Administration Of Ranibizumab Research Articles

Reactivation of retinopathy of prematurity after ranibizumab treatment

Retinopathy of prematurity (ROP) is one of the most common causes of visual disability in children born prematurely. Intravitreal injection of angiogenesis inhibitors (antivascular endothelial growth factor [VEGF] therapy) is considered one of the conservative methods of treating ROP. Aim: This study aimed to present a clinical case of ROP reactivation after intravitreal injection of the antiVEGF drug ranibizumab (Lucentis). MATERIAL AND METHODS: The course of retinopathy in a premature infant with extremely low birth weight was studied. RESULTS: A patient diagnosed with ROP, a posterior aggressive form of both eyes, received intravitreal injections of an angiogenesis inhibitor at 36 postconceptional weeks. During subsequent follow-up, disease progression was noted, which necessitated repeated ranibizumab administrations to both eyes. Over time, tractional retinal detachment developed in the right eye, and the disease progressed more slowly in the left eye. At the age of 1 year, ROP rapidly progressed to stage 4B in the left eye. Lens vitrectomy was performed sequentially on the right and then on the left eye. At the age of 1.5 years, the patient had coarse preretinal adhesions in the posterior pole of both eyes and had no spatial vision, whereas light perception was preserved. CONCLUSION: Intravitreal ranibizumab administration for posteriorly aggressive ROP does not exclude its reactivation both early and late after administrations. Further improvement in treatment methods for ROP is necessary.

Comparison of OCT Angiography Parameters after Administration of Intravitreal Brolucizumab versus Ranibizumab in Exudative Age-related Macular Degeneration

Abstract Purpose: To compare the OCT angiography (OCTA)–derived parametric changes before and after intravitreal administration of ranibizumab and brolucizumab in patients with neovascular age-related macular degeneration (ARMD) and to compare the changes between the two groups. Methods: This retrospective cohort study was done on 68 eyes with neovascular ARMD: 34 received injection ranibizumab and 34 received brolucizumab in a stratified manner. Central foveal thickness (CFT) and OCTA parameters like vessel density (VD), superficial capillary plexus (SCP), deep capillary plexus (DCP), foveal avascular zone, (FAZ), fractal dimension (FD) were assessed. The scans were repeated 1 month postinjection. Results: In total, 46% had type 1 CNVM and 54% had Type 2 CNVM. In both the ranibizumab and brolucizumab group, the corrected visual acuity showed comparable significant improvement 1 month postinjection. The CFT showed significant reduction in both, more significant in brolucizumab. OCTA showed a minimal nonsignificant reduction in the VD, SCP and DCP at 1 month, which were not significantly different. The FAZ and FD showed a significant increase and reduction, respectively, in the brolucizumab group, unlike the ranibizumab group. Conclusion: OCTA changes suggest that anti-VEGF drugs produce no change in the capillary density. A reduction in structural architecture of smaller capillary branches i.e. fractal dimension and increase in FAZ is noted with brolucizumab, suggesting that some structural alterations of retinal microvasculature do exist with the drug.

Elevated aqueous TNF-α levels are associated with more severe functional and anatomic findings in eyes with diabetic macular oedema.

Intravitreal ranibizumab for diabetic macular oedema (DMO) has been recently shown to modulate levels of aqueous cytokines. This study investigates the associations between changes in aqueous cytokine levels following intravitreal ranibizumab therapy and the corresponding anatomical and functional changes in the eye. Twenty-five patients comprising 30 eyes diagnosed with DMO were prospectively recruited. All eyes received three loading dose ranibizumab injections at baseline, week 4 and week 8, followed by pro re nata treatment based on best-corrected visual acuity (BCVA) and central macular thickness (CMT) up to week 48. Prior to ranibizumab administration, aqueous samples were collected from all eyes, and subsequent sampling was performed at week 8. Levels of 32 cytokines were assessed at baseline and at week 8. At baseline, higher aqueous TNF-α levels were associated with poorer BCVA (p = 0.033), greater macular volume (p = 0.017) and worse diabetic retinopathy (p = 0.047). Higher levels of IL-7 were associated with poorer BCVA and greater macular volume (MV). Following treatment with ranibizumab there was a significant correlation with reduction of aqueous TNF-α and improvements in BCVA and MV, both at 6 months (BCVA [r = -0.558, p = 0.001], MV [r = 0.410, p = 0.024]) and 12-months (BCVA [r = -0.413, p = 0.023], MV [r = 0.482, p = 0.008]). The change in VEGF concentration following ranibizumab treatment did not correlate with either BCVA or MV improvements (p > 0.05). Higher levels of aqueous TNF-α and IL-7 correlated with worse DMO, both anatomically and functionally. Reductions in levels of aqueous TNF-α, but not VEGF, post ranibizumab treatment were associated with improvement in BCVA and MV.

