Case report: Topical pilocarpine ameliorated the accommodation loss and pupillary dilation after micropulse transscleral laser treatment.

BACKGROUND: The present study elucidates a common significant postoperative complication of micropulse transscleral laser treatment (mTLT) and explores its potential management strategies for younger patients with good central vision. CASE PRESENTATION: Three younger Chinese glaucoma patients with good central vision maintained high intraocular pressures (IOPs) (36, 25, and 30 mmHg) on maximally tolerated topical anti-glaucoma medications. All patients were treated with mTLT because of a higher risk of complications with filtering surgery. After the procedure, their best-corrected visual acuities were not significantly changed, IOPs were significantly decreased, and the number of topical anti-glaucoma medicines was gradually decreased. However, all patients complained about reduced near visual acuity (NVA) for 1-5 months. Slit-lamp examination revealed pupillary dilation, and binocular accommodative function examination indicated accommodation loss. After treatment with 2% topical pilocarpine, all patients reported an improvement in NVA. Among them, we could observe pupillary constriction, recovery of accommodation function, and improved NVA, even discontinuation of pilocarpine in Patient 2. CONCLUSION: In younger patients with good central vision, topical pilocarpine might ameliorate accommodation loss and pupillary dilation after mTLT.

Effect of Topical Pilocarpine on Choroidal Thickness in Healthy Subjects.

SIGNIFICANCE: This is a proof-of-concept study showing the possibility of pharmacological control for choroidal thickness using pilocarpine as an agent that causes 2 to 5% choroidal thinning in healthy eyes after the instillation. PURPOSE: The purpose of this article was to study the effect of instillation of 1% pilocarpine on choroidal thickness in healthy subjects. METHODS: Sixteen healthy individuals (seven males and nine females; mean ± standard deviation age, 25.8 ± 3.3 years) were included. All participants received optical coherence tomography to evaluate subfoveal choroidal thickness (SCT) and choroidal area on cross-sectional scan within 4-mm central area. Axial length was measured using optical biometry. Optical coherence tomography was performed before and after pilocarpine was instilled six times for a 75-minute period in one eye; the fellow eye was used as the control. Subfoveal choroidal thickness and choroidal area were measured by two masked graders in random fashion and averaged for analysis. RESULTS: After instillation of 1% pilocarpine, percentage SCT change in study and control eye was -3.3 ± 3.8% and 0.4 ± 3.2%, respectively (P = .03). Percentage change choroidal area in study and control eye was -2.3 ± 2.5% and 0.8 ± 3.3%, respectively (P < .001). There was a correlation between percentage SCT change and axial length (r = -0.56, P < .001), as well as between percentage SCT change and baseline SCT (r = 0.72, P < .001). CONCLUSIONS: Instillation of 1% pilocarpine causes a decrease of choroidal thickness, which is more substantial in eyes with short axial length and thick choroid.

A retrospective evaluation of systemic and/or topical pilocarpine treatment for canine neurogenic dry eye: 11 cases.

OBJECTIVE: To assess the response to topical and/or systemic pilocarpine in dogs with neurogenic dry eye. METHOD: Medical records of dogs diagnosed with dry eye between 2015 and 2018 were reviewed. Cases were excluded if STT values were decreased bilaterally, if dogs were lost to follow-up, or if surgical measures (parotid duct transposition) were undertaken within thirty days of presentation. Dogs were on treatment with topical pilocarpine (0.1%, every 6 hours) and/or oral pilocarpine (starting dose 2%, one drop per 10 kg every twelve hours). RESULTS: Eleven cases were included in the study, seven females and four males with mean age of 10 years. Seven cases had xeromycteria, two cases had facial nerve paralysis, and one case had Horner's syndrome. Seven cases (63.6%) had successful outcome following pilocarpine treatment, return to normal STT (15-25mm/minute), in an average of 24 ± 5.1 days. Of these cases, five had both systemic and topical treatment, one had just topical treatment, and one had just systemic treatment. The average time to normal tear production on treatment with topical pilocarpine ± systemic was 23 days (range 9-48 days). The number of systemic drops until a positive response varied between individuals from 0.8drops/10kg to 7drops/10kg. CONCLUSION: Pilocarpine treatment (topical ± systemic) is an effective therapy for unilateral dry eye disease in cases suspected to be neurogenic in origin. Most cases responded within 30 days. Side effects included topical irritation to the ophthalmic solution and systemic effects from oral pilocarpine, such as diarrhea and regurgitation.

