Local therapy for cancer therapy-associated uveitis: a case series and review of the literature

Abstract

Background/aimsImmunotherapy and targeted therapy for metastatic cancer may cause immune-related adverse events (irAEs) such as uveitis. If irAEs are severe or require systemic steroids, cancer therapy is often held or discontinued. Local steroid therapy for cancer therapy-associated uveitis allows the continuation of cancer therapy. This series demonstrates successful management of cancer therapy-associated uveitis with local therapy based on uveitis subtype.MethodsThis is an Institutional Review Board-approved retrospective case series of patients with uveitis secondary to immunotherapy or targeted therapy managed with local treatment, and focused literature review.ResultsFive patients (median age: 54, range 31 to 75) were included. Time to uveitis onset following cancer therapy initiation was 3 to 12 months. All patients received checkpoint inhibitor therapy; one patient additionally received targeted therapy. Two patients presented with anterior uveitis, two with panuveitis and one with posterior uveitis. Four of five patients demonstrated evidence of posterior segment inflammation on multimodal imaging. Anterior uveitis was successfully treated with topical prednisolone acetate 1% (PA 1%) alone, and posterior segment involvement recalcitrant to topical PA 1% was treated successfully with topical difluprednate, intravitreal triamcinolone acetonide or a combination. Patients with isolated anterior uveitis did not require maintenance topical therapy; those with posterior and panuveitis required chronic low-dose topical therapy.ConclusionBased on our series as well as the existing literature demonstrating the use of local therapy for irAEs, we propose an approach to local therapy for cancer therapy-associated uveitis starting with topical steroids and initiating injectable steroids in cases of recalcitrant panuveitis or posterior uveitis. Subclinical inflammation on posterior segment imaging responds robustly to difluprednate or intravitreal steroid therapy, and patients with posterior segment involvement may require more aggressive management and long-term maintenance.

Ocular adverse events associated with immune checkpoint inhibitors: a novel multidisciplinary management algorithm

“…This can be challenging, because the ocular symptoms experienced may not directly correlate with the severity of inflammation identified. 14 Even so, in most of the case series published to date, the overwhelming majority of patients experiencing ocular irAEs have had their CPIs discontinued, 12,13 and uncertainty exists whether this line of action may impact overall treatment outcomes.…”

Ocular adverse events in PD-1 and PD-L1 inhibitors

“…Excluding trials that do not report lower grade adverse events to the routine adverse event database results in a higher end estimate of 242/3255 patients on study treatment arms reporting ocular adverse events (7.4% prevalence). Ocular events occurred early after drug initiation (routine database: median 6 weeks, IQR 0-16, serious adverse events database: median 11 weeks, IQR [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21]. The median Common Terminology Criteria for Adverse Events grade was grade 1 (mild) (IQR 1-2) and grade 2 (moderate) (IQR 2-3) for the routine database and the serious adverse events database, respectively.…”

“…3 PD-1/PD-L1 inhibitor-associated adverse events (AEs) in the eye are also known to occur, but are rare and therefore less wellstudied. Case reports, case series, safety analyses, and some observational studies have shown that these drugs can cause inflammatory eye disease, such as uveitis, [3][4][5][6][7][8][9] scleritis, 8 dry eye syndrome, 4 5 9 10 optic neuropathy 9 and orbital myopathy. 11 Additionally, ipilimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) checkpoint inhibitor in a similar class as PD-1/PD-L1 inhibitors, has been documented to cause potentially blinding conditions such as optic neuropathy, 12 13 orbital inflammation, 14 15 ophthalmopathy, 16 and orbital apex syndrome.…”

Atezolizumab-induced bilateral anterior uveitis: A case report

“… 17 Another study by Venkat et al reported a woman who had inflammatory superior limbic keratitis and subsequent bilateral posterior uveitis. 18 Fang et al also reported 3 cases of unspecified “eye inflammation” and 1 case of “uveitis”. 4 In our case, however, anterior segment inflammation was found in both eyes of the patient.…”