Treatment of Cancer-Associated Retinopathy: A Systematic Literature Review.

TOPIC: Systematic literature review of treatment efficacy of previously used protocols in treating patients with proven cancer-associated retinopathy (CAR). CLINICAL RELEVANCE: There is no universally accepted treatment algorithm for CAR and visual prognosis is very poor. We describe a patient with CAR with dramatic improvement in vision after treatment with high doses of corticosteroids followed by plasma exchange (PLEX) and present results of a systematic literature review of treatment efficacy of previously used protocols in treating patients with proven CAR. METHODS: We describe a 70-year-old man with CAR who demonstrated dramatic improvement in vision after treatment with high doses of systemic corticosteroids followed by 7 sessions of PLEX. We then report the results of a systematic review of all previously published English literature discussing visual outcomes of various treatment regimens used for patients with antibody-proven CAR. RESULTS: The index patient is a rare case of CAR with sustained significant improvement in vision after treatment with high doses of corticosteroids followed by PLEX. The systematic review identified 28 antibody-proven cases of CAR, 27 of which were treated with steroids, which resulted in varying degrees of improvement in visual acuity in 59% (16 of 27). The time from symptom onset to initiation of treatment and the dose of steroids did not influence the visual outcome. Three patients were also treated with PLEX in addition to steroids, and 2 of 3 patients demonstrated improvement in vision; however, there was no difference in visual outcome in patients treated with steroids only versus those treated with steroids + PLEX. CONCLUSION: Treatment with steroids or steroids + PLEX resulted in some improvements in visual acuity in 59% of patients. Removal of antirecoverin antibodies with PLEX can arrest the immune attack on the photoreceptors and potentially improve visual function; thus, it should be considered in addition to steroids. Further studies with larger cohorts are needed to establish a treatment protocol and further determine the effectiveness of the different approaches. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Paraneoplastic syndromes in ophthalmology.

Paraneoplastic syndromes consist on systemic manifestations associated with certain cancers which are not a direct consequence of tumor invasion or its metastases. It is known that autoimmunity and autoantibody synthesis play an important role in its pathophysiology due to a process of molecular mimicry. Paraneoplastic syndromes in ophthalmology are rare, but it is important to recognize them clinically because in some cases symptoms preceded the diagnosis of an underlying neoplasia. Most frequently involved cancer is small cell lung carcinoma, but there is also a relationship with other tumor etiologies such as thymoma, gynecological tumors or neuroblastoma in children. Paraneoplastic syndromes with ocular involvement can be divided into those that affect the afferent visual pathway, such as cancer-associated retinopathy, melanoma-associated retinopathy, or paraneoplastic optic neuropathy; and the ones that affect the efferent visual pathway, such as bilateral tonic pupils, Myasthenia Gravis, Lambert-Eaton syndrome or paraneoplastic cerebellar degeneration. The presence of autoantibodies is helpful in clinical practice but negativity does not exclude this diagnosis. Although evolution and prognosis is linked to primary disease, in some cases specific treatment, usually immunosuppressive therapy, can help improving patients quality of life.

Recurrent monocular exudative retinal detachment as the first manifestation of squamous cell lung cancer: A case report.

RATIONALE: In this report, we present an extremely rare case of recurrent monocular exudative retinal detachment without concomitant ocular metastases. This turned out to be the first symptom of squamous cell lung cancer. PATIENT CONCERNS: A 63-year-old woman was referred to our ophthalmology clinic by her primary care physician with a complaint of deteriorating vision in her right eye that had started four months prior, without concomitant pain. DIAGNOSES: We observed a detachment in the lower part of the retina during her ophthalmoscopy. We did not find any tears, holes, or degenerative changes in the periphery of the retina of the right eye during the surgery. In addition, plaques, tumor masses, and metastases were absent. Therefore, we diagnosed her with unilateral paraneoplastic exudative retinal detachment. Imaging tests performed before surgery revealed perihilar density with a visible air bronchogram in the middle field of the left lung. This turned out to be squamous cell carcinoma. INTERVENTIONS: Patient underwent pars plana vitrectomy and routine laboratory and imaging tests before the procedure that utilized 20-gauge instrumentation. The subretinal fluid and was drained and a tamponade using Densiron (Fluoron Co, Neu-Ulm, Germany) was applied. After ophthalmic treatment, patient underwent complex oncological treatment based on chemotherapy and radiotherapy. OUTCOMES: Despite the application of heavy silicone oil (Densiron) into the vitreous chamber, we observed a recurrence of retinal detachment in the right eye during the follow-up visit, 13 months after the first ophthalmic surgery. Following subsequent pars plana vitrectomy, the Densiron and subretinal membranes were removed. Despite oncological treatment, the patient died, twenty months after the appearance of the first ocular symptoms. LESSONS: Exudative retinal detachment without tumor metastasis to the eyeball can be one of the first signs of lung cancer in rare cases. Multidisciplinary care and imaging methods with greater accuracy will provide comprehensive care to the patients. It will not only facilitate timely detection and treatment of lung tumors but also for a plethora of oncological diseases.