New Approaches to Surgical Treatment of Patients with Advanced Stage of Proliferative Diabetic Retinopathy

Purpose. Development and evaluation of the clinical effectiveness and safety of a vitrectomy (VE) technique for patients with advanced stage proliferative diabetic retinopathy (ASPDR).Materials and methods. We observed 132 patients (mean age 62.8 ± 2.4 years) with the following criteria for inclusion in the study, corresponding to the classification criteria of ASPDR: it is impossible to estimate the area of neovascularization; the fundus of the eye is partially ophthalmoscoped or not ophthalmoscoped in the posterior pole; preretinal or vitreal hemorrhage in the posterior pole with an area of more than 4 optic discs; retinoschisis in the macular zone. All patients were divided into the following two groups, equal in age, gender and visual status of the “healthy” eye: the main group (MG, 69 patients, 69 eyes), who underwent VE was performed according to the developed method and a control group (CG, 63 patients, 63 eyes), in which VE was performed according to the traditional method.Results. The incidence of intraoperative complications in patients in the MG (5.8 %) was 8.1 % (p < 0.05) lower than in the CG (13.9 %). The incidence of postoperative complications in patients from the MG (5.5 ± 0.5 %) was 4.2 % (p < 0.01) lower than in the CG (9.7 ± 1.0 %). The increase in best-corrected visual acuity after surgery in patients from the MG was significantly (by 0.13 rel. units, p < 0.001) higher than in the CG. The value of the average decrease in the developed qualitative criteria for the condition of the fundus in patients in the MG (1.6 ± 0.1) was 23.1 % (p < 0.05), higher than in the CG (1.3 ± 0.1).Conclusion. Surgical treatment of patients with ASPDR using the developed technique provides (compared to the traditional approach) a higher level of safety and clinical effectiveness. The main advantage of the developed technique is an integrated approach to surgical intervention, including the improvement of ophthalmological “techniques” (use of one-stage combined surgery, endolaser coagulation technology, etc.) and drug support (administration of ranibizumab at a dose of 0.05 mg 3–5 days before surgery) and the choice of intravenous sedation as the optimal anesthetic aid.

Maximal Extension Interval and Visual Outcomes in a Treat-and-Extend Protocol: A Post Hoc Analysis of the CANTREAT Randomized Trial

Introduction: The Canadian Treat-and-Extend Analysis Trial with Ranibizumab (CANTREAT) was a 2-year, multicentred, randomized clinical trial to evaluate treat-and-extend (T&E) relative to monthly administration of ranibizumab in neovascular age-related macular degeneration (nAMD). This post hoc analysis of the CANTREAT trial explores the relationship between the maximal extension interval tolerated by patients receiving T&E ranibizumab and visual acuity outcomes. Methods: Treatment-naïve patients with nAMD were randomized to receive either a once-monthly dosing or T&E regimen of ranibizumab across 27 treatment centres in Canada and were followed for 24 months. For this post hoc analysis, patients in the T&E cohort were subdivided into the following groups based on maximum extension interval: 4 weeks, 6 weeks, 8 weeks, 10 weeks, and 12 weeks. The primary outcome was the change in ETDRS best-corrected visual acuity (BCVA) from baseline to month 24 while secondary outcomes included change in central retinal thickness (CRT). All results were reported using descriptive statistics. Results: A total of 285 participants undergoing T&E were enrolled in this post hoc analysis. At month 24, the change in BCVA from baseline was +8.5 ± 9.3, +7.7 ± 13.8, +4.4 ± 9.6, +4.4 ± 18.5, and +7.8 ± 14.8 letters in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. The change in CRT at month 24 was −79.2 ± 95.0, −143.9 ± 128.9, −97.7 ± 101.1, −120.9 ± 105.3, and −133.2 ± 108.8 μm in the 4-, 6-, 8-, 10-, and 12-week cohorts, respectively. Conclusion: The capacity to extend does not necessarily associate with improved visual acuity outcomes, with the poorest change in BCVA seen in those extended 8–10 weeks. The highest change in BCVA and lowest decrease in CRT was in the group maximally extended for 4 weeks. There was a correlation between change in BCVA and change in CRT for other extension groups. Future studies should establish the predictive factors for successful extension in patients undergoing T&E in nAMD.

