Chung-May Yang

Effects and Complications of Bevacizumab Use in Patients with Retinopathy of Prematurity: A Multicenter Study in Taiwan

PURPOSE To investigate the effects and complications of the anti-vascular endothelial growth factor agent bevacizumab in the treatment of retinopathy of prematurity (ROP) in Taiwanese patients. DESIGN A multicenter, retrospective case series study. PARTICIPANTS Twenty-seven patients (49 eyes) from 4 medical centers across Taiwan. METHODS This study included patients receiving intravitreal injections of bevacizumab (IVB) (0.625 mg) for the treatment of ROP between 2007 and 2009 at 4 major medical centers in Taiwan. The effects and complications associated with this treatment were analyzed. Patients were followed for at least 6 months after bevacizumab injection. MAIN OUTCOME MEASURES Regression of ROP and the complications associated with the injection of bevacizumab. RESULTS Forty-nine eyes of 27 patients (18 male and 9 female) were included in the study. Mean gestational age and birth weight were 26.0 ± 2.4 weeks and 971.6 ± 589.6 g, respectively. There were 41 eyes (23 patients) with stage 3 ROP, 6 eyes (3 patients) with stage 4A ROP, and 2 eyes (1 patient) with stage 5 ROP. All of the eyes received only a single injection of IVB. The mean injection time was 36.8 ± 2.6 weeks postmenstrual age for eyes with stage 3 ROP. A total of 37 of 41 eyes (90%) with stage 3 ROP regressed after bevacizumab injection only. Four eyes (10%) required additional laser treatment to regress the ROP. Of 6 eyes (3 patients) with stage 4A ROP, 2 eyes (1 patient; 33%) regressed after bevacizumab injection and 4 eyes (67%) regressed after bevacizumab injection and subsequent vitrectomy. The 2 eyes with stage 5 ROP exhibited decreased vascular tortuosity after bevacizumab injection, but the retina failed to reattach after vitrectomy surgeries. Major complications included vitreous or pre-retinal hemorrhage in 4 eyes (8%) and transient vascular sheathing in 2 eyes (4%). CONCLUSIONS Bevacizumab injection seems effective and well tolerated in some cases of ROP, especially in stage 3 ROP. Ocular complications could result from the injection of bevacizumab in pediatric eyes.

An Updated Study of the Use of Bevacizumab in the Treatment of Patients with Prethreshold Retinopathy of Prematurity in Taiwan

PURPOSE To investigate the effectiveness and complications associated with the use of bevacizumab, an anti-vascular endothelial growth factor agent, in the treatment of prethreshold retinopathy of prematurity (ROP). DESIGN A multicenter, retrospective case series. METHODS Data from patients who had received intravitreal bevacizumab (IVB) injections for the treatment of ROP were collected from 4 medical centers in Taiwan. The main outcome measures were the regression of ROP and the complications that were associated with the IVB injections. RESULTS In total, 162 eyes from 85 patients were included in the study. After receiving IVB injections, 143 eyes (88%) exhibited ROP regression. Fourteen eyes (9%) required additional laser treatment for ROP regression after the absence of a positive response to the IVB injections. Three eyes (2%) progressed to stage 4 ROP and required vitrectomies to reattach the retinas. Two eyes (1%) received 1 additional IVB injection to decrease persistent plus disease. All of the eyes (100%) had attached retinas after the various treatments that they received. The major ocular complications that were associated with IVB injections included vitreous or preretinal hemorrhage in 2 eyes (1%); cataract in 1 eye (1%); and exotropia in 1 eye (1%). No notable systemic complications related to the IVB injections were observed. CONCLUSIONS IVB injection seems to be an effective and well-tolerated method of treating prethreshold ROP. Laser therapy may still be required as a backup treatment for patients who do not respond to an IVB injection or for those in whom ROP worsens after an IVB injection.

Bevacizumab pretreatment in vitrectomy with silicone oil for severe diabetic retinopathy.

