Clinical comparative analysis of culture-proven bacterial keratitis according to prior topical steroid use: a retrospective study in a tertiary referral center of South Korea.

This study analyzed the clinical characteristics of patients exposed to topical steroids before bacterial keratitis diagnosis (the prior topical steroid use, PS group), and compared these with those of the non-exposed group (the no prior topical steroid use, NPS group). We retrospectively analyzed 194 patients (PS, 34; NPS, 160) with culture-proven bacterial keratitis between 2007 and 2016. The microbiological profiles, epidemiology, predisposing factors, clinical characteristics, and treatment outcomes of PS and NPS were compared, and the risk factors for surgical intervention were evaluated. Pseudomonas spp. and Staphylococcus spp. were the most common isolates in PS and NPS, respectively, and no significant difference in the strain distribution between the two groups were observed. Significant differences were observed between PS and NPS for previous ocular surface disease (41.2%: 23.8%), initial BCVA < 0.1 (70.6%: 49.4%), epithelial defect size ≥ 5 mm2 (64.7%: 41.2%), epithelial healing time > 14 days (55.9%: 37.3%), and surgical intervention (23.5%: 8.8%). Prior topical steroid use, strong steroid use, and long-term steroid use groups were included in significant risk factors for surgical intervention. Previous exposure to topical steroids before the diagnosis of bacterial keratitis was associated with a worse initial clinical presentation and treatment outcomes. Additional multicenter studies should be conducted in the future.

Clinical comparative analysis of bacterial keratitis according to contact lens use: a retrospective study in a tertiary referral center of South Korea.

PURPOSE: To compare the clinical aspects and treatment outcomes of contact lens-related bacterial keratitis (CLBK) and non-CLBK patients. METHODS: Altogether 217 patients of bacterial keratitis (CLBK; 62, non-CLBK; 155) hospitalized between January 2012 and December 2020 were retrospectively analyzed for epidemiology, microbiological profiles, predisposing factors, clinical characteristics, and treatment outcomes. Poor treatment outcomes (PTO) were defined as a final BCVA < 0.3 (Snellen), a decreased visual acuity after treatment, complications, or surgical intervention. Relative importance of the initial clinical features leading to PTO was assessed using the random forest model and two-proportion Z-test. RESULTS: The most common predisposing factors were sleeping with wearing CL (51.6%) in the CLBK group and trauma (55.5%) in the non-CLBK group. There were significant differences between the two groups in mean age (35.1:55.1 years, p < 0.001), female sex (56.5:34.8%, p = 0.003), symptom duration (6.2:6.9 days, p = 0.019), gram-negative organisms (83.3:48.3%, p = 0.008), epithelial healing time (8.5:14.1 days, p = 0.004), final BCVA (0.15:0.46 logMAR, p = 0.015), and PTO (9.7:21.9%, p = 0.035). For the entire group, the initial BCVA < 0.1 (27.9%), symptom duration ≥ 5 days (19.4%), age ≥ 60 years (16.4%), and hypopyon (14.0%) were important initial clinical features leading to PTO in the random forest model. In CLBK group, the type of CL or CL-related history was not significantly related to PTO. CONCLUSION: CLBK patients had a higher proportion of females, younger age, gram-negative bacteria, and better treatment outcomes than those of non-CLBK patients. There were no significant risk factors leading to PTO in either the type of CL or CL-related history.

Role of the JAK/STAT pathway in a streptozotocin-induced diabetic retinopathy mouse model.

PURPOSE: The Janus tyrosine kinase and signal transducers and activators of transcription (JAK/STAT) pathway is involved in vascular endothelial growth factor (VEGF) expression, but the role of this pathway in diabetic retinopathy (DR) remains unclear. We investigated the role of the JAK/STAT pathway on DR and VEGF expression using a streptozotocin (STZ)-induced DR mouse model. METHODS: Cultured ARPE-19 cells were exposed to high-glucose conditions and treated with JAK/STAT inhibitors (JAK inhibitor I [JAKiI], tofacitinib, STAT3 inhibitor [STAT3i]) for 48 h. Reverse-transcription polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay were used to investigate p-JAK/STAT and VEGF expression. Diabetes was induced by intraperitoneal injection of STZ (50 mg/kg) in C57BL/6 mice for 5 days. DR development was evaluated every 4 weeks. JAK/STAT inhibitors were administered for 8 weeks. Immunofluorescence was used to measure the activation status of the JAK/STAT pathway and VEGF production in the retinal tissue. RESULTS: In ARPE-19 cells exposed to high-glucose conditions, the mRNA and secretory protein levels of VEGF, p-JAK1, p-JAK2, p-STAT3, and p-STAT5 levels were significantly increased. Treatment with JAKiI, tofacitinib, and STAT3i significantly suppressed VEGF to basal levels at both the mRNA and secretory levels in vitro. In STZ-induced mice, retinal vascular leakage, p-JAK1, p-JAK2, p-JAK3, p-STAT3, and VEGF were significantly increased after diabetes induction. Diabetes-induced retinal vascular leakage was significantly reduced by treatment with JAKiI and tofacitinib. Increased p-JAK1 and VEGF in STZ-induced mice were significantly reduced by JAKiI (p < 0.05, p < 0.001) and tofacitinib (p < 0.001, respectively). CONCLUSION: JAK1 may be more involved in VEGF production and DR progression in mice than JAK2, JAK3, and STAT3.

