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At least 793 records · Page 44Linked to original sources

Intraocular human thrombin infusion in diabetic vitrectomies.

The effectiveness of intravitreal thrombin infusion during vitrectomy was prospectively evaluated in eight diabetic patients with persistent vitreous hemorrhages and severe proliferative vitreoretinopathy. A concentration of 80 units/ml of human thrombin diluted in BSS-plus infusion fluid was used. Bleeding time ranged between 2 and 15 seconds (mean, 5 seconds). The reduction of bleeding facilitated surgery. In five of the eight cases the vitreous was clear one day postoperatively. One month postoperatively six eyes had clear media. No additional postoperative intraocular inflammation developed. These results suggest that human thrombin causes less inflammation than bovine thrombin.

Diabetic Retinopathy↗

Management of cornea-lens touch after filtering surgery for glaucoma.

The success of filtering surgery for glaucoma may be compromised by a postoperative flat anterior chamber associated with cornea-lens touch, hypotony, and absence of wound leakage. The clinical course of eight patients with this complication was reviewed. Six patients had chronic angle-closure glaucoma. Only one patient responded to medical therapy which included frequent topical application of atropine sulfate 3.0% for 1 hour. Reformation of the anterior chamber with air and drainage of any suprachoroidal fluid was immediately performed in the remaining seven. At the time of follow-up (mean, 16 months), the glaucoma was controlled in all eyes except one. The mean intraocular pressure (IOP) was 14 mmHg in those eyes not requiring reoperation. Six (75%) of eight eyes had diffuse, succulent filter blebs. Five eyes (63%) required no antiglaucoma medications, one eye (12%) required one, one eye (12%) required two, and one eye (12%) underwent repeat filtering surgery. The results suggest that, once medical therapy is not immediately successful, prompt surgical reformation of the anterior chamber along with drainage of any suprachoroidal fluid may preserve the filter blebs in these eyes.

Adult↗

Thin-film coupled fluid-solid analysis of flow through the Ahmed glaucoma drainage device.

The Ahmed glaucoma valve (AGV) is a popular glaucoma drainage device, allowing maintenance of normal intraocular pressure in patients with reduced trabecular outflow facility. The uniquely attractive feature of the AGV, in contrast to other available drainage devices, is its variable resistance in response to changes in flow rate. As a result of this variable resistance, the AGV maintains a pressure drop between 7 and 12 mm Hg for a wide range of aqueous humor flow rates. In this paper, we demonstrate that the nonlinear behavior of the AGV is a direct result of the flexibility of the valve material. Due to the thin geometry of the system, the leaflets of the AGV were modeled using the von Kármán plate theory coupled to a Reynolds lubrication theory model of the aqueous humor flow through the valve. The resulting two-dimensional coupled steady-state partial differential equation system was solved by the finite element method. The Poisson's ratio of the valve was set to 0.45, and the modulus was regressed to experimental data, giving a best-fit value 4.2 MPa. Simulation results compared favorably with previous experimental studies and our own pressure-drop/flow-rate data. For an in vitro flow of 1.6 microL/min, we calculated a pressure drop of 5.8 mm Hg and measured a pressure drop of 5.2 +/- 0.4 mm Hg. As flow rate was increased, pressure drop rose in a strongly sublinear fashion, with a flow rate of 20 microL/min giving a predicted pressure drop of only 10.9 mm Hg and a measured pressure drop of 10.5 +/- 1.1 mm Hg. The AGV model was then applied to simulate in vivo conditions. For an aqueous humor flow rate of 1.5-3.0 microL/min, the calculated pressure drops were 5.3 and 6.3 mm Hg.

Aqueous Humor↗

Intraocular ciprofloxacin levels after oral administration in silicone oil-filled eyes.

