Intracameral Pilocarpine Research Articles

Exploring the Distinct Characteristic of Two Procedures for Sulcus Implementation following Posterior Capsular Rupture during Phacoemulsification: Single-piece Foldable IOLs and Polymethylmethacrylate IOLs

Introduction : Posterior capsular rupture (PCR) is one of the most feared complications of phacoemulsification. In? the?bag implantation of the lens becomes difficult if the PCR was large. Implantation of rigid polymethylmethacrylate (PMMA) or single?piece foldable IOL is implanted in the sulcus
 Case Illustration : After noting the PCR on both patients, single?piece foldable IOL of the same power was implanted in the ciliary sulcus. Same action was implemented to PMMA IOLs by enlarging the main port twice. Intracameral pilocarpine was injected and vitrectomy anterior was performed. The wound was closed with hydration on single-piece foldable IOL, meanwhile on PMMA IOLs, one hecting is required in the middle of mainport wound. The postoperative VA on day 1 from 0.12 on single-piece foldable IOLs and 0.25 on PMMA IOLs. Corneal edema, increased anterior chamber reaction was seen on single-piece foldable IOLs. Raised IOP was not found on both patients
 Discussion : Complications implantation single?piece foldable IOLs such as pigment dispersion syndrome, increased IOP. A surgical peripheral iridectomy can be created as a solution. Complication less likely occurred on the patient with longer axial length. The AL on this patient is AL 23.33 mm (single?piece foldable IOLs) and 24.08 mm (PMMA IOLs). The weakness of single piece foldable acrylic lenses are poor choice for ciliary sulcus placement and PMMA IOLs can induce astigmatism.
 Conclusion : Single-piece foldable IOLs are not designed for sulcus implantation. PMMA IOLs implantation can induce astigmatism.

Preservative Free Intracameral Pilocarpine for Intraoperative Miosis

We describe use of 0.5% intracameral preservative free pilocarpine during cataract and glaucoma surgery for pupillary miosis, as alternative to commonly used intraoperative intracameral miotic agents such as acetyl choline and carbachol. This agent is safe and effective in achieving intraoperative miosis and free of corneal toxicity and causing intraocular inflammation.

The role of aromatic ring number in phenolic compound-conjugated chitosan injectables for sustained therapeutic antiglaucoma efficacy

The development of long-lasting therapeutic drug delivery system is greatly desired for effective treatment of glaucoma, a chronic and multifactorial disease. Herein, the roles of aromatic ring number in phenolic compound-conjugated chitosan injectables are exploited for achieving an advanced drug carrier with potent anti-inflammatory and anti-oxidant properties. Low and high number of aromatic rings can induce deleterious impacts on the pharmaceutical applications of injectables, whereas the compound with a moderate ring number is proved as the most efficient agent for boosting drug delivery performances and endowing the chitosan injectables with therapeutic properties. Kaempferol–conjugated injectable formulation reveals a remarkable effectiveness for intracameral pilocarpine administration, which can alleviate progressive glaucoma via simultaneously exerting multiple pharmacological activities to suppress ocular hypertension, inflammation, and oxidative stress. These findings provide a significant advance in understanding structure-property relationship of the phenolic compound-conjugated chitosan injectables as long-lasting therapeutic drug delivery systems for medical management of glaucoma.

Amination degree of gelatin is critical for establishing structure-property-function relationships of biodegradable thermogels as intracameral drug delivery systems