СТРУКТУРА ЗАБОЛЕВАЕМОСТИ И ИСХОДЫ У ДЕТЕЙ, РОДИВШИХСЯ С ОЧЕНЬ И ЭКСТРЕМАЛЬНО НИЗКОЙ МАССОЙ ТЕЛА В РЕГИОНАЛЬНОМ ПЕРИНАТАЛЬНОМ ЦЕНТРЕ

Introduction. The provision of medical care to children born with very low body weight (VLBW) and extremely low body weight (ELBW) belongs to the category of tertiary level neonatal intensive care (TINC) and reflects the effectiveness of regional obstetric-gynecological, neonatology and pediatric services; and the study of the structure of morbidity and outcomes in this category of newborn babies determines methodological, organizational and medical problems of the territory. The aim of the study. To assess the structure of morbidity and outcomes in premature newborns with ELBW and VLBW at birth in the setting of a Regional Perinatal Center during one year follow-up. Materials and methods. As part of the study, a retrospective analysis of 132 inpatient medical records of infants born preterm with VLBW and ELBW in the Regional Perinatal Center of the Novosibirsk State Regional Clinical Hospital in 2022 was performed. Patients were divided into two groups. Group 1 included 80 babies born with VLBW (birth weight 1000–1499 g), group 2 included 52 babies with ELBW at birth (less than 1000 g). Results. These children with VLBW and ELBW at birth are heterogeneous in the structure of prematurity, which is due to the presence of intrauterine growth retardation (IUGR) in some of them. At the same time, only the group of children born with VLBW is heterogeneous: 77.5% were registered as extremely premature, of which 63.7% were very preterm, and 13.7% were moderately preterm and 8.8% were late preterm. The category of extremely preterm prevailed among children with ELBW – 71,2%. 28% of children born prematurely had IUGR. Its structure was also heterogeneous: among children with VLBW at birth, there were equally wasty for gestational age (GA) – 15% and small for GA – 13.8%. Among children with ELBW, the small for GA – 21.1% dominated, against 5.8% – light for GA. Operative delivery (cesarean section) was chosen as the predominant method in both groups – 77.5 and 78.8% of cases, respectively. Diseases associated with prematurity were more often registered among children with ELBW at birth: severe asphyxia at birth (34.6%) vs VLBW (5%), p < 0.001; HS PDA (38.5%) vs VLBW (17.5%), p < 0.01; IVH III deg. (13.5%) vs VLBW (1.3%), p < 0.01; RP = retinopathy (32.7%) vs VLBW (8.8%), p < 0.001; severe form of BPD (23.8%) vs VLBW (5.6%), p < 0.05; NEC II-III stages (17.3%) vs ONMT (5%), p < 0.05; neonatal sepsis (34.6%) vs VLBW (12.5%), p < 0.01. The duration of inpatient treatment is 2 times higher in children with ELBW at birth: 92 ± 6.4 vs 48.8 ± 2 bed/patient days In the structure of morbidity, there were no differences in grade II IVH, PVL, mild and moderate BPD and Congenital Disorder (p > 0.05). Children with ELBW needed more treatment at birth: treatment of RP required intravitreal administration of ranibizumab (53%) vs VLBW (28.6%); surgical treatment of NEC stage III was carried out only in children with ELBW; the duration of respiratory support, regardless of the method, was longer in children with ELBW and amounted to 686.9 ± 130.3 vs 156.3 ± 26 hours . The mortality rate among all premature infants born with ONMT and ENMT was 13.6% and was 5 times higher in the group of children with ELBW who were mostly born extremely preterm. In terms of nosology, the main cause of death among all children with ELBW and VLBW is neonatal sepsis – in 50% of cases, mortality is 1.9 times higher in the group of children with ELBW at birth (38.8%) vs VLBW (20%), p < 0.05. Conclusion. The presented analysis indicates that preterm neonates with VLBW and ELBW in the setting of a Regional Perinatal Center are a rather heterogeneous group in the structure of prematurity, which, among other things, affects the formation of both extremely negative outcomes (lethal) and the structure of morbidity, the amount of care provided to them at different stages, its comprehensiveness and specialization, as well as the duration of inpatient treatment. Based on the all above, it follows, that of the entire category of preterm children born with VLBW and ELBW, the most difficult, economically costly, with prognostically worse outcomes, is the category of extremely preterm newborns.

