Journal of Pediatric Ophthalmology and Strabismus

The articles prior to January 2013 are part of the back file collection and are not available with a current paid subscription. To access the article, you may purchase it or purchase the complete back file collection here

SHORT SUBJECTS 

Glaucoma in Mucopolysaccharidosis 1-H/S

Paul Mullaney, FRCSI, FRCOphth; Abdulaziz H Awad, MD; Lynn Millar, MIScT

Abstract

INTRODUCTION

Glaucoma has been reported in mucopolysaccharidosis (MPS) 1-S (Scheie syndrome) and MPS 1-H (Hurler syndrome).1-3 The mechanisms of glaucoma in these patients are thought to be related to the abnormal deposition of acid mucopolysaccharides (AMP) in anterior segment structures. Quigley et al described acute angle closure glaucoma in two patients with MPS 1-S1; thickening of anterior ocular structures was considered a contributing factor. However, Spellacy et al, described open-angle glaucoma in MPS 1-H due to trabecular meshwork occlusion by AMP-laden cells.2 Nowaczyk et al, also considered this to be the mechanism in their three cases.3 The presence of goniodysgenesis in the Hurler-Scheie phenotype also has been noted.4

We report the case of an 11-year-old boy with chronic angle-closure glaucoma associated with MPS 1-H/S (Hurler-Scheie syndrome). The MPS 1-H/S is intermediate in phenotype between MPS 1-H and MPS 1-S.5

CASE REPORT

An 11-year-old boy with a diagnosis of MPS 1-H/S was referred to King Khaled Eye Speciahst Hospital for further management of his glaucoma. Cultured fibroblast activity of -L-iduronidase was 0 pmol/g/h/37C (control cell activity= 153.1±13.0 [N=14J). The patient had a characteristic facial habitus (Fig 1), corneal clouding (Fig 2), umbilical hernia, and clawing deformities of the fìngere and toes. There was no evidence of hepatosplenomegaly. He had a 2-year history of glaucoma, with pressures characteristically in the 30 mm Hg to 40 mm Hg range in both eyes. Topical pilocarpine 2% drops four times a day and Betagan 0.5% drops twice a day had failed to control intraocular pressure.

His record of compliance with both topical medications and outpatient appointments was poor. His age equivalency on the Beery VMI was 5 years, 2 months, with a standard score of 63. His language skills were consistent with his mental age.

Visual acuity was 20/20 OD and 20/25 OS. Marked conjunctival injection was present. Both corneas were thickened and opaque. Corneal epithelial edema also was present. Both anterior chambers were shallow centrally, and, peripherally, appeared closed (Fig 2). Indentation gonioscopy confirmed bilaterally closed angles (Fig 3). Intraocular pressures ranged from 35 mm Hg to 40 mm Hg in both eyes. The retina was normal. He had enlarged cup-to-disc ratios in both eyes, 0.5 in the left and 0.7 in the right. Axial lengths in both eyes were marginally reduced at 22.0 mm. B-scan echography did not show any thickening of sclera, choroid, or retina. Visual fields were unobtainable.

Two days postoperatively, an aqueous misdirection with a partially flat anterior chamber developed in the left eye. This was successfully treated with daily courses of intravenous mannitol (1 g/kg) and maximal mydriasis. Intraocular pressure in the left eye on discharge was 10 mm Hg by Goldmann applanation tonometry. The postoperative course of the right eye was uneventful. Intraocular pressures remained controlled 6 months after surgery.

MATERIALS AND METHODS

Specimens of conjunctiva, Tenon's capsule, the trabeculectomy site, and iris from each eye were processed for light microscopy and stained with colloidal iron and alcian blue 1%.

Specimens for transmission electron microscopy were fixed in 2.6% glutaraldehyde buffered to pH 7.4 with 0.1 M Sorensen's phosphate buffer and 0.18 M sucrose. Postfixation followed in 1% osmium tetroxide buffered with 0.1 M Sorensen's phosphate buffer. Specimens were then dehydrated in graded alcohols and embedded in araldite epoxy resin. Ultramicrotome (Ricart Ultracut E) was used to section; all were examined by electron microscopy (Philips 420).

