Influence of miosis and laser peripheral iridotomy on intraocular lens power calculation in patients with primary angle closure disease.

OBJECTIVES: To evaluate the effect of miosis and laser peripheral iridotomy (LPI) on intraocular lens (IOL) power prediction and ocular biometry in eyes with primary angle closure disease (PACD). METHODS: In this prospective observational study, primary angle closure suspects (PACS), and subjects classified with primary angle closure (PAC)/primary angle-closure glaucoma (PACG) undergoing LPI were enrolled. Ocular biometric parameters were measured with IOLMaster700 at baseline (T0), one week after pilocarpine instillation (T1), and another week post LPI (T2). Biometric changes and the IOL power predicted for emmetropia using Barrett Universal II, Haigis, Holladay2, Hoffer Q and SRK/T formulae were analysed and compared among different time points. RESULTS: 100 eyes of 50 PACS and 50 PAC/PACG patients were enrolled. Following pilocarpine-induced miosis, lens thickness (LT) increased and anterior chamber depth (ACD) decreased (all groups p < 0.01), while white-to-white diameter decreased and central corneal thickness increased significantly only in the PACS cohort (both p < 0.01). Compared to baseline, LPI induced an increase of ACD and a slight decrease of LT in PACS (both p < 0.01), whereas only axial length changed significantly (p = 0.012) in the PAC/PACG cohort. Regardless of the formula used, no significant difference to the predicted IOL power for emmetropia existed among the three time points in each group (all p > 0.1). CONCLUSION: We report the changes of anterior segment parameters induced by miosis and LPI in PACD. These interventions do not significantly affect the IOL power calculation predicted for emmetropia in Chinese eyes when common third-, fourth-and new generation IOL formulae are used.

Evaluating the effects of betaine on testicular ischemia/reperfusion injury induced by torsion/detorsion in the rat.

In this research, the effects of betaine on testicular ischemia-reperfusion were evaluated. Forty rats were randomly divided into 4 groups of sham, torsion/detorsion (TD), torsion/detorsion with two different dosage of betaine 200 mg/kg, and 300 mg/kg, respectively. At the end of the experiment, the testosterone concentration, sperm motility, concentration and vitality, oxidative stress biomarkers including Malondialdehyde (MDA), Glutathione peroxidase (GPx), Catalase (CAT), and total antioxidant capacity (TAC) were assessed. Moreover, histopathological parameters including seminiferous tubules diameter (STD), seminiferous epithelium thickness (SET), spermatogonia nuclei diameter (SpND), Sertoli cell nuclei diameter (StND) and miotic index were evaluated. The testosterone concentration altered during torsion/detorsion and betaine could increase slightly the testosterone concentration after 15 days. Sperm motility and vitality significantly increased in the betaine treated groups compared to the TD group on days 3 and 15. Among oxidative stress biomarkers, only CAT on day 3 and GPx on day 15 were significantly higher in the betaine groups compared to the TD group. Among histopathological parameters an increase in the STD and SET in betaine-200 and betaine-300 groups were observed on 15th day of post-surgery, compared to the TD group. These findings indicate that betaine can ameliorate testicular damages triggered by torsion/detorsion.

Retinal Detachments Associated With Topical Pilocarpine Use for Presbyopia.

