Cancer-associated Retinopathy Developing After 10 Years of Complete Breast Cancer Remission

A 73-year-old female with a past medical history of breast cancer, who 10 years earlier experienced complete remission, complained of bilateral visual field disturbances and photopsia, 2 months prior. Tumour recurrence and metastatic lesions were not found during the medical examination, but antibodies against recoverin were detected in her serum. Despite immunosuppressive treatment with prednisolone and plasmapheresis, rapid and diffuse degeneration of the patient’s photoreceptors and deterioration of her visual field were observed. This is a rare case of cancer-associated retinopathy with a long interval (10 years) between the diagnosis of the malignancy and visual loss.     

Cancer-Associated Retinopathy: Update on Pathogenesis and Therapy

Paraneoplastic retinopathies comprise a diverse group of immune-mediated conditions affecting the eye. Cancer-associated retinopathy (CAR) typically has a sudden onset of severe visual loss and an ominous association with an occult malignancy. CAR is one of the best studied and better understood conditions in the multifarious group of autoimmune retinopathies. Recent developments have correlated the disease presentation, course, and therapeutic response to the underlying immune mediators and the inciting antigens. Signaling involving cytotoxic T-lymphocytes antigen 4 (CTLA-4) and vascular endothelial growth factor (VEGF) receptor-1 appears to play a role in the pathogenesis and may offer novel avenues for therapeutic intervention in CAR. Future developments in rapid identification and longitudinal quantification of antibody levels would enable individualized management in these patients. The goal of this review is to analyze the clinical features of diagnosis and management of retinopathy in the context of recent advances in the elucidation of CAR pathogenesis.     

Paraneoplastic retinopathies and optic neuropathies

Unusual neuro-ophthalmologic symptoms and signs that go unexplained should warrant a thorough investigation for paraneoplastic syndromes. Although these syndromes are rare, these clinical manifestations can herald an unsuspected, underlying malignancy that could be treated early and aggressively. This point underscores the importance of distinguishing and understanding the various, sometimes subtle, presentations of ocular paraneoplastic syndromes. Outlined in this review article are diagnostic features useful in differentiating cancer-associated retinopathy, melanoma-associated retinopathy, and paraneoplastic optic neuropathy. These must also be distinguished from non-cancer-related eye disorders that may clinically resemble cancer-associated retinopathy. The associated antibodies and histopathology of each syndrome are presented to help in the understanding of these autoimmune phenomena. Treatment outcomes from reported cases are summarized, and some potential novel immunotherapies are also discussed.     

Paraneoplastic retinopathy associated with occult bladder cancer

The aim was to report the first case of cancer-associated retinopathy (CAR) presenting before bladder cancer diagnosis. A 71-year-old woman with a history of bilateral vision loss underwent subsequent complete ophthalmic examination include a fluorescein angiography, full-field electroretinogram (ERG), serology including serum antibodies for CAR, and positron emission tomography-computed tomography (PET-CT) scan. The patient was diagnosed with bladder carcinoma revealed by PET-CT. Timely recognition of this entity may be crucial for an increased patient survival thus adult onset progressive photoreceptor dysfunction, confirmed by ERG, should alert to a possible remote effect of known or occult malignancy. In the latter, PET-CT may be exploited as a powerful diagnostic tool.     

Valsalva Retinopathy Associated With an Oratorical Contest

A 17-year-old man presented to us with a chief complaint of decreased visual acuity accompanied by central scotoma. There was nothing unusual in his medical history other than a recent oratorical contest. At the time of initial diagnosis, the corrected visual acuity was 20/20 in the right eye and 20/100 in the left eye. No significant findings were apparent on ophthalmic evaluation. On fundoscopy, there was a dumbbell-shaped macular bleed with a well-defined margin in the left eye. The clinical course was closely monitored along with drug therapy. Four weeks post presentation, the pre-retinal hemorrhage had nearly resolved. On fluorescein angiography, no significant findings were observed. In the left eye, the corrected visual acuity had improved to 20/25. Valsalva retinopathy is a pathology that occurs when a sudden increase in intra-thoracic pressure or abdominal pressure occurs in an otherwise healthy person. Here we report a case of Valsalva retinopathy occurring following an oratorical contest along with a review of the relevant literature.     

