Loading Doses Of Ranibizumab Research Articles

Prevalence of Serous Macular Detachment in Recurrent Macular Edema Secondary to Retinal Vein Occlusion.

Objectives:To evaluate the prevalence of serous macular detachment (SMD) accompanying recurrent cystoid macular edema (CME) in patients initially treated for CME secondary to retinal vein occlusion (RVO) with accompanying SMD, and discuss the factors that affect the prevalence.Materials and Methods:We retrospectively evaluated the medical records of 71 patients with RVO-associated CME and SMD who achieved complete anatomical resolution after treatment with either a single dexamethasone implant or three loading doses of ranibizumab and developed recurrent CME during follow-up.Results:Initial treatment was a single intravitreal dexamethasone implant in 45 patients (63.4%) (Group 1) and three loading doses of intravitreal ranibizumab in 26 patients (36.6%) (Group 2). The mean time to CME recurrence was 4.7±0.8 months (range, 4-7 months) and was similar in both groups (p=0.984). At the time of CME recurrence, SMD was present in 41 patients (57.7%) and absent in 30 patients (42.3%). SMD was present in 27 (60.0%) of the 45 Group 1 patients and 14 (53.8%) of the 26 Group 2 patients (p=0.613). SMD was present in 48.8% of branch RVO and 71.4% of central RVO patients at the time of recurrence (p<0.001).Conclusion:SMD accompanied recurrent CME in only 57.7% of patients previously treated for CME and SMD and seems to be more frequent in patients with central RVO. Initial intravitreal treatment choice of either ranibizumab or dexamethasone implant did not affect the prevalence of concurrent SMD in patients with recurrent CME.

Aggravation of retinal hard exudates after intravitreal anti-vascular endothelial growth factor therapy for cystoid macular edema and the risk factors: a retrospective study

Background/aimsTo evaluate retinal hard exudates (HEs) progression in patients with cystoid macular edema (CME) secondary to diabetic retinopathy (DR) or branch retinal vascular occlusion (BRVO) after intravitreal injections of ranibizumab (IVR) treatment and identify the risk factors for the deterioration of HEs.MethodsThis retrospective study enrolled 288 eyes with center-involving CME secondary to DR or BRVO from 288 patients (one eye per patient). All patients were treated with three loading doses of ranibizumab intravitreally at a monthly interval. The morphologic features of HEs were observed, and the HEs areas were quantified using a semi-automatic method at baseline, 1 month after the first dose of IVR and 1 month after the third dose of IVR therapy. HEs progression was defined as having a > =2-grade increase in the HEs severity scale. The best-corrected vision acuity (BCVA) and alterations in HEs areas were compared between DR and BRVO groups. And logistic regression analyses were used to identify the risk factors for HEs exacerbation.ResultsMorphological changes of retinal HEs occurred in all eyes after IVR therapy, although HEs area was not significantly changed in some eyes. DR group has a higher percentage of eyes with progressed HEs area than the BRVO groups (34.9% vs. 21.8%, P = 0.019) 1 month after the first dose of IVR. Both DR and BRVO groups had a decreased percentage of enlarged HEs 1 month after the third injection, but the DR group is still higher than the BRVO group (17.1% vs. 8.4%, P = 0.027). At baseline, there was no correlation between VA and HEs areas. After the first and third doses of IVR, there still was no consistent correlation between HEs severity and change in VA over time. Furthermore, CME with subretinal fluid (SRF) is associated with a higher risk of HEs progression (P = 0.001). Long CME duration and high serum low-density lipoprotein cholesterol (LDL-C) level were identified as risk factors for HEs progression following IVR treatment in both univariable and multivariable regression analyses (Odds ratio (OR) = 1.88, P = 0.012 and OR = 1.14, P = 0.021, respectively).ConclusionsAlterations in the area of retinal HEs are widely observed after IVR treatment for CME. The eyes with CME secondary to DR have a higher percentage of progressed HEs than the BRVO eyes. DME with SRF, extended duration of CME, and high LDL-C level are potential risk factors of deteriorated HEs after IVR treatment.

