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Ocular amyloidosis and secondary glaucoma
Ocular Amyloidosis and Secondary Glaucoma Gregory A. Nelson, MD, Deepak P. Edward, MD, Jacob T. Wilensky, MD Objective: To report the clinical and histopathologic findings in two cases of secondary glaucoma associated with amyloidosis. Design: Two case reports. Methods: Retrospective review of clinical findings, course, and treatment of the two patients. The histopathologic findings from available biopsy material were also reviewed. Main Outcome Measures: Intraocular pressure (IOP), visual field changes, and surgical outcome. Results: The first case describes a 76-year-old woman with orbital amyloidosis who developed gradual unilateral elevation of IOP that was poorly responsive to medical therapy and underwent filtration surgery. Episcleral venous pressure was elevated on the affected side, and histopathologic analysis of the conjunctival tissue confirmed perivascular amyloid deposits, further suggesting raised episcleral venous pressure to be a possible mechanism of glaucoma. The second case describes a 47-year-old white woman with familial amyloid neuropathy with a transthyretin cys-114 mutation. The association of glaucoma with this mutation has not been described previously. Persisting elevation of IOP in one eye was initially responsive to topical antiglaucoma medications but eventually required filtration surgery. Amyloid particles were found in the aqueous and on the lens surface. Histopathologic analysis of the aqueous and sclerectomy specimens demonstrated amyloid, suggesting outflow obstruction as a possible mechanism of glaucoma. Conjunctival buttonholing complicated filtration surgery in both cases, and the leaks eventually resolved with good control of IOP. Conclusions: Amyloid associated with glaucoma may involve different pathophysiologic mechanisms. The elevated IOP may not respond well to medical therapy. Cautious surgical manipulation of the conjunctiva is warranted in these cases. Ophthalmology 1999;106:1363–1366 Deposition of amyloid has been described in most ocular tissues and may occur purely as a localized ocular disease or a part of a systemic disorder. Elevated intraocular pressure (IOP) is an uncommon manifestation of ocular amyloidosis.1– 6 We describe two unusual cases of ocular amyloidosis resulting in elevated IOP in which different mechanisms may have been involved in raising the IOP.
Case Reports Case 1. A 76-year-old black woman (JM) had left-sided painless proptosis. At presentation, her visual acuity was 20/25 in both eyes. She had 3 mm of proptosis on the left eye with resistance to retropulsion. Red desaturation and color vision were normal in both eyes. Her pupils were equally reactive without an afferent
Originally received: November 14, 1998. Revision accepted: March 29, 1999. Manuscript no. 98729. From the Department of Ophthalmology and Visual Sciences, University of Illinois–Chicago, Chicago, Illinois. Supported by a gift from the Laura K. Binder Foundation, Chicago Illinois (DPE); the Otsuka Research fellowship from the American Glaucoma Society, San Francisco, California (DPE); and a Department of Ophthalmology Core Grant EY001792 from the National Eye Institute, Bethesda, Maryland. Address correspondence to Deepak P. Edward, MD, Ophthalmology Associates, 1201 Summit Avenue, Fort Worth, TX 76102.
