Intravitreal Ranibizumab Injection as an Adjuvant in the Treatment of Neovascular Glaucoma Accompanied by Vitreous Hemorrhage after Diabetic Vitrectomy.
ABSTRACT: Purpose. To determine the efficacy of intravitreal ranibizumab injection as adjuvant therapy in the treatment of neovascular glaucoma (NVG) accompanied by postvitrectomy diabetic vitreous hemorrhage (PDVH). Methods. Eighteen NVG patients (18 eyes) accompanied by PDVH were enrolled in this prospective, monocenter, 12-month, interventional case series. The consecutive 18 patients with an IOP ? 25?mmHg despite being treated with the maximum medical therapy were treated with intravitreal ranibizumab injections. Vitreous surgery or/with Ahmed valve implantation were indicated if no clinical improvement in vitreous haemorrhage and uncontrolled IOP was shown. Results. Ten patients got clear vitreous and controlled IOP only with 2.7 ± 1.8 injections of ranibizumab without additional surgery. Vitrectomy or/with Ahmed valve implantation was administered in the other 8 eyes due to uncontrolled VH and IOP. At follow-up month 12, all the 18 eyes gained clear vitreous. At month 12 BCVA improved significantly compared to baseline. The baseline and follow-up at month 12 IOP/medication usage were 36.7 ± 8.1?mmHg on 3.4 ± 0.7 medications and 16.2 ± 4.9?mmHg on 0.67 ± 0.77 medications, respectively. Conclusions. The findings suggest that intravitreal ranibizumab injection as adjuvant therapy for treatment of NVG accompanied by PDVH may be safe and potentially effective. This clinical trial is registered with NCT02647515.
Project description:INTRODUCTION: The present study aimed to evaluate the effects of intravitreal ranibizumab (IVR) as adjunctive treatment for trabeculectomy with mitomycin C (TMC) in neovascular glaucoma (NVG). METHODS: This is a prospective study of 15 eyes from 14 consecutive patients with NVG carried out between December 2008 and December 2009. Each eye received IVR (0.5 mg/0.05 ml) 1 week before TMC. Trabeculectomy was performed with fornix-based conjunctival flap method. After TMC, additional panretinal photocoagulation (PRP), subconjunctival five fluorouracil injection, and bleb needling may be performed if indicated. The primary outcome measures were post-TMC intraocular pressure (IOP) and numbers of anti-glaucoma medication. The secondary outcome measures included of the recurrence of neovascularization at iris (NVI) and complications. RESULTS: Six eyes underwent adequate PRP before IVR but iris rubeosis still persisted. All eyes showed regression of NVI within 1 week after IVR. After TMC, mean IOP was significantly decreased from 37.9 mmHg preoperatively to 15.6 mmHg postoperatively (P < 0.001). Intraoperative hyphema was observed in four eyes. Thirteen eyes had controlled IOP (<21 mmHg) at last visit among which only one eye needed anti-glaucoma medication. Two eyes were considered as failure and needed further intervention. Visual acuity was maintained or improved in eight eyes. Recurrent NVI was not detected. All patients were symptom-free at last visit. Mean follow-up was 39 weeks. CONCLUSION: IVR is an effective treatment adjunctive to TMC for NVG. The occurrence of intraoperative complications was low and the short-term outcomes after trabeculectomy were favorable.
