Vitreoretinal Involvement Research Articles

An International Multicenter Study of Primary Vitreoretinal Lymphoma from the Australasian Lymphoma Alliance and Collaborators

Background: Primary vitreoretinal lymphoma (PVRL) is a rare high-grade extranodal non-Hodgkin lymphoma characterized by frequent and often fatal central nervous system (CNS) relapse. Despite improved outcomes for patients with primary CNS lymphomas over the last decade, approaches to the diagnosis and management of PVRL remain contentious. Given limited prospective data to date, there is need to better elucidate current international practice in the modern era to optimize outcomes for this patient group. Methods: Patients with pathologically confirmed PVRL diagnosed between January 2010 and December 2022 were identified from ten sites across Australia, Singapore, Canada and the United Kingdom. Patients were aged ≥18 years, with isolated PVRL at diagnosis (i.e. no concomitant CNS involvement at baseline or secondary vitreoretinal involvement). Variables included were baseline demographic data, presenting symptoms, diagnostic procedures undertaken and sample characteristics such as cytological, immunocytochemical and flow cytometric features. Where available, molecular results and biomarkers such as IL-10 and IL-6 were also collected. Treatment approaches including local, systemic and combined local/systemic therapies were captured. Outcomes measured included response rates, patterns of relapse, progression-free (PFS) and overall survival (OS). Results: 36 patients were identified with a median age at diagnosis of 68 years (range 38-89) with a female predominance (58%). Most patients presented with bilateral involvement (72%) with decreased visual acuity being the predominant presenting symptom (53%). Most patients received a PVRL diagnosis within weeks to months of symptom onset, however a third of patients had >12 months delay to diagnosis. Ancillary diagnostic tests such as flow cytometry, molecular and cytokine measurements performed in a minority of patients only, largely due to sample viability and paucity. Concurrent CNS involvement was evaluated by brain MRI in 97% with diagnostic lumbar punctures performed in 64%. Exclusion of systemic disease was predominantly done via PET or PET/CT (69%) with the remainder via CT alone (Table 1). Upfront treatment choices were highly varied across participating sites with incorporation of systemic therapy in the majority (64%) of cases, either alone (25%) or in combination with local therapies (39%). For those who received systemic therapy, all incorporated high-dose methotrexate with the median dose delivered of 3.5g/m 2 per cycle and rituximab was incorporated in 48%. Autologous stem cell transplantation (ASCT) was part of frontline management in 19% of cases, and the median age of those receiving frontline ASCT was 55 years versus 71 years in those who did not. With median follow-up of 57 months (IQR 24-74 months), the median OS was 90 months whilst median PFS was only 23 months (Figures 1 and 2). 18 patients experienced disease relapse during follow up, only 2 of which had received frontline ASCT. The median PFS and OS of those who received frontline ASCT was not reached and 92 months respectively. Patients who had systemic treatment incorporated into frontline management had a trend toward improved OS than those who did not (Figure 3). Of those with relapsing disease, 14 (78%) had CNS involvement, and 29% of these patients experienced concurrent CNS and systemic involvement at relapse. Median OS from time of relapse was 8 months (IQR: 3-89 months). Of the 14 deaths occurring during follow up, 6 (43%) were secondary to lymphoma, 2 (14%) were related to toxicities of treatment and the rest were unknown or related to other co-morbidities. Conclusion: To our knowledge, this is the largest international multicenter cohort of patients with isolated PVRL reported in the modern era. The apparent improvement in OS compared with historical cohorts may reflect improvements in therapy in the recent decade, and incorporation of systemic therapy in frontline management demonstrated a trend to improved OS. However, high rates of CNS relapse continue to be a challenge. Delays in diagnosis and variation in diagnostic and management pathways reflect the need to develop prospective studies and international consensus guidelines for managing this rare lymphoma.

Vitreoretinal Involvement by Indolent T-cell Lymphoproliferative Disorder of the Gastrointestinal Tract Diagnosed by Fluorescence In Situ Hybridization.