PURPOSE: To present a case series of retinal detachments associated with the use of pilocarpine for presbyopia. DESIGN: Multicenter case series of 3 eyes from 2 patients. RESULTS: Patient 1, a 47-year-old man, presented with flashes and floaters in both eyes. The patient had started pilocarpine 1.25% drops 1 month prior for presbyopia in both eyes. He noted the onset of flashes and floaters 3 days after he initiated the drops. A dilated examination revealed an inferotemporal retinal detachment in the right eye with an associated retinal tear inferotemporally. The left eye demonstrated a retinal detachment in the superior quadrant with an associated horseshoe tear at 12 o'clock. Patient 2, a 46-year-old man, presented 5 weeks after initiating topical pilocarpine 1.25% drops for presbyopia. He noted a nasal visual field defect in his left eye that progressed to include his central vision. A dilated examination revealed a superior retinal detachment from 11 to 3 o'clock with subretinal fluid extending into the macula. CONCLUSIONS: Pilocarpine and other miotics have long been suspected to be associated with an increased risk of retinal detachment. Prior to prescribing pilocarpine for presbyopia, physicians should inform patients of this potential adverse event and consider that these patients undergo a screening dilated examination, particularly if they are myopic, to determine if they are at higher risk for retinal detachment. Before the initiation of therapy, patients should be appropriately informed regarding symptoms of retinal tears or detachment, which include flashes, floaters, and visual field loss.

Effect of over-the-counter brimonidine tartrate 0.025% ophthalmic solution on pupil size in healthy adults.

PURPOSE: To evaluate the effect of brimonidine tartrate 0.025% ophthalmic solution on pupil size under scotopic conditions in healthy adults METHODS: Pupil size was measured in 56 eyes of 28 volunteer participants using a pupillometer under scotopic conditions. Age, gender, and iris color were recorded. Subjects using any ophthalmic medications other than artificial tears were excluded. The pupil size was subsequently measured again under scotopic conditions 60 min after instillation of brimonidine tartrate 0.025% ophthalmic solution. RESULTS: Statistically significant miosis was seen after instillation of brimonidine tartrate 0.025% (p = 0.04). Average pupil size prior to brimonidine 0.025% instillation was 7.28 ± 1.05 mm, and average pupil size after instillation of brimonidine 0.025% was 6.36 ± 1.68 mm, a reduction of - 23.7% in pupil area. Subjects with light irides demonstrated a greater miotic effect than subjects with dark irides (1.55 mm vs. 0.67 mm, p < 0.0001), with a pupil area reduction of - 37.6% and - 17.4%, respectively. The amount of miosis was independent of initial pupil size. CONCLUSIONS: Brimonidine tartrate 0.025% causes significant miosis in scotopic settings, although the effect is not as great in darker colored eyes. Further studies are needed to determine the latency and duration of the effect and whether the amount of miosis is clinically significant.

Acute Inhibitory Effects of Antidepressants on Lacrimal Gland Secretion in the Anesthetized Rat.

Purpose: Patients that medicate with antidepressants commonly report dryness of eyes. The cause is often attributed to the anticholinergic properties of the drugs. However, regulation of tear production includes a substantial reflex-evoked component and is regulated via distinct centers in the brain. Further, the anticholinergic component varies greatly among antidepressants with different mechanisms of action. In the current study it was wondered if acute administration of antidepressants can disturb production of tears by affecting the afferent and/or central pathway. Methods: Tear production was examined in vivo in anesthetized rats in the presence or absence of the tricyclic antidepressant (TCA) clomipramine or the selective serotonin reuptake inhibitor (SSRI) escitalopram. The reflex-evoked production of tears was measured by challenging the surface of the eye with menthol (0.1 mM) and cholinergic regulation was examined by intravenous injection with the nonselective muscarinic agonist methacholine (1-5 µg/kg). Results: Acute administration of clomipramine significantly attenuated both reflex-evoked and methacholine-induced tear production. However, escitalopram only attenuated reflex-evoked tear production, while methacholine-induced production of tears remained unaffected. Conclusions: This study shows that antidepressants with different mechanisms of action can impair tear production by attenuating reflex-evoked signaling. Further, antimuscarinic actions are verified as a likely cause of lacrimal gland hyposecretion in regard to clomipramine but not escitalopram. Future studies on antidepressants with different selectivity profiles and mechanisms of action are required to further elucidate the mechanisms by which antidepressants affect tear production.

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.

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.

