iERM is a relatively common condition affecting the vitreous-macular junction. The patient has no clear history of eye disease, and the condition is most prevalent in the elderly. It has been established that the formation of iERM is associated with PVD, inflammation, and renin-angiotensin (RAS) system activation[4, 21–23]. According to previous reports, approximately 95% of clinically significant iERM occurs following vitreous body detachment [24]. The iERM is primarily composed of retinal pigment epithelial cells and retinal glial cells (astrocytes and Müller cells) [25]. Histological studies have revealed that myofibroblasts, fibroblasts, clear cells, and macrophages may play roles in the occurrence and progression of iERM [25]. Myojin S et al.[26] examined the vitreous lavage fluid of participants with iERM (15 eyes) and found that pro-inflammatory genes were overexpressed (IL6, GFAP, VEGFA, TGFB2, CXCL1, TNC, and RELA). Multiple interleukins (IL- 1 IL-6, IL-13, IL-17) and TGF-β1, TGFβ2 interferon necrosis factor and other inflammatory factors are also involved in the formation of iERM [23, 26]. Furthermore, in the development of iERM, the RAS system is implicated[23, 27]. RAS can induce retinal vascular inflammation and mediate and regulate the factors involved in iERM fibrosis (FGF2, GDNF, NGF, TGF-β1).
Monocytes are pro-inflammatory during inflammation, whereas lymphocytes can help regulate inflammation [28, 29]. MLR has been used to investigate the staging and prognosis of COVID-19 and cardiovascular disease [9, 13]. In the current study, we found the monocyte count was significantly higher, and the lymphocyte count was significantly lower in the iERM participants. We used MLR to predict the development of iERM, and found good sensitivity and specificity. According to Joshi [4] and Zhao et al.[30], the major cell types in iERM are hyalocytes and müller cells. Hyalocytes are classified as macrophages (a kind of inflammation cells) [31].
Another two popular markers associated with the prognosis of systemic inflammatory diseases are NLR and PLR [32]. Previous studies have established a link between NLR, PLR, and RAO, RVO, and Keratoconus [15, 18, 33, 34]. Additionally, NLR and PLR were also used to classify the severity of dry eye [14]. Though we found that iERM participants had significantly higher PLR and NLR values than the control group in the current study, that is inconsistent with the previous studies [33], in which the sensitivity or the specificity were low. However, the lower sensitivity (52.6%) of NLR in predicting iERM was also reported in the study by Uzlu et al. [20] They attributed this difference to the small sample size.
Macular edema and macular holes could be caused by iERM traction. Triamcinolone acetonide (a long-acting adrenaline glucocorticoid) has the effects of an anti-inflammatory, inhibiting cell proliferation, reducing capillary permeability, stabilizing the retinal barrier, etc., and can reduce and control the progression of macular edema. Past studies have suggested that intravitreal injection of triamcinolone acetonide while removing the macular membrane can effectively reduce macular edema [35, 36].That hint suggests that eyes with macular edema might be more associated with inflammation than usual. In addition, some clinical studies suggest that NLR and MLR can be used as inflammatory markers for diabetic macular edema [37, 38]. But we didn’t find any significant difference in MLR, PLR, and NLR between iERM participants with macular edema and those without macular edema in this study. The possible explanation is that macular edema in iERM eyes might be due to the physical traction, and inflammation might play a comparable role in the iERM with or without macular edema.
This study was limited by a number of factors. First, the vitreous fluid and postoperative macular membrane tissue tests were not available due to retrospective design. Second, we were unable to compare additional inflammatory markers simultaneously, such as interleukin-1 and TGF. However, to our knowledge, this is the first research to examine the link between MLR and iERM using a large sample size.
To summarize, it is possible that systemic inflammation may be associated with iERM. IERM patients may be prone to have high MLR, NLR and PLR values. Additional laboratory studies on iERM's mechanism are necessary to gain a better understanding of the relationship between iERM and blood biomarkers.