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Editors Selection IGR 7-3

Clinical Forms of Glaucoma: Cytokines and Exfoliation Glaucoma

Comment by Ursula Schlötzer-Schrehardt on:

66368 Proinflammatory Cytokines Induce XFG Development, Sarenac Vulovic TS; Pavlovic SM; Zdravkovic NS, Ocular Immunology and Inflammation, 2015; 0: 1-7

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Dysregulated expression of proinflammatory cytokines has been implicated in the initiation of various fibrotic disorders and in the pathophysiology of glaucoma. Based on elevated aqueous humor levels of IL-6 and IL-8 in early stages of pseudoexfoliation (PEX) syndrome, previous studies have provided evidence for a stress-induced, spatially, and temporally restricted subclinical inflammation in the onset of the fibrotic PEX process.¹ Subsequent studies confirmed elevated aqueous levels of IL-8² and extended the findings to increased concentrations of TNF-α in aqueous humor³ and of IL-6 in serum⁴ samples obtained from PEX patients without or with glaucoma. A positive correlation of aqueous IL-8 (and TGF-β1) concentrations with IOP led the authors to suggest a critical role for aqueous IL-8 and TGF-β1 in IOP elevation.²

The study by Sarenac Vulovic et al. further analyzed the levels of IL-6, IL-17 and TNF-α in aqueous humor and serum of patients with early and late stages of PEX syndrome as well as PEX glaucoma, using cataract patients as control (n = 30 in each group) by ELISA assays. The authors reported significantly elevated levels of TNF-α and IL-17 in the aqueous humor of all PEX groups compared to controls, whereas increased IL-6 levels were observed in early PEX and PEX glaucoma only. Serum levels of IL-6 were significantly elevated in early and late PEX syndrome but not in PEX glaucoma. The authors concluded from their findings that 'local conditions cause chronic inflammation in the eye, subsequently activating fibrotic process with fibrotic tissue deposits in the eye'.

Apart from the first-time detection of increased levels of IL-17 in aqueous samples of PEX patients, the study unfortunately does not make any significant contribution to the subject

Unfortunately, however, the data presented are difficult to interpret and to compare with previous publications, particularly because aqueous and serum concentrations of IL-6 and TNF-α were considerably higher than those reported from the literature. In particular, the unusually high concentrations of TNF-α (300-500 pg/ml) are in stark contrast to published studies showing undetectable or rather low levels (up to 20 pg/ml depending on disease background) in the aqueous humor of patients. Moreover, an exact definition of early and late stages of PEX syndrome was not provided by the authors further impeding a comparative analysis. Finally, cytokine levels were illogically correlated between different groups, instead of correlating cytokine levels with PEX stage, IOP or other glaucoma parameters. Thus, apart from the first-time detection of increased levels of IL-17 in aqueous samples of PEX patients, the study unfortunately does not make any significant contribution to the subject and does not give evidence of an 'induction of XFG development by pro-inflammatory cytokines' as indicated in the title.

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