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A new Fluorescein Angiography finding in Retinopathy of Prematurity patients

Choroidal insufficiency, characterized by various types of hypoperfusion patterns, is observed in patients with retinopathy of prematurity (ROP).

The retrospective case series involved infants with ROP who were treated with intravitreal bevacizumab or laser photocoagulation from 2011 to 2020 at the Hospital for Sick Children in Toronto, Canada.

While the damages to the retinal vessels have been elucidated and well understood in ROP, the involvement of the choroid has not been thoroughly studied, prompting the investigators to explore the impact on the choroid of ROP.

In previously published research, the investigators had used the oxygen-induced retinopathy (OIR) rodent model to study any possible impact on the choroid. They found that in the first postnatal week during OIR, choroidal degeneration commences and the choroid remains thin throughout the life of the OIR animals. Following the initial choroidal degeneration, there is an increase in the number of pleomorphic and dysfunctional retinal pigment epithelium (RPE) cells, as well as a gradual decline in photoreceptor population and function.

Given the findings that emerged in their research with an animal model, the investigators sought to assess whether a similar impact on the choroid could be observed in neonates. They initially identified 118 patients with ROP and included those patients for whom intravenous fluorescein angiography (IVFA) had been conducted, leaving 79 patients. Three cases were excluded because of poor image quality and 2 were excluded because of severe phenotypes that precluded proper visualization of the choroid, leaving 74 cases for analysis.

The 74 infants with ROP had an average birth weight of 600.4 g and an average gestational age of 23.9 weeks. About 7 of 10 infants (69.4%) had zone 1, stage 3+ ROP, and the average age at which they underwent IVFA was 9.7 months. With respect to choroidal patterns, 64 eyes (86.5%) demonstrated multifocal areas of choroidal hypoperfusion. Four eyes showed central hypoperfusion (ie, the hypoperfused areas overlapping the macula), and 4 eyes demonstrated peripheral hypoperfusion (ie, hypoperfused areas outside of the macula). Only 2 eyes were deemed to have a normal choroidal pattern.

These study results suggest that choroidal involution is another component in OIR/ROP.

As per the investigators, the choroid being the major blood supply to the photoreceptors, so when it is thinned, it cannot deliver enough oxygen and nutrients to the photoreceptors. This leads to problems such as starved photoreceptors that cannot function properly, which can impact the vision.

Indeed, in a subsequent study, the investigators described signs of premature aging in the RPE cells and photoreceptors in OIR rodents.

In this pre-clinical study, by the time the OIR animals reached mid-adulthood, an equivalent to 50 years old in humans, their RPE cells and photoreceptors were similar to those seen in patients with age-related macular degeneration. This prompted the investigators to wonder if early insults to the choroid during infancy could precipitate a long-lasting impact throughout one’s adulthood.

Because the doses of intravitreal anti-VEGF medications used in patients with ROP are very low, it is very unlikely that anti-VEGF agents like bevacizumab and ranibizumab are affecting the choroid as per the investigators.

This study, as per the investigators, provides valuable clinical data to support a finding first demonstrated in an animal model of ROP. It also reminds us that ROP can be a disease that affects both the retinal and choroidal vasculatures.

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