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The purpose of the study described was to establish prediction models to initially screen the beneficiary patients with unresectable hepatocellular carcinoma (HCC) in the treatment of anti-vascular endothelial growth factor (VEGF) agents plus anti-programmed cell death-1 (PD-1) antibody. A total of 62 patients were enrolled in this study. All patients underwent ultrasound (US), color ddoppler flowing imaging (CDFI), contrast-enhanced ultrasound (CEUS) and laboratory examinations within 2 wk before the treatment. Tumor response was assessed according to mRECIST criteria. Univariate and multivariate analyses were used to select the independent predictors. US + CDFI, CEUS and FULL models were established. Three models were displayed by nomography. Receiver operating characteristic (ROC) and calibration curves were drawn to evaluate the predictive ability of models. Decision curve analysis (DCA) was used to assess the clinical utility of models. On univariate and multivariate analysis, the US boundary (p = 0.037), halo (p = 0.002) and CDFI (p = 0.024) were included in the US + CDFI model. CEUS boundary (p = 0.001) and washout time (p < 0.001) were included in the CEUS model. The number of lesions (p = 0.104), halo on US (p = 0.014), CDFI (p = 0.057) and washout time on CEUS (p = 0.015) were incorporated into the FULL model. The C indices of the US + CDFI, CEUS and FULL models were 0.918, 0.920 and 0.973. CEUS and FULL models yielded a good net benefit for almost all threshold probabilities. Nomograms based on US, CDFI, CEUS and clinical characteristics could help to non-invasively predict the response to treatment with anti-PD-1 antibodies plus anti-VEGF agents. [ABSTRACT FROM AUTHOR]

In this meta‐analysis, we aim to compare the efficacy and safety of pars plana vitrectomy (PPV) versus tap‐and‐inject (TAI) of intravitreal antibiotics for the management of endophthalmitis secondary to intravitreal injections of anti‐vascular endothelial growth factor (VEGF) agents. A systematic literature search was conducted on Ovid MEDLINE, EMBASE, and Cochrane Central (January 2005–October 2022). The primary analysis compared initial PPV versus TAI and the secondary analysis examined the efficacy and safety of TAI alone compared to TAI followed by PPV. The quality of non‐randomized observational studies was assessed using the Newcastle‐Ottawa Scale. The quality of the evidence was assessed for each outcome. A random effects meta‐analysis was performed. Weighted mean differences (WMDs) with 95% confidence intervals were reported. Of the 7474 screened studies, nine studies reporting on 153 eyes were included. The change in mean best corrected visual acuity (BCVA) between endophthalmitis presentation and last follow‐up did not significantly differ between the initial TAI versus PPV groups (WMD = 0.05 units; 95% CI −0.12 to 0.22; p = 0.59; heterogeneity p = 0.41). The difference in pre‐ to post‐treatment mean BCVA did not significantly differ between eyes that received TAI alone or TAI followed by PPV (WMD = 0.04 units; 95% CI −0.42 to 0.51; p = 0.85; heterogeneity p = 0.74). While the meta‐analysis revealed no significant difference in the change in BCVA between PPV and TAI to treat endophthalmitis secondary to anti‐VEGF agents, the quality of evidence was low with potential for confounding and selection bias. Further well‐designed studies in this setting are needed. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity(ROP)is a proliferative vascular disorder of the immature retina, and it is a major eye disease that causes blindness in children of developing and developed countries. Retinal laser photocoagulation and cryotherapy are the conventional treatment used for ROP but could cause permanent damage to retina, with a risk of complications such as visual field defect and high myopia. With more normal growth of retinal function and convenience and shorter time than coagulation therapy, intravitreal injection of anti-vascular endothelial growth factor(VEGF)agents has gradually gained popularity and has even been advocated as the treatment of choice in treating zone I, zone II posterior or aggressive ROP. However, the serious systemic complications, minimum effective dose and late recurrence caused by anti-VEGF drugs in the treatment of ROP still need to be further studied. This review focuses on the use of anti-VEGF agents for the treatment of ROP.

