Diagnostic Challenges in PD-1 Inhibitor Induced Panuveitis in a Teenage Girl with Chest Soft Tissue Sarcoma - A Case Report.

PURPOSE: To report a case of programmed cell death receptor-1 (PD-1) inhibitor induced panuveitis. METHOD: Observational case report of a 13-year-old Chinese girl presented as panuveitis. The clinical course, imaging performance, laboratory examination, differential diagnosis, treatment and prognosis were described. RESULT: Patient presented with bilateral anterior granulomatous uveitis, vitritis, papillitis, and various creamy yellow nodular lesions in the mid-peripheral fundus. She had a history of biopsy proven alveolar soft tissue sarcoma on the chest wall and pulmonary metastasis, and a PD-1 inhibitor (sintilimab) was intravenously administered. Blood tests, magnetic resonance imaging of the cranium and the orbit, aqueous humor assay of inflammatory cytokines and microbial DNA were performed to distinguish infectious and non-infectious uveitis, choroidal metastases, and intravenous injection-related endophthalmitis. The oncologist evaluated that the sarcoma was stable and terminated sintilimab dosage. After sintilimab withdrawal, the blurred vision improved. Then, the patient received oral corticosteroids, resulted in resolution of the panuveitis. A diagnosis of PD-1 inhibitor induced panuveitis was made. CONCLUSION: For patients taking PD-1 inhibitors, the major diagnostic challenge is to identify whether the cause of the uveitis is due to the antitumor treatment or not. It is suggested to be screened by eye care specialist and timely referral to uveitis specialist with any suspicion of intraocular inflammation for these patients.

SYPHILITIC OUTER RETINOPATHY: A MASQUERADING DIAGNOSIS REVEALED AFTER STEROID-INDUCED PROGRESSION TO PANUVEITIS.

PURPOSE: To report a case of syphilitic outer retinopathy revealed after progression to panuveitis after a course of oral steroids for suspected poison ivy. METHODS: Retrospective case report. RESULTS: A 44-year-old diabetic man presented with progressive symptoms of nyctalopia and color vision changes associated with outer retinal disruption on macular imaging but minimal evidence of intraocular inflammation on examination. A short course of oral steroids for an unrelated skin condition induced rapid progression to frank panuveitis with retinal vascular sheathing and retinal whitening. Systemic workup identified syphilis as the etiology. The patient's visual symptoms and disruption of the photoreceptor and retinal pigment epithelial layers on OCT improved after treatment with IV penicillin. CONCLUSION: Syphilitic outer retinopathy represents an unusual manifestation of ocular syphilis that can present with minimal examination findings. We present here a case of oral steroid use resulting in the progression of syphilitic outer retinopathy to a more fulminant form of syphilitic uveitis that ultimately revealed the correct diagnosis and prompted the correct intervention. This case highlights the importance of maintaining a high level of suspicion for this treatable condition.

Bilateral Panuveitis Mimicking Vogt-Koyanagi-Harada Disease following the First Dose of ChAdOx1 nCoV-19 Vaccine.

METHOD: We report a case of bilateral panuveitis and its resolution based on multimodal retinal images after she was administered the first dose of a viral vector-based vaccine against SARS-CoV-2. CASE REPORT: A 72-year-old woman complained of bilateral blurred vision with headache, neck stiffness, and tinnitus 3 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine. Initial examination revealed anterior chamber reactions, left optic disc hyperemia, and bilateral chorioretinal folds with choroidal thickening. Fluorescein and indocyanine green angiography revealed bilateral choroiditis and papillitis. Systemic steroid therapy dramatically alleviated panuveitis and meningeal signs. No recurrence was noted until 3 months after discontinuation of steroids. CONCLUSIONS: Bilateral panuveitis mimicking Vogt-Koyanagi-Harada disease can develop shortly after the first dose of the ChAdOx1 nCoV-19 vaccine. Ophthalmologists should consider bilateral panuveitis as a presumed post-vaccination adverse event. Systemic steroid therapy may be effective for the nCoV-19 vaccine-associated panuveitis.

