Neuro-Oncology

Updated 03.20.2023
Released 11.11.1994
Expires For CME 03.20.2026

Paraneoplastic retinopathy

Authors: Shira S Simon MD MBA, Nicholas J Volpe MD

Editor: Rimas V Lukas MD

Introduction

Overview

Paraneoplastic disorders or remote effects of cancer can affect any part of the nervous system. Neurologists, oncologists, and ophthalmologists need to be aware that this includes the retina and optic nerve. Retinal neuronal dysfunction and degeneration may occur in association with a number of systemic neoplasms, including--most notably--melanoma and small cell lung carcinoma. For many patients, vision loss is the presenting feature of the associated tumor. Some affected patients have circulating antibodies against retinal antigens; these antibodies serve as diagnostic markers for the condition and may also play a role in causing retinal dysfunction. In this article, the authors summarize the clinical features, autoimmune pathogenesis, and treatment options for patients with paraneoplastic retinal degeneration.

Key points

	• Paraneoplastic retinopathy is a rare entity associated with a variety of neoplasms, most commonly small cell lung carcinoma or melanoma.
	• In most patients with cancer-associated paraneoplastic retinopathy, subacute vision loss is the presenting feature of the malignancy, whereas vision loss develops after the melanoma diagnosis in the majority of patients with melanoma-associated paraneoplastic retinopathy.
	• The pattern of vision loss and degree of retinal dysfunction can vary depending on the type of tumor, and a diagnosis is confirmed by retinal dysfunction on electroretinogram (ERG).
	• Most patients with paraneoplastic retinopathy have one or more antiretinal autoantibodies with varying immunohistochemical staining patterns and specificity for a number of retinal antigens.
	• Immunosuppressive therapy should be offered to patients with vision loss from paraneoplastic retinopathy; early diagnosis may lead to a better outcome.

Historical note and terminology

The first well-documented cases of "photoreceptor degeneration as a remote effect of cancer" were reported in 1976 by Sawyer and colleagues (130). The cases were of three female patients with bronchial carcinoma. The term "paraneoplastic autoimmune retinopathy" encompasses patients with heterogeneous tumor associations and clinical features and probably represents more than one pathophysiologic mechanism.

Clinical manifestations

Presentation and course

In nearly all patients with cancer-associated autoimmune paraneoplastic retinopathy, the visual symptoms are the presenting feature of the tumor, preceding discovery of the tumor by intervals ranging from several months to 2 or more years. The signs and symptoms of paraneoplastic retinopathy nearly always involve both eyes, but asymmetry can be often present, especially early in the course of the disease process. The initial symptoms most frequently entail a progressive, otherwise unexplained vision loss with midperipheral scotomata (missing spots in vision). There may be dimming or blurring of vision; night blindness is common and may be the sole initial complaint. Because the disease causes dysfunction of retinal neurons, many patients report episodic obscurations or photopsias described as distortions, "sparkles," "shimmering," or bizarre images reflecting the dysfunction of damaged photoreceptors (76; 125). Some patients report increased glare or photosensitivity, so-called hemeralopia or day blindness due to cone dysfunction, and many have visual field changes: visual field constriction, midperipheral loss, or central or paracentral scotomata (68; 106; 133). Some patients have central sparing of their visual fields (26; 30). In most patients, the visual symptoms worsen over weeks to months, either in a steady or stepwise fashion. No well-documented cases of spontaneous improvement exist.

The examination of patients with cancer-associated paraneoplastic retinopathy is abnormal. Visual acuity is usually severely impaired and color vision can be affected as well. As a result of widespread, sometimes asymmetric retinal dysfunction, approximately one half of reported patients have afferent pupillary defects. Funduscopic exam shows mild or moderate attenuation of the retinal arterioles in the majority of patients but is otherwise often unremarkable except for occasional vitreous cells and some instances of optic nerve pallor and mild retinal pigment epithelial changes. Some patients have vascular leakage evident on fluorescein angiography. Chorioretinal atrophy and optic nerve atrophy may eventually be seen later in the disease course (106).

The clinical features of patients in whom retinopathy is associated with melanoma differ somewhat from the clinical features of patients with cancer-associated retinopathy (82; 79; 91). The majority of these patients develop visual symptoms after the diagnosis of melanoma (cutaneous or mucosal), with intervals of up to 10 years or more (121). Visual symptoms can lead to the discovery of previously unsuspected systemic metastases (21; 11; 120). Subacute night blindness is a common feature of melanoma-associated retinopathy. Most patients additionally report floaters, shimmering, flickering, or pulsating photopsias early in the course of the disease. Visual acuity, visual fields, color vision, and funduscopic exam can seem unremarkable earlier on; most patients eventually develop decreased visual acuity and visual field abnormalities including generalized constriction, central or paracentral scotomata, or arcuate defects (99; 152; 120; 79). Some patients develop optic disc pallor, retinal vessel attenuation, retinal pigmentary changes, or vitreous cells (79). Uveitis or retinal vasculitis manifesting as leakage around vessels on fluorescein angiography have also been reported (75; 123).

Another recognized variant of melanoma-associated retinopathy is "paraneoplastic vitelliform retinopathy" (70; 22; 15). Patients present with mild loss of visual acuity and frequently have night blindness and photopsias. Funduscopic exam shows multiple serous detachments of the retinal pigment epithelium and neurosensory retina.

Prognosis and complications

The clinical course of cancer-associated paraneoplastic retinopathy is usually one of deterioration over the course of weeks to months, in a gradual or stepwise fashion, to a level of severe visual impairment. No well-documented instances of significant spontaneous improvement are known.

Clinical vignette

A 64-year-old man with a past medical history notable for a 40-pack-per-year history of cigarette smoking developed painless blurring and dimming of the central field of vision in his left eye, with associated light sensitivity, especially when outside. Three weeks later, similar symptoms developed in his right eye, and the vision in both eyes progressively deteriorated. He also noted intermittent, colorful "sparkles" or halos around objects. Examination 6 weeks after the onset of symptoms demonstrated visual acuities of 20/400 in the right eye and 20/200 in the left eye with severe dyschromatopsia. Both pupils were minimally reactive to light, and there was no relative afferent pupillary defect. Ophthalmoscopy was normal except for attenuation of the retinal arterioles. Visual field testing revealed severe constriction bilaterally with a ring scotoma evident in the right eye. Electroretinogram demonstrated near absence of the cone response in both eyes. Brain MRI with and without contrast was within normal limits. Chest x-ray showed suspicious mediastinal widening, and chest CT scan showed hilar adenopathy. Bronchoscopy was diagnostic for small cell lung carcinoma. Staging workup showed no metastatic tumor. Serum was found to contain antirecoverin antibodies. The patient was placed on prednisone 60 mg/day (1 mg/kg) and chemotherapy with cisplatin and etoposide. After 1 month of prednisone and one cycle of chemotherapy, the patient's visual acuity and visual fields remained essentially stable. Steroids were tapered and discontinued, and complete tumor remission was attained after four cycles of chemotherapy. The patient's vision deteriorated but returned to its previous baseline again after 3 weeks of prednisone (60 mg/day).

Biological basis

Etiology and pathogenesis

As with other neurologic paraneoplastic disorders, the leading theory of the pathogenesis of paraneoplastic retinopathy is that an autoimmune response initially directed against tumor cell antigens subsequently "spills over" to attack photoreceptor cells and other retinal neurons (35). The mechanism by which these antibodies cross the blood-retinal barrier is less clear (88). It is possible that a cell-mediated immune process with the ability to more readily cross blood–CNS barriers could also be playing a role.