Nobuhiro Kato, Masatoshi Haruta, Kei Furushima, Rikki Arai, Yu Matsuo, Shigeo Yoshida Department of Ophthalmology, Kurume University School of Medicine, Kurume, JapanCorrespondence: Masatoshi Haruta, Department of Ophthalmology, Kurume University School of Medicine, 67 Asahi-machi, Kurume, Fukuoka, 830-0011, Japan, Tel +81 942 31 7574, Fax +81 942 37 0324, Email haruta_masatoshi@med.kurume-u.ac.jpPurpose: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) agents such as brolucizumab and aflibercept are used widely to treat neovascular age-related macular degeneration (nAMD); however; they may theoretically affect the ocular blood flow. We investigated the short-term changes in the ocular blood flow between eyes with nAMD treated with intravitreal brolucizumab injections (IVBr) and intravitreal aflibercept injections (IVA).Methods: This study included 21 eyes of 21 Japanese patients with nAMD treated with either IVBr or IVA at Kurume University Hospital from April 2021 through June 2022. The rates of ocular blood flow at the optic nerve head (ONH mean blur rate [MBR]-vessel) and at the choroid (CHOR MBR) were analyzed before and 30 minutes after injections using laser speckle flowgraphy.Results: In the IVBr-treated group, the ONH MBR-vessel and CHOR MBR rates decreased significantly by 10.6% and 16.9% from baseline to 30 minutes after IVBr, respectively. In the IVA-treated group, ONH MBR-vessel and CHOR MBR rates decreased significantly by 9.4% and 6.1% from baseline to 30 minutes after IVA, respectively. There was no significant difference in the rates of decrease in the ONH MBR-vessel or CHOR MBR between the IVBr-treated and IVA-treated groups.Conclusion: Intravitreal injections of brolucizumab and aflibercept in eyes with nAMD cause significant decreases in ocular blood flow at the ONH and the choroid 30 minutes after injection. The rate of decrease in ocular blood flow was not significant between the eyes treated with brolucizumab and aflibercept. However, 3 of 10 eyes treated with brolucizumab but none of 11 eyes treated with aflibercept had more than a 30% decrease in the ocular blood flow at the choroid 30 minutes after injection.Keywords: anti-vascular endothelial growth factor agents, choroid, laser speckle flowgraphy, mean blur rate, optic nerve head

Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 μg/μL of aflibercept (Af), or 25 μg/μL of bevacizumab (Be), or 10 μg/μL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety. [ABSTRACT FROM AUTHOR]

Purpose: To assess the effect of switching to brolucizumab from aflibercept on eyes with type 1 macular neovascularization (MNV) and polypoidal choroidal vasculopathy (PCV) at 18 months. Methods: This study was a retrospective, observational case series that included 19 eyes of 19 patients with type 1MNV and 23 eyes of 22 patients with PCV. We compared the injection intervals, visual acuity, total lesion size, and the number of polypoidal lesions between baseline and 18 months. The correlations between the data including treatment interval, total lesion size, and the number of polyps were also assessed. Results: Treatment intervals were significantly extended; from 7.4 ± 1.4 weeks to 11.6 ± 2.6 weeks for type 1 MNV, p < 0.001; from 6.9 ± 1.3 to 11.7 ± 3.1 weeks for PCV, p < 0.001. In type 1 MNV eyes, strong correlation was found between total lesion size and brolucizumab injection intervals (r = − 0.81; p = 0.0002) and moderate correlation was found between treatment frequency with aflibercept and that with brolucizumab (r = 0.76; p = 0.040). In PCV eyes, we found strong correlation between the number of polyps and brolucizumab treatment frequency (r = − 0.81; p = 0.0016) and moderate correlation between total lesion size and brolucizumab treatment interval (r = − 0.48; p = 0.034). Intraocular inflammation occurred in 2 of 19 eyes (10.3%) with type 1 MNV and 5 of 23 eyes (21.7%) with PCV. Conclusion: The properties to extend brolucizumab injection intervals might be the smaller lesion size and lower aflibercept frequency for type 1 MNV and the smaller number of polyps and the smaller size of lesion for PCV. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate anatomical and visual results of eyes with naive myopic choroidal neovascularization (mCNV) in patients treated with intravitreal anti-vascular endothelial growth factor (VEGF) therapies. Material and methods: This is a retrospective, non-randomized, comperative, intervetional study. One hundred fourteen eyes of 114 patients with mCNV who underwent intravitreal bevacizumab (IVB), intravitreal ranibizumab (IVR) or intravitreal aflibercept (IVA) monotherapy injections were enrolled into the study. The best corrected visual acuity (BCVA), central macular thickness (CMT) and subfoveal choroidal thickness (SFCT) were compared among the groups during the follow-up periods at the beginning, months 1, 3, 6, 12, and the final visit. Results: The mean age of the patients was 47.76 ± 10.57 years (range, 33–72 years) and the mean follow-up period was 23.34 ± 6.81 months (range, 13–38 months). The mean BCVA denoted a significantly improve at each group (p < 0.05). In terms of an inter-group analysis of all 3 groups, at months 1, 6, and 12 and final visit, the BCVA were statistically significantly better in the IVA group when compared to both IVB and IVR groups (p = 0.021, p = 0.032, p = 0.024, p = 0.012). There was a significant decrease in CMT following IVB (236.49 ± 40.91 μm–190.74 ± 50.12 μm), IVA (232.91 ± 46.29 μm–193.73 ± 46.81 μm) and IVR (234.78 ± 45.37 μm–192.21 ± 37.27 μm) between baseline and final visit (p = 0.018, p = 0.002, p < 0.001, respectively). There was a statistically significant decrease in SFCT values between baseline and final examination only in the IVA group (p < 0.001). The mean number of injections were 9.18 ± 3.18 (range; 3 to 13) in IVB, 6.46 ± 2.93 (range; 3–11) in IVR and 4.45 ± 1.42 (range; 2–7) in IVA (p = 0.028). Conclusion: All three anti-VEGFs were found to be effective in terms of visual results in patients with mCNV. However, we demonstrated that IVA reduces the need for anti-VEGF when compared to patients who received both IVB and IVR. Furthermore, IVA induced a prominent reduction in SFCT, whereas IVR and IVB did not have a significant action on SFCT. [ABSTRACT FROM AUTHOR]