To describe an exceedingly rare presentation of secondary vitreoretinal involvement by the uncommon entity "indolent T-cell lymphoproliferative disorder of the gastrointestinal tract" and illustrate the utility of fluorescence in situ hybridization for diagnosis. Case report. 57-year-old female. A 57-year-old female with presumed iritis on chronic topical prednisolone acetate presented with increased vitreous opacities in the right eye. She had a history of biopsy-confirmed indolent T-cell lymphoproliferative disorder (iTLPD-GI) involving the stomach and duodenum, JAK2-rearrangment-positive, controlled on maintenance oral methotrexate. Vitreous biopsy was unremarkable with small CD3 and CD4-positive, CD-20 negative lymphocytes, along with histiocytes and fibroblasts. Immunostains showed CD4 positivity, and fluorescence in situ hybridization revealed a JAK2 gene rearrangement, consistent with the patient's previously diagnosed iTLPD-GI. Intravitreal methotrexate injections were started in the right eye. Brain MRI and lumbar puncture with cytology, MYD88, IL10, and flow cytometry performed at the time of right eye vitreoretinal lymphoma diagnosis revealed no evidence of central nervous system lymphoma, but subsequent bone marrow biopsy demonstrated 5% involvement by iTLPD-GI, JAK2-rearrangment-positive, with a lung nodule on PET-CT. She returned four months later with fatigue, night sweats, and blurry vision in the left eye with vitreous and anterior chamber cellular infiltration and retinal vasculitis. T-cell vitreoretinal lymphoma is rare, and diagnosis can be challenging. Despite inconclusive cytology in this case, interphase fluorescence in situ hybridization detected a JAK2 gene rearrangement, which confirmed involvement by iTLPD-GI and prompted appropriate treatment and workup for recurrent systemic or central nervous system lymphoma.

Vitreoretinal involvement of caterpillar hairs

Vitreoretinal involvement of caterpillar hairs

Clinical Profile and Visual Outcome of Traumatic Glaucoma Patients Following Closed Globe Injury in the Rural Part of Eastern Uttar Pradesh at a Tertiary Eye Care Centre: A Retrospective Cohort Study

Introduction: Glaucoma is a significant cause of ocular morbidity following ocular trauma, particularly Closed Globe Injury (CGI), which frequently leads to elevated Intraocular Pressure (IOP). This type of trauma can result in various tissue damages such as radial sphincter tears, iridodialysis, angle recession, cyclodialysis, trabecular meshwork tears, zonule separation, or peripheral retinal dialysis. Damage in these areas can lead to early or delayed onset glaucoma. Aim: To evaluate the clinical profile, assess visual outcomes, and analyse management strategies in post-traumatic glaucoma with CGI. Materials and Methods: The retrospective cohort study was conducted at a tertiary eye care centre in Department of Ophthalmology, Regional Institute of Ophthalmology (RIO), Sitapur, Uttar Pradesh, India. from January 2020 to December 2022. Retrospective data of patients presenting with CGI and developing elevated IOP (>21 mmHg) were collected. Only patients with a minimum follow-up of three months were included. Various parameters, including demographics, IOP, Best-Corrected Visual Acuity (BCVA), and the effects of medical and surgical treatments on IOP and BCVA, were analysed. The Ocular Trauma Score (OTS) was also calculated. Statistical analysis was performed using Microsoft excel and Statistical Package for Social Sciences software version 21.0, with a significance level of 5%. Continuous variables were described as mean±Standard Deviation (SD), and an unpaired t-test was used for comparisons between pre- and postmanagement visual acuity and IOP. Results: Out of 259 eyes with ocular trauma, 93 (35.90%) were diagnosed with CGI and developed elevated IOP. The most common causes of elevated IOP were hyphema (37.63%) and angle recession mechanisms (32.25%). The median IOP at presentation was 35 mmHg (range: 12 to 71 mmHg) and decreased to 16.5 mmHg (range: 4 to 52 mmHg) at the last follow-up (p-value <0.001). Surgical management was required in 30 (32.25%) eyes, with 13 (13.97%) eyes undergoing trabeculectomy. Conclusion: Post-traumatic IOP elevation occurred in 93 (35.90%) eyes with CGI, and 13.97% of these eyes required glaucoma filtering surgery for IOP control. Overall, medical management was necessary in 67.74% of eyes, while 32.25% required surgical intervention. Eyes with posterior segment involvement had poor visual acuity. Poor baseline vision and vitreo-retinal involvement increased the risk of a poor visual outcome.

Primary extranodal diffuse large B-cell lymphoma in the rituximab era: a single center, retrospective analysis

ABSTRACT Objectives To analyse the clinical characteristics and therapeutic response of Chinese patients with primary extranodal diffuse large B-cell lymphoma DLBCL (PE-DLBCL). Methods We analysed the clinical features and outcomes of 197 patients who were newly diagnosed with PE-DLBCL between January 2015 and December 2020. Results The gastrointestinal tract showed the highest rate of involvement (34%), followed by the central nervous system (CNS) and intraocular system (31.5%). The 3-year overall survival (OS) rate was 81% for the entire group and 79% for those with CNS and vitreoretinal involvement. Ann Arbour stage, lactate dehydrogenase level, International Prognostic Index > 2, and complete remission (CR) were significantly related to the survival of patients with PE-DLBCL. The lack of CR was the only independent adverse prognostic factor for OS. Conclusion The clinical outcomes of patients with PE-DLBCL at our centre were encouraging, especially for patients with CNS and vitreoretinal involvement.

