Ranibizumab in patients with dense cataract and proliferative diabetic retinopathy with rubeosis.
ABSTRACT: BACKGROUND:To evaluate the safety of ranibizumab as a surgical adjunct during cataract surgery in patients with proliferative diabetic retinopathy (PDR) with rubeosis, and to evaluate the efficacy and adverse effects of ranibizumab in treating PDR with rubeosis. MATERIALS AND METHODS:Three intravitreal injections of 0.5 mg ranibizumab were administered on day-1, months-1 and -2 with cataract surgery 6-16 days after first injection. Retreatments with ranibizumab injections and pan-retinal photocoagulation (PRP) were given if recurrence or persistence of PDR was noted between months-3 and -11. Safety observation visits occurred at months-12, -18 and -24. Primary end points were incidence and severity of adverse events (AEs) that were related to both cataract surgery and treatment of PDR with rubeosis through month -12. RESULTS:Of six patients screened, four (mean age 61.3 years) were enrolled. No AEs were noted with either cataract surgery or treatment of PDR. Neovascularization of iris (NVI) promptly regressed by 4 days after first ranibizumab injection, prior to cataract surgery in three of four patients (one had significantly regressed NVI by post-injection day-3 visit); NVI was not noted in any patient at 2 weeks after first ranibizumab injection. Recurrence of rubeosis or NVA after 3 monthly injections was not observed in any. At month-12, PDR was not present when assessed clinically and by fluorescein angiogram (FA). Only one patient developed neovascularization of disc and neovascularization elsewhere and required retreatments at months-5 and -9. CONCLUSIONS:Multiple intravitreal injections of ranibizumab may be a safe, effective treatment adjunct for PDR and diabetes-related rubeosis.
Project description:<h4>Introduction</h4>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).<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusion</h4>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:This study investigates the safety and efficacy of conbercept injection through different routes for neovascular glaucoma (NVG) treatment, in which seventy-four patients (81 eyes) with NVG caused by ischemia retinopathy had participated. Patients were divided into three stages according to the progression of NVG and were randomly assigned to receive intracameral or intravitreal conbercept injection. After conbercept injection, patients experienced improved best-corrected visual acuity (BCVA), good intraocular pressure (IOP) control, and neovascularization of Iris (NVI) regression. In stage III, patients required trabeculectomy with mitomycin C plus pan-retinal photocoagulation (PRP) to achieve complete NVI regression. Compared to the intravitreal group, the intracameral group had significantly lower IOP in 2 days in stage III and 1 day in stages I and II after injection, complete NVI regression before PRP in stages I and II, and better NVI regression in stage III. The rates of hyphema after trabeculectomy and malfunction filtering bleb suffering needle bleb revision were lower in the intracameral group, but only the hyphema rate was significantly different. Injections through different routes are all safe. We recommend intravitreal injections for patients in stages I and II, but for stage III, intracameral injection is better, and trabeculectomy with mitomycin C should be conducted within 2 days after injection to maximally reduce the risk of perioperative hyphema. <b>Trial Registration:</b> ClinicalTrials.gov, identifier NCT03154892.
Project description:PURPOSE:To compare rates and identify predictive factors for events that represent worsening of proliferative diabetic retinopathy (PDR) in eyes treated with panretinal photocoagulation (PRP) or ranibizumab. DESIGN:Randomized clinical trial (55 United States sites). PARTICIPANTS:Three hundred ninety-four study eyes from 305 adults with PDR, visual acuity (VA) 20/320 or better, and no history of PRP. INTERVENTION:Panretinal photocoagulation or intravitreous ranibizumab injections (0.5 mg/0.05 ml). MAIN OUTCOME MEASURES:Time from randomization to a composite PDR-worsening outcome defined as the first occurrence of vitreous hemorrhage, retinal detachment, anterior segment neovascularization, or neovascular glaucoma. RESULTS:Through 2 years, the cumulative probability of worsening PDR was 42% (PRP) versus 34% (ranibizumab; hazard ratio [HR], 1.33; 99% confidence interval [CI], 0.90 to 1.98; P = 0.063). Worse baseline levels of diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study scale) were associated with increased risk of worsening PDR, regardless of treatment group (64% [high-risk PDR or worse] vs. 23% [moderate PDR or better]; HR, 3.97; 99% CI, 2.48 to 6.36; P < 0.001). In the PRP group, eyes receiving pattern scan versus conventional single-spot PRP also were at higher risk for worsening PDR (60% vs. 39%; HR, 2.04; 99% CI, 1.02 to 4.08; P = 0.008), regardless of the number of spots placed or the number of sittings to complete the initial PRP. Eyes in both groups with vision-impairing (VA 20/32 or worse) center-involved diabetic macular edema (DME) at baseline were required to receive ranibizumab for center-involved DME. Therefore the composite outcome was compared by treatment in the subgroup of eyes that did not have vision-impairing center-involved DME at baseline. For these eyes, the rate of PDR-worsening was greater with PRP than ranibizumab (45% vs. 31%; HR, 1.62; 99% CI, 1.01 to 2.60; P = 0.008). CONCLUSIONS:In eyes with PDR, ranibizumab resulted in less PDR worsening compared with PRP, especially in eyes not required to receive ranibizumab for center-involved DME. Although anti-vascular endothelial growth factor therapy requires a more frequent visit schedule than PRP, these findings provide additional evidence supporting the use of ranibizumab as an alternative therapy to PRP for PDR, at least through 2 years.