Glaucoma is a lifelong disorder that necessitates continuous medical therapy to manage its symptoms and preserve the vision of patients; accordingly, it is highly beneficial to develop a long-acting injectable depot system that can exhibit better drug delivery capability. This study aims to investigate the effect of the amination degree of gelatin on the carbodiimide-mediated grafting of thermo-responsive poly(N-isopropylacrylamide) segments onto biodegradable protein backbone molecules. Moreover, the potential applications of these carrier materials for intracameral pilocarpine administration in glaucomatous subjects will be considered. The gelatins with different amination degrees that are prepared by controlling the feed amount of adipic acid dihydrazide are further used for the synthesis of graft copolymers. The results of chemical characterization and electron microscopy studies showed that both grafting reaction effectiveness and gelling carrier ultrastructure vary in response to biomaterial amination. Compared to unmodified biopolymer thermogel without gel formation, graft copolymers that are composed of aminated gelatin networks showed a more remarkable temperature-triggered pilocarpine capture under physiological conditions. This could create more stable depot-forming carrier systems with improved in vivo pharmacological efficacy. Although the increase in amination degree enhances the biodegradation resistance of graft copolymers for achieving extended drug release profiles and provides significant therapeutic benefits, carriers with excess positive charges may potentiate the cytotoxic actions of oxidative stress signals and may cause damage in cellular barrier integrity. Consequently, unfavorable ocular tissue responses and poor treatment outcomes are observed in glaucomatous rabbits. For the first time, our findings suggest that the amination degree of gelatin performs a crucial function in guiding the development of structure-property-function relationships of biodegradable thermogels as intracameral drug delivery systems.

Chitosan-g-poly(N-isopropylacrylamide) copolymers as delivery carriers for intracameral pilocarpine administration

This study reports, for the first time, the development of a chitosan-g-poly(N-isopropylacrylamide) (Chi-PN) biodegradable in situ gelling delivery system for ocular pilocarpine administration through intracameral injection. The number of thermo-responsive polymer segments grafted onto the chitosan via carbodiimide-mediated formation of amide linkages was greatly affected by varying the feeding amount of carboxyl-terminated poly(N-isopropylacrylamide) in the synthesis, thereby determining the phase transition temperature and enzymatic degradability of Chi-PN materials. The increase in grafting ratio facilitated temperature triggered gelation and drug encapsulation at physiological conditions. Additionally, the slow biodegradation process of delivery carriers was responsible for the delayed pilocarpine release, which allowed that the drug concentration could reach minimum therapeutic level for treating glaucoma during 42days of the study. All of the synthesized Chi-PN carriers demonstrated good ocular biocompatibility with lens epithelial cell cultures. In a rabbit model of experimental glaucoma, the intraocular pressure-lowering and miotic as well as corneal endothelial preservation responses to pilocarpine strongly depended on the drug release profiles. It is concluded that injectable biodegradable chitosan-based thermogels can be potentially utilized as intracameral biomaterials for extended release of antiglaucoma medications and improved performance of delivery carriers.

On the importance of Bloom number of gelatin to the development of biodegradable in situ gelling copolymers for intracameral drug delivery

To overcome the drawbacks associated with conventional antiglaucoma eye drops, this work demonstrated the feasibility of an effective alternative strategy to administer pilocarpine directly via intracameral injections of drug-containing biodegradable in situ gelling GN copolymers composed of gelatin and poly(N-isopropylacrylamide). Specifically, this study aims to understand the importance of Bloom number of gelatin, a physicochemical parameter, to the development of GN carriers for intracameral drug delivery in glaucoma therapy. Our results showed that both imino acid and triple-helix contents increased with increasing Bloom index from 75⿿100 to 300. The drug encapsulation efficiency in response to temperature-triggered phase transition in GN copolymers was affected by the Bloom index of gelatin. In addition, the differences in protein secondary structure significantly influenced the degradation rates of GN carriers, which were highly correlated with drug release profiles. The increase in released pilocarpine concentration led to a high intracellular calcium level in rabbit ciliary smooth muscle cell cultures, indicating a beneficial pharmacological response to a drug. Irrespective of Bloom number of gelatin, all carrier materials exhibited excellent in vitro and in vivo biocompatibility with corneal endothelium. In a glaucomatous rabbit model, intracameral injections of pilocarpine-containing GN synthesized from gelatins with various Bloom numbers had different abilities to improve ocular hypertension and induce pupillary constriction, indicating distinct antiglaucoma efficacies due to in vivo drug release. It is concluded that the effects on pharmacological treatment using GN carriers for intracameral pilocarpine administration demonstrate a strong dependence on the Bloom number of gelatin.

