Single Intracameral Injection Research Articles

Safety of intracameral injection of levofloxacin 0.5% eye drops single dose 0.6 ml preservative free on rabbit eye

Background This was an experimental, parallel, and randomized study to evaluate the safety of single intracameral injection of 0.6 ml 0.5% preservative-free levofloxacin eye drops on rabbit eye. Methods In total, 24 eyes of 12 New Zealand white rabbits were divided into three groups. The first group (LFX) was treated with 0.1 ml intracameral injection of levofloxacin 0.5% eye drops of 0.6 ml preservative-free (n = 6), the second group (CRAV) was treated with 0.1 ml intracameral injection of levofloxacin 0.5% eye drops 5 ml commercially available eye drops preservative-free (n = 6), and the third group (BSS) were treated with 0.1 ml intracameral injection of balanced salt solution (n = 12). All groups received a single dose. The clinical evaluation was performed on the 1st, 3rd, 5th, and 7th day after injection. Each eye was enucleated on the 7th day and underwent a histopathology examination. Results The clinical scores among the three groups did not show any significant difference on days 1st, 2nd, 3rd, and 7th (p>0.05). The only ones noted in clinical scores were mild corneal opacity, mild cells, and flares in the anterior chamber. The histopathology score demonstrated no statistically significant difference between the three groups (p>0.05). Vacuolization of corneal endothelial cells was noted in all groups but was not statistically significant. Conclusions A single intracameral injection of 0.6 ml 0.5% preservative-free levofloxacin eye drops was safe for rabbit eye, according to clinical and histopathology scores, similar to levofloxacin 0.5% eye drops in 5 ml bottle preservative free.

Safety of intracameral injection of levofloxacin 0.5% eye drops single dose 0.6 ml preservative free on rabbit eye.

This was an experimental, parallel, and randomized study to evaluate the safety of single intracameral injection of 0.6 ml 0.5% preservative-free levofloxacin eye drops on rabbit eye. In total, 24 eyes of 12 New Zealand white rabbits were divided into three groups. The first group (LFX) was treated with 0.1 ml intracameral injection of levofloxacin 0.5% eye drops of 0.6 ml preservative-free (n = 6), the second group (CRAV) was treated with 0.1 ml intracameral injection of levofloxacin 0.5% eye drops 5 ml commercially available eye drops preservative-free (n = 6), and the third group (BSS) were treated with 0.1 ml intracameral injection of balanced salt solution (n = 12). All groups received a single dose. The clinical evaluation was performed on the 1 st, 3 rd, 5 th, and 7 th day after injection. Each eye was enucleated on the 7 th day and underwent a histopathology examination. The clinical scores among the three groups did not show any significant difference on days 1 st, 2 nd, 3 rd, and 7 th (p>0.05). The only ones noted in clinical scores were mild corneal opacity, mild cells, and flares in the anterior chamber. The histopathology score demonstrated no statistically significant difference between the three groups (p>0.05). Vacuolization of corneal endothelial cells was noted in all groups but was not statistically significant. A single intracameral injection of 0.6 ml 0.5% preservative-free levofloxacin eye drops was safe for rabbit eye, according to clinical and histopathology scores, similar to levofloxacin 0.5% eye drops in 5 ml bottle preservative free.

Machine learning-driven multifunctional peptide engineering for sustained ocular drug delivery

Sustained drug delivery strategies have many potential benefits for treating a range of diseases, particularly chronic diseases that require treatment for years. For many chronic ocular diseases, patient adherence to eye drop dosing regimens and the need for frequent intraocular injections are significant barriers to effective disease management. Here, we utilize peptide engineering to impart melanin binding properties to peptide-drug conjugates to act as a sustained-release depot in the eye. We develop a super learning-based methodology to engineer multifunctional peptides that efficiently enter cells, bind to melanin, and have low cytotoxicity. When the lead multifunctional peptide (HR97) is conjugated to brimonidine, an intraocular pressure lowering drug that is prescribed for three times per day topical dosing, intraocular pressure reduction is observed for up to 18 days after a single intracameral injection in rabbits. Further, the cumulative intraocular pressure lowering effect increases ~17-fold compared to free brimonidine injection. Engineered multifunctional peptide-drug conjugates are a promising approach for providing sustained therapeutic delivery in the eye and beyond.

