Elsevier

Ophthalmology

Volume 122, Issue 2, February 2015, Pages 414-428
Ophthalmology

Original article
Management of Posterior Uveal Melanoma: Past, Present, and Future: The 2014 Charles L. Schepens Lecture

Presented as the 2014 Charles L. Schepens Lecture at the American Academy of Ophthalmology Retina Subspecialty Day, Chicago, Illinois, October 17, 2014 (JAS).
https://doi.org/10.1016/j.ophtha.2014.08.046Get rights and content

Purpose

To review the management of ciliary body and choroidal melanoma (posterior uveal melanoma [PUM]) over the last century with an emphasis on changing concepts.

Design

Retrospective review.

Participants

Review of personal experience over 40 years and pertinent literature on management of PUM.

Methods

Diagnosis and therapy for PUM.

Main Outcome Measures

Patient survival.

Results

In the early 1900s, most patients presented with a large symptomatic melanoma that necessitated enucleation, and the systemic prognosis was poor. In the 1970s, controversy erupted regarding the role of enucleation for PUM. Some authorities advocated prompt enucleation, and others proposed that enucleation promoted metastasis, known as the “Zimmerman hypothesis.” Others recommended observation, withholding treatment until tumor growth was documented. During the 1970s, there was a trend toward eye-saving procedures, including laser photocoagulation, surgical removal of tumor, and techniques of radiotherapy. Despite local treatment success, systemic prognosis remained guarded with approximately 40% mortality overall. However, there was convincing evidence that smaller tumors offered a significantly better prognosis. Currently, there is a movement toward earlier identification and treatment of small melanomas using clinical factors predictive of malignant potential, in keeping with similar philosophy regarding other cancers. Further understanding of melanoma cytogenetics and molecular pathways have helped to recognize patients at risk for metastasis. At-risk patients are offered systemic therapeutic trials to prevent metastasis. We anticipate that the future management of PUM will focus on detection of clinical and imaging clues for earliest diagnosis, prompt local tumor treatment, and systemic targeted therapies for microscopic metastasis or prevention of metastasis. Personalized evaluation of patient-specific melanoma molecular pathway signature could allow for therapeutic intervention at a site specific to the pathway abnormality that leads to the development of melanoma.

Conclusions

Management of PUM has made major strides over the past century from the days of enucleation for massive, fatal tumor to early detection of smallest tumors with a more favorable prognosis. Current and future targeted specific tumor pathway interruption using systemic agents could improve survival.

Section snippets

The Past

In the early part of the 20th century, there was little published information on the treatment of PUM. At that time, patients often presented to their physician with tumor filling the globe, frequently causing inflammation, secondary glaucoma, pain, or proptosis due to orbital extension of the tumor. Such cases displayed high mortality secondary to metastasis to liver and other sites.1

In a review of his experience with 22 cases of uveal melanoma and 239 cases from other clinicians, Fuchs,2 in

The Present

All of the aforementioned developments have provided groundwork information for the current management of PUM. In the selection of treatment, one must take into account information collected from the numerous clinical reports on treatment, including the COMS and the AJCC classification results.

The management selected for PUM depends on several factors, including tumor size and extent, patient age, general health, status of the opposite eye, and other factors, including patient personal desires

The Future

The management of PUM is gradually transforming from focal ophthalmic therapy to combination ophthalmic and systemic therapies, based on detection of cytogenetic and molecular pathway events that lead to the development of melanoma and metastatic disease. We have gained tremendous knowledge in our understanding of tumors at risk for metastasis and basic tumor development, but there is more to discover. Improved patient prognosis will rely on earliest detection, better local treatments with

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      Ninety percent of tumors are in the choroid, six percent are in the ciliary body, and four percent in the iris (2). Before the 1970s, enucleation was the standard of care in treatment of posterior uveal melanomas (3). The Collaborative Ocular Melanoma Study (COMS) randomized clinical trial found no significant difference in survival outcomes between I125 plaque brachytherapy and enucleation (4).

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    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Support provided by the Schepens Award of the Retina Research Foundation, Houston, Texas (JAS), the Eye Tumor Research Foundation, Philadelphia, Pennsylvania (J.A.S., C.L.S.), the Paul Kayser International Award of Merit in Retina Research, Houston, Texas (J.A.S.), Lift for a Cure, Morrisdale, Pennsylvania (J.A.S., C.L.S.), and the Lucille Wiedman Fund for Pediatric Eye Cancer, Philadelphia, Pennsylvania (J.A.S., C.L.S.). The funders had no role in the design and conduct of the study; the collection, analysis, and interpretation of the data; or the preparation, review, or approval of the manuscript. J.A.S. has had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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