Tear film imager may shift paradigm in the treatment of dry eye disease

Masako Chen, MD, performs a tear film test at The Shelley and Steven Einhorn Clinical Research Center at New York Eye and Ear Infirmary of Mount Sinai.

A surge in dry eye disease among people of all ages has put the tear film under a spotlight as researchers explore the many ways its ultrathin protective layers can break down, as well as the most effective therapies to repair those surface pathologies. Their work is being propelled by a new era of cutting-edge technological advancements in tear film imaging.

Specifically, new abilities to image and measure the muco-aqueous and lipid sublayers of the tear film with nanometer resolution are allowing clinicians to assess the efficacy over time of various topical medications to treat not just dry eye but other conditions that result in a lack of tear homeostasis. These include glaucoma, Sjögren syndrome, refractive and retinal surgery, nerve dysfunction, diabetes, and meibomian gland dysfunction.

“We’re moving into an age of many new therapies for dry eye and trying to objectively understand which are best suited for individual patients is a real challenge for our field,” said Richard B. Rosen, MD, vice chairman and director of research at New York Eye and Ear Infirmary of Mount Sinai (NYEE). “The tear film imager [TFI] takes us to a new level of sophistication in dynamically assessing the tear film layers, in the same way OCT [optical coherence tomography] allows us to measure incremental improvements or worsening of conditions in the back of the eye to better understand the degenerative process, as well as the effects of therapy.”

Several diagnostic tests have been developed over the years to examine ocular surface health, such as fluorescein-assisted tear breakup time (TBUT), which evaluates tear stability; Schirmer strips to assess tear production; and vital dyes to highlight epithelial irregularity. Additional information can be gleaned from imaging technologies to quantify TBUT noninvasively and measure tear meniscus height and detect meibomian gland dropout, or to measure blink rate and central lipid layer thickness. A glaring gap in these technologies, however, are their mostly static metrics that fail to assess changes in tear film dynamics over time.

The TFI is at the forefront of new devices combining spectrometry and imaging to analyze the intricate structure of the tear film layers. Developed by Advanced Optical Methods, based in Israel, the TFI employs spectral interference technology to image and map
the corneal surface with a large field of view
(6 mm diameter) and high axial resolution, allowing for measurement of muco-aqueous layer thickness (MALT) and lipid layer thickness (LLT) over time.

Measurements are taken as frequently as
10 times per second over 40 seconds, throughout natural blinking. Along with time-resolved measurements at the center of the eye, the TFI produces a large field of view, 3-dimensional map of the lipid layer with a sampling resolution of 5 nm/pixel.^1-3

“The uniqueness of the TFI device lies in its ability to slice and quantify the various layers of the tear film with nanometer resolution. This provides valuable scientific information that will allow a better understanding of surface diseases of the eye and the impact of various therapeutics,” explains Alon Harris, MS, PhD, FARVO, professor and vice chairman of Ophthalmologyand codirector of the Center for Ophthalmic Artificial Intelligence and Human Health at Icahn School of Medicine at Mount Sinai, who is an internationally recognized glaucoma scientist.

Paul Sidoti, MD, chairman of the Department of Ophthalmology at NYEE, who advocated for bringing this technology to NYEE and Mount Sinai, offered clarification.

Example of a report from the tear film imager showing thickness of the tear film inner layers (muco-aqueous layer and lipid layer) using spectral interference technology. (Image courtesy of NYEE)

“The TFI provides precise muco-aqueous thickness measurements and reports lipid layer thickness at high resolution,” Sidoti said. “These measurements enable us to track both the aqueous and lipid layer interblink dynamics.”

TFIs are currently in place at academic medical centers worldwide, including one of the first at Mount Sinai. Sidoti; Gal Antman, MD; Alice Verticchio, MD, PhD; Anna Fabczak-Kubicka, MD; and Masako Chen, MD, are lead investigators using the TFI at NYEE.

Taking the guesswork out of artificial tear products

The repertoire of TFI capabilities was pivotal in a recent study investigating the effects of a number of popular artificial tear (AT) products on the sublayers of the tear film. As reported in Cornea, MALT and LLT thickness from 198 images taken from 11 individuals with meibomian gland dysfunction were measured before and after exposure to 3 AT preparations.⁴

“A wide assortment of over-the-counter AT products is available today for the major subtypes of dry eye disease, including evaporative, aqueous deficient, and mixed,” said Chen, an assistant professor of Ophthalmology at Icahn Mount Sinai, and senior author of the study. “With limited methods to objectively assess the effects of these options, patients and clinicians alike often resort to a trial-and-error approach of product selection. We realized that quantification of the tear film sublayers could help in tailoring products to the specific dry eye disorder of the patient.”

For the first time, the NYEE researchers provided new insight through the TFI, describing how a substantial acute mean MALT increase occurs 1 minute after AT instillation with all the agents tested, but that clear differences in response and durability exist according to the specific AT drop used, suggesting benefits of choosing a specific AT according to individual needs.

Using the TFI, Mount Sinai researchers also analyzed and quantified the impact of facial creams and lotions on the sublayers of the tear film in patients with meibomian gland dysfunction. Compared to a cohort of nonlotion users, significant increases in the LLT and lipid map uniformity were found in those using lotion products, suggesting that cosmetics may increase ocular surface irritation.⁵

Applications for glaucoma and cataract surgery

The pervasiveness of topical medications for glaucoma, cataract and refractive surgery, and many other ophthalmic disturbances hints at the potential impact of high-resolution tear film analysis.

“Some patients do very well on one type of compound for controlling intraocular pressure, but not on another,” Rosen explained. “We could greatly improve the science of treating glaucoma by quantifying the impact of eye drops on the various layers of the tear film and surface epithelium. This will help identify which glaucoma treatments lower pressure but avoid injury to the tear film.”

Studying glaucoma

Work is currently underway at NYEE using TFI to study glaucoma patients before and after using topical therapies to evaluate their effect on the tear film layers. Likewise, the TFI is being employed to study the most effective drops for use in cataract surgery and to provide insights into which surgical techniques may influence the tear film postoperatively.

Harris can already envision the next generation of tear film analyzer.

“As this device provides quantification of the various layers of the tear film in a short, noninvasive test, it could eventually be used to help clinicians tailor AT therapies and other medications,” Harris concluded.

References:

1. Cohen Y, Trokel S, Arieli Y, Epshtien S, Gefen R, Harris A. Mapping the lipid layer of the human tear film. Cornea. 2020;39(1):132-135. doi:10.1097/ICO.0000000000002101

2. Segev F, Geffen N, Galor A, et al. Dynamic
   assessment of the tear film muco-aqueous and lipid layers using a novel tear film imager (TFI). Br J Ophthalmol. 2020;104(1):136-141. doi:10.1136/bjophthalmol-2018-313379

3. Mangwani-Mordani S, Baeza D, Acuna K, Antman G, Harris A, Galor A. Examining tear film dynamics using the novel tear film imager. Cornea. Published online March 28, 2024. doi:10.1097/ICO.0000000000003529

4. Antman G, Tessone I, Rios HA, et al. The short-term effects of artificial tears on the tear film assessed by a novel high-resolution tear film imager: a pilot study. Cornea. Published online February 28, 2024. doi:10.1097/ICO.0000000000003505

5. Alabi D, Assessing the effects of facial creams on the tear film using a novel tear film imager. Presented at: Association for Research and Vision in Ophthalmology Annual Meeting; May 5-9, 2024; Seattle, Washington.