Project description:BACKGROUND:The aim of the present study was to evaluate the efficacy and safety of intravitreal conbercept combined with trabeculectomy and panretinal photocoagulation for neovascular glaucoma (NVG). METHODS:Fifty patients (54 eyes) with NVG were included in this prospective study. Fifty-two eyes initially underwent intravitreal conbercept (0.5 mg/0.05 ml) treatment followed by trabeculectomy and panretinal photocoagulation. Preoperative and postoperative best-corrected visual acuity (BCVA), intraocular pressure (IOP), the number of antiglaucoma medications, and surgical complications were recorded. The levels of VEGF-A, TGF-β1 and PLGF in aqueous humour samples collected during surgery were measured by enzyme-linked immunosorbent assay (ELISA). Light microscopy and transmission electron microscopy were used to observe the surgically excised trabecular tissue; enucleation was performed in 2 eyes, and light microscopy was used as the histopathological control. RESULTS:The follow-up period after trabeculectomy was 1 year. Of the 52 eyes, 39 completed 1 year of follow-up, and 13 were lost to follow-up. Recurrence of iris neovascularization was observed in 5 eyes, 9 had hyphema, 16 had filter-bled scarring, and no eye had complications attributable to the drug. The mean IOP was reduced from 48.1 ± 14.2 to 23.2 ± 8.7 mmHg, and the mean number of antiglaucoma medications used decreased from 3.0 (3.0, 4.0) to 1.0 (0.0, 1.0) after 1 year (both P < 0.05). The complete success rate was 76.9, 76.9, 71.0, 51.6, and 32.3% at 1 week, 1 month, 3 months, 6 months and 12 months, respectively, when the cut-off IOP was 18 mmHg. After patients underwent intravitreal injection, the concentrations of VEGF-A and TGF-β1 in the aqueous humour in NVG patients decreased from 168.8 ± 13.4 and 159.6 ± 15.4 pg/ml to 160.2 ± 7.6 and 151.9 ± 2.3 pg/ml, respectively (both P < 0.05). Light microscopy revealed neovascularization regression in the iris in specimens treated with intravitreal conbercept. Electron microscopy revealed trabecular endothelial cell degeneration in the conbercept-treated specimens. CONCLUSIONS:Our initial findings suggest that intravitreal conbercept is an effective treatment for managing NVG that has fewer short-term postoperative complications. TRIAL REGISTRATION:Current Controlled Trials ChiCTR1800019918 , 8 December 2018, retrospectively registered.
Project description:To study the prevalence of sustained intraocular pressure (IOP) elevation associated with intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents.Prospective comparative study. Non-glaucomatous patients scheduled to receive intravitreal injection of anti-VEGF therapy were recruited from an outpatient eye clinic, Songklanagarind Hospital between April 2013 and March 2014. The IOP was measured by Goldmann applanation tonometer before and at 1 hour, 1 week, 1 month, 3 months, and 6 months after injection. The IOP was compared using the repeated measures analysis. Sustained IOP elevation was defined as either an IOP > 21 mmHg or an increase from baseline ? 5 mmHg on two consecutive visits.Seventy eyes of 54 patients met the inclusion criteria. The most common diagnosis was diabetic macular edema (48%). The mean IOP ± standard deviation (SD) before treatment was 13.7 ± 2.8 mmHg. The means ± SDs after treatment at 1 hour, 1 week, 1 month, 3 months, and 6 months were 11.3 ± 2.6, 13.7 ± 3.6, 14.1 ± 3.3, 14.0 ± 2.3, and 13.7 ± 2.4 mmHg, respectively. A mean of IOP difference at 1 hour postinjection and at baseline was -2.36 ± 2.5 mmHg (P < 0.001). Four of 70 treated eyes (5.7%) developed sustained IOP elevation (IOP ? 5 mmHg from baseline on two consecutive visits). The IOP returned to baseline levels after 1 month, in three eyes. One eye had sustained IOP elevation at 3 and 6 months follow-up. Thereafter, IOP returned to baseline level. There was no need of anti-glaucoma medication.After receiving intravitreal injection of anti-VEGF agent, a small proportion of non-glaucomatous eyes developed a sustained IOP elevation without requiring IOP-lowering treatment. At 1 hour postinjection, there was a significant reduction of the mean IOP compared with the baseline level.
