Successful treatment of bilateral diffuse Uveal melanocytic proliueration with plasmapheresis

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome characterized by the benign proliferation of choroidal melanocytes resulting in serous retinal detachments and severe vision loss. J. Donald M. Gass in 1990 described the 5 ocular signs of BDUMP: multiple, round, red patches of the retinal pigment epithelium, multifocal areas of hyperfluorescence corresponding with the red patches, multiple slightly elevated pigmented uveal melanocytic tumors, exudative retinal detachment, and rapidly progressing cataracts.¹ The mortality rate following a diagnosis of BDUMP is high, with survival ranging from 8 to 24 months.² The cause of death is typically due to complications associated with underlying malignancies. Nearly half of patients are diagnosed with cancer following the onset of ocular symptoms.³ Nonetheless,BDUMP remains a rare condition with fewer than 60 cases documented in literature.⁴ We present a case of BDUMP in a patient with recently diagnosed ovarian cancer who demonstrated significant improvement following plasmapheresis.

Figure 1

(a) Fundus photos on initial presentation with area of subretinal fluid involving the entire macula with extension superior past the vascular arcade in the left eye. (b) Fundus autofluorescence photography demonstrating leopard pattern patches of hypo-autofluorescence superior and inferior to the left optic nerve.

Image courtesy of Oscar Chen, MD, MS; Fred Crawford, MD; and Veena Raiji, MD, MPH

Case

A 49-year-old female, diagnosed with ovarian cancer 2 months prior, presented with metamorphopsias and blurry vision. She completed her first cycle of chemotherapy with carboplatin and paclitaxel with significant reduction in CA125 levels when she started to develop
visual symptoms 1 week later.

Figure 2

OCT retina of both eyes. (a) Subretinal and intraretinal fluid in the left eye on initial presentation. (b) Rapid progression of subretinal fluid with involvement of both eyes. (c) Significant improvement in the subretinal fluid after 3 cycles of plasmapheresis. (d) Complete resolution of subretinal fluid in the right eye with residual fluid in the left eye.

Image courtesy of Oscar Chen, MD, MS; Fred Crawford, MD; and Veena Raiji, MD, MPH

Best-corrected visual acuities were 20/20 OD and 20/40-1 OS on initial presentation. Anterior segment exam was unremarkable, but there was subretinal fluid and outer retinal irregularity in the left eye more so than the right eye (Figure 1a) with corresponding areas of leopard-patterned hypo-autofluorescence seen on autofluorescence imaging (Figure 1b). Optical coherence tomography (OCT) demonstrated a serous retinal detachment in the left eye (Figure 2a). The infectious workup and MRI brain were unremarkable. High-dose oral steroids were started, but subretinal fluid continued to progress with binocular involvement (Figure 2b). Best-corrected visual acuity deteriorated to 20/50+2 OD and 20/150+1 OS. At this time, the patient was admitted for plasmapheresis and further oncology evaluation.

After 3 rounds of plasmapheresis every other day, visual acuity started to improve with a significant decrease in subretinal fluid (Figure 2c). At this time, the patient started to develop nuclear sclerotic cataracts that were not present in the initial presentation. The patient continued to receive chemotherapy while admitted and was discharged and received outpatient plasmapheresis 3 times weekly. Best corrected visual acuity was 20/30 OU with minimal subretinal fluid on OCT (Figure 2d) on outpatient follow-up, but the leopard-pattern lesions continued to persist on autofluorescence imaging (Figure 3).

Figure 3

Fundus autofluorescence photography demonstration diffuse area leopard pattern hypo-autofluorescence lesions that starts from macula and extends to the midperipheral retina in both eyes.

Image courtesy of Oscar Chen, MD, MS; Fred Crawford, MD; and Veena Raiji, MD, MPH

The patient subsequently underwent a successful total hysterectomy, salpingectomy, and oophorectomy. There was a decrease in frequency of plasmapheresis while the patient was recovering, and she developed worsening vision and recurrence of serous retinal detachment in the left eye. Once plasmapheresis was restarted at 3 times per week, her vision and the serous retinal detachments improved.

Discussion

BDUMP is a rare paraneoplastic syndrome associated with high morbidity and mortality. Given the rarity of this condition, there are no set treatment guidelines for the ocular manifestations of BDUMP. The most successful treatment documented in the literature is plasmapheresis.5 Plasmapheresis involves filtering the blood plasma, which nonselectively removes proteins such as paraneoplastic antibodies. While there are no clinical trials demonstrating the efficacy of plasmapheresis in managing BDUMP, multiple case reports have demonstrated significant improvement in visual acuity and serous retinal detachments following this treatment.^5-11

However, the interval, duration, and long-term efficacy of plasmapheresis for the management of BDUMP remains unknown. Our case demonstrated significant improvement in serous detachments following 5 rounds of plasmapheresis. Other documented cases required significantly more sessions to achieve significant clinical improvement.⁶

