Systemic implications highlighted in retinal tumor findings


Retinal tumors have taken on a new importance because of links to systemic disease, according to Carol Shields, MD. Through these links, specialists are improving the diagnosis and treatment of retinal tumors. Dr. Shields highlighted astrocytic hamartoma, retinoblastoma, and retinal capillary hemangiomoblastoma.

Reviewed by Carol Shields, MD

San Francisco–Retinal tumors have taken on a new importance because of links to systemic disease, according to Carol Shields, MD. Through these links, specialists are improving the diagnosis and treatment of retinal tumors.

Dr. Shields highlighted astrocytic hamartoma, retinoblastoma, and retinal capillary hemangiomoblastoma. “There has been so much progress in the last 10 years with retinoblastoma, you can’t believe it,” she said.

Dr. Shields, of the Ocular Oncology Service, Wills Eye Hospital, Philadelphia, presented an overview of this research in her Founders Award Lecture at the American Society of Retina Specialists 2016 Annual Meeting.

Astrocytic hamartoma

Astrocytic hamartoma can be a calcified or non-calcified mass. Using spectral domain optical coherence tomography (SD-OCT) to study their cases, Dr. Shields and colleagues found that astrocytic hamartoma appeared in the nerve fiber layer– and in over 91% of cases–presents a “moth-eaten,” micro-cavitary appearance.

This tumor causes mild retinal traction and is sometimes associated with tuberous sclerosis complex (TSC). A fundus finding of retina achromic patches, otherwise known as retinal pigment epithelium (RPE) punched-out lesions, can clinch the diagnosis of tuberous sclerosis complex.

“This retina achromic patch is really not clearly understood,” Dr. Shields said. “Some people feel it’s a flat astrocytic tumor. We really don’t think it represents that condition. We think it’s simply RPE depigmentation, for some reason.”

Courtesy of Carol Shields, MD

In studying 56 patients with tuberous sclerosis complex, Dr. Shields and colleagues found a retina achromic patch in 21% of cases. In their published report, they also noted significant relationship of achromic patch with increasing number of astrocytic hamartomas, peripheral location of the astrocytic hamartomas, cognitive impairment, and seizures in these patients.

Another study of 907 patients from the Tuberous Sclerosis Alliance and 132 from the Cleveland Clinic Tuberous Sclerosis Complex program showed that 35% had astrocytic hamartoma and 12% had achromic patches. If patients had either of these findings, they were at increased risk for brain astrocytomas, renal angiomyolipomas, cognitive impairment, and seizures.

These findings suggest that identifying a retinal astrocytic hamartoma or an achromic patch can be ominous, she said. “So keep that in mind when you see such patients.”




The news on retinoblastoma is more upbeat, with intra-arterial chemotherapy gaining popularity worldwide. “This is the most successfully treated pediatric cancer, and its targeted chemotherapy is making it happen,” said Dr. Shields. “Hardly ever do we use radiotherapy for retinoblastoma anymore.”

Dr. Shields and colleagues also have abandoned the use of subtenon chemotherapy for these tumors because of a high rate of complications, including fibrosis.

Her team compared intra-arterial and intravenous chemotherapy for unilateral retinoblastoma in a head-to-head retrospective trial and found better tumor control with intra-arterial chemotherapy for these eyes.

On the other hand, they prefer systemic intravenous chemotherapy for bilateral retinoblastoma and high-risk eyes and intravitreal chemotherapy for active vitreous seeds.

Administering these treatments can be challenging, Dr. Shields said.  “It’s an art and a science,” she added. “It’s not just a recipe.”

Dr. Shields gave the example of using 6 cycles of vincristine, etoposide, and carboplatin in intravenous chemotherapy. After administering this treatment, she and colleagues look for tumor regression on OCT.

Courtesy of Carol Shields, MD

For intra-arterial chemo, they refer patients to neurosurgeons or interventional neuro-radiologists. “This requires excellent skills in catheterization,” she said.

Intra-arterial chemotherapy can cause complications, Dr. Shields said. Melphalan hydrochloride can cause ischemia to the retina. Since it is a nitrogen mustard-alkylating drug, it can cause pancytopenia and leukemia, or if more than 7 doses are given, male infertility. “So we limit the amount of doses to 3 or 4,” she pointed out.

