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Urate Deposition in the Iris and Anterior Chamber
Urate Deposition in the Iris and Anterior Chamber Marco Coassin, MD,1,3 Omar Piovanetti, MD,1,3 Walter J. Stark, MD,2 W. Richard Green, MD1,3 Objective: To report on a patient with clear gelatinoid deposits on the iris and in the anterior chamber (AC). Design: Observational case report. Methods: Examination of AC aspirate and iris and conjunctival biopsies by light and transmission electron microscopy. Main Outcome Measures: Clinical and histopathological findings. Results: Analysis of the aqueous humor and iris ultrastructure disclosed the presence of urate deposits. Conclusions: Urate deposition in the iris and anterior chamber rarely occurs. Ophthalmology 2006;113: 462– 465 © 2006 by the American Academy of Ophthalmology.
Hyperuricemia occurs secondary to a number of diseases, such as hematological or renal disorders, or may be idiopathic.1 Prolonged hyperuricemia leads to gout, a syndrome first described by Hippocrates and characterized by acute arthritis due to urate deposition in joint spaces. Urate deposition has been reported in many tissues. In the eye, precipitation of urate crystal has been described in eyelids, tarsal plates, conjunctiva, cornea, sclera, tendons of extraocular muscles, orbit, and lens.2–9 For the first time, we present the clinical and histopathological findings of urate deposition in the iris and anterior chamber (AC) in a patient with gout.
Case Report A 68-year-old woman was referred for evaluation of ocular hypertension and corneal decompensation. Medical history was remarkable for gout, essential arterial hypertension, chronic obstructive pulmonary disease, fibromyalgia, diverticulosis, uric nephrolithiasis (status after stone extraction with stent placement in the setting of left hydronephrosis), and multiple renal cysts. Her medications included hydrochlorothiazide and triamterene 37.5/ 12.5 mg daily, valdecoxib 20 mg daily, estropipate 0.625 mg daily, glucosamine and chondroitin 3 times a day, vitamin E daily, and
potassium citrate. Her best-corrected visual acuities were 20/25 (right eye) and 20/40 (left eye). Intraocular pressure (IOP) was 21 mmHg in both eyes by applanation tonometry. Slit-lamp examination of the left eye disclosed severe corneal edema in the inferior third of the cornea. Multiple clear gelatinoid deposits were present superiorly on the iris surface (Fig 1), at the pupillary margin (Fig 2), and inferiorly in the AC angle (Fig 3) of the left eye. The material had rare crystalline refractile particles. Mild cataractous changes were present in both eyes. No visual field defects were detectable, and the Heidelberg retina tomographic scan was borderline for glaucomatous damage. An ultrasound B-scan described foreign material in the AC and anterior angle that did not throw a shadow. Laboratory analysis was remarkable for blood urea nitrogen (40 mg/dl), creatinine (1.3 mg/dl), uric acid (11.0 mg/dl [normal range, 2.4 – 6.4]), lactate dehydrogenase (275 mg/dl), C4 complement fraction (4 mg/dl), and positive anti–antinuclear antibody immunoglobulin G (1:160) with a homogeneous pattern. She underwent surgical iridectomy and removal of the gelatinous material. The AC aspirate and iris and bulbar conjunctiva biopsies were submitted for pathologic evaluation (one in 4% buffered formaldehyde and the other in 100% alcohol). Follow-up (20 months after the surgery) disclosed vision of 20/30 and a clear cornea and AC in the left eye.
Pathologic Findings Originally received: May 25, 2005. Accepted: November 17, 2005. Manuscript no. 2005-463. 1 Eye Pathology Laboratory, Wilmer Eye Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland. 2 Cornea Service, Wilmer Eye Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland. 3 Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland. Supported in part by The Independent Order of Odd Fellows, WinstonSalem, North Carolina (WRG), and “G. B. Bietti” Foundation, Rome, Italy (MC). Correspondence and reprint requests to W. R. Green, MD, Eye Pathology Laboratory, Wilmer Eye Institute at Johns Hopkins Hospital, Maumenee 427, 600 North Wolfe Street, Baltimore, MD 21287-9248. E-mail: wrgreen@ jhmi.edu.
462
© 2006 by the American Academy of Ophthalmology Published by Elsevier Inc.
