Diamond Bur Microblepharoexfoliation Combined With Intense Pulse Light and Meibomian Gland Expression for Evaporative Dry Eye: A Short-term Controlled Study
Phase: NA
Conditions: Dry Eye Disease
Sponsor: University of Seville

Study protocol 
 
 
 
 
 
 
 
 
Diamond bur Microblepharoexfoliation Combined with Intense Pulse Light and 
Meibomian Gland expression for Evaporative Dry Eye: A Short-term Controlled Study. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Date: May 9, 2023. 

1. Introduction 
 
Dry eye disease (DED) is a chronic multifactorial disease of the ocular surface characterized by a loss of 
homeostasis of the tear film, which is accompanied by ocular symptoms caused by hyperosmolarity, ocular 
surface inflammation and neurosensory abnormalities [1,2]. DED prevalence varies according to the 
definition used and the characteristics of the population studied, but it ranges from 5% to 50%, is more 
frequent in women and increases with age [3]. Currently, evidence suggests that all forms of DED have an 
evaporative component because without evaporation, hyperosmolarity cannot occur [4]. 
Meibomian gland dysfunction (MGD) is the most common etiology of tear film evaporation, and it is 
characterized by the obstruction of meibomian glands due to terminal duct obstruction and/or changes in 
meibum quality and quantity [4,5]. The management and therapy subcommittee of the TFOS DEWS II 
recommended intense pulsed light (IPL) as a second step therapy for MGD when education, lid hygiene, 
warm compresses and ocular lubrications do not achieve the desired effect [6]. IPL is a form of light therapy 
that uses flash lamps to emit noncoherent, polychromatic high-intensity light of determined wavelength 
spectrum, ranging from 500 to 1200 nm [7]. Using these wavelengths, the potentially harmful ultraviolet 
radiation, which occurs below 500 nm, is filtered [8]. In 2002, Toyos et al. reported that patients with dry 
eye disease (DED) who received IPL treatment for rosacea, acne or other skin disorders reported 
improvements in their dry eye symptoms [9]. This finding led to the development of different IPL devices 
to specifically treat DED. Currently, different studies have shown that IPL is a safe and effective treatment 
that improves the signs and symptoms of patients with DED owing to MGD [9–15]. The main mechanism 
of action of IPL is thermal. IPL energy absorbed by hemoglobin which causes thrombosis of abnormal 
blood vessels reduces the concentration of inflammatory mediators in the eyelid and meibomian glands, 
thus preventing their dysfunction and improving meibum flow [16]. 
Combined or additional therapies in MGD treatment have emerged such as Microblepharoexfoliation 
(MBE). MBE is a novel in-office treatment that works by exfoliating the eyelid margins to remove the 
accumulated biofilm debris, epithelial keratinization and capped meibomian glands, resulting in better 
meibum outflow. Different studies have shown that MBE improves DED symptoms [17,18], demodex 
blepharitis [17–20] and meibomian gland function [18,19,21] In addition, meta-analyses recommend 
combining IPL with meibomian gland expression (MGX) compared to IPL or MGX alone [22–24]. 

However, to the best of our knowledge, we have not found any studies evaluating the benefits of MBE 
combined with IPL and MGX. 
Consequently, the purpose of the current study is to evaluate whether MBE combined with IPL and MGX 
leads to an improvement of symptoms and signs in patients with DED due to MGD. 
2. Methods 
 
This prospective, unmasked, non-randomized and controlled study was approved by the clinical research 
ethics committee of the University of Murcia (ID: 4097/2022), adhered to the tenets of the Declaration of 
Helsinki, and was performed at the Novovision Ophthalmology Clinic from April 2022 to January 2023. 
Informed consent was obtained from each patient before enrollment in the study. 
2.1 Subjects 
 
Patients with DED due to MGD attending Novovision Ophthalmology Clinic were enrolled. The inclusion 
criteria were as follows: (1) age ≥ 18 years old; (2) DED diagnosis according to DEWS II [25] meeting one 
of the following conditions: (2.1) ocular surface disease index (OSDI) score ≥ 13; (2.2) NIBUT < 10 
seconds; and (2.3) ocular surface staining with > 5 or 9 corneal or conjunctival stains, respectively, and (3) 
MGD diagnosis according to the international workshop on MGD [26] meeting two of the following 
conditions: (3.1) irregularity of the eyelid margin or mucocutaneous junction; (3.2) vascularity of the eyelid 
margin; (3.3) plugged or capped Meibomian gland orifices; (3.4) Meibomian gland atrophy; or (3.5) 
decreased meibum quality and quantity. The exclusion criteria included: (1) skin pathologies that prevent 
IPL treatment; (2) all corneal disorders that affect diagnostic tests, such as: (2.1) active corneal infections; 
and (2.2) corneal dystrophies; (3) active ocular allergy; (4) pregnant or lactating women; and (5) patients 
who did not understand or comprehend the informed consent. Systemic or ocular diseases, previous 
systemic or ocular treatments and ocular surgeries with more than 6 months of postoperative evolution were 
not considered exclusion criteria to better reflect the patient population. Contact lens users were instructed 
not to wear their contact lenses one week before baseline and follow-up examinations. 
2.2 Experimental design 
 