Primary vitreoretinal involvement and immunopositivity for BRAFV600E help distinguish metastatic from primary intraocular melanoma: a detailed histopathologic study of metastatic cutaneous melanoma to the eye.

To evaluate the clinicopathologic characteristics of metastatic cutaneous melanoma to the eye and identify potential distinguishing characteristics from the more common primary uveal melanoma; particularly, tumour location within the eye, cytomorphology and immunohistochemical/specific molecular genetic features. A retrospective observational case series using surgical enucleation and diagnostic vitrectomy cytologic specimens from seven patients with suspected intraocular melanoma, eventually diagnosed as metastatic melanoma, was conducted. Haematoxylin and eosin-stained sections of tumour and immunohistochemical (IHC) stains for BRAFV600E and Ki-67 were critically reviewed; BAP1 IHC was also evaluated in cases where additional tissue was available. Clinical imaging studies and medical records were reviewed. The majority of patients (86%) with metastatic melanoma have primary vitreoretinal (not uveal) involvement and epithelioid, highly malignant cytomorphology (100%); many (50%) harbour BRAFV600E mutations, a finding not seen in large cohorts of primary uveal melanoma. Characteristics favouring or defining metastatic intraocular melanoma over primary uveal melanoma include high-grade epithelioid cytology, predominant involvement of the vitreous cavity and/or retina, and presence of positive immunostaining for BRAFV600E.

A proposed protocol of intravitreal injection of methotrexate for treatment of primary vitreoretinal lymphoma.

Primary central nervous system lymphoma (PCNSL) is a non-Hodgkin lymphoma involving the brain with possible leptomeningeal and ocular involvement. This study aimed to evaluate the safety and efficacy of modified intravitreal injection regimen of methotrexate (MTX) for therapeutic management of vitreoretinal lymphoma. Forty human immunodeficiency virus (HIV)-negative Chinese patients with primary vitreoretinal lymphoma were included in this retrospective noncomparative interventional case series study. Patients were treated with a modified protocol of intravitreal injection of MTX (400 µg/0.1 ml) according to the Intensive-Consolidation-Maintenance regimen. The Intensive phase of once-weekly intravitreal injections for 1 month, followed by the Consolidation phase of one injection every 2 weeks for 1 month, and then the Maintenance phase of once monthly for 1 month, for a total of 7 injections. The primary main outcome measures were clinical response to intravitreal chemotherapy, number of injections for clinical remission, progression-free survival (PFS), overall survival (OS), visual acuity (VA), complications during the study period, and cause of death were investigated. The duration of follow-up from the commencement of injection of MTX was 12-73 months (median 28, 30.55 ± 14.73 months). A total of 61 eyes of 40 patients were cleared clinically from malignant cells after a median 6.57 ± 3.12 (median 6, range 1-14) times of injection of MTX. A second remission was induced in 3 patients, who were treated with a further course of intravitreal chemotherapy after tumour recurred in their eyes. The median PFS and OS were 20.82 months (95% CI 14.64-27.01) and 29.29 months (95% CI 16.16-42.41), respectively. Complications that occurred during the period of treatment and follow-up included corneal epitheliopathy (3 of 61 eyes) and cataract (6 of 61 eyes). There were no cases of maculopathy, vitreous haemorrhage, optic atrophy, and sterile endophthalmitis. No patient had an irreversible loss of vision that could be attributed to the intravitreal injection of MTX. It can be concluded that the modified intravitreal injection regimen of MTX is an effective therapeutic approach in inducing clinical remission of intraocular involvement in PCNSL patients, associated with few complications. However, further study needs to be conducted to indicate whether the proposed approach extends life expectancy. Primary central nervous system lymphoma (PCNSL) can involve the vitreous and retina and is associated with a poor clinical outcome, with a survival rate of less than 3 months in absence of undergoing an effective therapeutic strategy. Methotrexate (MTX) is the most efficient cytotoxic drug for patients with vitreoretinal involvement in primary vitreoretinal lymphoma (PVRL), through intravitreal injection of MTX. In our experience, the modified protocol of intravitreal MTX according to the Intensive-Consolidation-Maintenance regimen, was effective in inducing clinical remission of PVRL with few complications. The accumulating clinical results brought us to propose the consideration of this protocol as a good first-line treatment option for PVRL.

Vitreoretinal abnormalities in corona virus disease 2019 patients: What we know so far.