The most common histopathologic features of paraneoplastic retinopathy associated with small cell lung carcinoma (cancer-associated retinopathy) are severe; sometimes there is total loss of the inner and outer segments of rods and cones, and widespread degeneration of the outer nuclear layer (130; 26; 125; 05). Some eyes show patchy, mild infiltration of mononuclear cells around retinal arterioles. Varying changes in ganglion and bipolar cells as well as photoreceptor cells may be present (55). A proposed mechanism of photoreceptor loss is that autoantibodies anchor to the photoreceptors and activate the complement pathway, leading to cell lysis. It remains unclear why photoreceptors often degenerate whereas the retinal pigment epithelium does not (36).

A few reported autopsies of patients with melanoma-associated retinopathy showed preservation of the photoreceptor cell layers but marked depletion of cell nuclei in the inner nuclear and bipolar layers (52). A single autopsied case of paraneoplastic vitelliform retinopathy showed multifocal retinal edema as well as atrophy affecting mainly the inner nuclear layer, outer plexiform layer, and outer nuclear layers (15).

Most patients with paraneoplastic retinopathy have circulating antiretinal autoantibodies. As with other neurologic paraneoplastic disorders (35; 54; 127), the autoantibody specificities among patients with paraneoplastic retinopathy are heterogeneous (08; 01). The most prevalent antiretinal antibodies are polyclonal IgG antibodies against the 23 kd calcium-binding protein recoverin. The majority of patients with paraneoplastic retinopathy and antirecoverin antibodies have small cell lung carcinoma (68; 118; 08). Antirecoverin antibodies may also be present in patients with gynecologic or other carcinomas (146; 41; 106; 08; 129). Antirecoverin antibodies stain the inner and outer segment layers, the outer nuclear layer of the retina, and to a lesser degree the inner nuclear layer of the retina (145; 118; 78).

Recoverin is expressed by retinal rods, cones, and bipolar cells. It functions in the phototransduction cascade by modulating the phosphorylation of rhodopsin (20). Recoverin is expressed by the majority of small cell lung carcinomas (95; 96; 19). Patients' antirecoverin antibodies exert a cytotoxic effect and induce apoptosis in rat retinal cells in vitro (06; 29; 28; 135; 09). Intravitreous injection of antirecoverin antibodies into rats produces abnormal electroretinograms and thinning of the inner and outer nuclear retinal layers (104; 96). These effects are enhanced when antibodies against heat-shock protein are injected into the vitreous together with antirecoverin antibodies. Rats or mice immunized with purified recoverin develop antirecoverin antibodies, uveoretinitis with cellular infiltrates, and degeneration of photoreceptors (07; 94; 90). These same histopathologic changes can be reproduced by passive transfer of stimulated lymphocytes from rats immunized with recoverin into naive animals.

Some patients with retinopathy associated with small cell lung carcinoma or other carcinomas have no identifiable antiretinal antibodies, have autoantibodies that react with retinal target antigens distinct from recoverin (77), or have antibodies against recoverin plus antibodies against one or more other retinal antigens (62). Other identified retinal target antigens include a 65 kd heat shock protein (105; 157; 106); retinal enolase (03; 57; 08; 153); neurofilament triplet proteins (56; 139); the 48 kd retinal S-antigen (125; 108; 141); carbonic anhydrase (59; 10); a photoreceptor cell nuclear receptor (40); a 78 kd retinal protein that belongs to the "tubby" gene family (80); 35 and 40 kd photoreceptor membrane proteins (112; 110; 154); anti-paraneoplastic antigen MA2 (48); and antibodies against one or more as yet unidentified retinal proteins (107; 102; 131; 148; 106; 132; 89; 45; 97). Anti-aldolase autoantibodies have been proposed as a possible biomarker associated with colon cancer–associated retinopathy, anti-carbonic anhydrase II with prostate cancer–associated retinopathy, and anti-arrestin in melanoma–associated retinopathy (04).

The immunoreactivity of autoantibodies from patients with melanoma-associated retinopathy is also heterogeneous. Sera from some patients with melanoma-associated retinopathy stain a subset of approximately 30% of retinal bipolar cells, and, to a lesser degree, outer rod segments (99; 152; 75; 123; 23). There is a single reported patient with retinal degeneration and antibipolar cell antibodies associated with colon carcinoma (67). The molecular target(s) of antibipolar cell antibodies have not been well characterized (60). One of the known targets is TRPM1 (transient receptor potential cation channel, subfamily M, member 1), a cation channel that mediates the light response in bipolar cells (33; 84; 39; 149; 38; 81). Three isoforms of TRPM1 have been identified in patients with melanoma-associated retinopathy (151). There is a single reported case of anti-TRPM1 antibodies in a patient with retinopathy and small cell lung carcinoma (84).

Other patients with melanoma-associated retinopathy have autoantibodies distinct from the "typical" antibipolar cell antibodies. Retinal antigens reacting with these antibodies include the photoreceptor proteins rhodopsin or transducin (119; 60), recoverin, enolase, S-arrestin, heat shock protein, and aldolase (91). Reported patients with melanoma-associated paraneoplastic vitelliform retinopathy also have varied antiretinal antibodies, including antibodies against bipolar cells, or against one of a number of identified proteins including alpha-enolase or carbonic anhydrase II, or other as yet unidentified autoantibodies (22; 15).

Injection of IgG from patients with melanoma-associated retinopathy into the vitreous of monkeys produces electroretinographic changes similar to those seen in human patients (86). Adoptive transfer of splenocytes from transgenic melanoma-bearing mice into wild-type mice produced retinopathy in some recipients (18).

Differential diagnosis

Confusing conditions

The differential diagnosis of vision loss in cancer patients includes direct tumor spread, adverse effects of treatment, and remote effects of tumors on the visual system. Magnetic resonance imaging scanning should rule out infiltration or compression of the optic nerve or chiasm by metastatic tumor. Many patients with leptomeningeal metastases from solid tumors develop vision loss during the course of their illness, either from papilledema or from direct tumor cell infiltration in and around the optic nerves (128). In some of these patients, vision loss is the presenting complaint.

Radiation-induced retinal damage may occur following focal cobalt plaque radiotherapy for choroidal melanoma or following external beam radiotherapy for orbital tumors, usually when the doses are in excess of 50 Gy (25; 122). The peak time of onset of vision loss is 14 to 18 months after radiotherapy. Funduscopic exam shows “cotton wool spots,” telangiectasias, neovascularization, and in some patients, hemorrhages with neovascular glaucoma. Fluorescein angiography shows areas of retinal capillary nonperfusion.

Radiation-induced optic neuropathy most commonly occurs after fractionated radiotherapy for tumors of the orbit, paranasal sinus, nasopharynx, pituitary adenoma, or craniopharyngioma, or less commonly, following whole-brain radiotherapy for primary or metastatic brain tumors (126). Optic neuropathy may also occur after stereotactic radiosurgery for pituitary adenoma or meningioma (51). The peak incidence of radiation optic neuropathy is 12 to 18 months following completion of radiation. Patients present with painless unilateral or bilateral subacute loss of visual acuity, central scotoma, and afferent pupillary defects. Funduscopic exam may show swollen optic nerves, telangiectasias, exudates, and retinal arteriolar narrowing. MRI scanning shows patchy contrast enhancement of one or both optic nerves, and occasionally of the optic chiasm. Microvascular injury is thought to be the underlying mechanism.

Several antineoplastic agents can, in rare instances, damage the retina or optic nerve and cause vision loss. Toxic retinopathy has been reported following use of cisplatin, carboplatin, nitrosoureas, procarbazine, tamoxifen, and interferon (65; 12). Optic neuritis or optic atrophy may occur following use of cisplatin, vincristine, fludarabine, methotrexate, nitrosoureas, procarbazine, paclitaxel, and 5-fluorouracil (93). The risk of retinal or optic nerve toxicity from chemotherapy is greatly increased when the agents (particularly cisplatin or carmustine) are administered via the internal carotid artery for treatment of brain tumors. Immune checkpoint inhibition has also been associated with findings characteristic of autoimmune retinopathy, and cancer-associated retinopathy has been seen in the case of a patient being treated for hepatocellular carcinoma with a PD-1 antibody (27; 63).