pupillary defect. Ocular motility examination was full. The anterior segment examination of both eyes was unremarkable. Fundus examination showed healthy-appearing nerves with a cup-to-disc ratio of 0.3 ⫻ 0.3 in both eyes. There were choroidal folds noted in the posterior pole of the left eye. The IOPs were 20 mmHg in both eyes. Goldmann visual field testing revealed full fields in both eyes. A workup that included complete blood count, thyroid function tests, and liver function tests was within normal limits. There was no family history of amyloidosis or glaucoma elicited. Imaging studies demonstrated a large, enhancing orbital mass with multiple calcifications resembling phleboliths (Fig 1). The radiologic findings were interpreted as being consistent with a left orbital sclerosing hemangioma. In view of the patient’s good visual function and minimal symptoms, observation was recommended. Eighteen months later, she had elevated IOP in the left eye to 30 mmHg. There was 1-mm increase in proptosis. Her visual acuity was 20/25 in both eyes, and other clinical findings remained unchanged. Goldmann visual field testing revealed full fields. A computed tomographic scan was repeated and showed no change in the size of the retrobulbar mass. On gonioscopy, both angles were open to scleral spur 360° with mild pigmentation of the trabecular meshwork. The elevated IOP responded poorly to multiple topical medications. In the following 17 months, the IOPs ranged from 24 to 38 mmHg with the patient receiving a topical beta blocker, pilocarpine, dipivefrin, and acetazolamide, and the best-corrected visual acuity was decreased to 20/40 in the affected eye. Red desaturation was abnormal, and a left afferent pupillary defect was noted. An increase in her left optic nerve cup size with persistent choroidal folds was noted (Fig 2). Venous engorgement and a few dot blot hemorrhages were also seen. Goldmann visual field testing
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Ophthalmology Volume 106, Number 7, July 1999
Figure 1. Axial computed tomography with enhancement showing an orbital mass involving the posterior and nasal aspects of the globe with focal areas of enhancement and calcification.
remained unchanged. These findings were attributed to a combination of direct optic nerve compression and the elevated IOP. A left lateral orbitotomy with biopsy and debulking of the tumor was performed. Pathologic examination revealed extensive amyloid infiltration into the orbital fat with occluded orbital blood vessels and areas of calcification (Fig 3). The IOP remained elevated after the orbital surgery and ranged from 30 to 35 mmHg with further enlargement of the optic cup. Gonioscopic findings remained unchanged. Venomanometry was done using the method described by Zeimer and colleagues7 and was elevated at 15 mmHg in the left eye (normal range, 7.6 ⫾ 1.3 mmHg). In view of the uncontrolled IOPs and evidence of increased optic nerve cupping, a trabeculectomy with mitomycin C was performed on the left eye. The procedure was complicated by friable conjunctiva creating multiple buttonholes as well as difficulty in closing the conjunctiva and scleral flap. A scleral patch graft was used to tightly cover the scleral flap. Pathologic examination of the conjunctival specimen showed heavy subconjunctival deposition of amyloid in the substantia propria (Fig 4A) that also surrounded the blood vessels (Fig 4B). Moderate infiltration of lymphocytes was seen in the substantia propria (Fig 4B). A Descemet’s punch was used to create the sclerostomy, and the specimen from this site was inadequate for pathologic examination. During the postoperative course, bleb leakage was observed but eventually resolved without surgical intervention. Three years later, her visual acuity, appearance of the optic nerve, and visual field have remained stable with the IOP in the left eye ranging from 12 to 16 mmHg with a topical beta blocker. On last examination, her visual acuity was 20/40. A shallow diffuse bleb was noted in the region of the scleral patch graft. Thickening of the superotemporal conjunctiva and subepithelial corneal deposits suggestive of amyloid were also noted (Fig 5). Her IOP was 18 mmHg, and the visual fields remained stable. Case 2. A 47-year-old white woman (SS) was referred for evaluation of elevated IOP in the left eye. Her ocular history was significant for bilateral vitrectomies 4 years ago for vitreous opacification secondary to familial amyloid polyneuropathy. The patient and other family members were found to have the transthyretin cys-114 mutation, which is an unusual but known site of mutation in families with familial amyloid polyneuropathy.10 Multiple members of the family showed findings typical of autosomaldominant familial amyloid polyneuropathy that included renal insufficiency, progressive disability, encephalopathic features, hepatic failure, and cardiac involvement. The patient’s visual acuity