Purpose: To evaluate the effects of intravitreal bevacizumab pretreatment in vitrectomy with silicone oil infusion for severe diabetic retinopathy. Methods: Forty-one eyes (39 patients) that underwent primary vitrectomy with silicone oil tamponade for severe diabetic retinopathy were enrolled in this prospective, comparative case–control clinical study. Cases were alternately divided into the following Group 1, intravitreal bevacizumab (1.25 mg) injection 1 week before surgery; or Group 2, no bevacizumab injection. Cases were followed-up for at least 6 months. Postinjection retinal changes, intra- and postoperative findings, and outcomes were compared between groups. Results: Bevacizumab injections induced regression of neovascularization after 1 week. One case developed increased retinal detachment. In Group 1, there were significantly more cases of subretinal bleeding (P < 0.01). The severity of intraoperative and postoperative bleeding was significantly lower in Group 1. The blood reabsorption time was 11.1 ± 6.3 days in Group 1 and 34.8 ± 12.0 days in Group 2 (P < 0.01). One case in Group 1 and 2 cases in Group 2 had ultimate retinal detachment. Multiple regression analyses indicated bevacizumab significantly reduced intra- and postoperative bleeding. Conclusion: Bevacizumab may reduce intra- and postoperative hemorrhage in diabetic vitrectomy with silicone oil infusion. Increased subretinal bleeding are potential complications.

Attained Adult Height in Juvenile Rheumatoid Arthritis with or without Corticosteroid Treatment

Abstract: Growth impairment has been described in patients with juvenile rheumatoid arthritis (JRA). Both the direct action of underlying disease and prolonged corticosteroid usage for disease management may contribute to growth impairment. The purpose of this retrospective study was to evaluate the effect of systemic corticosteroid treatment on attained adult height in patients with JRA. We reviewed patients who first visited our hospital from 1973 to 1995 with a diagnosis of JRA. Adult height (AH) and the reported parental heights of these patients were recorded. Target height (TH) is estimated according to midparental height. Patients who never had or had only transient (less than 1 week) systemic corticosteroid therapy were classified as group 1. Group 2 included patients who had corticosteroid therapy for more than 1 week but never continuously for more than 12 months, and group 3 included patients on long-term steroid treatment (continuously for more than 1 year). Height data were analysed using adult height and the difference between adult height and target height (AH minus TH). Thirty-three patients fulfilling the diagnostic criteria for JRA were reviewed. Fourteen belonged to group 1, 13 to group 2 and six to group 3. The difference between adult height and target height in group 1 was 2.96 ± 4.54 cm, in group 2 0.71 ± 6.08 cm (group 1 vs. group 2, P = 0.28), and in group 3 −11.65 ± 10.71 cm (group 1 vs. group 3, P<0.05). In 15 patients who never received corticosteroid therapy continuously for more than 1 year, AH–TH was statistically correlated neither with the cumulative corticosteroid exposure dose nor with cumulative corticosteroid exposure period by linear regression (P= 0.408, P= 0.278, respectively). We concluded that continuous systemic corticosteroid usage for less than 1 year does not affect attained adult height in JRA patients; however, prolonged corticosteroid treatment for more than 1 year can lead to irreversible growth impairment.

Surgical treatment for severe diabetic macular edema with massive hard exudates.

Purpose: Massive diabetic macular exudates respond poorly to conventional laser treatment. The purpose of this study was to analyze the surgical results of eyes with massive hard exudates secondary to diabetic macular edema treated with combined pars plana vitrectomy, posterior hyaloid removal, focal endolaser treatment, and panretinal photocoagulation. Methods: The author retrospectively analyzed the surgical outcome of 13 consecutive eyes (11 patients) with massive diabetic macular exudates. All patients had had at least one session of focal and/or grid laser treatment without any effect. Pars plana vitrectomy, posterior hyaloid removal, focal macular endolaser treatment, and intraoperative panretinal photocoagulation were performed. Postoperative visual acuity, evolution of macular edema, and hard exudates were recorded. Results: All 13 eyes showed significant decreases in macular edema and hard exudates, a process that became clinically obvious 3 months after the operation. Eleven eyes had improved vision of at least two lines during an average follow‐up period of 14.8 months. Intraoperative and postoperative complications included angle closure glaucoma (one eye), persistent vitreous hemorrhage (two eyes), choroidal detachment (one eye), intravitreal fibrin formation (one eye), epiretinal membrane formation (one eye), and neovascular glaucoma (one eye). Conclusion: Combined surgery may offer an opportunity for improvement of vision and reduction of massive macular exudates in patients with severe diabetic macular edema.

