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Keywords = intravitreal ranibizumab

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14 pages, 1118 KB  
Article
Systemic Immune and miRNA Signatures Associated with Long-Term Ranibizumab Response in Neovascular Age-Related Macular Degeneration
by Laura García-Quintanilla, Pablo Almuiña-Varela, María José Rodríguez-Cid, María Gil-Martinez, Maximino J. Abraldes, Francisco Gomez-Ulla, Miguel González-Barcia, Diana Carolina Castro-Fernández, Antonio Cañizo-Outeiriño, Andrea Cuartero-Martínez, Ana Estany-Gestal, Francisco J. Otero-Espinar, Maribel Fernández-Rodríguez and Anxo Fernández-Ferreiro
Pharmaceuticals 2026, 19(6), 955; https://doi.org/10.3390/ph19060955 - 19 Jun 2026
Viewed by 388
Abstract
Objectives: To characterize the one-year functional, anatomical, and molecular responses to intravitreal Ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), and to identify systemic immune and miRNA signatures associated with treatment response. Methods: This prospective longitudinal observational study included [...] Read more.
Objectives: To characterize the one-year functional, anatomical, and molecular responses to intravitreal Ranibizumab in treatment-naïve patients with neovascular age-related macular degeneration (nAMD), and to identify systemic immune and miRNA signatures associated with treatment response. Methods: This prospective longitudinal observational study included 44 treatment-naïve patients with nAMD. Patients received up to four monthly intravitreal Ranibizumab injections, followed by a treat-and-extend regimen. Best-corrected visual acuity using ETDRS letters, central retinal thickness by optical coherence tomography, fluorescein angiography, and OCT angiography were assessed at baseline and 12 months. Peripheral blood samples were collected at both time points to quantify seven circulating cytokines using an IMMULITE chemiluminescent immunoassay and to profile 37 candidate miRNAs by TaqMan OpenArray RT-qPCR from leukocyte-derived RNA. Treatment response was classified using composite anatomical and functional criteria, including intraretinal/subretinal fluid resolution, ≥25% central retinal thickness reduction, and a ≥5 ETDRS letter gain. Results: At one year, patients showed significant central retinal thickness reduction and overall visual stabilization, although good and poor responders differed according to composite response criteria. Statin use was numerically more frequent among poor responders, although this difference was not statistically significant. Soluble IL-2R increased significantly over time in the overall cohort, mainly driven by good responders who showed higher median levels at both visits. IL-8 also increased globally, without significant between-group differences. Among differentially expressed miRNAs, miR-3121 was the only candidate reaching statistical significance and was downregulated in good responders. ROC analysis showed moderate discriminative performance for miR-3121, with an AUC of 0.76. Conclusions: One-year response to Ranibizumab in nAMD may involve systemic immune activation and miRNA regulation. miR-3121 emerges as a candidate biomarker of treatment response, supporting further validation in larger independent cohorts. Full article
(This article belongs to the Section Biopharmaceuticals)
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13 pages, 1043 KB  
Article
Involvement of Oxidative Stress-Related Inflammatory Mediators in the Pathogenesis and Treatment Response of Macular Edema Secondary to Branch Retinal Vein Occlusion
by Takuto Yamamoto, Hidetaka Noma, Tatsuya Mimura, Shotaro Sasaki, Taro Otawa, Kanako Yasuda and Masahiko Shimura
Antioxidants 2026, 15(5), 607; https://doi.org/10.3390/antiox15050607 - 11 May 2026
Viewed by 456
Abstract
Background: Branch retinal vein occlusion (BRVO) represents a segmental retinal ischemic disorder characterized by localized oxidative–inflammatory activation. While redox-driven cytokine responses have been described in central retinal vein occlusion, their role in BRVO-specific macular edema and treatment responsiveness remains unclear. This study [...] Read more.