Paraneoplastic optic neuritis is a rare complication of breast carcinoma, small cell lung carcinoma, thymoma, or other tumors. Nothing is clinically distinctive about the optic neuritis in these patients, who have decreased visual acuity, afferent pupillary defects, cecocentral scotomata, and disc edema. Paraneoplastic optic neuritis may occur in isolation (87; 134; 156) or in conjunction with retinopathy (31; 45). Some patients with optic neuritis also have cerebellar ataxia (98; 32; 92; 144), multifocal encephalomyelitis (31), or a syndrome resembling Devic disease (neuromyelitis optica) (31; 14; 37; 117). Some patients have serum collapsin response-mediator protein-5 (CRMP5) antibodies, which can be associated with a variety of malignancies including small cell lung cancer, renal cell carcinoma, and thyroid papillary carcinoma, among others (158; 17; 101; 71). CRMP5 paraneoplastic processes can present with multiple neurologic and visual symptoms such as cognitive dysfunction, imbalance, and blurred vision. Other patients may have anti-CV2 antibodies (32; 144; 31; 134), anti-aquaporin-4 antibodies (117), or other antineuronal antibodies (87; 14; 137).

Rarely, progressive bilateral vision loss may be caused by diffuse uveal melanocytic proliferation occurring as a remote effect of ovarian, lung, breast, gastrointestinal, or other genitourinary carcinomas (49; 24; 34; 150). In most reported patients, vision loss was the presenting feature of an otherwise occult tumor. Fundoscopy classically reveals a pattern of multiple, round, red subretinal patches that are hyperfluorescent on fluorescein angiography. Additionally, patients have multiple pigmented and nonpigmented uveal melanocytic tumors, exudative retinal detachment, and cataracts. Other retinopathies such as acute exudative polymorphous vitelliform maculopathy and autosomal recessive bestrophinopathy can resemble fundoscopic findings in paraneoplastic retinopathy as well (16). It is also important to remember that there are numerous other etiologies of bilateral vision loss, independent of cancer history, such as retinitis pigmentosa, cone dystrophy, toxic retinopathies, toxic and nutritional optic neuropathies, and hereditary optic neuropathies, among many others; working closely with ophthalmology (often neuro-ophthalmology, uveitis, and retina subspecialists) becomes critical to ensuring all possible etiologies are explored.

The finding of serum antirecoverin antibodies in patients with vision loss is a highly suggestive, but not absolute, indicator of the presence of an underlying tumor, especially small cell lung carcinoma. When antirecoverin antibodies were first characterized they were believed to be absolutely specific for paraneoplastic retinal degeneration (77). Antirecoverin antibodies have been detected in several patients presenting with retinal degeneration in whom no associated tumor was detected, even after long periods of follow-up (155; 61). Positive serologic testing should also not exclude other possible inflammatory or autoimmune etiologies such as birdshot chorioretinopathy or acute zonal occult outer retinopathy (143; 133).

Nonparaneoplastic autoimmune retinopathy. There is increasing recognition of autoimmune retinopathy occurring in persons without an associated neoplasm (62; 47; 142). The clinical features of nonparaneoplastic autoimmune retinopathy do not reliably differ from those of cancer-associated retinopathy (also present with photopsias or blind spots and have rapid vision changes). The consensus statement on this entity concluded that essential diagnostic criteria include ERG abnormalities, an absence of fundus lesions or retinal dystrophy or other clear cause of vision loss, along with an absence of significant ocular inflammation and the presence of antiretinal antibodies on serologic testing (47). Some patients with nonparaneoplastic autoimmune retinopathy have serum autoantibodies against one or more retinal antigens, including antienolase antibodies (08; 153), or autoantibodies reacting with antigens other than recoverin or enolase (100; 113; 114; 115). Still, there remain limitations with testing for serum antiretinal antibodies as there remains no standardization or validation of testing approaches to date (46).

The antibipolar cell antibodies associated with melanoma and retinopathy have not been reported in patients with other conditions, except for a single reported patient in whom no melanoma or other tumor was detected after several years of follow-up.

Diagnostic workup

The electroretinogram (ERG) in almost all patients with cancer-associated paraneoplastic retinopathy shows reduced amplitude of the a-wave, and it may be nearly flat, reflecting diffuse dysfunction of both rod and cone photoreceptor cells (146; 68). The ERG can be severely abnormal in the face of relatively preserved visual acuity and normal ophthalmoscopic exam. The ERG in patients with melanoma-associated retinopathy usually shows a marked reduction in the amplitude of the dark-adapted b-wave and a normal dark-adapted a-wave (21; 11; 13; 82; 152; 75; 79; 72). This resembles the abnormalities in patients with "congenital stationary night blindness" and indicates dysfunction of retinal bipolar cells. In some patients with melanoma the ERG a-wave is reduced, reflecting photoreceptor cell degeneration (79). ERG of a small number of reported patients with melanoma-associated vitelliform retinopathy suggests involvement of both rods and cones (15).

Other retinal studies, including fluorescein angiography, fundus autofluorescence, and optical coherence tomography (OCT) are also important ancillary tests to rule out other retinal pathology and have demonstrated varied patterns of abnormalities in these patients (22; 116; 97; 109).

In the small number of reported patients tested, cerebrospinal fluid was normal, except for slightly elevated protein or a mild lymphocytic pleocytosis in a few patients (85; 68).

A reasonable starting workup for patients with suspected paraneoplastic retinopathy includes MR imaging of the brain and orbits with contrast with attention to the optic pathways, ERG, and serum assay for antiretinal antibodies (ideally a paraneoplastic panel that includes this antibody). Screening for serum antirecoverin antibodies can be done by a number of commercial or research laboratories. It should be noted that a negative assay for antirecoverin or other antiretinal antibodies does not rule out paraneoplastic retinopathy or the presence of an underlying tumor, and that a few patients with antiretinal antibodies never develop an identifiable associated neoplasm. Similarly, the presence of these antibodies is not in itself diagnostic and there remain difficulties with antibody detection and consistency in results among different laboratories (53; 138). A study by Faez and colleagues demonstrated a concordance rate of any antiretinal antibody around 60% and noted a poor interobserver agreement on lab detection and measurement (43). Clinical correlation remains of paramount importance.

For patients with suspected paraneoplastic retinopathy, with or without identifiable antiretinal antibodies, a complete oncologic work-up should be pursued, including CT chest/abdomen/pelvis or equivalent MRI. Whole-body FDG-PET scanning may reveal a tumor in the lung or elsewhere that was not clearly imaged by other techniques (111; 58). PET scanning does have some false positives and negatives. It is not uncommon for patients’ initial evaluations for an occult tumor to be unrevealing; in these patients, the workup should be repeated every several months.

Management

Empiric antitumor treatment without a histologic cancer diagnosis in patients with suspected paraneoplastic retinopathy is not recommended. When the tumor is diagnosed, it should be treated with the appropriate surgical, chemotherapeutic, or radiation measures, with the realization that progressive visual loss often occurs despite successful antitumor treatment. In conjunction with treatment of the tumor, patients with paraneoplastic retinopathy should receive steroids. Intravenous methylprednisolone may result in a more favorable outcome compared to prednisone and is generally dosed around 1 mg/kg/day (69; 136). Local therapy with intravitreal or sub-Tenon triamcinolone as well as intravitreal long-acting steroid implants have been utilized (73; 124). Prednisone should also be offered to patients with a clinical diagnosis of retinopathy and positive serum antirecoverin antibodies or other antiretinal antibodies, but no detectable neoplasm. In one series the majority of patients with antibody-associated carcinoma-associated retinopathy or nonparaneoplastic autoimmune retinopathy showed improved visual acuity and visual fields after treatment with a regimen of prednisone, azathioprine, and cyclosporin (44). Reports exist of patients whose vision improved with intravenous immunoglobulin (57; 140) or with rituximab, a monoclonal antibody against CD20-expressing B lymphocytes (109); some of these patients failed to respond to prior corticosteroids. There is a single reported case of significant visual improvement after treatment with the monoclonal antibody alemtuzumab, which causes depletion of T lymphocytes and B lymphocytes bearing the CD52 cell surface antigen (42).

