History of present illness
We present a case of a 64-year-old female patient who presented to the emergency department (ED) with progressive weakness, weight loss, dizziness, and dyspnea. The ophthalmology team was consulted because of severe visual decline that had started about 6 months prior. The patient had been previously evaluated elsewhere and had undergone cataract surgery in the left eye (OS) but continued to experience visual decline in both eyes (OU). Her past ocular history was otherwise insignificant. Her past medical history included type 2 diabetes mellitus, hypertension, and coronary artery disease.
Ocular examination findings
Best-corrected visual acuity (BCVA) was 20/400 OU. Intraocular pressure was within normal limits. External and slit lamp examination showed multiple iris nevi OU, moderate cataract in the right eye (OD), and posterior chamber intraocular lens OS. Dilated fundus examination showed a large area of choroidal hyperpigmentation at the posterior pole OU with multiple overlying orange deposits. There was a discrete pigmented choroidal lesion in the inferonasal midperiphery OD and in the superior periphery OS. Shallow exudative retinal detachments were also present OU.
Imaging
Fundus photos captured ophthalmoscopic findings of diffuse choroidal hyperpigmentation with multiple overlying patches of orange subretinal deposits, most prominent at the posterior pole in both eyes, as well as pigmented choroidal lesions in the inferonasal midperiphery OD and in the superior periphery OS ( Fig. 69.1 A, B). Fundus autofluorescence (FAF) demonstrated alternating zones of hypo- and hyperautofluorescence, corresponding to areas of retinal pigment epithelium (RPE) loss and RPE thickening secondary to lipofuscin deposition, respectively ( Fig. 69.1 C, D). On fluorescein angiography (FA), these areas appeared hyperfluorescent due to window defects and hypofluorescent due to blockage ( Fig. 69.1 E). Indocyanine green angiography (ICGA) similarly revealed alternating zones of hypo- and hyperfluorescence and demonstrated hypofluorescence of the superior choroidal lesion OS ( Fig. 69.1 F). Optical coherence tomography (OCT) of the macula revealed alternating areas of RPE atrophy with increased signal transmission and irregular RPE thickening. Shallow subretinal fluid was noted OU ( Fig. 69.1 G, H).
Labs obtained in the ED revealed anemia, likely explaining the referred weakness, dizziness, and dyspnea. Computed tomography (CT) of the abdomen and pelvis revealed a pelvic mass, for which the patient was admitted and underwent endometrial biopsy revealing high-grade endometrial carcinoma.
Questions to ask
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How quickly did the patient notice visual decline? Bilateral diffuse uveal melanocytic proliferation (BDUMP) usually presents with bilateral, rapid-onset, progressive, painless vision loss. ,
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Patient noticed significant visual decline about 6 months before presenting to the ED. She was evaluated elsewhere and underwent cataract surgery OS but continued to experience visual decline OU after surgery.
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How severe is vision loss? BDUMP often causes progressive, profound vision loss.
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BCVA was 20/400 OU, despite previous cataract surgery OS.
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What is the age of the patient? BDUMP typically occurs in patients in their 50s through 80s and affects both sexes equally.
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Patient is a 64-year-old woman.
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Does the patient have a history of rapidly evolving cataracts? Patients with BDUMP experience rapid development of cataracts, reported in up to 73% of cases. Many patients undergo cataract surgery, but the expected visual improvement is not typically obtained after surgery.
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Patient developed visually significant cataracts within 2 to 3 months, but there was very limited visual improvement after surgery OS.
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Are there any other identifiable causes of vision loss? The clinical scenario most frequently encountered with BDUMP is that of sudden, bilateral vision loss in a middle-aged person with no clear underlying etiology. Visual function is usually disproportionate to fundus findings.
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Patient developed rapid, bilateral vision loss and fundus was remarkable for subtle background hyperpigmentation with overlying orange, subretinal patches. No other causes of vision loss could be identified.
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Does the patient report any systemic symptoms of an underlying malignancy (e.g., weakness, fatigue, weight loss, respiratory/gastrointestinal/neurological symptoms)? BDUMP often precedes the diagnosis of cancer by months to years, so the ophthalmologist might be the first person to assess the patient and should investigate associated symptoms suggestive of malignancy.
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Patient reported weakness, dizziness, and dyspnea and was found to have severe anemia upon workup in the ED.
