Kepler University Hospital, Med Campus 3 Krankenhausstraße 9, 4020 Linz; Austria.

To report a case of bilateral diffuse uveal melanocytic proliferation (BDUMP), which led to leopard spot retinopathy, and how it was managed with steroidal eye drops.

As a rare paraneoplastic intraocular illness, bilateral diffuse uveal melanocytic proliferation (BDUMP) is one of the few conditions that can result in leopard spot retinopathy. Multiple round or oval red spots at the level of the retinal pigment epithelium (RPE), multifocal hyperfluorescences corresponding to these fundus lesions, serous retinal detachment, diffuse choroidal thickening with focal nodules, and rapidly progressing cataracts are the main features of this intraocular syndrome [1].

The median age of patients with BDUMP has been found to be 65 years old, with a range from 34 to 89 years [2]. Patients with BDUMP typically present with painless, bilateral vision impairment. This disease is frequently linked to male lung cancer and female urogenital cancer among other systemic cancers. Due to its low incidence, the pathophysiology and incidence are unknown.

A 62-year-old woman arrived at our department with vision problems in both eyes, with the right eye notably affected. Her prior medical history included a diagnosis of metastatic ovarian cancer made at our hospital's gynecologic division two years prior. A weakly differentiated clear cell entity was discovered using histology. Chemotherapy was recommended after primary debulking surgery. Three cycles of 175 mg/m2 paclitaxel (taxol®, Bristol-Myers Squibb Company, USA) and 10 mg/ml carboplatin (carboplatin AUC-5®, Accord Healthcare Limited, UK) made up the adjuvant therapy regimen. After that, due to the growth of the tumour, chemotherapy therapy was replaced with six cycles of 2 mg/ml doxorubicin (Caelyx pegylated liposomal, Janssen Pharmaceutica NV, Belgium). This treatment plan was discontinued and replaced with three cycles of 0.05 mg/ml trabectedin (Yondelis, Pharma Mar S.A., Spain) for the same reason.

One month before to initial presentation, an abdominal computer tomography (CT) scan was performed, and the results revealed lower left quadrant metastasis of the abdominal wall 0.5 logMAR in both eyes was her best corrected visual acuity when she first came into our clinic. Bilateral incipient corticonuclear cataract was discovered during a slit-lamp examination. Both eyes' aplanation tonometry results were unimpressive. A paracentral hyperpigmented lesion in the left eye and multiple bilateral red patches with subretinal detachment were funduscopic findings in mydriasis.

The leopard spot pattern is similar to these red dots since they are circular in shape and have modest borders dispersed throughout the posterior pole (Figure 1). Hypoautofluorescent subretinal red patches in fundus autofluorescence (FAF, Heidelberg Engineering Inc., Heidelberg, Germany) were seen. The multifocal hyperfluorescences in the relevant lesions were seen on fundus fluorescein angiography (FFA; Heidelberg Engineering Inc., Heidelberg, Germany), which is indicative of BDUMP. Furthermore, in the later stages of FFA, exudative retinal detachment manifested (Figure 2). Optical coherence tomography (OCT, Heidelberg Engineering Inc., Heidelberg, Germany) revealed subretinal fluid with neurosensory detachment in both eyes, RPE atrophy, interspersed with increased retinal thickness, hyperreflective subretinal areas as a result of lipofuscin deposition within the RPE, and subretinal fluid.

In terms of the syndrome's reduced scotopic and photopic a- and b-wave amplitude, neither the full-field electroretinogram (ERG, Metrovision, Pérenchies, France) nor the flicker ERG revealed any distinctive abnormalities. One day later, a thoracic x-ray was taken to rule out systemic disease, and it revealed a moderate pleural effusion. When compared to the prior CT scan, which was performed one month before to the initial presentation, the preexisting abdominal wall metastasis found during the abdominal ultrasound examination remained stable in size and showed no signs of advancement. Blood tests ruled out any infectious disorders that were actively causing the exudative retinal detachment.

The patient was told to utilise 10 mg/ml prednisolonacetate eye drops (Prednifluid®, mibe GmbH Arzneimittel, Germany) six times a day for one week in both eyes after declining a prescribed intravitreal injection of 4 mg triamcinolon acetonide (Volon A®, mibe GmbH Arzneimittel, Germany). After therapy, both eyes' visual acuity had reached 0.2 logMAR, and an OCT scan revealed a small reversal of bilateral subretinal fluid. Prednisolonacetate eye drops were used as the local steroid therapy, which was tapered off over a six-week period. Due to visual decline and blurring in both eyes, a re-examination was performed three months following the initial presentation. The highest corrected visual acuity was 0.6 logMAR, and a slit-lamp examination indicated bilateral corticonuclear and posterior subcapsular cataract.

