Successful treatment of bilateral diffuse uveal melanocytic proliferation with plasmapheresis

Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a rare paraneoplastic syndrome characterised by benign proliferation of choroidal melanocytes resulting in serous retinal detachments and severe vision loss. Gass in 1990 described the five ocular signs of BDUMP including: 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

Mortality following diagnosis of BDUMP is high with survival rates ranging from 8 to 24 months.² The cause of death is typically due to complications associated with underlying malignancies. Furthermore, nearly half of patients receive a cancer diagnosis following the onset of ocular symptoms.³ BDUMP remains a rare condition with fewer than 60 cases documented in the literature.⁴ We presented a case of BDUMP in a patient with recently diagnosed 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 demonstrates leopard pattern patches of hypo-autofluorescence superior and inferior to the left optic nerve.

Case

A 49-year-old woman with a past medical history of ovarian cancer who presents with metamorphopsias and blurry vision. The patient had received a diagnosis of ovarian cancer 2 months prior to presentation and was receiving carboplatin and paclitaxel. She was responding well with significant reduction in CA125 levels but started to develop visual symptoms 1 week after starting her first dose of chemotherapy.

Best-corrected visual acuities were 20/20 OD and 20/40-1 OS on initial presentation. The anterior segment exam was unremarkable, but the posterior fundus was significant for subretinal fluid in the macula in the left 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, there was concern for BDUMP given the patient’s history of ovarian cancer. The decision was made to admit the patient for plasmapheresis and for further oncology evaluation.

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.

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 with biweekly outpatient plasmapheresis. 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 photography (Figure 3). 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, vision improved. The serous retinal detachment improved but at a slower rate than previously seen.

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 removes nonselective 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

Figure 3. Fundus autofluorescence photography demonstrates diffuse area leopard pattern hypo-autofluorescence lesions that start from macula and extend to the midperipheral retina in both eyes. (Images courtesy of the authors)

Our case demonstrated significant improvement in serous detachments following five rounds of plasmapheresis. Other documented cases required significantly more sessions to achieve significant clinical improvement.⁶ Interestingly, our patient experienced worsening vision and a return of serous retinal detachment when plasmapheresis frequency was inadvertently decreased and improvement in both vision and serous retinal detachment when it was increased to threetimes per week.

This could suggest the need for plasmapheresis more frequently during times of stress and/or slower frequency taper. Therefore, plasmapheresis should be considered when treating patients with deteriorating visual acuity 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 | E: Oscar_chen@rush.edu

Financial Disclosures: None

Dr Oscar Chen is a third-year ophthalmology resident at Rush University Medical Centre, Chicago, Illinois. He completed his medical degree at Rush University in 2021. He is pursuing an ophthalmology fellowship in cornea and refractive surgery.

Fred Crawford, MD | E: Fred_Crawford@rush.edu

Financial Disclosures: None

Fred Crawford graduated from Rush University Medical College in 2021 and is an ophthalmology resident at Rush University Medical Center. He is interested in comprehensive ophthalmology or pursuing a glaucoma fellowship.

Veena R. Raiji. MD, MPH | E: Veena.Raiji@gmail.com

Financial Disclosures: Consultant and advisory boards for Alimera Sciences, EyePoint Pharmaceuticals and Bausch & Lomb

Dr Veena Raiji is a uveitis and medical retina specialist at Illinois Retina Associates and Rush University Medical Centre, Chicago. She completed her undergraduate and medical degree at Michigan State University, her ophthalmology residency at George Washington University and uveitis fellowship at the Doheny Eye Institute.