CLINICAL SCIENCE

Combination Therapy of Intense Pulsed Light Therapy and

Meibomian Gland Expression (IPL/MGX) Can Improve Dry
Eye Symptoms and Meibomian Gland Function in Patients
With Refractory Dry Eye: A Retrospective Analysis
Sravanthi Vegunta, BS,* Dharmendra Patel, MD,† and Joanne F. Shen, MD†

Purpose: To assess the improvement in meibomian gland function and Dry eye disease is a common condition that causes ocular discomfort
and reduces visual acuity. 1 The 2 categories of dry eye disease are
dry eye symptoms in patients with refractory dry eye treated with a evaporative dry eye and aqueous-
combination therapy of intense pulsed light (IPL) and meibomian gland
deficient dry eye.2 Both conditions can involve pathology of
expression (MGX).
the meibomian glands, lacrimal glands, lids, tear film, and
Methods: Medical records of 81 consecutive patients with dry eye surface cells.2,3 Meibomian gland dysfunction (MGD) is the
treated with serial IPL/MGX were retrospectively examined to leading cause of evaporative dry eye 4 and contributes to
determine the outcome. All patients had a minimum of 6 months of aqueous-deficient dry eye.5
follow-up after the first IPL/MGX treatment. Patients typically received Meibomian glands are modified sebaceous glands
1 to 4 IPL treatments spaced 4 to 6 weeks apart. Each IPL session located along the upper and lower eyelid margins. Twenty to
included MGX. Thirty-five charts had complete data for inclusion in 40 glands are located along each lid 6 and secrete meibum,
analysis. We reviewed demographics, ocular histories, Standard Patient
Evaluation of Eye Dryness 2 (SPEED2) symptom survey scores, slit- the lipid component of tears.7 MGD is defined by the
lamp examinations, and meibomian gland evaluations (MGE) at International Workshop on Meibomian Gland Dysfunction 4
baseline and at each visit before IPL/MGX treatments. as “a chronic, diffuse abnormality of the meibomian glands,
commonly characterized by terminal duct obstruction and/or
Results: The paired t test showed a significant (P , 0.0001) decrease
qualitative/quantitative changes in the glandular secretion.”
in SPEED2 with IPL/MGX therapy. Of the 35 patients, 8 (23%) had a
Patients may experience symp-toms of eye irritation and
$50% decrease in SPEED2, 23 (66%) had a 1% to 49% decrease in
SPEED2, 1 (3%) had no change in SPEED2, and 3 (9%) had an
clinically observable ocular surface disease and
increase in SPEED2. The Paired t test showed a significant increase in inflammation due to alteration of the tear film.
MGE in the left eye but not in the right eye (OD P = 0.163 and OS P = MGD is a disease commonly encountered by oph-
0.0002). Thirteen patients (37%) had improved MGE bilaterally. Eight thalmologists. The impact of dry eye on quality of life is
patients (23%) had either a decrease in MGE bilaterally or a decrease in comparable to the effect of moderate to severe angina or
1 eye with no change in the other eye. dialysis treatment.8,9 The goal of MGD therapy is to provide
long-term improvement of symptoms for patients by
Conclusions: This retrospective analysis shows that the combina-tion improving the quality of meibum, increasing meibum flow,
of IPL and MGX can significantly improve dry eye symptoms (in 89% improving tear film stability, and decreasing inflammation.
of patients) and meibomian gland function (in 77% of patients in at Commonly used therapies include preservative-free drops,
least 1 eye). omega-3 fatty acid supplementation, topical cyclosporine,
Key Words: meibomian gland dysfunction, ocular rosacea, intense serum tears, topical azithromycin, oral doxycycline, mois-
pulsed light, dry eye disease ture chambers, intraductal probing, lid margin exfoliation,
automated thermal pulsation, warm compresses, and others.
(Cornea 2016;35:318–322) Despite the variety of treatment options available, patients
often do not experience complete or long-term relief of
symptoms.
Received for publication May 23, 2015; revision received November 7,
2015; accepted November 10, 2015. Published online ahead of print Forced meibomian gland expression (MGX) was first
January 19, 2016. described in 1921 by Gifford 10 as an effective method of
From the *University of Arizona College of Medicine-Phoenix, Phoenix, rehabilitating meibomian glands and improving dry eye
AZ; and †Department of Ophthalmology, Mayo Clinic, Scottsdale, AZ. symptoms. The eyelid margins are forcefully compressed to
Presented, in part, at the ARVO 2014 meeting, Orlando, FL, ARVO meeting
abstract, May 4–8, 2014. express gland contents. Korb and Greiner 11 described an
The authors have no funding or conflicts of interest to disclose. improvement in lipid layer thickness and symptoms in 10
Reprints: Joanne F. Shen, MD, Department of Ophthalmology, Mayo Clinic, 13400 patients with MGD treated with MGX. Forceful expression
E. Shea Boulevard, Scottsdale, AZ 85259 (e-mail: [email protected]).
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is painful for patients, and some patients are unable to
tolerate the pain.
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Cornea Volume 35, Number 3, March 2016 IPL/MGX Therapy for Refractory Dry Eye

