Ocular Oncology Research

Research is of vital importance in preventing and treating disease. Besides treating our patients we are also expected to learn as much as possible from our unique experience and to share our findings with the rest of the world. We, and therefore our patients, benefit greatly from the teachings of others and we reciprocate by sharing our own discoveries in a similar way.

In general, research is conducted in the following way:

  1. An idea is defined into a discrete statement (i.e., 'hypothesis').
  2. Observations are meticulously recorded, taking care to ensure that the results are not distorted by including some bits of information and leaving out others.
  3. The data are analyzed statistically to determine whether the results are genuine or due to chance.
  4. Whenever possible, the mathematical results are supported by photographic evidence, so that any message is easily understood. If it is necessary to publish a photograph of a face, then parts of that face are either blotted out to prevent the patient from being recognizable or, if this is not possible, the patient's signed consent is obtained. There is an increasing tendency to obtain signed consent from all patients, whether or not they can be identified from the photographs.
  5. Any important finding is broadcast to other interested workers by lectures at conferences and in other hospitals, publications in textbooks and scientific journals, and, increasingly, on computer programs and over the internet. Several precautions exist to safeguard the rights of patients. Everyone working with patient data has a legal duty to keep all information confidential. Whenever possible, any details that enable patients to be identified are removed. Before any research project can be started, it has to be approved by the Local Research Ethics Committee. This independent committee ensures that the research is feasible, well planned and worthwhile. It checks that the project is safe and that any risks are fully justifiable when considered in relation to the potential rewards. It also reviews any patient consent forms to confirm that patients participating in the study are given every opportunity to choose sensibly whether or not they should participate.

Clinical research

The clinical research that we tend to perform in Liverpool consists of (1) evaluating different forms of treatment and (2) case reports.

Our centre provides special opportunities for research. Firstly, it is one of only half-a-dozen centres worldwide where, each year, more than 300 new patients with ocular melanoma are treated. Secondly, whereas other centres tend to offer one or perhaps two different kinds of conservative treatment, we can evaluate all established forms of treatment. Thirdly, our database contains one of the largest collections of information on ocular melanoma in the world.

The database was first established in 1985 and has continued to develop with the help of professional software consultants. Since 1987, this database has been maintained by a succession of data managers, who have ensured that the database is as complete as possible. In 1994, a terminal was installed in the outpatient clinic for clinical information to be saved just after each patient is seen thereby minimizing the chances of any errors. A key to the success of the database is the way in which it is in constant daily use so that any errors quickly come to light. The database is used by our secretary for writing letters, organizing clinics and theatre lists. It is also used by our specialist ocular oncology nurse, when she needs to communicate with patients or when a new patient asks to speak to a previously treated patient. It has often proved invaluable in patient care, for example, if the case sheet is not available when a referring ophthalmologist phones with query about a patient. Information is collected and stored indefinitely so that long-term outcomes can be analyzed.

We have good collaborative links with the cancer registry at the NHS Central Register. We inform it of any new patients with ocular tumours such as melanoma so that it is possible for epidemiologists to study the incidence of these tumours across the country. If any of our patients pass away, the cancer registry automatically inform us of the date and cause of death so that we can analyze the success of our treatment.

According to the Data Protection Act, every patient has the right to view any information held about him or her. Strict guidelines exist to ensure that patient confidentiality is respected at all times and that any results are published with full patient anonymity.

Whilst there is no problem obtaining patients' consent prospectively for specific studies, the situation is more difficult when we wish to perform new research using old data and tissues collected many years previously. This is because it is difficult or impossible to get in touch with all the patients to obtain consent. To alleviate this problem, we have prepared a form that would enable current patients to give consent for data to be stored indefinitely and used in future research on matters that cannot yet be foreseen. These studies would be performed according to regulations existing at the time and under the supervision of the Local Research Ethics Committee.

Research Topics

Our clinical research has tended to report the results of treatments. Outcomes such as survival, conservation of the eye, preservation of vision, and tumour control are correlated with pre-treatment characteristics (i.e., 'variables') such as patient age, pre-treatment vision, tumour dimensions and so on. These studies have enabled us to inform other specialists about what can be achieved when a patient presents with a particular problem. It has also made it possible for us to advise patients on their own prospects for success after a particular treatment, so that they have been able to select the best treatment for their own particular condition. Importantly, this research has demonstrated to us the circumstances likely to give rise to various complications so that we have been able to develop ways of avoiding problems.

The second form of research is to prepare a 'case report', which is useful for drawing attention to rare conditions and unexpected outcomes after treatment.

Basic science research

Basic science research is essential for understanding the cause and the behaviour of uveal melanoma. The availability of numerous tumour specimens and blood samples creates special opportunities for making a contribution to current knowledge in this field. Several years ago we decided that if patients had a voice and knew what to ask of us they would encourage us to do more to prevent ocular tumours from recurring in other parts of the body. We have therefore collaborated closely with scientists having special expertise in tumour genes. They have been investigating abnormalities in chromosomes 3, 6 and 8, which influence tumour behaviour profoundly.

