Pupil Size Measurements Research Articles

Assessment of the autonomic nervous system function in infants: the pupillary light reflex: normative data and physiological observations

The pupil size and its reaction to light (PLR) are an ideal indicator of autonomic functionality. Using modern infrared video techniques very reliable results can be generated. So far, normative data of PLR parameters in healthy infants are not available. We measured pupil size and PLR in 100 healthy infants aged 6–14 years by infrared pupillometry. The following PLR parameters were computed: Pupillary diameter, latency, amplitude, relative amplitude, constriction velocity and time, redilatation velocity (early/late) and 1/3 redilatation-time. Contrary to previous studies we observed no significant (p<0.05) differences of pupil size or PLR parameters with respect to different ages in infants. The data of PLR parameters are presented as means, standard deviations, medians and the 5th and 95th percentiles. Normative data of PLR parameters allows the interpretation of clinical data in diseases affecting the autonomic nervous system (ANS) in infants. Although not scope of the present study, we found significant differences in PLR in comparison of the right vs. left eye. These differences might support the theory of functional lateralization of the ANS – even in infants. This has to be corroborated in future studies.

Effects of mydriatics on intraocular pressure and pupil size in the normal feline eye

To determine the effect of various mydriatics (1% atropine, 1% cyclopentolate, 0.5% tropicamide, 10% phenylephrine) on intraocular pressure (IOP) and pupil size (PS) in normal cats. The mydriatics were tested in 10 adult ophthalmoscopically normal European Domestic Short-haired cats. Procedure Single-dose drug studies were divided into placebo (vehicle of phenylephrine), 10% phenylephrine, 0.5% tropicamide, 1% cyclopentolate and 1% atropine. After measurement of IOP and pupil size (PS) at 8 a.m. on the first day, one drop of the tested drug was applied to one randomly selected eye. The IOP and PS were measured for a minimum of 36 h until the pupil returned to pretest size. Ten per cent phenylephrine had no significant effect on IOP, and the effect on the pupil size was minimal (<or= 1 mm difference). One per cent atropine showed a maximal mean difference of 4.3 mmHg +/- 4.1 mmHg in IOP compared to the untreated eye. These differences were statistically significant at 1, 3, 6, 12 and 16 h post-treatment. At 1, 1.5 and 2 h after unilateral application of 1% cyclopentolate, the IOP in the treated eye was significantly higher than the IOP in the untreated eye with a maximal mean difference of 4.1 mmHg +/- 4.5 mmHg. With 0.5% tropicamide, IOP of the treated eye was significantly higher than IOP of the untreated eye at 1 and 1.5 h after treatment with a maximal mean difference of 3.5 mmHg +/- 3.3 mmHg. One per cent atropine caused the greatest increase in IOP, followed by 1% cyclopentolate and 0.5% tropicamide. The dilating effect of atropine, cyclopentolate and tropicamide lasted longer than the effect on intraocular pressure. The parasympatholytics 1% atropine, 1% cyclopentolate and 0.5% tropicamide caused a statistically significant elevation of IOP and produced mydriasis in the treated eye in normal cats, while the sympathomimetic 10% phenylephrine had no significant effect on IOP or pupil size.

Comparison of the effects of topical administration of a fixed combination of dorzolamide–timolol to monotherapy with timolol or dorzolamide on IOP, pupil size, and heart rate in glaucomatous dogs