Effect of topical pilocarpine on refractive surgery outcomes.

PURPOSE: To investigate the effect of topical pilocarpine on topical cycloplegia and on the results of refractive surgery. METHODS: The study included 100 eyes of 100 patients who underwent laser-assisted in situ keratomileusis. Group 1 comprised patients who wanted to undergo surgery on the same day after cycloplegic examination and were applied with 2% pilocarpine hydrochloride; group 2 comprised patients whose pupils spontaneously went into the natural position. Corneal thickness, mean refractive spherical equivalent (MRSE), uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), pupil diameter, pupil center shift and high-order aberrations (HOAs) were compared between the two groups. RESULTS: There were no statistically significant differences between the groups in respect of preoperative age, gender, corneal thickness, MRSE, UDVA and CDVA. The pupil diameter was not statistically significant between the groups. Pupil diameter after pilocarpine was not statistically significant when compared with the natural pupil diameter. There were no statistically significant differences in postoperative HOA between the two groups. CONCLUSIONS: The pupillary dilatation and the associated pupillary shift were reduced with pilocarpine. Postoperative refractive values and aberrations showed no difference between the groups.

A Novel Phytantriol-Based Lyotropic Liquid Crystalline Gel for Efficient Ophthalmic Delivery of Pilocarpine Nitrate.

The purpose of this paper was to investigate the potential of liquid crystalline (LC) gels for ophthalmic delivery, so as to enhance the bioavailability of pilocarpine nitrate (PN). The gels were prepared by a vortex method using phytantriol and water (in the ratio of 73:27 w/w). Their inner structures were confirmed by crossed polarized light microscopy, small-angle X-ray scattering, attenuated total reflectance-Fourier transform infrared spectrum, and rheology. The in vitro release studies revealed that PN could keep sustained release from the gels over a period of 12 h. The ex vivo apparent permeability coefficient of the gels demonstrated a 3.83-folds (P < 0.05) increase compared with that of eye drops. The corneal hydration levels of the gel maintained in the normal range of 79.46 ± 2.82%, hinting that the gel could be considered non-damaging and safe to the eyes. Furthermore, in vivo residence time evaluation suggested that a better retention performance of LC gel was observed in rabbit's eyes compared to eye drops. In vivo ocular irritation study indicated that LC gel was nonirritant and might be suitable for various eye applications. In conclusion, LC gels might represent a potential ophthalmic delivery strategy to overcome the limitations of eye drops.

Time Course of Pupil Center Location after Ocular Drug Application.

PURPOSE: To investigate the time course of pupil centration after application of common topical ocular drugs. METHODS: Single drops of 2.5% phenylephrine hydrochloride, 1% tropicamide, and 2% pilocarpine hydrochloride were applied on different days to the right eyes of 12 participants. Anterior eye images were captured, at 5-min intervals for an hour, using an infrared-sensitive camera. The images were analyzed to determine pupil diameter and pupil center, the latter with respect to the limbal center. As a control, natural pupil size and pupil center were determined under different illuminances. RESULTS: Pupil centers of natural pupils shifted temporally as pupils dilated. At common pupil sizes, drug-induced pupil centers were different from natural pupil centers. Phenylephrine produced a center shift in the nasal and inferior directions that peaked after a mean of 30 min, whereas dilation was continuing up to 60 min. Tropicamide produced transient center shifts in the nasal and inferior directions that peaked at about 10 min before reducing toward baseline values, whereas dilation reached a peak at about 25 min. Pilocarpine produced a small sustained superior shift that, like constriction, reached a peak after about 25 min. CONCLUSIONS: Application of topical ophthalmic drugs cause shifts in pupil center that do not match those produced by natural changes in pupil size and that, in the cases of phenylephrine and tropicamide, follow a different time course than the pupil size changes.

