Pupil assessment with a new handheld pupillometer in healthy subjects.

OBJECTIVE: To assess the pupil response with a new handheld pupillometer in healthy subjects. METHODS: Sixty-four eyes of 32 healthy subjects (mean age 21.2 years) were tested. After dark adaptation for 10 min, pupil responses to 1 s red and blue light stimuli at 100 cd/m2 were measured in the order from right to left eyes with a 1 min interval. The initial pupil size (D1, mm), minimum pupil size (D2, mm), and constriction rate (CR, %) were obtained. Intra-examiner reproducibility was examined using the coefficient of variation (CV, %) and the Bland-Altman plot. Inter-examiner consistency was examined using the interclass correlation coefficient (ICC) and the agreements with a conventional device, by Pearson's correlation coefficient (r). RESULTS: The CV of all parameters have high reproducibility in the red (11.0-20.7%) and blue (5.5-12.1%) light stimuli. Bland-Altman plot analysis showed no bias with both light stimuli. "Almost perfect" and "substantial" correlations between the examiners were obtained in the red (ICC = 0.78-0.94) and blue (ICC = 0.71-0.89) light stimuli. "Excellent" and "good" correlations between the devices were obtained, except for the CR parameter in the red (D1: r = 0.90; p < 0.001, D2: 0.72; p < 0.001, and CR: 0.08; p = 0.631, respectively) and blue (D1: r = 0.87; p < 0.001, D2: 0.70; p < 0.001, and CR: 0.19; p = 0.274, respectively) light stimuli. CONCLUSION: The novel pupillometer is useful for assessing pupil response. However, because of their different constructions, the CR values cannot be compared directly between the devices.

Morphological Changes and Potential Mechanisms of Intraocular Pressure Reduction after Micropulse Transscleral Cyclophotocoagulation in Rabbits.

INTRODUCTION: Micropulse transscleral cyclophotocoagulation (MP-TSCPC) is a method for intraocular pressure (IOP) reduction in patients with glaucoma; however, the specific mechanisms underlying its ability to reduce IOP remain unclear. We therefore investigated the morphological changes and mechanisms of IOP reduction after MP-TSCPC. METHODS: The right eyes of 4 pigmented rabbits were treated with MP-TSCPC with power setting corresponding to those used in glaucoma patients (1 power: 2,000 mW; time: 160 s; duty cycle: 31.3%). Power settings of 1, 1/8, 1/16, and 1/32 power were applied to the right eyes. The left eyes were used as controls. A light microscope and electron microscope were used to observe morphological findings after 1 week of MP-TSCPC. IOP and IOP reduction rate were compared before and after MP-TSCPC application on days 1, 3, and 5, and at 1 week. RESULTS: In the pre-MP-TSCPC, IOP was 16.7 ± 0.6 mm Hg. The IOP of rabbit treated with the 1 power was 3 mm Hg, with an IOP reduction rate of 80%; however, the eyes developed phthisis bulbi. The IOP was 7.0 ± 0.0 mm Hg 1 week after MP-TSCPC (IOP reduction rate: 59%) in rabbit treated with the 1/8 power. Reduction in IOP was observed, but there was significant tissue invasion to the ciliary body. The IOP was 10.3 ± 0.6 mm Hg (IOP reduction rate: 40%) 1 week after MP-TSCPC in rabbit treated with the 1/16 power, which was more effective to reduce IOP than that with the 1/8 power. Tissue invasion to the ciliary body was negligible, nonpigmented epithelial cells of the pars plicata were damaged, basal infoldings were destroyed, and repair was accompanied by proliferating tissue. No IOP reduction or tissue change was observed in rabbit treated with the 1/32 power. CONCLUSION: A potential mechanism for IOP reduction in pigmented rabbits is aqueous humor transport dysfunction due to damage to the nonpigmented epithelial cells of the pars plicata and destruction of basal infoldings. The power of MP-TSCPC was consistent with both morphological changes and IOP reduction.

The Effects of Chewing Gum in Preventing Eyestrain.

