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A 56-year-old woman presented with floaters and diminution of vision in the right eye for 1 week. On examination, visual acuity was 20/400 in the right eye and 20/60 in the left eye. Indirect ophthalmoscopy revealed vitritis in the right eye and subretinal deposits in both eyes. Vitreous biopsy of the right eye revealed large B-cell-type primary intraocular lymphoma and the patient underwent multiple intravitreal methotrexate injections (400 μg/0.1 mL) in the right eye and systemic chemotherapy for bilateral disease. Following biweekly injections of methotrexate, her visual acuity improved considerably from 20/400 to 20/60 with resolution of vitritis. However, following eighth dose of intravitreal methotrexate, she experienced visual decline to 20/120 along with photophobia, redness and watering. Whorl-shaped opacities, limbitis and corneal haze were noted on slit-lamp examination. Intravitreal methotrexate was stopped, and the patient was started on frequent topical lubricants, loteprednol, topical folinic acid and oral folic acid. Complete resolution of corneal toxicity was observed at 3 weeks and the injections were suspended as there was no recurrence at 6 months follow-up.

Background Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, generally affects the orbit by direct extension. It can even rarely present as severe intraocular inflammation mimicking endophthalmitis. Delayed diagnosis and treatment are frequently reported. Case presentation A 43-year-old woman presented with 2-month blurred vision in her left eye. Ocular examination revealed hypopyon panuveitis. She was initially diagnosed with endogenous endophthalmitis, which proved irresponsive to antimicrobial therapy. High-dose prednisolone was given afterward, but this failed to stop the development and continuous progression of ocular inflammation. The diagnosis of ENKTL was finally confirmed from the pathological findings of oral ulcers and cervical lymph nodes and chemotherapy was prescribed. After the first cycle of chemotherapy, the patient’s ocular inflammation subsided. Unfortunately, her left eye became phthisis with progressive visual loss within 9 months following the diagnosis. Conclusions The diagnosis of intraocular ENKTL is frequently delayed, which can lead to severe problems for treatment as the disease is aggressive with a poor prognosis. It can be found not only in elderly patients but also in a middle-aged individual. In patients with ocular inflammation, a thorough systemic evaluation and histopathological examination of the associated systemic findings is extremely helpful and may reveal the cause of the ocular inflammation, including revealing possible ENKTL.

Purpose To describe a case of IgG4-related choroiditis mimicking intraocular lymphoma. Methods The patient underwent a complete ophthalmological evaluation including multimodal imaging, with structural optical coherence tomography (OCT), fluorescein angiography (FA), indocyanine green angiography (ICGA), Ultra-Wide Field color and autofluorescent fundus photographies to assess the ocular involvement. Results Patient BCVA was of 20/25 in the right eye and 20/20 in the left eye. Fundus appearance showed abnormal yellowish choroidal lesions and moderate vitritis in both eyes . FA was within normal limits while ICGA showed areas of choroiditis in both eyes and structural OCT scans disclosed retinal small roundish lesions in the corresponding regions. Laboratory exams and lymph node biopsy led to the final diagnosis of IgG4-related disease. Conclusions We describe a case of IgG4-related choroiditis mimicking intraocular lymphoma. The proper use of multimodal imaging associated with laboratory investigations was useful to reach the correct diagnosis.

Background Intraocular lymphoma accounts for fewer than 1% of intraocular tumors. When the posterior segment is involved, it can be further classified as vitreoretinal or choroidal lymphoma. Vitreoretinal lymphoma (VRL) can rarely masquerade as an infectious retinitis making diagnosis and management challenging. Results A 73-year-old woman with a history of non-central nervous system (CNS) involving diffuse large B-cell lymphoma (DLBCL) was referred for worsening blurry vision—visual acuity of count figures at 2 ft—in her right eye for 8 months. Dilated fundus examination of the right eye was significant for retinal whitening and dot-blot hemorrhages, which was concerning for a viral retinitis and guided initial management. Secondary intraocular lymphoma was also considered. The retinal disease continued to progress despite intravitreal and systemic antiviral therapy, and a diagnostic vitrectomy was inconclusive. A retinal biopsy was then performed, which showed DLBCL, confirming a diagnosis of secondary VRL. Three subsequent treatments with intravitreal methotrexate led to regression of the VRL. Conclusions Our case highlights the utility of a retinal biopsy after an inconclusive diagnostic vitrectomy in a challenging scenario of VRL to establish a diagnosis and initiate successful treatment. A multidisciplinary team of providers was essential for diagnosis, comprehensive workup, medical and surgical management of the patient.

Purpose Various immune mediators have crucial roles in the pathogenesis of intraocular diseases. Machine learning can be used to automatically select and weigh various predictors to develop models maximizing predictive power. However, these techniques have not yet been applied extensively in studies focused on intraocular diseases. We evaluated whether 5 machine learning algorithms applied to the data of immune-mediator levels in aqueous humor can predict the actual diagnoses of 17 selected intraocular diseases and identified which immune mediators drive the predictive power of a machine learning model. Design Cross-sectional study. Participants Five hundred twelve eyes with diagnoses from among 17 intraocular diseases. Methods Aqueous humor samples were collected, and the concentrations of 28 immune mediators were determined using a cytometric bead array. Each immune mediator was ranked according to its importance using 5 machine learning algorithms. Stratified k-fold cross-validation was used in evaluation of algorithms with the dataset divided into training and test datasets. Main Outcome Measures The algorithms were evaluated in terms of precision, recall, accuracy, F-score, area under the receiver operating characteristic curve, area under the precision-recall curve, and mean decrease in Gini index. Results Among the 5 machine learning models, random forest (RF) yielded the highest classification accuracy in multiclass differentiation of 17 intraocular diseases. The RF prediction models for vitreoretinal lymphoma, acute retinal necrosis, endophthalmitis, rhegmatogenous retinal detachment, and primary open-angle glaucoma achieved the highest classification accuracy, precision, and recall. Random forest recognized vitreoretinal lymphoma, acute retinal necrosis, endophthalmitis, rhegmatogenous retinal detachment, and primary open-angle glaucoma with the top 5 F-scores. The 3 highest-ranking relevant immune mediators were interleukin (IL)-10, interferon-γ-inducible protein (IP)-10, and angiogenin for prediction of vitreoretinal lymphoma; monokine induced by interferon γ, interferon γ, and IP-10 for acute retinal necrosis; and IL-6, granulocyte colony-stimulating factor, and IL-8 for endophthalmitis. Conclusions Random forest algorithms based on 28 immune mediators in aqueous humor successfully predicted the diagnosis of vitreoretinal lymphoma, acute retinal necrosis, and endophthalmitis. Overall, the findings of the present study contribute to increased knowledge on new biomarkers that potentially can facilitate diagnosis of intraocular diseases in the future.

A 56-year-old man complaining of blurred vision was referred to the ophthalmologist. He was initially diagnosed with uveitis and showed no response to steroid treatment. Diagnostic vitrectomy and skin lesion biopsy performed later confirmed the diagnosis of extranodal NK/T cell lymphoma (ENKTL), nasal type. Despite sufficient systemic chemotherapy, the patient developed central nervous system (CNS) relapse 3 months after achieving systemic remission. The diagnosis and treatment of this patient required multidisciplinary teamwork between ophthalmologists, pathologists, and hematologists. This report focused on the diagnostic planning and optimal treatment strategy for this patient.