Effects of mydriasis and miosis on kinetic perimetry findings in normal participants.

PURPOSE: To evaluate the effects of pharmacologically induced mydriasis and miosis on kinetic perimetry findings in normal participants. METHODS: Thirty-eight eyes of 38 healthy young participants underwent kinetic perimetry (Octopus 900 perimeter) with III4e, I4e, I3e, I2e, and I1e stimuli. For each participant, 24 predetermined meridians with 15° intervals were automatically tested with a velocity of 3°/s under normal, mydriatic, and miotic conditions. Mydriasis and miosis were induced by one drop of 0.4 % tropicamide and 2 % pilocarpine hydrochloride, respectively. The isopter area and kinetic sensitivity were compared between the three pupil conditions. RESULTS: The average pupil size in the normal condition was 5.6 ± 0.9 mm, and it significantly increased to 8.5 ± 0.7 mm after mydriasis (p < 0.01) and decreased to 3.4 ± 0.8 mm after miosis (p < 0.01). Compared to the normal pupil, the isopter area of the dilated pupil was not significantly different under the III4e stimulus; however, it significantly decreased under the I4e, I3e, I2e, and I1e stimuli (p < 0.01). Compared to the normal pupil, the isopter area of the constricted pupil significantly decreased (p < 0.01) with the III4e stimulus and significantly increased with the I3e and I2e stimuli (p < 0.05). CONCLUSIONS: For both pupil conditions, kinetic sensitivity at each meridian showed a similar trend to the isopter area under each stimulus. The isopter area of the dilated pupil generally decreased, whereas the isopter area of the constricted pupil showed various findings. Therefore, careful attention should be paid to changes in the isopter area associated with changes in the pupil size.

Three-dimensional evaluation of accommodating intraocular lens shift and alignment in vivo.

OBJECTIVE: To quantify 3-dimensionally the anterior segment geometry, biometry, and lens position and alignment in patients before and after implantation of the Crystalens-AO (Bausch & Lomb, Rochester, NY) accommodating intraocular lens (A-IOL). DESIGN: Prospective, observational study. PARTICIPANTS: Ten patients (20 eyes) with cataract before and after implantation of the Crystalens-AO A-IOL. METHODS: Custom full anterior segment 3-dimensional (3-D) spectral optical coherence tomography (OCT) provided with quantification tools was used to image the cornea, iris, and natural lens preoperatively and intraocular lens postoperatively. Measurements were obtained under phenylephrine preoperatively and under natural viewing conditions and phenylephrine (for accommodative efforts ranging from 0 to 2.5 diopters [D]) and pilocarpine postoperatively. MAIN OUTCOME MEASURES: Three-dimensional quantitative anterior segment images, corneal geometry and power, anterior chamber depth (ACD), lens thickness, pupil diameter, A-IOL shift with accommodative effort or drug-induced accommodation, and A-IOL alignment. RESULTS: Crystalline lens and IOLs were visualized and quantified 3-dimensionally. The average ACD were 2.64±0.24 and 3.65±0.35 mm preoperatively and postoperatively (relaxed state), respectively, and they were statistically significantly correlated (although their difference was not statistically correlated with lens thickness). The A-IOL did not shift systematically with accommodative effort, with 9 lenses moving forward and 11 lenses moving backward (under natural conditions). The average A-IOL shift under stimulated accommodation with pilocarpine was -0.02±0.20 mm. The greatest forward shift occurred bilaterally in 1 patient (-0.49 mm in the right eye and -0.52 mm in the left eye, under pilocarpine). The high right/left symmetry in the horizontal tilt of the crystalline lens is disrupted on IOL implantation. Accommodative IOLs tend to be slightly more vertically tilted than the crystalline lens, with increasing tendency with accommodative effort. Two subjects showed postoperative IOL tilts >9 degrees. Changes in pupillary diameter correlated with pilocarpine-induced A-IOL axial shift. Intermediate accommodative demands (1.25 D) elicited the greater shifts in axial A-IOL location and tilt and pupil diameter. CONCLUSIONS: Quantitative 3-D anterior segment OCT allows full evaluation of the geometry of eyes implanted with A-IOLs preoperatively and postoperatively. High-resolution OCT measurements of the Crystalens 3-D positioning revealed small (and in many patients backward) A-IOL axial shifts with both natural or drug-induced accommodation, as well as tilt changes with respect to natural lens and accommodative effort.

