Doses Of Ranibizumab Research Articles

Aflibercept vs. dexamethasone implant for recalcitrant diabetic macular edema in pseudophakic eyes - 1-year outcomes from a quazi-randomized study in India.

To assess the safety and efficacy of intravitreal Aflibercept (IVA) versus dexamethasone (DEX) implant for treating recalcitrant diabetic macular edema (DME) in pseudophakic eyes at 1-year follow-up. Retrospective comparative case series. Data of all patients diagnosed with DME between January 2019 and December 2021, who underwent 4-monthly doses of intravitreal ranibizumab but had persistent DME [central macular thickness (CMT) within 10% of baseline value] were extracted from a computerized database. Of these, only pseudophakic eyes that underwent either IVA or DEX implant and had at least 1-year follow-up were included for analysis. DEX implant was preferred before December 2020 and IVA after this time point. In the IVA group, patients were followed up every month while DEX were followed at least every 3 months. Reinjections were considered when vision dropped by at least 1 Snellen's line or CMT increased by at least 10% from the previous visit in both groups. Comparison of change in vision and CMT at 1-year follow-up in DEX versus IVA groups. Eighty-four eyes of 84 patients aged 54.4 + 4.4 years were included, 39 (46%) received DEX and 45 (54%) received IVA. Groups were comparable for baseline vision and CMT. Vision improved equally in both groups from 0.83 + 0.15 logMAR to 0.52 + 0.10 logMAR at 3 months ( P < 0.01) and then stabilized till 1 year. However, eyes in the IVA group were 6.5 times more likely (Odds ratio = 6.45, 95% CI = 1.3 - 31.9) to achieve >3-line improvement in vision. The CMT reduction was also comparable between groups (-169 + 51 in DEX vs. -174 + 49 in IVA, P = 0.67). More eyes in the IVA group required >3 injections (91% vs. 69% in DEX, P = 0.01). The IOP was significantly higher at 6 and 9 months in the DEX group and 5 eyes (13%) required IOP lowering medications. In pseudophakic eyes with recalcitrant DME not responding to ranibizumab, switching to IVA or DEX implant results in equal visual improvement and CMT reduction. Though >3-line improvement occurs more frequently with IVA, this comes at the expense of a greater number of injections and follow-up visits.

Lack of Response to Intravitreal Ranibizumab Treatment in Adult Onset Foveomacular Vitelliform Dystrophy Complicated with Choroidal Neovascularization: A Case Report

Adult-onset foveomacular vitelliform dystrophy (AOFVD) is a rare disease characterized by accumulation of yellowish deposits in the macula. Rarely, it may be complicated by choroidal neovascularization (CNV). Cases with CNV may be confused with occult CNV in age-related macular degeneration. In our case, we will present the visual and anatomical results of a patient with AOVF-related CNV, in which we administered 3 doses of intravitreal ranibizumab (IVR). A 59-year-old female patient, who attended our clinic with the complaint of decreased vision in both eyes, was diagnosed with AOVF-related CNV in both eyes and was treated with 3 doses of IVR for 3 months. Despite the improvement in visual and anatomical functions 1 month after the first dose, vision decreased, and anatomical functions regressed to the pre-injection state in continued injections. IVR therapy is not an appropriate treatment option in the treatment of AOVF-associated CNV.

Ranibizumab Modifies the Expression of Metalloproteinases and Their Tissue Inhibitors in Peripheral Blood Mononuclear Cells in Patients with Exudative Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of vision loss in people over 60 years of age. Despite research, the causes of AMD remain unclear. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are known to be involved in AMD development, and anti-vascular endothelial growth factor therapy has revolutionized its treatment. This study aims to analyze the changes in gene expression in MMPs and TIMPS in patients with neovascular AMD before and after three doses of ranibizumab. The study involved 29 patients with neovascular AMD treated with ranibizumab. Peripheral blood mononuclear cells were collected before treatment and 24 h after the third dose of ranibizumab. We assessed MMP and TIMP gene expression profiles through oligonucleotide microarrays and validated selected differential genes using RT-qPCR. A statistically significant change in the expression of six MMP- and TIMP-related genes was observed using oligonucleotide microarray. The mRNA levels of the two genes with the most significant fold changes, MMP15 and TIMP2, were then quantified using RT-qPCR. The results confirmed a statistically significant increase in MMP15 expression and a decrease in TIMP2 levels, although this change was not statistically significant in the group before and after the third dose of ranibizumab. Ranibizumab affects the systemic expression of MMP and TIMP-related genes in patients with neovascular AMD. Results from our exploratory study suggest that MMP15, in particular, may play a role in the treatment response, but further research is necessary.

