Hsi-Kung Kuo

Outdoor activity during class recess reduces myopia onset and progression in school children.

PURPOSE The aim of this study was to investigate the effect of outdoor activity during class recess on myopia changes among elementary school students in a suburban area of Taiwan. DESIGN Prospective, comparative, consecutive, interventional study. PARTICIPANTS Elementary school students 7 to 11 years of age recruited from 2 nearby schools located in a suburban area of southern Taiwan. INTERVENTION The children of one school participated in the interventions, whereas those from the other school served as the control group. The interventions consisted of performing a recess outside the classroom (ROC) program that encouraged children to go outside for outdoor activities during recess. The control school did not have any special programs during recess. MAIN OUTCOME MEASURES Data were obtained by means of a parent questionnaire and ocular evaluations that included axial length and cycloplegic autorefraction at the beginning and after 1 year. RESULTS Five hundred seventy-one students were recruited for this study, of whom 333 students participated in the interventional program, and 238 students were in the control school. At the beginning of the study, there were no significant differences between these 2 schools with regard to age, gender, baseline refraction, and myopia prevalence (47.75% vs. 49.16%). After 1 year, new onset of myopia was significantly lower in the ROC group than in the control group (8.41% vs. 17.65%; P<0.001). There was also significantly lower myopic shift in the ROC group compared with the control group (-0.25 diopter [D]/year vs. -0.38 D/year; P = 0.029). The multivariate analysis demonstrated that the variables of intervention of the ROC program and higher school year proved to be a protective factor against myopia shift in nonmyopic subjects (P = 0.020 and P = 0.017, respectively). For myopic subjects, school year was the only variable significantly associated with myopia progression (P = 0.006). CONCLUSIONS Outdoor activities during class recess in school have a significant effect on myopia onset and myopic shift. Such activities have a prominent effect on the control of myopia shift, especially in nonmyopic children. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Topical bevacizumab eyedrops for limbal-conjunctival neovascularization in impending recurrent pterygium.

Purpose: To report a case of impending recurrent pterygium treated with topical bevacizumab eyedrops. Methods: A 53-year-old woman with impending recurrent pterygium was treated with topical bevacizumab eyedrops (25 mg/mL) administered 4 times daily for 3 weeks. Two months previously, she had undergone excision of a primary ptergyium in the same eye by bare sclera recision and application of mitomycin C. Results: Treatment with topical bevacizumab for 3 weeks produced prominent regression of limbal-conjunctival neovascularization. At 6-month follow-up, no recurrent pterygium was noted. Symptoms were resolved with no ocular irritation, burning, or any systemic adverse effects. Conclusions: These data suggest that off-label short-term use of topical bevacizumab may be effective to prevent recurrence in a patient with impending recurrent pterygium. We believe that this is the first known successful use of topical bevacizumab in such a patient.

Cyclin-dependent Kinase Inhibitor Roscovitine Induces Cell Cycle Arrest and Apoptosis in Rabbit Retinal Pigment Epithelial Cells

AIMS Cyclin-dependent kinases (CDKs) play essential roles in the intracellular control of the cell cycle. It has been postulated that roscovitine, a potent CDK2, CDK5, and CDC2 inhibitor, might inhibit cellular proliferation by arresting the cell cycle. This in vitro study investigated the antiproliferative and apoptotic effects of roscovitine in cultured rabbit retinal pigment epithelial (RPE) cells. METHODS Experiments using rabbit RPE from young pigmented rabbits were carried out using roscovitine dissolved in dimethylsulfoxide at concentrations ranging from 1 to 100 micromol. Cell proliferation was measured by an MTT assay. The cell cycle response of RPE cells to roscovitine was analyzed by flow cytometry of propidium iodide-stained nuclei. Proteins related to DNA damage in the RPE cells were then assayed by Western blot. RESULTS Roscovitine inhibited proliferation of RPE cells in a dose-dependent manner. Cell cycle analysis after treatment demonstrated an accumulation of cells arrested in the S- and G2/M phases. Flow cytometry showed that 40 microM of roscovitine increased the cell population in the sub-G1 peak, which is considered a marker of cell death by apoptosis. Western blot analysis revealed Bcl-2 decreased and Bax increased after treatment of RPE cells with roscovitine. CONCLUSIONS This study of the response of RPE cells to roscovitine demonstrated a bidirectional relationship between cell cycle control and apoptosis.