The patterns of uveitis in Tokyo have recently changed due to advances in examination tools. We aimed to investigate the changes in the patterns of uveitis between 2004–2015 and 2016–2018. We retrospectively reviewed the data of 732 patients who visited the Uveitis Clinic at the University of Tokyo Hospital between January 2016 and December 2018. Background characteristics, laboratory results, and imaging findings were analysed. We compared the incidences of uveitis in 2016–2018 and 2004–2015 to identify changes in the patterns. The most frequent diagnoses were sarcoidosis (8.9%), herpetic iridocyclitis (6.7%), intraocular lymphoma (5.5%), Vogt–Koyanagi–Harada disease (4.8%), unclassified acute anterior uveitis (4.6%), Behcet’s disease (4.5%), bacterial endophthalmitis (2.9%), and Posner-Schlossman syndrome (2.6%). Suspected sarcoidosis (20.9%) was the most common cause of unclassified uveitis. The incidence of intraocular lymphoma was significantly higher in 2016–2018 than in 2004–2015. Between 2004 and 2018, herpetic iridocyclitis, bacterial endophthalmitis, and juvenile chronic iridocyclitis exhibited an increasing trend, and the incidences of Posner-Schlossman syndrome, unclassified acute anterior uveitis, Behcet’s disease, and Vogt–Koyanagi–Harada disease exhibited a decreasing trend. The changing patterns of uveitis were characterised by increases in the incidence of intraocular lymphoma. This may be attributed to recent advances in examination tools, the changes in the referred patient population, and the aging Japanese population.

BACKGROUND/AIMS: Intravitreal rituximab is an off-label treatment option for primary vitreoretinal lymphoma (PVRL). The objective of this study was to monitor the therapeutic response and safety profile of intravitreal rituximab in a cohort of PVRL patients. METHODS: In this retrospective, uncontrolled, open label, multicentre study, 20 eyes from 15 consecutive patients diagnosed with PRVL received at least one intravitreal injection of 1mg in 0.1ml rituximab. Biodata of the PVRL patients was recorded as well as visual acuity and vitreous haze score immediately before rituximab intravitreal injection and at follow-up examinations. Intravitreal rituximab safety data was also recorded. Additional rituximab injections were made during control visits on a pro re nata (PRN) regime using increased vitreous haze to indicate recurrence. RESULTS: There was significant vitreous haze reduction (p=0.0002) followed by significant improvement of visual acuity (mean best visual acuity before therapy 0.57 logMAR, after therapy 0.20 logMAR (p=0.0228) during the follow-up time up to 4 years. Only mild ocular side effects were reported. Median follow-up time was 565 days (range, 7-1253 days). CONCLUSION: Intravitreal rituximab therapy shows promising PVRL regression without any severe side effects. Although our clinical data support rituximab as intravitreal therapy in PVRL disease, further study is warranted.

Several neoplastic processes can involve the eye, either primarily or secondary to a systemic malignancy. The most common primary tumors of the eye include conjunctival and uveal melanoma, retinoblastoma, conjunctival and intraocular lymphoma, and ocular surface squamous neoplasia. Metastatic spread from systemic malignancies, especially of the breast and lung, also can involve the eye. A combination of ophthalmologic examination, ancillary testing, and cytologic/histopathologic evaluation leads to accurate diagnosis. Management consists of surgery, radiotherapy, chemotherapy, and immunotherapy delivered in various forms.

AIM: To investigate the clinical manifestations, diagnostic approaches, treatments, and outcomes of intraocular lymphoma. METHODS: In this retrospective study, 16 patients (28 eyes) with intraocular lymphoma were recruited in the Department of Ophthalmology, Peking Union Medical College Hospital, from 2004 to 2019. All patients underwent comprehensive ophthalmic examinations. Vitreous specimens of 13 patients were sent for cytopathology examination and other adjunctive diagnostic procedures. Three patients were diagnosed with intraocular lymphoma according to analysis of the histopathological results of systemic lymphoma by one clinician. Twenty-three eyes were treated with intravitreal administration of methotrexate, 4 eyes could not receive ocular treatment due to life-threatening lymphoma, and 1 eye did not require ocular treatment because the fundus lesions regressed after systematic chemotherapy. RESULTS: In 28 eyes, 25 eyes were diagnosed with vitreoretinal lymphoma, and 3 eyes were diagnosed with ciliary body lymphoma, all of which were non-Hodgkin diffuse large B cell lymphomas. The final visual acuity improved in 15 eyes (54%), remained unchanged in 5 eyes (18%), and decreased in 8 eyes (29%). Anterior segment inflammation disappeared or reduced in 8 and 5 eyes, respectively; and 15 eyes had no anterior segment reaction. Twenty eyes had mild vitreous opacity, 1 eye had mild vitritis, and 7 eyes had pars plana vitrectomy combined with silicone oil tamponade. Fundus lesions disappeared in 9 eyes and were relieved in 5 eyes; 4 eyes showed no changes, and the remaining 10 eyes' fundus were normal. CONCLUSION: The clinical manifestations of intraocular lymphoma are diverse, and the misdiagnosis rate is high. Cytopathological analysis of vitreous is one of the gold standards for the diagnosis. Immunohistochemistry, gene rearrangement and flow cytometric immunophenotypic analysis can improve the diagnostic rate. Ocular chemotherapy or radiotherapy regimens may preserve visual acuity, and a multidisciplinary team can provide individualized treatment for the patients.

To characterize the imaging features in eyes with vitreoretinal lymphoma (VRL) using ultra-widefield fundus photography (UWF-FP), swept-source optical coherence tomography (SSOCT) and fundus autofluorescence (FAF) that are correlated to ongoing treatment with intravitreal Rituximab(IVR).Retrospective observational imaging-based study of 15 treatment-naive eyes with VRL treated with IVR. All patients with primary VRL underwent vitreous biopsy using 23/25G microincision vitrectomy system for confirmation of diagnosis. All eyes received monthly IVR (1 mg/0.1 mL) injections till disease remission. Baseline clinical characteristics, treatment details, outcomes, and sequential imaging features on UWF-FP, FAF, and SSOCT were analyzed.Baseline features and changes in UWF-FP, FAF patterns, and SSOCT features in response to treatment RESULTS: Clinically, patients presented with sub-RPE deposits (n = 15), superficial retinal hemorrhages (n = 2), 'giant' RPE (retinal pigment epithelium) holes (n = 2), and anterior segment reaction (n = 1). Eyes were treated with mean 5.7 IVR injections (median: 5; range 1-13) over a mean 7.2 ± 4.9 months. During the course of treatment, two eyes developed superficial retinal hemorrhages with spontaneous resolution, 2 eyes developed CME, and 4 eyes developed characteristic 'leopard skin' pigmentation. Hyper-autofluorescence corresponding to areas of active lesions decreased with each treatment cycle and was finally replaced by hypo-autofluorescence. Serial OCTs showed regression of sub-RPE/subretinal deposits (n = 15), ellipsoid zone disruption (n = 9), and its resolution with treatment (n = 3), epiretinal membrane (ERM; n = 6), choroidal hyperreflective foci (HRF; n = 4), disorganization of retinal inner layers (DRIL; n = 3), RPE-rip (n = 2), cystoid macular edema (CME; n = 2), and hyperreflective lesions in the choroid (n = 1). Complete resolution was observed in all eyes with extensive hypo-AF. The central foveal thickness decreased from 237 ± 113 μ to 182 ± 114 μ (p = 0.1) and subfoveal choroidal thickness decreased from 258 ± 66 μ to 220 ± 64 μ (p = 0.12) at final follow-up. The mean baseline BCVA was logMAR 0.9 ± 0.9 that deteriorated to mean logMAR 1 ± 1 final visit (p = 0.7). The mean recurrence-free follow-up was 5.9 ± 5.1 months CONCLUSION: Multimodal imaging provides novel insights into features of VRL, a better understanding of regression patterns, and prognostication of outcomes when treated with intravitreal rituximab. Larger, multicentric studies with longer follow-up will help unravel imaging biomarkers to understand these aspects better.

