Sang Yeul Lee

Quercetin Inhibits IL-1β-Induced Inflammation, Hyaluronan Production and Adipogenesis in Orbital Fibroblasts from Graves' Orbitopathy

Management of Graves orbitopathy (GO) is challenging, as no reliable, specific, and safe medical therapeutic agents have yet been developed. We investigated the effect of quercetin in primary cultured orbital fibroblasts from GO, targeting pathways of inflammation, aberrant accumulation of extracellular matrix macromolecules, and adipose tissue expansion. Quercetin significantly attenuated intercellular adhesion molecule-1 (ICAM-1), interleukin (IL) -6, IL-8, and cyclooxygenase (COX) -2 mRNA expression, and inhibited IL-1β-induced increases in ICAM-1, IL-6, and IL-8 mRNA. Increased hyaluronan production induced by IL-1β or tumor necrosis factor-α was suppressed by quercetin in a dose- and time-dependent manner. Treatment with noncytotoxic doses of quercetin inhibited accumulation of intracytoplasmic lipid droplets and resulted in a dose-dependent decrease in expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer-binding protein (C/EBP) α, and C/EBPβ proteins. In conclusion, inhibition of inflammation, hyaluronan production, and adipogenesis by the natural plant product quercetin in vitro provides the basis for further study of its potential use in the treatment of GO.

Increased serum interleukin-17 in Graves' ophthalmopathy.

BackgroundInterleukin (IL)-17 and T helper 17 (Th17) cells are reported to be involved in many autoimmune diseases. The aim of this study is to investigate the involvement of IL-17 in the pathogenesis and disease activity of Graves’ ophthalmopathy (GO).MethodsSixty-two GO patients and 19 healthy controls were recruited. Serum concentrations of cytokines, IL-17, IL-6, IL-23, and IL-16, were measured using multiplexed microsphere-based flow cytometric immunoassays. GO hormonal parameters, clinical activity score (CAS), exophthalmometry, and extraocular muscle involvement were evaluated, and relationships with cytokine concentrations were analyzed.ResultsThe concentration and positive detection rates of serum IL-17 were significantly higher in patients with GO than in controls. The serum levels of IL-17 in active GO patients were higher than that of inactive GO patients. Serum IL-17 concentration had significant correlation with CAS (pu2009<u20090.001).ConclusionThe increased serum level of IL-17 and related cytokines in GO patients and the correlation of IL-17 concentration with the clinical activity scores suggest that IL-17 may play a pathophysiological role in GO.

Bone marrow-derived progenitor cells promote corneal wound healing following alkali injury

PurposeTo determine whether bone marrow-derived progenitor cells can be stimulated by inflammatory mediators and play a role in corneal wound healing following alkali injury.MethodsSixty rabbits were divided into two groups( Group I and Group II). Group I served as a bone marrow-suppression model, and received 200xa0mg/kg cyclophosphamide. Corneal alkali injury was created in one eye of each rabbit in each group; the other eye served as control. Three days after corneal burn, inflammatory cells in peripheral blood were counted. At the end of 4xa0weeks follow-up, corneas of all rabbits were subjected to histochemical examination to assess infiltrated CD34 and C-kit positive cells. Clinical outcome was determined at the end of 4xa0weeks.ResultsCyclophosphamide suppressed bone marrow function in Group I by reducing cellularity by more than 30% and neutrophil distribution by 3.18u2009±u20091.83%. The number of bone marrow hematopoietic and mesenchymal progenitor cells were all suppressed by cyclophophamide, as demonstrated by statistically significant differences between Group I and Group II of CD34+ cells (tu2009=u2009−21.62, Pu2009<u20090.01) and C-Kit cells (tu2009=u2009−21.62, Pu2009<u20090.01). Fewer inflammatory cells were released into circulation in Group I (14.42u2009±u20095.70%) than in Group II (44.36u2009±u20098.64%). Clinical observation revealed that Group II rabbits had much greater reepithelization (tu2009=u20096.999, Pu2009<u20090.01) and clearer corneas (X2u2009=u20094.417, Pu2009<u20090.01) than Group I.ConclusionsCorneal alkali injury is a stimulus that induces a rapid bone marrow reaction to release not only inflammatory cells but also progenitor cells into circulation. Migrated bone marrow-derived progenitor cells can home to local sites to promote wound healing.