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on presentation was 20/30 in both eyes with a mild myopic refraction. The pupil margins were regular, and no afferent pupillary defect was noted. However, the left pupil was larger and poorly reactive. No Krukenberg spindles or transillumination defects were noted. Anterior segment examination of both eyes was remarkable for whitish fibrillar material on the posterior corneal surface, in the anterior chamber, and on the anterior lens surfaces. The findings were more prominent in the left eye (Figs 6A, B). Gonioscopic analysis showed open angles with heavy pigmentation in both eyes. The IOP was 17 mmHg in the right eye and 33 mmHg in the left eye with the patient being treated with 0.5% timolol and 0.5% apraclonidine in the left eye and acetazolamide 500 mg sequels twice a day. The view to the right optic nerve was hindered by vitreous debris. The left optic nerve showed moderate glaucomatous cupping with an intact rim that demonstrated mild pallor. Goldmann visual field testing results showed an enlarged blind spot in the right eye and generalized constriction of the left visual field. One month after presentation, the patient underwent trabeculectomy with mitomycin C in the left eye. Intraoperatively, the conjunctiva was noted to be thin and friable, resulting in tears that were repaired. The postoperative course was complicated by bleb leaks that were treated with histoacrylic glue and bandage contact lenses. The bleb leaks eventually resolved without surgical intervention. Aqueous cytologic analysis performed on a centrifuged pellet showed congophilic amyloid fibrils. The sclerostomy specimen submitted consisted of fragments of ciliary body and sclera. No trabecular meshwork was identified on serial sections, suggesting that inadvertent excision of tissue posterior to the trabecular meshwork had occurred. Patchy amyloid deposition was noted in the sclera. However, no amyloid infiltration was seen in the ciliary muscle or the ciliary processes. At 2 years after the filtration procedure, her IOP in the left eye remained at or below 18 without medications. However, Goldmann visual field testing showed increased generalized constriction.
Discussion In the article, we present two patients with ocular amyloidosis involving different ocular structures that resulted in secondary glaucoma. Multiple mechanisms related to the
Figure 2. Case 1. Fundus photograph after the orbitotomy showing persistent choroidal folds in the posterior pole and a prominent optic nerve cup in the left eye.
Nelson et al 䡠 Ocular Amyloidosis and Secondary Glaucoma
Figure 3. Photomicrograph of the orbital biopsy showing the orbital amyloid deposits (A) with foreign body giant cell reaction (arrow) and calcification (C) (stain, hematoxylin and eosin; original magnification, ⫻40).
amyloid deposition appear to be involved in the etiology of the elevated IOP. In case 1, the orbital and ocular findings were consistent with primary localized orbital amyloidosis. However, the
Figure 4. A, microphotograph of conjunctival biopsy showing amorphous eosinophilic amyloid deposits (A) in the subconjunctival space (stain, hematoxylin and eosin; original magnification, ⫻25). B, note the congophilic amyloid deposits (A) in the subconjunctival space and around the blood vessels and infiltration by lymphocytes (L) (stain, Congo red; original magnification, ⫻25).
Figure 5. Clinical photograph showing anterior segment of case 1, 2 years after filtration surgery. Note the scleral patch graft seen superonasally. The temporal conjunctiva (T) is thickened and has a yellowish appearance.
initial findings on computed tomographic scan suggested a sclerosing cavernous hemangioma. Levine and Buckman8 described a similar case in which multiple calcifications resembling phleboliths were noted in the orbit, and a pre-
Figure 6. Case 2. A, slit-lamp photograph showing fibrillar deposits on the posterior corneal surface. B, extensive deposits are seen over the anterior lens surface.
