of AMD using the Minnesota grading system (MGS).
- Eye bank eyes were graded using MGS, and fellow eyes underwent detailed histopathologic examination, including immunohistochemistry and transmission electron microscopy (TEM).
- Findings correlate MGS grades with specific pathological features such as drusen, basal laminar deposits, and choroidal neovascularization.
Key Insights:
- The MGS provides a framework for correlating clinical AMD staging with underlying histopathology.
- Histopathologic analysis revealed distinct features at each MGS grade, including basal laminar deposits and thickening of Bruch's membrane.
- TEM confirmed the presence of basal laminar deposits and electron-dense material in AMD tissues.
Outlook:
- Eye bank tissues graded by MGS are valuable for linking clinical and histopathologic data from large cohorts like AREDS.
- This approach facilitates a deeper understanding of AMD pathophysiology and disease progression.
- Further research can leverage these findings to explore novel therapeutic targets for AMD.