Young-Jung Roh

One-year results of intravitreal ranibizumab for neovascular age-related macular degeneration and clinical responses of various subgroups

PurposeTo report 1-year clinical outcomes of intravitreal ranibizumab treatment for choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and to identify predictive factors that may influence visual acuity (VA) outcomes in Korean patients.MethodsSixty patients (64 eyes) with subfoveal CNV were followed up over 12 months after intravitreal injection (0.5 mg) of ranibizumab at baseline and subsequent injections on an as-needed basis. The VA outcomes over 12 months were compared with baseline VA and evaluated across subgroups based on sex, age, baseline VA, CNV size, CNV type, and presence or absence of systemic disease and prior photodynamic therapy.ResultsVA improved or remained stable in 46 of 64 eyes (71.9%) at 12 months. Subgroup analysis showed that both baseline VA and CNV size influenced VA outcomes after ranibizumab treatment (P = 0.039, P = 0.042, respectively). However, the patients’ sex (P = 0.643), baseline age (P = 0.361), CNV type (P = 0.940), and the presence or absence of systemic disease (P = 0.775) and prior photodynamic therapy (P = 0.890) did not affect VA outcomes.ConclusionsIntravitreal injections of ranibizumab improve mean VA in patients with subfoveal CNV secondary to AMD, and baseline VA and CNV lesion size were predictive factors of VA outcomes after ranibizumab treatment in Korean patients.

One-Year Results of Intravitreal Ranibizumab with or without Photodynamic Therapy for Polypoidal Choroidal Vasculopathy

Purpose: To evaluate the safety and efficacy of intravitreal ranibizumab with or without photodynamic therapy (PDT) in the treatment of polypoidal choroidal vasculopathy (PCV) in Korean patients. Methods: A retrospective chart review of 22 patients (24 eyes) with PCV was conducted. Nine eyes were treated with intravitreal ranibizumab combined with a single session of PDT (group 1), and 15 eyes were treated only with ranibizumab (group 2). Such clinical evaluations as best-corrected Snellen visual acuity, central retinal thickness (CRT) by optical coherence tomography (OCT), fluorescein angiography (FA) and indocyanine green angiography (ICGA) were done at baseline, 1, 3, 6, 9 and 12 months after the first injections. Ranibizumab was reinjected on an as-needed basis guided by OCT, FA and ICGA, or at the doctor’s discretion. Results: The mean follow-up duration was 22.5 months (range 12–37). The mean best-corrected visual acuity (logMAR) improved, and the mean CRT decreased throughout 12 months in both groups; no statistically significant difference between the groups was found (p = 0.327, p = 0.073, respectively). The number of ranibizumab injections was not significantly different either (p = 0.555). Conclusions: Intravitreal ranibizumab with or without PDT for PCV in Korean patients resulted in visual and anatomical improvement over the 1-year follow-up period.

Antiangiogenic Effects of Axitinib, an Inhibitor of Vascular Endothelial Growth Factor Receptor Tyrosine Kinase, on Laser-Induced Choroidal Neovascularization in Mice

Purpose: To investigate the effects of axitinib, an inhibitor of vascular endothelial growth factor receptors, on choroidal neovascularization (CNV) in an animal model of neovascular age-related macular degeneration (AMD). Methods: Experimental CNV lesions were induced in C57BL/6 mice by laser photocoagulation. Beginning 1 day after CNV induction, mice were treated with axitinib (5 mg/kg/day) or vehicle for 2 weeks. In other groups of mice, axitinib or vehicle treatment was started 7 days after the laser application to determine the effect of the drug on established CNV. Untreated mice were used as a baseline group. Two weeks after laser injury, the extent of CNV was assessed from choroidal flat mounts perfused with fluorescein-labeled dextran. Immunofluorescence staining with isolectin IB4 was also used to quantify the CNV lesions. Results: Orally administered axitinib inhibited CNV growth in the laser-induced CNV model. Axitinib caused a 70.1% inhibition of CNV lesions compared to vehicle-treatment (p < 0.001). Axitinib also caused a significant regression of established CNV, reducing the area by 71.1% compared to vehicle treatment (p < 0.001). Moreover, immunofluorescence staining showed that the area of isolectin IB4 labeled vessels was smaller in the axitinib-treated group compared to the vehicle-treated group (p < 0.001). Conclusions: Axitinib effectively inhibits the progression of CNV in an experimental animal model. These results suggest that axitinib could constitute a therapeutic alternative for the treatment of neovascular AMD.

