Pei-Chang Wu

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

AIMSnCyclin-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.nnnMETHODSnExperiments 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.nnnRESULTSnRoscovitine 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.nnnCONCLUSIONSnThis 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 (0.714u2009±u20090.393) was better than Landolt C acuity (0.845u2009±u20090.579), but the differences were not statistically significant (pu2009=u20090.152). Furthermore, if after dividing visual acuity into subgroups, >20/200 andu2009≤20/200 by Landolt C acuity, the latter subgroup had significant differences between the two tests (pu2009<u20090.001). ETDRS acuity (1.014u2009±u20090.319) was better than Landolt C acuity (1.419u2009±u20090.385). The average acuity difference was 4 lines.ConclusionsFor maculopathy patients with VAu2009≤u200920/200, 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

PURPOSEnTo evaluate the effect of adjunctive intravitreal bevacizumab (ivBe) with trabeculectomy versus trabeculectomy alone in the management of patients with neovascular glaucoma (NVG).nnnMETHODSnRetrospective, 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.nnnRESULTSnOf 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).nnnCONCLUSIONSnIntravitreal 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.

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

PURPOSEnThe 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.nnnMETHODSnPatients diagnosed with myopic CNV who had not received previous treatment were given intravitreal injections of bevacizumab (2.5u2009mg/0.1u2009mL). All patients were retrospectively evaluated using best-corrected visual acuity (BCVA) and central macular thickness (CMT) measured with optical coherence tomography (OCT).nnnRESULTSnTwenty-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±47u2009μm at baseline to 228±35, 218±35, 212±25, 210±29, and 209±30u2009μm 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.nnnCONCLUSIONSnAlthough 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 2.5u2009mg bevacizumab is effective and safe in patients with myopic CNV.

Intravitreal Bevacizumab Injection Therapy for Persistent Macular Edema After Idiopathic Macular Epiretinal Membrane Surgery

PURPOSEnThe purpose of this study was to evaluate the effects of intravitreal bevacizumab (ivBe) injection in patients with persistent macular edema after macular epiretinal membrane (ERM) removal.nnnMETHODSnThis retrospective study included 26 patients (26 eyes) with marked macular edema after complete removal of idiopathic macular ERM who received single ivBe injection (12 patients) or no treatment (controls, 14 patients). Main outcome measurements were central macular thickness (CMT) and best-corrected visual acuity (BCVA).nnnRESULTSnIn the ivBe group, the mean CMT±standard deviation (SD) changed significantly from 323±43u2009μm at baseline to 306±41, 301±42, and 296±41u2009μm at weeks 4, 8, and 12, respectively, after treatment (P= 0.025, <0.0001, and <0.0001, respectively). The BCVA in logarithm of the minimum angle of resolution (logMAR)±SD did not change significantly from 0.50±0.15 at baseline to 0.46±0.11, 0.44±0.14, 0.44±0.14, and 0.42±0.13 at weeks 1, 4, 8, and 12, respectively, after treatment (P>0.05 for all). In the control group, the mean CMT±SD changed significantly from 326±32u2009μm at baseline to 314±29, 308±29, and 307±30u2009μm at weeks 4, 8, and 12, respectively, after treatment (P=0.002, <0.0001, and <0.0001, respectively). The BCVA in logMAR±SD did not change significantly from 0.52±0.22 at baseline to 0.49±0.20, 0.47±0.22, 0.45±0.16, and 0.47±0.23 at modified weeks 1, 4, 8, and 12, respectively, after treatment (P>0.05 for all). No significant differences were found for CMT or BCVA between the ivBe group and the control group at baseline and at any checkpoints after treatment (P>0.05 for all).nnnCONCLUSIONnivBe injection therapy provided no beneficial effects on CMT or visual acuity improvement for eyes with persistent macular edema after idiopathic macular ERM removal.

Twisting maneuver for sutureless vitrectomy trocar insertion to reduce intraoperative intraocular pressure rise.

