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.

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.

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.

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.

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 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.

Unilateral Malignant Glaucoma Postbilateral Implantable Collamer Lens: Effect of Miotics.

An implantable collamer lens® (ICL) V4c model (STAAR Surgical, Monrovia, CA, USA) was placed in the eye of a 31-year-old male patient with high myopia followed by the development of malignant glaucoma. After failing medical treatment for 5 days, a noncomplicated pars plana vitrectomy and anterior hyaloidectomy succeeded in breaking the aqueous misdirection. Sixteen months later, intraoperative miotics were purposefully withheld from the ICL surgery in the fellow eye and malignant glaucoma did not develop. Even though the patient's visual acuity postoperatively was 20/20, OU, a single small atrophic iris patch in the affected eye resulted in slightly more halos and glare in mesopic conditions as compared to the fellow eye. Earlier surgical intervention may have prevented iris ischemia and iridocorneal touch with its subsequent iris atrophy and resulted in an even more favorable visual outcome. Withholding intraoperative miotics during ICL surgery appeared to be beneficial in this case.

The effect of co-administration of pentylenetetrazole with pilocarpine: New modified PTZ models of kindling and seizure.

BACKGROUND: Drug resistance is a major problem in the treatment of epilepsy. There is a critical need for new epilepsy models to evaluate antiepileptic compounds. Pentylenetetrazole- (PTZ) and pilocarpine-induced seizures are well-established models of human epilepsy. Generally, PTZ or pilocarpine has been used to produce seizures in experimental models. In this study, we explored the possibility of creating new epilepsy and seizure models by co-administration of PTZ and pilocarpine. METHODS: The protocol was divided into three parts: A) Kindling experiments: the animals received PTZ or co-administration doses of PTZ and pilocarpine every other day for a period of 26 days. B) Seizure experiments, for induction of seizure, the animals received one dose of PTZ, pilocarpine or co-administration doses of PTZ and pilocarpine. C) Evaluation of antiepileptic drugs: the animals received phenytoin or sodium valproate 20 min before injection of PTZ, pilocarpine or co-administration doses of PTZ and pilocarpine. RESULTS: The co-administration of pilocarpine and PTZ could induce seizure, which has behavioral similarity between electrical and chemical kindling. Pilocarpine (50 mg/kg) + PTZ (37.5 mg/kg) was the appropriate dose for kindling induction. Animals with this dose reached the stage five seizures significantly faster than those with PTZ alone. Unlike the seizure induced by PTZ, or pilocarpine, induction of seizure by PTZ + pilocarpine was resistant to phenytoin and sodium valproate treatment. As compared to the PTZ model of kindling, this model visualized the seizure behavior better and had resistance to two most popular antiepileptic drugs. CONCLUSION: Our results indicated that co-administration of pilocarpine and PTZ could provide a new modified model of seizure and kindling resisting to phenytoin and sodium valproate.

Self-assembled hexagonal liquid crystalline gels as novel ocular formulation with enhanced topical delivery of pilocarpine nitrate.

The aim of this paper was to develop hexagonal liquid crystalline (HII) gels that can be used as a novel ocular delivery system for pilocarpine nitrate (PN). HII gels were prepared by a vortex method using phytantriol/triglyceride/water (71.15: 3.85: 26, w/w) ternary system. The gels were characterized by crossed polarized light microscopy, small-angle X-ray scattering, differential scanning calorimetry and rheology. And, in vitro drug release behavior and ex vivo corneal permeation were investigated. Finally, preocular residence time evaluation, eye irritation test, histological examination and miotic tests were studied in vivo and compared with carbopol gel. Based on various characterization techniques, the inner structure of the gels were HII mesophase and exhibited a pseudoplastic fluid behaviour. In vitro release results revealed that PN could be released continuously from HII gel over a period of 24 h. The ex vivo apparent permeability coefficient of HII gel was 3.15-fold (P < 0.01) higher than that of the Carbopol gel. Compared with Carbopol gel, HII gel displayed longer residence time on the eyeballs surface using fluorescent labeling technology. Furthermore, the HII gel caused no ocular irritation was estimated by corneal hydration levels, Draize test and histological inspection. Additionally, in vivo miotic study showed that HII gel had a remarkably long-lasting decrease in the pupil diameter of rabbits. In conclusion, HII gels would be a promising sustained-release formulation for ocular drug delivery.

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.

A Rare Case of Blebharitis: Phthiriasis Palpebrarum.