Applying Lucentis for the treatment of retinopathy of prematurity

Purpose: to evaluate the efficacy of Lucentis for the treatment of retinopathy of prematurity (ROP). Material and methods. 51 infants (102 eyes) with the gestational age between 24 and 33 weeks were given intravitreal injections of Lucentis, All patients selected had ROP stages I+, II+, III or III+ in zone 1, stage III+ in zone 2, or aggressive posterior ROP. The procedure was performed under general anesthesia; the dose, technique and the number of Lucentis injections conformed with the recommendations given in Lucentis instruction for use. If indicated, retinal laser photocoagulation was given after intravitreal injections using Supra (Quantel Medical, France) and Lachta-Mylon (Russia, Lasermedservis) laser equipment. Results. Clinical efficacy of intravitreal administration of Ranibizumab in infants with aggressive posterior ROP, zone 1 ROP, Stage III of zone 2 ROP was determined at 86.3 % (with no more than two injections). If ROP remains active after two injections, a change of therapy is recommended. Vascularization was noted to be complete in 51 % of cases. Conclusion. To achieve a maximum treatment effect of ROP with Lucentis, strict observation of indications criteria must take place.

Low-dose ranibizumab administration in retinopathy of prematurity.

To evaluate the efficiency of low-dose intravitreal ranibizumab therapy in the treatment of aggressive retinopathy of prematurity (A-ROP). A total of 124 eyes of 62 patients who underwent intravitreal ranibizumab after an A-ROP diagnosis between January 2015 and January 2021 were evaluated retrospectively. After receiving family-approved informed consent, low-dose intravitreal ranibizumab was administered, and regular follow-ups were performed. Patients included in the study had a mean birth week of 26.6 (23-33weeks), a mean birth weight of 905 (450-1970) grams, and an average injection postnatal time of 9.1 (4-19) weeks. The mean follow-up period was 63 (24-250) weeks. In all eyes, ROP regressed in the first week after injection, and no asymmetrical response was observed in the eyes of any baby. A total of 58 eyes recovered with a single dose of intravitreal injection therapy, and peripheral retinal vascularization was completed. A second injection was required in 38 eyes. Rescue treatment was applied in addition to intravitreal ranibizumab treatment in 22 eyes of 11 babies. None of the patients had any ocular or systemic side effects. Low-dose intravitreal ranibizumab injection with close follow-up and appropriate timing is an effective treatment modality in A-ROP. Even among patients undergoing rescue laser treatment, the treatment can be completed with a wide visual field.

Intravitreal Ranibizumab for Treatment of Posttraumatic Choroidal Neovascularization: a Case Report

An analysis of the case of applying a course of fibrinolytic therapy and one intravitreal injection of an angiogenesis inhibitor in a patient with traumatic rupture of the choroid complicated by choroidal neovascularization (CNV) is presented. Patient B., 20 years old, complained of a lack of objective vision after a blunt injury to his right eye in March 2018. Visual acuity decreased to 0.01 (ETDRS 0 characters). During the examination revealed: partial hemophthalmus, rupture of the choroid, Berlin retinal opacification. Local fibrinolytic conservative therapy with positive dynamics was carried out in the form of increasing visual acuity to 0.3 (ETDRS 21 characters) and partial resolution of hemophthalmus. According to optical coherence tomography angiography (OCTA), minimally active CNV was detected. Due to the weak activity of the pathological process, a decision was made on dynamic observation. A follow-up examination in August 2018 revealed an increase in CNV activity according to OCTA and fluorescence angiography (FAG), in connection with which intravitreal administration of ranibizumab (lucentis) was performed. Subsequently, the patient was under dynamic observation for one year. Positive dynamics was revealed in the form of an increase in visual acuity, first to 0.7 (ETDRS 48 characters) 3 months after intravitreal injection, and after a year — to 0.9 (ETDRS 55 characters). After treatment according to OCTA and FAG, the activity of CNV was not determined. Despite the favorable result of treatment, further monitoring of the patient is necessary, since the long-term prospects for maintaining the achieved high visual functions remain unclear due to the insufficient experience in treating patients with this pathology according to the literature.

