Cancer-associated retinopathy 4 years after surgery for ovarian cancer.

A 71-year-old woman presented with progressive, bilateral, blurred vision and nyctalopia for the last 6 months. Her past medical history included total hysterectomy and chemotherapy for ovarian cancer 4 years ago, without metastases. Optical coherence tomography revealed outer retinal layers' thinning bilaterally, while diffuse retinal pigment epithelium abnormalities were found in fundus autofluorescence. Full-field electroretinogram showed abnormalities in both a- and b-waves with significant reduction of retinal sensitivity, affecting however more the rod system. The patient was positive for alpha-enolase and was diagnosed with cancer-associated retinopathy (CAR), which developed 4-year primary cancer. Computerized tomography scan revealed an enlarged para-aortic lymph node at the left kidney, and the patient was started on chemotherapy, combined with immunosuppressive treatment. In conclusion, CAR should be suspected in patients experiencing unexplained visual disturbances, especially in the context of previous cancer. Copyright:

Introduction

Cancer-associated retinopathy (CAR) is a paraneoplastic, autoimmune retinopathy caused by antiretinal antibodies generated against aberrant expression of retinal antigen in cancer cells, causing subacute retinal visual disorders due to photoreceptors' cell death.[1] CAR was first described by Sawyer et al. in 1976 in three patients with nonophthalmic anaplastic tumor, presenting with the clinical triad of photosensitivity, attenuated retinal arterioles, and visual field loss.[2] The prevalence is unknown, but it is thought to occur in 10%–15% of cancer patients.[1] Herein, we report a case of CAR, who presented about 4 years after surgery for ovarian cancer.

Case Report

A 71-year-old, Caucasian, woman presented with progressive, bilateral, blurred vision for the last 6 months, especially in the night (nyctalopia). Her past ocular history included bilateral cataract extraction 3 years ago and high myopia. Regarding her past medical history, the patient has undergone total hysterectomy and chemotherapy for ovarian cancer 4 years ago, without metastases.

At the current presentation, best-corrected visual acuity was 20/25 in the right eye and 20/32 in the left eye. Anterior segment examination and intraocular pressure were normal in both eyes. The pupils were normal with no relative afferent pupillary defect bilaterally. Dilated fundoscopy demonstrated narrowed retinal arteries and attenuation of retinal vessels bilaterally [Figure 1]. Optical coherence tomography (OCT) revealed outer retinal layers' thinning with the absence of photoreceptor layer parafoveally [Figure 2b and d], while fundus autofluorescence demonstrated diffuse retinal pigment epithelium abnormalities as hypo-autofluorescent areas around the fovea bilaterally [Figure 2a and c]. Fluorescein angiography was normal in both eyes. Visual field examination showed reduced sensitivity with constriction of visual field [Figure 3]. Electroretinogram (ERG) showed abnormalities in a- and b-waves with significant reduction of retinal sensitivity, affecting more the rod system [Figure 4].

Figure 1

Color fundus photograph in the right (a) and left eyes (b), showing narrowing and attenuation of retinal vessels

Figure 2

Fundus autofluorescence in the right (a) and left eyes (c), showing diffuse retinal pigment epithelium abnormalities as hypo-autofluorescent areas (white arrowhead); infra-red photograph and optical coherence tomography of the right (b) and left eyes (d), showing outer retinal layer thinning with the absence of photoreceptors layer, sparring the foveal area in both eyes (white arrows). Both fundus autofluorescence and optical coherence tomography were performed using Heidelberg Spectralis

Figure 3

Visual field chart (grayscale) in the right and left eyes, showing constriction of visual field in both eyes

Figure 4

Electroretinogram (TOMEY) in both eyes, showing abnormalities in a- and b-waves with significant reduction of retinal sensitivity in both eyes

On suspicion of CAR, anti-retinal antibody test was performed using Western blot, which was positive for alpha-enolase. Based on the above findings, the patient was diagnosed with CAR, which developed 4 years after primary cancer, and referred to oncologists for further investigation. Computerized tomography (CT) scan revealed an enlarged para-aortic lymph node at the level of the left kidney, and the patient was started on chemotherapy, combined with immunosuppressive treatment.

Written informed consent was obtained by the patient to publish her data.

Discussion

Since its first description, CAR has been increasingly recognized in patients with several carcinomas.[3] Patients with CAR may often present with bilateral, progressive vision loss, which can be developed over weeks to months, although unilateral cases have been also reported.[4] The main symptoms include photophobia, photosensitivity, and nyctalopia and are dependent on the affected photoreceptor system. Specifically, cone system dysfunction is mainly suggested by visual acuity decrease, color vision impairment, photosensitivity, glare, and photopsias, while rod system dysfunction includes predominantly nyctalopia, ring scotomas, or other visual field defects.[1] Fundus examination may be unremarkable or show waxy optic disk pallor, attenuated retinal arterioles, retinal pigment epithelial abnormalities, and diffuse retinal atrophy.[1] OCT typically reveals severe macular atrophy, often associated with loss of the inner segment/outer segment junction and of the inner highly reflective layer.[5]

It is worthy to mention that the diagnosis of CAR is mainly based on the clinical symptoms, ERG typically showing severely reduced or even extinguished a- and b- waves and involving rods and cones,[6] as well as on the detection of anti-retinal antibodies in the serum. However, anti-retinal antibody positivity is not necessary to make the diagnosis of CAR, since in up to 35% of CAR patients, specific antibodies cannot be detected.[7] The most sensitive and specific autoantibody for CAR is recoverin, a calcium-binding protein found in photoreceptors, while another frequently identified antibody in CAR is alpha-enolase.[7] Other potential CAR antigens continue to be described, such as carbonic anhydrase II, transducin beta, tubby-like protein 1, heat shock cognate protein 70, and glyceraldehyde 3-phosphate dehydrogenase.[8] On the other hand, it should be noted that anti-retinal antibodies could also be present in normal subjects.[8] Therefore, a comprehensive diagnostic work-up is needed to end up in CAR diagnosis.

It is worthy to note that melanoma-associated retinopathy (MAR) should be considered in the differential diagnosis, taking into account that visual disturbance in CAR often precedes the diagnosis of cancer in about 50% of cases, while diagnosis is already established when visual symptoms occur in MAR.[3] In any case, if the diagnosis of CAR is made, potential occult cancer investigation is crucial. Traditionally, CT of the chest and pelvis for lung, breast, and gynecologic cancers have been advised, although full-body positron emission tomography scan has been indicated in most studies.[9]

Regarding the treatment of CAR, immunosuppression remains the gold standard of therapy, although other treatment modalities have been also tried, including steroid pulse therapy, plasmapheresis, immunoglobulin, intravitreal injection of steroids, and chemotherapy for the primary disease.[1] Recent reports show maintained or improved vision, using newer monoclonal pan-lymphocytic (CD52, alentuzamab) and B-cell (CD20, rituximab) antibodies, if other therapies fail.[10] Treatment of the underlying malignancy alone does not improve the vision, thus the intervention must be targeted at the ocular disorder.[1] However, one should take into account the balance between the treatment of CAR and that of the original disease before starting any intervention.

In conclusion, we report a case of CAR, who presented 4 years after successfully treated ovarian cancer, while a metastasis was detected after CAR diagnosis. CAR should be suspected in patients experiencing unexplained visual disturbances, especially in the context of previous cancer. If diagnosis is made, CAR treatment should be performed promptly, considering the condition of the original tumor and quality of patient's life.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.