Cyclosporine A inhibits TGF-ß2-induced myofibroblasts of primary cultured human pterygium fibroblasts.

Cyclosporine A (CsA), an immunomodulatory drug, and is increasingly used to treat moderate dry eye syndrome and ocular surface inflammation. However, any inhibitory effect on differentiation of fibroblasts to myofibroblasts remains unclear. Here, we show that the inhibitory effect of CsA on transforming growth factor-beta2 (TGF-ß2)-induced myofibroblasts in primary cultured human pterygium fibroblasts. CsA significantly decreased mRNA and protein expression of myofibroblast-related markers including α-SMA, laminin, and fibronectin. These findings were supported by the results from immunofluorescence staining. Taken together, these results indicate the therapeutic potential of CsA against pterygium progression. Further studies are necessary to elucidate the precise intracellular signal mechanism responsible for CsA-induced downregulation of myofibroblast markers in pterygium fibroblasts.

ADAM10 mediates N-cadherin ectodomain shedding during retinal ganglion cell differentiation in primary cultured retinal cells from the developing chick retina.

Here, we examined the role of ADAM10 during retinal cell differentiation in retinal sections and in vitro cultures of developing chick retinal cells from embryonic day 6 (ED6). Immunohistochemistry showed that ADAM10 is abundantly expressed in the inner zone of neuroblastic layer at ED5, and it becomes more highly expressed in the ganglion cell layer at ED7 and ED9. Western blotting confirmed that ADAM10 was expressed as an inactive pro-form that was processed to a shorter, active form in control cultured cells, but in cultures treated with an ADAM10 inhibitor (GI254023X) and ADAM10-specific siRNA, the level of mature ADAM10 decreased. Phase-contrast microscopy showed that long neurite extensions were present in untreated cultures 24 h after plating, whereas cultures treated with GI254023X showed significant decreases in neurite extension. Immunofluorescence staining revealed that there were far fewer differentiated ganglion cells in ADAM10 siRNA and GI254023X-treated cultures compared to controls, whereas the photoreceptor cells were unaltered. The Pax6 protein was more strongly detected in the differentiated ganglion cells of control cultures compared to ADAM10 siRNA and GI254023X-treated cultures. N-cadherin ectodomain shedding was apparent in control cultures after 24 h, when ganglion cell differentiation was observed, but ADAM10 siRNA and GI254023X treatment inhibited these processes. In contrast, N-cadherin staining was strongly detected in photoreceptor cells regardless of ADAM10 siRNA and GI254023X treatment. Taken together, these data indicate that the inhibition of ADAM10 can inhibit Pax6 expression and N-cadherin ectodomain shedding in retinal cells, possibly affecting neurite outgrowth and ganglion cell differentiation.

Comparison of Vision-related Quality of Life Between Normal Tension Glaucoma and Primary Open-angle Glaucoma.

PRCIS: Although there was little difference in overall vision-related quality of life (VRQOL) between patients with normal tension glaucoma (NTG) and primary open-angle glaucoma (POAG) after controlling for confounding factors, POAG tended to have poorer VRQOL, especially in social functioning and dependency, than NTG. PURPOSE: The fundamental goal of treatment of patients with glaucoma is to preserve their VRQOL. The aim of this study was to compare VRQOL between patients with NTG and those with POAG. MATERIALS AND METHODS: The self-reported National Eye Institute Visual Function Questionnaire (NEI VFQ-25) survey was performed, including clinical, demographic, and socioeconomic data from 506 Korean patients with NTG and 287 with POAG. The mean deviation of the integrated binocular visual field was calculated using the best location method. The NEI VFQ-25 results were evaluated by Rasch analysis to control item difficulty and variation in individual response ability. Propensity score matching was used to control for various confounding factors affecting VRQOL. RESULTS: Although patients with POAG tended to have worse VRQOL than those with NTG, there was no statistically significant between-group difference in ocular pain, near and distance activities, mental health, role difficulties, ability to drive, and the overall composite score. However, the social functioning (P=0.016) and dependency (P=0.026) were significantly poorer in POAG patients. CONCLUSIONS: Overall VRQOL in patients with NTG and POAG was found to be similar. However, social functioning and dependency were significantly worse in those with POAG. These findings are relevant to supporting glaucoma patients.