Impact on visual acuity and psychological outcomes of ranibizumab and subsequent treatment for diabetic macular oedema in Japan (MERCURY)

PurposeThe MERCURY study aimed to evaluate the effects on visual acuity and psychological symptoms, and safety, of ranibizumab and subsequent treatment in patients with diabetic macular oedema (DME) and impaired visual acuity (VA). We report data from the prespecified 12-month interim analysis.MethodsThis was a 24-month, phase 4, open-label, single-arm, prospective, observational study conducted at 20 specialised retinal centres in Japan. Participants were 209 patients with DME and impaired VA, not previously treated with either intravitreal or systemic anti-vascular endothelial growth factor (anti-VEGF) agents, who initiated ranibizumab 0.5 mg per investigator discretion. Following ranibizumab administration, patients were treated per routine clinical practice. Other treatments were allowed. The main outcome measure was the mean change in best-corrected VA (BCVA) in logarithmic minimum angle of resolution (logMAR) from baseline to month 12. An exploratory objective was to assess patients’ psychological status using the Hospital Anxiety and Depression Scale (HADS).ResultsThe mean ± standard deviation BCVA at baseline was 0.43 ± 0.39 logMAR. The mean number of injections of ranibizumab and anti-VEGF agents from baseline to month 11 was 3.2 ± 2.0 and 3.6 ± 2.4, respectively. The BCVA change from baseline to 12 months was − 0.08 ± 0.34 logMAR (p = 0.011), showing a significant improvement; the HADS-anxiety score also decreased significantly (p = 0.001) and the depression score decreased numerically (p = 0.080).ConclusionMERCURY study data confirm the effectiveness of real-world treatment initiated with ranibizumab in Japanese patients with DME. In addition, treatment was able to positively influence anxiety via VA improvement.

Comparison of intravitreal injections of Ranibizumab and Aflibercept in neovascular age related macular degeneration

ABSTRACT Clinical relevance: Pivotal studies are based on strict treatment regimens of vascular endothelial growth factor blocking drugs in neovascular age-related macular degeneration. However, looser regimens with poorer results have been reported in real-world studies with various outcomes. This results in a search of more precise data to rely on in the management of patients with neovascular age-related macular degeneration. Background: The aim of this study is to analyse the real-world outcome of vascular endothelial growth factor blocking agents in neovascular age-related macular degeneration. Methods: This is a retrospective comparative study of treatment-naïve patients who received intravitreal aflibercept or ranibizumab administration for neovascular age-related macular degeneration for at least 12 months on an as needed regimen following a loading phase of three-monthly injections. Full eye examination and optical coherence tomography scans were provided at all visits. The drugs were compared on the basis of visual acuity, central macular thickness, and subfoveal choroidal thickness. The baseline optical coherence tomography features were analysed seeking a correlation with the outcome. Results: One hundred and forty-one eyes were enrolled. The mean age was 71.7 ± 8.5 years. Sixty-eight (48.2%) patients received aflibercept and 73 (51.8%) received ranibizumab injections. The mean number of injections was 6.5 ± 2.5. The mean number of injections were also similar between groups (6.4 ± 2.5 vs. 6.5 ± 2.6, respectively, p = 0.783). At one year, both drugs caused significant increase in visual acuity and decrease in central macular thickness and subfoveal choroidal thickness. Conclusion: In a real-world setting, aflibercept and ranibizumab yielded similar results at one year in the management of neovascular age-related macular degeneration.

P4568Effect of intravitreal anti-vascular endothelial growth factor therapy on aortic stiffness and serum interleukin-6 levels in hypertensive patients with age-related macular degeneration