Intravitreal ranibizumab and dexamethasone implant injections as primary treatment of diabetic macular edema: simultaneously double protocol

PurposeTo assess the 12-month efficacy and safety of simultaneously administered intravitreal dexamethasone implant (DEX implant) and ranibizumab (simultaneous double protocol) injections in comparison with ranibizumab monotherapy as the first-line treatment of diabetic macular oedema (DMO).MethodsProspective, consecutive, clinical interventional study. Patients were randomized into two groups: 24 naive DMO patients (34 eyes) who received simultaneous double-protocol therapy and 22 DMO patients (34 eyes) who received ranibizumab monotherapy were included. Monthly ranibizumab (0.5 mg) was administered for the first 6 months and later on, an as-needed treatment basis. DEX implant injection was performed at any time during the loading dose of the three consecutive monthly injections of ranibizumab, and with as-needed reinjections of ranibizumab from 6th month onwards. Change in visual acuity was the primary efficacy endpoint. Secondary efficacy endpoints were a gain of ≥15 letters and a change in the central foveal thickness.ResultsMean BCVA increased from baseline to month 12 in the simultaneously double-protocol therapy group compared with the ranibizumab monotherapy group (21.6 versus 9.6 letters [P < 0.001]). The corresponding proportions of eyes gaining ≥15 letters were 60% versus 29.4% (P < 0.0001). Moreover, the mean reductions in the central foveal thickness were 413 versus 282 µm (P = 0.001). At 12 month, the simultaneous double-protocol therapy decreased a significant number of foveal cysts and subfoveal neuroretinal detachment compared with those by ranibizumab monotherapy.ConclusionsThe simultaneous addition of DEX implant at any time during the three monthly loading doses of ranibizumab in patients with DMO significantly improved the visual outcomes and revealed superior anatomic outcomes than those with the ranibizumab monotherapy.

The effect of single dose adjunctive dexamethasone implant on diabetic macular edema in patients on anti-vascular endothelial growth factor treatment: 1 year follow-up from a real-life practice

To evaluate the effect of single-dose intravitreal dexamethasone (Dx) implant as an adjunctive treatment for patients undergoing anti-vascular endothelial growth factor (anti-VEGF) treatment with poor response. Eighty-four eyes of 72 patients with non-proliferative diabetic retinopathy and diabetic macular edema with a poor response to 3 loading doses of intravitreal ranibizumab (IVR) were included in this study. Group 1 consisted of forty-four eyes which went on a Pro re Nata (PRN) dose regimen of IVR injections after 3 loading doses of ranibizumab, and Group 2 consisted of 40 eyes which received a single dose Dx implant as the 4th injection after 3 loading doses of ranibizumab injections and then went on PRN IVR injections. Patients whose macular edema was unchanged or decreased by<25% and gained three letters or less on the Early Treatment Diabetic Retinopathy Study visual acuity (VA) chart were defined as poorly responsive. Follow-up time was 12 months. After the 12-month follow-up, Group 1 gained a median of five letters, and Group 2 gained a median of three letters. After the fourth injection, both groups had statistically significant VA gains at 4, 6, 7, and 12 months when compared with controls (P<.05). Group 2 had a significantly increased VA at 4 and 6 months when compared with controls. However, beginning at 7 months, Group 1 had significantly increased VA when compared with Group 2. At both 4 and 6 months, controls (first 3 months after Dx implantation) in Group 2 had significantly decreased central macular thickness (CMT) when compared with Group 1. However, after 7 months, there was no significant difference between groups with regard to CMT (P>.05). A single-dose Dx implant after three consecutive IVR injections for poorly responsive diabetic macular edema has limited effect on either VA or CMT. The need for IVR injections did not decrease with a Dx implant.

Visual Outcomes Following Intravitreal Ranibizumab for Diabetic Macular Edema in a Pro Re Nata Protocol from Baseline: A Real-World Experience.