Factors influencing vision-related quality of life according to glaucoma severity.

PURPOSE: To identify factors influencing vision-related quality of life (VRQOL) according to glaucoma severity. METHODS: A total of 901 patients with varying stages of glaucoma were recruited from the prospectively designed LIGHT (Life Quality of Glaucoma Patients Who Underwent Treatment) study organized by the Korean Glaucoma Society. Participants completed a basic questionnaire collecting socioeconomic status and clinical information, in addition to the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Subjects were classified by mean deviation (MD) of integrated binocular visual field (IVF) into mild, moderate and severe damage groups. Factors were evaluated for their influence on VRQOL according to glaucoma severity using univariate and multivariable regression models between Rasch-analysed NEI VFQ-25 subscale scores and different variables. RESULTS: The mild, moderate and severe groups contained 720, 111 and 70 patients, respectively; the mean IVF MD in each group was -1.4, -8.5 and -17.9 dB. Significant differences were observed among the three groups with respect to age, IVF MD, visual acuity (VA), education level, income level, number of glaucoma medications prescribed and follow-up period. The most influential factor associated with VRQOL according to glaucoma severity was VA. The VA of the better eye was much more influential on VRQOL than the VA of the worse eye in the moderate and severe defect groups, and the impact of VA on VRQOL was more prominent in advanced glaucoma. CONCLUSIONS: Visual acuity is the most influential factor on VRQOL in patients with glaucoma. Preservation of VA should be strongly prioritized to maintain good VRQOL.

Vision-related quality of life according to location of visual field loss in patients with glaucoma.

PURPOSE: To assess influence of the location of visual field (VF) loss on vision-related quality of life (VRQOL) in patients with glaucoma. METHODS: We included 826 patients with primary open-angle glaucoma (POAG) enrolled in the prospectively designed Life Quality of Glaucoma Patients Who Underwent Treatment (LIGHT) study organized by the Korean Glaucoma Society. We divided the integrated binocular visual field (IVF) into four regions and evaluated the associations between Rasch-analysed 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) and location of the IVF using univariate and hierarchical multivariable linear regression. RESULTS: Mean deviation (MD) of the IVF at superior centre showed the lowest value among the four regions. Multivariable linear regression analysis revealed significant correlation of the composite score and all subscales of the NEI VFQ-25 except ocular pain and near activities at each of four IVF regions. Mean deviation at superior centre showed significant correlation with composite score (R2  = 0.181), near activities (R2  = 0.175), and social functioning (R2  = 0.166); MD at superior periphery showed highest correlation with role difficulties (R2  = 0.137); MD at inferior centre showed highest correlation with driving (R2  = 0.145); and MD at inferior periphery showed significant correlation with distance activities (R2  = 0.214) and dependency (R2  = 0.119). CONCLUSION: Four different regions of the IVF had a similarly important impact on subscales of the NEI VFQ-25 in glaucoma patients. Preservation of the superior field should be considered as much as that of the inferior field for maintaining a good VRQOL in patients with glaucoma.

Conjunctivolimbal autograft using a fibrin adhesive in pterygium surgery.

PURPOSE: To evaluate the efficacy and safety of fibrin bioadhesive in conjunctivolimbal autograft surgery for primary pterygium. METHODS: Thirty-six eyes in 34 patients were reviewed with nasal primary pterygium who were treated with pterygium excision with superior conjunctivolimbal transplantation with fibrin bioadhesive. Surgical durations were recorded and the patients were followed up on the first day after surgery and then at 1, 2, 4, 8 and 12 weeks postoperatively. The graft-recipient site attachments were examined and subjective symptoms of patients were recorded at every follow-up examinations. RESULTS: The mean patient age was 57.9+/-10.1 (ranging from 33 to 83) years. The mean follow-up period was 22.05+/-5.78 weeks. The mean surgery time was 18.04+/-5.65 minutes. The subjective symptoms (pain, foreign body sensation, tearing and discomfort) disappeared in 23 of 36 eyes (64%) in one week after surgery, and all discomforts subsided within two weeks after surgery in all patients. The conjunctivolimbal autograft was correctly positioned and fixed in 34 of 36 eyes (94.4%) throughout the follow-up period. Graft dehiscence was seen in two eyes (5.6%), one eye was treated with remedial sutures, and the other eye showed a spontaneous healing without remedial sutures. Transient graft edema occurred in four eyes (11.2%) but subsided spontaneously within a month. There were no cases of pterygium regrowth or complications due to the fibrin bioadhesive. CONCLUSIONS: The use of fibrin bioadhesive in conjunctivolimbal autograft surgery in primary pterygium simplifies surgical techniques, shorten surgical duration, and produce less postoperative subjective symptoms . Therefore, the fibrin bioadhesive is a safe and effective tool to attach conjunctivolimbal autograft in primary pterygium surgery.