Gallic acid grafting effect on delivery performance and antiglaucoma efficacy of antioxidant-functionalized intracameral pilocarpine carriers

Functionalization of therapeutic carrier biomaterials can potentially provide additional benefits in drug delivery for disease treatment. Given that this modification determines final therapeutic efficacy of drug carriers, here, we investigate systematically the role of grafting amount of antioxidant gallic acid (GA) onto GN in situ gelling copolymers made of biodegradable gelatin and thermo-responsive poly(N-isopropylacrylamide) for intracameral delivery of pilocarpine in antiglaucoma treatment. As expected, increasing redox reaction time increased total antioxidant activities and free radical scavenging abilities of synthesized carrier biomaterials. The hydrophilic nature of antioxidant molecules strongly affected physicochemical properties of carrier materials with varying GA grafting amounts, thereby dictating in vitro release behaviors and mechanisms of pilocarpine. In vitro oxidative stress challenges revealed that biocompatible carriers with high GA content alleviated lens epithelial cell damage and reduced reactive oxygen species. Intraocular pressure and pupil diameter in glaucomatous rabbits showed correlations with GA-mediated release of pilocarpine. Additionally, enhanced pharmacological treatment effects prevented corneal endothelial cell loss during disease progression. Increasing GA content increased total antioxidant level and decreased nitrite level in the aqueous humor, suggesting a much improved antioxidant status in glaucomatous eyes. This work significantly highlights the dependence of physicochemical properties, drug release behaviors, and bioactivities on intrinsic antioxidant capacities of therapeutic carrier biomaterials for glaucoma treatment. Statement of SignificanceDevelopment of injectable biodegradable polymer depots and functionalization of carrier biomaterials with antioxidant can potentially provide benefits such as improved bioavailability, controlled release pattern, and increased therapeutic effect in intracameral pilocarpine administration for glaucoma treatment. For the first time, this study demonstrated that the biodegradable in situ gelling copolymers can incorporate different levels of antioxidant gallic acid to tailor the structure-property-function relationship of the intracameral drug delivery system. The systematic evaluation fully verified the dependence of phase transition, degradation behavior, drug release mechanism, and antiglaucoma efficacy on intrinsic antioxidant capacities of carrier biomaterials. The report highlights the significant role of grafting amount of gallic acid in optimizing performance of antioxidant-functionalized polymer therapeutics as new drug delivery platforms in disease treatment.

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

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. No author has a financial or proprietary interest in any material or method mentioned.

Live Wuchereria bancrofti in anterior chamber of the eye: A case report

We are reporting a case of live filarial worm in the anterior chamber (AC), with in toto removal for microbiological evaluation without damaging the ocular structures. A 34-year-old male presented with sudden-onset redness in the left eye for 4 days, associated with irritation and photophobia. On examination, his best corrected visual acuity was 6/6, with circumcorneal congestion. Slit-lamp examination of the AC showed cells and flare, along with a long translucent thin motile worm, with wriggling movement. Iris showed a thin, irregular, white atrophic patch nasally through which the worm had entered the AC. The worm was isolated surgically from AC in toto with the forceps, assisted by intracameral pilocarpine and viscoelastics. Microbiological examination of the worm by a parasitologist was suggestive of a growing adult male Wuchereria bancrofti.

Aceclidine effects on outflow facility after ciliary muscle disinsertion.