New Diagnostic and Therapeutic Approaches for Preventing the Progression of Diabetic Retinopathy

Diabetic retinopathy (DR) is a severe sight-threatening complication of diabetes mellitus. Retinal laser photocoagulation, antivascular endothelial growth factors, steroid therapy, and pars plana vitrectomy are now used extensively to treat advanced stages of diabetic retinopathy. Currently, diagnostic devices like ultrawide field fundus fluorescein angiography and the improvement of optical coherence tomography have provided quicker and more precise diagnosis of early diabetic retinopathy. Thus, treatment protocols have been modified accordingly. Various types of lasers, including the subthreshold micropulse laser and RPE-targeting laser, and selective targeted photocoagulation may be future alternatives to conventional retinal photocoagulation, with fewer complications. The new developed intravitreal medications and implants have provided more therapeutic options, with promising results.

Ranibizumab Treatment Administered as Needed for Occult and Minimally Classic Neovascular Membranes in Age-Related Macular Degeneration

PurposeTo report the clinical experience of intravitreal ranibizumab administered as needed for the treatment of neovascular age-related macular degeneration (AMD).MethodsWe retrospectively reviewed the charts of 41 patients (41 eyes) with occult and minimally classic neovascular membrane in AMD. Patients received intravitreal injections (0.5 mg) of ranibizumab and were monitored monthly for 12 months. Forty-one eyes were retreated at the discretion of the treating physician on an as-needed basis after the first injection, instead of initially giving three monthly injections. The main outcomes measured were change in mean visual acuity and central retinal thickness, and the total number of injections received by patients during the 12 months.ResultsAt 12 months, the mean logarithm of the minimum angle of resolution (logMAR) visual acuity improved by 0.078 logMAR units (P = 0.046) and the mean central retinal thickness decreased by 85.7 μm (P < 0.001). Thirty of 41 eyes (73.2%) avoided any loss of vision, and 20 eyes (48.8 %) showed improved visual acuity. A mean of 4.07 injections were given over the 12 months.ConclusionsRanibizumab administered on an as-needed basis may stabilize visual acuity in patients with neovascular AMD.

Automatic irradiation control by an optical feedback technique for selective retina treatment (SRT) in a rabbit model

Selective Retina Therapy (SRT) targets the Retinal Pigment Epithelium (RPE) without effecting neighboring layers as the photoreceptors or the choroid. SRT related RPE defects are ophthalmoscopically invisible. Owing to this invisibility and the variation of the threshold radiant exposure for RPE damage the treating physician does not know whether the treatment was successful or not. Thus measurement techniques enabling a correct dosing are a demanded element in SRT devices. The acquired signal can be used for monitoring or automatic irradiation control. Existing monitoring techniques are based on the detection of micro-bubbles. These bubbles are the origin of RPE cell damage for pulse durations in the ns and μs time regime 5μs. The detection can be performed by optical or acoustical approaches. Monitoring based on an acoustical approach has already been used to study the beneficial effects of SRT on diabetic macula edema and central serous retinopathy. We have developed a first real time feedback technique able to detect micro-bubble induced characteristics in the backscattered laser light fast enough to cease the laser irradiation within a burst. Therefore the laser energy within a burst of at most 30 pulses is increased linearly with every pulse. The laser irradiation is ceased as soon as micro-bubbles are detected. With this automatic approach it was possible to observe invisible lesions, an intact photoreceptor layer and a reconstruction of the RPE within one week.

The Antiangiogenic Effects of Gold Nanoparticles on Experimental Choroidal Neovascularization in Mice

