Research Technique: Pupilometry

SUMMARY

Pupillary light reflex (PLR) can be used as an objective measure of light sensitivity of the eye since ambient light interacts with previous light history to effect the pupil diameter. In mammals, PLR is driven by light photons absorbed in rod and cone photoreceptors of the outer retina as well as those absorbed by the intrinsically photoreceptive retinal ganglion cells (ipRGCs) of the inner retina. Our group has used the transient PLR (TPLR) as an objective outcome of outer retinal function in preclinical animal models (43,61,86) as well as patients with severe loss of light sensitivity (61,86,98,103,109,113,122,128,172,175,180,199,207,219,220).

Our recording method of TPLR was custom developed specifically for relevance to LCA patients and their animal models (61). Specifically, we use the direct TPLR where light stimulation and pupil measurement is performed in the same eye; eyes are tested sequentially. We use short duration (100 ms or 1 s) stimuli presented in the dark to dark-adapted eyes in order to preferentially evaluate the function of rods and cones, and minimize involvement of ipRGCs. We use full-field stimuli to make the measurement independent of oculomotor control. We use chromatic stimuli to attempt to distinguish rod responses from cone responses, and we use a very wide dynamic range of lights (>7 log units) in order to quantitatively evaluate large losses of light sensitivity. We have previously used TPLR to determine outcomes of retinoid (61) and gene therapy (43,86) in preclinical models, evaluate sensitivity loss in different genetic forms of LCA (61,86,103,113,128,172,175,180,199), and quantify the outcomes of gene therapy in clinical trials (98,122,219,220,227).


17 PUBLICATIONS DESCRIBING OR USING PUPILOMETRY

227. CIDECIYAN AV, Jacobson SG, Ho AC, Krishnan AK, Roman AJ, Garafalo AV, Wu V, Swider M, Sumaroka A, Van Cauwenbergh C, Russell SR, Drack AV, Leroy BP, Schwartz MR, Girach A. Restoration of cone sensitivity to individuals with congenital photoreceptor blindness within the phase 1/2 sepofarsen trial. Ophthalmology Science, 2022 (Epub ahead of print). [PubMed] [DOI]

220. Jacobson SG, CIDECIYAN AV, Ho AC, Peshenko IV, Garafalo AV, Roman AJ, Sumaroka A, Wu V, Krishnan AK, Sheplock R, Boye SL, Dizhoor AM, Boye SE. Safety and improved efficacy signals following gene therapy in childhood blindness caused by GUCY2D mutations. iScience, 24, 102409, 2021. [PubMed] [DOI] [Clinicaltrials.gov] [Penn Press Release]

219. CIDECIYAN AV, Jacobson SG, Ho AC, Garafalo AV, Roman AJ, Sumaroka A, Krishnan AK, Swider M, Schwartz MR, Girach A. Durable vision improvement after a single treatment with antisense oligonucleotide sepofarsen: a case report. Nature Medicine, 27:785-789, 2021. [PubMed] [DOI] [Clinicaltrials.gov] [Penn Press Release]

207. Krishnan AK, Jacobson SG, Roman AJ, Iyer BS, Garafalo AV, Héon E, CIDECIYAN AV. Transient pupillary light reflex in CEP290- or NPHP5-associated Leber congenital amaurosis: Latency as a potential outcome measure of cone function. Vision Research, 168:53-63, 2020. [PubMed] [PMC PDF]

199. CIDECIYAN AV, Jacobson SG. Leber Congenital Amaurosis (LCA): Potential for improvement of Vision. Investigative Ophthalmology & Visual Science, 60(5):1680-1695. [PubMed]

180. Charng J, Jacobson SG, Heon E, Roman AJ, McGuigan DB, Sheplock R, Kosyk MS, Swider M, CIDECIYAN AV. Pupillary light reflexes in severe photoreceptor blindness isolate the melanopic component of intrinsically photosensitive retinal ganglion cells. Investigative Ophthalmology & Visual Science 58:3215-3224, 2017. [PubMed]

175. Jacobson SG, CIDECIYAN AV, Sumaroka A, Roman AJ, Charng J, Lu M, Choi W, Sheplock R, Swider M, Kosyk MS, Schwartz SB, Stone EM, Fishman GA. Outcome measures for clinical trials of Leber congenital amaurosis caused by the intronic mutation in the CEP290 gene. Investigative Ophthalmology & Visual Science 58:2609-2622, 2017. [PubMed]

