Systemic immune indexes include several different cell types involved in the immune response, including neutrophils, lymphocytes and platelets, as well as monocyte counts. These indexes have been identified as biomarkers, particularly for predicting the course of diseases and their response to treatment. Systemic immune indexes determined by cell counts obtained from complete blood count and their combination have been investigated in many diseases in the literature. A meta-analysis by Shirvani et al. showed that NLR is a valuable marker of systemic inflammation and is significantly increased in many eye diseases, suggesting that it may play an important role in the pathophysiology of these diseases [11].

Two studies in retinal artery occlusion (RAO) patients also reported that NLR was higher in RAO patients [12, 13]. In two studies evaluating inflammation indexes in retinal vein occlusion (RVO) patients, leukocytes, neutrophils, NLR and SIII were significantly higher in RVO patients compared to controls. In these studies, SIII and NLR were identified as promising indicators for predicting the development of RVO [14, 15]. Studies in keratoconus patients have shown that SIII, NLR and PLR are higher in patients compared to healthy controls [16,17,18,19,20].

Yalınbaş Yeter et al. showed that MHR and NLR are simple and cost-effective biomarkers to predict diabetic macular edema and that high NLR may cause insufficient reduction in central retinal thickness after treatment [21]. Özarslan Özcan et al. investigated inflammatory status in dry eye syndrome patients using biomarkers. They reported that SIII, which is used as a new tool, may be a more reliable marker than NLR and PLR [22]. Kurtul et al. found that SIII, as a new index of inflammation, may be a more important tool than NLR and PLR in determining the severity of uveitis and may be a potential index in clinical practice to monitor and manage response to anti-inflammatory therapy in these patients [23].

All these literature data suggest that systemic immune indexes can be used to evaluate and monitor the inflammatory status in patients. Systemic immune indexes may provide new perspectives in understanding the pathophysiology of diseases affecting many tissues and systems, especially PXS, and in developing possible treatment methods.

There are many studies on the pathogenesis of PXS in the literature. In a study by Yıldırım et al. PXS patients were compared with healthy controls. The mean IL-6 level was found to be higher in the patient group compared to the control group [24].

In a study by Schlötzer-Schrehardt et al., both total and active TGF-β concentrations were significantly increased in the aqueous humor of PXS eyes and glaucoma compared to control eyes. Increased levels of latent and active TGF-β have been reported to support the formation of abnormal extracellular elastic material characteristic of PXS [25].

Elucidating the pathogenesis of PXS and predicting the complications that may develop in PXS eyes may make patient management more effective. Recognizing risk factors and identifying prognostic factors may improve patient follow-up. Systemic immune indexes are a set of inexpensive and simple criteria derived from peripheral blood. In PXS patients, the level of these parameters obtained from peripheral blood may provide insight into the course of the disease.

Vidal-Villegas et al. found that the levels of three cytokines were significantly different in the aqueous humor of primary open angle glaucoma patients (POAG) and pseudoexfoliation glaucoma (PXG). IL-12 and IL-13 were higher in the POAG, while monocyte chemoattractant protein-1 (monocyte chemotactic and activating factor) was higher in the PXG [26].

In a study investigating YKL-40, a protein involved in aqueous and chronic inflammation, there was a significant difference in mean aqueous humor YKL-40 levels in the PXS compared to the healthy control. The results of this study suggest that increased aqueous humor levels of YKL-40 are a local marker for inflammation in PXS patients [27].

In a similar study in the literature, both SIII and NLR were significantly higher in PXS patients. Compared to the control group, there was a statistically significant difference only in NLR in PXG patients [28].

In our study, leukocyte, monocyte and platelet counts were found to be higher in the PXS compared to healthy controls. NLR, MLR, PLR, SIII, SIMI, SIRI and AISI levels calculated with these parameters were also significantly higher in PXS patients compared to healthy controls. According to the results obtained, the presence of systemic inflammation in PXS patients can be mentioned. Systemic inflammation may be an indicator of intraocular inflammation and may also indicate systemic involvement of PXS. Prospective and large participatory studies are needed to understand the importance of the parameters and to estimate their power.

In the ROC analysis, SIRI and SIMI were found to be markers of higher significance among these parameters. These systemic immune indexes are calculated by a series of mathematical formulations based on cell counts obtained from peripheral blood samples. Since these indexes include multiple cell subtypes, they can provide more detailed information about disease pathogenesis. They may be useful in the follow-up of patients and may play a role in predicting complications.

All these findings and literature data suggest that inflammation may play a role in the pathogenesis of PXS. Moreover, these findings obtained from peripheral blood samples may be an indicator of multisystemic complications in PXS. It is noteworthy that monocyte count and monocyte activating factor were elevated in PXS patients in a study in the literature and in our study.

As known, platelets regulate monocyte function by modulating the activity and differentiation of monocytes [29, 30]. Activated platelets bind to monocytes and initiate the proinflammatory monocyte response [31, 32]. In addition, platelet-derived signals both directly and indirectly regulate the expression of proinflammatory cytokines. Activated platelets and platelet-derived microvesicles enhance monocyte activation and lead to the release of complement factor [33, 34].

In our study, monocyte count and SIMI -a newly defined index using monocyte count- were higher in PXS patients compared to healthy controls. This finding may give an idea for future studies to investigate the role of monocytes in the pathogenesis of the disease in PXS patients. Medications that regulate monocytes and/or monocytes-released factors from may be a treatment option in PXS patients in the future. Another perspective is that treatment response in PXS patients could be assessed using systemic immune indexes such as monocyte count or SIMI.

Among the limitations of our study, the impact of these systemic immune indexes on prognosis could not be assessed because it was a cross-sectional case-control study. Although other clinical manifestations of active infection are exclusion criteria, the impact of asymptomatic disease may have influenced the findings. Furthermore, the contribution of pseudoexfoliation to the development of pseudoexfoliation glaucoma in PXS patients could not be analyzed. The strengths of our study include the fact that it is one of the first studies to investigate several systemic immune indexes in PXS patients, including SIRI, AISI and a newly described index, the systemic inflammation modulation index (SIMI).

In conclusion, systemic immune indexes (NLR, MLR, PLR, SIII, SIRI, AISI and SIMI) were elevated in PXS patients compared to healthy controls. These indexes may serve as an easy, simple and cost-effective tool to assess the degree of systemic inflammation in patients, playing an important role in recognizing the underlying mechanisms of diseases and thus potentially guiding treatment.