Physiologically Based Pharmacokinetic Modeling and Clinical Extrapolation for Topical Application of Pilocarpine on Eyelids: A Comprehensive Study.

Exploiting a convenient and highly bioavailable ocular drug delivery approach is currently one of the hotspots in the pharmaceutical industry. Eyelid topical application is seen to be a valuable strategy in the treatment of chronic ocular diseases. To further elucidate the feasibility of eyelid topical administration as an alternative route for ocular drug delivery, pharmacokinetic and pharmacodynamic studies of pilocarpine were conducted in rabbits. Besides, a novel physiologically based pharmacokinetic (PBPK) model describing eyelid transdermal absorption and ocular disposition was developed in rabbits. The PBPK model of rabbits was extrapolated to human by integrating the drug-specific permeability parameters and human physiological parameters to predict ocular pharmacokinetic in human. After eyelid topical application of pilocarpine, the concentration of pilocarpine in iris peaked at 2 h with the value of 18,724 ng/g and the concentration in aqueous humor peaked at 1 h with the value of 1,363 ng/mL. Significant miotic effect were observed from 0.5 h to 4.5 h after eyelid topical application of pilocarpine in rabbits, while that were observed from 0.5 h to 3.5 h after eyedrop instillation. The proposed eyelid PBPK model was capable of reasonably predicting ocular exposure of pilocarpine after application on the eyelid skin and based on the PBPK model, the human ocular concentration was predicted to be 10-fold lower than that in rabbits. And it was suggested that drugs applied on the eyelid skin could transfer into the eyeball through corneal pathway and scleral pathway. This work could provide pharmacokinetic and pharmacodynamic data for the development of eyelid drug delivery, as well as the reference for clinical applications.

Comparison between carbachol iontophoresis and intravenous pilocarpine stimulated accommodation in anesthetized rhesus monkeys.

Rhesus monkeys are an animal model for human accommodation and presbyopia and consistent and repeatable methods are needed to stimulate and measure accommodation in anesthetized rhesus monkeys. Accommodation has typically been pharmacologically stimulated with topical pilocarpine or carbachol iontophoresis. Intravenous (i.v.) pilocarpine has recently been shown to produce more natural, rapid and reproducible accommodative responses compared to topical pilocarpine. Here, i.v. pilocarpine was compared to carbachol iontophoresis stimulated accommodation. Experiments were performed under anaesthesia on five previously iridectomized monkeys aged 10-16 years. In three monkeys, accommodation was stimulated with carbachol iontophoresis in five successive experiments and refraction measured with a Hartinger coincidence refractometer. In separate experiments, accommodation was stimulated using a 5 mg/kg bolus of i.v. pilocarpine given over 30 s followed by a continuous infusion of 20 mg/kg/hr for 5.5 min in three successive experiments with the same monkeys as well as in single experiments with two additional monkeys. Refraction was measured continuously using photorefraction with baseline and accommodated refraction also measured with the Hartinger. In subsequent i.v. pilocarpine experiments with each monkey, accommodative changes in lens equatorial diameter were measured in real-time with video-image analysis. Maximum accommodation of three monkeys with carbachol iontophoresis (five repeats) was (mean ± SD; range) 14.0 ± 3.5; 9.9-20.3 D and with i.v. pilocarpine stimulation (three repeats) was 11.1 ± 1.1; 9.9-13.0 D. The average of the standard deviations of maximum accommodation from each monkey was 0.8 ± 0.3 D from carbachol iontophoresis and 0.3 ± 0.2 from i.v. pilocarpine. The average latency to the start of the response after carbachol iontophoresis was 2.5 ± 3.9; 0.0-12.0 min with a time constant of 12.7 ± 9.5; 2.3-29.2 min. The average latency after i.v. pilocarpine was 0.31 ± 0.03; 0.25-0.34 min with a time constant of 0.19 ± 0.07; 0.11-0.31 s. During i.v. pilocarpine stimulated accommodation in five monkeys, lens diameters decreased by 0.54 ± 0.09; 0.42-0.64 mm with a rate of change of 0.052 ± 0.002; 0.050-0.055 mm/D. Accommodative responses with i.v. pilocarpine were more rapid, consistent and stable than those with carbachol iontophoresis. The accommodative decrease in lens diameter with i.v. pilocarpine as a function of age was consistent with previous results using constant topical pilocarpine. Intravenous pilocarpine stimulated accommodation is safe, more consistent and more rapid than carbachol iontophoresis and it requires no contact with or obstruction of the eye thus allowing continuous and uninterrupted refraction and ocular biometry measurements.

Long-term reproducibility of Edinger-Westphal stimulated accommodation in rhesus monkeys.

If longitudinal studies of accommodation or accommodation restoration procedures are undertaken in rhesus monkeys, the methods used to induce and measure accommodation must remain reproducible over the study period. Stimulation of the Edinger-Westphal (EW) nucleus in anesthetized rhesus monkeys is a valuable method to understand various aspects of accommodation. A prior study showed reproducibility of EW-stimulated accommodation over 14 months after chronic electrode implantation. However, reproducibility over a period longer than this has not been investigated and therefore remains unknown. To address this, accommodation stimulation experiments in four eyes of two rhesus monkeys (13.7 and 13.8 years old) were evaluated over a period of 68 months. Carbachol iontophoresis stimulated accommodation was first measured with a Hartinger coincidence refractometer (HCR) two weeks before electrode implantation to determine maximum accommodative amplitudes. EW stimulus-response curves were initially measured with the HCR one month after electrode implantation and then repeated at least six times for each eye in the following 60 months. At 64 months, carbachol iontophoresis induced accommodation was measured again. At 68 months, EW stimulus-response curves were measured with an HCR and photorefraction every week over four consecutive weeks to evaluate the short-term reproducibility over one month. In the four eyes studied, long-term EW-stimulated accommodation decreased by 7.00 D, 3.33 D, 4.63 D, and 2.03 D, whereas carbachol stimulated accommodation increased by 0.18 D-0.49 D over the same time period. The short-term reproducibility of maximum EW-stimulated accommodation (standard deviations) over a period of four weeks at 68 months after electrode implantation was 0.48 D, 0.79 D, 0.55 D and 0.39 D in the four eyes. Since the long-term decrease in EW-stimulated accommodation is not matched by similar decreases in carbachol iontophoresis stimulated accommodation, the decline in accommodation cannot be due to the progression of presbyopia but is likely to result from variability in EW electrode position. Therefore, EW-stimulated accommodation in anesthetized monkeys is not appropriate for long-term longitudinal studies of age-related loss of accommodation or accommodation restoration procedures.

Pilocarpine-induced flare is physiological rather than pathological.