Microbial safety implications of in-use topical diagnostic ophthalmic medications in eye clinics in Ghana / Implicaciones sobre seguridad microbiana de los fármacos oftálmicos diagnósticos tópicos utilizados en las clínicas oftalmológicas de Gana

PURPOSE: To determine the microbial contaminants and its clinical importance in topical diagnostic ophthalmic medications (cycloplegics/mydriatics and miotics) in eye clinics in Ghana. Method: A cross-section of eye clinics was sampled for the diagnostic agents (Atropine, Phenylephrine, Tropicamide and Cyclopentolate, Pilocarpine). Standard laboratory procedures and protocols were observed in culturing the samples on different Agars. Microscopy and various biochemical tests were performed to identify microbial species. Antimicrobial susceptibility testing was also performed to ascertain the clinical importance of the isolated microbes. RESULTS: A total of 113 samples were obtained, from which 334 bacteria were isolated which included Bacilli spp. 91(27.25%), Coagulase Negative Staphylococci spp. 59(17.66%), Moraxella spp. 47(14.07%), Staphylococcus aureus 41(12.27%), Streptococcus spp. 21(6.29%), Klebsiella spp. 20(5.99%), Pseudomonas spp. 13(3.89%), Proteus spp. 12(3.59%), Escherichia coli. 12 (3.59%), Serratia spp. 10(2.99%), Shigella spp. 7(2.09%), Salmonella spp. 1(0.3%). There were 96 isolated fungal contaminants mainly Penicillium spp. 41(42.71%), Cephalosporium spp. 19(19.79%), Cladosporium spp. 15(15.63%), Aspergillus spp. 13(13.54%), Cercospora spp. 8(8.33%). The diagnostic agent with the most bacteria contamination was Phenylephrine 90 (26.95%) and the least being Pilocarpine 49 (14.67%). Also, the diagnostic agent with the most fungal contamination was Cyclopentolate 29 (30.2%) and the least was Tropicamide and Pilocarpine with 15 (15.63%) each. Gentamicin and Ciprofloxacin were the only antibiotics that showed 100% activity against all the bacterial isolates. Fungal contaminants were more susceptible to Ketoconazole as compared to Fluconazole. Conclusion: Topical diagnostic ophthalmic preparations used in clinical settings in Ghana are contaminated with clinically important bacteria and fungi

OBJETIVO: Determinar los contaminantes microbianos y su importancia clínica en los fármacos oftálmicos diagnósticos tópicos (ciclopléjicos/midriáticos y mióticos) en clínicas oftalmológicas de Gana. MÉTODO: Se realizó una muestra transversal de clínicas oftalmológicas para los agentes diagnósticos (Atropina, Fenilefrina, Tropicamida y Ciclopentolato, Pilocarpina). Se observaron procedimientos y protocolos de laboratorio estándar en cuanto al cultivo de muestras en diferentes soluciones de Agar. Se realizaron diversas pruebas microscópicas y bioquímicas para identificar las especies microbianas. También se realizó la prueba de susceptibilidad antimicrobiana para comprobar la importancia clínica de los microbios aislados. RESULTADOS: Se obtuvieron un total de 113 muestras, de las cuales se aislaron 334 bacterias que incluyeron Bacilli spp. 91(27,25%), Staphylococci spp. Coagulasa negativos 59(17,66%), Moraxella spp. 47(14,07%), Staphylococcus aureus 41(12,27%), Streptococcus spp. 21(6,29%), Klebsiella spp. 20(5,99%), Pseudomonas spp. 13(3,89%), Proteus spp. 12(3,59%), Escherichia coli. 12(3,59%), Serratia spp. 10(2,99%), Shigella spp. 7(2,09%), Salmonella spp. 1(0,3%). Se encontraron 96 contaminantes fúngicos aislados, principalmente Penicillium spp. 41 (42,71%), Cephalosporium spp. 19 (19,79%), Cladosporium spp. 15 (15,63%), Aspergillus spp. 13 (13,54%), Cercospora spp. 8 (8,33%). El agente diagnóstico con mayor contaminación bacteriana fue Fenilefrina 90(26,95%), siendo Pilocarpina 49 (14,67%) el que reflejó una menor contaminación bacteriana. De igual modo, el agente diagnóstico con mayor contaminación fúngica fue Ciclopentolato 29 (30,2%), siendo Tropicamida y Pilocarpina, con 15 (15.63%) cada uno, los que reflejaron menos contaminación fúngica. Gentamicina y Ciprofloxacina fueron los únicos antibióticos que reflejaron un 100% de actividad frente a todos los aislados bacterianos. Los contaminantes fúngicos fueron más susceptibles a Ketoconazol, en comparación con Fluconazol. CONCLUSIÓN: Los preparados oftálmicos diagnósticos tópicos en entornos clínicos en Gana están contaminados por bacterias y hongos clínicamente importantes

