Post-Cxl Corneal Flattening Syndrome: A Complication Following Accelerated Cross-Linking

Corneal cross-linking (CXL) is widely used to stabilize keratoconus and post-refractive ectasia. Accelerated CXL has lately gained popularity due to its reduced treatment time compared to Dresden protocol. Although a mild flattening of 1-2 Diopters (D) is expected postoperatively, some patients develop extreme flattening and thinning, potentially impacting vision. Progressive post-CXL flattening has been documented with the Dresden protocol, but studies reporting its occurrence in accelerated CXL treated eyes are scarce. This study aims to describe the first case series of Post-CXL Flattening Syndrome (PCFS), assessing whether it represents a distinct remodeling process in accelerated CXL.

This is a retrospective, multi-centre case series from Curitiba, Brazil.

We included adults with progressive documented ectasia who underwent accelerated CXL (9 mW/cm² UVA for 10 minutes) between 2014 and 2023, regardless of riboflavin type. We included patients with ≥4D of post-CXL corneal flattening confirmed by corneal tomography. Keratometric changes were compared between preoperative values and the most recent post-CXL follow-up. Descriptive statistics summarized patient characteristics, reporting mean (Standard Deviation), minimum, and maximum values. We used paired t-tests to evaluate differences in keratometry and pachymetry and Pearson correlation to assess associations between flattening, thinning, and follow-up duration. Statistical analysis was conducted using Python (pandas data analysis library).

A total of 9 eyes from 9 patients were included. The mean age was 26.2 years (SD 7.6), with a mean follow-up of 4.6 years (SD 3.0). Mean pre-CXL Kmax was 58.0 D (SD 7.8), and pre-CXL pachymetry was 423.7 µm (SD 66.3). We observed a mean flattening of 7.3 D (4.8-10.0 D), which showed a strong correlation with follow-up time (r = 0.70, p = 0.051). Postoperatively, mean pachymetry decreased to 355.5 µm, with an average thinning of 68.2 µm (p = 0.013). A trend was observed where steeper preoperative Kmax values were associated with greater thinning (r = -0.62, p = 0.072). One patient exhibited 10.0 D of flattening, while another had a pachymetric reduction from 425 µm to 272 µm and was referred for corneal transplantation.

This study presents the first case series of progressive flattening and thinning after accelerated CXL, a phenomenon previously thought to be exclusive to the Dresden protocol. While mild flattening is expected, extreme cases may be underrecognized and clinically significant. One patient in this study was referred for corneal transplantation, and others had substantial BCVA decline, emphasizing the severity of this condition. The late onset and gradual progression over time suggest PCFS may be underreported, particularly in studies with shorter follow-up periods. Given the lack of treatment options, further studies should include a longer follow-up period,  investigate post-CXL remodeling mechanisms, and identify potential risk factors.