As a result, the patient had bilateral cataract surgery, which improved his or her vision to 0.2 logMAR.The patient's ovarian cancer was also given a second opinion by the oncological department. A CT scan showed that the metastasis in the abdominal wall had grown in size.Predictive molecular indicators were examined since tumour development persisted despite the use of three distinct chemotherapy regimens, and they revealed a gene mutation (MET-amplification). In the debate that followed, the tumorboard decided to plan an individual therapy trial with crizotinib based on this gene change. Visual acuity was 0.2 logMAR seven months after the original presentation, and an OCT revealed that the bilateral subretinal fluid had cleared up.

BDUMP is a very unusual paraneoplastic condition with a low 5-year survival rate due to the underlying cancer. Ocular symptoms frequently appear before systemic problems and include bilateral visual impairment without a known cause. By early identification and diagnosis, ophthalmologists can therefore affect their patients' morbidity and mortality. Even if the discovery of metastatic spread takes years, a screening for underlying systemic neoplasia is recommended.

Therefore, practitioners need to be made aware of the value of long-term follow-up exams in ovarian cancer patients [3]. A primary benign uveal melanocyte proliferation that is unusually enhanced is referred to as BDUMP [2]. The question of whether BDUMP has enough malignant cells to support the diagnosis of malignant melanoma is hotly debated. The malignant melanoma that frequently coexists in instances described in earlier papers often exhibits very aggressive behaviour without the distinctive leopard spot lesions [4-6]. To enter text, click or touch this link. Although they do not exhibit a significant infiltration of melanocytes, bilateral uveal nevi can be used as a differential diagnosis [7].

In our case, a single hyperpigmented lesion in the left eye served as the only evidence of increased uveal melanocyte proliferation, but the bilateral presence, the rapidly developing cataracts, and the typical relationship with ovarian carcinomas all supported the probable diagnosis. Serous retinal detachment in both eyes, whose pathophysiology is yet unknown, is one defining feature of BDUMP. We view a dysfunctional RPE and a breakdown in the blood-retinal barrier as coexisting processes. Fast-progressing cataracts are another feature of BDUMP, while the aetiology of rapid lens opacification is similarly unknown [8]. The medical history of our patient fits the conventional description of BDUMP, however we were unable to rule out fast cataract formation as a result of local steroidal therapy.

There is still no effective strategy for managing BDUMP. Basically, the neoplasia must be addressed as the main priority.

Plasmapheresis has showed some promise in stabilising vision decline and removing antibodies in BDUMP syndrome.

The elimination of a specific IgG component from the serum, which preferentially activates melanocytes, may account for this impact [9]. However, not all patients respond well to this therapy, and immunosuppression-related complications are a concern [3, 10]. According to some publications, BDUMP was treated with local or systemic steroids, with varying degrees of success. Systemic steroid therapy temporarily restored visual acuity in one case [11], while periocular triamcinolone acetonide injection resolved subretinal fluid in another case.[12] To the best of our knowledge, this patient is the first to have increased visual acuity and serous detachment reduction following topical steroid administration. 44 percent of the 59 documented cases of BDUMP were found to have an undetected malignancy following the onset of visual degeneration, according to research done in 2017 by Klemp and colleagues.

In light of the likelihood that BDUMP signals the beginning of a systemic neoplasia, thorough screening for numerous malignant entities is necessary. After BDUMP is identified, the prognosis is still bleak because the majority of patients pass away from their aggressive malignancy. The reported mean overall survival is 15.7 months [2].It is crucial to recognise the clinical symptoms in order to make a quick diagnosis of this unusual creature. Additionally, it is crucial to screen for and treat systemic malignancy if it hasn't already been mentioned in the patient's medical history. To fully comprehend the pathogenic mechanism and origin of BDUMP, more study is necessary. In order to enhance the prognosis of individuals with this disabling ocular illness, a systematic therapy plan might be created.

The median age of patients with BDUMP has been found to be 65 years old, with a range from 34 to 89 years [2]. Patients with BDUMP typically present with painless, bilateral vision impairment. This disease is frequently linked to male lung cancer and female urogenital cancer among other systemic cancers. Due to its low incidence, the pathophysiology and incidence are unknown.A primary benign uveal melanocyte proliferation that is unusually enhanced is referred to as BDUMP

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2. 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):439-45.

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9. 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 (Philadelphia, Pa). 2012; 32(9):1959-1966.

10. Mets RB, Golchet P, Adamus G, Anitori R, Wilson D, Shaw J, Jampol LM. Bilateral Diffuse Uveal Melanocytic Proliferation With a Positive Ophthalmoscopic and Visual Response to Plasmapheresis. Arch Ophthalmol. 2011; 129(9):1235-8.

Fuchs Barbara. A rare instance and analysis of the literature on leopard spot chorioretinopathy linked to ovarian cancer: Signs of progression. Insights of Clinical and Medical Images 2022.