Po-Ting Yeh

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.

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.

In Vivo Confocal Microscopic Findings of Corneal Wound Healing after Corneal Epithelial Debridement in Diabetic Vitrectomy

PURPOSE To study healing of corneal wounds using in vivo confocal microscopy in patients who received corneal epithelial debridement during pars plana vitrectomy for proliferative diabetic retinopathy and to investigate risk factors for delayed healing. DESIGN Prospective, observational case series. PARTICIPANTS Forty-four eyes of 40 patients were enrolled. METHODS In vivo confocal microscopy was used to evaluate selected images of the corneal basal and apical surface epithelial cells and subbasal nerves before surgery, weekly for the first month, and at 3 and 6 months after surgery. Slit-lamp biomicroscopy was carried out at the same time. Multiple linear regression analysis of selected potential risk factors was performed to investigate the main determinants of delayed corneal healing. MAIN OUTCOME MEASURES Healing rate of corneal epithelial cells and subbasal nerves and factors influencing the healing. RESULTS By slit-lamp biomicroscopy, corneal epithelial defects were found in 22.8% of eyes at 2 weeks and in 5.4% at 1 month after surgery. In vivo confocal microscopy demonstrated incomplete healing of basal epithelial cells in 72.1%, 15.2%, and 0% of eyes and incomplete healing of surface apical epithelial cells in 81.1%, 9.1%, and 0% of eyes at 1, 3, and 6 months after surgery. The percentage of subbasal nerves regaining preoperative appearance was 0%, 6.8%, and 89.3% at 1, 3, and 6 months after surgery. Regression analysis revealed infusion of silicone oil (P = 0.020) and C(3)F(8) (P = 0.017) resulted in delayed healing by slit-lamp biomicroscopy; age (P = 0.028), diabetic treatment regimen (P = 0.014), and scleral buckling (P = 0.001) correlated with delayed recovery of basal cells by in vivo confocal microscopy. The latter 2 factors also were related to delayed reconformation of apical cells (P = 0.011 and 0.004, respectively). Neither healing of apical and basal cells showed a significant correlation to findings by slit-lamp biomicroscopy (r = 0.19 and 0.09). CONCLUSIONS Healing of corneal epithelial wounds in diabetic eyes is slow. Both the basal and apical epithelial layers were involved in the slow healing process. Age, diabetic treatment regimen, and several intraoperative factors may alter healing rates. FINANCIAL DISCLOSURE(S) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Combined rhegmatogenous and traction retinal detachment in proliferative diabetic retinopathy: clinical manifestations and surgical outcome.

BACKGROUND Combined rhegmatogenous and traction retinal detachment (combined detachment) is a serious complication in proliferative diabetic retinopathy. The common clinical findings and surgical results of this complication were investigated. METHODS Forty eyes of 36 consecutive patients with combined detachment undergoing pars plana vitrectomy at a teaching hospital in a 4.5-year period were retrospectively reviewed. All cases had been followed up for at least 6 months. RESULTS Only 10 of the 40 cases had a preoperative visual acuity better than finger counting vision. Extensive proliferation with multiple, thickened, plaque-like vitreoretinal adhesions and large areas of detachment were noted in 38 cases, 19 cases showing predominantly fibrous tissue and 19 cases presenting with predominantly active fibrovascular proliferation. Two cases had minimal fibrovascular proliferation. Retinal breaks were identified in 7 eyes (17.5%) before surgery and in 33 eyes (82.5%) during surgery. Thirty-seven eyes (92.5%) achieved long-term retinal reattachment. Silicone oil was used in 23 eyes (57.5%). Visual acuity improved in 28 eyes (70%), was unchanged in 6 (15%), and became worse in 6 (15%). In 19 eyes postoperative vision was better than 20/400. Multiple regression analysis showed preoperative visual acuity as the single factor associated with postoperative visual outcome. INTERPRETATION Combined retinal detachment in proliferative diabetic retinopathy may occur during the stage of active fibrovascular proliferation or as a late complication. It is frequently associated with tightly adherent preretinal tissue and extensive detachment. Preoperative visual acuity best predicts visual prognosis.

Subconjunctival injection of bevacizumab in the treatment of corneal neovascularization associated with lipid deposition.