To assess morphological changes and visual results in eyes with pachychoroid neovasculopathy (PNV) that underwent different intravitreal anti-vascular endothelial growth factor (VEGF) agents. This is a retrospective, observational, comparative study that included 76 PNV eyes in 76 patients that were allocated to three groups according to the monotherapy injection procedure, as follows: the intravitreal bevacizumab (IVB) group, intravitreal ranibizumab (IVR) group, and intravitreal aflibercept (IVA) group. Central macular thickness (CMT), best-corrected visual acuity (BCVA), and subfoveal choroidal thickness (SFCT) were measured at baseline, after treatment 1st month, 3rd month, 6th month, and 12th month, and at the final post-treatment examination. Mean age of the patients was 57.31 ± 5.91 years (range: 34–67 years). The mean duration of follow-up was 31.50 ± 12.91 months (range: 13–60 months). The IVB group included 30 eyes, the IVR group included 22 eyes, and the IVA group included 24 eyes. There weren't any significant differences in BCVA changes between the groups at any post-baseline measurement time point. Although CMT did not change significantly in the IVB group from baseline to the final follow-up visit (baseline: 376.33 ± 86.31 µm; final visit: 340.80 ± 122.70 µm) (p = 0.172), CMT did change significantly in the IVA group (baseline: 383.41 ± 131.83 µm; final visit: 297.33 ± 103.81 µm) (p = 0.029) and IVR group (baseline: 379.18 ± 97.93 µm; final visit: 335.72 ± 111.45 µm) (p = 0.041). SFCT decreased significantly in the IVR and IVA groups (p = 0.015 and p < 0.001, respectively). The mean number of injections was 12.06 ± 4.72 (range: 6–20) in the IVB group, 11.81 ± 3.31(range: 7–17) in the IVR group, and 7.16 ± 3.15 (range: 4–13) in the IVA group (p = 0.004). All three anti-VEGFs were effective in terms of visual results in patients with PNV. Patients treated with IVA required fewer injections than those treated with IVB or IVR. Furthermore, IVR and IVA treatment significantly decreased SFCT, whereas IVB did not. [ABSTRACT FROM AUTHOR]