INTENSE PULSED LIGHT THERAPY plugs, oral doxycycline, topical cyclosporine, topical steroid,
Intense pulsed light (IPL) devices have long been used in topical nonsteroidal antiinflammatory, topical azithromycin,
the field of dermatology to treat acne rosacea, acne vulgaris, automated thermal pulsation, and intraductal probing. Patient
hyperpigmentation, essential telangiectasias, unwanted hair, and selection and the IPL treatment protocol followed the
photodamaged skin. IPL is a high-intensity light source established technique of Toyos et al. 17 In brief, potential IPL
consisting of visible light in the wavelength range of 515 to candidates underwent Fitzpatrick skin typing to classify their
1200 nm. The light is both polychromatic and incoherent. 12 skin response to ultraviolet exposure by the degree of burning
Most patients with dry eye undergoing IPL receive this and tanning. Fitzpatrick skin types I, II, III, and IV were
treatment as a last resort after trying several other therapies. included as recommended by the manufacturer, and V and VI
They often have severe MGD and few to no expressible glands. were excluded. The Quadra Q4 IPL Machine (DermaMed
The specific mechanism of IPL therapy in improving dry eye Solutions, LLC, Lenni, PA) was used for all patients. Patients
symptoms is unknown. It is postulated that oxyhemoglobin in did not have active lesions, skin cancer, or specific skin
blood vessels located on the surface of the skin absorbs light pathology that would exclude treatment with IPL.
emitted from the flash lamp. The absorption generates heat that Patients received 1 to 4 IPL treatments, each spaced 4 to
coagulates the red blood cells, leading to thrombosis of the 6 weeks apart. At the first treatment, each patient underwent
blood vessels.13–16 Given the proposed mechanism of IPL, Fitzpatrick skin typing, and the IPL machine was set to
patients with ocular rosacea and associated lid margin appropriate settings—1D, 2D, or 4A. At each treatment, the
telangiectasias would be the best candidates for treatment. eyelids were bilaterally closed and sealed shut with IPL-Aid
Treatments are spaced 4 to 6 weeks apart, and patients typically disposable eye shields (Honeywell Safety Products, Smith-field,
receive 1 to 4 treatments with no established limit on the RI). After generous application of ultrasonic gel to the treated
number of treatments. skin, patients received approximately 30 pulses (with slight
There are approximately 40 centers performing IPL overlapping applications) from the right preauricular area,
nationally; however, specific guidelines on selecting the ideal across the cheeks and nose to the left preauricular area, treating
IPL candidate have not been published. Two peer-reviewed up to the inferior boundary of the eye shields. Each treatment
studies have been reported to date on the efficacy of combined was followed by MGX with a cotton tip applicator and digital
IPL/MGX for treating MGD as Dr Rolando Toyos, the pressure to empty meibum from bilateral upper and lower
ophthalmologist who introduced IPL to patients with dry eye, eyelids. Patients used preservative-free ketorolac drops twice a
has described. In their 3-year retrospective review of 91 patient day for 2 days after IPL treatment. Slit-lamp examination was