Background: Branch retinal vein occlusion (BRVO) represents a segmental retinal ischemic disorder characterized by localized oxidative–inflammatory activation. While redox-driven cytokine responses have been described in central retinal vein occlusion, their role in BRVO-specific macular edema and treatment responsiveness remains unclear. This study investigated whether novel redox-related inflammatory mediators in the aqueous humor are associated with disease severity and structural response to anti-vascular endothelial growth factor (VEGF) therapy in BRVO. Methods: Aqueous humor samples were collected from 30 treatment-naïve patients with BRVO and 19 control patients. Levels of VEGF and the novel redox-related inflammatory factors FMS-related tyrosine kinase 3 ligand (Flt-3L), fractalkine, CXCL-16, and endocan-1 were measured by suspension array, and the severity of macular edema was evaluated by measuring central macular thickness and neurosensory retinal thickness (TNeuro) by spectral-domain optical coherence tomography. Therapeutic response was assessed one month after intravitreal ranibizumab injection (IRI). Results: Aqueous levels of VEGF, Flt-3L, and endocan-1 were significantly higher in the BRVO group, and levels of Flt-3L, CXCL-16, and endocan-1—markers associated with oxidative endothelial damage and leukocyte recruitment—correlated significantly with each other and with aqueous flare values. Notably, baseline Flt-3L levels significantly correlated with the reduction in TNeuro, suggesting that this redox-sensitive signaling molecule is a potential biomarker for treatment sensitivity. Conclusions: These findings suggest that novel inflammatory factors, potentially driven by oxidative-nitrosative stress, play a pivotal role in the pathophysiology of BRVO. Baseline Flt-3L may serve as a predictive biomarker for structural responsiveness to anti-VEGF therapy in BRVO, suggesting that oxidative–inflammatory signaling contributes not only to disease severity but also to therapeutic heterogeneity. Full article
(This article belongs to the Special Issue Redox Regulation of Immune and Inflammatory Responses)
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12 pages, 517 KB  
Article
Real-World Comparison of Biosimilar Ranibizumab (Ranieyes) and Innovator Ranibizumab (Lucentis/Accentrix) Across Multiple Retinal Vascular Diseases (The BRIO Study)
by Debdulal Chakraborty, Tushar Kanti Sinha, Sourav Sinha, Rupak Kanti Biswas, Arnab Das, Aniruddha Maiti, Ranabir Bhattacharya, Shouvick Dan, Dinesh Rungta and Shibashis Das
Pharmaceuticals 2026, 19(5), 747; https://doi.org/10.3390/ph19050747 - 11 May 2026
Viewed by 656
Abstract
Background: Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV), often require repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Although ranibizumab is well established, long-term affordability remains challenging. Objective: [...] Read more.
Background: Retinal vascular diseases, including neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), retinal vein occlusion (RVO), and myopic choroidal neovascularization (mCNV), often require repeated intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy. Although ranibizumab is well established, long-term affordability remains challenging. Objective: To compare the functional, anatomical, treatment-burden, and safety outcomes of biosimilar ranibizumab (Ranieyes) and innovator ranibizumab (Lucentis/Accentrix) in routine clinical practice. Methods: This multicenter retrospective comparative study included 4997 eyes from 3577 patients treated across five tertiary eye-care centers in India. The biosimilar group comprised 2543 eyes from 1812 patients (10,893 injections), and the innovator group comprised 2454 eyes from 1765 patients (10,136 injections). Eligible indications were nAMD, DME, BRVO, CRVO, mCNV, and an exploratory miscellaneous preoperative adjunct subgroup. BCVA (logMAR), central subfield thickness (CST; µm), injection burden, and ocular/systemic adverse events were assessed over 24 months. Results: Both groups showed early improvement in BCVA and CST across the major disease categories, followed by long-term stabilization. Between-group differences were generally small, not sustained over follow-up, and of limited clinical magnitude. Serious ocular and systemic adverse events were rare in both groups, and no new safety signal emerged. Conclusions: In this large real-world cohort, the biosimilar ranibizumab Ranieyes showed outcomes broadly comparable to innovator ranibizumab across the major retinal disease subgroups, although these findings should be interpreted as observational comparative evidence rather than formal proof of equivalence. Full article
(This article belongs to the Section Biopharmaceuticals)
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11 pages, 245 KB  
Article
Impact of Vascular Risk Factors on Longitudinal Changes in Diabetic Macular Edema After Intravitreal Therapy
by Carmen Alba-Linero, José Coín Ruiz, Marta Mérida Luque, Javier Espíldora-Hernández and Mario Gutiérrez Bedmar
Diabetology 2026, 7(4), 65; https://doi.org/10.3390/diabetology7040065 - 1 Apr 2026
Viewed by 787
Abstract
Objectives: The aim of this study was to analyze the association between cardiovascular risk factors such as glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), hypertension, overweight, and smoking and longitudinal anatomical and functional changes in diabetic macular edema (DME) during intravitreal therapy. Materials [...] Read more.