BILATERAL SEROUS RETINAL DETACHMENT AND UVEITIS ASSOCIATED WITH PEMBROLIZUMAB TREATMENT IN METASTATIC MELANOMA.

PURPOSE: To describe the pathological features, treatment, and resolution of pembrolizumab-associated retinal detachment. METHODS: A case report with a brief review of the literature and details of patient presentation, physical examination, systemic workup, fluorescein angiography, and indocyanine angiography. RESULTS: A 25-year-old white woman was diagnosed with unresectable metastatic melanoma of the skin with a BRAF V600E mutation. The patient was treated with pembrolizumab injections every 3 weeks, upon which quick remission was seen of the metastases. After five injections, visual acuity of the patient deteriorated to 20/32 in the right eye. Ocular examination revealed bilateral panuveitis, papillitis, and serous retinal detachments. Treatment consisted of an oral prednisone taper schedule, topical prednisolone drops, and cessation of the pembrolizumab therapy, after which complete resolution of the subretinal fluid was seen. CONCLUSION: Pembrolizumab therapy may cause the development of panuveitis, papillitis, and serous retinal detachment, symptoms which are able to be controlled with lengthy steroid therapy.

Ponatinib Inducing a Panuveitis with Choroidal Effusions and Neurosensory Retinal Detachment in a Patient with Chronic Myeloid Leukaemia.

CASE SUMMARY: We present the case of a 50 year old male patient being treated for chronic myeloid leukemia by the tyrosine kinase inhibitor, Ponatinib. After 3 months of treatment, he developed a sight-threatening granulomatous panuveitis in both eyes, with choroidal effusions and neurosensory retinal detachments. Except for a positive interferon-gamma release assay suggesting previous Tuberculosis exposure, all uveitis investigations were normal. Discontinuation of the suspected causative drug led to resolution of signs and a consequent improvement in visual acuity. CONCLUSION: Ponatinib use may be associated with with a uveitic phenotype that is reminiscent of Harada's disease. We compare and contrast this rare ocular phenomenon with Vogt-Koyanagi-Harada syndrome and discuss a possible immunological basis.

Use of fluocinolone acetonide intravitreal implant to manage chronic panuveitis for long-term inflammatory control without interfering with systemic immunity.

We report 2 patients with chronic panuveitis who were treated with fluocinolone acetonide intravitreal implant (Yutiq, EyePoint Pharmaceuticals Inc, Watertown, MA) intended to control ocular inflammation long term without interfering with systemic immunity. The first case was a man in his 50s referred for ocular complaints in the setting of ongoing immunotherapy for the treatment of metastatic melanoma. He was diagnosed with bilateral drug-induced panuveitis. Treatment objectives were outlined as reduction of inflammation, prevention of uveitis recurrence, and continuation of systemic immunomodulatory therapy in order to maintain malignancy remission; the patient was treated with fluocinolone acetonide intravitreal implant bilaterally and at 18 months' follow-up had 20/20 bilateral visual acuity and no inflammation. In case 2, a woman in her 70s, presented with a 2-month history of worsening floaters and blurry vision. She was phakic, with bilateral nuclear sclerotic cataracts, 1+ vitreous cells and 2+ haze, diffuse vasculitis, and central leakage around the optic nerve and posterior pole. She was diagnosed with bilateral idiopathic panuveitis with retinal vasculitis. The patient continued to do well at 1 year following intravitreal implantation with fluocinolone acetonide.

Interferon-induced sarcoidosis with uveitis as the initial symptom: a case report and review of the literature.