The coronavirus disease 2019 (COVID-19) has become a global pandemic since December 2019. Although COVID-19 primarily affects the respiratory systems, it has become abundantly clear that it involves multiple organs including the heart, kidney, skin, and brain. Neuro-ophthalmic signs and anterior segment inflammation of the eyes were documented in COVID-19 patients recently. Small but growing number of literatures has also reported the cases of new onset vitreoretinal disorders related to COVID-19 infection. A comprehensive search from four online databases was done. Findings show vitreoretinal involvement in COVID-19 patients including the central retinal vein occlusion, central retinal artery occlusion, reactivation of previous uveitis, chorioretinitis, macular hemorrhage, acute macular neuroretinopathy, paracentral acute middle maculopathy, vitritis with outer retinal abnormalities, varicella zoster virus-related acute retinal necrosis in immunocompromised patient, and other posterior segment pathological changes. The hypotheses for potential pathogenesis of these manifestations are direct viral ocular infection and thromboembolic complications secondary to the hyperinflammatory response. This is the first review article, which provides an overview of current evidence regarding the vitreoretinal manifestations in COVID-19 patients.

Rituximab, Methotrexate, Procarbazine and Lomustine (R-MPL) for the Treatment of Primary CNS Lymphoma

Introduction: Primary central nervous lymphoma (PCNSL) is a rare type of non-Hodgkin lymphoma that may involve the brain, spinal cord, leptomeninges and vitreous. The median age at diagnosis is in the fifth decade and most patients (pts) present with significant neurologic deficit and a low performance status. The optimal treatment of PCNSL is controversial. High dose methotrexate (HDMTX) is a standard treatment of PCNSL and is more effective when given in combination with other CNS-penetrating medications, which, however, add to the toxicity of the treatment. We aimed to evaluate the effectiveness and the safety of the combination of rituximab, HDMTX, procarbazine and lomustine (R-MPL) in pts with PCNSL. Patients and methods: We retrospectively reviewed the files of PCNSL pts treated in Hadassah Medical Center, Jerusalem, Israel, between the years 2006-2019. The medical records were reviewed for demographic details and initial disease characteristics (age, sex, performance status, laboratory results, cerebrospinal fluid (CSF) content and tumor location), and for therapeutic details including chemotherapy protocol, toxicity, response to treatment and survival. We excluded pts who could not receive HDMTX. The R-MPL is a 42-day cycle protocol, consisting IV Rituximab 375 mg/m2 on days 1, 15 and 28, IV HDMTX 5 g/m2 (3.5 g/m2 for pts > 60 Years (y)) on days 2, 15 and 29, PO procarbazine 100 mg/m2 (60 mg/m2 for pts > 60 y) on days 3-9, PO lomustine 60 mg/m2 (40 mg/m2 for pts > 60 y) on day 2. Six to nine intrathecal (IT) injections of MTX / cytarabine were included for pts with positive CSF cytology, tumor adjacent to ventricles, or per physician's decision. Rituximab was given for no more than 8 doses in total. A total of 3-4 courses of R-MPL were given. Responsive pts could proceed to autologous stem cell transplant (ASCT) with TECAM conditioning or 2 cycles of intermediate dose cytarabine (IDAC, 1.5 g/m2), 2 doses in each cycle. Those who achieved less than CR or had significant toxicity to R-MPL received additional ifosfamide/etoposide or high dose cytarabine or temazolamide or topotecan. Radiation was given only for salvage. Results: Fifty-two pts were included in the study. Median age was 62 years (range 28-94). Three (6%) had leptomeningeal involvement, thirteen (25%) had vitreoretinal involvement, 30 (58%) had involvement of the deep brain. Mean ECOG, IELSG and MSKCC scores were 1.98, 2.53 and 1.94 respectively. The median number of HDMTX doses was 8 (range 3-16). Forty-five (87%) pts completed at least one 42-day cycle of R-MPL. Among this group, 29 (64%) pts received at least 3 IT injections, 12 (27%) underwent ASCT, 10 (22%) received IDAC, and 7 (16%) received other chemotherapies. The median follow-up was 27 months (m) (range 0.4-140m). The overall response rate (ORR) was 79% (41/52), and the complete response (CR) rate was 52% (27/52). The median progression free survival (PFS) was 15.5m and the median overall survival (OS) was 27m. Among the 45 pts who received at least one R-MPL cycle, the ORR was 87% (39/45), the CR rate was 60% (27/45), the median PFS was 84m and the median OS was not reached (figure 1). Known prognostic factors correlated with OS: age (p<0.01), ECOG performance status (p<0.01), CSF protein (p=0.01) and IELSG/MSKCC scores (p=0.05/0.04). Patients who received at least 3 IT injections had a trend to longer PFS (32.4m Vs 19.2m, p=0.09), and a significant OS benefit (48.6m Vs 20.8m, p<0.01). In a multivariable model, the effect of IT injections was independent of age, sex and IELSG score, and attenuated by number of HDMTX doses. ASCT/IDAC did not improve PFS/OS, however numbers were small. Achieving CR at the end of treatment strongly correlated with PFS/OS, but timing of best response (after one 42-day cycle Vs later) did not. Grade 3-4 adverse events included infections (21%) and kidney injury (13%). Two pts died during therapy, both in the 1st cycle due to disease progression. Ten pts (19%) discontinued therapy due to toxicity. No treatment related mortality (TRM) was documented. Conclusions: The R-MPL protocol achieved a favorable ORR/PFS/OS as described, with reasonable grade 3-4 toxicity and no TRM. The advantage of ASCT/IDAC could not be assessed due to small number of pts. IT injections (at least 3) and achievement of CR at the end of treatment correlated with survival. The R-MPL protocol was reported in previous trials only among the elderly, and should further be evaluated in all age groups. Disclosures Goldschmidt: Abbvie Inc: Consultancy, Research Funding.

Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue Intraocular Involvement: Clinicopathologic Characteristics and the Treatment Outcome of Intravitreal Injection of Methotrexate

Background：Primary intraocular and periocular mucosa-associated lymphoid tissue lymphoma (MALT-lymphoma) was a rare type of non-Hodgkin lymphoma (NHL) with marked differences from other indolent B-cell lymphomas. Transformation to large-cell aggressive lymphomas could occur in a few cases. The initial therapeutic modality has not been fully established for the disease. Methotrexate (MTX), as the most efficient cytotoxic drug for patients with vitreoretinal involvement in primary intraocular lymphoma (PIOL), through intravitreal injection of MTX. Here we reported long-term activity and treatment outcomes of the MALT-lymphoma intraocular and periocular involvement. Patients and Methods: Adult patients with histologically/cytologically confirmed unilateral primary intraocular and periocular B-cell MALT-lymphoma at Beijing Tongren hospital were enrolled. Patients were randomly assigned 1:1 to receive intravitreal injection of MTX (IV-MTX group, 400 µg/0.1 ml) according to a standard Intensive-Consolidation-Maintenance regimen, or Wait-and-See management as a control group. Primary end points were progression-free-survival (PFS), best-corrected visual acuity (BCVA), clinical response to intravitreal chemotherapy, complications during the study period. Results: A total of 10 patients were enrolled (IV-MTX, n=5; Wait-and-See, n=5). Median follow-up was 5.5 years (QIR, 2.0-9.0 years). At the end follow-up, no death and systemic metastasis occurred in all patients. PSF at 5 years was excellent (70% and 80%, respectively) and did not differ between two groups. For the IV-MTX group, the BCVA was not obviously improved and the tumor tissues were unchanged clinically in size after a median 7 times of vitreous injection of MTX in all 5 eyes (P>0.05) and had lower rates of treatment-related complications. For the control group, one of five eyes had worsening BCVA and four remained stable. The volume of tumor tissue increased slowly, and the tumor basal and thickness increased 1.08±1.63 mm and 0.32±0.80 mm on average, respectively. Conclusions: According to our current sample size and the duration of follow-up, it suggests that no clinical benefit of IV-MTX has been found to primary intraocular and periocular MALT-lymphoma. The observing management for these patients with primary intraocular and periocular lymphoma of MALT-type was reasonable, with relatively excellent long-term outcomes. Funding Statement: The National Natural Science Foundation of China (Nr. 81272981), the Beijing Natural Science Foundation (Nr. 7151003), and the priming scientific research foundation for the junior research in Beijing Tongren Hospital Capital Medical University (2017-YJJ-ZZL-009) provided financial support. Declaration of Interests: All authors declare that they have no conflict of interest in this manuscript. Ethics Approval Statement: This study followed the tenets of the Declaration of Helsinki and its ethical standards of 1964. The study was approved by the Medical Ethics Committee of the Beijing Tongren Hospital, and written informed consent was obtained from all participants. All methods were performed in accordance with the relevant guidelines and regulations.

