Purchase this article with an account.
Alan Hopkins, Natalie Hudson, Sarah Doyle, Mark Cahill, Matthew Campbell; Fundus fluorescein angiography (FFA) in human subjects displays circadian variation. Invest. Ophthalmol. Vis. Sci. 2019;60(9):5268.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
The relationship between retinal inner blood-retina barrier (iBRB) permeability, the circadian clock and their possible role in retinal pathology is unknown. We performed quantitative FFA in the morning and evening in healthy human subjects aged 18 – 30 years old to assess for any changes in retinal vascular integrity.
15 healthy human volunteers aged 18 to 30 were recruited, and informed consent was obtained from all participants. Fundus colour photography and FFA were performed at a defined time in the morning and again in the evening with a minimum of 48 hours between each investigation. The chronotype of each person was determined using the Munich chronotype questionnaire. Volunteers were excluded if they had any pre-defined medical history as outlined in our ethical approval documentation. Sodium fluorescein (500 mcg), followed by a 5mL flush of 0.9% sodium chloride, was injected via a peripheral cannulation site. FFA images of the posterior pole were captured every 15 s from completion of the infusion to 10 min. Fundal images were independently reviewed by a consultant ophthalmologist and ImageJ analysis was used for quantification of FFA images.
The macula was divided into 3 regions for analysis, based on the Early Treatment Diabetic Retinopathy Study grid, comprising the central fovea, inner macula and outter macula. Fluorescin signal was evident and more prolonged in the evening compared to the morning in the same subject and this was significantly increased in all macular regions analysed (n = 15 subjects, ***P < 0.001).
We have shown that there is a significant increase and more prolonged fluorescein signal in the evening compared to the morning in healthy volunteers. This indicates a systemically injected tracer molecule in human subjects undergoes a potential size-selective passive diffusion from the inner retinal vasculature to the retinal parenchyma with diffusion towards the outer retina and RPE. An inner retina derived supply of systemically derived components to the photoreceptor outer segments and RPE has not been described previously and may represent a critically important physiological process central to the development of a range of retinopathies including age-related macular degeneration (AMD).
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
This PDF is available to Subscribers Only