Evaluation of intravitreal injection of blank microspheres in a new chronic glaucoma rat model

AbstractPurpose: To evaluate the intravitreal injection of PLGA/VitE non‐loaded microspheres as a potential platform to deliver neuroprotective active compounds in a chronic glaucoma animal model. In this model, a gradual increase in intraocular pressure (IOP) is observed due to physical and pharmacological damage to the trabecular meshwork by the intracameral injection of fibronectin‐loaded PLGA microspheres.Methods: Microspheres (Ms) employed to create the animal model were made by a double water‐in‐oil‐in‐water emulsion technique where fibronectin was included in the inner aqueous phase (F‐Ms). PLGA/VitE blank Ms (B‐Ms) were made by a single oil‐in‐water emulsion. Ms were characterized regarding mean particle size, particle size distribution and morphology. In vivo studies were carried out in Long‐Evans rats divided into two groups: control (n = 30) and treated (n = 20). To create the model, both groups received a single intracameral injection of F‐Ms suspension (10% w/v) in the right eye (RE). Two weeks later, a suspension of B‐Ms (5% w/v) was intravitreally injected into the RE (treated group). Clinical signs and IOP were assessed in both groups for 12 weeks.Results: Ms were spherical with a smooth surface and some porous in the case of F‐Ms and with a typical “golf‐ball like” surface in the case of B‐Ms. Size distribution was unimodal with an average size of 16.45 ± 0.37 μm for F‐Ms and 29.95 ± 0.42 μm for B‐Ms. Both ocular injections were well tolerated. In all cases, IOP values significantly increased over time (p < 0.05) with a rise of 6–7 mmHg at 12 weeks. No significant differences were found between the IOP in the treated and the control group.Conclusions: Intravitreal injections of B‐Ms were well tolerated and did not affect the IOP increase of the animal model. These findings underline the suitability of the glaucoma animal model created by the intracameral injection F‐Ms for the evaluation of treatments based on intravitreal injection of PLGA/VitE‐based microsystems.

Mimicking chronic glaucoma over 6 months with a single intracameral injection of dexamethasone/fibronectin-loaded PLGA microspheres

To create a chronic glaucoma animal model by a single intracameral injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (Ms) co-loaded with dexamethasone and fibronectin (MsDexaFibro). MsDexaFibro were prepared by a water-in-oil-in-water emulsion method including dexamethasone in the organic phase and fibronectin in the inner aqueous phase. To create the chronic glaucoma model, an interventionist and longitudinal animal study was performed using forty-five Long Evans rats (4-week-old). Rats received a single intracameral injection of MsDexafibro suspension (10%w/v) in the right eye. Ophthalmological parameters such as clinical signs, intraocular pressure (IOP), neuro-retinal functionality by electroretinography (ERG), retinal structural analysis by optical coherence tomography (OCT), and histology were evaluated up to six months. According to the results obtained, the model proposed was able to induce IOP increasing in both eyes over the study, higher in the injected eyes up to 6 weeks (p < 0.05), while preserving the ocular surface. OCT quantified progressive neuro-retinal degeneration (mainly in the retinal nerve fiber layer) in both eyes but higher in the injected eye. Ganglion cell functionality decreased in injected eyes, thus smaller amplitudes in PhNR were detected by ERG. In conclusion, a new chronic glaucoma animal model was created by a single injection of MsDexaFibro very similar to open-angle glaucoma occurring in humans. This model would impact in different fields such as ophthalmology, allowing long period of study of this pathology; pharmacology, evaluating the neuroprotective activity of active compounds; and pharmaceutical technology, allowing the correct evaluation of the efficacy of long-term sustained ocular drug delivery systems.

Evaluation of the Effectiveness of a Chronic Ocular Hypertension Mouse Model Induced by Intracameral Injection of Cross-Linking Hydrogel.

