Combined fluocinolone acetonide intravitreal insertion and glaucoma drainage device placement for chronic uveitis and glaucoma.

PURPOSE: To determine whether a fluocinolone acetonide sustained-release intravitreal drug delivery system can be implanted safely at the same time that a glaucoma drainage device is placed for eyes with uveitis and elevated intraocular pressure (IOP) receiving maximum tolerated IOP-lowering therapy. DESIGN: Retrospective, observational case series. METHODS: Subjects had chronic noninfectious intermediate or posterior uveitis and elevated IOP while receiving maximum tolerated medical therapy. Fluocinolone acetonide implantation and glaucoma tube shunt placement were performed in a single surgical session. The main outcome measures were inflammatory recurrences, visual acuity (VA), use of adjunctive anti-inflammatory therapy, IOP, and adverse events. RESULTS: Seven eyes of 5 patients were studied. The average number of recurrences 12 months before implantation was 3 episodes per eye; of the 3 eyes followed up for more than 30 months, none had an inflammatory recurrence within 30 months after implantation. The mean Snellen visual acuity 12 months after the combined surgery was 20/114, compared with 20/400 at baseline. Adjunctive steroid use decreased. Average IOP decreased from 27.3 mm Hg at baseline to 14.6 mm Hg 12 months after the combined surgery (P = .019). CONCLUSIONS: The favorable results observed in all eyes suggest that fluocinolone acetonide implantation can be safely combined with glaucoma tube shunt placement in a single surgical session in eyes with uveitis and elevated IOP receiving maximum tolerated IOP-lowering therapy. Uveitis recurrences decreased, visual acuity improved, and IOP decreased. There were no adverse events during insertion of the fluocinolone acetonide implant and placement of the glaucoma tube shunt.

The gel state of the vitreous and ascorbate-dependent oxygen consumption: relationship to the etiology of nuclear cataracts.

OBJECTIVE: To investigate the rate and mechanism of oxygen consumption by the vitreous. METHODS: Oxygen consumption was measured with a microrespirometer. Vitreous ascorbate was measured spectrophotometrically and by gas chromatography-mass spectrometry. Vitreous degeneration was related to the rate of oxygen consumption and ascorbate concentration in samples obtained during vitrectomy. RESULTS: Prolonged exposure to oxygen or treatment with ascorbate oxidase eliminated oxygen consumption by the vitreous. Adding ascorbate restored oxygen consumption. Oxygen consumption persisted after boiling or treating the vitreous with the chelating agents EDTA and deferoxamine. In patients undergoing retinal surgery, liquefaction of the vitreous and previous vitrectomy were associated with decreased ascorbate concentration and lower oxygen consumption. CONCLUSIONS: Ascorbate in the vitreous decreases exposure of the lens to oxygen. The catalyst for this reaction is not known, although free iron may contribute. The gel state of the vitreous preserves ascorbate levels, thereby sustaining oxygen consumption. Vitrectomy or advanced vitreous degeneration may increase exposure of the lens to oxygen, promoting the progression of nuclear cataracts. CLINICAL RELEVANCE: Determining how the eye is protected from nuclear cataracts should suggest treatments to reduce their incidence.

A neuroactive steroid 5alpha-androstane-3alpha,17beta-diol regulates androgen receptor level in astrocytes.

Optic nerve head (ONH) astrocytes from patients with glaucomatous optic neuropathy exhibit increased production of 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), a neuroactive metabolite of 5alpha-dihydrotestosterone (5alpha-DHT). To determine whether ONH astrocytes are androgen target cells, and whether 3alpha-diol is capable of regulating astrocyte functions, we studied the response of human ONH astrocytes to 3alpha-diol compared with 17beta-hydroxy-17alpha-methyl-estra-4,9,11-trien-3-one (R1881), a synthetic 5alpha-DHT agonist. In ONH astrocytes, both 3alpha-diol and R1881 increased protein levels of androgen receptor (AR) and glial fibrillary acidic protein (GFAP), however, only R1881 also increased the AR mRNA level and astrocyte proliferation. Both R1881 and 3alpha-diol rapidly activate the mitogen-activated protein kinase (MAPK) signaling pathway in ONH astrocytes, as confirmed by phosphorylation of extracellular signal-regulated kinase (ERK). 3Alpha-diol also activates the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. 3Alpha-diol regulates the increase of AR protein level and the phosphorylation through the PI3K/Akt pathway, whereas R1881 regulates them through the MAPK/ERK pathway. Our findings demonstrate that human ONH astrocytes are androgen target cells and respond to androgens by the rapid activation of cell signaling. The activation of the PI3K/Akt pathway by 3alpha-diol may regulate various properties of astrocytes, including cell motility and survival, and may play a role in the formation and maintenance of the reactive phenotype of ONH astrocytes in glaucoma.