Combination of Intense Pulse Light and Meibomian Gland Probing (IPL MGP together) & the Risk of Meibomian Gland Probing: Does Meibomian Gland Probing increase scar tissue?

Since my original post, I have been having more and more success by using a combined approach of Intense Pulse Light and Meibomian Gland Probing (IPL MGP together) as discussed in the below paper. **
I have found the following over the last few months:
1. If we do IPL and little meibum/oil is coming out, there is likely scar tissue in the meibomian glands and probing may likely help break open the scar tissue and stimulate the gland to produce more oil.
2. After Meibomian Gland Probing, it is important to keep stimulating the gland to produce oil with warm compresses (if the patient and patient’s skin can tolerate this), blinking, minimal screen time, and frequently IPLs as described in the paper: after 2-3 weeks start IPLs for 3 sessions. Then depending on symptoms scores and meibographies, we repeat IPL with expression every 2-10weeks.  
3. We have treated some patients with probing first followed by IPL as noted below but have also done IPL first with probing as needed. I have also treated patients with IPL first followed by probing and expression: this seems to produce the most amount of expressible oil but we are still studying this and its long term results. 
3. This is a chronic condition and there is still no cure, so we have to keep blinking and doing everything we can to keep the oil pumping.
4. We have followed now 30 patients with compbined IPL and MGP approach and have seen no complications. We have not seen a stye after these procedures yet as well. Symptoms scores and meibography scores in some patients have improved, but we are evaluating Image J scores on these scans to see if there is a significant difference after the procedure. Still we need a randomized controlled study to prove its effects and to see which protocol is the best: the one below or IPL first followed by probing or doing them at the same time: IPL first then probing with expression or probing first, then IPL and expression. All these treatments remain non-FDA approved and experimental. 
In summary of the paper: 
Patients in group I received an IPL treatment course (treated with IPL 3 times at 3-week intervals). 

Patients in group II received an MGP treatment course (treated with MGP one time). 

In group III, 3 weeks after initial MGP treatment, patients also received IPL 3 times at 3-week intervals

Results below: Group 3 did the best in symptoms scores. 
I have found that doing IPL every 1-2 weeks, if the skin response to IPL will allow this frequency, yields the best results in helping get the meibomian glands to produce better quality oil. 


Original Post:
Meibomian Gland Probing is still a controversial procedure where some surgeons are concerned it does not help and actually increases meibomian gland scar tissue. There is 1 randomized, controlled, prospective study of 90 patients performed in China below that shows IPL plus MGP worked better than either alone. There are issues with the study below (ie, small number of patients, 6 month follow up is short, while authors report no competing interests, does China still pay researchers to publish?).

Still, the below result is what I have been seeing in my patients as a reluctant, skeptical surgeon who has been shocked by the numbers of young people who are coming in with dry eye symptoms and meibomian gland atrophy on meibography.

The facts are that aging and screen time appears to worsen meibomian gland scar tissue and atrophy. Doing nothing (like warm compresses, blinking, etc) seems to allow atrophy and scarring to progress. Thermopulsation like Lipiflow, Intense Pulse Light, and Meibomain gland probing seem to delay the progression of atrophy and in some patients help these priceless oil glands to “grow back”/fill up with oil again. I have seen this time and again so a larger randomized controlled study performed in the US is needed with an experienced,  meibomian gland probing surgeon, who does not have a financial interest in these procedures.

No studies I could find showed scarring from meibomian gland probing. No studies I could find showed glands worsened after IPL. There are 2 reports I know of severe uveitis after IPL in a patients who were treated without a metal shield over their eyeballs. I have not seen any styes or chalazia after IPL or probing yet, but it has been reported. I have seen 2 patients develop a stye after Lipiflow (likely because the oil is coming out more but the orifice gets clogged with debris, Demodex, dead cells, makeup, etc) but they were able to resolve it with warm compresses and gentle expression.

I have not seen anyone develop an eye infection after any of these procedures.
I have seen many patient who live a life of miser with dry eye disease and are frustrated FDA approved drops such as Xiidra, Restasis, Cequa do not help or make them feel worse.

I think Meibomian Gland probing, Intense Pulse Light, Lipiflow, iLux (though I felt Lipiflow was much less painful than iLux when I had both done at separate times) is safe and effective with little risk.

