Fumiatsu Maeda

Analysis of retinal function using chromatic pupillography in retinitis pigmentosa and the relationship to electrically evoked phosphene thresholds

To analyse pupil responses to specific chromatic stimuli in patients with advanced retinitis pigmentosa (RP) to ascertain whether chromatic pupillography can be used as an objective marker for residual retinal function. To examine correlations between parameters of the pupil response and the perception threshold of electrically evoked phosphenes.

Association between a relative afferent pupillary defect using pupillography and inner retinal atrophy in optic nerve disease

Purpose The aim of this study was to compare the asymmetrical light reflex of the control subjects and patients with optic nerve disease and to evaluate the relationships among the relative afferent pupillary defect (RAPD), visual acuity (VA), central critical fusion frequency (CFF), ganglion cell complex thickness (GCCT), and circumpapillary retinal nerve fiber layer thickness (cpRNFLT) using spectral-domain optical coherence tomography. Materials and methods Using a pupillography device, the RAPD scores from 15 patients with unilateral optic nerve disease and 35 control subjects were compared. The diagnostic accuracy of the RAPD amplitude and latency scores was compared using the area under the receiver operating characteristic curve. Thereafter, we assessed the relationships among the RAPD scores, VA, central CFF, GCCT, and cpRNFLT. Results The average RAPD amplitude score in patients with optic nerve disease was significantly higher than that of the control subjects (P<0.001). The average RAPD latency score in patients with optic nerve disease was significantly higher than that of the control subjects (P=0.001). The area under the receiver operating characteristic curve for the RAPD amplitude score was significantly higher than that for the latency score (P=0.010). The correlation coefficients for the RAPD amplitude and latency scores were 0.847 (P<0.001) and 0.874 (P<0.001) for VA, −0.868 (P<0.001) and −0.896 (P<0.001) for central CFF, −0.593 (P=0.020) and −0.540 (P=0.038) for GCCT, and −0.267 (P=0.337) and −0.228 (P=0.413) for cpRNFLT, respectively. Conclusion Our results suggest that pupillography is useful for detecting optic nerve disease.

Color Pupillography in Dorsal Midbrain Syndrome

Objective: The purpose of this study was to evaluate the pupil response to chromatic stimuli in patients with lesions in the dorsal midbrain and possibly gain new insights into the afferent pupillary pathways. Methods: Color pupillography was performed in 5 patients with dorsal midbrain syndrome (DMS), and their results were compared with those of 20 healthy control subjects. We used full-field red stimuli (605 nm) that primarily address the rod/cone system and blue stimuli (420 nm) that preferentially activate intrinsically photosensitive retinal ganglion cells (ipRGCs) directly, with a duration of 4 seconds and a stimulus intensity of 28 lx corneal illumination under mesopic conditions. One eye was stimulated, and the consensual pupil response was recorded and analyzed. Results: The pupillary light reflex in patients with DMS was reduced, differed in shape, and showed a prolonged latency time compared to normal subjects. The blue response was less affected than the red response: the mean maximal relative amplitude (M) was 15.8% (SD = 7.8) in patients with DMS compared with 43.0% (SD = 5.5) in normal subjects for red stimulation, and M = 40.8%, SD = 8.4 (DMS) with M = 58.3%, SD = 4.8 (normals) for blue stimulation. The reduction was 63% for red stimulation but only 30% for blue stimulation in patients with DMS. Moreover, there was a preserved postillumination pupil response to blue stimulation in DMS patients. Conclusions: In DMS, the melanopsin-mediated ipRGC pathway appeared relatively preserved.

Development of a Chromatic Pupillography Protocol for the First Gene Therapy Trial in Patients With CNGA3-Linked Achromatopsia

Purpose To establish a feasible and sensitive pupillographic protocol to assess outer and inner retinal function for the first gene therapy trial in achromatopsia patients (ACHM) with mutations in CNGA3. Methods Twenty-seven CNGA3-ACHM patients and 22 age-matched control subjects were tested using chromatic pupillography. Three different protocols were established to assess the pupillary light reflex parameters and to create the final protocol. In the individual protocols, various stimulus parameters (i.e., intensity, duration, wavelength, adaptation states) were applied to evaluate the impact of these stimuli on the pupillary response in untreated ACHM patients. Results In the light-adapted conditions, CNGA3-ACHM patients showed significantly reduced maximal amplitudes compared with the control group when using a 1-second high intensity (28-lux corneal illumination) blue or red stimulus (P < 0.005). In the dark-adapted conditions, CNGA3-ACHM patients unexpectedly revealed significantly increased maximal amplitudes when stimulating with red (1 second) or blue (4 ms and 1 second) stimuli of low intensity (0.01-lux corneal illumination; P < 0.05). Pupil responses of CNGA3-ACHM patients after high intensity (28 lux) red and blue 1-second stimuli were within the normal range. Conclusions Chromatic pupillography demonstrated significant reduced pupil responses to stimuli addressing primarily cone function, an increased sensitivity to rod-favoring stimuli and evidence for disinhibition of intrinsically photosensitive retinal ganglion cells in CNGA3-ACHM patients. A final protocol was established based on these findings. These conclusions may be useful for the objective assessment of efficacy gained by gene therapy or other innovative interventions in this hereditary retinal disorder.