Many medicines are ineffective in the treatment of ischaemic optic neuropathy (ION). The effects of all ten medicines for the treatment of ION were assessed through a meta-analysis using direct and indirect comparisons of multiple treatments. This systematic review of nine randomised controlled trials (1,012 participants) from April 1994 to May 2022 compared the efficacy of placebo (PLA), ranibizumab (RAN), dexamethasone (DEX), prednisolone (PRE), oxygen (OX), troxerutin (TRO), RPh201, erythropoietin (ERY), levodopa + carbidopa (LEV+CAR), and prednisolone + ranitidine (PRE+RA) for the treatment of ION. The primary measure of success was the percentage of patients who either responded to the treatment or discontinued the study. Intention-to-treat analysis was conducted. DEX, PRE, OX, TRO, ERY, LEV+CAR, and PRE+RA were significantly more effective than PLA (odds ratios (ORs) 43.64, 1.19, 1.17, 4.22, 2.64, 3.32, and 1.10, respectively). RAN was significantly more effective than DEX (OR 1.67). RPh201 is significantly less effective than all other medicines. Acceptance of PLA was good. RAN and DEX are the best options for treating ION. Therefore, these results should be considered in clinical practice. Key Words: Ischaemic optic neuropathy, Meta-analysis, Treatment.

Fig. 1 Comparable improvements by 8-week oral levosulpiride (LSP) or intravitreal ranibizumab (RBZ) on the change from baseline in visual and structural parameters.Longitudinal changes from baseline in best-corrected visual acuity (BCVA) (A), central foveal thickness (CFT) (B), and mean macular volume (MMV) (C) after 8 weeks of treatment.Boxplots show median and individual values distribution of placebo (P, 18 eyes), LSP (22 eyes), and RBZ (16 eyes) groups.Statistical analysis was performed using one-way ANOVA-Sidak's multiple comparisons (A) or Kruskal-Wallis-Dunn's multiple comparisons (B, C) tests.*P < 0.05, ***P < 0.001, ns (non-significant).

ABSTRACTAngiogenesis, particularly driven by the overexpression of vascular endothelial growth factor (VEGF), plays a crucial role in the growth and metastasis of tumors, making VEGF a significant target in the diagnosis and therapy of non‐small cell lung cancer (NSCLC). In this work, the potential of 99mTc‐labeled ranibizumab was investigated for the non‐invasive diagnosis of NSCLC. To that end, ranibizumab (RNB), a VEGF‐neutralizing antibody, was conjugated with S‐2‐(4‐isothiocyanatobenzyl)‐1,4,7,10‐tetraaza1,4,7,10‐tetra(2‐carbamoylmethyl) cyclododecane (TCMC) followed by labeling with technetium‐99m (99mTc) using different reaction parameters. The 99mTc‐TCMC‐RNB was characterized in terms of the percent radiochemical purity (% RCP) up to 6 h, in vitro stability in serum up to 16 h, internalization kinetics in A549 cells, and biodistribution using the NSCLC Sprague Dawley rat model. The 99mTc‐labeled TCMC‐RNB exhibited 98.3 ± 0.2% RCP in normal saline, stability in rat serum with an overall decay of 32.10% within 18 h, and specific binding to A549 NSCLC cells. Biodistribution studies showed significant tumor uptake. These findings suggest that 99mTc‐labeled TCMC‐RNB holds promise as a specific imaging agent for the diagnosis and monitoring of VEGF‐related malignancies, particularly in NSCLC.