Should intravitreal dexamethasone implant in refractory diabetic macular edema be used as an adjuvant therapy or switch therapy?

To compare the outcomes of intravitreal dexamethasone implant used as either an adjuvant or a switching therapy for diabetic macular edema in patients with poor anatomic response after three consecutive monthly injections of ranibizumab. This retrospective study included patients with diabetic macular edema who received three consecutive doses of ranibizumab as initial therapy and demonstrated poor response. A single dose of intravitreal de xamethasone implant was administered to these patients. The patients were divided into two groups according to the treatment modalities: the adjuvant therapy group, consisting of patients who continued treatment with ranibizumab injection after receiving intravitreal dexamethasone implant, and the switch therapy group, consisting of patients who were switched from ranibizumab treatment to intravitreal dexamethasone implant as needed. The main outcome measurements were best corrected visual acuity and central retinal thickness at baseline and at 3, 6, 9, and 12 months of follow-up. In this study that included 64 eyes of 64 patients, the best corrected visual acuity and central retinal thickness values did not significantly differ between the groups at baseline and at 6 months of follow-up (p>0.05). However, at 12 months, the best corrected visual acuity values in the adjuvant and switch therapy groups were 0.46 and 0.35 LogMAR, respectively (p=0.012), and the central retinal thickness values were 344.8 and 270.9, respectively (p=0.007). In a real-world setting, it seems more reasonable to use intravitreal dexamethasone implant as a switch therapy rather than an adjuvant therapy for diabetic macula edema refractory to ranibizumab despite three consecutive monthly injections of ranibizumab. Patients switched to intravitreal dexamethasone implant were found to have better anatomic and visual outcomes at 12 months than those who continued ranibizumab therapy despite their less-than-optimal responses.

Safety and efficacy profile of intravitreal ranibizumab vs dexamethasone in treatment of naïve diabetic macular edema.

To compare the safety and efficacy parameters of intravitreal ranibizumab vs intravitreal dexamethasone (IVD) in the treatment of patients with naïve diabetic macular edema (DME) in terms of best-corrected visual acuity (BCVA), central macular thickness (CMT), and possible complications like intraocular pressure (IOP) rise and cataract progression. A hospital-based prospective and comparative study of naïve DME patients was conducted between November 2020 and October 2021 with a minimum follow-up (F/U) period of 6 months. Thirty phakic patients received one dose of IVD implant (Group A) and the other 30 (Group B) received three consecutive monthly doses of ranibizumab. The main exclusion criteria were steroid responders and the presence of ocular inflammation. The mean pre-injection CMT in Group A was 405µ and reduced to 297.07µ at 3 months and 278.35µ at 6 months. Mean increase in logMAR BCVA was 0.55. The mean pre-injection IOP was 16.28 and 17.64 mm of Hg at 6 months. In Group B, the mean pre-injection CMT was 401.07µ and reduced to 276.1µ at 3 months and 292.9µ at 6 months. Mean BCVA increased to 0.37. The mean pre-injection IOP was 17.28 mm Hg and 16.42 mm Hg at 6 months. There was no significant progression of cataract in both groups. The mean decrease in CMT was comparable in both the groups at 6 months F/U with an improvement of BCVA with no significant IOP fluctuation or cataract progression. Hence, IVD appears to be noninferior to ranibizumab in the treatment of naïve DME.

Successful management of rubella retinopathy–related subretinal neovascular membrane with intravitreal ranibizumab

A seven-year-old boy with a known case of bilateral rubella retinopathy presented to us as part of his annual follow-up. Best-corrected visual acuity (BCVA) at presentation was 20/80 in the right eye and 20/600 in the left eye. On dilated fundoscopy, the right eye showed the presence of subretinal neovascular membrane (SRNVM), subretinal fluid, and classical salt-and-pepper retinopathy, all of which was documented by imaging. The left eye was poorly dilating and showed a pale disc. The right eye was treated with two doses of intravitreal ranibizumab at an interval of two months. Post-treatment examination showed resolution of SRNVM accompanied by scarring and significant improvement in BCVA.

