Combined central retinal artery and vein occlusion in a child with systemic non-Hodgkin's lymphoma

Purpose: To report on a case of systemic non-Hodgkin's lymphoma and unilateral combined central retinal artery and vein occlusion. Method: We examined a 14-year-old boy who experienced a sudden unilateral visual loss five months after the initial diagnosis of systemic non-Hodgkin's lymphoma. Result: Visual loss was due to combined central retinal artery and vein occlusion in association with tumoral optic nerve involvement. Conclusion: Alhough very rare systemic non-Hodgkin's lymphoma may present with central retinal artery and vein occlusion prior to overt central nervous system involvement. This revised version was published online in July 2006 with corrections to the Cover Date.     

Ocular involvement in Castleman's disease. Response to radiotherapy

A 21-year-old man with known Castleman's disease, a lymphoproliferative disorder with both local and systemic manifestations, presented with decreased vision in the left eye and chromatopsia. He had infiltration of the left disc and choroid with elevation of the retina, multiple bilateral depigmented areas at the level of the choroid or retinal pigment epithelium (RPE) (also thought to represent infiltrates), and left exophthalmos. A serious retinal detachment (RD) evolved, but then responded to radiotherapy, with recovery of good vision. Occult leptomeningeal involvement resolved during a period of observation. There was no systemic evidence of malignant lymphoma.     

Systemic non-Hodgkin's lymphoma simulating primary intraocular lymphoma

PURPOSE: To describe a case of an unusual presentation of systemic non-Hodgkin's lymphoma with clinical and histopathologic findings closely resembling that of primary intraocular lymphoma. DESIGN: Observational case report. METHODS: A 58-year-old woman with a history of treated systemic non-Hodgkin's lymphoma presented 2 years later with a subretinal lesion and intraocular inflammation in her left eye. RESULTS: Diagnostic enucleation and histopathologic studies revealed findings consistent with primary intraocular lymphoma including intraretinal, subretinal, and subretinal pigment epithelial tumor cells without involvement of the choroid. CONCLUSIONS: We conclude that systemic non-Hodgkin's lymphoma can present remotely with findings resembling primary intraocular lymphoma and should be included in the differential diagnosis of intraocular inflammation and subretinal infiltrates.     

Retinal manifestations of ocular lymphoma (reticulum cell sarcoma).

BACKGROUND: Diagnosis and treatment of ocular large cell lymphoma may lessen visual loss and prolong life. Although reports in the literature have described retinal infiltrates in eyes with large cell lymphoma, they have focused on the more prominent vitreous and subretinal pigment epithelial findings. Eyes with retinal infiltrates and hemorrhagic retinal necrosis are usually believed to harbor a microbial infection. The authors describe 5 patients, aged 57 to 85 years, with ocular lymphoma in whom the most prominent initial findings were in the retina. METHOD: Patients presented with findings suggestive of an infectious retinal necrosis. When the initial therapy failed, investigators performed a vitreous biopsy. Two patients had a concomitant retinal biopsy. Radiation therapy was given to four patients. RESULTS: All five patients had vitreous cells. Three patients had prominent perivascular exudate. Four patients had grayish-white retinal infiltrates, and three patients had associated retinal hemorrhage. Three patients had subretinal small white spots. An edematous thickened retina developed in three patients, and hemorrhagic retinal necrosis developed in three patients. The initial diagnosis was believed to be acute retinal necrosis (ARN) in three patients, toxoplasmosis in one patient, and frosted branch angiitis in one patient. Vitreous biopsy was positive in two patients but negative in three patients. In two of these three patients, the diagnosis was established by retinal biopsy. CONCLUSION: Ocular lymphoma should be considered in the differential diagnosis of retinal vasculitis or necrotizing retinitis in a middle-aged or older patient. Retinal biopsy may be helpful in establishing the diagnosis.     

Systemic non-Hodgkin's lymphoma with optic nerve infiltration in a patient with AIDS

PURPOSE: To report the clinicopathologic features of a patient with AIDS and clinically regressed systemic non-Hodgkin's lymphoma who subsequently developed lymphomatous infiltration of the optic nerve and occlusion of the central retinal vein in both eyes. METHODS: The eyes of this patient were examined ophthalmologically and by fluorescein angiography. The eyes, brain, and body were obtained after death and studied by light microscopy. RESULTS: Ophthalmic examination and fluorescein angiography revealed optic nerve swelling and central retinal vein occlusion first in the left eye and shortly thereafter in the right eye. Postmortem histopathologic examination showed dense infiltration of both optic nerves by lymphoma as well as necrotizing vasculitis involving the retinal vessels near the left optic nerve head. Examination of the brain revealed lymphomatous involvement in the paraventricular region with associated necrosis and inflammation. No bone marrow recurrence or other residual systemic lymphoma was present. CONCLUSION: This case demonstrates that infiltrative optic neuropathy may occur as the sole ocular manifestation of disease recurrence in a patient with systemic non-Hodgkin's lymphoma otherwise thought to be in clinical remission.     