Photodynamic Therapy With or Without Intravitreal Bevacizumab for Polypoidal Choroidal Vasculopathy: Two Years of Follow-Up

PURPOSE To compare the long-term results of the efficacy of photodynamic therapy (PDT) with or without intravitreal bevacizumab (IVB) injections for polypoidal choroidal vasculopathy. DESIGN Retrospective, comparative, interventional case series. METHODS We included 69 eyes of 69 patients with macula-involved polypoidal choroidal vasculopathy. All patients were followed up for more than 2 years. We compared the treatment outcomes between groups and investigated the factors influencing visual improvement at 24 months of follow-up. RESULTS Thirty-six patients received PDT combined with IVB and 33 patients received PDT monotherapy. At 3 months, the mean logarithm of minimal angle of resolution (logMAR) best-corrected visual acuity (BCVA) improved from 0.73 to 0.53 in the combined therapy group (P < .001) and from 0.79 to 0.72 in the PDT monotherapy group (P = .02), with a significant difference in treatment efficacy between the 2 groups (P < .001). However, the improvements in BCVA were not statistically significant after 21 months in the combined therapy group and 15 months in the monotherapy group. The difference in treatment efficacy between the 2 groups was not significant after 6 months. Initial BCVA (P = .005), lesion size (P = .011), patient age (P = .018), and location of polyps (P = .006) significantly predicted the final visual outcome rather than treatment modality (P = .243). CONCLUSIONS PDT combined with IVB for symptomatic PCV was temporarily superior to PDT monotherapy, and the treatment efficacy decreased with time. Initial BCVA, lesion size, and location were more significant than treatment modality as the factors influencing final visual improvement.

Sterile Endophthalmitis Following Intravitreal Injection of Triamcinolone Acetonide

Purpose: To investigate clinical findings and ocular characteristics of sterile endophthalmitis following intravitreal injection (IVI) of triamcinolone for the treatment of macular edema. Methods: IVI is an institutional practice at our hospital. From March 2002 to January 2003, a total of 21 IVIs of triamcinolone acetonide were performed on 19 patients with macular edema secondary to various retinal disorders. Cases diagnosed as sterile endophthalmitis after IVI of triamcinolone were selected for the study. Fishers discriminant linear analysis was used to determine whether a significant correlation existed between specific ocular features and the occurrence of post-injection sterile endophthalmitis. Results: Five of 21 eyes (23.8%) had sterile endophthalmitis with hypopyon formation after the injection. Of the five sterile endophthalmitis patients, three were pseudophakic with impaired posterior capsule and four had a diagnosis of Irvine-Gass syndrome. The rate of sterile endophthalmitis was significantly higher in pseudophakic patients with impaired posterior capsule (p = 0.0075) and in patients with Irvine-Gass syndrome (p = 0.0008). The best-corrected visual acuity (BCVA) in these patients remained unchanged or even improved when the inflammation subsided. Conclusion: Pseudophakia with impaired posterior capsule and the diagnosis of cystoid macular edema due to Irvine-Gass syndrome are two risk factors of sterile endophthalmitis following IVI triamcinolone. No loss of BCVA was noted in the patients with post-injection sterile endophthalmitis.

Intravitreal bevacizumab and panretinal photocoagulation for proliferative diabetic retinopathy associated with vitreous hemorrhage.

