BASICS
DESCRIPTION
- Fuchs (pronounced Fooks) endothelial corneal dystrophy is a bilateral, progressive, noninflammatory disease of the eye characterized by corneal endothelial dysfunction, leading to corneal edema and blurred vision.
- Keratoplasty (full- or partial-thickness corneal transplant) is the definitive management step for restoration of vision.
EPIDEMIOLOGY
- Typically presents in the 5th and 6th decades, with rare early-onset Fuchs dystrophy in the 1st decade of life
- The leading indication for corneal transplant in the United States
- Accounts for >15,000 cases of keratoplasty in the most recent year (1)
Incidence
Unknown
Prevalence
- 5% of the U.S. population >40 years old (2)
- Women appear more susceptible than men, 3 to 4:1 (3)
ETIOLOGY AND PATHOPHYSIOLOGY
- The cornea provides 74% of the refractive power of the human eye and is composed of 5 layers: epithelium, Bowman layer, stroma, Descemet membrane, and endothelium.
- The endothelium provides vital barrier and ion transport functions, enabled by Na+/K+ ATPase pumps, which regulate corneal hydration and transparency.
- Attrition of endothelial cells accompanies normal aging: Endothelial cell density averages 2,400 cells/mm2 in adults, contrasted with 6,000 cells/mm2 in infants.
- Endothelial cell density is also adversely impacted by intraocular insults, notably cataract surgery and elevated intraocular pressure.
- In Fuchs dystrophy, endothelial stress manifests as endothelial cell morphologic changes and decreased cellular density, abnormal deposition of collagen and extracellular matrix in Descemet membrane, resulting in progressive stromal edema.
- Changes in Descemet membrane can be visualized microscopically as thickening and characteristic anvil-shaped refractive granules known as guttae (Latin: drops) which are first visible in the central cornea and spread progressively toward the periphery.
- As endothelial barrier and ion transport functions are increasingly overwhelmed, endothelial cell attrition accelerates and the central cornea becomes grossly thickened.
- Epithelial edema develops late in the disease course, associated with painful epithelial bullae, subepithelial fibrosis, and superficial corneal neovascularization.
Genetics
- Most commonly presents without known inheritance (category 3)
- Late-onset familial and sporadic cases less commonly are linked to genetic loci (category 2)
- 13pTel-13q12.13, 15q, 18q21.2-q21.32
- Complex and heterogeneous genetic inheritance, with at least 21 distinct loci under investigation (3)
- Early-onset variant genetic locus (category 1)
- 1p34.3-p32, associated with collagen type VIII α2 (COL8A2) gene
- Inheritance patterns are autosomal dominant with incomplete penetrance.
- A strong correlation between clinical severity of known disease and expansion of CTG repeats has been reported on 18q21.2, at the locus coding for the widely expressed transcription factor TCF4, but its role in pathogenesis remains unclear (2)[B]
RISK FACTORS
- Age >50 years
- Female gender
- Elevated intraocular pressure
- Ocular inflammation
- Family history of Fuchs dystrophy
COMMONLY ASSOCIATED CONDITIONS
- Bullous keratopathy
- Angle-closure glaucoma
- Open-angle glaucoma
- Cataracts
DIAGNOSIS
HISTORY
- Blurred vision, particularly with halos, glare, or a foggy appearance often worse upon awakening
- Eye pain and/or photophobia
- Epiphora (excessive tearing) from corneal bullae or erosions
- Past history of glaucoma or uveitis
- Previous ocular surgery, particularly cataract surgery
PHYSICAL EXAM
- Slit-lamp examination
- Direct illumination and retroillumination reveal central cornea guttae in early stages of disease.
- Visualization of guttae in the peripheral cornea suggests later stages of disease, often with guttate pigmentation and thickening of Descemet membrane together described as a "beaten metal"ť appearance.
- Corneal edema initially is confined to the posterior stroma.
- Advanced disease is indicated by folds in Descemet membrane from stromal edema, epithelial bullae, and superficial neovascularization.
- Measurement of intraocular pressure and dilated fundus examination are indicated to assess for associated conditions.