Bilateral ischemic optic neuropathy and retinal vascular occlusions associated with lymphoma and sepsis. Clinicopathologic correlation

The authors report the clinicopathologic correlation of a patient with non-Hodgkin's mixed-cell lymphoma who had impairment of the circulation of the optic nerve and retina in both eyes. The results of histopathologic examination showed that the pial septa of the optic nerves were infiltrated by lymphoma and that there was extensive infarction of the orbital portions of both optic nerves and occlusion of both central retinal arteries and the right central retinal vein by thrombi with bacteria. The infiltration of the optic nerves seemed to be resistant to therapy.     

Anterior chamber infiltrates associated with systemic lymphoma: report of two cases and review of the literature

PURPOSE: To describe the clinicopathologic features of two patients with systemic lymphoma who developed anterior chamber (AC) infiltrates of lymphoma cells. DESIGN: Two case reports and literature review. METHODS: The clinical and pathologic findings in two patients with AC infiltrates secondary to systemic B-cell lymphoma are reviewed. MAIN OUTCOME MEASUREMENTS: Clinical observation and cytologic/flow cytometric examination of the infiltrate after AC aspiration. RESULTS: One patient presented with uveal infiltration, an exudative retinal detachment and an AC infiltrate. Systemic evaluation revealed a follicular lymphoma involving several groups of lymph nodes. The second patient with a known history of abdominal lymphoma was found to have blurred vision, photophobia and an AC infiltrate. Flow cytometric analysis of the AC infiltrate in both patients showed phenotypes consistent with the patients' systemic lymphomas. CONCLUSIONS: A pseudohypopyon in an adult may represent either the initial manifestation or a later complication of systemic lymphoma, similar to what has been reported in acute leukemia.     

Systemic non-Hodgkin's lymphoma masquerading as Vogt-Koyanagi-Harada disease in an HIV-positive patient

A 29-year-old man presented with decreased visual acuity in both eyes secondary to exudative retinal detachment resembling Vogt-Koyanagi-Harada disease. Although fluorescein angiographic pictures supported the clinical findings, there was no choroidal thickening evident with ultrasonography. In 3 days he developed increased disc oedema with peripapillary haemorrhages in both eyes. Further evaluation revealed HIV-positive status and a systemic non-Hodgkin's lymphoma. The patient responded favourably to the treatment for systemic non-Hodgkin's lymphoma confirming our diagnosis of intraocular metastasis. In bilateral exudative detachment, an absence of choroidal thickening on ultrasonography and the presence of peripapillary haemorrhages should prompt a systemic evaluation for causes other than Vogt-Koyanagi-Harada disease, especially in HIV-positive patients.     

Extranodal B-cell lymphoma of the uvea: a case report

CASE REPORT: Ocular involvement by non-Hodgkin's lymphoma is a rare condition that can result from a primary intraocular lymphoma of the retina or an intraocular manifestation of systemic lymphoma. Uveal involvement is seldom the initial manifestation of extranodal lymphoma. We describe an 80-year-old patient with a blind and painful left eye and a history of recurrent uveitis. After ultrasound evaluation, the eye was enucleated and histopathologic examination revealed a malignant B-cell lymphoma of the uveal tract. The patient has been followed for 8 years after surgery, but she has had no further systemic manifestations of lymphoma and has not required subsequent treatment. COMMENTS: Primary extranodal lymphoma can be easily mistaken for recurrent uveitis or primary intraocular lymphoma of the retina and central nervous system; it is a differential diagnosis to be considered in cases of recurrent uveitis-like symptoms evolving to blind painful eye.     

A point prevalence study of 150 patients with idiopathic retinal vasculitis: 1. Diagnostic value of ophthalmological features.

