Eun Jee Chung

Effects of macular ischemia on the outcome of intravitreal bevacizumab therapy for diabetic macular edema.

Purpose: To evaluate the effects of macular ischemia on visual outcomes in patients with diabetic macular edema (DME), after intravitreal bevacizumab injections. Methods: Data on 59 eyes of 53 consecutive patients treated with intravitreal bevacizumab for DME were retrospectively reviewed. Data from preoperative fluorescein angiography (FA) tests were examined. Patients with an enlarged foveal avascular zone (FAZ), ≥1000 &mgr;m, or a broken perifoveal capillary ring at the border of the FAZ, with a distinct area of capillary nonperfusion within one disk diameter of the foveal center in the transit phase of fluorescein angiography, were defined as having macular ischemia. The patients were thus divided into two groups: with or without macular ischemia. Early Treatment Diabetic Retinopathy Study (ETDRS) scores, and foveal thicknesses measured using third generation ocular coherence tomography (OCT), were evaluated at baseline and at 1 month and 3 months after treatment. Results: At 3 months after treatment, the mean visual acuity (VA) score decreased from a baseline VA of 0.52 ± 0.27 (approximate Snellen equivalent, 20/63) to 0.57 ± 0.21 (20/80) in the ischemic group. In the nonischemic group, by contrast, the VA improved from 0.66 ± 0.34 (20/100) at baseline to 0.59 ± 0.33 (20/80) at 3 months post-treatment. Nine of 18 eyes (50%) in the ischemic group, but only 9 of 41 eyes (21%) in the nonischemic group, experienced visual losses of ≥1 line on the ETDRS chart (P = 0.031, Pearson chi-square test). Four eyes (22%) in the ischemic group, but only 2 eyes (5%) in the nonischemic group, lost ≥3 lines (P = 0.042, Pearson chi-square test). Conclusion: Macular ischemia may have a negative effect on short term visual outcomes after intravitreal bevacizumab injections in patients with DME.

Structural and functional predictors of visual outcome of epiretinal membrane surgery.

PURPOSE To evaluate the utility of preoperative optical coherence tomography (OCT) and multifocal electroretinography (mfERG) in prediction of visual outcomes after idiopathic epiretinal membrane (ERM) surgery. DESIGN Retrospective, observational case series. METHODS One hundred eyes of 100 patients with idiopathic unilateral ERM who underwent vitrectomy for ERM removal were retrospectively reviewed. Correlations between preoperative data (OCT and mfERG) and final best-corrected visual acuity (BCVA) were investigated using Pearson correlation analysis. One-way analysis of variance (ANOVA) was used to determine whether final BCVA and mfERG values differed among subgroups varying in photoreceptor integrity status. Receiver operating characteristic (ROC) curve analysis was performed to obtain a cutoff value of the P1 implicit time predicting visual recovery (final BCVA ≥20/25). RESULTS BCVA significantly improved, and 65 of 84 eyes (77%) achieved visual recovery of more than 2 Snellen lines after ERM surgery. Final BCVA was significantly correlated with preoperative photoreceptor integrity and P1 implicit time. The area under the ROC (AUROC) curve was statistically significant when P1 implicit time was examined, and the cutoff value for good visual prognosis was 40.81 msec (sensitivity: 72.7%; specificity: 81.3%). CONCLUSION Photoreceptor disruption detected by OCT and P1 implicit time delay on mfERG were significant predictors of poor visual recovery after ERM surgery.

Retinal Detachment with Macular Hole Following Combined Photodynamic Therapy and Intravitreal Bevacizumab Injection

Purpose To report a case of retinal detachment with a macular hole following photodynamic therapy (PDT) using verteporfin and intravtreal bevacizumab injection in the treatment of myopic choroidal neovasclarization (CNV). Methods A 58-year-old woman was diagnosed with myopic CNV and treated with a combination of PDT with verteporfin and intravitreal bevacizumab injection that same day. She received the second injection of intravitreal bevacizumab four weeks after the initial treatment. Results The patient developed a sudden decline in vision one week after the second injection; and was subsequently diagnosed with retinal detachment associated with a macular hole. She underwent standard three-port pars plana vitrectomy with internal limiting membrane peeling, fluid-air exchange and silicone oil injection. The retina was still firmly attached at the patients final follow-up visit. Conclusions PDT and intravitreal bevacizumab injection used for the treatment of myopic CNV can be associated with retinal detachment with a macular hole. Patients need to be informed about this potential complication, and a higher index of suspicion may be warranted in patients who report sudden vision loss after the treatment.