Purpose To provide recommendations for diagnosis of vitreoretinal lymphoma (VRL). Methods Literature was reviewed for reports supporting the diagnosis of VRL. A questionnaire (Delphi 1 round) was distributed to 28 participants. In the second round (Delphi 2), items of the questionnaire not reaching consensus (75% agreement) were discussed to finalize the recommendations. Results Presenting symptoms include floaters and painless loss of vision, vitreous cells organized into sheets or clumps. Retinal lesions are usually multifocal creamy/white in the outer retina. Other findings include retinal lesions with "leopard-skin" appearance and retinal pigment epithelium atrophy. Severe vitreous infiltration without macular edema is the most likely presentation. Diagnostic vitrectomy should be performed. Systemic corticosteroid should be discontinued at least 2 weeks before surgery. An interleukin (IL)-10:IL-6 ratio > 1, positive mutation for the myeloid differentiation primary response 88 gene and monoclonality are indicators of VRL. Multi-modal imaging (optical coherence tomography, fundus autofluorescence) are recommended. Conclusions A consensus meeting allowed the establishment of recommendations important for the diagnosis of VRL.

We describe the electroretinographic findings of a case of primary intraocular lymphoma (PIOL) wherein the patient received intravitreal injections of methotrexate (ivMTX). A 62-year-old man developed blurred vision and complained of decreased visual acuity (VA) in his right eye. Fundus examination showed vitreous opacity and multiple subretinal yellowish lesions. Optical coherence tomography (OCT) revealed subretinal and intraretinal infiltrations. The full-field electroretinogram (ffERG) showed subnormal combined rod-cone response and multifocal electroretinogram (mfERG) recorded using skin electrodes showed severe attenuation of the response compared with the other eye. Pars prana vitrectomy, phacoemulsification, and lens implantation were performed to remove the opacity, and vitreous biopsy revealed a high ratio of interleukin 10–6 (76.0). There was no systemic malignant lesion, and the patient was diagnosed with PIOL. Treatment with ivMTX (400 μg/0.1 mL) was started. One month later, the intraretinal infiltration had disappeared, and mfERG revealed recovery of the response density from the central area. Two months later, OCT showed recovery of the foveal ellipsoid and interdigitation zones, and VA recovered to 20/17; mfERG showed maintenance of macular function. However, the amplitude of a- and b-waves in the ffERG gradually decreased. Macular function recovered, but there was also a decrease in total retinal function. mfERG and ffERG recorded using skin electrodes were useful in monitoring macular and entire retinal function with repeated examinations and showed recovery and maintenance of macular function in a case of PIOL treated with ivMTX.

A 67-year-old previously healthy woman presented with progressive visual impairment including bitemporal hemianopsia. A brain magnetic resonance imaging revealed a contrast-enhancing mass in the optic chiasm, spreading along the left optic tract. The patient underwent a transcranial biopsy of the left optical tract that yielded a diagnosis of diffuse large B-cell lymphoma. CT scans of the chest, abdomen, and pelvis, PET-CT, and bone marrow biopsy revealed no evidence of systemic lymphoma. Thus, the final diagnosis was of primary central nervous system lymphoma of the optic chiasm. Systemic treatment was initiated with full response. Six months after the end of the treatment, recurrence at cerebellum parenchyma and left tentorium was recorded. A new systemic treatment achieved full response. A second recurrence was noted in an optical coherence tomography of the right eye, 2 years after the initial diagnosis. The patient was treated with intravitreal methotrexate with initial success, but eventual failure after 10 months. Intravitreal rituximab was used with no effect. The patient was then referred to radiotherapy and underwent external beam radiotherapy with VMAT. There were no acute toxicities to report. After the radiotherapy treatment, at 1-year follow-up, the patient has no evidence of disease. Long-term toxicities were recorded and are considered manageable. The present case emphasizes the role of ocular irradiation as an option in the management of intraocular lymphoma patients, including in the salvage setting, with an acceptable ocular toxicity profile.

Background/aimsThe primary aim of this study was to describe the causes of de novo uveitis in individuals 60 years and older. Secondary objectives were to determine the incidence of intraocular lymphoma and the clinical predictors of lymphoma.MethodsRetrospective chart review of all subjects presenting to the uveitis service at Auckland District Health Board (Auckland, New Zealand) between January 2006 and October 2020Results686 subjects (900 eyes) were aged ≥60 years at first presentation with uveitis, representing 23.4% of all subjects with uveitis during the study period. Non-infectious aetiology occurred in 631 (70.1%) eyes and infectious etiologies occurred in 269 (29.9%) eyes. The most frequent causes were idiopathic (36.3%), herpes zoster (14.8%), HLAB27 (8.7%) and sarcoidosis (4.8%). Twenty (2.2%) eyes of 13 (1.9%) subjects had a diagnosis of lymphoma. Lymphoma represented 11.2% of all intermediate uveitis. Subjects diagnosed with lymphoma did not develop posterior synechiae, epiretinal membrane, cystoid macular oedema or ocular hypertension.ConclusionsIntraocular lymphoma was uncommon in the overall cohort, but an important cause of intermediate uveitis. A diagnosis of lymphoma needs to be considered in any older subject with de novo intermediate uveitis. The lack of posterior synechiae, cystoid macular oedema, epiretinal membrane and ocular hypertension further increases the suspicion for lymphoma.

Introduction Most intraocular T-cell lymphomas arise from metastatic source. We are reporting a rare case of intraocular T-cell lymphoma masquerading as pseudo-hypopyon and vitritis. The eye involvement proved to represent a metastatic spread from a co-existing adrenal T-cell lymphoma, which was discovered after the initial ophthalmic presentation. Presentation of case Our patient was a 71-year-old Saudi man, who was admitted for workup of anemia and weight loss. He also noticed a gradual, painless decline in his vision of both eyes, for which he was referred to the ophthalmology unit. Ocular examination revealed left eye 3 mm pinkish hypopyon. A diagnosis of T-cell lymphoma was made based on careful microscopic examination of the left aqueous fluid, immunohistochemical (IHC) and Flow cytometry analysis. Computerized tomography showed a large invasive left adrenal mass, which has proven to be a primary adrenal lymphoma with multiple metastasis including the intraocular involvement. Discussion Primary intraocular lymphoma is the most common lymphoma in the eye. Intraocular T-cell lymphoma is rare and is mostly metastatic. On the other hand, primary adrenal lymphoma (especially T-cell lymphoma) is also rare. There are only 5 cases of primary adrenal lymphoma, two of which, resulted in eye metastasis similar to our case. Primary adrenal lymphoma is known to be aggressive. Our patient eventually passed away. Conclusion This report stresses the importance of referring patients with systemic lymphoma to an ophthalmologist to be evaluated for ocular involvement. Even though intraocular metastatic adrenal T cell lymphoma is rare, high clinical suspicion in patients who are presenting with pinkish hypopyon in the presence of other constitutional symptoms is essential., Highlights • Intraocular metastatic adrenal T-cell lymphoma is a rare condition. • Diagnosis is essentially histopathological and can be made through aqueous tap. • We report the rare occurrence of metastatic adrenal T-cell lymphoma to the eye. • Intraocular lymphoma may present with pinkish hypopyon as a masquerade syndrome.

Purpose To describe the morphological patterns of keratic precipitates (KPs) in vitreoretinal lymphoma (VRL) using in vivo confocal microscopy (IVCM). Methods Six eyes of three biopsy-proven VRL patients were included. KPs were identified and analyzed on IVCM. Results On examination, pigmented KPs in four eyes, white central KPs in two eyes and anterior chamber cells with flare in six eyes and pseudo hypopyon in one eye were identified. A typical floral pattern of KPs on IVCM was noted in all eyes. Three eyes each showed the complete and incomplete floral patterns, respectively. Resolution of KPs on IVCM was noted after chemotherapy. Conclusion In addition to the routinely used clinical and imaging markers like the visual acuity, presence of lymphomatous cells in the vitreous and optical coherence tomography findings, the presence and appearance of KPs on IVCM can also be considered as a useful, diagnostic and treatment monitoring marker in VRL.

Purpose: Vitreoretinal lymphoma (VRL) is the most common intraocular lymphoma (IOL). This can be either primary or secondary to the central nervous system lymphoma. The diagnosis of primary intraocular lymphoma (PIOL) currently relies on clinical diagnosis and cytological analysis of the vitreous or subretinal biopsy. Although most cases are diagnosed without much issue, the limited amount of vitreous fluid, subjectivity in cytological reporting, and special expertise in ocular pathology make the diagnosis challenging. MYD88 L265P mutation has been implicated to have diagnostic utility in PIOL. In this study, we screened consecutive vitreous biopsies for the presence of MYD88 L265P mutation to understand its diagnostic utility compared to conventional cytological analysis. Methods: Cytological analysis and MYD88 L265P mutation by PCR-based sequencing and restriction fragment length polymorphism (RFLP) were carried out on consecutive vitreous and subretinal biopsies collected from 21 patients. The diagnostic utility of the cytology and MYD88 L265P mutation analysis were compared. Results: Out of the 21 patients, 15 had clinical suspicion of having PIOL. Out of these suspected cases of PIOL, nine were confirmed on follow-up, while six were diagnosed as other intraocular pathologies. Diagnostic utility of MYD88 L265P mutation analysis revealed a sensitivity of 88.9%, specificity of 91.6%, positive and negative predictive value of 88.9% and 91.7%, respectively. Diagnostic accuracy of 90.5% was achieved with the mutation analysis that shows the superiority of MYD88 in both ruling in and ruling out PIOL. The diagnostic utility of MYD88 L265P mutation was superior to conventional cytological analysis. Conclusion: The analysis of MYD88 L265P mutation is reliable and efficient in the diagnosis of PIOL.

Purpose In 2012, four patients with multiple asymptomatic, indolent, unilateral, choroidal lesions were described. We suspected benign-behaving lymphocytes infiltrating the choroid. This article expands the number of patients and duration of follow-up and speculates further on the etiology. Although histopathologic confirmation of these lesions is still unknown, the natural course of these patients is excellent and should be distinguished from aggressive choroidal lymphoma. Methods To qualify for the study, the patients had to meet the following criteria: 1) Patients collected had asymptomatic choroidal infiltrates as demonstrated in the figures; 2) absence of vitreous cells; 3) no evidence of concomitant systemic malignancy; 4) no systemic inflammatory diseases, including sarcoidosis; 5) no birdshot chorioretinopathy; 6) no conjunctival or orbital lesions; and 7) advanced multimodal imaging and clinical follow-up were performed. Results There were 11 eyes of 11 patients seen. Follow-up ranged from 4 months to 12 years and 1 month (mean 50.2 months; median 24 months). Systemic workup was unrevealing. No patients in this cohort developed systemic, conjunctival, orbital, or vitreoretinal lymphoma or inflammatory disease. No patients developed symptoms or vision loss. Conclusion This entity is an indolent choroidal infiltrative disease. It resembles some cases of choroidal lymphoma and may represent an indolent lymphocytic infiltrate.

Background: Intraocular lymphoma (IOL) presents a real challenge in daily diagnostics. Cyto- and/or histopathology of vitreous body represent the diagnostic cornerstones. Yet, false negative results remain common. Therefore, we analyzed the diagnostic significance of flow cytometry (FC) within the workup algorithm of IOL and compared its sensitivity with the results obtained from routine cytopathology and molecular genetics; Methods: Seven patients undergoing vitrectomy due to suspected IOL were investigated by FC and parallel cytopathology and, if available, digital droplet PCR (ddPCR) for MYD88 L265P; Results: Four out of seven patients were finally diagnosed with IOL. Among the IOL patients, cytopathology confirmed the presence of lymphoma cells in only two cases. In contrast, FC was positive for IOL in all four cases, and FC additionally confirmed the lack of IOL in the remaining patients. In IOL patients diagnosed by FC and with available ddPCR, the diagnosis of IOL was confirmed by the presence of the MYD88 L265P mutation in all three patients; Conclusions: The combination with FC was superior to cytopathology alone in the diagnostic work-up of IOL, and it showed an excellent correlation with ddPCR results. A comprehensive diagnostic panel consisting of cytopathology, FC and molecular genetics should be considered for the work-up of suspected IOL.

Purpose. Herein, we report a case of primary intraocular lymphoma (PIOL) with the first presentation of bilateral Epstein-Barr virus- (EBV-) associated panuveitis. Case Presentation. A 69-year-old male was referred with a three-day history of blurred vision and pain and redness in his left eye following cataract surgery. Examination revealed panuveitis, vitritis, and necrotizing retinitis with retinal hemorrhage. A month later, the right eye was also involved. Polymerase chain reaction-based analysis of the vitreous sample was positive for EBV, and cytological evaluation was compatible with the diagnosis of B-cell lymphoma. A significant improvement was observed following serial intravitreal rituximab and methotrexate injections. The central nervous system and lungs were involved after 6 months, and the patient expired despite systemic chemotherapy. Conclusion. There may be an association between EBV panuveitis and primary intraocular B-cell lymphoma.

The purpose of this study is to investigate matrix metalloproteinases (MMPs) expression in human intraocular lymphoma (IOL).Two enucleated eyes and seven cell-block samples obtained from patients with IOL who underwent vitrectomy were used. Immunopathological examinations were performed for detection of MMP-2, MMP-9, and TIMP-4 expressions.In the enucleated eye with primary IOL (PIOL), MMP-2 was negative, and MMP-9 and TIMP-4 were positive in the lymphoma cells, while in the enucleated eye with secondary IOL (SIOL), all the molecules were positive. Among the cell-block samples with PIOL, the positive rate in lymphoma cells of MMP-2, MMP-9, and TIMP-4 was 75%, 100%, and 75%, respectively. In the cell-block samples with SIOL, the positive rates of MMP-2, MMP-9, and TIMP-4 were all 100%.MMP-2, MMP-9, and TIMP-4 were expressed in lymphoma cells using the specimens of human IOL, suggesting that MMPs may play an important role in the development of IOL.

Cytomegalovirus (CMV) retinitis is a vision-threatening condition seen with CD4+ count below 50/μL. In the presence of systemic lymphoma, CMV retinitis may pose a diagnostic dilemma due to similar clinical features with intraocular lymphoma. We, hereby, report a rare case of bilateral CMV retinitis in a patient with normal CD4+ counts and a past history of diffuse large B-cell lymphoma (DLBCL). A 51-year-old male presented with sudden-onset painless diminution of vision in the right eye (RE) for a 2-week duration. He had a past history of DLBCL and had been treated with chemotherapy. On examination, his best-corrected visual acuity was perception of light in RE and 20/20 in the left eye (LE). RE fundus examination showed yellowish-white deep retinal lesions with scanty superficial retinal hemorrhages and perivascular exudates. LE fundus examination showed only one focal area of yellowish-white deep retinal lesions along the inferotemporal arcade. A provisional diagnosis of bilateral intraocular lymphoma was made based on the past history of systemic lymphoma. RE vitreous tap was done, and intravitreal injection of methotrexate was given. Vitreous sample revealed CMV DNA on polymerase chain reaction but no evidence of malignant cells on cytology. CD4 count was 393 cells/μl. The patient was subsequently treated with intravenous ganciclovir and oral valganciclovir for bilateral CMV retinitis. This case report highlights the importance of vitreous sample analysis in patients of systemic lymphoma presenting with atypical retinal necrotic lesions to establish an accurate diagnosis and to differentiate between closely mimicking lesions of intraocular lymphoma and viral retinitis.

Purpose To report a case of primary vitreoretinal lymphoma in which a macular hole developed after a diagnostic pars plana vitrectomy. Methods A retrospective interventional case report. Results A 65-year-old woman presented with worsening vision in the left eye. Fundus examination showed vitreous haze and multifocal, yellow-white infiltrates in the retina and under the retinal pigment epithelium in the left eye. She underwent a diagnostic pars plana vitrectomy in that eye. Undiluted vitreous specimen showed an increased interleukin-10 level (1,470 pg/mL) with an elevated interleukin-10 to interleukin-6 ratio of 15.1; cytologic analysis of the vitreous showed atypical lymphoid cells with large irregular nuclei and scanty cytoplasm. The retinal and sub-retinal pigment epithelial infiltrates responded well to intravitreal methotrexate injections, but a macular hole developed in the left eye. The second pars plana vitrectomy with internal limiting membrane peeling and 20% sulfur hexafluoride gas tamponade successfully closed the macular hole. Conclusion Macular hole closure can be accomplished in eyes receiving intravitreal methotrexate injections for treating primary vitreoretinal lymphoma.

Purpose: To report the outcome of a previously vitrectomized eye having less lymphoma disease burden compared with the contralateral nonvitrectomized eye over the course of 3.5 years while on systemic chemotherapy. Methods: Case report. Results: A 51-year-old man with vitreoretinal lymphoma with central nervous system involvement underwent vitrectomy in his left eye. Over the following 3.5 years on systemic chemotherapy, the left eye had less lymphoma disease burden compared with the contralateral nonvitrectomized right eye. Conclusion: Therapeutic vitrectomy may be a useful adjunct to systemic chemotherapy in vitreoretinal lymphoma, particularly in cases of vitreous predominant disease manifestation.

A 69-year-old female presented with right vitreous cells and cystoid macular oedema (CMO). One year previously, she had received two cycles of attenuated methotrexate-based chemotherapy for primary central nervous system (CNS) lymphoma, abandoned due to toxicity. There was no past ocular history of note aside from mild cataract. Due to her history of previous CNS lymphoma, we suspected vitreoretinal lymphoma (VRL), but the presence of the CMO made this unlikely. She underwent a diagnostic vitrectomy. Histology and immunohistochemistry showed the presence of a high-grade B-cell VRL.

Background: Currently, transvitreal fine-needle aspiration biopsy is the most widely used tissue biopsy technique in cases of suspected intraocular lymphoma due to its relative simplicity and low trauma. The small sample produced, however, may be inadequate for diagnostic and prognostic analyses due to mechanical artefacts, insufficient material, or sampling errors. Small case series have demonstrated choroidal biopsy via vitrectomy to be safe and effective. With smaller-gauge vitrectomy instruments, visual recovery is rapid, and post-operative inflammation and conjunctival scarring is minimised. Furthermore, smaller-gauge instrumentation does not appear to affect the diagnostic yield of biopsies for intraocular lymphoma in vitro. We report a case of primary choroidal lymphoma successfully diagnosed with 27-gauge pars plana vitrectomy choroidal biopsy. Case Presentation: A 72-year-old female presented with a 6-month history of painless blurred vision in her right eye. Fundus examination revealed a large pale choroidal mass centred on the posterior pole with overlying exudative retinal detachment. Enhanced depth imaging optical coherence tomography revealed a markedly thickened choroid with an undulating appearance. B-scan ultrasonography demonstrated diffuse, smooth thickening of the choroid, and retrobulbar extrascleral hypoechoic nodules. A 27-gauge pars plana vitrectomy was performed and choroidal biopsy taken. Histopathologic, immunohistochemical, and flow cytometry studies confirmed a diagnosis of extranodal marginal zone B-cell lymphoma. Systemic workup found no evidence of systemic lymphoma. As such, the patient was diagnosed with primary choroidal lymphoma. She underwent intensity-modulated external beam radiotherapy with subsequent resolution of disease. Conclusions: Primary choroidal lymphoma can be safely and effectively diagnosed via 27-gauge vitrectomy choroidal biopsy.

AimsPeculiar retinal signs of vitreoretinal lymphoma (VRL) have been identified. However, limited information on the vitreous features of VRL is available. This study aims to characterise the vitreous involvement in VRL with the help of multimodal imaging.MethodsIn this retrospective, observational study, we reviewed charts and imaging of all patients with biopsy-proven VRL seen from January 2016 to April 2018 at a single referral centre. These included ultrawide-field imaging, ophthalmic ultrasonography and slit-lamp photography. The main outcome measures were patterns of vitreous haze of VRL, as observed by combining clinical and multimodal imaging information.ResultsTwenty-six eyes of 13 patients were included. At presentation, vitreous haze was present in 24 eyes (92%) and was the only sign of VRL in 4 eyes (15%). Three patterns of vitreous haze were identified in VRL. An aurora borealis pattern was present in 12 eyes and showed linear opacities with a myriad of cells aligned along the vitreous fibrils. A string of pearls pattern was present in two eyes at baseline and developed in other four eyes after vitrectomy, showing fine fibrils connecting bunches of inflammatory material. A non-specific pattern was observed in 10 eyes. Ophthalmic ultrasound showed corpuscular material correlating with the grading of vitreous haze.ConclusionVRL shows different patterns of vitreous haze. Multimodal imaging, including ultrawide-field imaging and slit-lamp photography, helps in recognising these patterns, raising suspicion for VRL.