Interestingly, our patient experienced worsening vision and return of serous retinal detachment when plasmapheresis frequency was decreased at the time of her tumor resection, and improvement in both vision and serous retinal detachment when increased to 3 times per week. This suggests the need for continuous plasmapheresis to maintain visual improvement. It is uncertain what the end point for this patient might be, but as her tumor burden has diminished, plasmapheresis restored her visual acuity and has allowed her to maintain useful vision in the setting of BDUMP. •

References

1. Gass JDM, Gieser RG, Wilkinson CP, Beahm DE, Pautler SE. Bilateral diffuse uveal melanocytic proliferation in patients with occult carcinoma. Arch Ophthalmol. 1990;108(4):527-533. doi:10.1001/archopht.1990.01070060075053

2. O’Neal KD, Butnor KJ, Perkinson KR, Proia AD. Bilateral diffuse uveal melanocytic proliferation associated with pancreatic carcinoma: a case report and literature review of this paraneoplastic syndrome. Surv Ophthalmol. 2003;48(6):613-625. doi:10.1016/j.survophthal.2003.08.005

3. Ulrich JN, Garg S, Escaravage GK Jr, Meredith TM. Bilateral diffuse uveal melanocytic proliferation presenting as small choroidal melanoma. Case Rep Ophthalmol Med. Published online December 20, 2011. doi:10.1155/2011/740640

4. Klemp K, Kiilgaard JF, Heegaard S, Nørgaard T, Andersen MK, Prause JU. Bilateral diffuse uveal melanocytic proliferation: case report and literature review. Acta Ophthalmol. 2017;95(5):439-445. doi:10.1111/aos.13481

5. Miles SL, Niles RM, Pittock S, et al. A factor found in the IgG fraction of serum of patients with paraneoplastic bilateral diffuse uveal melanocytic proliferation causes proliferation of cultured human melanocytes. Retina. 2012;32(9):1959-1966. doi:10.1097/IAE.0b013e3182618bab

6. Mets RB, Golchet P, Adamus G, et al. Bilateral diffuse uveal melanocytic proliferation with a positive ophthalmoscopic and visual response to plasmapheresis. Arch Ophthalmol. 2011;129(9):1235-1238. doi:10.1001/archophthalmol.2011.277

7. Jaben EA, Pulido JS, Pittock S, Markovic S, Winters JL. The potential role of plasma exchange as a treatment for bilateral diffuse uveal melanocytic proliferation: a report of two cases. J Clin Apher. 2011;26(6):356-361. doi:10.1002/jca.20310

8. Navajas EV, Simpson ER, Krema H, et al. Cancer-associated nummular loss of RPE: expanding the clinical spectrum of bilateral diffuse uveal melanocytic proliferation. Ophthalmic Surg Lasers Imaging. 2011;42:e103-e106. doi:10.3928/15428877-20111020-02

9. Moreno TA, Patel SN. Comprehensive review of treatments for bilateral diffuse uveal melanocytic proliferation: a focus on plasmapheresis. Int Ophthalmol Clin. 2017;57(1):177-194. doi:10.1097/IIO.0000000000000156

10. Jansen JCG, Van Calster J, Pulido JS, et al. Early diagnosis and successful treatment of paraneoplastic melanocytic proliferation. Br J Ophthalmol. 2015;99(7):943-948. doi:10.1136/bjophthalmol-2014-305893

11. Schelvergem KV, Wirix M, Nijs I, Leys A. Bilateral diffuse uveal melanocytic proliferation with good clinical response to plasmapheresis and treatment of the primary tumor. Retin Cases Brief Rep. 2015;9(2):106-108. doi:10.1097/ICB.0000000000000104

Oscar Chen, MD, MS

Email: Oscar_chen@rush.edu

Financial Disclosures: None

Chen is a third-year ophthalmology resident at Rush University Medical Center. He received his undergraduate and master’s degrees from the University of Southern California and completed his medical degree at Rush University in Chicago, Illinois, in 2021. He is interested in pursuing an ophthalmology fellowship in cornea and refractive surgery.

FRED Crawford, MD

Email: Fred_Crawford@rush.edu

Financial Disclosures: None

Crawford grew up in northern Virginia and graduated with a Bachelor of Arts in chemistry from the University of Virginia in 2014. He graduated from Rush University Medical College in Chicago, Illinois, in 2021 and is an ophthalmology resident at Rush University Medical Center. He is interested in pursuing either comprehensive ophthalmology or a glaucoma fellowship.

Veena R. Raiji, MD, MPH

Email: Veena.Raiji@gmail.com

Financial Disclosures: On consultant and advisory boards for Alimera, Eyepoint, and Bausch & Lomb

Raiji is a uveitis and medical retina specialist at Illinois Retina Associates and Rush University Medical Center in Chicago, Illinois. She completed her undergraduate and medical degrees at Michigan State University, ophthalmology residency at George Washington University in Washington, DC, and uveitis fellowship at the Doheny Eye Institute in California. Raiji enjoys collaborating with her colleagues and attending national and international ophthalmology conferences.