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Ophthalmology Volume 106, Number 7, July 1999 sumed diagnosis of cavernous hemangioma was made. Orbital amyloidosis should therefore be considered when computed tomographic scans show phlebolith-like lesions in association with an enhancing orbital mass. The association of localized orbital amyloidosis with secondary glaucoma is quite rare and, to the best of our knowledge, only one case of secondary glaucoma complicating primary orbital amyloidosis has been reported previously.1 In that report, angle closure, with perhaps a minimal contribution from elevated episcleral venous pressure, was thought to be the mechanism of glaucoma. In our patient, however, gonioscopic analysis revealed open angles with raised episcleral venous pressure, making it likely that the perivascular amyloid in the conjunctiva contributed to the elevation of episcleral venous pressure and IOP. It is also possible that direct infiltration of the trabecular meshwork may have occurred, thus decreasing the outflow facility. Unfortunately, tissue from the trabecular meshwork was not available for study nor were outflow studies performed to definitively confirm the latter possibility. The second patient with amyloidosis had familial amyloid polyneuropathy with a transthyretin cys-114 mutation. Familial amyloid polyneuropathy is an autosomal-dominant heredofamilial amyloidosis.9 The transthyretin cys-114 mutation is one of many transthyretin gene mutations described in familial amyloid polyneuropathy.10 This variant is unusual, is more common in the Japanese population, and its association with secondary glaucoma has not been described previously. The ocular and systemic findings in our patient are similar to those reported previously.2–5,11 However, findings such as liver failure, cardiac involvement, and other cerebral features as seen in our patient and the affected relatives are unusual in this disorder. Glaucoma in heredofamilial amyloidoses is uncommon and manifests between the third and fifth decades. The IOP may be markedly elevated with open angles that show increased pigmentation, as noted in our patient.2,3–5 The elevated IOP in familial amyloid polyneuropathy appears to be secondary to amyloid deposition in the trabecular meshwork. The abundance of intraocular amyloid in case 2 suggests that was probably an important mechanism in the elevation of IOP. The glaucoma in this disorder tends to be difficult to treat, as seen in our patient. One study reported that 17% of patients with vitreous amyloidosis required filtration surgery.12 A finding that was remarkable in both patients was the increased tissue friability that resulted in intraoperative buttonholing of the conjunctiva that was difficult to repair. We attribute this problem to conjunctival infiltration by amyloid that was demonstrated by pathologic examination in the first patient. Although no conjunctival sample was available in the second patient, conjunctival amyloid deposits were well described in familial amyloid polyneuropathy,13 and it is possible that the conjunctiva was also involved in the second patient.
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The management of glaucoma in these patients is unclear in the literature. It is possible that these patients may be more suitable candidates for shunt procedures as opposed to trabeculectomy. Nevertheless, despite the intraoperative difficulty and postoperative bleb leaks, both patients have continued to have functional filtration blebs. One may postulate that the inflammatory reaction seen in response to amyloid deposition in the subconjunctival space aided in the closure of bleb leaks. However, it is unclear why these blebs still continue to function for more than 1 year after surgery despite the expected inflammatory response to amyloid in the subconjunctival space.
References 1. Bansal RK, Gupta A, Agarwal A. Primary orbital amyloidosis with secondary glaucoma. A case report. Orbit 1991;10: 105– 8. 2. Sandgren O. Ocular amyloidosis, with special reference to the hereditary forms with vitreous involvement. Surv Ophthalmol 1995;40:173–96. 3. Ando E, Ando Y, Okamura R, et al. Ocular manifestations of familial amyloidotic polyneuropathy type I: long-term follow up. Br J Ophthalmol 1997;81:295– 8. 4. Futa R, Inada K, Nakashima H, et al. Familial amyloidotic polyneuropathy: ocular manifestations with clinicopathological observation. Jpn J Ophthalmol 1984;28:289 –98. 5. Kaufman HE. Primary familial amyloidosis. Arch Ophthalmol 1958;60:1036 –143. 6. Tsukahara S, Matsuo T. Secondary glaucoma accompanied with primary familial amyloidosis. Ophthalmologica 1977; 175:250 – 62. 7. Zeimer RC, Gieser DK, Wilensky JT, et al. A practical venomanometer. Measurement of episcleral venous pressure and assessment of the normal range. Arch Ophthalmol 1983; 101:1447–19. 8. Levine MR, Buckman G. Primary localized orbital amyloidosis. Ann Ophthalmol 1986;18:165–7. 9. Andrade C. A peculiar form of peripheral neuropathy. Familiar atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain 1952;75:408 –27. 10. Ueno S, Uemichi T, Yorifuji S, Tarui S. A novel variant of transthyretin (Tyr 114 to Cys) deduced from the nucleotide sequences of gene fragments from familial amyloidotic polyneuropathy in Japanese sibling cases. Biochem Biophys Res Commun 1990;169:143–7. 11. Ciulla TA, Tolentino F, Morrow JF, Dryja TP. Vitreous amyloidosis in familial amyloidotic polyneuropathy. Report of a case with the Val30Met transthyretin mutation. Surv Ophthalmol 1995;40:197–206. 12. Doft BH, Machemer R, Skinner M, et al. Pars plana vitrectomy for vitreous amyloidosis. Ophthalmology 1987;94:607– 11. 13. Ando E, Ando Y, Maruoka S, et al. Ocular microangiopathy in familial amyloidotic polyneuropathy, type 1. Graefes Arch Clin Exp Ophthalmol 1992;230:1–5.