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.

Microbial safety implications of in-use topical diagnostic ophthalmic medications in eye clinics in Ghana.

PURPOSE: To determine the microbial contaminants and its clinical importance in topical diagnostic ophthalmic medications (cycloplegics/mydriatics and miotics) in eye clinics in Ghana. METHOD: A cross-section of eye clinics was sampled for the diagnostic agents (Atropine, Phenylephrine, Tropicamide and Cyclopentolate, Pilocarpine). Standard laboratory procedures and protocols were observed in culturing the samples on different Agars. Microscopy and various biochemical tests were performed to identify microbial species. Antimicrobial susceptibility testing was also performed to ascertain the clinical importance of the isolated microbes. RESULTS: A total of 113 samples were obtained, from which 334 bacteria were isolated which included Bacilli spp. 91(27.25%), Coagulase Negative Staphylococci spp. 59(17.66%), Moraxella spp. 47(14.07%), Staphylococcus aureus 41(12.27%), Streptococcus spp. 21(6.29%), Klebsiella spp. 20(5.99%), Pseudomonas spp. 13(3.89%), Proteus spp. 12(3.59%), Escherichia coli. 12 (3.59%), Serratia spp. 10(2.99%), Shigella spp. 7(2.09%), Salmonella spp. 1(0.3%). There were 96 isolated fungal contaminants mainly Penicillium spp. 41(42.71%), Cephalosporium spp. 19(19.79%), Cladosporium spp. 15(15.63%), Aspergillus spp. 13(13.54%), Cercospora spp. 8(8.33%). The diagnostic agent with the most bacteria contamination was Phenylephrine 90 (26.95%) and the least being Pilocarpine 49 (14.67%). Also, the diagnostic agent with the most fungal contamination was Cyclopentolate 29 (30.2%) and the least was Tropicamide and Pilocarpine with 15 (15.63%) each. Gentamicin and Ciprofloxacin were the only antibiotics that showed 100% activity against all the bacterial isolates. Fungal contaminants were more susceptible to Ketoconazole as compared to Fluconazole. CONCLUSION: Topical diagnostic ophthalmic preparations used in clinical settings in Ghana are contaminated with clinically important bacteria and fungi.

Role of TRPP2 in mouse airway smooth muscle tension and respiration.