Baseline characteristics and treatment response predictive of nAMD outcomes with ranibizumab therapy in treatment-naive patients: the RACER subgroup analysis

BackgroundThe Ranibizumab AMD Clinical Efficacy Study (RACER) conducted in treatment-naive adult Taiwanese patients with neovascular age-related macular degeneration (nAMD) suggested the importance of early and intensive dosing of ranibizumab for optimal treatment outcomes. This subgroup analysis aims to provide clinical information on treatment response that can potentially guide on maintaining the treatment or switching anti-VEGF agents in the real-world setting.MethodsVisual acuity (VA) and central retinal thickness (CRT) were assessed in the RACER subgroup population. Subgroup analysis sets were categorised based on: (1) baseline best-corrected VA (BCVA; ≤ 48 and > 48 letters); (2) baseline CRT (≤ 325 or > 325 μm); and (3) treatment response after three monthly initial injections: < or ≥ 5-letter gain in BCVA and reduction of < or ≥ 50 μm in CRT.ResultsPatient age, sex, nAMD duration and number of ranibizumab injections did not differ significantly between the treatment subgroups. Poor baseline BCVA (≤ 48 letters) and baseline CRT severity (> 325 µm) were predictors of maximum BCVA gains (9.6 ± 12.9 letters [95%CI: 6.3 to 12.9] and 5.1 ± 18.3 letters [95%CI: − 0.5 to 10.8] at Months 3 and 12, respectively) and better CRT reductions (− 127.6 ± 104.2 µm and − 104.2 ± 107.4 µm at Months 3 and 12, respectively; both P < 0.001). For the subgroup showing favourable treatment improvement with BCVA gains ≥ 5 letters after three monthly initial injections, 75.6% of patients maintained follow-up at Month 12 with a mean of 6.5 ± 14.3 letter gains (95% CI: 1.2 to 11.7). The BCVA gains < 5-letter subgroup nevertheless had stable BCVA (0.4 ± 12.1 letter gains) and CRT (− 41.9 ± 61.2 µm) at Month 12, respectively. In the subgroup with ≥ 50 µm CRT reduction after three monthly initial injections, there are significantly higher BCVA improvements vs. the < 50 µm CRT reduction subgroup at Month 3 (5.0 ± 8.6 letter gains vs. 1.5 ± 11.6 letter gains, respectively; intergroup P = 0.005).ConclusionLower baseline BCVA and higher baseline CRT were associated with BCVA gains and CRT reductions throughout the 12-month study period. Early CRT improvements after three monthly initial injections were associated with BCVA gains as early as Month 3.

Predictors of As-Needed Ranibizumab Injection Frequency in Patients With Macular Edema Following Retinal Vein Occlusion

To evaluate spectral-domain optical coherence tomography (SD-OCT) biomarkers associated with ranibizumab injection frequency after 7 monthly doses in the prospective, multicenter SHORE study for macular edema due to retinal vein occlusion (RVO). Prospective phase IV clinical trial data. Post hoc analysis of 95 patients who received 7 monthly doses of ranibizumab followed by either pro re nata (PRN) or nonrandomized monthly injections from months 7-15 in eyes with macular edema secondary to RVO. Baseline SD-OCT biomarkers assessed include central subfield thickness (CST), epiretinal membrane presence, intraretinal and subretinal fluid, hyperreflective foci, disorganization of retinal inner layers (DRIL), and disruption of the external limiting membrane, ellipsoid zone, or interdigitation zone. Univariate and multivariable regression analyses evaluated the association between SD-OCT biomarkers and ranibizumab injection frequency. Mean age of patients was 65.3 (SD, 12.7) years. Overall, 57.9% had BRVO/HRVO and 42.1% of eyes had CRVO. Mean BCVA improved (+17.5 [SD, 1.2] Early Treatment of Diabetic Retinopathy Study [ETDRS] letters) during the 7-month fixed dosing period, remaining stable from baseline (+20.1 [SD, 1.5] ETDRS letters) during the PRN phase from months 7-15. The mean number of PRN injections was 4.32 (SD, 2.35). On multivariate regression, greater baseline DRIL (β=0.021, P=.0275) and higher CST at month 3 (β=0.01, P < .001) were associated with a higher total number of PRN injections. Greater baseline DRIL and higher CST at 3 months after starting ranibizumab treatment are associated with more frequent ranibizumab injections in PRN-treated patients with macular edema due to RVO.

