New metrics, new therapies for dry eye

By James McLaughlin; Reviewed by Joseph B. Ciolino, MD

Dry eye disease (DED) is like an iceberg when it comes to both diagnosis and treatment: What could be described simply as tired, burning, or irritated eyes belies a complex spectrum of disorders involving secretory and immune function dysregulation, inflammation, and a significant impact on quality of life.¹

Diagnosis is complicated by the diversity of  patient signs and symptoms, often occurring without strong correlation. Some patients complain of severe discomfort without displaying any of the hallmark signs of corneal damage or tear film dysfunction, while others experience only modest symptoms despite significant surface epithelial damage.

Together with myriad underlying etiologies and contributing co-morbidities, the challenge of effective therapy has remained despite decades of concerted effort.

For most clinicians, artificial tears represent the first step in the treatment of an initial presentation of DED. The choice of drop is primarily empirical and patients may go through a trial-and-error process with several products before they find symptomatic relief. Clinical assessments of drop formulations have historically focused on pairwise assessment of signs and symptoms (e.g., corneal staining and ocular discomfort) as a basis for measuring treatment efficacy.

‘Real-life’ assessment

Recently, there has been a greater interest in metrics focused upon the impact of DED on everyday activities, such as reading, driving, or use of various visual display devices.² These efforts provide a “real-life” assessment of how DED impacts vision-related activities, and thus can be a valuable tool in measuring the relief provided by various treatment regimens outside the clinical setting.

The recently-published study by Torkildsen and colleagues3 provides a clear example of this new approach to DED therapy assessment.

The study was a single-center, parallel group comparison of a new artificial tear product (Rohto Dry-Aid, Mentholatum Co.) and a well-known artificial tear in patients 18 years of age or older (n= 80) diagnosed with mild to moderate DED.

Subjects were assigned to one of the two products over a 30-day trial (twice-daily dosing for each treatment group), and were monitored at 2 and 4 weeks during the course of the study.

At each visit, standard dry eye metrics, such as tear film break-up time, corneal fluorescein staining, and ocular surface disease index (OSDI) discomfort scores were collected. Quality-of-life and visual acuity tests were also included for these visits.

In addition to these measures subjects kept diaries over the course of the study, noting ocular discomfort over the course of the day.

Both products were well-tolerated by study participants, and there were no dropouts over the course of the trial. Both products yielded significant improvements over baseline measures of corneal staining, tear film break-up, and OSDI. By these standard criteria, the two products tested were comparable in terms of  duration and relief of signs and symptoms of DED.

Differences between the two test compounds were evident in both the quality-of-life and the diary data, however.

The quality of life measurement (Ora Calibra QOL questionnaire) posed four questions at baseline and at the two study visits; the questions focused on impact of DED on daily activity, reading, watching movies or television, and driving. Only the Dry-Aid-treated group showed statistically significant improvements in 3 of 4 questions at 4 weeks, and showed statistically significant improvement in 1 of 4 questions in as soon as 2 weeks. 

Daily diary

For daily diary entries subject were asked to score their ocular comfort in terms of five standard terms of DED assessment: burning, dryness, grittiness, stinging, and overall discomfort. Scores were recorded morning and evening over the 30-day treatment period.

An intriguing pattern emerged from this exercise. It is well established that untreated DED tend to get progressively worse over the course of the day. Those with the condition typically note that activities, such as reading or driving are more difficult in the evening, at least in part due to an exacerbation of symptoms. This pattern of an increase in symptoms was seen in diaries of the subjects in the group (4 of the 5 scores), but not in subjects in the Dry-Aid group.

This was an important study for several reasons. Head-to-head studies are essential for developing a true sense of the comparative treatment value of various DED therapies.

This study was also one of the first trials to look at QOL metrics, an essential “real-world” measure that provides one of the best means to judge overall efficacy.

Finally, the diary assessment allows for another real world measure, that of duration with respect to everyday visual tasking activities that suffer for those with DED. Improving these specific outcomes should be a central goal of any dry eye therapy.

References

1.   Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017;15:276-283.

2.   Uchino M, Uchino Y, Dogru M, et al. Dry eye disease and work productivity loss in visual display users: The Osaka study. Am J Ophthalmol. 2014;157:2:294-300.

3.   Torkildsen G, Brujic M, Cooper MS. Evaluation of a new artificial tear formulation for the management of tear film stability and visual function in patients with dry eye. Clin Ophthalmol. 2017,11:1883-1889.

Joseph B. Ciolino, MD

e: joseph_ciolino@meei.harvard.edu

Dr. Ciolino is associate professor of ophthalmology at Harvard Medical School. He served as medical monitor for this study.