To determine whether the combination multiple-dose dorzolamide-timolol administered topically has any greater effects on the reduction of intraocular pressure, pupil size, and heart rate in dogs with glaucoma than do either timolol or dorzolamide alone. Applanation tonometry, pupil size, and heart rate measurements were made at 7 a.m., 1 p.m., and 7 p.m. daily of 12 laboratory Beagles with inherited primary open-angle glaucoma during each active phase of this study. Timolol 0.5% was administered first twice daily for 4 consecutive days. Dorzolamide 2.0% was administered next three times daily for 4 consecutive days. The fixed combination of the two (timolol 0.5% and dorzolamide 2.0%) was administered twice daily for 4 consecutive days during the final week of the study. Between administration of each drug, a withdrawal period of at least 10 days was instituted. Statistical comparisons between the effects of the three drugs were performed. Intraocular pressure (IOP) was decreased with the administration of all three drugs: timolol alone, dorzolamide alone, and the combination of the two decreased IOP after 1 day of treatment 2.83 +/- 0.70 mmHg, 6.47 +/- 0.32 mmHg, and 6.56 +/- 0.37 mmHg, respectively. After 4 days of treatment, the IOP decreased even further: timolol alone, dorzolamide alone, and the combination of the two decreased IOP 3.75 +/- 0.88 mmHg, 7.50 +/- 0.29 mmHg, and 8.42 +/- 0.58 mmHg, respectively. Heart rate was significantly decreased with timolol (-11.9 +/- 2.0 bpm) and the combination preparation (-8.6 + 2.4 bpm), but not with dorzolamide (-3.7 +/- 1.8 bpm) alone. Pupil size was significantly decreased with timolol (-1.42 + 0.40 mm) and the combination preparation (-1.3 + 0.33 mm), but not with dorzolamide (0.97 +/- 0.36 mm) alone. The combination dorzolamide-timolol appears to be more effective at reducing intraocular pressure in glaucomatous dogs than is either timolol or dorzolamide alone.

A landmark study finds that when we look at sad faces, the size of the pupil we look at influences the size of our own pupil

A landmark study finds that when we look at sad faces, the size of the pupil we look at influences the size of our own pupil

Dynamic Measurement of Accommodation and Pupil Size Using the Portable Grand Seiko FR-5000 Autorefractor

The purpose of this study was to evaluate the potential of the portable Grand Seiko FR-5000 autorefractor to allow objective, continuous, open-field measurement of accommodation and pupil size for the investigation of the visual response to real-world environments and changes in the optical components of the eye. The FR-5000 projects a pair of infrared horizontal and vertical lines on either side of fixation, analyzing the separation of the bars in the reflected image. The measurement bars were turned on permanently and the video output of the FR-5000 fed into a PC for real-time analysis. The calibration between infrared bar separation and the refractive error was assessed over a range of 10.0 D with a model eye. Tolerance to longitudinal instrument head shift was investigated over a +/-15 mm range and to eye alignment away from the visual axis over eccentricities up to 25.0 degrees . The minimum pupil size for measurement was determined with a model eye. The separation of the measurement bars changed linearly (r2 = 0.99), allowing continuous online analysis of the refractive state at 60 Hz temporal and approximately 0.01 D system resolution with pupils >2 mm. The pupil edge could be analyzed on the diagonal axes at the same rate with a system resolution of approximately 0.05 mm. The measurement of accommodation and pupil size were affected by eccentricity of viewing and instrument focusing inaccuracies. The small size of the instrument together with its resolution and temporal properties and ability to measure through a 2 mm pupil make it useful for the measurement of dynamic accommodation and pupil responses in confined environments, although good eye alignment is important.

Intérêt de l’auto-réfractomètre et de l’orbscan pour la mesure du diamètre pupillaire

We compared pupil size measurements obtained with the Orbscan and autorefractometer to the Colvard Infrared pupillometer in order to determine their respective clinical advantages. We prospectively measured the pupil diameter in 94 eyes of 47 normal patients using the Colvard device, the Nikon NKR 8000 autorefractometer, and the Orbscan device. For each device, two successive measurements were taken to determine its reproducibility. We also studied the relationship with the contralateral eye (i.e., difference and correlation). The measurements obtained with the different devices in different light intensities were compared and studied using regression analysis. Pupil diameter measured using the Orbscan had the highest reproducibility (mean difference between the two successive measurements: 3.8% or 0.15mm) and showed the smallest difference between the two eyes (5.0% or 0.19mm) and the strongest correlation with the contralateral eye (r=0.93; p<0.001). Scotopic Colvard measurements and autorefractometer measurements with low light settings were not significantly different (5.86mm versus 5.86mm; p=0.48). Autorefractometer measurements with low light settings showed the strongest correlation with the scotopic Colvard measurements (r=0.84; p<0.001). The Orbscan measurements were less correlated with the scotopic or photopic Colvard measurements (r=0.73; p<0.001 and r=0.51; p=0.003, respectively). For the Colvard pupillometer, the correlation between photopic measurements and scotopic measurements was also poor (r=0.51; p<0.001). Pupil size measurements with the autorefractometer may be advantageous before refractive surgery. Measuring pupil size in photopic conditions, as with the Orbscan, cannot screen people with large pupils in mesopic conditions.