DIAGNOSTIC TESTS & INTERPRETATION
- Corneal pachymetry to measure central corneal thickness
- Normal corneal thickness is 520 to 560 microns, >620 microns suggests Fuchs dystrophy.
- In the setting of profound endothelial dysfunction and advanced disease, corneal thickness can approach 1,000 microns.
- Corneal central-to-peripheral thickness ratio increases as disease advances and has been suggested as an objective means to distinguish between a normal cornea, mild to moderate disease, and advanced Fuchs dystrophy (4).
- Specular microscopy to assess endothelial cell count, morphology, and density and to measure guttae
TREATMENT
GENERAL MEASURES
- No treatment is recommended if asymptomatic.
- Initial treatment aims to relieve pain and reduce corneal edema.
- Use of a hair dryer held at arm's length for 5 to 10 minutes upon awakening may help dehydrate the cornea and transiently ameliorate symptoms.
- Supportive care for epithelial bullae can be provided by use of a soft bandage contact lens. In the setting of ruptured epithelial bullae, the risk of corneal ulcer is increased.
MEDICATION
- Hypertonic agents are first-line therapy.
- Topical 5% hypertonic saline eye drops are instilled (1 drop QID) during the day to increase the osmolarity of the tear film. Hypertonic sodium chloride ointment is applied at bedtime (5)[C].
- No contraindications
- Lowering the intraocular pressure (IOP) may be useful as an adjunctive therapy.
- If IOP is>20 to 22 mm Hg, lower the IOP with antiglaucoma medications such as topical timolol 0.5% BID if there are no systemic contraindications.
- Topical carbonic anhydrase inhibitors drops should be avoided, as they impair endothelial pump activity.
- Medical therapies are employed to palliate symptoms until corneal transplantation.
ISSUES FOR REFERRAL
- Corneal ulcer
- Worsening vision
SURGERY/OTHER PROCEDURES
- Palliative procedures indicated for pain relief alone include anterior stromal puncture and use of a conjunctival flap.
- Vision restoration requires full- or partial-thickness corneal transplant.
- For decades, the only method to restore corneal transparency was penetrating (full-thickness) keratoplasty.
- Visual outcomes are generally good, with 40-50% of patients achieving 20/40 best corrected visual acuity or better at 1 year postoperatively.
- Despite postoperative complications which include wound dehiscence, high astigmatism, and graft rejection, graft survival at 5 years in excess of 75% (6)[B].
- Penetrating keratoplasty remains a favorable option for patients with complications of advanced Fuchs dystrophy, such as central anterior corneal scarring or subepithelial fibrosis.
- Since their introduction in 2004, partial-thickness endothelial keratoplasty techniques have overtaken penetrating keratoplasty as the predominant procedure for patients with endothelial dysfunction due to their favorable complication profile and excellent prognosis.
- Endothelial keratoplasty techniques retain the native anterior cornea, minimizing postoperative changes in refraction, accelerating postoperative visual rehabilitation, and markedly reducing the risk of allograft rejection.
- In Descemet stripping endothelial keratoplasty (DSEK/DSAEK), visual outcomes are consistent with PK, with >50% of patients achieving 20/40 best corrected visual acuity or better at 6 months postoperatively but with a superior graft survival rate of 93% (5)[C].
- Descemet membrane endothelial keratoplasty (DMEK) is considered the most advanced technique and yields superior visual outcomes with 95% of patients achieving 20/40 best corrected visual acuity or better at 6 months, and with a graft survival rate of 97% at 5 and 8 years. (6)[B].
- The next generation of therapy, currently under investigation, includes "nonkeratoplasty"ť techniques such as Descemet membrane endothelial transfer (DMET) to the anterior chamber of the recipient eye without surgical implantation, or removal of central Descemet membrane without allograft, or use of an investigational Rho-associated kinase inhibitor (ROCK inhibitor) to facilitate native endothelial regeneration (5)[C].
ONGOING CARE
PATIENT EDUCATION
- Fuchs dystrophy is a chronic, progressive condition.
- Hypertonic saline drops can slow or halt progression in some cases.
- Hypertonic saline drops sting the eyes when applied, and patients should be reassured that this is normal.
- Hypertonic saline ointment generally does not sting but can cause significant blurring of vision after it is applied. Therefore, it is recommended to be applied at bedtime.
