Ophthalmology clinical research has seen a proliferation of exciting advances in recent years. The focus of clinical trials in ophthalmology has now expanded to include research into gene therapy, immunomodulation, and regenerative medicine.\(^1\) With this expansion of clinical research interests, more diagnostic and therapeutic options are becoming available for ophthalmology patients. In particular, patients with retinopathy, macular degeneration, uveitis, glaucoma, and cataracts are the focus of most current ophthalmology clinical trials.
Gene therapy is an emerging treatment modality that alters a patient’s DNA by inserting a gene into the patient’s cells. In this way, it is best positioned to treat diseases that emerge from genetic mutations. Retinal degenerative diseases, such as age-related macular degeneration and retinitis pigmentosa, are hereditary genetic mutation diseases which have benefited from gene therapy research. These retinopathies were, in fact, the subject of the first FDA-approved gene therapy,\(^2\) which marked an important milestone in ophthalmology research.
Immunomodulation is a therapy that uses monoclonal antibodies to target and modify the cells involved in immune system-mediated diseases. This type of therapy is useful for ocular inflammatory diseases, such as scleritis, uveitis, and keratitis.\(^3\) With the use of immunomodulation therapy, these patients can avoid long-term steroid use, which carries a significant risk profile.
Regenerative medicine involves the development of cells and tissue to replace those lost in damaged organs. As such, this type of therapy holds significant potential to treat such ophthalmic diseases as glaucoma and cataracts.\(^1\) Clinical research in ophthalmology is currently exploring such treatment options as glaucoma stem cells to improve aqueous outflow and decrease intraocular pressure,\(^4\) and cataracts stem cells to replace the damaged ocular lens. Regenerative therapies bring treatment options to patients who otherwise would suffer from irreversible disease and disability.
Clinical trials in ophthalmology are unique from other areas of clinical research. The eyes are an immune privileged organ, which is a protective mechanism that shields the eyes from local inflammatory responses. This immune privilege involves physical barriers to limit the entry and exit of molecules, and inhibitory factors within the eyes to suppress immune responses.\(^5\) Within the context of ophthalmology clinical research, this necessitates unique approaches to inducing or inhibiting immune responses, which are central to such ophthalmology therapies as immunomodulation. Systemic therapies and treatments that can easily access other organs would not be effective in many ocular diseases.
Another unique aspect of ophthalmology clinical trials is the duality of the eyes, with sometimes one or sometimes both eyes being diseased.\(^6\) When one eye is involved, the assessment of vision and ocular function after treatment in the diseased eye can be compared to the healthy eye, which serves as a built-in healthy control. When both eyes are involved, there is an opportunity for built-in matched subjects design, where one eye can be randomized to the treatment arm of a study while the other is in the control arm.
A challenge of conducting ophthalmic trials is the quantitative assessment of visual function.\(^7\) Vision is inherently a subjective experience, but clinical trials must use quantitative measures to assess the improvement after treatment. For example, the Basic Assessment of Light and Motion (BaLM) was developed to test light perception, temporal resolution, light localization, and motion.\(^7\) Developing quantitative measures that meaningfully capture the subjective experience of a patient’s vision, is important for the success of ophthalmology clinical trials.
Dokumeds is a leading ophthalmology CRO with experience managing and conducting clinical trials for ophthalmologic indications, since 2001. In the past twenty years, Dokumeds has developed expertise in helping partners achieve clinical trial success, and expertise specific to the field of ophthalmology clinical research. Dokumeds has managed trials for both medical devices and pharmaceuticals, including new and emerging therapeutic modalities.
Dokumeds has experience with global regulatory authorities, and is able to navigate the often-unpaved path to approval for emerging therapeutics. Dokumeds is skilled at site selection and over the years has developed relationships with experienced and well-equipped clinical sites. In particular, Dokumeds has experience in regions where the ophthalmology disease burden is high and thus the patient population for clinical trials is high, such as Europe, Russia and Africa. This expertise ensures robust and timely patient recruitment in clinical trials, excellent patient diversity for enrollment, and effective inclusion of patients in traditionally non-enrolling regions.
Dokumeds has significant experience as an ophthalmology CRO, and is looking forward to opportunities to engage in new and emerging ophthalmology clinical research.