VISUAL ACUITY AND MULTIFOCAL ELECTRORETINOGRAPHIC CHANGES AFTER ARTERIOVENOUS CROSSING SHEATHOTOMY FOR MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN OCCLUSION

Purpose: To evaluate the influence of arteriovenous (AV) sheathotomy on retinal function with central multifocal electroretinography (mfERG) in eyes with macular edema secondary to branch retinal vein occlusion (BRVO). Methods: Fifteen patients (15 eyes) who underwent AV sheathotomy for macular edema secondary to BRVO were included in the study. Best-corrected visual acuity and mfERG responses from the most central seven hexagons were analyzed before and 6 months after the operation. Results: The mean preoperative Early Treatment Diabetic Retinopathy Study (ETDRS) score ± SD was 34.1 ± 12.7 letters (Snellen equivalent, 20/50) and significantly improved up to 40.5 ± 10.9 letters (Snellen equivalent, 20/40) at 6 months after AV sheathotomy (P = 0.027, Wilcoxon signed rank test). The mean preoperative P1 amplitude ± SD of the most central 7 hexagons was 39.30 ± 10.86 nV/deg2 for the affected eye versus 47.72 ± 6.67 nV/deg2 for the normal fellow (control) eye (P = 0.013, Mann–Whitney U test) and significantly increased up to 50.71 ± 15.58 nV/deg2 at 6 months after the operation (P = 0.014, Wilcoxon signed rank test). Significant correlations between preoperative and postoperative ETDRS score and preoperative P1 amplitude were present (r = 0.929, P < 0.001; r = 0.768, P = 0.001; respectively [Spearman correlation]). Conclusions: AV sheathotomy improved macular function and anatomical outcome as measured by ETDRS score and mfERG responses in patients with macular edema due to BRVO.

Effect of intravitreal bevacizumab on vascular endothelial growth factor expression in patients with proliferative diabetic retinopathy.

Purpose To investigate the effect of bevacizumab (Avastin; Genentech, San Francisco, CA, USA) on vascular endothelial growth factor (VEGF) expression and inflammation in fibrovascular membranes in patients with proliferative diabetic retinopathy (PDR). Materials and Methods Fibrovascular membranes from 19 eyes of 18 patients with PDR were studied using immunohistochemistry and analyzed in the following 3 groups; group 1: 4 inactive PDR eyes, group 2: 10 active PDR eyes treated preoperatively with adjunctive intravitreal bevacizumab, group 3: five active PDR eyes not treated preoperatively with bevacizumab. Immunohistochemical staining for VEGF, CD31 and CD68 were done. Results The immunoreactivity to VEGF and CD 31-positive blood vessels was significantly higher in membranes from group 3 than group 1 (p = 0.007 for VEGF, 0.013 for CD 31-positive vessels). Intravitreal bevacizumab caused a reduction in VEGF expression and vascular densities in 4 out of 10 (40%) excised membranes from eyes with PDR. However, six membranes (60%) in group 2 still demonstrated relatively strong VEGF expression and high vascular density. Infiltration of macrophages was observed in 16 out of the 19 membranes, and the density of macrophages was increased in group 2 compared with group 1 (p = 0.043). Conclusion Intravitreal bevacizumab injections caused some reduction in VEGF expression and vascular densities in a limited number of active PDR patients. A single intravitreal bevacizumab injection may not be enough to induce complete blockage of VEGF and pathologic neovascularization in active PDR patients. Repeated injections, panretinal photocoagulation and/or PPV may be necessary following intravitreal bevacizumab to reinforce the anti-VEGF effect of the drug.

OCT-guided hyaloid release for vitreomacular traction syndrome.

Purpose To evaluate the usefulness of OCT retinal mapping in determining the configuration of a vitreomacular adhesion and selecting a meridian for entry into the subhyaloid space in patients with vitreomacular traction syndrome. Methods Six consecutive patients (6 eyes) with vitreomacular traction syndrome underwent vitrectomy with peeling of posterior hyaloid. Ocular coherence tomography (OCT) retinal mapping was performed preoperatively. Access to the subhyaloid space was made by creating an opening with a 25 gauge needle at a location where the detached posterior hyaloid membrane was farthest from the retinal surface. The location was selected based on six preoperative meridional OCT scans. The posterior hyaloid was then gently peeled off in a circular fashion around the fovea with a micropick. Visual acuity and foveal thicknesses were measured before the operation and 3 months afterwards. Results After the operation, visual acuity improved and central macular thicknesses were reduced significantly in all six patients. The best corrected visual acuity improved from 0.4 to 0.75 with a mean increase by 3.5 lines on a Snellen chart 3 months after the operation. The mean foveal thickness was reduced from 406 µm to 241 µm. The restoration of foveal pit was observed in five patients. Neither intraoperative nor postoperative complications were observed during the follow up period. Conclusions An OCT retinal mapping program is a valuable diagnostic tool in understanding the configuration of vitreomacular adhesion and planning the surgical approach for operating on vitreomacular traction syndrome.