This paper describes the ophthalmological features of 150 patients with idiopathic retinal vasculitis, 67 of whom had isolated retinal vasculitis (RV) and 83 had RV associated with systemic inflammatory disease (RV + SID). The diagnosis of retinal vasculitis was made by ophthalmoscopy and fluorescein angiography, and patients with any identifiable cause (infection, ischaemia, or malignancy) were excluded from the study. Patients with isolated RV tended to have peripheral vascular sheathing, macular oedema, and diffuse capillary leakage. Those with RV accompanying Behçet''s disease often had branch vein retinal occlusions and retinal infiltrates together with macular oedema and diffuse capillary leakage; the retinal infiltrates were pathognomonic for Behçet''s disease. In sarcoidosis the retina typically showed features of periphlebitis associated with focal vascular leakage. Patients with uveomeningitis, multiple sclerosis, arthritis, or systemic vasculitis showed diffuse retinal capillary leakage associated with a mixture of the other features. Poor visual function was particularly associated with macular oedema and branch vein retinal occlusion, while the retina appeared to ''withstand'' the impact of vascular sheathing, periphlebitis, or neovascularisation alone. Within the limitations of a point prevalence study it was concluded that different patterns of retinal vasculitis occur in different systemic inflammatory diseases, and that in isolated retinal vasculitis there is a particular association between peripheral vascular sheathing, macular oedema, and diffuse capillary leakage. In Part 2 we describe the results of examining the sera of these patients for the presence of antiretinal antibodies and circulating immune complexes.     

Oculocerebral malignant non-Hodgkin lymphoma. A report of 5 cases

Five patients, age 35 to 77, with histologically proven malignent ocular non-Hodgkin's lymphoma (previously known as reticulum cell sarkoma) are presented. The clinical ocular findings (vitreous infiltrates, retinal infiltrates, anterior uveitis) were initially misinterpreted as "panuveitis". The usual antiinflammatory therapie a temporary diminution of the "uveitis" could be observed. Four cases showed a histologically proven CNS involvement. All the patients (except the one in whom the correct diagnosis was made post mortem) received cerebral radiation therapie, including the eyes. Under the radiation therapy the ocular findings disappeared within a few weeks. The longtime prognosis for the eye and quoad vitam is unfortunately not promissing.     

Clinical and pathologic characteristics of malignant lymphoma of the retina

Two cases of malignant non-Hodgkin lymphoma of the retina and choroid with cerebral involvement are reported. In both cases, early infiltrates appear to have originated in the capillary layer of the choroid. Subsequently, Bruch's membrane was penetrated and tumorous infiltrates were found beneath the retinal pigment epithelium. The resulting reactions created a distinctive ophthalmoscopic picture, for which the term "leopardskin pattern" was coined. It may be helpful in early diagnosis, which with suitable therapy can prolong life.     

Non-Hodgkin's lymphoma causing fundus picture simulating fundus flavimaculatus

Two apparently healthy patients experienced visual loss and had a peculiar flecked retina simulating fundus flavimaculatus in one eye some months before developing signs and symptoms of the systemic form of non-Hodgkin's large-cell lymphoma. Both experienced spontaneous improvement in visual symptoms and partial resolution of the fundus changes.     

High-grade malignant B-cell lymphoma of the retina in a patient with concomitant gastric MALT lymphoma

Purpose To report the unexpected finding of a primary retinal B-cell lymphoma in a patient with previous breast carcinoma and subsequent lymphoma of the stomach. Methods Histopathologic and immunohistochemical findings in the enucleated eye are described in conjunction with clinical features and investigations. Results An 80-year-old woman with previous breast cancer presented with moderate loss of vision associated with vitreous opacities, circumpapillary retinal haemorrhages, and attenuated retinal vessels in her left eye. Treatment with systemic steroids and oral immunosuppressive drugs was initiated on suspicion of carcinoma-associated retinopathy. Two years later, the patient was diagnosed with MALT lymphoma of the stomach. Unfortunately, the ocular symptoms did not improve, and the patient developed neovascular glaucoma, for which the eye was eventually enucleated. Histopathology and immunohistochemistry as well as a molecular analysis revealed a primary B-cell lymphoma of the retina. Conclusion Non-Hodgkin B-cell lymphoma of the retina should be considered as a differential diagnosis in cases of non-specific retinopathies even in the presence of other primary neoplastic co-morbidities.     

Cytomegalovirus retinitis in a patient with non-Hodgkin's lymphoma: a diagnostic dilemma

PURPOSE: Patients with lymphoma can rarely develop cytomegalovirus (CMV) retinitis. Clinically it is difficult to distinguish from intraocular lymphoma. Also, in such cases the CD4+ count may be high. The authors report a rare case of bilateral CMV retinitis in a patient with non-Hodgkin's lymphoma with high CD4+ counts. METHODS: Observational case report with review of literature. RESULTS: CMV retinitis was clinically suspected due to the presence of large areas of retinal necrosis and hemorrhages in one eye and a demarcation line with white mottled retina in the other eye. Other differential diagnoses considered were intraocular lymphomatous infiltration and acute retinal necrosis due to herpes group of viruses. The diagnosis of CMV retinitis was confirmed by polymerase chain reaction performed on vitreous sample. CONCLUSIONS: CMV retinitis can develop in cases of lymphoma despite high CD4+ counts. An early diagnosis can be established by performing PCR on vitreous biopsy.     

