PURPOSE: Long-term use of topical medication is needed for glaucoma treatment. One of the most commonly prescribed classes of hypotensive agents are prostaglandin analogs (PGs) used as both first-line monotherapy; as well as in combination therapy with other hypotensive agents. Several side effects of eye drops can be caused by preservatives. The purpose of this study was to evaluate the effects of PGs with varying concentrations of benzalkonium chloride (BAC), alternative preservatives, or no preservatives on human conjunctival fibroblast cells. METHODS: Primary human conjunctival fibroblast cells were used in these experiments. Cells were exposed to the following drugs: BAC at different concentrations, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), tafluprost 0.0015% with/without 0.001% BAC and travoprost 0.004% (with 0.001% Polyquad) for 15 and 30 minutes. Cell cytotoxicity was evaluated by phase-contrast microscopy to monitor morphological changes of cells, Counting Kit-8 (CCK-8) assay to cell viability, and fluorescent activated cell sorting (FACS) analysis to measure apoptosis. RESULTS: BAC caused cell shrinkage and detachment from the plate in a dose-dependent manner. Morphological changes were observed in cells treated with bimatoprost 0.01% and latanoprost 0.005%. However, mild cell shrinkage was noted in cells treated with tafluprost 0.0015%, while a non-toxic effect was noted with travoprost 0.004% and preservative-free tafluprost 0.0015%. CCK-8 assay and FACS analysis showed all groups had a significantly decreased cell viability and higher apoptosis rate compared with the control group. However, travoprost 0.004% and preservative-free tafluprost 0.0015% showed lower cytotoxicity and apoptosis rate than other drugs. CONCLUSIONS: This in vitro study revealed that BAC-induced cytotoxicity is dose-dependent, although it is important to emphasize that the clinical significance of toxicity differences observed among the different PGs formulations has not yet been firmly established. Alternatively preserved or preservative-free glaucoma medications seem to be a reasonable and viable alternative to those preserved with BAC.
Apoptosis ; Cell Line ; Cell Survival/drug effects ; Conjunctiva/drug effects/*pathology ; Fibroblasts/drug effects/pathology ; Glaucoma/drug therapy/pathology ; Humans ; Preservatives, Pharmaceutical/*pharmacology ; Prostaglandins, Synthetic/*pharmacology

PURPOSE: The purpose of this study was to investigate the myotoxicity of bevacizumab on extraocular muscles in a rabbit model. METHODS: Thirty New Zealand white rabbits were used for this study. The animals were evenly divided into two groups. In the first group, 15 rabbits were treated with intramuscular injections of bevacizumab (1.25 mg/0.05 mL) in the right superior rectus muscle and normal saline solution (0.05 mL) in the left superior rectus muscle. In the second group, 15 rabbits were treated with subconjunctival injections of bevacizumab (2.5 mg/0.1 mL) in the right superior subconjunctival area and normal saline solution (0.1 mL) in the left superior subconjunctival area. Five rabbits in each group were sacrificed at one day, two weeks and four weeks after the injections. Extraocular muscle samples were prepared for light microscopic (LM) and electron microscopic (EM) examination. Degrees of acute inflammation were evaluated via CD-11b immunohistochemistry, and global muscle change was investigated using hematoxylin and eosin stains. Intensity of fibrosis was evaluated using Masson trichrome stains, and ultrastructural changes were observed on EM. RESULTS: We observed no significant inflammatory cell infiltration, muscle necrosis or fibrotic change in treated and control eyes. EM findings revealed no significant damage to muscle or vascular tissue after bevacizumab injection. CONCLUSIONS: We found no signs of extraocular muscle toxicity after LM and EM intramuscular and subconjunctival bevacizumab injections in a rabbit model.
Angiogenesis Inhibitors/*administration & dosage/toxicity ; Animals ; Antibodies, Monoclonal, Humanized/*administration & dosage/toxicity ; Conjunctiva/drug effects ; Injections ; Oculomotor Muscles/*drug effects ; Rabbits

