Study on the Ocular involvement in metastatic and systemic malignancies

Systemic malignancies affecting the eye often involve the choroid or the orbital area of the eye, leading to different ocular manifestations. Ocular malignancies are relatively rare compared to malignancies of other parts of the human body. The American Cancer Society estimates there will be about 3,300 new eye cancer cases in the United States in 2021, and predicts about 400 deaths from cancers of the eye and orbit. However, many eye metastases go unrecognized, perhaps because a bit of blurred vision doesn’t always spark serious concern to most people, so eye evaluation is delayed. 

Ocular malignancies account for about 7% of all cancers. Ocular malignancies are one of the least discussed and studied overall in oncology forums. Most available data are in the form of case reports instead of research papers. Ophthalmologists and ocular oncologists encounter lesions suspicious of eye cancer within all age groups, ranging from neonates to old age.  

On average, 20% of patients have orbital metastasis as the initial manifestation of systemic malignancies. Therefore, ocular manifestations of systemic malignancies should be studied well and known by both medical oncologists and ophthalmologists. The rare occurrence of metastatic carcinomas to the orbit has been a historical barrier to thorough research in the area.

Retinoblastoma is the primary ocular malignancy in children while in adults the following are most common: melanoma, squamous cell carcinoma of conjunctiva, and adenocarcinomas. Secondary malignancies from adjacent structures such as paranasal sinuses, infiltration from systemic cancers like leukemia, and even distant metastatic from other parts of the body are found. Metastasis to ocular structures are either orbital or intraocular, with the intraocular structures being the most common site of metastasis from distant sites.  

 

Purpose of The Study 

The chief purpose of the study is to evaluate orbital structures involved in secondary ocular and metastatic diseases. A secondary objective of this study is to describe clinical manifestations and outline the management that should be provided in metastatic carcinomas invading the eye and orbital structures.  

Methods 

This was a retrospective study of newly diagnosed patients with ocular metastasis managed in the department of ocular oncology at a tertiary eye care hospital in Nepal. This is a noncomparative and descriptive study done on this timeline: October 2017- September 2019.  The researchers recorded data from electronic medical record files. Data includes the demography, age, and sex of the subjects. The researchers also recorded findings on detailed examinations of the eye as well as the patient’s history of illness. 

Patients were segregated into secondary or metastatic ocular malignancies. Researchers examined the intraocular distribution of metastatic tumors and all patients underwent checkups by a medical oncologist. Primary ocular malignancies were excluded from the study. 

Also included was a detailed study on metastatic disease to the eye in relation to the symptoms, site of cancer, and treatment. Biopsy and imaging were also noted including clinical photographs, imaging films, and fundus photographs. Treatments provided in all forms including surgical or medical were recorded. All of the data obtained have a written informed consent. 

Results 

The subjects: 28 patients whose age group from 9 to 69 years with a median age of 43 years.

46% of patients in the study are female. Dual eye malignancies were present in 9 patients or 32% of the total study group. 

Paranasal sinus tumors and Non-Hodgkin lymphoma were present in 7 patients. The ocular metastasis was found most commonly in bronchogenic carcinoma (four patients) and breast carcinoma (three patients).

Simultaneous metastasis to other parts of the body occurred in 61% of patients. The most common presenting feature is a diminution of vision (49%), followed by proptosis, and palpable mass (14%). The most common ocular structure involved is an orbit, which occurred in 43% of all cases. Histopathologic diagnosis was recorded for 32% of cases and the rest were imaging alone. Chemotherapy was the most common form of treatment (57%). 

In this study, researchers also found intraocular metastasis in 39% of all patients. Ferry AP also reported in Archives of Ophthalmology that in 227 cases, 196 patients had intraocular, 28 had orbital, and only three had optic nerve metastasis. Therefore we conclude that metastatic cancer is more common than primary ocular carcinoma. 

Because of the inclusion of secondary and metastatic cancers, the researchers found the orbit to be the most common site (43%), followed by choroid (39%) of ocular malignancy. Other sites were recorded, but that were very rare, include the eyelid and conjunctiva. 

Most paranasal sinus cancers tend to spread to adjacent orbits which often present as a proptosis of the eyeball as the initial manifestation of the tumor. Four patients in the study experienced complete vision loss. 

Metastatic and secondary ocular malignancy occurs in almost any age group. But the mean age often goes from 47 to 62 years old. Most of the children in the study were found to have hematogenic cancers which are seen infiltrating their vitreoretinal which causes diminution of vision. Metastatic tumors are found in ocular regions and are more common to neuroblastoma and Ewing sarcoma.

The most common source of ocular metastasis is usually breast carcinoma, with incidence between 29% to 53% of patients based on various studies. The second most common source is lung, which occurred in around 8% of all cases. In this study, the researchers found that lung carcinoma was the most common tumor metastasizing the eye (14%), then followed by breast carcinoma (11%). The researchers believe this is due to the inclusion of different types of carcinomas such as local invasion and hematogenic malignancies. 

A parallel study from China reports different findings showing nasopharyngeal carcinoma as the primary tumor to invade ocular structures. Other sites of tumors which can invade ocular structures include the liver, gastrointestinal carcinomas, renal cell carcinoma, prostate carcinoma, and skin melanoma. It was common knowledge that metastatic tumors often involve bilateral eyes, but in this study, we found that only 32% of the subjects had bilateral diseases.

Ocular metastasis is a signifier of increased mortality and morbidity among patients because it’s associated with simultaneous metastasis to other organs in the body. A study on choroidal metastasis shows that 92% of patients also have metastasis on other organs as well. Yet 30% of the patients have disseminated metastasis. Because of this, most patients are treated with chemotherapy. 

In the study, 57% received systemic chemotherapy while 14% had surgery and chemotherapy combined. The most common surgery is enucleation for painful blind eye (11%) and excision biopsy (7%).  

Limitations of the Study 

The study is retrospective in nature which means the outcome of the treatment could not be recorded as most patients did not follow-up. The researchers believe that another prospective study in collaboration with medical oncologists should be done to evaluate the final outcome of patients. The study provides a base knowledge and vital information that can help both ophthalmologists and oncologists to diagnose correctly and manage patients with the correct treatment. 

 

Conclusion 

Ocular metastasis tends to display a vast array of of clinical and imaging features, therefore a high degree of suspicion is required for early diagnosis. Ocular metastasis is also associated with simultaneous metastasis, hence the importance of a prompt metastatic workup. 

 

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