Woohyok Chang

Angiopoietin-1 Guides Directional Angiogenesis Through Integrin αvβ5 Signaling for Recovery of Ischemic Retinopathy

Angiopoietin-1 supplementation stimulates guided angiogenesis and promotes the formation of a healthy vascular network in a mouse model of ischemic retinopathy. A Shot at Healthy Growth for Retinal Blood Vessels Abnormalities of retinal blood vessels, such as vascular leakage and inappropriate angiogenesis, contribute to a variety of retinal diseases such as diabetic retinopathy and retinopathy of prematurity. Current targeted treatments for these disorders include antibodies against vascular endothelial growth factor (VEGF) and specially designed proteins that can trap VEGF to inhibit excessive proliferation of abnormal blood vessels in the eye. Unfortunately, these treatments have multiple drawbacks in that they require repeated intraocular injections and may also interfere with the formation of healthy blood vessels in the eye. Now, Lee and coauthors have discovered that angiopoietin-1 (Ang1), another protein involved in angiogenesis, may present a viable target for more specific and longer-lasting treatment of retinopathies. In a mouse model of oxygen-induced retinopathy, the authors showed that a loss of Ang1 led to abnormalities in retinal vasculature, whereas an increase of Ang1 in the retina not only stimulated blood vessel formation but also promoted a normalization of vascular network structure. The authors achieved these results not only by genetic overexpression of Ang1 but also by treating the mice with an injectable form of this protein. The authors also confirmed that Ang1 treatment protected retinal neurons from damage and successfully preserved their function. Future studies will be necessary to confirm the long-term stability of Ang1-stimulated blood vessels and retinal neurons, as well as to translate these results into human patients. Nevertheless, these early findings on injectable Ang1 offer the possibility of a new and more effective treatment approach for retinopathy patients. Retinopathy of prematurity (ROP) and proliferative diabetic retinopathy (PDR) are ischemic retinal diseases caused by insufficient vascular network formation and vascular regression in addition to aberrant angiogenesis. We examined the role of angiopoietin-1 (Ang1) in retinal vascular network formation during postnatal development using Ang1 gain- and loss-of-function mouse models, and tested the effects of intraocular administration of Ang1 in an oxygen-induced retinopathy (OIR) mouse model that mimics cardinal features of ROP and PDR. We observed that Ang1 plays a substantial role in the formation of the retinal vascular network during postnatal development and that Ang1 supplementation can rescue vascular retinopathies by simultaneously promoting healthy vascular network formation and inhibiting subsequent abnormal angiogenesis, vascular leakage, and neuronal dysfunction in the retinas of the OIR model. We attribute these Ang1-induced effects to a dual signaling pathway—Tie2 signaling in the vascular region and integrin αvβ5 signaling in the astrocytes. The activation of integrin αvβ5 signaling promoted fibronectin accumulation and radial distribution along the sprouting endothelial cells, which consequently stimulated guided angiogenesis in the retina. These findings shed light on the role of Ang1 in the recovery of ischemic retinopathies such as ROP, PDR, and retinal vascular occlusive disease.

Application of Intravitreal Bevacizumab for Circumscribed Choroidal Hemangioma

We report 3 cases of circumscribed choroidal hemangioma (CCH) effectively managed with intravitreal bevacizumab. One patient (case 1) who had recurrent CCH (1.6 mm in thickness) with prior laser photocoagulation was treated with intravitreal bevacizumab alone. Two patients (case 2 and 3) who had CCH (2.4 mm and 2.2 mm in thickness, respectively) with recent visual impairment were treated with bevacizumab followed by photodynamic therapy (PDT). Ophthalmic evaluations included visual acuity, ophthalmoscopic examination, fluorescein angiography, ultrasonography, and optical coherence tomography. Patients were followed up for 6-9 months. After therapy, all patients showed improved visual acuity due to complete resorption of subretinal fluid and macular edema. Ultrasonography demonstrated a reduction of the thickness of CCH in case 1 and complete regression of the lesions in case 2 and 3. No patient showed tumor recurrence. Intravitreal bevacizumab, alone or in combination therapy with PDT, may be a useful alternative for the treatment of symptomatic CCH with subretinal fluid.