References:

1. https://bmcophthalmol.biomedcentral.com/articles/10.1186/s12886-019-1219-6

2. https://bjo.bmj.com/content/102/1/59

3. https://journals.lww.com/corneajrnl/Fulltext/2019/07000/Expressible_Meibomian_Glands_Have_Occult_Fixed.16.aspx

**

Full article and more references:
1. https://bmcophthalmol.biomedcentral.com/articles/10.1186/s12886-019-1219-6

Clinical results of Intraductal Meibomian gland probing combined with intense pulsed light in treating patients with refractory obstructive Meibomian gland dysfunction: a randomized controlled trial

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Abstract

Background

This study aims to optimize the therapeutic regimen for refractory obstructive meibomian gland dysfunction (o-MGD) patients by combining intraductal meibomian gland probing (MGP) and intense pulsed light (IPL) to enhance their positive effects and reduce their limitations.

Methods

This randomized, assessor blind study includes 45 patients (90 eyes) with refractory o-MGD who were divided into 3 groups via allocation concealment: IPL (group I, received an IPL treatment course: 3 times at 3-week intervals), MGP (group II, received MGP one time), and combined MGP-IPL (group III, MGP first followed by an IPL treatment course). Standard Patient Evaluation of Eye Dryness score (SPEED), tear break-up time (TBUT), corneal fluorescein staining (CFS), meibum grade, and lid margin finding results were assessed at baseline, 3 weeks after final treatment for groups I and III, 3 and 12 weeks after MGP for group II. Six months after final treatment, the SPEED and willingness to receive any treatment again were also collected for all groups. Paired Wilcoxon, Mann-Whitney U with Bonferroni correction, and Kruskal-Wallis tests were used for data analysis.

Results

For all 3 groups, all previously mentioned indexes improved significantly following treatment (P<0.01). MGP-IPL was better than IPL and MGP in terms of post-treatment SPEED, TBUT, meibum grade, and lid telangiectasia (P<0.05/3). Furthermore, the MGP-IPL was better than IPL in terms of lid tenderness and better than MGP in terms of orifice abnormality (P< 0.05/3). Six months later, the SPEED for the MGP-IPL was also significantly lower than other groups (P<0.05/3). Moreover, no patients in the MGP-IPL group expressed the need to be treated again compared to 35.7% or 20% of patients in the IPL or MGP groups, respectively.

Conclusions

Compared with IPL or MGP alone, the combination MGP-IPL produced best results in relieving all signs and symptoms and helping patients attain long-lasting symptom relief.

Clinical results of Intraductal Meibomian gland probing combined with intense pulsed light in treating patients with refractory obstructive Meibomian gland dysfunction: a randomized controlled trial

Abstract

Background

This study aims to optimize the therapeutic regimen for refractory obstructive meibomian gland dysfunction (o-MGD) patients by combining intraductal meibomian gland probing (MGP) and intense pulsed light (IPL) to enhance their positive effects and reduce their limitations.

Methods

This randomized, assessor blind study includes 45 patients (90 eyes) with refractory o-MGD who were divided into 3 groups via allocation concealment: IPL (group I, received an IPL treatment course: 3 times at 3-week intervals), MGP (group II, received MGP one time), and combined MGP-IPL (group III, MGP first followed by an IPL treatment course). Standard Patient Evaluation of Eye Dryness score (SPEED), tear break-up time (TBUT), corneal fluorescein staining (CFS), meibum grade, and lid margin finding results were assessed at baseline, 3 weeks after final treatment for groups I and III, 3 and 12 weeks after MGP for group II. Six months after final treatment, the SPEED and willingness to receive any treatment again were also collected for all groups. Paired Wilcoxon, Mann-Whitney U with Bonferroni correction, and Kruskal-Wallis tests were used for data analysis.

Results

For all 3 groups, all previously mentioned indexes improved significantly following treatment (P<0.01). MGP-IPL was better than IPL and MGP in terms of post-treatment SPEED, TBUT, meibum grade, and lid telangiectasia (P<0.05/3). Furthermore, the MGP-IPL was better than IPL in terms of lid tenderness and better than MGP in terms of orifice abnormality (P< 0.05/3). Six months later, the SPEED for the MGP-IPL was also significantly lower than other groups (P<0.05/3). Moreover, no patients in the MGP-IPL group expressed the need to be treated again compared to 35.7% or 20% of patients in the IPL or MGP groups, respectively.

Conclusions

Compared with IPL or MGP alone, the combination MGP-IPL produced best results in relieving all signs and symptoms and helping patients attain long-lasting symptom relief.