PURPOSE: To investigate the effects of chewing gum and tablet candy to reduce eyestrain in healthy individuals. MATERIALS AND METHODS: A double-blinded crossover trial was conducted. Forty-six healthy individuals (23 men, 23 women) between 20 and 59 years old, feeling eyestrain, were enrolled. Each 10-year age group included 12 individuals except the 30s group, which included 10 individuals. A visual task was performed on reading material displayed on a computer screen at a fixed distance for 60 min. Gum or tablet candy of two pieces were chewed for two 15-min periods starting 15 and 45 min after starting to read. Subjects chewed gum on Day 1 and tablet candy on Day 2, and vice versa. Primary outcome is as follows: subjective eye fatigue (eye tiredness, eye heaviness, blurred vision, double vision, and eye dryness) using a visual analog scale (VAS). Secondary outcomes are as follows: subjective accommodation from near and far points of accommodation measured with a D'ACOMO, spherical equivalent refraction, and eye dryness by analyzing ring break-up time (RBUT) measured with the RT-7000 Auto Ref-Topographer. RESULTS: The VAS scores of subjective eye fatigue were not significantly changed between chewing gum and tablet candy (P = 0.397 - P = 0.909). Those scores of eye tiredness and eye heaviness were significantly longer before and after the visual task with tablet candy (P = 0.013 and P = 0.025, respectively) but not with chewing gum. The changes of subjective accommodation were significantly lower after the visual task between chewing gum and candy (P = 0.043). There were significant differences among each age group (20 s vs. 30 s, P = 0.594; 20 s vs. 40 s, P = 0.002; 20 s vs. 50 s, P = 0.002). After reading, the changes of spherical equivalent refraction did not indicate a shift toward myopia (P = 0.267). In the RBUT, there were no significant differences between the samples (P = 0.680). CONCLUSIONS: Chewing gum helps improve the ability of the eye to focus, especially in young adults.

Challenges to detect glaucomatous visual field loss with pupil perimetry.

We evaluated the pattern deviation of pupil fields to differentiate a glaucomatous damage using the head-mounted perimeter "imo". Thirty-four eyes of 26 glaucoma patients (mean age, 55.1 years) were examined. The pattern deviation (85th percentile) of pupil fields was calculated from the difference between age-matched normal and abnormal percentage pupil constriction. Consequently, glaucomatous damages were remarkably distinguished from the normal pupil fields using the pattern deviation of the imo.

Effects of 0.4% ripasudil hydrochloride hydrate on morphological changes in rabbit eyes.

We evaluated the cellular structure changes after continuous use of ripasudil hydrochloride hydrate in rabbit eyes which might affect its own efficacy and adverse effects. Two pigmented Dutch rabbits and 1 Japanese white rabbit were instilled with 0.4% ripasudil hydrochloride hydrate to the left eye twice daily. The right eye was observed as the control. Both eyes of all 3 rabbits were then enucleated for histopathologic examination by light and electron microscope at 1mo in 1 of the pigmented Dutch rabbits, 3mo in the other pigmented Dutch rabbit, and in the Japanese white rabbit after instillation. Microscopic observations showed increase intercellular space in trabecular meshwork, ciliary body, and iris stoma, increase pigmented granule number and size in iris epithelial cells, and decrease actin filament in iris muscle fiber cells. Consequently, ripasudil hydrochloride hydrate decreases the intraocular pressure by improving the conventional outflow and may also facilitate the unconventional outflow via intercellular space widening without serious side effects.

Adaptation time, electroretinography, and pupillography in healthy subjects.

PURPOSE: To investigate the relationship between adaptation time and the parameters of electroretinography (ERG) and pupillography in healthy subjects. METHODS: Forty-six eyes of 23 healthy women (mean age 21.7 years) were enrolled. ERG and pupillography were tested in each of the right and left 23 eyes, respectively. ERG with a skin electrode was used to determine amplitude and implicit time by the records of rod-, flash-, cone-, and flicker-responses with white light (0.01-30 cd s/m2). Infrared pupillography was used to record the pupillary light reflex to 1-s stimulation of red light (100 cd/m2). Cone- and flicker- (rod-, flash- and pupil) responses were recorded after light (dark) adaptation at 1, 5, 10, 15, and 20 min. RESULTS: Amplitude (µV) was significantly different between 1 min and ≥ 5 or ≥ 10 min after adaptation in b-wave of cone- or rod-response, respectively. Implicit time (ms) differed significantly between 1 min and ≥ 5 min after adaptation with b-wave of cone- and rod-response. There were significant differences between 1 min and ≥ 10 or ≥ 5 min after dark adaptation in parameter of minimum pupil diameter (mm) or constriction rate (%), respectively. CONCLUSIONS: Cone-driven ERG can be recorded, even in 5 min of light adaptation time without any special light condition, whereas rod-driven ERG and pupillary response results can be obtained in 10 min or longer of dark adaptation time in complete darkness.