Normalization of electroretinogram and symptom resolution of melanoma-associated retinopathy with negative autoantibodies after treatment with programmed death-1 (PD-1) inhibitors for metastatic melanoma.

Melanoma-associated retinopathy (MAR) is a paraneoplastic syndrome that involves the production of autoantibodies which can cross-react with retinal epitopes leading to visual symptoms. Autoantibodies can target intracellular proteins, and only a few are directed against membrane proteins. This discrepancy in autoantibody-protein target can translate into different immune responses (T-cell mediated vs B-cell mediated). Historically, treatment of MAR has focused on surgical reduction or immunosuppressive medication, mainly glucocorticoids. However, tumor resection is not relevant in metastatic melanoma in which MAR is mostly encountered. Moreover, the use of glucocorticoids can reduce the efficacy of immunotherapy. We report the first case to our knowledge with subjective resolution of visual symptoms and objective evidence of normalization of electroretinogram of MAR with undetectable autoantibodies after administration of programmed death-1 (PD-1) inhibitor (pembrolizumab) without the use of surgical reduction or systemic immunosuppression. This case highlights the potential improvement and resolution of negative autoantibody MAR with the use of PD-1 inhibitors and emphasizes the importance of multidisciplinary approach and team discussion to avoid interventions that can decrease immunotherapy-mediated anti-tumor effect.

Non-paraneoplastic autoimmune retinopathy that developed in fellow eye 10 years after onset in first eye: a case report.

BACKGROUND: Evidence-based criteria for the treatment of autoimmune retinopathy (AIR) have not been established. The pathology and clinical features of each antibody causing AIR, and its long-term course are still undetermined. We report our findings in a case of non-paraneoplastic AIR (npAIR) that developed in the fellow eye 10 years after the onset in the first eye. CASE PRESENTATION: Our patient had photophobia in both eyes and a rapidly progressing visual field defect in his right eye at the initial examination. He was diagnosed with non-paraneoplastic AIR based on the clinical findings and immunoblot analyses for anti-retinal antibodies, and he was treated with steroids. Ten years later, a visual field defect developed in the fellow eye, and a diagnosis of npAIR was made. Immunoblot analyses were positive for anti-α-enolase antibodies. He was treated with steroids, immunosuppressants, and plasma exchange. However, the response to the treatment was poor and both eyes eventually became blind. CONCLUSIONS: As best we know, this is the first case report of npAIR that developed in the fellow eye over 10 years after the development in the first eye. Long-term follow-up and a search for tumor lesions are necessary in cases of npAIR. Further understanding of the long-term course of AIR can contribute to an understanding of the pathology and treatment of npAIR.

Paraneoplastic neuromyelitis optica spectrum disorder associated with breast cancer.

Neuromyelitis optica spectrum disorder (NMOSD) is a group of inflammatory disease involving the central nervous system. Although most commonly an idiopathic autoimmune condition, NMOSD may also occur as a paraneoplastic syndrome in rare instances. Herein, we report a rare case of a 60-year-old woman with paraneoplastic NMOSD associated with breast cancer. Our findings increase the recognition that NMOSD may present as a paraneoplastic neurological syndrome associated with breast cancer. Our case also raises awareness of an important complication of neurological complications of breast cancer. Early diagnosis of paraneoplastic NMOSD may be imperative for a better prognosis.

Paraneoplastic phenomenon in mesothelioma.

A 71-year-old man presented with breathlessness and visual disturbance. On examination of the chest, he had signs suggestive of a right-sided pleural effusion and a neurological examination yielded conjugate vertical gaze palsy. Subsequent investigations revealed pleural thickening and mesothelioma. His anti-Ma2 antibodies were positive indicating a paraneoplastic syndrome as the cause of the vertical gaze palsy.

[Melanoma-associated vitelliform retinopathy (a clinical case study)]. / Melanoma-assotsiirovannaia vitelliformnaia retinopatiia (klinicheskoe nabliudenie).

Melanoma-associated vitelliform retinopathy is a manifestation of paraneoplastic syndrome in skin melanoma. Paraneoplastic syndrome, while not being a tumor or a metastatic disease, is regarded as a tumor-associated disease related to extraocular localization of neoplasm. In this clinical case, the diagnosis of melanoma-associated vitelliform retinopathy was based on a combination of clinical, angiographic, autofluorescence and morphometric signs of bilateral lesion. Analysis of the case showed that in common oncological diseases and complaints of visual impairment, examination of eye fundus is mandatory in order to timely diagnose the changes associated with tumor lesion. Detection of bilateral lesions with oval grey-yellow multiple foci at the level of retinal pigment epithelium may indicate melanoma-associated vitelliform retinopathy that requires diagnostic search for skin melanoma. A complex of instrumental studies including fluorescent angiography, optical coherence tomography and autofluorescence with feature identification allowed establishing the correct diagnosis in the particular case.

