The Optic UK Lecture: bench-to-bedside adventures of a diabetes researcher: results past, results present.

This presentation covers two topics. First is a basic laboratory study, designed to explore the mechanism for the phenomenon of 'early worsening,' in which individuals with type 1 diabetes and early to moderate retinopathy are rapidly placed on 'tight' blood glucose control, after which about 10% of these individuals develop a worsening of retinopathy with the appearance of multiple 'cotton wool' spots. Our studies on cultured retinal cells used vascular endothelial growth factor (VEGF) production as an index of cellular ischaemia. VEGF production increases substantially when cells are cultured in low oxygen, but VEGF production in these hypoxic cultures decreases when the medium contains a fivefold excess glucose concentration. Cultures with no medium glucose also show increased VEGF production. In the clinical situation, we infer from these results that retinas with early retinopathy have a reduced blood supply and are therefore relatively ischaemic, thus increasing their VEGF production. Adding glucose provides an alternative energy supply, thus reducing the demand for VEGF and hence, reducing the likelihood of 'early worsening.' However, reducing the glucose supply to these already compromised retinas further increases their ischaemia and, therefore, the stimulus to produce more VEGF. The second part of this presentation is a clinical exploration of possible reasons for the frequent, wide discrepancy between measured central macular thickness by optical coherence tomography (OCT) and visual acuity in eyes with diabetic macular oedema. I explore the influence of different diseases in which macular oedema appears, the presence or absence, and size, of cystoid cavities; duration of the oedema; age of the subject, different anatomic derangements including epiretinal membranes and disruptions of the photoreceptor layer, and various biochemical and physiological mechanisms.