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 [12
]. 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 [10
]. 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 [14
]. 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 [3
]. 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 [26
]. 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
]. 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.