Acute retinal necrosis (ARN) is a form of infectious uveitis caused by alpha herpesviruses, including herpes simplex virus type 1 (HSV-1). We previously found that the long non-coding RNA (lncRNA) U90926 is upregulated in murine retinal photoreceptor cells following HSV-1 infection, leading to host cell death. However, to date, an orthologous transcript has not been identified in humans. We investigated U90926 orthologous transcript in humans and examined its utility as a prognostic marker for visual acuity in patients with ARN. We identified two human orthologous transcripts (1955 and 592 bases) of lncRNA U90926. The amount of the longer human U90926 transcript was approximately 30- and 40-fold higher in the vitreous fluid of patients with ARN than in those with sarcoidosis and intraocular lymphoma, respectively. Furthermore, the expression of the longer human U90926 transcript in the vitreous fluid was highly correlated with the final best-corrected logarithm of the minimum angle of resolution visual acuity in patients with ARN (r = 0.7671, p = 0.0079). This suggests higher expression of the longer human U90926 transcript in the vitreous fluid results in worse visual prognosis; therefore, expression of the longer human U90926 transcript is a potential negative prognostic marker for visual acuity in patients with ARN.

Purpose To report the enface optical coherence tomography (OCT) features of intraocular lymphoma. Methods Retrospective, observational case reportCase description A 59-year-old man, a known case of primary testicular carcinoma complained of right eye blurred vision since 1-week. He had undergone systemic intravenous chemotherapy (R-CHOP regime), orchiectomy and external beam radiotherapy for the primary malignancy previously. His right eye vision was 20/30, 6/6 RS. The right eye anterior segment examination was normal. Fundus examination showed vitreous cells 1+ and a large, bumpy, sub retinal dull-yellow lesion sparing the fovea with multiple discrete yellow retinal lesions at the posterior pole. Magnetic resonance imaging of the brain was normal. Multimodal imaging was used to document the clinical features. On the enface OCT, multiple hyperreflective lesions were identified on the superficial, deep and outer retinal slabs of the scan corresponding to the vertical hyperreflective lesions extending from the retinal nerve fibre layer to the RPE. The sub-RPE lesion can be well-delineated in the choriocapillaris segment. He was treated with multiple injections of intravitreal Methotrexate 400µg/0.1ml along with systemic chemotherapy in conjunction with the oncologist. At 6-months follow-up, fundus lesions had regressed. In addition, resolution of the lesions was noted on the OCT and enface OCT scans. Conclusion Enface OCT imaging can be considered for monitoring the therapeutic efficacy following intravitreal chemotherapy in intraocular lymphoma.

Purpose: Herein, we report a case of primary intraocular lymphoma (PIOL) with the first presentation of bilateral Epstein-Barr virus (EBV)-associated panuveitis and retinitis.Case presentation: A 69-year-old male was referred with a three-day history of blurred vision and pain and redness in his left eye following cataract surgery. Ophthalmic examination revealed panuveitis, vitritis, and necrotizing retinitis with retinal hemorrhage. A month later, the right eye was also involved. Initially, the clinical diagnosis of acute retinal necrosis was made based on clinical manifestation; however, the partial response to intravenous and intravitreal antiviral treatment in the left eye and involvement of the right eye resulted in further investigation of masquerade syndromes. Polymerase chain reaction-based analysis of vitreous sample was positive for EBV, and cytological evaluation was compatible with the diagnosis of B-cell lymphoma. A significant improvement was observed following serial intravitreal rituximab and methotrexate injections. The central nervous system and lungs were involved after 6 months, and the patient expired despite treatment with systemic chemotherapy. Conclusion: There may be an association between EBV panuveitis and primary intraocular B-cell lymphoma.

Purpose: To report a case of primary choroidal lymphoma that was confirmed by polymerase chain reaction-based clonality testing. Case report: A 50-year-old woman presented with unilateral progressive vision loss. Fundus examination and B-ultrasonography demonstrated diffuse choroidal thickening without vitritis. Pars plana vitrectomy and subretinal biopsy were performed, and histopathologic analysis revealed choroidal B-cell lymphoid hyperplasia without evidence of neoplasia. Extraocular extension was ruled out, and transitory improvement was observed with oral steroids. After 1-year follow-up, she was referred to our hospital and clonality testing was performed using the samples taken months before. First, we used a forensic DNA extraction kit, and then, a multiplex polymerase chain reaction was carried out using the IgH Rearrangements Molecular Analysis Kit. Clonal rearrangement was identified for the immunoglobulin heavy chain framework regions 1 and 2, and B-cell choroidal lymphoma was confirmed. The patient began treatment with intravitreal rituximab, but no response was observed. Finally, complete regression was achieved using external beam radiotherapy. Conclusion: Polymerase chain reaction-based clonality testing can be a valuable tool to confirm a choroidal lymphoproliferative process.

A 66-year-old man presented with a 1-month history of hazy vision in his left eye, worsening over the past 2 days. His medical history included hypothyroidism and hypertension. Best-corrected Snellen visual acuity was 6/9 and hand movements in the right and left eyes, respectively, with no evidence

Background Vitreoretinal lymphoma (VRL) is a subtype of central lymphoma, which at present is hard to diagnose. The gold standard of VRL diagnosis is vitreous cytology, but the vitreous specimen needs to be obtained by the invasive surgery of vitrectomy. Aqueous humor is easier to obtain, has better stability, and has a lower operating risk than vitreous specimens. Methods We studied the diagnostic value of interleukin 10 (IL-10), IL-10/ IL-6 ratio and interleukin score for intraocular lymphoma diagnosis (ISOLD) in both vitreous and aqueous humor for vitreoretinal lymphoma, to determine if aqueous humor could be used to assist in the diagnosis of vitreoretinal lymphoma (VRL) by detecting IL-6 and IL-10. Results The area under ROC curve (AUC) of vitreous fluid IL-10, IL-10/IL-6 ratio and ISOLD at the diagnosis of VRL diagnosis were 93.5%, 93.6% and 93.8%, respectively. The AUC of the aqueous humor IL-10, IL-10/IL-6 and ISOLD for VRL diagnosis were 83.8%, 72.8% and 85.9%, respectively. Conclusions Aqueous humor can thus replace vitreous humor as a potential sample type for the diagnosis of intraocular lymphoma.