Pupil response to tropicamide following LASIK

Pupil response to tropicamide following LASIK

Correlation of infrared pupillometers and CCD camera imaging from aberrometry and videokeratography for determining scotopic pupil size

We read with interest the article by Kohnen et al.1 on the assessment of the correlation of infrared pupillometers and CCD-camera imaging from aberrometry for determining scotopic pupil size. In the study, the authors used a Zywave aberrometer, which takes 3 consecutive measurements and calculates the mean. Being an investigational unit, this version of Zywave can electively turn off the illumination fixating target. It was concluded from the study that Zywave with the fixating target turned off gives the pupil diameter closest to the Procyon, although smaller in size. With the fixating target turned on, Zywave underestimates the pupil size significantly more. In our commercial version of Zywave software, version Zywave V5.09, there is a dynamic pupillometer that tracks the pupil size in real-time and records the largest pupil size during the tracking period. In our study of 19 eyes, the mean pupil size was 6.06 mm ± 0.78 SD using the Zywave and 5.70 ± 0.71 mm using Procyon. Using a pared sample t test, the difference was 0.36 ± 0.28 mm (P<.001). This shows a pupil size measurement with Zywave significantly larger than that with Procyon. We feel that using the largest recorded pupil size rather than the mean of the 3 may give a better representation for the scotopic pupil. After all, it is the largest natural pupil size we are interested in and it is this pupil size that one should cover in planning for refractive surgery to avoid side effects like glare.

Modulation of the central nervous effects of levomethadone by genetic polymorphisms potentially affecting its metabolism, distribution, and drug action

Our aim was to judge the importance of candidate pharmacogenetic modulators of the central nervous effects of levomethadone by both magnitude of the modulatory effect and frequency of the mutation to assess the utility of genotyping for clinical levomethadone therapy in a random sample of subjects that, by distribution of genotypes, resembled the clinical setting. Candidate pharmacogenetic modulators were polymorphisms reported to be of functional consequence and therefore potentially important for metabolism, distribution, or pharmacodynamic action of levomethadone, consisting of genes coding for cytochrome P450 (CYP) 2B6 and 3A, as well as 1A2, 2C8, 2C9, 2C19, and 2D6, for P-glycoprotein (ABCB1), and for mu-opioid receptors (OPRM1). The central nervous effects of levomethadone were investigated by means of measuring pupil size in a random sample of 51 healthy volunteers for 9 hours after oral administration of 0.075 mg/kg levomethadone. Plasma concentrations of levomethadone and its metabolites were assessed concomitantly, and to judge the role of metabolites, the affinities of levomethadone and its metabolites at mu-opioid receptors were estimated by use of displacement of the selective mu-opioid receptor agonist [(3)H]-DAMGO ((3)H-[D-Ala(2),N-MePhe(4),Gly-ol(5)]-enkephalin). Pupil size decreased to -41.8% +/- 9.6% from baseline at 3.5 +/- 1.1 hours after levomethadone administration. Miosis was still manifest to a lower degree (-25.1% +/- 12.3%) at the end of the observation period. In carriers of the variant 118G allele (118A>G single-nucleotide polymorphism) of the mu-opioid receptor gene (OPRM1), levomethadone had a 1.74 times (95% confidence interval, 1.4-2.2 times) lower miotic potency (P < .001) as compared with noncarriers (concentration at half-maximum effects, 52.3 nmol/L; 95% confidence interval, 36.7-66.2 nmol/L). The maximum percent decrease in pupil diameter from baseline was 44.9% +/- 7.6%, 33% +/- 6.5%, and 24% +/- 6.9% for carriers of the OPRM1 118AA, AG, and GG genotypes, respectively (P < .001 for AG and GG versus wild type, without significant differences between AG and GG). Other candidate polymorphisms in the ABCB1 or in CYP genes had no significant influence on the effects of levomethadone, either because of lack of functional consequences or because of their low allelic frequency. The metabolites of levomethadone did not contribute to the effects as indicated by low metabolite plasma concentrations and their 120- to 1300-fold lower affinities at mu-opioid receptors as compared with levomethadone. Among polymorphisms in OPRM1, ABCB1, and CYP genes previously associated with functional consequences in a different context, the most important pharmacogenetic factor modulating the short-term effects of levomethadone is a polymorphism (OPRM1 118A>G) affecting mu-opioid receptors.

