Ocular manifestations of mucopolysacchridosis
Praddep Sagar Arsikere, Pradeep Venkatesh, Yog Raj Sharma
Mucopolysaccharidoses (MPS) are a group of disorders caused by the inherited deficiency of lysosomal enzymes involved in the metabolism of glycosaminoglycan (GAG), resulting in the widespread intracellular and extracellular accumulation of GAG.
Ocular manifestations
1. Ocular adnexa
Eyelid thickening occurs due to the accumulation of GAG. Hypertelorism has been reported in MPS types III, II and VII. Pseudoproptosis due to shallow orbit has been reported in a patient with MPS VI and MPS II.
2. Cornea
The extracellular matrix of corneal stroma contains dermatan sulfate and keratan sulfate in equal proportion. Both dermatan sulfate and keratan sulfate are synthesized by stromal keratocytes. Dermatan sulfate proteoglycans are involved in the control of interfibrillar spacing and in the lamellar adhesion of corneal collagens. Keratan sulfate proteoglycans are involved in the regulation of collagen fibril diameter. Mainly, epithelial cells synthesize heparan sulfate proteoglycans, and they are minor components of cornea.
Since dermatan sulfate and keratan sulfate are the major GAGs in the corneal stroma, corneal involvement is mainly seen in MPS types I, IV, VI and VII. In corneas of patients with MPS, the excessive accumulation of dermatan sulfate or keratan sulfate in the form of vacuoles can be seen in epithelial cells, keratocytes, histiocytes and extracellular matrix. An increase in the mean fibril diameter of collagen and an increase in fibril spacing are noted in the corneal stroma of patients with MPS I. These structural alterations in collagen fibrils may contribute to light scattering. But the corneal clouding is mainly due to the accumulation of GAGs in all the layers of cornea with enlarged stromal keratocytes.
Corneal involvement is typically not seen in type III, as the metabolism of heparan sulfate is impaired in type III and heparan sulfate is not synthesized by stromal keratocytes.
Symptoms include gradually progressive painless diminution of visual acuity and light intolerance due to scattering of light. In early cases, fine grey punctuate opacities in anterior stroma are visible. In advanced cases, there is diffuse corneal clouding. Corneal thickness is variable, and it may be increased or normal. Corneal hysteresis is increased. Corneal oedema occurs in cases with increased intra-ocular pressure (IOP).
3. Optic nerve
GAGs are the major components of the extracellular matrix of the optic nerve head. Proteoglycans containing chondritin sulfate and dermatan sulfate are located in lamina cribrosa, supporting tissues of the optic nerve head like septae, pia. Proteoglycans containing heparan sulfate are located in margins of laminar plates of lamina cribrosa. The optic nerve involvement can be due to accumulation of GAG in the extracellular matrix of the optic nerve, narrowing of pores in lamina cribrosa, thickening of dura and narrowing of bony optic canal that leads to disc oedema (pseudopapilloedema). It can also be due to raised intracranial pressure manifesting as true papilloedema. Long-standing axonal compression or papilloedema can lead to secondary optic atrophy. The accumulation of GAG in ganglion cells of retina can lead to axonal degeneration and optic atrophy.
Optic nerve involvement is more commonly seen in types I, II, VI and VII, as the major GAGs in optic nerve and lamina cribrosa are dermatan sulfate and chondritin sulfate.
Optic nerve involvement is less with type III, as heparan sulfate is located in the margins of lamina cribrosa, and in type IV, as keratan sulfate is not present in the optic nerve head in human.
4. Glaucoma
5. Retina
Heparan sulfate, dermatan sulfate, chondroitin sulfate and hyaluronan are present throughout the retina and choroid. Heparan sulfate is particularly located in the basement membrane containing structures, the RNFL and RPE. Keratan sulfate is absent in the retina and choroid. GAGs are integral components of the basement membrane of retinal microvasculature, and heparan sulfate is the predominant variety. Tapetoretinal degeneration has been reported in MPS types I, II, III and IV.
6. Sclera
Scleral thickening may lead to the uveal effusion syndrome.
Suggested Reading
1. Villas-Boas FS, Fernandes Filho DJ, Acosta AX. Ocular findings in patients with mucopolysaccharidosis. Arq Bras Oftalmol 2011; 74(6): 430–434.
2. Viestenz A, Shin YS, Viestenz A, Naumann GO. Ocular manifestation of mucopolysaccharidosis I-S (Scheie’s syndrome). Klin Monbl Augenheilkd 2002; 219(10): 745–748.