Short-term impact of glycaemic control and intravitreal ranibizumab treatment on serum cytokine levels and diabetic macular edema in patients with unregulated blood glucose

Objective: To evaluate the short-term effect of glycaemic control and intravitreal ranibizumab treatment on diabetic macular edema (DME) and to assess the correlation between HbA1c and certain serum cytokines. Design: A prospective study of 43 participants with HbA1c levels exceeding 53 mmol/mol (7%) and with DME, as detected by spectral domain optical coherence tomography (SDOCT). Subjects: Participants were grouped according to their initial best corrected distance visual acuity (BCVA). Group 1 was treated with three monthly doses of intravitreal ranibizumab (0.5 mg) injections, and Group 2 was followed without treatment. Methods: Serum cytokine levels, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1(MCP-1), and vascular endothelial growth factor (VEGF) were analysed at the beginning and at the end of 3 months, using enzyme-linked immunosorbent assays (ELISA). Results: A significant decrease in macular thicknesses (except for one quadrant) was observed in Group. Changes in serum cytokine levels were not correlated with HbA1c decrease. Serum VEGF level was significantly increased in Group 1, despite the intravitreal treatment. Conclusion: Short-term glycaemic control alone had limited value in the treatment of DME. The therapeutic effect of intravitreal treatment on DME supports the role of the local cytokine milieu in the pathophysiology.

The safety of ranibizumab and bevacizumab on senescent retinal pigment epithelial cells

AbstractPurpose: Retinal pigment epithelial (RPE) cells in patients with age‐related macular degeneration are presumably senescent. This study investigated the effects of ranibizumab and bevacizumab on the viability of senescent RPE cells.Methods: Premature senescence of human RPE (ARPE‐19) cells was induced by exposure to low‐dose pulsed H2O2 stress for 5 days and confirmed with senescence‐associated 𝛽‐galactosidase (SA‐𝛽‐gal) staining. After treatment with clinical doses of ranibizumab and bevacizumab, the MTT [3‐(4,5‐Dimethylthiazol‐2‐yl)‐2,5‐Diphenyltetrazolium Bromide] assay and flow cytometry were used to determine cell viability. A caspase 3/7 assay, cell cycle analysis, SA‐𝛽‐gal staining, and in vitro wound healing assay were also performed to investigate the effects of the drugs on senescent ARPE‐19 cells.Results: Ranibizumab and bevacizumab did not have deleterious effects on apoptosis, cell viability, additional senescence, or the migration capacity of senescent RPE cells.Conclusions: Clinical dosages of ranibizumab and bevacizumab do not produce significant cytotoxicity in senescent RPE cells.Reference1. Klein R, Klein BE, Jensen SC, Meuer SM. The five‐year incidence and progression of age‐related maculopathy: the Beaver Dam Eye Study. Ophthalmology. 1997; 104: 7–21.

Comparison in Retreatments between Bevacizumab and Ranibizumab Intravitreal Injections for Retinopathy of Prematurity: A Multicenter Study

To compare the types and dosages of anti-vascular endothelial growth factors (VEGFs) to ascertain whether specific dosages or types of injection were associated with retreatment in clinical practice in the United States. Multicenter, retrospective, consecutive series. Patients with retinopathy of prematurity (ROP) treated with anti-VEGF injections from 2007 to2021. Sixteen sites from the United States participated. Data collected included demographics, birth characteristics, examination findings, type and dose of anti-VEGF treatment, retreatment rates, and time to retreatment. Comparisons of retreatment rates between bevacizumab and ranibizumab intravitreal injections were made. Relative rate of retreatment between varying types of anti-VEGF therapy, including bevacizumab and ranibizumab, and the various dosages used for each. Data from 873 eyes of 661 patients (61% male and 39% female) were collected. After exclusion of 40 eyes treated with laser before anti-VEGF injection and 266 eyes re-treated with laser at or beyond 8 weeks after the initial anti-VEGF treatment, 567 eyes of 307 patients (63% male and 37% female) remained and were included in the primary analysis. There was no difference between the no retreatment and retreatment groups in terms of birthweight, gestational age, age at first injection, ROP stages, or number of involved clock hours. The retreatment group had a larger percentage of aggressive ROP (34% vs. 18%, P < 0.001) and greater percentage of zone 1 ROP (49 vs. 34%, P= 0.001) than the no retreatment group. Ranibizumab use was associated with a higher rate of retreatment than bevacizumab use (58% vs. 37%, P < 0.001), whereas the rate of retreatment was not associated with a specific dose of ranibizumab (R2= 0.67, P= 0.32). Meanwhile, lower doses of bevacizumab were associated with higher rates of retreatment compared with the higher doses (R2= 0.84, P= 0.01). There was a dose-specific trend with higher doses trending toward lower retreatments for bevacizumab. In a multicenter study of ROP patients initially treated with anti-VEGF therapy, ranibizumab and lower-dose bevacizumab use were associated with an increased rate of retreatment when compared with higher-dose bevacizumab. Proprietary or commercial disclosure may be found after the references.