David J Browning,1 Paul B Greenberg2 1Charlotte, Eye, Ear, Nose, and Throat Associates, Charlotte, NC, 28210, USA; 2Division of Ophthalmology, Alpert Medical School, Brown University, Providence, RI, USACorrespondence: David J Browning Email djbrowning179@gmail.comPurpose: To quantify the economic incentives associated with the choice of anti-VEGF drugs for retinal diseases.Methods: An economic model was created based on the distribution of use and number of injections of bevacizumab (B), versus aflibercept or ranibizumab (AR); published Medicare reimbursement rates; published rebates; estimated unreimbursed drug use; estimated use of drug company samples; and published costs-of-drugs. Differential economic incentives associated with the choice of drugs were calculated over a range of distributions of drug use.Results: The splits in drug choice ranged from 92% AR/8% B to 31% AR/69% B, and in annual injection numbers from 2000 to 6000 with a median of 4000 in one 5-person retina service. Assumed values for rebates were 1% for drug company rebate, 1% for group purchasing organization rebate, and 5 for number of unreimbursed injections per year. The differential economic incentive of a 92% AR/8% B split compared to a 31% AR/69% B split for the median annual number of injections was $266, 893.Conclusion: Using real-world data, the economic incentive associated with a choice of more expensive anti-VEGF drugs is large. Accounting for unreimbursed drug use and the cost of additional staff required to manage expensive drug inventory does not nullify the incentive. To what degree this financial incentive influences ophthalmologists’ choice of drugs is unknown, but not trivial. Financial disclosure of the conflicts of interest in the drugs recommended for treatment should be discussed with patients.Keywords: anti-vascular endothelial growth factor agents, conflict of interest, economic incentives

Ranibizumab has proven its efficacy in various retinal diseases and particularly in neovascular age-related macular degeneration (nAMD). The number of injections and the frequent follow-up visits has been burdensome to patients particularly during the COVID era. Ranibizumab port delivery system (RPDS) seems to be a boon in prolonging the action of the drug without the need for frequent injections and follow-up visits. This review article highlights the dosage, adverse effects, and visual outcome associated with various trials of RPDS. For this article, we conducted a PubMed search and review of literature on nAMD, the incidence of AMD, anti-vascular endothelial growth factor (anti-VEGF) agents, RPDS, phase-1 trial of RPDS, phase-2 (LADDER trial) of RPDS, phase-3 (ARCHWAY trial) of RPDS, PORTAL trial of RPDS, results of phase-1 trial of RPDS, results of phase-2 (LADDER) trial of RPDS, and results of phase-3 (ARCHWAY) trial of RPDS. [ABSTRACT FROM AUTHOR]

Retinopathy of prematurity(ROP)is an immature proliferative retinal vascular disease that may lead to permanent blindness in preterm infant. Retinal laser photocoagulation is used for ablation of peripheral retina and treatment of ROP, however, it is destructive. Especially for the cases with lesions in Zone I region, retinal laser photocoagulation may cause severe complications. Recently, studies have demonstrated that vascular endothelial growth factor(VEGF)plays a causal role in the pathogenesis of ROP, and intravitreal injection of anti-VEGF agents can not only effectively impede ROP progression, but also gain timing for revascularization of a vascular retinal region. This article reviews the treatment indications, drug selection, injection site, dosage recommendation, follow-up of efficacy and complications of intravitreal injection of anti-VEGF agents in the treatment of ROP.

Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 μg/μL of aflibercept (Af), or 25 μg/μL of bevacizumab (Be), or 10 μg/μL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety.

Purpose: To report the long-term changes of the size of myopic choroidal neovascularization (mCNV) using optical coherence tomography angiography (OCTA). Methods: This was a retrospective, observational case study of eleven eyes in eleven patients with mCNV followed with OCTA for a minimum of 3 years. The flow area of mCNV on OCTA, the size of chorioretinal atrophy (CRA) and central choroidal thickness were analyzed. The relationship between the changes of mCNV size and recurrences treated with anti-vascular endothelial growth factor (VEGF) agents was also assessed. Results: Three eyes out of eleven eyes showed enlargement of the mCNV over 3 years. In two of the three eyes, the mCNV recurrences had not been treated immediately (the examination intervals were 4 months and 5 months, respectively), and we found obvious enlargement of the mCNV. In three eyes, the mCNV size decreased in 1 year and was stable thereafter without recurrences. In five eyes, mCNV size did not show remarkable changes for 3 years. In three of the five eyes, no recurrences were detected and two of the five eyes underwent prompt treatments against recurrences. Conclusion: Regular examination and prompt treatments against recurrences are critical to prevent enlargement of mCNV. [ABSTRACT FROM AUTHOR]