Background: Glaucoma is an irreversible and blinding neurodegenerative disease that is characterized by progressive loss of retinal ganglion cells. The current animal models of glaucoma fail to provide a chronic elevated intraocular pressure and cannot maintain the optical media clarity for a long time, which brings some difficulties to the study of glaucoma. Here, we developed a new chronic ocular hypertension model of mice induced by cross-linking hydrogel intracameral injection.Methods: C57BL/6J mice aged 6–8 weeks were randomly divided into the control group and the operation group. The mice of the operation group were injected with cross-linking hydrogel to induce ocular hypertension. Intraocular pressure was measured preoperatively, 3 days after surgery, and weekly until the end of the study. Flash visual evoked potential (F-VEP) was used to observe optic nerve function at different times (preoperatively and 2, 4, and 6 weeks) after chronic ocular hypertension (COH). Retinal TNF-α, IL-1β, and IL-17A protein expression were measured by western blotting in the control group and in mice at 2, 4, and 6 weeks after COH. Microglial cell activation was evaluated by immunofluorescence staining and western blotting. Apoptosis and loss of retinal ganglion cells after 2, 4, and 6 weeks of intracameral injection of cross-linking hydrogel were observed by the TUNEL assay and Brn3a protein labeling. The loss of optic nerve axons in COH mice was evaluated by neurofilament heavy polypeptide protein labeling.Results: Intracameral injection of the cross-linking hydrogel induces increased intraocular pressure (IOP) to a mean value of 19.3 ± 4.1 mmHg, which was sustained for at least 8 weeks. A significant difference in IOP was noted between COH mice and sham-operation mice (p < 0.0001). The success rate was 75%. The average amplitude of F-VEP in mice with COH was reduced (p = 0.0149, 0.0012, and 0.0009 at 2, 4, and 6 weeks after COH vs. the control group, respectively), and the average latent period in mice with COH was longer (p = 0.0290, <0.0001, and <0.0001 at 2, 4, and 6 weeks after COH vs. the control group, respectively) compared with that in the control group. TNF-α, IL-1β, IL-17A, Iba-1, and CD68 protein expression increased in COH mice. During the processing of COH, the number of microglial cells increased along with cellular morphological changes of rounder bodies and thicker processes compared with the control group. Apoptosis of retinal ganglion cells (RGCs) was clearly observed in mice at 2, 4, and 6 weeks after COH (p = 0.0061, 0.0012, <0.0001, and 0.0371 at 2, 4, and 6 weeks after COH vs. the control group, respectively). The RGC density decreased significantly in the COH mice compared with the control group (p = 0.0042, 0.0036, and <0.0001 at 2, 4, and 6 weeks after COH vs. the control group, respectively). There was a significant loss of optic nerve axons in mice after intracameral injection of cross-linking hydrogel (p = 0.0095, 0.0002, and <0.0001 at 2, 4, and 6 weeks after COH vs. the control group, respectively).Conclusions: A single intracameral injection of cross-linking hydrogel can effectively induce chronic ocular hypertension in mice, which causes progressive loss of retinal ganglion cells, increased expression levels of inflammatory cytokines and microglial cell activation, and deterioration of optic nerve function.

Efficacy, Drug Sensitivity, and Safety of a Chronic Ocular Hypertension Rat Model Established Using a Single Intracameral Injection of Hydrogel into the Anterior Chamber.

BackgroundChronic ocular hypertension (COH) models mostly focus on changes in intraocular pressure (IOP) and loss of retinal ganglion cells (RGCs). The present study evaluated important glaucoma-related changes in visual function, response to common ocular hypotensive drugs, and safety for our previously developed rat model.Material/MethodsThe model was established through a single injection of hydrogel into the anterior chambers. Efficacy was assessed through F-VEP by measuring latency and amplitude of P1. We evenly divided 112 rats into 4 groups: control and COH at 2, 4, and 8 weeks. Response to 5 common drugs (brimonidine, timolol, benzamide, pilocarpine, and bimatoprost) were each tested on 6 rats and assessed using difference in IOP. Safety assessment was conducted through histological analysis of 24 rats evenly divided into 4 groups of control and COH at 2, 4, and 8 weeks. Corneal endothelial cells (CECs) of 24 additional rats were used to determine toxic effects through TUNEL and CCK-8 assays.ResultsP1 latency and amplitude of VEP demonstrated the model is effective in inducing optic nerve function impairment. Only the drug pilocarpine failed to have an obvious hypotensive effect, while the other 4 were effective. CECs at 2, 4, and 8 weeks showed no significant differences from control groups in results of histological analysis, TUNEL, and CCK-8 assays.ConclusionsA single injection of hydrogel into the anterior chamber is effective for modeling COH, can respond to most commonly used hypotensive drugs, and is non-toxic to the eyes.