Two-year visual and psychological outcomes of ranibizumab and subsequent treatment for diabetic macular oedema in Japan (MERCURY)

ObjectiveWe report the 2-year visual and psychological outcomes of the MERCURY study, examining the long-term effectiveness and safety of ranibizumab and subsequent therapy in Japanese patients with diabetic macular oedema...

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.

Appropriate dose of intravitreal ranibizumab for ROP: a retrospective study

ObjectiveTo compare the recurrence rate of retinopathy of prematurity (ROP) after treatment with 0.3 mg vs. 0.25 mg ranibizumab.SubjectsAll patients with ROP who underwent intravitreal injection of ranibizumab in Hainan General Hospital between January 2014 and May 2020 were included in this retrospective study.MethodsEighty-two cases (146 eyes) who received intravitreal injection of 0.25 mg ranibizumab were included in the conventional-dose group, and 59 cases (108 eyes) who received intravitreal injection of 0.3 mg ranibizumab were included in the high-dose group. The two groups were further divided into the 25-28-week, 29-31-week, 32-34-week, and 35-36-week GA subgroups. The differences between the conventional-dose group and the high-dose group in gestational age (GA), birth weight (BW), age at initial injection (weeks), incidence of systemic diseases, the recurrence rate of ROP, and age at retinal vascularization completed (weeks) were analyzed.ResultsGA, BW, age at initial injection, and the incidence of systemic diseases were not significantly different between the conventional-dose group and the high-dose group (p > 0.05). The recurrence rates of ROP were significantly lower in the 25-28-week, 29-31-week, and 32-34-week subgroups of the high-dose group than in the same subgroups of the conventional-dose group (p < 0.05). Within the conventional-dose group, the recurrence rate of ROP was significantly lower in the 32-34-week and 35-36-week subgroups than in the 25-28-week and 29-31-week subgroups (p < 0.05). Within the high-dose group, the recurrence rate of ROP was not significantly different between the four subgroups (p > 0.05). Retinal vascularization was completed at a later age in the 32-34-week subgroup of the high-dose group than in the 32-34-week subgroup of the conventional-dose group (p < 0.05) but was not significantly different between the two groups at any other GA range (p > 0.05). No severe ocular or systemic complications occurred in any patient.ConclusionTreatment with 0.3 mg ranibizumab can reduce the recurrence rate of ROP without prolonging retinal vascularization or causing serious systemic complications. Therefore, this dose may be an appropriate therapeutic dose for ROP.

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.

Anti-VEGF Drugs Dynamics: Relevance for Clinical Practice.

Background: A drug and disease assessment model was used to evaluate the impact of different treatment regimens on intravitreal ranibizumab, bevacizumab, aflibercept, and brolucizumab concentrations and the proportion of free vascular endothelial growth factor (VEGF) to total VEGF. Methods: A time-dependent mathematical model using Wolfram Mathematica software was used. The pharmacokinetic and pharmacodynamic data for anti-VEGFs were obtained from published reports. The model simulated drug concentration after single and multiple doses of ranibizumab, bevacizumab, aflibercept, and brolucizumab, and it extrapolated time-dependent intraocular free VEGF proportion values. Various fixed treatment regimens (q4, q8, q10, q12) were simulated and evaluated as candidates for clinical utilization. Results: Our mathematical model shows good correlation between intraocular VEGF proportion values and clinical data. Simulations suggest that each anti-VEGF agent would allow for distinct treatment intervals to keep the proportion of free VEGF under threshold levels. Regimens scheduling q8 ranibizumab, q8 bevacizumab, q12 aflibercept, and q10 brolucizumab administration permit to maintain the proportion of unbound VEGF below 0.001%. Conclusions: Fixed q8 ranibizumab, q8 bevacizumab, q12 aflibercept, or q10 brolucizumab regimens may produce adequate intraocular VEGF inhibition.