Objectives: The aim of this study was to analyze the association between cardiovascular risk factors such as glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), hypertension, overweight, and smoking and longitudinal anatomical and functional changes in diabetic macular edema (DME) during intravitreal therapy. Materials and Methods: This is a retrospective, observational, descriptive study conducted on a sample of 318 patients with DME associated with some degree of diabetic retinopathy (DR). They were treated with aflibercept, ranibizumab, and/or dexamethasone, assessing anatomical and functional outcomes through visual acuity, retinal thickness, and macular volume. Simultaneously, serum HbA1c and LDL-C levels, blood pressure, body mass index (BMI) and tobacco use were measured at baseline, 6, and 12 months to determine their association with treatment response using linear mixed models. Results: Of the variables analyzed in this study, HbA1c and degree of retinopathy were significantly associated with greater retinal thickness over time. Likewise, we found that, compared with aflibercept, dexamethasone intravitreal treatment was associated with greater retinal thickness over time. Concerning visual acuity, we found an inverse relationship with age, tobacco use and degree of retinopathy. Associations between outcomes and the initial intravitreal agent were observed; however, these findings should be interpreted cautiously. Conclusions: This study was consistent with previous research suggesting an association between glycemic control and DME response and progression. It also highlighted the importance of degree of retinopathy and intravitreal treatment in diabetic macular edema progression. Treatment-related findings represent exploratory associations and should not be interpreted as evidence of comparative effectiveness. Full article
11 pages, 1514 KB  
Article
Use of Aflibercept to Treat Retinopathy of Prematurity in Children with Extremely Low Birth Weight
by Maria Szwajkowska, Beata Jaroszewska-Świątek and Małgorzata Woś
J. Clin. Med. 2026, 15(5), 1912; https://doi.org/10.3390/jcm15051912 - 3 Mar 2026
Viewed by 626
Abstract
Background: Aflibercept is one of the anti-VEGF drugs used, among others, for the treatment of retinopathy of prematurity, alongside the widely used bevacizuab and ranibizumab. It is a recombinant fusion protein composed of the human VEGFR-1 and VEGFR-2 domains combined with the Fc [...] Read more.
Background: Aflibercept is one of the anti-VEGF drugs used, among others, for the treatment of retinopathy of prematurity, alongside the widely used bevacizuab and ranibizumab. It is a recombinant fusion protein composed of the human VEGFR-1 and VEGFR-2 domains combined with the Fc part of human IgG, called VEGF-TRAP. The paper describes a group of premature infants treated with aflibercept due to retinopathy of prematurity at the Regional Specialized Children’s Hospital in Olsztyn, Poland, in the years 2017–2019. Methods: Eleven children (22 eyes) with extremely low birth weight and type 1 ROP and A-ROP qualified for treatment. The birth weight of the children was 460–940 g (average 677 g). Children were treated between 32 and 38 weeks of postconceptional age (on average in 33.3 week). We administered 1 mg (0.025 mL) of aflibercept intravitreal to each eye under local anesthesia. Results: In all cases, the retinopathy regressed. Between 2 and 7 weeks after treatment, the disease reactivated in five children (45%) in the form of ROP type 2, and these children underwent retinal laser photocoagulation. One child had a complication in the form of a cataract in one eye, while the remaining children had no complications after the injection and laser therapy. In all children, there was complete regression of ROP, and retinal vascularization was observed up to the end of zone III or up to the border of laser therapy. A child with cataract underwent lensectomy. All children are under the care of our center, and were examined ophthalmologically and strabologically; the results of these tests will be presented in a separate study. Conclusions: Aflibercept differs from other anti-VEGF drugs in its point of action and pharmacodynamics of action. In the literature, its effectiveness is estimated at over 80%, but there are also studies in which the reactivation of ROP after treatment reaches over 40%. In this study, the treated children were characterized by extremely low birth weight and, as a result, numerous complications related to prematurity occurred, such as bronchopulmonary dysplasia, sepsis, anemia, heart defects, and others. Many of them were in the intensive care unit. These factors may influence ROP reactivation and complications. The description compares studies in which aflibercept was administered at the same dose—1 mg. Currently, large studies (e.g., Firefleye and Butterfleye) describe the effects of a new aflibercept therapy at a dose of 0.4 mg. Studies on aflibercept obviously require further observations, so all reports, even from small groups, are important. Full article
(This article belongs to the Section Clinical Pediatrics)
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11 pages, 217 KB  
Article
The Effect of Intravitreal Ranibizumab Injection on Retinal Nerve Fiber Layer Thickness and Optic Disc Parameters
by Gülin Tuğba Ongun and Ramazan Yağcı
J. Clin. Med. 2026, 15(2), 449; https://doi.org/10.3390/jcm15020449 - 7 Jan 2026
Viewed by 905
Abstract
Objectives: To evaluate the effects of intravitreal ranibizumab on retinal nerve fiber layer (RNFL) thickness and optic disc parameters in patients treated for exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Methods: This retrospective study analyzed the [...] Read more.