Long-term efficacy and safety of ExPress implantation for treatment of open angle glaucoma.

AIM: To compare the long-term efficacy and safety of ExPress implantation and standard trabeculectomy in patients with primary open angle glaucoma (POAG). METHODS: In this retrospective study, we compared 17 eyes treated by ExPress implantation with 23 eyes treated by trabeculectomy. Efficacy was assessed according to the relevant intraocular pressure (IOP) values and success rates during the first year of follow-up. Postoperative corneal endothelial cell loss was also compared. RESULTS: The number of antiglaucoma medications and the IOP reduction were similar between the 2 groups during the follow-up period. Although the mean IOP was similar, the IOP-fluctuation rate during the early postoperative period was significantly lower in the ExPress group than in the trabeculectomy group (P=0.038). A Kaplan-Meier survival curve analysis showed no significant success-rate difference between the groups (P=0.810). The corneal endothelial cell loss rate, moreover, was significantly lower in the ExPress group (P=0.05). CONCLUSION: ExPress implantation compared with trabeculectomy showed similar IOP-reduction and success rates along with lower IOP fluctuation and endothelial cell loss rates. For this reason, it can be considered to be the treatment of choice for patients with advanced glaucoma or low corneal endothelial cell density.

Choroidal Thickness Variation According to Refractive Error Measured by Spectral Domain-optical Coherence Tomography in Korean Children.

PURPOSE: To assess choroidal thickness (CT) variation according to refractive errors using enhanced-depth imaging optical coherence tomography. METHODS: Eighty-nine eyes (in 89 children) <±6 diopter were categorized into three groups: hyperopia, emmetropia, and myopia, according to refractive error, and underwent choroidal scans using enhanced-depth imaging-optical coherence tomography. CT was measured at the fovea and at 1 mm and 3 mm nasal (N1 and N3), temporal (T1 and T3), superior (S1 and S3), and inferior (I1 and I3) from the fovea. RESULTS: Mean foveal CTs were 346.86 µm, 301.97 µm, and 267.46 µm in the hyperopia, emmetropia, and myopia groups, respectively (p < 0.05). CTs at N3 and T3 were 214.59 µm and 318.68 µm, 163.92 µm and 320.79 µm, and 153.93 µm and 295.61 µm in the hyperopia, emmetropia, and myopia groups, respectively (p < 0.05). All CTs in the hyperopia group were thicker than those of other groups (p < 0.05). Fovea was thickest and was significantly thicker than at N3 and I3 in hyperopia (p < 0.05). T3 thickness in the emmetropia and myopia groups was greater than thickness at other areas, particularly the nasal and inferior choroids (p < 0.05). CT was positively correlated with spherical equivalent (p = 0.029). CONCLUSIONS: In Korean children, CTs were greater in the hyperopia group than in the emmetropia and myopia groups. The temporal choroid was thicker than the nasal choroid, regardless of the refractive error. The thickest location in the hyperopia group was the fovea; however, the temporal choroid was thickest in the emmetropia and myopia groups.

Inhibition of Pterygium Fibroblast Migration and Outgrowth by Bevacizumab and Cyclosporine A Involves Down-Regulation of Matrix Metalloproteinases-3 and -13.