Management of wet AMD in an elderly patient - case report

Introduction: Age-related macular degeneration (AMD) is the most common cause of central vision loss in elderly people over 50 years of age. It is characterized by the presence of drusen on the fundus and may be associated with choroidal neovascularization (CNV) or geographic atrophy. AMD is a condition caused by many factors including environmental, genetic, and vascular. Currently, it affects over 25 million people worldwide, but with the progressive aging of the population, the incidence of the disease is increasing. Disease is therefore an important issue in geriatrics.Case report: A 75-year-old patient was referred to the General and Pediatric Ophthalmology Clinic of the Medical University of Lublin due to the three-week deterioration of visual acuity in the left eye. The visual acuity of the left eye was: counting fingers at a distance of 1.5 m. Initial cataracts of this eye and wet AMD were diagnosed. In July 2018. an injection of ranibizumab was administered into the vitreous humor of the left eye. After achieving an improvement in visual acuity to 0.2 (on Snellen charts), in September the patient was qualified to the Drug Program for the treatment of the wet form of AMD. From September to October 2019. the patient received 9 doses of ranibizumab. In October 2019. visual acuity improved to 0.4. In November, due to the unsatisfactory results of the therapy, the drug was changed to aflibercept. The patient received a total of 3 injections of this drug and his visual acuity improved to a value of 0.7. The last injection was given in July 2020 and the clinical condition and visual acuity stabilized. After the end of the drug program, the patient regularly shows up for checkups, and the visual acuity of the left eye has normalized since July 2020. and is now 0.4 (due in part to atrophic changes and scarring).Conclusions: Treatment of the wet form of AMD is a difficult and lengthy process. Early diagnosis of the disease, starting treatment as soon as possible, regular checkups and cooperation with the patient are very important for the success of the therapy. During 3 years of treatment, the patient experienced a significant improvement in visual acuity for one year. The treatment allowed the disease progression to slow down. The morphological condition of the retina improved. The applied treatment and management of the elderly patient turned out to be effective, and the achieved effects of the therapy are satisfactory.

The prognostic role of optical coherence tomography in diabetic macular edema patients undergoing early dexamethasone implant shift.

To determine the prognostic characteristics of optical coherence tomography (OCT) parameters by evaluating diabetic macular edema (DME) patients with early dexamethasone (DEX) shift after three doses of intravitreal ranibizumab (RNB) injection. Fifty-four eyes of 34 patients who had DEX implant after three doses of RNB were included in this retrospective study. Early DEX shift includes patients who received direct DEX implant replacement after three doses of RNB load. Baseline OCT values and factors affecting best corrected visual acuity (BCVA) and central macular thickness (CMT) response were analyzed with logistic regression analyses. The presence of subretinal fluid and hyperreflective spot (HRS) >20 were found to be a negative predictive factor for anatomical response. (p = 0.009, p = 0.001, respectively) Low initial BCVA creates a positive effect on visual gain.( p = 0.041) Giant outer nuclear layer cysts, completely disrupted inner segment-outer segment and HRS > 20 have a negative effect on visual gain. (p = 0.025, p = 0.043, p = 0.023, respectively) According to the receiver operating characteristic analysis, the subretinal fluid volume threshold at which >20% reduction in CMT occurs was determined to be 0.85 mm3. (sensitivity 70%, specificity 84% area under the curve 0.817, p = 0.021). The presence of high number of HRS and high subretinal fluid volume at the baseline negatively affect prognosis even in patient groups with early DEX shift.

Clinical Features, Prognosis, and Long-Term Response to Ranibizumab of Macular CNVs in Pattern Dystrophies Spectrum: A Pilot Study.

