Introduction Because of the advent of monoclonal antibodies in the treatment of metastatic melanoma, patients with this disease are surviving longer. Early recognition of the disease has therefore become even more important. Case report We present a patient with vitelliform maculopathy, a paraneoplastic retinal maculopathy that is under-recognized. Clinically the retinal findings of serous detachments and pigmentary macular changes are remarkable, while at the same time these patients have surprisingly very few symptoms. This is in contrast to patients who develop melanoma associated retinopathy (MAR) who are very symptomatic early in the disease, but with more subtle retinal findings. Conclusion Monoclonal antibody treatment is changing the survival rates in metastatic disease making early diagnosis even more important. Exudative polymorphous vitelliform maculopathy (EPVM) needs to be recognized early to avoid delay in diagnosis of metastatic disease.

Purpose: To report the case of a patient whose retinal disease was found to be associated with a diffuse large B-cell lymphoma found 30 years after the apparent successful treatment of a classical Hodgkin lymphoma. Methods: Observational case report. Results: The authors describe the case of a 69-year-old man referred to their Department because of progressive, bilateral vision loss over the last few months. Deterioration in color vision and intense photophobia were also present. His best-corrected visual acuity was 20/400 in the right eye (RE) and 20/800 in the left eye (LE). Slit lamp and fundus examination failed to show any abnormalities. Spectral domain optical coherence tomography (SD-OCT) detected diffuse attenuation of the ellipsoid layers in addition to a focal subfoveal defect in both eyes. Both fluorescein and indocyanine angiographies (FA and ICGA) were normal. Full flash electroretinogram (ERG) revealed bilateral cone rod dysfunction with decreased amplitudes of both a and b waves. Conclusion: Because of the late onset of the disease, poor visual acuity compared with a small macular anatomical lesion and a history of Hodgkin lymphoma 30 years ago, a neoplastic etiology was investigated. Poor performance status and chest pain led to a thoracic CT scan, which identified a massive mediastinal tumor. Serum analysis found an abnormal amount of antibody activity within the 40 kD region of Western blot of retina. The diagnosis of diffuse large B-cell lymphoma was established. Systemic examinations found a Stage IV non-Hodgkin lymphoma.

Auto-antibodies assist with the diagnosis of ocular paraneoplastic syndromes and autoimmune ocular conditions; however, the frequency of positive test results as a possible precursor to future disease is unknown. The frequency of positive antibodies in heavy smokers who may be at risk for autoimmune-related retinopathy and optic neuropathy was evaluated. Serum antibody activity was evaluated through the use of Western blot reactions from pig retina and optic nerve extract. Fifty-one patients were included: 35 patients were smokers (average: 40.9 pack-year history) and 26 patients had no past smoking history. None of the patients had any visual complaints or known eye disease. Of the patients studied, 76.5% (39 patients: 18 smokers, 21 non-smokers) had positive antiretinal antibodies, and 19.6% (10 patients: 3 smokers, 7 non-smokers) had positive antioptic nerve antibodies. Anti-retinal antibodies were seen in a majority of randomly selected patients with and without a past smoking history. Anti-optic nerve bodies were less common, but more prevalent in those who never smoked. The specificity of these antibodies remains greatly uncertain and clinical correlation is warranted.

The authors describe two rare cases of autoimmune retinopathy associated with follicular cell lymphoma, including a 54-year-old man who experienced nyctalopia for 1 year (patient 1) and a 59-year-old man who had bilateral loss of central vision for 6 months (patient 2). Visual field testing of patient 1 revealed nonspecific defects, and multifocal electroretinogram (ERG) testing showed mildly subnormal amplitudes more pronounced in the left than the right eye. Serologic testing detected antibodies against a 47-kD protein, presumed to be alpha-enolase. Goldmann perimetry of patient 2 showed dense central scotomas, and a full-field ERG revealed reduced amplitudes of bright scotopic responses. Serological testing yielded anti-bipolar cell antibodies. A variable presentation of autoimmune retinopathy can occur in the setting of follicular cell lymphoma. Disparate serum autoantibodies may have mediated the pathogenesis of retinal degeneration in these two patients and could explain the difference in course and severity of retinopathy.

A 68-year-old woman presented with bilateral visual loss as the only clinical manifestation of an occult pancreatic nonsecretory neuroendocrine tumor (NET). The suspected diagnosis of paraneoplastic optic neuropathy was confirmed using immunofluorescence assays to demonstrate the presence of antibodies in the patient's serum that reacted with antigen(s) in the optic nerve and in the pancreatic NET hepatic metastasis. Treatment of the underlying cancer was followed by marked improvement in visual function.