PURPOSE: To evaluate penetration of oral ciprofloxacin in the retro-silicone oil space fluid (RSOF) in silicone oil (SO)-filled eyes. METHODS: One dose of 750 mg ciprofloxacin was given to two groups of five patients with vitrectomized eyes with SO endotamponade, 4 hours (group I) and 8 hours (group II) before SO removal. In 10 vitrectomized eyes with SO endotamponade (group III) and another 10 patients scheduled for vitrectomy for the first time (group IV), two 750-mg doses every 12 hours, with the last dose 12 hours before surgery, were given. Blood samples were taken at the time of collection of RSOF samples in groups I, II, and III and of the vitreous in group IV. All samples were assayed for ciprofloxacin by high-performance liquid chromatography. RESULTS: The mean drug concentration in the RSOF was 0.34 +/- 0.09, 0.37 +/- 0.04, 0.84 +/- 0.29, and 0.44 +/- 0.11 micro g/mL in groups I, II, III, and IV respectively. The mean serum concentration was 1.29 +/- 0.63, 1.08 +/- 0.14, 1.93 +/- 0.84, and 1.34 +/- 0.55 micro g/mL in groups I, II, III, and IV respectively with no statistically significant difference between groups III and IV (P = 0.081). CONCLUSIONS: Antibiotic levels in the RSOF in SO-filled eyes after oral administration of ciprofloxacin in two 750-mg doses exceeded the minimal inhibitory concentration for 90% of isolates (MIC(90)) for most bacterial species and was higher than levels reached in the vitreous in nonvitrectomized eyes (P = 0.001).

Administration, Oral↗

Correlation of aqueous humor ascorbate with intraocular pressure and outflow facility in hereditary buphthalmic rabbits.

The hypotensive effect of ascorbate on intraocular pressure has been reported following topical application, oral administration, or anterior chamber infusion in animals. The present report describes the correlation of aqueous humor ascorbate concentration with intraocular pressure as well as outflow facility in vivo. Low aqueous ascorbate level was seen in buphthalmic eyes with high intraocular pressure and low outflow facility. The opposite correlation was observed in normal eyes. Ascorbate concentration in the anterior chamber of the rabbit eye is apparently related to the alteration of outflow facility and the movement of fluid in the anterior chamber.

Animals↗

Carbonic anhydrase inhibitors. Water-soluble, topically effective intraocular pressure lowering agents derived from isonicotinic acid and aromatic/heterocyclic sulfonamides: is the tail more important than the ring?

Reaction of twenty aromatic/heterocyclic sulfonamides containing a free amino, imino, hydrazino or hydroxyl group, with isonicotinoyl chloride afforded a series of water-soluble compounds (as hydrochloride or triflate salts). The new derivatives were examined as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form). Efficient inhibition was observed against all three isozymes, but especially against CA II and CA IV (K(I) in the nanomolar range), the two isozymes known to play a critical role in aqueous humor secretion within the ciliary processes of the eye. Some of the most potent inhibitors synthesized were applied as 2% water solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them, and the active drug was detected in eye tissues and fluids. According to others the IOP lowering effect of topically effective antiglaucoma sulfonamides is due to the intrinsic nature of the specific heterocyclic sulfonamide considered, among which the thienothiopyran-2-sulfonamide derivatives represent the best studied case e.g. dorzolamide. In order to prove that the tail (in this case the isonicotinoyl moiety) conferring water solubility to a sulfonamide CA inhibitor is more important than the ring to which the sulfonamido group is grafted a dorzolamide derivative to which the isonicotinoyl moiety was attached was also prepared. This new compound is more water soluble than dorzolamide (as hydrochloride salt), behaves as a strong CA II inhibitor and acts similarly to the parent derivative in lowering IOP in experimental animals. Thus, it seems that the tail conferring water solubility is more important for topical activity as an antiglaucoma drug than the heterocyclic/aromatic ring to which the sulfonamido moiety is attached.

Administration, Topical↗

Role of NF-kappaB-mediated interleukin-8 expression in intraocular neovascularization.

PURPOSE: To investigate the role of interleukin (IL)-8 in intraocular neovascularization and the mechanism of its production. METHODS: Interleukin-8 was measured with enzyme-linked immunosorbent assays in vitreous and aqueous fluid obtained from patients with neovascular diseases. Localization of IL-8 was examined by immunohistochemistry. An in vitro angiogenesis assay was performed on collagen gels, by using bovine aortic endothelial cells to determine the effect of the vitreous fluid. In bovine retinal glial cells under hypoxia, NF-kappaB activation was evaluated by immunoblot analysis and by electrophoretic mobility shift assay, and IL-8 and vascular endothelial growth factor (VEGF) mRNA expression was determined by semiquantitative reverse transcription-polymerase chain reaction. RESULTS: The concentration of IL-8 in vitreous fluid of patients with retinal neovascularization was significantly higher than that of patients without neovascular disease. Interleukin-8 immunostaining was detected in vascular endothelial cells and glial cells in the retinas with neovascularization. Vitreous fluid with high concentrations of IL-8 induced tubular morphogenesis in endothelial cells, and this effect was inhibited to a similar extent by neutralizing antibodies to IL-8 or to VEGF. In glial cells, in vitro, hypoxia induced NF-kappaB activation and increased IL-8 and VEGF mRNA. Furthermore, pyrrolidine dithiocarbamate, a specific inhibitor of NF-kappaB activation, prevented the induction of the IL-8 gene, but not that of the VEGF gene. CONCLUSIONS: These results suggest that IL-8 induced by hypoxia and mediated by NF-kappaB may contribute to the pathogenesis of intraocular neovascularization.