Trial registration

http://clinicaltrials.govChiCTR1900021273 (retrospectively registered February 9, 2019).
Peer Review reports

Background

Dry eye has always being considered as a significant health concern that threatens individuals’ life quality as well as their personal and economic well-being [12]. Among various types of dry eye diseases, obstructive meibomian gland dysfunction (o-MGD) causing evaporative dry eye has attracted the attention of clinicians and scientists for its chronic course, recurrent potential, and high incidence rate [34]. Moreover, the obstruction of the terminal tract of the meibomian gland (MG) leads to hyposecretion and quality change of meibum from the orifices [5]. These changes of meibum in ocular surfaces can result in instability of the tear film as well as irritation symptoms such as dryness and foreign body sensation [3]. Additionally, unusually elevated intraglandular pressure and aggravated local inflammation caused by meibum stasis further exacerbate the disease course, creating a vicious cycle.
Traditional treatments for o-MGD include warm compress, massage, artificial tears, etc. However, studies have showed that these treatments are not sufficient for symptom relief [67]. And it is difficult for patients to comply with continuous medical therapies. Chinese o-MGD patients, in particular, always meet serious initial symptoms with MG orifices obstruction and no meibum secretion, making the treatment processes even more difficult [89]. In recent years, great strides have been made in terms of new treatment options for refractory o-MGD patients, one of which is intense pulsed light (IPL). IPL, which has long been used in medical cosmetology, can also be effective for dry eye treatment mainly due to its inhibition of telangiectasias along the eyelid that block the way of inflammatory cytokine and its heating effects [1011]. Another relatively new method is intraductal meibomian gland probing (MGP), which was first described by Maskin in 2010. MGP uses a special meibomian cannula to probe the plugged meibomian gland, releasing abnormal elevated intraductal pressure and reestablishing a healthy microenvironment favoring the growth of MG tissues [12].
Although the safety and effectiveness of IPL and MGP have been proven in previous studies [810111314], their deficiencies can also be observed through day-to-day clinical observation. Specifically, the effect of IPL in alleviating stubborn intraductal congestion or intraductal scarring is comparatively limited. And for patients with severe intraductal inflammation or apparent blepharitis, the use of MGP alone is insufficient for decreasing excessive inflammation. Besides, probing is an invasive method for patients. Sik Sarman et al. reported that 20% of patients require repeated probing after an average of 4.6 months [13]. Repeated Probing may bring psychological burden to patients and would possibly cause scar proliferation. It is thus an urgent matter to identify an optimal therapeutic regimen that can reduce the number of invasive treatments, open the MG obstruction, promote the discharge of meibum, and at the same time, control inflammation.
Here, a new treatment method that combined the MGP and IPL courses was devised and then compared with MGP, IPL alone, with the aim of identifying a way in which to strengthen the advantages of MGP and IPL, and at the same time, offset their side-effects. All participating patients had serious refractory o-MGD and more than half of their evaluated meibomian gland orifices obstructed with no lipid secretion. Additionally, their Meibo-Scans showed no extensively atrophied areas.

Methods

This randomized controlled, assessor blind study was conducted between July 1, 2018 and December 30, 2018.

Patient selection and study design

45 patients clinically diagnosed with refractory o-MGD enrolled in this study. The inclusion criteria included: (1) older than 18 years, (2) Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire≥6, (3) more than half of the 15 evaluated meibomian gland orifices in each eyelid were obstructed and had no lipid secretion with extrusion, (4) meibum grade ≤ 24, (5) breakup time of tear film (TBUT) ≤ 5 s, (6) Schirmer test>5 s, (7) Meibo-Scan (OCULUS) revealed less than 1/3 atrophy area of the meibomian gland in both the upper and lower eyelids, (8) refractory was defined as lack of symptom relief with conservative treatment (eyelid warming, massage, and artificial tears) for at least 1 year prior to study treatment. All patients were informed of possible treatment-related complications and the possibility of being assigned to an invasive treatment group. All agreed to receive the possible therapeutic regimen and signed an informed consent form. Patients with a history of corneal contact lens, mite blepharitis, acute eye inflammation, or infection and apparent eyelid margin scarring as well as patients using a lacrimal plug or receiving LASIK (Laser Assisted In-situ Keratomi) were excluded from the study.
The multiple rate comparison method performed with PASS version 15 was used to estimate sample size. The pilot study, which involved 5 patients per group, showed that 20, 20, and 80% of patients in IPL, MGP and MGP-IPL groups experienced effective symptom improvement following treatment (with a decrease in SPEED score before treatment and half a year after final treatment>5). Power calculations with a type I error of 0.05 and type II error of 0.9 were executed. The results showed a sample size of 38 achieves 90% power in detecting an effect size (W) of 0.5774 using a 2 degrees of freedom Chi-Square Test with a significance level (alpha) of 0.05. So, each group needed at least 13 patients.
Participants were randomly divided into 3 groups (15 patients per group) via block randomization, and allocation concealment was implemented using a closed envelop method. Patients in group I received an IPL treatment course (treated with IPL 3 times at 3-week intervals). Patients in group II received an MGP treatment course (treated with MGP one time). In group III, 3 weeks after initial MGP treatment, patients also received IPL 3 times at 3-week intervals. The clinical effects were assessed at baseline, 3 and 12 weeks following MGP treatment for group II and 3 weeks after final treatment for groups I and III. Furthermore, 6 months following final treatment for all 3 groups, all patients completed SPEED and answered a question in terms of requiring to receive any treatment once more. Patient enrollment, random allocation sequence generation, and intervention assignment were performed by the first author (HXD).