A 62-year-old Hispanic female with no prior history of malignancy presented with 3-year history of painless, simultaneous, and progressive bilateral constriction of her visual fields. The patient was otherwise healthy and denied hematochezia, melena, or changes in bowel habit. During this 3-year period, the patient was evaluated by multiple ophthalmologists, but no clear or formal diagnosis was made. Initial examination 3 years before presentation to us showed optic disc edema OU and mild generalized constriction of visual fields OU. Evaluation for the optic disc edema and visual field loss was negative: orbital computed tomography and cranial magnetic resonance imaging with contrast; lumbar puncture showed a cerebrospinal fluid (CSF) protein elevation of 122 mg/dL but normal CSF cell count and glucose. CSF cytology was negative. Chest radiograph, serum rapid plasma regain, fluorescent treponemal antibody, angiotensin-converting enzyme, antinuclear antibody, antiphospholipid antibody, plasma homocysteine, vitamin B12, folate, erythrocyte sedimentation rate, complete blood count, routine chemistries, and serum protein electrophoresis were all normal. On our examination, the best corrected visual acuity was 20/60 OD and 20/25 OS. There was a left relative afferent pupillary defect. The intraocular pressure, slit-lamp, and motility examinations were normal. Funduscopic examination at time of presentation revealed diffusely pale discs with cup-to-disc ratio of 0.3 and peripapillary atrophy bilaterally. There was also moderate arteriolar narrowing with no bone spicule formation and diffuse nonspecific peripheral retinal pigment epithelium changes (Fig. 1A, 1B). Optical coherence tomography showed bilateral retinal nerve fibre loss, at 50 μm, consistent with bilateral optic atrophy (Fig. 2). Humphrey visual field (24-2) testing revealed bilateral generalized, peripheral constriction OU (Fig 3A, 3B). A possible diagnosis of autoimmune or paraneoplastic optic neuropathy (PON) and retinopathy was made.Fig. 2Optical coherence tomography demonstrating bilateral retinal nerve fibre loss.View Large Image Figure ViewerDownload (PPT)Fig. 3A, Humphrey visual field 24-2 revealed generalized visual field constriction in right eye. B, Humphrey visual field 24-2 revealed generalized visual field constriction in left eye.View Large Image Figure ViewerDownload (PPT) Serum paraneoplastic antibody panel (Mayo Clinic) including anti-neuronal nuclear antibodies (ANNA-1), collapsin response mediator protein 5 (CRMP5) antibody, and anti-Yo was negative. Visual-evoked potential showed delay OU with decreased amplitude OS.1Fisherman G.A. Birch D.G. Holder G.E. Brigell M.G. Ophthalmology Monograph 2.Electrophysiologic Testing in Disorders of the Retina, Optic Nerve, and Visual Pathway. 2nd ed. American Academy of Ophthalmology, San Francisco2001Google Scholar Full-field electroretinography (ERG) showed nonspecific widespread dysfunction in the rod and cone systems to the outer and middle retina. Multifocal ERG revealed abnormal bilateral foveal responses and multiple attenuated, misshaped, or extinguished responses in the perifoveal region. Serum was sent to the University of California, Davis Ocular Immunology Laboratory. Western blots were reactive with 47 and 40 kDa of this tissue. The 47-kDa protein is presumed to be an isoform of α-enolase, and the 40-kDa reaction is suspected to represent immunologic activity with α-transducin previously reported to be associated with paraneoplastic syndromes.2Gitlits V.M. Toh B.H. Sentry J.W. Disease association, origin, and clinical relevance of autoantibodies to the glycolytic enzyme enolase.J Investig Med. 2001; 49: 138-145Crossref PubMed Scopus (63) Google Scholar, 3Adamus G. Reng G. Weleber R.G. Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy.BMC Ophthalmol. 2004; 4: 5-14Crossref PubMed Scopus (200) Google Scholar Empiric oral steroid therapy was started, and she underwent a complete evaluation for malignancy, including colonoscopy, which revealed a 25- to 30-cm ulcerated mass in her sigmoid colon (Fig. 4). Histopathology of this mass revealed invasive, primary, and moderately differentiated colon adenocarcinoma, grade II, which invaded through the muscularis propria and into the subserosal connective tissue. Two of 23 lymph nodes were positive for lymphatic invasion. The patient was treated with leucovorin calcium with folinic acid, fluorouracil, and oxaliplatin (FOLFOX), and local radiation therapy. One year after the initial diagnosis, the patient’s best corrected visual acuity improved to 20/30 OD and 20/25 OS. Her visual fields have been unchanged, and follow-up examinations do not show any evidence of malignancy recurrence. Many cases of cancer-associated retinopathy (CAR) and PON have been described in the literature, but to our knowledge, this is the first reported case in the English language ophthalmic literature of an immunologically reactive patient with both PON and paraneoplastic retinopathy who was subsequently found to have colon adenocarcinoma. Patients with PON typically present with painless, subacute, usually bilateral vision loss most commonly associated with small cell lung cancer and Lambert-Eaton syndrome.4Arés-Luque A. Garcia-Tuñón L.A. Saiz A. et al.Isolated paraneoplastic optic neuropathy associated with small-cell lung cancer and anti-CV2 antibodies.J Neurol. 2007; 254: 1131-1132Crossref PubMed Scopus (15) Google Scholar, 5Sheorajpanday R. Slabbynck H. Van De Sompel W. Galdermans D. Neetens I. De Deyn P.P. Small cell lung carcinoma presenting as collapse response-mediating protein (CRMP)-5 paraneoplastic optic neuropathy.J Neuroophthalmol. 2006; 26: 168-172Crossref PubMed Scopus (30) Google Scholar Optic disc edema may be present in the acute stage of PON, and later progresses to pallor and atrophy, similar to that occurring in this patient. Analysis of CSF may also reveal increased protein content, lymphocytosis, and oligoclonal bands on electrophoresis. Our patient’s CSF showed elevated protein, which is consistent with, but not exclusively associated with, the diagnosis of PON. In many case reports of PON, the anti-CV2/CRMP-5 antibody in the serum and/or CSF is positive and plays a critical role in forming the final diagnosis.4Arés-Luque A. Garcia-Tuñón L.A. Saiz A. et al.Isolated paraneoplastic optic neuropathy associated with small-cell lung cancer and anti-CV2 antibodies.J Neurol. 2007; 254: 1131-1132Crossref PubMed Scopus (15) Google Scholar, 6Murakami Y. Yoshida S. Yoshikawa H. et al.CRMP-5-IgG in patients with paraneoplastic optic neuritis with lung adenocarcinoma.Eye (Lond). 2007; 21: 860-862Crossref PubMed Scopus (10) Google Scholar Anti-CV2 is an autoantibody that reportedly binds exclusively to oligodendrocytes in the cerebellum, brainstem, spinal cord, and optic chiasm.7Chan J.W. Paraneoplastic retinopathies and optic neuropathies.Surv Ophthalmol. 2003; 48: 12-38Abstract Full Text Full Text PDF PubMed Scopus (182) Google Scholar This antibody recognizes CRMP-5, a neuronal cytoplasmic protein expressed in adult central and peripheral neurons, and coincidentally in some small cell carcinomas and thymomas. However, we present a patient with PON associated with colon adenocarcinoma who was negative for the anti-CV2/CRMP-5 antibody and was positive for only the 40- and 47-kDa antigens. The ~47-kDa protein is presumed to be α-enolase, and the 40-kDa antigen has been associated with different types of cancer, but in 60% of cases no neoplasm is found.3Adamus G. Reng G. Weleber R.G. Autoantibodies against retinal proteins in paraneoplastic and autoimmune retinopathy.BMC Ophthalmol. 2004; 4: 5-14Crossref PubMed Scopus (200) Google Scholar To our knowledge, there has been only 1 prior case described in literature that reported paraneoplastic visual disturbance associated with colon adenocarcinoma. In 2001, Jacobson et al.8Jacobson D.M. Retinal anti-bipolar cell antibodies in a patient with paraneoplastic retinopathy and colon carcinoma.Am J Ophthalmol. 2001; 131: 806-808Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar reported a case of CAR in a patient with colon adenocarcinoma. The patient presented with 1-year history of daytime-induced blurred vision and glare (hemeralopia) with improved vision during twilight and at night. Examination revealed visual acuity of 20/15-1 in both eyes and mild pallor in the right optic disc; no other abnormalities were noted to support the diagnosis of optic neuropathy. Similar to our patient, testing for this patient revealed visual field and retinal dysfunction: Goldmann perimetry showed scattered paracentral scotomas in the right eye, and ERG elicited no responses in the right eye. During evaluation for an occult malignancy, a sessile mass was discovered in the sigmoid colon, much like the one described in this reported case. Interestingly, as in our patient, the patient reported by Jacobsen et al.8Jacobson D.M. Retinal anti-bipolar cell antibodies in a patient with paraneoplastic retinopathy and colon carcinoma.Am J Ophthalmol. 2001; 131: 806-808Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar also had no gastrointestinal complaints before the discovery of the malignancy. Other patients with paraneoplastic disease including paraneoplastic retinopathy and optic neuropathy may have a course lasting up to several years without discovering the primary underlying neoplasm. Neuropathologic evaluation in these cases has revealed nonspecific perivascular inflammation, axonal loss, or demyelination of the optic nerve.9Boghen D. Sebag M. Michaud J. Paraneoplastic optic neuritis and encephalomyelitis. Report of a case.Arch Neurol. 1988; 45: 353-356Crossref PubMed Scopus (61) Google Scholar, 10Lambrecht E.R. van der Loos T.L. van der Eerden A.H. Retrobulbar neuritis as the first sign of the glucagonoma syndrome.Int Ophthalmol. 1987; 11: 13-15Crossref PubMed Scopus (19) Google Scholar, 11Maik S. Furlan A.J. Sweeney P.J. Kosmorsky G.S. Wong M. Optic neuropathy a rare paraneoplastic syndrome.J Clin Neuroophthalmol. 1992; 12: 137-141PubMed Google Scholar Currently, it is thought that treatment of the underlying malignancy is the mainstay treatment for PON. There have been variable outcomes for patients with PON treated with steroids and intravenous immunoglobulin.6Murakami Y. Yoshida S. Yoshikawa H. et al.CRMP-5-IgG in patients with paraneoplastic optic neuritis with lung adenocarcinoma.Eye (Lond). 2007; 21: 860-862Crossref PubMed Scopus (10) Google Scholar, 12Calvert Preston C.A. CR(I)MP in the optic nerve: recognition and implications of paraneoplastic optic neuropathy.J Neuro-Ophthalmol. 2006; 26: 165-167Crossref PubMed Scopus (11) Google Scholar In summary, we report a rare case of PON and paraneoplastic retinopathy caused by presumed colon adenocarcinoma. Early clinical and immunologic detection of paraneoplastic visual syndromes can lead to prompt diagnosis of underlying malignancy and its treatment. This work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., NY, NY.