Measurement of the spatial shift of the pupil center

Purpose To evaluate the effectiveness of the pupil center as an anatomic landmark for excimer laser treatments. Setting Sekal-Microchirurgia-Rovigo Centre, Rovigo, Italy. Methods Pupillometry with the Costruzione Strumenti Oftalmici S.R.L. (CSO) pupil-measuring module (incorporated in Eye Top videokeratoscope) was performed in 52 patients with a diagnosis of myopia and in 25 patients with a diagnosis of hyperopia. Measurements both in mesopic and photopic conditions consisted of pupil diameters, spatial shift of the pupil center, and the distance between the pupil center and keratoscopic axis. Results The mean pupil diameter in photopic conditions of illumination in myopic eyes was 3.52 mm ± 0.56 (SD), while in mesopic conditions it was 5.37 ± 0.78 mm; in hyperopic eyes the mean photopic pupil diameter was 3.01 ± 0.46 mm, while the mean mesopic diameter was 5.12 ± 0.48 mm. The mean spatial shift of the pupil center in myopic eyes was 0.086 mm (maximum 0.269 mm), while in the hyperopic eyes it was 0.095 mm (maximum 0.283 mm). The mean distance between the pupil center and keratoscopic axis in myopic eyes was 0.226 ± 0.13 mm (maximum 0.75 mm), while in hyperopic eyes it was 0.45 ± 0.19 mm (maximum 0.8 mm). Conclusions The mean of the measured pupil sizes was greater in myopic eyes than in hyperopic eyes. The spatial shift of the pupil center, as the pupil dilates, was relatively small in all groups; therefore, the pupil center is a good anatomic landmark for both traditional refractive surgery and wavefront-guided treatments. The mean distance between the keratoscopic axis and pupil center was greater in the hyperopic group than in the myopic group. Therefore, centration of any laser treatment on the basis of the keratoscopic analysis should be done carefully, especially in hyperopic eyes and in cases in which the pupil center is meaningfully shifted from keratoscopic axis, even in photopic conditions of illumination.

Pilocarpine's effects on the blood-aqueous barrier of the human eye as assessed by high-resolution, contrast magnetic resonance imaging

The purpose of this research was to reassess the effects of topical pilocarpine on the integrity of the blood-aqueous barrier, using high resolution, magnetic resonance imaging, and the standard intravenous contrast agent gadolinium dimeglumine. It has long been known that topical pilocarpine gives rise to an increase in protein levels in the anterior chamber of the eye. This protein scatters light and is referred to clinically as ‘flare’. Prior studies concluded that pilocarpine-induced flare resulted from disruption of the blood-aqueous barrier. These studies relied upon indirect methods that precluded direct visualization of the posterior chamber of the eye. Five normal, human volunteers (age 22–40) received a single drop of 3% pilocarpine in one eye, following baseline measurements of pupil size and anterior chamber ‘flare’. These measurements were repeated every 15 min for 45 min. The subject was then positioned in the magnet and the eye that received pilocarpine was taped closed and covered with a 3 in.-diameter receive-only surface coil. The open contralateral eye focused on a target to maintain fixation of the imaged eye. A baseline image of the eye was obtained and the contrast agent was administered intravenously. A series of additional images was obtained during the following 60 min to track the movement of contrast material from the bloodstream into the tissues and compartments of the eye. Percent enhancement was calculated from selected regions of interest in the images, including the ciliary body, and the anterior and posterior chambers. Within the 45 min after administration of pilocarpine, pupil size in mm decreased from (mean± s.d.) 5.7±1.5 to 2.5±0.5 ( p=0.0106). During this period, average flare/ s.d. (photons msec −1) increased from 3.7±1.1 to 12.5±4.7 ( p=0.0151). In all cases, MRI images showed rapid enhancement of the ciliary body, followed by a progressive increase in signal in the anterior chamber but not the posterior chamber. These studies confirm that topical pilocarpine gives rise to ‘flare’ in the anterior chamber. But the lack of enhancement in the posterior chamber strongly suggests that the presence of this added protein in the anterior chamber is not the result of increased permeability of the blood-aqueous barrier of the ciliary body. These studies also introduce the novel concept that not all clinically observed flare is the result of blood-aqueous barrier compromise.