Aceclidine increases outflow facility with little accommodative effect. To determine whether this dissociation resides in the ciliary muscle (CM) or trabecular meshwork (TM), we measured aceclidine effects on perfusion outflow facility in both eyes of 8 rhesus monkeys after unilateral disinsertion of the CM from the TM. Facility in the control eyes increased by approximately 250% following intravenous pilocarpine and by an additional approximately 250% following intracameral pilocarpine, relative to baseline and uncorrected for washout. In CM-disinserted eyes, the facility response to intravenous and intracameral pilocarpine averaged approximately 25% of that in contralateral controls. Cytochalasin B, which acts directly on the TM to increase facility but is not additive to maximal pilocarpine doses in normal eyes, had no additional effect beyond that of pilocarpine in control eyes but induced an additional 100% facility increase relative to baseline in CM-disinserted eyes. The accommodative response to carbachol in CM-disinserted eyes was approximately 80% of that in contralateral controls, consistent with retention of CM contractility and the gonioscopic appearance of shallow CM disinsertion. Intracameral aceclidine HCl doses of 5 and 50 micrograms increased outflow facility by approximately 80 and 250%, respectively, in control eyes, and by approximately 0 and 80% in CM-disinserted eyes. Either the low aceclidine dose affected facility via the CM, while the high dose exerted an additional effect on the TM, or aceclidine acted only via the CM, with the low dose being ineffective and the high dose modestly effective in CM-disinserted eyes because only a few CM-TM attachments remained.

Argon Laser Trabeculoplasty and Pilocarpine Effects on Outflow Facility in the Cynomolgus Monkey

We sought to determine whether and how prior argon laser trabeculoplasty (ALT) alters outflow facility, the pilocarpine-induced facility increase, and the morphology of the trabecular meshwork in cynomolgus monkeys. Eleven cynomolgus monkeys underwent unilateral 360 degrees argon laser trabeculoplasty, eight in two 180 degrees sessions (seven 3 months apart, one 11 days apart) and three in a single session. Intraocular pressure (IOP, Golmann ap-planation tonometry), aqueous humor flow rate (AHFR, fluorophotometry), total outflow facility (two-level constant pressure perfusion) and response to intracameral pilocarpine, and morphology (light and scanning/transmission electron microscopy) were determined at various times. Resting total perfusion outflow facility 3 and 6 months after 360 degrees ALT was 30% higher in ALT-treated than in contralateral untreated eyes. There were no consistent or statistically significant differences between ALT-treated and contralateral untreated eyes in (a) IOP or AHFR before ALT, 5 weeks after initial 180 ALT, or 5 weeks after the second 180 ALT; (b) post-intracameral pilocarpine facility, or the dose-dependent facility response to pilocarpine 10 weeks after the initial 180 ALT or 3 and 6 months after the second 180 ALT; or (c) light or electron microscopic appearance of the trabecular meshwork or inner wall of Schlemm's canal 3-17 months after 360 ALT. This study indicates that (a) ALT alters the biomechanical properties of the monkey trabecular meshwork so as to modestly increase its hydraulic conductivity without affecting the facility response to pilocarpine-induced ciliary muscle contraction; and (b) young healthy monkey outflow tissues exhibit remarkable reparative and homeostatic capabilities.

Dissociation between the effect of aceclidine on outflow facility and accommodation

The dose/effect relationships for intracameral doses of aceclidine HCl and pilocarpine HCl on total facility of outflow and accommodative amplitude were compared in the cynomolgus monkey eye in vivo. The largest dose of aceclidine tested (20 μg), resulted in an average increase of 270% in outflow facility, whereas accommodation was limited to an average of 5 diopters. In contrast, 20 μg of intracameral pilocarpine (which is submaximal in increasing facility) resulted in an average of 19 diopters of accommodation. These results provide further evidence for a dissociation between the accommodative and outflow facility functions of the ciliary muscle.

Subsensitivity to Pilocarpine of the Aqueous Outflow System in Monkey Eyes After Topical Anticholinesterase Treatment

Cynomolgus and vervet monkeys were treated unilaterally with topical echothiophate iodide twice daily for eight to 25 weeks. The effect of intracameral pilocarpine on outflow facility was determined in the ganglionic-blocked animal during and after echothiophate treatment. The echothiophate-treated eyes demonstrated marked subsensitivity to pilocarpine, and required several weeks to months to recover normal pilocarpine sensitivity.