History of Present Illness
A 73-year-old Caucasian man was diagnosed with cutaneous melanoma 10 months ago and underwent resection of the tumor, sentinel lymph node biopsy, and regional lymph node dissection. Three months ago he was diagnosed with metastatic melanoma and started on an immune checkpoint inhibitor, pembrolizumab (Keytruda), 2 mg/kg intravenously (IV) every 3 weeks. Within the past 3 weeks he has noted bilateral red, painful eyes with marked photophobia and was referred for evaluation and treatment.
| OD | OS | |
|---|---|---|
| Visual acuity | 20/60 | 20/80 |
| IOP (mm Hg) | 2 | 8 |
| Lids/brows | Poliosis lashes and brows | Poliosis lashes and brows |
| Sclera/conjunctiva | Moderate perilimbal injection | Moderate perilimbal injection |
| Cornea | Multiple folds in Descemet membrane. ( Fig. 74.1A and B ). Diffuse nongranulomatous (NG) keratic precipitate (KP) | Diffuse NG KP |
| Anterior chamber (AC) | 2+ cell/3+ flare | 2+ cell/3+ flare |
| Iris | No posterior synechiae (PS) | Extensive PS |
| Lens | Pseudophakic | Phakic/clear |
| Vitreous cavity | 2+ vitreous cell, ciliary body (CB) detachment ( Fig. 74.2A and B ) | 2+ vitreous cell, CB detachment |
| Retina/optic nerve | Choroidal thickening/folds, macula swelling (see Fig. 74.2C ) and optic disc edema (see Fig. 74.2D ) | Choroidal thickening/folds macula swelling and optic disc edema |
Questions to Ask
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Why did you have surgery in your right eye (OD)?
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How was metastatic disease detected? Are you symptomatic?
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Have you noticed any neck stiffness, changes in your hearing, or changes in the color of your skin or hair?
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Do you have Native American ancestry?
Ten years ago he developed a rhegmatogenous retinal detachment (RRD) OD and underwent phacoemulsification and pars plana vitrectomy (PPV) for repair of his retinal detachment, with best-corrected visual acuity (VA) 20/40. Routine testing with positron emission tomography/computed tomography (PET/CT) imaging after diagnosis of cutaneous melanoma detected metastasis in the abdominal lymph nodes, lung and liver. He noticed increased shortness of breath recently. He has not noticed any neck stiffness or issues with hearing, but his eyelid lashes and brows have recently turned white. None of his grandparents were of Cherokee descent.
Assessment
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Panuveitis with severe hypotony, ciliary body detachments, and choroidal effusions, OU, right eye greater than left eye (OD > OS)
Differential Diagnosis
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Adverse reaction to checkpoint inhibitor
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Vogt–Koyanagi–Harada (VKH) syndrome
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Sympathetic ophthalmia
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Rare: systemic leukemia/lymphoma
Working Diagnosis
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Adverse reaction to checkpoint inhibitor
Testing
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The presentation of bilateral, nongranulomatous panuveitis with severe hypotony, ciliary body detachment, and optic nerve swelling are consistent with an adverse reaction to checkpoint inhibitors; hypotonus maculopathy explains the central posterior segment changes. Poliosis can be associated with this diagnosis, as well as VKH (or simply Harada syndrome if there is no systemic involvement). However, the absence of multifocal large serous neurosensory detachments would exclude that diagnosis. The history of surgery to the OD raises the possibility of sympathetic ophthalmia, although severe hypotony with bilateral ciliary body detachments at onset is most unusual.
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Laboratory data: normal complete blood count (CBC) with differential.
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Fundus fluorescein angiography (FFA): late frames of the OD did not demonstrate leakage from multiple hyperfluorescent spots and pooling of fluorescein into multiple areas of serous retinal detachment, excluding a diagnosis of VKH.
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Indocyanine green chorioangiography (ICGA): no leakage or hypoperfusion from choroidal vasculature.
Management
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Discontinuation of pembrolizumab
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Admit to the hospital or infusion center and begin methylprednisolone 1000 mg IV daily for 3 to 5 days
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Discharge on prednisone 100 mg by mouth (PO) daily
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Continue prednisone 0.75 mg/kg/day with taper after 2 weeks
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Topical prednisolone acetate 1% every 2 hours (q2h) and 1% Cyclogyl twice a day (BID) to treat anterior uveitis
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Follow up in 2 weeks
Follow-up Evaluation
The patient returns 2 weeks later with further decrease in vision and profound bilateral hypotony (0 to 2 mm Hg), even though his panuveitis is slowly resolving.
Follow-up Assessment
Intraocular pressure (IOP) has not responded despite discontinuation of checkpoint inhibitor and continued high-dose prednisone. Although panuveitis is decreased, VA is worse because of a hypermetropic shift (R +10.5, L 8.0) and severe hypotonus maculopathy OU ( Fig. 74.3 ).
