Paraneoplastic Optic Neuritis Research Articles

Neuro-ophthalmic manifestations of cancer: a narrative review.

Neuro-ophthalmic manifestations of cancer are vast and early recognition of a serious ocular condition due to either cancer or its therapy is important for both vision preservation as well as providing valuable treatment and prognostic information regarding the underlying malignancy. This review focuses on direct and indirect effects of cancer on the eye and its adnexa, hematologic malignancy, complications of traditional and novel oncologic therapies, and paraneoplastic syndromes as they relate to the eye as these disorders can lead to potentially devastating or irreversible vision loss. PubMed was searched primarily for the following topics: optic nerve infiltration, primary vitreoretinal lymphoma (PVRL), ocular paraneoplastic disorders, and ophthalmic complications of cancer therapeutics. Literature was selected based on historical significance and landmark studies (e.g., Cross et al. series of paraneoplastic optic neuritis patients; Chan's textbook on primary intraocular lymphoma) as well as publications published after 2000. References from select studies were additionally included. Given the sparsity of literature on many subjects, most publications were included during this time frame in our review. There are several ophthalmic entities that the oncologist should be aware of including leukemic optic nerve infiltration, PVRL, paraneoplastic syndromes as they related to the eye, and adverse effects of therapeutics. Unfortunately, given the rarity of some of these entities [e.g., paraneoplastic optic neuropathy (PON), cancer-associated retinopathy (CAR)], diagnosis can be difficult and treatment options are often limited. Oncologists can develop a set of basic ophthalmology examination skills that will help to triage and manage patient eye complaints. In certain instances, oncologists have the potential to avert devastating vision loss with early recognition of neuro-ophthalmic complications.

Ocular Paraneoplastic Syndromes.

Ocular-involving paraneoplastic syndromes present a wide variety of clinical symptoms. Understanding the background pathophysiological and immunopathological factors can help make a more refined differential diagnosis consistent with the signs and symptoms presented by patients. There are two main pathophysiology arms: (1) autoimmune pathomechanism, which is presented with cancer-associated retinopathy (CAR), melanoma-associated retinopathy (MAR), cancer-associated cone dysfunction (CACD), paraneoplastic vitelliform maculopathy (PVM), and paraneoplastic optic neuritis (PON), and (2) ectopic peptides, which is often caused by tumor-expressed growth factors (T-exGF) and presented with bilateral diffuse uveal melanocytic proliferation (BDUMP). Meticulous systematic analysis of patient symptoms is a critical diagnostic step, complemented by multimodal imaging, which includes fundus photography, optical coherent tomography, fundus autofluorescence, fundus fluorescein angiography, electrophysiological examination, and sometimes fundus indocyjanin green angiography if prescribed by the clinician. Assessment of the presence of circulating antibodies is required for diagnosis. Antiretinal autoantibodies are highly associated with visual paraneoplastic syndromes and may guide diagnosis by classifying clinical manifestations in addition to monitoring treatment.

Collapsin Response-Mediator Protein 5–Associated Retinitis, Vitritis, and Optic Disc Edema