A flowchart showing the experimental design of the study is presented in Fig.1. Patients with MGD were 
classified into the treatment and control groups. All patients received a home-based therapy based on 
Therapearl eye mask warming compress (Bausch & Lomb, Madrid, Spain) twice a day and Eyestil synfo 

eyedrops (Sifi Iberica SL, Madrid, Spain) 4 times a day during the study including the follow-up period. 
Treatment group patients also underwent a series of three combined treatment sessions of MBE, IPL and 
MGX at 2-week intervals. All patients underwent a 2-months follow-up from baseline. 
2.3 Clinical assessment 
 
Parameters were assessed with the S390L Firefly WDR slit lamp (Shangai Mediworks Precision 
Instruments Co. Shangai, China) that includes a dry eye module designed to perform objective and non- 
invasive measures, which are analyzed by an artificial intelligence (AI) identification system (Mediview 
R3.0 software). To asses treatment efficacy, parameters were measured at baseline and the last visit. DED 
symptoms were assessed with the ocular surface disease index (OSDI) and symptom assessment in dry eye 
(SANDE) questionnaires. Ocular surface measurement was carried out by one examiner (ABS) in the 
following sequence to best preserve the integrity of the tear film to avoid affecting the test results: (1) tear 
film stability and volume; (2) ocular hyperemia; (3) ocular surface staining (OSS) and (4) meibomian gland 
analysis. Except for OSDI and SANDE questionnaires, which were collected per subject, all other clinical 
outcomes were collected per eye. To evaluate treatment safety, post-treatment adverse events were reported. 
2.3.1 Tear film stability and volume 
 
Tear film stability was evaluated automatically by the AI identification system via detection of the first (F- 
NIBUT) and average noninvasive tear film break-up time (A-NIBUT) using a Placido disc. To assess the 
lipid layer grade (LLG), the lipid layer interferometric pattern was compared with the lipid layer thickness 
(LLT) grading scale template provided by the device, which has the following values: 1; LLT < 30 nm; 2, 
LLT of 30-60 nm; 3, LLT of 60-80 nm and 4, LLT >80 nm. Regarding tear volume, tear meniscus height 
(TMH) and tear meniscus area (TMA) were also automatically assessed by the AI identification system 
through focused image of the lower eyelids. 
2.3.3 Ocular Hyperemia 
 
Ocular hyperemia was assessed through complete picture of the ocular surface focused on the bulbar 
conjunctiva. Nasal ciliary hyperemia (NCIH), temporal ciliary hyperemia (TCIH), nasal conjunctival 
hyperemia (NCOH) and temporal conjunctival hyperemia (TCOH) were analyzed automatically the AI 
identification system with a value between 0% (no hyperemia) and 100% (the highest level of hyperemia). 

2.3.4 Ocular surface staining 
 
OSS was subjectively and invasively evaluated with the oxford grading schema reported by Bron et al. [27]. 
Prior to assess OSS, a single drop of unit dose saline was instilled onto a fluorescein-impregnated strip. The 
right lower lid was then pulled down and the strip was tapped onto the lower tarsal conjunctiva. The same 
procedure was carried out on the left. A cobalt-blue filter with yellow Kodak Wratten 12 barrier filter was 
used for a better detection of fluorescein staining. 
2.3.5 Meibomian gland analysis 
 
Meibomian gland analysis was performed on the upper and lower eyelid using infrared light after everting 
the eyelids with a cotton swab. the AI identification system automatically analyzed the meibomian glands, 
obtaining the upper loss area Meibomian gland (U-LAMG) and lower loss area Meibomian gland (L- 
LAMG) with a value between 0% (no glandular dropout) and 100% (the highest level of glandular 
dropout), and upper meibomian gland dysfunction grade (U-MGD grade) and lower meibomian gland 
dysfunction grade (L-MGD grade), which have the following values: 0, no MGD; 1, mild MGD; 2, 
moderate MGD and 3, severe MGD. 
Meibomian gland secretion was assessed by MGX. Fifteen glands on the lower eyelids were evaluated. For 
each gland, the secretion had the following scores: 0, no secretion; 1, inspissated/toothpaste consistency; 2, 
cloudy liquid secretion; and 3, clear liquid secretion. Then, three meibomian gland parameters were 
assessed: meibomian gland yielding secretion score (MGYSS) (range: 0-45), which was defined as the sum 
of the grades for all 15 glands, meibomian gland yielding clear secretion (MGYCS) (range: 0-15) and 
meibomian gland yielding liquid secretion (MGYLS) (range: 0-15). 
2.4 Combined treatment with MBE, IPL and MGX 
 