records, Toyos et al17 found a statistically significant performed before each treatment. Patients underwent 4 monthly
improvement in tear film breakup time (P , 0.001). Physician- examinations and IPL/MGX treatments or until symptoms were
judged improvement in meibum and lid margins was present in resolved to their satisfaction, treat-ments became intolerable, or
94% and 98% of patients, respectively. Eighty-seven percent of they were unable to continue the treatment protocol.
patients showed improvement in clinical signs, and 93% had
subjective amelioration of their evapo-rative dry eye disease. The medical records of 81 patients with dry eye treated
Thirteen percent of patients experi- with IPL/MGX between January 2013 and December 2014
enced an adverse event. Vora and Gupta18 conducted were retrospectively examined to determine outcomes.
a retrospective review of 37 patient records and found Thirty-five charts had adequate records for inclusion in data
a statistically significant decrease in scoring of lid margin analysis. Patients were excluded if records were missing
edema, facial telangiectasia, and lid margin vascularity and MGD and Standard Patient Evaluation of Eye Dryness 2
improvement in the meibum quality score (P , 0.001). They (SPEED2) data or if patients withdrew from therapy after 1
also found a significant increase in the oil flow score and tear IPL treatment. Demographics, ocular histories, SPEED2
film breakup time (P , 0.001) and a significant decrease in scores, slit-lamp examinations, and meibomian gland evalua-
ocular surface disease index scoring (P , 0.001). One tions (MGE) at baseline and 6 to 20 months after the start of
prospective trial has been conducted on the efficacy of IPL IPL treatments were reviewed. SPEED2 is a validated 14-
(without MGX) for treating MGD. In their study, Craig et item questionnaire to evaluate the severity and frequency of
al19 reported that IPL alone was effective in improving the dry eye symptoms, use of drops or ointment, and frequency
of vision problems that patients subjectively experience.
lipid layer and patient symptoms. Gland function was
MGE is the number of lower eyelid meibomian glands
measured indirectly using lipid layer grading. In this study, observed yielding liquid secretion with application of
we report on our early results of serial IPL/MGX in patients 2 2
with ocular rosacea and dry eye disease. consistent gentle pressure between 0.8 g/mm and 1.2 g/mm
to the external eyelid margin. The MGE value correlates
with dry eye symptoms.20
MATERIALS AND METHODS Patients completed a 14-item SPEED2 questionnaire
Mayo Clinic institutional review board approval was before treatments began and up to 6 to 20 months after the
obtained for a chart review. In our referral practice at the start of treatment. Compared with the established ocular
Mayo Clinic in Arizona, patients undergoing IPL/MGX had surface disease index, SPEED2 is a validated, shorter
previously failed or refused (because of side effects/cost) questionnaire that is easier to interpret. 21 The purpose of
attempts with conventional treatments such as artificial tears, SPEED2 is to evaluate the severity and frequency of dry eye
hot compresses, lid hygiene, omega-3 fatty acids, punctal symptoms, use of drops or ointment, and frequency of vision

