The deposits in macular dystrophy are glycosaminoglycans (GAGs), or acid mucopolysaccharides, and they stain with colloidal iron and alcian blue (see Table 7-4). They accumulate in the endoplasmic reticulum and not in lysosomal vacuoles, as seen in systemic mucopolysaccharidoses. Electron microscopy reveals keratocytes and endothelial cells that stain positive for GAGs, as well as extracellular clumps of fibrogranular material that also stains for GAGs. On confocal microscopy, blurred accumulations of light-reflective material are seen in the anterior corneal stroma.
Macular dystrophy occurs less frequently than the stromal dystrophies associated with mutations in the TGFBI gene. Unlike most corneal dystrophies, it has an autosomal recessive inheritance. It involves all layers of the cornea, including the endothelium, and extends to the periphery. The corneas are clear at birth and begin to cloud between 3 and 9 years of age.
Patients with macular dystrophy initially show superficial, irregular, whitish, flecklike opacities that evolve into focal, gray-white, superficial stromal opacities with intervening haze. The opacities tend to be more superficial centrally and more posterior peripherally. Macular spots have indefinite edges (Fig 7-13). Involvement of the Descemet membrane and endothelium is indicated by the presence of guttate excrescences, but corneal edema does not occur. Dystrophic opacities in the periphery may also appear similar to keratic precipitates. Epithelial erosions rarely develop, but a severe decrease in vision typically occurs between 10 and 30 years of age. Hypoesthesia has been noted. Central corneal thinning is common and may appear similar to long-standing interstitial keratitis (IK), but the ghost vessels and thickened Descemet membrane seen in IK help differentiate the conditions.
There are 3 variants of macular dystrophy, and they are distinguished based on bio-chemical differences. In type I, the most prevalent form of macular dystrophy, antigenic keratan sulfate (AgKS) is lacking in the cornea, serum, and cartilage. In affected patients, there is normal synthesis of dermatan sulfate proteoglycan. Errors occur in the synthesis of keratan sulfate and in the activity of specific sulfotransferases involved in the sulfation of the keratan sulfate lactose aminoglycan side chain. In type IA, keratocytes show AgKS reactivity, but the extracellular material does not. There is no AgKS in the serum. In macular dystrophy type II, all of the abnormal deposits react positively with AgKS, and the serum has normal or lower levels of AgKS.
Figure 7-13 Macular dystrophy. A, Diffuse illumination shows involvement to the limbus with diffuse haze. B, Slit view. Typically, the cornea is thin with dense opacities that occur more posteriorly in the periphery.
(Courtesy of Robert S. Feder, MD.)
An enzyme-linked immunosorbent assay (ELISA) measures sulfated keratan sulfate. This test can help in the diagnosis of macular dystrophy, even in preclinical forms and carriers.
Recurrent erosions should be treated, and photophobia may be reduced with tinted contact lenses. PTK may be used for symptomatic anterior macular dystrophy. Definitive treatment requires PK or DALK, and recurrences are uncommon.
Aldave AJ, Vo RC, de Sousa LB, Mannis MJ. The stromal dystrophies. In: Mannis MJ, Holland EJ, eds. Cornea. Vol 1. 4th ed. Philadelphia: Elsevier; 2017:781–799.
Weiss JS, Møller HU, Aldave AJ, et al. IC3D classification of corneal dystrophies— edition 2. Cornea. 2015;34(2):117–159.