Intraocular-central nervous system lymphoma: clinical features, diagnosis, and outcomes.

OBJECTIVE: To analyze the clinical features, laboratory investigations, and diagnosis of intraocular-central nervous system (CNS) lymphoma in a cohort of patients who underwent diagnostic vitrectomy. DESIGN: Retrospective case series. METHOD AND STUDY MATERIALS: Thirty-four vitreous biopsy specimens obtained from 26 patients with treatment-resistant or unusual uveitis were re-evaluated in a masked fashion. The specimens were classified into three groups: "negative," "suspicious of malignancy," and "positive" based on the cytologic features, immunomarkers, and flow cytometry. The medical records of the patients were reviewed retrospectively. MAIN OUTCOME MEASURES: The reliability of vitreous cytology in diagnosing intraocular-CNS lymphoma and the differences in clinical features of patients with intraocular-CNS lymphoma and uveitis. RESULTS: The two ocular pathologists concurred in their criteria for interpretation of all specimens. There was 100% concordance between the cytologic reports read independently by the two ocular pathologists over the 5-year period and the read-out done in a masked fashion at the time of the study. Ten patients were diagnosed with intraocular-CNS lymphoma based on the vitreous cytology and clinical features. The time interval between the initial presentation and vitreous biopsy was 1 week to 2 years, with 80% of the patients diagnosed within the first year. Retinal involvement in the form of lymphomatous subretinal pigment epithelial infiltrates, vasculitis, and apparent retinochoroiditis was present in six cases. Initial neuroimaging studies revealed concomitant CNS involvement in three patients, and an additional three developed CNS lymphoma following diagnosis by vitreous biopsy. Patients were treated with radiotherapy, chemotherapy, or both. Two of the four patients with a follow-up of greater than 12 months died due to CNS involvement. CONCLUSIONS: Vitreous cytology is a sensitive, reliable, and reproducible method of diagnosing intraocular-CNS lymphoma. A high index of suspicion based on the clinical findings and course of the uveitis is critically important in decision-making for diagnostic vitrectomy. Central nervous system involvement is frequent and associated with a high mortality rate. Ophthalmology 1999;106:1805-1810     

Case of spontaneous regression of intraocular lymphoma demonstrated by subretinal biopsy

PURPOSE: To report a case of intraocular lymphoma suspected of spontaneous regression based on ocular fundus findings, subretinal biopsy, and observation of clinical course. CASE: A 64-year-old woman presented at our clinic with multiple yellowish-white patchy lesions in the left fundus and focal atrophy of the retinal pigment epithelium in the right fundus. No inflammatory infiltrates were observed in either eye. Intraocular lymphoma was suspected based on the clinical manifestations including fluorescein angiography and optical coherence tomography. Vitrectomy and subretinal biopsy were subsequently performed for diagnostic purposes. Histological examination showed that the subretinal lesion was composed mostly of necrotic tissue derived from the lymphoid corpuscle and that there was no cellular component except the retinal pigment epithelium. Interleukin-10 in the vitreous humor was low at 9 pg/ml. No serious postoperative complications were observed after surgery and the residual retinal lesions gradually regressed spontaneously. Laboratory data and whole body evaluation including the central nervous system (CNS) showed no remarkable findings for 1 year after surgery. CONCLUSIONS: It is suggested that the present case was an intraocular lymphoma which regressed spontaneously. However, careful follow-up including the possible occurrence of CNS lesions is required in such cases.     

Massive hemorrhage complicating age-related macular degeneration. Clinicopathologic correlation and role of anticoagulants

Reported are 15 cases of age-related macular degeneration (AMD) complicated by massive subretinal and/or vitreous hemorrhage. Clinicopathologic correlation is presented in four of the seven cases studied histopathologically. Salient histologic findings include: subretinal and subretinal pigment epithelium (sub-RPE) fibrovascular scar in the posterior pole; discontinuities in Bruch's membrane with choroidal neovascularization; extensive hemorrhagic detachment of the RPE and sensory retina; and vitreous hemorrhage. In three cases, a choroidal artery, emerging from breaks in Bruch's membrane, had ruptured walls. The authors have reviewed the previously reported cases of AMD complicated by massive hemorrhage and found that 19% of the patients were taking Coumadin (warfarin) or aspirin treatment when the bleeding occurred. Forty percent had a positive history of systemic hypertension and cardiovascular diseases. Although the occurrence of hypertension is expected in the aged population with AMD, use of anticoagulants or antithrombotics by such patients may predispose them to serious ocular hemorrhagic complications.     