To investigate long-term outcomes of pro re nata (PRN) treatment protocol of ranibizumab for diabetic macular edema (DME) adopted from the first month of therapy without 3 loading doses. Retrospective interventional study. We analyzed 180 eyes of 144 patients treated with ranibizumab for DME with a minimum follow-up of 1 year during December 2013 to December 2017. Data of all patients with treatment-naive center-involving DME who received at least 1 intravitreal injection of ranibizumab during the study period were drawn from a locally adapted electronic form for DME. The primary outcome measure was change in best-corrected visual acuity (BCVA) from baseline at 1-year follow-up, with intergroup comparisons in BCVA between eyes receiving 1, 2, and 3 injections in the first 3 months of treatment. The mean baseline BCVA was 0.47 ± 0.30 logMAR, which improved to 0.38 ± 0.3 logMAR (P = 0.003) at 3 months and stabilized at 0.35 ± 0.27 logMAR at 1 year (P = 0.46 vs BCVA at 3 months) and 0.34 ± 0.26 logMAR at 2 years of follow-up (P = 0.44 vs BCVA at 3 months). At 3 months, 24 eyes (13%) underwent 1 intravitreal injection, 52 eyes (29%) had 2 injections, and the majority (n = 104 eyes, 58%) had 3 injections on a monthly basis. During the first year, the group that received only 1 injection in the first 3 months also required fewer injections and fewer follow-up visits compared with those receiving 2 or 3 injections in the first 3 months. One-third of eyes with DME responded well to PRN treatment strategy from the first month without 3 loading doses of ranibizumab. Baseline visual acuity is the best predictor of vision at 1 and 2 years of follow-up.

The Effect of Ranibizumab on Normal Neurosensory Retina in the Eyes of Patients with Exudative Age Related Macular Degeneration.

Background:Anti-vascular endothelial growth factors have become the mainstay treatment for neovascular age related macular degeneration. Prolonged suppression of vascular endothelial growth factor raises concerns as it may result in harmful effects on retina.Objective:The purpose of this retrospective chart review is to evaluate the 1-year effect of treatment with intravitreal injections of ranibizumab on normal neurosensory retinal tissue of patients with exudative age related macular degeneration using the Optical Coherence Tomography (OCT).Method:The study included sixty five eyes of 62 patients (32 male and 30 female; mean age 74.97±8.5 years) with exudative age related macular degeneration treated with intravitreal injections of ranibizumab with a pro re nata treatment regimen over a period of 1 year. The MM5 thickness maps acquired with the Optovue RTVue-100 Fourier-domain OCT at baseline, at 3 months, after the 3 loading doses of ranibizumab, and at the 1 year follow-up visit were used for analysis. Changes of inner and outer retinal thickness in four selected points of normal retina on the MM5 scan were evaluated.Results:The patients received a mean of 6.4 ± 1.8 (median 6, range 3-11) intravitreal injections of ranibizumab over a period of 12 months. No significant change was observed in inner and outer retinal thickness at pre-selected spots of normal retina during the first year of intravitreal administration of ranibizumab.Conclusion:One year treatment with ranibizumab on an individualized, according to need dosing regimen does not seem to induce any detectable structural damage in the unaffected, normal retina.

Effectiveness of Intravitreal Injection of Ranibizumab for Neovascular Age-Related Macular Degeneration with Serous Pigment Epithelial Detachment

BackgroundWe sought to observe the effectiveness of intravitreal injection of ranibizumab in treating neovascular age-related macular degeneration (nAMD) with serous pigment epithelial detachment (sPED).Material/MethodsA retrospective, noncomparative case series was performed. Twenty-3 eyes of 23 patients with sPED secondary to nAMD who had received intravitreal injections of ranibizumab were included in this study. All patients underwent best-corrected visual acuity (BCVA), synchronous fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT) examinations. All patients were treated with pro re nata intravitreal injections after 3 loading doses of ranibizumab and were followed up for 12 months. The differences in the BCVAs, maximum PED heights, PED volumes and CFTs of the affected eyes were compared between the baseline and last visit.ResultsTwelve months after the first injection, improved visual acuity was observed in 16 of the 23 eyes. 4 eyes exhibited stable visual acuity, and 3 eyes exhibited impaired visual acuity. The mean post-injection logMAR BCVA was 0.58±0.05, which was much better than that at baseline (0.76±0.08; t=1.751, P=0.0869). The mean maximum PED height at baseline was 350.17±35.73μm and it was decreased to 238.87±36.87μm (t=2.192, P=0.0337) at the last visit. The mean PED volume after injection was 0.34±0.1 mm3, which was significantly decreased compared with that at baseline (0.81±0.21 mm3; t=2.021, P=0.0494).The mean CFT decreased, but this difference was not statistically significant (t=1.003, P=0.3211). None of the patients exhibited endophthalmitis, uveitis or RPE tears.ConclusionsIntravitreal injection of ranibizumab for the treatment of neovascular age-related macular degeneration with serous pigment epithelial detachment safely and effectively improved the patients’ visual acuities and decreased their PED heights volumes.