Outcomes

Patients treated with immunosuppression therapy may show initial improvement in visual acuity, even before discovery of the underlying neoplasm, but generally disease stabilization is the best outcome (76; 83; 125; 108; 41; 64). Improvement in outer retinal structures including the photoreceptor layer has been demonstrated in a case report following chemotherapy as well as topical steroid drops; such structural improvement has also been demonstrated with rituximab therapy (66). There does not seem to be a difference in the response to prednisone between patients with antirecoverin antibodies and patients with other antiretinal antibodies or no antibodies. No definite reports mention visual improvement following surgery or chemotherapy of small cell lung cancer without concomitant corticosteroid therapy.

Patients with melanoma-associated retinopathy generally suffer progressive vision loss despite tumor treatment or immunomodulatory therapy. Some patients do, however, have visual improvement after cytoreductive tumor surgery, corticosteroids, or intravenous immunoglobulin (11; 99; 75; 123; 23; 79; 69; 129; 147).

References

01: Adamus G. Are anti-retinal autoantibodies a cause or a consequence of retinal degeneration in autoimmune retinopathies? Front Immunol 2018;9:765. PMID 29713325
02: Adamus G, Amundson D, MacKay C, Gouras P. Long-term persistence of antirecoverin antibodies in endometrial cancer-associated retinopathy. Arch Ophthalmol 1998a;116:251-2. PMID 9488286
03: Adamus G, Amundson D, Seigel GM, Machnicki M. Anti-enolase-alpha autoantibodies in cancer-associated retinopathy: epitope mapping and cytotoxicity on retinal cells. J Autoimmun 1998b;11(6):671-7. PMID 9878089
04: Adamus G, Champaigne R, Yang S. Occurrence of major anti-retinal autoantibodies associated with paraneoplastic autoimmune retinopathy. Clin Immunol 2019;210:108317. PMID 31770612
05: Adamus G, Guy J, Schmied JL, Arendt A, Hargrave PA. Role of anti-recoverin autoantibodies in cancer-associated retinopathy. Invest Ophthalmol Vis Sci 1993;34:2626-33. PMID 7688357
06: Adamus G, Machnicki M, Seigel GM. Apoptotic retinal cell death induced by antirecoverin autoantibodies of cancer-associated retinopathy. Invest Ophthalmol Vis Sci 1997;38:283-91. PMID 9040460
07: Adamus G, Ortega H, Witkowska D, Polans A. Recoverin: a potent uveitogen for the induction of photoreceptor degeneration in Lewis rats. Exp Eye Res 1994;59:447-56. PMID 7859820
08: Adamus G, Ren G, Weleber RG. Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy. BMC Ophthalmol 2004;4:5-13. PMID 15180904
09: Adamus G, Webb S, Shiraga S, Duvoisin RM. Anti-recoverin antibodies induce an increase in intracellular calcium, leading to apoptosis in retinal cells. J Autoimmun 2006;26(2):146-53. PMID 16426815
10: Adamus G, Yang S, Weleber RG. Unique epitopes for carbonic anhydrase II autoantibodies related to autoimmune retinopathy and cancer-associated retinopathy. Exp Eye Res 2016;147:161-8. PMID 27185162
11: Alexander KR, Fishman GA, Peachey NS, Marchese AL, Tso MO. "On" response defect in paraneoplastic night blindness with cutaneous malignant melanoma. Invest Ophthalmol Vis Sci 1992;33:477-83. PMID 1544774
12: Al-Tweigeri T, Nabholtz JM, Mackey JR. Ocular toxicity and cancer chemotherapy: a review. Cancer 1996;78:1359-73. PMID 8839540
13: Andreasson S, Ponjavic V, Ehinger B. Full-field electroretinogram in a patient with cutaneous melanoma-associated retinopathy. Acta Ophthalmol (Copenh) 1993;71:487-90. PMID 8249579
14: Antoine JC, Camdessanche JP, Absi L, Lassabliere F, Feasson L. Devic disease and thymoma with anti-central nervous system and antithymus antibodies. Neurology 2004;62(6):978-80. PMID 15037705
15: Aronow ME, Adamus G, Abu-Asab M, et al. Parneoplastic vitelliform retinopathy: clinicopathologic correlation and review of the literature. Surv Ophthalmol 2012;57(6):558-64. PMID 22784677
16: Barbazetto I, Dansingani KK, Dolz-Marco R, et al. Idiopathic acute exudative polymorphous vitelliform maculopathy: clinical spectrum and multimodal imaging characteristics. Ophthalmology 2018;125(1):75-88. PMID 28844323
17: Bataller L, Dalmau J. Neuro-ophthalmology and paraneoplastic syndromes. Curr Opin Neurol 2004;17(1):3-8. PMID 15090871
18: Bazhin AV, Dalke C, Willner N, et al. Cancer-retinal antigens as potential paraneoplastic antigens in melanoma-associated retinopathy. Int J Cancer 2009;124(1):140-9. PMID 18814277
19: Bazhin AV, Savchenko MS, Shifrina ON, et al. Recoverin as a paraneoplastic antigen in lung cancer: the occurrence of anti-recoverin autoantibodies in sera and recoverin in tumors. Lung Cancer 2004;44(2):193-8. PMID 15084384
20: Bazhin AV, Schadendorf D, Philippov PP, Eichmuller SB. Recoverin as a cancer-retina antigen. Cancer Immunol Immunother 2007;56(1):110-6. PMID 16444517
21: Berson EL, Lessell S. Paraneoplastic night blindness with malignant melanoma. Am J Ophthalmol 1988;106:307-11. PMID 2971322
22: Bianciotto C, Shields CL, Thirkill CE, Materin MA, Shields JA. Paraneoplastic retinopathy with multiple detachments of the neurosensory retina and autoantibodies against interphotoreceptor retinoid binding protein (IRBP) in cutaneous melanoma. Br J Ophthalmol 2010;94(12):1684-5. PMID 19286685
23: Boeck K, Hofmann S, Klopfer M, et al. Melanoma-associated paraneoplastic retinopathy: case report and review of the literature. Br J Dermatol 1997;137:457-60. PMID 9349350
24: Bourruat FX, Othenin-Girard P, Uffer S, Othenin-Girard B, Regli F, Hurlimann J. Natural history of diffuse uveal melanocytic proliferation. Ophthalmology 1992;99:1698-704. PMID 1454345
25: Brown GC, Shields JA, Sanborn G, Augsburger JJ, Savino PJ, Schatz NJ. Radiation retinopathy. Ophthalmology 1982;89:1494-501. PMID 7162794
26: Buchanan TA, Gardiner TA, Archer DB. An ultrastructural study of retinal photoreceptor degeneration associated with bronchial carcinoma. Am J Ophthalmol 1984;97:277-87. PMID 6322591
27: Chen Q, Feng C, Sun C, et al. Cancer-associated retinopathy after anti-programmed death 1 (PD-1) antibody for treating hepatocellular carcinoma--a case report of a Chinese patient. Am J Ophthalmol Case Rep 2022;25:101370. PMID 35243142
28: Chen W, Cao W, Achyuthan AM, McGinnis JF. In vitro inhibition of antirecoverin immunoglobulin-mediated death of mammalian photoreceptor cells. J Neurosci Res 2001;63:116-23. PMID 11169621
29: Chen W, Elias RV, Cao W, Lerious V, McGinnis JF. Anti-recoverin antibodies cause the apoptotic death of mammalian photoreceptor cells in vitro. J Neurosci Res 1999;57:706-18. PMID 10462694
30: Crofts JW, Bachynski BN, Odel JG. Visual paraneoplastic syndrome associated with undifferentiated endometrial carcinoma. Can J Ophthalmol 1988;23:128-32. PMID 3285978
31: Cross SA, Salomao DR, Parisi JE, et al. Paraneoplastic autoimmune optic neuritis with retinitis defined by CRMP-5-IgG. Ann Neurol 2003;54:38-50. PMID 12838519
32: de la Sayette V, Bertran F, Honnorat J, Schaeffer S, Iglesia S, Defer G. Paraneoplastic cerebellar syndrome and optic neuritis with anti-CV2 antibodies: clinical response to excision of the primary tumor. Arch Neurol 1998;55(3):405-8. PMID 9520015
33: Dhingra A, Fina ME, Neinstein A, et al. Autoantibodies in melanoma-associated retinopathy target TRPM1 cation channels of reinal ON bipolar cells. J Neurosci 2011;31(11):3962-7. PMID 21411639
34: Donovan JT, Prefontaine M, Gragoudas ES. Blindness as a consequence of a paraneoplastic syndrome in a woman with clear cell carcinoma of the ovary. Gynecol Oncol 1999;73:424-9. PMID 10366472
