Ocular Changes in Mucopolysaccharidosis IV A (Morquio A Syndrome) and Long-Term Results of Perforating Keratoplasty

Abstract

Background: The mucopolysaccharidoses (MPS) are an inhomogeneous group of disorders of errors in the carbohydrate metabolism with severe ocular involvement (corneal opacification, retinal degeneration, optic atrophy). Patient Presentation: We report on a boy aged 12 years, with Morquio A (MPS IV A) syndrome. Ocular findings: progressive pseudoexophthalmus due to shallow orbits, increasing corneal stromal clouding, intermittent dissociated manifest nystagmus of the left eye, nyctalopia. Visual acuity OD cc = 0.16, OS cc = 0.05. Electrophysiology: changes suggesting a symptomatic tapetoretinal degeneration and optic atrophy. Treatment and Course of Disease: OS: perforating keratoplasty. Postoperative improvement of visual acuity to 0.25 for nearly a year, followed by progressive reopacification of the corneal graft. Both eyes: progressive signs of tapetoretinal degeneration and optic atrophy. Visual acuity now reduced to OD 0.05, OS 0.1. Conclusions: Success of a keratoplasty is limited by (1) reopacification of the cornea, (2) visual impairment due to (a) retinal degeneration and (b) optic atrophy. The indication for perforating keratoplasty has to be thought about very carefully in these multimorbid patients. In our patient, beside progressive visual impairment there is a progressive deafness which dominates his social and school life. Attending school is severely complicated by the double handicap. Perforating keratoplasty enabled the boy to attend a school for physically handicapped without a special low-vision care for another year. Progressive visual loss without further treatment options now renders optical and electronic low-vision aids necessary. Although the time of improved visual acuity lasted less than a year, we think patients with a life expectancy of less than 20 years should have every possible improvement of their situation – even if it does not last permanently. We therefore propose perforating keratoplasty in spite of insufficient long-term results.

In vivo confocal microscopy of the cornea in Morquio syndrome

“…1 A deficiency of N-acetyl-galactosamine-6-sulphate sulphatase leads to keratin sulphate deposition in the cornea and other tissues. Predominant systemic features include skeletal abnormalities, hearing loss and dental caries.…”

Diagnosis and management of ophthalmological features in patients with mucopolysaccharidosis

“…Although no systematic studies on the outcome of keratoplasty in patients with MPS have been performed, good results with the maintenance of clear donor cornea for a period of 3 months up to 5 years (without systemic therapies) were obtained in various cases 50–54. However, while clearing of the host cornea has been noted,55 GAGs may re-accumulate in the grafted tissue 51 56. Re-opacification, as early as 1 year post-surgery,51 56 probably correlates with disease severity51 and could be attributable to anterior–posterior spread of host keratocytes and gradual replacement of epithelial cells by host epithelium 56.…”

“…However, while clearing of the host cornea has been noted,55 GAGs may re-accumulate in the grafted tissue 51 56. Re-opacification, as early as 1 year post-surgery,51 56 probably correlates with disease severity51 and could be attributable to anterior–posterior spread of host keratocytes and gradual replacement of epithelial cells by host epithelium 56. In addition, concomitant optic nerve atrophy, glaucoma or other dysfunctions may limit the success of PK in terms of visual improvement (figure 3).…”

“…In addition, concomitant optic nerve atrophy, glaucoma or other dysfunctions may limit the success of PK in terms of visual improvement (figure 3). 2 51 Therefore, the potential benefits to vision and quality of life, even if temporary, must be weighed against co-existent eye pathologies, anaesthetic risks, intensive postoperative care and risk of complications in patients with MPS 2…”

Clinical and Neuroradiological Aspects of the Different Types

“…Good results are propagated for a combination of ERT with stem cell transplantation without any significant complication, although many patients develop antibodies against exogenous enzyme [129]. Still needed and very important in the treatment of patients with MPS is the symptomatic therapy: corneal transplantation because of corneal clouding improves visual capacity [130,131], however, poor vision caused by retinal degeneration or optic nerve atrophy cannot be reversed [10]. Airway obstruction may be alleviated by diverse operations or even with tracheobronchial stent or tracheostoma (Figures 1 and 14) insertion [63,64,[132][133][134], while cardiac valve replacement is occasionally needed [135,136].…”