ABSTRACT
Gene transfer provides an exciting new approach for the treatment of retinal and choroidal diseases. Two areas of concern are the potential for vector-related toxicity and uncertainties associated with prolonged transgene expression. One way to address these concerns for transfer of genes encoding secreted proteins is to transduce cells on the outside of the eye, provided the gene product can gain access to the eye and have the desired effect. In this study, we investigated the feasibility of this approach. Periocular injection of an adenoviral vector encoding beta-galactosidase (AdLacZ.10) resulted in LacZ-stained cells throughout the orbit and around the eye. Compared to periocular injection of 5 x 10(9) particles of control vector, periocular injection of 5 x 10(9) or 1 x 10(9) particles of an adenoviral vector expressing pigment epithelium-derived factor (PEDF) regulated by a CMV promoter (AdPEDF.11) resulted in significantly elevated intraocular levels of PEDF and suppression of choroidal neovascularization. Periocularly injected recombinant PEDF was also found to diffuse through the sclera into the eye. Although similar experiments are needed in an animal with a human-sized eye, these data suggest that periocular gene transfer deserves consideration for the treatment of choroidal diseases.
Subject(s)
Adenoviridae/genetics , Choroidal Neovascularization/therapy , Eye Proteins , Genetic Therapy/methods , Genetic Vectors/administration & dosage , Nerve Growth Factors , Proteins/genetics , Serpins/genetics , Animals , Eye/metabolism , Gene Expression , Injections , Mice , Mice, Inbred C57BL , Models, Animal , Orbit/metabolism , Proteins/metabolism , Serpins/metabolism , beta-Galactosidase/genetics , beta-Galactosidase/metabolismABSTRACT
PURPOSE: To report the management and outcome of late-onset traumatic dislocation of laser in situ keratomileusis (LASIK) flaps. DESIGN: Retrospective, observational case series. PARTICIPANTS: Four patients with late-onset LASIK flap dislocation occurring after mechanical trauma at various intervals (10 days-2 months) after the procedure. INTERVENTION: In all cases of postoperative traumatic LASIK flap dislocation, the flap was refloated with scraping and irrigation of the underlying stromal bed within 12 hours of the injury. A bandage contact lens was placed, and a regimen including topical antibiotics and corticosteroids was instituted in all cases. MAIN OUTCOME MEASURES: Best spectacle-corrected visual acuity and complications associated with the surgery were monitored. RESULTS: Postoperative follow-up ranged from 4 to 21 months. Nonprogressive epithelial ingrowth was noted in one patient and diffuse lamellar keratitis developed in another patient. All patients recovered pretrauma spectacle-corrected visual acuity. CONCLUSIONS: Corneal LASIK flaps are prone to mechanical dislocation as late as 2 months after the procedure. Appropriate management results in recovery of optimal visual outcomes.