Project description:To compare the lamina cribrosa between eyes with and without neovascular glaucoma (NVG) using enhanced depth imaging spectral-domain optical coherence tomography.Forty-six patients with proliferative diabetic retinopathy were enrolled in this cross-sectional study. The patients were divided into two groups based on the absence or presence of NVG (the non-NVG group and the NVG group, respectively). The intraocular pressure (IOP), circumpapillary retinal nerve fiber layer (cpRNFL) thickness, anterior lamina cribrosa depth (ALD), and laminar thickness (LT) were compared between the groups.In the non-NVG group, the mean age was 66.2 ± 2.4 (mean ± standard error) years, mean maximum IOP was 18.8 ± 1.8 mmHg, mean cpRNFL thickness was 91.2 ± 3.9 ?m, mean ALD was 407.0 ± 22.9 ?m, and mean LT was 155.0 ± 4.7 ?m. In the NVG group, the mean age was 61.4 ± 2.1 years, mean maximum IOP was 33.1 ± 1.6 mmHg, mean cpRNFL thickness was 73.6 ± 3.4 ?m, mean ALD was 403.9 ± 20.1 ?m, and mean LT was 156.9 ± 4.2 ?m. The IOP was significantly higher and the cpRNFL was significantly thinner in the NVG group (P < 0.001 and P = 0.002, respectively). However, the age, ALD, and LT were not statistically different between the groups (P = 0.151, 0.919, and 0.757, respectively).Although the cpRNFL was thinner, the structure of the lamina cribrosa was unchanged in the NVG eyes. Axonal loss of the retinal ganglion cells in NVG patients was prior to lamina cribrosa deformation.
Project description:To compare the effect and safety of intravitreal conbercept (IVC), intravitreal ranibizumab (IVR), or intravitreal triamcinolone acetonide (IVTA) injection on 23-gauge (23-G) pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR).Fifty patients (60 eyes) of varying degrees of PDR were randomly grouped into 3 groups (1?:?1?:?1) (n = 20 in each group). The 23-G PPV was performed with intravitreal conbercept or ranibizumab injection 3-7?days before surgery or intravitreal TA injection during surgery. The experiment was randomized controlled, with a noninferiority limit of five letters. Main outcome measures included BCVA, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, and silicone oil tamponade.At 6 months after surgery, there were no significant differences of BCVA improvements, operation time, incidence of iatrogenic retinal breaks, endodiathermy rate, silicone oil tamponade, vitreous clear-up time, and the incidence of intraoperative bleeding between the IVC and IVR groups (all P values ? 0.05), but they were significantly different from the IVTA group (all P values < 0.05). IOP increases did not show significant differences between the IVC and IVR groups, but both were significantly different with the IVTA group. More patients had higher postoperative IOP in the IVTA group.The intravitreal injection of conbercept, ranibizumab, or TA for PDR had a significant different effect on outcomes of 23-G PPV surgery. Conbercept and ranibizumab can reduce difficulty of the operation, improve the success rate of PPV surgery, and decrease the incidence of postoperative complications.
Project description:Vascular endothelial growth factor plays a role in proliferative diabetic retinopathy (PDR). Intravitreal injection of saline has been shown potentially to lead to improved visual acuity compared with observation alone in eyes with vitreous hemorrhage. Therefore, it is important to determine if intravitreal anti-vascular endothelial growth factor can reduce vitrectomy rates (and risks associated with vitrectomy) compared with saline for vitreous hemorrhage from PDR that precludes placement or confirmation of complete panretinal photocoagulation.To evaluate intravitreal ranibizumab compared with intravitreal saline injections on vitrectomy rates for vitreous hemorrhage from PDR.Phase 3, double-masked, randomized, multicenter clinical trial. Data reported were collected from June 2010 to March 2012 and include 16 weeks of follow-up.Community-based and academic-based ophthalmology practices specializing in retinal diseases.Two hundred sixty-one eyes of 261 study participants, who were at least 18 years of age with type 1 or type 2 diabetes mellitus. Study eyes had vitreous hemorrhage from PDR precluding panretinal photocoagulation completion.Eyes were randomly assigned to 0.5-mg intravitreal ranibizumab (n = 125) or intravitreal saline (n = 136) at baseline and 4 and 8 weeks.Cumulative probability of vitrectomy within 16 weeks.Cumulative probability of vitrectomy by 16 weeks was 12% with ranibizumab vs 17% with saline (difference, 4%; 95% CI, -4% to 13%) and of complete panretinal photocoagulation without vitrectomy by 16 weeks was 44% and 31%, respectively (P = .05). The mean (SD) visual acuity improvement from baseline to 12 weeks was 22 (23) letters and 16 (31) letters, respectively (P = .04). Recurrent vitreous hemorrhage occurred within 16 weeks in 6% and 17%, respectively (P = .01). One eye developed endophthalmitis after saline injection.Overall, the 16-week vitrectomy rates were lower than expected in both groups. This study suggests little likelihood of a clinically important difference between ranibizumab and saline on the rate of vitrectomy by 16 weeks in eyes with vitreous hemorrhage from PDR. Short-term secondary outcomes including visual acuity improvement, increased panretinal photocoagulation completion rates, and reduced recurrent vitreous hemorrhage rates suggest biologic activity of ranibizumab. Long-term benefits remain unknown. Whether vitrectomy rates after saline or ranibizumab injection are different than observation alone cannot be determined from this study.The study is listed on www.clinicaltrials.gov, under identifier NCT00996437 (website registration date October 14, 2009).