Project description:PURPOSE:To assess the effect of single versus multiple subconjunctival ranibizumab injections in patients with an early pterygium recurrence. SETTING:Single-center, academic practice. STUDY POPULATION:Nine patients with early pterygium recurrence. OBSERVATIONAL PROCEDURE:Subconjunctival ranibizumab (0.5 mg/0.05 mL) was administered adjacent to pterygium recurrence. Group 1 (n = 5) received one injection; group 2 (n = 4) received three injections (time points 0, 2, and 4 weeks) with the ability to retreat as needed. MAIN OUTCOME MEASURES:Effect of ranibizumab on conjunctival hyperemia and corneal neovascular area over a 6-month follow-up period. RESULTS:In the single injection group, a decrease in conjunctival hyperemia was noted in all patients on postinjection day 1. At follow up, hyperemia grade fluctuated, although all patients had less hyperemia than at baseline. In the recurrent injection group, the median number of injections was 8.5 (range 7 to 9) over the 6 months. In spite of the repeated injections, the pattern of conjunctival hyperemia was similar to that of the single injection group. In group 1, corneal neovascularization remained relatively unchanged over the 6-month period in four patients and decreased in one patient by 24%. In group 2, corneal neovascularization increased in one patient by 39%, remained stable in one patient, and decreased in two patients by 34% and 44%. CONCLUSION:This is the first study to evaluate the role of ranibizumab in the treatment of an early pterygium recurrence and the first to compare multiple versus single injections. Recurrent injections did not appear to be superior to a single injection with regards to conjunctival hyperemia.
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:Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents including ranibizumab and aflibercept are used to treat patients with ocular disorders such as neovascular age-related macular degeneration (nAMD); however, the injections are associated with rare instances of severe ocular inflammation. This study compared severe ocular inflammation rates in patients treated with ranibizumab versus aflibercept.United States physician-level claims data covering an 18-month period for each therapy were analyzed. The primary analysis compared severe ocular inflammation event rates per 1000 injections. Sensitivity and subgroup analyses evaluated the impact of factors including intraocular surgery, intravitreal antibiotic administration, and previous intravitreal injections.The analysis included 432,794 injection claims (ranibizumab n = 253,647, aflibercept n = 179,147); significantly, more unique severe ocular inflammation events occurred in patients receiving aflibercept than ranibizumab (1.06/1000 injections, 95% confidence interval [CI], 0.91-1.21, vs. 0.64/1000 injections, 95% CI 0.54-0.74; p < 0.0001). Comparable results were observed for analyses of patients who had undergone glaucoma or cataract surgeries, had antibiotic-associated endophthalmitis, had non-antibiotic-associated endophthalmitis, and were non-treatment-naive. In contrast, no significant differences in severe ocular inflammation claims were recorded in treatment-naive patients who had no record of anti-VEGF treatment in the 6 months preceding the index claim. No significant change occurred in the rate of severe ocular inflammation claims over time following ranibizumab treatment.Severe ocular inflammation was more frequent following intravitreal injection with aflibercept than with ranibizumab during routine clinical use in patients with nAMD. This highlights the importance of real-world, post-approval, observational monitoring of novel medicines, and may aid clinical decision-making, including choice of anti-VEGF agent.
