By Pippa Wysong
Beware when making a diagnosis of uveitis. There are a variety of conditions that can appear to be some form of uveitis, but are actually signs of cancer.

Indeed, the uveitis can be a red flag for conditions known as Masquerade Syndrome, according to Dr. Nupura Bakshi, a staff ophthalmologist at Mt. Sinai Hospital and St. Michael’s Hospital in Toronto. She spoke at the recent annual meeting of the Canadian Ophthalmological Society.

“Masquerade syndrome is a non-specific term that’s used for conditions that mimic chronic idiopathic uveitis but is not actually autoimmune,” she told Optical Prism in an interview. (Idiopathic means the cause is unknown). There are malignant and non-malignant forms, are rare, and are easy for both optometrists and ophthalmologists to miss. Dr. Bakshi has a subspecialty practice that focuses on uveitis and retinal disease, and presented tips for identifying malignant masquerades syndromes along with a general review of the topic.

While it is unlikely for most eye care specialists to see many cases of Masquerade Syndromes, optometrists and ophthalmologists alike should be aware of them and maintain a high index of suspicion for them, especially since many cases can have devastating consequences. She noted non-malignant cases of Masquerade Syndromes can include inherited retinal degeneration, chronic retinal detachment, and many other problems. Masquerade Syndromes essentially include conditions that can look like inflammation but unlike many forms of classic uveitis do not have an autoimmune cause.

Masquerade Syndromes were first described in 1967 and the malignant conditions range from certain eye cancers, to leukemia and more. The key list of possible malignancies include primary intraocular lymphoma (there are about 30 cases per year in Canada), leukemia, carcinomas that are metastatic to the eye, uveal melanoma, pediatric malignancy, and paraneoplastic syndromes. Masquerade syndromes present as either an anterior or posterior uveitis, but are not primarily inflammatory.

“Despite having the appearance of inflammation in their eye, patients with a Masquerade Syndrome typically don’t develop posterior synechiae. Whereas someone with a more classic uveitis who has a lot of inflammation will usually develop posterior synechiae,” she said.

In addition, patients with Malignant Masquerades usually don’t develop cystoid macular edema, which is something many patients with severe or chronic uveitis patients will develop.

There are a variety of warning signs that are possibly indicative of malignancy that both optometrists and ophthalmologists should watch for, she said. A key item, as is true with many things, is to start with a patient history. A history of prior malignancy, and use of immunosuppression are both potential red flags. Systemic or neurological symptoms such as unusual weight loss or headache can be indicative too. Importantly, watch for a new onset of uveitis in elderly patients. Uveitis often occurs in younger populations, but be suspicious if an older patient presents with this, she said.

“Your garden variety of uveitis patient presents with red, painful, light sensitive eye and it’s tender. But some patients with Masquerade Syndrome come in with insidious blurred vision without pain. They may just have floaters. It doesn’t always present with the acute, painful symptoms that make people want to go see a doctor,” Dr. Bakshi said.

Another thing to watch for is a non or temporary response to steroids. “Patients with malignancy may respond initially to steroids because, along with tumor cells, there are inflammatory cells as part of the process. The steroids help treat the inflammatory component and things will look better initially. But over time, it keeps getting worse because of the underlying malignancy,” she said.

Be suspicious too if a patient has a previous history of cancer. Significant intermediate or posterior uveitis should be present on examination. There may also be choroidal, subretinal, or retinal infiltrates. There can be a lack of posterior synechiae or cystoids macular edma despite severe uveitis.

A variety of investigations can help with the diagnosis too, she said. Ocular investigations that the ophthalmologist will order include intravenous Fluorescein Angiography (IVFA), Indocyanine green angiography (ICG) and fundus autofluorescence (FAF). Performing a biopsy of the aqueous or vitreous is often very important. Performing a B-scan ultrasound. Electroretinography (ERG) can help in some instances

The insidious thing about masquerade malignant syndromes is that it may take three or four biopsies before tumour cells are detected. The vitreous samples are small, are easy to damage if not handled properly, and there may not be enough tumour cells present for the pathologist to detect, she said.

A variety of systemic tests can help confirm the diagnosis too. Among these are complete blood count (CBC)-blood work and sending the patient for magnetic resonance imaging (MRI). Computed tomography (CT) of the chest, abdomen, pelvis or breast; and lumbar puncture. Ultrasound tests can help detect malignancies too. If there is suspicion of a malignancy, then refer to an oncologist.

But if one suspects something unusual, especially if it’s not an obvious problem, keep pushing for more tests. Even ophthalmologists miss the condition. In her own subspecialty clinic, Dr. Bakshi finds patients are often referred to her after they have already seen two or three eye care specialists including other optometrists and ophthalmologists. After being in practice for a year in a busy urban speciality clinic, she has seen only about 10 malignant masquerade syndromes, demonstrating how rare these cases are.

And if there is a suspected case, try to refer to an ophthalmologist who is a uveitis subspecialist, she said. •