Prognosis of Congenital Hereditary Endothelial Dystrophy (CHED)
Congenital hereditary endothelial dystrophy has a generally favorable prognosis with early surgical intervention, though visual outcomes may be limited by amblyopia and patients should be monitored for potential progressive sensorineural hearing loss if they have Harboyan syndrome.
Clinical Presentation and Diagnosis
- CHED is characterized by diffuse bilateral corneal opacity (edema) that is apparent at birth or within the neonatal period 1
- Symptoms include:
- Bilateral symmetrical progressive corneal cloudiness starting in early infancy
- Increased corneal thickness
- Profound corneal edema
- Thickening of the Descemet membrane due to endothelial dysfunction 2
- May be misdiagnosed as congenital glaucoma in some cases 3
- Genetic basis: Mutations in the SLC4A11 gene located on chromosome 20p13-p12, which encodes a membrane-bound sodium-borate cotransporter 4
- Inheritance pattern: Primarily autosomal recessive (CHED2), though autosomal dominant forms (CHED1) have been reported 1
Visual Outcomes
Without treatment, patients typically experience:
With corneal transplantation:
- Surgical success rates are favorable with 69-92% of grafts maintaining clarity 5, 3
- Visual improvement of at least 1 Snellen line occurs in approximately 50% of cases 5
- However, only about 40% of patients achieve visual acuity of 20/200 or better 5
- Earlier intervention may help mitigate amblyopia development
Treatment Options and Timing
Definitive treatment is corneal transplantation:
- Penetrating keratoplasty (PK) has been the traditional approach
- Descemet's Stripping Automated Endothelial Keratoplasty (DSAEK) is now preferred as it:
- Results in fewer complications
- Expedites visual recovery
- Helps mitigate amblyopia development 2
Timing of surgery:
- Should be determined on a case-by-case basis
- Early intervention is supported by:
- Threat of irreversible amblyopia in untreated eyes
- Good surgical success rates even in very young children
- However, delaying surgery may be appropriate in some less severe cases 5
Associated Conditions and Monitoring
- Harboyan syndrome: CHED with progressive, postlingual sensorineural hearing loss
- Hearing deficit typically becomes apparent between ages 10-25 years
- However, significant hearing loss can be detected in children as young as 4 years
- All patients with CHED2 should undergo audiometric monitoring
- Hearing aids may become necessary in adolescence 1
Neurodevelopmental Considerations
Children with congenital conditions often require developmental monitoring. For CHED patients:
Regular neurodevelopmental assessment should be considered, particularly for:
- Cognitive functioning
- Language and communication
- Motor skills
- Attention and executive functioning
- Social-emotional functioning 6
Periodic reevaluation at key developmental stages (12-24 months, 3-5 years, and 11-12 years) may be beneficial 7
Long-term Management
Post-transplantation management:
- In children, suture removal should begin approximately 3 months postoperatively 3
- Regular ophthalmological follow-up to monitor graft clarity and rejection
- Visual rehabilitation including correction of refractive errors and amblyopia therapy
Emerging treatments under investigation:
- Nonsteroidal anti-inflammatory agents targeting restoration of water-flux activity
- Gene editing using CRISPR-Cas9 technology 2
Prognostic Factors
- Earlier surgical intervention generally leads to better visual outcomes
- Parental consanguinity is associated with more than 50% of reported cases, suggesting potential genetic severity 1
- Presence of associated conditions (such as hearing loss in Harboyan syndrome) may affect overall prognosis and quality of life
The key to optimizing outcomes in CHED is early diagnosis, appropriate timing of surgical intervention, comprehensive management of associated conditions, and regular monitoring for developmental issues.