A novel rat model of ocular hypertension by a single intracameral injection of cross-linked hyaluronic acid hydrogel (Healaflow® ).

To create a novel animal model of ocular hypertension via the intracameral injection of Healaflow. Unilateral chronic ocular hypertension model of rats was created by the intracameral injection of 3μL Healaflow. The IOP of subjects was monitored. Dynamic morphological changes were evaluated by fundus imaging, OCT and histological examination. Visual function changes were measured by electroretinography and flash visual-evoked potentials. 24 and 72hours after injection, the retinal tissue was collected for transcriptome analysis. The expression levels of related genes and proteins were further evaluated by qRT-PCR and Western blotting. The IOP peaked within 1day after a single intracameral injection of Healaflow and then decreased gradually within 4weeks. Furthermore, the persistently degenerating retinal ganglion cells occurred within 4weeks. The visual function of these rats was also impaired. The results of transcriptome analyses, qRT-PCR and Western blotting showed that the expression levels of B2m, Ikzf1 and Stat3 were up-regulated, while the expression levels of Six3 and Prss56 were down-regulated in the retinal tissues. Intracameral injection of Healaflow is an effective approach to induce glaucomatous neurodegeneration in rats. Six3 and Prss56 may be involved in the pathogenesis of progressive glaucomatous damage.

Nonclinical Pharmacokinetic and Pharmacodynamic Assessment of Bimatoprost Following a Single Intracameral Injection of Sustained-Release Implants.

PurposeTo assess the pharmacokinetic (PK)/pharmacodynamic (PD) relationship following intracameral Bimatoprost sustained-release (SR) implants (8, 15, 30, and 60 µg) in dogs to determine the optimal investigative dose in humans.MethodsForty-four male normotensive beagle dogs were assigned to 1 of 8 groups receiving 8-, 15-, 30-, and 60-µg implants (PD assessment [n = 8/group, 4 groups]; PK assessment [n = 3/group, 4 groups]). Intraocular pressure (IOP) in PD animals and aqueous humor/blood concentrations of bimatoprost and its acid in PK animals were assessed. PK/PD correlation analysis was performed using steady-state data. Residual implants were recovered to assess polymer degradation.ResultsDose-dependent IOP lowering was observed for all dose groups for at least 3 months postdose. Blood concentrations of bimatoprost and bimatoprost acid were below the limit of quantification (<0.25 ng/mL), whereas dose-dependent concentration-time profiles were observed in the aqueous humor. At steady state, observed and predicted correlation between aqueous humor drug concentration and IOP lowering was similar and translatable to findings in humans following topical bimatoprost eyedrop administration. Implants at all doses were well tolerated and polymer degradation was apparent.ConclusionsDose-dependent IOP lowering with Bimatoprost SR was maintained for at least 3 months in dogs, and the implants were well tolerated. The established PK/PD relationship appears to translate to humans. Doses between 8 and 15 µg appear to provide the best benefit/risk profile for clinical development of the implants.Translational RelevanceThe close PK/PD relationship between dog and human helps inform which bimatoprost dose should be investigated in clinical studies.

Induction of significant intraocular pressure diurnal fluctuation in rats using a modified technique of microbead occlusion.

To investigate the effect of microbead iridocorneal angle occlusion on intraocular pressure (IOP) diurnal fluctuation in rat eyes. Male Dark Agouti (DA) rats, 8-10 week old, were each given a single intracameral injection of microbeads, followed by injection of dispersive viscoelastic solution. The right eye served as the experimental eye, while the left eye served as the control. IOP was measured twice daily postoperatively for 3wk and compared between groups. At the end of 3wk, the rats were sacrificed and the eyes were harvested for histological analysis and retinal ganglion cell (RGC) counting. After microbead injection, experimental eyes had significantly higher dark time IOP than controls from the second week to the third week [2nd week: 22.92±1.631 mm Hg (n=5) vs 17.35±0.751 mm Hg (n=5); 3rd week: 23.59±1.494 mm Hg vs 17.73±0.592 mm Hg (n=5)], while light time IOP was comparable between groups. The fluctuation levels of IOP in the experimental eyes were 7.21±0.398 mm Hg (n=5), 9.50±1.017 mm Hg (n=5) and 10.66±0.894 mm Hg (n=5) from the first week to the third week after injection. Comparatively, they were significantly lower in the control eyes, which were 4.69±0.323 mm Hg (n=5), 2.84±1.122 mm Hg (n=5) and 4.98±0.603 mm Hg (n=5) respectively. However, at the end of 3wk, the larger fluctuations in IOP in the experimental eyes was not associated with a significant loss of RGCs. Microbead occlusion exacerbates diurnal IOP fluctuation in rats. This reported model may serve as a method of investigating the pathological effects of IOP fluctuation. A longer observation period, or repeated injections, may be needed to observe a significant change in RGC density.