A six-year-old male patient was admitted to our hospital due to itching and scalding crusts that persisted 10-15 days in both eyes. Upon biomicroscopic examination, 5-6 semi-translucent, yellowish brown living lice attached to the upper eyelashes and a large number of eggs were observed. Following application of pilocarpine hydrochloride (Pilomann 2%, Bausch-Lomb) and topical proparacaine hydrochloride (Alcaine 0.5%, Alcon), the paralyzed parasites and eggs were manually removed by pulling with forceps. The lice were identified as adult forms of pubic louse, Pthirus pubis, and its eggs. The patient was treated with pilocarpine hydrochloride, which was applied thrice a day combined with pure vaseline. One week later, no lice or eggs were seen on the eyelashes.

Acetylcholine chloride 1% usage for intraoperative cataract surgery miosis / Cloridrato de Acetilcolina 1% na obtenção da miose intraoperatória na cirurgia de catarata

Abstract Objective: To test the efficacy of Acetylcholine chloride use in obtaining intraoperative miosis on phacoemulsification cataract surgery. Methods: Patients with cataract diagnosis and elected for surgical phacoemulsification procedure were selected. All patients underwent conventional phacoemulsification procedure performed by a single surgeon and all patients had 0.2 ml of Acetylcholine chloride 1% irrigated in the anterior chamber at the end of the surgery. The pupillary diameter was measured immediately before the beginning of surgery, immediately before and two minutes after the use of acetylcholine chloride 1%. Results: A total of 30 eyes from 30 patients were included in the study. 18 were female, and mean age was of 69.5 years with a 7.2y standard deviation on the population study. The mean pupillary diameter immediately before the beginning of surgery was 7.5 mm with a standard deviation of 0.56 mm; the mean pupillary diameter immediately before the acetylcholine chloride 1% use (after the intraocular lens im-plantation) was 7.1 mm with a standard deviation of 0.57 mm. The mean pupillary diameter two minutes after the use of acetylcholine chloride 1% in the anterior chamber was 3.4 mm with standard deviation of 0.66 mm. The mean maximum action time of ACH chloride 1% was 64 seconds, with a standard deviation of 8 seconds. The mean intraocular pressure on the first postoperative day was 19.1 mmHg with a standard deviation of 2.45 mmHg. Conclusion: We conclude that acetylcholine chloride 1% is an important drug to obtaining intraoperative miosis in cataract surgery.

Resumo Objetivo: Demonstrar a eficácia do cloridrato de acetilcolina 1% na obtenção da miose intraoperatória na cirurgia de catarata pela técnica de facoemulsificação. Métodos: Pacientes com diagnóstico de catarata e indicação de cirurgia foram selecionados para participar do presente estudo. Todos os pacientes foram operados pela técnica de facoemulsificação convencional pelo mesmo cirurgião, todos foram submetidos à aplicação de 0,2 ml do cloridrato de acetilcolina 1% na câmara anterior ao final do procedimento cirúrgico. A medida do diâmetro pupilar foi realizada imediatamente antes do início da cirurgia, imediatamente antes do uso do cloridrato de acetilcolina 1% e após 2 minutos. Resultados: Foram estudados 30 olhos de 30 pacientes, destes, 18 eram do sexo feminino, a média de idade do estudo foi de 69,5 anos com desvio padrão de 7,2 anos. A média do diâmetro pupilar imediatamente antes do início da cirurgia foi 7,55 mm com desvio padrão de 0,56mm, a média do diâmetro pupilar imediatamente antes do uso do cloridrato de acetilcolina 1% (após implante da lente intraocular no saco capsular) foi 7,1mm com desvio padrão de 0,57mm. A média do diâmetro pupilar após 2 minutos da aplicação da acetilcolina na câmara anterior foi de 3,4 mm com desvio padrão de 0,66mm. O tempo médio de ação máxima do medicamento foi de 64 segundos, com desvio padrão de 8 segundos. A média da pressão intraocular no primeiro dia do pós-operatório foi de 19,1 mmHg com desvio padrão de 2,45mmHg. Conclusão: O estudo acima mostrou que a acetilcolina apresenta boa eficácia na obtenção de miose intraoperatória na cirurgia de facoemulsificação, permitindo uma maior facilidade na confecções das suturas corneanas ou corneo-escleral, reduzindo a incidência de sinéquias anteriores periféricas. Concluimos que o cloridrato de acetilcolina 1% é um importante medicamento na obtenção da miose intraoperatória na cirurgia de catarata.