Case Reports Case 1. A 76-year-old black woman (JM) had left-sided painless proptosis. At presentation, her visual acuity was 20/25 in both eyes. She had 3 mm of proptosis on the left eye with resistance to retropulsion. Red desaturation and color vision were normal in both eyes. Her pupils were equally reactive without an afferent
Originally received: November 14, 1998. Revision accepted: March 29, 1999. Manuscript no. 98729. From the Department of Ophthalmology and Visual Sciences, University of Illinois–Chicago, Chicago, Illinois. Supported by a gift from the Laura K. Binder Foundation, Chicago Illinois (DPE); the Otsuka Research fellowship from the American Glaucoma Society, San Francisco, California (DPE); and a Department of Ophthalmology Core Grant EY001792 from the National Eye Institute, Bethesda, Maryland. Address correspondence to Deepak P. Edward, MD, Ophthalmology Associates, 1201 Summit Avenue, Fort Worth, TX 76102.
pupillary defect. Ocular motility examination was full. The anterior segment examination of both eyes was unremarkable. Fundus examination showed healthy-appearing nerves with a cup-to-disc ratio of 0.3 ⫻ 0.3 in both eyes. There were choroidal folds noted in the posterior pole of the left eye. The IOPs were 20 mmHg in both eyes. Goldmann visual field testing revealed full fields in both eyes. A workup that included complete blood count, thyroid function tests, and liver function tests was within normal limits. There was no family history of amyloidosis or glaucoma elicited. Imaging studies demonstrated a large, enhancing orbital mass with multiple calcifications resembling phleboliths (Fig 1). The radiologic findings were interpreted as being consistent with a left orbital sclerosing hemangioma. In view of the patient’s good visual function and minimal symptoms, observation was recommended. Eighteen months later, she had elevated IOP in the left eye to 30 mmHg. There was 1-mm increase in proptosis. Her visual acuity was 20/25 in both eyes, and other clinical findings remained unchanged. Goldmann visual field testing revealed full fields. A computed tomographic scan was repeated and showed no change in the size of the retrobulbar mass. On gonioscopy, both angles were open to scleral spur 360° with mild pigmentation of the trabecular meshwork. The elevated IOP responded poorly to multiple topical medications. In the following 17 months, the IOPs ranged from 24 to 38 mmHg with the patient receiving a topical beta blocker, pilocarpine, dipivefrin, and acetazolamide, and the best-corrected visual acuity was decreased to 20/40 in the affected eye. Red desaturation was abnormal, and a left afferent pupillary defect was noted. An increase in her left optic nerve cup size with persistent choroidal folds was noted (Fig 2). Venous engorgement and a few dot blot hemorrhages were also seen. Goldmann visual field testing
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Ophthalmology Volume 106, Number 7, July 1999
Figure 1. Axial computed tomography with enhancement showing an orbital mass involving the posterior and nasal aspects of the globe with focal areas of enhancement and calcification.