Treatment procedure

Intraductal meibomian canal probing

With the help of SuZhou LiuLiu Medical Equipment co. LTD, we designed a private probe based on the original Maskin probe and a rinse hollow tube (Fig. 1). The probe was 4.5 mm in length with a blunt end 0.12 mm in diameter. The hollow tube was 2.0 mm in length and 0.16 mm in diameter. The process of intraductal MGP proceeded as follows: (1) to ease the pain of probing, 4% lidocaine was injected into the upper and lower eyelids parallel to the palpebral margin, resulting in a local bulgy of the skin. (2) the eyelids were flipped outward with a cotton swab and an operating microscope was positioned over the target eyelid to more clearly show the orifices. Then, the operator inserted the probe into the glands vertically to the orifices. Impact force was required when resistance from the orifices or intraductal was encountered. After probing, chalazion forceps were used to squeeze out remnant meibum. Self-limited hemorrhage was the most common complication, for which a blood point and blood trickle could be observed and no particular treatment was needed. (3) then, a hollow tube was used to swash the meibomian gland by injecting 0.1% Dexamethasone (Guangzhou Baiyun Mountain Pharmaceutical co. LTD, China) and 0.25% Amikacin (Qilu Pharmaceutical co. LTD, China) repeatedly (Fig. 1). (4) eventually, Tobradex eye ointment (Alcon, Belgium) was applied to the conjunctival sac. All MGP procedures were performed by the first author (HXD).
Fig. 1
figure1
The treatment procedure and structure of our private probe and rinse hollow tube. a the operator inserted the probe into the glands vertically to the orifices. b After probing, chalazion forceps were used to squeeze out remnant meibum. c Then, a hollow tube was used to swash the meibomian gland by injecting

Intense pulsed light

A M22 Multi-pulse therapeutic apparatus was used for treatment. Prior to treatment, 1–2 mm thick ultrasound gel was applied to participants’ faces, covering the area from tragus to tragus beneath the eyelid margin, temple, and forehead. Then, the Pre-set Toyos parameters were administered to 1 or 2 treatment area test points to test patient tolerance and comfort. The intensity of the IPL treatment was adjusted to 14 J/cm2-15 J/cm2, which was determined via Fitzpatrick Skin Type Grading. Placement of an IPL eye shield over the eyes was necessary to protect eyes from the stimulus of bright light. After this, one back-and-forth flash emitted by an IPL hand piece was placed on each skin area without pressure. Finally, chalazion forceps were used to squeeze MG tissues. Care should be taken to ensure that the treatment areas were identical for each participant and all procedures were conducted by the same doctor (LL).
All participants were required to use artificial tears (Hailu, German) four times a day during the entire follow-up period.

Clinical evaluation

The eye examiners (Jiao Zheng and Linping Wang) were blind in regard to the groups participants were assigned to.

SPEED, CFS and TBUT

A Standard Patient Evaluation of Eye Dryness (SPEED) validated questionnaire (0–28) was used to assess the symptoms, as previously described [15]. Corneal fluorescein staining (CFS) was evaluated by dividing the cornea into four equal quadrants, and the staining of each section was recorded on a 0–3 scale: 0 = no punctate staining; 1 = less than half staining; 2 = more than half staining; 3 = whole staining; and a composite score for each quadrant (0–12 score) [16]. Tear break-up time (TBUT) was evaluated 3 times and an average value was recorded [17].

Meibum grade

The lower and upper eyelids were divided into 3 parts– nasal, bitamporal, and middle– with a total of 15 glands in each eyelid. The characteristics of each glandular expressate were graded on a scale of 0 to 3: 0 = no secretion; 1 = inspissated-filamentary secretion; 2 = cloudy liquid secretion; and 3 = clear liquid secretion. The scores of each expressed orifice in the 3 different eyelid sections were added together to provide the final meibum grade scores (0–90 score) for the right and left eyes [18].