Purpose: To describe treatment patterns in patients diagnosed with neovascular age-related macular degeneration (nAMD), retinal vein occlusion (RVO), or diabetic macular edema (DME), newly-treated with anti-vascular endothelial growth factor (anti-VEGF) agents as recorded in the Japanese Medical Data Center (JMDC) database. Study design: This non-interventional, descriptive, retrospective, observational cohort study included insured Japanese patients aged ≥ 21 and ≤ 75 years at index date (anti-VEGF treatment initiation). Methods: Patients with minimum one claim in JMDC database with a diagnosis code for nAMD, RVO, or DME between October 2007–May 2015 and with minimum of one claim for anti-VEGF agents on or after the date of diagnosis were included. Frequency and proportion of claims submitted for anti-VEGF injections were assessed during 12 months post-index date. Results: The median (interquartile range) number of claims for anti-VEGF injections during 12 months post-index date were 3 (1, 4) for nAMD (n = 255), 2 (1, 3) for RVO (n = 223) and 2 (1, 4) for DME (n = 125) patients. Frequencies of nAMD, RVO and DME patients with one or more claims for a retinal disease treatment other than an anti-VEGF agent were 4 (1.57%), 59 (26.46%) and 68 (54.40%) during the 12 months pre-index date and 21 (8.24%), 85 (38.12%) and 62 (49.60%) in the 12 months post-index date, respectively. Conclusions: The median number of anti-VEGF injections per patient was lower than those reported in clinical trials. Although various pre- and concomitant treatments were used in RVO and DME, anti-VEGF monotherapy was the first-line treatment in > 90% of nAMD patients. [ABSTRACT FROM AUTHOR]

AIM: To evaluate the efficacy and safety of combined anti-vascular endothelial growth factor (VEGF) agents, oral glucocorticoid, and laser photocoagulation therapy for macular edema (ME) secondary to retinal vein occlusion (RVO). METHODS: This study included 16 eyes of 16 patients with RVO-associated ME. Patients were initially treated with oral prednisone and an intravitreal anti-VEGF agent. Two weeks later, patients underwent standard laser photocoagulation. Best-corrected visual acuity (BCVA), central retinal thickness (CRT), and retinal vessel oxygenation were examined over 12mo. RESULTS: Patients received 1.43±0.81 anti-VEGF injections. Mean baseline and 12-month logMAR BCVA were 0.96±0.51 (20/178) and 0.31±0.88 (20/40), respectively, in eyes with central retinal vein occlusion (CRVO) (P

Purpose: To evaluate efficacy and safety of intravitreal injections of aflibercept (IVT-AFL) treat-and-extend (T&E) dosing regimens in treatment-naïve patients with exudative age-related macular degeneration (AMD).Methods: Adults aged at least 50 years old with exudative AMD and best-corrected visual acuity (BCVA) of 73-25 Early Treatment Diabetic Retinopathy Study (ETDRS) letters were included. Patients received three monthly doses of IVT-AFL 2 mg. At week 16, patients were randomized 1:1 to IVT-AFL T&E with either 2- or 4-week adjustments. The primary endpoint was mean change in BCVA from baseline to week 52. Outcomes were assessed at weeks 52 and 96.Results: Baseline characteristics were comparable between the groups (n = 123 each). Over 52 weeks, mean number of injections was 7.2 and 6.9 and mean last injection interval was 10.7 and 11.8 weeks, for the 2- and 4-week groups, respectively. From baseline, mean change in BCVA was + 9.0 and + 8.4 letters (week 52) and + 7.6 and + 6.1 letters (week 96); mean change in central retinal thickness was - 134.4 µm and - 126.1 µm (week 52) and - 130.5 µm and - 125.3 µm (week 96). Last injection interval before week 52 was at least 12 weeks in 42.3% and 49.6% of patients and 56.9% and 60.2% before week 96. Over 96 weeks, mean number of injections was 10.4 (both groups). The safety profile of IVT-AFL was consistent with previous reports.Conclusions: IVT-AFL administered using two different T&E regimens for treatment-naïve exudative AMD improved functional and anatomic outcomes at week 52 and outcomes were maintained to week 96. Outcomes were similar between the 2- and 4-week groups.Trial Registration: ClinicalTrials.gov identifier, NCT02305238. [ABSTRACT FROM AUTHOR]

The management of uveitis is challenging for most treating ophthalmologists. The treatment of uveitis often requires the use of high dose of systemic corticosteroid and immunosuppressive agents, which are almost always associated with potential side effects. Intravitreal medications have become a popular mode of drug administration in uveitis patients as they provide high volume of drug to the target tissues, eliminating the risk of systemic toxicity. There has been tremendous development in the intravitreal therapeutics over the last few years. With the advent of sustained-release technique, increasing patient compliance, biodegradable nature of the implant, and introduction of newer agents with better safety profile, the intravitreal medications have become more popular in recent years. This review presents evidence in the scientific literature supporting the use of intravitreal medications for the management of uveitis and its complications.