Variations in the Presentation of Primary Intraocular Lymphoma: Case Reports and a Review

Primary intraocular lymphoma is a distinct subset of primary non-Hodgkin's lymphoma of the central nervous system (CNS). Diagnosis can be difficult and is often delayed, as the clinical presentation can mimic a number of other ocular conditions. This report describes four different presentations of intraocular lymphoma and focuses on its modes of clinical presentation. Primary intraocular lymphoma can present with a wide variety of manifestations frequently mimicking diffuse uveitis that is refractory to corticosteroids. Subretinal pigment epithelium tumors may be seen. However, other presentations may include multiple deep white dots in the retina secondary to tumor infiltration; retinal infiltration, causing a necrotizing retinitis; or infiltration of the retinal vasculature, causing arterial or venous obstruction. Finally, optic nerve invasion may be seen. CNS lymphoma develops in the majority of patients before, in conjunction with, or after the development of eye disease. Intraocular lymphoma often has a fatal outcome, but recognition of its modes of presentation facilitates early diagnosis and treatment that may improve prognosis.     

Ocular masquerade syndrome due to intraocular lymphoma--two forms of retinal pigment epithelium involvement: case reports

Ocular masquerade syndrome was diagnosted in two patients with chronic uveitis. The patients presented non-Hodgkin's lymphoma as the final diagnosis two forms of intraocular retinal pigment epithelium involvement was seen. One case was flecks of the retinal pigment epithelium and another case was a solid retinal pigment epithelium detachment. These unusual presentations of non-Hodgkin's lymphoma is an alert to all involved in lymphoma care.     

Diagnosis of systemic metastatic retinal lymphoma

Purpose: Systemic metastatic retinal lymphoma (SMRL) is exceptionally rare, as systemic lymphomas most often metastasize to the uvea. We have evaluated a series of SMRL cases to elucidate the clinical and pathological features of SMRL. Methods: The pathological specimens of intraocular lymphomas (IOLs) at the National Eye Institute from 1991 to 2009 were retrospectively reviewed. These cases were diagnosed by cytology, cytokine measurement (ELISA for interleukin (IL)‐10 and IL‐6 levels) and Immunoglobulin‐Heavy (IgH) and T‐cell‐receptor (TCR) gene analyses. Results: There were nine B‐cell SMRLs (B‐SMRL) among 96 B‐cell retinal lymphomas (9.4%) and three T‐cell SMRLs (T‐SMRL) among five T‐cell retinal lymphomas (60%) from a total of 116 IOLs, in which 101 were retinal lymphoma. The original sites were nasopharynx (3), testis (2), skin (2), breast (1), blood (1), retroperitoneum (1), ileo‐caecum (1) and stomach (1). Cytology of vitreous samples illustrated atypical lymphoma cells with either B‐ or T‐monoclonality. More B‐SMRLs had a high ratio of vitreal IL‐10 to IL‐6 than T‐SMRLs. Molecular pathology demonstrated lymphoma cells with gene rearrangements of IgH in all B‐SMRLs and TCR in all T‐SMRLs. Conclusions: SMRL and primary retinal lymphoma present with similar clinical manifestations. Systemic T‐cell lymphoma invades the retina and vitreous more aggressively than systemic B‐cell lymphoma. A diagnosis of SMRL is made when there is a clinical history of systemic lymphoma (particularly from nasopharynx, testis and skin), and lymphoma cells are identified in the vitreous or retina. Molecular analysis is more useful than vitreal cytokine measurement for SMRL diagnosis.     

Indocyanine green angiographic features of systemic non-Hodgkin's lymphoma and bilateral choroidal involvement.

A 35-year-old man with systemic non-Hodgkin's lymphoma and bilateral choroidal involvement is described. Indocyanine green angiography depicts choroidal involvement much better than fluorescein angiography and seems to be superior in diagnosing and monitoring patients with systemic non-Hodgkin's lymphoma and choroidal involvement.     

Combined central retinal artery and vein occlusion secondary to systemic non-Hodgkin's lymphoma

We report a rare case of low-grade systemic B-cell non-Hodgkin's lymphoma (NHL) causing central retinal artery and vein occlusion, which was the only manifestation of disease recurrence. A young man with resolved systemic NHL underwent fluorescein angiography, magnetic resonance imaging and computed tomography to investigate a severe unilateral visual loss. A combined vascular occlusion was observed in the right eye. Neuroimaging detected optic nerve infiltration; but no systemic/ central nervous system involvement was observed. The patient was treated with high-doses of corticosteroids and optic nerve irradiation. The optic neuropathy and vascular occlusion were resistant to treatment. The subsequent neovascular glaucoma was treated by panretinal photocoagulation, which relieved the pain, but vision was not recovered. No further recurrence was observed over the following year.