Author Response: Transforming Growth Factor Beta Switch in Aqueous Humor of Patients With Fuchs' Endothelial Corneal Dystrophy

We thank de Roo and colleagues¹ for their interest in our study² and congratulate them on complementing the existing data with their results,¹ providing new insights into Fuchs' endothelial corneal dystrophy (FECD) pathogenesis. 

Our study, “Epithelial–Mesenchymal Transition (EMT)–Related Cytokines in the Aqueous Humor of Phakic and Pseudophakic Fuchs‘ Dystrophy Eyes,” demonstrates elevated expression of cytokines tumor growth factor (TGF)-β1, TGF-β2, and monocyte chemoattractant protein (MCP)-1 in the aqueous humor of pseudophakic FECD patients compared with phakic FECD patients and phakic (cataract) controls.² These results confirm data from previous studies showing that cataract surgery leads to long-term alterations of the intraocular microenvironment.^3–5 Changes in aqueous TGF-β1 and MCP-1 expression show high significance (P < 0.001, respectively).² Positive correlation of both cytokine expression levels with central-to-peripheral thickness ratio at 3.5 mm from the corneal center indicate involvement of these cytokines in corneal decompensation after cataract surgery.² 

In their letter to the editor, De Roo and colleagues¹ present results from complementary experiments. Inclusion of an extended range of analytes and an additional cohort of pseudophakic controls (Edema_psph), composed of eyes diagnosed with graft failure or pseudophakic bullous keratopathy, allow for a more detailed analysis. The authors confirm the results from our study with respect to elevated aqueous MCP-1 expression in pseudophakic FECD eyes and demonstrate increased expression of aqueous IL-8 after cataract surgery.¹ Their results describe increased TGF-β2 levels in phakic FECD patients compared with phakic (cataract) controls and increased TGF-β2 levels in pseudophakic FECD patients compared with pseudophakic controls (Edema_psph).¹ Moreover, they find increased TGF-β3 expression in the aqueous humor of phakic FECD eyes compared with all three other groups.¹ 

The authors correctly conclude that, based on their more detailed analyses, altered aqueous TGF-β2 and TGF-β3 levels may be involved in FECD pathogenesis and based on our results regarding aqueous TGF-β1 levels, there may be a switch to TGF-β1 after cataract surgery.¹ We feel that these conclusions describe interesting new aspects in the pathogenesis of the genetically heterogeneous FECD disease and agree that additional cytokine analyses focused on TGF-β isoforms will help to refine these new results.