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Vitreous Opacities and Retinal Vascular Abnormalities in Gaucher Disease
Arch Ophthalmol. 2004;122:1395-1398.
Gaucher disease is an autosomal recessive lipid-storage disease. Deficiency in the enzyme glucosylceramidase, normally present in macrophage lysosomes, leads to accumulation of glucosylceramide in scavenger macrophages and subsequent deposition in the organs of the reticuloendothelial system (liver, spleen, and bone marrow). Enlarged macrophages with a foamy cytoplasm, likened to "crinkled tissue paper," with an eccentrically placed nucleus (Gaucher cells) are abundant, leading to organomegaly with resultant pancytopenia.1 In the past, many affected patients were treated with splenectomy at an early age to eliminate splenomegaly and resultant splenic sequestration of platelets. During the past decade, enzyme replacement therapy with intravenous infusions of glycosylceramidase has proven safe and effective for treating the visceral manifestations of Gaucher disease.2
Report of a Case
A 20-year-old white woman had best-corrected visual acuities of 20/160 OD and 20/60 OS. There was a small-angle esotropia in the right eye. Although she had long complained of floaters, her visual acuity had been correctable to 20/25 OU until 2 years earlier. Results of anterior segment examination were normal. The posterior segment examination showed moderate to dense vitreous opacities in both eyes, overlying the optic nerve head, vessels, and vitreous (Figure 1). There was a conspicuous absence of inflammatory cells in the vitreous bilaterally. Fluorescein angiography showed normal dye transit, blockage of fluorescence due to the vitreal opacities, and marked vascular tortuosity (Figure 2).
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Figure 1. Fundus photographs of both eyes showing prominent vitreous opacities.
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Figure 2. Fluorescein angiograms of both eyes in transit phase showing blockage of fluorescence caused by vitreal opacities, and vascular tortuosity.
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The patient underwent standard 20-gauge pars plana vitrectomy in the right eye. A vitreous aspirate specimen obtained before infusion instillation was stained with hematoxylin-eosin (Figure 3). The material was paucicellular, with some degenerated and a few typical Gaucher cells. The entire vitrectomy specimen was sent for centrifugation and analyzed via thin-layer chromatography, which showed a large amount of glucosylceramide (Figure 4).
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Figure 3. Vitreous aspirate showing a Gaucher cell (hematoxylin-eosin, original magnification x250).
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Figure 4. Thin-layer chromatography of lipids from vitreous and control lipids. Phospholipids were removed by alkaline methanolysis, dried under nitrogen gas, and resolved on borate-impregnated silica gel plates. Note intense staining of the glucosylceramide band in the patient.
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Postoperative photographs of the operated-on eye showed a few remaining preretinal white dots studding the retina and around the optic nerve head. A macular pucker was evident (Figure 5). Visual acuity was 20/40 at 6 months of follow-up.
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Figure 5. Color fundus photograph obtained 6 months postoperatively. A few preretinal white dots stud the retina and optic nerve. A macular pucker is evident.
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Comment
Gaucher disease often occurs in Ashkenazi Jews but is panethnic.2 Type 1 Gaucher disease is characterized by an absence of central nervous system involvement, in contrast to types 2 and 3, which have primary central nervous system disease. Classic descriptions of this disease mention multiple ocular and neurologic associations, such as conjunctival pterygia, strabismus, and trismus with retroflexion of the neck. Vitreous opacities in this disorder were first noted by Cogan et al3 and Gass.4 The incidence of vitreous opacities was found to be approximately 3% in a series of 80 consecutive patients with type 1 Gaucher disease.5 Only those who have undergone splenectomy have a tendency to form vitreous aggregates. Perhaps this is due to the occurrence of more circulating glucosylceramide in these patients, resulting in manifestations in unusual systemic locations, such as the eye. Our case is, to our knowledge, both the most severe that has been reported and the first noting retinal vascular tortuosity. The corkscrew vascular pattern is reminiscent of that in Fabry disease, a related disorder of sphingolipid metabolism. In our case, there were Gaucher cells in the vitreous cavity, while the vitreous gel contained large amounts of glucosylceramide.
The pathophysiologic mechanism of glucosylceramide deposition in the vitreous cavity is unclear. The material is a by-product of breakdown of myelin, leukocytes, red blood cells, and endothelial cells; myelin may be deposited within the eye when oligodendroglial cells migrate through the lamina cribrosa. Alternatively, deposition may occur by leakage from the vasculature. The latter is less likely, as glucosylceramide is not deposited within neurons in type 1 Gaucher disease, although Gaucher cells do accumulate in the periadventitial macrophages of the brain.1
We have shown that vision may be improved with vitrectomy in patients with Gaucher disease. It is unknown whether vitreal opacities will recur in our patient, as has been reported in patients who have undergone vitrectomy for vitreous opacities in familial amyloidotic polyneuropathy syndrome.6 The relationship of long-term enzyme replacement therapy to the vitreous opacities in our patient is speculative.
The authors have no relevant financial interest in this article.
This study was supported by the Kentucky Lions Eye Foundation, Louisville, and in part by a grant from Research to Prevent Blindness Inc, New York, NY.
AUTHOR INFORMATION
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Eric M. Shrier, DO;
Charles C. Barr, MD;
Gregory A. Grabowski, MD
Correspondence: Dr Barr, Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E Muhammad Ali Blvd, Louisville, KY 40202 (ccbarr{at}pol.net).
REFERENCES
1. Beutler E, Grabowski GA. Glucosylceramide lipidosis: Gaucher disease. In: Scriver CR, Sly WS, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill Book Co; 2001:3635-3668.
2. Grabowski GA, Leslie N, Wenstrup RW. Enzyme therapy in Gaucher disease: the first 5 years. Blood Rev. 1998;12:115-133.
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3. Cogan DG, Chu FC, Gittinger J, Tychsen L. Fundal abnormalities of Gaucher's disease. Arch Ophthalmol. 1980;98:2202-2203.
ABSTRACT
4. Gass JDM. Stereoscopic Atlas of Macular Disease and Treatment. St Louis, Mo: CV Mosby; 1997:408-409.
5. Wollstein G, Elstein D, Strassman I, Seelenfreund M, Zylbermann R, Zimran A. Preretinal white dots in adult-type Gaucher disease. Retina. 1999;19:570-571.
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6. Koga T, Ando E, Hirata A, et al. Vitreous opacities and outcome of vitreous surgery in patients with familial amyloidotic polyneuropathy. Am J Ophthalmol. 2003;135:188-193.
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SECTION EDITOR: W. RICHARD GREEN, MD
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