Macular Corneal Dystrophy

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Background

Macular corneal dystrophy (MCD) is a rare but severe stromal corneal dystrophy. Macular corneal dystrophy is an IC3D category 1 dystrophy and is an autosomal-recessive condition. It is characterized by multiple irregular gray-white opacities in the corneal stroma that extend out into the peripheral cornea and down to the Descemet membrane.

Corneal dystrophy is defined as a bilateral noninflammatory clouding of the cornea, the clear outer layer of the front of the eye. Corneal dystrophies can be placed into categories based on their location within the cornea and their etiologies, as follows:[1]

Whereas macular corneal dystrophy is now classified as a stromal corneal dystrophy, granular and lattice corneal dystrophies are now classified as epithelial-stromal TGFBI dystrophies owing to their involvement in multiple layers of the cornea.[1] The age of onset for most corneal dystrophies is less than 20 years (exceptions include map-dot-fingerprint dystrophy and Fuchs corneal dystrophy). Patients with macular corneal dystrophy tend to have more severe vision loss earlier than patients with lattice or granular dystrophy; however, macular corneal dystrophy is less common than both lattice and granular dystrophies.

Most corneal dystrophies are inherited in an autosomal-dominant pattern. Exceptions that are autosomal recessive include macular corneal dystrophy and congenital hereditary endothelial dystrophy (CHED) (previously known as autosomal recessive CHED2, differentiated from autosomal dominant CHED1, which has been eliminated owing to its similarity to posterior polymorphous corneal dystrophy).[1]

Macular corneal dystrophy, unlike granular corneal dystrophy, has no clear areas between opacities.[2] Opacities usually first appear in adolescence but may become apparent anytime from early infancy to the sixth decade of life. Affected individuals usually experience severe visual impairment before the fifth decade of life once opacities have coalesced and the entire stroma becomes cloudy.[3] Examples of macular dystrophy are shown in the images below.



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Macular dystrophy. Image courtesy of James J. Reidy, MD, FACS, Associate Professor of Ophthalmology, State University of New York, School of Medicine ....



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Macular dystrophy.

Pathophysiology

The metabolic defect for macular corneal dystrophy appears to be an error in the synthesis of keratan sulfate, which leads to accumulation of glycosaminoglycans in the cornea. Subgroups of macular dystrophy can be identified by immunohistochemical methods. Keratan sulfate was not detected in the serum of patients with histopathologically confirmed macular corneal dystrophy. Because keratan sulfate in the serum appears to be predominantly derived from the normal turnover of cartilage,[4] these studies strongly suggest that the defect in keratan sulfate synthesis in macular corneal dystrophy is not restricted to corneal cells and that this condition is one manifestation of a systemic disorder of keratan sulfate.

Epidemiology

Frequency

United States

Macular corneal dystrophy is uncommon, but areas with the highest prevalence include parts of the United States.

International

Although relatively uncommon, macular corneal dystrophy is most prevalent in India, Saudi Arabia, Iceland, and parts of the United States.[3]

Mortality/Morbidity

Corneal changes become visible in the first decade of life. A significant reduction in vision usually occurs by age 20-40 years. Patients can develop decreased corneal sensitivity. Eye pain due to recurrent corneal erosions is rare is much less common than in patients with lattice or granular corneal dystrophies.

Sex

No sexual predilection has been reported.

Age

Corneal changes become visible in the first decade of life; vision may be significantly reduced by age 20-40 years.

Prognosis

Of all the stromal corneal dystrophies, macular corneal dystrophy results in the earliest visual loss. This visual loss is due to the lack of clear spaces between the denser gray-white macular opacities.

Symptomatic patients are eligible for either excimer laser phototherapeutic keratectomy (PTK) when the bulk of the opacity is superficial or, more commonly, corneal transplantation.

History

In many patients, macular corneal dystrophy (MCD) is first visible in the cornea during the first decade of life. Visual acuity decreases over time, and patients develop photosensitivity. They may also experience eye pain from recurrent corneal erosions.

Causes

Macular corneal dystrophy is autosomal recessive. The gene responsible for macular dystrophy is CHST6 (carbohydrate sulfotransferase 6 gene), located on chromosome 16.

The metabolic defect for this condition appears to be an error in the synthesis of keratan sulfate, which leads to accumulation of glycosaminoglycan in the cornea. Three variants of macular corneal dystrophy exist based on the immunoreactivity of the macular deposits. Macular corneal dystrophy type I has no keratan sulfate reactivity in the cornea or serum. Macular corneal dystrophy type IA has keratan sulfate reactivity in keratocytes but not in serum. Macular corneal dystrophy type II has keratan sulfate reactivity in the cornea, and the serum has normal or low levels of keratan sulfate.[2]

Physical Examination

Macular dystrophy is characterized by multiple irregular gray-white opacities that are present in the corneal stroma and extend into the peripheral cornea. This is in contrast to granular corneal dystrophy, in which the deposits are located centrally. As the gray-white opacities develop in macular corneal dystrophy, a diffuse haze simultaneously progresses to involve the entire corneal stroma. The lack of clear spaces between stromal opacities differentiates macular corneal dystrophy from granular corneal dystrophy, in which there are usually clear zones between opacities.[1] The corneal epithelium is typically unaffected; however, it can develop corneal erosions. In advanced disease, corneal endothelium and the Descemet membrane may be affected.[2]

Macular corneal dystrophy involves the entire thickness of the corneal stroma and is more superficial centrally and deeper peripherally. The central cornea in this condition may be thinned. Significant cornea guttata may be present in severe disease, although endothelial decompensation is very rare.[1]

Complications

Complications of macular corneal dystrophy include photophobia, loss of vision, and, less commonly, recurrent corneal erosions.