Single stranded adeno-associated virus achieves efficient gene transfer to anterior segment in the mouse eye.

Adeno-associated viruses (AAVs) are used extensively as a gene delivery vehicle for retinal gene therapy, yet its ability to target the anterior segment of the eye, critical to unlocking therapeutic opportunities, is less characterized. Previously, self-complimentary (sc) AAV was shown to be necessary for transduction of the cornea and trabecular meshwork (TM), limiting the size of the gene transfer cassette, likely due to a block in second strand synthesis thought to be required for functional transduction. Here, we evaluated several AAV capsids in a single stranded (ss) genome conformation for their ability to overcome the need for scAAV for targeting corneal endothelium and TM. AAV2, 8, and a recently synthetically developed AAV called Anc80L65 were evaluated in vitro and in vivo by intracameral injection in mice. Results show that although scAAV2 demonstrated superior infectivity in vitro including Human Trabecular meshwork (HTM) immortalized cell lines; Anc80L65 transduced following a single intracameral injection efficiently all components of the mouse anterior segment, including the TM, corneal stroma, and endothelial cells. These results suggest that Anc80L65 is able to overcome the requirement for scAAV genomes to enable TM and corneal targeting, expanding the potential experimental and therapeutic use of AAV gene transfer in the anterior segment of the eye.

Ocular tolerance in rabbits after intracameral administration of a fixed combination of tropicamide, phenylephrine, and lidocaine with and without rinsing

To evaluate the safety and tolerability of a single intracameral administration of a combined mydriatic (tropicamide and phenylephrine) and anesthetic (lidocaine) formulation (Mydrane) with or without rinsing. Iris Pharma, La Gaude, France. Experimental study. Sixty pigmented rabbits received 100μL or 200μL of the combination product or a placebo (sodium chloride 0.9%) by intracameralinjection. For the combination product, separate groups were included with and without rinsing after administration. From day 1day to day 7, assessments included general clinical and ocular observations,pupil diameter measurements, corneal assessments, confocal microscopy, and electroretinography (ERG). Necropsy examinationswere performed at study completion at day8. Rapid mydriasis, stable24minutes after injection and returning to baseline levels by day 1, was induced in all groups that received the combination mydriatic and anesthetic drug. Rinsing had no effect. The combination product induced no adverse effects on the anterior or posterior segment of the eye (ie, no increased corneal thickness and endothelial cell loss, no abnormalities in ERG). Slitlamp examination showed slightly increased anterior chamber inflammation with rinsing in both the study group and placebo group. This observation was not confirmed by aqueous flare examination. No toxic effects of the products were found on histological evaluation. The combination mydriatic and anesthetic drug administered to pigmented rabbits as a single intracameral injection at volumes of 100μL and 200μL was well tolerated with no ocular adverse effects and no effect on the corneal endothelium.

Optic neuropathy and increased retinal glial fibrillary acidic protein due to microbead-induced ocular hypertension in the rabbit.