Purpose: To determine the effects on corneal neovascularization (NV) and lipid deposition after subconjunctival injection of bevacizumab in patients who had NV associated with lipid keratopathy. Methods: A case interventional study enrolled 18 patients (18 eyes) with lipid keratopathy. We gave monthly subconjunctival injections of bevacizumab from 3 to 10 times during the follow-up period according to the clinical response. We evaluated the centricity, extent, and percentage of involved corneal surface (PICS) of the corneal NV; the density and PICS of the corneal lipid deposition; and best-corrected visual acuity before and after treatment. We analyzed the treatment effects using Wilcoxon and Student t tests. Results: After the treatment, the change in best-corrected visual acuity was less than 2 lines. The extent, centricity, and PICS of the corneal NV and the density and PICS of the corneal lipid deposition decreased significantly after treatment (P = 0.014/0.002/0.001 and 0.001/<0.001, respectively). No eyes had side effects. Conclusions: The effects of subconjunctival injection of bevacizumab in treating corneal NV associated with lipid deposition were significant in some patients.

Clinical Outcomes in Cytomegalovirus-Positive Posner-Schlossman Syndrome Patients Treated With Topical Ganciclovir Therapy

PURPOSE To evaluate the clinical characteristics and therapeutic outcomes of cytomegalovirus (CMV)-positive Posner-Schlossman syndrome patients undergoing topical ganciclovir treatment. DESIGN Retrospective, comparative, and interventional case series. METHODS One eye of each of 126 consecutive Posner-Schlossman syndrome patients was investigated using aqueous polymerase chain reaction (PCR) between January 2006 and June 2013. The initial presentations and follow-up data of the CMV-positive patients (68 eyes) and CMV-negative patients (58 eyes) were compared. RESULTS Severe endothelial cell loss (P < .001) and a higher number of eyes requiring glaucoma filtering surgery (P = .017) were observed in CMV-positive Posner-Schlossman syndrome patients. All CMV-infected eyes treated with continual topical 2% ganciclovir exhibited an undetectable CMV level at the following taps. During follow-up, the average number of antiglaucomatous agents decreased, and a similar frequency of intraocular pressure (IOP) spikes was observed in both groups (P = .358). Patients with CMV-positive eyes with a disease duration over 5 years were likely to require glaucoma surgery (P = .024, log-rank test). All patients receiving surgery exhibited CMV-negative PCR during the IOP attack, but experienced severe peripheral anterior synechiae and pigment clogging. Both groups exhibited a similar endothelial cell decrease (P = .243) and probability of progressive endothelial cell loss (P = .219, log-rank test). CONCLUSION Ganciclovir treatment was effective for clearing the viral load, assisting the IOP control, and preserving the corneal endothelium of CMV-positive Posner-Schlossman syndrome patients. Early diagnosis and proper treatment could decrease the risk of advanced glaucoma and avoid glaucoma surgery in long-lasting cases.

Comparison of In Vivo Confocal Microscopic findings between epi-LASIK procedures with different management of the epithelial flaps

PURPOSE To use in vivo confocal microscopy to compare the wound-healing process in epikeratome laser-assisted in situ keratomileusis (epi-LASIK) with different management of the epithelial flaps. METHODS This prospective study comprised 46 eyes in the on-flap group and 47 eyes in the off-flap group. Epithelial flaps were repositioned or removed in the on- and off-flap eyes, respectively. In vivo confocal microscopy was performed before surgery and at 1 and 2 weeks and 1, 3, and 6 months after surgery. Corneal epithelial thickness, basal/apical surface epithelial morphology, and stromal reactions were analyzed. RESULTS Complete epithelialization by slit lamp biomicroscopy was faster for mitomycin C (MMC)-treated off-flap (4.27 ± 0.70 days) than on-flap (5.84 ± 0.08 days) eyes (P = 0.01). The percentage of eyes recovering to preoperative basal epithelial cell confocal morphology in the on- and off-flap groups was 87.5% and 92.3% for MMC-treated eyes and 86.3% and 90.5% in eyes without MMC treatment at 1 month after surgery. Of the studied eyes, with or without MMC, 50% and 100% returned to their preoperative apical epithelial morphology by 3 months in the on-flap and off-flap groups, respectively. Regression analysis revealed that the repositioned flap resulted in significant delay of epithelialization and apical-basal epithelial recovery (P < 0.01). Stromal reaction did not differ significantly at any of the time points. Corneal epithelial thickness was significantly thicker in the on-flap eyes (54.2 ± 4.5 μm) than in the off-flap eyes (26.7 ± 5.8 μm) at 1 month after surgery (P < 0.01). CONCLUSIONS On- and off-flap epi-LASIK showed comparable clinical outcomes after surgery. Off-flap epi-LASIK had more rapid re-epithelialization and normalization of epithelial morphology than did on-flap epi-LASIK, when observed by in vivo confocal microscopy. (ClinicalTrials.gov number, NCT00491439.).

Intravitreal gas injection for macular hole with localized retinal detachment in highly myopic patients.

Purpose:  This study aimed to evaluate treatment effects of intravitreal gas for macular hole with localized retinal detachment (RD) in highly myopic eyes and to examine how the vitreomacular relationship and other factors may influence treatment outcomes.