The findings from this non-randomized, prospective observational clinical study demonstrate that chalazion causes meibomian gland loss, and the range of meibomian gland loss after complete chalazion resolution is related to the range of chalazion itself, that is, the range of chronic granulomatous inflammation. Interestingly, despite our initial concern, surgery did not expand the range of meibomian gland loss. One previous study reported that chalazion itself or chalazion excision may cause meibomian gland loss; however, due to the limitations of the retrospective study design, the factor responsible for meibomian gland loss was unclear.15 This finding clearly supplemented the conclusions of the study. According to monitoring of the progression of chalazia by infrared meibomian gland photography, we found that the meibomian gland morphology could not be observed in the chalazion area before treatment (conservative treatment or surgery), and after complete chalazion resolution, the area showed meibomian gland loss. Moreover, no statistically significant difference was found between the range of meibomian gland loss after complete chalazion resolution and the range of the initial chalazion area before treatment using either method. The reasons for these results are discussed below.
Chalazion formation is a typical physiological response to chronic granulomatous diseases1. Previous studies have shown that chalazia mainly involves macrophages, neutrophils and epithelial cells.16,17 Moreover, the lipid component of chalazion differs from normal meibomian gland lipids.17 However, infrared meibomian gland photography is based on the theory that the lipid particles in a meibomian gland are excited by infrared rays and emit scattered light.18 A chalazion is composed of granulomatous substances and abnormal lipids before treatment. Therefore, the meibomian gland morphology cannot be observed in the chalazion area.
A previous study reported that when inflammatory cells infiltrated the meibomian glands, normal meibum secretion was blocked, but abnormal meibum continued to be produced, and these changes led to increased pressure in the glands, which may cause meibomian gland structure destruction.19 Accordingly, the chalazion area showed meibomian gland loss after complete resolution.
The normal tarsal plate is composed of a dense connective tissue plate, and meibomian glands are embedded in the tarsal plate of the eyelid,9 with no cystic cavity formation. Because of the local granulomatous reaction, a chalazion (cystic cavity) forms on the tarsal plate, which is an inflammatory lesion. The range of incision and curettage is the range of the cystic cavity. Therefore, regardless of whether conservative treatment or surgery is applied, self-absorption or curettage involves only the granuloma reaction and does not involve the normal tarsal tissue. Therefore, the range of meibomian gland loss is related to the range of chalazion itself rather than the treatment method. One previous study also found that surgery did not damage normal meibomian glands near the lesions; however, the results showed the normal area of the meibomian gland significantly increased at 1 month after surgery. The reasons for the different results may be as follows: the observation indicators and calculation methods differed between the previous study and our study. In the previous study, the observation indicator was “average ratio of 'normal meibomian gland/normal meibomian gland and dark area'”, which was rated according to meibomian gland meiboscore (grade 0, no loss of meibomian glands; grade 1, area loss of less than one-third of the total meibomian gland area; grade 2, area loss of between one-third and two-thirds of the total area; and grade 3, area loss of more than two-thirds of the total area). In our study, the observation indicator was the proportion of the chalazion area. We used ImageJ software to calculate the area of the chalazion and the whole area of the tarsal plate on which the chalazion was located. The proportion of chalazion area =chalazion area/the whole area of the tarsal plate. The whole area of the tarsal plate was also used to calculate the proportion of meibomian gland area; that is, the denominator was unchanged.