The transient receptor potential polycystin-2 (TRPP2) is encoded by the Pkd2 gene, and mutation of this gene can cause autosomal dominant polycystic kidney disease (ADPKD). Some patients with ADPKD experience extrarenal manifestations, including radiologic and clinical bronchiectasis. We hypothesized that TRPP2 may regulate airway smooth muscle (ASM) tension. Thus, we used smooth muscle-Pkd2 conditional knockout (Pkd2SM-CKO) mice to investigate whether TRPP2 regulated ASM tension and whether TRPP2 deficiency contributed to bronchiectasis associated with ADPKD. Compared with wild-type mice, Pkd2SM-CKO mice breathed more shallowly and faster, and their cross-sectional area ratio of bronchi to accompanying pulmonary arteries was higher, suggesting that TRPP2 may regulate ASM tension and contribute to the occurrence of bronchiectasis in ADPKD. In a bioassay examining isolated tracheal ring tension, no significant difference was found for high-potassium-induced depolarization of the ASM between the two groups, indicating that TRPP2 does not regulate depolarization-induced ASM contraction. By contrast, carbachol-induced contraction of the ASM derived from Pkd2SM-CKO mice was significantly reduced compared with that in wild-type mice. In addition, relaxation of the carbachol-precontracted ASM by isoprenaline, a ß-adrenergic receptor agonist that acts through the cAMP/adenylyl cyclase pathway, was also significantly attenuated in Pkd2SM-CKO mice compared with that in wild-type mice. Thus, TRPP2 deficiency suppressed both contraction and relaxation of the ASM. These results provide a potential target for regulating ASM tension and for developing therapeutic alternatives for some ADPKD complications of the respiratory system or for independent respiratory disease, especially bronchiectasis.

Efficacy of treatments for Demodex blepharitis: A systematic review and meta-analysis.

PURPOSE: We conducted a systematic review and meta-analysis to evaluate the efficacy of different treatment for Demodex blepharitis. Parameters studied were mites count, improvement of symptoms and mites' eradication, stratified on type of treatments and mode of delivery of treatments (local or systemic). METHOD: The PubMed, Cochrane Library, Embase, ClinicalTrials.gov, Google scholar and Science Direct databases were searched for studies reporting an efficacy of treatments for Demodex blepharitis. RESULTS: We included 19 studies (14 observational and 5 randomized clinical trials), for a total of 934 patients, 1741 eyes, and 13 different treatments. For mites count, eradication rate, and symptoms improvement, meta-analysis included fifteen, fourteen and thirteen studies, respectively. The overall effect sizes for efficiency of all treatments, globally, were 1.68 (95CI 1.25 to 2.12), 0.45 (0.26-0.64), and 0.76 (0.59-0.90), respectively. Except usual lid hygiene for mites count, Children's Hospital of Eastern Ontario ointment (CHEO) for both eradication rate and symptoms, and CHEO, 2% metronidazole ointment, and systemic metronidazole for eradication rate, all treatments were efficient. Stratified meta-analysis did not show significant differences between local and systemic treatments (1.22, 0.83 to 1.60 vs 2.24, 1.30 to 3.18 for mites count; 0.37, 0.21 to 0.54 vs 0.56, 0.06 to 0.99 for eradication rate; and 0.77, 0.58 to 0.92 vs 0.67, 0.25 to 0.98 for symptoms improvement). CONCLUSION: We reported the efficiency of the different treatments of Demodex blepharitis. Because of less systemic side effects, local treatments seem promising molecules in the treatment of Demodex blepharitis.

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.

Small-aperture strategies for the correction of presbyopia.

PURPOSE OF REVIEW: The recent scientific literature provides evidence of long-term results with small-aperture corneal inlays, as well as new evidence from a multicenter postmarket study of small-aperture intraocular lenses (IOLs) and early reports of the use of topical agents for presbyopia correction through pupil constriction. The field of small-aperture optics is growing and changing rapidly. RECENT FINDINGS: This article reviews what is known to date about various small-aperture optics platforms, including a posterior chamber IOL, add on device, corneal inlay, contact lenses, and pupil-constricting drops. Additionally, the impact of small-aperture technologies on light perception and visual performance, as well as the relative merits of monocular versus binocular small apertures are discussed. SUMMARY: Small-aperture optics are a dynamic, physiologic solution to the problem of presbyopia. They are effective throughout the range of accommodation loss and in pseudophakia. Small-aperture optics offer an opportunity to improve vision in presbyopes with and without cataracts. In some forms, they may also be able to reduce the impact of aberrations or improve vision in eyes with corneal irregularities, scars, or iris damage.

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.