Check for Checkpoint Therapy

If you’ve kept an eye on the oncology field, you’ll know that checkpoint therapies are shaking it up. These drugs intercede key interactions between immune cells and their environment, facilitating a vigorous immune response. For example, PD-1 antibodies block inhibitory ligand interactions with the PD-1 receptor on T cells, keeping the cellular arm of the immune system stimulated. In oncology, this matters: firstly, because the immune system is far more effective at clearing disseminated disease than any drug; and secondly, because tumors are adept at usurping mechanisms of immune inhibition (many tumors express PD-1 ligand to depress T-cell function).

But therapies that turbocharge the immune system can also have some off-target consequences; some immunotherapy patients develop inflammation of the skin, endocrine or gastrointestinal systems. Might some adverse effects manifest in the eye? It seems so: a team from the University of Michigan Kellogg Eye Centre, Ann Arbor, MI, USA, have reported three cases where significant ocular symptoms were associated with checkpoint inhibitor therapy (1). Hakan Demirci, corresponding author on the paper, said: “We noticed large uveal effusions. In addition, there was anterior chamber inflammation in two of our patients” (2). And the uveal effusions happened suspiciously quickly: one to three months after commencing treatment, according to Merina Thomas, senior vitreoretinal fellow at Kellogg Eye Center and first author on the paper (2). Furthermore, in the two patients who discontinued therapy, the effusion resolved within 12 weeks; in the patient who continued the therapy, it persisted. So what did these three cases actually look like? 

Case 1: Visual acuity (VA) at presentation, 20/25 OD and 20/150 OS; exudative retinal detachment and retinal hemorrhage apparent on fundus exam; 360° serous choroidal detachment visible by B-scan ultrasonography; and subretinal fluid visible by SD-OCT. Discontinuation of checkpoint therapy resulted in visual improvement (20/40 OS), and complete resolution of choroidal effusion and subretinal fluid.

Case 2: VA at presentation, 20/100 OD and 20/40 OS; elevated IOP (38 mmHg OD and 53 mmHg OS), and 360° annular serous choroidal detachment on fundus exam and B-scan ultrasonography. Discontinuation of checkpoint therapy resulted in improvements in choroidal detachment; decreased IOP (15 mmHg OD, 25 mmHg OS); and improved vision (20/60 OD, 20/30 OS).

Case 3: VA at presentation, 20/20 OD and 20/200 OS; periorbital swelling of left eye; serous choroidal detachment visible by fundus exam; and bullous choroidal detachment visible by B-scan ultrasonography. This patient continued therapy.

The upshot? Although ocular toxicities are relatively uncommon in checkpoint therapy, the authors point out that high levels of PD-1 ligand are found in many ocular tissues, and recommend that: “ocular toxicity, including uveal effusion, should be considered when evaluating patients taking PD-1 checkpoint inhibitors” (1).