Comparative Analysis of the Clinical Aspects and Treatment Outcomes of Stenotrophomonas maltophilia Keratitis and Pseudomonas aeruginosa Keratitis.

OBJECTIVES: We analyzed the clinical aspects and treatment outcomes of Stenotrophomonas maltophilia (SM) keratitis and Pseudomonas aeruginosa (PA) keratitis. METHODS: Medical records of 55 inpatients with culture-proven SM (n=21) and PA (n=34) keratitis were retrospectively reviewed. Predisposing factors, clinical characteristics, and treatment outcomes were compared between the SM and PA groups. RESULTS: The mean symptom duration was longer in the SM group than in the PA group (10.4:4.3 days; P=0.012). The most common predisposing factor was corneal trauma (47.6%) in the SM group and contact-lens wear (38.2%) in the PA group. There were no differences in the mean epithelial defect size (12.7:11.9 mm2; P=0.861), hypopyon (33.3%:44.1%; P=0.428), surgical treatment (4.8%:14.7%; P=0.390), or poor clinical outcomes (26.8%:30.3%; P=0.760) between the SM and PA groups. In multivariate logistic regression, risk factors for poor clinical outcomes were hypopyon (odds ratio [OR], 52.00; P=0.010) in the SM group and symptom duration≥7 days (OR, 44.32; P=0.015), age≥60 years (OR, 21.13; P=0.019), and hypopyon (OR, 15.20; P=0.038) in the PA group. CONCLUSION: Compared with PA keratitis, SM keratitis had slower progression, and its clinical characteristics and treatment results were not worse. In both groups, hypopyon was the risk factor for a poor clinical outcome.

Clinical analysis of microbiologically proven fungal keratitis according to prior topical steroid use: a retrospective study in South Korea.

BACKGROUND: To compare the clinical characteristics and treatment outcomes of microbiologically proven fungal keratitis between users and non-users of prior topical steroids (PS and NPS, respectively). METHODS: Eighty-three cases with microbiologically proven fungal keratitis between January 2000 and December 2016 were reviewed retrospectively. Diagnosis of fungal keratitis was made through potassium hydroxide smear, culture, PCR, or biopsy. Baseline epidemiology, predisposing factors, clinical characteristics, microbiological profiles, and treatment outcomes were evaluated and compared between the PS and NPS groups. Treatment failure was defined as any case with complications or requiring surgery. The risk factors for treatment failure were evaluated using multivariate logistic regression in the overall cohort. RESULTS: A total of 30 cases with PS group and 53 cases with NPS group were included. Of these, sixteen fungal isolates were identified in the PS group and 14 isolates in the NPS group. Candida was the most common organism in both groups (6 cases, respectively), while Aspergillus (4 cases) was found only in the PS group (p = 0.103). No significant differences were observed in the mean age, sex, occupational distribution, epithelial defect size, hypopyon, and presenting best-corrected visual acuity (BCVA) between the two groups. Differences were observed between the PS and NPS groups in terms of previous ocular surface disease (OSD) (43.3% vs. 22.6%, p = 0.048) and deep infiltration (53.3% vs. 32.1%, p = 0.057). Regarding treatment outcomes, final BCVA < 0.1 (60% vs. 44.2%, p = 0.133), the use of voriconazole (topical 10% vs. 0%, p = 0.044; systemic 23.3% vs. 1.9%, p = 0.003), surgical intervention (43.3% vs. 20.8%, p = 0.029), and treatment failure (46.7% vs. 22.6%, p = 0.023) were more common in the PS group than in the NPS group. The significant risk factors for treatment failure were hypopyon (odds ratio [OR] 6.01, p = 0.005) and deep infiltration (OR 4.38, p = 0.013). CONCLUSIONS: Previous OSD and deep infiltration were more common in the PS group compared to the NPS group. The PS group also experienced worse disease progression and treatment outcomes. These results highlight the need for paying attention to the use of steroids in clinical practice.

Comparison of clinical characteristics and antibiotic susceptibility between Pseudomonas aeruginosa and P. putida keratitis at a tertiary referral center: a retrospective study.