Evaluation of Pupil Fields Using a Newly Developed Perimeter in Glaucoma Patients.

PURPOSE: To evaluate objective pupil fields using a newly developed perimeter for the detection of glaucomatous damage. MATERIALS AND METHODS: Forty-three eyes of 32 glaucoma patients (42-69 years) were examined. Glaucomatous eyes were classified into three stages using the Hodapp-Anderson-Parrish grading scale (early, 16; moderate, 14; and severe, 13 eyes). The head-mounted perimeter "imo" was used to measure the percentage pupil constriction (PPC) of the pupil fields at 36 test points. A stimulus target size of Goldmann V with 0 decibels (dB) light under 31.4 apostilbs (asb) background was presented. Visual fields were measured with the Humphrey Field Analyzer 10-2 program. Using the 3D OCT-2000, 10 × 10 grid of the macular thickness were also obtained. Median correlation coefficients (r) of each examined eye were analyzed between the PPC and visual field sensitivity (dB), and the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCL)+ (GCL + inner plexiform layer [IPL]), and GCL++ (RNFL + GCL + IPL), respectively. RESULTS: Moderate correlations between the PPC and dB (r = 0.44-0.55), and GCL++ (r = 0.43-0.45) were obtained in the correspondence analysis of 12 test points. There were no significant differences in glaucoma severity (P = 0.924-1.000). However, some patients with extremely early stage glaucoma (visual field index ≥90%) tended to have poor correlation. CONCLUSIONS: Pupil fields of the imo generally corresponded to the visual fields and the RNFL + GCL + IPL thickness, even in early glaucoma; however, the examiner must clearly understand the criteria of patient selection.

Evaluation of Pupil Fields Using a Newly Developed Head-mounted Perimeter in Healthy Subjects.

PURPOSE: The purpose of this study was to evaluate the accuracy of pupil fields and determine the normative pupillary response data by age using a newly developed head-mounted perimeter. METHODS: A total of 100 healthy subjects (age, 20 to 68 y) were enrolled. The newly developed head-mounted perimeter "imo" was used to measure the percentage pupil constriction (PPC) as response to a stimulus at all 36 test points of the visual field. Goldmann size III and V stimuli at 0, 8, and 11 decibels (dB) under 31.4, 6, and 3 apostilbs (asb) background were presented. The PPC correlations (r) of the right and left eyes were examined. Reproducibility was determined with the coefficient of variation (CV) and a Bland-Altman plot. By a simple bootstrap method, the mean PPC were analyzed as normative data in all 36 test points. RESULTS: Excellent correlation between both eyes was obtained for Goldmann size V stimuli, target luminance of 0 dB, and a background luminance of 31.4 asb (r=0.83; P<0.001). From the test-retest CV peripheral areas have low reproducibility compared with central areas. With a Goldmann size V target, there was a steeper decline of the PPC from the center field to the periphery field, and the temporal field PPC was larger than the nasal field. No major differences were observed between the PPC data and the age groups by decade (eg, center 3 degrees; P=0.223-0.913). CONCLUSIONS: Normative PPC data might well be useful for assessing objective visual fields with the newly developed head-mounted perimeter.

Evaluation of a Relative Afferent Pupillary Defect using the RAPDx® Device Before and After Treatment in Patients with Optic Nerve Disease.

We evaluated the amplitude and latency scores in the RAPDx® device together with other ophthalmic examinations, before and after treatment in four patients with optic nerve disease. In all patients, the visual acuity (VA) and visual field (VF) after treatment was resolved. Both scores after treatment were lower, with reduced laterality-based differences in VA and critical flicker fusion frequency (CFF). Even after treatment, 3 patients had laterality-based differences in circumpapillary retinal nerve fiber layer thickness (cpRFNLT). Both scores for evaluation of RAPD by RAPDx® correlated with subjective examinations and were useful for evaluation of the efficacy of treatment.

