PURPOSE. We assessed the in vivo release profile of bevacizumab from and biocompatibility of poly(ethylene glycol)-poly-(serinol hexamethylene urethane), or ESHU, a thermoresponsive hydrogel administered intravitreally for drug delivery.METHODS. The technical feasibility of injection was assessed quantitatively via mechanical testing. For in vivo studies, New Zealand White rabbit eyes were injected intravitreally with 0.05 mL of either: ESHU dissolved in 25 mg/mL bevacizumab, ESHU dissolved in PBS, or 25 mg/mL bevacizumab. Clinical examination included IOP measurements and examination with indirect ophthalmoscopy for signs of inflammation. Additionally, eyes were examined histologically following euthanasia. To quantify bevacizumab release, aqueous humor samples were obtained via anterior chamber paracentesis and ELISA was used to determine the concentration of drug weekly. In vitro cytotoxicity testing also was performed using bovine corneal endothelial cells. RESULTS.The ESHU was injected easily through a 31-gauge needle, was well tolerated in vivo, and caused minimal cell death in vitro when compared to other common materials, such as silicone oil. The long-term presence of the gel did not affect IOP, and there was no evidence of inflammation histologically or through indirect observation. The ESHU sustained the release of bevacizumab for over 9 weeks and maintained a drug concentration that averaged 4.7 times higher than eyes receiving bolus bevacizumab injections.CONCLUSIONS. To our knowledge, this is the first report demonstrating sustained bevacizumab release in vivo from an intravitreally injected hydrogel formulation, suggesting that this delivery system may be a promising candidate for ocular drug delivery.Keywords: thermally responsive hydrogel, ocular drug delivery, sustained release, biocompatibility, injectable gel C horoidal neovascularization (CNV) is the hallmark of many blinding disorders, most notably wet age-related macular degeneration (AMD) and diabetic retinopathy. It is characterized by pathologic blood vessel growth, which originates in the choroid and progresses through the Bruch's membrane into the subretinal space.1 These vessels are fragile and permeable, causing hemorrhage, retinal detachment, scarring, and ultimately, loss of central vision. Elevated levels of VEGF is a central cause of CNV.2-4 Thus, intravitreal injection of anti-VEGF medications, such as bevacizumab (Avastin) or ranibizumab (Lucentis), has emerged as a leading treatment strategy. [5][6][7] The efficacy of these drugs, however, is limited severely by rapid clearance from the eye; their half-lives are on the order of 7 days. 8,9 This necessitates frequent injections, imposing a significant burden on patients and increasing healthcare costs as well as procedure-related complications, such as endophthalmitis, retinal detachment, cataract, and uveitis.10-13 Therefore, a delivery system that extends the presence of intravitreal drugs in the eye is highly desirable for reducing injection frequency and adverse effects, w...
The goal of radiotherapy is to produce maximal damage to the tumor yet at the same time produce minimal damage to the surrounding tissues. Here we discuss anterior chamber complications of radiotherapy. These can vary from ocular surface irritation to blindness and can be subdivided into acute (<4 weeks) and chronic (>4 weeks). Prevention and management is also discussed and subdivided by affected tissue.
A 22-year-old African American female with neurofibromatosis type 1 and multifocal conjunctival melanoma with scleral invasion. The lesion was detected during pregnancy, and after early induction of childbirth, staging by sentinel lymph node biopsy and imaging studies were performed. Systemic evaluation was negative, and the patient was treated with excisional biopsy and cryotherapy. The recurrent multifocal melanoma with scleral extension was treated with brachytherapy by a 2-stage procedure. Follow-up at 2 years reveals the absence of recurrence and 20/25 visual acuity.
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