Page 151 - A Magyar Szemorvostársaság 2023. évi kongresszusa - Tudományos program és előadáskivonatok

quantification of the retinal improvements following gene therapy. Here we evaluated
photoreceptoral (cone and intrinsically photosensitive retinal ganglion cells, ipRGCs) function
by recording PLRs in patients with LCA before and after the subretinal injection of adeno-
associated virus (AAV) delivering RPE65 cDNA (voretigene-neparvocec) to rescue RPE65
protein expression in retinal pigment epithelium (RPE) cells. Two siblings with RPE65 gene
associated LCA were included in the study: 28yo female and 36yo male patients who had both
eyes treated, the first eye previously treated at another European gene therapy center and the
second eye at the Department of Ophthalmology of Semmelweis University. PLRs were
measured monocularly in both eyes with the RetEval portable device (LKC, United States) up
to six months after the surgical intervention. The protocol included a dark adaptation period of
10 minutes preceding the light stimulation. PLRs were recorded in response to one-second
light flashes using two different wavelengths: red light (peak wavelength ~ 640 nm), which falls
away from the peak of the melanopsin absorption spectrum (insignificant direct activation of
the ipRGCs), followed by blue light (peak wavelength ~ 470 nm), which is close to the peak
absorption of the melanopsin (direct activation of the ipRGCs). A two-minute interval between
the flashes was observed. Photopic luminance was set to 250 cd/m2 for both red and blue
lights. PLR recordings were analyzed with self-written MatLab routines. The results are given
as i) baseline pupil diameter, ii) peak constriction, iii) time to peak and IV) post-illumination
pupil response (PIPR). The results showed that PLR parameters may change after gene
therapy as an effect of photoreceptoral improvements that allows more light to be captured by
the treated retinal neurons. The peak pupil constriction and the time to peak were slightly
changed after the treatment while baseline pupil diameter changes were more evident. PIPR
was comparable before and after the treatment, showing that ipRGC function was preserved
before the treatment and remained unaffected. The results emphasize the relevance of
recording pupillary light reflex to objectively evaluate retinal function in low vision patients and
serve as a valuable outcome measure in gene therapy trials.