Cancer associated retinopathy (CAR): An autoimmune-mediated paraneoplastic syndrome

Cancer associated retinopathy (CAR) is an uncommon paraneoplastic retinopathy in which antibodies are directed against retinal antigens. Vision loss is associated with abnormal ERG findings. Few case reports and lack of controlled clinical trials make management of this syndrome especially challenging for the clinician. Herein, we describe the clinical, histopathologic and electrophysiologic features of CAR, along with a summary of previously employed management options. Cancer associated retinopathy syndrome has been recognized as a paraneoplastic disorder, most commonly associated with small cell lung cancer, in which cross-reacting autoantibodies against retinal antigen cause retinal dysfunction. Bilateral vision loss as a result of both rod and cone dysfunction in CAR may occur over a period of months, and visual symptoms may precede diagnosis of the systemic malignancy. The heterogeneity in antigens that have been identified as targets of antibody-mediated retinal damage perhaps help to explain the complexity of symptoms and the treatment challenges posed by patients with CAR.     

Radiation Retinopathy Associated with Central Retinal Vein Occlusion

Purpose: To report a case of radiation retinopathy associated with central retinal vein occlusion. Methods: The clinical features and fundus fluorescein angiography of this case were analyzed. Results: The patient had been treated with radiotherapy for her nasopharyngeal carcinoma, and presented with sudden visual loss in the left eye. The funduscopic examination and fluorescein angiography showed the features of radiation retinopathy in both eyes, and central retinal vein occlusion in the left eye. Conclusions: Radiation retinopathy can be associated with central retinal vein occlusion in the same eye, and it seems that the endothelial cell loss caused by radiation retinopathy may lead to retinal vein occlusion.     

Cancer-associated retinopathy (CAR) with electronegative ERG: a case report

Cancer-associated retinopathy (CAR) should be suspected in patients who present with visual symptoms such as rapid unexplained visual loss and seeing shimmering lights, with an abnormal ERG. Electronegative ERG responses are not exclusive to melanoma-associated retinopathy (MAR) but may be seen in CAR as well. We describe a patient with CAR who presented with an electronegative ERG. A 67-year old woman, who presented with complaints of seeing shimmering lights, underwent an extensive ophthalmological and electrophysiological examination. Best-corrected visual acuity was 7/10 in the right and 9/10 in the left eye. Goldmann visual fields showed relative central scotomata and concentric narrowing. Slit-lamp and fundus examination were normal as was fluorescein angiography. Rod-specific ERG responses were severely reduced, with electronegative maximal combined rod-cone responses and delayed cone-responses with normal amplitudes. Melanoma-associated retinopathy was suspected. Extensive dermatological and internal evaluation eventually revealed an oat-cell carcinoma in the right lung. The patient died of pneumonia 2 years after presentation.     

Paraneoplastic and non-paraneoplastic retinopathy and optic neuropathy: Evaluation and management

Paraneoplastic syndromes involving the visual system are a heterogeneous group of disorders occurring in the setting of systemic malignancy. Timely recognition of one of these entities can facilitate early detection and treatment of an unsuspected, underlying malignancy, sometimes months before it would have otherwise presented, and gives the patient an increased chance at survival. We outline the clinical features, pathogenesis, and treatment strategies for the retinal- and optic nerve–based paraneoplastic syndromes: cancer-associated retinopathy; melanoma-associated retinopathy; paraneoplastic vitelliform maculopathy; bilateral diffuse uveal melanocytic proliferation; paraneoplastic optic neuropathy; and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Distinguishing these disorders from their non-paraneoplastic counterparts (e.g., autoimmune-related retinopathy and optic neuropathy, and acute zonal occult outer retinopathy) and determining appropriate systemic evaluation for the responsible tumor can be challenging. In addition, we discuss the utility and interpretation of autoantibody testing.     

