Purpose: To determine the rate at which clinically normal eyes in unilateral keratoconus (KC) patients progress to KC and to identify the risk factors that might predict the development of KC in a longitudinal study.
Design: Prospective observational study.
Participants: We recruited 778 patients with KC and 252 normal controls in Los Angeles, California. One hundred sixteen of 778 patients (14.9%) were diagnosed with clinically unilateral KC at baseline.
Methods: Both eyes of these unilateral KC patients were examined at baseline, and 85 patients were followed up with clinical evaluation and videokeratography for a period ranging from 6 months to 8 years.
Main outcome measures: Progression to clinical KC from previously normal fellow eyes. Quantitative and qualitative videokeratography variables, contact lens wear, and demographic variables were analyzed as potential predictive factors for this progression.
Results: During the follow-up period, 30 of 85 (35.3%) clinically normal fellow eyes had KC develop, and 25 of these 30 (83.3%) had KC develop within the first 6 years after the initial KC diagnosis. By use of the time period from the patients' first diagnosis of unilateral KC to the end of the follow-up period (range, 6 months-41 years), the median time (estimated from the survival analysis) to the development of KC was 16.7 years (95% confidence interval, 11.34, 28.91). Fellow eyes with higher inferior-superior dioptric asymmetry value (I-S) or KC percentage index (logKISA) values had higher risk for KC developing (I-S, risk ratio [RR] = 1.348, P = 0.022; log(KISA), RR = 4.245, P = 0.003). Asymmetric patterns also showed an increased risk for KC developing (P = 0.03), especially the asymmetric bowtie with skewed radial axes (AB/SRAX) pattern.
Conclusions: Approximately 50% of clinically normal fellow eyes will progress to KC within 16 years. The greatest risk is during the first 6 years of the onset. Quantitative indices (I-S and KISA values) and qualitative patterns (AB/SRAX) might predict this progression.