RESULTS

Direct Microscopy and Histochemistry

The conjunctiva and Tenon's capsule were morphologically normal. Both contained large granular cells that stained positively with colloidal iron and alcian blue, indicating the presence of AMP. The trabecular meshwork, which was fibrosed and occluded, was difficult…

INTRODUCTION

Glaucoma has been reported in mucopolysaccharidosis (MPS) 1-S (Scheie syndrome) and MPS 1-H (Hurler syndrome).1-3 The mechanisms of glaucoma in these patients are thought to be related to the abnormal deposition of acid mucopolysaccharides (AMP) in anterior segment structures. Quigley et al described acute angle closure glaucoma in two patients with MPS 1-S1; thickening of anterior ocular structures was considered a contributing factor. However, Spellacy et al, described open-angle glaucoma in MPS 1-H due to trabecular meshwork occlusion by AMP-laden cells.2 Nowaczyk et al, also considered this to be the mechanism in their three cases.3 The presence of goniodysgenesis in the Hurler-Scheie phenotype also has been noted.4

We report the case of an 11-year-old boy with chronic angle-closure glaucoma associated with MPS 1-H/S (Hurler-Scheie syndrome). The MPS 1-H/S is intermediate in phenotype between MPS 1-H and MPS 1-S.5

CASE REPORT

An 11-year-old boy with a diagnosis of MPS 1-H/S was referred to King Khaled Eye Speciahst Hospital for further management of his glaucoma. Cultured fibroblast activity of -L-iduronidase was 0 pmol/g/h/37C (control cell activity= 153.1±13.0 [N=14J). The patient had a characteristic facial habitus (Fig 1), corneal clouding (Fig 2), umbilical hernia, and clawing deformities of the fìngere and toes. There was no evidence of hepatosplenomegaly. He had a 2-year history of glaucoma, with pressures characteristically in the 30 mm Hg to 40 mm Hg range in both eyes. Topical pilocarpine 2% drops four times a day and Betagan 0.5% drops twice a day had failed to control intraocular pressure.

His record of compliance with both topical medications and outpatient appointments was poor. His age equivalency on the Beery VMI was 5 years, 2 months, with a standard score of 63. His language skills were consistent with his mental age.

Visual acuity was 20/20 OD and 20/25 OS. Marked conjunctival injection was present. Both corneas were thickened and opaque. Corneal epithelial edema also was present. Both anterior chambers were shallow centrally, and, peripherally, appeared closed (Fig 2). Indentation gonioscopy confirmed bilaterally closed angles (Fig 3). Intraocular pressures ranged from 35 mm Hg to 40 mm Hg in both eyes. The retina was normal. He had enlarged cup-to-disc ratios in both eyes, 0.5 in the left and 0.7 in the right. Axial lengths in both eyes were marginally reduced at 22.0 mm. B-scan echography did not show any thickening of sclera, choroid, or retina. Visual fields were unobtainable.

Figure 1: The patient.

Figure 1: The patient.

Figure 2: A slit-lamp photograph shows corneal haze.

Figure 2: A slit-lamp photograph shows corneal haze.

Figure 3: A slit-lamp gonio-photograph shows the closed angle.

Figure 3: A slit-lamp gonio-photograph shows the closed angle.

Figure 4: Photomicrography of intracellular acid mucopolysaccharide (alcian blue X400).

Figure 4: Photomicrography of intracellular acid mucopolysaccharide (alcian blue X400).

Because of the persistently elevated intraocular pressures, bilateral consecutive trabeculectomies were performed. He was pretreated with topical Pred Forte drops every 2 hours to reduce the conjunctival injection. Intraoperative ultrasonic pachymetry (DGH 2000) measurements revealed marked corneal thickening (Table).6

A standard limbus-based flap of conjunctiva and Tenon's capsule was constructed and dissected forward to the cornea. A 4 × 4 mm half-thickness scleral flap was fashioned, with its base at the limbus. Pockets were dissected on either side of the trapdoor. Discs of filter paper impregnated with mitomycin 0.4 mg/mL were placed under the trapdoor and in the pockets between the sclera and Tenon's capsule and left in this position for 5 minutes. After the discs were removed, the treated area was copiously irrigated with balanced salt solution. A paracentesis was performed and Healon introduced into the anterior chamber. After the Healon was introduced, it was difficult to deepen the chamber substantially.

Trabeculectomy was performed uneventfully with a punch.

