Previous researches have proved that both intraductal meibomian gland probing and intense pulsed light had significant efficacy in helping o-MGD patients achieve relief of symptoms and signs; yet, they also showed this improvement was just for the vast majority and recurrence may appear during the follow up period12. Up to 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 the MG orifices, it is limited in controlling inflammation. And it is an invasive treatment, so the repeated MGP should be restricted for patients. 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 the MG obstruction and scar is limited. So, we need a fire new treatment combination that could give full play to the best therapeutic effect of the two treatments, and reduce the complications and times of invasive probing.
Reiko Arita et al recently observed 81% of IPL treated refractory o-MGD eyes showed amelioration of ocular symptoms and 70% showed an improvement in TBUT15. Zeba A et al reported that 91.4% of their patients received MGP described subjective symptomatic improvement during follow up16. Similar results were also obtained in our study, with 85.7% and 100% of treated eyes in IPL and MGP group revealing relief of symptoms and 96.4% and 93.3% showing increase in TBUT respectively. However, in MGP-IPL group, all patients (100%) showed alleviation of dry eye related symptoms and extension of TBUT.
As the meibomian gland of 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 is evitable13. And with recurrent attacks of o-MGD, atrophy of meibomian glands can be usually noticed17. It has long been 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 MGs10,17. Meibomian gland probing opened the obstructed orifices and ducts mechanically. With the pop up of constrained meibum, keratinized epithelium and debris, vicious cycle of o-MGD progression was broken and the majority of patients received immediate relief of symptoms11,16. However, the quantity of meibum in ocular surface is not a decisive factor in retarding the evaporation of aqueous and stabilizing the tear film. The meibum lipid quality was found to play an even more important role in maintaining the ocular surface equilibrium13,18. Nakayama et al showed all cases had improvements in meibum viscosity (grade 3–0, 3–1, and 3–2) after MGP, as the abnormal meibum was released promptly with the sudden open of orifices and then gradually eliminated by blinking13. But there was just only one case returning to normal level. And growing 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 increased melting point and viscosity3,19. We assumed that the single mechanical function of MGP to improve the meibum lipid quality is limited. Xiao Ma et al recommended the use of 0.1% fluorometholone after MGP to diminish inflammation, as MGP predispose the lid margin to a topical corticosteroid effect11. But we think, although MGP increased the accessibility of gland to anti-inflammatory drugs, traditional application of eyedrops or eye ointment after MGP can hardly deliver drugs to the deepest gland lumens. Since the inflammation of o-MGD has been proved to exist not only in eyelid margin and ocular surface but also within the glands20, the unthorough evacuation of inflammation after MGP may be an essential reason for the re-obstruction and may also explain that why not all the patients attained the improvement after MGP and why a considerable number of patients need to receive repeated probing.
In 2002, Dr. Rolando Toyos noticed one of his patients with rosacea had obvious improvement of dry eye related symptoms after IPL therapy21. From then on, IPL has drawn more and more attention of ophthalmologists and has been proved to be effective and safe to treat patients with moderate or severe MGD. The surprising efficacy of IPL to ease symptoms of MGD patients can be mainly attributed to its effect of vasculature destruction and meibum melting21,22. Lid telangiectasia is a common characteristic of o-MGD and these tiny vessels along the eyelid margin also increase the access of inflammatory mediators, resulting in aggravated chronic inflammation above the palpebral edge or within the glands23–25. 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. And thus abnormal vessels gradually shut down and bacterial loading reduces21. Apart from that, the heat from either photothermolysis or light energy itself can enhance the liquidity of meibum. And compared with the traditional eyelid warming, the heat effect delivered by intense pulsed light is far more lasting and permeable26. Surprisingly, instead of showing reduction in symptoms, 2 patients (14.8%) in our study had even more serious symptoms at the end of single IPL treatment course. We speculate that this deterioration may relate to obstruction sites within the glands. Maskin has proposed 6 types of o-MGD according to the depths of fixed obstruction and function of MG17. In 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 gland that was completely fixed in 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 pressure caused by forceps may paradoxically increase the intraductal pressure and exacerbate the inflammatory response, thus IPL alone may not alleviate disease but irritate the condition. This effect can also be indirectly seen from our data that posttreatment lid tenderness of IPL, albeit showed alleviation compared with baseline, was still significantly higher than MGP and MGP-IPL group.
It seems like neither IPL nor MGP is absolutely perfect method to treat all refractory o-MGD patients, while their unique advantages can effectively make up their inherent deficiency. This assumption was also confirmed by our research, as patients received MGP-IPL showed the best improvement results. With the opening of blocked glands by probing at first, meibum within glands can flow without any restriction. And the followed 3 times IPL treatments further attenuate inflammation and eliminate the abnormal meibum, leading to optimal therapeutic effect. Compared with single IPL or MGP, MGP combined IPL gained significant superiority in improving SPEED, TBUT, meibum grade and lid telangiectasia.
Once MGP cannot help all patients obtain continued symptom relief in our 6 months observation. 20% of patients still need repeated invasive probing, but these treatments would aggravate patients’ misery. The combination of MGP with noninvasive IPL helped 100% of patients attain the most enduring symptom relief in our study. 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 some limitations of our research: First, the participated patients in our study were comparatively small and the duration of follow-up was not long enough. Further investigation is warranted to evaluate the long-term results of these treatments with a large number of cases. Second, MGP is an invasive method that is more suitable for MGD patients with severe gland obstruction or gland scar, while IPL treatment is better in relieving intraductal inflammation. In this study, we found the combination of these two treatments could attain the best results, but we can’t deny that this treatment mode would bring patients more financial, time and psychological burdens at the same time. Based on our results, we recommend patients that have at least half of 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 MGP combined IPL therapy to exert the best curative effect of probing and anti-inflammation simultaneously.