We examined the connection between matrix metalloproteinase (MMP) expression/activity and pterygium fibroblast migration, and how these were affected by bevacizumab and/or cyclosporine A (CsA). Fibroblasts were obtained from 20 pterygia and 6 normal conjunctival specimens. Expression levels of MMP-3 and MMP-13 were examined after bevacizumab administration. Immunofluorescence staining was used to examine expression of both MMPs in fibroblasts migrating out from explanted pterygium tissues. Rates of cell migration from explant-cultured pterygia tissues and scratch-wounded confluent pterygium fibroblasts were examined in the presence of MMP-3 or MMP-13 inhibitors, as well as bevacizumab and/or CsA. A scratch wound healing migration assay was performed to determine the effects of bevacizumab and/or CsA. Protein expression of both MMPs in pterygium tissues and in cells migrating from organ-cultured pterygium tissues was greater than that observed in normal cells. Inhibition of the activities of both MMPs decreased their expression levels; these were also significantly reduced in bevacizumab-injected pterygium tissues. Bevacizumab significantly reduced the expression of both MMPs and cell migration. Pretreatment with CsA prior to bevacizumab exposure markedly inhibited cell migration and the expression of both MMPs. CsA enhanced the inhibitory effects of bevacizumab on pterygium fibroblast migration in vitro, possibly by inhibiting expression of both MMPs. These findings suggest that combined CsA and bevacizumab treatment may provide a potential therapeutic strategy for reducing the rate of pterygium recurrence.

Vision-related Quality of Life in Korean Glaucoma Patients.

PURPOSE OF THE STUDY: The purpose of the study was to evaluate vision-related quality of life in Korean glaucoma patients and to explore the associated factors. METHODS: A total of 907 glaucoma patients were recruited from the prospectively designed LIGHT (Life quality of the glaucoma patient who underwent treatment) study organized by the Korean Glaucoma Society. Basic questionnaire that included items related to socioeconomic status, comorbidity, and lifestyle, and the validated Korean version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were collected. The Rasch score, a logit-based interval scale estimate to summarizing the NEI VFQ-25 responses, was calculated. The univariate and multivariable regression models were used to evaluate associations between the Rasch score and variables. RESULTS: The mean patient age was 58.1±14.1 years, visual field mean deviation (VF MD) of the better and worse eyes was -4.92±6.14 and -9.77±8.31 dB, binocular-integrated VF (IVF) MD was -3.55±5.31 dB, respectively. The lower NEI VFQ-25 Rasch score showed a significant association with the presence of other ocular diseases (P=0.020), a high school level of education or less [vs. university (P=0.006), vs. graduate school or higher (P=0.019)], an anxious personality [vs. a moderate personality (P<0.001), vs. a relaxed personality (P<0.001)], the number of glaucoma medications in use (P=0.049), worse eye visual acuity (P<0.001), and IVF MD (P<0.001). CONCLUSIONS: Visual function parameters are important for the vision-related quality of life of Korean glaucoma patients, notably for worse eye visual acuity and IVF MD. However, social factors, self-assessed personality, and treatment-related issues are also substantial predictors of overall life quality.

Comparison of the Efficacy of Fluorometholone With and Without Benzalkonium Chloride in Ocular Surface Disease.

PURPOSE: The purpose of this study was to compare the cytotoxicity and antiinflammatory effect of preserved and unpreserved 0.1% fluorometholone (FML). METHODS: Drug-induced morphological changes and cytotoxicity were examined in human corneal epithelial cells. Dry eye was induced in mice by treatment with 0.2% benzalkonium chloride (BAC) for the first 2 weeks, and then, the eyes (4 groups; Normal saline, BAC, preserved FML, and unpreserved FML) were treated thrice daily with each formulation for the next 2 weeks. Corneal tissues were embedded in paraffin and stained with hematoxylin and eosin for histopathological examination. Immunofluorescence staining was performed for tumor necrosis factor-α, interleukin-6, and human leukocyte antigen-DR. Terminal deoxynucleotidyl transferase dUTP nick end labeling assay was performed to evaluate drug-induced cytotoxicity. RESULTS: BAC and preserved FML caused cell shrinkage and detachment from the plate in a dose-dependent manner, and cell viability decreased significantly. However, cytotoxicity was reduced on treatment with unpreserved FML. Hematoxylin-eosin staining revealed surface desquamation, irregular surface, loss of cell borders, and stromal shrinkage in the group treated with BAC. On BAC exposure, tumor necrosis factor-α, interleukin-6, and human leukocyte antigen-DR were strongly detected, and cytotoxicity was markedly increased, as evidenced by a positive result in the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Ocular surface damage and inflammation were slightly reduced on treatment with preserved FML. In comparison, unpreserved FML did not induce morphological changes; moreover, decreased cell cytotoxicity and ocular surface inflammation were observed. CONCLUSIONS: The cytotoxicity of antiinflammatory eye drops evaluated in this study was induced by the preservative BAC. Accordingly, unpreserved FML is more effective than preserved eye drops in decreasing ocular inflammation.