An elevated aqueous humor protein level (aka flare) has always been considered to represent a pathological breakdown of the blood-aqueous barrier (BAB), regardless of the etiology. Recent studies in humans, using magnetic resonance imaging (MRI) to directly observe BAB kinetics in the posterior chamber of the human eye in-vivo, showed that pilocarpine-induced flare resulting from administration of a single drop of pilocarpine is not the result of breakdown of the BAB in the ciliary body. These MRI studies could not confirm whether pilocarpine caused an increase in iris vascular permeability. In the current studies we completed combined cell-flare meter and intravascular tracer studies, using intravenous horseradish peroxidase (HRP) in rabbits. One hour after receiving 3% pilocarpine in one eye, pupil size significantly decreased and aqueous flare significantly increased in pilocarpine-treated eyes. Light and electron microscopy demonstrated no leakage across either the iris vascular endothelium or the non-pigmented ciliary epithelium in either pilocarpine-treated or control eyes. One animal received HRP directly after pilocarpine to control for a transient increase in permeability before the peak flare response occurred. No leakage was found in the ciliary body or iris of this animal. Additional animals received topical pilocarpine in one eye but after 1 h they were sacrificed without tracer studies. Uveal tissues from these animals were used to assess the distribution of non-HRP protein in the ocular anterior segment and to assess the amount of elutable protein in the iris stromas of both treated and untreated eyes. Immunohistochemistry confirmed the presence of a reservoir of protein in the iris stroma. Analysis of elutable total protein from the iris stroma of pilocarpine-treated and control eyes showed significantly less total elutable protein in pilocarpine-treated eyes. Eyes with the greatest percent change in pupil size (i.e. the strongest miosis) correlated with lowest amounts of residual protein in the iris stroma. The tracer studies confirmed recent MRI studies in humans showing that the source of pilocarpine-induced flare is not disruption of the ciliary epithelial barrier. Extending this work, the current studies also showed no pilocarpine-induced leakage from the iris vasculature. The elutable protein experiments suggested that a primary source of pilocarpine-induced flare was extrusion of a portion of the reservoir of protein in the iris stroma. Taken together, these studies strongly suggest that not all clinically observable flare results from breakdown of the BAB.

Ultrasound biomicroscopy of anterior segment accommodative changes with posterior chamber phakic intraocular lens in high myopia.

PURPOSE: To investigate changes in anterior chamber depth (ACD) and the distance between the Visian implantable Collamer lens (ICL) and the crystalline lens during pharmacologic accommodation in high myopia. DESIGN: Prospective, comparative case series. PARTICIPANTS: Thirty-three phakic eyes of 18 high myopic patients (range, -8.63 to -23.86 diopters) with a mean age of 29 years (range, 20-44 years) were examined at least 1 year after ICL implantation. METHODS: Ultrasound biomicroscopy was used to measure distance changes between the corneal endothelium, the ICL, and the crystalline lens after inducing pharmacologic accommodation with topical pilocarpine in 1 eye. The contralateral eye served as the control. MAIN OUTCOME MEASURES: Mean changes of ACD measured from the posterior corneal surface to the crystalline lens (ACD-L), from the posterior corneal surface to the anterior surface of the ICL (ACD-ICL), and the distance between the ICL and the crystalline lens (ICL-L) at the central and peripheral regions of the eye. RESULTS: For each eye, the ICL was in contact with the iris, but it was never in contact with the crystalline lens. At baseline, the mean distance between the ICL and the crystalline lens was 0.609 ± 0.165 mm at the central horizontal meridian, 0.588 ± 0.157 mm at the central vertical meridian, 0.281 ± 0.106 mm at the peripheral temporal sulcus, and 0.290 ± 0.098 mm at the peripheral nasal sulcus. After instillation of pilocarpine, a significant decrease in ICL-L was accompanied by a significant reduction in ACD-L and an increase in ACD-ICL (P<0.01). There were no significant changes in the control eyes (P>0.05). The central ICL-L reduction in the study group was significantly larger than that in the control group (P<0.01), but the peripheral ICL-L changes in the study group were not significantly different from those in the controls (P>0.05). CONCLUSIONS: During pharmacologic accommodation, the ICL and the crystalline lens came closer as the ICL was pushed backward by the iris as a result of pupillary constriction. Simultaneously, the anterior surface of the crystalline lens became more convex and moved forward. Reduction of the distances at peripheral sulci was not as obvious as at the center. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Reproducibility of carbachol stimulated accommodation in rhesus monkeys.