Although the exact pathogenetic mechanisms leading to age-related macular degeneration (AMD) have not been clearly identified, oxidative damage in the retina and choroid due to an imbalance between local oxidants/anti-oxidant systems leading to chronic inflammation could represent the trigger event. Different in vitro and in vivo models have demonstrated the involvement of reactive oxygen species generated in a highly oxidative environment in the development of drusen and retinal pigment epithelium (RPE) changes in the initial pathologic processes of AMD; moreover, recent evidence has highlighted the possible association of oxidative stress and neovascular AMD. Nitric oxide (NO), which is known to play a key role in retinal physiological processes and in the regulation of choroidal blood flow, under pathologic conditions could lead to RPE/photoreceptor degeneration due to the generation of peroxynitrite, a potentially cytotoxic tyrosine-nitrating molecule. Furthermore, the altered expression of the different isoforms of NO synthases could be involved in choroidal microvascular changes leading to neovascularization. The purpose of this review was to investigate the different pathways activated by oxidative/nitrosative stress in the pathogenesis of AMD, focusing on the mechanisms leading to neovascularization and on the possible protective role of anti-vascular endothelial growth factor agents in this context.

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is increasingly used for the treatment of a wide variety of retinal diseases including age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions, and retinopathy of prematurity. Despite encouraging results in halting the disease and improving the vision, intravitreal injection of anti-VEGF agents may be associated with marked side effects. The present case describes a 75-year-old female with known complications of hypertension, Type II DM, and hypothyroidism, who received intravitreal injections of Lucentis (ranibizumab) due to diabetic macular edema. After 10 days, the patient admitted with chief complaints of slurred speech. Further, radiological and clinical investigations conferred the case to be a left middle cerebral artery territory infarct with right-sided hemiparesis and aphasia. Although well-designed randomized clinical trials have shown the efficacy of these agents in visual improvement in various retinal diseases, each intravitreal injection poses the risk of postinjection- and drug class-associated adverse events. Clinicians should be more vigilant as patients receiving intravitreal injections are at a small risk of developing complications, which is often unrecognized or underreported.

The management of uveitis is challenging for most treating ophthalmologists. The treatment of uveitis often requires the use of high dose of systemic corticosteroid and immunosuppressive agents, which are almost always associated with potential side effects. Intravitreal medications have become a popular mode of drug administration in uveitis patients as they provide high volume of drug to the target tissues, eliminating the risk of systemic toxicity. There has been tremendous development in the intravitreal therapeutics over the last few years. With the advent of sustained-release technique, increasing patient compliance, biodegradable nature of the implant, and introduction of newer agents with better safety profile, the intravitreal medications have become more popular in recent years. This review presents evidence in the scientific literature supporting the use of intravitreal medications for the management of uveitis and its complications. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the results of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for retinopathy of prematurity (ROP) in infants with active adenoviral keratoconjunctivitis (AKC). Material and methods: A retrospective analysis was performed using the medical records of all infants treated with intravitreal injections of anti-VEGF agents during an AKC outbreak previously reported in the literature at a tertiary center for treatment of ROP. The infants were divided into two groups. Group 1 included nine infants (18 eyes) with AKC, while Group 2 included 13 infants (26 eyes) without AKC. Results: During the AKC outbreak, 22 infants were treated with anti-VEGF agents for treatment-requiring ROP. In all patients in both groups, the ROP and plus disease displayed a significant regression within 2 days after the intravitreal injections. Moreover, no serious complications such as endophthalmitis, retinal detachment, cataract or intravitreal hemorrhage were observed after the treatment and there were no statistically significant differences between the groups in terms of postoperative complications. Conclusion: Immediate and appropriate intervention is very important in cases of treatment-requiring ROP otherwise it can result in blindness. However, laser treatment for ROP is technically difficult in infants with active AKC. The results of this study showed that favorable outcomes without serious ocular complications could be obtained via intravitreal injections of anti-VEGF agents in infants with active AKC. [ABSTRACT FROM PUBLISHER]

Anti-vascular endothelial growth factor (VEGF) currently used to treat eye diseases have included monoclonal antibodies, antibody fragments, and an aptamer. A different method of achieving VEGF blockade in retinal diseases includes the concept of a cytokine trap. Cytokine traps technology are being evaluated for the treatment of various diseases that are driven by excessive cytokine levels. Traps consist of two extracellular cytokine receptor domains fused together to form a human immunoglobulin G (IgG). Aflibercept/VEGF trap-eye (VTE) is a soluble fusion protein, which combines ligand-binding elements taken from the extracellular components of VEGF receptors 1 and 2 fused to the Fc portion of IgG. This protein contains all human amino acid sequences, which minimizes the potential for immunogenicity in human patients. This review presents the latest data on VTE in regard to the pharmacokinetics, dosage and safety, preclinical and clinical experiences. Method of the literature search: A systematic search of the literature was conducted on PubMed, Scopus, and Google Scholar with no limitation on language or year of publication databases. It was oriented to articles published for VTE in preclinical and clinical studies and was focused on the pharmacokinetics, dosage and safety of VTE.