Reduced-Fluence Photodynamic Therapy Combined With Intravitreal Bevacizumab for Polypoidal Choroidal Vasculopathy

PURPOSE To evaluate the efficacy and safety of reduced-fluence photodynamic therapy (PDT) combined with bevacizumab for polypoidal choroidal vasculopathy (PCV). DESIGN Prospective, noncomparative, interventional case series. METHODS Sixteen treatment-naïve patients with polypoidal choroidal vasculopathy were treated with reduced-fluence PDT combined with bevacizumab. All patients were followed up monthly for 12 months with measurements of best-corrected visual acuity (BCVA) and central foveal thickness by optical coherence tomography. Indocyanine green angiography and fluorescein angiography were performed every 3 months. Patients were re-treated with reduced-fluence PDT combined with bevacizumab or with sole injection of bevacizumab when indicated. RESULTS The mean logMAR BCVA showed significant improvement from 0.76 at baseline to 0.46 at 12 months (P = .002). At 12 months, the BCVA improved in 9 eyes (56.3%) by 3 lines or more, was stable in 6 eyes (37.5%), and decreased in 1 eye (6.3%) because of recurrence of polyps. During the study period, 3 patients (18.8%) had recurrence of polyps and 2 patients (12.5%) had persistent polyps. Mean episodes of reduced-fluence PDT and mean injections of intravitreal bevacizumab over 12 months were 1.44 and 2.44, respectively. Although 3 patients had mild choroidal nonperfusion-1 eye after 1 session of PDT and 2 eyes after 2 sessions-no severe complications, including endophthalmitis, uveitis, or subretinal hemorrhage, developed. CONCLUSION Reduced-fluence PDT combined with bevacizumab for PCV seemed to be effective for improving vision and reducing complications. Further study to optimize the light dose of PDT in combination therapy is needed in order to achieve better treatment outcomes for PCV.

Angiopoietin-1 Suppresses Choroidal Neovascularization and Vascular Leakage

PURPOSE To investigate the role of angiopoietin-1 (Ang1) in choroidal neovascularization (CNV) and vascular leakage. METHODS We generated laser-induced CNV in mice and measured the size of CNV and vascular leakage after intravitreal administration of Ang1. The expressions and distributions of endothelial junctional proteins were analyzed using immunohistochemistry and Western blot. Moreover, we compared the sizes of CNV and vascular leakage in Ang1-overexpressing, Ang1-deficient, and their littermate control mice. In addition, following the transplantation of GFP(+) bone marrow cells into these Ang1-genetically modified mice, we evaluated the recruitment of VEGF-A producing macrophages from the bone marrow after CNV induction. RESULTS Intravitreal administration of Ang1 was as effective as VEGF-Trap in inhibiting CNV formation. Furthermore, Ang1 suppressed vascular leakage by increasing endothelial junctional proteins, which was more effective than VEGF-Trap. Genetic deletion of Ang1 exacerbated, while overexpression of Ang1 suppressed CNV formation and vascular leakage. We attribute these Ang1-induced, anti-angiogenic, and anti-leakage effects to its inhibitory actions against the recruitment and infiltration of VEGF-A-producing macrophages from bone marrow into the inflammatory lesions. CONCLUSIONS Ang1 supplementation can be established as a therapeutic strategy to suppress the CNV formation and vascular leakage by inhibiting the recruitment of angiogenic macrophages and tightening the endothelial junctions.

Learning curve of the scleral buckling operation: lessons from the first 97 cases.

Background/Aims: To provide an insight into the learning curve associated with scleral buckling surgery for an ophthalmologist on a fellowship course and to evaluate risk factors affecting outcomes during this period. Methods: Retrospective data were collected on 97 consecutive scleral buckling procedures (divided into 3 consecutive groups) performed by one surgeon (W.C.) beginning his first fellowship year. We evaluated the anatomic results, operative times and complications, and sought to identify risk factors of anatomic failure. Results: The single-operation success rate was 71.9% (23 of 32 eyes) in the first group, which was lower than 87.5% (28 of 32 eyes) in the second and 84.8% (28 of 33 eyes) in the third. The operative time was 106.3 min in the first, which is longer than 86.5 min in the second and 73.8 min in the third group. Factors predictive of unfavorable anatomic outcome were multiple breaks and multiple buckling procedures in the first 32 cases, and multiple breaks and breaks located posterior to the equator in the latter 65. Conclusion: Surgical experience of approximately 30 cases was required to achieve stable clinical results. Thus, a retinal surgeon at the beginning of his career may increase his success rate by careful case selection avoiding high-risk groups until he reaches the level of experience indicated by the learning curve.

Bilateral Serous Retinal Detachment as a Presenting Sign of Acute Lymphoblastic Leukemia

We present a case of bilateral serous retinal detachment (SRD) as a presenting sign of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). A 45-year-old woman presented with decreased vision and was found to have bilateral serous retinal detachment. Peripheral blood smears revealed leukocytosis of 53.9×103/µL with 64.6% lymphoblasts. A bone marrow aspirate revealed the presence of lymphoblasts. Cytogenetic and molecular genetic analysis detected a reciprocal translocation between chromosome 9 and 22, t(9;22) (q34;q11). A diagnosis of Ph+ ALL was made. Following systemic chemotherapy, the bilateral SRD resolved completely with full recovery of vision. The sudden appearance of SRD should raise suspicion for leukemia. Prompt recognition of this disease is important for early systemic treatment and restoration of visual function.

