Evaluation of Sustained Release of PLC-Loaded Prednisolone Acetate Microfilm on Postoperative Inflammation in an Experimental Model of Glaucoma Filtration Surgery

Ang, Marcus; Peng, Yan; Ma, Zhen; Foo, Selin; Venkatraman, Subbu S.; Wong, Tina

doi:10.3109/02713683.2011.627489

Cited by 17 publications

(16 citation statements)

References 20 publications

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“…This pilot study further supports the potential usefulness of surgical implantation of sustained-released drug implants within the subconjunctival space to treat ocular inflammation [6], [7]. The subconjunctival location provides a surgically accessible place for insertion and if necessary, easily accessed for removal.…”

Section: Discussionsupporting

confidence: 67%

“…Prednisolone acetate achieves the highest aqueous concentration within 2 hours and maintains higher levels for 24 hours, compared to dexamethasone and other commonly used corticosteroids[5]. We have demonstrated in previous studies the anti-fibrotic and anti-inflammatory properties of a subconjunctivally implanted prednisolone acetate (PA)-preloaded microfilm in the rabbit model of subconjunctival scarring following glaucoma filtration surgery [6] and rat keratoplasty model[7]. Our in vivo studies have shown that PA-loaded poly[d,l-lactide-co-ε-caprolactone] (PLC) microfilms display good biocompatibility, feasibility, and desirable sustained drug release profiles, maintaining high anterior chamber PA levels at 76.7±5.9, 70.3±2.3, and 42.7±4.1 ng/mL at 2, 4, and 12 weeks, respectively[8], [9].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of a Prednisolone Acetate-Loaded Subconjunctival Implant for the Treatment of Recurrent Uveitis in a Rabbit Model

Ang

Wong

et al. 2014

PLoS ONE

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AimTo assess the efficacy of a biodegradable, prednisolone acetate implant in a rabbit uveitis model.MethodsRandomized, controlled study of biodegradable microfilms preloaded with prednisolone acetate (PA) in a rabbit uveitis model. Experimental uveitis was induced by unilateral intravitreal injection of Mycobacterium tuberculosis H37Ra antigen (50 ug; 1 ug/uL) in preimmunized rabbits. PA-loaded poly[d,l-lactide-co-ε-caprolactone] (PLC) microfilms (n = 10) and blank microfilms (n = 6) were implanted subconjunctivally. An estimate of PA release in vivo was calculated from measured residual PA amounts in microfilms after the rabbits were sacrificed. The eyes were clinically monitored for ocular inflammation for 28 days. Histopathological examination of the enucleated eyes was performed at the end of the study period.Results In vitro studies revealed that sandwich PA-loaded microfilm formulations exhibited higher release kinetic compared to homogenous PA-loaded microfilms. The 60–40–60% microfilm released an average of 0.034 mg/day of PA over the period of 60 days in vitro; and we found that approximately 0.12 mg/day PA was released in vivo. Animals implanted with the PA-loaded microfilms exhibited significantly lowered median inflammatory scores when compared against the control group in this model for recurrent uveitis (P<0.001). The implants were clinically well tolerated by all the animals. Histology results showed no significant scarring or inflammation around the PA-loaded microfilms.ConclusionOur pilot study demonstrated that a subconjunctival PA-loaded implant is effective in suppressing inflammation in the rabbit model of uveitis, by providing therapeutic levels of PA that attenuated the inflammatory response even after a rechallenge. Longer term studies are now needed to establish the therapeutic potential of such a delivery system for treatment of ocular inflammation.

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Section: Discussionsupporting

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Evaluation of a Prednisolone Acetate-Loaded Subconjunctival Implant for the Treatment of Recurrent Uveitis in a Rabbit Model

Ang

Wong

et al. 2014

PLoS ONE

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“…A second explanation is that rabbits did not have increased IOP because they did not develop glaucoma in this study [38]. These results are consistent with data suggesting that IOP may not correlate with scarring in a subconjunctival wound healing animal model [29,38,39]. …”

Section: Discussionsupporting

confidence: 80%

Tissue Response to Implanted Ahmed Glaucoma Valve with Adjunctive Amniotic Membrane in Rabbit Eyes