To characterize whether a glaucoma model with chronic elevation of the intraocular pressure (IOP) was able to be induced by anterior chamber injection of microbeads in rabbits. In order to screen the optimal dose of microbead injection, IOP was measured every 3d for 4wk using handheld applanation tonometer after a single intracameral injection of 10 µL, 25 µL, 50 µL or 100 µL microbeads (5×106 beads/mL; n=6/group) in New Zealand White rabbits. To prolong IOP elevation, two intracameral injections of 50 µL microbeads or phosphate buffer saline (PBS) were made respectively at days 0 and 21 (n=24/group). The fellow eye was not treated. At 5wk after the second injection of microbeads or PBS, bright-field microscopy and transmission electron microscopy (TEM) were used to assess the changes in the retina. The expression of glial fibrillary acidic protein (GFAP) in the retina was evaluated by immunofluorescence, quantitative real-time polymerase chain reaction and Western blot at 5wk after the second injection of microbeads. Following a single intracameral injection of 10 µL, 25 µL, 50 µL or 100 µL microbead, IOP levels showed a gradual increase and a later decrease over a 4wk period after a single injection of microbead into the anterior chamber of rabbits. A peak IOP was observed at day 15 after injection. No significant difference in peak value of IOP was found between 10 µL and 25 µL groups (17.13±1.25 mm Hg vs 17.63±0.74 mm Hg; P=0.346). The peak value of IOP from 50 µL group (23.25±1.16 mm Hg) was significantly higher than 10 µL and 25 µL groups (all P<0.05). Administration of 100 µL microbead solution (23.00±0.93 mm Hg) did not lead to a significant increase in IOP compared to the 50 µL group (P=0.64). A prolonged elevated IOP duration up to 8wk was achieved by administering two injections of 50 µL microbeads (20.48±1.21 mm Hg vs 13.60±0.90 mm Hg in PBS-injected group; P<0.05). The bright-field and TEM were used to assess the changes of retinal ganglion cells (RGCs). Compared with PBS-injected group, the extended IOP elevation was associated with the degeneration of optic nerve, the reduction of RGC axons (47.16%, P<0.05) and the increased GFAP expression in the retina (4.74±1.10 vs 1.00±0.46, P<0.05). Two injections of microbeads into the ocular anterior chamber of rabbits lead to a prolonged IOP elevation which results in structural abnormality as well as loss in RGCs and their axons without observable ocular structural damage or inflammatory response. We have therefore established a novel and practical model of experimental glaucoma in rabbits.

Ocular tolerance in rabbits of intracameral administration of MYDRANE, a fixed combination of tropicamide, phenylephrine, and lidocaine for cataract surgery

PurposePreclinical studies have been done to evaluate the ocular tolerance of MYDRANE (tropicamide 0.02%, phenylephrine 0.31% and lidocaïne 1%) after a single intracameral (IC) injection in rabbits.Methods60 pigmented rabbits were divided in 3 groups of 10 animals by injection volume (100 or 200 μl of MYDRANE or 0.9% NaCl). One group injected with MYDRANE and the group injected with NaCl had their anterior chamber rinsed with NaCl, 1 min after IC injection. This wash was not performed for the second MYDRANE‐group in order to extend the presence of the product in the anterior chamber well beyond what is expected in clinical use. Animals were held in observation for 7 days. The following evaluations were performed: general tolerance, slit‐lamp observations, laser flare, cornea thickness, cell density of the corneal endothelium, electroretinography. After euthanasia, eyes were sampled for histology.ResultsMYDRANE was very well tolerated with or without rinsing. Very slight conjunctival effects were observed for 3 or 4 animals from groups after 200 μl‐injection and very slight corneal vascularization was observed for one animal from NaCl‐group. Inflammation in the anterior chamber was mainly observed in the eyes who were rinsed and this inflammation decreased in the course of time. Iris, fundus and lens were normal, except for 4 animals in whom a needle impact was observed on the lens, probably due to rinsing. In addition, whatever the group, cornea thickness, endothelium cell density, electroretinography parameters and ocular histology were not affected.ConclusionsFollowing IC injection of 100 or 200 μl of MYDRANE, which is the maximal injectable volume in rabbits, the ocular tolerance of MYDRANE was very good for 7 days and the ocular effects observed were attributed mainly to the method of injection and to the rinsing.