Résultats fonctionnels et facteurs pronostiques des traumatismes oculaires à globe ouvert avec acuité visuelle initiale à perception lumineuse négative

To analyse the clinical ocular characteristics and determine prognostic factors for functional recovery in eyes presenting with no light perception (NLP) after open globe ocular trauma. In this retrospective study were included all the patients with no light perception after open globe trauma who presented to Amiens University Hospital between October 2014and June 2018. Fifteen eyes of 15patients were included in this study. The main mechanism of the trauma was globe rupture (80%, n=12). The most common location was zone III (66%, n=10). The wound size was greater than 10mm in 9patients (60%). The ocular lesions included expulsion of the crystalline lens or posterior chamber intraocular lens, hyphema, retinal detachment, vitreous hemorrhage and ciliochoroidal lesions. Damage to the ciliary body was a negative prognostic factor for functional recovery (P=0.04). Nine patients remained with no light perception, whereas 6patients experienced an improvement in visual acuity (2.3logMAR in 3patients, 0.7logMAR in 1patient, 0.4logMAR in 1patient and 0.2logMAR in 1patient). These 6patients had undergone posterior vitrectomy due to vitreoretinal involvement (P<0.001). In the case of open globe trauma with no light perception on presentation, a functional recovery is possible if there is no irreversible anatomical damage.

Primary Ocular Lymphoma: A SEER Database Analysis of Patterns of Involvement and Outcomes

BACKGROUND: Malignant lymphomatous involvement of the eye and its surrounding structures is a rare phenomenon. Due to the unique location, non-specific symptomatology, limitations for invasive procedures, physician experience, and significant effect on the quality of life related to vision, it poses many challenges in the diagnosis and management. Ocular involvement can be primary or secondary in lymphoma. Primary ocular lymphoma, based on its clinical and pathological characteristics, has been divided into 2 main groups: those involving the orbit and adnexal tissues including lacrimal gland, conjunctiva and cornea and, those affecting intra-ocular structures mainly vitreous and retina. We aim to evaluate the SEER database to assess patterns and outcomes in patients with primary ocular involvement with lymphoma. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients (≥18 years) diagnosed with primary ocular lymphomas between 1975 and 2016. B-cell and T-cell lymphomas with stage I disease and primary site labeled as ocular (orbital, retina, conjunctiva, cornea, choroid, ciliary, lacrimal gland) were included. Treatment effect (surgery, radiation, systemic therapy) was analyzed when available.Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the Log-Rank test. Cox proportional hazards models were used for adjusted survival analyses. RESULTS: We identified 3610 patients with primary lymphoma of the eye and adnexa. The median age was 66 years (18-103). 70% of the patients were Caucasians, followed by Hispanic (10%). Slight female preponderance was noted (55%). Most common site of involvement was orbit (n = 2063; 57%) followed by conjunctiva (n = 986; 27.3%). 8% (n = 292) of the patients were noted to have bilateral involvement. MALT (n = 2208; 61.2%) was the most common histology followed by DLBCL (n = 576; 16%) and follicular lymphoma (n = 519; 14.4%). Other histologies were rare (see Table 1). Most common treatment modality was radiation (n = 2117; 58.6%). Systemic therapy was utilized in only about 25% of the patients. Radiation treatment was associated with improved survival HR = 0.44 (0.23-0.83 95%CI, p = 0.01). Interestingly, patients that received systemic therapy had worse survival in univariate analysis (p&lt;0.05) but was not significant in multivariate analysis. Site-specific survival suggested conjunctiva had the best median OS (19 years [16.3 - 21.7 95% CI]), followed by orbital and lacrimal gland involvement (median OS 12 years [10.92-13.23 95% CI]) - Figure 1. Retina (median OS 1.9 years) and choroid/ ciliary body (median OS 6.3 years) involvement were associated with shorter survival (p&lt;0.05). DISCUSSION: Ocular lymphoma is a rare occurrence. Overall MALT was the most common subtype followed by DLBCL and FL. Very few instances of Burkitt's lymphoma, T-cell, and CLL were identified. Site-specific data in our subset, albeit with low numbers, suggest worse survival in the ciliary body and choroid similar to what is seen within vitreoretinal involvement. Due to small numbers in our subset, this requires confirmation in a larger dataset to identify potential change in management similar to primary vitreoretinal lymphoma, which is now recognized and managed as primary CNS lymphoma. Patients receiving systemic therapy showed a trend towards worse survival, which may be explained by a selection bias for more aggressive disease. Our study highlights the small but relevant prevalence of primary ocular lymphomas and reports the interesting observation of different survival patterns based on the site of involvement. Disclosures Yazbeck: Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

B-scan ultrasound and cytology of the vitreous in primary central nervous system lymphoma with vitreoretinal involvement.