BACKGROUND: To compare clinical characteristics and antibiotic susceptibilities in patients with Pseudomonas aeruginosa (PA) and P. putida (PP) keratitis at a tertiary referral center in South Korea. METHODS: Forty-nine cases of inpatients with culture-proven PA and PP keratitis were reviewed retrospectively between January 1998 and December 2017. We excluded cases of polymicrobial infection. Epidemiology, predisposing factors, clinical characteristics, antibiotic susceptibilities, and treatment outcomes were compared between the PA and PP groups. The risk factors for poor clinical outcome were evaluated on the basis of the total cohort and analyzed using multivariate logistic regression. RESULTS: A total of 33 eyes with PA keratitis and 16 eyes with PP keratitis were included. The mean age was 47.0 years in the PA group and 59.3 years in the PP group (p = 0.060). Differences were observed between the PA and PP groups in hypopyon (45.5% vs 6.3%, p = 0.006) and symptom duration (4.3 vs 9.5 days, p = 0.022). The most common predisposing factor for PA was wearing contact lenses (36.4%) and that for PP was corneal trauma (62.5%). No significant differences were observed in sex, previous topical steroid use, systemic disease, or duration of hospitalization between the two groups. The PA and PP groups both demonstrated good efficacy of colistin (both 100%), tobramycin (93.3%, 100%), ceftazidime (93.9%, 87.5%), and ciprofloxacin (96.6%, 87.5%). Imipenem (100% vs 81.3%, p = 0.030), piperacillin (96.6% vs 75%, p = 0.047), and ticarcillin (85% vs 0%, p < 0.001) showed significantly lower efficacy in the PP group than in the PA group. A poor clinical outcome was observed in 31.2% of the PA group and 37.5% of the PP group (p = 0.665). The risk factors for poor clinical outcome were previous ocular surface disease (odds ratio 10.79, p = 0.012) and hypopyon (odds ratio 9.02, p = 0.024). CONCLUSIONS: The PA group was more closely associated with younger age, wearing contact lenses, shorter symptom duration, and hypopyon, whereas the PP group was more closely associated with elderly age, corneal trauma, and decreased efficacy of the beta-lactams. Clinical outcomes were not significantly different between the two groups. Previous ocular surface disease and hypopyon were the risk factors for poor clinical outcome.

Biodegradable collagen matrix (Ologen™) implant and conjunctival autograft for scleral necrosis after pterygium excision: two case reports.

BACKGROUND: Scleromalacia, in the form of scleral thinning, melting, and necrosis, is a potentially serious complication of pterygium excision. This study introduces a new biodegradable material, Ologen™ collagen matrix (OCM), to repair scleral thinning as an alternative to preserved scleral tissue, and evaluates the long-term outcomes of OCM for ocular surface reconstruction surgery. CASE PRESENTATION: Two cases of possibly mitomycin C (MMC)-associated marked scleral thinning after pterygium excision with 0.02 % topical MMC for 2-weeks were included in this study. An OCM graft at the scleral thinning area and conjunctival autograft (CAU) were performed on both patients. The scleral defect size was measured and its margin was marked with a biopsy punch. The margin of the scleral thinning area was trimmed by Vannas scissors and the OCM was cut using a circular-shape biopsy punch of the same size. The OCM was sutured with a recipient scleral wall using 10-0 nylon interrupted sutures. Free CAU was harvested from the superonasal bulbar conjunctiva with a punch biopsy 1-mm larger in diameter than that of the OCM. The previously sutured OCM bed was covered with CAU and the graft was secured with 10-0 nylon interrupted sutures. Both patients were examined periodically for over two years by assessing graft thickness and surface vascularization using a slit lamp biomicroscope. Reepithelialization of the ocular surface was observed within three to six days after surgery. Ocular discomfort and inflammation ceased in both patients as the ocular surface quickly stabilized. The entire graft site remained intact and provided a good healthy ocular surface with fluorescein stain negative intact epithelium and good vascularization of grafted conjunctiva. Epithelial defects and scleral thinning did not recur in either patient over the two year follow-up period. CONCLUSION: For treatment of a possibly MMC-associated scleral necrosis following the surgical excision of the pterygium, an OCM graft with CAU is highly recommended for good clinical outcomes and low recurrence rates. With the clinical results of this study, the new biodegradable Ologen™ collagen matrix qualifies as an alternative treatment to scleral tissue for ocular surface reconstruction.

Binding of Cdc42 to phospholipase D1 is important in neurite outgrowth of neural stem cells.

We previously demonstrated that phospholipase D (PLD) expression and PLD activity are upregulated during neuronal differentiation. In the present study, employing neural stem cells from the brain cortex of E14 rat embryos, we investigated the role of Rho family GTPases in PLD activation and in neurite outgrowth of neural stem cells during differentiation. As neuronal differentiation progressed, the expression levels of Cdc42 and RhoA increased. Furthermore, Cdc42 and PLD1 were mainly localized in neurite, whereas RhoA was localized in cytosol. Co-immunoprecipitation revealed that Cdc42 was bound to PLD1 during differentiation, whereas RhoA was associated with PLD1 during both proliferation and differentiation. These results indicate that the association between Cdc42 and PLD1 is related to neuronal differentiation. To examine the effect of Cdc42 on PLD activation and neurite outgrowth, we transfected dominant negative Cdc42 (Cdc42N17) and constitutively active Cdc42 (Cdc42V12) into neural stem cells, respectively. Overexpression of Cdc42N17 decreased both PLD activity and neurite outgrowth, whereas co-transfection with Cdc42N17 and PLD1 restored them. On the other hand, Cdc42V12 increased both PLD activity and neurite outgrowth, suggesting that active state of Cdc42 is important in upregulation of PLD activity which is responsible for the increase of neurite outgrowth.