Asymmetry analysis of the retinal nerve fiber layer thickness in normal eyes using optical coherence tomography.

PURPOSE: To investigate the asymmetry of the retinal nerve fiber layer thickness (RNFLT) with respect to the horizontal and vertical meridian and between the right and left eye in normal subjects. METHODS: The RNFLT was measured in 121 normal volunteers by optical coherence tomography (OCT). The RNFLT was analyzed by dividing the circle scanning area (diameter 3.4 mm) around the optic disc into 4 quadrants and 12 sectors. RESULTS: There was a significant difference between the RNFLT of the nasal and temporal quadrant in individual eyes. There was a significant difference between the RNFLT of corresponding sectors with respect to the vertical or horizontal meridian in individual eyes. The nasal and temporal RNFLTs were asymmetrical between the right and left eye in the quadrant and sector analysis. The RNFLT of the nasal and temporal quadrant was thicker in the right eye. The nasal and inferior RNFLT measured by OCT had a significant correlation with degree of refractive error. CONCLUSIONS: In normal subjects without significant anisometropia, there was significant asymmetry of the RNFLT for each eye as well as between the right and left eye.

Efficacy and Safety of Glaucoma Patients' Switch from a 2% Dorzolamide/0.5% Timolol Fixed-Combination Brand-Name Drug to Its Generic Counterpart.

PURPOSE: To compare the efficacy and safety of the brand-name and generic 2% dorzolamide/0.5% timolol fixed-combination (DTFC) drugs in glaucoma patients. METHODS: This was a prospective single-center study, in which patients using only the brand-name DTFC (Cosopt(®); Merck and Co, Inc.) drug and those using Cosopt with prostaglandin analogs (PGs) were enrolled. In the patients using Cosopt (Group A) and Cosopt with PGs (Group B), Cosopt was switched to its generic counterpart (Batidor(®); Bausch & Lomb, Inc.). The intraocular pressure (IOP) was measured before the switch and 4, 8, and 12 weeks after the switch in both groups. The questionnaire on the discomfort symptoms and on the discomfort score for the use of eye drops was answered by the patients in both groups before the switch and 12 weeks after the switch. RESULTS: A total of 112 patients were enrolled in the study, 62 in Group A and 50 in Group B. The IOPs before the switch and 4, 8, and 12 weeks after the switch showed no statistical difference in both groups (P>0.05). There were higher incidences of bitter taste and blurring with Cosopt, and there was a higher incidence of headache with Batidor in both groups, but no significant differences (P>0.05) were noted. There was, likewise, no significant difference in the discomfort score between 2 drugs in both groups (P>0.05). CONCLUSIONS: After the switch, the IOP-lowering effect of the generic drug Batidor was similar to that of the brand-name drug Cosopt in the monotherapy and combination therapy with PGs. No significant differences were found in terms of the discomfort symptoms and discomfort score between the 2 drugs.

In Vivo Effects of Preservative-free and Preserved Prostaglandin Analogs: Mouse Ocular Surface Study.

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-α, 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.

Cyclosporine A Downregulates MMP-3 and MMP-13 Expression in Cultured Pterygium Fibroblasts.