Diagnostic vitreous biopsy in patients with uveitis: a useful investigation?

PURPOSE: To assess whether the results of microbial and cytological investigations of vitreous biopsy specimens are useful in the management of patients with intraocular inflammation. METHOD: A retrospective review of the medical records of 59 consecutive patients from consulting rooms, outpatient clinics and inpatient consultation who underwent intravitreal sampling between January 1997 and December 2003. Results of the biopsies were examined to determine if they altered management of the patient. RESULTS: The clinical diagnosis was correct in 37 of 59 patients (62.7%) with ocular inflammation. The organism was identified in 50% (7/14) of vitreous biopsies in patients with postoperative endophthalmitis. Of patients with endogenous bacterial endophthalmitis 16.7% (1/6) had the diagnosis confirmed by vitreous tap and 83.3% (5/6) had positive cultures from other sites that provided the diagnosis. Of the fungal endophthalmitis 80% (4/5) grew the fungus from the vitreous biopsy. Viral polymerase chain reaction identified the causative organism in 87.5% (7/8) of patients with clinical diagnosis of viral infection. 30.8% (4/13) vitreous biopsies in patients with clinically suspected masquerade syndromes were diagnosed as lymphoma. Vitreous biopsy results altered management significantly in seven (11.9%) patients. These patients included toxoplasmosis that was thought to be viral retinitis; malignant melanoma thought to be fungal endophthalmitis; chronic inflammation secondary to retinal detachment that was thought to be a neoplasm; three patients with infective endophthalmitis thought to be idiopathic uveitis and a patient with known lung carcinoma thought to have metastases who had lymphoma. In 67.8% (40/59) the vitreous sample helped to either confirm the diagnosis or exclude an infective cause. Complications from vitrectomy were hypotony (1/29) and retinal detachment (1/29). CONCLUSION: Clinical diagnosis based on examination findings and vitreous biopsy is highly accurate. Vitreous sampling altered the management of seven of 59 patients. Vitreous biopsy is a safe and useful method for diagnosing and excluding malignancy and infection in patients with ocular inflammation. Viral polymerase chain reaction is highly sensitive and accurate. The sensitivity of microbiological culture techniques for bacteria and fungi limits their usefulness.     

Endogenous bacterial retinitis in AIDS

We studied two patients, one with histologically confirmed endogenous bacterial retinitis associated with the acquired immunodeficiency syndrome and a second with ophthalmoscopically identical findings who also responded to antibiotic treatment. Both patients had focal, discrete patches of retinitis that enlarged slowly over weeks and ultimately accumulated large amounts of subretinal fluid and retinal exudate. One patient underwent retinal biopsy after systemic and vitreous cultures were negative. Histopathologic sections showed necrotic retina infiltrated with multiple histiocytes containing intracytoplasmic, iodine-positive, pleomorphic, encapsulated bacterial forms. The organism was not grown from the retinal biopsy specimen. Treatment with antibiotics resulted in improved vision in both patients. Our results indicate that endogenous bacterial infection should be considered in the differential diagnosis of retinitis associated with the acquired immunodeficiency syndrome.     

Flecked retina in systemic large-cell non-Hodgkin's lymphoma: case report

We report on a patient with a past medical history of successfully treated systemic large-cell non-Hodgkin's lymphoma (SNHL), who presented with multifocal yellowish retinal infiltrates (flecked retina) involving the post-equatorial retina of one eye. Fluorescein angiography revealed that the retinal infiltrates were hypofluorescent throughout the examination. The correct diagnosis of this ocular picture was important because the retinal lesions indicated central nervous system recurrence of systemic large-cell non-Hodgkin's lymphoma.     

