Ocular changes after photodynamic therapy.
OBJECTIVE
The aim of this study was to identify the changes in the primate visual system after a single session of photodynamic therapy (PDT) in an intact nonhuman primate retina.


METHODS
As part of a larger study, PDT (wavelength 689 nm, 50 J/cm2, 600 mW/cm2, 83 seconds, 4-mm spot size) with verteporfin (6 mg/m2 intravenous infusion) was performed in one eye each of two cynomolgus monkeys. Fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICG), optical coherence tomography (OCT), and multifocal electroretinography (mfERG) were performed at baseline and 12 time points (1-283 days) after PDT. In addition, retinal histopathologic findings were evaluated at 9 months.


RESULTS
Various morphologic changes, including whitening of the treated area, RPE proliferation, closure of the choroidal vasculature, and subretinal edema (followed by foveolar thinning) were observed. Most of the changes persisted and were detectable in histopathologic evaluation at 9 months. Reductions of the mfERG amplitude, followed by varying degrees of recovery from the treated and the border regions, were observed. This was accompanied by progressive delay of P1 peak time up to 3 months after treatment, followed by complete recovery at 9 months. In addition, the nontreated area showed amplitude and timing mfERG deficits, which underwent gradual (but not complete) recovery.


CONCLUSIONS
In a primate model, under standard clinical parameters, a single PDT treatment resulted in various dynamic morphologic and functional retinal changes detectable for up to 9 months after treatment. The significance of the observed changes and possible ways of pharmacologic interference with PDT adverse effects are discussed.
Tzekov
Radouil
R
Department of Biological Sciences, Allergan Inc., Irvine, California 92612, USA. tzekov_radouil@allergan.com
Lin
Ton
T
Zhang
Kai-Ming
KM
Jackson
Brittany
B
Oyejide
Adelekan
A
Orilla
Werhner
W
Kulkarni
Amol D
AD
Kuppermann
Baruch D
BD
Wheeler
Larry
L
Burke
James
J
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000139:chemically induced* / Q000175:diagnosis; D002829:Choroid / Q000098:blood supply* / Q000473:pathology; D015862:Choroid Diseases / Q000139:chemically induced* / Q000175:diagnosis; D004596:Electroretinography / Q000187:drug effects; D005260:Female; D005451:Fluorescein Angiography; D005500:Follow-Up Studies; D007208:Indocyanine Green; D008252:Macaca fascicularis; D008269:Macular Edema / Q000139:chemically induced* / Q000175:diagnosis; D010778:Photochemotherapy / Q000009:adverse effects*; D017319:Photosensitizing Agents / Q000009:adverse effects; D011166:Porphyrins / Q000009:adverse effects; D012160:Retina / Q000187:drug effects* / Q000473:pathology; D041623:Tomography, Optical Coherence; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin; D007208:Indocyanine Green