BACKGROUND: In recent years, numerous studies have reported the development or exacerbation of sarcoidosis due to interferon therapy. However, ocular lesions rarely present as initial symptoms. Herein, we describe a rare case of interferon-α-induced sarcoidosis with uveitis as the initial symptom, and present a review of the relevant literature. CASE PRESENTATION: This case involved a 62-year-old-Japanese woman with a history of a combination treatment of pegylated interferon-α-2a, ribavirin, and simeprevir, after which she developed granulomatous panuveitis. She was subsequently diagnosed with sarcoidosis following histological examination of skin biopsy specimens. In addition to reporting this case, we performed a literature review of 27 cases (24 case reports) of histopathologically diagnosed interferon-α-induced sarcoidosis published between January 2009 and November 2018. CONCLUSIONS: Among the reviewed cases, 23 (85.1%) cases developed skin lesions and 19 (70.1%) had lung lesions. Only three cases (11.1%) had accompanying eye lesions. Interferon-α therapy was discontinued in 16 cases (52.9%), and the majority exhibited improvement after systemic corticosteroid treatment. There are few reported cases of interferon-α-induced sarcoidosis with uveitis as the initial symptom. However, if uveitis develops during or after interferon-α treatment, it might represent an initial symptom of interferon-α-induced sarcoidosis, as observed in the present case.

Panuveitis Presumed Secondary to Ibrutinib Therapy.

Although a small number of cases of secondary uveitis have been documented in the setting of ibrutinib therapy, panuveitis has not previously been described with this medication. The authors describe a presumed case of panuveitis in a patient on ibrutinib for chronic lymphocytic leukemia. The purpose of this report is to document a case of asymmetric, bilateral panuveitis in the setting of ibrutinib use. Panuveitis may develop in the setting of ibrutinib use, and local steroid therapy can be successfully used for treatment without cessation of systemic cancer therapy. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:160-164.].

Panuveitis in patient on ipilimumab/nivolumab combination for small-cell lung cancer treated with an intravitreal dexamethasone implant.

BACKGROUND: Immunotherapy with checkpoint inhibitors has demonstrated durable responses and remarkable antitumor effects in a variety of cancers. Although these agents are generally well-tolerated, patients can experience immune-related adverse events (irAEs) that require prompt recognition by healthcare providers. Immune-related ocular toxicities are rare, but serious adverse events have been reported with the use of checkpoint inhibitors.Case presentation: Here, we describe a rare case of panuveitis during Nivolumab and Ipilimumab combination treatment in a patient being treated for recurrent Small Cell Lung Cancer (SCLC). The patient was managed with an injection of Ozurdex (Allergan, Madison, NJ), a dexamethasone intravitreal implant. The patient had a resolution of inflammation and an improvement in her vision and was able to resume nivolumab monotherapy without recurrence of the panuveitis. CONCLUSION: This case highlights the importance of early recognition of ocular irAEs by ocular oncologists and the successful approach to treatment of immunotherapy-induced panuveitis in order to avoid permanent cessation of therapy.

Vogt-Koyanagi-Harada disease-like uveitis following nivolumab administration treated with steroid pulse therapy: a case report.

BACKGROUND: Immune checkpoint inhibitors can cause various adverse effects. Recently it has been shown that Vogt-Koyanagi-Harada (VKH) disease-like uveitis can occur in patients treated with nivolumab. CASE PRESENTATION: A 69-year-old man developed bilateral panuveitis after nivolumab treatment for recurrent hypopharyngeal cancer. Slit lamp examination revealed bilateral granulomatous keratic precipitates, anterior chamber cells and partial synechiae. Fundus examination revealed bilateral optic disc edema and diffuse serous retinal detachment. His human leukocyte antigen (HLA) typing showed HLA-DRB1*04:05 allele. A lumbar puncture did not demonstrate pleocytosis. Bilateral sub-tenon injections of triamcinolone acetonide were initiated. As his panuveitis did not regress completely, steroid pulse therapy was administered. That therapy led to the resolution of his serous retinal detachment and to rapid improvement in his vision. Following this, we treated him with 50 mg/day of prednisolone for 1 week and then reduced it by 5 mg every week. No bilateral uveitis relapse had occurred by his 3-month follow-up; however, he subsequently died because of his cancer. CONCLUSION: To our knowledge, this is the first report of a patient with NVKH who underwent a lumbar puncture. Unlike VKH, our case did not show meningismus or pleocytosis. NVKH may, therefore, have a different etiology from VKH. In cases of NVKH with posterior uveitis, steroid pulse therapy may be considered as a treatment option, as it is in VKH.