Rare manifestation of familial vitreous amyloidosis caused by Gly103Arg transthyretin

AIM: To identify and analyze the genotype of the patients with special ocular manifestations of familial vitreous amyloidosis (FVA) in a Chinese Han family. METHODS: Pars plana vitrectomy (PPV) surgery was performed on a 52-year-old Chinese woman presented with vitreous amyloidosis and progressive visual impairment, without evidence of cardiac, renal, gastrointestinal, central nervous system or peripheral nervous system dysfunction. During the surgery, the patient presented with a gray-white dense and thick cotton wool-like change in the vitreous body, accompanied by complete retinal detachment. Additionally, hard, free and movable yellow-white deposits were observed in the posterior pole and surrounding retina, the vitreous and subretinal deposits were examined by Congo red staining and immunohistochemical pathological examination, and whole exome sequencing was performed on blood samples from the patient and her cousin. RESULTS: During the operation, it was discovered that there was a complete detachment of the retina and a significant amount of hard, free-floating yellow-white deposits were observed beneath the posterior pole and surrounding retina. This is an exceedingly rare ocular manifestation. Pathological examination of the vitreous and subretinal deposit specimens revealed positive Congo red staining, as well as elevated vascular endothelial growth factor (VEGF) expression in vascular endothelial cells within the sediment specimens upon immunohistochemical examination. The patient and her cousin both exhibited a heterozygous mutation in Glyl03Arg within the transthyretin (TTR) gene, resulting in a substitution of glycine (Gly) at position 103 with arginine (Arg). CONCLUSION: FVA may present with various ocular manifestations, but panretinal detachment is a rare occurrence. In cases where retinal detachment persists for an extended period of time, amyloid deposits may form under the retina through retinal tears, leading to subretinal deposits that can impede retinal reattachment and negatively impact visual prognosis. Elevated levels of VEGF in the eyes of FVA patients may indicate an overexpression state, necessitating careful postoperative follow-up. The heterozygous mutation Gly103Arg may represent a unique pathogenic site in Chinese individuals.     

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.     

Intraocular T-cell Lymphoma: Clinical Presentation,Diagnosis, Treatment,and Outcome

Purpose: To report on the clinical data of seven patients with T-cell intraocular lymphoma (IOL).Methods: Retrospective case series.Results: Seven immunocompetent patients, 12 eyes, 6 women, with T-cell-IOL were included from five countries. Mean age was 53.5 years (range: 25–82). Four patients had systemic-ocular lymphoma, two had CNS-ocular lymphoma, and one had systemic-CNS- ocular lymphoma. Vitritis was the most frequent clinical sign, followed by anterior uveitis and serous retinal detachment. Cytopathologic examination was performed on all ocular specimens (vitreous in six and iris mass biopsy in one patient). Adjunctive diagnostic procedures included immunohistochemistry, molecular tests, and cytokine profiling of vitreous samples. Treatment modalities included systemic chemotherapy (five patients), intravitreal methotrexate (three patients), globe radiotherapy, and intrathecal chemotherapy. Mean survival from diagnosis was 21.7 months (range: 2–69). Two patients are still alive.Conclusions: T-cell IOL has variable clinical manifestations and prognosis. Systemic involvement, SRD, and vitreoretinal involvement were frequently observed.     

Case of retinochoroiditis associated with porcine ascarids diagnosed by antibodies in subretinal fluid

PURPOSE: To determine the cause of retinochorioditis in a patient with a granulomatous retinal exudate and an exudative retinal detachment. CASE: A 45-year-old man presented at another hospital with increased visual disturbances of the left eye. He was diagnosed with uveitis, and treated with topical steroids for 1 month. However, the uveitis worsened, and he was referred to our hospital. Ophthalmoscopy showed a yellowish-white granulomatous exudate, and an exudative retinal detachment in the lower peripheral retina. The retinal detachment worsened and affected the macula. Pars plana vitrectomy was performed, and the retina was reattached. During the surgery, ocular samples were collected for further examinations. The titers of antibodies against 12 kinds of ascaridis were examined, and elevated titers of specific antibodies against porcine ascarids were detected in the subretinal fluid, but not in the aqueous humor, vitreous, or serum. CONCLUSIONS: Vitrectomy with the collection of ocular samples, especially subretinal fluid, was a key procedure in the diagnosis and treatment of retinochoroiditis associated with the porcine ascarids.     