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Vegunta et al Cornea Volume 35, Number 3, March 2016

problems that patients subjectively experience. The score

can range from 0 to 28; a higher score indicates more severe TABLE 2. Relevant Ocular Histories of Patients
symptoms. No. Patients Percentage of
Surgery or Condition (N = 35) Patients
Cataract extraction, intraocular lens 7 20
placement
Statistical Analysis Laser in situ keratomileusis 6 17
Statistical software GraphPad Prism (GraphPad Soft- Retinal detachment 0 0
ware, Inc, La Jolla, CA) was used for data analysis. Descriptive Blepharoplasty 7 20
statistics for all patient data were obtained. Paired t tests were Eyeliner tattooing 1 3
performed to compare the mean pre- and post-treatment MGE Other surgeries* 7 20
and SPEED2 scores. Linear regression and Pearson correlation Incomplete blink 4 11
analyses were performed to evaluate the correlation between the Contact lens wear 11 31
change in SPEED2 and change in MGE. Results were GVHD 8 23
considered statistically significant for P , 0.05. Sjögren syndrome 1 3
Glaucoma 2 6
Lacrimal duct obstruction 2 6
RESULTS Other corneal conditions† 8 23
Table 1 illustrates the demographics of our patient Medications: antihypertensive, 21 60
group. The mean patient age was 61 (median, 64; range 20– anticholinergic, antidepressants,
84) years, which reflects our retired population that is overall opioids, benzodiazepines
older than other dry eye studies (Craig et al, mean = 45 *Lid surgery for actinic keratosis, conjunctival cautery, RK, or lacrimal duct stent.
years19; Korb and Greiner, range = 25–35 years11). As †Other corneal conditions: Fuchs dystrophy, map dot fingerprint changes, SLK, or
expected, the majority (77%) of the patients were women. keratoconus.
GVHD, graft-versus-host disease.
More than half (63%) of the patients had undergone previous
ocular surgery and/or blepharoplasty. The average duration
of dry eye disease was 4 years (range, 0–30). The average
number of IPL treatments received was 4 (range, 2–6). SPEED2 scores (paired t test). Patients showed various
Table 2 outlines previous surgeries and comorbid levels of improvement of their symptoms and rarely
conditions that may contribute to dry eye symptoms in the worsening of symptoms. Of the 35 patients, 8 (23%) had a
total patient population. Many patients had previous ocular $50% decrease in SPEED2, 23 (66%) had a 1% to 49%
surgeries and were taking systemic medications that may decrease in SPEED2, 1 (3%) had no change in SPEED2, and
impact dry eye. Table 3 shows the frequency of other dry eye 3 (9%) had an increase in SPEED2 (Table 2).
therapy used. The majority of the patients had been treated After 1 IPL/MGX treatment, 71% of patients perceived
with artificial tears, omega-3 fatty acid oral supplementation, improvement in symptoms. After a third treatment, an
and oral doxycycline. Some patients had specific etiologies additional 12% of patients noted a marked decrease in dry eye
of dry eye disease such as graft-versus-host disease or symptoms. After a third treatment, the remaining 12% of
Sjögren syndrome. Within 3 months of starting IPL, 11
patients (31%) had started concurrent therapy with topical
azithromycin, punctal occlusion for aqueous deficiency, TABLE 3. Previous Therapies Tried by Patients
doxycycline, and/or omega-3 fatty acid oral No.
supplementation. Table 4 details pre-IPL and post-IPL Past Therapies Tried Without Patients Percentage of
SPEED2 and MGE values of the patient population. Improvement of Symptoms (N = 35) Patients
After a series of IPL/MGX treatments, patients dem- Omega-3 fatty acids 31 89
Preserved artificial tears 29 83
onstrated a statistically significant (P , 0.0001) decrease in
Hot compresses 23 66
Preservative-free artificial tears 22 63
Topical azithromycin 22 63
TABLE 1. Patient Population Demographics Punctal plugs 19 54
Demographic Factor N (Frequency) Doxycycline/minocycline 15 43
Sex Punctal occlusion* 9 26
Female 27 (77%) Moisture chambers 6 17
Male 8 (23%) Topical azithromycin 5 14
Age, mean (range), yrs 61 (20–84) Lid hygiene† 5 14
Duration of dry eye disease, mean (range), yrs 4 (0–30) Occlusive dressing 5 14
Previous ocular surgery/blepharoplasty 22 (63%) Blinking exercises 4 11
Previous LipiFlow 22 (63%) Maskin probing 4 11
$20 points on pretreatment SPEED2 15 (43%)
*Punctal cautery.
SPEED2, Standard Patient Evaluation of Eye Dryness 2. †Ocusoft scrub, baby shampoo.

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Cornea Volume 35, Number 3, March 2016 IPL/MGX Therapy for Refractory Dry Eye

TABLE 4. Changes in SPEED2 Scores and MGE

Subjects by Change Average % Change in Average Change in Average Change in MGE Average Change in MGE
in SPEED2 N (%) SPEED2 (Range) SPEED2 (Range) OD (Range) OS (Range)
All 36 (100) 35% (247% to 100%) 5 (27 to 15) 2 (23 to 14) 3 (22 to 13)
$50% decrease 8 (23) 61% (50% to 100%) 9 (5 to 15) 3 (21 to 12) 2 (21 to 7)
1%–49% decrease 23 (66) 28% (5% to 48%) 5 (1 to 10) 1 (23 to 10) 3 (22 to 13)
No change 1 (3) 0% 0 21 5
Increase 3 (9) 32% (22% to 47%) 24 (22 to 27) 3 (21 to 14) 0 (21 to 3)

MGE, meibomian gland evaluation; SPEED2, Standard Patient Evaluation of Eye Dryness 2.