Posterior lip sclerectomies were performed in rabbits and cytosine arabinoside (Ara-C) was applied by topical instillation or subconjunctival injection. In both groups, the mean intraocular pressure (IOP) of the treated eyes was significantly lowered at postoperative week 1 and 2, but there was no significant difference between the mean IOP of the control eyes and that of the treated eyes at postoperative week 3 and 4. In both groups, at postoperative week 2, the sclerectomy sites of the control eyes were totally occluded by granulation tissue, but those of the treated eyes were partially replaced by granulation tissue. At postoperative week 4, the sclerectomy sites of the treated eyes were totally occluded by the granulation tissue ultimately in both groups. There were no differences in the mean IOP and the histologic finding of the treated eyes between the topical instillation group and the subconjunctival injection group. We concluded that either topical instillation or subconjunctival injection of Ara-C can delay wound healing at the surgical site after glaucoma filtering surgery in rabbits.
Administration, Topical ; Animals ; Conjunctiva ; Cytarabine/*administration & dosage/therapeutic use ; Glaucoma/pathology/*surgery ; Injections ; Intraocular Pressure/drug effects ; Ophthalmic Solutions ; Rabbits ; *Sclerostomy ; Wound Healing/drug effects

Adult ; Anti-Bacterial Agents ; therapeutic use ; Conjunctiva ; drug effects ; microbiology ; Female ; Humans ; Keratomileusis, Laser In Situ ; adverse effects ; methods ; Levofloxacin ; therapeutic use ; Male ; Povidone-Iodine ; therapeutic use ; Prospective Studies

In adjustable strabismus surgery, a satisfactory final result would be achieved with delayed adjustment. However, the postoperative adhesions following strabismus surgery make delayed adjustment impossible. We evaluated the efficacy of mitomycin C in reducing the severity of postoperative adhesions following strabismus surgery and in delaying the time adjustment after surgery. Experimental rabbits underwent a hang-back recession procedure in the superior rectus muscle. A topical application of mitomycin C was made between the conjunctiva and the sclera for 5 minutes during the operation. We then studied the possible time of delayed adjustment and estimated the minimal forces required for the adjustment. The topical application of 0.1 mg/ml mitomycin C between the conjunctiva and sclera allowed for a 2-week delayed adjustment after surgery, and 0.2 mg/ml mitomycin C prevented the adhesions between these tissues and the muscle 5 weeks after surgery. These results suggest that topical mitomycin C may enhance the success rate of strabismus surgery with delayed adjustment and reduce postoperative adhesions.
Administration, Topical ; Animals ; Chemotherapy, Adjuvant ; Conjunctiva/drug effects ; Mitomycin/administration & dosage/*pharmacology ; Oculomotor Muscles/drug effects/pathology/*surgery ; Ophthalmic Solutions ; Postoperative Complications/prevention & control ; Rabbits ; Sclera/drug effects ; Strabismus/drug therapy/pathology/*surgery ; Suture Techniques ; Tissue Adhesions/prevention & control

Sodium hyaluronate can be used during a trabeculectomy to prevent early postoperative hypotony and shallow anterior chamber. To determine its long-term effect on the outcome of filtration surgery, fifteen rabbits underwent a osterior-lip sclerectomy in both eyes. Into their right eyes 0.2ml sodium hyaluronate, and into left eyes 0.2ml balanced salt solution were injected intracamerally. Gross and histopathological differences of bleb were observed. There was no statistically significant difference in longevity of the filtration bleb.
Animals ; Anterior Chamber/*drug effects/pathology ; Conjunctiva/pathology ; Connective Tissue/pathology ; Follow-Up Studies ; Hyaluronic Acid/*administration & dosage ; Ocular Hypotension/prevention & control ; Rabbits ; Sclera/pathology ; *Sclerostomy

The inhibitory mechanism of interferon-gamma (IFN-gamma) on the fibroblasts from Tenon's capsule was studied. By using immunohistochemical SP method and pathological image system, the inhibitory effects of IFN-gamma on the expression of transforming growth factor beta receptor I in the in vitro cultured fibroblasts from Tenon's capsule were quantitatively analyzed. The results showed that IFN-gamma could reduce the expression of transforming growth factor beta receptor I in the fibroblasts with the following dose-effect relationship: Y = 1937.5-134.2 Igx (r=-0.971, P<0.01). It was concluded that IFN-gamma could inhibit the expression of transforming growth factor beta receptor I in the fibroblasts from Tenon's capsule. The modulation of the transforming growth factor beta receptor I expression by IFN-gamma may be beneficial to the alleviation of the hyperplasia of scar after trabeculectomy.
Conjunctiva ; metabolism ; pathology ; Connective Tissue ; drug effects ; Fibroblasts ; metabolism ; pathology ; Filtering Surgery ; Glaucoma ; pathology ; surgery ; Humans ; Interferon-gamma ; biosynthesis ; genetics ; Receptors, Transforming Growth Factor beta ; analysis