Procedures

Corneal biopsy, which is not clinically indicated in patients with macular corneal dystrophy (MCD), reveals deposits of glycosaminoglycans, which stain with Alcian blue and colloidal iron.

Histologic Findings

Deposits in macular dystrophy are composed of glycosaminoglycans, which stain with Alcian blue and colloidal iron.

Light microscopy demonstrates glycosaminoglycan deposits within stromal keratocytes. Thickening of the Descemet membrane can be seen, in addition to guttata.[1]

Two types of macular dystrophy are noted based on the absence or presence of keratan sulfate within the corneal stroma. Corneas affected by macular corneal dystrophy type I lack keratan sulfate, whereas keratan sulfate is present in corneas of patients with macular corneal dystrophy type IA and II.[2]

Imaging Studies

Anterior-segment optical coherence tomography (OCT) reveals stromal hyper-reflectivity in areas that correspond to the stromal opacities.

Medical Care

When recurrent corneal erosions occur with macular corneal dystrophy (MCD), they are treated like any other form of recurrent corneal erosion. Under the care of an ophthalmologist, frequent application of an antibiotic ointment can be used. Alternatively, bandage contact lens along with topical antibiotics can be prescribed.

Once the acute episode of recurrent corneal erosions has resolved, preventive treatment may include sodium chloride 5% drops (eg, Muro 128) or artificial tear lubricating drops during the day and sodium chloride 5% ointment (eg, Muro 128) or lubricating ointment at bedtime.

Sunglasses are often helpful for severe glare symptoms.

Surgical Care

If recurrent corneal erosions occur despite medical therapy, excimer laser phototherapeutic keratectomy (PTK) may be considered in early cases of macular corneal dystrophy.[5] The excimer laser removes superficial corneal opacities, smooths the corneal surface, and allows the epithelium to re-adhere more tightly. However, macular corneal dystrophy tends to recur quickly and at a high rate after PTK,[6] making it less suitable for PTK than lattice or granular corneal dystrophy.

If visual acuity worsens and the opacities are deep, lamellar or full-thickness corneal transplantation can be performed. Although the success rate for corneal transplantation is high, macular corneal dystrophy deposits can recur with time and tend to recur at a higher rate in grafts of patients with macular corneal dystrophy than in grafts of patients with lattice or granular corneal dystrophies.[5]

Both deep anterior lamellar keratoplasty (DALK) and full-thickness penetrating keratoplasty (PKP) are viable options for the treatment of macular corneal dystrophy. DALK is associated with a higher risk of recurrence, while PKP is associated with a larger decrease in endothelial cell count and higher rate of graft failure due to endothelial rejection.[7, 8]

The use of fibrin glue in lamellar therapeutic keratectomy for the treatment of anterior corneal opacities has been assessed as safe and effective for attachment. However, the technique needs to be refined for ease and safety.[9]

Long-Term Monitoring

Patients with epithelial defects from recurrent corneal erosions need to be observed every few days to ensure that defects are healing.

Inpatient & Outpatient Medications

Patients with epithelial defects from recurrent corneal erosions are treated with topical antibiotics to prevent corneal infection.

Medication Summary

Medical therapy for recurrent corneal erosions includes hypertonic saline, which is thought to increase adherence of the epithelium to the underlying stroma. Lubrication may also help prevent corneal erosions.

Sodium chloride 5% (Muro 128, Adsorbonac, Afrin)

Clinical Context:  Used for temporary relief of corneal edema.

Class Summary

This agent dehydrates the epithelium, allowing it to better adhere to the underlying stroma.

Artificial tears (GenTeal, Refresh tears, TheraTears, Bion tears, Refresh Plus)

Clinical Context:  Contains equivalent of 0.9% NaCl and used to maintain ocular tonicity. Acts to stabilize and thicken precorneal tear film and prolong tear film breakup time, which is decreased in dry eye states.

Class Summary

Moistens the ocular surface and decreases the frequency of recurrent erosions.

Author

Anna M Edmiston, MD, Resident Physician, Department of Ophthalmology, University of Colorado School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

Karen L Christopher, MD, Assistant Professor of Cornea, External Disease, and Refractive Surgery, Department of Ophthalmology, University of Colorado School of Medicine

Disclosure: Nothing to disclose.

Michael Taravella, MD, Director of Cornea and Refractive Surgery, Rocky Mountain Lions Eye Institute; Professor, Department of Ophthalmology, University of Colorado School of Medicine

Disclosure: Received income in an amount equal to or greater than $250 from: J&J Vision (Consultant)/Proctor<br/> for: Coronet Surgical (Consultant), no income received.