Project description:The standard care for proliferative diabetic retinopathy (PDR) usually is panretinal photocoagulation, an inherently destructive treatment that can cause iatrogenic vision loss. Therefore, evaluating the effects of therapies for diabetic macular edema on development or worsening of PDR might lead to new therapies for PDR.To evaluate the effects of intravitreal ranibizumab or triamcinolone acetonide, administered to treat diabetic macular edema, on worsening of diabetic retinopathy.Exploratory analysis was performed on worsening of retinopathy, defined as 1 or more of the following: (1) worsening from no PDR to PDR, (2) worsening of 2 or more severity levels on reading center assessment of fundus photographs in eyes without PDR at baseline, (3) having panretinal photocoagulation, (4) experiencing vitreous hemorrhage, or (5) undergoing vitrectomy for the treatment of PDR.Community- and university-based ophthalmology practices.Individuals with central-involved diabetic macular edema causing visual acuity impairment.Eyes were assigned randomly to sham with prompt focal/grid laser, 0.5 mg of intravitreal ranibizumab with prompt or deferred (?24 weeks) laser, or 4 mg of intravitreal triamcinolone acetonide with prompt laser.Three-year cumulative probabilities for retinopathy worsening.For eyes without PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening (P value comparison with sham with prompt laser) were 23% using sham with prompt laser, 18% with ranibizumab with prompt laser (P = .25), 7% with ranibizumab with deferred laser (P = .001), and 37% with triamcinolone with prompt laser (P = .10). For eyes with PDR at baseline, the 3-year cumulative probabilities for retinopathy worsening were 40%, 21% (P = .05), 18% (P = .02), and 12% (P < .001), respectively. CONCLUSIONS AND RELEVANCE Intravitreal ranibizumab appears to be associated with a reduced risk of diabetic retinopathy worsening in eyes with or without PDR. Intravitreal triamcinolone also appears to be associated with a reduced risk of PDR worsening. These findings suggest that use of these drugs to prevent worsening of diabetic retinopathy may be feasible. Given the exploratory nature of these analyses, the risk of endophthalmitis following intravitreal injections, and the fact that intravitreal triamcinolone can cause cataract or glaucoma, use of these treatments to reduce the rates of worsening of retinopathy, with or without PDR, does not seem warranted at this time.
Project description:<h4>Purpose</h4>To evaluate the efficacy and safety of ranibizumab 0.5 mg in adolescent patients with any choroidal neovascularization etiology enrolled in the 12-month MINERVA study.<h4>Methods</h4>In the open-label, non-randomized study arm, ranibizumab 0.5 mg was administered to five adolescents (aged 13-17 years). The findings were assessed descriptively as individual case reports at Month 12. Best-corrected visual acuity changes, central subfield thickness, treatment exposure, and safety were described over 12 months.<h4>Results</h4>Baseline choroidal neovascularization etiologies of the study eye included choroidal neovascularization secondary to Best disease (n = 2), idiopathic chorioretinopathy (n = 2), and optic disk drusen (n = 1). At Months 2, 6, and 12, the observed mean best-corrected visual acuity changes in the study eye from baseline were +9.2, +16.6, and +16.6 letters, respectively, and the observed mean central subfield thickness change from baseline was -31.4, -87.6, and -116.4 μm, respectively. Adolescent patients received a mean of three (range, 2-5) ranibizumab injections in the study eye. No adverse events or serious adverse events related to ranibizumab were reported.<h4>Conclusion</h4>Ranibizumab 0.5 mg treatment was beneficial in improving visual acuity and stabilizing or reducing central subfield thickness in five adolescents with differing choroidal neovascularization etiologies requiring infrequent injection. No new safety findings were observed over 12 months.
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:BACKGROUND:Numerous cytokines have been proven to participate in the pathogenesis of neovascular age-related macular degeneration (nAMD). The present study aimed to investigate the aqueous humor cytokine expression profile in nAMD patients before and after ranibizumab treatments in comparison to cataract patients. METHODS:This prospective study included 20 treatment-naïve nAMD eyes of 20 patients who received three consecutive monthly injections of ranibizumab. Aqueous humor samples were collected before the first (baseline), second (1?month later), and third (2?months later) injections. Controls were 20 age- and gender-matched cataract patients without any other ocular disease. The aqueous concentrations of 28 cytokines were measured using a multiplex bead assay. Central macular thickness (CMT) and maximum retinal thickness (MRT)-3?mm were measured by spectral domain optical coherence tomography (SD-OCT). The greatest linear diameter (GLD) was measured by fundus fluorescein angiography (FA). RESULTS:Three cytokines in aqueous humor, including angiogenin, interleukin-36? (IL-36?), and fibroblast growth factor-acidic (FGF-?) were significantly higher in nAMD patients in comparison to cataract patients, both before and after two consecutive monthly ranibizumab injections. Compared with the nAMD patients' basal levels, two consecutive monthly ranibizumab injections effectively reduced the aqueous concentrations of VEGF-A and placental growth factor (PlGF), as well as the values of CMT, MRT-3?mm, and GLD. CONCLUSIONS:Angiogenin, IL-36?, and FGF-? have higher expression levels in nAMD patients in comparison to cataract patients, both before and after 2?months of ranibizumab therapy. These cytokines may have correlations with the pathogenesis of nAMD.