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Immune checkpoint inhibitors and targeted therapies are two classes of pharmacologic therapies used to treat metastatic malignancy by amplifying the immune system activity against cancerous cells. However, these drugs can consequently cause immune-related adverse events (irAEs). Albeit rare, cases of ocular IRAEs occurring among patients taking these drugs have been documented in literature, including a spectrum of uveitis findings. The classes of immune checkpoint inhibitors explored here include anti-CTLA4 (ipilimumab), anti-PD-1 (pembrolizumab, nivolumab) and anti-PDL-1 (atezolizumab, avelumab, durvalumab). Targeted therapies include the MEK inhibitors (trametinib) and BRAF enzyme inhibitors (dabrafenib, vemurafenib), both of which are involved in the MAPK/ERK signaling pathway responsible for cell proliferation. Reported cases of ocular irAEs caused by these drugs include anterior uveitis, posterior uveitis, panuveitis, and Vogt-Koyanagi-Harada (VKH)-like syndrome. Treatment can be determined on a case-by-case basis and depending on the severity of the irAE, may include temporary cessation of the offending drug, local corticosteroids, or systemic corticosteroids. Although the mechanism by which these ocular toxicities occur is not clearly elucidated, it is hypothesized that they are secondary to increased activity of auto-reactive T-cells. Further investigation into mechanisms underlying these inflammatory findings are relevant for cancer targeting, as well as insights into ocular autoimmune diseases.

The differential diagnosis of patient with uveitis may be complex depending on the presenting clinical symptoms and signs. Based on the clinical features, both infectious and noninfectious causes should be considered. While treatment with corticosteroids either via local or systemic administration may be appealing for many patients with active inflammation, ruling out an infectious process is essential to avoid exacerbation of infectious uveitis in some patients. Viral causes of anterior uveitis and posterior uveitis must be considered in the differential diagnosis prior to initiation of therapy. The following is an overview of viral entities that should be considered when evaluating patients with uveitis.

The identification of an infectious or noninfectious uveitis syndrome is important to determine the range of therapeutic and prognostic implications of that disease entity. Diagnostic dilemmas arise with atypical history, atypical clinical presentations, inconclusive diagnostic workup, and persistent or worsened inflammation despite appropriate immunosuppression. More invasive intraocular testing is indicated in these situations particularly in infectious uveitis where a delay in treatment may result in worsening of the patient’s disease and a poor visual outcome. Laboratory analysis of vitreous fluid via diagnostic pars plana vitrectomy is an important technique in the diagnostic armamentarium, but the most important aspects of sample collection include rapid processing, close coordination with an ophthalmic pathology laboratory, and directed testing on this limited collected sample. Culture and staining has utility in bacterial, fungal, and nocardial infection. Polymerase chain reaction (PCR) analysis has shown promising results for bacterial endophthalmitis and infection with mycobacterium tuberculosis whereas PCR testing for viral retinitides and ocular toxoplasmosis has a more established role. Antibody testing is appropriate for toxoplasmosis and toxocariasis, and may be complementary to PCR for viral retinitis. Masquerade syndromes represent neoplastic conditions that clinically appear as infectious or inflammatory conditions and should be considered as part of the differential diagnosis. Diagnostic vitrectomy and chorioretinal biopsy are thus critical tools for the management of patients in whom an infectious etiology of uveitis is suspected.

Acute retinal necrosis is a viral syndrome characterized by a panuveitis with necrotizing retinitis that may be complicated by retinal detachment, vaso-occlusion, optic neuropathy, and other causes of decreased visual acuity. Polymerase chain reaction testing provides a rapid and sensitive method of identifying the viral etiology of acute retinal necrosis, which is most commonly caused by herpes simplex virus type 1, herpes simplex virus type 2, and varicella zoster virus. Prompt diagnosis and treatment is paramount to prevent further vision loss. We review the management of acute retinal necrosis including systemic, local intravitreal, and combination antiviral medications. We also discuss the appropriate and inappropriate use of corticosteroids, laser retinopexy, surgical therapy, and other adjunctive measures.