Diagnosing dry eye disease

New tools for detecting and quantifying inflammation could help with treatment

Howard Larkin

Posted: Friday, July 19, 2019

Developing new tools that can accurately characterise the types and quantity of inflammatory factors present in the clinic could help diagnose the causes and severity of dry eye disease, Jose Benitez-del-Castillo MD, PhD, told the 2018 Cornea Subspecialty Day at the 36th Congress of the ESCRS in Vienna.

Citing studies showing that dry eye disease has a significant, chronic inflammatory component (Pflugfelder SC et al. Cornea 27(Supple 1):S9-11. Massengale ML et al. Cornea. 2009;28:1023-7.), he described several tools in clinical and research use that may be helpful.

Fluorescein staining: Cytokines degrade the ocular epithelial barrier, and gaps in this barrier are revealed by fluorescein staining. Severity can be judged using tools such as a modified Oxford scale, said Dr Benitez-del-Castillo, of Clinica Rementeria, Madrid, Spain. However, this is an indirect method that does not provide information on specific inflammatory factors.

Tear osmolarity: Generally, tear osmolarity increases with disease severity, and hyperosmolarity is easily detected clinically with a TearLab or I-pen, Dr Benitez-del-Castillo noted. However, this, too, is an indirect measure of inflammation that is subject to fluctuation. The ocular system reflexively increases tear production to compensate for hyperosmolarity, sometimes resulting in normal or near-normal readings in eyes with severe disease.

MMP-9: Matrix metalloproteinases (MMPs) are proteolytic enzymes produced by stressed ocular epithelial cells (Chotikavanich S et al. IOVS. 2009;50:3203-9.). Their level in tears varies with dry eye type, with meibomian gland dysfunction evaporative disease generating a mean activity score of nearly 500 and Sjögren’s syndrome aqueous deficiency nearly 700 compared with normal level of 341 (Solomon A et al. IOVS, 2001;42:2283-92.). However, current clinical tests are binary, detecting dry eye disease in patients with more severe disease but missing less severe cases, and fail to distinguish among more severe cases, Dr Benitez-del-Castillo observed.

Confocal microscopy: This can quantify dendritic cells in the corneal epithelium as well as nerve density in the basal corneal plexus, which inversely correlates with dry eye disease – the higher the dendritic cell density the higher dry eye disease symptoms and the lower basal nerve density (Tapelus T et al. Graefes ACEO 2017;255:1 771-8).

HLA-DR: Flow cytometry is a research method that directly quantifies ocular surface cells, which correlates with fluorescein staining but is more precise (Brignole-Baudouin F et al. IOVS. 2017;58:2438-48).

Tear cytokines: Similarly, the level of tear cytokines detected in research assays correlates with ocular surface disease index (OSDI) scores.

“Dry eye is an inflammatory disease and new practical tools for detecting inflammation on the ocular surface are needed. Dry eye disease should be treated with anti-inflammatory drugs,” Dr Benitez-del-Castillo concluded.

Jose Benitez-del-Castillo: