The Short-Term Effect of 1% Tropicamide Drop on Pupillary Diameter and Intraocular Pressure Change in Patients With Pseudoexfoliation Material.

PRCIS: In this study, in patients with pseudoexfoliation syndrome (PXS) or glaucoma, changes in intraocular pressure (IOP) and pupil size after 1% tropicamide used for pupil dilation, compared with healthy patients were quantitatively demonstrated up to 4 hours after dilation. PURPOSE: The purpose of this study was to evaluate pharmacological dilatation with one drop of 1% tropicamide on pupillary diameter and IOP changes in patients with PXS and glaucoma (PXG). MATERIALS AND METHODS: Eighty-two patients with PXS, 78 Patients with PXG, and 35 healthy subjects were included in the study. PXG and PXS were diagnosed based on IOP assessment, corneal pachymetry, optic disc examination, visual field testing, and peripapillary retinal nerve fiber analysis. IOP and the diameter of pupil size were measured before dilatation and at postdilatation first, second, and fourth hours. RESULTS: The mean pupillary diameter values at postdilatation second and fourth hours were statistically significantly different between the patients with PXS and PXG ( P <0.001, for each). Also, there were significant differences between the PXS group and the control group in terms of the mean pupillary diameter values at predilatation and postdilatation at the first hour and postdilatation second hour ( P =0.007, <0.001, respectively). The mean pupillary diameter at all times was statistically significantly different between PXG and control groups ( P <0.001 for each). Significant IOP increases were observed in all groups after dilatation. The mean IOP at predilatation and postdilatation fourth hour was statistically significantly different between PXG and PXS groups ( P =0.042, <0.001, respectively). Whereas the mean IOP at predilatation, postdilatation first hour, postdilatation second hour, and postdilatation fourth hour were statistically significantly different between PXG and control group ( P <0.001 for each). CONCLUSIONS: Significant IOP increases have been observed in our study with 1% tropicamide in the PXG and PXS groups, with the peak effect at the second hour in the postdilatation period. Furthermore, the mean pupil diameter was found to be significantly lower in PXG patients compared with the control group.

Short-term effects of cyclopentolate and tropicamide eye drops on macular choroidal thickness in myopic children.

BACKGROUND: To investigate the short-term effects of cyclopentolate and tropicamide eyedrops on choroidal thickness (ChT) in myopic children using placebo or low-dose atropine eyedrops. METHODS: The analysis included 242 myopic individuals (7-19 years) enrolled in two randomised placebo-controlled clinical trials of low-dose atropine eyedrops. Cycloplegia was induced using either one drop of 1% cyclopentolate (n = 161), two drops of 1% cyclopentolate (n = 32) or two drops of 1% tropicamide (n = 49). ChT measurements were taken using swept-source optical coherence tomography before and 30 min after administering the cycloplegic eye drops. A subset of 51 participants underwent test-retest measurements prior to cycloplegia. RESULTS: Mean changes in subfoveal ChT after two drops of tropicamide and one and two drops of cyclopentolate were -2.5 µm (p = 0.10), -4.3 µm (p < 0.001) and -9.6 µm (p < 0.001), respectively. Subfoveal ChT changes after one and two drops of cyclopentolate were significantly greater than the test-retest changes (test-retest mean change: -3.1 µm; p < 0.05), while the tropicamide group was not significantly different (p = 0.64). Choroidal thinning post-cyclopentolate was not significantly different between atropine and placebo treatment groups (p > 0.05 for all macular locations). The coefficient of repeatability (CoR) in the tropicamide group (range: 8.2-14.4 µm) was similar to test-retest (range: 7.5-12.2 µm), whereas greater CoR values were observed in the cyclopentolate groups (one drop: range: 10.8-15.3 µm; two drops: range: 12.2-24.6 µm). CONCLUSIONS: Cyclopentolate eye drops caused dose-dependent choroidal thinning and increased variation in pre- to post-cycloplegia measurements compared with test-retest variability, whereas tropicamide did not. These findings have practical implications for ChT measurements when cyclopentolate is used, particularly for successive measurements.