Smears were prepared from the AC aspirate, and the remaining fluid was run through a Millipore filter (Millipore Corp., Billerica, MA). Light microscopic examination of 2 unstained smears and 2 Millipore filter preparations revealed occasional birefringent crystalline material. Iris and conjunctival tissues were processed for transmission electron microscopy. Evaluation of 1-m-thick plastic-embedded sections disclosed a folded segment of iris with deposits of homogeneous material in the stroma. Electron microscopy of the iris disclosed numerous irregular deposits of a moderate electron-dense extracellular granular material intermingling with collagen of iris stroma and within the walls of some blood vessels (Figs 4 – 6). The vascular endothelium was intact. Light microscopy and electron microscopy of the conjunctiva were unremarkable. ISSN 0161-6420/06/$–see front matter doi:10.1016/j.ophtha.2005.11.012
Figure 1. Anterior segment pictures of the left eye, showing multiple clear gelatinoid deposits superiorly on the iris surface. Figure 2. Retroillumination disclosed the gelatinoid material at the margin of the dilated pupil in the left eye. Figure 3. Gonioscopy revealed translucent material inferiorly in the anterior chamber angle of the left eye.
Ophthalmology Volume 113, Number 3, March 2006
Figure 4. Ultrastructural appearance of moderately electron-dense extracellular granular material (asterisk) in the iris stroma. An unremarkable melanocyte (arrow) and fibroblast (arrowhead) are present. No intracellular deposition of this material is present. Original magnification, ⫻9200.
Figure 5. Numerous irregular deposits of a moderately electron-dense extracellular granular material (asterisk) intermingling with the collagen of the iris stroma. Original magnification, ⫻19 200.
Discussion Uric acid is a product of purine metabolism. In gout, urate overproduction and reduced renal excretion account for the hyperuricemia. Precipitation of monosodium urate crystals into the synovial fluid, which is a poorer solvent than
464
plasma, accounts for transient attack of acute arthritis. The chronic deposition of urate crystals in joints or in other sites and the surrounding inflammatory reaction are defined as tophus.1 Although precipitation of urates in extravascular tissues is a well-established finding, urate deposition in ocular and periocular tissues is rare.
Coassin et al 䡠 Urate Deposition in the Iris and Anterior Chamber
Figure 6. Extracellular granular material intermingles with the collagen of iris stroma (asterisks) and is present within the walls of a blood vessel (arrows). No defects in the endothelium were observed. Original magnification, ⫻4600.
Clinical reports of ocular findings in gout have been noted since the late 18th century, but they seem to overestimate the problem.10 Only a few reports have histologically demonstrated the presence of urate in the periocular tissues and in the eye in the past 40 years. Histological or ultrastructural features of tophi have been demonstrated in conjunctiva,2– 4 cornea,5,6 lateral canthus,7 brow,8 and orbit.9 Ferry et al reported the clinical ocular abnormalities in 69 patients with severe gout.11 Gout was associated with red eye (62%), pinguecula (25%), elevated IOP (14%), asteroid hyalosis (4%), and corneal crystals (one patient). No uveitis, uveitis sequelae, or scleral tophi were reported in that study. Our clinical and histopathological findings strongly suggest that the material present in the iris and AC of this patient consists of urate. A review of the literature on gout revealed that in some instances urates appear as amorphous masses in tissues without crystalline formation.12 We reviewed the articles describing urate deposition in the ocular tissues present in the Medline database through May 2005, and publications were examined for references until no further studies were found. Interestingly, even if not histopathologically proven, in 1910 Doyne described older patients with gout who had “small, warty-looking, almost translucent excrescences [which resembled drops of lymph] on the pupillary margin of the iris,” which he termed guttate iritis.13
References 1. Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran Pathologic Basis of Disease. 7th ed. Philadelphia: Elsevier Saunders; 2005:1311– 4. 2. McWilliams JR. Ocular findings in gout; report of a case of conjunctival tophi. Am J Ophthalmol 1952;35:1778 – 83. 3. Yourish N. Conjunctival tophi associated with gout. AMA Arch Ophthalmol 1953;50:370 –1. 4. Martinez-Cordero E, Barreira-Mercado E, Katona G. Eye tophi deposition in gout. J Rheumatol 1986;13:471–3. 5. Fishman RS, Sunderman FW. Band keratopathy in gout. Arch Ophthalmol 1966;75:367–9. 6. Slansky HH, Kubara T. Intranuclear urate crystals in corneal epithelium. Arch Ophthalmol 1968;80:338 – 44. 7. Morris WR, Fleming JC. Gouty tophus at the lateral canthus. Arch Ophthalmol 2003;121:1195–7. 8. Margo CE. Use of standard hematoxylin-eosin to stain gouty tophus specimens [letter]. Arch Ophthalmol 2004;122:665. 9. Topping NC, Cassels-Brown A, Chakrabarty A, et al. Uric acid crystals presenting as an orbital mass [letter]. Eye 2003; 17:427–9. 10. Hutchinson J. The relation of certain diseases of the eye to gout. BMJ 1884;2:995–1000. 11. Ferry AP, Safir A, Melikian HE. Ocular abnormalities in patients with gout. Ann Ophthalmol 1985;17:632–5. 12. Talbot JH, Yu TF. Gout and Uric Acid Metabolism. New York: Stratton Intercontinental Medical Book Corp.; 1976:109. 13. Doyne RW. Guttate iritis. Trans Ophthalmol Soc U K 1910; 30:91–3.
