Comparison of Non-pharmaceutical Treatments for Evaporative Dry Eye

Dry Eye Clinical Trial

Official title:

Comparison of Non-pharmaceutical Treatments for Evaporative Dry Eye: A Randomized Controlled Study

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05923528
• Other study ID #: TREATDE2023
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 1, 2023
• Est. completion date: December 31, 2023

Study information

• Verified date: June 2023
• Source: He Eye Hospital
• Contact: Emmanuel Eric Pazo
• Phone: +8618612782131
• Email: ericpazo[@]outlook.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The lipid layer of the tear film is critical to maintaining the integrity of the tear film and deficiency in the tear film lipid layer (TFLL) is the cause of evaporative dry eye (EDE) in approximately 80% of dry eye disease patients, resulting in excessive evaporation (so-called hyperevaporative dry eye). This study protocol was designed to assess and compare the effects of intense pulsed light (IPL), heated eye mask (HEM), vectored thermal pulsation system (VTPS), and eyelid massage device (EMD) for improving signs and symptoms of EDE.

EDE patients will be randomly divided into IPL, HEM, VTPS, and EMD groups and will be followed up for four weeks. The primary outcome measure will be non-invasive tear breakup time (NITBUT). The secondary outcome measures will include, tear film lipid layer score (TFLL), meibomian gland function and secretion quality change from baseline conjunctival and cornea staining (CFS) with fluorescein and lissamine, tear meniscus height (TMH), conjunctival hyperemia (RS score) and ocular surface disease index (OSDI) questionnaire. Additionally, adverse events also were monitored and documented.

Description:

"A chronic, diffuse abnormality of the meibomian glands, frequently characterized by terminal duct obstruction and/or qualitative/quantitative abnormalities in glandular secretion," is how the International Workshop on meibomian gland (MG) hypofunction or dysfunction (MGD) describes MGD. These glands, which are repurposed sebaceous glands, secrete meibum onto the ocular surface. By improving the quality and quantity of meibum secretion, signs and symptoms of evaporative dry eye (EDE) and MGD can be alleviated.

Traditional remedies derived from natural sources have been utilized for treating anterior eye ailments since ancient times, predating the advent of contemporary pharmacological interventions. These remedies continue to be employed in diverse populations globally. The objective of this study is to examine the present non-pharmacological modalities that have been implemented and evaluate their efficacy. This encompasses alternative medicine, extant non-pharmaceutical therapeutic modalities, as well as contemporary low and high technological interventions. The most common approaches to relieving MGD involve the application of heat to the eyelids with and without physical massage of the eyelids in order to express the MGs.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 116
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Age = 18 years

• Able and willing to comply with the treatment/follow-up schedule

• Bilateral signs and symptoms of dry eye disease (a) the ocular surface disease index (OSDI) questionnaire = 13, (b) a non-invasive tear film breakup time (NITBUT) of =10 s, or a conjunctivocorneal staining score (CS) of = 3 points. The presence of two or more criteria was used to establish a positive DE diagnosis, based on the 2016 Asia Dry Eye Society criteria

• Lipid layer thickness score evaluation = 2.

Exclusion Criteria:

• existing ocular trauma, infectious diseases, recent surgical history

• skin defects, pigmentation, moles, scars in the treatment area, skin cancer

• autoimmune diseases, skin allergies

• pregnancy or lactation

• photophobia that may cause reflex tearing or difficulty in evaluating the patient's lipid layer.

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Keratoconjunctivitis Sicca

Intervention

Device:
• IPL
IPL treatment intensity was chosen based on the Fitzpatrick scale as follows: Fitzpatrick scale I, II, III, 10-15 J/cm2 with a 570-nm filter
• Heated eye mask
Heated eye mask will be used to assess its usefulness in dry eye signs and symptoms
• LipiFlow®
LipiFlow® can control the variables of temperature, pressure, and MG expression technique
• EyePeace®
The silicone-made flexible hand-held gadget applies regulated, vertical pressure to the closed eyelids.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
He Eye Hospital

References & Publications (13)

Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008. Epub 2017 Jul 20. — View Citation