To evaluate the diagnostic value of B-scan ultrasound and explore the cytological characteristics of patients with vitreoretinal lymphoma (VRL) and primary central nervous system lymphoma (PCNSL). The clinical data and pathologic specimens from patients with VRL diagnosed at the North Huashan Hospital from 2016 to 2017 were retrospectively reviewed. The patients were diagnosed by slit lamp ophthalmoscopy, B-scan ultrasound, cytology of the vitreous, which was obtained by vitrectomy, and cytokine measurements of interleukin (IL)-10 and IL-6. Twenty-six eyes (19.4%) out of 134 eyes of 67 patients (47 men and 20 women) with PCNSL were diagnosed with VRL by B-scan ultrasound, and 14 eyes (10.4%) were diagnosed by slit lamp ophthalmoscopy. Twenty-four eyes (17.9%) of 17 patients were confirmed as having VRL with cytology. No difference in the association between intracranial lesion location and ocular involvement was found. VRL patients had higher levels of vitreous IL-10 and IL-10/IL-6 when compared with macular hole cases, but the difference was not statistically significant. A total of 25.4% of the PCNSL patients had VRL, B-scan ultrasound examination had characteristic features and is recommended over slit lamp ophthalmoscopy for the screening diagnosis of PCNSL with intraocular involvement. Moreover, the cytological and immunohistochemical analyses performed after 25-gauge diagnostic vitrectomy were accurate diagnostic techniques.

Incidence, clinical profile, and short-term outcomes of post-traumatic glaucoma in pediatric eyes.

Purpose:To report the incidence, modes of injury, treatment, and short-term outcomes in eyes with post-traumatic elevated intraocular pressure (IOP).Methods:This was a 5-year hospital-based retrospective study of children ≤16 years who presented with open (OGI) or closed globe injury (CGI) and developed elevated IOP >21 mmHg. Those with a minimum follow up of 3 months were included. Analysis of various parameters such as influence of demographics, mode of injury, IOP, best-corrected visual acuity (BCVA), and effect of medical and surgical treatment on IOP and BCVA was done.Results:Out of 205 pediatric eyes with ocular trauma, 121 (59%) had CGI and the remaining 84 (41%) had OGI. Thirty-two eyes (15.6%) developed elevated IOP. The incidence of elevated IOP following CGI [25 eyes (20.6%)] was significantly higher than that following OGI [7 eyes (8.3%, P = 0.02)]. Hyphema (37.5%) and lens-related mechanisms (18.75%) were the most common causes of elevated IOP. The mean IOP at the time of diagnosis was 29.8 + 6.3 mmHg and reduced to 16.2 ± 2.2 mmHg at last follow up (P < 0.001). Surgical management was required in 12 eyes (37%) and significantly more eyes with CGI required trabeculectomy (24% in CGI vs. 0% in OGI, P = 0.03). Poor baseline vision and vitreoretinal involvement [0.67 line decrement, 95% confidence interval (CI) =0.1–1.25 lines, P = 0.025] increased risk of poor visual outcome.Conclusion:Post-traumatic IOP elevation occurred in 15% pediatric eyes, was more common with CGI compared to OGI and nearly one-fourth of eyes with CGI required glaucoma filtering surgery for IOP control. Overall, medical management was needed in 63% eyes and 37% required surgical management. Visual acuity was poor in eyes with OGI due to posterior segment involvement.

Multimodal imaging of retinal metastasis masquerading as an acute retinal necrosis

BackgroundTo report the multimodal imaging and histology of a case of metastatic esophageal cancer with vitreoretinal involvement resembling acute retinal necrosis (ARN) in a patient receiving systemic chemotherapy.Case presentationA 69-year-old Japanese man with a history of stage 4 esophageal carcinoma, treated with three cycles of 5-fluorouracil (5-FU) and cisplatin (CDDP) chemotherapy as well as 30 sessions of radiation therapy, presented with new onset of blurry vision in the right eye (OD). Visual acuity was 20/200 OD. Fundus examination OD revealed 2+ nuclear cataract, veil-like vitreous opacity, a tractional retinal detachment, and white retinal lesions in the macula and periphery masquerading as an ARN. Due to the poor view and uncertainty regarding diagnosis, combined cataract extraction and 25 gauge pars plana vitrectomy was performed. Polymerase chain reaction and cytologic analysis were performed on the vitreous samples, which was negative for all infectious entities but positive for poorly differentiated malignant cells. The vitreous biopsy was consistent with the primary endoscopic esophageal biopsy. Ultra-wide view fundus imaging revealed multifocal white intraretinal lesions in the macula and periphery. Optical coherence tomography through these white opacities displayed hyper-reflective inner retinal lesions with no choroidal involvement, suggestive of retinal metastasis. Observation and palliative support was continued until the patient passed away 3 months after diagnosis.ConclusionRetinal metastasis may mimic infectious syndromes such as ARN and are associated with a very poor prognosis. Outside of the retina, no further central nervous system metastasis was found. 5-FU is known to cross the blood–brain-barrier but may be inadequate in preventing retinal metastasis.

