Table 1.
Cases of Ocular Pathology Associated with Essential Monoclonal Gammopathy.
| Citation/Year of Report | Age | Sex (M/F) | Ig Isotype | Other Tissue Involvement | Treatment | Outcome | Notes |
|---|---|---|---|---|---|---|---|
| Crystalline Keratopathy | |||||||
| 12/1959 | 55 | F | IgG (light chain type not determined) | Iritis, conjunctivitis | None at the time of diagnosis | Five years after diagnosis of keratopathy, myeloma developed with crystals in myeloma cells | |
| 7/1979 | 74 | F | IgG-kappa | No | Keratoplasty and cataract extraction | Not reported | Posterior corneal stroma contained parallel structures with periodicity of 10–11 nm |
| 17/1980 | 57 | M | IgG-kappa | Iritis | Not reported | Not reported | History of Hodgkin lymphoma treated with radiation |
| 14/1980 | 39 | F | IgG-kappa | Tearing, photophobia | Not reported | Not reported | IgGk deposits in corneal stroma and Bowman membrane. Electron micrograph showed parallel rod-like structures with periodicity of 10 nm |
| 23/1985 | 65 | F | IgA-kappa | Macular drusen | Not reported | Not reported | Slit lamp examination showed needle-like refractile, coarse crystals in mid-deep corneal stroma, bilaterally |
| 16/1988 | 50 | F | IgG-kappa | Uveitis | Corneal graft and posterior chamber intraocular lens insertion | Recurrence of crystalline keratopathy by 4 months | TEM revealed paracrystals with periodicity of 16 nm |
| 25/1989 | 60 | M | IgG-kappa (essential cryo-immunoglobulin) | No | Superficial keratectomy | Improved visual acuity | Crystallization at the corneal subepithelium in this case thought to be related to that site being the coldest in the body (~32°C) |
| 28/1993 | 62 | F | IgG-kappa | No | Not reported | Not reported | Crystal deposits by TEM were all extracellular, located between keratocytes |
| 28/1993 | 65 | M | IgG-kappa | No | Not reported | Not reported | Majority of crystals by TEM were intracellular in stromal keratocytes |
| 29/1994 | 62 | M | IgG-kappa | No | Penetrating keratoplasty | Not reported | IgGk deposits in cornea; TEM showed intracytoplasmic Ig in keratocytes with 10 nm periodicity |
| 20/1996 | 52 | F | IgG-kappa | Photophobia and foreign body sensation | Not reported | Not reported | TEM of corneal biopsy found extracellular rectangular and arcuate crystalloids with 10 nm periodicity |
| 19/1999 | 55 | F | IgG-kappa | No | Penetrating keratoplasty, open-sky extracapsular cataract extraction, posterior chamber intraocular lens implantation | Not reported | Decreasing visual acuity led to diagnosis crystalline keratopathy and, subsequently, of IgG-kappa essential monoclonal gammopathy. IgG-kappa-positive deposits in corneal button removed at keratoplasty; TEM showed numerous bundles of electron dense deposits of filaments with a periodicity of 10–13 nm in the anterior stroma of the cornea. Some deposits were phagocytosed by keratocytes |
| 18/2011 | 62 | F | IgG-kappa | No | Three penetrating keratoplasty surgeries, right-sided: at diagnosis, then 9 years and 12 years later for recurrent loss of visual acuity in the right eye | Improvement for several months post-keratoplasty followed by gradual decrease in visual acuity over years | Left eye affected but to a lesser degree than right eye; no follow-up reported after 3rd keratoplasty |
| Crystal-storing Histiocytosis Involving the Eye | |||||||
| 35/1990 | 64 | F | IgA-kappa | No | Not described | Not described | Slit lamp exam revealed bilateral superficial corneal and conjunctival crystals. Diagnosed by conjunctival biopsy |
| 10/1993 | 62 | F | IgG-kappa | Crystalline keratopathy | 4 cycles of bortezomib-based chemotherapy followed by autologous stem cell transplantation | 18 months following autologous stem cell transplantation, patient in complete hematologic, renal, and ophthalmologic remission | Melphalan conditioning for auto-transplant. At 3 months post-transplant, orbital mass had significantly decreased, Fanconi syndrome resolved, and there was no detectable paraproteinemia |
| 34/2009 | 66 | M | IgG-lambda | Crystalline keratopathy | Not described | Not described | Right-sided keratoplasty for crystalline keratopathy 1 year prior to diagnosis of CSH. MRI revealed enhancement of retrobulbar fat and thickening of extraocular muscles; biopsy revealed CSH |
| Corneal Deposition of Immunoglobulin-bound Copper | |||||||
| 42/1967 | 69 | F | IgG | No | Not described | Not described | Myeloma diagnosed 1 year after slit lamp findings of greenish-blue granular discoloration of corneal epithelium and Descemet membrane. Serum copper 13 to 24 × values found in 11 other unaffected myeloma patients tested. Serum ceruloplasmin was normal. Mild increase in urinary copper |
| 44/1975 | 41 | F | IgG-lambda | No | Not described | Not described | 3 years before diagnosis of myeloma, patient had diagnosis of “cataracts” despite 20/20 vision. Soon thereafter cornea found to have dense brown staining reminiscent of Kayser–Fleischer type corneal rings. Serum copper 7 to 11 × normal serum value. Serum ceruloplasmin normal |
| 39/1983 | 60 | M | IgG-lambda | Not reported | Intracapsular cataract extraction and insertion of Binkhorst four-loop lens | Not reported | Concurrent diagnosis of lung carcinoma. Received radiation to lung. Slit lamp examination showed diffuse greenish-yellow discoloration of cornea. Serum copper 7 × normal serum value. Serum ceruloplasmin normal |
| 41/1996 | 65 | M | IgG-kappa | Copper depositions in anterior and posterior lens surface and appearance of sunflower cataract | Zinc gluconate | No change in serum copper | Bilateral blurred vision. Slit lamp examination revealed golden-brown deposits diffusely distributed centrally in cornea. Serum copper 12 × normal serum value. Serum ceruloplasmin normal. Special studies showed binding of copper to serum monoclonal IgG by two methods |
| 40/2005 | 49 | F | IgG-lambda | No | No | N/a | Patient asymptomatic. Slit lamp examination showed golden-brown metallic dust-like particles in Descemet membrane bilaterally. Serum copper 3 × normal. Serum ceruloplasmin normal |
| 38/2014 | 46 | F | IgG-lambda | No | Descemet-stripping endothelial keratoplasty and cataract extraction with intraocular lens implant of left eye | Complete return of normal visual acuity (20/20) | Posterior layer of both corneas had a confluent tan color with only a narrow rim of clear cornea peripherally. Serum copper 12 × normal. Serum ceruloplasmin normal |
| Maculopathy | |||||||
| 47/2013 | 37 | F | Not specified | No | Prednisone with inability to wean until rituximab was initiated | Marked and rapid improvement in inflammation and visual acuity with prednisone but recurrence with taper. Resolution of ocular findings without recurrence at 9 months once rituximab therapy was initiated | Bilateral serous macular detachments, iritis, vitritis. Details of how frequently and at what dose rituximab treatment and maintenance treatment were administered are not provided |
CSH, crystal-storing histiocytosis; F, female; M, male; MRI, magnetic resonance imaging; TEM, transmission electron microscopy.