The trapdoor in the left eye was closed with a single 100 nylon suture at either corner. However, because of postoperative complications in the left eye (outlined below), a further 9-0 polyglactin (Vicryl) suture was added to either side of the flap in the right eye to reduce filtration. Tenon's capsule was closed with a running 10-0 Dexon suture. Conjunctival closure was obtained with a continuous buried mattress 10-0 Dexon suture. Subconjunctival gentamicin 10 , mg/mL and Decadron 1 mg/mL were injected into the inferior fornix.

Figure 5: Transmission electron micrograph of the sclera shows vacuoles containing abnormal acid mucopolysaccharide (magnification 5.5K bar = 1 pm).

Figure 5: Transmission electron micrograph of the sclera shows vacuoles containing abnormal acid mucopolysaccharide (magnification 5.5K bar = 1 pm).

Figure 6: Transmission electron micrograph of the iris shows intracellular membrane with limited vacuoles of fibrillogranular material (magnification 16K bar = 1 pm).

Figure 6: Transmission electron micrograph of the iris shows intracellular membrane with limited vacuoles of fibrillogranular material (magnification 16K bar = 1 pm).

Table

TABLE 1: Corneal thickness in micrometers of MPS 1-HS measured with DGH ultrasonic pachometer and compared with normal 6.

TABLE 1: Corneal thickness in micrometers of MPS 1-HS measured with DGH ultrasonic pachometer and compared with normal 6.

Two days postoperatively, an aqueous misdirection with a partially flat anterior chamber developed in the left eye. This was successfully treated with daily courses of intravenous mannitol (1 g/kg) and maximal mydriasis. Intraocular pressure in the left eye on discharge was 10 mm Hg by Goldmann applanation tonometry. The postoperative course of the right eye was uneventful. Intraocular pressures remained controlled 6 months after surgery.

MATERIALS AND METHODS

Specimens of conjunctiva, Tenon's capsule, the trabeculectomy site, and iris from each eye were processed for light microscopy and stained with colloidal iron and alcian blue 1%.

Specimens for transmission electron microscopy were fixed in 2.6% glutaraldehyde buffered to pH 7.4 with 0.1 M Sorensen's phosphate buffer and 0.18 M sucrose. Postfixation followed in 1% osmium tetroxide buffered with 0.1 M Sorensen's phosphate buffer. Specimens were then dehydrated in graded alcohols and embedded in araldite epoxy resin. Ultramicrotome (Ricart Ultracut E) was used to section; all were examined by electron microscopy (Philips 420).

RESULTS

Direct Microscopy and Histochemistry

The conjunctiva and Tenon's capsule were morphologically normal. Both contained large granular cells that stained positively with colloidal iron and alcian blue, indicating the presence of AMP. The trabecular meshwork, which was fibrosed and occluded, was difficult to identify. There was some extracellular granular material that stained positively with colloidal iron. Specimens of sclera stained negatively for AMP with colloidal iron and alcian blue. However, the iris stroma contained cells with AMP (Fig 4).

Transmission Electron Microscopy

Specimens from Tenon's capsule, sclera, trabecular meshwork, and iris were examined. Little extracellular or intracellular vacuolar formation was seen in the fibrotic trabecular meshwork. Scattered vacuolar formation was present in the sclera (Fig 5) and Tenon's capsule. Marked intracellular and extracellular vacuolar formation was noted in the iris (Fig 6). The intracellular vacuoles were limited by a single membrane and contained fibrillogranular material. There was little membranous lamellar material. No corneal tissue was examined.

DISCUSSION

The incidence of glaucoma in MPS 1-H probably is underestimated.3 Corneal clouding as a result of AMP deposition may mask corneal changes associated with elevated intraocular pressures. Spellacy et al, suggested that patients with MPS 1-H may not Uve long enough to develop glaucoma.2 They speculated that milder forms of MPS storage disease develop in glaucoma.

