Some RCTs have evaluated the efficacy of aPDT in treating CADS and compared it with NYT 20, 27, 28. Despite finding only three RCTs meeting our inclusion criteria, we were able to conduct a meta-analysis to compare aPDT with NYT in reducing Candida colony count which was not conducted in the previously published qualitative systematic reviews31, 38. Moreover, the previous systematic review has not assessed the risk of bias in included studies38. Therefore, the current meta-analysis attempted to solve the shortcomings of the previous systematic reviews and provide an evidence-based conclusion based on the available literature.
Even though some in vitro and animal studies 39–42 have been evaluated aPDT on oral candidiasis, since the oral environment of humans is different from animals, and factors such as biofilm and microbiota composition, salivary flux, oral hygiene, and food habits might change the response to aPDT, it is difficult to compare the findings of RCTs with those of in-vitro and animal studies 20.
Qualitative results of all included RCTs showed that aPDT is effective in reducing Candida colony count, and thus in improving CADS. Additionally, RCTs did not show a statistically significant difference between aPDT and NYT in reducing Candida colony count in all time intervals (days 15, 30, 45, 60, and 90) 20, 27, 28 which was in line with the conclusion of the previously published systematic review31.
Qualitative results of this systematic review support the results of each included RCT and previously published systematic reviews31, 38 in terms of the efficacy of aPDT in reducing Candida colony count. Nevertheless, the meta-analysis results showed that NYT statistically is superior to aPDT in reducing Candida colony count at the end of the treatments (day 15) in both patients’ palate and denture. Although the results of each included study showed that there was no statistically significant difference between aPDT and NYT in reducing Candida colony count in all time intervals, it seems that the small sample size of these included studies caused the contradiction between their results and the pooled results of the performed meta-analysis.
On day 30, a statistically significant difference was observed between aPDT and NYT groups in reducing Candida colony count in patients’ palate, however, this difference was not significant in patients’ denture. This may be justified by the porous and uneven inner surface of acrylic resin dentures which act as a reservoir for microorganisms that leads for faster recolonization in patients’ denture compared to patients’ palate after treatments.
Also, the lack of significant difference between aPDT and NYT on day 60 may be justified by the inner surface of acrylic resin dentures which act as a reservoir for Candida species 43, and their tendency to recolonize on hard surfaces such as patients’ denture and palate immediately after treatments. The aforementioned recolonization may lead to the recurrence of CADS after therapeutic sessions.
Additionally, based on the meta-analysis more success in the NYT group in reducing Candida colony count on the aforementioned intervals is probably because NYT can eliminate Candida species in other areas of the mouth, such as the buccal mucosa and tongue; however, utilized aPDT technique among studies only affected the palatal mucosa 20, 27, 28. It seems that if aPDT is not limited to the palate of patients and is used in the whole oral cavity, the same results may be obtained compared to NYT. In addition, the size of fungal cells compared to bacterial cells seems to affect the success of aPDT in reducing Candida colony count, because larger cells need more amount of singlet oxygen to be killed 44. Besides, according to the meta-analysis, the lower success in reducing Candida colony count in the aPDT group can be justified by the fact that the number of aPDT sessions was less than that of NYT. On this basis, patients get aPDT only in the office; however, patients in the NYT group used nystatin several times a day 20, 27, 28. It is possible to achieve the same results compared to NYT by designing a low-cost aPDT devices for home use as is mentioned in a study 45.
It also seems that the parameters related to light sources and types of PSs in the aPDT group are associated with the reduction in Candida colony count in aPDT group 27. Even though the research designs of the included studies were the same, nonetheless, the methodologies used in aPDT varied significantly. One of the most important barriers was a lack of standardization of light source and PS parameters across trials. While conducting the meta-analysis, aPDT was utilized as a catch-all term for any aPDT setting (independent of parameters).
The current systematic review and meta-analysis has shown the promising effect of aPDT in reducing Candida colony count (Log10 CFU/mL) and this effect does not seem to be as effective as NYT. Moreover, the clinical significance of these results must be carefully weighed (Although statistically significant, the clinical significance should be questioned).
This meta-analysis had some limitations that must be considered and due to these limitations, the results should be interpreted with caution. The first limitation was the lack of an appropriate number of RCTs for inclusion. Another limitation was associated with the moderate quality of the included studies. Moreover, the small sample size was the obvious shortcoming of each included study which probably led to inconsistent results between the meta-analysis and the results of each included RCT in terms of comparing aPDT and NYT in reducing Candida colony count. Furthermore, Finding the most effective treatment parameters of aPDT has not yet been established in this review.