A Case of Autoimmune Retinopathy Associated with Thyroid Carcinoma

Purpose: To report a case of autoimmune retinopathy (AIR) associated with a thyroid carcinoma.

Design: Case report.

Method: A 51-year-old Caucasian woman presented with a rapid decline in vision. Initial visual field and immunohistochemical testing revealed autoimmune retinopathy without an apparent underlying malignancy. Conventional local and systemic immunosuppressive therapies failed to halt the progression.

Results: Rituximab treatments were initiated and a slowing of visual loss was seen. Continued surveillance for malignancy revealed a thyroid adenoma, and later a thyroidectomy revealed a thyroid carcinoma.

Conclusions: This report highlights the unique presentation of AIR associated with a thyroid carcinoma, the need for continued surveillance for malignancy in cases of AIR, and the possible new use of rituximab for the treatment of AIR.     

Photocoagulation Treatment of Proliferative Diabetic Retinopathy: Clinical Application of Diabetic Retinopathy Study (DRS) Findings,DRS Report Number 8

Additional follow-up confirms previous reports^1–4 from the Diabetic Retinopathy Study (DRS) that photocoagulation, as used in the study, reduces the risk of severe visual loss by 50% or more. Decreases of visual acuity of one or more lines and constriction of peripheral visual field due to treatment were also observed in some eyes. These harmful effects were more frequent and more severe following the DRS xenon technique.^3,4 The two-year risk of severe visual loss without treatment outweighs the risk of harmful treatment effects for two groups of eyes: (1) eyes with new vessels and preretinal or vitreous hemorrhage; and (2) eyes with new vessels on or within one disc diameter of the optic disc (NVD) equaling or exceeding 1/4 to 1/3 disc area in extent, (Fig 1), even in the absence of preretinal or vitreous hemorrhage. For eyes with these characteristics, prompt treatment is usually advisable. For eyes with less severe retinopathy, DRS findings do not provide a clear choice between prompt treatment or deferral unless progression to these more severe stages occurs.     

Vitrectomy for Proliferative Diabetic Retinopathy Associated with Vitreous Hemorrhage

This paper describes experience gained with 663 eyes of patients with diabetic vitreous hemorrhage treated by closed vitrectomy with a follow-up period of six months. Hemorrhages were nearly always associated with proliferative retinopathy (97%) and were thought to be caused always by ruptured proliferative vessels. Membrane removal was performed in 42% of all cases but in 60% when the retina was detached. The most common surgical complication was creation of retinal holes; more common when the posterior retina was detached (32%) than when it was attached (18%). The lens was removed in 73% of the cases. Eighty-two percent of the retained clear lenses remained clear at the six months follow-up period. Therefore, clear lenses should not be removed. Visual improvement could be achieved in 59% of the cases where the posterior retina was attached but only in 25% where it was detached resulting in an overall major visual improvement in 46% of the cases. If one adds to this group the cases that retained reasonable vision of 20/200 or better, the overall success rate was 51%. Posterior retinal detachment and rubeosis of the iris were the main factors for a bad prognosis. Forty-two percent of all eyes had at least some degree of rubeosis iridis. Most of the preoperative rubeotic eyes had rubeosis postoperatively (71%). Twenty-three percent of all eyes ended up with neovascular glaucoma.     

Characterization of a Case of Pigmentary Retinopathy in Sanfilippo Syndrome Type IIIA Associated with Compound Heterozygous Mutations in the SGSH Gene

Purpose: To report longitudinal phenotypic findings in a patient with Sanfilippo syndrome type IIIA, harboring SGSH mutations, one of which is novel.