Introduction To analyze the morphological and functional features of choroidal neovascularizations (CNVs) in eyes affected by pattern dystrophies (PD), evaluating their long-term response to intravitreal ranibizumab, and comparing them with CNVs in age-related macular degeneration (AMD). The mean goal is to identify possible disease biomarkers and to evaluate the long-term prognosis of CNVs in PD. Materials and Methods A retrospective study of 42 patients with naïve CNV (26 PD and 16 AMD), for a total of 47 eyes (29 eyes in the PD group and 18 eyes in the AMD group). Each patient received a loading dose of ranibizumab (one monthly for three months) followed by pro re nata (PRN) reinjection protocol for a period of at least three years. Morphological OCT parameters (CRT, central retinal thickness; SRF, subretinal fluid; IRF, intraretinal fluid; SHRM, subretinal hyperreflective material; HRF, hyperreflective foci; HCD, hyperreflective crystalline deposits; cCT, central choroidal thickness; slCT, sublesional choroidal thickness; EZd, ellipsoid zone disruption; and best corrected visual acuity (BCVA in logMAR scale)) were reported at baseline and last follow-up. Results At baseline, no significant differences were found between the two groups, except for choroidal thickness parameters that were significantly greater in the PD group (p = 0.009). Longitudinal PD analysis demonstrated reduction in BCVA (p = 0.009), decrease in CRT (p = 0.046), resolution of SRF in 61.6% of cases (p = 0.004) and SHRM in 30% (p = 0.034), and choroidal thinning both centrally (p = 0.004) and sublesional (p = 0.011) compared to baseline. At 3 years, the PD group received significantly more injections than the AMD (p = 0.011) and showed significantly thicker choroid (p = 0.033) and more frequent HRF (p = 0.006). Regarding the PD group, we found a negative correlation between age and choroidal thicknesses at baseline and at 3 years (p < 0.05); significant positive correlations were found between baseline BCVA and at 3 years (p < 0.001), BCVA at 3 years and IRF (p = 0.003) and SHRM at 3 years (p = 0.003); CRT baseline and CRT 3 years (p = 0.017); HCD at 3 years was associated with greater CRT (p = 0.04) and IRF at 3 years (p = 0.019). Conclusions Early and long-term morphofunctional features of CNVs in PD and in AMD are overlapping. CNVs in PD have poorer long-term response to ranibizumab and higher choroidal thickness suggesting different pathogenetic and evolutionary mechanisms.

Safety and efficacy of Razumab\u2122 (world\u2019s first biosimilar ranibizumab) in wet age-related macular degeneration: a post-marketing, prospective ASSET study

BackgroundRazumab™ (world’s first biosimilar ranibizumab) is approved for several macular disorders including wet age-related macular degeneration (AMD). We evaluated the safety and efficacy of biosimilar ranibizumab in wet AMD.MethodsThis prospective, multicentre, rAnibizumab bioSimilar Safety Efficacy postmarkeTing (ASSET) study enrolled patients aged ≥ 50 years with wet AMD having best-corrected visual acuity (BCVA) between 20/40 and 20/320. The patients received intravitreal biosimilar ranibizumab 0.5 mg every 4 weeks for 24 weeks. Safety endpoints included the incidence of adverse events (AEs), serious AEs (SAEs), and immunoreactivity after 6 months. The efficacy endpoints were the proportion of patients who lose fewer than 15 letters, increase in BCVA, change in central retinal thickness (CRT), and change in Visual Function Questionnaire-25 (VFQ-25) score, from baseline to 24 weeks.ResultsOf the 126 enrolled patients, majority (95.24%) of the patients received all 6 doses of biosimilar ranibizumab (total 3 mg). Nineteen AEs were reported (n = 16; 12.7%); majority (78.9%) were mild. There were no serious AEs reported, except one AE of death which was unrelated to the study drug. None of the patients discontinued the study due to an AE. The most common ocular AE was increase in intraocular pressure (4 events) and non-ocular AE was pyrexia (5 events). A total of 7.9% (10/126) patients prior to dosing and 7.1% (9/126) patients post-treatment were positive for anti-ranibizumab antibodies. No AEs suggestive of immunogenicity were noted. At 24-weeks, 97.60% patients in the intent-to-treat (ITT) population (N = 125) and 97.41% patients in the per-protocol (PP) population (N = 116) lost < 15 letters from baseline visual acuity. In the ITT and PP populations, 31.20% and 32.76% patients, respectively, showed improved visual acuity by ≥ 15 letters. Significant improvements in BCVA (mean difference: 8.8, 9.2, p < 0.001 for ITT, PP) and VFQ-25 (8.5, 9.2, p < 0.001 for ITT, PP) were seen; CRT reduced significantly (125 µm, 119.3 µm, p < 0.001 for ITT, PP).ConclusionRazumab™ (world’s first biosimilar ranibizumab) was well-tolerated without new safety concerns and significantly improved visual acuity in wet AMD patients.Trial registration CTRI/2016/03/006739. Registered 18 March 2016—Prospectively registered, http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=13141&EncHid=&userName=2016/03/006739