Microphthalmia, anophthalmia, and coloboma and associated ocular and systemic features: understanding the spectrum

JAMA Ophthalmol. 2013 Dec;131(12):1517-24. doi: 10.1001/jamaophthalmol.2013.5305.

Abstract

Importance: Microphthalmia, anophthalmia, and coloboma form an interrelated spectrum of congenital eye abnormalities.

Objective: To document the ocular and systemic findings and inheritance patterns in patients with microphthalmia, anophthalmia, and coloboma disease to gain insight into the underlying developmental etiologies.

Design, setting, and participants: This retrospective consecutive case series was conducted at a tertiary referral center. Included in the study were 141 patients with microphthalmia, anophthalmia, and coloboma disease without a recognized syndromic etiology who attended the Westmead Children's Hospital, Sydney, from 1981-2012.

Exposure: Cases were grouped on the basis of the presence or absence of an optic fissure closure defect (OFCD); those with OFCD were further subdivided into microphthalmic and nonmicrophthalmic cases. Anophthalmic cases were considered as a separate group.

Main outcomes and measures: Associated ocular and systemic abnormalities and inheritance patterns were assessed.

Results: Of 141 cases, 61 (43%) were microphthalmic non-OFCD (NOFCD), 34 (24%) microphthalmic OFCD, 32 (23%) nonmicrophthalmic coloboma (OFCD), 9 (6%) anophthalmic, and 5 (4%) were unclassified. Sixty-three (45%) had bilateral disease. Eighty-four patients (60%) had an associated ocular abnormality; of these, cataract (P < .001) and posterior segment anomalies (P < .001) were most common in the NOFCD group. Forty-eight (34%) had an associated systemic abnormality, most commonly neurological, musculoskeletal and facial, urological and genital, or cardiac. Neurological abnormalities were most common in the anophthalmic group (P = .003), while urological abnormalities were particularly seen in the OFCD groups (P = .009). Familial cases were identified in both the OFCD and NOFCD groups, with a likely autosomal dominant inheritance pattern in 9 of 10 families.

Conclusions and relevance: This series indicated that the OFCD/NOFCD distinction may be useful in guiding evaluation for ocular and systemic associations, as well as the direction and analysis of genetic investigation.

MeSH terms

  • Anophthalmos / complications
  • Anophthalmos / diagnosis*
  • Anophthalmos / genetics
  • Anterior Eye Segment / abnormalities
  • Cataract / complications
  • Cataract / diagnosis
  • Cataract / genetics
  • Child
  • Child, Preschool
  • Coloboma / complications
  • Coloboma / diagnosis*
  • Coloboma / genetics
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Inheritance Patterns
  • Male
  • Microphthalmos / complications
  • Microphthalmos / diagnosis*
  • Microphthalmos / genetics
  • Ocular Motility Disorders / complications
  • Ocular Motility Disorders / diagnosis
  • Ocular Motility Disorders / genetics
  • Retrospective Studies