Elsevier

Ophthalmology

Volume 126, Issue 7, July 2019, Pages 935-945
Ophthalmology

Original Article
Keratoconus Natural Progression: A Systematic Review and Meta-analysis of 11 529 Eyes

https://doi.org/10.1016/j.ophtha.2019.02.029Get rights and content

Purpose

We set out to describe the natural history of keratoconus. We included untreated patients, and our key outcome measures were vision, refraction, and corneal curvature.

Clinical Relevance

Keratoconus affects 86 in 100 000 people, causing visual loss due to increasing irregular corneal astigmatism, and the quality of life declines in patients. Interventions are used to stabilize the disease or improve vision, including corneal cross-linking (CXL) and grafting, but these carry risks. Detailed knowledge of the natural history of keratoconus is fundamental in making informed decisions on when their benefits outweigh these risks.

Methods

We included prospective or retrospective studies of pediatric or adult patients who reported 1 or more of visual acuity, refraction, and corneal curvature measures: steep keratometry (K2), mean keratometry (Kmean), or maximum keratometry (Kmax), thinnest pachymetry, corneal transplantation rates, corneal scarring incidence, and patient-reported outcome measures (PROMs). Databases analyzed included Medline, Embase, CENTRAL, and CINAHL. Searches were carried out until October 2018. Bias assessment was carried out using the Joanna Briggs Institute model of evidence-based healthcare.

Results

Our search yielded 3950 publication titles, of which 41 were included in our systematic review and 23 were incorporated into the meta-analysis. Younger patients and those with greater Kmax demonstrated more steepening of Kmax at 12 months. The meta-analysis for Kmax demonstrated a significant increase in Kmax of 0.7 diopters (D) at 12 months (95% confidence interval [CI], 0.31–1.14; P = 0.003). Our meta-regression model predicted that patients had 0.8 D less Kmax steepening over 12 months for every 10-year increase in age (P = 0.01). Patients were predicted to have 1 D greater Kmax steepening for every 5 D of greater baseline Kmax (P = 0.003). At 12 months, there was a significant increase in the average Kmean of 0.4 D (95% CI, 0.18–0.65; P = 0.004).

Conclusions

We report the first systematic review and meta-analysis of keratoconus natural history data including 11 529 eyes. Younger patients and those with Kmax steeper than 55 D at presentation have a significantly greater risk of progression of keratoconus. Closer follow-up and a lower threshold for cross-linking should be adopted in patients younger than 17 years and steeper than 55 D Kmax.

Section snippets

Inclusion Criteria

Prospective or retrospective studies including patients with untreated keratoconus. One or more outcome measure(s), including visual acuity: best-corrected visual acuity (BCVA) or uncorrected visual acuity (UCVA), refraction, corneal curvature measures: steep keratometry (K2), mean keratometry (Kmean), or maximum keratometry (Kmax), thinnest pachymetry, corneal transplantation rates, corneal scarring incidence, and patient-reported outcome measures (PROMs). Studies including 10 or more patients

Study Selection

Our search yielded 3950 publication titles, of which 41 were included in our systematic review and 23 were incorporated into the meta-analysis. The study selection process is shown in Figure 1. The experimental and patient characteristics of included studies are outlined in Table 1.25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61

Study Quality

Five of the 41 studies included in the systematic review were RCTs,

Discussion

We report a systematic review and meta-analysis of keratoconus natural history data including 11 529 eyes from 41 publications. Our meta-analysis of 12-month outcomes found that younger patients progress more aggressively: patients younger than 17 years old are likely to have more than 1.5 D of Kmax progression. Patients with steeper Kmax demonstrated more severe progression: patients with greater than 55 D Kmax are likely to progress by at least 1.5 D Kmax; in addition, Middle Eastern patients

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  • Cited by (0)

    Supplemental material available at www.aaojournal.org.

    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    A.C.F.: Support – Northcote Scholarship.

    S.L.W.: Support – Sydney Medical School Foundation.

    HUMAN SUBJECTS: No human subjects were included in this study. IRB/Ethics Committee ruled that approval was not required for this study. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.

    No animal subjects were used in this study.

    Author Contributions:

    Conception and design: Ferdi, Nguyen, Gore, Allan, Rozema, Watson

    Analysis and interpretation: Ferdi, Nguyen, Gore, Allan, Rozema, Watson

    Data collection: Ferdi

    Obtained funding: N/A

    Overall responsibility: Ferdi, Nguyen, Gore, Allan, Rozema, Watson

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