(Image Credit: AdobeStock/Alessandro Grandini)
A close look at the previously US FDA approved dry eye treatments showed a lack of homogeneity in pivotal study methodologies and outcomes.1 Along with high rates of drug discontinuation,2 these results suggest that the treatments to successfully address dry eye that can make measurable improvement in quality-of-life items and standardization of metrics and tools to measure them should be prioritized by the researchers, according to research from Esen Akpek, MD, The Bendann Professor of Ophthalmology and Rheumatology, The Johns Hopkins University School of Medicine, Baltimore.
In current clinical practice physicians rely largely on patient-reported symptoms to evaluate dry eye, and these do not always correlate with objective ocular surface and tear film parameters, she noted. Priya Matthews, MD presented Akpek's research at the 2023 Women in Ophthalmology Summer Symposium, Marco Island, FL.
She explained that in patients with significant dry eye and ocular surface inflammation, the patient-reported symptoms are likely dampened due to the neurotrophic state of the cornea, which accompanies any long-standing inflammatory ocular conditions. Staining of the corneal and conjunctival surface using vital dyes is an invaluable dry eye test to provide information normally not visible during a routine slit-lamp examination.
In support of the use of ocular surface staining, a number of studies3-7 over the past 10 years showed a correlation between findings on corneal staining with functional visual indices, ie,
- decline in visual acuity and functional visual acuity, likely due to higher-order optical aberrations
- decrease in contrast sensitivity comparable to patients with visually significant cataract
- and decrease in reading speed
And others have elucidated the relationship between inflammation and corneal staining.8-10
The take-home messages are as follows:
- Although a billion-dollar industry, treatments for dry eye are generally not informed by patient-centered outcome measures.
- Pivotal trials lack uniformity in outcome measures, and results are often not reproducible in clinical practice.
- Before we can expect clinical trials and therapeutics to produce meaningful results, researchers, clinicians, and patients must agree on meaningful dry eye measures.
- Corneal staining using vital dyes could potentially be the right approach.
- Correlation of tear film and ocular surface parameters to measurable quality-of-life items and standardization of metrics and tools to measure them is necessary.
USFood & Drug Administration. Devices@FDA. Accessed December 13, 2021.https://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm
\White DE, Ahao Y, Ogundele A, et al. Real world treatment patterns of cyclosporine ophthalmic emulsion and lifitegrast ophthalmic solution among patients with dry eye. Clin Ophthalmol. 2019;13:2285-92.
Kaido M, Matsumoto Y, Shigeno Y, et al. Corneal fluorescein staining correlates with visual function in dry eye patients. Invest Ophthalmol Vis Sci. 2011;52:9516-9522.
Kaido M, Ishida R, Dogru M, Tsubota K. The relation of functional visual acuity measurement methodology to tear functions and ocular surface status. Jpn J Ophthalmol. 2011;55:451-459.
Koh S, Maeda N, Ikeda C, et al. The effect of ocular surface regularity on contrast sensitivity and straylight in dry eye. Invest Ophthalmol Vis Sci. 2017;58:2647-2651.
Mathews PM, Ramulu PY, Swenor BS, et al. Functional impairment of reading in patients with dry eye. Br J Ophthalmol. 2017;101:481-486.
Karakus S, Mathews PM, Agrawal D, et al. Impact of dry eye on prolonged reading. Optom Vis Sci. 2018;95:1105-1113.
Luo L, Li D-Q, Corrales RM, Pflugfelder SC. Hyperosmolar saline is a proinflammatory stress on the mouse ocular surface. Eye Contact Lens. 2005;31:186-193.
Coursey TG, Henriksson JT, Barbosa FL, et al. Interferon-γ–induced unfolded protein response in conjunctival goblet cells as a cause of mucin deficiency in Sjögren syndrome. Am J Pathol. 2016;186:1547-1558.
Massingale ML, Li X, Vallabhajosyula M, et al. Analysis of inflammatory cytokines in the tears of dry eye patients. Cornea. 2009;28:1023-1027.
Esen Akpek, MD
She is from The Johns Hopkins University School of Medicine, Baltimore, and serves as a Consultant/Contractor toDompé, HanAll, Iolyx, Kyria, Novaliq, Sinqi, and Xequel Bio. She receives research support from the Department of Defense, IRIS Registry Research Fund, National Eye Institute, National Institutes of Health, Novartis, Ocular Therapeutics, and W.L. Gore Inc.