Measurement of the spatial shift of the pupil center

To evaluate the effectiveness of the pupil center as an anatomic landmark for excimer laser treatments. Sekal-Microchirurgia-Rovigo Centre, Rovigo, Italy. Pupillometry with the Costruzione Strumenti Oftalmici S.R.L. (CSO) pupil-measuring module (incorporated in Eye Top videokeratoscope) was performed in 52 patients with a diagnosis of myopia and in 25 patients with a diagnosis of hyperopia. Measurements both in mesopic and photopic conditions consisted of pupil diameters, spatial shift of the pupil center, and the distance between the pupil center and keratoscopic axis. The mean pupil diameter in photopic conditions of illumination in myopic eyes was 3.52 mm +/- 0.56 (SD), while in mesopic conditions it was 5.37 +/- 0.78 mm; in hyperopic eyes the mean photopic pupil diameter was 3.01 +/- 0.46 mm, while the mean mesopic diameter was 5.12 +/- 0.48 mm. The mean spatial shift of the pupil center in myopic eyes was 0.086 mm (maximum 0.269 mm), while in the hyperopic eyes it was 0.095 mm (maximum 0.283 mm). The mean distance between the pupil center and keratoscopic axis in myopic eyes was 0.226 +/- 0.13 mm (maximum 0.75 mm), while in hyperopic eyes it was 0.45 +/- 0.19 mm (maximum 0.8 mm). The mean of the measured pupil sizes was greater in myopic eyes than in hyperopic eyes. The spatial shift of the pupil center, as the pupil dilates, was relatively small in all groups; therefore, the pupil center is a good anatomic landmark for both traditional refractive surgery and wavefront-guided treatments. The mean distance between the keratoscopic axis and pupil center was greater in the hyperopic group than in the myopic group. Therefore, centration of any laser treatment on the basis of the keratoscopic analysis should be done carefully, especially in hyperopic eyes and in cases in which the pupil center is meaningfully shifted from keratoscopic axis, even in photopic conditions of illumination.

Determining scotopic pupil size

Reply: We would like to thank Khanani and Brown for their interst in our paper comparing different devices to determine scotopic pupil sizes. First, we do not think it matters that the measurements were conducted bilaterally since we compared only measurements between different methods but not intraindividual or interindividual variations in PD. Moreover, the concern that Colvard measurements could be affected by bilaterality is pure speculation and not proven by earlier studies. The term “gold standard” or “gold standard accuracy” was not used in our article. Khanani and Brown named the Procyon pupillometer the gold standard; we did not claim it was the gold standard, only that the PD values measured with the Procyon pupillometer were considered reference values in the comparison study we performed. The implication that we regard as the gold standard a device providing the largest PD values and that we rely on its accuracy for design or cost is pure fiction. We also did not claim that “clinicians should base their decisions on machine-specific scotopic PD values.” We stated that these values should be taken into consideration when planning a refractive surgical procedure. We agree with Khanani and Brown that scotopic pupil size has been determined for decades and newer approaches may have found different values. But the measurement of pupil size with digital infrared pupillometers seems to be the most precise and practical way to evaluate this factor for refractive surgery, particularly because they measure continual unrest and anisocoria. Thomas Kohnen MD Evdoxia Terzi MD Thomas Kasper MD Eva-Maria Kohnen MD Jens Bühren MD

Comparison of dynamic digital pupillometry and static measurements of pupil size in determining scotopic pupil size before refractive surgery

To compare 2 digital infrared pupillometers. Anterior Segment Service, Moorfields Eye Hospital, London, England. Eighty-eight eyes of 44 healthy subjects were recruited into the study. The scotopic pupil size was measured with 2 instruments, a digital pupillometer (Procyon) and a Hartman-Shack wavefront aberrometer (Visx WaveScan). Agreement between the instruments was assessed. There were 21 men and 23 women with a mean age 38.1 years +/- 9.2 (SD) (range 23 to 62 years). The mean scotopic pupil diameter was significantly larger with the WaveScan (6.61 +/- 0.92 mm) than with the Procyon pupillometer (6.40 +/- 0.90 mm), P<.001. There was good agreement in measurement of scotopic pupil size between the two instruments. The larger pupil diameter found with the Visx WaveScan than with the Procyon digital pupillometer probably represents the different illumination level used by each instrument, the effects of accommodation, and target fogging.