Two-year outcome of an observe-and-plan regimen for neovascular age-related macular degeneration: how to alleviate the clinical burden with maintained functional results.

The purpose of this study was to report the 2-year outcome of an individually tailored 'observe-and-plan' treatment regimen for neovascular age-related macular degeneration (nAMD), and to investigate its clinical value in terms of functional outcome. This regimen aimed to reduce the clinical burden (visits) by employing individually fixed injection intervals, based on the predictability of an individual's need for retreatment. This prospective case series included 104 patients (115 eyes) with nAMD. Following three loading doses of ranibizumab, the disease recurrence interval was determined in monthly observation visits. Retreatment was applied in a series of three injections with individually fixed intervals (2 weeks shorter than the recurrence interval), combined with periodic adjustment of the intervals. The allowed injection intervals in treatment plans ranged from 1 to 3 months. If there was no recurrence at 3 months, the patient could change to monitoring alone. Mean visual acuity (VA) improved by 8.7, 9.7, and 9.2 letters at months 3, 12, and 24, respectively. The mean number of injections was 7.8 and 5.8 during years 1 and 2, respectively, whereas the mean number of ophthalmic examinations was 4.0 and 2.9, respectively. The mean treatment interval (after the loading doses) was 2.0 months during year 1, and 2.2 months during year 2. The observe-and-plan regimen significantly improved and maintained VA over the course of 2 years. This favourable functional outcome was achieved with fewer clinic visits compared with other regimens. Therefore, this observe-and-plan regimen has the potential to alleviate the clinical burden of nAMD treatment.

Reducing the clinical burden of ranibizumab treatment for neovascular age-related macular degeneration using an individually planned regimen

AimsThe purpose of this study was to clinically validate an individually planned treatment regimen for neovascular age-related macular degeneration (nAMD), termed, observe and plan. This regimen was based on the...

A Randomized Trial to Assess Functional and Structural Effects of Ranibizumab versus Laser in Diabetic Macular Edema (the LUCIDATE Study)

To compare the functional and structural effects of ranibizumab versus macular laser therapy in patients with center-involving diabetic macular edema. Prospective, randomized, single-masked clinical trial. Single center. Thirty-three eyes of 33 patients with center-involving diabetic macular edema, with best corrected visual acuity of 55 to 79 Early Treatment Diabetic Retinopathy Study letters at baseline, completing the 48-week study period. Subjects were randomized 2:1 to 3 loading doses of ranibizumab then retreatment every 4weeks as required; or macular laser therapy at baseline, repeated as required every 12weeks. Exploratory Outcome Measures: Structural imaging studies included greatest linear dimension and area of foveal avascular zone, perifoveal capillary dropout grade, and presence of morphologic features of diabetic macular edema on Spectralis optical coherence tomography (Heidelberg Engineering GmbH, Heidelberg, Germany). Functional measures: Visual acuity, retinal sensitivity in the central 4 and 12 degrees on microperimetry, color contrast sensitivity protan and tritan thresholds, pattern and full-field electroretinogram amplitudes and implicit times, and multifocal electroretinogram amplitude distribution. These were reported at 12, 24, and 48weeks. Ranibizumab-treated subjects gained 6.0 vs 0.9 letters lost for laser, demonstrated improved tritan and protan color contrast thresholds, and improved retinal sensitivity. Electrophysiologic function also improved after ranibizumab therapy. No safety issues were evident. Better retinal thickness reduction and structural improvement in optical coherence tomography features of diabetic macular edema were seen with ranibizumab therapy than in the laser group. There was no evidence of progressive ischemia with ranibizumab therapy. Ranibizumab therapy in the treatment of diabetic macular edema seems to improve retinal function and structure as demonstrated by this evaluation of different assessment methods.