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Hyperuricemia occurs secondary to a number of diseases, such as hematological or renal disorders, or may be idiopathic.1 Prolonged hyperuricemia leads to gout, a syndrome first described by Hippocrates and characterized by acute arthritis due to urate deposition in joint spaces. Urate deposition has been reported in many tissues. In the eye, precipitation of urate crystal has been described in eyelids, tarsal plates, conjunctiva, cornea, sclera, tendons of extraocular muscles, orbit, and lens.2–9 For the first time, we present the clinical and histopathological findings of urate deposition in the iris and anterior chamber (AC) in a patient with gout.
Case Report A 68-year-old woman was referred for evaluation of ocular hypertension and corneal decompensation. Medical history was remarkable for gout, essential arterial hypertension, chronic obstructive pulmonary disease, fibromyalgia, diverticulosis, uric nephrolithiasis (status after stone extraction with stent placement in the setting of left hydronephrosis), and multiple renal cysts. Her medications included hydrochlorothiazide and triamterene 37.5/ 12.5 mg daily, valdecoxib 20 mg daily, estropipate 0.625 mg daily, glucosamine and chondroitin 3 times a day, vitamin E daily, and
potassium citrate. Her best-corrected visual acuities were 20/25 (right eye) and 20/40 (left eye). Intraocular pressure (IOP) was 21 mmHg in both eyes by applanation tonometry. Slit-lamp examination of the left eye disclosed severe corneal edema in the inferior third of the cornea. Multiple clear gelatinoid deposits were present superiorly on the iris surface (Fig 1), at the pupillary margin (Fig 2), and inferiorly in the AC angle (Fig 3) of the left eye. The material had rare crystalline refractile particles. Mild cataractous changes were present in both eyes. No visual field defects were detectable, and the Heidelberg retina tomographic scan was borderline for glaucomatous damage. An ultrasound B-scan described foreign material in the AC and anterior angle that did not throw a shadow. Laboratory analysis was remarkable for blood urea nitrogen (40 mg/dl), creatinine (1.3 mg/dl), uric acid (11.0 mg/dl [normal range, 2.4 – 6.4]), lactate dehydrogenase (275 mg/dl), C4 complement fraction (4 mg/dl), and positive anti–antinuclear antibody immunoglobulin G (1:160) with a homogeneous pattern. She underwent surgical iridectomy and removal of the gelatinous material. The AC aspirate and iris and bulbar conjunctiva biopsies were submitted for pathologic evaluation (one in 4% buffered formaldehyde and the other in 100% alcohol). Follow-up (20 months after the surgery) disclosed vision of 20/30 and a clear cornea and AC in the left eye.
Pathologic Findings Originally received: May 25, 2005. Accepted: November 17, 2005. Manuscript no. 2005-463. 1 Eye Pathology Laboratory, Wilmer Eye Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland. 2 Cornea Service, Wilmer Eye Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland. 3 Department of Pathology, The Johns Hopkins Medical Institutions, Baltimore, Maryland. Supported in part by The Independent Order of Odd Fellows, WinstonSalem, North Carolina (WRG), and “G. B. Bietti” Foundation, Rome, Italy (MC). Correspondence and reprint requests to W. R. Green, MD, Eye Pathology Laboratory, Wilmer Eye Institute at Johns Hopkins Hospital, Maumenee 427, 600 North Wolfe Street, Baltimore, MD 21287-9248. E-mail: wrgreen@ jhmi.edu.
462
© 2006 by the American Academy of Ophthalmology Published by Elsevier Inc.
Smears were prepared from the AC aspirate, and the remaining fluid was run through a Millipore filter (Millipore Corp., Billerica, MA). Light microscopic examination of 2 unstained smears and 2 Millipore filter preparations revealed occasional birefringent crystalline material. Iris and conjunctival tissues were processed for transmission electron microscopy. Evaluation of 1-m-thick plastic-embedded sections disclosed a folded segment of iris with deposits of homogeneous material in the stroma. Electron microscopy of the iris disclosed numerous irregular deposits of a moderate electron-dense extracellular granular material intermingling with collagen of iris stroma and within the walls of some blood vessels (Figs 4 – 6). The vascular endothelium was intact. Light microscopy and electron microscopy of the conjunctiva were unremarkable. ISSN 0161-6420/06/$–see front matter doi:10.1016/j.ophtha.2005.11.012
Figure 1. Anterior segment pictures of the left eye, showing multiple clear gelatinoid deposits superiorly on the iris surface. Figure 2. Retroillumination disclosed the gelatinoid material at the margin of the dilated pupil in the left eye. Figure 3. Gonioscopy revealed translucent material inferiorly in the anterior chamber angle of the left eye.