PurposeTo compare the anatomical and visual outcomes in eyes with submacular hemorrhage (SMH) treated with a combination of ranibizumab (RBZ) either innovator or biosimilar (Razumab) and intravitreal perfluoropropane gas (C3F8).MethodsTreatment naïve neovascular age related macular degeneration (n-AMD) patients with SMH were retrospectively analyzed. Patients received either innovator or biosimilar RBZ (3 loading doses followed by pro re nata regimen) and single injection of intravitreal C3F8. Optical coherence tomography (OCT) was performed at baseline, 1, 3 and 6 months. Changes in best corrected visual acuity (BCVA) and central macular thickness (CMT) were assessed at 6 months. P value ≤ 0.05 was considered statistically significant.ResultsA total of 67 eyes (35 and 32 eyes in innovator and biosimilar group respectively) were analyzed. BCVA improved from 1.15 ± 0.19 to 0.51 ± 0.23 logarithm of minimum angle of resolution (logMAR) in innovator RBZ group (p < 0.001) and from 1.17 ± 0.15 to 0.53 ± 0.20 logMAR in biosimilar RBZ group (p < 0.001). Similarly, mean CMT showed significant reduction in both groups at 6 months (innovator RBZ: 609.5 ± 50.1 μm to 254.3 ± 20.3 μm, p < 0.001; biosimilar RBZ: 602.3 ± 58.9 μm to 251.8 ± 22.3 μm, p < 0.001). Intergroup comparisons between innovator and biosimilar RBZ showed no differences in either BCVA or CMT at all time points (all p values > 0.05). Mean number of intravitreal injections was marginally higher in innovator group compared to biosimilar RBZ (4.37 ± 0.49 vs. 4.22 ± 0.42; p = 0.18).ConclusionBiosimilar RBZ may act as a viable alternative to innovator RBZ to treat SMH with comparable anatomical and visual outcomes at 6 months.

ABSTRACT The facilitation of targeted drug delivery within the ocular region presents a formidable challenge owing to its intricate physiological structure, which confers a biological barrier. This barrier is characterised by short retention times, diminished drug accumulation, and suboptimal bioavailability. To overcome these limitations, this study aimed to develop a hyaluronic acid-based nanoparticulate system encapsulating curcumin (CUR) and ranibizumab (RAN), designated as CUR-RAN@NPs with a uniform distribution of particle size and exhibited the capacity for sustained release of both CUR and RAN. The evaluation of biosafety and biocompatibility using cytotoxicity assays indicated that CUR-RAN@NPs are non-toxic and biologically compatible. Consequently, the CUR-RAN@NPs have promising potential for the advancement of ocular drug delivery systems. Finally, CUR-RAN@NPs demonstrated exceptional antibacterial activity and inhibition of neovascularization, thereby underscoring their therapeutic potential in ophthalmic applications.

Abstract This study aimed to determine how resveratrol combination separately with the anti-VEGF agents ranibizumab, aflibercept and ziv-aflibercept affects ARPE-19 cells in vitro. The cells were assigned to twelve groups as follows: Control, Cobalt Chloride (Cob), Resveratrol (RSV), Ranibizumab (RNZ), Aflibercept (AFL), Ziv-aflibercept (ZFL), RNZ + RSV, AFL + RSV, ZFL + RSV, RNZ + RSV + Cob, AFL + RSV + Cob and ZFL + RSV + Cob. The Control group was incubated for 48 hours with no treatment, while the remaining groups received RSV, RNZ, AFL or ZFL (alone or in combination) for 24 hours and then the cells in the relevant groups were exposed to CoCl2 for 24 hours more. Mitochondrial reactive oxygen species (MitROS), cytosolic reactive oxygen species (CytROS), mitochondrial membrane depolarization (MitDep), caspase-3, caspase-8, caspase-9, cell viability, apoptosis and VEGF-A levels were assessed by confocal microscopy, plate reader and ELISA techniques. Resveratrol, alone or in combination with anti-VEGF’s, significantly decreased the levels of MitROS, MitDep, CytROS, caspase-3, caspase-8 and caspase-9 (p &lt; 0.001). Resveratrol also increased cell viability and decreased apoptosis and VEGF-A levels (p &lt; 0.001). According to our findings, combining resveratrol with anti-VEGFs may have a beneficial therapeutic effect on the treatment of AMD.

