Associate Professor of Ophthalmology, Harvard Medical School
Co-director, Cornea Center of Excellence
Associate Scientist, Schepens Eye Research Institute of Mass. Eye and Ear
20 Staniford St, Room 246, Boston, MA 02114
- Fuchs Endothelial Corneal Dystrophy
- Oxidative Stress and aging of the corneal endothelium
- Ocular Surface reconstruction with stem cells
Pathology: Corneal endothelium (CE) forms a monolayer of hexagonal cells that is attached to its basement membrane, called Descemet’s membrane (DM) and is in direct contact with the aqueous humor. FECD is characterized by the morphological changes of the hexagonal mosaic, accelerated loss of endothelial cells, and a concomitant increase in the extracellular matrix deposition at the level of DM. As a result, the endothelial layer is eventually no longer able to support corneal deturgescence (a state in which corneal stroma is maintained relatively dehydrated), leading to corneal edema and decreased in visual acuity (Figure 1). These findings usually become clinically evident in the fourth and fifth decades of life. Initially, the patient notices blurred vision, then symptoms progress as the disease progresses through its stages—often ending in blindness.
Prevalence: FECD can be divided into early-onset (manifesting in the 3rd decade of life) and late-onset (manifesting in the 5th decade of life, on average). Both early- and late-onset forms have female predominance at a ratio of 2.5-3:1. In the USA, the prevalence is approximately 4% of the population over the age of 40.
Significance. It is one of the most common causes of blindness from corneal swelling and a second most common cause of corneal transplants done in the U.S. Because little is known of what triggers corneal endothelial cells to die in FECD, there is no effective treatment, and corneal transplantation is the only currently available measure to restore lost vision.
Figure 1. Pathogenesis of FECD. Genetic and environmental factors lead to corneal endothelial cell loss, resulting in corneal edema and blurring of vision. Some characteristic histological findings are endothelial cell morphological changes, thickened Descemet’s membrane, and guttae formation. [Ocul Surf. 2010 Oct;8(4):173-84.]
Figure 2. Specular microscopy of a patient with FECD. Arrowheads point to the variability observed in corneal endothelial cell size (polymegethism) and shape (pleomorphism). Stars represent guttae. [Ocul Surf. 2010 Oct;8(4):173-84.]
The second main area of our research is the development of autologous cultivated epithelial stem cell constructs for patients suffering from corneal blindness due to limbal stem cell deficiency. We have been collaborating with the Center for Human Cell Therapy Boston, a unique resource that functions across different departments and affiliated institutions of Harvard Medical School. Concurrently, we were awarded the Production Assistance for Cellular Therapies (PACT) grant from National Heart/Lung and Blood Program of NIH to aid in the translational development of stem cell therapy in corneal disorders. We are in the process of filing an Investigational New Drug (IND) application to FDA for performing the Phase I/II study to treat corneal blindness with the stem cells.
Associate in Ophthalmology, Massachusetts Eye and Ear
Clinical Associate, Massachusetts General Hospital
Board Certification: Ophthalmology
Mass. Eye and Ear
243 Charles St, Boston, MA 02114
Refractive surgery, cornea and external disease, endothelial dysfunction, Fuchs dystrophy (DMEK), corneal infection, corneal transplantation, limbal epithelial stem cell deficiency, and cataract surgery.
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