In Vivo Adaptive Optics Ophthalmoscopy Correlated with Histopathologic Results in Cancer-Associated Retinopathy.

PURPOSE: To demonstrate the validity of adaptive optics scanning laser ophthalmoscopy (AOSLO) imaging of the retina in human disease based on clinicopathologic correlation in a patient with cancer-associated retinopathy (CAR). DESIGN: Case report. PARTICIPANT: Sixty-four-year-old man with CAR. METHODS: Fundus photography, electroretinography, visual field testing, fundus autofluorescent imaging, spectral-domain OCT scans, AOSLO, and histopathologic analysis were performed. MAIN OUTCOME MEASURE: Comparison of AOSLO with histopathologic results. RESULTS: Changes in photoreceptor morphologic features were correlated highly between AOSLO and histopathologic results. CONCLUSIONS: We present a unique case where a patient with a rare and fatal disease, CAR, underwent AOSLO imaging during the course of the disease, and then shortly thereafter, postmortem histopathologic analysis of the eyes was carried out. This is the first report of use of AOSLO to elucidate further the retinal changes that occur in CAR and the first study to demonstrate correlation of AOSLO with histopathologic results in any human disease.

Paraneoplastic syndromes associated with gynecological cancers: A systematic review.

A number of paraneoplastic syndromes have been described with gynecological cancers. These syndromes are induced by substances secreted by the tumor or by an immune response triggered by the cancer. Each system of the human body can be affected by different syndromes. Indeed, paraneoplastic syndromes occurring from tumors of the gynecologic tract were found to involve the nervous, ophthalmologic, dermatologic, rheumatologic, endocrine, hematologic and renal systems. These syndromes can manifest before, at the time, or after the diagnosis of cancer. They can also occur at the time of a recurrence. Knowledge about these syndromes is important for physicians caring for patients with cancers, as they can result in severe morbidity and must be treated appropriately. Literature regarding paraneoplastic syndromes associated with tumors of the female genital tract is scattered and the subject has not been reviewed recently. A systematic literature search was thus conducted to identify paraneoplastic syndromes associated with gynecologic cancers. This review focuses on the cancers involved with each paraneoplastic syndrome, and on their pathophysiology, clinical manifestations, possible complications, outcomes, and treatments. As the mainstay of treatment in these conditions is often to address the underlying tumor, it is of upmost importance that physicians be aware of these rare cancer manifestations.

Parinaud «plus¼ syndrome in a patient with dysgerminoma. / Síndrome de Parinaud «plus¼ en paciente con disgerminoma.

CLINICAL CASE: A 33-year-old male diagnosed with Parinaud's syndrome, exotropia and post-papillary oedema optic atrophy in his left eye. A pineal germinoma was diagnosed after performing neuroimaging scans and a stereotactic biopsy. He was treated with chemotherapy and radiotherapy, showing a complete pathological response. The Parinaud's syndrome persists one year after diagnosis and the patient has refused to have strabismus surgery. DISCUSSION: Parinaud's syndrome consists of a supranuclear vertical gaze palsy resulting from damage to the midbrain tectum. The involvement of adjacent structures leads to the «Parinaud-plus¼ syndrome. When a Parinaud's syndrome is accompanied by diplopia («Parinaud-plus¼ syndrome), extension of the injury into adjacent areas must be considered.

Unilateral cancer-associated retinopathy: a case report.

We write to report a rare case of unilateral cancer-associated retinopathy previously undocumented in the literature. Cancer-associated retinopathy is an uncommon paraneoplastic syndrome. It is characterised by retinal antigen autoantibodies causing rod and cone dysfunction and abnormal electroretinography findings with consequent progressive visual loss.Our patient, known to have a primary cervical intraepithelial neoplasia, presented with unilateral blurred vision as well as a disturbance in colour and night vision. Electroretinography findings of reduced a and b waves in the right eye, together with a fundoscopic appearance of a mottled retinal pigment epithelium, attenuated blood vessels and optic disc pallor were consistent with unilateral cancer-associated retinopathy. Posterior subtenon injections of triamcinolone were administered to control active disease. With periocular steroid injections, at 4 years, our patient's visual acuity remained relatively stable and her condition persisted strictly unilaterally. Cancer-associated retinopathy may be the first presenting sign of an underlying malignancy or may indicate its recurrence. Moreover, in patients with a diagnosed gynaecological malignancy, visual symptoms could reflect cancer-associated retinopathy. In our patient visual symptoms came secondary to the diagnosis of cancer.

Lesson of the month 1: Seeing snowflakes.

Melanoma-associated retinopathy is a rare paraneoplastic complication of metastatic cutaneous malignant melanoma. It may present years after the original diagnosis of melanoma. We describe a patient with this condition who presented with persistent visual symptoms.