Ocular Oncology: It's Come a Long Way

American Academy of Ophthalmology 2012

Carol L. Shields, MD; Jerry A. Shields, MD


November 21, 2012

Editorial Collaboration

Medscape &

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Advances in Ocular Oncology

Carol L. Shields, MD: Hello, I'm Dr. Carol Shields, Co-Director of the Oncology Service at Wills Eye Institute in Philadelphia. Welcome to Medscape Ophthalmology Insights, coming from the American Academy of Ophthalmology Meeting (AAO) in Chicago. This is part of a series of commentaries produced in cooperation between Medscape and Wills Eye Institute. Joining me today is Dr. Jerry Shields, Director of the Wills Oncology Service.

We will be discussing the latest developments in ocular oncology. Several exciting new therapies and studies have been presented at the meeting this year. First we will discuss pigmented lesions on the conjunctiva, such as primary acquired melanosis, nevus, and melanoma. Next we will touch on pigmented lesions within the eye, such as nevus and melanoma. Finally, we will discuss the exciting new therapies for retinoblastoma, specifically chemotherapy -- intravenous and intra-arterial -- and the newest method, intravitreous chemotherapy.

Pigmented Lesions of the Conjunctiva

I would like to ask Dr. Jerry Shields a question. A patient comes in with a pigmented lesion on the eye. How do you tell if it's primary acquired melanosis, a nevus, or a melanoma?

Jerry A. Shields, MD: These are the 3 most common pigmented lesions that we see in our practice. The nevus is a circumscribed lesion, usually on the bulbar conjunctiva. It may have cysts and is seen in younger people.

Primary acquired melanosis occurs in slightly older people. The pigmentation is more diffuse rather than discrete, and it has the potential to develop into malignant melanoma in middle-aged people.

Malignant melanoma is a distinct lesion. It's larger, may encroach upon the cornea, and can be elevated. We have to make a decision in each case how to go about managing these. I would like you to comment on that, if you would.

Dr. Carol Shields: Most of the time when nevi are diagnosed in the office, it's in a child, and we like to wait until the child is old enough for us to perform surgery safely under local anesthesia. With primary acquired melanosis, I tend to treat it when it's more than 1 or 2 clock hours and it's a little bit more of a risk for melanoma. Some people call primary acquired melanosis "melanoma-in-situ." Melanoma is a deadly tumor, and I take that very seriously. Melanoma requires fairly urgent surgery and complete resection.

Pigmented Lesions Inside the Eye

Next we should focus on some of the pigmented lesions inside the eye, such as nevus or melanoma. You have been in practice for many years. You have helped us identify the differential features of nevus and melanoma. How do you tell the difference? When you see a patient with a small pigmented lesion, for example one that is maybe 5 mm in diameter and 2 mm in thickness, how do you know if it's a nevus or a melanoma?

Dr. Jerry Shields: Nevus is very common in the general population, whereas melanoma is very rare. The nevus is usually seen in adults. It's usually small, discrete, and has no significant risk factors, which we'll discuss in a moment. Nevi are generally flat, slate gray, and minimally elevated, if at all.

The melanoma is larger, and it has surface changes that we call risk factors, which you have published on quite extensively. These include the presence of orange pigment on the surface of the lesion, the secondary retinal detachment that we call subretinal fluid, and other features, such as nearness to the optic disk and thickness. We put all of these into the equation before we make a decision as to whether it's melanoma or nevus. Many cases are borderline, and if they occurred on the skin, like those seen by dermatologists, they can be resected almost anywhere. In the eye we don't have that privilege. We cannot resect them. We have to look at the risk factors and decide whether to continue observing them or to treat them depending on the presence of the risk factors.

Identifying Melanoma

Dr. Carol Shields: We have identified 5 main risk factors that help us to sort out nevus from melanoma. We remember these risk factors by a mnemonic, To Find Small Ocular Melanoma. These are 5 very important risk factors.

  • T stands for thickness over 2 mm;

  • F stands for fluid;

  • S stands for symptoms;

  • O stands for orange pigment; and

  • M stands for margin near the disk.

When I teach our residents, I always say, "Remember the mnemonic, To Find Small Ocular Melanoma: thickness, fluid, symptoms, orange pigment, margin near the optic disk." If the patient has a small lesion and it's more than 2 mm in thickness, if they have 3 of these risk factors, it's probably not a nevus. It's probably a melanoma. Have you ever seen a melanoma 1 mm in thickness?

Dr. Jerry Shields: We have, but it's extremely rare. Most melanomas are > 2 mm in thickness when detected. With the advent of newer diagnostic techniques such as optical coherence tomography (OCT) and enhanced depth imaging (EDI) OCT, we are starting to recognize these risk factors at an earlier stage compared with the older days when we had to just look with the ophthalmoscope.

Dr. Carol Shields: So, in a nutshell, a patient comes in with a nevus; what would you tell the general ophthalmologist to do? Which test? Photos? Do they need to do EDI OCT or OCT? Do they need to do an ultrasound?