Pre–Excimer Laser and Post–Excimer Laser Refractive Surgery Measurements of Scotopic Pupil Diameter Using 2 Pupillometers

To compare a digital infrared pupillometer with a handheld light amplification pupillometer for measuring scotopic pupil size and to evaluate if the postoperative refractive changes of the cornea can influence pupil measurements. Prospective noncomparative interventional case series. One hundred eyes, 50 myopic (mean spherical equivalent [SE] refraction [+/- standard deviation], -4.32+/-2.44 diopters [D]) and 50 hyperopic (mean SE refraction, +2.95+/-0.99 D), of 50 otherwise healthy subjects underwent photorefractive keratectomy or LASIK. The preoperative and postoperative scotopic pupil sizes were measured by 2 examiners (E1, E2) with both a handheld light amplification pupillometer (Colvard, Oasis Medical, Glendora, CA) and a digital infrared pupillometer (Eye World Pupillometer [EWP], Oculus Keratograph, Oculus Opikgerate GmbH, Wetzlar, Germany). The agreement and interrater repeatability were determined using the comparison method described by Bland and Altman. The paired Student's t test was used to evaluate the difference between the preoperative and postoperative measurements. Scotopic pupil diameter, topographic corneal refractive power, uncorrected visual acuity (VA), best spectacle-corrected VA, and manifest spectacle refraction. The preoperative mean scotopic pupil diameter was 6.12+/-0.90 mm with the EWP and 6.18+/-0.91 mm with the Colvard. After the surgery, mean SE refractions were -0.22+/-0.98 D (myopic patients) and +0.19+/-0.40 D (hyperopic patients). Postoperative mean scotopic pupil diameters were 6.12+/-0.89 mm (EWP) and 6.17+/-0.90 mm (Colvard). There was no statistically significant difference between preoperative and postoperative mean scotopic pupil sizes in either patient group. The limits of agreement between the 2 devices ranged from 2.24 mm (E1) to 2.12 mm (E2) preoperatively and from 2.27 mm (E1) to 2.08 mm (E2) postoperatively. The coefficient of interrater repeatability ranged from 0.56 mm (EWP) to 1.12 mm (Colvard) preoperatively and from 0.62 mm (EWP) to 1.14 mm (Colvard) postoperatively. The digital infrared pupillometer showed better preoperative and postoperative repeatability than the handheld light amplification pupillometer. In the present study, a mean correction of <3 D of the corneal refractive power did not seem to modify the preoperative scotopic pupil size measurements.