Lid margin finding results

Lid margin finding results we evaluated included the abnormality of meibomian gland orifices, lid tenderness and telangiectasia, and were noted on a 0–4 scale, with 0 being absent and 4 being the most severe [819].

Statistical analysis

Statistical significance was set at p < 0.05, and data analysis was performed using SPSS version 23. Continuous data was presented as means ± SD. A paired Wilcoxon test was employed to compare the parameters prior to and following treatment. Then, comparison was made between the different groups via non-parametric Mann-Whitney U tests with Bonferroni correction, Kruskal-Wallis tests.

Results

A total of 45 patients were at first enrolled in the study, with one patient in the IPL group ending the treatment course due to accidental pregnancy and one patient in the MGP-IPL group for home accidents. The ages of 43 enrolled patients (86 eyes) ranged from 24 to 56 years (mean age 37.56 ± 9.82), with a female to male ratio of 1.39. And there were no observed differences based on gender (P = 0.409) and age (P = 0.376) among the 3 groups.
During the follow-up period, several MGP-treated patients experienced subcutaneous ecchymosis of the eyelid skin caused by the injection of anesthetics, a symptom that can improve after the administration of a cold compress. And one patient in the IPL group suspended the treatment course due to occurred blepharokeratoconjunctivtis (BKC) after twice IPL treatments, with the final IPL not being performed until BKC was relieved via two-week administration of Tobradex.
The evaluation time for the MGP group was 3 and 12 weeks following MGP treatment, but no difference in all indexes was found to exist between 3 and 12 weeks after MGP treatment (SPEED: 11.87 ± 3.44 vs. 11.93 ± 3.26, P = 0.933; TBUT: 4.74 ± 1.28 vs. 4.81 ± 2.03, P = 0.539; CFS: 0.73 ± 1.34 vs. 0.80 ± 1.35, P = 0.801; meibum grade: 24.73 ± 10.66 vs. 26.57 ± 11.63, P = 0.534; lid telangiectasia: 1.73 ± 0.58 vs. 1.73 ± 0.64, P = 0.946; orifice abnormality: 2.00 ± 0.74 vs. 1.80 ± 0.85, P = 0.299; lid tenderness: 0.60 ± 0.67 vs. 0.57 ± 0.63, P = 0.901). In order to increase the comparability of the MGP and MGP-IPL groups (both assessed at 12 weeks after initial MGP treatment), the 12-week-data for the MGP-treated group II was selected as posttreatment data for analysis.
Prior to initial treatment, there were no observed differences among all parameters of the 3 groups (SPEED: P = 0.339; TBUT: P = 0.083; CFS: P = 0.517; meibum grade: P = 0.139; lid telangiectasia: P = 0.105; orifice abnormality: P = 0.180; lid tenderness: P = 0.175). After completion of the entire treatment course, all subjective symptoms and objective signs, including SPEED, TBUT, CFS, meibum grade, lid telangiectasia, orifice abnormality, and lid tenderness, were significantly improved for all groups (Table.1).
Table 1 Clinical parameters before and after treatment in refractory O-MGD patients
The improvement of ocular symptoms (SPEED) and TBUT was more apparent in the MGP-IPL group than the IPL and MGP groups (P = 0.003 or P = 0.012; Fig. 2). However, there were no observed differences in posttreatment CFS among 3 groups (group IPL vs. group MGP, P = 0.866; group IPL vs. group MGP-IPL, P = 0.084; group MGP vs. group MGP-IPL, P = 0.123; Fig. 2). Between group IPL and group MGP, no differences existed in SPEED, TBUT, CFS after treatment (SPEED: P = 0.339; TBUT: P = 0.083; CFS: P = 0.517; Fig. 2).
Fig. 2
figure2
Comparation of SPEED score, TBUT and CFS after treatment in 3 groups (IPL, MGP, MGP-IPL). Notes: all parameters prior treatment had no statistical differences among 3 groups. *P ≤ 0.05/3, **P<0.001; “AFTER” was determined as 3 weeks after final treatment for groups I and III and 12 weeks after final treatment for group II, the same below
As for lid margin related indexes, the posttreatment meibum grade and lid telangiectasia improved more for group MGP-IPL than group IPL or group MGP (P = 0.002 or P<0.001, respectively; Table.1, Fig. 3). Orifice abnormality after treatment was also significantly more improved for the MGP-IPL group than the MGP group (P = 0.016; Table.1, Fig. 3). In terms of lid tenderness, group MGP-IPL showed more significant improvement than group IPL (P<0.001; Table.1, Fig. 3). No differences in meibum grade, lid telangiectasia, and orifice abnormality were observed among group IPL and group MGP (meibum grade: P = 0.040; lid telangiectasia: P = 0.068; orifices abnormality: P = 0.315; Fig. 3) except for lid tenderness, in which better results were seen in group MGP (P<0.001; Table.1, Fig. 3).
Fig. 3
figure3
Comparation of meibum grade and lid margin finding results after treatment in 3 groups. Notes: all parameters prior treatment had no statistical differences among 3 groups. *P ≤ 0.05/3, **P<0.001
As shown in Fig. 4, no patient from any group displayed a SPEED score ≤ 9 before treatment; while following treatment, 14.29, 26.67, and 64.29% of patients in groups I, II, and III, respectively, obtained a score of 0–9 (P = 0.020, P was determined by the Fisher exact test). Moreover, it can be seen that all eyes in 3 groups showed a TBUT≤5 s before treatment, but 17.86, 36.67, and 92.9% of eyes in group I, II, and III, respectively, showed a TBUT more than 5 s after treatment (P = 0.009, χ2 = 7.335, P was determined by χ2 test; Fig. 5).
Fig. 4
figure4
Change in the SPEED questionnaire score between baseline and after treatment in three groups
Fig. 5
figure5
Change in TBUT between baseline and after treatment in three groups
Six months after final treatment, the SPEED was still significantly lower in patients receiving MGP-IPL than MGP or IPL alone (11.36 ± 2.10 vs. 14.50 ± 3.76 vs. 14.60 ± 3.11, P = 0.01 or P = 0.004). Additionally, 35.7% or 20% of patients treated with IPL or MGP alone reported requiring treatment again to rectify recurrent dry eye related symptoms; meanwhile, of the patients who received the combined MGP-IPL course, zero reported a need to be treated again.

