A New Method for Demarcation Line Evaluation: The Corneal Densitometry Graph

Objectives: To evaluate whether the corneal densitometry graph can visualise the demarcation line (DL) and measure its depth early after corneal collagen cross-linking (CXL). Methods: A total of 53 eyes of 53 patients with progressive keratoconus underwent accelerated CXL. Visual acuity and corneal topography were measured preoperatively and at 1 month. The apex of the cross-linking reaction (CLR) peak on corneal densitometry graph was compared with the DL depth on anterior segment optical coherence tomography (AS-OCT); the reaction-initiating and reaction-ending depths were compared with those on in vivo confocal microscopy (IVCM). Pearson correlation coefficient was used to assess the linear association between the densitometry-derived depths and the reference measurements. Agreement was evaluated with Bland–Altman analysis together with an absolute-agreement intraclass correlation coefficient (ICC) and changes were analysed with linear mixed-effects models. Results: At 1 month postoperatively, uncorrected distance visual acuity (UDVA) did not change significantly (p = 0.851), whereas CDVA improved slightly (p = 0.022). Corneal densitometry increased in the central region (0–2, 2–6, 6–10 mm) (p < 0.001). Corneal densitometry increased significantly in the central region (0–2, 2–6 and 6–10 mm annuli; total layer, all p ≤ 0.001) but not in the 10–12 mm annulus (p = 0.827). Correlation analysis showed a strong association with AS-OCT and IVCM (r = 0.82–0.88, p < 0.001). Agreement with AS-OCT and IVCM was good at the group level (ICC(2,1), 0.82–0.87), although all 95% limits of agreement exceeded the ±5% limit. A CLR peak was identified in all 53/53 eyes versus 50/53 eyes on AS-OCT, but the detection rates did not differ significantly (McNemar exact test, p = 0.25). Conclusions: The corneal densitometry graph provides an initial, non-contact evaluation of the depth and extent of the early cross-linking reaction, with good group-level agreement with AS-OCT and IVCM.