Prospective, Randomized Clinical Trial Of Intravitreal Triamcinolone Treatment Of Neovascular Age-related Macular Degeneration: One-year Results

Purpose: To investigate the effect of intravitreal injection of high-dose (20–25 mg) triamcinolone acetonide on minimally classic or occult choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). Methods: A prospective, double-masked, placebo-controlled, randomized clinical trial included 39 eyes with minimally classic or occult CNV secondary to AMD. The treatment group (21 eyes) received intravitreal injection (20–25 mg) of triamcinolone acetonide and the control group (18 eyes) received intravitreal injection (500 &mgr;g) of dexamethasone at 6-month intervals. Best-corrected ETDRS (Early Treatment Diabetic Retinopathy Study) score, contrast sensitivity score, and central macular volume were measured at 1 month, 3 months, 6 months, and 12 months. Results: Mean baseline best-corrected visual acuity (BCVA [logarithm of the minimal angle of resolution]) was 0.64 (Snellen equivalent, 20/80) in each group. At 1 month, 3 months, and 6 months after the injection, neither group had a significant change in BCVA. At 12 months, mean BCVA ± SD significantly decreased to 1.06 ± 0.34 (Snellen equivalent, 20/200) in the treatment group (paired t-test, P < 0.001), whereas it was 0.78 ± 0.52 (Snellen equivalent, 20/125) in the control group (P = 0.23). The difference was marginally significant (P = 0.06, Students t-test). All phakic eyes in the treatment group developed marked cataract progression. Conclusions: Intravitreal injection of high-dose triamcinolone had no beneficial effect on eyes with minimally classic or occult CNV secondary to AMD and was associated with outcomes similar to those associated with intravitreal injection of dexamethasone, which was used as placebo.

Comparison of Combination Posterior Sub-Tenon Triamcinolone and Modified Grid Laser Treatment with Intravitreal Triamcinolone Treatment in Patients with Diffuse Diabetic Macular Edema

Purpose To compare the efficacy of posterior sub-Tenons capsule triamcinolone acetonide injection combined with modified grid macular photocoagulation (PSTI + MP) with intravitreal triamcinolone acetonide (IVTA) injection in the treatment of diffuse diabetic macular edema (DME). Materials and Methods Forty eyes of 33 patients with diffuse DME were randomly allocated into either PSTI + MP (20 eyes) or IVTA (20 eyes). Best corrected visual acuity (VA) and foveal thickness were measured. Results The ETDRS scores at baseline were 25.2 ± 13.6 (mean ± SD) letters in the PSTI + MP group, whereas 21.7 ± 16.3 letters in the IVTA group. The ETDRS scores improved by 33.2 ± 15.9, 34.7 ± 16.6 and 30.9 ± 19.0 letters in the PSTI + MP group whereas by 30.9 ± 15.4, 30.1 ± 17.9 and 31.5 ± 15.0 letters in the IVTA group at 1, 3, and 6 months after the treatments, respectively. The VA improved significantly at 1 month and 3 months after both treatments (all p < 0.02, paired t-test). The VA improvements were no longer significant at 6 months in either group. There were no statistically significant differences at any time points between the 2 groups (all p > 0.05, Students t-test). The foveal thicknesses at baseline and 1, 3, and 6 months after the treatments were 382.8 ± 148.3, 309.1 ± 131.3, 319.3 ± 93.3, 340.4 ± 123.5 µm (mean ± SD) in the PSTI + MP group vs. 369.1 ± 123.1, 241.4 ± 52.3, 277.5 ± 137.4, 290.2 ± 127.9 µm in the IVTA group, respectively. Pairwise comparisons revealed significant decrease in foveal thickness at 1 month (p = 0.01, paired t-test) for the PSTI + MP group, and at both 1 month (p < 0.001) and 3 months (p = 0.016) for the IVTA group. There were no statistically significant differences at any time points between the 2 groups (all p > 0.05, Students t-test). In contrast to the PSTI + MP group, where no complications were noted, the elevation of intra-ocular pressure in 3 of 20 eyes (15%) and a significant increase in average cataract grading were observed in the IVTA group. Conclusion PSTI + MP treatment provides significant improvement of vision in patients with diffuse DME over 3 months, and achieves outcomes comparable to those after IVTA treatment, however, with fewer complications.

TGF-β-stimulated aberrant expression of class III β-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

The class III β-tubulin isotype (β(III)) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III β-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-β (TGF-β) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-β on the aberrant expression of class III β-tubulin and the intracellular signaling pathway mediating these changes. TGF-β-induced aberrant expression and O-linked-β-N-acetylglucosamine (O-GlcNac) modification of class III β-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-β also stimulated phosphorylation of ERK. TGF-β-induced aberrant expression of class III β-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-β stimulated aberrant expression of class III β-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-β stimulation and provide useful information towards understanding the pathogenesis of proliferative vitreoretinal diseases.

A retained lens fragment induced anterior uveitis and corneal edema 15 years after cataract surgery.

A 60-year-old male was referred to the ophthalmologic clinic with aggravated anterior uveitis and corneal edema despite the use of topical and systemic steroids. He had undergone cataract surgery in both eyes 15 years previous. Slit lamp examinations revealed a retained lens fragment in the inferior angle of the anterior chamber, with severe corneal edema and mild anterior uveitis. The corneal edema and uveitis subsided following surgical extraction of the lens fragment. That a retained lens fragment caused symptomatic anterior uveitis with corneal edema 15 years after an uneventful cataract surgery is unique. A retained lens fragment should be considered as one of the causes of anterior uveitis in a pseudophakic patient.