PURPOSE: Chronic use of topical hypotensive agents induces several side effects caused by preservatives. The purpose of this study was to evaluate the effects of prostaglandin analogs with varying concentrations of benzalkonium chloride (BAC), preservative-free (PF), and alternative preservatives on mouse corneal tissue. METHODS: Thirty-five, 8- to 10-week-old female C57BL/6 mice (five mice for each group) were used for this study. To the control group, we applied normal saline, and to each drug-treated group we applied 0.02% BAC, bimatoprost 0.01% (with BAC 0.02%), latanoprost 0.005% (with BAC 0.02%), travoprost 0.004% (with 0.001% polyquad) or tafluprost 0.0015% with/without 0.001% BAC, once a day (9 p.m.) for 4 weeks. Corneal fluorescein staining was evaluated in all groups. After harvest, the corneal tissues were embedded in paraffin and then Hematoxylin-Eosin stain was performed for histopathological examination. Immunofluorescence staining was done against TNF-alpha, IL-6, HLA DR, pJNK, and pAkt. RESULTS: In corneal fluorescein staining, severe punctate epithelial keratitis was seen in the groups of 0.02% BAC, 0.02% BAC containing bimatoprost 0.01% and latanoprost 0.005%. The surface desquamation, irregular surface, loss of cell borders, anisocytosis and stromal shrinkage were observed in the groups of BAC-containing eye drops. Moreover, the groups treated with BAC-containing eye drops have high inflammatory markers, significantly decreased cell viability-related signal, pAkt, and higher apoptosis-inducing signal, pJNK, than the control group. On the other hand, travoprost 0.004% and PF tafluprost 0.0015% have less cellular morphologic changes, lower inflammation, and higher cellular viability than BAC-containing formulations. CONCLUSIONS: Corneal damage, increased inflammation and apoptosis and low cell viability were observed in BAC-containing groups. PF or alternatively preserved glaucoma medications seem to be a reasonable and viable alternative to those preserved with BAC.
Animals ; Cell Survival ; Conjunctiva/drug effects/*pathology ; Disease Models, Animal ; Epithelium, Corneal/drug effects/*pathology ; Female ; Glaucoma/*drug therapy/pathology ; Mice ; Mice, Inbred C57BL ; Microscopy, Fluorescence ; Ophthalmic Solutions ; Preservatives, Pharmaceutical ; Prostaglandins, Synthetic/*administration & dosage

Vascular endothelial growth factor inhibitor is an emerging therapeutic modality for various ocular diseases with neovascularization (NV). However, for corneal NV, controversy remains regarding whether bevacizumab or ranibizumab is superior. A 32-year-old female diagnosed with herpetic keratoconjunctivitis with refractory corneal NV despite two previous subconjunctival and intrastromal bevacizumab injections, received two subconjunctival and intrastromal ranibizumab injections. Six months postoperatively, there was significant regression of the neovascular area and vessel caliber. Here, the authors report a case of improvement in corneal NV with subconjunctival and intrastromal ranibizumab injections, which was previously refractory to bevacizumab injection. The findings may suggest a new prospect in treating corneal NV.
Adult ; Angiogenesis Inhibitors/administration & dosage ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Conjunctiva/blood supply ; Corneal Neovascularization/*drug therapy ; Corneal Stroma/blood supply ; Female ; Humans ; Injections, Intraocular/methods ; Keratitis, Herpetic/*drug therapy ; Visual Acuity/drug effects

OBJECTIVETo study the cholelitholytic effect and safety of the preparation of Chinese medicine compound.

METHODExperiments were performed to study the efficacy of gallstones dissolution of the preparation of Chinese medicine compound in vitro and in vivo. The toxicity was studied by pathological and blood biochemical changes.

RESULTThe preparation of Chinese medicine compound dissolved cholesterol and mixing gallstones in 7 days in vitro and in vivo, no influence on the blood biochemistry and the other organs of the rabbits.

CONCLUSIONThe preparation of Chinese medicine compound is effective and safe for treatment of chololithiasis.

Animals ; Artemisia ; chemistry ; Cholelithiasis ; drug therapy ; Citrus ; chemistry ; Conjunctiva ; drug effects ; Drugs, Chinese Herbal ; isolation & purification ; therapeutic use ; toxicity ; Female ; Humans ; In Vitro Techniques ; Male ; Mice ; Plants, Medicinal ; chemistry ; Rabbits ; Random Allocation