Methods: Heparan-N-sulfatidase enzyme function testing in skin fibroblasts and white blood cells and SGSH gene sequencing were obtained. Clinical office examinations, examinations under anesthesia, electroretinogram, spectral domain optical coherence tomography (SD-OCT), and fundus photography were performed over a 5-year period.

Results: Fundus examination revealed a progressive breadcrumb-like pigmentary retinopathy with perifoveal pigmentary involvement. SD-OCT showed loss of normal neuroretinal lamination and cystic macular changes responsive to treatment with carbonic anhydrase inhibitors. Electroretinography exhibited complex characteristics indicative of a generalized retinal rod?>?cone dysfunction with significant ON?>?OFF postreceptoral response compromise. Sequencing revealed compound heterozygous mutations in the SGSH gene, the novel c.88G?>?C (p.A30P) change and a second, previously reported one (c.734G?>?A, p.R245H).

Conclusions: We have identified ocular features of a patient with Sanfilippo syndrome type IIIA harboring a novel SGHS mutation that were not previously known to occur in this disease – namely, a progressive retinopathy with distinctive features, cystic macular changes responsive to carbonic anhydrase inhibitors, and complex electroretinographic abnormalities consistent with postreceptoral dysfunction. SD-OCT imaging revealed retinal lamination changes consistent with previously reported histologic studies. Both the SD-OCT and the electroretinogram changes appear attributable to intraretinal deposition of heparan sulfate.     

Laser Photocoagulation for Central Serous Retinopathy Associated with Graft-Versus-Host Disease

Purpose: To describe the clinical characteristics and treatment of recurrent central serous retinopathy (CSR) following bone marrow transplantation (BMT). Methods: Between June 1998 and September 1999, 116 patients underwent allogeneic BMT at Hadassah Medical Center. Ocular complaints were expressed by 57.8% of these patients, who were examined and followed by the same ophthalmologist every 2–4 weeks. The ocular examination included Schirmer's test, slit-lamp examination, tonometry, and dilated funduscopy. If fundus abnormalities were noted, fluorescein angiography and indocyanine-green chorioangiography were performed. Results: Three patients presented with BMT-induced relapsing CSR. The severity of the CSR correlated well with the dosage of the systemic corticosteroids. These patients were eventually treated with laser photocoagulation, which, in all cases, resolved the CSR and improved visual acuity. During a 3-4 year follow-up period, no recurrence of CSR was documented despite continuous systemic corticosteroid treatment. Conclusions: In BMT patients, chronic corticosteroid treatment can cause a persistent/relapsing CSR. Since corticosteroids cannot be discontinued in such cases, photocoagulation should be considered at an early stage to prevent continuous ocular morbidity.     

The North Jutland County Diabetic Retinopathy Study (NCDRS)

Purpose: This study set out to map the associations between retinal lesions, visual acuity (VA) and the presence of clinically significant macular oedema (CSMO) in diabetes subjects. Methods: This cross‐sectional study comprised 656 type 1 and 328 type 2 diabetes subjects undergoing retinopathy screening in the County of North Jutland, Denmark. Numbers of specific retinal lesions were quantified from retinal photographic recordings. Associations between CSMO, number of specific retinal lesions and VA were established. The percentages of eyes with CSMO ascribed to retinal lesions were calculated. Results: The presence of CSMO, number of specific retinal lesions and VA were all significantly associated. The parameter with the highest statistical association with CSMO measured by Spearman’s correlation coefficient was hard exudates (type 1: 0.524; type 2: 0.715), followed by microaneurysms (type 1: 0.298; type 2: 0.508), retinal haemorrhages (type 1: 0.227; type 2: 0.595), cottonwool spots (type 1: 0.207; type 2: 0.259) and VA (type 1: ? 0.137; type 2: ? 0,175). Conclusions: All retinal lesions are significantly associated with CSMO and together can predict for up to 42.3% (in type 1 diabetes) and 64.3% (in type 2 diabetes) of CSMO cases.