Project description:Purpose:The 0.19 mg fluocinolone acetonide (FAc) intravitreal implant is approved in the United Arab Emirates (UAE) for treating diabetic macular edema (DME) in patients previously treated with a course of corticosteroids and that did not have a clinically significant rise in intraocular pressure (IOP). This ongoing study is assessing its effectiveness and safety in pseudophakic patients with DME in clinical practice from a single center in the UAE. Methods:A retrospective, ongoing 6-month audit study (NCT03590587), in which 22 eyes from 22 patients were treated with a single FAc intravitreal implant after treatment with a prior course of corticosteroids. Outcomes assessed included mean changes in best-corrected visual acuity (BCVA), central macular thickness (CMT), and IOP. Six-month follow-up data are presented. Results:After FAc implantation, mean BCVA improved rapidly, increasing by 25.4 ± 3.0 letters (mean±SEM) from baseline to Month 6 (p<0.0001). At 6 months, BCVA had improved by 15 letters or more in 91% of eyes (n=20/22). Mean CMT decreased by 267.0 ± 20.1 µm from baseline to Month 6 (p<0.0001). Over 85% of eyes (n=19/22) had a CMT less than 300 µm at 6 months. Mean IOP increased by 2.9 ± 0.7 mmHg from baseline to Month 6 (p<0.001). All eyes except 2 had an IOP of 21 mmHg or lower. At Month 6, five eyes (23%) needed IOP-lowering therapy. Conclusion:Injection of the FAc intravitreal implant rapidly and significantly improved BCVA and CMT within 6 months. These rapid and significant improvements exceed those reported in other real-world studies. Safety signals were consistent with corticosteroid class effects. The FAc implant may be a useful treatment option for patients in the UAE, particularly those with sight threatening DME requiring rapid functional improvements.
Project description:PURPOSE:To investigate the effect and complications of Combined Endoscope assisted Procedures (CEaP): endoscopic cyclophotocoagulation and pars plana ablation (ECP-plus), along with endoscopic panretinal photocoagulation (PRP). PATIENTS AND METHODS:The study design is a retrospective and noncomparative interventional case series from a tertiary referral center in Taiwan. Patients experiencing vessel growth at the iris and anterior chamber angle, along with an IOP > 21 mmHg were included. RESULTS:Twenty-five eyes from 23 patients were included over a 24-month period. After the procedures, all of them had a lower IOP value than their preoperative value. The mean IOP was 38.2± 7.1 mm Hg preoperatively, and 10.2± 4.7 mmHg (1 day), 13.8± 4.6 mmHg (1 week), 15.0± 5.3 mmHg (2 weeks), 17.4± 4.7 mmHg (1 month), 16.6± 4.1 mmHg (3 months), 16.0± 5.0 mmHg (6 months), and 15.7± 5.5 mmHg (12 months) postoperatively. At the 6th and 12th months, the IOP stabilized rate was 84% and 75%, respectively. Complications in the initial postoperative period (< 3 months) included uveitis (24%), and hyphema (16%), which were both resolved in the early postoperative period. Complications beyond 6 months included hypotony and phthisis bulbi in two patients (8%) in our study. There was no subject who suffered from retinal detachment, endophthalmitis or any other severe complications. CONCLUSIONS:The results of this study show that CEaP offers positive results in IOP lowering and NV regression. Additionally, CEaP is a complete treatment for NVG in controlling IOP and NV growth. The IOP lowering effects can be sustained upon completion of the treatment.