remained unchanged. These findings were attributed to a combination of direct optic nerve compression and the elevated IOP. A left lateral orbitotomy with biopsy and debulking of the tumor was performed. Pathologic examination revealed extensive amyloid infiltration into the orbital fat with occluded orbital blood vessels and areas of calcification (Fig 3). The IOP remained elevated after the orbital surgery and ranged from 30 to 35 mmHg with further enlargement of the optic cup. Gonioscopic findings remained unchanged. Venomanometry was done using the method described by Zeimer and colleagues7 and was elevated at 15 mmHg in the left eye (normal range, 7.6 ⫾ 1.3 mmHg). In view of the uncontrolled IOPs and evidence of increased optic nerve cupping, a trabeculectomy with mitomycin C was performed on the left eye. The procedure was complicated by friable conjunctiva creating multiple buttonholes as well as difficulty in closing the conjunctiva and scleral flap. A scleral patch graft was used to tightly cover the scleral flap. Pathologic examination of the conjunctival specimen showed heavy subconjunctival deposition of amyloid in the substantia propria (Fig 4A) that also surrounded the blood vessels (Fig 4B). Moderate infiltration of lymphocytes was seen in the substantia propria (Fig 4B). A Descemet’s punch was used to create the sclerostomy, and the specimen from this site was inadequate for pathologic examination. During the postoperative course, bleb leakage was observed but eventually resolved without surgical intervention. Three years later, her visual acuity, appearance of the optic nerve, and visual field have remained stable with the IOP in the left eye ranging from 12 to 16 mmHg with a topical beta blocker. On last examination, her visual acuity was 20/40. A shallow diffuse bleb was noted in the region of the scleral patch graft. Thickening of the superotemporal conjunctiva and subepithelial corneal deposits suggestive of amyloid were also noted (Fig 5). Her IOP was 18 mmHg, and the visual fields remained stable. Case 2. A 47-year-old white woman (SS) was referred for evaluation of elevated IOP in the left eye. Her ocular history was significant for bilateral vitrectomies 4 years ago for vitreous opacification secondary to familial amyloid polyneuropathy. The patient and other family members were found to have the transthyretin cys-114 mutation, which is an unusual but known site of mutation in families with familial amyloid polyneuropathy.10 Multiple members of the family showed findings typical of autosomaldominant familial amyloid polyneuropathy that included renal insufficiency, progressive disability, encephalopathic features, hepatic failure, and cardiac involvement. The patient’s visual acuity
1364
on presentation was 20/30 in both eyes with a mild myopic refraction. The pupil margins were regular, and no afferent pupillary defect was noted. However, the left pupil was larger and poorly reactive. No Krukenberg spindles or transillumination defects were noted. Anterior segment examination of both eyes was remarkable for whitish fibrillar material on the posterior corneal surface, in the anterior chamber, and on the anterior lens surfaces. The findings were more prominent in the left eye (Figs 6A, B). Gonioscopic analysis showed open angles with heavy pigmentation in both eyes. The IOP was 17 mmHg in the right eye and 33 mmHg in the left eye with the patient being treated with 0.5% timolol and 0.5% apraclonidine in the left eye and acetazolamide 500 mg sequels twice a day. The view to the right optic nerve was hindered by vitreous debris. The left optic nerve showed moderate glaucomatous cupping with an intact rim that demonstrated mild pallor. Goldmann visual field testing results showed an enlarged blind spot in the right eye and generalized constriction of the left visual field. One month after presentation, the patient underwent trabeculectomy with mitomycin C in the left eye. Intraoperatively, the conjunctiva was noted to be thin and friable, resulting in tears that were repaired. The postoperative course was complicated by bleb leaks that were treated with histoacrylic glue and bandage contact lenses. The bleb leaks eventually resolved without surgical intervention. Aqueous cytologic analysis performed on a centrifuged pellet showed congophilic amyloid fibrils. The sclerostomy specimen submitted consisted of fragments of ciliary body and sclera. No trabecular meshwork was identified on serial sections, suggesting that inadvertent excision of tissue posterior to the trabecular meshwork had occurred. Patchy amyloid deposition was noted in the sclera. However, no amyloid infiltration was seen in the ciliary muscle or the ciliary processes. At 2 years after the filtration procedure, her IOP in the left eye remained at or below 18 without medications. However, Goldmann visual field testing showed increased generalized constriction.