Application of anti-vascular endothelial growth factor antibody restores the function of saliva secretion in a type 2 diabetes mouse model

The ranibizumab (RBZ) port delivery system (PDS) is a device designed to continuously deliver RBZ in the vitreous chamber for the treatment of neovascular age-related macular degeneration (nAMD). It is implanted during a surgical procedure and can provide sustained release of the medication for several months. This review, updated to January 2024, focuses on past clinical studies as well as current and forthcoming trials looking into a PDS with RBZ. In the phase 2 LADDER trial, the mean time to first refill of a PDS with RBZ 100 mg/mL was 15.8 months, with the pharmacokinetic (PK) profile showing a sustained concentration of RBZ in the blood and aqueous humor. More recently, a PDS with RBZ (100 mg/mL) refilled every 24 weeks was shown to be non-inferior to a monthly intravitreal injection (IVI) with RBZ (0.5 mg) over 40 and 92 weeks in the phase 3 ARCHWAY trial. The refill every 24 weeks allowed for a RBZ vitreous exposure within the concentration range of monthly intravitreal injections (IVIs), and the expected half-life (106 days) was comparable with the in vitro results. Nonetheless, vitreous hemorrhage and endophthalmitis were more common side effects in PDS patients. In conclusion, a PDS continuously delivering RBZ has a clinical effectiveness level comparable with IVI treatment. However, a greater frequency of unfavorable occurrences highlights the need for procedure optimization for a wider adoption. Ongoing trials and possible future approaches need to be addressed.

BackgroundAge-related macular degeneration (AMD) stands as the foremost cause of irreversible central vision impairment, marked by choroidal neovascularization (CNV). The prevailing clinical approach to AMD treatment relies on intravitreal injections of anti-vascular endothelial growth factor (VEGF) drugs. However, this method is encumbered by diverse complications, prompting exploration of non-invasive alternatives such as ocular administration via eye drops for anti-VEGF therapy.MethodsTwo complexes, 5-FITC-CPP-Ranibizumab (5-FCR) and 5-FITC-CPP-Conbercept (5-FCC), were synthesized by incorporating the anti-VEGF drugs Ranibizumab (RBZ) or Conbercept (CBC) with cell-penetrating peptide (CPP). Circular dichroism spectrum (CD) facilitated complexes characterization. Eye drops was utilized to address laser-induced CNV in mice. Fluorescein fundus angiography (FFA) observe the CNV lesion, while FITC-dextran and IB4 dual fluorescent staining, along with hematoxylin-eosin (HE) staining, assessed in lesion size. Tissue immunofluorescence examined CD31 and VEGF expression in choroidal/retinal pigment epithelial (RPE) tissues. Biocompatibility and biosafety of 5-FCR and 5-FCC was evaluated through histological examination of various organs or cell experiments.ResultsBoth 5-FCR and 5-FCC exhibited favorable biocompatibility and safety profiles. VEGF-induced migration of Human umbilical vein endothelial cells (HUVECs) significantly decreased post-5-FCR/5-FCC treatment. Additionally, both complexes suppressed VEGF-induced tube formation in HUVECs. FFA results revealed a significant improvement in retinal exudation in mice. Histological examination unveiled the lesion areas in the 5-FCR and 5-FCC groups showed a significant reduction compared to the control group. Similar outcomes were observed in histological sections of the RPE-choroid-sclera flat mounts.ConclusionIn this study, utilizing the properties of CPP and two anti-VEGF drugs, we successfully synthesized two complexes, 5-FCR and 5-FCC, through a straightforward approach. Effectively delivering the anti-VEGF drugs to the target area in a non-invasive manner, suppressing the progression of laser-induced CNV. This offers a novel approach for the treatment of wet AMD.

The port delivery system (PDS) of anti-VEGF therapy provides continuous delivery of ranibizumab (RBZ). In October of 2021, the American Food and Drug Administration (FDA) approved the PDS with RBZ as a treatment option for neovascular age-related macular degeneration (nAMD). As the field of PDS with RBZ is progressing rapidly, this narrative review provides a much-needed overview of existing clinical trials as well as ongoing and upcoming trials investigating PDS with RBZ. The phase 2 LADDER trial reported that the mean time to first refill with RBZ PDS 100mg/ml was 15.8months (80% CI 12.1-20.6), and pharmacokinetic profiling revealed a sustained concentration of RBZ in serum and aqueous humor. Later, the phase3 ARCHWAY trial reported that PDS with RBZ (100mg/ml) refilled every 24weeks was non-inferior to monthly intravitreal injection (IVI) with RBZ (0.5mg) in patients with nAMD over 9months and 2years. However, patients with PDS had a higher rate of adverse events including vitreous hemorrhage and endophthalmitis. Patients indicate high treatment satisfaction with both PDS and IVI, but the lower number of treatments with PDS was reported as a preferred choice. Several ongoing and future clinical trials, of which details are discussed in this paper, are further exploring the potentials of PDS with RBZ. We conclude that the PDS provides continuous deliverance of RBZ and that clinical efficacy levels are non-inferior to IVI therapy for nAMD. Yet, a higher rate of adverse events remains a concerning detail for widespread implementation. Future studies are warranted to better understand which patients may benefit best from this treatment approach, if long-term efficacy can be sustained, and if safety of PDS can be further improved.

