Purpose
To describe the nature and evolution of acquired macular detachments in patients with immunogammopathies and to propose a mechanism for their development.
Design
Retrospective observational case series.
Methods
Three patients with multiple myeloma and 1 with light chain deposition disease were diagnosed with vitelliform macular detachments based on clinical examination, fundus autofluorescence, fluorescein angiography, and optical coherence tomography. These patients were followed over time and their clinical examinations and imaging studies were compared and contrasted.
Results
Three patients (5 eyes) with multiple myeloma and 1 patient (2 eyes) with light chain deposition disease presented with acquired macular yellowish subretinal deposits on funduscopic examination that corresponded to hyperautofluorescent lesions on fundus autofluorescence imaging and subretinal hyperreflective material on spectral-domain optical coherence tomography. One patient (2 eyes) had diffuse serous retinal detachments involving not only the macular region but also the midperiphery of the retina. These acquired macular vitelliform detachments were not associated with signs of hyperviscosity retinopathy in 5 eyes and resolved after successful treatment of the multiple myeloma in 6 eyes.
Conclusion
Patients with an immunogammopathy such as multiple myeloma or light chain deposition disease may develop serous elevations of the macula that we classify as acquired vitelliform detachments using multimodal imaging. Appropriate evaluation including serum protein electrophoresis and hematology consultation should be considered in the management of patients with acquired vitelliform detachments of uncertain etiology.
Immunogammopathies are clonal plasma cell proliferative disorders characterized by deposition of light or heavy chain immunoglobulin fragments in tissues, leading to organ dysfunction. Within this spectrum of diseases are multiple myeloma, Waldenstrom’s macroglobulinemia, and benign monoclonal gammopathy, as well as light chain deposition disease. Ocular manifestations of immunogammopathies have been described in a variety of ocular structures, including the conjunctiva, cornea, uvea, and retina.
Serous macular detachments in association with immunogammopathies, though rare, have been described. Ho and associates first reported serous macular detachments with or without subretinal precipitates or fundus signs of serum hyperviscosity in 1 patient with multiple myeloma, 1 patient with Waldenstrom’s macroglobulinemia, and 1 patient with benign polyclonal gammopathy. Specifically in multiple myeloma, only 1 report describes deposits on the posterior surface of the neurosensory retina and in the subretinal space anterior to the retinal pigment epithelium (RPE). This previous study did not include current imaging modalities such as spectral-domain optical coherence tomography (SD OCT) or fundus autofluorescence imaging.
This is a report on an additional 4 patients—3 with multiple myeloma and 1 with light chain deposition disease—who have associated serous detachments evaluated with multimodal imaging including fluorescein angiography, fundus autofluorescence, and SD OCT. We also propose a mechanism that would explain the advent and course of these particular exudative detachments.
Patients and Methods
The institutional review board (IRB) at Northshore Long Island Jewish Hospital waived IRB approval for this retrospective case series. The records of 4 patients with vitelliform macular detachments and an immunogammopathy were examined. The following data were collected for each of the 4 cases: Snellen visual acuity at presentation and subsequent visits, epidemiologic data, past medical history, and clinical signs of retinal vasculopathy. The following imaging was also collected: fundus photographs, fluorescein angiography, fundus autofluorescence, and optical coherence tomography (OCT).
Results
Case 1
A 58-year-old woman presented with bilateral, asymmetric decreased vision over the course of several weeks. Her past medical history included well-controlled diabetes, a remote history of skin melanoma removed from the leg 12 years prior with no metastasis, and multiple myeloma, for which she was undergoing treatment. The patient was enrolled in multiple myeloma trial IPH 2101-203, a multicenter, open-label phase II clinical trial designed to evaluate IPH 2101, an anti-KIR monoclonal antibody potentiating the antitumor activity of NK cells in patients with previously untreated smoldering multiple myeloma. As part of this trial, the patient underwent regular chemotherapy administrations for 1 year with no change in her multiple myeloma numbers. She presented to us on month 8 of this trial. Her past ocular history included a branch retinal vein occlusion (BRVO) in the left eye (OS). Her best-corrected visual acuity (BCVA) was 20/30 in the right eye (OD) and 20/70 OS with no relative afferent pupillary defect. Slit-lamp biomicroscopy showed a normal anterior segment examination. Dilated fundus examination revealed mild RPE changes, extending inferiorly from the discs in both eyes (OU) ( Figure 1 , Top row). On fundus autofluorescence, hyperautofluorescent macular lesions surrounded by a wider area of granular hypoautofluorescence were present, more prominently OS and associated with bilateral hypoautofluorescent atrophic descending tracts ( Figure 1 , Second row). Fluorescein angiography revealed diffuse intraretinal leakage, optic disc leakage, and some retinal microvascular abnormalities, but the area of detachment was hypofluorescent ( Figure 1 , Third row). No leak or pooling was noted in the area of the macular detachments. SD OCT at the level of these lesions showed a macular detachment with vitelliform deposition on the anterior surface of the RPE and the posterior surface of the neurosensory retina with associated subretinal and intraretinal fluid, more prominent OS and associated with intraretinal cysts at the level of the outer nuclear layer ( Figure 1 , Fourth row). Enhanced depth imaging (EDI) OCT revealed slightly increased subfoveal choroidal thickness measuring 347 μm OD and 305 μm OS.
