Case 3 -
Keratopathy of Monoclonal Gammopathy
Gordon K. Klintworth, Duke Univ Medical Center, Durham, NC
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A 55 year-old myopic white female presented to an ophthalmologist with progressive clouding of vision
in both eyes for eight years. Her vision could not be corrected with refraction. Her past medical
history was notable for hypertension, hypercholesterolemia, and seasonal allergies. She did not have any
significant previous ocular history other than spectacle corrected myopia and a chronic complaint of dry
eyes for which she took artificial tears. None of her family members were known to have any eye
disorders. The patient was a longtime smoker, but did not abuse alcohol or other substances. On
examination the patient's best corrected visual acuity was 20/50 -2 OD and 20/70 -1 OS. Bilateral
diffuse, geographic shaped stromal opacities were noted in her corneas. They involved the visual axis
and impeded good visualization of the rest of the anterior chamber and posterior eye structures. A
penetrating keratoplasty (PK) was performed in the left eye in 2004. The patient was followed
post-operatively at regular intervals and her visual acuity worsened to 200 E at 3 feet OD and 20/50 OS.
Six months after the PK subepithelial deposits were noted in the corneal graft. They appeared to be
similar to those previously seen in the pre-PK left cornea and to those currently seen in the right
corneal stroma. One year later a PK was performed on the right eye.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Corneal tissue removed at penetrating keratoplasty from each cornea was processed for light
microscopy. Microscopic examination of the excised corneal button from both disclosed large confluent
deposits of eosinophilic material within the corneal stroma. The Masson trichrome stain manifested
strong fuchsinophilia of the stromal deposits, but a Congo red stain was negative for amyloid. An
immunohistochemical stains for both kappa and lambda light chains within the stromal deposits was
Case 3 - Figure 1
Acellular abnormal material in posterior corneal stroma. Masson trichrome stain
Case 3 - Figure 2
Acellular abnormal material in posterior corneal stroma. Hematoxylin and eosin stain.
Case 3 - Figure 3
Multifocal markedly eosinophilic spindle shaped acellular regions in superficial corneal stroma. Hematoxylin and eosin stain.
Case 3 - Figure 4
Higher magnification of Fig 2. Hematoxylin and eosin stain.
Case 3 - Figure 5
Extensive acellular eosinophilic accumulation adherent to the corneal stroma. Descemet membrane is not evident. Hematoxylin and eosin stain.
Case 3 - Figure 6
Multifocal acellular spindle shaped foci in the superficial corneal stroma. Note similarity to Case 3-Fig 3. Masson trichrome stain.
The presence of eosinophilic deposits in the cornea have a differential diagnosis that includes
amyloid (lattice corneal dystrophy type 1 and 2) and the granular corneal dystrophies (granular corneal
dystrophy types 1, 2, and 3).
Keratopathy of monoclonal gammopathy.
After the diagnosis was established the patient was referred back to her primary care physician for an
evaluation of systemic disease. Her complete blood count, albumin, and electrolyte panel were normal,
but her total protein was slightly elevated (8.3 g/dl (compared to the control levels of 6.0-8.0 g/dl))
and the serum protein electrophoresis showed a monoclonal component in the gamma region (1.78 g/dl
compared to control values of 0.53-1.37 g/dl). Other than her corneal findings, she continued to be
asymptomatic and no other systemic abnormalities were noted by her primary care team.
Review of the Literature/Treatment Options:
Monoclonal gammopathy of undetermined significance (MGUS) has a prevalence of 1% in individuals 50
years and older and 10% in those 75 years and older . MGUS is often asymptomatic and sometimes it
presents clinically with crystals in the cornea. Identical crystals occur in patients having
hypergammaglobilinemia due to multiple myeloma and other disorders
In many cases the
systemic disease is diagnosed only after bilateral delicate scintillating corneal crystals initiate a
systemic work-up. Aside from the cornea, crystals may occur in the bulbar conjunctiva or lens.
Klintworth et al.  established that the crystalline corneal deposits in multiple myeloma were composed
of immunoglobulin and that these deposits were similar to those previously seen in the cytoplasm of
neoplastic or reactive plasma cells, in crystallized plasma gammaglobulins, and in the renal tubular
epithelium in multiple myeloma. The location of the corneal immunoglobulin deposits varies considerably
from case to case. They may involve different sites in the cornea and are sometimes dispersed throughout
the cornea. Later it was appreciated that the IgG deposits within the cornea in MGUS are not necessarily
crystalline in appearance  and that the deposits may resemble certain genetically determined diseases
of the cornea (corneal dystrophies)
A penetrating keratoplasty is often indicated to restore vision
in patients with immunoglobulin deposition in the cornea. The deposits may, however, recur in the graft.
The cornea may be affected in conditions associated with hypergammaglobulinemia such as a monoclonal
gammopathy of uncertain significance and multiple myeloma.
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