Duration of pupillary constriction in response to a photographic flash

Reply: We are pleased to receive insightful comments on our work by Brown and coauthors. They raise several important methodology issues with respect to studies of pupil measurement that deserve further discussion and wider consideration. Brown and coauthors suggest that our study was intended to measure the pupil under dark-adapted conditions. This, however, was not our intent. We make a strict distinction between the dark-room conditions described in our study and true dark adaptation, which we reserve for the unique physiological state of rod-driven retinal sensitivity occurring after approximately 35 minutes of complete darkness in the normal eye.1 Brown and coauthors are rightly concerned that the time interval between the first flash exposure and subsequent measurements by the second examiner could have been insufficient for full pupil recovery. If the order of examiner was not randomized, this would lead to a sequence effect whereby the second examiner would measure a consistently smaller pupil size. They provide a plot of pupil size as a function of time in 2 eyes photographed using their recently published technique2 to illustrate this point. In our original publication, we reported that examiner order was arbitrary. In fact, 1 examiner was first in all but 2 cases. This provided an opportunity to test Brown and coauthors' hypothesis. Using a 2-way repeated measures analysis of variance (ANOVA) model, we compared the mean pupil size measured at each light level across examiners and also tested for an interaction between examiner and light level for the digital photographic method of measurement. If the concerns expressed by Brown and coauthors were a factor in our experiments, we would expect to find a significant interaction between these 2 variables. We found no interaction between light level and examiner (Figure 1; P=.09) and no difference between the 2 examiners in pupil size measurements (P=.20).Figure 1.: Mean measured pupil diameter by examiner as a function of light level for the photographic measurement method.Because any observed differences in pupil size could be due to examiner effects or sequence effects, we further explored their concern by testing for differences between examiners in mean pupil diameter with a 2-way ANOVA comparing light level across methods of measurement for each examiner sequence (examiner 1 then examiner 2; examiner 2 then examiner 1). We did not find a significant sequence effect on pupil size when we compared light levels by method interactions or method of measurement for either test sequence and show the comparison of pupil size by light level for each examiner (Figure 1). These findings should satisfy the concerns expressed by Brown and coauthors. Although the concern about an examiner sequence effect is valid and they identify a methodological weakness of our design, it did not influence our reported results. Brown and coauthors suggest that the time between photographs was not controlled or measured. Although we elected not to report these data, they were recorded and provide further evidence to allay their concerns. We show the difference between examiners for pupil diameter measurements as a function of time (Figure 2). The slope of this function was not significantly different than zero by linear regression (−0.018 mm/min; 95% confidence interval −0.050 to +0.014). The time between pupil measurements was 3.5 minutes at the medium light level (5 lux) and 4.3 minutes at the low light level (<0.63 lux).Figure 2.: Difference in measured pupil diameter between examiner 1 and examiner 2 as a function of the time difference between the 2 measurements. Number = 45 (×3 light levels); r 2 = 0.00, P = .98, Y = (0.130)X. The slope of this function was not statistically different than zero.A second hypothesis proposed by Brown and coauthors is that the variations observed in pupil size measurements with the Colvard pupillometer were possibly due to a prolonged tonic proximal accommodative response, and they suggest that we repeat our study with a randomized examiner order to address this issue. This raises another important concern of any pupil measurement study; namely, control of accommodation. The normal time course of pupil recovery from a convergent accommodative stimulus is seconds.3 Given that more than 2 minutes had passed between each examiner's measurements, the pupil should have had sufficient time to completely recover from an accommodative stimulus. We are grateful for the comments of Brown and coauthors and appreciate the opportunity to respond to their concerns. Michael Twa OD Melissa Bailey OD, PhD Mark Bullimore MCOptom, PhD John Hayes PhD

Pupil Examination

Pupillary size and reactivity have long been a critical component of the clinical assessment of patients with neurological disorders. The pupillary examination may provide critical information related to new or worsening intracranial pathology and facilitate prompt intervention to minimize further neuronal damage. With this in mind, intensive care nurses caring for neurologically impaired patients frequently must perform pupillary examinations in concert with assigning a Glasgow Coma Scale score. The purpose of this study was to test the accuracy and reliability of an automated pupillometer compared with the standard manual examination as a preliminary step in assessing the usefulness of automated pupillometry in the critical care setting. Twenty patients in the intensive care units of a teaching hospital were examined by two groups of three examiners using both the manual examination with a penlight or similar light source and a portable automated pupillometer capable of measuring pupil size and reaction. Measurements by a static pupillometer before and after each pupillary examination were used to determine the mean "true" size of the pupil. This study found that the automated pupillometer is more accurate and reliable than the manual examination in measuring pupil size and reactivity. For these reasons, such a device may be a beneficial addition in the clinical assessment of neurologically impaired patients.