Abstract Purpose Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in adults over 65 years old and it is associated with moderate to severe arterial hypertension and increased aortic stiffness. Anti-vascular endothelial growth factor (anti-VEGF) agents, injected intravitreally, can reverse the symptoms of neovascular (wet) AMD. We sought to investigate whether intravitreal anti-VEGF therapy may influence aortic elastic properties of hypertensive patients with AMD. Methods 54 hypertensive patients with exudative (“wet”) AMD received intravitreal ranibizumab (0.5mg) and blood pressure (BP) and carotid-femoral pulse wave velocity (PWV) were measured at baseline (approximately 2 days before the first injection), 24 h after the first and second injection (time interval between the injections: 1 month) and 1 month after the second injection. Serum levels of high sensitivity interleukin-6 (hsIL-6) were measured at three time points (baseline, first injection, 1 month after the second injection). Results Systolic BP decreased by 3.2 mmHg and by 3.0 mmHg after the first and second injection respectively and remained decreased (by 2.6 mmHg) 1 month after the second injection (overall p=0.07, by ANOVA). The changes in diastolic BP were minimal (overall p=0.74). Ranibizumab injection caused a significant decrease of PWV after the first (by 0.34 m/s) and the second injection (by 0.31 m/s). Furthermore, as upper figure shows, PWV remained decreased 1 month after the second injection. Among the treated naïve eyes, 45 (83%) had a good response to ranibizumab while 9 (17%) were poor responders. Interestingly, PWV decreased significantly in good responders to AMD therapy (overall p=0.004) whereas, it increased in poor responders (overall p=0.21) over the study period. In responders to therapy serum hsIL-6 decreased after the first injection and remained decreased 1 month after the second injection (by 0.63 pg/ml, overall p=0.02, lower figure). The levels of hsIL-6 increased in poor responders (overall p=0.54). Ranibizumab, PWV and serum hsIL-6 levels Conclusions This is the first study showing that intravitreal administration of ranibizumab, a anti-VEGF used for improvement of wet AMD was associated with a beneficial acute and mid-term systematic effect on aortic elastic properties. Changes in systemic inflammatory activation may be involved. The findings have important implications for assessing the effect of anti-VEGF interventions on cardiovascular performance in hypertensive patients with exudative AMD.

35-LB: Response to Anti-VEGF Therapy in a Nonhuman Primate Model of Diabetic Macular Edema

Diabetic macular edema (DME) is one manifestation of diabetic retinopathy (DR), where fluids leak from the retinal vessels into the centre of the macula, causing swelling and blurred vision. VEGF inhibitors (e.g., ranibizumab), have demonstrated clinical efficacy in treating DME; however, it is known that ∼50% of patients do not respond to anti-VEGF therapy. Therefore, DME remains an unmet medical need. To discover novel therapies for DME, animal models that recapitulate clinical phenotypes and validated with anti-VEGF drugs will be of importance. Rodent models of DR have been developed using chemical or dietary induction to mimic the pathophysiological features observed in human. However, differences in the structural and biochemical characteristics of the visual system between rodents and humans hamper their clinical translation. Herein, we aimed to determine the effect of intravitreal administration of ranibizumab in aged, spontaneously dysmetabolic non-human primate with increased average retinal thickness (329 ± 6 µm, vs. age-matched controls 299 ± 10 µm). Seven of them showed signs of non-proliferative DR (NPDR) with presence of intra-retinal cysts, exudates or micro-aneurysms. Changes in retinal thickness and vascular leakage were measured by optical coherence tomography and fluorescein angiography, respectively. Plasma and vitreous levels of VEGF were also determined. Longitudinal data measured over 3-mo. period demonstrated modest, statistical insignificant reduction in average retinal thickness, plasma and vitreous VEGF levels. Some NPDR animals did showed potential improvement in vascular leakage. Considering anti-VEGF drugs are mostly effective in severe DR/DME patients, our results might be reconciled with the early stage of disease condition ascribed to these animals. Further investigation is needed to better understand heterogeneity of individual animal’s drug response and the relationship among imaging, plasma, and vitreous readouts in a longitudinal manner. Disclosure S. Chia: None. L. Gong: None. S. Tiu: Employee; Self; Merck Sharp & Dohme Corp. S.L. Conarello: None. S. Bellum: None. L. Pan: None. C. Lee: None. A. Abu Bakar Ali: Employee; Self; Merck & Co., Inc. L. Hong: Employee; Spouse/Partner; Illumina, Inc. Employee; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Spouse/Partner; Illumina, Inc. Stock/Shareholder; Self; Merck Sharp & Dohme Corp. W. Zeng: None. C. Chin: None. N.X. Li: Employee; Self; Merck & Co., Inc.

Treatment of idiopathic choroidal neovascular membrane with ranibizumab - our experience.