Outcomes of 4-snip punctoplasty for severe punctal stenosis: measurement of tear meniscus height by optical coherence tomography.

PURPOSEnTo investigate the surgical outcome of rectangular 4-snip punctoplasty, a modification of rectangular 3-snip procedures, using objective measurements.nnnDESIGNnNoncomparative case series.nnnMETHODSnThe medical charts of patients who underwent rectangular 4-snip punctoplasty for severe punctal stenosis with at least 6 months follow-up were reviewed. Before surgery and at 1 and 6 months after surgery, subjective evaluation of tearing was assessed using Munk scores. The size of the punctum was graded based on slit-lamp examination, and measurement of tear meniscus height was done using Fourier-domain optical coherence tomography.nnnRESULTSnA total of 45 eyes (26 patients) were studied. The subjective epiphora score was significantly reduced after surgery and maintained until 6 months after the surgery (χ2 for trend test, P<.001). The grade of the punctum size was also significantly enlarged after surgery and the enlarged punctum was maintained until 6 months after the surgery (χ2 for trend test, P<.001). The mean preoperative tear height (452.4±249.3 μm) was significantly reduced both at 1 month after surgery (341.6±207.9 μm; P=.003, paired t test) and at 6 months after surgery (362.1±212.6 μm; P=.004, paired t test). The functional success rate was 93.3% and anatomic success rate was 88.9% at 6 months after surgery.nnnCONCLUSIONSnRectangular 4-snip punctoplasty was an anatomically and functionally effective procedure for severe punctal stenosis patients, maintaining large puncta for fairly long periods.

Ocular surface inflammation, and nerve growth factor level in tears in active thyroid-associated ophthalmopathy

PurposeTo measure tear nerve growth factor (NGF) concentrations in cases of active thyroid-associated ophthalmopathy (TAO) before and after glucocorticoid treatment, and to correlate NGF levels with disease inflammatory activity and thyroid autoantibody concentration.MethodsThe study involved 20 patients with active TAO and 20 age- and gender-matched controls. Tear break-up time (BUT) was obtained, the Schirmer test was performed, and tear NGF/total protein ratio was measured in control subjects and patients with active TAO before, and 2 and 4xa0weeks after, steroid treatment.ResultsTear BUT and Schirmer values significantly increased after 2 and 4xa0weeks of steroid treatment (pu2009<u20090.001 and pu2009=u20090.004 respectively). Baseline tear NGF/total protein ratio was higher in patients with active TAO than in control subjects, and the ratio significantly decreased after 2 and 4xa0weeks of steroid treatment (pu2009<u20090.001). Tear NGF/total protein ratio did not correlate with inflammatory activity score, exophthalmos value and thyroid binding inhibiting immunoglobulin (TBII) level (pu2009>u20090.05).ConclusionsTear NGF may have a specific role in ocular surface inflammation, which protects against ocular surface damage in patients with active TAO. Anti-inflammatory treatment significantly reduced the level of NGF in tears, increased tear film stability and production, and decreased congestive symptoms.