Objectives: To evaluate the effects of intravitreal ranibizumab on retinal nerve fiber layer (RNFL) thickness and optic disc parameters in patients treated for exudative age-related macular degeneration (AMD), diabetic macular edema (DME), and retinal vein occlusion (RVO). Methods: This retrospective study analyzed the clinical records of 60 patients who received intravitreal ranibizumab injections for macular edema secondary to AMD, DME, or RVO between October 2014 and January 2016. All patients received intravitreal ranibizumab at a dose of 0.5 mg. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were recorded at baseline and during follow-up. RNFL thickness and optic disc parameters were assessed using optical coherence tomography (OCT) and Heidelberg Retina Tomograph III (HRT-3). Measurements were obtained before treatment and at 1 week, 1 month, 3 months, and 6 months after injection. Comparisons were performed within and between disease groups. Results: Of the 60 patients, 31 (51.7%) had DME, 20 (33.3%) had AMD, and 9 (15.0%) had RVO. Best-corrected visual acuity improved significantly during the follow-up period. Mean RNFL thickness measured by OCT showed a significant reduction in the DME and RVO groups (p = 0.0001 and p = 0.043, respectively). In contrast, no significant changes in RNFL thickness were detected using HRT-3, and no consistent alterations in other optic disc parameters were observed. Changes in optic disc parameters varied among disease groups. Conclusions: Intravitreal ranibizumab treatment was associated with a reduction in mean RNFL thickness measured by OCT in patients with DME and RVO during a six-month follow-up period, whereas no corresponding RNFL thinning was detected using HRT-3 in any disease group. The observed optic disc parameter changes appeared to be disease specific. Given the absence of untreated control eyes and the exclusion of patients with glaucoma, these findings apply only to non-glaucomatous eyes and should not be extrapolated to patients with glaucoma. Further prospective studies with larger cohorts, appropriate control groups, and longer follow-up durations are warranted to clarify the long-term effects of anti-VEGF therapy on the optic nerve. Full article
(This article belongs to the Section Ophthalmology)
11 pages, 1358 KB  
Article
Short-Term Effects of Intravitreal Ranibizumab Biosimilar Injections in Patients with Neovascular Age-Related Macular Degeneration on Retinal Nerve Fiber Layer Thickness
by Seung Yeon Lee and Daniel Duck-Jin Hwang
J. Clin. Med. 2025, 14(22), 8225; https://doi.org/10.3390/jcm14228225 - 20 Nov 2025
Cited by 1 | Viewed by 817
Abstract
Background/Objectives: Intravitreal anti–vascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration (nAMD), but concerns remain regarding its potential effects on optic nerve structure. Evidence on the structural safety of ranibizumab biosimilars, including LucenBS®, is still [...] Read more.
Background/Objectives: Intravitreal anti–vascular endothelial growth factor (anti-VEGF) therapy is the standard treatment for neovascular age-related macular degeneration (nAMD), but concerns remain regarding its potential effects on optic nerve structure. Evidence on the structural safety of ranibizumab biosimilars, including LucenBS®, is still limited. This study aimed to investigate the short-term effects of intravitreal LucenBS® injections on peripapillary retinal nerve fiber layer (RNFL) thickness in previously treated nAMD patients using optical coherence tomography (OCT). Methods: This retrospective, observational case series included 24 eyes from 24 nAMD patients who had previously received anti-VEGF agents other than ranibizumab biosimilar. In bilateral cases, the eye that developed nAMD earlier was selected. Patients received between one and three LucenBS® injections, and the mean follow-up period after the final injection was 11.92 ± 4.81 weeks. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), central macular thickness (CMT), and peripapillary RNFL thickness were assessed before and after each injection using spectral-domain OCT. Sectoral and global RNFL values were compared using the Wilcoxon signed-rank test. Results: The mean age of participants was 74.6 ± 9.0 years, and baseline BCVA and IOP were 0.83 ± 0.66 logMAR and 14.88 ± 2.80 mmHg, respectively. RNFL thickness showed no significant changes in either global or sectoral regions after any injection (all p > 0.05). CMT significantly decreased after the first injection (p = 0.007), but remained stable with subsequent treatments. BCVA remained stable after the first and second injections, but slightly worsened after the third injection (p = 0.012). IOP showed no significant changes at any time point. Conclusions: Short-term intravitreal LucenBS® injections did not induce structural alterations in the peripapillary RNFL, supporting their short-term ocular safety in previously treated nAMD patients. Although CMT improved after the first injection, functional and anatomical responses varied with repeated dosing. Larger, long-term studies are required to further validate the structural and functional safety of ranibizumab biosimilars in nAMD management. Full article
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19 pages, 899 KB  
Article
Evaluation of the Duration of Good Visual Acuity During Anti-VEGF Therapy for Age-Related Macular Degeneration in Routine Clinical Practice
by Andrea Gyenes, Lilla István, András Papp, Miklós Resch, Zsuzsa Récsán, Mónika Ecsedy, Zsuzsanna Szepessy, Antal Szabó, Balázs Lesch, György Barcsay, Ágnes Borbándy, Gábor László Sándor, Zoltán Z. Nagy and Illés Kovács
Int. J. Mol. Sci. 2025, 26(22), 10927; https://doi.org/10.3390/ijms262210927 - 11 Nov 2025
Cited by 1 | Viewed by 1926
Abstract
The aim of this study was to analyse data from a clinical database using a novel visual acuity parameter to determine whether anti-VEGF molecules that target multiple domains involved in neovascularisation are more likely to achieve good visual acuity than agents that solely [...] Read more.