Purpose: To report the presence of a hyperautofluorescent ring and corresponding spectral-domain optical coherence tomography (SD-OCT) features seen in patients with autoimmune retinopathy.Methods: All eyes were evaluated by funduscopic examination, full-field electroretinography, fundus autofluorescence, and SD-OCT. Further confirmation of the diagnosis was obtained with immunoblot and immunohistochemistry testing of the patient's serum. Humphrey visual fields and microperimetry were also performed.Results: Funduscopic examination showed atrophic retinal pigment epithelium (RPE) associated with retinal artery narrowing but without pigment deposits. The scotopic and photopic full-field electroretinograms were nondetectable in three patients and showed a cone-rod pattern of dysfunction in one patient. Fundus autofluorescence revealed a hyperautofluorescent ring in the parafoveal region, and the corresponding SD-OCT demonstrated loss of the photoreceptor inner segment-outer segment junction with thinning of the outer nuclear layer from the region of the hyperautofluorescent ring toward the retinal periphery. The retinal layers were generally intact within the hyperautofluorescent ring, although the inner segment-outer segment junction was disrupted, and the outer nuclear layer and photoreceptor outer segment layer were thinned.Conclusion: This case series revealed the structure of the hyperautofluorescent ring in autoimmune retinopathy using SD-OCT. Fundus autofluorescence and SD-OCT may aid in the diagnosis of autoimmune retinopathy and may serve as a tool to monitor its progression. RETINA 32:1385-1394, 2012