OCULAR TOXICITY AFTER INADVERTENT INTRACAMERAL INJECTION OF HIGH DOSE OF CEFUROXIME DURING CATARACT SURGERY: A CASE SERIES.

PURPOSE: To report ocular side effects after inadvertent intracameral injection of a high dose of cefuroxime. METHODS: Nineteen eyes of 19 patients were seen in our eye department 1 week after the referring surgeon had injected an erroneous dose of intracameral cefuroxime (12.5 mg/0.1 mL in 14 patients, Group A, and 10 mg/0.1 mL in 5 patients, Group B) at the end of a cataract surgery. A complete ophthalmic examination was performed postoperatively. RESULTS: Eight patients (42.10%) exhibited ocular side effects. One patient (Group A) developed a noninfectious panuveitis. One case (Group B) had a serous macular detachment. Five patients (4 from Group A and 1 from Group B) showed a disruption of the ellipsoid layer with temporary/permanent drop in visual acuity. One patient presented with color alteration (Group A), but electrodiagnostic studies did not reveal any significant alterations. CONCLUSION: Anterior and posterior inflammation has been described after intracameral injection of high dose of cefuroxime. In this study, 10 mg to 12.5 mg of intracameral cefuroxime is shown to be, principally, toxic to the retina with transient or permanent retinal changes on optical coherence tomography which correlate with visual outcomes postoperatively. Protocols to avoid dilution errors should be available in theaters during cataract surgery where such commercial preparations are not available.

Management of Chronic Hypotony Following Bilateral Uveitis in a Patient Treated with Pembrolizumab for Cutaneous Metastatic Melanoma.

Purpose: To describe the presentation and management of severe ocular adverse events following treatment with pembrolizumab for cutaneous metastatic melanoma. Methods: Interventional case report. Results: A 73-year-old Caucasian man receiving pembrolizumab treatment for metastatic melanoma presented with panuveitis and subsequent profound hypotony, choroidal effusions, and optic disk swelling bilaterally. Oral prednisolone controlled intraocular inflammation. However, bilateral hypotony persisted which was managed over a 12-month period with ocular viscoelastic device injections into the anterior chamber of both eyes. There was also phacoemulsification with pars plana vitrectomy (PPV) and silicone oil (SO) tamponade performed on the left eye only. Intraocular pressure (IOP) stabilized (>6 mmHg) with best-corrected visual acuity of 6/60. Conclusion: We report a severe adverse event from pembrolizumab therapy resulting in uveitis and persistent hypotony. Repeat injections of high viscosity OVD achieved an increase in IOP up to 12 months. This technique may be a useful adjuvant or alternative to PPV and SO.

Recurrent grade 4 panuveitis with serous retinal detachment related to nivolumab treatment in a patient with metastatic renal cell carcinoma.

Blockade of programmed cell death-1 (PD-1) has become one of the most promising immunotherapies for many human cancers. However, immune-related adverse events can be produced by anti-PD-1 therapy. Uveitis is a rare but potentially devastating side effect of anti-PD-1 therapy. Delay in diagnosis or improper treatment may eventually lead to irreversible blindness. Therefore, it is important for the oncologist and the ophthalmologist to recognize and manage this adverse event properly in patients receiving anti-PD-1 therapy in a timely manner. Here we present a grade 4 panuveitis with bilateral serous retinal detachment following treatment with nivolumab for metastatic renal cell carcinoma. Oral prednisone, topical steroid eye drops, periorbital injection of steroid and finally intravitreal injection of steroid implant were administered in our patient. We observed that intravitreal injection of dexamethasone implant, but not the periorbital injection of steroid or the steroid eye drops, was effective to control the posterior uveitis and serous retinal detachment. Oral prednisone was also effective, but it might affect the efficacy of anti-PD-1 therapy and promote tumor growth. We also summarize 15 cases of uveitis reported to date related to nivolumab or pembrolizumab therapy in the present study. The symptoms, signs, potential underlying mechanisms and treatment options regarding this adverse event are discussed.