Treatment of the macular edema with 10 anti–vascular endothelial growth factor (VEGF) intravitreal injections was initiated and response was followed by SD OCT. Five months after completing the multiple myeloma trial, she was started on 50 mg (oral [PO]) prednisone and underwent chemotherapy with 2 cycles of Velcade, a mitogen-activated protein kinase enzyme inhibitor; Revlimid; and Cytoxin. By this point she had received 9 anti-VEGF intravitreal injections as treatment for her BRVO, with improvement, but no resolution, of subretinal and intraretinal fluid. Three months later, she underwent induction chemotherapy again with Velcade, Revlimid, and 50 mg PO prednisone. It was during this month that her multiple myeloma immunoglobulin numbers came down for the first time in 20 months. This reduction in serum immunoglobulin from an M-spike of 5.63 to an M-spike of 0.94 coincided with a resolution of her vitelliform macular detachments and associated intraretinal and subretinal fluid for the first time since initiating treatment ( Figure 1 , Bottom row).
Case 2
A 59-year-old woman with light chain deposition disease presented with decreased vision OU. BCVA was 20/20 OD and 20/25 OS. Past medical history was positive for hypertension, anemia, and end-stage renal disease. Fundus examination revealed peculiar subretinal lesions ( Figure 2 , Top row). These lesions were hyperautofluorescent on fundus autofluorescence ( Figure 2 , Middle row). Although OCT OD was flat, OCT OS showed a subretinal deposit anterior to the RPE ( Figure 2 , Bottom row). After 7 years of follow-up, fundus examination revealed persistence of the subretinal lesions with progression to neurosensory detachments and 20/50 vision OU. At this time, 1 dot-blot hemorrhage in the midperiphery of each eye was identified with no associated vein occlusion, microaneurysms, or venous congenstion. As the patient had uncontrolled arterial hypertension at the time of this visit, the dot-blot hemorrhages were deemed to be secondary to the hypertension. Currently, the patient is referred for plasmapheresis.
Case 3
A 55-year-old man presented with multiple neurosensory detachments OU including the peripapillary retina and fovea. On fundus examination, there were also multifocal areas of subretinal yellow deposits OU ( Figure 3 , Top row). His past medical history was significant only for mild hypertension. Fluorescein angiogram and indocyanine green chorioangiography revealed no focal leakage, hyperpermeability, plaque, or hot spot, but the yellow deposits were hyperautofluorescent on fundus autofluorescence ( Figure 3 , Second row). SD OCT showed neurosensory detachments with vitelliform deposition on the posterior surface of the neurosensory retina OU ( Figure 3 , Third row). Over time the macular neurosensory detachment resolved OU, leaving RPE atrophy with a visual decline down to roughly the 20/50 level OD. Two years later, the patient returned with a nearly symmetrical neurosensory detachment in the peripapillary retina and central macula OS, in addition to several elevated areas along the arcades in both eyes. There were no hemorrhages, exudations, or vascular tortuosity. By this time, he had developed monoclonal gammopathy of undetermined significance. A new fluorescein angiogram revealed no focal leaks in the macula OU. There was RPE atrophy in the right eye, and again the yellow lesions were hyperautofluorescent OU. Fortunately, his vision remained at 20/20 OS, although he had a hyperopic shift, and there was some mild distortion. Half-fluence photodynamic therapy was applied to the left eye, which ultimately did not alter the neurosensory detachment or his vision in any way. Repeat laboratory evaluation at this point led to a new diagnosis of multiple myeloma. He subsequently developed a few intraretinal hemorrhages and mild vascular tortuosity indicative of hyperviscosity that was characterized as rather subtle. Although several sequential treatments with plasmapheresis yielded no change in the neurosensory detachment in the left eye, the hemorrhages and tortuosity improved. He underwent bone marrow transplant at this time. Three years after presentation, electrophysiologic testing revealed an electrooculogram (EOG) with a normal Arden ratio. The electroretinogram (ERG) showed a mildly abnormal scotopic and photopic response with significant cone dysfunction in both eyes, somewhat more advanced OD. After bone marrow transplant, SD OCT showed resolution of the vitelliform detachments with residual subretinal fibrosis OD ( Figure 3 , Bottom row).