Visual acuity as measured with Landolt C chart and Early Treatment of Diabetic Retinopathy Study (ETDRS) chart

BackgroundWe compared the Landolt C chart checked under normal clinical conditions and the Early Treatment of Diabetic Retinopathy Study (ETDRS) chart, using standard clinical research protocols for subjects with normal vision, cataract and maculopathy.MethodsThis prospective, comparative study was approved by the hospital Institutional Review Board. Patients with cataract and maculopathy were included, with the normal fellow eyes analyzed as normal vision group. Differences between the two charts were analyzed using Student’s t-test.ResultsNormal and cataract eyes showed no statistically significant differences between methods. In the maculopathy group, ETDRS acuity (0.714 ± 0.393) was better than Landolt C acuity (0.845 ± 0.579), but the differences were not statistically significant (p = 0.152). Furthermore, if after dividing visual acuity into subgroups, >20/200 and ≤20/200 by Landolt C acuity, the latter subgroup had significant differences between the two tests (p < 0.001). ETDRS acuity (1.014 ± 0.319) was better than Landolt C acuity (1.419 ± 0.385). The average acuity difference was 4 lines.ConclusionsFor maculopathy patients with VA ≤ 20/200, the ETDRS chart had a better score than the Landolt C chart.

Adjunctive Intravitreal Bevacizumab-Combined Trabeculectomy Versus Trabeculectomy Alone in the Treatment of Neovascular Glaucoma

PURPOSE To evaluate the effect of adjunctive intravitreal bevacizumab (ivBe) with trabeculectomy versus trabeculectomy alone in the management of patients with neovascular glaucoma (NVG). METHODS Retrospective, consecutive, interventional case series. NVG patients were divided into groups by treatment: with adjunctive ivBe and trabeculectomy (ivBe group, n = 14 eyes) and with trabeculectomy only (control group, n = 28 eyes). The main outcome measure was visual acuity. Regression of iris neovascularization (NVI), change(s) in intraocular pressure (IOP), NVI recurrence, additional glaucoma surgeries required, eyes of leading to total blindness, intraoperative and postoperative complications, and number of topical medications required after trabeculectomy were regarded as second outcome measures. In the ivBe group, intravitreal injections of 2.5 mg bevacizumab were delivered using a sharp 27-gauge needle through the inferotemporal quadrant. RESULTS Of 42 eyes of 42 patients identified, change in IOP, additional glaucoma surgeries required, and number of IOP-lowering topical medications required after trabeculectomy did not differ significantly between groups (P > 0.05 for all). However, the ivBe group had significantly higher frequency and rapidity of iris neovascular regression, improved visual acuity in the logarithm of minimum angle of resolution (logMAR), leading to total blindness in fewer eyes and intraoperative and postoperative complications in others than in the control group (P = 0.015, 0.002, 0.007, 0.023, and 0.008, respectively). The follow-up duration (mean +/- SD) from trabeculectomy surgery was 179 +/- 97 days (range, 93-315 days) and 196 +/- 108 days (range, 92-370 days) in the ivBe and control group (P = 0.324). CONCLUSIONS Intravitreal bevacizumab might be a useful adjunctive therapy in addition to trabeculectomy in the management of NVG. Large controlled randomized studies for treatment of bevacizumab on NVG are warranted.

Serum uric acid concentration is associated with worsening in severity of diabetic retinopathy among type 2 diabetic patients in Taiwan--a 3-year prospective study.

