Long-Term Keratoconus Follow-Up Identifies More With Progressive Disease

topography of the cornea with an unpleasant diagnosis of keratoconus stage 2-3
The zonal average analysis of corneal tomography data in the keratoconus cone area has identified 3 times more eyes with progressive disease than single-point indexes over 4-year follow-up.

Single-point tomography fails to capture progressive keratoconus in some patients, indicating that criteria for managing the disease may need to be reevaluated, according to long-term follow-up findings published in Clinical Science.

Patients (N=201) with confirmed keratoconus who were younger than age 40 years were recruited for this study at a center in Italy. Each patient underwent corneal tomography at baseline, 6, 12, 24, and 48 months. Structural and shape changes of the cornea were evaluated by calculating the average anterior and posterior curvature and thickness in four eye zones. The keratoconus cone zone was defined as the 3.1 mm2 area containing the maximum keratometry (Kmax). Standard progression criteria are defined as Kmax steeping of 1.0 D or more, or thinning of the minimum corneal thickness of 10 μm or more in the preceding year.

The patient population was comprised of 69 women or girls, and 132 men or boys who aged mean 28.2 (range, 15-37) years.

At baseline, the mean Kmax was 54.4±8.2 D, increasing to 54.8±6.6 D at the final follow-up (P >.05). Kmax increased by more than 1.0 D among 11% of patients at 4 years.

Changes in central corneal thickness and corneal thinnest point did not differ significantly from baseline to follow-up overall, however, 6% of patients had more than 10 μm of thinning throughout the study duration.

In time, the keratoconus cone zone gradually steepened from 49.6±4.5 to 50.7±5.3 D (P <.001), and by more than 1.0 D among 31% of patients. At the same time, the mirror-symmetric superior area of the anterior cornea steepened from 41.6±2.6 to 42.3±3.4 D (P <.01).

The zonal average thickness of the keratoconus cone area decreased from 496±43 to 482±40 μm (P <.001) and of the central area from 498±43 to 484±35 μm (P <.001).

In the 4 years, the changes in Kmax and central corneal thickness were correlated with the changes to the zonal average curvature (R, 0.98; P <.001) and thickness (R, 0.93; P =.01) of the keratoconus cone zone.

In an area under the receiver operating characteristic curve (AUC ROC) analysis, patients with progressive keratoconus were separated from those with stable disease by a cutoff of 1.00 D increase in Kmax spanning  a 4-year period (AUC ROC, 0.87). This cutoff had a positive predictive value (PPV) of 93% and negative predictive value (NPV) of 50%. Disease progression was also predicted by the average anterior curvature of the keratoconus cone zone (AUC ROC, 0.99; PPV, 98%; NPV, 100%).

These findings may not be generalizable among patients younger than 20 years of age, as age influences the rate of disease progression.

These data indicated that the change in corneal tomography data over time identified 3-times more patients who had progressive disease than a single assessment could. These findings may indicate that current keratoconus guidelines may need to be updated.


Lombardo G, Serrao S, Lombardo M. Long-term zonal average analysis of corneal tomography in keratoconus eyes. Cornea. Published online March 31, 2022. doi:10.1097/ICO.0000000000003016