Case 4
A 62-year-old man presented with decreased vision OD of 1 month’s duration. BCVA OD was 20/30-1. The left eye was asymptomatic, with BCVA of 20/30+1. Past medical history included hypertension and multiple myeloma. The patient was taking 20 mg dexamethasone daily and reported that he first noticed a change in his vision after using Velcade as part of the Velcade-Revlimid-Dexamethasone protocol for 15 weeks. At this time his M-spike was 0.61 and he was taken off the Velcade but restarted back on it 1 month later when his M-spike increased to 0.71. Fundus photographs showed serous pigment epithelial detachments OU ( Figure 4 , Top row) with hyperautofluorescent material on fundus autofluorescence more prominent OD ( Figure 4 , Second row), but no retinal vasculopathy OU. SD OCT showed vitelliform deposits below the neurosensory retina and above the RPE OD ( Figure 4 , Third row). EDI OCT revealed increased choroidal thickness measuring 450 μm OD and 350 μm OS. At this time he was started on a mineralocorticoid since he had findings resembling central serous chorioretinopathy (CSC), but this regimen did not produce any change for 3 months. Finally, his serous pigment epithelium detachments completely resolved 4 months later while he was still on the mineralocorticoid, 50 mg of oral prednisone, and Velcade ( Figure 4 , Bottom row). This improvement coincided with an M-spike of 0.34, a record-low multiple myeloma immunoglobulin number in this patient.
Results
Case 1
A 58-year-old woman presented with bilateral, asymmetric decreased vision over the course of several weeks. Her past medical history included well-controlled diabetes, a remote history of skin melanoma removed from the leg 12 years prior with no metastasis, and multiple myeloma, for which she was undergoing treatment. The patient was enrolled in multiple myeloma trial IPH 2101-203, a multicenter, open-label phase II clinical trial designed to evaluate IPH 2101, an anti-KIR monoclonal antibody potentiating the antitumor activity of NK cells in patients with previously untreated smoldering multiple myeloma. As part of this trial, the patient underwent regular chemotherapy administrations for 1 year with no change in her multiple myeloma numbers. She presented to us on month 8 of this trial. Her past ocular history included a branch retinal vein occlusion (BRVO) in the left eye (OS). Her best-corrected visual acuity (BCVA) was 20/30 in the right eye (OD) and 20/70 OS with no relative afferent pupillary defect. Slit-lamp biomicroscopy showed a normal anterior segment examination. Dilated fundus examination revealed mild RPE changes, extending inferiorly from the discs in both eyes (OU) ( Figure 1 , Top row). On fundus autofluorescence, hyperautofluorescent macular lesions surrounded by a wider area of granular hypoautofluorescence were present, more prominently OS and associated with bilateral hypoautofluorescent atrophic descending tracts ( Figure 1 , Second row). Fluorescein angiography revealed diffuse intraretinal leakage, optic disc leakage, and some retinal microvascular abnormalities, but the area of detachment was hypofluorescent ( Figure 1 , Third row). No leak or pooling was noted in the area of the macular detachments. SD OCT at the level of these lesions showed a macular detachment with vitelliform deposition on the anterior surface of the RPE and the posterior surface of the neurosensory retina with associated subretinal and intraretinal fluid, more prominent OS and associated with intraretinal cysts at the level of the outer nuclear layer ( Figure 1 , Fourth row). Enhanced depth imaging (EDI) OCT revealed slightly increased subfoveal choroidal thickness measuring 347 μm OD and 305 μm OS.