Project description:To evaluate the safety and tolerability of intravitreal ISTH0036, an antisense oligonucleotide selectively targeting transforming growth factor beta 2 (TGF-?2), in patients with primary open angle glaucoma (POAG) undergoing trabeculectomy (TE; glaucoma filtration surgery).In this prospective phase I trial glaucoma patients scheduled for TE with mitomycin C (MMC) received a single intravitreal injection of ISTH0036 at the end of surgery in escalating total doses of 6.75 ?g, 22.5 ?g, 67.5 ?g or 225 ?g, resulting in calculated intraocular ISTH0036 concentrations in the vitreous humor of approximately 0.3 ?M, 1 ?M, 3 ?M or 10 ?M after injection, respectively. Outcomes assessed included: type and frequency of adverse events (AEs), intraocular pressure (IOP), numbers of interventions post trabeculectomy, bleb survival, visual acuity, visual field, electroretinogram (ERG), slit lamp biomicroscopy and optic disc assessment.In total, 12 patients were treated in the 4 dose groups. Main ocular AEs observed were corneal erosion, corneal epithelium defect, or too high or too low IOP, among others. No AE was reported to be related to ISTH0036. All other safety-related analyses did not reveal any toxicities of concern, either. The mean medicated preoperative IOP at decision time-point for surgery was 27.3 mmHg +/- 12.6 mmHg (SD). Mean IOP (±SD) for dose levels 1, 2, 3, and 4 were at Day 43 9.8 mmHg ± 1.0 mmHg, 11.3 mmHg ± 6.7 mmHg, 5.5 mmHg ± 3.0 mmHg and 7.5 mmHg ± 2.3 mmHg SD; and at Day 85 9.7 mmHg ± 3.3 mmHg, 14.2 mmHg ± 6.5 mmHg, 5.8 mmHg ± 1.8 mmHg and 7.8 mmHg ± 0.6 mmHg, respectively. In contrast to IOP values for dose levels 1 and 2, IOP values for dose levels 3 and 4 persistently remained below 10 mmHg throughout the observation period.This first-in-human trial demonstrates that intravitreal injection of ISTH0036 at the end of TE is safe. Regarding IOP control, single-dose ISTH0036 administration of 67.5 ?g or 225 ?g at the time of TE resulted in IOP values persistently < 10 mmHg over the three month postoperative observation period.
Project description:<h4>Purpose</h4>To investigate the effect of ageing on the recovery of ocular blood flow, intravitreal oxygen tension and retinal function during and after intraocular pressure (IOP) elevation.<h4>Methods</h4>Long Evans rats (3- and 14-month-old) underwent acute stepwise IOP elevation from 10 to 120 mmHg (5 mmHg steps each 3 minutes). IOP was then returned to baseline and recovery was monitored for 2 hours. Photopic electroretinograms (ERG) were recorded at each IOP step during stress and at each minute during recovery. Ocular blood flow and vitreal oxygen tension (pO2) were assayed continuously and simultaneously using a combined laser Doppler flow meter (LDF) and an oxygen sensitive fibre-optic probe, respectively. The combined sensor was placed in the vitreous chamber, proximal to the retina. Data were binned into 3 minute intervals during stress and 1 min intervals during recovery. Recovery data was described using a bi-logistic function.<h4>Results</h4>Rats of both ages showed similar susceptibility to IOP elevation, with pO2 showing a closer relationship to ERG than LDF. During recovery, both ages showed a distinctive two-phased recovery for all three measures with the exception of the LDF in 3-month-old rats, which showed only 1 phase. In all animals, LDF recovered fastest (<1 minute), followed by pO2 (<10 minute) and ERG (>1 hour). 14-month-old rats showed surprisingly faster and greater LDF recovery compared to the younger group, with similar levels of pO2 recovery. However, the ERG in these middle-aged animals did not fully recover after two hours, despite showing no difference in susceptibility to IOP during stress compared to the young group.<h4>Conclusions</h4>Young and middle-aged eyes showed similar susceptibility to IOP elevation in terms of pO2, LDF and ERG. Despite this lack of difference during stress, older eyes did not completely recover function, suggesting a more subtle age-related susceptibility to IOP.