Pediatric Cataract Surgery and Intraocular Lens Implantation with and without Intracameral Triamcinolone Acetonide

Purpose: To evaluate the safety and efficacy of a single intracameral injection of triamcinolone acetonide in controlling postoperative ocular inflammation and improving the outcome of pediatric cataract surgery with intraocular lens implantation. Setting: Prospective interventional comparative Quasi study. Patients and methods: The study was performed on eyes of children between 6-12 years old having significant cataract and subjected to cataract extraction with primary IOL implantation. Patients were divided into two almost equal age and sex matched groups. The study group included eyes that received intracameral injection of 4 mg/0.13 ml of preservative-free triamcinolone acetonide at the end of surgery while the control group included eyes that did not receive intracameral injection of triamcinolone acetonide. Postoperative examinations were done on day 1 then weekly for 1 month, and monthly for another 2 months. Primary outcome measures included any sign of anterior segment inflammation, while secondary outcome measures included best corrected visual acuity, intraocular pressure and any reported complication caused by intracameral triamcinolone acetonide. Results: The study included 42 eyes (35 patients); 21 eyes in each group. Postoperative inflammatory membrane was statistically significant higher in the control group than in the study group (P=0.018). The mean duration of using topical steroids in the study group (17.2 ± 4.1 days) was statistically significant less than its mean duration (28.3 ± 3.4 days) in the control group (P<0.05). No statistically significant differences were detected between pre and postoperative intraocular pressure in each group and in between both groups. No significant complications related to intracameral triamcinolone acetonide were reported. Conclusion: A single intracameral injection of 4 mg preservative free triamcinolone acetonide at the end of uncomplicated pediatric cataract surgery could be an effective and safe adjunct to postoperative topical steroids in controlling postoperative ocular inflammation.

Effect of intracameral triamcinolone acetonide on postoperative intraocular inflammation in pediatric traumatic cataract.

To study the effect of a single intracameral injection of triamcinolone acetonide at the end of pediatric traumatic cataract surgery on postoperative inflammation. This prospective interventional study comprised 40 eyes of children with unilateral traumatic cataract. Patients were classified into 2 groups: the study group, in which intraoperative intracameral triamcinolone acetonide (2 mg) was used at the end of surgery; and a control group, which did not receive intracameral triamcinolone acetonide. The study group included 20 eyes of patients with an average age of 6 ± 2.8 years. The control group included 20 eyes of patients with an average age of 6 ± 2.1 years. No serious intraoperative complications occurred. In the immediate postoperative period, 3 eyes of the control group (15.0%) developed a fibrinous anterior chamber reaction. None of the study group eyes developed a similar reaction. There were no cases of endophthalmitis. In addition, 3 eyes (15%) in the control group had obscuration of the visual axis at the last follow-up. This complication was not encountered in the study group. Posterior synechiae and cellular deposits were observed in 4 eyes (20%) in the study group and 8 eyes (40%) in the control group at 1 month and at the last follow-up. The use of intracameral triamcinolone decreased anterior segment inflammation postoperatively in children who had surgery for traumatic cataract.

Intracameral bevacizumab as an adjunct to trabeculectomy: a 1-year prospective, randomised study

AimsTo investigate the efficacy and safety of a single intracameral bevacizumab injection to improve the outcome of trabeculectomy.MethodsA 12-month, prospective, randomised, double-masked, placebo-controlled trial. Patients with medically uncontrolled open-angle glaucoma...

Ocular biocompatibility and tolerance study of biodegradable polymeric micelles in the rabbit eye

Polymeric nanoparticles have been developed to improve the bioavailability of drugs applied in ocular drug delivery. However, there are few information on ocular biocompatibility of polymeric nanoparticles applied topically onto the eye. In this paper, the ocular biocompatibility and tolerance of methoxy poly(ethylene glycol)–poly(ɛ-caprolactone) (MPEG–PCL) micelles (∼50nm) were investigated in rabbit eyes after a single intracameral and intravitreal injections. In vitro cytotoxicity assays showed that MPEG–PCL micelles had no apparent cytotoxicity against human corneal epithelial cells (HCEC), human lens epithelial cells (HLEC), and retinal pigment epithelial cells (RPE cells) at micelle concentrations of 0–2mg/mL. After a single intracameral injection of 0.2mL MPEG–PCL micelles (200mg/mL) into rabbit eyes, MPEG–PCL micelles were slowly removed from aqueous humor in a period of 14 days, while the intraocular pressure (IOP) was maintained at nearly the same level for 15 days. Three days after intracameral injection, dual staining of corneal endothelium showed that the endothelial cells were nearly regular hexagon-shape with well-defined organization, similar to normal endothelial cells. Hematoxylin and eosin staining indicated that there was absence of any obvious changes in microstructure of the corneal tissue and retina after a single intracameral and intravitreal injection of 0.2mL MPEG–PCL micelles (100mg/mL, 150mg/mL, and 200mg/mL). This study provides valuable information (safety and biocompatibility) for biomedical researchers to develop MPEG–PCL micelles as candidates for ocular drug delivery.

