title: Paraproteinemic Keratopathy: The Expanding Diversity of Clinical and Pathologic Manifestations.
abstract: OBJECTIVE
  To describe 7 patients with paraproteinemic keratopathy and to highlight the clinical and pathologic diversity of this rare entity and the importance of timely, systemic evaluation.
  
  
  METHODS
  Retrospective, multicenter collaborative case series.
  
  
  METHODS
  Seven patients with paraproteinemic keratopathy.
  
  
  METHODS
  Clinical and pathologic records were reviewed to identify patients with well-documented corneal immunoglobulin deposits. Detailed ophthalmologic and medical histories were assembled. In 6 patients, corneal tissue was evaluated histochemically and immunohistochemically; in selected cases, corneal tissue was evaluated by in situ hybridization and ultrastructurally.
  
  
  METHODS
  Visual acuity and anterior segment examination at presentation and follow-up; local therapy; systemic diagnosis and management; and histopathologic, immunohistochemical, in situ hybridization, and ultrastructural findings.
  
  
  RESULTS
  Seven patients were identified with corneal immunoglobulin deposition. In addition to previously reported crystalline, nummular, patch-like, and lattice-like corneal opacities, prominent corneal vascularization was present in 2 patients mimicking interstitial keratitis and limbal stem cell deficiency. All patients had evidence of paraproteinemia in a setting of monoclonal gammopathy of undetermined significance, smoldering plasma cell myeloma, or Waldenström macroglobulinemia. Corneal findings were the first manifestation of systemic disease in 4 patients, and the diagnosis was not suspected in 3 of these patients. Pathologic evaluation of biopsied corneal and conjunctival tissues demonstrated immunoglobulin deposits. Previously unreported ultrastructural patterns in the cornea were noted: large scroll-like immunotactoid deposits, immune complex-like deposits, and randomly arranged fibrils morphologically intermediate between amyloid and immunotactoid deposits. Surgical intervention to improve vision was performed in 4 patients, with recurrence of deposits in 3 patients. Three patients underwent systemic therapy with diminution of the deposits and improvement in vision in 1 patient.
  
  
  CONCLUSIONS
  The clinical and pathologic expressions of corneal immunoglobulin deposits are protean and present a diagnostic challenge. Early recognition of this rare entity is important to address the potentially serious associated systemic disease.
authors.affiliation: Departments of Ophthalmology and Pathology, New York Eye and Ear Infirmary of Mount Sinai, New York, New York. Electronic address: tatyana.milman@gmail.com.
authors.forename: Tatyana
authors.initials: T
authors.lastname: Milman
authors.affiliation: Departments of Ophthalmology and Pathology, New York Eye and Ear Infirmary of Mount Sinai, New York, New York.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Kao
authors.affiliation: Metropolitan Eye Research and Surgery Institute, Palisades Park, New Jersey.
authors.forename: David
authors.initials: D
authors.lastname: Chu
authors.affiliation: Department of Ophthalmology, North Shore-Long Island Jewish Health System, Manhasset, New York.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gorski
authors.affiliation: Department of Ophthalmology, North Shore-Long Island Jewish Health System, Manhasset, New York.
authors.forename: Annie
authors.initials: A
authors.lastname: Steiner
authors.affiliation: Department of Ophthalmology, North Shore-Long Island Jewish Health System, Manhasset, New York.
authors.forename: Carrie Zaslow
authors.initials: CZ
authors.lastname: Simon
authors.affiliation: Department of Ophthalmology, North Shore-Long Island Jewish Health System, Manhasset, New York.
authors.forename: Carolyn
authors.initials: C
authors.lastname: Shih
authors.affiliation: The Jules Stein Eye Institute, University of California, Los Angeles, Los Angeles, California.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Aldave
authors.affiliation: Departments of Ophthalmology and Pathology, Wills Eye Hospital, Philadelphia, Pennsylvania.
authors.forename: Ralph C
authors.initials: RC
authors.lastname: Eagle
authors.affiliation: David G. Cogan Laboratory of Eye Pathology, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts.
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Jakobiec
authors.affiliation: Department of Ophthalmology, North Shore-Long Island Jewish Health System, Manhasset, New York.
authors.forename: Ira
authors.initials: I
authors.lastname: Udell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D003315:Cornea / Q000473:pathology; D003316:Corneal Diseases / Q000175:diagnosis* / Q000276:immunology / Q000601:surgery; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000097:blood; D007143:Immunoglobulin Heavy Chains / Q000276:immunology; D015948:Keratoplasty, Penetrating; D008297:Male; D008875:Middle Aged; D010265:Paraproteinemias / Q000175:diagnosis* / Q000276:immunology / Q000601:surgery; D012189:Retrospective Studies; D014792:Visual Acuity / Q000502:physiology
chemical_list: D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains