Optical coherence tomography features in vitreoretinal lymphoma compared with non-infectious uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.

[Isolated primary vitreoretinal lymphoma (case report)]. / Izolirovannaya pervichnaya vitreoretinal'naya limfoma (klinicheskoe nablyudenie).

This case report presents the diagnostic features of isolated primary intraocular lymphoma, which was initially misdiagnosed as neovascular age-related macular degeneration. A comprehensive examination using ultrasound, optical coherence tomography, and fundus autofluorescence revealed changes characteristic of vitreoretinal lymphoma. Molecular genetic analysis of the vitreous body showed the presence of a MYD88 gene mutation and B-cell clonality by immunoglobulin heavy chain (IGH) gene rearrangement tests, which confirmed the diagnosis.

Swept-source optical coherence tomography angiography findings in a case of primary vitreoretinal lymphoma over a three-year follow-up.

BACKGROUND: Vitreoretinal lymphoma (VRL) still represents a diagnostic challenge for retinal specialists. Early diagnosis and treatment are critical for a better prognosis. Several diagnostic tools have proven helpful in the identification of VRL abnormalities. However, swept-source OCT angiography (SS-OCT-A) findings and their long-term follow-up are yet to be explored. CASE PRESENTATION: a 42-year-old man presented with blurred vision in his left eye for 2 weeks. He denied any systemic symptoms. A multimodal imaging examination was performed, raising the clinical suspicion of VRL and guiding the ensuing diagnostic procedures. The patient underwent treatment and at the last FU visit three years later, no disease signs were present on fundus examination, nor on oncologic evaluation. Some novel SS-OCT-A features were identified, and uncommonly reported findings were examined over a long-term follow-up. At baseline multiple hyperreflective alterations were detected on the enface outer retina slabs and choriocapillary analysis revealed low reflectance areas in the foveal and parafoveal areas. One month after the first presentation, multiple hyperreflective retinal lesions in a vertical shape were detected on OCT which appeared on midretinal slabs of enface SS-OCT-A as hyperreflective spots mainly located near second-order retinal vessels. These alterations remarkably reduced after treatment. CONCLUSION: SS-OCT-A may be a useful imaging technique in the detection of VRL, providing ophthalmologists additional findings that assist the diagnosis and follow-up of this disease. This may prove useful for a more timely and precise diagnosis, prompt therapy, and treatment response monitoring. The original aspects found in this case may provide grounds for future studies, ultimately fostering a better understanding of the disease.

Factors related to central nervous system involvement of primary vitreoretinal lymphoma.

PURPOSE: This single center retrospective study aimed to investigate the factors associated with central nervous system (CNS) involvement of primary vitreoretinal lymphoma (PVRL). METHODS: Clinical features of patients with PVRL (Group 1), those diagnosed with vitreoretinal lymphoma (VRL) after primary CNS lymphoma diagnosis (Group 2), and those concurrently diagnosed with CNS lymphoma and VRL (Group 3), were compared. The main outcomes included sex, age, types of treatment, survival, visual acuity, diagnostic methods, VRL recurrence, ocular manifestations, and interleukin levels in the aqueous humor. RESULTS: Groups 1, 2, and 3 included 66 eyes in 38 patients, 29 eyes in 18 patients, and 14 eyes in 8 patients, respectively. Group 3 had shorter overall survival (OS) than Groups 1 and 2 (P = 0.042 and P = 0.009, respectively). The three groups did not differ in progression-free survival (P = 0.060). The 5-year survival rates of Groups 1, 2, and 3 were 56.5%, 44.0%, and 25.0%, respectively (P = 0.001). Patients with CNS involvement in Group 1 exhibited VRL recurrence (P < 0.001), high interleukin-10 (P = 0.024), and sub-retinal pigment epithelium (RPE) infiltration (P = 0.009). Patients experiencing VRL recurrence in Group 1 tended to show CNS involvement (P < 0.001). CONCLUSION: Patients concurrently diagnosed with CNS lymphoma and VRL had a shorter OS and a lower 5-year survival rate. In patients with PVRL, the recurrence of VRL, high interleukin-10, and sub-RPE infiltration were associated with CNS involvement.

Diagnostic methods for primary vitreoretinal lymphoma: A systematic review.

Primary vitreoretinal lymphoma is a potentially aggressive intraocular malignancy with poor systemic prognosis and sometimes significant diagnostic delays as it may masquerade as chronic uveitis. Despite the variety of diagnostic techniques, it is unclear which modality is most accurate in the diagnosis of PVRL. A systematic literature search was conducted on Ovid MEDLINE, EMBASE and the Cochrane Controlled Register of Trials for studies published between January, 2000, and June, 2023. Randomized controlled trials (RCTs) reporting on the following diagnostic tools used to diagnose patients with PVRL were included: cytology, flow cytometry, MYD88 L265P mutation, CD79B mutation, interleukin 10/interleukin-6 (IL-10/IL-6) ratio, polymerase chain reaction (PCR) for monoclonal immunoglobulin heavy chain (IgH) and immunoglobulin kappa light chain (IgK) rearrangements, and imaging findings. The aggregated sensitivity of each diagnostic modality was reported and compared using the chi-squared (χ2) test. A total of 662 eyes from 29 retrospective studies reporting on patients diagnosed with PVRL were included. An IL-10/IL-6 ratio greater than 1 had the highest sensitivity (89.39%, n = 278/311 eyes, n = 16 studies) for PVRL, where the sensitivity was not significantly different when only vitreous samples were drawn (88.89%, n = 232/261 eyes, n = 13 studies) compared to aqueous samples (83.33%, n = 20/24, n = 2) (p = 0.42). Flow cytometry of vitreous samples gave a positive result in 66/75 eyes (88.00%, n = 6 studies) with PVRL, and monoclonal IgH rearrangements on PCR gave a positive result in 354/416 eyes (85.10%, n = 20 studies) with PVRL. MYD88 L265P and CD79B mutation analysis performed poorly, yielding a positive result in 63/90 eyes (70.00%, n = 8 studies) with PVRL, and 20/57 eyes (35.09%, n = 4 studies) with PVRL, respectively. Overall, our systematic review found that an IL-10/IL-6 ratio greater or equal to one may provide the highest sensitivity in identifying patients with PVRL. Future studies are needed to employ multiple diagnostic tools to aid in the detection of PVRL and to further establish nuanced guidelines when determining the optimal diagnostic tool to use in diverse patient populations.

PRESUMPTIVE RECURRENCE OF INTRAOCULAR LYMPHOMA DESPITE CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY.

PURPOSE: To present the first reported case of presumptive intraocular recurrence of lymphoma following Chimeric Antigen Receptor (CAR) T-cell therapy despite systemic control by CD19-CAR T cells. METHODS: Observational case report. RESULTS: A 59-year-old man with diffuse, large, B-cell lymphoma subsequently developed secondary central nervous system disease despite chemotherapy. He underwent stem cell transplantation but relapsed again and was scheduled to receive CAR T-cell therapy. He developed vitritis several weeks before treatment, with vitreous biopsy showing non-Hodgkin B-cell lymphoma. He received CAR T-cell therapy following the vitrectomy. He presented 3 months following CAR T-cell therapy with nonspecific right eye floaters and discomfort, with the optical coherence tomography revealing subretinal saw-tooth deposits in the right eye, highly suggestive of lymphoma. This is despite having good systemic control with no other disease elsewhere in the body. He received intravitreal methotrexate to good effect. CONCLUSION: To our knowledge, this is the first case of a vitreoretinal lymphoma nonresponsive to CAR T-cell therapy, despite good central nervous system and systemic control. This is suggestive of anti-CD19 CAR T cells not trafficking into the eye in sufficient numbers to eliminate CD19-expressing neoplastic B cells. We suggest regular ophthalmic follow-up after CAR-T-cell therapy for patients where there is evidence of ocular involvement.

Diagnosis and management of vitreoretinal lymphoma: present and future treatment perspectives.

Intraocular lymphoma (IOL) is a rare malignant intraocular lymphocytic tumor that mimics uveitis. IOL is anatomically classified into vitreoretinal lymphoma (VRL) and uveal lymphoma; most IOLs are VRLs, while uveal lymphoma is rare. VRL is highly malignant, with 60%-85% of patients developing central nervous system (CNS) lymphoma; primary VRL (PVRL) is an ocular disease with poor prognosis. We aimed to review the management and both current and future treatments for VRL. VRL diagnosis is based on the results of cytopathological examination using vitreous biopsy. However, the positive ratio of vitreous cytology remains 29%-70%. A combination of adjunctive tests may improve diagnostic accuracy, but as yet no gold-standard regimen has been established. Methotrexate intravitreal injections are effective in controlling ocular lesions; however, this treatment allows CNS dissemination. The efficacy of systemic chemotherapy in suppressing CNS dissemination has been recently debated. A multicenter prospective study with a unified treatment protocol is required to clarify this issue. In addition, establishing a treatment protocol for elderly patients and those with poor general health is necessary. Moreover, relapsed/refractory VRL and secondary VRL are more difficult to treat than PVRL because they are prone to recurrence. Ibrutinib, lenalidomide with or without rituximab, and temozolomide are promising treatments for relapsed/refractory VRL. In Japan, Bruton's tyrosine kinase (BTK) inhibitors have been approved for treating refractory CNS lymphoma. Furthermore, a randomized prospective study of tirabrutinib, a highly selective BTK inhibitor, is ongoing for evaluating the suppressing of CNS progression in patients with PVRL.

DIAGNOSTIC YIELD OF IN VITRO VITREOUS BIOPSY FOR INTRAOCULAR LYMPHOMA AT VARIABLE VITREOUS CUTTER SPEEDS USING 25-GAUGE VITRECTOMY.

PURPOSE: Primary vitreoretinal lymphoma is the most common intraocular lymphoproliferative disorder. We evaluated the diagnostic yield of pars plana vitrectomy, specifically using modern high cut rate dual-cycle cutters, on in vitro cell viability and diagnostic yield. METHODS: Human Burkitt lymphoma cell line Namalwa at 2 x 10^5 cells/mL was aspirated by 25-gauge dual-blade guillotine-type vitrectomy at five speeds (500, 1,000, 4,000, 7,500, or 15,000 cuts per minute). Cell viability and diagnostic yield in each subtype group were determined using hemocytometry, viable cell count using Cell Counting Kit-8, and pathologist-guided manual count. RESULTS: No significant deviation in cell count was identified in any cut rate by ANOVA ( P = 0.61), and no trends in the number of viable cells were identified across cut rates (R 2 = 0.188, P = 0.47). Among histologic cell counts per cut-rate, neither linear regression (R = 0.531, P = 0.16) nor ANOVA ( P = 0.096) were statistically significant. CONCLUSION: There was no significant degradation in the number of viable cells with increasing cut speed. These results suggest that in contrast to previous findings using 20g or 23g vitrectomy for diagnostic vitrectomy, modern vitrectomy systems may be used at up to 15,000 cpm without compromising the viability of lymphoma cells.

Diagnosis, treatment, and prognosis of primary intraocular lymphoma: Single-center real-world clinical experience.

BACKGROUND: The diagnosis and management of primary intraocular lymphoma (PIOL) remain challenging. This study identified factors indicative of PIOL, described treatment outcomes, and determined modalities to prevent relapse. METHODS: We included 21 PIOL-diagnosed patients, seven via cytology, 12 via genetic evaluation, and two via interleukin (IL) level measurements, who underwent vitrectomy and received local intravitreal methotrexate (IV-MTX) injection. Clinical outcomes, including treatment response and relapse, were compared between patients receiving IV-MTX alone (n = 13) or IV-MTX with systemic high-dose methotrexate (HD-MTX) as prophylaxis (n = 8). RESULTS: Twelve ophthalmologic and eight central nervous system (CNS) relapse cases within a median of 20.3 and 11.6 months were shown, regardless of the treatment modalities, with a median progression-free survival of 21.3 (95% confidence interval, 9.5-36.7) months. There was no difference in demographic characteristics between the two groups, except with the poorer performance status in patients in the HD-MTX prophylaxis group. Furthermore, patients demonstrated rapid elevations in the vitreous fluid IL-10/IL-6 cytokine ratio before ophthalmologic and CNS relapse. Therefore, diagnosis should be based on clinical signs and assisted by vitrectomy, cytologic, molecular, and cytokine studies. CONCLUSION: For PIOL, aggressive systemic treatment equivalent to that of primary CNS lymphoma (PCNSL) is recommended because solely HD-MTX did not prevent or delay CNS relapse. To prevent PIOL relapse in the CNS efficiently, prospective trials with large numbers of patients and advanced therapeutic regimens are necessary. Furthermore, regular clinical follow-up is crucial, and the IL-10/IL-6 ratio can help evaluate relapse promptly.

Logistic regression models of cytokines in differentiating vitreoretinal lymphoma from uveitis.

BACKGROUND: Vitreoretinal lymphoma (VRL) can commonly masquerade as chronic idiopathic uveitis due to its nonspecific clinical presentation. Thus, its early diagnosis is difficult. In this study, new logistic regression models were used to classify VRL and uveitis. Additionally, the diagnostic performance of interleukin (IL)-10, the IL-10/IL-6, and the Interleukin Score for IntraOcular Lymphoma Diagnosis (ISOLD) are evaluated. METHODS: Sixty-nine aqueous humors (AH) (46 VRL, 23 uveitis) and 65 vitreous humors (VH) (49 VRL, 16 uveitis) were collected from a single-center retrospective cohort. Logistic regression models were conducted based on IL-6 and IL-10. The cut-off values, area under the receiver operating characteristic curve (ROC) curve (AUC), sensitivity and specificity of IL-10, the IL-10/IL-6, the ISOLD, and the models were calculated from the ROC. Furthermore, Spearman's rank correlation analysis was performed to determine cytokine levels in VH and AH. RESULTS: We redefined the cut-off values of IL-10, the IL-10/IL-6, the ISOLD, and the logistic regression models. In AH, the AUC values of IL-10, ISOLD, IL10/IL6, and the model were 0.91, 0.953, 0.952, and 0.967. In VH, they were 0.93, 0.95, 0.954, and 0.954, respectively. IL-6 (r = 0.7844) and IL-10 (r = 0.8506) in AH and VH showed a strong correlation. CONCLUSIONS: IL-6 and IL-10 levels were introduced into new logistic regression models. The diagnostic efficacy of the models improved compared to the indicators mentioned above among Chinese patients. Additionally, the models could predict the probability of VRL more accurately. A strong correlation of cytokine levels showed the great potential of AH as prioritized auxiliary diagnostic for VRL.

[Clinical procedures for intraocular lymphomas]. / Klinisches Vorgehen bei intraokulären Lymphomen.

BACKGROUND: The classification of intraocular lymphomas is based on their anatomical location. They are divided into uveal lymphomas with involvement of the choroid, ciliary body or iris and vitreoretinal lymphomas with isolated or combined involvement of the vitreous body and/or retina. Over the last decades it has become increasingly possible to work out the clinical and pathobiological features of the various subtypes, thereby reducing the diagnostic hurdles and creating improved treatment options. OBJECTIVE: A summary of the various types of intraocular lymphoma in terms of clinical features, diagnostics, treatment and prognosis is given as well as recommendations for follow-up care. METHODS: A selective literature search was carried out on the subject of intraocular lymphomas using PubMed and Google Scholar. RESULTS: Intraocular lymphomas affect different structures, so that the symptoms can also be very different. The diagnostic spectrum ranges from typical ocular examination methods to sample biopsies with subsequent cytological, histological and molecular pathological processing. The treatment pillars available are percutaneous irradiation and intravitreal drug administration as local treatment and systemic treatment or a combination of systemic and local treatment. The prognosis depends mainly on the subtype of the lymphoma and the extent of the infestation when the diagnosis is confirmed. Even though some effective treatment options are now available, it has not yet been possible to significantly reduce the mortality rate. CONCLUSION: Many different options are available for the diagnostics and treatment of intraocular lymphomas, which require close interdisciplinary cooperation. The further developments in the field of molecular pathology allow a faster and more accurate diagnosis and could open up new treatment options in the future.

First observation of intraocular extranodal natural killer/T-cell lymphoma secondary to a retroperitoneal tumour: a case report and comparative review.

BACKGROUND: Vitreoretinal lymphomas are difficult to diagnose due to their insidious onset and inaccessible focal points. Natural killer/T-cell derived malignancies are rare as intraocular lymphomas and usually have a rapid progression and a poor prognosis. Therefore, it is essential to make a definite diagnosis, especially differentially with B-cell-derived lymphomas, which account for most cases of vitreoretinal lymphomas. CASE PRESENTATION: This case report describes a 55-year-old female reporting a 10-month history of painless decline in her vision of the right eye. Optical coherence tomography of the patient revealed hyperreflective nodules and irregular humps in the retinal pigment epithelium layer. The right vitreous was aspirated for diagnostic assessment, revealing an interleukin-10 level of 39.4 pg/mL and an interleukin-10/interleukin-6 ratio of 1.05. The right vitreous humor was positive for Epstein-Barr virus DNA. Upon a systemic examination, a high metabolic nodule was found in the retroperitoneal area and proven to be positive for Epstein-Barr virus-encoded mRNA, CD2, CD3ε, TIA-1, and Ki-67. Considering the homology of the two lesions, the patient was diagnosed with metastatic vitreoretinal lymphoma secondary to retroperitoneal extranodal natural killer/T-cell derived lymphoma. The patient received systemic chemotherapy and regular intravitreal injections of methotrexate. Her visual acuity of the right eye had improved from 20/125 to 20/32 at the latest follow-up. No new lesions were found. CONCLUSIONS: A definitive diagnosis of vitreoretinal lymphoma is challenging. On some occasions in which pathological evidence is missing, the available examination results and clinical observations must be comprehensively considered. This study herein summarized pertinent pieces of literature and reports and reviewed available practicable methods to make a definitive diagnosis of intraocular extranodal natural killer/T-cell lymphoma, which was particularly distinct from the common diffuse large B-cell lymphomas.

Comprehensive Laboratory Diagnostic Workup for Patients with Suspected Intraocular Lymphoma including Flow Cytometry, Molecular Genetics and Cytopathology.

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.

Unusual presentation of cornea verticillata with intravitreal methotrexate in a case of primary intraocular lymphoma.

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.

Vitreous proteomics, a gateway to improved understanding and stratification of diverse uveitis aetiologies.

PURPOSE: The vitreous proteome might provide an attractive gateway to discriminate between various uveitis aetiologies and gain novel insights into the underlying pathophysiological processes. Here, we investigated 180 vitreous proteins to discover novel biomarkers and broaden disease insights by comparing (1). primary vitreoretinal lymphoma ((P)VRL) versus other aetiologies, (2). sarcoid uveitis versus tuberculosis (TB)-associated uveitis and (3). granulomatous (sarcoid and TB) uveitis versus other aetiologies. METHODS: Vitreous protein levels were determined by proximity extension assay in 47 patients with intraocular inflammation and a prestudy diagnosis (cohort 1; training) and 22 patients with a blinded diagnosis (cohort 2; validation). Differentially expressed proteins identified by t-tests on cohort 1 were used to calculate Youden's indices. Pathway and network analysis was performed by ingenuity pathway analysis. A random forest classifier was trained to predict the diagnosis of blinded patients. RESULTS: For (P)VRL stratification, the previously reported combined diagnostic value of IL-10 and IL-6 was confirmed. Additionally, CD70 was identified as potential novel marker for (P)VRL. However, the classifier trained on the entire cohort (cohort 1 and 2) relied primarily on the interleukin score for intraocular lymphoma diagnosis (ISOLD) or IL-10/IL-6 ratio and only showed a supportive role for CD70. Furthermore, sarcoid uveitis displayed increased levels of vitreous CCL17 as compared to TB-associated uveitis. CONCLUSION: We underline the previously reported value of the ISOLD and the IL-10/IL-6 ratio for (P)VRL identification and present CD70 as a potentially valuable target for (P)VRL stratification. Finally, we also show that increased CCL17 levels might help to distinguish sarcoid uveitis from TB-associated uveitis.

IMMUNOGLOBULIN G4-RELATED OPHTHALMIC DISEASE MIMICKING INTRAOCULAR LYMPHOMA: A CASE REPORT.

PURPOSE: To describe a case of immunoglobulin G4-related choroiditis mimicking intraocular lymphoma. METHODS: The patient underwent a complete ophthalmological evaluation including multimodal imaging, with structural optical coherence tomography, fluorescein angiography, indocyanine green angiography, ultra-widefield color, and autofluorescent fundus photographies to assess the ocular involvement. RESULTS: Patient's best-corrected visual acuity 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. Fluorescein angiography was within normal limits, whereas indocyanine green angiography showed areas of choroiditis in both eyes, and structural optical coherence tomography scans disclosed retinal small roundish lesions in the corresponding regions. Laboratory examinations and lymph node biopsy led to the final diagnosis of immunoglobulin G4-related disease. CONCLUSION: We describe a case of immunoglobulin G4-related choroiditis mimicking intraocular lymphoma. The proper use of multimodal imaging associated with laboratory investigations was helpful to reach the correct diagnosis.

Outcomes of intravitreal methotrexate to salvage eyes with relapsed primary intraocular lymphoma.

PURPOSE: To report the outcomes of intravitreal methotrexate (MTX) injections to rescue eyes with relapsed primary intraocular lymphoma (PIOL). METHODS: Retrospective case series of patients with ocular relapse of PIOL who had initially received systemic chemotherapy (all five cases) and external beam radiotherapy (EBRT) to brain and orbits (two cases). Injections of MTX (400 µg/0.1 mL) were given one time per week for 1 month, every other week for 4 months, followed by a maintenance phase of one injection one time per month for 8 months (total of 20 injections in a year). RESULTS: From April 2008 to February 2016, there were nine eyes of five patients (three men; average age at first presentation 62 years) treated with our rescue protocol of intravitreal MTX injections. Ocular relapse occurred at a mean interval of 15 months (range 5-34 months) after the completion of initial systemic treatment. At mean follow-up of 31 months (range 5-104 months), tumour control was achieved in eight out of nine eyes (89%); one eye failed, with persistent retinal infiltrates despite increasing the frequency of injections, resulting in severe keratopathy. The only other complication occurred in one eye, developing cystoid macular oedema from MTX injections that resolved with topical anti-inflammatory medications and reduced frequency of MTX. There were no cases of reduced vision or ocular relapse, but two patients died (one of central nervous system lymphoma). CONCLUSIONS: Intravitreal MTX was a safe and effective treatment modality for relapsed PIOL after systemic chemotherapy and radiotherapy, achieving local tumour control in 89%, and hence represents an optimal choice. However, given the rare nature of PIOL, larger collaborative studies with longer follow-up are needed to corroborate this.