Treatment of upper eyelid retraction related to thyroid-associated ophthalmopathy using subconjunctival triamcinolone injections

BackgroundTo evaluate the efficacy of subconjunctival triamcinolone injection for treating upper eyelid retraction caused by thyroid-associated ophthalmopathy (TAO).MethodsProspective single blind randomized clinical trial. Patients diagnosed with TAO-associated eyelid retraction and/or swelling <6xa0months before study onset were randomly assigned to triamcinolone-injected (group I; 55 patients, 75 eyes) or observation-only (group II; 40 patients, 59 eyes) populations. Group I received 1–3 injections of 20xa0mg triamcinolone acetate into the subconjunctival eyelid, between the conjunctiva and Muller’s muscle, at 3-week intervals. Group I was followed up at 3, 6, 9, and 24xa0weeks post-injection, and group II was evaluated at 9 and 24xa0weeks after initial visit. Eyelid swelling and retraction were each graded on a 0-3 scale. Treatment was stopped after 1–2 injections if both swelling and retraction resolved completely or if retraction and swelling scored 0/1 or 1/0 without functional or cosmetic patient concerns. Treatment success was defined at 9 and 24xa0weeks post-injection if eyelids were normal or when treatment was terminated because of early clinical resolution. We compared baseline clinical data between success and failure group evaluated at 9 and 24xa0weeks in group I, and investigated short-term and long-term success prognostic factor using multiple logistic regression analysis in each group I and II.ResultsSwelling and retraction decreased significantly more in group I than in group II. Significantly more eyes had severe swelling (≥ grade 2) in group I (67xa0%) than in group II (34xa0%) upon initial evaluation (pu2009<u20090.01); this difference disappeared at 9 and 24xa0weeks. Fewer severely retracted eyes were observed in group I than in group II at 9 and 24xa0weeks (pu2009<u20090.01). Significantly more eyes in group I achieved success at both 9 and 24xa0weeks (59xa0%, 75xa0%) than in group II (39xa0%, 57xa0%) (pu2009=u20090.03, pu2009=u20090.04 respectively). Higher initial retraction grades (2–3) predicted a higher chance of post-injection failure versus the reference group (grade 0–1) at 9 and 24xa0weeks in group I, with adjusted odds ratios (aOR) 45.4 (95xa0% CIu2009=u20095.9–351.1, pu2009<u20090.01) and aOR 11.6 (95xa0% CIu2009=u20092.3–58.5, pu2009<u20090.01) respectively. Similarly in group II, initial retraction grade was associated with the failure at 9 and 24xa0weeks, with aOR 10.3 (95 % CIu2009=u20091.8–59.6, pu2009<u20090.01) and aOR 5.9 (95xa0% CIu2009=u20091.3–25.9, pu2009<u20090.05) respectively. Transient intraocular pressure elevation was observed in three eyes of two patients, although all ocular pressures were normalized within 1xa0month using anti-glaucoma medication.ConclusionsSubconjunctival triamcinolone injections were very effective in resolving eyelid swelling and retraction in recent-onset TAO. However, the symptom-reducing effect of triamcinolone was modest and less effective in patients initially presenting with severe retraction grades. As intraocular pressure may rise after steroid injection at upper eyelid, the treatment should be avoided in patients suspected to have glaucoma.

Factors Associated with Diabetic Retinopathy and Nephropathy Screening in Korea: The Third and Fourth Korea National Health and Nutrition Examination Survey (KNHANES III and IV)

This cross-sectional study was done to identify and determine the socio-demographic and health-related factors associated with diabetic retinopathy and nephropathy screening in Korea. Participants included 2,660 adults, aged 40 or older, with diabetes. Of the 2,660 adults, 998 (37%) and 1,226 (46.1%) had received a diabetic retinopathy and a nephropathy screening within one year, respectively. Regarding retinopathy, subjects older than 65, living in urban areas, with high educational levels, and with self-reported unhealthy status were likely to receive annual screening. Subjects living in urban areas, with higher educational levels, with self-reported fair or unhealthy status, and with 1 to 2 co-morbidities were likely to receive annual nephropathy screening. The Korea Composite Stock Price Index (KOSPI) continued to rise until 2007 when it started to decline over the subsequent years, following the same curve as the diabetic retinopathy and nephropathy screening rates during that time. Together with the financial matter, lack of patient education proved to be a hindrance to diabetes-related screening. The relatively low screening rates in Korea compared to the Western countries are likely to be due to the difference in the health system, economic situations and national demographics.