Discussion In the article, we present two patients with ocular amyloidosis involving different ocular structures that resulted in secondary glaucoma. Multiple mechanisms related to the
Figure 2. Case 1. Fundus photograph after the orbitotomy showing persistent choroidal folds in the posterior pole and a prominent optic nerve cup in the left eye.
Nelson et al 䡠 Ocular Amyloidosis and Secondary Glaucoma
Figure 3. Photomicrograph of the orbital biopsy showing the orbital amyloid deposits (A) with foreign body giant cell reaction (arrow) and calcification (C) (stain, hematoxylin and eosin; original magnification, ⫻40).
amyloid deposition appear to be involved in the etiology of the elevated IOP. In case 1, the orbital and ocular findings were consistent with primary localized orbital amyloidosis. However, the
Figure 4. A, microphotograph of conjunctival biopsy showing amorphous eosinophilic amyloid deposits (A) in the subconjunctival space (stain, hematoxylin and eosin; original magnification, ⫻25). B, note the congophilic amyloid deposits (A) in the subconjunctival space and around the blood vessels and infiltration by lymphocytes (L) (stain, Congo red; original magnification, ⫻25).
Figure 5. Clinical photograph showing anterior segment of case 1, 2 years after filtration surgery. Note the scleral patch graft seen superonasally. The temporal conjunctiva (T) is thickened and has a yellowish appearance.
initial findings on computed tomographic scan suggested a sclerosing cavernous hemangioma. Levine and Buckman8 described a similar case in which multiple calcifications resembling phleboliths were noted in the orbit, and a pre-
Figure 6. Case 2. A, slit-lamp photograph showing fibrillar deposits on the posterior corneal surface. B, extensive deposits are seen over the anterior lens surface.
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Ophthalmology Volume 106, Number 7, July 1999 sumed diagnosis of cavernous hemangioma was made. Orbital amyloidosis should therefore be considered when computed tomographic scans show phlebolith-like lesions in association with an enhancing orbital mass. The association of localized orbital amyloidosis with secondary glaucoma is quite rare and, to the best of our knowledge, only one case of secondary glaucoma complicating primary orbital amyloidosis has been reported previously.1 In that report, angle closure, with perhaps a minimal contribution from elevated episcleral venous pressure, was thought to be the mechanism of glaucoma. In our patient, however, gonioscopic analysis revealed open angles with raised episcleral venous pressure, making it likely that the perivascular amyloid in the conjunctiva contributed to the elevation of episcleral venous pressure and IOP. It is also possible that direct infiltration of the trabecular meshwork may have occurred, thus decreasing the outflow facility. Unfortunately, tissue from the trabecular meshwork was not available for study nor were outflow studies performed to definitively confirm the latter possibility. The second patient with amyloidosis had familial amyloid polyneuropathy with a transthyretin cys-114 mutation. Familial amyloid polyneuropathy is an autosomal-dominant heredofamilial amyloidosis.9 The transthyretin cys-114 mutation is one of many transthyretin gene mutations described in familial amyloid polyneuropathy.10 This variant is unusual, is more common in the Japanese population, and its association with secondary glaucoma has not been described previously. The ocular and systemic findings in our patient are similar to those reported previously.2–5,11 However, findings such as liver failure, cardiac involvement, and other cerebral features as seen in our patient and the affected relatives are unusual in this disorder. Glaucoma in heredofamilial amyloidoses is uncommon and manifests between the third and fifth decades. The IOP may be markedly elevated with open angles that show increased pigmentation, as noted in our patient.2,3–5 The elevated IOP in familial amyloid polyneuropathy appears to be secondary to amyloid deposition in the trabecular meshwork. The abundance of intraocular amyloid in case 2 suggests that was probably an important mechanism in the elevation of IOP. The glaucoma in this disorder tends to be difficult to treat, as seen in our patient. One study reported that 17% of patients with vitreous amyloidosis required filtration surgery.12 A finding that was remarkable in both patients was the increased tissue friability that resulted in intraoperative buttonholing of the conjunctiva that was difficult to repair. We attribute this problem to conjunctival infiltration by amyloid that was demonstrated by pathologic examination in the first patient. Although no conjunctival sample was available in the second patient, conjunctival amyloid deposits were well described in familial amyloid polyneuropathy,13 and it is possible that the conjunctiva was also involved in the second patient.