Purpose: To investigate real-time intraocular pressure (IOP) during a new surgical technique-the “twisting maneuver”-when inserting a sutureless vitrectomy system trocar in porcine eyes. Methods: An interventional prospective study of 2 trocar insertion methods-direct insertion and gently twisting insertion-in a 25-gauge vitrectomy system (Alcon, Fort Worth, TX). These methods were used to create a scleral wound using a trocar blade and trocar cannula in freshly enucleated porcine eyes. The IOP changes induced by the procedures were recorded with a pressure transducer connected to the posterior chamber by direct cannulation. Results: Fourteen porcine eyes were studied in each group. During insertion, the mean of highest IOP rise (peak IOP rise) was 63.9 ± 25.5 mmHg in the direct insertion group compared with 30.3 ± 16.9 mmHg in the twisting insertion group (P = 0.001). During insertion, the mean of average IOP rise in the direct insertion group was 39.9 ± 16.5 mmHg compared with 21.5 ± 8.9 mmHg in the twisting insertion group (P = 0.002). The total time needed to complete the procedure in the twisting insertion group was significantly longer than that in the direct insertion group (43.3 ± 21.8 vs. 14.9 ± 8.1 seconds, P = 0.0003). Conclusion: A simple modification of surgical technique, namely, using a gently twisting insertion maneuver during trocar insertion, could significantly reduce the IOP elevation to allow a safer sutureless vitrectomy.

The flicker electroretinogram interocular amplitude ratio is a strong prognostic indicator of neovascularization in patients with central retinal vein occlusion

BackgroundTo evaluate the prognostic value of interocular amplitude ratio of flicker electroretinogram (ERG) in determining the development of neovascularization in patients with central retinal vein occlusion (CRVO).MethodsWe retrospectively reviewed the data obtained from flicker ERG in 51 CRVO patients. Of these, 22 eyes which had enough follow-up to differentiate ischemic CRVO from nonischemic CRVO were included for data analysis. The flicker ERG was recorded at a 30xa0Hz frequency after dark adaptation, and ten sweeps were averaged.ResultsEleven eyes were ischemic and 11 eyes were nonischemic. Three amplitude parameters had the potential to explain the type of CRVO. They were amplitude of lesion eye (pu2009=u20090.0001), interocular difference of amplitude (pu2009<u20090.0001), and interocular ratio of amplitude (pu2009<u20090.0001). Both an interocular amplitude difference of u2009−23xa0μV and interocular amplitude ratio of 60% were very good cutoff points to differentiate ischemic from nonischemic CRVO. Receiver operating characteristic curve analysis revealed that each of the two cutoff values had a sensitivity and specificity of 100%.ConclusionsInterocular comparison of amplitude is a good solution for avoiding the variability of ERG. An interocular amplitude ratio of flicker ERG of 60% is a succinct, useful parameter in clinical practices for differentiating ischemic from nonischemic CRVO.

Clinical Implications of Serous Retinal Detachment in Branch Retinal Vein Occlusion and Response After Primary Intravitreal Bevacizumab Injection

PURPOSEnTo evaluate the impact of macular serous retinal detachment (SRD) and its relationship to treatment outcome after primary intravitreal bevacizumab (IVB) injection in patients with branch retinal vein occlusion (BRVO) and macular edema (ME).nnnMETHODSnSeventy-three patients with ME secondary to BRVO who received primary IVB (2.5 mg/0.1 mL) were included in this study. The specific ME patterns were investigated using optical coherence tomography (OCT) examination. Visual acuity (VA), central macular thickness (CMT), and macular volume at baseline; at 1, 3, and 6 months; and at final visit after primary IVB were retrospectively analyzed and compared between patients with and without SRD.nnnRESULTSnSRD was found in 25 patients (34.2%). The baseline CMT was significantly thicker in patients with SRD than in those without it (648.4±200.5 μm vs. 440.3±119.6 μm, P<0.001). Six months after primary IVB injection, a greater reduction in CMT change from baseline was observed in the SRD group (412.5±227.2 μm) than in the group without SRD (118.5±175.2 μm) (P<0.001). The improvement of logarithm of the minimum angle of resolution VA was also greater in the SRD group than in the group without SRD (-0.64±0.52 and -0.28±0.62 respectively, P=0.015). Logistic regression analysis showed that the presence of SRD was an independent factor for visual improvement in BRVO (P=0.027).nnnCONCLUSIONnPatients with SRD had greater functional and morphological improvements at 6 months after primary IVB therapy. The results of this study suggest that the presence of SRD observed on OCT may be an indicator of favorable clinical response after IVB injections and that in BRVO patients with SRD, bevacizumab may be a good alternative for treatment.