The specimens we use for research mostly consist of material left over following diagnosis or treatment and surplus to clinical requirements. Recently, specimens used for research have come to be regarded as gifts so that our institution becomes the 'custodian' of this precious material. The specimens and related data are treated with full confidentiality. The samples are not be used for financial gain. If tissue is not used for research it is either incinerated or stored in case there is ever a clinical need to review the specimen.

Consent for the use of surplus tissues is always obtained from the patient if the results of the research can be linked to the individual and if there is any possibility that such results might affect the patient's interests. When obtaining consent, patients are informed of any physical risks associated with collecting the sample, how the sample will be used, and how the research results might impact their interests. It is considered acceptable to use tissue material surplus to clinical requirements without obtaining the patient's consent if the material was archived before April 2002 and if the sample is anonymous so that it can no longer be linked to the patient. Legislation regarding the use of human tissues for research is currently being revised.

When a specimen has been used for a particular research project, for which specific consent has been granted, any material left over might still be very useful for new experiments that could not be foreseen when initial consent was first granted. We therefore obtain a second consent for the storage of any surplus material and for future use in other research. However, it is emphasized that even when the research results are linked with the patient's clinical data such secondary research will not have any direct implications for the donor. Patients are not obliged to give consent for a specific research project or for secondary, unspecified studies. The patient's care will not be altered in any way if consent for research is withheld.

Before starting the study and before obtaining consent, a decision is made as to whether it is in the patients' best interests to be given the opportunity of receiving any feedback about the results of the study. Such feedback may be offered individually or generally by means of a website or newsletter. The summaries of any published articles can be seen by logging onto the Pubmed website and typing 'Damato B eye'. This provides a list of articles. Clicking on the authors' names should produce the summary. The link opens in a new window, so just close it to continue browsing this site.

International Ocular Oncology Research Societies

Collaboration between ocular oncologists from different countries creates opportunities for sharing clinical and laboratory data, making it possible to investigate rare situations, which cannot be adequately dealt with by any individual centre. Our centre has actively participated in the European Ocular Oncology Group, the International Society of Ocular Oncology and the Ocular Oncology Research Society.

Further information on research guidelines can be obtained at websites of the Medical Research Council, the General Medical Council, the World Medical Association and others (Chapter 22).

Research publications in 2005

  1. Damato B, Spalton DJ. The uveal tract. Chapter 9. In Atlas of clinical ophthalmology. Spalton DJ, Hitchings RA & Hunter PA. Third edition. 2005 Elsevier. "BMA Book of the Year"
  2. Kanski, JJ, Milewski SA, Damato BE, Tanner V. Diseases of the ocular fundus. Elsevier Mosby. Oxford (2004). "Winner, New Authored Book, The Society of Authors & The Royal Society of Medicine Book Awards, 2005."
  3. Damato B, Patel I, Campbell IR, Mayles H, Errington RD. Visual acuity after ruthenium 106 brachytherapy of choroidal melanomas. International Journal of Radiation Oncology*Biology*Physics. 2005. 63; 392-400.
  4. Damato B, Patel I, Campbell IR, Mayles H, Errington RD. Local tumor control after 106 brachytherapy of choroidal melanoma. International Journal of Radiation Oncology*Biology*Physics. 2005. 63; 385-391.
  5. Damato B, Kacperek A, Chopra M, Campbell IR, Errington RD. Proton beam radiotherapy of choroidal melanoma: the Liverpool-Clatterbridge Experience. International Journal of Radiation Oncology*Biology*Physics 2005; 62: 1405-11.
  6. Damato B, Kacperek A, Chopra M, Campbell IR, Errington RD. Proton beam radiotherapy of iris melanoma. International Journal of Radiation Oncology*Biology*Physics. 2005; 63: 109-15.
  7. Hughes S, Damato BE, Giddings I, Hiscott PS, Humphreys J, Houlston RS. Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3. Br J Cancer. 2005; 93: 1191-6.
  8. Jose Luis Ordonez, Luminita Paraoan, Paul Hiscott, Donna Gray, Ian Grierson, Bertil Damato. Differential expression of angioregulatory matricellular proteins in posgterior uveal melanoma. Melanoma Research 2005; 15: 495-502.
  9. Damato BE, Foulds WS. Surgical resection of choroidal melanomas. In: Ryan SJ, Ogden TE, Schachat AP, eds.Retina. Fourth Edition. St. Louis: The C.V. Mosby Company, 2006; 769-778.
  10. Purbrick RMJ, Tu KL, Damato B. The patient's role in the decision-making process - a perspective from the Liverpool Ocular Oncology Centre. Eye (E-publication ahead of print).
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