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Birgit Lorenz, Elisabeth Strohmayr, Steffen Zahn, Markus N. Preising, Christoph Friedburg, Knut Stieger; Chromatic Pupillography and RPE65 Deficiency. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3891.
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Patients with mutations in the RPE65 gene develop early onset severe retinal dystrophy (EOSRD) or Leber congenital amaurosis (LCA), depending on whether legal blindness appears within the first years (LCA) or from the second decade of life on (EOSRD). Objective methods for the characterization of photosensitive cells within the retina are highly needed not only for improving the quality of examination results but also for the analysis of treatment success following AAV mediated gene therapy strategies. The pupil light reflex is driven by rod-, cone-, and melanopsin mediated activation of ganglion cells, which represent inner and outer retinal cell populations. They are activated by light of different wavelengths and intensities and thus can be stimulated separately. The aim of this study was to evaluate the pupil light reflex in patients with mutations in the RPE65 gene, and to correlate the results with the clinical phenotype.
Fifteen healthy probands and 6 patients with mutations in the RPE65 gene were studied. A custom made binocular chromatic pupillometer (Bino I, AMTech) connected to the Colordome Ganzfeld stimulator (Diagnosys LLC) was used to assess changes in pupil diameter in response to red (640nm) and blue (462nm) light stimuli (1 Cd/m2, 10 Cd/m2, and 100 Cd/m2, 13 sec/stimulus) under mesopic conditions. In patients, visual field examination (Goldmann perimetry), visual acuity, and OCT/FAF imaging (Spectralis OCT, Heidelberg Engineering) was used to correlate pupil constriction with the clinical phenotype.
A significant change in pupil constriction was observed in patients with mutations in the RPE65 gene when compared to healthy probands. The strongest reduction in pupil responses correlated well with the most severe phenotype. Low intensity blue light, which is considered to stimulate rods, was most often the first parameter to be reduced. Patients showed a delayed redilation of the pupil following termination of the bright blue light stimulus compared to healthy probands. In all patients, sustained pupil constriction was diminished compared with the transient pupil constriction for all light stimuli except the bright blue light stimulus.
Chromatic pupillography represents a highly sensitive and objective testing method to quantify the function of cones, rods and melanopsin containing ganglion cells in patients with severe retinal dystrophies associated with mutations in the RPE65 gene. The new test method will be useful to gather further information on the treatment effects in patients enrolled in gene therapy trials.
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