Collapsin response-mediator protein 5 (CRMP5) immunoglobulin G (IgG) has been associated with paraneoplastic optic neuritis, vitritis, retinitis, or a combination thereof, but few reports of these findings exist in the literature. We reviewed the neuro-ophthalmic findings and visual outcomes in a large series of CRMP5 IgG-positive patients to characterize further its clinical phenotype and response to treatment. Retrospective case series. Seventy-six patients with CRMP5 autoimmunity examined at the Mayo Clinic, Rochester, Minnesota. Single academic medical center chart review of all CRMP5 IgG-positive (serum titer, >1:240) patients seen between 2001 and2017. Neuro-ophthalmic manifestations and outcomes of CRMP5 autoimmunity, coexisting neural autoantibody presence and paraneoplastic associations, and the impact of immunosuppressant therapy. Twenty-nine of 76 patients (38%) demonstrated neuro-ophthalmic manifestations. Of the 29 patients with neuro-ophthalmic findings, the median age was 67 years (range, 33-88 years) and 20 (69%) were women. Cancer was diagnosed in 62% of the patients (small-cell carcinoma in 83%). Neuro-ophthalmic symptoms occurred before the diagnosis of cancer in 72%. Seventeen of 29 patients (59%) showed ocular (i.e., anterior visual pathway or intraocular) manifestations; presenting median visual acuity was 20/50 (range, 20/20-counting fingers) and the final median visual acuity was 20/40 (range, 20/20-hand movements). Fourteen of 17 patients (82%) demonstrated optic neuropathy, with 12 of these patients also showing retinitis or uveitis. Three of 17 patients (18%) showed retinitis or uveitis without optic neuropathy. All 12 patients with optic neuropathy and a documented fundus examination at visual symptom onset demonstrated optic disc edema. No patients showed optic nerve enhancement on magnetic resonance imaging. Twelve of 29 patients (41%) demonstrated ocular motility dysfunction consisting of central nystagmus and diplopia. Among those receiving immunosuppressive therapy, visual function improved in 50%. In our cohort of 29 CRMP5 IgG-positive patients with neuro-ophthalmic manifestations, optic neuropathy presented with optic disc edema, often associated with uveitis, retinitis, or both. The combination of retinitis, vitritis, and optic disc edema without optic nerve enhancement should prompt serologic testing for CRMP5 IgG to expedite vision-sparing immunosuppressant therapy and a targeted search for a systemic cancer.

Immunopathogenesis of ophthalmological paraneoplastic syndromes: Recent findings

The aim of this study was to summarize the current knowledge of paraneoplastic syndromes involving eyes. The main interest was the immunopathogenesis of the abovementioned entities. A web search was conducted using Medline, Web of Science and Scopus engines. Key words concerning ocular paraneoplastic syndromes (OPS) such as: "ocular paraneoplastic syndrome", "cancer-associated retinopathy", "cancer-associated cone dysfunction", "melanoma-associated retinopathy", "bilateral diffuse uveal melanocytic proliferation", and "paraneoplastic optic neuritis" were combined with "immunology", "immune response", "antibodies", or "autoantibodies". Numerous papers were found as a result of "ocular paraneoplastic syndrome" search and many of them matched the chosen criteria. We focused on the most recent papers - published in the last 5 years - and eventually, 92 items were found. Only several papers from each detailed category fulfilled both OPS and immunologic criteria. Site-specific paraneoplastic syndromes still remain a difficult clinical challenge. The immunopathogenesis of some of them seems to be more complex than previously thought.

S60. Case series of anti-GABAb receptor antibody autoimmune limbic encephalitis - clinical data, EEG, brain imaging and treatment outcome