Purpose: To evaluate the efficacy of intravitreal bevacizumab with panretinal photocoagulation (PRP) in the treatment of proliferate diabetic retinopathy (PDR) with vitreous hemorrhage (VH). Methods: Forty cases (40 patients) with PDR and persistent VH were prospectively enrolled, with a follow-up period of 12 months or more. Intravitreal bevacizumab injection (1.25 mg) was given, followed by PRP when visualization of peripheral fundus could be obtained. A second injection was administered 4 weeks to 6 weeks after the first injection if no signs of VH decrease were noted. Vitrectomy was performed if VH persisted >12 weeks. The vitreous clear-up time (VCUT) and the rate of vitrectomy were compared with those in a historical control group (40 eyes in 40 patients) who were treated with conventional methods. Results: Thirty-one eyes had 1 injection and 9 eyes (22.5%) received 2 injections. Vitreous clear-up time in the study and control groups were 11.9 ± 9.5 weeks and 18.1 ± 12.7 weeks (P = 0.02), respectively. Rates of required vitrectomy were 10% in the study group and 45% in the control group (P = 0.01). Conclusion: One or 2 intravitreal injections of 1.25 mg bevacizumab with PRP are associated with rapid regression of VH and may reduce the need for vitrectomy.

Peripapillary intrachoroidal cavitation in high myopia: reappraisal

PurposeTo evaluate optical coherence tomography (OCT) and clinical findings of a peripapillary lesion in high myopia recently named peripapillary detachment in pathologic myopia (PDPM) or intrachoroidal cavitation.MethodsObservational case report by chart review, analysis of colour fundus photography, fluorescein angiography, and OCT in 16 eyes of 12 patients with myopic degeneration and the presence of a slightly elevated, patchy peripapillary, yellow-orange lesion on the fundus.ResultsPatients were mean age 53.1±10.7 years, with a spherical-equivalent refractive error of −10.99±3.33 D and mean axial length of 27.34±1.44 mm. The mean best-corrected visual acuity was log MAR 0.3±0.2 (between 20/100 and 20/20). Six eyes also showed myopic maculopathy. In 13 eyes, OCT showed an intrachoroidal hyporeflective space located below the normal plane of the retinal pigment epithelium. Six of these 13 eyes were found to have apparent communication between the intrachoroidal cavity and the vitreous space at the junction of the lesion and the myopic conus. In three eyes, OCT revealed intrachoroidal splitting. The fluorescein angiogram showed early hypofluorescence, without pooling or staining in late phase.ConclusionsThe yellow–orange elevated patchy lesions adjacent to the peripapillary conus in high myopic eyes may represent either intrachoroidal cavitation or choroidal schisis, which may be different stages of one disease spectrum. Vitreous fluid may be the source of the disruption of choroid and fluid accumulation.

Cyr61 induces the expression of monocyte chemoattractant protein-1 via the integrin ανβ3, FAK, PI3K/Akt, and NF-κB pathways in retinal vascular endothelial cells.

Diabetes causes a number of metabolic and physiological abnormalities in the retina. Many of the molecular and physiological abnormalities that develop during diabetic retinopathy are due to inflammation. Monocyte chemoattractant protein-1 (MCP-1) is an important factor involved in diabetic retinopathy. In a previous study, we found that cysteine-rich 61 (Cyr61), an important angiogenic factor, also plays an important role in diabetic retinopathy. In addition to the direct effects of Cyr61, we observed that Cyr61 can induce the expression of MCP-1. However, the mechanism through which this occurs is not completely understood in chorioretinal vascular endothelial cells. We therefore investigated the effects of Cyr61 on MCP-1 expression in this cell type. Cyr61 stimulated the expression of MCP-1 at the mRNA, protein, and secreted protein levels in a dose-dependent and time-dependent manner. Both total MCP-1 levels and secreted MCP-1 levels were attenuated during the response to Cyr61 stimulation by pretreatment with integrin ανβ3-blocking antibodies, a FAK inhibitor (PF573228), a PI3K inhibitor (LY294002), and an Akt inhibitor (A6730). Electrophoretic mobility shift assays revealed that the above inhibitors suppressed the activation of NF-κB. Additionally, deletion of the NF-κB-binding element in the MCP-1 gene promoter led to a decrease in expression in luciferase reporter assays. These results show that the induction of MCP-1 by Cyr61 is mediated through the activation of the integrin ανβ3, FAK, PI3K/Akt, and IKK/NF-κB pathways in chorioretinal vascular endothelial cells.