The aim of the article is to report the presentation, diagnosis, and treatment of two cases of unexplained painless vision loss attributed to 47-kDa (presumed alpha-enolase)-positive autoimmune-related retinopathy and optic neuropathy (ARRON); to describe 47-kDa (presumed alpha-enolase)-positive ARRON as a subtype of ARRON; and to propose that serum anti-enolase antibody might be a serologic marker of the disorder. We have reviewed retrospectively of two patients with ARRON positive for an antibody to a 47-kDa retinal antigen presumed to be alpha-enolase. The two patients had progressive bilateral visual acuity and/or visual field loss, electroretinographic evidence for retinal dysfunction, and evidence for serum anti-retinal antibodies to a 47-kDa antigen (presumed alpha-enolase). Although clinically the patients had symptoms of retinal-based visual loss, neither patient had optic disc oedema, optic atrophy, or any ophthalmoscopically visible retinal abnormalities. Both patients were treated with immunosuppressive therapy. One patient achieved improvement in visual acuity with oral corticosteroids alone, but the other patient did not respond to steroid treatment and only achieved improvement in vision following plasmapheresis. After immunosuppressive treatment, follow-up serum antibody levels to a 47-kDa antigen (presumed alpha-enolase) levels were retested and were undetectable in both patients. We hypothesize that these two patients have a constellation of clinical and electrophysiologic findings suggestive of a 47-kDa (presumed alpha-enolase)-positive ARRON that we believe is subtype of ARRON and that serum alpha-enolase antibody might be a marker of the disorder.

