The characteristics of patients who showed a change in the SPEED score for each eye from baseline to 4 weeks after the final treatment (ΔSPEED) of <5 or ≥5 are presented in Table 4. Age did not differ significantly between the 2 groups (P = 0.40). The duration of MGD was significantly longer for the patients with a ΔSPEED of ≥5 than for those with a ΔSPEED of <5 (P = 0.041). Eyes with a ΔSPEED of ≥5 underwent significantly more IPL-MGX treatment sessions than did those with a ΔSPEED of <5 (P < 0.001). There were no significant differences in sex distribution or the frequencies of at least 3 meibomian gland dropouts in 1 eyelid, history of contact lens wear, coincidence of aqueous-deficient dry eye, or previous ocular surgery between the 2 groups of patients (P = 1.0, 0.45, 1.0, 0.066, and 1.0, respectively).
This is the first prospective and multicenter study to show improvement in the subjective symptoms and objective signs of refractory severe MGD after a series of IPL treatments combined with MGX. Tear film stability, lipid layer dynamics, and meibomian gland function all responded positively to treatment, resulting in improvement in the condition of the tear film in the study patients. This study enrolled patients with refractory severe MGD at 3 centers and did not exclude those with a history of contact lens wear, ocular surgery, or any type of MGD management.
We found that IPL-MGX therapy was effective for management of refractory MGD, being associated with improvement in both lipid layer dynamics (tear interferometric fringe pattern) and NIBUT as determined with the DR-1α tear interferometer. IPL was also shown previously to improve the lipid layer grade as determined with the Tearscope Plus interferometer (Keeler, Windsor, United Kingdom) in patients with MGD.10 This latter study enrolled patients with mild to moderate MGD but not those with refractory MGD, with 82% of the treated eyes showing improvement in the lipid layer grade.10 In this study, after a course of 4 to 8 IPL-MGX treatments, 74% of eyes with refractory MGD showed a change in the tear interferometric fringe pattern from 1 characteristic of lipid deficiency to the normal condition, indicating that the balance between the lipid and aqueous layers of the tear film had improved. The NIBUT is characteristically reduced in patients with MGD.32 The previous study of the lipid layer grade also demonstrated a significant improvement in the NIBUT from 5.28 to 14.11 seconds after treatment of the patients with MGD with IPL.10 In this study, the NIBUT was increased from 3.3 to 7.8 seconds, representing a meaningful clinical improvement, with our previous study having shown that the cutoff value of the NIBUT for dry eye disease as measured by DR-1α is <5 seconds.25
Improvement of meibum quality and expressibility is a key factor in treatment of MGD. We found that meibum quality and expressibility were significantly better after IPL-MGX treatment in this study. Similar results were obtained in previous studies.9,12–15,17,20 IPL application increases skin temperature.10 Whereas the phase-transition temperature of meibum is 28°C in controls, it is >32°C in patients with MGD.33 Although eyelid warming at home has been found to be transiently effective for treatment of MGD,2 the temperature of the eyelid skin was found to increase to 34°C during the application of a warming device but then to decrease rapidly over 10 minutes after device removal.34 Such eyelid warming at home is thus not sufficient to support long-term melting of meibum.34 However, IPL has been found to increase the temperature of small vessels (diameter of < 60 μm) in the targeted skin area to between 45 degrees and 70°C,35 which is likely sufficient to increase the temperature of eyelid skin and the tarsal conjunctiva adjacent to the meibomian glands and thereby to melt meibum.16
Self-reported ocular symptoms covered by the SPEED questionnaire were significantly ameliorated after IPL-MGX treatment in this study, similar to the results of previous studies.10,13,15,17,18 Twenty-five (81%) and 20 (65%) of the 31 patients in this study thus showed a decrease in the SPPED score of at least 3 or 5 points, respectively. The CFS was also significantly reduced after the treatment sessions, again consistent with previous data.10,14,15,17,20 The patients enrolled in this study had MGD for 7.6 ± 5.8 years, and conventional therapies had not been effective. Indeed, >60% of enrolled eyes showed at least 3 meibomian gland dropouts in 1 eyelid, indicative of the disease severity. Such severe disease was too difficult to manage even with a combination of several conventional therapies. However, a series of IPL-MGX therapy sessions were able to improve subjective symptoms and objective findings including meibum quality and quantity, lid margin abnormalities, and stability and homeostasis of the tear film.
The potential mechanisms for ameliorating subjective symptoms and objective findings of MGD are considered, as mentioned above, to promote melting of meibum,9,16 to attenuate local release of inflammatory factors from the abnormal vessels,18,37,38 and to reduce bacterial load of the eyelid margin.39
There are several limitations to our study. First, the study design was single arm and was based on both eyes of a small number of patients. Further studies with a larger number of patients and a control group are necessary. Second, the duration of follow-up was limited to 4 weeks after the final treatment. Longer follow-up periods will be necessary to assess the long-term effectiveness and safety of IPL treatment. Third, all the patients at each site continued their current medications during the study. A more controlled experimental design will be preferable for future studies. Fourth, IPL treatment is not covered by national insurance in Japan. Although the enrolled patients did not pay for IPL treatment in this study, this situation might introduce inherent bias.
In conclusion, our results suggest that IPL-MGX therapy is effective for patients with refractory MGD whose severe disease is difficult to manage with other conventional therapies. IPL-MGX thus has the potential to help many patients with MGD and is a promising modality for refractory MGD in particular.
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