Tropicamide Versus Cyclopentolate for Cycloplegic Refraction in Pediatric Patients With Brown Irides: A Randomized Clinical Trial.

PURPOSE: To compare the final cycloplegic refraction of tropicamide 1% and cyclopentolate 1% in children 3-16 years of age with brown irides. DESIGN: Randomized, controlled, multicenter prospective clinical trial. METHODS: Included patients were randomized to either cyclopentolate 1% or tropicamide 1% in the first visit with autorefraction measurements. Each subject underwent a second cycloplegic refraction using the other agent on a separate visit with a minimum of 1-week interval and a maximum of 12 weeks. We measured the change in SE (ΔSE) for each eye by deducting the SE before cycloplegia from the SE after cycloplegia. RESULTS: A total of 185 eyes from 94 children aged 3-16 years (average= 8.79 ±3.11 years) were included. The average SE of both eyes before cycloplegia was -0.082 ± 4.8 diopters. The SE after instillation of cyclopentolate and tropicamide in both eyes was 1.07±5.2 and 0.96±5.1, respectively (P value < .001). The average ΔSE after cycloplegia was 1.15±1.2 for cyclopentolate and 1.04±1.2 for tropicamide (P value < .001). The difference between ΔSE of cyclopentolate and tropicamide was found statistically significant at 0.11±1.2 (P < .001), although clinically insignificant. The ΔSE between the 2 drops before and after cycloplegia in both eyes for all refractive error groups was clinically insignificant. The greatest effect of cyclopentolate and tropicamide was in hyperopic eyes with ΔSE of 1.54±1.4 and 1.39±1.4, respectively. CONCLUSIONS: Tropicamide might be an effective and safe replacement for cyclopentolate in the refracting nonstrabismic pediatric population 3-16 years of age regardless of their refractive error status.

Effects of pupil dilation with topical 0.5% tropicamide on retinal vascular parameters assessed by VAMPIRE® software in healthy cats.

Our study investigates the effects of mydriasis obtained with topical 0.5% tropicamide on retinal vascular parameters evaluated in cats using the retinal imaging software: Vascular Assessment and Measurement Platform for Images of the Retina (VAMPIRE®). Forty client-owned healthy adult cats were included in the study. Topical 0.5% tropicamide was applied to dilate only the right pupil. The left eye was used as a control. Before dilation (T0), infrared pupillometry of both pupils was performed and fundus oculi images were taken from both eyes. Right eye fundus images were then captured 30 min after topical application of tropicamide (T30), when mydriasis was achieved. The retinal vessel widths (3 arteries and 3 veins) were measured with VAMPIRE® in four standard measurement areas (SMA) identified with the letters A, B, C, D. Average value of the 3 vessel widths was used. After normality assessment, the t-test was used to analyse the mean difference in vascular parameters of the left and right eyes at T0 and T30, with p set <0.05. The two eyes showed no statistical differences in pupil and vascular parameter measurements at T0. At T30, only one artery measurement of the right eye (SMA A-peripapillary area) showed a small but statistically significant mean vasoconstriction of approximately 4%. The results indicate that local application of 0.5% tropicamide seems to be associated with a small retinal arteriolar vasoconstriction as assessed by VAMPIRE® in cats. However, this change is minimal, and should not affect the interpretation of the results when VAMPIRE® is used.

Effects of atropine and tropicamide on ocular biological parameters in children: a prospective observational study.

BACKGROUND: The effectiveness of cycloplegia in delaying the progression of myopia and its application in refractive examination in children have been extensively studied, but there are still few studies on the effects of atropine/tropicamide on ocular biological parameters. Therefore, the purpose of this study was to explore the effects of atropine/tropicamide on children's ocular biological parameters in different age groups and the differences between them. METHODS: This was a prospective observational study in which all school children were examined for dioptres and ocular biological parameters in the outpatient clinic, and 1% atropine or tropicamide was used for treatment. After examination, we enrolled the patients grouped by age (age from 2 to 12 years treated by atropine, 55 cases; age from 2 to 10 years treated by tropicamide, 70 cases; age from 14 to 17 years treated by tropicamide, 70 cases). The ocular biological parameters of each patient before and after cycloplegia were measured, and the difference and its absolute value were calculated for statistical analysis using an independent-samples t test. RESULTS: We compared the value and the absolute value of the differences in ocular biological parameters before and after cycloplegia in the same age group, and we found that the differences were not statistically significant (P > 0.05). There were significant differences in the corresponding values of AL, K1 and ACD among the different age groups (P < 0.05). Before cycloplegia, there were significant differences in AL, K, K1, K2 and ACD in different age groups (P < 0.05). However, the differences in AL, K, K1, K2 and ACD among different age groups disappeared after cycloplegia (P > 0.05). CONCLUSIONS: This study demonstrated that atropine/tropicamide have different effects on cycloplegia in children of different ages. The effects of atropine/tropicamide on ocular biological parameters should be fully considered when evaluating the refractive state before refractive surgery or mydriasis optometry for children of different ages.

Efficacy and safety of intraoperative use of tropicamide 0.02%/phenylephrine0.31%/lidocaine1% intracameral combination during pediatric cataract surgery.

BACKGROUND: To demonstrate the safety and efficacy of the intracameral use of tropicamide 0.02%/phenylephrine 0.31%/lidocaine 1% in pediatric cataract surgery, a combination widely used in adult patients but still off-label in children. METHODS: Design: two-center, prospective, observational study. SETTING: San Giuseppe Hospital, Milan and Meyer Children's Hospital, Florence. STUDY POPULATION: children from 0 to 4 years of age undergoing cataract surgery with or without intraocular IOL implantation, in the absence of clinically significant systemic conditions, history of ocular surgery, concurrent ocular medication, hypersensitivity to any of the substances and post-traumatic cataracts. During the surgery, patients received the combination drug after the primary access to the anterior chamber. Efficacy was evaluated by achieving an adequate mydriasis in order to perform capsulorhexis, while safety was assessed by recording vital signs (heart rate, blood pressure, respiratory rate, temperature) pre- and post-administration of the substance. RESULTS: This study included 53 surgical procedures of 36 patients: 41 eyes were left aphakic, while 12 eyes received primary IOL implantation. The pupil size was adequate to safely perform capsulorhexis in 52 procedures of 53. The difference in pupil enlargement was significant (6.0 ± 1.14 mm, P = < 0.001). There were no notable changes in vital parameters. CONCLUSIONS: The administration of intracameral tropicamide 0.02%/phenylephrine 0.31%/lidocaine 1% in pediatric cataract surgery is effective for obtaining an adequate mydriasis without any vital parameters changes throughout the procedure.

Comparison study between pilocarpine and tropicamide drops on corneal topography and their effect on IL-6 and TNF-α levels in tear.

Corneal stability is essential for contact lenses and refractive surgery. It seems that paralyzing eye drops or expansion of the ciliary muscle affect the radius of curvature and the strength of the cornea, and this effect is to increase the strength of the cornea during muscle spasm and decrease it in the relaxed state of the muscle. On the other hand, different factors (such as contact lens wear, ocular surface disorders, trauma, dry eye, and immunosuppression) could alter the immune defense mechanisms of the outer eye and permit microorganisms to invade the cornea. Therefore, the present study compared Pilocarpine and tropicamide drop on corneal topography and their effect on IL-6 and TNF-α levels in tear. This prospective study was performed on sixty normal and healthy eyes of sixty volunteers with a mean age of 38.19 years and without any ocular pathology. Volunteers were divided into two groups of thirty. In the first group, corneal topography of both eyes was measured before and 30 minutes after instillation of topical tropicamide 1% in only one eye. The other eye was the control eye, and no drop was given. The same routine was performed in the second group, except that subject received one drop of Pilocarpine 2% in one eye. Statistical comparison between groups for the central corneal power, corneal radius, and corneal astigmatism was performed using paired t-test. IL-6 and TNF-α levels in tear were analyzed using two Luminex commercial assays with Bio-Plex 200TM System (Bio-Rad, Hercules, California, USA). In group 1, no significant changes were found in corneal radius, power, and astigmatism. However, in group 2 subjects who received pilocarpine eye drops, the mean corneal radius value decreased significantly by 0.05 mm. The mean corneal power increased by +0.32 D. There was no significant difference change in corneal astigmatism in both groups. Evaluation of IL-6 levels in tears showed a significant difference between the control and treatment groups (P = 0.041). But no significant difference was observed between the Pilocarpine and the Tropicamide groups (P = 0.761). Evaluation of TNF-α level in tears also showed no significant difference between these groups (P = 0.088). Pilocarpine induced ciliary muscle contraction, which may cause pressure on the corneal limbus and scleral spur, resulting in changes in corneal curvature. But tropicamide eye drop did not affect corneal radius and other corneal parameters, and corneal topography can be carried out after the installation of tropicamide eye drop.

Cyclopentolate eye drops-induced anaphylaxis in an infant.

BACKGROUND: Cyclopentolate is frequently used as a mydriatic agent during ophthalmological examinations in childhood and hypersensitivity reactions associated with this drug are rare. We aim to report an infant who experienced anaphylaxis due to cyclopentolate eye drops. CASE: A nine-month-old girl, who was being followed up with a diagnosis of retinoblastoma, presented for consultation for urticaria, cough, stridor, and dyspnea that developed after the administration of topical cyclopentolate to the eyes. The patient was diagnosed with anaphylaxis and treated with adrenaline. During the follow-up, tropicamide was used safely as an alternative drug. CONCLUSIONS: In children, hypersensitivity reactions due to cyclopentolate are very rare. Only four pediatric patients were reported in the literature to have developed an allergic reaction after the administration of cyclopentolate eye drops. We present here the youngest patient who developed anaphylaxis with cyclopentolate eye drops. Anaphylaxis due to cyclopentolate should be kept in mind, rapidly recognized, and treated when a reaction develops.

Short-term anatomic response of the choroid to tropicamide in myopic patients.

We aimed to investigate how tropicamide alters subfoveal choroidal thickness (SFChT) and choriocapillaris flow density (CD) and determine the predictive factors of choroid thickness and vascular density in myopic eyes. This retrospective study was conducted from September 2018 to March 2019. SFChT was measured with enhanced depth spectrum-domain optical coherence tomography. The choriocapillaris was imaged using optical coherence tomography angiograms. Ocular parameters were measured thirty minutes before and after 1% tropicamide instillation. Twenty-five eyes of 15 patients (mean age 38.12 ± 6.35 years old and refractive error-8.57 ± 3.37 D) met the study criteria. The baseline linear regression model showed an association of thinner choroid with older age (P = .027) and high myopic patients (P = .001). Tropicamide substantially increased SFChT (P = .001), but had no significant influence on CD (P = .526). Moreover, SFChT variation after tropicamide instillation positively correlated with diopter changes in spherical equivalent (P = .005) and percentage changes in CD (P = .046). In myopic eyes, choroidal layer thickened substantially in response to tropicamide. The increase of SFChT only correlates with variations in spherical equivalent and CD. Short-term tropicamide installation altered both choroid thickness and choroid microvasculature, which implies an interplay among choroidal volume, perfusion, and ciliary muscle tone.

Changes in intraocular pressure after pharmacological pupil dilatation in an elderly Chinese population in Taiwan: The Shihpai eye study.

BACKGROUND: Mydriatic drugs are often used in ophthalmic clinics for pupil dilatation to assess the optic nerve and retina. Clinical studies have indicated that an increase in intraocular pressure (IOP) after pupil dilation is noted in open-angle glaucoma patients, those with narrow angles and in normal subjects. Asians are more likely to have narrow angles. Moreover, age-related cataract may increase the crowdedness of the angle. This study aimed to assess the effects of mydriatic pupil dilatation on IOP in an elderly Chinese population. METHODS: The Shihpai Eye Study was a community-based, cross-sectional survey of vision and eye diseases among noninstitutionalized subjects aged 65 years and older in Shihpai, Taipei, Taiwan. IOP was taken using noncontact tonometry. The pupil was dilated with 1% tropicamide. IOP was measured again after maximal pupil dilatation 1 hour after mydriasis. RESULTS: Of the 2045 participants, 1361 (66.6%) participated in both the questionnaire and eye examinations. The mean IOP before pupil dilatation was 12.9 ± 3.1 mmHg and was 12.8 ± 3.4 mmHg (range: 5-36 mmHg) after pupil dilatation. IOP higher than 21 mmHg after pupil dilation was noted in 17 (1.34%) participants, of whom IOP exceeded 30 mmHg in two (0.16%). Overall, the changes in IOP before and after pupil dilatation were insignificant ( p = 0.04). In the final regression analyses, refractive status toward hyperopia ( p < 0.01) was the only significant factor associated with an increase in IOP of at least 4 mmHg after pupil dilatation. CONCLUSION: Our results revealed that the increase in IOP after pharmacological pupil dilatation was minimal, and the incidence of acute angle-closure attack was insignificant. Hyperopic status was the only factor related to an increase in IOP of > 4 mmHg. Caution should be exercised if one is hyperopic or has a history of glaucoma and rechecking IOP in these subjects is suggested after pharmacological mydriasis.

Memory Consolidation Depends on Endogenous Hippocampal Levels of Anandamide: CB1 and M4, but Possibly not TRPV1 Receptors Mediate AM404 effects.

The endocannabinoid system is involved in the fine-tuning of local synaptic plasticity in the hippocampus during the initial steps of memory formation/transformation. In spite of extensive studies, endocannabinoid modulation of these processes is still poorly understood. Here we studied the effects of intra-CA1 infused AM404, an anandamide (AEA) transport/metabolism inhibitor, upon an aversive memory consolidation with or without prior systemic administration of metyrapone, as well the concomitant intra-CA1 administration of AM404 plus AM251 (CB1 receptor inverse-agonist), capsazepine (TRPV1 receptor antagonist) or tropicamide (M4 receptor antagonist). We also investigated the effect of AM404 on memory retrieval and Long-Term Potentiation induction. Adult male Wistar rats were trained in the Contextual Fear Conditioning task and tested 48 h later. AM404 disrupted both memory consolidation and retrieval, and abolished LTP induction. The post-training effect, however, was reverted by metyrapone - which was amnestic by itself - corroborating the known co-dependency between glucocorticoids and endocannabinoids, and suggesting that some level of aversiveness is necessary for an adequate consolidation. In the coadministration experiments, while AM251 and tropicamide were able to revert the AM404 amnestic effect, capsazepine had no effect. This confirms that CB1 actually mediate the amnestic effect caused by the augmented AEA pool, but TRPV1 does not. The tropicamide result suggests an interesting comodulatory interaction between the endocannabinoid and the cholinergic systems. We propose a steady-state model centered in the idea of an optimal, stable extracellular concentration of anandamide as a necessary condition to ensure the consolidation of a stable memory trace in the CA1 area.

Mucoadhesive Polymers Enhance Ocular Drug Delivery: Proof of Concept Study with 0.5% Tropicamide in Dogs.

Purpose: To assess the efficacy of 0.5% tropicamide applied after topical administration of 1.4% hydroxyethyl cellulose (HEC) or 1.2% hyaluronic acid (HA) at different time intervals. Methods: Eleven healthy Labrador retriever dogs were used. The study consisted of 7 trials in which pupil diameter (PD) was measured every 30 min for 7 h after drug administration. In trial 1, PD was measured after tropicamide application (control). In trials 2-7, PD was measured after treatment with tropicamide 10 s, 1 and 5 min after application of HEC or HA. Data were analyzed using analysis of variance and post hoc Holm-Sidak tests. Results: Maximal PD (mean ± standard deviation) was significantly greater (P < 0.001) in 5 of 6 experimental trials, with the greatest PD recorded when HEC was applied 1 min (12.2 ± 0.4 mm) and HA 10 s (12.3 ± 0.5 mm) before tropicamide, compared with 11.2 ± 0. 7 mm in control trial 1. PD >10 mm was maintained for 2.75-5 h in trials 2-7 and 2.25 h in trial 1 (P < 0.001). Area under the PD-time curve ranged from 61.9 to 71.3 ± 2.9 mm·hours in trials 2-7, significantly greater than 59.3 ± 1.8 mm·hours in control trial 1 (P ≤ 0.031). Conclusions: Tropicamide efficacy was enhanced by prior administration of a mucoadhesive polymer. Additional studies are needed to determine if HEC and HA of varying concentrations similarly extend and potentiate the effect of other topical ophthalmic drugs in canine eyes.

Effect of pupil dilation on intraocular pressure in preterm and term infants.

PURPOSE: To evaluate the effect of pupil dilation on intraocular pressure in preterm and term newborns. METHODS: This prospective study involved 55 eyes of 28 preterm infants and 38 eyes of 20 term infants. The infants were divided into two groups according to their gestational ages at birth as follows: preterm group, <37 weeks and term group, ≥37 weeks. Pupil dilation was attained with tropicamide 0.5% and phenylephrine 2.5%. Intraocular pressure measurements were performed with Icare PRO (Icare Finland Oy, Helsinki, Finland) before and after pupil dilation. A paired t test was used to compare the measurements before and after pupil dilation. RESULTS: The mean intraocular pressure change was -1.04 ± 3.03 mmHg (6.20/-11.40 mmHg) in the preterm group and -0.39 ± 2.81 mmHg (4.60/-9.70 mmHg) in the term group. A statistically significant difference in intraocular pressure was observed only in the preterm group after pupil dilation (p=0.01). CONCLUSION: An unexpected alteration in intraocular pressure in newborns may occur after pupil dilation, especially in preterm infants.

Early phase of pupil dilation is mediated by the peripheral parasympathetic pathway.

Pupil diameter fluctuates in association with changes in brain states induced by the neuromodulator systems. However, it remains unclear how the neuromodulator systems control the activity of the iris sphincter (constrictor) and dilator muscles to change the pupil size. The present study compared temporal patterns of pupil dilation during movement when each muscle was pharmacologically manipulated in the human eye. When the iris sphincter muscle was blocked with tropicamide, the latency of pupil dilation was delayed and the magnitude of pupil dilation was reduced during movement. In contrast, when the iris dilator muscle was continuously stimulated with phenylephrine, the latency and magnitude of rapid pupil dilation did not differ from the untreated control eye, but sustained pupil dilation was reduced until the end of movement. These results suggest that the iris sphincter muscle, which is under the control of the parasympathetic pathway, is quickly modulated by the neuromodulator system and plays a major role in rapid pupil dilation. However, the iris dilator muscle receives signals from the neuromodulator system with a slow latency and is involved in maintaining sustained pupil dilation.NEW & NOTEWORTHY By pharmacologically manipulating the pupil dilator and constrictor muscles of human eye separately, we found that the pupil constrictor muscle is a primary controller of rapid pupil dilation upon brain arousal. However, the pupil dilator muscle, which is innervated by the sympathetic nervous system and is generally considered as a major regulator of pupil dilation, is not involved in rapid pupil dilation, but was involved in long-lasting pupil dilation.

Muscarinic M1, but not M4, receptor antagonism impairs divided attention in male rats.

Divided attention may be more important than ever to comprehend, given ubiquitous distractors in modern living. In humans, concern has been expressed about the negative impact of distraction in education, the home, and the workplace. While acetylcholine supports divided attention, in part via muscarinic receptors, little is known about the specific muscarinic subtypes that may contribute. We designed a novel, high-response rate test of auditory sustained attention, in which rats complete variable-ratio runs on one of two levers, rather than emitting a single response. By doing this, we can present a secondary visual distractor task during some trials, for which a correct nosepoke response is reinforced with a more palatable food pellet. The nonspecific muscarinic antagonist scopolamine impaired performance, and slowed and reduced lever press activity. We then explored antagonists that preferentially block the M1 and M4 subtypes, because these receptors are potential therapeutic targets for cognitive enhancers. Telenzepine, an M1-preferring antagonist, impaired divided attention performance, but not performance of the attention task without distraction. Telenzepine also had fewer nonspecific effects than scopolamine. In contrast, the M4-preferring antagonist tropicamide had no effects. Analysis of overall behavior also indicated that accuracy in the main attention task decreased as a function of engagement with the distractor task. These results implicate the M1 receptor in divided attention.