PURPOSE: To investigate the regulation of matrix metalloproteinase (MMP)-3 and MMP-13 expression over time and in the presence of cyclosporine A (CsA) in primary cultured human pterygium fibroblasts. We also examined the effects of CsA on cultured human pterygium fibroblasts. METHODS: Primary cultured human pterygium fibroblasts subjected to scratch assays were exposed to 1 and 100 µg/mL of CsA for 3 or 10 minutes. Cells were washed with Dulbecco phosphate-buffered saline, and then incubated with serum-depleted Dulbecco modified Eagle medium/F-12 medium for 48 hours. Expression levels of MMP-3 and MMP-13 proteins and the corresponding mRNA transcripts were determined by western blotting and reverse transcription polymerase chain reaction assays, respectively. RESULTS: Migration of cultured pterygium fibroblast cells was suppressed by pretreatment with CsA compared with controls in a time-dependent and dose-dependent manner (3 minutes, 50.6% ± 1.1 in 1 µg/mL, 60.0% ± 1.2 in 100 µg/mL; 10 minutes, 59.8% ± 5.7 in 1 µg/mL, 60.5 ± 2.4 in 100 µg/mL, respectively, P < 0.01). Pretreatment with CsA also reduced the mRNA (P < 0.05) and protein expression levels (P < 0.05). CONCLUSIONS: CsA was actively involved in the migration of pterygium fibroblasts. Cell migration is inhibited in response to CsA through the inhibition of MMP-3 and MMP-13 expression. These findings reveal the therapeutic potential of CsA on pterygium progression. Further studies will be necessary to elucidate the precise intracellular signal mechanism responsible for CsA-induced downregulation of MMPs in pterygium fibroblasts.

Comparison of the thickness of the lamina cribrosa and vascular factors in early normal-tension glaucoma with low and high intraocular pressures.

PURPOSE: To compare the thickness of the lamina cribrosa (LC) and vascular factors of early normal-tension glaucoma (NTG) patients with high and low intraocular pressure (IOP) that are expected to be associated with the development of glaucoma. METHODS: Seventy-one Korean NTG patients with low IOP (the highest IOP <15 mmHg, 40 patients) and high IOP (the lowest IOP >15 mmHg, 31 patients) were included in this study. The thickness of LC and vascular factors were compared. The thickness of the LC was measured using the enhanced depth imaging method with spectral domain optical coherence tomography (Heidelberg Spectralis). RESULTS: The mean thickness of the central LC was 190.0 ± 19.2 µm in the low IOP group and 197.8 ± 23.6 µm in the high IOP group, but there was no statistical significant difference between the two groups (p > 0.05). The prevalence of self-reported Raynaud phenomenon was significantly higher in the low IOP group (33.0%) than the high IOP group (10.3%, p = 0.04). CONCLUSIONS: The laminar thickness did not significantly differ between the high and low IOP groups. However, the prevalence of Raynaud phenomenon was higher in the low IOP groups. These results suggest that the development of glaucoma with low IOP patients may be more influenced by peripheral vasospasm, such as Raynaud phenomenon, rather than laminar thickness in NTG.

In vitro effects of preservative-free and preserved prostaglandin analogs on primary cultured human conjunctival fibroblast cells.

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.

Prognostic factors for the success of laser iridotomy for acute primary angle closure glaucoma.

PURPOSE: To identify the prognostic factors for successful laser iridotomy for acute angle-closure glaucoma (AACG). METHODS: We retrospectively reviewed the medical records of 77 eyes of 77 patients with AACG with initial intraocular pressure (IOP) above 40 mmHg. All of the patients received maximum tolerable medical therapy (MTMT) followed by laser iridotomy. In order to comparatively analyze the factors affecting successful laser iridotomy, an increase in IOP on follow-up was defined as increase in IOP greater than 21 mmHg requiring medical or surgical treatment. RESULTS: Successful laser iridotomy was achieved in 59.7% (46/77 eyes). Thirty-one eyes (40.3%) exhibited increased IOP on follow-up, and of these, 30 eyes developed an increase in IOP within six months after the first attack. The success rate was higher (92.9%) in 42 patients who had greater than 30% IOP reduction by MTMT at the first attack compared to the 35 patients whose IOP reduction was less than 30%, of which 24 eyes (72.7%) showed more than 30% IOP reduction after intravenous hyperosmotic agent treatment (p=0.012). The success rate was higher in patients treated within seven days after the development of symptoms than in those treated after seven days (Odds ratio, 4.51; 95% confidence interval, 1.38 to 14.75). CONCLUSIONS: Our data suggest that we can expect successful IOP control after laser iridotomy in eyes with AACG if the patient can be treated within seven days after the development of symptoms and if the IOP reduction was more than 30% by MTMT.