Change in pupil size after implantation of an iris-fixated toric phakic intraocular lens

To evaluate the changes in pupil size after implantation of an iris-supported toric phakic intraocular lens (TPIOL) for correction of myopia and hyperopia with astigmatism. Department of Ophthalmology, Johannes Gutenberg-University, Mainz, Germany. Twenty-two myopic eyes and 9 hyperopic eyes were included in the study. The mean age of the 2 groups was 34 years and 40 years, respectively. The scotopic pupil size was measured with a handheld infrared pupillometer (Colvard, Oasis Medical) before and 6 months after implantation of the TPIOL. All examinations were performed under scotopic conditions after 2 minutes of dark adaptation with the fellow eye covered. Intraindividual comparisons were made between preoperative and postoperative pupil sizes. The relationship between implanted IOL power and postoperative pupil width in each group was studied to determine whether lens magnification could lead to misinterpretation of the results. The difference between horizontal and vertical postoperative pupil diameters was assessed in eyes with horizontally aligned IOLs to determine the potential mechanical effect of the TPIOL on pupil size. The mean scotopic pupil diameter decreased significantly from 4.7 mm (range 3.0 to 6.0 mm) preoperatively to 3.6 mm (range 2.0 to 5.0 mm) postoperatively in myopic eyes and from 5.0 mm (range 4.0 to 6.0 mm) to 4.0 mm (range 2.0 to 5.0 mm) in hyperopic eyes. No significant correlation between the power of the TPIOL and the postoperative pupil size diameter was found, confirming that the IOL did not distort measurements of pupil size. Comparing horizontal and vertical pupil diameters under medical mydriasis revealed reduced pupil size in the axis of enclavation. The scotopic pupil diameter decreased by a mean of 1.1 mm in myopic eyes and 1.0 mm in hyperopic eyes after implantation of the iris-supported TPIOL. Postoperative pupil size was not related to IOL power, patients' emotional states, or other factors. The slightly smaller pupil diameter in the axis of enclavation suggests that this fixation method restricts pupil size under scotopic conditions, which could reduce the incidence of postoperative photic phenomena.

Preliminary Observations on the Efficacy of Ocular Divergence Exercise for the Relax of Accommodation

Purpose: To study the effect of targeted divergence exercise on eye strain and relax of accommodation. Method: 60 myopic volunteers were recruited through poster advertisement and allocated into the test (41) and control (19) groups by order of presentation. The subjects were blinded to their allocations. All subjects wore a vision training device containing convex prism lenses (test) or plano lenses (control) and watched television at a three meter distance for ten sessions lasting one hour each over a three week period. Their refractive error and pupil size were measured before and after each session. Adverse symptoms were measured through questionnaires completed after each session. Results: After the tenth session, the test group showed a mean reduction in measured refractive error of 0.28±0.03D, while the Controls showed a mean reduction of 0.06±0.03D. A paired t-test yielded a significant difference in mean reduction between the groups (mean difference=0.22±0.05D, paired t=4.323, p=0.000). The measured pupil size in both groups did not reduce following training, thus showing the improvement in vision was not a result of pinhole effect by pupil miosis. The subjects experienced brief, fully reversible discomfort in initial sessions only. Conclusion: We found a statistically significant reduction in measured refractive error, likely due to the relax of accommodation or the reversal of over accommodation (e.g. pseudomyopia), when test subjects performed ocular divergency exercise using the ocular training device. Longitudinal studies are needed to evaluate the long term effect of ocular divergency vision training on myopic progression.

Monocular versus binocular pupillometry

To quantify differences between monocular and binocular pupil size measurement under scotopic and mesopic conditions. Department of Ophthalmology, Johannes Gutenberg-University, and Department of Medical Biometry, Epidemiology and Informatics, University of Mainz, Mainz, Germany. Computerized dynamic pupillometry (P2000 SA, Procyon Instruments Ltd.) was used at 3 illumination levels: scotopic at 0.03 lux, mesopic low at 0.82 lux, and mesopic high at 6.4 lux. One hundred forty eyes of 70 healthy volunteers without ocular pathology were examined. The subjects were divided into 2 groups. In the first group, the pupil diameter was measured binocularly first. In the second group, monocular measurement was performed first. For statistical analysis, data description was based on medians and quartiles of the respective pupil diameter measurements. Intraindividual significance was based on sign tests, and interindividual comparison were based on 2-sample Wilcoxon tests. In all eyes, statistically significant differences were found in pupil size, with higher values for the monocular measurement under low and high mesopic conditions (P=.000). For scotopic conditions, a trend toward higher values in monocular measurement was observed that approached statistical significance. Results indicate that binocular measurement may imitate the patient's life conditions more realistically. Therefore, in eyes with a large pupil diameter with the risk for postoperative scotopic phenomena, binocular measurement should be considered before refractive surgery.