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Purpose: Drug delivery to treat diseases of the posterior segment of the eye, such as choroidal neovascularization and its complications, is hampered by poor intraocular penetration and rapid elimination of the drug from the eye. The purpose of this study was to investigate the feasibility and tolerance of suprachoroidal injections of poly(ortho ester) (POE), a bioerodible and biocompatible polymer, as a biomaterial potentially useful for development of sustained drug delivery systems., Methods: After tunnelization of the sclera, different formulations based on POE were injected (100 microL) into the suprachoroidal space of pigmented rabbits and compared with 1% sodium hyaluronate. Follow-up consisted of fundus observations, echography, fluorescein angiography, and histologic analysis over 3 weeks., Results: After injection, POE spread in the suprachoroidal space at the posterior pole. It was well tolerated and progressively disappeared from the site of injection without sequelae. No bleeding or retinal detachment occurred. Echographic pictures showed that the material was present in the suprachoroidal space for 3 weeks. Angiography revealed minor pigment irregularities at the site of injection, but no retinal edema or necrosis. Histology showed that POE was well tolerated in the choroid., Conclusions: POE suprachoroidal injections, an easy, controllable, and reproducible procedure, were well tolerated in the rabbit eye. POE appears to be a promising biomaterial to deliver drugs focally to the choroid and the retina.

Purpose: Pharmacologic modulation of wound healing after glaucoma filtering surgery remains a major clinical challenge in ophthalmology. Poly(ortho ester) (POE) is a bioerodible and biocompatible viscous polymer potentially useful as a sustained drug delivery system that allows the frequency of intraocular injections to be reduced. The purpose of this study was to determine the efficacy of POE containing a precise amount of 5-fluorouracil (5-FU) in an experimental model of filtering surgery in the rabbit., Methods: Trabeculectomy was performed in pigmented rabbit eyes. An ointmentlike formulation of POE containing 1% wt/wt 5-FU was injected subconjunctivally at the site of surgery, during the procedure. Intraocular pressure (IOP), bleb persistence, and ocular inflammatory reaction were monitored until postoperative day 30. Quantitative analysis of 5-FU was performed in the anterior chamber. Histologic analysis was used to assess the appearance of the filtering fistula and the polymer's biocompatibility., Results: The decrease in IOP from baseline and the persistence of the filtering bleb were significantly more marked in the 5-FU-treated eyes during postoperative days 9 through 28. Corneal toxicity triggered by 5-FU was significantly lower in the group that received 5-FU in POE compared with a 5-FU tamponade. Histopathologic evaluation showed that POE was well tolerated, and no fibrosis occurred in eyes treated with POE containing 5-FU., Conclusions: In this rabbit model of trabeculectomy, the formulation based on POE and containing a precise amount of 5-FU reduced IOP and prolonged bleb persistence in a way similar to the conventional method of a 5-FU tamponade, while significantly reducing 5-FU toxicity.

In the anterior segment of the eye, fibrin clots must be rapidly resorbed to prevent further fibrosis and scarring. The aqueous humor of patients undergoing cataract surgery was analyzed for the presence of components of the fibrinolytic cascade. In 30 patients, aqueous humor and plasma were compared for their content of urokinase-type plasminogen activator (uPA), tissue-type plasminogen activator (tPA), plasminogen activators inhibitors (PAIs), plasminogen, and total proteins. With gel electrophoresis and zymographic assays of serial dilutions of plasma and aqueous humor, all these components were found to be present at lower concentrations in aqueous humor than in plasma. For total proteins, the aqueous/plasma ratio was approximately 0.003, and for plasminogen it was 0.001. Interestingly, the aqueous/plasma ratio for uPA was not as low and varied from 0.01 to 0.03. A significant proportion of the uPA in aqueous humor was present in the two-chain active form. In addition to uPA, aqueous humor contained lower levels of tPA, but no detectable levels of reactive plasminogen activators inhibitors (PAIs). The presence of a relatively high concentration of active uPA shows that the proteolytic balance of the aqueous humor in the anterior chamber of the eye is shifted toward fibrinolysis.

Intravitreal injection of aminoglycoside antibiotics is known to induce morphological changes in the retinal pigment epithelium (RPE) resembling a lipidosis. The RPE of netilmicin-treated rabbits displays a dose-related increase in autofluorescence compared to untreated controls. Netilmicin produces an accumulation of membrane-limited osmiophilic lamellated inclusions in the pigment epithelial cell. These inclusions measure from 1 to 3 microns in diameter, and have acid hydrolase activity demonstrated by cytidine monophosphate cytochemistry. These findings suggest that netilmicin-induced inclusions are residual bodies and that the accumulation of these residual bodies is responsible for the observed cellular lipidosis.