8.1 Background

The main areas of research required in ocular adnexal diseases are either in the causation and treatment of more common diseases (such as eyelid tumours) or of the rarer, but potentially blinding, diseases (such as orbital inflammatory disease or optic nerve tumours).

   8.2 Research Potential

  8.2.1 Tumours of the eyelid and orbit

Basal cell carcinoma and squamous carcinoma are the commonest eyelid tumours, with a rising incidence worldwide -- in common with skin tumours elsewhere in the body. Moreover, squamous carcinoma of the conjunctiva is reaching epidemic proportions wherever immuno-compromised young patients (generally with HIV infection) are exposed to sunlight. Research needs to be directed towards the epidemiology of these tumours and into the mechanisms of tumourgenesis and its prevention in "at risk" individuals. Further research into the tumour syndromes, such as Gorlin's syndrome or xeroderma pigmentosum would help in the understanding of tumour induction.

Orbital lymphoma, with or without systemic involvement, appears to be a much commoner disease than in the past. There is a significant morbidity and mortality with this condition and further investigation of the epidemiology and causation is merited.

Optic nerve meningiomas and gliomas, although rare, cause loss of vision and may be associated with systemic genetic abnormalities -- such as neurofibromatosis. There remains considerable uncertainty as to the cause of the tumours and their natural history; with this uncertainty, the methods of treatment (particularly the role of radiotherapy) remain controversial.

  8.2.2 Orbital inflammatory disease

Orbital inflammation can present as a wide spectrum, affecting one or more tissues within the orbit and, when active, these conditions are painful, impair function and threaten vision. In some cases there is a relentless fibrosis of orbital tissues with severe impairment of orbital function and blindness.

The most common orbital inflammatory disease is thyroid orbitopathy, for which there is increasing understanding of the mechanisms involved. Future research is required to elucidate the immune mechanisms of this disease and to direct therapy towards "blocking" this immune response before it arises. Current therapies treat the inflammation only after it is established and after the complications of the subsequent "healing" response have developed.

Other orbital inflammations that cause particular problems are myositis, scleritis and panorbital scirrhous inflammation. Myositis affects young people and can lead to dense scarring of the extraocular muscles, with consequent ocular motility problems and diplopia. Scleritis can present a significant risk of blindness and may be a primary process, or part of a more widespread orbital inflammatory disease. Pan-orbital scirrhous inflammation is relatively rare, but can cause relentless fibrosis with effect on ocular motility and optic nerve function. Treatment is often poor and these patients can be blinded by this painful condition.

The cause of orbital inflammatory diseases remains a mystery. Certain features suggest a "driving" antigen, with recruitment of a spectrum of inflammatory cells. Eosinophils appear to be prominent in certain types of orbital inflammation (particularly scirrhous inflammation) and the various substances generated by these cells may be potent factors in fibrosis. Research directed at elucidating this mechanism, and its therapeutic blocking, might be of value not only in these conditions, but also in other diseases characterised by excessive scarring.

Treatment of orbital inflammation is currently largely systemic therapy and often has gross side effects that may limit the duration and efficacy of treatment. An improved understanding of the mechanisms and "drivers" for the inflammation may encourage the development of better and "targeted" therapies

  8.2.3 Anophthalmos/microphthalmos

Although very rare, children with microphthalmos or anophthalmos are blind or grossly visually handicapped. Currently there is controversy as to whether the causes of these conditions are genetic or environmental and research should be directed towards clarifying this issue. The treatment of these conditions is poor, and these children undergo multiple operations to try and improve their life and social acceptability. Linked to this rehabilitation is the role of orbital implant and prosthetics materials.

  8.2.4 Trauma and reconstructive surgery

Tissue contracture during healing remains on of the most significant problems with trauma (either primary or surgical); not only is the healed area distorted, but it also tends to be of incorrect compliance - both of which affect function. Understanding of the healing processes might allow development of methods to prevent contracture of tissues and improve functional results after trauma and surgical reconstruction.

Other areas of significant research related to trauma and reconstructive surgery would be the development of periocular tissue expansion and the establishment of methods for tissue culturing (from the patient) for use in subsequent reconstruction. Biomaterials research for tissue substitution and implants requires more investigation.

The treatment of orbital wall fractures remains controversial and, in view of the frequency of this condition, merits further investigation.

  8.3 Research Priorities