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JAMA Ophthalmology Clinical Challenge
March 5, 2020

A Man With Bilateral Corneal Verticillata and Corneal Crystals

Author Affiliations
  • 1Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
JAMA Ophthalmol. Published online March 5, 2020. doi:10.1001/jamaophthalmol.2020.0128

Case

A 77-year-old man was referred to the cornea service for bilateral corneal verticillata noted first by his general ophthalmologist. One year prior to presentation, the patient had undergone coronary artery bypass grafting (CABG). He was discharged with amiodarone and used the medication for 6 weeks. He did not use amiodarone for the 10 months prior to presentation. Prior to his CABG procedure, the patient only used a low dose of lisinopril until he began experiencing progressive dyspnea and fatigue. He was found to have a 5-vessel blockage once he became symptomatic. His symptoms resolved after the CABG surgery, and he remained otherwise healthy. He denied any other symptoms, including headache, rash, joint pain, or chest pain. His medications at time of presentation were aspirin, atorvastatin, and carvedilol. His best-corrected visual acuity was 20/20 OD and 20/25 OS. A slitlamp examination revealed bilateral corneal verticillata and numerous fine anterior stromal crystals (Figure). He had mild nuclear sclerosis in both eyes. His pupils were round and equally reactive, and the remainder of the slitlamp examination and dilated fundus examination were within normal limits.

Figure.  Slitlamp photograph of the right eye showing corneal verticillata (yellow arrowheads) and fine interspersed corneal crystals (most visible in the white circle).
Slitlamp photograph of the right eye showing corneal verticillata (yellow arrowheads) and fine interspersed corneal crystals (most visible in the white circle).
Box Section Ref ID

What Would You Do Next?

  1. Provide reassurance, because the patient is no longer taking amiodarone

  2. Obtain genetic testing

  3. Initiate corneal scraping and culture

  4. Initiate laboratory testing for immunoglobulins

Discussion

Diagnosis

Paraproteinemic keratopathy from monoclonal gammopathy of unknown significance

What to Do Next

D. Initiate laboratory testing for immunoglobulins

Discussion

Although most patients taking amiodarone will eventually develop corneal verticillata, amiodarone does not classically cause a crystalline keratopathy, for which other conditions should be excluded before reassurance is provided (choice A). Genetic testing (choice B) could be useful in patients with Fabry disease or other metabolic causes of verticillata, but Fabry disease would be less likely in this context. There is no evidence of an infection or an infiltrate, so initiating corneal scraping and culture (choice C) would not be indicated.

Monoclonal gammopathy of unknown significance (MGUS) and multiple myeloma (MM) are dyscrasias of plasma cells that result in elevated levels of abnormal monoclonal antibodies in the blood (paraproteinemia). Patients with MGUS are often asymptomatic and may lack signs of pathology on physical examination. Often, the discovery of MGUS in a patient is incidental when a patient has had laboratory work done for another screening. Multiple myeloma and MGUS may appear similar, although the testing for MM usually reveals higher degrees of paraproteinemia and plasma-cell proliferation. Because of the rate of progression from MGUS to MM (approximately 1% per year), patients with MGUS must be monitored closely to detect conversion to MM.1

Deposition of immunoglobulins on tissues characterize MGUS and MM in both ocular and nonocular manifestations of the disease. Both conditions have both been found to cause a variety of ocular abnormalities, including crystalline keratopathies,2 corneal verticillata,3 and maculopathies.4 Because of the wide phenotypic array of immunoglobulin deposition in the cornea (paraproteinemic keratopathy), MGUS and MM should be entertained in the differential diagnosis of corneal opacities of unknown origin.

Diagnoses of MGUS and MM are most commonly done through bloodwork. Complete blood cell counts and creatinine, electrolyte, and albumin levels are all essential laboratory tests for diagnosing plasma-cell dyscrasias. Blood levels of immunoglobulins will help assess which antibody levels are abnormally high or low. Urine protein electrophoresis, urine immunofixation, and bone marrow biopsies are also performed. Finally, corneal biopsy or anterior chamber paracentesis are alternative approaches to confirm the diagnosis of paraproteinemic keratopathy in a patient with MGUS.5

Patient Outcome

The patient’s laboratory test results revealed an elevated IgG level of 2492 mg/dL (normal range, 600-1800 mg/dL; to convert to grams per liter, multiply by 0.01). The abnormal results were discussed with the patient’s primary care physician, and a decision was made to refer the patient to hematology-oncology for long-term follow-up. Additional laboratory testing revealed mild anemia, a slight elevation in serum calcium (10.8 mg/dL [to convert to millimoles per liter, multiply by 0.25]) and total protein (8.5 g/dL [to convert to grams per liter, multiply by 10.0]), with a γ gap of 4.3 g/dL, elevated κ light chains (340), and an elevated κ:λ ratio (21.29). A skeletal survey showed possible lytic lesions in the right ribs, but the patient did note remote trauma to that area. The patient was scheduled to undergo bone marrow aspiration and biopsy with hematology-oncology.

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Article Information

Corresponding Author: Vishal Jhanji, MD, Department of Ophthalmology, University of Pittsburgh School of Medicine, 203 Lothrop St, Pittsburgh, PA 15213 (jhanjiv@pitt.edu).

Published Online: March 5, 2020. doi:10.1001/jamaophthalmol.2020.0128

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
1.
Therneau  TM, Kyle  RA, Melton  LJ  III,  et al.  Incidence of monoclonal gammopathy of undetermined significance and estimation of duration before first clinical recognition.  Mayo Clin Proc. 2012;87(11):1071-1079. doi:10.1016/j.mayocp.2012.06.014PubMedGoogle ScholarCrossref
2.
Garibaldi  DC, Gottsch  J, de la Cruz  Z, Haas  M, Green  WR.  Immunotactoid keratopathy: a clinicopathologic case report and a review of reports of corneal involvement in systemic paraproteinemias.  Surv Ophthalmol. 2005;50(1):61-80. doi:10.1016/j.survophthal.2004.10.002PubMedGoogle ScholarCrossref
3.
Chierego  C, Merz  T, Fasolo  A, Lagali  N, Pedrotti  E.  In vivo confocal microscopy of verticillata-like paraproteinemic keratopathy in a patient with monoclonal gammopathy of uncertain significance evolving into smoldering multiple myeloma.  Am J Ophthalmol Case Rep. 2019;15:100505. doi:10.1016/j.ajoc.2019.100505PubMedGoogle Scholar
4.
Balderman  SR, Lichtman  MA.  Unusual manifestations of monoclonal gammopathy, I: ocular disease.  Rambam Maimonides Med J. 2015;6(3):e0026. doi:10.5041/RMMJ.10211PubMedGoogle Scholar
5.
Karakus  S, Gottsch  JD, Caturegli  P, Eghrari  AO.  Monoclonal gammopathy of “ocular” significance.  Am J Ophthalmol Case Rep. 2019;15:100471. doi:10.1016/j.ajoc.2019.100471PubMedGoogle Scholar
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