New Mydriasis-Free Electroretinogram Recorded with Skin Electrodes in Healthy Subjects.

PURPOSE: To evaluate the reproducibility and consistency of the new mydriasis-free electroretinogram (ERG) with a skin electrode (RETeval) device, to determine the normative values of parameters, and to clarify the usefulness of pupil records to colored-light stimulus. METHODS: A total of 100 eyes of 50 healthy subjects (mean age, 21.4 years) were enrolled. The diagnostic parameters obtained by the RETeval device were examined under the following conditions. The reproducibility was determined with the coefficient of variation (CV). The consistency was examined by intraclass correlation coefficients (ICCs). The mean value and the normal range were analyzed with a 95% confidence interval as the normative values of parameters. The correlation of parameters to pupil records (area ratio, constriction ratio) and flicker ERG was also examined in the diabetic retinopathy assessment protocol. RESULTS: From the CV for each of the two measurements, the amplitude has a low reproducibility compared with the implicit time. Generally good consistency was obtained with both ERG parameters (ICCs = 0.48-0.92). Moderate correlations were found for the white-, red-, and blue-light stimulus in the area ratio and the constriction ratio, respectively (r = 0.44-0.62; P = 0.010-<0.0001). No correlation was observed between pupil and flicker parameters (r = 0.06-0.34; P = 0.646-0.051). CONCLUSIONS: The RETeval device was suggested as a possible screening device to detect the visual afferent diseases by evaluating in combination with the ERG recording and the colored-light pupil response.

Effects of Ripasudil Hydrochloride Hydrate Instillation on Pupil Dynamics.

PURPOSE: We investigated the effects of instillation of ripasudil hydrochloride hydrate (GLANATEC®) on pupil dynamics. MATERIALS AND METHODS: Fourteen healthy participants (mean age: 30 years), who had no ophthalmic diseases other than refractive error, were enrolled in this study. A single dose of GLANATEC® was instilled into the left eye only. The pupillary response was measured before and 30 and 120 min after instillation; we also measured intraocular pressure (IOP) at the same time points. RESULTS: The IOP in the left eye was significantly lower at both 30 (p < 0.05) and 120 (p < 0.01) min after instillation than at baseline, whereas that in the right eye was not significantly different from baseline at either of the measured post-instillation time points. In contrast, the pupillary response did not significantly differ between the three time points. CONCLUSIONS: A single instillation of low concentration GLANATEC® may have no effect on pupil diameter and pupillary response.

Evaluation of Relative Afferent Pupillary Defect Using RAPDx Device in Patients with Optic Nerve Disease.

We previously reported the standard values of the amplitude and latency scores in the RAPDx device for evaluating relative afferent pupillary defect (RAPD). Here, we evaluated RAPD in patients with optic nerve disease by using these standard values. Twenty-eight patients with current or previous optic nerve disease were enrolled in this study. Additionally, the data of 84 healthy subjects from our previous report were used as control data. We measured the amplitude and latency scores using RAPDx. We then compared their mean values and the percentages of individuals with standard values within a certain range between the optic nerve disease group and healthy group. Additionally, we evaluated their correlation with visual acuity and the critical flicker fusion frequency in the optic nerve disease group. Both parameters were significantly higher in the optic nerve disease group than in the control group (p < 0.0001). The detection rate of RAPD when using the standard value of amplitude score was 75%. Additionally, both parameters showed a significant correlation with laterality-based differences in visual acuity and critical flicker fusion frequency values in the optic nerve disease group (r = 0.59-0.75, p < 0.001). The amplitude and latency scores determined using RAPDx are useful in evaluating RAPD, particularly the standard value of the amplitude score.

Histopathological Changes of Inner Retina, Optic Disc, and Optic Nerve in Rabbit with Advanced Retinitis Pigmentosa.