Background: Corneal neovascularization (CoNV) is the second major cause of blindness. Vascular endothelial growth factor (VEGF) inhibitors, e.g. , bevacizumab, have been used to prevent CoNV., Aim: We conducted an updated systematic review and meta-analysis of clinical trials to examine the efficacy and safety of anti-VEGF in CoNV., Methods: A literature search was conducted using three electronic databases. Mean difference (MD), standard mean difference (SMD), and relative risk (RR) are used to estimate the effect size., Results: Nine randomized controlled and three non-randomized trials were obtained. The pooled results demonstrated a significant reduction of CoNV area/Length (SMD = -1.17, 95%CI: -1.58 to -0.75), best corrected visual acuity (MD = -0.54, 95%CI: -0.91 to -0.17), and graft rejection (RR = 0.44, 95%CI: 0.24 to 0.8) and failure (RR = 0.39, 95%CI: 0.19 to 0.78) rates in the anti-VEGF group than the placebo group. A non-significant reduction of the epithelial defect was also observed in the bevacizumab group compared with the placebo (RR = 0.56, 95%CI: 0.30 to 1.06). Compared with a placebo, the unsynthesizable trials also support that bevacizumab improves visual acuity, CoNV, graft rejection, and failure rates. Trials reporting other comparisons revealed the superiority of combined remedy with bevacizumab compared to other treatments in reducing CoNV., Conclusion: Anti-VEGF agents, mainly bevacizumab, are an effective and safe treatment for CoNV of all causes and prevent corneal graft rejection and failure in corneal transplantation., Competing Interests: Conflict-of-interest statement: All authors declared no competing interests, (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: This was a cross-sectional survey to evaluate the physical and emotional impact of wet age-related macular degeneration (wAMD) on a global cohort of patients who were receiving (or had previously received) antivascular endothelial growth factor injections, and caregivers (paid and unpaid). Methods: The survey was performed in nine countries using an ophthalmologist-devised questionnaire. Results: A total of 910 patients and 890 caregivers completed the questionnaire. Most patients had been diagnosed and receiving antivascular endothelial growth factor injections for more than 1 year (74.7% and 63.8%, respectively), and many patients (82.1%) received support from a caregiver (usually a child/grandchild [47.3%] or partner [23.3%]). wAMD had a negative impact on most patients (71.6%); many rated fear (44.9%), sadness (39.9%), frustration (37.3%), and depression (34.0%) as common. It was linked to physical consequences, such as difficulty in reading (61.1%). Many effects were significantly greater in patients with a longer duration of disease or with wAMD in both eyes. Some caregivers (unpaid) also reported that caregiving had a negative impact on them (31.1%); many reported emotions such as sadness (34.9%) and depression (24.4%), but many also felt useful (48.4%). Overall, 27.2% of caregivers (unpaid) rated caregiving as inconvenient; this was linked to days of employment/personal obligations missed. Conclusion: wAMD has a significant negative impact on the lives of patients, including vision-related depression, poor mobility, and limitations in day-to-day activities. The impact on nonprofessional caregivers may be underestimated in terms of emotional impact (such as depression) and loss of productivity. [ABSTRACT FROM AUTHOR]

The authors present a 36-year-old female with pulmonary tuberculosis who developed a choroidal tuberculoma in the left eye. The choroidal tuberculoma successfully resolved with visual gain following oral anti-tubercular and oral steroid therapy leaving behind a chorioretinal scar. One year after the completion of anti-tubercular treatment, she developed visual loss due to the development of a secondary choroidal neovascular membrane at the fovea. This was treated successfully with one intravitreal injection of bevacizumab in the left eye. The fovea remained free of fluid until the last follow-up 10 months after the intravitreal injection. Intravitreal bevacizumab may be an effective modality for treating secondary choroidal neovascular membranes that may form at the edge of a healed choroidal tuberculoma. [ABSTRACT FROM AUTHOR]