The aim of this study was to analyse data from a clinical database using a novel visual acuity parameter to determine whether anti-VEGF molecules that target multiple domains involved in neovascularisation are more likely to achieve good visual acuity than agents that solely inhibit VEGF. This retrospective study analysed data from patients treated with anti-VEGF injections between 2015 and 2023. We set an ETDRS score threshold of 70 (equivalent to 20/40 Snellen acuity) to calculate ‘time in range’ (TIR). TIR is defined as ‘time spent with best-corrected visual acuity (BCVA) better than 20/40’ and can highlight significant variations in the time individuals spend above the threshold during their AMD treatment. Over nine years, 30,209 aflibercept and 10,876 ranibizumab injections were administered to 6043 patients. Patients received an average of 6.8 injections. The mean BCVA at the first injection was 57.00 ± 16.15 ETDRS letters for ranibizumab patients and 58.75 ± 15.82 for aflibercept patients, with a statistically significant difference (p < 0.001). Both groups showed significant improvement in visual acuity at follow-up (aflibercept: 60.21 ± 15.53; ranibizumab: 59.43 ± 15.81; both p < 0.001). The mean time between the two consecutive injections, including both the initial loading phase and the subsequent maintenance phase, was 67.22 ± 34.08 days for ranibizumab and 72.15 ± 31.00 days for aflibercept; the difference was statistically significant (p < 0.001). After controlling for the effect of initial BCVA and time between injections, patients who received aflibercept had a significantly higher average TIR (60.90 ± 36.27 days vs. 56.55 ± 38.78 days, p < 0.001), and significantly more likely to achieve >70 letters at the next visit (OR: 1.10; 95% CI: 1.05–1.15; p < 0.001) compared to patients receiving ranibizumab. Aflibercept treatment improves the likelihood of maintaining good BCVA by 10% compared to ranibizumab in patients receiving intravitreal anti-VEGF treatment for nAMD. Furthermore, the beneficial effects of aflibercept treatment are observed with less frequent dosing. Our results suggest that using anti-VEGF compounds that target multiple domains provides a detectable advantage in treating age-related macular degeneration, particularly when these agents have a longer duration of action. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Treatment of Retinal Diseases)
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12 pages, 4400 KB  
Article
A Pilot Study on Structural Changes of Choroidal Vasculature Following Intravitreal Anti-VEGF Injection in Neovascular Age-Related Macular Degeneration: Faricimab vs Ranibizumab
by Takeyuki Nishiyama, Hiromasa Hirai, Kimie Miyata, Tomo Nishi, Tetsuo Ueda and Satoru Kase
J. Clin. Med. 2025, 14(20), 7257; https://doi.org/10.3390/jcm14207257 - 14 Oct 2025
Cited by 2 | Viewed by 1807
Abstract
Objectives: This paper aims to explore optical coherence tomography (OCT)-based choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents, faricimab and ranibizumab, in a pilot study. Methods: This retrospective pilot cohort [...] Read more.
Objectives: This paper aims to explore optical coherence tomography (OCT)-based choroidal vascular changes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial growth factor (VEGF) agents, faricimab and ranibizumab, in a pilot study. Methods: This retrospective pilot cohort study enrolled 28 treatment-naïve nAMD patients who received three consecutive intravitreal anti-VEGF injections at Nara Medical University Hospital. In total, 17 patients (61%) were Type 1 MNV and 11 patients (39%) were Type 2 MNV. Patients were divided into a faricimab group (13 eyes) and a ranibizumab group (15 eyes). The type of macular neovascularization (MNV) and the presence of polyps were recorded. The central choroidal thickness (CCT) and the ratio of luminal area to choroidal area (L/C ratio), derived from binarized OCT images, were measured at baseline after the first and third injections. Results: Type 1 MNV was observed in 61% of eyes, with polyps confirmed in 53%. There was no significant difference in best corrected visual acuity (BCVA) for both faricimab and ranibizumab during treatment (p = 0.12, 0.94, respectively). After the third injection, a dry macula was achieved in 62% of the faricimab group and 60% of the ranibizumab group. In the ranibizumab group, CCT significantly decreased after the first injection, while no significant change was observed in the faricimab group. Conversely, the L/C ratio significantly decreased in the faricimab group after the third injection (p = 0.010). Among faricimab-treated eyes, those with type 1 MNV showed a significantly greater reduction in the L/C ratio compared to type 2 MNV (p = 0.017). Conclusions: This pilot study suggests that faricimab may exert combined anti-VEGF and Ang-2 effects predominantly on type 1 MNV, potentially leading to vascular constriction. These exploratory findings warrant confirmation in larger studies. Full article
(This article belongs to the Special Issue An Update on Retinal Diseases: From Diagnosis to Treatment)
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11 pages, 2135 KB  
Article
Hyperreflective Dots on SD-OCT: Implications for Predicting Treatment Outcomes in Diabetic Macular Edema
by Siying Li, Muzi Li, Aimin Sun and Hongwei Zhang
Diagnostics 2025, 15(19), 2539; https://doi.org/10.3390/diagnostics15192539 - 9 Oct 2025
Cited by 2 | Viewed by 1761
Abstract
Objectives: To evaluate the relationship between hyperreflective dots (HRDs) observed on spectral-domain optical coherence tomography (SD-OCT) and the outcomes following treatment with intravitreal ranibizumab or dexamethasone injections in patients with diabetic macular edema (DME). Methods: This retrospective study focused on individuals suffering from [...] Read more.
Objectives: To evaluate the relationship between hyperreflective dots (HRDs) observed on spectral-domain optical coherence tomography (SD-OCT) and the outcomes following treatment with intravitreal ranibizumab or dexamethasone injections in patients with diabetic macular edema (DME). Methods: This retrospective study focused on individuals suffering from diabetic macular edema (DME) who underwent a sequence of three intravitreal ranibizumab injections. Based on treatment response, the eyes were categorized into two groups: responders and non-responders. The non-responder group subsequently received intravitreal dexamethasone (IVO) implants. Treatment results were evaluated by changes in BCVA, HRD number, and central macular thickness (CMT). Results: This research involved 112 eyes from 78 participants who had been diagnosed with DME. Seventy-three eyes (65%) were identified as ranibizumab responders and 39 eyes (35%) as ranibizumab non-responders. Of the 39 individuals who had suboptimal response to ranibizumab and subsequently received treatment with an intravitreal dexamethasone implant, 26 eyes (66.67%) exhibited a favorable response, while 13 eyes (33.33%) showed an insufficient response. IVR responders demonstrated significantly greater improvements in BCVA (0.54 ± 0.73 to 0.35 ± 0.40 logMAR vs. 0.52 ± 0.61 to 0.47 ± 0.38 logMAR) and CMT (456.53 ± 109.73 μm to 235.47 ± 49.13 μm vs. 468.99 ± 127.10 μm to 427.45 ± 52.91 μm) reduction. Baseline analysis revealed IVR non-responders had higher counts of both inner and outer retinal HRDs compared to responders (9.09 ± 3.38 vs. 7.07 ± 2.32 and 5.46 ± 2.03 vs. 4.27 ± 1.87, p < 0.05, respectively). Eyes with initially higher numbers of inner retinal HRDs, outer retinal HRDs, and subretinal HRDs demonstrated a significantly enhanced response to dexamethasone therapy (9.03 ± 3.18 vs. 7.55 ± 2.72, 6.55 ± 2.46 vs. 4.79 ± 1.88 and 0.27 ± 0.54 vs. 0.21 ± 0.47, p < 0.05, respectively). Conclusions: HRDs could potentially be used as a predictive biomarker to assess the effectiveness of anti-VEGF therapy in treating DME. Patients exhibiting a greater number of retinal HRDs tend to have less favorable reactions to anti-VEGF treatments but experience improved results with dexamethasone. Full article
(This article belongs to the Special Issue Imaging Biomarkers for Pachychoroid Spectrum Disease)
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39 pages, 8071 KB  
Article
Re-Evaluating the Treatment Plan for Diabetic Macular Edema Based on Early Identification of Response and Possible Biochemical Predictors of Non-Response After the First Intravitreal Ranibizumab Injection
by Sameh Mohamed Elgouhary, Noha Rabie Bayomy, Mohamed Khaled Elfarash, Sara Zakaria Aboali, Sara Abdelmageed Barakat, Mona Abdelhamid Elnaggar and Noha Khirat Gaber
Biomedicines 2025, 13(10), 2438; https://doi.org/10.3390/biomedicines13102438 - 7 Oct 2025
Viewed by 1586
Abstract
Background: This study aimed to change the current concept of diabetic macular edema (DME) management through (1) early categorization of our DME patients into either responders or non-responders after the first intravitreal Ranibizumab (IVR) injection, and (2) finding a suitable clinical–biochemical diagnostic [...] Read more.