Glaucoma in MPS 1-H is thought to be due to AMPladen cells occluding the trabecular meshwork.2,3 Quigley et al described two cases of angle-closure glaucoma attributed to a generalized swelling of the anterior segment structures as a result of AMP deposition in MPS 1S.1 It would appear that there are two different mechanisms of glaucoma in MPS disease. It has been speculated that tissues, particularly the cornea, react in a specific way to each abnormality of AMP metabolism.7,8 The trabecular meshwork in MPS 1-H may be affected to a greater extent, leading to inter-trabecular occlusion. Kenyon found that in MPS 1-H, intracellular vacuoles merge and form large balloon-shaped cells in the conjunctiva.8

If the trabecular meshwork were similarly affected, this process could rapidly cause intertrabecular occlusion and elevated intraocular pressures. Large, swollen, balloon-shaped cells were not seen in MPS 1-S.8 In MPS 1-S, AMP deposition may be slower and more evenly spread through the anterior segment structures. This would thicken these structures, leading to angle crowding and subsequent angle closure. In this respect, the etiology of glaucoma in MPS 1-H/S would seem closer to that in MPS 1-S rather than that in MPS 1-H.

Kenyon suggests that the avascularity of the cornea may prevent the maintenance of normal thickness.8 Although he states that conjunctival extracellular AMP vacuoles reportedly are rarely seen in patients with MPS, previous reports have noted marked accumulation in the cornea.7 It is possible that conjunctival lymphatic and vascular channels may remove some of the extracellular AMP load. This would obviously not be possible in the cornea. Rosen et al found that deposition in MPS 1-H occurred mostly in corneal corpuscles.7 These corpuscles subsequently rupture, releasing AMP into the extracellular space.7,9 Corneal endothelial cells are altered upon vacuolation; whether this affects corneal deturgescence is unclear.7

Different morphological vacuoles are described in MPS.8"10 Fibrillogranular vacuoles contain an abnormally high accumulation of AMP. Glycolipid is deposited in vacuoles in a lamellar arrangement. Most of the vacuoles in our case were of the fibrillogranular type. Only sparse lamellar material was evident. Our patient had marked corneal thickening and haze as a result of combined elevated intraocular pressures and abnormal AMP deposition.

Although we were unable to obtain corneal tissue for examination, pachymetry confirmed abnormal corneal thickening. Electron microscopy of the iris and scleral specimens showed the presence of vacuoles containing fibrillogranular material consistent with abnormal AMP deposition. Gradual thickening of anterior segment structures was the most likely cause of chronic angle-closure in this child.

REFERENCES

1. Quigley HA, Maumenee AE, Stark WJ. Acute glaucoma in systemic mucopolysaccharidosis 1-S. Am J Ophthalmol. 1975;80:70-72.

2. Spellacy E, Kennerley Bankes JL, Crow J, Dourmashkin R, Shah D. Watts RWE. Glaucoma in a case of Hurler disease. Br J Ophthalmol. 1980;64:773-778.

3. Nowaczyk MJ, Clarke JTR, Morin JD. Glaucoma as an early complication of Hurler's disease. Arch Dis Child. 1988;63:1091-1093.

4. Chijiwa T, Inomata H, Yamana Y, et al. Ocular manifestations of Hurler-Scheie phenotype in two sibs. Jpn J Ophthalmol. 1983;27:5462.

5. Mckusick VA, Neufeld EF. The mucopolysaccharide storage diseases. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Goldstein JL, Brown MS, eds. The Metabolic Basis of Inherited Diseases. 5th ed. New York, NY: McGraw-Hill; 1983:751-777.

6. Reader AL, SaIz JJ. Differences among ultrasonic pachymeters in measuring corneal thickness. J Refract Corneal Surg. 1987;3:7-11.

7. Rosen DA, Haust MD, Yamashita T, Bryans AM. Keratoplasty and electron microscopy of the cornea in systemic mucopolysaccharidosis (Hurler's disease). Can J Ophthalmol. 1968;3:218-230.

8. Kenyon KR, Quigley HA, Hussels IE, Wyllie RG, Goldberg MF. The systemic mucopolysaccharidoses: ultrastructural and histochemical studies of conjunctiva and skin. Am J Ophthalmol. 1972;73:811-833.

9. Tripathi RC, Ashton N. Application of electron microscopy to the study of inborn errors of metabolism. In: Birth Defects. Original Article Series, Vol XII, No.3, 1976;69-104.

10. Topping TM, Kenyon KR, Goldberg MF, Maumenee AE. Ultrastructural ocular pathology of Hunter's syndrome. Arch Ophthalmol. 1971;86:164-177.

TABLE 1: Corneal thickness in micrometers of MPS 1-HS measured with DGH ultrasonic pachometer and compared with normal 6.

10.3928/0191-3913-19960301-13

Sign up to receive

Journal E-contents