Ophthalmology Volume 113, Number 3, March 2006
Figure 4. Ultrastructural appearance of moderately electron-dense extracellular granular material (asterisk) in the iris stroma. An unremarkable melanocyte (arrow) and fibroblast (arrowhead) are present. No intracellular deposition of this material is present. Original magnification, ⫻9200.
Figure 5. Numerous irregular deposits of a moderately electron-dense extracellular granular material (asterisk) intermingling with the collagen of the iris stroma. Original magnification, ⫻19 200.
Discussion Uric acid is a product of purine metabolism. In gout, urate overproduction and reduced renal excretion account for the hyperuricemia. Precipitation of monosodium urate crystals into the synovial fluid, which is a poorer solvent than
464
plasma, accounts for transient attack of acute arthritis. The chronic deposition of urate crystals in joints or in other sites and the surrounding inflammatory reaction are defined as tophus.1 Although precipitation of urates in extravascular tissues is a well-established finding, urate deposition in ocular and periocular tissues is rare.
Coassin et al 䡠 Urate Deposition in the Iris and Anterior Chamber
Figure 6. Extracellular granular material intermingles with the collagen of iris stroma (asterisks) and is present within the walls of a blood vessel (arrows). No defects in the endothelium were observed. Original magnification, ⫻4600.
Clinical reports of ocular findings in gout have been noted since the late 18th century, but they seem to overestimate the problem.10 Only a few reports have histologically demonstrated the presence of urate in the periocular tissues and in the eye in the past 40 years. Histological or ultrastructural features of tophi have been demonstrated in conjunctiva,2– 4 cornea,5,6 lateral canthus,7 brow,8 and orbit.9 Ferry et al reported the clinical ocular abnormalities in 69 patients with severe gout.11 Gout was associated with red eye (62%), pinguecula (25%), elevated IOP (14%), asteroid hyalosis (4%), and corneal crystals (one patient). No uveitis, uveitis sequelae, or scleral tophi were reported in that study. Our clinical and histopathological findings strongly suggest that the material present in the iris and AC of this patient consists of urate. A review of the literature on gout revealed that in some instances urates appear as amorphous masses in tissues without crystalline formation.12 We reviewed the articles describing urate deposition in the ocular tissues present in the Medline database through May 2005, and publications were examined for references until no further studies were found. Interestingly, even if not histopathologically proven, in 1910 Doyne described older patients with gout who had “small, warty-looking, almost translucent excrescences [which resembled drops of lymph] on the pupillary margin of the iris,” which he termed guttate iritis.13
References 1. Kumar V, Abbas AK, Fausto N, eds. Robbins and Cotran Pathologic Basis of Disease. 7th ed. Philadelphia: Elsevier Saunders; 2005:1311– 4. 2. McWilliams JR. Ocular findings in gout; report of a case of conjunctival tophi. Am J Ophthalmol 1952;35:1778 – 83. 3. Yourish N. Conjunctival tophi associated with gout. AMA Arch Ophthalmol 1953;50:370 –1. 4. Martinez-Cordero E, Barreira-Mercado E, Katona G. Eye tophi deposition in gout. J Rheumatol 1986;13:471–3. 5. Fishman RS, Sunderman FW. Band keratopathy in gout. Arch Ophthalmol 1966;75:367–9. 6. Slansky HH, Kubara T. Intranuclear urate crystals in corneal epithelium. Arch Ophthalmol 1968;80:338 – 44. 7. Morris WR, Fleming JC. Gouty tophus at the lateral canthus. Arch Ophthalmol 2003;121:1195–7. 8. Margo CE. Use of standard hematoxylin-eosin to stain gouty tophus specimens [letter]. Arch Ophthalmol 2004;122:665. 9. Topping NC, Cassels-Brown A, Chakrabarty A, et al. Uric acid crystals presenting as an orbital mass [letter]. Eye 2003; 17:427–9. 10. Hutchinson J. The relation of certain diseases of the eye to gout. BMJ 1884;2:995–1000. 11. Ferry AP, Safir A, Melikian HE. Ocular abnormalities in patients with gout. Ann Ophthalmol 1985;17:632–5. 12. Talbot JH, Yu TF. Gout and Uric Acid Metabolism. New York: Stratton Intercontinental Medical Book Corp.; 1976:109. 13. Doyne RW. Guttate iritis. Trans Ophthalmol Soc U K 1910; 30:91–3.
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