Diagnosis of intraocular lymphoma is difficult. Among the hurdles in the diagnosis are the variety of reactive inflammatory and ischemic changes among intraocular lymphoma patients. Thus, a novel diagnostic method is desired such that lymphoma cells can be distinguished by the signals intrinsic to the cells, not by those from the surrounding tissues with reactive changes. Raman spectroscopy is a technique that can detect intrinsic signals from each cell. Therefore, Raman spectroscopy is a good candidate for an intraocular evaluation technology that could contribute to improve the diagnosis of intraocular lymphoma. In this study, we tested whether the intrinsic Raman signals from malignant lymphoma cells, in the absence of surrounding tissue, were sufficient for the discrimination of malignant lymphoma cells from leukocytes. We acquired spectra from dissociated lymphoma cells, along with spectra from normal B cells and other leukocytes involved in intraocular inflammatory diseases. We analysed the spectra using principal component analyses and quadratic discriminant analyses. We found that Raman spectra from dissociated cells without confounding tissues showed high discriminating ability, regardless of the variation due to day-to-day differences and donor differences. The present study demonstrates the possible effectiveness of Raman spectroscopy as a tool for intraocular evaluation.

Diagnosis of intraocular lymphoma (IOL) is usually achieved by histopathological analysis. However, it may lead to inconclusive results due to the scarcity of malignant cells obtained by biopsy, hence leading to delayed diagnosis. We report two cases of IOL with pseudo-hypopyon, a rare feature of IOL, as their initial ocular feature, diagnosed using a multidisciplinary diagnostic approach. Common clinical features of IOL with pseudo-hypopyon were also investigated.Retrospective case series and literature review.Two cases of IOL, a 78-year-old female and a 59-year-old male, whom had been diagnosed with systemic B-cell lymphoma developed pseudo-hypopyon and visual impairment during the course of their chemotherapy. Diagnosis of IOL was achieved from anterior chamber aspiration samples with supplementary diagnostic tools including flow cytometric immunophenotyping, interleukin and IgH gene rearrangement analysis in addition to the conventional histopathological analysis. Generally, pseudo-hypopyon was more commonly seen in secondary IOL and may associate with hyphema and high intraocular pressure.Pseudo-hypopyon is a rare feature of IOL, more commonly seen in secondary IOL, which can be accompanied by hyphema and high intraocular pressure. Supplementary diagnostic tools such as flow cytometric immunophenotyping, interleukin analysis, and immunogloblin H gene rearrangement analysis are useful for supporting the diagnosis of IOL with pseudo-hypopyon.

Vitreous biopsy is essential for establishing a definitive diagnosis and guiding potential therapy in patients with refractory vitritis and posterior uveitis, among other indications. Especially in cases where one must rule out intraocular lymphoma, obtaining a significant amount of undiluted vitreous increases diagnostic yield. We demonstrate our technique for obtaining a significant amount of undiluted vitreous using pars plana vitrectomy with air infusion.

Introduction: Intraocular lymphoma is rare. There are very few studies on intraocular lymphoma published from Asian countries. Objective: To report our case series of intraocular lymphoma patients from a tertiary eye centre in Singapore. Subjects and methods: Nine patients with intraocular lymphoma managed between January 2005 and December 2014 were identified from Ocular Autoimmune Systemic Inflammatory Infectious Study (OASIS) database. Demographic characteristics, clinical presentation, investigations performed and outcomes recorded. Results: There were almost equal distribution between males (four patients) and females (five patients) with mean age of presentation was 60.3 years. Five patients had bilateral involvement and vitreo-retina was the most common site of infiltration. All of our patients had central nervous system involvement although four of them had presented with ocular manifestations initially. Anterior chamber fluid cytology, as a less invasive alternative to vitreous analysis was proven to be useful. The time from ocular presentation to diagnosis of ocular lymphoma was variable; from one day to 18 months. Mortality in our study group was 55% with death occurring 1 month to 8 years from diagnosis of intraocular lymphoma. Conclusion: Intraocular lymphoma is a masquerade syndrome that mimics chronicuveitis and poses a diagnostic challenge. The diagnosis is often delayed and despite the eventual diagnosis, the disease prognosis is poor even with aggressive treatment.

In this case series, 3 unique cases of severe immune-mediated pathologies (primary ocular lymphoma, toxoplasmosis chorioretinitis, and syphilitic retinitis) after dropless cataract surgery with intraocular steroid injection are reported. Patient immune status and subsequent local immunosuppression after dropless cataract surgery played roles in the worsening of these pathologies. This report demonstrates the need for vigilance when administering immunosuppressive agents locally during cataract surgery.

Purpose: To describe a case of primary vitreous retinal lymphoma (PVRL) complicated with choroidal neovascularization (CNV) and presented with severe macular edema (ME). Case description: A 52-year-old female patient was diagnosed with bilateral PVRL. Optical coherence tomography (OCT) showed severe macular edema (ME) and subretinal hyperreflective material in the left eye at the first visit. No sign of choroidal neovascularization (CNV) was found with fundus fluorescein angiography (FFA) or indocyanine green angiography (ICGA). The ME was resolved after standard intraocular chemotherapy, while the subretinal hyperreflective material remained stable. Optical coherence tomography angiography (OCTA) was performed 2 years after chemotherapy. OCTA revealed a well-circumscribed CNV network in the subretinal hyperreflective material. Conclusion: It is a rare occurrence that CNV and ME developed in this PVRL patient. The presence of ME is not an exclusion criterion for PVRL. This case should also raise awareness of the importance of OCTA as a method for monitoring intraocular lymphoma during follow-up.

Background/purpose To describe a case of histopathologic clinical correlation of sarcoidosis-related multifocal chorioretinitis in an elderly individual. Methods This is a single case report and review of the pertinent literature. A 72-year-old white woman with a history of asthma was referred with bilateral asymmetric low-grade chronic panuveitis with advancing peripheral punched-out chorioretinal lesions despite systemic corticosteroid treatment. Results Coalescent chorioretinal punched-out lesions on fundus examination in the more severely affected right eye did not respond to corticosteroid treatment, and the refractory nature resulted in a suspicion of intraocular lymphoma despite a previous inconclusive diagnostic vitrectomy result. A transvitreal chorioretinal biopsy in the vitrectomized eye demonstrated a chorioretinal noncaseating granuloma centered on the choriocapillaris and invading Bruch membrane and the outer retina. This case illustrates an example of the second peak of incidence in sarcoidosis that can occur in ages >50 in Caucasians and Japanese patients, as well as a tendency to develop chronic disease in Caucasians, and to have extrapulmonary sarcoidosis in the elderly. Conclusion This case emphasizes the differences in presentation of ocular sarcoid in older Caucasian women as well as the histopathologic findings in multifocal peripheral chorioretinitis associated with sarcoidosis.