Synthesis and evaluation of mucoadhesive acryloyl-quaternized PDMAEMA nanogels for ocular drug delivery.

Poly((2-dimethylamino)ethyl methacrylate) (PDMAEMA) nanogels were synthesized via surfactant-free free-radical polymerization technique in aqueous conditions utilizing N,N'-methylene-bis-acrylamide (MBA) as a crosslinking agent. The PDMAEMA nanogels were subsequently quaternized with acryloyl chloride in order to yield mucoadhesive materials which incorporate two mucoadhesive concepts; electrostatic interactions and covalent bond forming acrylate groups. The native PDMAEMA nanogels were found to exhibit good mucoadhesive properties on ex vivo bovine conjunctival tissues, which was found to increase proportionally with the degree of quaternization. With a view to determine the ocular drug delivery capabilities of the materials, both quaternized and native nanogels were loaded with pilocarpine hydrochloride via an absorption method, and their in vitro release profiles were analysed. The nanogels were found to exhibit a high loading capacity (>20% of total weight) and a sustained release over 6h.

Acute Primary Angle Closure in the Fellow Eye as a Complication of Facedown Position After Vitrectomy Surgery.

PURPOSE: To report a case of acute primary angle closure that developed in the fellow eye rapidly after facedown position after vitrectomy surgery. PATIENTS AND METHODS: A 66-year-old female developed acute primary angle closure in the fellow eye approximately 1.5 hours after facedown position after vitrectomy surgery for macular hole. RESULTS: The intraocular pressure was controlled after treatment that included halting the facedown position, intravenous mannitol injection, and topical pilocarpine instillation. Facedown position was continued after laser peripheral iridotomy was performed. The intraocular pressure was controlled within normal range even after pilocarpine was withdrawn. CONCLUSIONS: Although rare, the potential risk of acute-angle closure should be explicitly explained to patients being considered for facedown position after vitrectomy. Prophylactic intervention, such as laser peripheral iridotomy, could be considered for anatomically predisposed eyes.

Effect of Pilocarpine Hydrochloride on the Schlemm Canal in Healthy Eyes and Eyes With Open-Angle Glaucoma.

IMPORTANCE: The in vivo effect of pilocarpine hydrochloride on the Schlemm canal may help explain its pharmacologic mechanism of action and better indicate its clinical use. OBJECTIVE: To investigate the effect of pilocarpine on the structure of the Schlemm canal in vivo in healthy eyes and eyes with glaucoma. DESIGN, SETTING, AND PARTICIPANTS: In this case-control study, healthy individuals and patients with open-angle glaucoma were prospectively enrolled between September 1, 2013, and June 30, 2014, after a complete ophthalmologic examination at a tertiary glaucoma referral practice. Eighty-one serial, horizontal, enhanced depth imaging optical coherence tomographic B-scans (interval between B-scans, approximately 35 µm) of the nasal corneoscleral limbus were performed before and 1 hour after topical administration of pilocarpine, 1%, in 1 eye of healthy volunteers and pilocarpine, 2%, in 1 eye of patients with glaucoma. Fifty B-scans in the overlapping area (circumferential length, approximately 1.7 mm) between the 2 sets of serial scans (before and after pilocarpine administration) were selected for analysis based on the structures of aqueous and blood vessels as landmarks. The cross-sectional area of the Schlemm canal was measured in each selected B-scan. Volume of the Schlemm canal was calculated using commercially available 3-dimensional reconstruction software. MAIN OUTCOMES AND MEASURES: Mean cross-sectional area of the Schlemm canal. RESULTS: Enhanced depth imaging optical coherence tomographic scans of the Schlemm canal were performed successfully before and after administration of pilocarpine, 1%, in 9 healthy eyes (9 individuals) and pilocarpine, 2%, in 10 eyes with glaucoma (10 patients) (mean [SD] age, 31.9 [7.8] and 68.7 [13.2] years, respectively). Following pilocarpine administration, mean (SD) intraocular pressure decreased from 14.3 (1.3) to 13.7 (1.1) mm Hg in healthy eyes (P = .004) and from 17.5 (6.0) to 16.6 (6.1) mm Hg in eyes with glaucoma (P = .01). The mean (SD) cross-sectional area of the Schlemm canal increased by 21% (4667 [1704] to 5647 [1911] µm2) in healthy eyes (P < .001) and by 24% (3737 [679] to 4619 [692] µm2) in eyes with glaucoma (P < .001) (mean difference in percent increase, 2.2%; 95% CI, -8.5% to 12.9%). The mean (SD) volume of the Schlemm canal in the overlapping area increased from 8 004 000 (2 923 000) to 9 685 000 (3 277 000) µm3 in healthy eyes (P < .001) and from 6 468 000 (1 170 000) to 7 970 000 (1 199 000) µm3 in eyes with glaucoma (P < .001). CONCLUSIONS AND RELEVANCE: These data suggest that pilocarpine expands the Schlemm canal in eyes with and without glaucoma. No differences in the effect were identified between the 2 groups. Enhanced depth imaging optical coherence tomography may be useful in investigating the effect of pharmacologic agents on the Schlemm canal.