Introduction Autoantibodies to extracellular epitopes of neurons and associated neurological disorders, especially autoimmune limbic encephalitis (LE), are increasingly recognized. GABAb receptor antibody associated autoimmune LE often presents with refractory seizures. Timely recognition and diagnosis are critical, as prompt immunotherapy achieves more favorable outcomes. Methods We identified 3 autoimmune LE cases associated with anti-GABAb receptor antibody (Ab). Clinical data was retrospectively obtained and evaluated. Broad neuronal autoantibody panels were also examined. Results The initial clinical presentation of LE was new onset seizures with altered mental status, two patients had prodromal infectious symptoms prior to the onset of seizures. When symptoms evolved, seizures became pharmacologically refractory to anti-epileptics. One patient had convulsive status, and two others had non-convulsive status confirmed by either repetitive EEG tests or continuous EEG monitoring. The patients also presented with behavioral symptoms including agitation, behavioral outbursts, and one patient had hypersomnia. Two patients were with diagnosed with small cell lung cancer prior to the seizure onset, one of whom also had recurrent refractory optic neuritis. The other patient had a negative malignancy workup. CSF studies showed mild pleocytosis with lymphocyte predominance, and two patients were found to have positive oligoclonal bands in CSF. GABAb receptor Abs were found in CSF from all three patients, two patients were also found to have positive GABAb receptor Abs in serum. Other neuronal autoantibodies were also detected, CRMP5 (in serum/CSF from patient with optic neuritis), P/Q, or N-type calcium channel antibodies were found in serum from all three patients. Brain T2/FLAIR signal changes were seen in the temporal lobe and hippocampus in two. The other one patient’s brain MRI was unrevealing. All patients underwent IV Steroid and IVIG or plasma exchange treatment, which helped seizure control and briefly improved mental status. Two patients received further treatment with Rituximab due to persistent cognitive deficits (short term memory loss, poor attention/concentration) or persistent hypersomnia. Rituximab treatment resulted in partial clinical improvement. Though there was no seizure recurrence in these patients followed for 3–9 months, both patients continued to have cognitive deficits and memory loss. Follow-up CSF study showed resolved CSF pleocytosis, however, serum and CSF serology showed persistent positivity of GABAb receptor Abs in these patients. Thus, the patients continued with long term immuno-therapies. Conclusion We report 3 cases of GABAb receptor antibody associated autoimmune LE including one unique case with concurrent CRMP5 associated paraneoplastic optic neuritis. Though coexistence of other neuronal autoantibodies were noted, the neurological presentations in our cohort were likely directly due to the pathogenic effects medicated by GABAb receptor antibodies.

CRMP-5 Antibody in Paraneoplastic Optic Neuritis and Sensory Motor Neuropathy Associated with Small Cell Lung Cancer (P4.236)

CRMP-5 Antibody in Paraneoplastic Optic Neuritis and Sensory Motor Neuropathy Associated with Small Cell Lung Cancer (P4.236)

Neuritis óptica paraneoplásica en carcinoma microcítico pulmonar desconocido definida por marcador CRMP-5-IgG

The case of a 64-year-old patient with bilateral, progressive and painless diminution of visual acuity is presented. Ophthalmologic evaluation revealed optic neuritis and vitreous cells in both eyes, at different stages. Suspecting a paraneoplastic optic neuritis, the study of antibodies was requested. This showed positivity to the marker CRMP-5-IgG. After mediastinoscopy, a small cell lung carcinoma was diagnosed. Autoantibody CRMP-5-IgG defines a paraneoplastic entity of combined optic neuritis and vitreous inflammatory cells. The serological positivity avoids the vitreous biopsy and expedites the search for cancer. In our case, it allowed the diagnosis a previously unidentified tumor.

CRMP-5-IgG in patient with paraneoplastic optic neuritis with lung adenocarcinoma

CRMP-5-IgG in patient with paraneoplastic optic neuritis with lung adenocarcinoma

Neuro-ophthalmological paraneoplastic syndromes: a review

Lesions involving the visual system due to the remote effect of cancer are uncommon. Their clinical manifestations are protean. The main symptoms are visual loss, caused by retinopathy or optic neuritis, and abnormal eye movements. Cancer-related retinopathy (CAR) has been primarily described in patients with small-cell lung carcinoma, and it is distinct from melanoma associated retinopathy (MAR), and the retinopathy caused by bilateral diffuse uveal melanocytic proliferation (BDUMP) observed in patients with various neoplasias. The main underlying tumours in patients with paraneoplastic optic neuritis are lung and breast carcinomas. Eye movement disorders consist of opsoclonus, associated with neuroblastoma in infants and children and various tumours in adults, and ophtalmoplegia caused by paraneoplastic myasthenia gravis or paraneoplastic brainstem encephalitis. The differential diagnosis of the neuro-ophthalmological paraneoplastic syndromes includes primarily metastatic and treatment-related lesions. In some patients the paraneoplastic nature of the ophthalmological disorder my by proven by specific serum antibodies. These antibodies are also markers of the underlying and often non-diagnosed cancer, but their pathogenic role remains unproven.