Purpose The purpose of this study was to evaluate the antiangiogenic effect of gold nanoparticles (AuNPs) on experimental choroidal neovascularization (CNV) in mice. Methods Choroidal neovascularization was induced by rupturing the Bruchs membrane using laser photocoagulation in C57BL/6 mice. The following day, intravitreal injections of AuNPs were administered. The control group received PBS injection of the same volume. Two weeks after laser injury, CNV lesions were evaluated by examination of choroidal flat-mounts using fluorescein-labeled dextran and immunofluorescence staining with isolectin B4. The effects of AuNPs on endothelial cell tube formation, proliferation, and cytotoxicity were evaluated using human umbilical vein endothelial cells (HUVECs) or human RPE cells. The activity of extracellular signal-regulated kinase (ERK)1/2, protein kinase B (Akt), and focal adhesion kinase (FAK) signaling pathways was also analyzed. Results The AuNPs reduced the extent of CNV. Mice treated with intravitreal AuNPs injections exhibited a 67.9% reduction in the extent of CNV lesions compared with the control group (P < 0.001). The size of the isolectin B4-labeled area was also significantly smaller in AuNP-treated groups compared with the control group (P < 0.001). Gold nanoparticles decreased vascular endothelial growth factor-induced HUVEC tube formation and proliferation but showed no RPE cell toxicity with the treatment doses administered. The phosphorylation of ERK1/2, Akt, and FAK in HUVECs was suppressed by AuNPs. Conclusions Gold nanoparticles can inhibit laser-induced CNV in mice and may have an indication for the treatment of CNV.

A Comparative Study of Retinal Function in Rabbits after Panretinal Selective Retina Therapy versus Conventional Panretinal Photocoagulation.

Purpose. This study evaluates functional changes in electroretinographic findings after selective retina therapy (SRT) compared to panretinal photocoagulation (PRP) in rabbits. Methods. The right eyes of 12 Chinchilla rabbits received 200 laser treatment spots. The right eyes of six rabbits received SRT (SRT group), whereas the other six animals were treated using PRP on the right eye (PRP group). The eyes were investigated using full-field ERG 1 hour and 3 weeks after treatment. Histologic exam to assess the tissue response of lasers was performed on 3 weeks. Results. No significant changes in the mean ROD or CR b-wave amplitudes of the SRT lesions were evident, compared to baseline, 1 h after laser treatment (p = 0.372 and 0.278, resp.). In addition, the OPs and 30 Hz flickers of the SRT lesions were not significantly altered (p = 0.17 and 0.243, resp.). At 3 weeks, similar results were found. Comparing the two groups, the ROD b-wave amplitude was reduced in the PRP and SRT groups to 60.04 ± 4.2% and 92.32 ± 6.43% of baseline (p < 0.001). Histologically, there was no visible photoreceptor alterations on week 3. Conclusions. SRT in rabbit eyes induced less functional loss than PRP in both rod-mediated retinal function and cone-mediated retinal function. In addition, SRT irradiated eyes had no functional loss compared to its control.

Toward automated selective retina treatment (SRT): an optical microbubble detection technique

Selective retina therapy (SRT) is an ophthalmological laser technique, targeting the retinal pigment epithelium (RPE) with repetitive microsecond laser pulses, while causing no thermal damage to the neural retina, the photoreceptors as well as the choroid. The RPE cells get damaged mechanically by microbubbles originating, at the intracellular melanosomes. Beneficial effects of SRT on Central Serous Retinopathy (CSR) and Diabetic Macula Edema (DME) have already been shown. Variations in the transmission of the anterior eye media and pigmentation variation of RPE yield in intra- and inter- individual thresholds of the pulse energy required for selective RPE damage. Those selective RPE lesions are not visible. Thus, dosimetry-systems, designed to detect microbubbles as an indicator for RPE cell damage, are demanded elements to facilitate SRT application. Therefore, a technique based on the evaluation of backscattered treatment light has been developed. Data of 127 spots, acquired during 10 clinical treatments of CSR patients, were assigned to a RPE cell damage class, validated by fluorescence angiography (FLA). An algorithm has been designed to match the FLA based information. A sensitivity of 0.9 with a specificity close to 1 is achieved. The data can be processed within microseconds. Thus, the process can be implemented in existing SRT lasers with an automatic pulse wise increasing energy and an automatic irradiation ceasing ability to enable automated treatment close above threshold to prevent adverse effects caused by too high pulse energy. Alternatively, a guidance procedure, informing the treating clinician about the adequacy of the actual settings, is possible.

Anti‐angiogenic effect of ALS‐L1023, an extract of Melissa officinalis L., on experimental choroidal neovascularization in mice

The effect of ALS‐L1023, an extract of Melissa officinalis L. (Labiatae; lemon balm) leaves, on experimental choroidal neovascularization (CNV) in mice was evaluated.