Malignancy causing Autoimmune retinopathy in Asymptomatic Woman: Case report

A 65-year-old woman was referred for symptoms of painless and progressive bilateral loss of central and peripheral vision over the last 6 months, associated with floaters in the left eye.

The patient reported difficulty in performing essential daily tasks, such as driving and walking without assistance. She denied photopsias. Her previous ocular and medical history were unremarkable. She denied any systemic symptoms as well as any family history of inherited ocular diseases.

On examination

Best-corrected visual acuity was 20/32 OU.

Fundus examination results showed attenuated arterial and venous retinal vessels and slight retinal pigmented epithelium changes at the posterior pole, consisting of atrophy and pigment migration in both eyes, associated with vitreous opacities in the left eye.

Fluorescein angiography examination results showed a mild leakage of arterial and venous retinal vasculature.

Spectraldomain optical coherence tomography exhibited disruption at the photoreceptor level and multifocal hyperreflective material depositions at the retinal pigmented epithelium level.

Computerized perimetry demonstrated severe visual field bilateral constriction. Full field electroretinography showed decreased scotopic and photopic responses.

Cranial magnetic resonance imaging was unremarkable, and an extensive workup for underlying infectious or inflammatory causes was unrevealing.

The women was diagnosed as a case of Paraneoplastic autoimmune retinopathy by investigating serum positivity for antiretinal antibodies and obtaining an extensive workup for a malignant neoplasm.

Autoimmune retinopathy (AIR) is a rare form of immune-mediated retinal degeneration. It is characterized by progressive vision loss along with electroretinographic, visual field abnormalities, and the presence of circulating ARAs. Autoimmune retinopathy can be categorized as paraneoplastic (pAIR), which includes cancer associated retinopathy and melanoma-associated retinopathy, or non paraneoplastic in the absence of a malignant neoplasm.

Diagnosis remains a challenge because of its variable presentation and fundus appearance, which may be initially normal or with minimal unrevealing alterations despite central vision loss and a severely decreased visual field. Moreover, in contrast with previous reported cases, the above patient did not show any systemic symptoms that would have been helpful toward the diagnosis.

A differential diagnosis might include heritable retinal degenerations, because clinical findings in AIR, including peripheral visual field loss, reduced electroretinogram waveforms, retinal pigmented epithelium atrophic changes, pigment migration, and photoreceptor loss on optical coherence tomography, can be suggestive of heritable diseases, such as retinitis pigmentosa.

In this case, molecular analysis for heritable retinal degenerations would not have been the preferred next step because the patient had no family history of inherited ocular diseases and did not experience typical symptoms, such as nyctalopia, photophobia, or dyschromatopsia. Furthermore, the relatively rapid progression of photoreceptor loss was not typical for retinitis pigmentosa and no bone spicule-like pigmentary changes were present during the fundus examination.

The presence of circulating ARAs is important in the pathophysiology and diagnosis of AIR, although it is not pathognomonic, as they have been identified in other retinal diseases, such as uveitis, in patients with systemic autoimmune disorders and in healthy controls.

Given the absence of standardized diagnostic criteria, it has been proposed that an AIR diagnosis should require serum positivity for ARAs associated with progressive loss of visual acuity, visual field defects, and abnormal responses on electroretinography, in the absence of fundus lesions or degenerative retinal disease that might explain these pathologic findings.

Therefore, given the clinical features found in the patient, investigating the presence of ARAs was considered to be the most suitable next step to confirm the diagnostic suspicion of AIR. Furthermore, because serum positivity for ARAs and visual symptoms may be present many years before detecting malignant neoplasms in patients with pAIR, an oncologic workup was deemed appropriate for clarifying the paraneoplastic nature of the AIR.

Obtaining a diagnostic pars plana vitrectomy with vitreous and aqueous sampling for cytologic analysis would not have provided useful information for definitively clarifying the diagnosis and would not have guided towards the detection of malignant neoplasms.

Obtaining a temporal artery biopsy specimen because of suspicion of Horton disease would not have been the proper management option. In fact, the patient did not experience typical symptoms, such as headache, jaw claudication, sensitivity on the scalp, or prominent temporal arteries.

Patient Outcome

The patient underwent antiretinal antibody testing that demonstrated reactivity to multiple ARAs. She was referred to the oncology department to undergo a systemic workup for malignant neoplasms and was found to be affected by stage IV, poorly differentiated, gastric adenocarcinoma with multiple metastasis to the abdominal and supraclavicular lymph nodes.

She started palliative chemotherapy with FLOT regimen (5-fluorouracil, leucovorin, oxaliplatin, and docetaxel). After 4 months, the treatment helped to slow the progression of visual field loss, with preservation of central vision and best-corrected visual acuity improvement to 20/25 OU. In addition, a regression of the vitreous opacities in the left eye was detected.

Source: Emilia Maggio; Andrea Palamara; Grazia Pertile; JAMA Ophthalmology Clinical Challenge