This trial showed that two groups using IPL treatment of MGD alone, without MGX, and with different distances of the IPL beam with respect to the lower lid margin (3 and 10 mm) had similar outcomes regarding improved meibomian gland function in both upper and lower eyelids (evaluated by MGYSS) and relief of related dry eye symptoms (evaluated by SPEED questionnaire). The results answered the question that motivated us at first place. We may move the beam farther from the eye to guarantee a safer and equally helpful protocol. The results further corroborate indirect effects of IPL. To date, there has not been theory explaining the indirect effects of IPL. In other light therapy areas, there are studies reporting similar stories on indirect effects and placing photobiomodulation (PBM) as an important explanation. We speculate that PBM may also be the mechanism of IPL indirect effects.
PBMs are produced by coherent or noncoherent light sources or both within the visible and near-infrared (NIR) spectra. Its effects start from the chromophore inside cells absorbing the energy. A series of photophysical and photochemical reactions are elicited at the molecular and cellular levels. Eventually, various effects on tissues, such as changes in cell proliferation and differentiation, RNA and protein synthesis, oxidative stress and inflammatory processes are produced by irradiation with different parameters.[13–15] Since IPL, a broadband source, with a filtered wavelength ≥ 590 nm, includes the visible and NIR spectra, it is reasonable to consider PBM as a key mechanism [14, 15].
PBM has been used in many areas, such as wound healing, pain release, acne, hair regeneration, anti-inflammation, neurophysiological applications [15]. Some cases took advantage of the indirect effects of PBM; a typical example is in the field of neurophysiology. Several studies have shown that a helmet that blocks the light from being applied directly to the head does not inhibit the beneficial effects of PBM in models of Parkinson’s disease [16–18]. Therefore, the PBM theory might be a proper explanation for the indirect effects of light therapies and helpful to understand the effects IPL has on areas to which it is not directly applied.
MGD is a leading cause of dry eye disease, which is a common complaint in eye clinics [19]. Obstruction, telangiectasia, inflammation, and acini atrophy are the main concerns in regard to MGD. Currently, with the theory of PBM that has effects on inflammation, protein synthesis, oxidative stress, PBM might be an adequate solution to MGD and a crucial mechanism of IPL in treating MGD.
With regard to the TBUT results, neither of the two groups had statistically significant improvement simultaneously when MGYSS had improved. In our previous study, we had baseline TBUTs of 6.86 ± 2.69 s and 7.64 ± 2.23 s. We performed IPL and MGX and showed a statistically significant improvement in TBUT [4]. When we looked back to the baseline valued this time, we noticed that 90.3% of the subjects in Group A and 92.3% in Group B had a TBUT of less than 5 s. Furthermore, some of them did not have fluorescein staining with such short TBUTs. This reminded us of a special kind of dry eye condition called short TBUT dry eye.
Short TBUT dry eye is characterized by a TBUT of less than 5 s, with dry eye symptoms. Patients with this condition show no insufficiency in tear production, nor staining of the ocular surface. Simply, any change in the three layers (lipid, aqueous, or mucin) of the tear film would have an influence on the film’s stability. To date, there have been several reports on goblet cell reduction, changes in mucin components, chronic inflammation, and allergies, all associated with short TBUT dry eye [20]. MGD, as a chronic disease, is inevitably accompanied by chronic inflammation of the lid margins and ocular surface, which can lead to goblet cell death and mucin abnormalities. In short-term observation, there may not be sufficient time for goblet cells and mucin to recover. In addition, if tear film stability follows the Buckets effect, TBUT will not be prolonged if other layers of the tear film do not recover in time.
And considering that corneal nerves play a key role on ocular surface homeostasis, the central corneal subepithelial nerves (CCSN) were also observed before and after the IPL intervention, and no difference was found. However, given longer observation, there might be interesting and inspiring changes.
In addition, this time, we did not perform MGX after each treatment as usual, as we were interested in observing the indirect effects of IPL, not to be mixed or covered by the effects of MGX. Thus, quality-improved meibum may not be sufficiently secreted onto the ocular surface in time. As a result, there would not be enough time for a better environment to be created for goblet cells and mucin to recover.
There were limitations in this study. First, we used moist fluorescein sodium strips for the TBUT measurements. The components of fluorescein sodium strips may change the characteristics of the tear film, although this is a small effect. Second, we only observed the short-term outcomes. We believe longer observation is necessary especially in TBUT and corneal nerves.