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.     

Polymerase chain reaction for the detection of the varicella-zoster genome in ocular samples from patients with acute retinal necrosis.

We used the polymerase chain reaction to detect the virus genome in ocular samples from patients with clinically diagnosed acute retinal necrosis. Four samples from four patients with acute retinal necrosis, and five samples from three patients with other ocular diseases (sarcoidosis, rhegmatogenous retinal detachment, and epiretinal membrane of unknown origin) were evaluated. The samples consisted of aqueous humor, vitreous, or subretinal fluid. Primers were specific for varicella-zoster virus, herpes simplex virus, or cytomegalovirus. The varicella-zoster virus genome was detected in three of the four samples from patients with acute retinal necrosis. Among these three positive samples, two had PstI-site-less point mutation, strains that have been described only in Japan and of low prevalence. Samples from patients with diagnoses other than acute retinal necrosis yielded negative results when varicella-zoster virus primer was used. No sample was positive for herpes simplex virus or cytomegalovirus primers.     

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.     

Effects and distribution of intravitreally or subretinally injected silicone oil identified in rabbit retina using osmium tetroxide method.

Silicone oil was injected into the eyes of 28 rabbits. Utilizing the specific affinity of osmium tetroxide for lipids, the pathological features and histochemical localization of silicone oil within the retina were studied. This osmium tetroxide technique makes it possible to identify the presence of silicone oil particles in the ocular tissues. It was demonstrated that in eyes with silicone oil injected into the vitreous cavity or subretinal space, silicone oil was detected in the inner retinal layer and in phagocytes in the vitreous cavity but not in the outer retinal layer, retinal pigment epithelium and choroid. In addition, prominent subretinal and epiretinal proliferation with abundant phagocytes containing silicone oil particles were noted in the eyes with subretinal injection of silicone oil through an artificial retinal break. This study suggests that when injected subretinally silicone oil induces excessive subretinal and epiretinal proliferation.     

Vasoproliferative tumours of the retina

BACKGROUND: Vasoproliferative tumours of the retina (VPTR) are benign tumours of unknown origin, occurring mostly in otherwise healthy patients. VPTR may be associated with other chorioretinal diseases, such as uveitis. The tumours, which histologically represent reactive gliovascular proliferations, are characterised by a pink to yellow appearance on funduscopy and are accompanied by exudative and haemorrhagic changes of the retina. METHODS: 22 cases of VPTR in 21 patients were examined with a follow up period between 1 month and 6 years. Ophthalmological changes associated with VPTR were intraretinal and subretinal exudations (n=18), exudative detachments of the surrounding sensory retina (n=13), intraretinal and subretinal haemorrhages (n=10), exudative changes within the macula (n=10), hyperpigmentation of the retinal pigment epithelium at the border of the exudative retinal changes (n=9), and vitreous haemorrhages (n=4). Tumour biopsy was performed in two cases. Treatment consisted of plaque radiotherapy (n=14), plaque radiotherapy and cryotherapy (two), cryotherapy only (two), observation (three), and enucleation in one case of a blind and painful eye. RESULTS: Regression of the tumour and the associated exudative changes could be observed in all treated cases. Visual acuity at last follow up improved two lines or more in two cases, remained within two lines of the initial visual acuity in 15 cases, and worsened in the remaining five. Histopathological examination of the biopsy specimens and the tumour of the enucleated eye showed massive capillary proliferation with perivascular spindle-shaped glial cells of retinal origin. CONCLUSION: The correct diagnosis of VPTR is of importance as these lesions may lead to visual loss. Further, VPTR must be differentiated from angiomas associated with von Hippel-Lindau disease as well as from ocular and systemic malignancies. Regression of tumour thickness and associated retinal changes can be achieved with brachytherapy or cryotherapy.     