35: Dropcho EJ. Remote neurologic manifestations of cancer. Neurol Clin 2002;20(1):85-122. PMID 11754303
36: Dryja TP, Demirs JT, Twarog M, Lee V. Completement proteins in the retina in cancer-associated retinopathy. JAMA Ophthalmol 2019;137(12):1458-60. PMID 31670788
37: Ducray F, Weil R, Garcia PY, et al. Devic's syndrome-like phenotype associated with thymoma and anti-CV2 antibodies. J Neurol Neurosurg Psychiatr 2007;78:325-7. PMID 17308295
38: Dutta Majumder P, Marchese A, Pichi F, et al. An update on autoimmune retinopathy. Indian J Ophthalmol 2020;68(9):1829-37. PMID 32823399
39: Duvoisin RM, Haley TL, Ren G, Strycharska-Orczyk I, Bonaparte JP, Morgans CW. Autoantibodies in melanoma-associated retinopathy recognize an epitope conserved between TRPM1 and TRPM3. Invest Ophthalmol Vis Sci 2017;58(5):2732-8. PMID 28549093
40: Eichen J, Dalmau J, Demopoulos A, Wade D, Posner JB, Rosenfeld MR. The photoreceptor cell-specific nuclear receptor is an autoantigen of paraneoplastic retinopathy. J Neuroophthalmol 2001;21(3):168-72. PMID 11725181
41: Eltabbakh GH, Hoogerland DL, Kay MC. Paraneoplastic retinopathy associated with uterine sarcoma. Gynecol Oncol 1995;58:120-3. PMID 7789878
42: Espandar L, O'Brien S, Thirkill C, Lubecki LA, Esmaeli B. Successful treatment of cancer-associated retinopathy with alemtuzumab. J Neurooncol 2007;83(3):295-302. PMID 17252185
43: Faez S, Lowenstein J, Sobrin L. Concordance of antirational antibody testing results between laboratories in autoimmune retinopathy. JAMA Ophthalmol 2013;131(1):113-5. PMID 23307224
44: Ferreyra HA, Jayasundera T, Khan NW, He S, Lu Y, Heckenlively JR. Management of autoimmune retinopathies with immunosuppression. Arch Ophthalmol 2009;127(4):390-7. PMID 19365013
45: Finger ML, Thirkill CE, Borruat FX. Unusual paraneoplastic cause of vision loss: combined paraneoplastic cone dystrophy and optic neuropathy. Arch Ophthalmol 2012;130(5):660-2. PMID 22652860
46: Forooghian F. Consensus on the diagnosis and management of nonparaneoplastic autoimmune retinopathy using a modified Delphi approach. Am J Ophthalmol 2016;170:241-24. PMID 27544042
47: Fox AR, Gordon LK, Heckenlively JR, et al. Consensus on the diagnosis and management of nonparaneoplastic autoimmune retinopathy using a modified Delphi approach. Am J Ophthalmol 2016;168:183-90. PMID 27210277
48: Fukushima A, Tabuchi H. Autoimmune retinopathy caused by anti-paraneoplastic antigen MA2: a case study. Case Rep Ophthalmol 2022;13(2):419-23. PMID 35811772
49: Gass JD, Gieser RG, Wilkinson CP, Beahm DE, Pautler SE. Bilateral diffuse uveal melanocytic proliferation in patients with occult carcinoma. Arch Ophthalmol 1990;108:527-33. PMID 2322154
50: Ghadiri N, Yang Y, Burton BJ. Cancer-associated retinopathy in ampullary pancreatic cancer. BMJ Case Rep 2019;12(11). PMID 31712238
51: Girkin CA, Comey CH, Lunsford LD, Goodman ML, Kline LB. Radiation optic neuropathy after stereotactic radiosurgery. Ophthalmology 1997;104(10):1634-43. PMID 9331204
52: Gittinger JW, Smith TW. Cutaneous melanoma-associated paraneoplastic retinopathy: histopathologic associations. Am J Ophthalmol 1999;127:612-4. PMID 10334362
53: Grange L, Dalal M, Nussenblatt RB, Sen HN. Autoimmune retinopathy. Am J Ophthalmol 2014;157(2):266-72. PMID 24315290
54: Graus F, Dalmau J. Paraneoplastic neurological syndromes. Curr Opin Neurol 2012;25(6):795-801. PMID 23041955
55: Grunwald GB, Kornguth SE, Towfighi J, et al. Autoimmune basis for visual paraneoplastic syndrome in patients with small cell lung carcinoma: retinal immune deposits and ablation of retinal ganglion cells. Cancer 1987;60:780-6. PMID 3036336
56: Grunwald GB, Simmonds MA, Klein R, Kornguth SE. Autoimmune basis for visual paraneoplastic syndrome in patients with small cell lung carcinoma. Lancet 1985;1:658-61. PMID 2858616
57: Guy J, Aptsiauri N. Treatment of paraneoplastic visual loss with intravenous immunoglobulin. Arch Ophthalmol 1999;117:471-7. PMID 10206574
58: Hadjivassiliou M, Alder SJ, Van Beek EJ, et al. PET scan in clinically suspected paraneoplastic neurological syndromes: a 6-year prospective study in a regional neuroscience unit. Acta Neurol Scand 2009;119(3):186-93. PMID 18855873
59: Harmon JP, Purvin VA, Guy J, Aptsiauri N, Sutton GP. Cancer-associated retinopathy in a patient with advanced epithelial ovarian carcinoma. Gynecol Oncol 1999;73:430-2. PMID 10366473
60: Hartmann TB, Bazhin AV, Schadendorf D, Eichmuller SB. SEREX identification of new tumor antigens linked to melanoma-associated retinopathy. Int J Cancer 2005;114(1):88-93. PMID 15523688
61: Heckenlively JR, Fawzi AA, Oversier J, Jordan BL, Aptsiauri N. Autoimmune retinopathy: patients with antirecoverin immunoreactivity and panretinal degeneration. Arch Ophthalmol 2000;118(11):1525-33. PMID 11074809
62: Heckenlively JR, Ferreyra HA. Autoimmune retinopathy: a review and summary. Semin Immunopathol 2008;30(2):127-34. PMID 18408929
63: Heng JS, Kim JM, Jones DK, et al. Autoimmune retinopathy with associated anti-retinal antibodies as a potential immune-related adverse event associated with immunotherapy in patients with advanced cutaneous melanoma: case series and systematic review. BMJ Open Ophthalmol 2022;7(1):e000889. PMID 35047671
64: Hoodgewood F, Butori P, Blanche P, Brezin AP. Cancer-associated retinopathy preceding the diagnosis of cancer. BMC Ophthalmol 2018;18(1):285. PMID 30390655
65: Imperia PS, Lazarus HM, Lass JH. Ocular complications of systemic cancer chemotherapy. Surv Ophthalmol 1989;34:209-30. PMID 2694416
66: Irizarry FJ, Kopplin LJ, Salek SS, et al. Recovery of outer retinal laminations on optical coherence tomography after treatment of cancer associated retinopathy. Am J Ophthalmol Case Rep 2017;8:11-3. PMID 29260107
67: Jacobson DM, Adamus G. Retinal anti-bipolar cell antibodies in a patient with paraneoplastic retinopathy and colon carcinoma. Am J Ophthalmol 2001;131:806-8. PMID 11384586
68: Jacobson DM, Thirkill CE, Tipping SJ. A clinical triad to diagnose paraneoplastic retinopathy. Ann Neurol 1990;28:162-7. PMID 2171418
69: Jacobzone C, Cochard C, Kupfer I, et al. Corticosteroid treatment for melanoma-associated retinopathy. Arch Dermatol 2004;140:1258-61. PMID 15492190
70: Jampol LM, Kim HH, Bryar PJ, Shankle JB, Lee RT, Johnston RL. Multiple serous retinal detachments and subretinal deposits as the presenting signs of metastatic melanoma. Retina 2004;24(2):320-2. PMID 15097904
71: Jarius S, Wadinger KP, Borowski K, Stoecker W, Wildemann B. Antibodies to CV2/CRMP5 in neuromyelitis optica-like disease: case report and review of the literature. Clin Neurol Neurosurg 2012;114(4):331-5. PMID 22138095
72: Jiang X, Mahroo O. Negative electroretinograms: genetic and acquired causes, diagnostic approaches and physiological insights. Eye (Lond) 2021;35(9):2419-37. PMID 34127841
73: Karatsai E, Robson AG, Taylor SRJ. Outcomes associated with sustained-release intraocular fluocinolone implants in a case of melanoma-associated retinopathy treated without systemic immunosuppression. JAMA Ophthalmol 2019; 137(5):564-7. PMID 30896772
74: Katsuta H, Okada M, Nakauchi T, Takahashi Y, Yamao S, Uchida S. Cancer-associated retinopathy associated with invasive thymoma. Am J Ophthalmol 2002;134(3):383-9. PMID 12208250
75: Kellner U, Bornfeld N, Foerster MH. Severe course of cutaneous melanoma associated paraneoplastic retinopathy. Br J Ophthalmol 1995;79:746-52. PMID 7547786
76: Keltner JL, Roth AM, Chang RS. Photoreceptor degeneration: possible autoimmune disorder. Arch Ophthalmol 1983;101:564-9. PMID 6838414