Dr. Jerry Shields: The general ophthalmologist doesn't have to do these because they often don't have them in the office. But when the patient comes to our office, specifically referred for a suspicious nevus, we do a good clinical examination, careful fundus drawings, fundus photography, sometimes fluorescein angiography if indicated, and more often we will use this information to decide whether we're going to treat it.

Dr. Carol Shields: One test that I have found to be particularly useful in differentiating nevus from melanoma is autofluorescence. With the nevus, autofluorescence tends to be dark, and with melanoma it tends to be hyper-autofluorescent, very bright. That has been very helpful in sorting out nevus from melanoma.

Dr. Jerry Shields: In many cases, it is going to remain borderline and we're not going to know until we follow the patient for a period of time.

When to Observe, When to Treat

Dr. Carol Shields: So, what is your recommendation? If you can't make a decision as to whether it's a nevus or a melanoma, get a second opinion. If you can't do that, follow the patient cautiously?

Dr. Jerry Shields: Yes. We generally recommend that if it's a suspicious nevus, then see the patient back in our office within 3 months if possible. If the patient comes from a great distance, which many of them do, we will send photographs and a letter to the referring doctor and have the referring doctor do the examination every 3-6 months. If the patient lives a great distance away, we'll see the patient once a year. At each visit, we carefully examine the previous pictures and the newer pictures and look at the ultrasound thickness, to help us decide whether to continue observation or to proceed with some form of treatment.

Dr. Carol Shields: The treatment for melanoma, as most people understand it, is eye removal and plaque radiation or proton beam radiation. Sometimes, if the tumor is very small, we can treat it with lasers or thermotherapy. The most exciting thing in the field of melanoma work is genetically typing melanoma using DNA or RNA analysis. All patients that we see are offered genetic typing, and we have classes of melanoma. The high-risk melanoma, patients who carry monosomy 3, are at highest risk for metastatic disease. Patients who don't carry monosomy 3 are at low risk. Those at high risk get adjuvant chemotherapy or adjuvant systemic treatment to prevent metastatic disease.

Dr. Jerry Shields: We tend to stress to our ophthalmology colleagues that in contrast to the past, this is not just an eye disease. This is a systemic disease that may often have already spread to the liver or other organs before even being detected as a small lesion. Our emphasis in the future is going to be not just to treat the eye but to do targeted therapy to the liver where there might be subclinical metastasis that might emerge later.

Retinoblastoma: Saving the Eye

Dr. Carol Shields: The last topic is retinoblastoma. You have been in the field for years -- since the time when we used to enucleate and treat with radiotherapy. What are some of your feelings about the new chemotherapy regimens?

Dr. Jerry Shields: We used to have only 2 choices: Either remove the eye or give external beam radiation. Then gradually, with the advent of laser and cryotherapy, we began to use those techniques. Now we are finding that we rarely have to enucleate the eye because of newer methods of treatment that are hot topics now. You have been on the forefront of that, so I would like to hear what you have to say.

Dr. Carol Shields: The newest treatment for retinoblastoma is chemotherapy, but there are different ways to give it. It can be given intravenously, which we use for bilateral retinoblastoma. It can be given intra-arterially, through the ophthalmic artery behind the eye. We use that targeted delivery for unilateral retinoblastoma. Chemotherapy can be given under Tenon's fascia to boost the dose in the eye. Perhaps one of the most exciting methods is giving chemotherapy directly into the eye, into the vitreous cavity to treat recurrent seeds. We have many different ways to give chemotherapy.

I foresee in the future that most of us will be using either intravenous or intra-arterial chemotherapy in combination with sub-Tenon's or intravitreal chemotherapy. In the past our goal was to save the child's life at all costs. That is still our goal, to save the child's life, but now we are able to save their eye and their vision. About 50% of the children that we see with retinoblastoma wind up with 20/40 vision or better, having never had radiotherapy and not requiring enucleation. What is happening with retinoblastoma is really exciting.

Dr. Jerry Shields: Having followed a lot of these patients in the older days, I find it absolutely remarkable that we can achieve goals that were almost impossible 20-30 years ago.

Dr. Carol Shields: The genetic testing that we discussed for melanoma is the same for retinoblastoma, or for any cancer that we see around the eye. We always send a specimen for genetic testing. It's well established that retinoblastoma is related to a mutation on chromosome 13, and we can predict whether that child is at risk for passing this trait on to their own children by doing a genetic test on the tumor and on the child's blood. The traits that can be inherited are called germline mutations, and those that aren't are called somatic mutations. Patients with germline mutations carry many risks. Besides passing on the trait, they are at risk for second cancers. It is important to keep abreast of what is going on in the field of ocular oncology.

I would like to thank you for joining us. This is Dr. Carol Shields and Dr. Jerry Shields from Medscape Ophthalmology and Wills Eye Institute.