Long-term efficacy and safety of intravenous injection of clonal mesenchymal stem cells derived from bone marrow in five adults with moderate to severe atopic dermatitis.

Atopic dermatitis is a chronic and relapsing inflammatory skin disease that is treated with immunosuppressants. However, long-term use of immunosuppressants may cause toxicity and severe side-effects. To confirm the long-term efficacy and safety of clonal mesenchymal stem cell therapy, we performed investigator-initiated clinical trials and long-term observation in five adult patients with moderate to severe atopic dermatitis that was refractory to conventional treatments. The clinical response assessment values such as Eczema Area and Severity Index (EASI) improved significantly at 16 weeks, and 80% (4/5) of the patients achieved EASI-50 after one or two treatment cycles. Patients were observed for long-term efficacy and safety for an average of 38 weeks (range, 16-86) and showed no serious side-effects. Among the cytokines tested, CCL-17, interleukin (IL)-13, and IL-22 significantly decreased at the end-point of the five participants, two patients who maintained good clinical response over 84 weeks showed increased IL-17 cytokine levels in the blood.

Acrosyringeal variant of extragenital lichen sclerosus et atrophicus.

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory dermatosis of the anogenital area, and approximately 15% to 20% of patients with LSA have extragenital lesions. Here, we report the case of an 18-year-old Korean man presenting with multiple asymptomatic punctated hypopigmented atrophic macules on the dorsa of both feet. Dermoscopic examination revealed hypopigmented atrophic macules with several central keratotic plugs. The histopathologic findings indicated LSA but were confined to the acrosyringium. Based on the clinical and histopathological findings, the patient was diagnosed with an acrosyringeal variant of extragenital LSA. The patient in this case showed a unique histopathological finding in which the typical features of LSA were confined to the acrosyringium, as well as an unusual clinical presentation of non-coalescing atrophic punctate macules on the dorsum of the feet.

Therapeutic Effect of Glucosamine on an Atopic Dermatitis Animal Model.

BACKGROUND: Recent studies have reported that glucosamine (GlcN) showed therapeutic effects in allergic diseases such as asthma and rhinitis, and its mechanisms include the suppression of T helper type 2 immune responses and the nuclear factor-κB pathway. OBJECTIVE: We aimed to investigate the effect of GlcN on atopic dermatitis (AD) in an animal model. METHODS: Twenty-five BALB/c mice were divided into five groups (groups A~E). Group A was the phosphate-buffered saline (PBS)-treated group without AD induction. Group B was the PBS control group with AD induction. Groups C to E were the AD induction groups, which were treated with three different doses of GlcN (10 mg, 20 mg, and 40 mg, respectively). Histopathological examination was performed after GlcN administration. Interleukin (IL)-4, IL-13, and IL-17 cytokine levels were measured by enzyme-linked immunosorbent assay using skin biopsy specimens. Serum total immunoglobulin E (IgE) concentrations were measured before and after administration with GlcN or PBS. RESULTS: Clinical dermatitis scores decreased with increasing GlcN dose (p<0.001). Concentrations of tissue IL-13 and IL-17 decreased after GlcN administration (each group: p=0.002 and p<0.001, respectively), but the concentrations of tissue IL-4 did not show differences across groups. Serum IgE levels tended to be lower after GlcN administration (p=0.004). Histopathological scores were not significantly different among groups B~E (p=0.394). CONCLUSION: GlcN improved AD symptoms and decreased tissue IL-13, IL-17, and serum total IgE levels in an animal model.

Baseline predictors of visual acuity and retinal thickness in patients with retinal vein occlusion.

This study investigated the baseline predictors of best corrected visual acuity (BCVA) and central retinal thickness (CRT) at 6 months in patients with treatment-naïve branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). This multicenter, interventional case series included 208 BRVO and 123 CRVO patients with follow-up period of 6 months or more. Outcome measures of BCVA (logMAR) included absolute change from baseline and a gain or loss of ≥ 0.3 from baseline. Outcome measures of CRT included absolute change from baseline and a measurement of ≤ 250 µm or ≥ 400 µm at 6 months. Univariate and multiple regression analyses were done to find baseline predictors. For BRVO, younger age, worse baseline BCVA, and shorter duration of symptom were associated with more gain in BCVA. For CRVO, worse baseline BCVA was associated with more gain in BCVA. For CRT outcomes, higher baseline CRT predicted greater decrease at 6 months in both BRVO and CRVO. Younger age and better baseline BCVA were associated with an increased likelihood of measurement of a ≤ 250 µm outcome for BRVO and CRVO, respectively. For CRVO, smoking was associated with greater decrease from baseline and decreased likelihood of measurement of a CRT ≥ 400 µm at 6 months. In conclusion, several baseline factors including age, symptom duration, and baseline BCVA and CRT are associated with BCVA and CRT outcomes at 6 months, which may help to predict disease course for RVO patients.

