History of present illness
A 46-year-old man with the diagnosis of T2a superficial spreading metastatic melanoma presented with blurry vision and photophobia in both eyes for 1 week. His history was unremarkable for ocular diseases or surgeries. Six weeks before his visual reports, he had started on ipilimumab (3 mg/kg) chemotherapy for his metastatic disease. His vision was worse after the third and most recent cycle of ipilimumab.
Ocular examination findings
At the initial examination, visual acuity (VA) was 20/100 in both eyes. There were fine, nongranulomatous keratic precipitates bilaterally. Dilated fundus examination showed multiple pockets of serous retinal detachments (RDs) in the macula.
Imaging
Initial evaluation with fundus photography, autofluorescence, and spectral-domain optical coherence tomography (OCT) ( Figs. 58.1 and 58.2 ) revealed bilateral serous RD in the macula. Fluorescein angiography (FA) demonstrated mild pooling of dye in the areas corresponding to serous RD, along with normal vasculature and absence of active leakage bilaterally. OCT of both eyes showed serous RD involving the fovea with irregular retinal pigment epithelium (RPE).
Questions to ask
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Does the patient have any risk factors for serous RD? Does the patient have a history of systemic diseases such as hypertension or renal failure? Bilateral serous RD (exudative RD) can be seen in patients with uncontrolled high blood pressure and renal failure.
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No.
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Does the patient use any medications that could lead to serous RD? Medications like mitogen-activated protein kinase inhibitors can cause drug-related exudative RD bilaterally.
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Yes. The patient was started on ipilimumab for the metastatic melanoma.
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Assessment
This is a case of a 46-year-old man with a T2a superficial spreading metastatic melanoma demonstrating bilateral serous RD after the third infusion of ipilimumab chemotherapy.
Differential diagnosis
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Idiopathic
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Coats disease
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Central serous chorioretinopathy
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Uveal effusion syndrome
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Congenital
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Nanophthalmos
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Optic nerve colobomas (morning glory syndrome)
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Familial exudative vitreoretinopathy
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- 3.
Neoplastic
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Choroidal melanoma
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Choroidal nevus
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Choroidal hemangioma
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Choroidal metastasis
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Retinoblastoma
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Primary intraocular lymphoma
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- 4.
Iatrogenic
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Panretinal photocoagulation
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Scleral buckle
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Hemorrhagic choroidal detachment
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After retinal detachment surgery
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- 5.
Inflammatory
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Scleritis
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Orbital cellulitis
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Orbital pseudotumor
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- 6.
Uveitis associated
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Infectious
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Syphilis
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Toxoplasma chorioretinitis
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Cytomegalovirus retinitis
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Herpes zoster ophthalmicus
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Autoimmune
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Vogt-Koyanagi-Harada (VKH) disease
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Sympathetic ophthalmia
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Vascular factors and systemic causes
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Age-related macular degeneration
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Preeclampsia/eclampsia in pregnancy
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Hypertensive retinopathy
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Chronic renal failure
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Congestive heart failure
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Diabetic retinopathy
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Sarcoidosis
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Inflammatory bowel disease
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Disseminated intravascular coagulation
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Hyperviscosity
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Immunoglobulin A nephropathy
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Polyarteritis nodosa
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Wegener granulomatosis
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Rheumatoid arthritis
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Systemic lupus erythematosus
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Carotid-cavernous fistula
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Working diagnosis
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Ipilimumab-associated retinopathy presenting with bilateral serous RD
Ipilimumab is a humanized monoclonal antibody against cytotoxic T-cell associated antigen 4 (CTLA-4) that enhances immune response against tumors by inhibition of CTLA-4–mediated T-cell suppression. Therefore immune-related adverse events can be observed, particularly in the skin and gastrointestinal tract. Overall, ocular side effects are rare (about 1.3% of ipilimumab-treated patients) but include anterior uveitis, , optic neuropathy, Graves-like disease, orbital inflammation, and VKH-like syndrome.
Bilateral, severe hypertensive fibrinous anterior uveitis, mild disc edema, choroidal folds, and choroidal lesions on indocyanine green angiography constituting a VKH-like picture have been related to ipilimumab use. A granulomatous panuveitis, with vitritis and choroiditis simulating VKH disease, has been previously described to be associated with ipilimumab chemotherapy. One study reported bilateral serous RD without overt inflammatory signs in a patient with aural lentiginous melanoma during ipilimumab treatment. A rare case of bilateral choroidal neovascular membranes was also documented in a man taking ipilimumab for metastatic melanoma.
Multimodal testing and results
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Fundus photography
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Wide-angle colored fundus photographs showed bilateral multiple pockets of serous macular RD.
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In one case, at 1 year after completing ipilimumab chemotherapy, a “sunset-glow” fundus appearance developed and mimicked the classic late stage of VKH syndrome.
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Autofluorescence
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Fundus autofluorescence showed the presence of hyperautofluorescent areas corresponding to the serous RD areas.
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FA
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FA showed mild pooling in the areas corresponding to serous RD, with no active leakage bilaterally, similar to an earlier study. Acute presentation with bilateral vitritis, choroiditis, and serous RD similar to VKH disease may demonstrate multiple areas of pinpoint leakage at the level of RPE.
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OCT
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At initial presentation, OCT in the right eye demonstrated serous RD involving the fovea with subretinal hyperreflective deposits. OCT of the left eye similarly indicated large serous RD involving the fovea. RPE appeared irregular in both eyes.
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At 1-week follow-up, both eyes showed marked reduction in the subretinal fluid, and the right eye revealed decreased hyperreflective material. OCT performed at 2-week follow-up indicated complete and near-complete resolution of the serous RD in right and left eyes, respectively.
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Management
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At 1-week follow-up, VA improved to 20/60 in the right eye and 20/40 in the left eye. Bilateral serous RD resolved spontaneously after cessation of ipilimumab.
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Given the spontaneous resolution of the subretinal fluid, the patient was observed without any treatment or intervention. The subsequent dose of chemotherapy was withheld until the resolution of ocular findings.
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Currently, there are no established treatment guidelines for this condition, and management of these patients demands close cooperation with the oncologist.
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One case with severe hypertensive anterior uveitis, disc edema, and VKH-like presentation secondary to ipilimumab chemotherapy was controlled with topical prednisolone acetate and systemic prednisone (1 mg/kg), which was slowly tapered, in addition to antiglaucoma drugs. Ipilimumab therapy was discontinued because of ocular inflammation in agreement with the oncologists.
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In one study, bilateral multifocal serous RD without signs of inflammation was managed with the addition of oral dexamethasone (4 mg daily) to the initial regimen of 1 month of topical prednisolone acetate.
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One patient with suggestive signs of VKH disease related to ipilimumab chemotherapy was initiated on high-dose intravenous corticosteroids for 3 days followed by oral corticosteroids. Three weeks after the presentation, the patient’s serous RD totally resolved, and oral corticosteroid was tapered to discontinuation in 4 weeks.
Follow-up care
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There are no established guidelines for follow-up.
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If the patient demonstrates persistence or progression of subretinal fluid, more frequent and longer follow-up with more intensive treatment, including topical and systemic steroids, should be considered.
Algorithm 58.1 : Exudative retinal detachment workup, systemic associations, and fundus examination findings
