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Dry eye may be associated with corneal endothelial cell loss
In dry eye, it is important to pay attention to not only the ocular surface, but also the endothelium.
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A significant decrease in corneal endothelial cell density was found in eyes with moderate to severe dry eye disease compared with normal eyes, according to a cross-sectional study.
The mean endothelial cell density (ECD) was 2,596 cells/mm2 in 90 eyes of 45 patients in the dry eye disease (DED) group and 2,813 cells/mm2 in the control group of 30 eyes of 15 normal subjects, which translates to an approximately 8% lower endothelial cell density in the dry eye disease group.
“The ECD showed correlation with dry eye severity: the more severe DED, the lower ECD,” study co-author Reza Dana, MD, MSc, MPH, Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School, told Ocular Surgery News.
“We know that the cornea has the highest nerve density of any tissue in the body and that these nerves play a significant role in maintaining corneal health and function,” Dana said.
Based on a few published papers, the authors realized that corneal nerve damage may be associated with a reduction in corneal endothelial cell density.
“Because DED has been shown to be associated with reduced corneal nerve density, we hypothesized that it may also have reduced ECD,” Dana said. “That is why we decided to perform this study.”
The study
All study subjects were recruited from the Cornea and Refractive Surgery Service at the Massachusetts Eye and Ear Infirmary in Boston, with an average subject age of 53.7 years in the dry eye disease group and 50.7 years in the normal age- and sex-matched control group.
The dry eye disease group consisted of patients with dry eye symptoms, along with an Ocular Surface Disease Index score greater than 22 and corneal fluorescein staining of at least 4, based on the National Eye Institute grading scale.
In all subjects, the central corneas of both eyes were measured by in vivo confocal microscopy using a Heidelberg Retina Tomograph 3 with the Rostock Cornea Module to determine the density of the corneal endothelium, sub-basal immune dendritic cells and sub-basal nerves.
The reduction in endothelial cell density in patients with dry eye disease somewhat surprised the investigators.
“We usually think of DED as an ocular surface disease limited to the epithelium,” Dana said. “However, our findings suggest that corneal involvement in DED is much more extensive than we traditionally think, and it can also affect deep cells such as the endothelium.”
Although the reason for reduced endothelial cell density in this patient population is unclear, Dana said it may be due to a decrease in the potentially supportive role of corneal nerves for endothelium in dry eye disease.
“Alternatively, this may be due to inflammation. Since it is known that inflammation plays a significant role in pathogenesis in DED, we surmise that this inflammation may also cause endothelial cell damage,” he said.
What it means
The authors think that with treatment of dry eye disease, the mechanisms responsible for the reduced endothelial cell density will be controlled, resulting in prevention of further endothelial loss.
“We should pay attention not only to the ocular surface, but also to the endothelium,” Dana said of patients with DED, particularly those with moderate or severe disease or those who are candidates for intraocular surgery. “These patients may have endothelial compromise.”
Dry eye disease is a prevalent but often neglected disease that can have more extensive effects than previously believed, Dana said.
The authors are now investigating the mechanisms by which dry eye disease causes corneal endothelial loss.
“We hope that by finding these mechanisms, we can prevent or stop the endothelial cell damage in DED and related conditions,” Dana said. – by Bob Kronemyer
- Reference:
- Kheirkhah A, et al. Am J Ophthalmol. 2015;doi:10.1016/j.ajo.2015.03.011.
- For more information:
- Reza Dana, MD, MSc, MPH, can be reached at 20 Staniford St., Boston, MA 02114; email: reza_dana@meei.harvard.edu.
Disclosure: Dana reports no relevant financial disclosures.
Perspective
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David R. Hardten, MD
Much information is being published on the harmful effects of inflammation on the human body from diseases. This has long been known for diseases such as rheumatoid arthritis, but it is increasingly accepted in other diseases such as Alzheimers. We have been increasingly concerned about the effects of inflammation related to dry eye on the long-term health of the ocular surface. This interesting paper reports that we also may need to be concerned about deeper structures in the cornea such as the endothelium. This lends increasing support to treating the underlying inflammation associated with dry eye to reduce the chances of dry eye progression. Damage to the corneal epithelium, stroma, nerves and now endothelium seems to result from this inflammation and potentially can be slowed through pharmacologic control of that inflammation.
Reference: Heneka MT, et al. Lancet Neurol. 2015;doi:10.1016/S1474-4422(15)70016-5.
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