Fu J, Chou Y, Hao R, Jiang X, Liu Y, Li X. Evaluation of ocular surface impairment in meibomian gland dysfunction of varying severity using a comprehensive grading scale. Medicine (Baltimore). 2019 Aug;98(31):e16547. doi: 10.1097/MD.0000000000016547. — View Citation

Heidari M, Noorizadeh F, Wu K, Inomata T, Mashaghi A. Dry Eye Disease: Emerging Approaches to Disease Analysis and Therapy. J Clin Med. 2019 Sep 11;8(9):1439. doi: 10.3390/jcm8091439. — View Citation

Ikonne EU, Ikpeazu VO, Ugbogu EA. The potential health benefits of dietary natural plant products in age related eye diseases. Heliyon. 2020 Jul 10;6(7):e04408. doi: 10.1016/j.heliyon.2020.e04408. eCollection 2020 Jul. Erratum In: Heliyon. 2021 May 17;7(5):e07069. — View Citation

Ma J, Pazo EE, Zou Z, Jin F. Prevalence of symptomatic dry eye in breast cancer patients undergoing systemic adjuvant treatment: A cross-sectional study. Breast. 2020 Oct;53:164-171. doi: 10.1016/j.breast.2020.07.009. Epub 2020 Aug 5. — View Citation

Matsumoto Y, Dogru M, Goto E, Ishida R, Kojima T, Onguchi T, Yagi Y, Shimazaki J, Tsubota K. Efficacy of a new warm moist air device on tear functions of patients with simple meibomian gland dysfunction. Cornea. 2006 Jul;25(6):644-50. doi: 10.1097/01.ico.0000208822.70732.25. — View Citation

Olson MC, Korb DR, Greiner JV. Increase in tear film lipid layer thickness following treatment with warm compresses in patients with meibomian gland dysfunction. Eye Contact Lens. 2003 Apr;29(2):96-9. doi: 10.1097/01.ICL.0000060998.20142.8D. — View Citation

Song Y, Yu S, He X, Yang L, Wu Y, Qin G, Zhang Q, Deep Singh Talwar G, Xu L, Moore JE, He W, Pazo EE. Tear film interferometry assessment after intense pulsed light in dry eye disease: A randomized, single masked, sham-controlled study. Cont Lens Anterior Eye. 2022 Aug;45(4):101499. doi: 10.1016/j.clae.2021.101499. Epub 2021 Aug 22. — View Citation

Wang MTM, Feng J, Wong J, Turnbull PR, Craig JP. Randomised trial of the clinical utility of an eyelid massage device for the management of meibomian gland dysfunction. Cont Lens Anterior Eye. 2019 Dec;42(6):620-624. doi: 10.1016/j.clae.2019.07.008. Epub 2019 Jul 26. — View Citation

Wu MF, Gao H, Zhao LJ, Chen H, Huang YK. Real dynamic assessment of tear film optical quality for monitoring and early prevention of dry eye. Medicine (Baltimore). 2020 Jul 31;99(31):e21494. doi: 10.1097/MD.0000000000021494. — View Citation

Wu Y, Xu L, Song Y, Zhang Q, Qin G, Yang L, Ma J, Palme C, Moore JE, Pazo EE, He W. Management of Post-LASIK Dry Eye with Intense Pulsed Light in Combination with 0.1% Sodium Hyaluronate and Heated Eye Mask. Ophthalmol Ther. 2022 Feb;11(1):161-176. doi: 10.1007/s40123-021-00418-2. Epub 2021 Nov 6. — View Citation

Xu L, Wu Y, Song Y, Zhang Q, Qin G, Yang L, Ma J, Palme C, Moore JE, Pazo EE, He W. Comparison Between Heated Eye Mask and Intense Pulsed Light Treatment for Contact Lens-Related Dry Eye. Photobiomodul Photomed Laser Surg. 2022 Mar;40(3):189-197. doi: 10.1089/photob.2021.0094. — View Citation