Background: This study aimed to change the current concept of diabetic macular edema (DME) management through (1) early categorization of our DME patients into either responders or non-responders after the first intravitreal Ranibizumab (IVR) injection, and (2) finding a suitable clinical–biochemical diagnostic panel to identify the possible cause(s) of non-response in each non-responder and changing the treatment plan in each particular patient accordingly. Patients and methods: Our study included 64 eyes of 40 patients with DME (Group A, DME patients) and 40 eyes of 40 healthy individuals matched for age and sex (Group B, controls). Blood and aqueous samples were collected from the study participants before and one month after IVR injection. The DME patients were further subdivided into responders and non-responders according to their response to the first IVR injection. Lymphocyte activation markers, NETosis markers, angiogenic factors, astrocytes, innate immunity, and inflammasome markers were assessed in both groups. Results: Multivariate regression analysis revealed that macular ischemia, aqueous levels of hexokinase 1, SELL CD62L, ELANE, MPO, VEGFA, and SEMA4D were the most significant factors affecting the response to IVR (p < 0.05). Conclusions: defining our DME patients as responders and non-responders after the first IVR injection, combined with potential utilization of a clinical–biochemical panel (macular ischemia- PCR array of combined Hexokinase 1, MPO, and SEMA4D) in each non-responder, may represent a good starting point for changing the current DME management strategy. Full article
(This article belongs to the Section Molecular and Translational Medicine)
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11 pages, 3101 KB  
Case Report
Macular Neovascularization in Pediatric Patients with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency: A Retrospective Analysis of a Case Series
by Magdalena Hubert, Maciej Gawęcki and Andrzej Grzybowski
J. Clin. Med. 2025, 14(17), 6062; https://doi.org/10.3390/jcm14176062 - 27 Aug 2025
Cited by 1 | Viewed by 1013
Abstract
Background: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare autosomal recessive metabolic disorder affecting long-chain fatty acid β-oxidation. A hallmark feature of LCHADD is progressive chorioretinopathy, which may lead to severe visual complications, including macular neovascularization (MNV). The goal of the study was [...] Read more.
Background: Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) is a rare autosomal recessive metabolic disorder affecting long-chain fatty acid β-oxidation. A hallmark feature of LCHADD is progressive chorioretinopathy, which may lead to severe visual complications, including macular neovascularization (MNV). The goal of the study was to analyze MNV in patients with genetically confirmed LCHADD. Methods: Data of 8 patients with LCHADD from the Kaszubia region in Poland followed in the clinic were retrospectively analyzed. The analyses included genetic confirmation, ophthalmologic examinations, spectral-domain optical coherence tomography (SD-OCT), and treatment responses. Results: Two patients with MNV in the course of LCHADD were identified. In Patient 1, a 9-year-old female, unilateral MNV at the fibrotic stage with a visual acuity of counting fingers was diagnosed in the right eye. No treatment was administered. The left eye remained stable, maintaining a best corrected visual acuity (BCVA) of 0.9 on the decimal Snellen chart. Patient 2, male, was followed from age 8 to 16 and during that time developed bilateral MNV. The right eye presented with inactive MNV at the age of 9, resulting in BCVA reduction to 0.3 without active fluid, and remained stable without intervention. The left eye developed active MNV at age 15 with subretinal fluid and retinal edema. Treatment with five intravitreal injections of ranibizumab led to complete resolution and recovery of BCVA to 1.0. Conclusions: MNV, although rare, can develop in pediatric LCHADD patients silently and bilaterally. Early detection through regular ophthalmologic screening is crucial, as timely anti-VEGF treatment can preserve or restore vision. Delayed diagnosis may result in irreversible damage and limited therapeutic benefit. Full article
(This article belongs to the Section Ophthalmology)
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13 pages, 1280 KB  
Article
Seven-Year Outcomes of Aflibercept in Neovascular Age-Related Macular Degeneration in a Teaching Hospital Setting
by Antoine Barloy, Florent Boulanger, Benjamin Jany and Thi Ha Chau Tran
J. Clin. Transl. Ophthalmol. 2025, 3(3), 14; https://doi.org/10.3390/jcto3030014 - 30 Jul 2025
Viewed by 1567
Abstract
Background: In clinical practice, visual outcomes with anti-VEGF therapy may be worse than those observed in clinical trials. In this study, we aim to investigate the long-term outcomes of neovascularization treated with intravitreal aflibercept injections (IAI) in a teaching hospital setting. Methods: This [...] Read more.
Background: In clinical practice, visual outcomes with anti-VEGF therapy may be worse than those observed in clinical trials. In this study, we aim to investigate the long-term outcomes of neovascularization treated with intravitreal aflibercept injections (IAI) in a teaching hospital setting. Methods: This is a retrospective, single-center study including 81 nAMD patients (116 eyes), those both newly diagnosed and switched from ranibizumab. All patients had a follow-up duration of at least seven years. Treatment involved three monthly injections followed by either a pro re nata (PRN) or treat and extend regimen. Follow-up care was primarily conducted by training physicians. The primary endpoint was the change in best-corrected visual acuity (BCVA) over seven years. Secondary endpoints included central retinal thickness changes, qualitative OCT parameters, macular atrophy progression, injection frequency, and treatment adherence. Results: Among the 116 eyes, 52 (44.8%) completed the seven-year follow-up. Visual acuity improved by +2.1 letters in the overall population (+6.3 letters in treatment-naive eyes) after the loading phase but gradually declined, resulting in a loss of −12.3 letters at seven years. BCVA remained stable (a loss of fewer than 15 letters) in 57.7% of eyes. Central retinal thickness (CRT) decreased significantly during follow-up in both naive and switcher eyes. Macular atrophy occurred in 94.2% of eyes, progressing from 1.42 mm2 to 8.55 mm2 over seven years (p < 0.001). The mean number of injections was 4.1 ± 1.8 during the first year and 3.7 per year thereafter. Advanced age at diagnosis was a risk factor for loss to follow-up, with bilaterality being a protective factor against loss to follow-up (p < 0.05). Conclusions: This study highlights the challenges faced by a retina clinic in a teaching hospital. Suboptimal functional and anatomical outcomes in real life may derive from insufficient patient information and inconsistent monitoring, which contributes to undertreatment and affects long-term visual outcomes. It also raises concerns about supervision in a teaching hospital which needs to be improved. Full article
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12 pages, 985 KB  
Article
Immediate and Short-Term Intraocular Pressure Changes Following Intravitreal Injection and Associated Factors
by Manabu Yamamoto, Kumiko Hirayama, Akika Kyo, Gen Kinari, Yuki Kojima, Takeya Kohno and Shigeru Honda
J. Clin. Med. 2025, 14(14), 4821; https://doi.org/10.3390/jcm14144821 - 8 Jul 2025
Cited by 6 | Viewed by 3596
Abstract
Objectives: To evaluate the immediate and short-term changes in intraocular pressure (IOP) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents and to identify the clinical and procedural factors associated with IOP elevation after treatment. Methods: This retrospective study [...] Read more.
