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Clinicopathologic Reports, Case Reports, and Small Case Series |

Isolated Vitreoretinal Amyloidosis in the Absence of TransthyretinMutations FREE

Fina C. Barouch, MD; Merrill D. Benson, MD; Shizuo Mukai, MD
[+] Author Affiliations

Section Editor: W. Richard Green, MD


Arch Ophthalmol. 2004;122(1):123-125. doi:10.1001/archopht.122.1.123.
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Published online

Vitreoretinal amyloidosis is believed to be associated universally withmutations in the genes encoding transthyretin and found exclusively as partof the familial amyloidotic polyneuropathy (FAP) syndrome.1 Wedescribe herein an unusual case of biopsy-proved vitreoretinal amyloidosiswithout systemic involvement and demonstrate that vitreoretinal amyloidosiscan occur with intact wild-type transthyretin genes.

A 70-year-old woman with a history of hypercholesterolemia, chronicobstructive pulmonary disease, a distant cerebrovascular accident, and bilateralcataract extractions was first seen by us with "black snow" clouding her visionin both eyes. Review of systems was otherwise unremarkable, and her familyhistory was negative for amyloidosis. Her visual acuity was 20/50 OD and 20/60OS and worsened with pinhole examination. There was no relative afferent pupillarydefect, intraocular tensions were within normal limits, and slitlamp examinationdisclosed quiet anterior segments and clear well-centered posterior chamberintraocular lens implants bilaterally. Dilated fundus examination showed multiple,white, refractile vitreous opacities dispersed in a syneretic vitreous inboth eyes (Figure 1A). Yellow depositswere also seen deep to the retina in the periphery (Figure 1B). A therapeutic and diagnostic left vitrectomy was thenperformed.

Place holder to copy figure label and caption
Figure 1.

A, Preoperative fundus photographdemonstrating white vitreous deposits. B, Postoperative fundus photographof the peripheral retina demonstrating yellow deposits under the retina.

Graphic Jump Location

Histopathologic analysis of the vitreous biopsy specimen showed eosinophiliclobules that stained positively with Congo red (Figure 2A) and demonstrated birefringence when examined under polarizedlight (Figure 2B). These findingswere diagnositic of amyloidosis. Oil-red-O stain was negative for lipids andvon Kossa stain was negative for calcium phosphate salts. Genomic DNA wasthen isolated from peripheral blood, and exons corresponding to the entiretransthyretin protein were amplified by the polymerase chain reaction. DirectDNA sequence analysis of the amplified fragments revealed no mutations inthe entire coding sequence, demonstrating that this patient was homozygousfor wild-type transthyretin. Moreover, single-stranded conformational polymorphismand isoelectric focusing analyses did not show any abnormal patterns for transthyretin.The patient subsequently underwent vitrectomy of the right eye. With 7 yearsof clinical follow-up at this report, she has not developed any signs or symptomsof systemic amyloidosis, although there have been increases in the vitreousdeposits in both eyes.

Place holder to copy figure label and caption
Figure 2.

Histopathologic analysis of thevitreous biopsy specimen. A, Positive staining for eosinophilic lobules withCongo red is evident (original magnification ×250). B, Birefringenceis seen when the specimen is examined under polarized light (original magnification×250).

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Amyloidosis is a heterogeneous group of disorders involving the depositionof insoluble fibrillar hyaline aggregates in peripheral tissues. Amyloidosisaffecting the vitreous was first reported in 1953 in individuals with FAP,an autosomal dominant disorder that includes vitreopathy, cardiomyopathy,and peripheral neuropathy.2 In fact, vitreoretinalamyloidosis is thought to be found exclusively in individuals with FAP andassociated universally with mutations in the transthyretin gene. To date,more than 80 such transthyretin mutations have been described.1 Incontrast, systemic amyloidosis can result from a number of distinct amyloiddeposits, including wild-type transthyretin3 aswell as other fibrillar proteins.4

To our knowledge, this is the first case report of vitreoretinal amyloidosisin the absence of transthyretin mutations. In addition, no signs of systemicamyloidosis suggestive of FAP were evident 7 years after the patient's initialpresentation, although we cannot exclude the possibility of a subclinicallevel of amyloid deposition in other tissues.5,6 Thesefindings raise the possibility that isolated vitreoretinal amyloidosis mayrepresent a disorder separate from FAP. We conclude that vitreoretinal amyloidosisencompasses a more heterogeneous group of disorders than has been previouslydescribed.

Corresponding author and reprints: Shizuo Mukai, MD, Department ofOphthalmology, Retina Service, Massachusetts Eye and Ear Infirmary, 243 CharlesSt, Boston, MA 02114 (e-mail: shizuo_mukai@meei.harvard.edu).

Bhisitkul  RBMukai  S Vitreous amyloidosis. Albert  DMJakobiec  FAedsPrinciples andPractice of Ophthalmology. 2nd Philadelphia, Pa WB Saunders Co2000;2530- 2539
Kantarian  ADDe Jong  RN Familial primary amyloidosis with nervous system involvement. Neurology. 1953;3399- 409
PubMed Link to Article
Westermark  PSletten  KJohansson  BCornwell  GG  III Fibril in senile systemic amyloidosis is derived from normal transthyretin. Proc Natl Acad Sci U S A. 1990;872843- 2845
PubMed Link to Article
Lachmann  HJBooth  DRBooth  SE  et al.  Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002;3461786- 1791
PubMed Link to Article
Sandgren  O Ocular amyloidosis, with special reference to the hereditary formsof vitreous involvement. Surv Ophthalmol. 1995;40173- 196
PubMed Link to Article
Schwartz  MFGreen  WRMichels  RMKincaid  MCFogle  J An unusual case of ocular involvement in primary systemic nonfamilialamyloidosis. Ophthalmology. 1982;89394- 401
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

A, Preoperative fundus photographdemonstrating white vitreous deposits. B, Postoperative fundus photographof the peripheral retina demonstrating yellow deposits under the retina.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Histopathologic analysis of thevitreous biopsy specimen. A, Positive staining for eosinophilic lobules withCongo red is evident (original magnification ×250). B, Birefringenceis seen when the specimen is examined under polarized light (original magnification×250).

Graphic Jump Location

Tables

References

Bhisitkul  RBMukai  S Vitreous amyloidosis. Albert  DMJakobiec  FAedsPrinciples andPractice of Ophthalmology. 2nd Philadelphia, Pa WB Saunders Co2000;2530- 2539
Kantarian  ADDe Jong  RN Familial primary amyloidosis with nervous system involvement. Neurology. 1953;3399- 409
PubMed Link to Article
Westermark  PSletten  KJohansson  BCornwell  GG  III Fibril in senile systemic amyloidosis is derived from normal transthyretin. Proc Natl Acad Sci U S A. 1990;872843- 2845
PubMed Link to Article
Lachmann  HJBooth  DRBooth  SE  et al.  Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis. N Engl J Med. 2002;3461786- 1791
PubMed Link to Article
Sandgren  O Ocular amyloidosis, with special reference to the hereditary formsof vitreous involvement. Surv Ophthalmol. 1995;40173- 196
PubMed Link to Article
Schwartz  MFGreen  WRMichels  RMKincaid  MCFogle  J An unusual case of ocular involvement in primary systemic nonfamilialamyloidosis. Ophthalmology. 1982;89394- 401
PubMed Link to Article

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