Improved visual outcome with early treatment in macular edema secondary to retinal vein occlusions: 6-month results of a Korean RVO study.

PURPOSE: To determine the correlation between the duration of macular edema (ME) and visual outcomes among Korean patients with retinal vein occlusion (RVO). METHODS: Multicenter, interventional case series. Treatment-naive patients (n = 249) with branch or central RVO (BRVO/CRVO) and ME for <6 months were included. We assessed the correlation between the duration of ME and treatment outcomes including the mean logarithm of the minimum angle of resolution best-corrected visual acuity (logMAR BCVA) improvement, the proportion of patients achieving at least a 3-line gain in BCVA, and the mean reduction in central retinal thickness (CRT) at 6 months. RESULTS: One hundred and fifty-six patients with BRVO and 93 patients with CRVO were divided into five groups based on the duration of ME (<2, 2-4 weeks, 1-2, 2-3, 3-6 months); the mean baseline BCVA and CRT among the groups did not differ significantly. In BRVO, the mean logarithm of the minimum angle of resolution (logMAR) BCVA improvements in the groups were 0.51, 0.32, 0.17, 0.19, and 0.13, respectively (P = 0.002). The respective percentages of at least 3-line gains were 64, 53, 39, 38, and 21 % (P < 0.001). The BCVA didn't significantly improve in CRVO. The decrease in CRT was not correlated significantly with the duration of ME in either disease. CONCLUSIONS: Treatment of BRVO as early as 2 weeks after onset of ME enhanced the visual outcome; there was no correlation in the patients with CRVO. This finding supports the current trend favoring early treatment to obtain better visual outcomes in patients with BRVO.

Baseline characteristics and risk factors of retinal vein occlusion: a study by the Korean RVO Study Group.

We investigated the demographic characteristics and risk factors of Korean patients with naÏve central or branch retinal vein occlusion (CRVO or BRVO). This study enrolled 41 clinical sites throughout Korea and included 557 consecutive patients with retinal vein occlusion (RVO) from May through November 2010. A total of 557 patients with new-onset RVO participated in this study. Two hundred and three (36.4%) patients were diagnosed with CRVO and 354 (63.6%) patients were diagnosed with BRVO. Comparisons between the two groups showed that the prevalence of diabetes mellitus was significantly higher in CRVO patients and hypertension was significantly higher in BRVO patients (P = 0.001 and 0.002, respectively). Poor baseline visual acuity was significantly associated with female and old age in BRVO patients (P = 0.002 and 0.013, respectively), whereas the wide intraretinal hemorrhage (CRVO, P = 0.029; BRVO, P < 0.001) and the macular ischemia (CRVO, P < 0.001; BRVO, P < 0.001) were associated with both groups. The study results show the clinical features of RVO in Korean patients. Hypertension is strongly associated with BRVO and diabetes mellitus is more strongly associated with CRVO in Korean patients with RVO. As the first nationwide study performed by the Korean Retinal Society, the results of this study can be applied to future studies on RVO.

Cytoplasmic and nuclear anti-apoptotic roles of αB-crystallin in retinal pigment epithelial cells.

In addition to its well-characterized role in the lens, αB-crystallin performs other functions. Methylglyoxal (MGO) can alter the function of the basement membrane of retinal pigment epithelial (RPE) cells. Thus, if MGO is not efficiently detoxified, it can induce adverse reactions in RPE cells. In this study, we examined the mechanisms underlying the anti-apoptotic activity of αB-crystallin in the human retinal pigment epithelial cell line ARPE-19 following MGO treatment using various assays, including nuclear staining, flow cytometry, DNA electrophoresis, pulse field gel electrophoresis, western blot analysis, confocal microscopy and co-immunoprecipitation assays. To directly assess the role of phosphorylation of αB-crystallin, we used site-directed mutagenesis to convert relevant serine residues to alanine residues. Using these techniques, we demonstrated that MGO induces apoptosis in ARPE-19 cells. Silencing αB-crystallin sensitized ARPE-19 cells to MGO-induced apoptosis, indicating that αB-crystallin protects ARPE-19 cells from MGO-induced apoptosis. Furthermore, we found that αB-crystallin interacts with the caspase subtypes, caspase-2L, -2S, -3, -4, -7, -8, -9 and -12 in untreated control ARPE-19 cells and that MGO treatment caused the dissociation of these caspase subtypes from αB-crystallin; transfection of S19A, S45A or S59A mutants caused the depletion of αB-crystallin from the nuclei of untreated control RPE cells leading to the release of caspase subtypes. Additionally, transfection of these mutants enhanced MGO-induced apoptosis in ARPE-19 cells, indicating that phosphorylation of nuclear αB-crystallin on serine residues 19, 45 and 59 plays a pivotal role in preventing apoptosis in ARPE-19 cells. Taken together, these results suggest that αB-crystallin prevents caspase activation by physically interacting with caspase subtypes in the cytoplasm and nucleus, thereby protecting RPE cells from MGO-induced apoptosis.