A recent study published in Cornea assessed the natural progression of keratoconus (KC) with respect to age, gender, and disease severity at presentation.
Give me some background.
KC is a progressive ectatic corneal disease characterized by thinning and conical protrusion that typically manifests during adolescence and becomes clinically evident in the second or third decade of life.
The rate of disease progression is generally higher in younger individuals, as 77% to 88% of pediatric patients with KC exhibit signs of progression, and 17% develop corneal scarring and significant visual morbidity.
- However: Previous studies have indicated that disease progression can also occur in older individuals (< 48 years) with advanced KC.
The study authors noted that in spite of the above-mentioned findings, there is a limited number of studies investigating the risk of KC progression across different age groups.
Now let’s get into the research.
In this retrospective analysis, investigators included 949 eyes from 503 patients (53.9% male) with KC who presented to the Eskişehir Osmangazi University in Eskişehir, Turkey and Istanbul University–Cerrahpaşa in Istanbul, Turkey, between 2009 and 2023.
Patients with ≥ 1 year of follow-up and ≥ 3 Pentacam (OCULUS) scans spaced ≥ 3 months apart were included in the analysis.
How was KC progression measured?
KC progression was identified using the Belin ABCD Progression Display using two baseline visits.
- Median time-to-progression (M-TTP) for progressive eyes was calculated with reference to the first presentation.
Plus: Progression rates were analyzed according to age groups and KC severity as follows:
- Age groups
- ≤ 18 years
- > 18 to ≤ 24 years
- > 24 to ≤ 30 years
- > 30 to < 35 years
- ≥ 35 years
- KC severity (based on Topographic KC Classification [TKC] in Pentacam imaging software)
- Subclinical
- Early stage (TKC 1-2)
- Advanced stage (TKC 3-4)
Findings?
Overall, disease progression was observed in 55.3% of cases, and KC progression rates declined significantly with age (P < 0.001).
However: In patients aged ≥ 35 years, 44.3% still showed progression, with the highest rate in those ≤ 18 years (86.4%).
And for the older age group?
In patients ≥ 35 years, advanced-stage disease (TKC 3 and 4) markedly increased progression risk (odds ratio [OR]: 10.5, P = 0.03 and OR: 20.0, P = 0.008, respectively).
Across all TKC stages: The highest progression was in the < 18 years group, particularly in those with advanced disease (91.7%).
What about the time-to-progression?
The shortest time-to-progression occurred in patients aged ≤ 18 years (M-TTP: 8.6 and 5.8 months in TKC 1-2 and 3-4, respectively).
Conversely: In those aged ≥ 35 years, advanced-stage disease progressed significantly sooner than early-stage (M-TTTP: 18.9 vs. 38.2 months).
Anything else?
The progression rate in men (56.1%) was comparable to that in women (54.3%).
Bilateral progression was most common in patients aged < 18 years (50%), but showed no significant distribution across age groups (P = 0.352).
Expert opinion?
In line with the findings from this study, the study authors noted that the literature also supports that patients with a steeper initial maximum keratometry exhibit a higher likelihood of progression.
In fact: A meta-analysis reported that for every 5 diopters (D) of greater baseline maximum keratometry, an additional 1 D increase in steepening was observed.
Limitations?
These included:
- Bilateral corneal tomographic data was not available for all patients
- The Belin ABCD progression criteria may be prone to overdiagnosing KC progression compared with other conventional metrics, such as Kmax
- There was a shift in clinical decision-marking during the study period, leading to mandatory referral for corneal cross-linking (CXL) in patients < 18 years of age, regardless of documented progression at both centers
- Thus: Pediatric patients included in this study represent cases from a period preceding the adoption of this practice
Take home.
These findings suggest that while KC progression typically slows with age, 44% of patients ≥ 35 years still progressed.
The shorter time-to-progression in younger individuals and in older patients with advanced disease at presentation highlight the need for close monitoring in both groups.