Choroidal and Retinal Changes After Systemic Adrenaline and Photodynamic Therapy in Non-Human Primates

Abstract

To determine the tomographic, angiographic, and histologic changes in the choroid and retina of cynomolgus monkeys after systemic adrenaline and verteporfin photodynamic therapy (vPDT). METHODS. Six cynomolgus monkeys (12 eyes) were treated with vPDT only (n = 2), adrenaline only for eight weeks (n = 2), adrenaline for eight weeks with vPDT at week 4 (n = 4), and adrenaline for 12 weeks and vPDT at week 8 (n = 4). Spectral-domain optical coherence tomography, angiography, and autofluorescence were performed at baseline and every 14 days thereafter until 28 days after adrenaline therapy or vPDT. Choroid parameters included choroidal thickness (CT) changes and structural changes using semiautomated image binarization. Histology with light and electron microscopy was performed. RESULTS. Adrenaline resulted in subfoveal CT increase at week 4 compared with baseline (3.4%, P = 0.010), with further increase at week 8 (3.9%, P = 0.007). This correlated with choroidal luminal area increase (16.0% at week 8 compared with baseline, P = 0.030). Outer retinal changes included subretinal fluid, ellipsoid zone (EZ) disruption, photoreceptor elongation, and sub/intraretinal bright dots. Hypocyanescent spots surrounded by leakage was observed. Histology showed dilated choroidal vessels, intracytoplasmic vacuoles, and retinal pigment epithelium (RPE) enlarged basal infoldings. The vPDT decreased subfoveal CT at four weeks after vPDT (−7.5%, P = 0.007). This correlated with choroidal stromal area decrease (−18.0%, P < 0.010). Within the treatment spot, there was outer retinal atrophy, EZ disruption, irregular RPE thickening, intense hypoautofluorescence, hyperfluorescence, and hypocyanescence. On histology, there were outer retina, RPE, and choroid changes. CONCLUSIONS. Adrenaline induces choroidal vessel dilation and CT increase. The vPDT decreases CT because of a reduction in choroidal stromal component.

Retinal Toxicity Induced by Chemical Agents

“…Treatment with epinephrine induced a small, but rapid increase in what the authors called “short-circuit current” (current required to reduce the potential across the epithelial membrane to zero) [ 137 ]. Angiographic changes such as choroidal vessel dilation, increase on choroidal thickness, disruption and effacement of the ellipsoid zone, and elongation and protrusion of photoreceptor outer segments have been reported after epinephrine treatment for 8 weeks in cynomolgus monkey [ 138 ].…”

The effect of systemic and topical ophthalmic medications on choroidal thickness: A review

“…In a study investigating the effects of systemic adrenaline on CT in monkeys, daily administration up to 8 weeks was found to cause increased SFCT 5 . This effect was seen even after 4 weeks.…”

Central serous chorioretinopathy

“…[ 10 ] Phenylephrine and sympathomimetics have also been linked with CSC,[ 12 13 14 ] and animal models of adrenaline-induced CSC support these observations. [ 15 16 ] Altered ChBF is a frequent mechanism that leads to increased hydrostatic pressure and increased capillary permeability. Still, it is intriguing that both vasoconstrictors such as sympathomimetics and vasopressin and vasodilators such as phosphodiesterase inhibitors (PDIs) and minoxidil are associated with CSC.…”

“…Alternatively, the counter-regulatory mechanisms aimed at maintaining the ocular perfusion may lead to increased choroidal thickness in response to epinephrine. [ 16 ] The effects of mydriatics and cycloplegics on choroidal vasculature have been studied mostly in normal subjects. [ 20 ] It remains unclear if the autonomic dysfunction[ 5 ] would lead to a different outcome in CSC patients.…”