Artificial Intelligence Assisted Eye Care

Shail Vasavada, MD; Samaresh Srivastava, MD; Ashok Puri, MD; Vaishali Vasavada, MD; and Abhay Vasavada, MD

Eyetube

The Benefits of a “Boring” Day

Paul Walton, MD; Blake Williamson, MD, MPH; and Gary Wörtz, MD

Eyetube

Paul Walton, MD, joins Blake Williamson, MD, MPH, and Gary Wörtz, MD, to share concepts to help cataract and refractive surgeons avoid horror stories in the OR. He says the goal should always be to have a “boring” day, emphasizing the importance of communication and understanding with patients. The surgeons also detail their approaches to anesthesia and how to best comfort patients before, during, or after surgery.

Ocular Effects of CAR-T Cell Therapy

Know the risks and potential therapeutic benefits associated with this treatment modality.

Lars H. Andersen, MD; Jaskirat S. Takhar, MD; and Jose J. Echegaray, MD

Retina Today

The advent of chimeric antigen receptor-T (CAR-T) cell therapy in the late 2010s heralded a new era in the treatment of hematologic malignancies and provided new hope in refractory cases. To date, the FDA has approved CAR-T cell class therapies for B-cell acute lymphoblastic leukemia (B-ALL), B-cell non-Hodgkin lymphoma, mantle cell lymphoma, and multiple myeloma.1-5 Leukemia can affect nearly any structure of the eye either due to direct tissue infiltration or, more commonly, secondary to anemia, thrombocytopenia, blood hyperviscosity, or immunosuppression.6,7 Treatment options for ocular disease in the setting of systemic leukemia include systemic chemotherapy, intrathecal chemotherapy, radiotherapy, and bone marrow transplantation.7 In cases of isolated ocular disease, intravitreal methotrexate and adjunct intrathecal chemotherapy are alternative management options.8 ABOUT CAR-T CELLS CAR-T cells are manufactured from autologous T-cells that have been isolated and genetically modified to express cancer-specific antigen recognition domains on their cell surface.9,10 This is typically achieved via DNA transfection or transduction via a viral vector into an isolated T-cell population to express CAR-T molecules.10 These consist of an extracellular domain, an attached transmembrane domain, and an intracellular domain.10 An effector cellular response can be activated by these CAR-T cells in response to malignant cells expressing specific antigens independent of major histocompatibility complexes, which may be downregulated by malignant cells.11 The process of manufacturing CAR-T cells takes 2 to 5 weeks, and patients are lymphodepleted prior to the readministration.12,13 The effects of CAR-T cell agents on the eye, both therapeutic and deleterious, have been increasingly described in the literature since the initial approval of tisagenlecleucel (Kymriah, Novartis) in 2017. Herein, we present a review of the ocular therapeutic benefits and adverse effects related to CAR-T cell therapies. THERAPEUTIC POTENTIAL While the systemic benefits of CAR-T cell therapy are promising, comparatively little is known about the efficacy of CAR-T cell therapy in cases of ocular involvement of hematologic malignancy or in primary malignancies arising in the eye. Prospective studies remain limited due to the infrequency of primary ocular malignancy compared with systemic malignancy. Preclinical investigations have determined a possible role for CAR-T cell therapy in the treatment of retinoblastoma; in one study, use of chimeric receptors against CD171 and GD2 resulted in destruction of nearly all retinoblastoma lines in vitro.14 In addition, in vitro assays and mouse models of uveal melanoma have shown promising responses to CAR-T cell agents targeted to HER2.15 A key determinant in the efficacy of CAR-T cell therapy for ocular disease is its ability to penetrate the blood-aqueous and blood-retina barriers. There is single-case evidence demonstrating cytology-proven anterior chamber CAR-T infiltration in a 2-year-old patient treated for combined central nervous system relapse of B-ALL.16 In addition, promising clinical results have been reported with use of tisagenlecleucel in conjunction with radiotherapy for isolated ocular relapse of B-ALL in a 21-year-old patient.17 Another case involved a 61-year-old patient with intravascular lymphoma presenting with a primary vitreoretinal lymphomatous-like lesion. This patient experienced mild benefit from local intravitreal methotrexate, rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone, and systemic high-dose methotrexate therapy, but, thereafter, responded more robustly to CAR-T cell therapy with resolution of the retinal lesion.18 A recent patient of ours with relapsing ALL (Figure 1) also responded to CD19-targeted CAR-T cell therapy with complete resolution (Figure 2). Figure 1. Ocular recurrence of acute lymphoblastic leukemia with pseudohypopyon, iris neovascularization, and nodularity.