Updates on congenital hereditary endothelial dystrophy

Abstract

Congenital hereditary endothelial dystrophy (CHED) is a rare genetic corneal disorder causing progressive cornea clouding and significant visual impairment. CHED remains a leading indication for pediatric corneal transplantation despite its infrequency, particularly in regions with high consanguinity rates like Southeast Asia. Identifying the Solute Carrier Family 4 Member 11 (SLC4A11) gene as the genetic basis of CHED has led to the discovery of it's various genetic variations. However, a comprehensive understanding of its clinical-genetic correlation, pathophysiology, and optimal management is ongoing. This review aims to consolidate current knowledge about CHED, covering its genetic origins, pathophysiological mechanisms, clinical presentation, and management strategies. Surgical intervention, such as penetrating keratoplasty (PK), Descemet stripping automated endothelial keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK), remains the primary treatment. DSAEK and DMEK offer advantages over PK, including quicker visual recovery, reduced complications, and longer graft survival, especially in the pediatric age group. The timing of surgical interventions depends on disease severity, age at presentation, comorbidities, and visual potential. Elevated oxidative stress in CHED corneal tissue suggests potential benefits from anti-inflammatory drugs to rescue mutated endothelial cells. Considering the limitations of corneal graft surgeries, exploring novel gene-based molecular therapies are essential for future management. Early diagnosis, appropriate surgical interventions, amblyopia control, and genetic counseling for predictive analysis are pivotal for optimizing CHED management. A multidisciplinary approach involving ophthalmologists, researchers, and genetic counselors is essential for precise diagnosis and optimal care for CHED patients.

Keywords: Congenital hereditary endothelial dystrophy; Solute Carrier Family 4 Member 11 (SLC4A11); corneal endothelial dystrophies in childhood.

Figure 1

Congenital hereditary endothelial dystrophy 1 (CHED1) autosomal dominant and CHED2 autosomal recessive initially linked to a 2.7 centimorgan (cM) interval on chromosome 20. CHED 2 locus was excluded later and positioned between markers D20S113 and D20S882 within an 8 cM interval on chr. 20p13, and further delineated to identify Solute Carrier Family 4 Member 11 as a candidate gene

Figure 2

Histopathological image of hematoxylin and eosin stained corneal button of congenital hereditary endothelial dystrophy patient, post penetrating keratoplasty (right) and comparison to its anterior segment optical coherence tomography image (left). Image showing involvement of all layers with fragmentation noted at the Bowman membrane (white arrow head) and thickened Descemet membrane (white arrow)

Figure 3

Slit lamp photographs. (a) Congenital hereditary endothelial dystrophy (CHED) with grey-white ground glass corneal opacity, (b) mucopolysaccharidosis Type IH (Hurler’s syndrome) with normal corneal thickness as seen on the slit beam, (c) Congenital hereditary stromal dystrophy with corneal opacity and a normal epithelium, (d) Primary congenital glaucoma with large horizontal corneal diameter and presence of Haab’s stria, (e) Posterior polymorphous corneal dystrophy (PPCD) showing thickening and opacity at Descemet membrane and endothelial layer, (f) CHED with large central epithelial bulla

Figure 4

Shows the slit-lamp biomicroscopy photographs. (a) Congenital hereditary endothelial dystrophy (CHED) with the ground-glass appearance of the cornea with the slit beam suggestive of increased corneal thickness, (b) Mucopolysaccharidosis Type IH (Hurler’s Syndrome) with corneal cloudiness with slit beam suggesting a normal corneal thickness, (c) Anterior segment optical coherence tomography showing CHED with a thickened epithelial layer with underlying irregular Bowman membrane, increased stromal thickness, and abnormally thickened Descemet membrane, (d) Hurler’s syndrome with a thickened corneal stromal layers and hyperreflective stroma

Figure 5

Subjective grading of corneal cloudiness into (a), mild (c), moderate (e) severe; with corresponding densitometry shown, respectively, in images labelled as (b, d and f)