Assessing the Clinical Requirement of 2.5% Phenylephrine for Diagnostic Pupil Examination.

Purpose: To evaluate whether the standard dilating drop regimen consisting of phenylephrine, tropicamide, and proparacaine produces clinically significant improvement in pupil size compared to tropicamide and proparacaine during diagnostic eye examination. Methods: Sixty-three adult patients at Washington University School of Medicine Eye Clinic were enrolled in this prospective, randomized trial. Each patient received one of two dilating drop regimens: phenylephrine + tropicamide + proparacaine (PE+T+PP), which is considered the standard therapy, or tropicamide + proparacaine (T+PP). Main outcome measures were the proportion of pupils able to achieve successful clinical examination without need for additional dilating drops and change in predilation to postdilation pupil size. Comparisons were made using McNemar's test, repeated measures analysis of variance, and Fisher's test to determine whether PE is a necessary component of the standard eye examination. Results: There were no statistically significant differences between the PE+T+PP and T+PE treatment groups in predilation to postdilation changes in average resting pupil size (1.58 ± 0.66 and 2.61 ± 0.79; P = 0.57) or constricted pupil size (2.52 ± 0.93 and 3.56 ± 0.96; P = 0.15). There was no statistically significant difference between patients who obtained a successful dilated pupil examination between those receiving PE+T+PP and those receiving T+PP as determined by the examining physicians (Fisher's, P = 0.67). Conclusion: The addition of phenylephrine to tropicamide and proparacaine did not improve pupillary dilation size or ability to conduct a clinical examination. A single dilating agent using tropicamide should be considered in clinical practice.

Moderate oxidative stress promotes epithelial-mesenchymal transition in the lens epithelial cells via the TGF-ß/Smad and Wnt/ß-catenin pathways.

The epithelial-mesenchymal transition (EMT) plays a significant role in fibrosis and migration of lens epithelial cells (LECs), and eventually induces posterior capsule opacification (PCO). In the past, it was generally believed that the TGF-ß/Smad pathway regulates lens EMT. A recent study found that attenuated glutathione level promotes LECs EMT via the Wnt/ß-catenin pathway, which suggests a more complex pathogenesis of PCO. To test the hypothesis, we used the mouse cataract surgery PCO model and tested both canonical Wnt/ß-catenin and TGF-ß/Smad signaling pathways. The results showed that both TGF-ß/Smad and Wnt/ß-catenin pathways were activated during the lens capsule fibrosis. Compared with the freshly isolated posterior capsule, the expression level of phosphorylated Smad2 was highest at day3 and then slightly decreased, but the expression level of Wnt10a gradually increased from day0 to day7. It shows that these two pathways are involved in the lens epithelium's fibrotic process and may play different roles in different periods. Subsequently, we established oxidative stress-induced EMT model in primary porcine lens epithelial cells and found that both the TGF-ß/Smad and Wnt/ß-catenin pathways were activated. Further study suggests that block Wnt/ß-catenin pathway using XAV939 alone or block TGF-ß/Smad pathway using LY2109761 could partially block pLECs fibrosis, but blocking Wnt/ß-catenin and TGF-ß/Smad pathway using combined XAV939 and LY2109761 could completely block pLECs fibrosis. In conclusion, this study demonstrates that both TGF-ß/Smad and canonical Wnt/ß-catenin pathways play a significant role in regulating epithelial-mesenchymal transformation of lens epithelial cells but might be in a different stage.

In vitro evaluation of anti-fungal activity of tropicamide against strains of Candida spp. resistant to fluconazole in planktonic and biofilm form.

Candida spp. is considered to be the third or fourth most common cause of bloodstream infections associated with healthcare services in the world. Currently, several strains exhibit resistance to the traditional treatments, making the development of new therapeutic molecules necessary. Drug repositioning is an alternative that can be used to work around problems such as toxicity, cost and time in the development of new drugs. This study aims to evaluate the in vitro antifungal effect of tropicamide, molecule of anticholinergic action, against planktonic cells of Candida spp. and biofilm of C. albicans. Six strains of different Candida species were used to determine the minimum inhibitory concentration (MIC) of tropicamide and fluconazole according to CLSI document M27-A3 and one strain of C. albicans was used to evaluate the activity of tropicamide against biofilms. In concentrations of 64µg/mL, the tropicamide exhibited 50% of inhibitory activity in planktonic cell and in concentrations of 128µg/mL is able to inhibit the formation of C. albicans biofilm. Despite the inhibitory activity shown at the present study, the use of a larger number of strains, as well as in vivo cytotoxicity assays, is necessary to confirm the hypothesis that tropicamide can be used as an adjuvant agent in the treatment of infections by the Candida genus.

Iris stromal cell nuclei deform to more elongated shapes during pharmacologically-induced miosis and mydriasis.

Nuclear shape alteration in ocular tissues, which can be used as a metric for overall cell deformation, may also lead to changes in gene expression and protein synthesis that could affect the biomechanics of the tissue extracellular matrix. The biomechanics of iris tissue is of particular interest in the study of primary angle-closure glaucoma. As the first step towards understanding the mutual role of the biomechanics and deformation of the iris on the activity of its constituent stromal cells, we conducted an ex-vivo study in freshly excised porcine eyes. Iris deformation was achieved by activating the constituent smooth muscles of the iris. Pupillary responses were initiated by inducing miosis and mydriasis, and the irides were placed in a fixative, bisected, and sliced into thin sections in a nasal and temporal horizontal orientation. The tissue sections were stained with DAPI for nucleus, and z-stacks were acquired using confocal microscopy. Images were analyzed to determine the nuclear aspect ratio (NAR) using both three-dimensional (3D) reconstructions of the nuclear surfaces as well as projections of the same 3D reconstruction into flat two-dimensional (2D) shapes. We observed that regardless of the calculation method (i.e., one that employed 3D surface reconstructions versus one that employed 2D projected images) the NAR increased in both the miosis group and the mydriasis group. Three-dimensional quantifications showed that NAR increased from 2.52 ± 0.96 in control group to 2.80 ± 0.81 and 2.74 ± 0.94 in the mydriasis and miosis groups, respectively. Notwithstanding the relative convenience in calculating the NAR using the 2D projected images, the 3D reconstructions were found to generate more physiologically realistic values and, thus, can be used in the development of future computational models to study primary angle-closure glaucoma. Since the iris undergoes large deformations in response to ambient light, this study suggests that the iris stromal cells are subjected to a biomechanically active micro-environment during their in-vivo physiological function.

The effect of topical tropicamide and phenylephrine on macular and peripapillary microvasculature: an optical coherence tomography angiography study.

PURPOSE: To evaluate the effect of topical tropicamide 1% and phenylephrine 2.5% instillation on macular and peripapillary microvasculature measurements with optical coherence tomography angiography (OCTA). METHODS: Forty eyes of 40 consecutive healthy adults with no known systemic or ocular disease were recruited for this prospective consecutive case study. After complete ophthalmological examination, all patients underwent OCTA measurements (OptoVue Inc, Freemont, CA, USA) to assess foveal avascular zone (FAZ) area, FAZ perimeter, acircularity index of FAZ, foveal density, vessel density of superficial and deep capillary plexus and peripapillary capillary plexus. 6 × 6 mm macular and 4.5 × 4.5 mm peripapillary OCTA images were undertaken before and 30 min after instillation of tropicamide (20 eyes) or phenylephrine (20 eyes) instillation to the right eye, and these were compared to each other and to fellow control eye. RESULTS: 15 male and 25 female patients with a mean age of 43.3 (18-60) years were recruited for the study. Superficial, deep and peripapillary capillary plexus measurements of tropicamide 1% and phenylephrine 2.5% instilled right eyes and left control eyes were similar before and 30 min after instillation (P > 0.05 for all). FAZ assessment tool variables were also similar before and after instillation (P > 0.05 for all) for both eyes. CONCLUSION: Topical pupillary dilatation with tropicamide 1% and phenylephrine 2.5% did not affect macular and peripapillary OCTA measurements. Follow-up OCTA images in retina and glaucoma patients can be captured with a dilated or undilated pupil which seems not to be affected by tropicamide or phenylephrine.