Zhang X, Wang L, Zheng Y, Deng L, Huang X. Prevalence of dry eye disease in the elderly: A protocol of systematic review and meta-analysis. Medicine (Baltimore). 2020 Sep 11;99(37):e22234. doi: 10.1097/MD.0000000000022234. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-invasive tear breakup time (NITBUT)	Non-invasive initial tear film breaking time will be assessed using the Keratograph 5M (Oculus, Germany) topographer. Three sequential readings will be captured, and the median value will be included in the final analysis. The median value will be recorded	• Changes at day-14, day-28 and day-42will be compare with baseline measurements. • Comparison between groups at baseline, day-14, day-28 and day-42will also be examined.
Secondary	Tear Film Lipid Layer Score (TFLL)	Tear film lipid layer interferometry will be assessed using DR-1 (Kowa, Nagoya, Japan). The results will be graded as follows: grade 1, somewhat gray color, uniform distribution; grade 2, somewhat gray color, nonuniform distribution; grade 3, a few colors, nonuniform distribution; grade 4, many colors, nonuniform distribution; grade 5, corneal surface partially exposed	• Changes at day-14, day-28 and day-42will be compare with baseline measurements. • Comparison between groups at baseline, day-14, day-28 and day-42will also be examined.
Secondary	Meibomian gland function and secretion quality	Five meibomian glands in the middle parts of the eyelid will be assessed using a scale of 0 to 3 for each gland (0 represented clear meibum; 1 represented cloudy meibum; 2 represented cloudy and granular meibum; and 3 represented thick, toothpaste-like consistency meibum)	• Changes at day-14, day-28 and day-42will be compare with baseline measurements. • Comparison between groups at baseline, day-14, day-28 and day-42will also be examined.
Secondary	Ocular Surface Disease Index (OSDI)	The patient will answer each question on a scale ranging from 0 to 4, with 0 indicating 'none of the time' and 4 indicating 'all of the time'. If a certain question is deemed irrelevant, it will be marked as 'not applicable (N/A)' and excluded from the analysis. The OSDI total score is calculated according to the following formula. The scale ranges from 0 to 100, with higher scores representing more severe cases of dry eye syndrome	• Changes at day-14, day-28 and day-42will be compare with baseline measurements. • Comparison between groups at baseline, day-14, day-28 and day-42will also be examined.
Secondary	Fluorescein and lissamine conjunctival and cornea staining (CFS)	Fluorescein and lissamine staining of the ocular surface will be divided into three zones comprising nasal conjunctival, corneal, and temporal conjunctival areas. The staining score ranged from 0 to 3 for each zone, yielding a total score of 0-9 for the ocular surface	• Changes at day-14, day-28 and day-42will be compare with baseline measurements. • Comparison between groups at baseline, day-14, day-28 and day-42will also be examined.
Secondary	Tear meniscus height (TMH)	Non-invasive first tear film breakup time using the Keratograph 5M (Oculus, Germany) topographer will be measured three times consecutively and the median value was recorded	• Changes at day-14, day-28 and day-42will be compare with baseline measurements. • Comparison between groups at baseline, day-14, day-28 and day-42will also be examined.
Secondary	Conjunctival hyperemia (RS score)	Conjunctival hyperemia (RS score) will be assessed by Keratograph image (Oculus, Germany) of 1156*873 pixels, redness score (RS) (accurate to 0.1 U) was displayed on the computer screen that ranged from 0.0 (normal) to 4.0 (severe)	• Changes at day-14, day-28 and day-42will be compare with baseline measurements. • Comparison between groups at baseline, day-14, day-28 and day-42will also be examined.
Secondary	Thermal imaging: Ocular surface temperature (OST)	All measurements were taken in the same room with controlled temperature and humidity. Prior to ocular thermography or other tests, participants were acclimatized to the room for 20 minutes. Morgan and colleagues described the following criteria for recording OST: The patients were instructed to blink normally, close their eyes for 3 seconds, and the first image was captured soon after the eyelids opened. The temperature was taken in the central cornea, which was defined as a circular area 4 mm in diameter in the middle of the cornea	• Changes at day-14, day-28 and day-42will be compare with baseline measurements. • Comparison between groups at baseline, day-14, day-28 and day-42will also be examined.