The present study demonstrated that one session of the RF thermal treatment was safe and effective for the treatment of obstructive MGD with respect to lid margin abnormality, corneal staining score, and meibomian gland structure. In cases of obstructive MGD, abnormal meibum secretion by the primary obstructive hyperkeratinization of the meibomian gland and changes in glandular secretion result in tear film instability and eyelid and corneal inflammation[31, 32]. It can damage the ocular surface directly or indirectly by initiating an inflammatory cascade that generates immunological responses and microbiological changes[31, 32]. The blockage in obstructive MGD is caused by the inspissated secretions resulting from the hyperkeratinization, and an elevated melting point of the solidified oils from the stagnation and bacterial activity[32].
LipiFlow Thermal Pulsation System is currently the only FDA approved treatment, which works by direct eyelid heating and meibomian gland massage to express the waxy blockage and restore the meibomian gland function. Here, sufficient and direct eyelid heating is important to melt the modified or deficient meibum lipids for unblocking the obstructed meibomian gland[33]. Compared with this system, the use of RF energy for heating via the Pellevé Wrinkle Reduction System showed similar results with regard to improvements in subjective symptoms, meibomian gland expression grade and plugging score, and conjunctival staining score[22]. Pellevé Wrinkle Reduction System has been utilized to decrease the skin laxity and improve rhytids of the face, including the periocular area, by heating the dermis and achieving a higher temperature[34]. High-frequency electron flow RF generates heat in the surrounding tissues as a result of the difference in impedance between the tissue types, which turns the kinetic energy into thermal energy[35]. It not only eliminates the problem of heating the unwanted target chromophores in the skin, such as melanin, as seen with the IPL treatment, but also allows heating of the deep dermis. A recent clinical study conducted by Jaccoma et al. only evaluated 10 participants that were recruited from a diverse age group, thus necessitating further studies to elucidate the mechanisms of the RF treatment for the management of MGD[22]. However, we assumed that the RF energy via the Pellevé Wrinkle Reduction System might be insufficient to achieve complete melting of the abnormal meibum lipids because it was designed to apply the heat only externally to the outer eyelid surface. Furthermore, considering that the electrode should be continuously moved by the physician over the eyelid to deliver the RF energy, there could be an uneven distribution of the RF energy over the eyelid. Thus, we hypothesized that transfer of heat to both the outer and inner eyelid surfaces was important for the treatment of obstructive MGD.
Based on our results, we demonstrated that the lid margin abnormality score significantly improved after the RF thermal treatment in the treatment group as compared with the control group, with the former having a significantly lower score. Hence, the RF thermal treatment could be effective for obstructive MGD through its heating of the eyelid and opening of the meibomian gland orifice.
Corneal staining scores increased at 4 weeks after without the RF thermal treatment in the control group, when compared with baseline and 4 weeks after meibomian gland orifice closure. Gilbard et al have shown an abnormal rose bengal staining of the cornea 4 weeks after the meibomian gland closure, which is in contrast with the results of our study[36] Possible explanations would be incomplete coagulation of the meibomian gland orifices of the central two-thirds of eyelids, sparing the nasal and temporal meibomian glands or an inherent homeostatic system providing a compensatory tear fluid production[37]. The corneal staining score in our study remained unchanged throughout the experiment in the RF treatment group. We considered this to be due to the ocular surface stabilization via the RF thermal treatment accompanied with the compensatory tear fluid production in obstructive MGD.
The histologic sections showed that the sizes of the secretory acini were reduced with the widening of the central ducts after the meibomian gland orifice closure in both the groups. Accordingly, a significant increase in the meibomian gland loss rate was noted at 4 weeks after the meibomian gland orifice closure in both the groups. After 1 session of the RF thermal treatment, there was an improvement in the meibomian gland loss rate for the upper and lower eyelids, which was almost normalized to baseline condition. Moreover, there were improvements in the mean area of the secretory acini and the dilated central ducts as well. Moreover, there was a significant difference in the mean area of the secretory acini between both the groups at 4 weeks after the RF thermal treatment.
There was no difference in the number of PMN cells between the groups at 4 weeks after the RF thermal treatment. According to previous studies, inflammatory cells around the meibomian gland ducts were normalized to a baseline condition in less than 4 weeks after the meibomian gland orifice closure. Hence a long-term observation is needed to detect the differences in the number of PMN cells between the control and RF treatment groups[28, 36].
In the present study, the use of ICP MGD meibography device was helpful to evaluate the integrity of the meibomian gland before and after the MGD treatment in an animal MGD model because it could detect relatively early changes in the meibomian gland acini after the closure of the orifice or the RF thermal treatment. In a previous study, the meibography obtained from a Meiboviewer for animal experiments (Visual Optics, Chuncheon, South Korea) could not detect early changes in the meibomian gland acini after the closure of the orifice[28]. There might be some functional differences between the instruments, although both use the infrared light for the detection of the meibomian gland structure. Therefore, in animal MGD studies, considerable observation and comparison between the histologic examination and meibography is essential to detect subtle changes in the meibomian gland structure.
The coagulation of the meibomian gland orifices of the central two-thirds of the upper and lower eyelid margins was performed twice, at 2-week intervals using a 5-MHz high-frequency electrosurgical unit. In a previous study evaluating the effects of one-time electrosurgical coagulation of the meibomian gland orifices on the meibomian gland structure and ocular surface changes in rabbits, meibography showed a normal morphology, although the mean area of the secretory acini of the coagulation group was significantly smaller than that of the non-coagulation group[28]. Additionally, the effects of the thermal damage of the meibomian gland caused by the coagulation, resolve within 14 days. This is based on the normalization in the numbers of PMN cells, CD-11b-positive cells, and apoptotic cells around the meibomian gland and meibomian gland orifice[28]. Hence, the electrosurgical coagulation of the meibomian gland orifices was performed twice to guarantee an improved and sophisticated version of the obstructive MGD animal model.
This study had several limitations, including a short duration of follow-up period and a small sample size. Since the duration of follow-up after 1 session of the RF thermal treatment was limited to 4 weeks, it is thus recommended to observe the differences over a longer period for any meaningful conclusions. Further, the choice of rabbits for the animal experiments to study the biochemistry and biophysics of tear films, could be a shortcoming because of the differences between the rabbit and human meibum[38]. Nevertheless, a low-level RF thermal treatment was found to be safe and effective for the treatment of obstructive MGD, although the exact mechanism and significance of the RF thermal treatment remains uncertain. Further human studies to investigate the effects of the RF thermal treatment device, used in this study, for the treatment of MGD are needed.
In summary, the use of a low-level of RF energy for heating the inner and outer eyelid surfaces is safe and effective for the treatment of obstructive MGD in a rabbit animal model of MGD.