Approaches are being explored to restore accommodation to the presbyopic eye. Some of these approaches can be tested in monkeys by stimulating accommodation in various ways including using carbachol iontophoresis. Knowledge of the repeatability of carbachol iontophoresis stimulated accommodation in the monkey phakic eye is necessary to understand the variability of this method of evaluating accommodation. Data from 9 to 10 separate carbachol iontophoresis experiments performed on phakic eyes from 8 monkeys were retrospectively analyzed. For each experiment, carbachol was applied iontophoretically to the eyes of anesthetized monkeys and refraction generally measured every two minutes until accommodation reached a plateau. Repeated experiments were performed in each monkey over periods ranging from 10 to 18 months. Maximum accommodation measured for each monkey ranged from 11.1 D to 18.3 D with standard deviations from 0.8 D to 2.1 D and differences in accommodative amplitude varying from 2.2 D to 7.5 D. Time to reach maximum accommodation ranged from 18 to 64 min in individual experiments. Averaged time-courses indicate that maximum accommodation is generally achieved between 10 and 20 min after carbachol administration. Although carbachol iontophoresis is considered a reliable method to stimulate maximum accommodation in anesthetized monkeys, the amplitude achieved typically varies by more than 2 D. Presbyopia treatments evaluated in this way in phakic monkeys would need to show an increase in accommodation of over 2 D to clearly demonstrate that the treatments work when being tested with carbachol iontophoresis stimulation.

Medical treatment of crystalline lens dislocation into the anterior chamber in a patient with Marfan syndrome.

We report the case of a 32-year-old male with spontaneous crystalline lens dislocation into the anterior chamber with corneal touch and increased intraocular pressure. The case was handled in a conservative way: before bringing the patient to supine position, pharmacological pupil dilation with tropicamide plus phenylephrine was performed. One drop was instilled every 15 min for 1 hour. Once the posterior displacement of the lens behind the iris was confirmed, 2 % pilocarpine was used to reverse pupil dilation. The patient remained on topical 2 % pilocarpine and 5 % sodium chloride solution.

The concave iris in pigment dispersion syndrome.

OBJECTIVE: To visualize the changes of the iris contour in patients with pigment dispersion syndrome after blinking, accommodation, and pharmacologic miosis using anterior segment optical coherence tomography. DESIGN: Observational case series. PARTICIPANTS: A total of 33 eyes of 20 patients with pigment dispersion syndrome. METHODS: Each eye was imaged along the horizontal 0- to 180-degree meridian using the Visante Anterior Segment Imaging System (Carl Zeiss Meditec, Dublin, CA). Scans were performed at baseline and after focusing on an internal fixation target for 5 minutes, forced blinking, accommodation, and pharmacologic miosis with pilocarpine 2%. MAIN OUTCOME MEASURES: Quantitative analysis of the changes in the iris configuration. RESULTS: After 5 minutes of continual fixation, the iris became planar with the mean ± standard deviation curvature decreasing from 214 ± 74 µm to 67 ± 76 µm (P < 0.05). The iris remained planar in all patients with pigment dispersion syndrome after forced blinking, but the iris concavity recovered to 227 ± 113 µm (P = 0.34) and 238 ± 119 µm (P = 0.19) with the -3.0 and -6.0 diopter lenses, respectively. Pilocarpine-induced miosis caused the iris to assume a planar configuration in all subjects. CONCLUSIONS: This study shows that the iris in pigment dispersion syndrome assumes a planar configuration when fixating and that the concavity of the iris surface is not restored by blinking. Accommodation restored the iris concavity, suggesting that the posterior curvature of the iris in pigment dispersion syndrome is induced and probably maintained, at least in part, by accommodation.