MBE was performed using the yokefellow instrument (Youke Electronic Corporation, Guangzhou, China), 
which contains a handpiece with a 1.80 mm diameter medical-grade diamond bur. To ensure a well-tolerated 
procedure, topical application of 0.1% tetracaine hydrochloride and 0.4% oxybuprocaine hydrochloride 
was applied. After placing topical anesthetic, a corneal shield was used to protect the ocular surface and a 
jojoba anesthetic ointment (JAO) (O´Brien Pharmacy, Kansas City, USA) containing 8% lidocaine and 25% 
jojoba wax were place on the lid margin. Patients underwent MBE on the upper and lower lid margin of 
both eyes at 500 rpm until complete removal of accumulated biofilm debris, epithelial keratinization or 

capped meibomian glands. MBE was carried out only in the first combined treatment session. Immediately 
after MBE, JAO was cleaned with a cotton swab and IPL was performed. 
IPL treatment was carried out with Thermaeye Plus (MDS Medical Technologies SL, Barcelona, Spain). 
The procedure began by applying an ultrasound gel (Carmado SL, Alicante, Spain) to the patient’s 
periocular areas and upper eyelids. In the periocular areas, 6 light pulses were applied; 4 light pulses on the 
skin below the lower eyelid (with handpiece placed horizontally in the first pass and vertically in the second 
pass) and 2 light pulses on the canthal area (with handpiece placed vertically in first and second pass). The 
parameters were as follows: (1) Filter: 650 nm; (2) fluence: 9 j/cm2; (3) pulses: 2; (4) duration: 3 ms; (5) 
Delay: 20 ms; and (6) Cooling: 70%. In the upper eyelids, 4 light pulses were applied; 2 light pulses in the 
first and second pass, respectively. The parameters were as follows: (1) Filter: 650 nm; (2) Fluence: 5 j/cm2; 
(3) pulses: 1; (4) duration: 3 ms and (5) Cooling: 70%. Fitzpatrick skin typing [28] was assessed prior to 
IPL treatment. 
Finally, the MGX was realized on both upper and lower eyelids of each eye with a Collins forceps (Medi 
Instrument Inc, New York, USA). After first combined treatment session, patients were instructed to apply 
0.5% dexamethasone sodium phosphate and 1% chloramphenicol topically twice a day during the first 
week and once a day during the second week. White Sun protection cream was recommended for the first 
48 hours in the IPL treatment area. 
2.6 Statistical analysis 
 
 
Statistical analyses were performed with SPSS statistics software, version 26.0 (IBM Corporation, Armonk, 
NY, USA). The sample size was estimated using the GRANMO calculator, version 7.12 (Municipal 
Institute of Medical Research, Barcelona, Spain). It was calculated on the basis of assumed mean 
differences in F-NIBUT and MGYSS between the treatment and control groups at 2 months after the 
treatment onset, with values of 3.04 ± 3.86 and 19.75 ± 5.45, respectively. These assumed differences were 
based on the findings of a pilot study with 16 eyes of 8 patients in each group. With these assumptions, a 
sample size of 26 eyes per group would yield a power > 80% and a statistically significant paired difference 
of 95% confidence. Continuous variables were displayed as the mean ± standard deviation (SD) with 
interquartile ranges [IQRs], while ordinal categorical variables were expressed as frequencies (n) and 
percentages (%). After testing for normality and homogeneity of variance, the paired Student’s t-test 
(parametric) or Wilcoxon’s signed-rank test (nonparametric) was performed to compare intra-group clinical 

outcomes. Within each group, the increment (Δ) was calculated. It was defined as the change from the last 
visit (LV) to baseline (B) “Δ = LV – B”. Inter-group clinical outcomes, were analyzed. with the unpaired 
Student’s t-test (parametric) or Mann-Whitney’s U test (nonparametric). Between each group, the 
differences were calculated as “Δ Treatment group – Δ Control group”. The Pearson’s (parametric) or Spearman’s 
Rho correlation coefficient (nonparametric) was used to analyze the correlations between the variables. 
Stepwise multiple linear regression analysis was performed to detect the influential factors in dry eye 
symptoms (ΔOSDI and ΔSANDE). In addition, One-Way ANOVA (parametric) was performed to 
determine if there were statistically significant differences in ΔMGYSS according to baseline L-MGD- 
grade. A post hoc analysis by Bonferroni’s test was carried out to determine statistically significant 
differences between baseline L-MGD grade. The level of significance was P < 0.05 for all of the 
comparisons. 

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