Serous retinal detachment in a patient with aplastic anemia associated with parvovirus B19 infection

Background We report a case of unilateral serous retinal detachment (RD) associated with parvovirus B19 infection. Case report A 28-year-old woman had a clinical history of autoimmune hemolytic anemia and pure red cell aplasia associated with parvovirus B19 infection. She demonstrated focal serous RD without retinal exudates. A focal cataract and anterior vitreous cells were also observed. Fluorescein angiography (FA) revealed accumulation of subretinal fluid, but no vascular leakage. After vitrectomy, the retina was re-attached and visual acuity returned to 20/20. IgM antibody to parvovirus and viral DNA were detected by polymerase chain reaction in the vitreous fluid obtained at surgery. Conclusion To our knowledge, this is the first reported case of the presence of anti-viral IgM and viral DNA in vitreous sample. Furthermore, the ocular findings in our patient are definitively different from previously reported cases of parvovirus-associated ocular disorders.     

Progressive enlargement of acquired retinal astrocytoma in 2 cases

PURPOSE: To document 2 cases of progressively enlarging retinal astrocytoma that caused exudative retinal detachment, vitreous hemorrhage, and tumor seeding, simulating retinoblastoma in 1 case and choroidal melanoma in the other. DESIGN: Interventional case reports. PARTICIPANTS: Two patients. METHODS: Two patients with visual loss from an atypical, enlarging amelanotic retinal mass were evaluated. The first patient, a 14 year-old otherwise healthy girl, had a noncalcified gelatinous retinal mass with prepapillary involvement and surrounding retinal traction, as well as overlying vitreous hemorrhage and vitreous seeds. Over 37 months, the tumor grew in basal dimension from 4 mm to 10 mm. Retinal astrocytoma was suspected, but the presence of tumor enlargement and vitreous seeding raised concern for possible retinoblastoma. Fine-needle aspiration biopsy was performed. The second patient, a 33-year-old woman, had an amelanotic mass develop in the macula of her amblyopic left eye. Over 2 years, the mass enlarged to 9.5 mm in basal dimension and 6.3 mm in thickness, and total serous retinal detachment developed. Choroidal melanoma with retinal invasion was clinically suspected. Enucleation was performed. RESULTS: In patient 1, cytologic examination revealed bland spindle cells with fibrillar cytoplasm consistent with an astrocytic tumor of the retina. Enucleation was subsequently performed because of continued tumor growth, progressive retinal detachment, and visual loss. Histopathologic examination confirmed astrocytoma of the retina and optic disc. In patient 2, enucleation revealed astrocytoma of the retina and optic disc with total retinal detachment. There was no evidence of systemic tuberous sclerosis in either patient. CONCLUSIONS: Retinal astrocytoma can show progressive enlargement, retinal detachment, and vitreous seeding, findings that can mislead the clinician toward the diagnosis of retinoblastoma or choroidal melanoma.     

Intraocular involvement with subretinal pigment epithelium infiltrates by mycosis fungoides.

We report a case of intraocular mycosis fungoides in a 48-year-old man. The patient presented with decreased visual acuity, white subretinal lesions, and vitritis. Post-mortem histopathology revealed malignant T cell infiltrates consistent with mycosis fungoides in the retina, vitreous, and between the retinal pigment epithelium (RPE) and Bruch's membrane Focal atrophy of the RPE, along with the sub-RPE infiltrates, correlated with the clinically visible fundus lesions.     

Acute retinal necrosis in children caused by herpes simplex virus

PURPOSE: To report the diagnosis, management, and outcome of acute retinal necrosis syndrome in children. METHOD: Case series of three consecutive children aged 11 years and younger who were diagnosed with acute retinal necrosis. In addition to full ocular and systemic examinations, the children underwent vitreous biopsy (Patients 1 and 2) or aqueous tap (Patient 3) for polymerase chain reaction analysis. RESULTS: All patients had unilateral retinitis that was associated with preexisting chorioretinal scars, and two patients (Patients 1 and 3) had concurrent extraocular central nervous system abnormalities. Intraocular herpes simplex virus was detected in all three children: Type 1 in Patient 1 and Type 2 in Patients 2 and 3. In addition, all three children had a history of extraocular herpes simplex virus infection. CONCLUSIONS: Retinitis associated with preexisting chorioretinal scars and detectable intraocular herpes simplex virus on polymerase chain reaction was common to all three children with acute retinal necrosis.