A previous study found that the ratio of cholesterol/cholesterol esters (Chl/CE) was increased in the abnormal lipid component of chalazion and suggested that an increase in Chl levels might send a chemotactic signal to inﬂammatory cells to invade the meibomian gland.17 The inﬂammatory cells may cause a physical blockage of the meibomian gland or meibum thickening, which would obstruct the expression of meibum. As a result, this abnormal lipid material might invade the surrounding tissues and intensify the inﬂammatory response in the meibomian glands. This vicious cycle may exist during the formation and expansion of a chalazion before treatment, and occasionally, a chalazion may enlarge even during conservative treatment. As mentioned above, the range of meibomian gland loss was related to the range of chalazion itself. Therefore, the best strategy to reduce the range of meibomian gland loss is to cure the chalazion as soon as possible. Based on our observation, chalazion can be cured rapidly by surgery. In fact, one study showed that complete resolution rates were low for three conservative treatment methods and suggested that ophthalmologists, particularly those in subspecialty clinics such as oculoplastics, can use surgical or invasive therapy earlier during treatment.6 Another study showed that incision and curettage was a good therapeutic choice for all chalazia.8 Despite such recommendations, many ophthalmologists choose to try conservative treatment first even if the chalazion size is large and the chalazion duration is long because they fear that surgery will damage the meibomian glands. However, our result showed that surgery did not expand the range of meibomian gland loss. In addition, a previous study considered that starting with surgical options earlier may also reduce patients’ exposure to antibiotics and/or steroids, which may cause antibiotic resistance or increased intraocular pressure and steroid-induced glaucoma when overused. Therefore, we suggest that ophthalmologists perform surgery sooner during treatment to cure chalazion rapidly and thus control the range of meibomian gland loss in a short time.
In this study, we found meibomian orifice plugging and toothpaste-like meibum in one or several meibomian glands where chalazion was located before treatment, which may suggest that local meibomian gland function had already changed before chalazion formed, and meibomian gland obstruction may lead to chalazion, which was also one of the causes of chalazion formation.9 As the results showed, meibomian gland function improved at 1 month after complete chalazion resolution with conservative treatment. However, no statistically significant differences were noted before and after surgery, likely because patients with conservative treatment used hot masks before complete chalazion resolution, and frequent and regular heating melted the meibum of the non-chalazion part, allowing the meibum to discharge on the eyelid margin.20-22
Notably, complete chalazion resolution does not indicate the end of treatment. If meibomian gland function in the non-chalazion area does not improve, the meibomian glands will become obstructed and cause chalazion again, which is why some people are prone to suffer from chalazion. No specific preventive strategy is available for chalazia because chalazion is closely related to the meibomian gland. Previous studies have shown that meibomian gland function can be improved by various methods. A hot compress combined with meibomian gland massage is considered a traditional and effective method,6,21 while LipiFlow treatment and intense pulsed light (IPL) treatment are optional choices,23,24 and intraductal meibomian gland probing can be used in patients with severe meibomian gland obstruction.25 Therefore, further research on personalized treatments according to the condition of meibomian glands after complete chalazion resolution is needed.
In this study, only 3 patients had a chalazion located near the eyelid margin, and we found that the acinar structure was incomplete after complete chalazion resolution. The reason for this result may be that the meibomian gland is a special type of sebaceous gland with a holocrine acinar secretion pattern, indicating that the contents of the whole glandular cells form the meibum. Normally, the basal layer of meibocytes in the periphery of the acinus contains a proliferating progenitor cell population that constantly gives rise to new meibocytes, and the above process is repeated.3 However, when inflammatory cells infiltrate the gland, new meibocytes cannot be formed in the short term; therefore, the complete acinar structure was not observed in the chalazion area. However, this result does not indicate that new meibocytes will never regenerate. A previous study reported stem cells of the meibomian glands located at the circumference of each acinus, which were responsible for the continuous generation of meibocytes; approximately 13 days is required for newly formed meibocytes to eventually shed in the mouse meibomian gland26. Perhaps due to the effects of inflammation, new meibocytes need more time to regenerate. Moreover, another study showed that the meibomian gland can regenerate with meibomian gland probing.27 Therefore, whether meibocytes can regenerate and the regeneration time after chalazion resolution require further study.
In this study, patients could not be randomly divided into conservative treatment or surgery groups because such stratification was not possible given the actual clinical situation. The treatment decision depends on the chalazion size, the lesion duration, the patient's consent and so on. In addition, the number of cases observed by confocal microscopy was small and not representative. To determine whether the acinar also disappears in the meibomian gland loss area, a larger sample size is needed.