77: Keltner JL, Thirkill CE. Cancer-associated retinopathy versus recoverin-associated retinopathy. Am J Ophthalmol 1998;126:296-302. PMID 9727525
78: Keltner JL, Thirkill CE, Tyler NK, Roth AM. Management and monitoring of cancer-associated retinopathy. Arch Ophthalmol 1992;110:48-53. PMID 1310001
79: Keltner JL, Thirkill CE, Yip PT. Clinical and immunologic characteristics of melanoma-associated retinopathy syndrome: eleven new cases and a review of 51 previously published cases. J Neuroophthalmol 2001;21(3):173-87. PMID 11725182
80: Kikuchi T, Arai J, Shibuki H, Kawashima H, Yoshimura N. Tubby-like protein as an autoantigen in cancer-associated retinopathy. J Neuroimmunol 2000;103:26-33. PMID 10674986
81: Kim MS, Hong HK, Ko YJ, et al. A case of melanoma-associated retinopathy with autoantibodies against TRPM1. Doc Ophthalmol 2020;141(3):313-8. PMID 32472235
82: Kim RY, Retsas S, Fitzke FW, Arden GB, Bird AC. Cutaneous melanoma-associated retinopathy. Ophthalmology 1994;101:1837-43. PMID 7800366
83: Klingele TG, Burde RM, Rappazzo JA, Isserman MJ, Burgess D, Kantor O. Paraneoplastic retinopathy. J Clin Neuroophthalmol 1984;4:239-45. PMID 6240497
84: Kondo M, Sanuki R, Ueno S, et al. Identification of autoantibodies against TRPM1 in patients with paraneoplastic retinopathy associated with ON bipolar cell dysfunction. PLoS ONE 2011;6(5):e19911. PMID 21611200
85: Kornguth SE, Klein R, Appen R, Choate J. Occurrence of anti-retinal ganglion cell antibodies in patients with small cell carcinoma of the lung. Cancer 1982;50:1289-93. PMID 6286090
86: Lei B, Bush RA, Milam AH, Sieving PA. Human melanoma-associated retinopathy antibodies alter the retinal ON-response of the monkey ERG in vivo. Invest Ophthalmol Vis Sci 2000;41:262-6. PMID 10634629
87: Lieberman FS, Odel J, Hirsh J, Heinemann M, Michaeli J, Posner J. Bilateral optic neuropathy with IgGk multiple myeloma improved after myeloablative chemotherapy. Neurology 1999;52:414-6. PMID 9932972
88: Ling CP, Pavesio C. Paraneoplastic syndromes associated with visual loss. Curr Opin Ophthalmol 2003;14(6):426-32. PMID 14615650
89: Link B, Schlotzer-Schrehardt U, Junemann A. Carcinoma-associated retinopathy - an electrophysiological and immunohistochemical correlation. Retina 2009;29(1):69-72. PMID 18728619
90: Lu Y, He S, Jia L, Khan NW, Heckenlively JR. Two mouse models for recoverin-associated autoimmune retinopathy. Mol Vis 2010;16:1936-48. PMID 21031137
91: Lu Y, Jia L, He S, et al. Melanoma-associated retinopathy: a paraneoplastic autoimmune complication. Arch Ophthalmol 2009;127(12):1572-80. PMID 20008709
92: Luiz JE, Lee AG, Keltner JL, Thirkill CE, Lai EC. Paraneoplastic optic neuropathy and autoantibody production in small-cell carcinoma of the lung. J Neuroophthalmol 1998;18:178-81. PMID 9736201
93: Macdonald DR, Rottenberg DA, Schutz JS, Posner JB. Radiation-induced optic neuropathy. In: Rottenberg DA, editor. Neurological complications of cancer treatment. Boston: Butterworth-Heinemann, 1991:37-61.
94: Maeda A, Maeda T, Ohguro H, Palczewski K, Sato N. Vaccination with recoverin, a cancer-associated retinopathy antigen, induces autoimmune retinal dysfunction and tumor cell regression in mice. Eur J Immunol 2002;32(8):2300-7. PMID 12209643
95: Maeda A, Ohguro H, Maeda T, et al. Aberrant expression of photoreceptor-specific calcium-binding protein (recoverin) in cancer cell lines. Cancer Res 2000;60:1914-20. PMID 10766180
96: Maeda T, Maeda A, Maruyama I, et al. Mechanisms of photoreceptor cell death in cancer-associated retinopathy. Invest Ophthalmol Vis Sci 2001;42:705-12. PMID 11222531
97: Makiyama Y, Kikuchi K, Otani A, et al. Clinical and immunological characterization of paraneoplastic retinopathy. Invest Ophthalmol Vis Sci 2013;54(8):5424-31. PMID 23860756
98: Malik S, Furlan AJ, Sweeney PJ, Kosmorsky GS, Wong M. Optic neuropathy: a rare paraneoplastic syndrome. J Clin Neuroopthalmol 1992;12:137-41. PMID 1328306
99: Milam AH, Saari JC, Jacobson SG, Lubinski WP, Feun LG, Alexander KR. Autoantibodies against retinal bipolar cells in cutaneous melanoma-associated retinopathy. Invest Ophthalmol Vis Sci 1993;34:91-100. PMID 8425845
100: Mizener JB, Kimura AE, Adamus G, Thirkill CE, Goeken JA, Kardon RH. Autoimmune retinopathy in the absence of cancer. Am J Ophthalmol 1997;123:607-18. PMID 9152066
101: Moss HE, Liu GT, Dalmau J. Glazed (vision) and confused. Surv Ophthalmol 2010;55(2):169-73. PMID 19804892
102: Murphy MA, Thirkill CE, Hart WM. Paraneoplastic retinopathy: a novel autoantibody reaction associated with small-cell lung carcinoma. J Neuroophthalmol 1997;17:77-83. PMID 9176775
103: Neena R, Jain A, Anantharaman G, et al. Carcinoma -associated retinopathy(CAR): role of electroretinography(ERG) and optical coherence tomography(OCT) in diagnosis and predicting treatment outcome. Am J Ophthalmol Case Rep 2021;21:101008. PMID 33511304
104: Ohguro H, Ogawa K, Maeda T, Maeda A, Maruyama I. Cancer-associated retinopathy induced by both anti-recoverin and anti-hsc70 antibodies in vivo. Invest Ophthalmol Vis Sci 1999b;40:3160-7. PMID 10586938
105: Ohguro H, Ogawa K, Nakagawa T. Recoverin and Hsc70 are found as autoantigens in patients with cancer-associated retinopathy. Invest Ophthalmol Vis Sci 1999a;40:82-9. PMID 10586938
106: Ohguro H, Yokoi Y, Ohguro I, et al. Clinical and immunologic aspects of cancer-associated retinopathy. Am J Ophthalmol 2004;137:1117-9. PMID 15183799
107: Ohkawa T, Kawashima H, Makino S, et al. Cancer-associated retinopathy in a patient with endometrial cancer. Am J Ophthalmol 1996;122:740-2. PMID 8909222
108: Ohnishi Y, Ohara S, Sakamoto T, Kohno T, Nakao F. Cancer-associated retinopathy with retinal phlebitis. Br J Ophthalmol 1993;77:795-8. PMID 8110675
109: Or C, Collins DR, Merkur AB, Wang Y, Chan CC, Forooghian F. Intravenous rituximab for the treatment of cancer-associated retinopathy. Can J Ophthalmol 2013;48(2):e35-8. PMID 23561621
110: Parc CE, Azan E, Bonnel S, Sahel JA, Kaplan J, Thirkill CE. Cone dysfunction as a paraneoplastic syndrome associated with retinal antigens approximating 40 kiloDaltons. Ophthalmic Genet 2006;27:57-61. PMID 16754207
111: Patel RR, Subramaniam RM, Mandrekar JN, Hammack JE, Lowe VJ, Jett JR. Occult malignancy in patients with suspected paraneoplastic neurologic syndromes: value of positron emission tomography in diagnosis. Mayo Clin Proc 2008;83(8):917-22. PMID 18674476
112: Peek R, Dijkstra BG, Meek B, Kuijpers RW. Autoantibodies to photoreceptor membrane proteins and outer plexiform layer in patients with cancer-associated retinopathy. Clin Exp Immunol 2002;128(3):498-503. PMID 12067305
113: Peek R, Verbraak F, Coevoet HM, Kijlstra A. Muller-cell specific autoantibodies in a patient with progressive loss of vision. Invest Ophthalmol Vis Sci 1998a;39:1976-9. PMID 9727423
114: Peek R, van Gelderen BE, Bruinenberg M, Kijlstra A. Molecular cloning of a new angiopoietinlike factor from the human cornea. Invest Ophthalmol Vis Sci 1998b;39:1976-9 PMID 9727400
115: Peek R, Verbraak F, Bruinenberg M, Van der Lelij A, Van den Horn G, Kijlstra A. Cytomegalovirus glycoprotein B genotyping in ocular fluids and blood of AIDS patients with cytomegalovirus retinitis. Invest Ophthalmol Vis Sci 1998c;39:1976-9 PMID 9620078
116: Pepple KL, Cusick M, Jaffe GJ, Mruthyunjaya P. SD-OCT and autofluorescence characteristics of autoimmune retinopathy. Br J Ophthalmol 2013;97(2):139-44. PMID 23221966
