Ocular characteristics and complications in patients with osteogenesis imperfecta: a systematic review

Abstract

Purpose: Osteogenesis imperfecta (OI) is a rare inherited heterogeneous connective tissue disorder characterized by bone fragility, low bone mineral density, skeletal deformity and blue sclera. The dominantly inherited forms of OI are predominantly caused by mutations in either the COL1A1 or COL1A2 gene. Collagen type I is one of the major structural proteins of the eyes and therefore is the eye theoretically prone to alterations in OI. The aim of this systematic review was to provide an overview of the known ocular problems reported in OI.

Methods: A literature search (in PubMed, Embase and Scopus), which included articles from inception to August 2020, was performed in accordance with the PRISMA guidelines.

Results: The results of this current review show that almost every component of the eye could be affected in OI. Decreased thickness of the cornea and sclera is an important factor causing eye problems in patients with OI such as blue sclera. Findings that stand out are ruptures, lacerations and other eye problems that occur after minor trauma, as well as complications from standard surgical procedures.

Discussion: Alterations in collagen type I affect multiple structural components of the eye. It is recommended that OI patients wear protective glasses against accidental eye trauma. Furthermore, when surgery is required, it should be approached with caution. The prevalence of eye problems in different types of OI is still unknown. Additional research is required to obtain a better understanding of the ocular defects that may occur in OI patients and the underlying pathology.

Keywords: collagen alteration; collagen type I; eye disease; ophthalmology; osteogenesis imperfecta.

Fig. 1

Schematic presentation of COL1A1 and COL1A2 genes and the production of collagen type I molecules. COL1A1 codes for two pro‐α1 chains and COL1A2 codes for one pro‐α2 chain. Two pro‐α1 and one pro‐α2 chains combine to a triple helix. After extensive post‐translational modifications, the mature collagen type I is formed. A quantitative collagen defect can be produced by gene deletions by which the produced collagen type I is reduced to 50%; this usually leads to mild OI (type I). A quantitative collagen defect can be caused by mutations affecting the collagen type I folding; these usually lead to more severe OI forms (type II, III and IV). Qualitative defects delay the folding of collagen leading to excessive post‐translational modification; this can lead to lower packing density of collagen molecules in the fibril dysregulating mineralization. In the case of quantitative defects, some level of increased overmodification can be also potentially expected due to the increased ratio of collagen‐modifying enzymes to collagen but the consequences of that remain unclear. Created with BioRender.com.

Fig. 2

Prisma diagram of study selection process.