Anti-vascular endothelial growth factor (VEGF) currently used to treat eye diseases have included monoclonal antibodies, antibody fragments, and an aptamer. A different method of achieving VEGF blockade in retinal diseases includes the concept of a cytokine trap. Cytokine traps technology are being evaluated for the treatment of various diseases that are driven by excessive cytokine levels. Traps consist of two extracellular cytokine receptor domains fused together to form a human immunoglobulin G (IgG). Aflibercept/VEGF trap-eye (VTE) is a soluble fusion protein, which combines ligand-binding elements taken from the extracellular components of VEGF receptors 1 and 2 fused to the Fc portion of IgG. This protein contains all human amino acid sequences, which minimizes the potential for immunogenicity in human patients. This review presents the latest data on VTE in regard to the pharmacokinetics, dosage and safety, preclinical and clinical experiences. Method of the literature search: A systematic search of the literature was conducted on PubMed, Scopus, and Google Scholar with no limitation on language or year of publication databases. It was oriented to articles published for VTE in preclinical and clinical studies and was focused on the pharmacokinetics, dosage and safety of VTE. [ABSTRACT FROM AUTHOR]

What is known and objective Vascular endothelial growth factor ( VEGF) proteins are involved in the regulation of vascular endothelium, and their inhibition led to the development of a number of drugs used for malignancies or exudative neo-vascular age-related macular degeneration ( AMD). Case summary We report a case of ischemic stroke in an 87-year-old woman having received intravitreal aflibercept, a new anti- VEGF for AMD. She had been treated with ranibizumab since 2007. In 2013, ranibizumab was replaced with aflibercept, followed by a decrease in the International Normalized Ratio, complicated by a stroke a few days later. The rechallenge was positive. What is new and conclusion A potential time-dependent interaction between aflibercept and VKA antagonist and/or a direct effect of aflibercept may have contributed to the occurrence of the ischaemic stroke. Currently available data suggest some pharmacokinetic and pharmacodynamic effects of aflibercept by explaining its pro-thrombotic profile. [ABSTRACT FROM AUTHOR]

Although the exact pathogenetic mechanisms leading to age-related macular degeneration (AMD) have not been clearly identified, oxidative damage in the retina and choroid due to an imbalance between local oxidants/anti-oxidant systems leading to chronic inflammation could represent the trigger event. Different in vitro and in vivo models have demonstrated the involvement of reactive oxygen species generated in a highly oxidative environment in the development of drusen and retinal pigment epithelium (RPE) changes in the initial pathologic processes of AMD; moreover, recent evidence has highlighted the possible association of oxidative stress and neovascular AMD. Nitric oxide (NO), which is known to play a key role in retinal physiological processes and in the regulation of choroidal blood flow, under pathologic conditions could lead to RPE/photoreceptor degeneration due to the generation of peroxynitrite, a potentially cytotoxic tyrosine-nitrating molecule. Furthermore, the altered expression of the different isoforms of NO synthases could be involved in choroidal microvascular changes leading to neovascularization. The purpose of this review was to investigate the different pathways activated by oxidative/nitrosative stress in the pathogenesis of AMD, focusing on the mechanisms leading to neovascularization and on the possible protective role of anti-vascular endothelial growth factor agents in this context. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is the most common cause of visual loss among working age individuals. Diabetic macular edema (DME) is an important complication of DR that affects around one third of the patients with DR. Several treatments have been approved for DME ranging from blood pressure and glycemic control to photocoagulation and more recently the use of vascular endothelial growth factor (VEGF) antagonists. The index review discusses aflibercept (EYLEA(®)-Regeneron Pharmaceuticals, Inc., Tarrytown, New York, NY, and Bayer Healthcare Pharmaceuticals, Berlin, Germany) in the context of other VEGF antagonists currently available for the treatment of DME. A systematic search of literature was conducted on PubMed, Scopus, and Google Scholar with no limitation on language or year of publication. Pre-clinical studies of aflibercept have shown a higher affinity of this molecule for vascular endothelial growth factor A (VEGF-A) along with a longer duration of action as compared to other VEGF antagonists. Recent clinical trials have shown visual outcome results for aflibercept to be similarly favorable as compared to other available agents with the added benefit of fewer required injections and less frequent monitoring. Aflibercept presents a potential exciting new addition to the armamentarium of current VEGF antagonists available for the treatment of DME and other retinal vascular diseases. However, further studies are indicated to confirm the role, safety, and efficacy of aflibercept for DME.