Discussion

Previous research has proven that both intraductal meibomian gland probing and intense pulsed light are significantly efficient in helping o-MGD patients achieve relief of symptoms and signs; yet, they also showed that this improvement was only experienced by the majority and symptom recurrence could emerge during the follow-up period [13]. Until now, no research has offered in-depth discussion for these exceptions. It seems researchers all focused on the pleasantly impressive results of these new treatments, but seldom noticed their inadequacies. Although MGP can re-open MG orifices, it is limited in terms of controlling inflammation. Moreover, it is an invasive treatment, so the repeated use of MGP should be restricted. IPL treatment is minimally invasive and can promote the discharge of eyelid lipids, reducing the inflammation of the eyelid margin. However, the effect of IPL on MG-obstruction and scarring is limited. Therefore, a new treatment combination that could fully realize the best therapeutic effects of two treatments and reduce the complications of invasive probing is essential.
Reiko Arita et al. recently observed that 81% of IPL-treated refractory o-MGD eyes showed amelioration of ocular symptoms, and 70% showed an improvement in TBUT [20]. Zeba A et al. reported that 91.4% of their patients received MGP described subjective symptomatic improvement during follow-up [21]. Similar results were also obtained in the present study, with 85.7 and 100% of treated eyes in the IPL and MGP groups revealing relief of symptoms, and 96.4 and 93.3% exhibiting increase in TBUT, respectively. However, in the MGP-IPL group, all patients (100%) showed alleviation of dry eye related symptoms as well as the extension of TBUT.
As the meibomian gland of an o-MGD patient is usually ill-conditioned, in which abnormal meibum stasis accumulates rather than flows to the ocular surface, increased intraglandular pressure and duct expansion are inevitable [14]. Furthermore, with the recurrent attacks of o-MGD, atrophy of meibomian glands is frequently observed [22]. It was long considered that this atrophy was irreversible until Maskin proposed intraductal meibomian gland probing and proved this treatment can increase MG tissue area and growth of atrophied MGs [1222]. Maskin showed that they used transillumination to ensure the gland was longer than the length of the probe before probing. Their most common length of probe was 4 mm. And they showed their probes can probe to the most distal aspects of the duct [12]. Our private probe was 4.5 mm in length, and before probing, we used infrared meibography (IR-M) to know the length of glands, so we believe that our MGP treatment is also enable to affect far distal part of meibomian gland to reopen the blocked sites effectively. Meibomian gland probing mechanically opened the obstructed orifices and ducts. With the pop up of constrained meibum, keratinized epithelium, and debris, the vicious cycle of o-MGD progression was broken, and the majority of patients received immediate symptom relief [1021]. However, the quantity of meibum on the ocular surface is not a decisive factor in the retardation of the evaporation of aqueous and the stabilization of the tear film. The meibum lipid quality was found to play an even more important role in maintaining ocular surface equilibrium [1423]. Nakayama et al. showed all cases exhibited improvements in meibum viscosity (grades 3–0, 3–1, and 3–2) after MGP treatment, as the abnormal meibum was rapidly released with the sudden orifice opening and then gradually eliminated through blinking [14]. However, there was only one case returning to normal level. Furthermore, a growing amount of evidence has suggested the inflammation reaction played an essential role in the formation of abnormal meibum. The enzymes produced by bacterial flora could result in altered lipid composition with an increased melting point and viscosity [324]. Thus, it was assumed that the single mechanical function of MGP in improving meibum lipid quality is limited. Xiao Ma et al. recommended the use of 0.1% fluorometholone after MGP treatment to diminish inflammation, since MGP predisposes the lid margin to a topical corticosteroid effect [10]. However, it is believed that although MGP increased the responsiveness of the gland to anti-inflammatory drugs, the traditional application of eyedrops or eye ointment following MGP can hardly deliver drugs to the deepest gland lumens. Since the inflammation of o-MGD has been proven to not only exist in the eyelid margin and ocular surface but also within the glands [25], the unthorough evacuation of inflammation after MGP treatment may be essential for the re-obstruction, possibly explaining why not all patients experienced improvement after MGP treatment and why a considerable number of patients needed to receive repeated probing.