1366
The management of glaucoma in these patients is unclear in the literature. It is possible that these patients may be more suitable candidates for shunt procedures as opposed to trabeculectomy. Nevertheless, despite the intraoperative difficulty and postoperative bleb leaks, both patients have continued to have functional filtration blebs. One may postulate that the inflammatory reaction seen in response to amyloid deposition in the subconjunctival space aided in the closure of bleb leaks. However, it is unclear why these blebs still continue to function for more than 1 year after surgery despite the expected inflammatory response to amyloid in the subconjunctival space.
References 1. Bansal RK, Gupta A, Agarwal A. Primary orbital amyloidosis with secondary glaucoma. A case report. Orbit 1991;10: 105– 8. 2. Sandgren O. Ocular amyloidosis, with special reference to the hereditary forms with vitreous involvement. Surv Ophthalmol 1995;40:173–96. 3. Ando E, Ando Y, Okamura R, et al. Ocular manifestations of familial amyloidotic polyneuropathy type I: long-term follow up. Br J Ophthalmol 1997;81:295– 8. 4. Futa R, Inada K, Nakashima H, et al. Familial amyloidotic polyneuropathy: ocular manifestations with clinicopathological observation. Jpn J Ophthalmol 1984;28:289 –98. 5. Kaufman HE. Primary familial amyloidosis. Arch Ophthalmol 1958;60:1036 –143. 6. Tsukahara S, Matsuo T. Secondary glaucoma accompanied with primary familial amyloidosis. Ophthalmologica 1977; 175:250 – 62. 7. Zeimer RC, Gieser DK, Wilensky JT, et al. A practical venomanometer. Measurement of episcleral venous pressure and assessment of the normal range. Arch Ophthalmol 1983; 101:1447–19. 8. Levine MR, Buckman G. Primary localized orbital amyloidosis. Ann Ophthalmol 1986;18:165–7. 9. Andrade C. A peculiar form of peripheral neuropathy. Familiar atypical generalized amyloidosis with special involvement of the peripheral nerves. Brain 1952;75:408 –27. 10. Ueno S, Uemichi T, Yorifuji S, Tarui S. A novel variant of transthyretin (Tyr 114 to Cys) deduced from the nucleotide sequences of gene fragments from familial amyloidotic polyneuropathy in Japanese sibling cases. Biochem Biophys Res Commun 1990;169:143–7. 11. Ciulla TA, Tolentino F, Morrow JF, Dryja TP. Vitreous amyloidosis in familial amyloidotic polyneuropathy. Report of a case with the Val30Met transthyretin mutation. Surv Ophthalmol 1995;40:197–206. 12. Doft BH, Machemer R, Skinner M, et al. Pars plana vitrectomy for vitreous amyloidosis. Ophthalmology 1987;94:607– 11. 13. Ando E, Ando Y, Maruoka S, et al. Ocular microangiopathy in familial amyloidotic polyneuropathy, type 1. Graefes Arch Clin Exp Ophthalmol 1992;230:1–5.