mented edges.The anterior scleritis resolved.Prednisone treatment was slowly tapered once improvement was seen in the vitritis, and the patient reported a resolution of her symptoms. Comment.Toxoplasmosis is believed to be the most common cause of posterior uveitis. 2 Scleritis in association with toxoplasmic retinochoroiditis is an uncommon entity. 1 Accordingly, in a review of 243 patients with scleritis, no patient was reported to have toxoplasmic infection as a cause; furthermore, 37% had a systemic rheumatologic disorder, only 7% had an infection, and 44% had an associated medical disorder.Herpes zoster virus was the most commonly reported infectious cause and rheumatoid arthritis was the most common rheumatic disease. 4 In cases of toxoplasmic scleritis, the inflammatory response is believed to extend from the active retinochoroiditis to involve the overlying sclera.Accordingly, pathologic specimens from eyes that were enucleated secondary to severe toxoplasmic scleritis displayed granulomatous inflammation of the retina, uvea, and episclera with associated retinal thickening.In many cases, the entire sclera extending outward from the retinitis was inflamed; however, in some cases, a region of uninflamed sclera separated the active scleritis from the underlying retinitis. 1 Isolated toxoplasmic retinochoroiditis can rapidly spread and lead to severe permanent vision loss when treated with steroids alone. 5 In our patient with scleritis, a dilated fundus examination revealed an area of typical toxoplasmic retinochoroiditis, allowing for prompt diagnosis and treatment with appropriate antibiotic therapy.The patient improved and maintained excellent visual acuity.This patient's course underscores the importance of a complete examination in cases of scleritis, including a dilated fundus examination, to rule out an infectious retinochoroiditis in association with the scleritis.

PURPOSE:To correlate visual function with high-resolution images of retinal structure using adaptive optics scanning laser ophthalmoscopy (AOSLO) in 4 patients with acute zonal occult outer retinopathy (AZOOR). DESIGN:Observational case series. METHODS:Four women, aged 18 to 51, with acute focal loss of visual field or visual acuity, photopsia, and minimal funduscopic changes were studied with best-corrected visual acuity (BCVA), Goldmann kinetic and automated perimetry and fundus-guided microperimetry, full-field and multifocal electroretinography (ffERG and mfERG), spectral-domain optical coherence tomography (SD-OCT), and AOSLO imaging. Cone spacing was measured in 4 eyes and compared with 27 age-similar normal eyes. Additional functional testing in 1 patient suggested that cones were absent but rods remained. Serum from all patients was analyzed for anti-retinal antibody activity. RESULTS:In all patients vision loss was initially progressive, then stable. Symptoms were unilateral in 2 and bilateral but asymmetric in 2 patients. In each patient, loss of retinal function correlated with structural changes in the outer retina. AOSLO showed focal cone loss in most patients, although in 1 patient with central vision loss such change was absent. In another patient, structural and functional analyses suggested that cones had degenerated but rods remained. Anti-retinal antibody activity against a ∼45 kd antigen was detected in 1 of the patients; the other 3 patients showed no evidence of abnormal anti-retinal antibodies. CONCLUSIONS:Focal abnormalities of retinal structure correlated with vision loss in patients with AZOOR. High-resolution imaging can localize and demonstrate the extent of outer retinal abnormality in AZOOR patients.