Animals↗

Carbonic anhydrase inhibitors. Synthesis of topically effective intraocular pressure lowering agents derived from 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide.

Reaction of the acyl chlorides of phthalimido-glycine or phthalimido-beta-alanine with 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded after hydrazinolysis and deprotection of the phthalimido group the corresponding 5-(omega-aminoalkylcarboxamido)-1,3,4-thiadiazole-2-sulfonamides. Reaction of 5-(beta-aminoethylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide with sulfonyl halides or acyl halides afforded a series of compounds possessing beta-alkyl/arylsulfonyl/carbonylamidoethylcarboxamido moieties in the 5 position of the thiadiazole-2-sulfonamide ring. The new derivatives were efficient inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form), but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play an important role in aqueous humor secretion within the ciliary processes of the eye. Some of the synthesized inhibitors possessed good water solubility (as hydrochlorides or sodium salts) and were applied as 2% solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them for prolonged periods of 1-2 h, and the active drug was detected in eye tissues and fluids indicating that the antiglaucoma effect is due to CA inhibition within the eye.

Administration, Topical↗

Carbonic anhydrase inhibitors. Part 71. Synthesis and ocular pharmacology of a new class of water-soluble, topically effective intraocular pressure lowering sulfonamides incorporating picolinoyl moieties.

Reaction of 20 aromatic/heterocyclic sulfonamides containing a free amino, imino, hydrazino or hydroxyl group, with picolinic acid in the presence of carbodiimide derivatives afforded a series of water-soluble (as hydrochloride or triflate salts) compounds. The new derivatives were assayed as inhibitors of three carbonic anhydrase (CA) isozymes, CA I, II (cytosolic forms) and IV (membrane-bound form). Efficient inhibition was observed against all three isozymes, but especially against CA II and CA IV (in nanomolar range), the two isozymes known to play a critical role in aqueous humor secretion within the ciliary processes of the eye. Some of the best inhibitors synthesized were applied as 2% water solutions directly into the eye of normotensive or glaucomatous albino rabbits. Very strong intraocular pressure (IOP) lowering was observed for many of them, and the active drug was detected in eye tissues and fluids. This result prompted us to reanalyze the synthetic work done by other groups for the design of water soluble, topically effective antiglaucoma sulfonamides. According to these researchers, the IOP lowering effect is due to the intrinsic nature of the specific heterocyclic sulfonamide considered, among which the thienothiopyran-2-sulfonamide derivatives represent the best studied case. Indeed, the first agents developed for such applications, such as dorzolamide, are derivatives of this ring system. In order to prove that the tail (in this case the picolinoyl moiety) conferring water solubility to a sulfonamide CA inhibitor is critically important for its topical effectiveness, similarly to the ring to which the sulfonamido group is grafted, we also prepared a dorzolamide derivative to which the picolinoyl moiety was attached. This new compound is more water soluble than dorzolamide (as hydrochloride salt), behaves as a strong CA II inhibitor, and acts similarly to the parent derivative in lowering IOP in experimental animals. Thus, it seems that the tail conferring water solubility is more important for topical activity as antiglaucoma drug, than the heterocyclic/aromatic ring to which the sulfonamido moiety is grafted.

Administration, Topical↗

Recombinant hirudin for prevention of experimental postoperative intraocular fibrin.