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Assessment
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This is a case of a 64-year-old female patient with bilateral severe vision loss, areas of choroidal thickening and hyperpigmentation, overlying orange subretinal lesions, and bilateral shallow exudative retinal detachment on OCT in the context of constitutional symptoms and presence of an abdominal mass.
Differential diagnosis
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Multifocal choroidal nevi
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Multifocal choroidal melanoma
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Metastatic cutaneous melanoma
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BDUMP
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Uveal melanocytosis
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Uveal effusion syndrome
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Multifocal congenital hypertrophy of the RPE
Working diagnosis
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BDUMP
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Alternative name: bilateral diffuse melanocytic uveal hyperplasia
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Multimodal testing and results
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Fundus photography
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Fundus photography in patients with BDUMP shows diffuse hyperpigmentation with multiple orange patches of subretinal lipofuscin.
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Multiple focally elevated pigmented and nonpigmented tumors can also be seen and documented on fundus photography.
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FAF
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FAF often demonstrates nummular patches of alternating hypo- and hyperautofluorescence, most prominent at the posterior pole.
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Hyperautofluorescence corresponds to areas of lipofuscin pigment deposition, whereas hypoautofluorescence corresponds to areas of RPE loss.
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This pattern has been described as a “giraffe pattern,” and it is considered typical for BDUMP.
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OCT
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OCT is helpful in demonstrating the alternating areas of RPE atrophy with increased signal transmission and RPE hypertrophy, corresponding to the alternating pigmented and orange subretinal patches seen ophthalmoscopically.
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Subretinal fluid is frequently found in BDUMP and can be easily detected on OCT.
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Enhanced-depth imaging OCT and swept source OCT allow for better visualization of diffuse choroidal thickening and discrete elevated choroidal tumors, when present.
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FA
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Multifocal areas of early hyperautofluorescence corresponding to the nummular patches seen on fundus examination are considered typical of BDUMP.
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FA demonstrates a reversed pattern compared with autofluorescence, with hyperfluorescent areas corresponding to regions of RPE loss and hypofluorescent areas corresponding to lipofuscin accumulation.
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ICGA
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ICGA can be helpful in delineating the uveal melanocytic tumors, which appear hypofluorescent when present.
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Ultrasonography (B-scan)
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B-scan ultrasonography is helpful in demonstrating choroidal thickening, as well as uveal melanocytic tumors, when present.
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Ultrasound biomicroscopy (UBM)
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UBM is helpful in documenting the presence of iris pigment epithelium cysts and angle closure, two rare findings described in some cases of BDUMP.
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Systemic imaging
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CT scan of the chest, abdomen, and pelvis, magnetic resonance imaging of the brain, and positron emission tomography (PET) should be considered to identify an underlying malignancy.
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Management
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No standard of care exists for BDUMP. Several management strategies have been attempted, with variable results.
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Ocular radiation, intraocular surgery with drainage of the subretinal fluid, and intravitreal anti–vascular endothelial growth factor injections seem to be ineffective.
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Local and systemic corticosteroids have been used in several reported cases but showed limited improvement in a small number of cases. ,
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To date, the most effective treatments have been plasmapheresis and plasma exchange, along with treatment of the underlying malignancy. It is believed that plasmapheresis effectively removes cultured melanocyte elongation and proliferation factor, which is ectopically produced by the underlying malignancy and is responsible for melanocyte proliferation. ,
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It is important to remember that BDUMP might be the first manifestation of an underlying malignancy in almost half the cases. The most commonly associated malignancies are urogenital cancer in women and lung cancer in men. Therefore it is important to order systemic testing and appropriately refer the patient to hematology/oncology for further care.
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Our patient underwent PET and CT, which revealed the presence of an abdominal mass, with possible involvement of the retroperitoneal and pelvic lymph nodes. She subsequently had an endometrial biopsy, which demonstrated high-grade endometrial carcinoma, and she underwent a hysterectomy and received oncologic follow-up elsewhere.
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Follow-up care
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There is no standardized follow-up protocol for BDUMP.
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Follow-up care varies based on the patient’s symptoms and treatment course, as well as the systemic status of the patient.
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Although there is wide variability in the course of the disease, patients should be monitored regularly by the ophthalmologist, if their systemic status allows.
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Prognosis is poor, with a median survival of 12 to 18 months after diagnosis of BDUMP.
Algorithm 69.1 : Algorithm for differential diagnosis for bilateral diffuse uveal melanocytic proliferation ( BDUMP )