- Corneal edema increases while sleeping due to decreased evaporation from the surface of the eyes when the eyelids are closed. Therefore, vision is predictably worse in the morning.
- A cataract operation can worsen underlying endothelial dysfunction, and keratoplasty can worsen cataracts. Therefore, concurrent cataract extraction and keratoplasty should be considered.
PROGNOSIS
- Fuchs dystrophy worsens slowly over time.
- Endothelial cell loss predictably occurs following intraocular surgery.
- Prognosis following penetrating keratoplasty is good: Corrected visual acuity of 20/40 or better can be attained in half of patients, and graft survival is 75% or better at 5 years.
- Prognosis following endothelial keratoplasty is even better: Visual acuity is 20/40 or better in 50-95% of patients, and graft survival is over 90% at 5 years.
COMPLICATIONS
- Painful bullous keratopathy
- Corneal ulceration
- Infectious keratitis
- Progressive vision loss
- Postkeratopathy complications (above)
REFERENCES
11 Park CY, Lee JK, Gore PK, et al. Keratoplasty in the United States: a 10-year review from 2005 through 2014. Ophthalmology. 2015;122(12):2432-2442.22 Soliman AZ, Xing C, Radwan SH, et al. Correlation of severity of Fuchs endothelial corneal dystrophy with triplet repeat expansion in TCF4. JAMA Ophthalmol. 2015;133(12):1386-1391.33 OĹ‚dak M, Ruszkowska E, Udziela M, et al. Fuchs endothelial corneal dystrophy: strong association with rs613872 not paralleled by changes in corneal endothelial TCF4 mRNA level. Biomed Res Int. 2015;2015:640234.44 Repp DJ, Hodge DO, Baratz KH, et al. Fuchs' endothelial corneal dystrophy: subjective grading versus objective grading based on the central-to-peripheral thickness ratio. Ophthalmology. 2013;120(4):687-694.55 Fern ˇndez L łpez E, Lam CF, Bruinsma M, et al. Fuchs endothelial corneal dystrophy: current treatment recommendations and experimental surgical options. Exp Rev Ophthalmol. 2015;10(3):301-312.66 Baydoun L, Ham L, Borderie V, et al. Endothelial survival after Descemet membrane endothelial keratoplasty: effect of surgical indication and graft adherence status. JAMA Ophthalmol. 2015;133(11):1277-1285.
ADDITIONAL READING
- Amin SR, Baratz KH, McLaren JW, et al. Corneal abnormalities early in the course of Fuchs' endothelial dystrophy. Ophthalmology. 2014;121(12):2325-2333.
- Hamill CE, Schmedt T, Jurkunas U. Fuchs endothelial cornea dystrophy: a review of the genetics behind disease development. Semin Ophthalmol. 2013;28(5-6):281-286.
- Hamzaoglu EC, Straiko MD, Mayko ZM, et al. The first 100 eyes of standardized Descemet stripping automated endothelial keratoplasty versus standardized Descemet membrane endothelial keratoplasty. Ophthalmology. 2015;122(11):2193-2199.
- Iliff BW, Riazuddin SA, Gottsch JD. The genetics of Fuchs' corneal dystrophy. Expert Rev Ophthalmol. 2012;7(4):363-375.
- Sugar A, Gal RL, Kollman C, et al. Factors associated with corneal graft survival in the cornea donor study. JAMA Ophthalmol. 2015;133(3):246-254.
- Watanabe S, Oie Y, Fujimoto H, et al. Relationship between corneal guttae and quality of vision in patient with mild Fuchs' endothelial corneal dystrophy. Ophthalmology. 2015;122(10):2103-2109.
CODES
ICD10
H18.51 Endothelial corneal dystrophy
ICD9
371.57 Endothelial corneal dystrophy
SNOMED
Fuchs' corneal dystrophy
CLINICAL PEARLS
- Fuchs' endothelial corneal dystrophy is a bilateral, progressive, noninflammatory disease of the eye.
- Patients may complain of slowly progressive blurred vision, haze, halos, or glare that is worst upon awakening from sleep.
- Hypertonic saline drops can be used to ameliorate symptoms; corneal transplant is curative.