Ocular Pharmacokinetics, Safety and Efficacy of Intracameral Moxifloxacin 0.5% Solution in a Rabbit Model

Purpose: This study was carried out to determine the ocular pharmacokinetics, efficacy and potential endothelial toxicity of moxifloxacin (MF) after a single intracameral bolus injection of 500 µg/0.1 ml in a rabbit model.Materials and methods: Forty-eight eyes of 24 New Zealand White Rabbits were separated into six groups, each including four rabbits. 0.1 ml of 0.5% intracameral moxifloxacin (500 µg) injection was injected to the right eyes and 0.1 ml of balanced salt solution to the left eyes (control). Aqueous humor (AH) and vitreous samples were collected at the 0.5th, 1st, 3rd, 6th, 12th and 24th hours from both eyes of group 1, 2, 3, 4, 5 and 6, respectively. MF concentrations were determined by high performance liquid chromatography. These were compared with the minimum inhibitory concentrations (MIC) and mutant prevention concentrations (MPC) for frequent endophthalmitis pathogens. Electron and light microscopical evaluation of the corneas were performed.Results: Moxifloxacin reaches higher concentration than the MIC of all common endophthalmitis pathogens in the AH and exceeds the mutant prevention concentration levels for Streptococcus pneumonia, Streptococcus viridans, flouroquinolone susceptible Coagulase-negative staphylococcus and flouroquinolone susceptible Staphylococcus aureus for 6 h. The half-life of moxifloxacin in the AH was 2.2 h. Electron and light microscopic evaluation revealed no noticeable sign of toxicity.Conclusions: Peroperative intracameral moxifloxacin injection for endophthalmitis prophylaxis is a safe and effective method in uncomplicated phacoemulsification surgery.

PHARMACOKINETIC COMPARISON OF KETOROLAC AFTER INTRACAMERAL, INTRAVITREAL, AND SUPRACHOROIDAL ADMINISTRATION IN RABBITS

To investigate the concentrations and pharmacokinetics of ketorolac in the rabbits by three different routes of administrations: a single intracameral, intravitreal, and suprachoroidal injection. Fifty-four New Zealand white rabbits received ketorolac (250 μg/0.05 mL) in one eye by a single intracameral injection (group A, n = 18), single intravitreal injection (group B, n = 18), and single suprachoroidal injection (group C, n = 18). Drug concentrations in the vitreous, retina-choroid (RC), and plasma were determined by the methods of high-performance liquid chromatography at 0.5, 1, 2, 4, 8, and 24 hours after injection. The concentrations in the opposite eyes were also investigated. The mean maximum concentrations (Cmax) of ketorolac in the vitreous and RC were 0.378 ± 0.19 μg/mL and 3.15 ± 0.49 μg/g (at 0.5 hours), respectively, in group A; 156.2 ± 20.74 μg/mL (at 0.5 hours) and 208.0 ± 21.67 μg/g (at 1 hours), respectively, in group B; and 0.873 ± 0.34 μg/mL and 56.71 ± 22.64 μg/g (at 0.5 hours), respectively, in group C. In the RC, the area under the curve (AUC0-t) in group B (866.1 ± 52.67 μg/g·h) was higher (P < 0.01) than that in group C (77.10 ± 25.90 μg/g·h). The elimination half-life (t1/2) in group B (3.09 hours) was longer (P < 0.01) than that in group C (1.19 hours). In the control eyes, a drug level below 2 μg/g was detected in the RC in group C. Plasma concentrations were below 0.4 μg/mL in all 3 groups. Ketorolac was detectable in the RC till 24 hours after the intravitreal injection and 8 hours after the suprachoroidal injection. Intravitreal injection of ketorolac produced higher intraocular drug concentrations for a longer period compared with the other two routes. Suprachoroidal injection of ketorolac could reach an effective drug level in the RC with short half-lives and low drug levels in the vitreous. The plasma drug concentrations were low by all three routes.