To evaluate the anatomical and functional outcome of ranibizumab therapy in patients with idiopathic choroidal neovascularization (CNV). File and Methodology: The group consists of 6 patients. Patients were older 18 years but they were under 50 years of age. The monitoring period lasted 12 months. We confirmed active idiopathic CNV in subfoveal position with fluorescein angiography (FAg) and optical coherence tomography (OCT). The activity of idiopathic CNV we demonstrated with leakage of dye by FAg examination. The presence of serous retinal pigment epithelium detachment and / or subretinal fluid and / or intraretinal edema in the form of intraretinal cysts demonstrated activity of CNV on OCT scans. Adecrease of the visual acuity under 85 letters was observed at the ETDRS (Early Treatment Diabetic Retinopathy Study) visual acuity chart. After the initial administration of ranibizumab apro re nata regimen was used. We indicated repeated injection of ranibizumab in patients with signs of activity of idiopathic CNV on OCT scans or by FAg. Also we indicated repeated injection of ranibizumab in patients with new loss of visual acuity on the ETDRS visual acuity chart connected with signs of activity of CNV on OCT scans or by FAg. On average, we observed the gain of +11 letters on the ETDRS visual acuity chart after 12 months of the follow-up period. On average we observed reduction of central macular thickness -233μm. At the 12th month of follow-up we observed in all patients of our group only inactive scar without exudation. No serous retinal pigment eithelium detachment, subretinal fluid or intraretinal cysts were observed. Only 3 injections of ranibizumab were administered on average to each patient during the 12 months of the follow-up period. In our study, we observed the positive effect of ranibizumab on the course of idiopathic CNV. With ranibizumab treatment we achieved regression of CNV with resorption of macular edema in all patients of our group. With the disappearance of the activity of idiopathic CNV ranibizumab gives real hope to improve visual acuity.

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.

Systemic side effects after intravitreal administration of antivascular endothelial growth factors for neovascular age-related macular degeneration

Age-related macular degeneration is a chronic and progressive disease of the retina that occurs with increasing frequency with age, representing the leading cause of irreversible blindness in patients over 50 years of age. The loss of visual perception occurs due to neovascular proliferation. Antivascular endothelial growth factors revolutionized the treatment of exudative age-related macular degeneration. Our aim was to assess the systemic safety of intravitreal administration of ranibizumab, bevacizumab, or aflibercept in patients with neovascular age-related macular degeneration. The study was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. The primary outcomes included: all-cause death and all serious systemic adverse events. We calculated the incidence of systemic adverse events, relative risk of the outcomes, and 95% confidence intervals. This review included representative outcome data on 12,292 participants from 24 trials, which included both men and women aged 50 years or older with neovascular age-related macular degeneration. In bevacizumab-treated patients, the most frequent systemic adverse event in our analysis was nonocular hemorrhage. In ranibizumab-treated patients, systemic adverse events were not dose-dependent. The number of systemic adverse events was similar in patients treated with ranibizumab (4.73%) or with aflibercept (4.76%). This meta-analysis did not find any statistically significant difference regarding the occurrence of death or other serious systemic adverse events such as treatment-emergent hypertension, myocardial infarction, stroke, or nonocular hemorrhage after intravitreal use of antivascular endothelial growth factors.

Central corneal thickness and intraocular pressure before the intravitreal administration of ranibizumab and in the early period following the injection.

The aim of the study was to determine the differences in the central corneal thickness and intraocular pressure measured before intravitreal administration of ranibizumab and at 30 to 60 minutes after the injection. The intraocular pressure was analysed as a stand-alone parametre and in correlation with the central corneal thickness. 72 patients (144 eyes) were enrolled. The treated eyes were compared to the fellow, non-treated eyes. The mean central corneal thickness in a treated eye was 558 /Im and 596,μm at baseline (before the injection) and after the injection, respectively (p< 0.05). The mean intraocular pressure not correlated to the central corneal thickness in a treated eye 15.29 mmHg and 16.83 mmHg at baseline and post-injection, respectively (p< 0.05). When assessed in correlation with the central corneal thickness, the intraocular pressure did not increase post-injection in the treated eyes.

The effect of intravitreal ranibizumab on apoptosis induction in rat retinal tissue.

