Comparison of the ocular distribution of a model oligonucleotide after topical instillation in rabbits of conventional and new dosage forms.

The distribution of a model 16-mer oligothymidylate (pdT16) in several ocular tissues (cornea, conjunctiva, sclera, iris, lens, aqueous and vitreous humors) was determined after instillation in the eye of various dosage forms in a rabbit model. Radiolabelled pdT16 was applied as a simple solution, a 27% poloxamer 407 gel, a suspension of liposomes or liposomes dispersed within a 27% poloxamer 407 gel. pdT16 concentrations were measured in the tissues and fluids by radioactivity counting at time intervals of 10 min, 2 h and 24 h. When the pdT 16 solution was used, the highest concentrations were observed in the conjunctiva and the cornea, while a substantial amount of drug was also present in the sclera. Low concentrations were measured in the iris. Using the same treatment protocol, the two liposomal formulations (liposomes suspension or liposomes dispersed within the poloxamer gel) delivered low amounts of pdT16 to all ocular tissues, and particularly to the conjunctiva and the cornea. The poloxamer gel provided higher tissue concentrations of pdT16 than liposomes but lower than those observed with the solution except 10 min after administration in the iris where the amounts of pdT16 were higher when administered under the gel form. These findings indicate that liposomal forms may not be considered useful delivery systems for topical administration of oligonucleotides in superficial ocular diseases.

Management of delayed massive suprachoroidal hemorrhage: a clinical retrospective study.

Suprachoroidal hemorrhages, both expulsive and delayed non-expulsive, are among the most devastating complications of intraocular surgery. We reviewed the charts of 13 patients with a delayed non-expulsive suprachoroidal hemorrhage (DNSCH) after cataract extraction (3 patients), glaucoma filtering surgery (6 patients), penetrating keratoplasty (3 patients), or vitrectomy (1 patient). All had large hemorrhagic choroidal detachments with nine eyes presenting kissing choroidal detachment, five eyes with associated retinal detachment, and one eye with intravitreous hemorrhage. All patients were treated with systemic corticosteroids before surgery. Eleven eyes underwent anterior drainage sclerotomy, followed by SF6 gas injection in eight eyes, and pars plana vitrectomy with silicon oil tamponade in three eyes. Mean follow-up was 22 months. These procedures gave good anatomical results in eleven cases and good visual results in nine. The results suggest that not all DNSCH need to be drained surgically but that, when surgical drainage is indicated, the use of gas to maintain internal tamponade appears to be beneficial.

[Choroid melanoma associated with 2 other primary malignant lesions. Apropos of a case]. / Mélanome choroïdien associé à deux autres lésions malignes primitives. A propos d'un cas.

A case of choroidal melanoma associated to two other primitive malignancies is reported. The patient, a 65-year-old woman had an amelanotic choroidal tumor of her left eye. In her clinical history was found a previously treated kidney carcinoma eight years ago. A choroidal metastasis was therefore diagnosed. After radiation therapy, an initial regression was observed. Fifteen months later, the tumor grew again. Enucleation was performed, and histopathology concluded on choroidal malignant melanoma. Three years later, a mammal carcinoma was discovered and treated by mammectomy. Her ophthalmologic and general status remained normal until now. Amelanotic choroidal tumors are difficult to diagnose. Regular follow-up can lead to a change in the diagnosis. The occurrence of multiple cancers is still not fully understood.

[Rigid endoscope with Gradient-index lenses. Preliminary studies]. / Endoscope rigide à lentilles de GRIN. Premiers essais.

PURPOSE: Endoscopes for use in ophthalmology can be manufactured in dimensions smaller than 0.89 mm. MATERIALS: Gradient-index lenses that give a higher resolution than fiber bundles can be miniaturized down to 0.35 mm. RESULTS: We used this new endoscope in 6 eyes of 6 patients during anterior segment surgery. Preliminary clinical experience has demonstrated the usefulness and practical application of this new instrument. CONCLUSION: The clear views the instrument provides of the ciliary sulcus and ciliary body behind the iris make it useful in secondary posterior chamber intraocular lens implantation, retroprosthetic membrane behind keratoprosthesis, Molteno valve, and in endolaser photocoagulation.

[Gene therapy in ophthalmology]. / Thérapie génique en ophtalmologie.