Objectives: To evaluate the immediate and short-term changes in intraocular pressure (IOP) following intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) agents and to identify the clinical and procedural factors associated with IOP elevation after treatment. Methods: This retrospective study included 118 eyes from 115 patients who underwent IVI with anti-VEGF agents at Osaka Metropolitan University Hospital between September 2024 and January 2025. IOP was measured at three time points, namely before injection, within 1 min after injection, and at 30 min, in selected eyes with a post-injection IOP ≥ 25 mmHg. Differences in IOP elevation were analyzed according to the disease type and anti-VEGF agent. Univariate and multivariate linear regression analyses were performed to identify clinical factors associated with IOP elevation. Results: Mean IOP significantly increased from 13.9 ± 3.3 mmHg at baseline to 39.2 ± 12.4 mmHg immediately after injection (p < 0.001), with 79.7% of eyes showing an IOP ≥ 25 mmHg. Among those remeasured, IOP decreased to 17.7 ± 6.5 mmHg at 30 min. Significant differences in IOP elevation were observed among anti-VEGF agents (p < 0.001), with aflibercept at 2 mg and 8 mg showing greater increases than other agents. Multivariate analysis identified higher baseline IOP, history of glaucoma, absence of prior vitrectomy, and use of aflibercept (2 mg or 8 mg) as significant risk factors for greater post-injection IOP elevation. Conclusions: Transient IOP elevation ≥ 25 mmHg was observed in the majority of eyes after IVI but typically resolved within 30 min. Aflibercept use, high baseline IOP, glaucoma history, and absence of prior vitrectomy were associated with greater IOP elevation. Careful monitoring and attention to injection volume may be warranted, particularly in high-risk patients. Full article
(This article belongs to the Special Issue An Update on Retinal Diseases: From Diagnosis to Treatment)
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22 pages, 5475 KB  
Article
Planned vs. Performed Treatment Regimens in Diabetic Macular Edema: Real-World Evidence from the PACIFIC Study
by Christos Haritoglou, Matthias Iwersen, Bettina Müller, Erik Beeke, Hüsnü Berk, Matthias Grüb, Katrin Lorenz, Martin Scheffler and Focke Ziemssen
J. Clin. Med. 2025, 14(9), 3120; https://doi.org/10.3390/jcm14093120 - 30 Apr 2025
Cited by 1 | Viewed by 1834
Abstract
Background: Intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors are standard for diabetic macular edema (DME), yet a gap exists between clinical guidelines and actual practices. This study aimed to investigate the extent of deviation between physician-planned and actually performed treatment regimens. [...] Read more.
Background: Intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors are standard for diabetic macular edema (DME), yet a gap exists between clinical guidelines and actual practices. This study aimed to investigate the extent of deviation between physician-planned and actually performed treatment regimens. Methods: The PACIFIC study (NCT04847895) was a prospective, multicenter, non-interventional study conducted in Germany, the Netherlands, and Switzerland. A total of 910 patients with DME receiving ranibizumab were enrolled. Physicians documented the intended treatment regimen at baseline, and actual treatment patterns were retrospectively derived from the timing of visits and injections over a 24-month observation period. Results: Although most physicians initially planned fixed or pro re nata (PRN) regimens, 77% of pretreated and 73% of treatment-naïve patients ultimately followed a monitor and extend strategy. Treatment discontinuation was frequent (58.8% and 59.4%, respectively), and injection frequencies remained below recommended levels, although central retinal thickness improved over time. Conclusions: The study highlights a consistent and clinically relevant discrepancy between planned and actual treatment delivery in DME care, underscoring the need for better adherence to guideline-informed strategies in routine practice. Full article
(This article belongs to the Special Issue Diabetic Retinopathy: Current Concepts and Future Directions)
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