Specialty Editors

Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Sidney Kimmel Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Hospital

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Cornea Society, AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab<br/>Serve(d) as a speaker or a member of a speakers bureau for: Avedro; Bio-Tissue; Shire<br/>Received income in an amount equal to or greater than $250 from: AAO, OMIC, Avedro; Bio-Tissue; GSK, Kala, Novartis; Shire; Sun Ophthalmics; TearLab.

Chief Editor

Hampton Roy, Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Fernando H Murillo-Lopez, MD, Senior Surgeon, Unidad Privada de Oftalmologia CEMES

Disclosure: Nothing to disclose.

Joanne W Ho, University of California, San Diego, School of Medicine

Disclosure: Nothing to disclose.

Natalie A Afshari, MD, MA, FACS, Stuart I Brown, MD, Chair in Ophthalmology In Memory of Donald P Shiley, Professor of Ophthalmology, Chief of Cornea and Refractive Surgery, Director of Education, Fellowship Program Director in Cornea and Refractive Surgery, Shiley Eye Center, University of California, San Diego, School of Medicine

Disclosure: Nothing to disclose.

William B Trattler, MD, Ophthalmologist, The Center for Excellence in Eye Care; Volunteer Assistant Professor of Ophthalmology, Bascom Palmer Eye Institute

Disclosure: Received consulting fee from Allergan for consulting; Received consulting fee from Alcon for consulting; Received consulting fee from Bausch & Lomb for consulting; Received consulting fee from Abbott Medical Optics for consulting; Received consulting fee from CXLUSA for none; Received consulting fee from LensAR for none.

William Lloyd Clark, MD, Palmetto Retina

Disclosure: Nothing to disclose.

References

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  2. Weiss JS, Møller HU, Lisch W, Kinoshita S, Aldave AJ, Belin MW, et al. The IC3D classification of the corneal dystrophies. Cornea. 2008 Dec. 27 Suppl 2:S1-83. [View Abstract]
  3. Klintworth GK. Corneal dystrophies. Orphanet J Rare Dis. 2009 Feb 23. 4:7. [View Abstract]
  4. Quantock AJ, Young RD, Akama TO. Structural and biochemical aspects of keratan sulphate in the cornea. Cell Mol Life Sci. 2009 Dec 27. [View Abstract]
  5. Al-Swailem SA, Al-Rajhi AA, Wagoner MD. Penetrating keratoplasty for macular corneal dystrophy. Ophthalmology. 2005 Feb. 112(2):220-4. [View Abstract]
  6. Hafner A, Langenbucher A, Seitz B. Long-term results of phototherapeutic keratectomy with 193-nm excimer laser for macular corneal dystrophy. Am J Ophthalmol. 2005 Sep. 140 (3):392-6. [View Abstract]
  7. Reddy JC1, Murthy SI, Vaddavalli PK, et al. Clinical outcomes and risk factors for graft failure after deep anterior lamellar keratoplasty and penetrating keratoplasty for macular corneal dystrophy. Cornea. 2015 Feb. 34(2):171-6. [View Abstract]
  8. Cheng J1, Qi X, Zhao J, et al. Comparison of penetrating keratoplasty and deep lamellar keratoplasty for macular corneal dystrophy and risk factors of recurrence. Ophthalmology. 2013 Jan. 120(1):34-9. [View Abstract]
  9. Hashemi H, Dadgostar A. Automated lamellar therapeutic keratoplasty with fibrin adhesive in the treatment of anterior corneal opacities. Cornea. 2011 Jun. 30(6):655-9. [View Abstract]
  10. Kannabiran C. Genetics of corneal endothelial dystrophies. J Genet. 2009 Dec. 88(4):487-94. [View Abstract]
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  13. Hafner A, Langenbucher A, Seitz B. Long-term results of phototherapeutic keratectomy with 193-nm excimer laser for macular corneal dystrophy. Am J Ophthalmol. 2005 Sep. 140(3):392-6. [View Abstract]
  14. Klintworth GK, Meyer R, Dennis R, et al. Macular corneal dystrophy. Lack of keratan sulfate in serum and cornea. Ophthalmic Paediatr Genet. 1986 Dec. 7(3):139-43. [View Abstract]
  15. Krachmer J. Cornea. Vol 2: 1996.
  16. Wirtitsch MG, Ergun E, Hermann B. Ultrahigh resolution optical coherence tomography in macular dystrophy. Am J Ophthalmol. 2005 Dec. 140(6):976-983. [View Abstract]

Macular dystrophy. Image courtesy of James J. Reidy, MD, FACS, Associate Professor of Ophthalmology, State University of New York, School of Medicine & Biomedical Sciences, Buffalo, New York.

Macular dystrophy.

Macular dystrophy. Image courtesy of James J. Reidy, MD, FACS, Associate Professor of Ophthalmology, State University of New York, School of Medicine & Biomedical Sciences, Buffalo, New York.

Macular dystrophy.