Replication-deficient adenoviral vectors have been used to transfer foreign DNA into a variety of cells including post-mitotic cells, in vivo. They constitute the obligatory targets of gene transfer for a number of ocular diseases that have been elucidated at the molecular level and are potential targets for gene therapy. We have therefore analysed the ability of an adenoviral vector to transfer in vivo the E. coli LacZ gene into ocular cells of mice and rabbits. Injection of up to 3 10(7) pfu in mice and 10(9) pfu in rabbits, into the vitreous cavity, the anterior chamber or the peribulbar space did not result in any detectable cytopathic effect and was associated with endocytosis of viral particles in corneal endothelial, photoreceptor, bipolar, ganglionic and oculomotor muscle cells, depending on the administration route. At the viral titer used (3 10(7) or 10(9) pfu), the expression was detected for at least 50 days. These results open new prospects for the treatment of some retinal hereditary disorders and acquired corneal or retinal alterations due to inflammatory disease.

In vivo adenovirus-mediated gene transfer into ocular tissues.

Replication-deficient adenoviruses have been successfully used to transfer foreign DNA into a variety of cells including post-mitotic cells, in vivo. In the eyes, most of the cells are quiescent or slowly dividing. They constitute the obligatory targets of gene transfer for a number of ocular diseases that have been elucidated at the molecular level and are potential targets for gene therapy. We have therefore analysed the ability of an adenovirus vector to transfer in vivo the Escherichia coli lacZ gene into ocular cells of mice. Injection of up to 3 x 10(7) p.f.u. into the vitreous body, the anterior chamber or the peribulbar space, did not result in any detectable cytopathic effect and was associated with endocytosis of viral particles in corneal endothelial, photoreceptor, bipolar, ganglionic and oculomotor muscle cells, depending on the administration route. At the viral titer used (3 x 10(7) p.f.u.), the expression was detected for at least 50 days. These results open new prospects for the treatment of some retinal hereditary disorders and acquired corneal or retinal alterations due to inflammatory disease.

Encapsulation of scleral buckling materials. A study of sixty specimens.

OBJECTIVE: The purpose of the study was to obtain information on the encapsulation of two nonabsorbable biomaterials (silicone and hydrogel) used as explants in scleral buckling in retinal detachment surgery. DESIGN: The study design was a histopathologic study on a cohort of capsule fractions and complete eyes. PARTICIPANTS: Fifty-nine patients participated in this study, in which 60 specimens, including 37 hydrogel and 21 silicone capsule specimens as well as 2 whole eyes, were gathered. There were no control subjects. INTERVENTION: The capsule specimens were obtained from eyes operated on previously for scleral buckling for retinal detachment. The two whole eyes were enucleated. All specimens were studied with routine optic microscopy. MAIN OUTCOME MEASURES: Patient characteristics, type of scleral buckling, and number of operations performed were analyzed. Histologically, the capsular structure, its interface with the explant, and its different components also were studied. Remnants of the buckling material also were investigated. RESULTS: There were 45 male and 14 female patients, with a mean age of 49 years. Histologically, capsule specimens had a fibrous matrix with fibroblasts and few inflammatory cells. Eighteen (48.6%) of 37 hydrogel capsule specimens displayed hydrogel fragments surrounded by a foreign body giant cell granuloma in 16 cases. CONCLUSION: Nonabsorbable materials undergo encapsulation after implantation on the eye surface. Giant cell granuloma was observed in some hydrogel capsule specimens in relation to hydrogel fragmentation. The exact origin of this fragmentation remains unknown.

Dispensable role of the NF-kappa B sites in the UV-induction of the HIV-1 LTR in transgenic mice.

We have previously reported the epidermis-specific expression of the HIV-1 LTR in transgenic mice and its induction by UV-B rays. To dissect the underlying mechanism of the UV induction of the LTR in mice, we developed two approaches. We first demonstrated by gel mobility shift analysis, using mice epidermal extracts, that the NF-kappa B sites of the HIV-1 LTR were one of the targets of the UV induction. The Sp-1 sites and the potential AP-1 sites of the LTR were not involved in this phenomenon. The transient transfection assays of modified LTR in HeLa cells also demonstrated the involvement of the NF-kappa B sites in the UV induction and were consistent with previously published data. Secondly, to study the regulation acting on an integrated gene, we generated transgenic mice carrying the lacZ gene under the control of the partially deleted LTR. All the transgenic lines and unexpectedly those carrying the LTR deleted for the kappa B sites displayed a UV-inducible epidermal expression. This suggests that, in mice, the UV induction might be mediated through other sites than the kappa B sites and may also depend on changes of the chromatin state.