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: To evaluate the clinical characteristics of newly diagnosed glaucomatous subjects who had a history of refractive corneal ablation surgery (RCAS). METHODS: Sixty-eight glaucomatous subjects who had a history of RCAS and 68 age- and visual field (VF) mean deviation-matched glaucomatous subjects with no history of RCAS were included. Intraocular pressure (IOP), central corneal thickness (CCT), VF, and retinal nerve fiber layer thickness determined by optical coherence tomography were assessed. Parameters were compared between patients with and without a history of RCAS. Between-eye comparisons in the same participant (more advanced vs. less-advanced eye, in terms of glaucoma severity) were performed in the RCAS group. RESULTS: With similar levels of glaucoma severity, those with a history of RCAS showed significantly lower baseline IOP and a thinner CCT than the eyes of individuals without a RCAS history (13.6 vs. 18.7 mmHg, 490.5 vs. 551.7 micrometer, all p < 0.001). However, the extent of IOP reduction after anti-glaucoma medication did not significantly differ between the two groups (17% vs. 24.3%, p = 0.144). In the between-eye comparisons of individual participants in the RCAS group, the more advanced eyes were more myopic than the less-advanced eyes (-1.84 vs. -0.58 diopter, p = 0.003). CONCLUSIONS: Eyes with a history of RCAS showed a similar level of IOP reduction as eyes without such a history after anti-glaucoma medication. Our finding that the more advanced eyes were more myopic than the less-advanced eyes in the same participant may suggest an association between glaucoma severity and myopic regression.
Adult ; Female ; Glaucoma/*complications/drug therapy/pathology ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; Myopia/*complications/pathology/*surgery ; *Refractive Surgical Procedures ; Retrospective Studies ; Severity of Illness Index ; Tomography, Optical Coherence

PURPOSE: To evaluate the clinical characteristics of newly diagnosed glaucomatous subjects who had a history of refractive corneal ablation surgery (RCAS). METHODS: Sixty-eight glaucomatous subjects who had a history of RCAS and 68 age- and visual field (VF) mean deviation-matched glaucomatous subjects with no history of RCAS were included. Intraocular pressure (IOP), central corneal thickness (CCT), VF, and retinal nerve fiber layer thickness determined by optical coherence tomography were assessed. Parameters were compared between patients with and without a history of RCAS. Between-eye comparisons in the same participant (more advanced vs. less-advanced eye, in terms of glaucoma severity) were performed in the RCAS group. RESULTS: With similar levels of glaucoma severity, those with a history of RCAS showed significantly lower baseline IOP and a thinner CCT than the eyes of individuals without a RCAS history (13.6 vs. 18.7 mmHg, 490.5 vs. 551.7 micrometer, all p < 0.001). However, the extent of IOP reduction after anti-glaucoma medication did not significantly differ between the two groups (17% vs. 24.3%, p = 0.144). In the between-eye comparisons of individual participants in the RCAS group, the more advanced eyes were more myopic than the less-advanced eyes (-1.84 vs. -0.58 diopter, p = 0.003). CONCLUSIONS: Eyes with a history of RCAS showed a similar level of IOP reduction as eyes without such a history after anti-glaucoma medication. Our finding that the more advanced eyes were more myopic than the less-advanced eyes in the same participant may suggest an association between glaucoma severity and myopic regression.
Adult ; Female ; Glaucoma/*complications/drug therapy/pathology ; Humans ; Intraocular Pressure ; Male ; Middle Aged ; Myopia/*complications/pathology/*surgery ; *Refractive Surgical Procedures ; Retrospective Studies ; Severity of Illness Index ; Tomography, Optical Coherence

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

Progressive loss of retinal ganglion cells (RGCs) and their axons is the main pathogenesis of glaucoma. The cause of glaucoma is not fully understood, but the neurodegeneration of glaucoma involves many mechanisms such as oxidative stress, glutamate toxicity and ischemia/reperfusion insult. In order to target these mechanisms, multiple neuroprotective interventions have been investigated to prevent the death of RGCs. Of note are some tonic herbs from the traditional Chinese medicine (TCM) pharmacopeia that have shown neuroprotective effects in glaucoma. TCM differs from Western medicine in that TCM exhibits complicated bioactive components, triggering many signaling pathways and extensive actions on vital organs. Modern scientific approaches have demonstrated some of their underlying mechanisms. In this review, we used Lycium barbarum and Ginkgo biloba as examples to elaborate the characteristics of TCM and their potential applications in neuroprotection in glaucoma.
Clinical Trials as Topic ; Drugs, Chinese Herbal ; therapeutic use ; Ginkgo biloba ; Glaucoma ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Neuroprotective Agents ; therapeutic use ; Retinal Ganglion Cells ; pathology

Because of the widespread use of ant-obesity medications, bariatricians need to be aware not only of common adverse events but also uncommon serious events in the pharmacotherapy of obesity. Safety and tolerability must be considered in selecting the drug, titrating the dosage, and monitoring patients. In Korea, orlistat and lorcaserine are the two anti-obesity drugs that can be used for long-term treatment, and in the US, liraglutide, phentermine/topiramate, and naltrexone/bupropion have been recently approved. In general, all of these drugs have very good safety and tolerability profiles. Common adverse events of these drugs are well understood, and they can be coped with or prevented by adjusting the dosage properly. In addition, patients can recover from serious events by stopping the medication. However, there are other serious side effects that need to be monitored for. These include liver injury, acute kidney injury, and pancreatitis for orlistat; valvulopathy for lorcaserine; thyroid C-cell pathology and pancreatitis for liraglutide; metabolic acidosis, urolithiasis, acute angle closure glaucoma, and teratogenic effects for phentermine/topiramate; and severe nausea and heart disease for naltrexone/bupropion.
Acidosis ; Acute Kidney Injury ; Anti-Obesity Agents ; Drug Therapy ; Glaucoma, Angle-Closure ; Heart Diseases ; Humans ; Korea ; Liver ; Liraglutide ; Nausea ; Obesity ; Pancreatitis ; Pathology ; Thyroid Gland ; Urolithiasis

