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Bilateral Asymmetrical Corneal Deposits in an Asymptomatic Patient

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.
1 Credit CME

A 70-year-old White woman with a history of hypertension and hyperlipidemia was referred to our institution for evaluation of bilateral asymmetric corneal lesions by her primary eye care professional. The patient required spectacles for best-corrected visual acuity but otherwise had no other significant ocular complaints. She was not taking medications known to cause corneal depositions, nor was there a known family history of corneal dystrophy. Best-corrected visual acuity was 20/20 OU. Slitlamp examination of the cornea of the right eye revealed multiple, discrete nodular opacities in the superior and inferior quadrants without neovascularization or surface elevation. Similar findings were seen in the left eye, but the superior lesions were notable for possessing well-circumscribed, plaquelike features located in the posterior stroma without involvement of the anterior surface (Figure, A). No crystalline changes were noted with these deposits.

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Monoclonal gammopathy of undetermined significance

B. Additional laboratory workup

When encountering asymmetrical, bilateral anterior and posterior stromal corneal lesions, clinicians should consider systemic causes (infectious, autoimmune, and hematologic) and pursue laboratory workup. Salzmann nodular degeneration was deemed less likely, given the variable lesion depth and lack of surface elevation. The following diagnostic workup was pursued: complete blood cell count, comprehensive metabolic panel, serum and urine protein electrophoresis, HIV, cytomegalovirus, Epstein-Barr virus, herpes simplex virus/herpes zoster virus, Lyme antibody titers (IgG/IgM), rapid plasma reagin, fluorescent treponemal antibody absorption, QuantiFERON Gold, angiotensin-converting enzyme, lysozyme, antinuclear antibody, rheumatoid factor, cyclic citrullinated peptide, antineutrophil cytoplasmic antibodies, and anti-SSA (Ro)/anti-SSB (La) antibodies. Results revealed an elevated γ globulin M spike (0.8 g/dL), cytomegalovirus IgG, and herpes simplex virus IgG. Notably, herpes simplex virus IgM, Epstein-Barr virus, and other autoimmune laboratory values were negative. The abnormal serum proteins prompted referral to a hematologist. Monoclonal gammopathies encompass a spectrum of diseases, including multiple myeloma and monoclonal gammopathy of undetermined significance (MGUS). While multiple myeloma is one of the most common hematologic malignancies, a forme fruste, premalignant stage-termed MGUS may precede it.1,2 Estimated to have a prevalence of 3% to 4% in individuals older than 50 years, MGUS progresses to multiple myeloma at a rate of 0.5% to 1% per year.2 Traditionally, it has been considered an asymptomatic disease stage and requires the absence of hypercalcemia, kidney failure, anemia, and bone lesions.2,3 Although visual symptoms are minimal in MGUS, ocular findings may be the first sign of systemic disease, providing ophthalmologists with an important role in diagnosing underlying disease.

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Article Information

Corresponding Author: Kamran M. Riaz, MD, Department of Ophthalmology, Dean McGee Eye Institute/University of Oklahoma, 608 Stanton L. Young Blvd, Oklahoma City, OK 73104 (kamran-riaz@dmei.org).

Published Online: March 11, 2021. doi:10.1001/jamaophthalmol.2020.4656

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for granting permission to publish this information. We also would like to thank Donald Stone, MD (Spokane Eye Clinic, Spokane, WA), for academic and clinical contributions to this case. Dr Stone did not receive compensation.

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Aragona  P , Allegra  A , Postorino  EI ,  et al.  Corneal structural changes in nonneoplastic and neoplastic monoclonal gammopathies.   Invest Ophthalmol Vis Sci. 2016;57(6):2657-2665.PubMedGoogle ScholarCrossref
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Milman  T , Kao  AA , Chu  D ,  et al.  Paraproteinemic keratopathy: the expanding diversity of clinical and pathologic manifestations.   Ophthalmology. 2015;122(9):1748-1756.PubMedGoogle ScholarCrossref
Stiefel  HC , Sandhu  RK , Miller  AK , Wilson  DJ , Chamberlain  WD .  Characterization of corneal deposition keratopathy in the setting of blood cell dyscrasia and a minimally invasive technique to clear the cornea in a single case.   Am J Ophthalmol Case Rep. 2018;13:83-88.PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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