The surprising efficacy of IPL in easing the symptoms of MGD patients can be mainly attributed to its effect of vasculature destruction and meibum melting [2627]. Lid telangiectasia is a common characteristic of o-MGD, and these tiny vessels along the eyelid margin also increase the accessibility of inflammatory mediators, resulting in aggravated chronic inflammation above the palpebral edge or within the glands [28,29,30]. The 580 nm wavelength released by intense pulsed light can be absorbed by intravascular hemoglobin and then activate selective photothermolysis, leading to the development of blood clotting. Thus, abnormal vessels gradually shut down and bacterial loading reduces [26]. Apart from that, the heat from either photothermolysis or light energy itself can enhance the liquidity of meibum. And compared to traditional eyelid warming, the heat effect delivered by intense pulsed light is far more lasting and permeable [31]. Surprisingly, instead of showing reduction in symptoms, 2 patients (14.8%) in the present study reported even more serious symptoms at the end of the IPL treatment course. It can be speculated that this deterioration may relate to obstruction sites within the glands. Maskin has proposed six types of o-MGD according to the depths of fixed obstruction and the function of MG [22]. In a meibomian gland with a deep-seated intratubal obstruction or partial distal obstruction, IPL may work well as the vast melting meibum ahead the fixed area can easily move out under the extrusion force caused by forceps or daily blinking. While for the gland that was completely fixed in the distal part, it’s actually the opposite, as the stagnant meibum was confined between the terminal of glands and the obstruction site, analogous to staying in a blind alley. The heat released by IPL and the pressure caused by the forceps might paradoxically increase the intraductal pressure and exacerbate the inflammatory response; thus, treatment with IPL alone may not alleviate disease symptoms but instead irritate the condition. This effect can also be indirectly observed in the present data in terms of the posttreatment lid tenderness of the IPL group, despite showing symptom alleviation compared with baseline, still being significantly higher than the MGP and MGP-IPL groups.
It appears that neither IPL nor MGP is the absolute perfect method for treating all refractory o-MGD patients; however, their unique advantages can effectively make up for their inherent deficiencies. This assumption was also confirmed by the present research, as patients receiving MGP-IPL treatment exhibited the best improvement results. With the initial opening of blocked glands via probing, meibum within the glands can flow without restriction. Additionally, the followed 3 times IPL treatments further restrict inflammation and eliminate the abnormal meibum, resulting in an optimal therapeutic effect. Compared with single IPL or MGP treatment, MGP combined IPL proved to be significantly superior in improving SPEED, TBUT, meibum grade, and lid telangiectasia.
One time MGP did not provide all patients continued symptom relief in the present 6-month observation. Specifically, 20% of patients still required repeated invasive probing, yet such treatment would increase patients’ sense of misery. In contrast, the combination of MGP with noninvasive IPL in the present study helped 100% of patients attain enduring symptom relief. This combination treatment may achieve the maximum therapeutic effect of MGP and IPL, reducing the possibility of trauma and scarring caused by repeated probing.
Despite positive outcomes, there are still certain limitations of the present research: First, the participants in the study were comparatively small and the follow-up duration was rather short. Further investigation is thus suggested to evaluate the long-term results of these treatments with a larger number of cases. Second, MGP is an invasive method that is more suitable for patients with severe gland obstruction or gland scarring, while IPL treatment is better for relieving intraductal inflammation. This study found the combination of these two treatments could attain the best results, but it cannot be denied that this treatment mode would bring patients more financial, time and psychological burdens at the same time. Based on these results, it is recommended that patients have at least half of their orifices obstructed in each eyelid but with no apparent meibomian gland atrophy, and at the same time, have higher inflammatory index like lid telangiectasia scores receive combined MGP-IPL therapy to exert the best curative effect of probing and anti-inflammation simultaneously.

Conclusions

IPL, MGP, and combined MGP-IPL are all effective methods for refractory o-MGD patients; however, the combination MGP-IPL method could maximize the therapeutic benefits, which is especially helpful for patients who have severe meibomian gland obstruction and obvious intraductal or eyelid margin inflammation, who want to gain the greatest amelioration in all clinical signs and subjective symptoms or still remain frustrated to either MGP or IPL treatment.

Availability of data and materials

The datasets obtained and/or analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

BKC:
Blepharon- keratoconjunctivtis
CFS:
Corneal fluorescein staining
IPL:
Intense pulsed light
IR-M:
infrared meibography
LASIK:
Laser Assisted In-situ Keratomi
MG:
Meibomian gland
MGP:
Intraductal meibomian gland probing
o-MGD:
Obstructive meibomian gland dysfunction
SPEED:
Standard Patient Evaluation of Eye Dryness score
TBUT:
Tear break-up time

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Acknowledgements

Not applicable.

Additional statement

Our randomized controlled trial study adheres to the CONSORT guidelines.

Funding

Design of the study and collection of data were supported by National Natural Science Foundation of China [grant numbers: 81870624]; Analysis and interpretation of data in this study were financed by another National Natural Science Foundation of China [grant numbers: 81700802]; Manuscript writing was funded by Major Science and Technology Projects of Zhejiang Province [grant numbers: 2017C03046].

Author information

Affiliations

Contributions

XH: research design, manuscript preparation, and treatment operation; QQ: data analysis and manuscript preparation; LW: data acquisition; JZ: data acquisition; LL: treatment operation; XJ: research design, manuscript preparation. All authors read and approved the final version of this manuscript.

Corresponding author

Correspondence to Xiuming Jin.

Ethics declarations

Ethics approval and consent to participate

This study was approved by the Ethics Committee at the Affiliated Second Hospital, School of Medicine, Zhejiang University in Hangzhou, China. All the procedures adhered to the tenets of the Declaration of Helsinki. Written informed consent was obtained from each participant.

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Not applicable.

Competing interests

The authors declare that they have no competing interests.

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2.

https://clinicaltrials.gov/ct2/show/NCT02256969

3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6630046/pdf/opth-13-1203.pdf.


4. 

Intraductal Meibomian Gland Probing in Patients With Obstructive Meibomian Gland Dysfunction

Cornea

PURPOSE

To assess the efficacy and safety of intraductal meibomian gland probing in patients with obstructive meibomian gland dysfunction who experienced little improvement with eyelid warming, massage, or artificial tears.

METHODS

Forty-nine patients with obstructive meibomian gland dysfunction were randomly divided into 2 groups: intraductal meibomian gland probing with 0.1% fluorometholone (group I), and 0.1% fluorometholone alone (group II). Subjective symptom scores and objective signs, including lid margin abnormalities, meibum quality and expressibility, meibomian gland dropout, fluorescein staining, tear break-up time (TBUT), and Schirmer I test results, were recorded before treatment and after 1 day, 1 week, and 1 month posttreatment.

RESULTS

Clinical subjective symptoms and objective signs including meibum grade, TBUT, lid margin abnormalities, and fluorescein staining demonstrated significant improvements in both groups after treatment over time (all P < 0.05), and group I was better than group II 1 month after treatment in meibum grade (6.1 ± 3.3 vs. 10.4 ± 4.9, respectively; P < 0.001), lid margin abnormalities (0.8 ± 0.1 vs. 1.3 ± 0.3, respectively; P < 0.001), and TBUT (8.2 ± 2.1 vs. 7.0 ± 3.0, respectively; P = 0.0293). Before applying any medications, 76% of patients obtained immediate symptom relief 1 day after probing. However, the Schirmer I test results and meibomian gland dropout were insignificant pre- and posttreatment in either group (P > 0.1, respectively).

CONCLUSIONS

Intraductal meibomian gland probing demonstrated significant efficacy in symptom relief and tear film stabilization. Probing helped release accumulated meibum and could help increase the accessibility of diseased meibomian glands to topical corticosteroids.
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