16 and 24 Gy Low-voltage X-ray Irradiation With Ranibizumab Therapy for Neovascular Age-Related Macular Degeneration: 12-Month Outcomes

To describe the 12-month safety and efficacy outcomes of 16 or 24Gy radiation using low-voltage x-ray irradiation in conjunction with intravitreal ranibizumab for neovascular age-related macular degeneration (AMD). Prospective, phase I, open-label, nonrandomized uncontrolled safety study. setting: Institutional. study population: Neovascular AMD patients. intervention: One x-ray irradiation treatment at 16 or 24Gy was administered externally through 3 locations in the inferior pars plana. After 2 initial monthly loading doses of ranibizumab, subsequent ranibizumab was administered according to predetermined criteria. main outcome measures: Visual acuity, number of ranibizumab injections, safety and efficacy metrics at 12months. Forty-seven eyes of 47 patients were enrolled and completed 12months of follow-up: 16Gy (n= 28) and 24Gy (n= 19). There was no evidence of radiation retinopathy, optic neuropathy, or cataract. The mean visual acuity improved in both groups:+8.4 ± 11.9 letters and+7.8 ± 12 letters for 16 and 24 Gy, respectively. In both groups, 100% of subjects lost <15 letters, with 76% and 79% gaining ≥0 letters in the 16Gy and24Gy groups, respectively. Patients received a mean of 1.0 additional injection over 12months. Themean change in optical coherence tomography central subfield thickness from baseline to month 12 was-107 and-87μm for the 16Gy and 24Gy groups, respectively. One treatment of 16 or 24Gy low-voltage x-ray therapy with as-needed ranibizumab appears safe in subjects with neovascular AMD at 12months. An overall improvement in visual acuity was observed. No radiation-related adverse effects were reported.

Comparison of two intravitreal ranibizumab treatment schedules for neovascular age-related macular degeneration

IntroductionRanibizumab (Lucentis), a humanised antibody fragment that inhibits vascular endothelial growth factor (VEGF)-A, is widely used for the treatment of neovascular age-related macular degeneration (NV-AMD). The objective of this study...

A randomised prospective double-masked exploratory study comparing combination photodynamic treatment and intravitreal ranibizumab vs intravitreal ranibizumab monotherapy in the treatment of neovascular age-related macular degeneration

The aim of this study is to evaluate the effect of standard-fluence verteporfin photodynamic therapy (PDT) delivered on the first day of a ranibizumab regimen for choroidal neovascularisation secondary to age-related macular degeneration compared with ranibizumab monotherapy. Patients were randomised to sham or standard-fluence verteporfin PDT at baseline. The first of three monthly loading doses of ranibizumab was given on the same day, and thereafter patients received monthly treatment with ranibizumab as required. All patients underwent monthly visual acuity and OCT assessment and 3-monthly fluorescein angiography with follow-up to 1 year. In all, 18 patients were recruited. The PDT group gained a mean of 2.2 ETDRS letters at 1 year and the sham group gained a mean of 4.4 letters (P=0.47). Both groups required a mean of 1.3 injections of ranibizumab following the 3-month loading phase. Fluorescein angiography at 1 month demonstrated marked choroidal hypoperfusion in all patients treated with PDT with reduced choroidal perfusion persisting to month 12. This did not occur in the sham group. The addition of standard-fluence verteporfin PDT at baseline to a ranibizumab regimen conferred no benefit in terms of visual acuity or number of ranibizumab injections required at 1 year. The combination of these treatments resulted in persistent reduced choroidal perfusion, which raises potential safety concerns.