172. Jacobson SG, CIDECIYAN AV, Sumaroka A, Roman AJ, Charng J, Lu M, Choudhury S, Schwartz SB, Heon E, Fishman GA, Boye SE. Defining outcomes for clinical trials of Leber congenital amaurosis caused by GUCY2D mutations. American Journal of Ophthalmology 77:44–57, 2017. [PubMed]

128. Jacobson SG, CIDECIYAN AV, Peshenko IV, Sumaroka A, Olshevskaya EV, Cao L, Schwartz SB, Roman AJ, Olivares MB, Sadigh S, Yau K-W, Heon E, Stone EM,Dizhoor AM. Determining consequences of retinal membrane guanylyl cyclase (RetGC1) deficiency in human Leber congenital amaurosis en route to therapy: residual cone-photoreceptor vision correlates with biochemical properties of the mutants. Human Molecular Genetics, 22:168-183, 2013. [PubMed]

122. Jacobson SG, CIDECIYAN AV, Ratnakaram R, Heon E, Schwartz SB, Roman AJ, Peden MC, Aleman TS, Boye SL, Sumaroka A, Conlon TJ, Calcedo R, Pang J-J, ErgerKE, Olivares MB, Mullins CL, Swider M, Kaushal S, Feuer WJ, Iannaccone A, Fishman GA, Stone EM, Byrne BJ, Hauswirth WW. Gene therapy for Leber congenital amaurosis caused by RPE65 mutations: Safety and efficacy in fifteen children and adults followed up to three years. Archives of Ophthalmology 130:9-24, 2012.[PubMed]ed]

113. Jacobson SG, CIDECIYAN AV, Aleman TS, Sumaroka A, Roman AJ, Swider M, Schwartz SB, Banin E, Stone EM. Human retinal disease from AIPL1 gene mutations: foveal cone loss with minimal macular photoreceptors and rod function remaining. Investigative Ophthalmology & Visual Science, 52:70-79, 2011. [PubMed]

109. CIDECIYAN AV. Leber congenital amaurosis due to RPE65 mutations and its treatment with gene therapy. Progress in Retinal and Eye Research, 29:398-427, 2010.[PubMed]

103. Jacobson SG, Aleman TS, CIDECIYAN AV, Sumaroka A, Schwartz SB, Windsor EAM, Swider M, Herrera W, Stone EM. Leber congenital amaurosis caused by Lebercilin (LCA5) mutation: Retained photoreceptors adjacent to retinal disorganization. Molecular Vision, 15:1098-1106, 2009. [PubMed] [PDF]

98. CIDECIYAN AV, Aleman TS, Boye SL, Schwartz SB, Kaushal S, Roman AJ, Pang J-j, Sumaroka A, Windsor EAM, Wilson JM, Flotte TR, Fishman GA, Heon E, Stone EM, Byrne BJ, Jacobson SG, Hauswirth WW. Human gene therapy for RPE65-isomerase deficiency activates the retinoid cycle of vision but with slow rod kinetics. Proceedings of the National Academy of Sciences USA, 105: 15112-15117, 2008. [PubMed] [PDF]

86. Aguirre GK, Komáromy AM, CIDECIYAN AV, Brainard DH, Alemán TS, Roman AJ, Avants BB, Gee JC, Korczykowski M, Hauswirth WW, Acland GM, Aguirre GD, Jacobson SG. Canine and human visual cortex intact and responsive despite early retinal blindness from RPE65 mutation. PLoS Medicine, 4:e230, 2007. [PubMed] [PDF]

61. Aleman TS, Jacobson SG, Chico JD, Scott ML, Cheung AY, Windsor EAM, Furushima M, Redmond TM, Bennett J, Palczewski K, CIDECIYAN AV. Impairment of the transient pupillary light reflex in Rpe65-/- mice and humans with Leber congenital amaurosis. Investigative Ophthalmology & Visual Science 45:1259-1271, 2004. [PubMed]

43. Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, CIDECIYAN AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, Jacobson SG, Hauswirth WW, Bennett J. Gene therapy restores vision in a canine model of childhood blindness. Nature Genetics 28:92-95, 2001. [PubMed]


Last updated August 3, 2017