PURPOSE: To evaluate changes in anterior chamber depth (ACD) and angle width induced by phacoemulsification and intraocular lens (IOL) implantation in eyes with glaucoma, using anterior segment optical coherence tomography (AS-OCT). METHODS: Eleven eyes of 11 patients with angle-closure glaucoma (ACG) and 12 eyes of 12 patients with open-angle glaucoma (OAG) underwent phacoemulsification and IOL implantation. Using AS-OCT, ACD and angle parameters were measured before and 2 days after surgery. Change in intraocular pressure (IOP) and number of ocular hypotensive drugs were evaluated. RESULTS: After surgery, central ACD and angle parameters increased significantly in eyes with glaucoma (p < 0.05). Prior to surgery, mean central ACD in the ACG group was approximately 1.0 mm smaller than that in the OAG group (p < 0.001). Post surgery, mean ACD of the ACG group was still significantly smaller than that of the OAG group. No significant differences were found in angle parameters between the ACG and OAG groups. In the ACG group, postoperative IOP at the final visit was significantly lower than preoperative IOP (p = 0.018) and there was no significant change in the number of ocular hypotensive medications used, although clinically, patients required fewer medications. In the OAG group, the IOP and number of ocular hypotensive drugs were almost unchanged after surgery. CONCLUSIONS: The ACD and angle width in eyes with glaucoma increased significantly after phacoemulsification and IOL implantation. Postoperative ACD significantly differed between the ACG and OAG groups, whereas angle parameters did not differ.
Aged ; Aged, 80 and over ; Anterior Chamber/anatomy & histology/*surgery ; Female ; Glaucoma, Angle-Closure/drug therapy/pathology/*surgery ; Glaucoma, Open-Angle/drug therapy/pathology/*surgery ; Humans ; Intraocular Pressure ; Lens Implantation, Intraocular/*adverse effects ; Male ; Middle Aged ; Phacoemulsification/*adverse effects ; Postoperative Period ; Preoperative Period ; Tomography, Optical Coherence

PURPOSE: To present a case of a unilateral diffuse retinal hemorrhage in a 15-year-old girl, who underwent bilateral trabeculectomy for steroid induced glaucoma. METHODS: Despite the maximally tolerable medical treatment, IOP in the right eye remained above 50 mmHg for four months, and was simultaneously elevated in the left eye. So we performed bilateral trabeculectomy. RESULTS: On the first postoperative day, diffuse retinal hemorrhages were observed in the right eye; however, no retinal hemorrhage was found in the left eye. The hemorrhages resolved completely without consequences two months later. CONCLUSIONS: In the case of high IOP for a long period, sudden lowering of IOP may acutely increase the blood flow and consequently rupture multiple retinal capillaries because of altered autoregulatory function. Special care is therefore needed to prevent an abrupt fall in IOP before, during, and after surgery, especially when IOP has been highly elevated for an extended period.
Administration, Topical ; Adolescent ; Female ; Fluorescein Angiography ; Fundus Oculi ; Glaucoma/chemically induced/*surgery ; Humans ; Retinal Hemorrhage/diagnosis/*etiology/pathology ; Steroids/administration & dosage/adverse effects/therapeutic use ; Trabeculectomy/*adverse effects ; Uveitis/drug therapy

PURPOSE: To investigate the effects of topical prostaglandin analogue drugs on the differentiation of adipocytes. METHODS: Differentiation of 3T3-L1 preadipocytes was induced with isobutylmethylxanthine, dexamethasone, and insulin. 3T3-L1 cells were exposed to 0.008, 0.08, 0.2 microM of latanoprost and travoprost. Reverse transcription polymerase chain reaction for mRNA expression of lipoprotein lipase and peroxisome proliferator-activated receptor gamma 2 (PPARgamma2), and glycerol-3-phosphate dehydrogenase (G3PDH) assays were performed to examine the effects on early and late differentiation, respectively. Also, glycerol assays were done to evaluate the effect of prostaglandin analogues on lipolysis after differentiation. RESULTS: Both prostaglandin analogues inhibited differentiation of preadipocytes. Topical prostaglandin analogues significantly decreased G3PDH activity, a marker of late differentiation. However, topical prostaglandin analogues did not change mRNA expressions of lipoprotein lipase and PPARgamma2, markers of early differentiation. The activities of the early markers of differentiation were not changed significantly before and after growth arrest. Compared to latanoprost, travoprost decreased G3PDH activity more significantly (p < 0.05). Both prostaglandin analogues did not affect the lipolysis of differentiated adipocytes (p > 0.05). CONCLUSIONS: Prostaglandin analogues display an inhibitory effect on the differentiation of adipocytes when the cells start to differentiate especially in the late stage of differentiation. Thus, commercial topical prostaglandin analogues may decrease the fat contents of eyelids.
3T3-L1 Cells ; Adipocytes/drug effects/*pathology ; Animals ; Antihypertensive Agents/administration & dosage ; Cell Differentiation/drug effects ; Disease Models, Animal ; Glaucoma/*drug therapy/pathology ; Lipolysis/*drug effects ; Mice ; Neuroprotective Agents/administration & dosage ; Ophthalmic Solutions/administration & dosage ; Prostaglandins F, Synthetic/*administration & dosage ; Prostaglandins, Synthetic/*administration & dosage