Lee¹,

Park²,

Kim³

et al. 2014

Ophthalmic Res

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Aims: To investigate the histopathology of the fibrous capsule around Ahmed glaucoma valves (AGVs) implanted with adjunctive amniotic membranes in rabbits. Methods: AGV implantation with or without adjunctive amniotic membrane was performed in a single eye of 20 albino rabbits. The upper surface of the AGV body was covered with amniotic membrane in the study group. After 2 months, histology was used to compare the thickness and characteristics of the fibrous capsule, transdifferentiation of myofibroblasts, and density of blood vessels and leukocytes between the study and control groups. Results: The fibrous capsule along the roof of the bleb was composed of compact collagen fibers with minimal vascularization in the control group. In contrast, in the study group, the fibrous capsule was looser and had a more disorganized collagen architecture. The thickness of the fibrous capsule and the myofibroblast layer was significantly thinner in the study group than in the control group (p < 0.001). The number of CD31-positive blood vessels did not differ between the two groups (p = 0.235). CD45-positive inflammatory cells were more frequently observed in the study group than the control group (p = 0.001). The groups did not differ in the thickness of the fibrous capsule or myofibroblast layer, or the density of blood vessels and leukocytes along the floor of the bleb. Conclusions: Adjunctive amniotic membranes could reduce the risk of encapsulation and aqueous outflow resistance by altering the tissue response to implanted AGVs and subsequent formation of a loose thin capsule.

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“…The ideal dose and mode of delivery have yet to be determined. Microfilms are being developed to carry various types of ocular medications and may be a more standardized method to deliver steroids at the time of surgery 23,24. More study is needed to evaluate the ideal delivery of adjunctive steroids during AGV implantation to prevent encapsulation with its attendant poor hydraulic conductivity of aqueous humor.…”

Section: Discussionmentioning

confidence: 99%

Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide

Turalba

Pasquale²

2014

OPTH

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ObjectiveTo evaluate intraoperative subtenon triamcinolone acetonide (TA) as an adjunct to Ahmed glaucoma valve (AGV) implantation.DesignRetrospective comparative case series.ParticipantsForty-two consecutive cases of uncontrolled glaucoma undergoing AGV implantation: 19 eyes receiving intraoperative subtenon TA and 23 eyes that did not receive TA.MethodsA retrospective chart review was performed on consecutive pseudophakic adult patients with uncontrolled glaucoma undergoing AGV with and without intraoperative subtenon TA injection by a single surgeon. Clinical data were collected from 42 eyes and analyzed for the first 6 months after surgery.Main outcome measuresPrimary outcomes included intraocular pressure (IOP) and number of glaucoma medications prior to and after AGV implantation. The hypertensive phase (HP) was defined as an IOP measurement of greater than 21 mmHg (with or without medications) during the 6-month postoperative period that was not a result of tube obstruction, retraction, or malfunction. Postoperative complications and visual acuity were analyzed as secondary outcome measures.ResultsFive out of 19 (26%) TA cases and 12 out of 23 (52%) non-TA cases developed the HP (P=0.027). Mean IOP (14.2±4.6 in TA cases versus [vs] 14.7±5.0 mmHg in non-TA cases; P=0.78), and number of glaucoma medications needed (1.8±1.3 in TA cases vs 1.6±1.1 in the comparison group; P=0.65) were similar between both groups at 6 months. Although rates of serious complications did not differ between the groups (13% in the TA group vs 16% in the non-TA group), early tube erosion (n=1) and bacterial endophthalmitis (n=1) were noted with TA but not in the non-TA group.ConclusionsSubtenon TA injection during AGV implantation may decrease the occurrence of the HP but does not alter the ultimate IOP outcome and may pose increased risk of serious complications within the first 6 months of surgery.

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Evaluation of Sustained Release of PLC-Loaded Prednisolone Acetate Microfilm on Postoperative Inflammation in an Experimental Model of Glaucoma Filtration Surgery

Abstract: Subconjunctival insertion of a PA-loaded biodegradeable microfilm exhibit sustained release of PA to reduce postoperative inflammation and prolong bleb survival in rabbit GFS.

Cited by 17 publications

References 20 publications

Evaluation of a Prednisolone Acetate-Loaded Subconjunctival Implant for the Treatment of Recurrent Uveitis in a Rabbit Model

Evaluation of a Prednisolone Acetate-Loaded Subconjunctival Implant for the Treatment of Recurrent Uveitis in a Rabbit Model

Tissue Response to Implanted Ahmed Glaucoma Valve with Adjunctive Amniotic Membrane in Rabbit Eyes

Hypertensive phase and early complications after Ahmed glaucoma valve implantation with intraoperative subtenon triamcinolone acetonide

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