Purpose: Despite the rapidly accumulating knowledge on pharmacokinetic properties and dosage of ranibizumab, the influence of this vascular endothelial growth factor inhibitor on retinal cell survival/apoptosis homeostasis remains unclear. The aim ofthisstudy was to investigate the biological effects of a single intravitreal injection of ranibizumab on retinal tissue with a focus on apoptosis-related signaling pathways in the rat retina. Material and methods: Male Wistar rats were treated with an intravitreal injection of ranibizumab or anti-rat vascular endothelial growth factor antibody in the right eye. The left eyes were injected with the same volume of physiological saline. On the 3rd and 7thday post-injection, the eyes were enucleated, and the retinas were isolated for further molecular analysis of the expression of selected apoptosis-related molecules at mRNA (BAX, BCL-2) and protein (caspase-3) levels using quantitative RT-PCR and western blot techniques, respectively. Results: Following a 3-day-exposure to ranibizumab at the established concentration, the BAX/BCL-2 mRNA expression ratio was significantly increased compared to the saline-treated controls and the healthy control eyes. Furthermore, on day 3. post ranibizumab injection, caspase-3 cleavage, detected qualitatively using western blotting, confirmed potential activation oftheir­reversible phase of apoptosis. In contrast, on day 7. post-injection, there were no significant differences in the BAX/BCL-2 mRNA expression ratios or caspase-3 cleavage between different groups. Conclusions: Intravitreal administration of ranibizumab leads to a transient induction of apoptosis in retinal cells, with an onset directly after the vascular endothelial growth factor inhibitor administration and apparent down-regulation shortly afterwards. These results must be considered when intravitreal injections of ranibizumab are administered to treat retinal diseases.

The effect of vitreomacular adhesion in exudative age-related macular degeneration on the results of ranibizumab intravitreal injection.

PurposeTo investigate whether vitreomacular adhesion (VMA) affects the outcome of anti-vascular endothelial growth factor (VEGF) therapy for the treatment of exudative age-related macular degeneration (AMD) in Japanese patients.Subjects and methodsOf 88 Japanese AMD patients (28 men and 60 women, mean age: 72.7±7.5 years) who underwent intravitreal injection of ranibizumab for 3 years from 2010 to 2013, this study involved 12 eyes of 12 patients (10 men and two women) in whom VMA was observed based on optical coherence tomography (OCT) findings (VMA [+] group) and 17 eyes of 16 patients (seven men and nine women, control group) in whom no VMA was observed (VMA [−] group). In all enrolled patients, ranibizumab was administered monthly for 3 months, and then administered as needed (ie, pro re nata) when deterioration was observed. The two groups were then compared in regard to changes in visual acuity (VA) and the frequency of ranibizumab administration over a 1-year period.ResultsNo significant difference was found between the two groups in regard to the transformation of the mean logarithm of the minimum angle of resolution VA change after the first visit. Over the 1-year treatment, the mean frequency of ranibizumab administration for the VMA (+) group was 5.6±2.5 times and for the VMA (−) group was 3.8±1.1 times, thus illustrating a significant difference between the two groups (Mann–Whitney’s U-test: P<0.05).ConclusionOur findings show that the mean frequency of ranibizumab administration for the VMA (+) group was higher than that in the VMA (−) group, thus indicating that VMA might possibly be involved in the progress of AMD pathology.

Клинический анализ эффективности комбинированного лечения макулярного отека сетчатки

Purpose: to assess the effectiveness of combined treatment of macular edema (ME) of varied etiology. Materials and methods. The results of combined treatment of 32 patients (38 eyes) aged 55 to 75. Of these, 13 patients (15 eyes) had postocclusion MO, 12 patients (14 eyes) had diabetic MO and 7 patients (9 eyes) had an exudate form of age-related maculardegeneration. Two groups of patients were formed depending on the treatment administered. Group 1 (14 patients) intravitreally received an inhibitor of neoangiogenesis, Ranibizumab, whilst group 2 (18 patients) received combined treatment which included a prolonged corticosteroid (Diprospan) administered into sub-Tenon’s space, laser coagulation and intravitreal administration of Ranibizumab. All patients underwent high-definition optical coherent tomography examinations (HDOCT, OCT 4.000 Cirrus Humphrey - Zeiss, San Leandro, USA) and computer tonometry, performed on a visual field analyzer Peritest 30/50/100 using the Macula software. Results. The combined treatment of patients with ME resulted in a stable improvement of visual acuity (averagely by 0.55 in 88 % of cases), rapid retinal edema reduction (its thinning) in 74 % of cases, reduction of risk of neovascular complications, and stabilization of the results achieved. Conclusion. Due to a number of components involved and pathogenetic emphasis, the combined treatment promotes the effectiveness of functional rehabilitation of patients with ME of varied origin // Russian Ophthalmological Journal, 2017; 1: 5-8. doi: 10.21516/2072-0076-2017-10-1-5-8