Introduction: The purpose of this study is to analyze incidence rates of endophthalmitis after intravitreal injection(s) of bevacizumab (BEVA), brolucizumab (BROL), aflibercept (AFL), ranibizumab (RAN), dexamethasone implant (DEXA), and triamcinolone acetonide (TRIA). Methods: In this retrospective cohort study data was collected from patients who received intravitreal injections from January 2020 through November 2021, of AFL, BEVA, BROL, DEXA, TRIA and RAN. Data collected includes patient identification number, injection dates, medication injected, and procedure codes. Endophthalmitis rates were compared amongst medications and total percentage tabulated. Result: From January 2020 through November 2021, 109,202 injections were administered. Of the 109,202 injections administered: 66,095 were aflibercept, 28,762 bevacizumab, 8,650 ranibizumab, 3,010 brolucizumab, 1,958 dexamethasone implant, and 95 triamcinolone acetonide. Thirty-nine (0.036%) endophthalmitis cases occurred. Of the 39 endophthalmitis cases, 22 of the cases occurred (0.033% of total aflibercept injections) after aflibercept injection(s), 5 (0.688% of total triamcinolone acetonide injections) after triamcinolone acetonide injection(s), 5 (0.03% of total bevacizumab injections) after bevacizumab injection(s), 3 (0.153% of total dexamethasone implants) after dexamethasone implantation(s), 2 (0.066% of total brolucizumab injections) after brolucizumab injection(s), 2 (0.023% of total ranibizumab injections) after ranibizumab injection(s).(Table 1) Using a student’s t-test, the rate of endophthalmitis for TRIA versus all other medications was statistically significant with a p-value of 0.00152. Conclusion: Results show an endophthalmitis incidence rate of 0.036% after intravitreal injection(s) administration. This review suggests triamcinolone acetonide (TRIA) yielded a significantly higher incidence rate of endophthalmitis as compared to the other medications.

Introduction: Corneal neovascularization disease is an important clinical symptom of many ocular surface disorders, and the use of anti-vascular endothelial growth factor (anti-VEGF) drugs is considered the most promising treatment method. Method: Ranibizumab (RB) is one of the few anti-VEGF drugs approved by the FDA in the treatment of ophthalmic diseases, but the special synthetic route leads to a short biological half-life, and therapeutic concentration cannot be maintained for a long time in clinical treatment. Therefore, we aim to develop a low immunogenicity sustained release system to improve the bioavailability of RB. RB was loaded on bovine milk-derived exosomes (MEXOs), and the in vitro release profile and pharmacokinetic characteristics were detected. RB was continuously release from the MEXOs (2 days, 60 h). The tubular network formation experiment of human umbilical vein endothelial cells showed that the MEXOs enhanced the inhibitory effects of RB on VEGF-induced tube formation, as confirmed by a cell proliferation experiment. Results: In vivo experiments showed that RB-loaded bovine milk-derived exosomes (RB-MEXOs) increased the precorneal residence time and half-life period of RB in New Zealand white rabbits. Conclusion: These results suggested that RB-MEXOs is conducive to the maintenance of effective RB concentration in vivo, and their use is potential strategy for treating corneal vascularization.