We observed the histopathological changes of retinal ganglion cells (RGCs), optic disc, and optic nerve in rabbit with advanced retinitis pigmentosa (RP). Wild-type (WT) and rhodopsin transgenic (Tg) of RP rabbits were used at age 24 months. Light and electron microscopy were used to observe the retina, optic disc, and optic nerve. RGCs were also confirmed by immunofluorescent staining with a TUJ-1 monoclonal antibody. In addition to the rod and cone degeneration, we observed the astrocyte infiltration of the optic disc due to the damage of small RGCs and nerve fibres and atrophy of small optic nerve fibres. They subsequently lead to the optic disc excavation and atrophy of the optic nerve. Consequently, our histopathological study clarified that not only the outer retina but also the inner retina, the optic disc, and the optic nerve were also affected in the late stages of RP rabbit.

Electroretinography and Pupillography in Unilateral Foveal Hypoplasia.

The authors describe a 3-year-old boy with unilateral foveal hypoplasia and an absence of other ocular or systemic findings. Electroretinography obtained predominantly affecting cones. Laterality of pupil constriction to red but not to blue light was observed. The colored-light pupil response can be used to predict the retinal state.

Effects of Age and Sex on Values Obtained by RAPDx® Pupillometer, and Determined the Standard Values for Detecting Relative Afferent Pupillary Defect.

PURPOSE: To determine the effects of age and sex on the amplitude and latency scores obtained by the RAPDx® pupillometer, and to determine the standard values for detecting relative afferent pupillary defect (RAPD) in healthy subjects. METHODS: The study was conducted on 84 healthy subjects (52 males, 32 females), who had no ophthalmic diseases other than refractive errors with a mean age of 32 years. The amplitude and latency scores of the males were compared to that of females and also among the different age groups. The correlations between the amplitude and latency scores and age were determined. The standard values with the 90%, 95%, and 99% prediction intervals of the measured values were also calculated. RESULTS: The differences in the amplitude and latency scores between the sexes were not significant. In addition, both scores were not significantly related with age. The mean amplitude score for all subjects with prediction intervals of 90%, 95%, and 99% was 0.02 (-0.26 to 0.30, -0.32 to 0.35, and -0.42 to 0.46, respectively); the latency score was -0.02 (-0.24 to 0.20, -0.28 to 0.25, and -0.37 to 0.33, respectively). CONCLUSIONS: RAPD is not present when the absolute values of the amplitude score and latency scores, measured by the RAPDx® pupillometer, are ≤ 0.2 log units. RAPD is present when either of the values are ≥ 0.5 log units. TRANSLATIONAL RELEVANCE: Results of this study can be used for detection of RAPD in the clinic and it will be the basic data of RAPDx® pupillometer for future research.

Functional and morphological study of retinal photoreceptor cell degeneration in transgenic rabbits with a Pro347Leu rhodopsin mutation.

PURPOSE: To investigate the process of retinal degeneration by analyzing the functional and morphological findings in transgenic rabbits with a Pro347Leu rhodopsin mutation. METHODS: Wild-type (WT) and transgenic (Tg) rabbits at ages 4, 8 and 12 months were used. We conducted functional evaluation by recording the changes in the pupil response to red and blue light stimulation and the amplitude of the electroretinography (ERG). Morphologically, rod and cone distribution was examined using light and electron microscopy. Immunostaining for the identification of retinal ganglion cells (RGCs) was also confirmed by injecting a TUJ-1 monoclonal antibody. RESULTS: Pupil constriction for infrared pupillography and the a- and b-waves for ERG in Tg rabbits decreased with increasing age; the differences were compared to the age-matched WT rabbits. The subnormal ERG in the Tg rabbits, especially the a-wave decrease and pupil constriction with a long latency time, was induced only during exposure to blue light stimulation at 12 months. Light and electron microscopic findings showed a progressive loss of photoreceptor cells over time manifesting by 8 months in the peripheral retina. Moreover, pyknotic nuclei of the outer nuclear layer in the center of the visual streak were observed. At 12 months, there was disappearance of the rods and ballooning degeneration of the cones. Some remaining RGCs had large cell bodies with long branching dendrites. CONCLUSIONS: The changes in the pupil light response and amplitude of the ERG could be used to predict the state of retinal degeneration in the Tg rabbit.