117: Pittock SJ, Lennon VA. Aquaporin-4 autoantibodies in a paraneoplastic context. Arch Neurol 2008;65(5):629-32. PMID 18474738
118: Polans AS, Buczylko J, Crabb J, Palczewski K. A photoreceptor calcium binding protein is recognized by autoantibodies obtained from patients with cancer-associated retinopathy. J Cell Biol 1991;112:981-9. PMID 1999465
119: Potter MJ, Adamus G, Szabo SM, Lee R, Mohaseb K, Behn D. Autoantibodies to transducin in a patient with melanoma-associated retinopathy. Am J Ophthalmol 2002;134(1):128-30. PMID 12095824
120: Potter MJ, Thirkill CE, Dam OM, Lee AS, Milam AH. Clinical and immunocytochemical findings in a case of melanoma-associated retinopathy. Ophthalmology 1999;106:2121-5. PMID 10571347
121: Przezdziecka-Dołyk J, Brzecka A, et al. Ocular paraneoplastic syndromes. Biomedicines 2020;8(11):490. PMID 33182708
122: Ratnayake G, Oh T, Mehta R, et al. Long-term treatment outcomes of patients with primary optic nerve sheath meningioma treated with stereotactic radiotherapy. J Clin Neurosci 2019;68:162-7. PMID 31401001
123: Remulla JF, Pineda R, Gaudio AR, Milam AH. Cutaneous melanoma-associated retinopathy with retinal periphlebitis. Arch Ophthalmol 1995;113(7):854-5. PMID 7605271
124: Ribeiro F, Falcao MS. Off-label use of 0.19 mg fluocinolone acetonide intravitreal implant: a systematic review. J Ophthalmol 2021;2021:6678364. PMID 34055398
125: Rizzo JF, Gittinger JW. Selective immunohistochemical staining in the paraneoplastic retinopathy syndrome. Ophthalmology 1992;99:1286-95. PMID 1325045
126: Roden D, Bosley TM, Fowble B, et al. Delayed radiation injury to the retrobulbar optic nerves and chiasm. Clinical syndrome and treatment with hyperbaric oxygen and corticosteroids. Ophthalmology 1990;97(3):346-51. PMID 2336273
127: Rosenfeld MR, Dalmau J. Paraneoplastic neurologic syndromes. Neurol Clin 2018;36(3):675-85. PMID 30072076
128: Sabater AL, Sabada LM, de Nova E. Ocular symptoms secondary to meningeal carcinomatosis in a patient with lung adenocarcinoma: a case report. BMC Ophthalmol 2012;12:65. PMID 23249254
129: Sakamori Y, Kim YH, Okuda C, et al. Two cases of cancer-associated retinopathy combined with small-cell lung cancer. Jpn J Clin Oncol 2011;41(5):669-73. PMID 21385760
130: Sawyer RA, Selhorst JB, Zimmerman LE, Hoyt WF. Blindness caused by photoreceptor degeneration as a remote effect of cancer. Am J Ophthalmol 1976;81:606-13. PMID 179323
131: Sekiguchi I, Suzuki M, Sato I, Ohkawa T, Kawashima H, Tsuchida S. Rare case of small-cell carcinoma arising from the endometrium with paraneoplastic retinopathy. Gynecol Oncol 1998;71:454-7. PMID 9887249
132: Sen HN, Chan CC, Caruso RC, Fariss RC, Nussenblatt RB, Buggage RR. Waldenstrom's macroglobulinemia-associated retinopathy. Ophthalmology 2004;111(3):535-9. PMID 15019332
133: Sen HN, Grange L, Akanda M, Fox A. Autoimmune retinopathy: current concepts and practices. Trans Am Ophthalmic Soc 2017;115:T8. PMID 29576753
134: Sheorajpanday R, Slabbynck H, van de Sompel W, Galdermans D, Neetens I, De Deyn PP. Small cell lung carcinoma presenting as CRMP-5 paraneoplastic optic neuropathy. J Neuro-Ophthalmol 2006;26:168-72. PMID 16966932
135: Shiraga S, Adamus G. Mechanism of CAR syndrome: anti-recoverin antibodies are the inducers of retinal cell apoptotic death via the capsase 9- and capsase 3-dependent pathway. J Neuroimmunol 2002;132(1-2):72-82. PMID 12417436
136: Singh D, Tripathy K. Cancer associated retinopathy. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2023. PMID 35201711
137: Slamovits TL, Posner JB, Reidy DL, Thirkill CE, Keltner JL. Pancreatic neuroendocrine paraneoplastic optic neuropathy: confirmation with antibody to optic nerve and hepatic metastasis. J Neuroophthalmol 2013;33(1):21-5. PMID 22926698
138: Sobrin L. Progress toward precisely diagnosing autoimmune retinopathy. Am J Ophthalmol 2018;188:xiv-xv. PMID 29396036
139: Stanford MR, Edelsten CE, Hughes JD, et al. Paraneoplastic retinopathy in association with large cell neuroendocrine bronchial carcinoma. Br J Ophthalmol 1995;79:617-20. PMID 7626582
140: Subhadra C, Dudek AZ, Rath PP, Lee MS. Improvement in visual fields in a patient with melanoma-associated retinopathy treated with intravenous immunoglobulin. J Neuroophthalmol 2008;28(1):23-6. PMID 18347454
141: Suhler EB, Chan C, Caruso RC, et al. Presumed teratoma-associated paraneoplastic retinopathy. Arch Ophthalmol 2003;121:133-6. PMID 12523906
142: Takiuti JT, Takahashi VKL, Xu CL, Jauregui R, Tsang SH. Non-paraneoplastic related retinopathy: clinical challenges and review. Ophthalmic Genet 2019;40(4):293-7. PMID 31394964
143: Ten Berge JC, van Rosmalen J, Vermeer J, et al. Serum autoantibody profiling of patients with paraneoplastic and non-paraneoplastic autoimmune retinopathy. PLoS One 2016;11(12):e0167909. PMID 27930731
144: Thambisetty MR, Scherzer CR, Yu Z, Lennon VA, Newman NJ. Paraneoplastic optic neuropathy and cerebellar ataxia with small cell carcinoma of the lung. J Neuroophthalmol 2001;21(3):164-7. PMID 11725180
145: Thirkill CE, FitzGerald P, Sergott RC, Roth AM, Tyler NK, Keltner JL. Cancer-associated retinopathy (CAR syndrome) with antibodies reacting with retinal, optic nerve, and cancer cells. N Engl J Med 1989;321:1589-94. PMID 2555714
146: Thirkill CE, Roth AM, Keltner JL. Cancer-associated retinopathy. Arch Ophthalmol 1987;105:372-5. PMID 2950846
147: Tian JJ, Coupland S, Karanjia R, Sadun AA. Melanoma-associated retinopathy 28 years after diagnosis. JAMA Ophthalmol 2017;135(11):1276-7. PMID 28975251
148: To KW, Thirkill CE, Jakobiec FA, Lessell S, Berson EL. Lymphoma-associated retinopathy. Ophthalmology 2002;109:2149-53. PMID 12414431
149: Ueno S, Inooka D, Nakanishi A, et al. Clinical course of paraneoplastic retinopathy with anti-TRPM1 autoantibody in Japanese cohort. Retina 2019;39(12):2410-8. PMID 30260920
150: van Noort BC, Keunen JEE, Schlingmann RO, Marinkovic M. Long survival and preservation of good visual acuity in a patient with bilateral diffuse uveal melanocytic proliferation. Ocul Oncol Pathol 2019;5(1):75-8. PMID 30675481
151: Varin J, Reynolds MM, Bouzidi N, et al. Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy PLoS One 2020;15(4):e0231750. PMID 32324760
152: Weinstein JM, Kelman SE, Bresnick GH, Kornguth SE. Paraneoplastic retinopathy associated with antiretinal bipolar cell antibodies in cutaneous malignant melanoma. Ophthalmology 1994;101:1236-43. PMID 8035987
153: Weleber RG, Watzke RC, Shults WT, et al. Clinical and electrophysiologic characterization of paraneoplastic and autoimmune retinopathies associated with antienolase antibodies. Am J Ophthalmol 2005;139(5):780-94. PMID 15860281
154: Weppelmann TA, Khalil S, Zafrullah N, Amir S, Margo CE. Ocular paraneoplastic syndromes: a critical review of diffuse uveal melanocytic proliferation and autoimmune retinopathy. Cancer Control 2022;29:10732748221144458. PMID 36473045
155: Whitcup SM, Vistica BP, Milam AH, Nussenblatt RB, Gery I. Recoverin-associated retinopathy: a clinically and immunologically distinctive disease. Am J Ophthalmol 1998;126(2):230-7. PMID 9727517
156: Xu Q, Du W, Zhou H, et al. Distinct clinical characteristics of paraneoplastic optic neuropathy. Br J Ophthalmol 2019;103(6):797-801. PMID 30021813
157: Yamada G, Ohguro H, Aketa K, et al. Invasive thymoma with paraneoplastic retinopathy. Hum Pathol 2003;34:717-9. PMID 12874770
158: Yu Z, Kryzer TJ, Griesmann GE, Kim K, Benarroch EE, Lennon VA. CRMP–5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001;49(2):146-54. PMID 11220734