Dr. Shields’ team has been treating more advanced cases, and about 6% of the eyes they treat develop a rhegmatogenous retinal detachment. This finding is particularly noted in older children with advanced, diffuse infiltrating retinoblastoma and vitreous seeding.

“It happens because the tumor has infiltrated the retina and destroyed the retina to such a degree that when we give the chemotherapy, the retina is left with gaping holes,” Dr. Shields explained. “Often there is more than one retinal hole.”

Her team is only able to fix the retina in about half of these cases.

Retinal capillary hemangioblastoma


Retinal capillary hemangioblastoma

The news about retinal capillary hemangioblastoma relates to its relationship to von Hippel Lindau disease. Clinicians can identify these tumors by their red-orange retinal mass with feeder vessels and exudative retinopathy.

Invisible retinal capillary hemangioblastoma can be discovered using SD-OCT, said Dr. Shields. “Super-early detection is key,” she added.

Patients with 2 or more of these lesions can be diagnosed with von Hippel Lindau disease. And patients with von Hippel Lindau disease run an increased risk of brain hemangioblastoma and renal cell carcinoma, said Dr. Shields.

The first tumor to occur in von Hippel Lindau patients is the retinal tumor,” she added, “so it will be up to you to identify and get it sent through for testing,” said.

Courtesy of Carol Shields, MDOn average, patients with this disease live about 50 years, dying from tumors in their brains or kidneys. “So it’s important to have other consultants involved in their care,” said Dr. Shields.

Clinicians can anticipate the risk of pheochromocytoma by learning about their patients’ genotypes, she said. Those with type 1 mutations have pheochromocytoma, while those with type 2 do not.

A recent National Eye Institute study showed that poor vision in these cases is related to older age, juxtapapillary location, an increased number of tumors and increased tumor size. For example, in patients whose tumors were in a juxtapapillary location, the risk of poor vision was 2.8 times greater than in those patients whose tumors were in a peripheral position.

Patients with 5 or more tumors had an 8 times greater risk of poor vision, compared to those with fewer tumors.

And patients with more than 2 quadrants of retinal hemangioblastoma had 26 times the risk of those with less than 1 quadrant. “So the clinical features do correlate with the risk of poor vision,” she said.

To treat these patients, Dr. Shields and colleagues use laser photocoagulation, photodynamic therapy, cryotherapy, or plaque radiotherapy.

In the future, she anticipates more targeted treatment of these tumors, possibly with sunitinib or sirolimus.




Dr. Shields referred to solitary circumscribed retinal astrocytic proliferation (SCRAP) as “an amazing little tumor that occurs in the fundus and can simulate other tumors.”

Courtesy of Carol Shields, MD

This pearl white retinal mass looks like an astrocytic hamartoma or a retinoblastoma, except for its color. “We used to think this arose in the nerve fiber layers, until we had SD-OCT,” Dr. Shields said. “We were wrong.”

Instead, it arises deep in the retina. “We think it might even be arising from the RPE and draping the retina,” she said.


Fairly easy to diagnose as a flat black mass in the fundus, Congenital hypertrophy of the retinal pigment epithelium (CHRPE) shows enlargement in over 83% of cases, Dr. Shields said. This is a low-grade neoplasm, which develops adenoma or adenocarcinoma in less than 1% of cases.

Combined hamartoma, torpedo maculopathy


Combined hamartoma of the retina and retinal pigment epithelium

Combined hamartoma of the retina and retinal pigment epithelium can be associated with neurofibromatosis 2 (NF2), branchial cleft syndrome, and Potter’s syndrome.

It can have a mini-peak or maxi-peak vitreoretinal retraction appearance. “The mini-peak sort of looks like a sawtooth pattern, where the retina is pulled by the vitreous adhesion,” said Dr. Shields. “The maxi-peak is where the retina is actually folded from extensive vitreoretinal traction. Sometimes there is a combination of both on OCT.”

She cautioned clinicians that there is an increased risk of brain tumors in patients who have NF2 and an epiretinal membrane.

Torpedo maculopathy

Torpedo maculopathy, a congenital, usually is a depigmented tumor temporal to the foveola that “looks like a torpedo heading to the foveola.” It usually does not impair vision. But it merits attention because of a new finding that it can be associated with microcephaly, for example of the type caused by Zika virus. Previously it had not been linked to any systemic disease.


Dr. Shields did not indicate any financial interests related to this subject matter.

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