patients noted a marked decrease in dry eye symptoms. This response to IPL/MGX therapy. An improvement in MGE in
result guides counseling of our patients regarding IPL/MGX. at least 1 eye was seen in 77% of patients.
If no response is perceived after the third IPL/MGX Although MGE is known to correlate with dry eye
treatment, further IPL/MGX is unlikely to be therapeutic. symptoms,20 subjective improvement (SPEED2) did not always
Clinically, the MGE significantly improved in the left correlate with physical improvement in MGE in our study. We
eye, but the right eye did not achieve statistical significance suspect that there is an alternate path of reduction of symptoms
with IPL/MGX serial treatment (OD P = 0.163 and OS P = through lessening of inflammation that cannot be explained in
0.0002, paired t test). Fourteen patients (40%) had improved our study. The mechanism of action of IPL/ MGX on dry eye
MGE bilaterally. Twenty-seven (77%) patients had improved symptoms is not known at this time. It is postulated that the
MGE in 1 or both eyes. Eight patients (23%) had either a oxyhemoglobin of superficial skin blood vessels absorbs the
decrease in MGE bilaterally or a decrease in 1 eye with no yellow wavelength of IPL and converts light energy to heat
change in the other eye. The Pearson correlation coefficient energy that thromboses the vessels, decreasing superficial blood
between the change in SPEED2 and change in MGE was flow, which decreases inflam-mation to the lid margin.13–16 We
inversely related but not statistically significant (OD 0.039, P know that the heat of the lamp itself does not liquefy the
= 0.825 and OS 0.057, P = 0.745). Patients who responded meibum, because heat is not applied to the glands directly and
adversely with either an increase in SPEED2 or a decrease in the temperature of the skin only increases by 1°C. 19 Our
MGE did not develop skin or ocular abnormalities on slit- experience does support treating ocular rosacea with IPL/MGX
lamp examination. to improve dry eye symptoms.
Our cohort had a severe level of disease overall, It is possible that patients experienced improvement in
reflecting possibly more decades of MGD combined with symptoms because of the effect of MGX or other confound-
arid desert climate. Forty-three percent (15/35) of patients ing variables, and not from IPL. However, in support of
scored $20 in their pretreatment SPEED2 (Table 1). One efficacy of IPL alone, Craig et al 19 found a benefit of IPL
hundred percent of these severely affected subjects experi- treatment without MGX in a prospective, double-masked,
enced improvement in the SPEED2 score (ranging from 5% placebo-controlled, paired-eye study in a younger patient
to 65%), which is a greater percentage of improvement than population (mean age 45 years) of 28 subjects. Subjects had
that of the total study population. Improvement in MGE in 1 an improved lipid layer grade (P , 0.001), noninvasive tear
or both eyes was present in 80% (12/15) of these patients, film breakup time (P , 0.001), and visual analog scale
which is also a higher percentage than that of the total study symptom scores (P = 0.015) in the study eye but had no
population. changes in the tear meniscus height or tear evaporation rate.
Interestingly, 22 patients (63%) in the study had Craig et al found improvement in symptoms after IPL
previously undergone thermal pulsation treatment 22 (Lipi-Flow; therapy, as was observed in our study.
TearScience, Inc, Morrisville, NC) without improve-ment of In our study, IPL/MGX did not show any improvement in
symptoms after 3 months. Subanalysis shows that the majority a few patients with dry eye. One nonresponder had challenging
of these prior thermal pulsation–treated patients had conditions including incomplete blink or lagoph-thalmos
improvement in SPEED2 in response to IPL (86%, 19/22). In possibly related to a cosmetic face-lift procedure, which could
this group of patients with improved SPEED2 scores, 21% (4/ not be expected to resolve with IPL/MGX. Additional factors
19) had a $50% decrease in their SPEED2 scores. that may have caused the complex nature of dry eye disease
among these nonresponders were bleph-aroplasty, laser in situ
keratomileusis, contact lens wear, benzodiazepine use, tricyclic
DISCUSSION antidepressant use, and diuretic use. Meibography was not
Evaporative dry eye is the most common cause of dry available at our center at the time of patient evaluation, which
eye. Quality-of-life is significantly adversely affected by dry would have otherwise allowed for detection of end-stage gland
eye disease.8,9 The typical referral dry eye clinic treats atrophy. We would hypoth-esize that, like in the case of
patients who have had the disease for many years and have periodontal disease, there may be some patients whose long-
failed multiple modalities of dry eye treatment. In our standing MGD with end-stage disease and atrophy cannot be
experience, SPEED2 scores improved in 89% of patients in significantly reversed with

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Vegunta et al Cornea Volume 35, Number 3, March 2016

IPL/MGX. Possibly, there is a therapeutic window of Definition and Classification Subcommittee. Invest Ophthalmol Vis Sci.
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IPL/MGX to these patients earlier in the disease process may 5. Nichols KK, Foulks GN, Bron AJ, et al. The international workshop on
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who do not show improvement with automated thermal Eye Res. 1993; 12:247–254.
pulsation. Sixty-three percent of our study patients had 8. Buchholz P, Steeds CS, Stern LS, et al. Utility assessment to measure
previously tried thermal pulsation without improvement of the impact of dry eye disease. Ocul Surf. 2006;4:155–161.
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treatment are counseled that the pain associated with MGX patients with dry eye disease. Ophthalmology. 2003;110:1412–1419.
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Ophthalmol. 1921;4:489–494.
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