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Paraneoplastic retinopathy

Associated Disorders

Melanoma
Small cell lung carcinoma

Differential Diagnosis

telangiectasias
neovascular glaucoma
direct tumor spread
adverse effects of treatment
infiltration or compression of the optic nerve
- metastatic tumor
- radiation-induced retinal damage
- toxic retinopathy
- optic neuritis
- breast carcinoma
- retinitis pigmentosa
- chiasm by metastatic tumor
- macular degeneration
- leptomeningeal metastases
- pituitary tumors
- parasellar tumors
- radiation-induced optic neuropathy
- brain tumors
- swollen discs
- papilledema
- direct tumor cell infiltration
- retinal arteriolar narrowing
- afferent pupillary defects
- multifocal paraneoplastic encephalomyelitis
- microvascular injury
- disc edema
- genitourinary carcinoma
- uveal melanocytic tumors
- cataracts
- small cell lung cancer
- renal cell carcinoma
- thyroid papillary carcinoma

Also Relevant

Chemotherapy: neurologic complications
Common retinopathies
Cortical blindness
Optic neuritis
Paraneoplastic syndromes
- Unusual retinopathies

Clinical Categories

Patient Handouts

Paraneoplastic syndromes

Paraneoplastic retinopathy …

Paraneoplastic retinopathy

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Outcomes

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Overview of neuropathology updates for infiltrating gliomas

Anti-IgLON5 disease

Anti-LGI1 encephalitis

Transient visual loss

CNS germinoma

Circumscribed astrocytic gliomas [Brief]

Adult-type diffuse gliomas [Brief]

Glioneuronal and neuronal tumors [Brief]

Paraneoplastic retinopathy

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Diagnostic workup

Management

Outcomes

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Overview of neuropathology updates for infiltrating gliomas

Anti-IgLON5 disease

Anti-LGI1 encephalitis

Transient visual loss

CNS germinoma

Circumscribed astrocytic gliomas [Brief]

Adult-type diffuse gliomas [Brief]

Glioneuronal and neuronal tumors [Brief]

This is an article preview.
Start a Free Account
to access the full version.