BACKGROUND To describe the various neuro-ophthalmic presentations, key exam features, and clinical findings associated with 5 common primary and secondary intracranial malignancies. EVIDENCE ACQUISITION Retrospective PubMed search and review of published case reports, case series, observational studies, book chapters, and review articles examining the neuro-ophthalmic features of intracranial malignancies including primary glial neoplasms (e.g., glioblastoma multiforme), primary and secondary lymphoma, intracranial metastases, carcinomatous/lymphomatous meningitis, and intracranial germ cell tumors. The search strategy used to perform the retrospective review included the aforementioned tumor type (e.g., glioblastoma multiforme) and the following terms and Boolean operators: AND ("visual loss" OR "papilledema" OR "diplopia" OR "ophthalmoplegia" or "neuro-ophthalmology" OR "proptosis"). RESULTS The rate of growth and the location of an intracranial tumor are essential factors in determining the neuro-ophthalmic presentation of certain intracranial malignancies. Primary malignant brain glial neoplasms commonly present with visual afferent complaints (e.g., unilateral or bilateral visual acuity or visual field defects, bitemporal or homonymous hemianopsia), pupil abnormalities (relative afferent pupillary defect), and optic atrophy or papilledema. Primary intraocular lymphoma (with or without central nervous system lymphoma) typically presents as a painless bilateral vitritis. Secondary intracranial malignancies have variable afferent and efferent visual pathway presentations. Carcinomatous/lymphomatous meningitis is associated with diplopia (e.g., multiple ocular motor cranial neuropathies with or without vision loss from papilledema or compressive/infiltrative optic neuropathy). Intracranial germ cell tumors can present with a chiasmal syndrome or dorsal midbrain syndrome. CONCLUSION Intracranial malignancies can present with neuro-ophthalmic symptoms or signs depending on topographical localization. Specific neuro-ophthalmic presentations are associated with different malignant intracranial tumors. Clinicians should be aware of the common malignant intracranial tumors and their associated clinical presentations in neuro-ophthalmology.

Purpose: We investigated the changes in etiology of uveitis at the Uveitis Clinic of Tokyo Medical University Hospital in recent years.Methods: Medical records of patients with uveitis diagnosed between 2011 and 2017 (Group A) and between 2001 and 2007 (Group B) were reviewed.Results: 1,587 patients in group A and 1,507 patients in group B were analyzed. For noninfectious uveitis, frequencies of Vogt-Koyanagi-Harada disease, intraocular lymphoma (IOL) and iridocyclitis in young girls increased, while those of sarcoidosis and Behcet's disease decreased in the recent era. For infectious uveitis, herpetic iridocyclitis, ocular toxoplasmosis, ocular syphilis, and bacterial endophthalmitis increased, while acute retinal necrosis and ocular toxocariasis decreased. Unclassified uveitis decreased, whereas infectious uveitis and IOL increased due to the availability of new diagnostic tests.Conclusion: Etiologies of uveitis have changed over the years. Further development of novel tests and diagnostic criteria would increase definitive diagnosis for unclassified uveitis. (147/150 words).

Treatment of uveitis is complicated because of its multiple aetiologies and elevation of various inflammatory mediators. To determine the mediators that are elevated in the vitreous humor according to the aetiology of the uveitis, we examined the concentrations of 21 inflammatory cytokines, 7 chemokines, and 5 colony-stimulating/growth factors in vitreous samples from 57 eyes with uveitis associated with intraocular lymphoma (IOL, n = 13), sarcoidosis (n = 15), acute retinal necrosis (ARN, n = 13), or bacterial endophthalmitis (BE, n = 16). Samples from eyes with idiopathic epiretinal membrane (n = 15), which is not associated with uveitis, were examined as controls. Heat map analysis demonstrated that the patterns of inflammatory mediators in the vitreous humor in eyes with uveitis were disease-specific. Pairwise comparisons between the 5 diseases showed specific elevation of interferon-α2 in ARN and interleukin (IL)-6, IL-17A, and granulocyte-colony stimulating factor in BE. Pairwise comparisons between IOL, ARN, and BE revealed that levels of IL-10 in IOL, RANTES (regulated on activation, normal T cell expressed and secreted) in ARN, and IL-22 in BE were significantly higher than those in the other 2 types of uveitis. These mediators are likely to be involved in the immunopathology of specific types of uveitis and may be useful biomarkers.

Purpose. To demonstrate the importance of subretinal biopsy to reach a diagnosis when vitreous biopsy is negative or inconclusive. Methods. A 54-year-old Caucasian gentleman presented with bilateral anterior uveitis at JCUH. He initially responded to topical steroids and dilating agents. Subsequently he developed bilateral panuveitis and cataract with poor response to treatment. Detailed workup had been done to rule out infectious etiology. A suspicion of lymphoma was considered and vitreous biopsy sample was taken from one eye, which was inconclusive. Then, to help with definitive diagnosis vitreous sample, subretinal aspirate and retinal biopsy were taken. Results. Subretinal aspirate revealed Aspergillus niger. Treatment was initiated accordingly. Conclusions. Subretinal aspirate and retinal biopsy can help with diagnosis of unusual clinical panuveitis like presentation.

Background Fuchs’ uveitis (FU) is occasionarlly complicated with heavy vitreous opacity. We have performed vitrectomy procedures to remove vitreous opacity in affected patients as part of differential diagnosis for primary vitreoretinal lymphoma (PVRL). Case presentation We retrospectively reviewed the clinical records of five patients who first visited the Uveitis Clinic of the University of Tokyo Hospital between 2009 and 2013, were diagnosed with FU and underwent a vitrectomy for removal of dense vitreous opacity. All were diagnosed as FU by ocular findings and elevation of Goldmann-Witmer coefficient (GWC) value for the rubella virus (RV) antibody. In examinations of the vitreous body, cytological diagnosis, elevation of IL-10/IL-6 ratio, and the kappa/lambda ratio in flow cytometry findings were negative in all cases, whereas monoclonal immunoglobulin heavy chain (IgH) gene rearrangement was positive in 4 cases and negative in 1 case. Conclusions Although monoclonal IgH gene rearrangement is thought to be a reliable biomarker for PVRL, a high percentage of vitreous specimens from our FU patients showed pseudo-positive results. Ophthalmologists must take care regarding possible pseudo-positive findings when performing differential diagnosis between FU and PVRL. Combinations of results of cytological diagnosis, IL-10/IL-6 ratio, kappa/lambda ratio, and IgH gene rearrangement may be necessary for a definitive diagnosis of PVRL and differentiation from FU.

Purpose: To report a case of extranodal natural killer/T-cell lymphoma (ENKTCL), nasal type metastatic to the space beneath the retinal pigment epithelium (RPE) with coincident paraneoplastic lymphoma-associated retinopathy. Methods: Findings of clinical and histopathologic examination are presented with differential diagnoses and a literature review. Case Report: A 53-year-old man presented with bilateral blindness and had exudative retinal detachments overlying subretinal masses in both eyes. Flow cytometry of pericardial fluid revealed malignant T lymphocytes. After two cycles of chemotherapy, the patient was hospitalized and quickly expired. Autopsy revealed lymphoma involving the eyes, heart, right lung, and two subcarinal lymph nodes focally. Histopathologic examination of the eyes revealed intraocular metastases from ENKTCL, nasal type. Expression of CD3 and CD56, along with expression of Epstein-Barr virus by in situ hybridization, confirmed the diagnosis. Lymphomatous infiltrates were confined to the space beneath the neurosensory retina and between the RPE and the Bruch membrane, sparing the uveal tissue, similar to other metastatic T-cell lymphomas. Extensive RPE and photoreceptor loss in regions with and without underlying tumor was typical of a concurrent paraneoplastic lymphoma-associated retinopathy. Conclusion: Patients diagnosed with ENKTCL should be evaluated by an ophthalmologist, as ophthalmic involvement portends a poor prognosis.