Purpose To compare combined phacoemulsification and intravitreal Ranibizumab (RBZ) injection versus sequential Intravitreal Raibizumab injection and phacoemulsification on the progression of diabetic macular edema (DME) both clinically (through best corrected visual acuity) and by optical coherence tomography (OCT). Setting and design This observational study was conducted in October 6 University, Faculty of Medicine, Department of Ophthalmology. Patient and methods Patients with non-ischemic diabetic macular edema (DME); along with, clinically significant cataract were randomly divided into two groups. Both groups received three intravitreal 0.5 mg/0.05 ml RBZ injections on monthly basis. Group (I), received the first dose combined with phacoemulsification followed by the other two injections, one and two months postoperatively. Group (II), received the first dose two weeks before phacoemulsification followed by the other two injections, one and two months from the first one. Results The baseline mean central macular thickness (CMT) was comparable in both groups (P&gt;0.05); however, the CMT one month after the third injection was 261±36 µm for Group (II) vs 320±65 µm for Group (I), which was statistically significant (P&lt;0.001). Both study groups were comparable regarding the baseline mean best corrected visual acuity (BCVA) (P&gt;0.05); however, the mean BCVA at the end of follow-up was 0.32±0.23 LogMAR for Group (II) vs 0.50±0.19 LogMAR for Group (I), which was statistically significant (P&lt;0.001). Conclusion Intravitreal RBZ injection has a significant clinical improving effect on both CMT and BCVA in diabetic patients with diabetic macular edema (DME) undergoing phacoemulsification; although, it is preferred to inject a single intravitreal injection two weeks before phacoemulsification to reach its peak effect in counteracting the high levels of VEGF released during the surgery.

The purpose of this study was to compare the efficacy and safety of aflibercept (AFL) versus ranibizumab (RAN) for the treatment of diabetic macular edema (DME). The PubMed, Embase, Cochrane Library, and CNKI databases were searched up to September 2022 to identify prospective randomized controlled trials (RCTs) comparing AFL with RAN for the treatment of DME. Review Manager 5.3 software was used for data analysis. We used the GRADE system to evaluate the quality of the evidence for each outcome. A total of 8 RCTs involving 1067 eyes (939 patients) were included; there were 526 eyes in the AFL group and 541 eyes in the RAN group. Meta-analysis revealed that there was no significant difference between RAN and AFL in the best-corrected visual acuity (BCVA) of DME patients at 6 months (WMD: -0.05, 95% CI = -0.12 to 0.01, moderate quality) and 12 months after injection (WMD: -0.02, 95% CI = -0.07 to 0.03, moderate quality). Additionally, there was no significant difference between RAN and AFL in the reduction of central macular thickness (CMT) at 6 months (WMD: -0.36, 95% CI = -24.99 to 24.26, very low quality) and 12 months after injection (WMD: -6.36, 95% CI = -16.30 to 3.59, low quality). Meta-analysis showed that the number of intravitreal injections (IVIs) for AFL was significantly lower than that for RAN (WMD: -0.47, 95% CI = -0.88 to -0.05, very low quality). There were fewer adverse reactions to AFL than to RAN, but the difference was not significant. This study found that there was no difference in BCVA, CMT or adverse reactions between AFL and RAN at 6 and 12 months of follow-up, but AFL needed fewer IVIs than RAN.

Purpose: To evaluate the incidence and clinical characteristics of intravitreal injection-related endophthalmitis cases with antivascular endothelial growth factor (anti-VEGF) medications manufactured as prefilled syringes or non-prefilled preparations. Methods: This retrospective chart review comprised eyes that received intravitreal anti-VEGF at a single-specialty retina practice from January 1, 2014, to December 31, 2019. Eyes diagnosed with injection-related endophthalmitis were identified. Demographic and clinical data were abstracted from medical records, including the type of anti-VEGF agent, baseline and follow-up corrected visual acuity (VA), and microbiologic findings. Results: The review identified 88 cases of intravitreal anti-VEGF injection-related endophthalmitis and 325 990 total injections. Total injections included 32 045 (9.8%) bevacizumab (BEV), 93 073 (28.6%) ranibizumab (RAN), 122 947 (37.7%) aflibercept (AFL), and 77 925 (23.9%) ranibizumab prefilled syringe (RANPFS). Ten of the endophthalmitis cases were related to BEV, 21 to RAN, 45 to AFL, and 12 to RANPFS. The endophthalmitis rate was lowest for RANPFS (0.0154%) (BEV, 0.0312%; RAN, 0.0226%; AFL, 0.0366%) (P = .030). Thirty-four (41.5%) of 82 samples were culture positive. RANPFS had a significantly lower rate of culture-proven postinjection endophthalmitis than the other agents (P = .003). The mean VA for endophthalmitis cases related to RANPFS vs non-prefilled agents was similar at presentation (Snellen 20/2092 vs 20/2327) and at the 3-month follow-up (Snellen 20/201 vs 20/272) (both P > .05). Conclusions: Anti-VEGF medications in prefilled syringes may reduce the risk for medication contamination during injection preparation. RANPFS was associated with a lower rate of injection-related endophthalmitis than non-prefilled anti-VEGF medications.