Combined treatment of primary vitreoretinal lymphomas significantly prolongs the time to first relapse

BackgroundVitreoretinal lymphomas belong to the family of central nervous system (CNS) lymphomas. The optimal approach for the treatment of isolated primary vitreoretinal lymphoma is unclear because of the lack of...

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

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

Vitreoretinal Presentation of Secondary Large B-Cell Lymphoma in Patients With Systemic Lymphoma

Intraocular lymphomas represent a diverse group of hematologic malignant neoplasms involving different tissues within the eye. Predominant involvement of the retina and vitreous without uveal infiltration in systemic lymphoma, mimicking a primary vitreoretinal lymphoma, is extremely rare. Our study emphasizes the importance of systemic evaluation in addition to central nervous system evaluation in all patients with newly diagnosed vitreoretinal lymphoma. To determine the incidence of secondary intraocular lymphoma presenting as vitreoretinal infiltrates without central nervous system involvement, mimicking primary vitreoretinal lymphoma in patients with systemic lymphoma. DESIGN Retrospective review of all vitreous aspiration biopsy samples acquired because malignant neoplasm was suspected clinically that were obtained at our institution from January 1, 2000, through December 31, 2010. Review included patient clinical history, radiographic study findings, cytologic and/or histologic preparations, immunophenotypic study findings, treatment, and outcomes. SETTING Mayo Clinic pathology database. Fifty-five patients with vitreous specimens available for review. Vitreous aspiration biopsy. Confirmation of the diagnosis of diffuse large B-cell lymphoma (DLBCL). Of the 55 patients with vitreous specimens available for review, 3 (5%) had a DLBCL infiltration in the vitreous without any central nervous system involvement as a manifestation of systemic lymphoma. All 3 patients were men, aged 54, 66, and 73 years, and had blurred vision and floaters for several weeks before undergoing diagnostic vitrectomy. Ophthalmic examinations revealed clumps of vitreous cells but no choroidal involvement. One patient had no history of lymphoma; the diagnosis of vitreoretinal lymphoma was followed by DLBCL after a lymph node biopsy. The other 2 patients had low-grade B-cell lymphoma and chronic lymphocytic leukemia for 29 and 7 months before large-cell transformation in the eye. Patients were treated with systemic chemotherapy plus intraocular injections of rituximab or methotrexate sodium. Vitreoretinal symptoms of DLBCL in patients with systemic lymphoma may be more frequent than previously thought (5% in our study). Not all lymphomas with vitreoretinal involvement represent primary intraocular lymphomas; thorough ophthalmologic evaluation in patients with visual symptoms and complete staging in patients with documented ocular lymphoma are of utmost importance.

Intravitreal methotrexate for treating vitreoretinal lymphoma: 10 years of experience

Aim:To describe our experience in treating vitreoretinal involvement of primary central nervous system lymphoma, by intravitreal injections of methotrexate (MTX).Methods:Patients with suspected intraocular lymphoma underwent a diagnostic vitrectomy. Samples were...

Using intravitreal methotrexate for treating vitreoretinal lymphoma

Abstract Purpose: Vitreoretinal involvement occurs in approximately one‐quarter of patients with primary CNS lymphoma (PCNSL), and in some patients with systemic lymphoma who may later develop CNS lymphoma. The traditional method for treating vitreoretinal lymphoma, which is the common type of intraocular lymphoma, is by external beam radiation, or intravenous or intrathecal chemotherapy; however, recurrences are common. We describe our ten years of experience in treating vitreoretinal involvement of PCNSL by intravitreal injections of methotrexate (MTX). Methods: Biopsy‐proven vitreoretinal lymphoma has been treated by intravitreal injections of 400 μg/ml methotrexate. According to our protocol, injections are administered twice weekly for 4 weeks, once weekly for 8 weeks, and then once monthly for 9 months for a total of 25 injections. Results: Forty‐four eyes of 26 patients have been treated; 7 patients had monocular involvement and 19 binocular. Twenty‐three patients had B‐cell lymphoma and 3 patients had T‐cell lymphoma. In all patients remission of the intraocular lymphoma was achieved after 6.1 + 3.5 injections (range 2 – 16 injections). None of the patients had an intraocular recurrence. Among the side effects, the most common were conjunctival hyperemia and corneal epitheliopathy, which usually subsided when the interval between the injections increased. Conclusions: In our experience, treatment by intravitreal injections of methotrexate provides complete remission of vitreoretinal lymphoma with, so far, no recurrences and with bearable side effects, and can be considered as alternative treatment to radiotherapy and systemic or intrathecal chemotherapy.