PURPOSE: To determine the efficacy of a specific antithrombin agent (recombinant desulphatohirudin variant 1 [Revasc, Ciba-Geigy, Ltd., Basel, Switzerland]) administered in the infusion fluid to prevent early postoperative fibrin formation in a rabbit lensectomy and vitrectomy model. METHODS: Standard fragmatome lensectomies and core vitrectomies were performed prospectively in a masked fashion on ten control eyes with lactated Ringer's infusion and on ten eyes treated with 10 microgram of recombinant hirudin/ml in the infusate. The amounts of fibrin and hemorrhage were graded in a masked fashion by using slit-lamp examination and indirect ophthalmoscopy on postoperative days 1 through 5 and on day 7. RESULTS: The difference in the mean grade of fibrin formed on the first postoperative day in the eyes treated with recombinant hirudin (mean, 0.9) in relation to the mean grade of fibrin in the control eyes (mean, 3.5) was statistically significant (P = .004). This difference was also significant on the second postoperative day (P = .01). None of the treated eyes developed intraoperative or postoperative hemorrhage. CONCLUSIONS: Recombinant desulphatohirudin variant 1 is an effective inhibitor of postoperative fibrin formation in a rabbit model and is not associated with an increased risk of intraoperative or postoperative bleeding at the tested dose. This drug may be a useful adjunct in vitreous surgery for both proliferative vitreoretinopathy and the complications of proliferative diabetic retinopathy.

Animals↗

Design and control of in-vivo magnetic microrobots.

This paper investigates fundamental design, modeling and control issues related to untethered biomedical microrobots guided inside the human body through external magnetic fields. Immediate application areas for these microrobots include cardiovascular, intraocular and inner-ear diagnosis and surgery. A prototype microrobot and steering system are introduced. Experimental results on fluid drag and magnetization properties of the robots are presented along with an analysis of required magnetic fields for application inside blood vessels and vitreous humor.

Diagnosis, Computer-Assisted↗

Intravitreal use of bevacizumab (Avastin) for choroidal neovascularization due to ARMD: a preliminary multifocal-ERG and OCT study. Multifocal-ERG after use of bevacizumab in ARMD.

PURPOSE: To evaluate by MFERG and OCT the macular function before and after intravitreal use of bevacizumab (Avastin) in eyes suffering from CNV due to ARMD. METHODS: Eighteen eyes with subfoveal CNV due to ARMD were studied before and after intravitreal use of bevacizumab with MFERG and OCT. The post treatment follow up was three months. RESULTS: Before treatment, OCT shows an increase of the retinal thickening of the fovea and the electrical response densities in the fovea and parafovea were decreased in all patients. Three months after treatment, OCT showed a real resolution of the subretinal fluid. The electrical responses in the fovea and parafovea remained the same or slightly improved in some cases. The intraocular pressure remained normal and no inflammation was observed. CONCLUSION: The intravitreal use of bevacizumab may provide anatomical correlates that support the concept of disease amelioration but the functional improvement of the macula three months after treatment is not obvious. However the method is promising and needs further evaluation.

Aged↗

Postoperative intraocular pressure spikes: the need to treat.

Raised intraocular pressure (IOP) still holds pride of place as the principal risk factor for developing glaucoma. The detrimental effects of chronically elevated IOP on the optic disc are well known. However, the clinical significance of acutely raised IOP is less certain. Transient acute elevations of intraocular pressure (IOP spikes) occur following many surgical and laser procedures. Cataract extraction, glaucoma surgery, pars plana vitrectomy with fluid air exchange, Nd-YAG capsulotomy, or peripheral iridotomy, and laser trabeculoplasty all have been reported to be associated with variable IOP spikes in the early postoperative period. There is considerable diversity of opinion concerning how these IOP spikes should best be managed. We have reviewed the nature and quality of the available experimental and clinical data relating to IOP spikes and we offer some broad, general guidelines for their clinical management.

Animals↗

Advances in diagnosis and management of herpetic uveitis.

Herpetic eye disease is common and is frequently associated with intraocular inflammation or uveitis. Despite recent advances in measuring anti-herpes virus antibodies and viral DNA in ocular fluids, diagnosis remains largely clinical. The two more common syndromes include anterior uveitis, often associated with keratitis, and the acute retinal necrosis (ARN) syndrome. Treatment is complex and requires careful monitoring to provide the appropriate balance of antiviral medication and corticosteroids. Long-term prophylaxis with oral antiviral agents may be required in selected patients to help prevent the vision-compromising complications associated with recurrences.

Antiviral Agents↗