Molecular profiling of vitreous fluid by massively parallel sequencing: a case series.

INTRODUCTION: In cases of suspected intraocular malignancy, vitreous may be the preferred pathologic sample; however, cellularity may be insufficient for definitive cytopathological diagnosis. Ancillary methodology to study vitreous fluid aspiration for mutational analysis may assist in treatment decisions. MATERIALS AND METHODS: Three individual patient vitreous humor samples were received in the laboratory for mutation testing. The samples were collected during standard of care and analyzed for routine cytopathology. In each case, cytopathology was inconclusive and mutational analyses to support diagnostic suspicions were clinically requested. Based on the clinically and pathologically suspected diagnoses, an appropriate massively parallel sequencing assay previously validated for clinical use was performed using DNA extracted from vitreous samples that had previously undergone various processing. Nucleic acid yield was assessed by fluorometric or spectrophotometric methods, with yield ranging from 2.7 to 86.5 ng. Library preparations were performed using standard laboratory protocols. RESULTS: Two of the cases were suspicious for melanoma and a 50-gene solid tumor panel was performed. The third case was worrisome for vitreoretinal lymphoma and a 49-gene myeloid panel was performed. CONCLUSIONS: In all cases, the molecular profiling assisted with the clinical assessment and/or management of each patient.

Tumor Control and Visual Acuity Outcomes in Vitreoretinal Lymphoma with and without Sub-Retinal Pigment Epithelium Infiltration: Analysis of 125 Eyes of 70 Patients at a Single Ocular Oncology Center.

PURPOSE: To investigate outcomes in vitreoretinal lymphoma (VRL) presenting with or without sub-retinal pigment epithelial (sub-RPE) infiltration. DESIGN: Retrospective, comparative analysis. SUBJECTS: Patients with VRL at a single center from January 1, 1984, through July 30, 2018. METHODS: Record review was conducted for clinical features, treatments, and outcomes of tumor control, visual acuity (VA), and death. MAIN OUTCOME MEASURES: Ocular tumor control and VA outcome. RESULTS: The study involved 168 eyes of 95 patients with VRL, of which 45 (27%) eyes of 32 patients had sub-RPE infiltration. Comparison (of patients with vs. without sub-RPE infiltration) showed similar presenting features of mean patient age (65 vs. 68 years, P = 0.30), percentage of males (53% vs. 56%, P = 0.83), white race (84% vs. 87%, P = 0.77), bilateral ocular involvement (78% vs. 75%, P = 0.80), and VA of 20/40 or better (40% vs. 50%, P = 0.30), 20/50 to 20/200 (42% vs. 31%, P = 0.20), or worse than 20/200 (18% vs. 19%, P = 0.99). Lymphoma subtype was diffuse large B cell (59% vs. 52%) or unspecified (41% vs. 44%, P = 0.85). Follow-up data were available for 125 eyes of 70 patients. Overall treatment included systemic chemotherapy (53% vs. 64%, P = 0.29), intravitreal chemotherapy (59% vs. 28%, P = 0.005), and external beam radiotherapy (59% vs. 94%, P < 0.001). Initial ocular tumor control occurred (91% vs. 94%, P = 0.68) with subsequent recurrence (35% vs. 17%, P = 0.07). Outcomes at final follow-up (mean 24 vs. 25 months, P = 0.82) revealed ocular tumor complete regression (68% vs. 86%, P = 0.03), partial regression (3% vs. 7%, P = 0.44), or active persistent or recurrent disease (29% vs. 7%, P = 0.002). Final VA was 20/40 or better (39% vs. 53%, P = 0.18), 20/50 to 20/200 (26% vs. 34%, P = 0.53), or worse than 20/200 (34% vs. 13%, P = 0.007). Vitreoretinal lymphoma was associated with central nervous system lymphoma (41% vs. 59%, P = 0.13) or systemic lymphoma (16% vs. 21%, P = 0.60). Death occurred (63% vs. 54%, P = 0.51) at mean age (69 vs. 69 years, P = 0.94). CONCLUSION: Sub-RPE infiltration in VRL is associated with more persistent or recurrent ocular tumor and poorer VA outcome, but no difference in frequency of central nervous system/systemic lymphoma or death. Further studies are required to determine whether earlier, more aggressive, or prolonged ocular therapy for patients with VRL presenting with sub-RPE infiltration could improve these factors.

[Radiotherapy of primary intraocular lymphoma associated with primary central nervous system lymphoma]. / Radioterapiya pervichnykh intraokulyarnykh limfom, assotsiirovannykh s pervichnoi limfomoi tsentral'noi nervnoi sistemy.

AIM: The aim of the study was to define indications for stereotactic radiotherapy (SRT) of primary intraocular lymphoma (PIOL) and to evaluate the SRT efficacy and toxicity level. MATERIAL AND METHODS: Twelve immunocompetent patients with PIOL associated with primary CNS lymphoma underwent SRT of the affected eye/both eyes area. Three patients underwent repeated SRT due to PIOL recurrence. RESULTS: An improvement in visual acuity occurred in 6 patients. No changes in the visual function were observed in patients with high visual acuity, patients with amaurosis, and patients with concomitant eye diseases. Tumoral infiltration of the vitreous body resolved/decreased in all patients, except one case with retinal PIOL. PIOL recurrence developed in 6 patients. The disease-free period ranged from 1 to 24 months. The development/progression of cataract was found in 2 patients. Temporary radiation epidermitis occurred in 7 patients. Three patients developed ocular hypertension. One patient had lower eyelid ectropion. CONCLUSION: SRT is indicated for PIOL recurrence after intravitreal methotrexate injections, and in the case when local chemotherapy can not be used. In the case of combined injury to the brain and eyes, it is recommended that planned whole brain irradiation to involve the eyeball area. Local SRT is recommended if lymphoma locally affects the eye (or both eyes) without involvement of the brain. PIOL radiotherapy enables achieving persistent local disease control with minimal toxicity manifestations.

Acute and late toxicity of bilateral orbital irradiation in the management of primary intraocular lymphoma.

Primary intraocular lymphoma (PIOL) is a rare malignancy with poor outcomes. Concerns regarding toxicity lead some clinicians to exclude orbital radiation therapy (RT). We aimed to quantify the ocular toxicity of RT in 11 PIOL patients treated with chemoimmunotherapy and bilateral orbital RT (median 36 Gy). A multidisciplinary team, including an ocular oncologist, followed patients for a median of 42 months after RT. Common adverse events included dermatitis (100%), conjunctivitis (82%), xerophthalmia (64%), and keratopathy (45%). All phakic eyes developed cataracts (100%); correction resulted in good vision recovery. New, visually significant retinopathy was observed in only one eye (<5%) and affected a patient with preexisting diabetes. This report suggests that severe, vision-threatening complications following orbital RT are uncommon. In the absence of comorbidities, orbital RT should not be withheld due to fear of vision-threatening toxicity. The risk of toxicity may be augmented by comorbidities, so an individualized approach is recommended.