AIMS To explore the role of serum uric acid (SUA) concentration in diabetic retinopathy (DR) for patients with type 2 diabetes mellitus (T2DM). METHODS A 3-year prospective study in 749 patients with T2DM and without proliferative diabetic retinopathy (PDR) was conducted at a medical center. Baseline SUA concentration and parameters of glycemic control, blood pressure, kidney disease, and lipid profiles were analyzed to determine their contribution to DR. RESULTS Fundus examination showed that 184 patients (24.6%) had non-proliferative retinopathy and 565 (75.4%) without DR at baseline. After 3 years, increase in the severity of DR was recognized in 103 patients (13.8%), including 81 patients with newly developed DR. Patients with increase in severity of DR positively associated with duration of DM (11.9 vs. 9.4 years, p = 0.001), HbA1c (7.6 vs. 7.2%, p = 0.001), albuminuria (45.5 vs. 31.0%, p = 0.006), and SUA (6.47 vs. 5.87 mg/dl, p<0.001) than did those without change in DR stage. Cox regression showed that patients with SUA in the 3rd (5.9-6.9 mg/dl) and 4th (≥ 7.0mg/dl) quartiles had hazard ratios for DR worsening of 2.57 and 3.66 (95% C.I. 1.30-5.08 and 1.92-7.00) when compared with patients with SUA in the 1st quartile (<4.9 mg/dl). CONCLUSIONS SUA concentration is associated with the increase in severity of DR over a 3-year period in patients with T2DM. Further study is required to define the exact role of SUA in DR.

Intravitreal injection of 2.5 mg bevacizumab for treatment of myopic choroidal neovascularization in treatment-naive cases: a 2-year follow-up.

PURPOSE The purpose of this study was to evaluate the safety and efficacy of intravitreal bevacizumab in treatment-naive patients with choroidal neovascularization (CNV) secondary to pathologic myopia over a 2-year interval. METHODS Patients diagnosed with myopic CNV who had not received previous treatment were given intravitreal injections of bevacizumab (2.5 mg/0.1 mL). All patients were retrospectively evaluated using best-corrected visual acuity (BCVA) and central macular thickness (CMT) measured with optical coherence tomography (OCT). RESULTS Twenty-six eyes of 26 patients aged 15-81 years (mean, 42.6 years) were enrolled. OCT images demonstrated that the mean CMT±standard deviation (SD) significantly changed from 270±47 μm at baseline to 228±35, 218±35, 212±25, 210±29, and 209±30 μm in the 1st, 3rd, 6th, 12th, and 24th post-treatment months, respectively (P<0.001 for all). The BCVA in logarithm of the minimum angle of resolution±SD significantly changed from 0.75±0.43 at baseline to 0.57±0.44, 0.42±0.44, 0.39±0.47, 0.41±0.44, and 0.42±0.41 in the 1st, 3rd, 6th, 12th, and 24th post-treatment months, respectively (P<0.001 for all). The mean number of injections was 1.69 (range, 1-4) within the 24-month period. The follow-up period ranged from 24 to 35 months (mean, 28 months). No other ocular or systemic adverse effects were observed. CONCLUSIONS Although the present study lacked a control group, the results in this small series of patients over the 2-year follow-up period indicate that intravitreal injection of 2.5 mg bevacizumab is effective and safe in patients with myopic CNV.

Refractive Error in Patients with Retinopathy of Prematurity after Laser Photocoagulation or Bevacizumab Monotherapy

Purpose: To evaluate the refractive development of premature infants with retinopathy of prematurity (ROP) after treatment with laser photocoagulation or intravitreal injection of bevacizumab (IVB). Methods: The medical records of patients with ROP treated between 2003 and 2012 who underwent yearly follow-ups were retrospectively reviewed. Patients with residual ROP abnormalities were excluded. The cycloplegic refraction at 3 years of age, assessed using an autorefractometer, was recorded. Results: In total, 54 eyes from 54 patients were enrolled. Patients were divided into 4 groups: group 1, including 14 eyes of 14 patients treated with laser therapy; group 2, 15 eyes of 15 patients treated with IVB; group 3, 13 eyes of 13 patients with non-type 1 ROP under conservative follow-up, and group 4, 12 eyes of 12 premature patients without ROP. The mean spherical equivalent at 3 years of age was -1.71 ± 1.27 dpt in group 1, -1.53 ± 2.20 dpt in group 2, 0.63 ± 1.37 dpt in group 3, and 0.41 ± 1.95 dpt in group 4. The mean refractive error differed significantly among the 4 groups (p < 0.001). Patients in groups 1 and 2 were more prone to myopia compared with those in groups 3 and 4. Furthermore, patients with type 1 ROP treated by laser photocoagulation (group 1) and those treated by IVB (group 2) had similar refraction (p = 1). Conclusions: The results of this study suggest that treatment-demanding ROP eyes are susceptible to more severe myopia with age compared with eyes without ROP or those with spontaneously regressed ROP. In addition, the myopic status between laser and IVB treatment did not differ statistically.

Using WINROP as an adjuvant screening tool for retinopathy of prematurity in southern Taiwan.

OBJECTIVE To study the efficacy of the WINROP (https://winrop.com) algorithm in Taiwan, a middle income, moderately developed country in Asia. STUDY DESIGN We enrolled all preterm infants born with a gestational age less than 32(+0) weeks from September 2008 to August 2010. The results of serial retinopathy of prematurity examinations according to the screening guidelines in our hospital were recorded. Weekly body weight was also recorded for the WINROP algorithm. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS Overall, 148 infants were included. Seventeen infants (11.5%) received treatment for retinopathy of prematurity. But, six infants (35.3%) were missed when severe retinopathy of prematurity was predicted with WINROP algorithm. The sensitivity is only 64.7%. However, when focusing on the preterm infants with a birth weight < 1,000 g or gestational age < 28 weeks, it could predict the need for treatment up to 13 weeks in advance. CONCLUSION The WINROP algorithm is a very effective noninvasive screening tool for retinopathy of prematurity, especially in preterm infants with a birth weight  < 1,000 g or a gestational age < 28 weeks. However, the overall sensitivity in this report from Taiwan was not as high as that reported in highly developed countries.

Attenuated glial reaction in experimental proliferative vitreoretinopathy treated with liposomal doxorubicin.

PURPOSE We investigated the therapeutic effect of liposomal doxorubicin (Lipo-dox) on experimental proliferative vitreoretinopathy (PVR). METHODS The toxicity of Lipo-dox was determined in vitro in cultured rabbit retinal pigment epithelium (RPE) cells by tetrazolium-based (MTT) assay for cell viability performed 48 and 96 hours after treatment, and in vivo by electroretinography and histopathology. The therapeutic effect of intravitreous injection of Lipo-dox was evaluated in a rabbit model of PVR induced by injection of rabbit RPE cells after gas compression of the vitreous. The presence of PVR was determined by indirect ophthalmoscopy on days 1, 7, 14, 21, and 28 after injection. Western blot and immunofluorescence studies were performed to evaluate the expression of the glial markers vimentin and glial fibrillary acidic protein (GFAP). A pharmacokinetic study also was performed and analyzed by liquid chromatography coupled with tandem mass spectrometry (LC-MS). RESULTS The 50% inhibitory concentrations (IC₅₀) of doxorubicin (Doxo) and Lipo-dox in RPE cells were 0.01-0.1 and 0.1-1.0 μg/mL, respectively. Lipo-dox (10 μg/mL) did not reduce the amplitude reduction in the ERG study or produce obvious retinal toxicity. Lipo-dox still could be detected in the vitreous 7 days after injection. The Lipo-dox (10 μg/mL)-treated eyes showed lower grade PVR than did the untreated eyes. Lipo-dox also decreased the retinal expression levels of vimentin and GFAP. CONCLUSIONS Lipo-dox can attenuate the severity of experimental PVR, and reduces the glial cell expression of intermediate filaments in PVR retinas. Lipo-dox has a wider safe dosage range and a longer half-life in the vitreous than does primary Doxo.