A case of oculomotor nerve palsy and choroidal tuberculous granuloma associated with tuberculous meningoencephalitis.

We report a rare case of oculomotor nerve palsy and choroidal tuberculous granuloma associated with tuberculous meningoencephalitis. A 15-year-old male visited our hospital for an acute drop of the left eyelid and diplopia. He has been on anti-tuberculous drugs (isoniazid, rifampin) for 1 year for his tuberculous encephalitis. A neurological examination revealed a conscious clear patient with isolated left oculomotor nerve palsy, which manifested as ptosis, and a fundus examination revealed choroidal tuberculoma. Other anti-tuberculous drugs (pyrazinamide, ethambutol) and a steroid (dexamethasone) were added. After 3 months on this medication, ptosis of the left upper eyelid improved and the choroidal tuberculoma decreasedin size, but a right homonymous visual field defect remained. When a patient with tuberculous meningitis presents with abrupt onset oculomotor nerve palsy, rapid re-diagnosis should be undertaken and proper treatment initiated, because the prognosis is critically dependent on the timing of adequate treatment.

Efficacy and Safety of a Dexamethasone Implant in Patients with Diabetic Macular Edema at Tertiary Centers in Korea.

Purpose. To evaluate the real-world efficacy and safety of the dexamethasone implant (DEX implant) in patients with diabetic macular edema (DME). Methods. Retrospective, multicenter, and noncomparative study of DME patients who were treated with at least one DEX implant. A total of 186 eyes from 165 patients were included. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), complications, and number of retreatments were collected. Data at baseline and monthly for 6 months were analyzed. Results. The average baseline BCVA and CRT were 0.60 LogMAR and 491.6 μm, respectively. The mean BCVA improved until 3 months and then decreased up to 6 months of follow-up (0.53, 0.49, and 0.55 LogMAR at 1, 3, and 6 months; p = 0.001, <0.001, and 0.044, resp.). The change of mean CRT was similar to BCVA (345.0, 357.7, and 412.5 μm at 1, 3, and 6 months, p < 0.001, <0.001, and <0.001, resp.). 91 eyes (48.9%) received additional treatment with anti-VEGF or DEX implant. The average treatment-free interval was 4.4 months. In group analyses, the DEX implant was more effective in pseudophakic eyes, DME with subretinal fluid (SRF), or diffuse type. Conclusions. Intravitreal dexamethasone implants are an effective treatment for patients with DME, most notably in pseudophakic eyes, DME with SRF, or diffuse type. A half of these patients require additional treatment within 6 months.

Intravitreal Bevacizumab for the Treatment of Neovascular Glaucoma Associated With Central Retinal Artery Occlusion

We report three cases of neovascular glaucoma secondary to central retinal artery occlusion (CRAO) which were effectively managed with intravitreal bevacizumab (IVB) followed by panretinal photocoagulation (PRP). Neovascular glaucoma without peripheral anterior synechiae developed between one and five weeks following CRAO onset. All patients received 0.75 mg (0.03 ml) IVB. In all patients, complete regression of the iris and anterior chamber angle neovascularization was confirmed within one week. PRP was applied two weeks after the injection. The follow-up period was four to seven months (average, five months). Intraocular pressure was controlled in all patients using topical antiglaucoma medications alone. However, one patient experienced a recurrence of neovascularization three months after the initial combination treatment. This patient received another IVB injection and additional PRP, and the recurrent neovascularization resolved. There were no local or systemic adverse events in any patients. Therefore, intravitreal bevacizumab may be an effective adjunct in the treatment of neovascular glaucoma associated with CRAO.

Valsalva retinopathy following esophagogastroduodenoscopy under propofol sedation: A case report

We report a case of Valsalva retinopathy associated with esophagogastroduodenoscopy (EGD) under propofol sedation. A 43-year-old woman who had no previous history of systemic or ocular disease presented with a complaint of decreased vision in her left eye, which developed one day after EGD under propofol sedation. According to the referring physician, the patient had experienced multiple sustained Valsalva maneuvers during EGD. The fundus examination of the left eye showed a large preretinal hemorrhage surrounded by multiple small retinal hemorrhages in the posterior pole. One month later, fundus examination revealed a floating organized vitreous hemorrhage. The pars plana vitrectomy was performed to treat persistent vitreous hemorrhage. One month after vitrectomy, fundus examination showed normal retina and the patients vision recovered to 20/20. Valsalva maneuver can occur during EGD under sedation, and Valsalva retinopathy should be considered as a possible cause. Valsalva retinopathy should be included in the differential diagnosis when a patient complains of blurred vision following EGD.