Intraoperative intracameral pilocarpine after capsular tension ring and capsule/iris hook insertion in pediatric eyes with subluxated cataract.

UNLABELLED: Capsular tension rings and iris hooks have proved to be useful devices in cataract surgery in cases of zonular weakness and dialysis. We describe the use of intracameral pilocarpine-induced pupillary miosis to couple the iris and the capsulorhexis edge with iris hooks during phacoemulsification in pediatric cases with posttraumatic subluxated cataractous lens. The coupled iris and capsule act as a single unit, eliminating the space between them and significantly reducing the possibility of vitreous or ophthalmic viscosurgical device passing through the zonular defect. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Nanoparticle cross-linked collagen shields for sustained delivery of pilocarpine hydrochloride.

Glaucoma is a common progressive eye disorder which remains the second leading cause of blindness worldwide. Current therapy involves frequent administration of eye drops which often results in poor patient adherence and therapeutic outcomes. The aim of this study was to overcome these limitations by developing a novel nanoparticle cross-linked collagen shield for sustained delivery of pilocarpine hydrochloride (PHCl). Three metal oxide nanoparticles (NPs); titanium dioxide (TiO2), zinc oxide (ZnO) and polyvinylpyrrolidone (PVP) capped zinc oxide (ZnO/PVP), were evaluated for their cytotoxicity as well as shield transparency before selecting ZnO/PVP NPs as the ideal candidate. Cross-linked collagen shields were then characterized for their mechanical strength, swelling capacity and bioadhesive properties, with ZnO/PVP NP cross-linked shields showing the most favorable characteristics compared to plain films. The shield with the best properties was then loaded with PHCl and in vitro release of zinc ions as well as PHCl was measured without and with further cross-linking by ultraviolet irradiation. The concentration of zinc ions released was well below the IC50 rendering them safe for ocular use. Moreover, collagen shields cross-linked with ZnO/PVP NPs released PHCl over a period of 14 days offering a promising sustained release treatment option for glaucoma.

The use of pilocarpine eye drops for estimating the time since death.

OBJECTIVE: The objective of this study was to estimate the time since death using pilocarpine eye drops. METHODS: In this study, 100 postmortem cases with known time of death were included. In each case, the left pupil was measured in millimeter units using a vernier caliper, and pilocarpine eye drops were applied. The pupil was measured again 10 min later, and statistical analysis was used to analyze the correlation between the time since death and the change in the pupil. RESULTS: The longest duration since death that the pupils showed reaction to pilocarpine was 15 h. The correlation between the change in the pupil and the postmortem interval was found (Spearman's rho, r = -0.304, p = 0.002), and the change in the pupil may be used to predict the postmortem interval by the following regression equation: postmortem interval (PMI) = 8.310-3.702 (Diff) ± 0.735 (PMI was postmortem interval in hours and Diff was the difference in the size of the pupil after administering pilocarpine in millimeter units). CONCLUSION: The present study showed that pilocarpine eye drops can be used to estimate the time since death.

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.

Controversies in Glaucoma: Current Medical Treatment and Drug Development.

Elevated eye pressure is the main risk factor for glaucoma; intraocular pressure rises when the ratio between aqueous humor formation (inflow) and its outflow is unbalanced. Currently, the main goal of medical treatment is the reduction of intraocular pressure. Five main classes of topical drugs are available; they include betablockers, carbonic anhydrase inhibitors, prostaglandin derivatives, sympathomimetics and miotics. Beta-blockers and carbonic anhydrase inhibitors slow the formation of aqueous humor and may be considered as "inflow" drugs; the other three classes reduce the resistance to the drainage of aqueous humor and may be considered as "outflow" drugs. Despite the variety of drugs accessible in the market, there is a real need for ophthalmologists to have more potent medications for this disease. This review focuses on medical treatment of glaucoma with particular attention to novel molecules in pre-clinical or clinical development.