The aim of this study was to compare the outcomes of diabetic macular edema (DME) treated with aflibercept (AFB) or ranibizumab (RNB) only, and after switching from RNB to AFB. This was a retrospective, real-world, multicenter (7 cities) 24 month study. Overall, 212 eyes in the AFB group, 461 in the RNB group, and 141 in the RNB to AFB group were included. The primary endpoints were differences in visual acuity (VA) and central macular thickness (CMT) from baseline to the final visit. The secondary outcomes were the percentage of eyes that achieved ≥10 letters gain and ≥10 letters loss in vision at month 12 and 24, and the percentage of eyes that achieved a thinning of ≥20% in CMT at month 3 and month 6. The results showed that VA did not significantly differ at baseline (AFB: 0.62 ± 0.38, RNB: 0.61 ± 0.36, RNB to AFB: 0.61 ± 0.38), at checkpoints, or at the final visit (AFB: 0.46 ± 0.38, RNB: 0.5 ± 0.37, RNB to AFB: 0.53 ± 0.36) (p > 0.05). Though the mean CMT at baseline was significantly thicker in the RNB to AFB group (479 ± 129.6 μm) when compared to the AFB (450.5 ± 122.6 μm) and RNB (442 ± 116 μm) groups (p < 0.01), similar measurements were obtained after 12 months. The percentages of eyes that gained or lost ≥10 letters in the AFB, RNB, and RNB to AFB groups at year 1 and 2 were similar, as was the percentages of eyes that demonstrated ≥20% CMT thinning at month 3 and 6. Our study showed similar visual improvements in non-switchers (AFB and RNB groups) and switchers (RNB to AFB group) through 2 years follow-up, however, AFB patients required fewer injections, visits, or need for additional treatments.

Vascular Endothelial Growth Factor A (VEGFA) is a glycoprotein that mediates various biological processes, including angiogenesis, vascular permeability, and cellular migration. Aberrant VEGFA signaling is also one of the hallmarks of many types of cancer and has been implicated in various ophthalmological conditions such as diabetic macular edema and age-related macular degeneration. Consequently, a number of therapeutic monoclonal antibodies (mAb) targeting VEGFA have been developed and are widely used to treat these conditions. Bevacizumab (BVZ) and Ranibizumab (RBZ) are two such antibodies that are commercially available and used to treat various cancers and ophthalmological conditions. Nevertheless, a very high rate of non-responsiveness to these mAb treatments has been reported. Therefore, it is important to predict the response to these therapeutic mAb treatments in patients in a personalized approach. This study was aimed at analyzing the impacts of missense variants in the respective VEGFA epitopes for these two therapeutic anti-VEGFA mAbs (BVZ and RBZ) on their interaction with VEGFA through the use of multiple in silico tools. Three missense variants (VEGFAR82W, VEGFAR82Q, and VEGFAG92R) in VEGFA epitopes appear to significantly destabilize VEGFA-BVZ interaction, while only two variants (VEGFAR82W and VEGFAR82Q) affect interaction of VEGFA with RBZ. The VEGFAR82W variant may be pathogenic as well. These missense variants may play roles in the observed heterogeneous response to anti-VEGFA mAb treatments in patients and, therefore, may be used as pharmacogenetic markers for the prediction of responses before administration, and thus for the improvement of therapeutic outcomes.