A case of congenital orbital malignant rhabdoid tumor: systemic metastasis following exenteration.

A newborn girl presented with massive proptosis of the right eye. Physical and radiologic examination disclosed that the primary orbital mass was confined to the site. A diagnosis of malignant rhabdoid tumor was made by histopathologic examination of an incisional biopsy specimen. Exenteration was performed, and the resection margins were free from tumor cells. However, distant metastasis developed in the liver 1 month after surgery. Despite chemotherapy, the patient died 2 months later due to tumor invasion into the central nervous system, which was confirmed by autopsy. To the best of our knowledge, this is the first case of congenital orbital malignant rhabdoid tumor showing systemic metastasis after exenteration, which suggests the need for aggressive systemic treatment rather than exenteration, even in a case of locally confined tumor.

Prediction of Postoperative Eyelid Height After Frontalis Suspension Using Autogenous Fascia Lata for Pediatric Congenital Ptosis

PURPOSEnTo predict eyelid height after frontalis suspension using autogenous fascia lata for congenital ptosis.nnnDESIGNnRetrospective, observational case series.nnnMETHODSnEighty eyes of 54 children who underwent frontalis suspension using autogenous fascia lata were included. The amount of intraoperative eyelid lift and the postoperative change in eyelid height were assessed 6 months after surgery by reviews of photographs and medical records. The amount of operative eyelid lift was measured from 2 different baselines, and each amount was compared with the amount of real change in eyelid height after surgery. The difference between those was measured.nnnRESULTSnThe postoperative eyelid height stabilized 3 months after surgery. The average amount of operative eyelid lift was 5.91 mm with anesthesia-induced lagophthalmos and 3.51 mm without. The amount of real change in eyelid height after surgery was 3.24 ± 1.14 mm. In less severe ptosis (< 3 mm of lift), an average operative lift of 2.03 mm resulted in 2.53 mm of elevation, whereas in more severe ptosis (≥ 4 mm of lift), an average operative lift of 3.98 mm resulted in only 3.72 mm of elevation 6 months after surgery. The preoperative palpebral fissure (P = .002) and anesthesia-induced lagophthalmos (P < .001) were significant factors influencing postoperative eyelid height.nnnCONCLUSIONSnPostoperative eyelid height may predicted be more accurately by compensating for anesthesia-induced lagophthalmos and adjusting the palpebral fissure to be larger than the desired eyelid height for patients with more severe ptosis.

Variations in the degree of epiblepharon with changes in position and induction of general anesthesia

BackgroundTo investigate the changes of epiblepharon by evaluating the severity of epiblepharon before and after induction of general anesthesia.MethodsSixty-three pediatric patients (126 eyes) underwent surgery for epiblepharon between April 2008 and September 2008 (35 females, 28 males; average age: 4.74xa0years). The severity of epiblepharon in each eye was scored according to skin-fold height (scored 1–4) and area of ciliocorneal touch (scored 1–3) while the patient was in upright and supine positions before induction of general anesthesia and in supine position after induction of anesthesia.ResultsThe severity of epiblepharon was significantly reduced by a positional change to supine position and induction of general anesthesia. Skin-fold height scores decreased when patients were moved from upright (estimated mean ± standard error [SE]; 2.98u2009±u20090.08) to supine position (2.63u2009±u20090.09) (Pu2009<u20090.001) prior to induction of anesthesia, and decreased further after induction of general anesthesia (2.12u2009±u20090.08) (Pu2009<u20090.001). Ciliocorneal touch scores also decreased after patients were moved to supine position and after induction of general anesthesia (upright: 2.17u2009±u20090.05; supine: 1.95u2009±u20090.06; general anesthesia: 1.64u2009±u20090.07, Pu2009<u20090.001).ConclusionsOur study demonstrates that positional changes and general anesthesia using muscle relaxants affect the degree of epiblepharon. Surgeons should be aware of these variations for operative planning of epiblepharon.