[Chitosan-coated ophthalmic submicro emulsion for pilocarpine nitrate].

The study is to design chitosan-coated pilocarpine nitrate submicro emulsion (CS-PN/SE) for the development of a novel mucoadhesive submicro emulsion, aiming to prolong the precorneal retention time and improve the ocular absorption. CS-PN/SE was fabricated in two steps: firstly, pilocarpine nitrate submicro emulsion (PN/SE) was prepared by high-speed shear with medium chain triglycerides (MCT) as oil phase and Tween 80 as the main emulsifier, and then incubated with chitosan (CS) acetic solution. The preparation process was optimized by central composite design-response surface methodology. Besides the particle size, zeta potential, entrapment efficiency and micromorphology were investigated, CS-PN/SE's precorneal residence properties and miotic effect were especially studied using New Zealand rabbits as the animal model. When CS-PN/SE was administered topically to rabbit eyes, the ocular clearance and the mean resident time (MRT) of pilocarpine nitrate were found to be dramatically improved (P < 0.05) compared with PN/SE and pilocarpine nitrate solution (PNs), since the K(CS-PN/SE) was declined to 0.006 4 +/- 0.000 3 min(-1) while MRT was prolonged up to 155.4 min. Pharmacodynamics results showed that the maximum miosis of CS-PN/SE was as high as 46.3%, while the miotic response lasted 480 min which is 255 min and 105 min longer than that of PNs and PN/SE, respectively. A larger area under the miotic percentage vs time curve (AUC) of CS-PN/SE was exhibited which is 1.6 folds and 1.2 folds as much as that of PNs and PN/SE, respectively (P < 0.05). Therefore, CS-PN/SE could enhance the duration of action and ocular bioavailability by improving the precorneal residence and ocular absorption significantly.

[Glaucoma treatment during pregnancy and lactation].

4 cases of glaucoma during pregnancy and lactation are represented to study individual treatment approach in situations like these. Clinical characteristic of medications used and other treatment options are described.

Gellan gum and its methacrylated derivatives as in situ gelling mucoadhesive formulations of pilocarpine: In vitro and in vivo studies.

Gellan gum was chemically modified by the reaction with methacrylic anhydride to produce derivatives with 6, 14 and 49% methacrylation. The structure and substitution degrees of these derivatives were confirmed by 1H NMR- and FTIR-spectroscopy. These derivatives are more hydrophobic compared to pristine gellan and form turbid solutions in water. In vitro study performed with formulations of sodium fluorescein containing gellan gum and its methacrylated derivatives indicated that methacrylation enhances their retention on bovine conjunctival mucosa. In vivo experiments with the formulations of pilocarpine hydrochloride containing gellan gum and methacrylated derivatives have demonstrated that all polymers enhance the drug effect significantly, but best performance is observed for the polysaccharide with 6% methacrylation.

Laserinterferometric measurements of accommodative changes in the position of an optic-shift intraocular lens.

PURPOSE: To measure optically and pharmacologically induced movement of an optic-shift intraocular lens (HumanOptics 1CU). METHODS: The change in position as well as the accommodative effect of the 1CU was determined using an anterior chamber laser interferometer (Zeiss ACMaster) in 15 eyes of 9 patients. Accommodation was induced by optical stimulus and pharmacologically by pilocarpine 2%. RESULTS: The mean forward movement due to optical-induced accommodation stimulation was 5 +/- 14 microm (range: -10 to + 40 microm). Pharmacological stimulation with 2% pilocarpine caused mean anterior movements of 93 +/- 162 microm (range: -321 to +/- 402 microm). CONCLUSIONS: A maximum accommodative effect of 0.50 diopters was measured with this method. This relatively small accommodative effect of the 1CU is in agreement with other studies. Pharmacologically induced optic shift differs significantly from optically induced shift and allows no conclusion on a clinically expected accommodative effect.