Objectives:This study aimed to compare the effects of dexamethasone (DEX) implants and ranibizumab (RAN) injections in younger patients with macular edema due to branch retinal vein occlusion (RVO) in a 6-month follow-up.Methods:The treatment-naive patients with macular edema secondary to branch RVO were included retrospectively. Medical records of patients who were treated with intravitreal RAN or DEX implant were evaluated before and at the 1st, 3rd, and 6th months after the injection. Primary outcome measures were the change in best-corrected visual acuity (BCVA) and central retinal thickness. The level of statistical significance was set at 0.05/3=0.016, according to the Bonferroni correction.Results:Thirty-nine eyes of 39 patients were included in the study. The mean age of the study population was 53.82±5.08 years. Median BCVA in the DEX group (n=23) at baseline, 1st, 3rd, and 6th month was 1.1, 0.80 (p=0.002), 0.70 (p=0.003), and 1 (p=0.018) logarithm of the minimum angle of resolution (log-MAR), respectively (p<0.05). Median BCVA in the RAN group (n=16) at baseline, 1st, 3rd, and 6th months was 0.90, 0.61, 0.52, and 0.46 logMAR, respectively (p<0.016 for all comparisons). Median central macular thickness (CMT) in the DEX group at baseline, 1st, 3rd, and 6th months was 515, 260, 248, and 367 μm, respectively (p<0.016 for all comparisons). Median CMT in the RAN group at baseline, 1st, 3rd, and 6th months was 432.5 (p<0.016), 275 (p<0.016), 246 (p<0.016), and 338 (p=0.148) μm.Conclusion:There is no significant difference in treatment efficacies in both visual and anatomical outcomes at the end of the 6th month. However, RAN can be considered the first choice in younger patients with macular edema secondary to branch RVO because of the lower side effect profile.

Extracellular signalling proteins interact in networks rather than in isolation. In this context we investigated vitreous protein levels, including placental growth factor (PlGF), angiopoietin-2 (ANG2) and vascular endothelial growth factor (VEGF), in patients with proliferative diabetic retinopathy (PDR) with variable disease severities, and after anti-VEGF pre-treatment. Vitreous samples of 112 consecutive patients undergoing vitrectomy for PDR and of 52 non-diabetic patients with macular holes as controls were studied. A subset of the PDR patients were treated with either aflibercept (AFB, n = 25) or bevacizumab (BVZ)/ranibizumab (RZB) (n = 13), before surgery. Antibody-based analysis of 35 proteins (growth factors and cytokines) showed a significant increase in expression levels of 27 proteins in PDR patients as compared to controls. In network analysis of co-regulated proteins, a strong correlation in expression levels between VEGF, PlGF, MCP1 and ANG2 was found, mostly clustered around ANG2. In the AFB treatment group, concentrations of several proteins were decreased, including VEGFR1, whereas interleukin 6 and 8 were increased as compared to untreated PDR patients. The observed differences in vitreous protein levels between the different treatments and untreated PDR patients may underlie differences in clinical outcomes in patients with PDR.

PurposeTo investigate the baseline characteristics in patients with diabetic macular edema (DME) during 7 years according to the need for additional treatments after intravitreal ranibizumab (RBZ) loading injections.MethodsThe medical records of 32 patients treated with intravitreal RBZ loading for DME during 7 years were reviewed. After three-consecutive monthly RBZ injections, additional treatment was decided according to the patient’s response to RBZ loading. Based on whether the patients received treatment with or without additional injections, including intravitreal antivascular endothelial factor or steroid injection, they were divided into the “no add (NA)” or “add” groups, respectively. The baseline best-corrected visual acuity (BCVA), macular volume (MV), central subfoveal thickness, and other clinical factors were analyzed, and their 7-year changes were compared between the two groups.ResultsThe BCVA of the NA group was better than that of the add group at 2, 3, 5, and 7 years (year 2, 3, and 5; p < 0.01, respectively). Baseline MV was significantly smaller in the NA group than in the add group (10.72 ± 0.88 μm vs. 11.98 ± 1.64 μm, p = 0.008). The DME duration before treatment in the NA group was significantly shorter than in the add group (1.03 ± 0.98 years vs. 1.91 ± 1.33 years, p = 0.042). The proportion of patients with serous retinal detachment or cystic macular edema was significantly lower in the NA group than in the add group (35.3% vs. 73.3%, p = 0.042). The NA group had smaller MV until 2 years than the add group (year 1, p = 0.002; year 2, p = 0.006).ConclusionsThe DME patients without additional treatments during 7 years after the initial loading treatment had shorter duration of DME and diffuse retinal thickening morphologic type with lower MV at baseline, and better long-term visual prognosis.