anti-VEGF Therapy Research Articles

Comparison of pigment epithelium detachment composition indices between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

PurposeTo compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months.MethodsThis was a retrospective chart review of treatment-naïve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F).ResultsA total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p > 0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p < 0.001 and PCV, r = − 0.06; p = 0.74) and the need for fewer anti-VEGF injections (n-AMD, r = − 0.53; p < 0.001 and PCV, r = − 0.09; p = 0.58).ConclusionPEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months.

Conversion to faricimab after prior anti-vascular endothelial growth factor therapy for persistent diabetic macular oedema

BackgroundTo assess the anatomical and functional outcomes in eyes with persistent diabetic macular oedema (pDME) on chronic anti-vascular endothelial growth factor therapy switched to intravitreal faricimab.MethodsPatients with pDME on chronic...

Different Retinopathy of Prematurity Severity, Onset Therapy and Outcomes in Triplet Babies: A Case Report

Introduction : Retinopathy of prematurity (ROP) is a vasoproliferative disease of the premature infants, characterized by abnormal vascularization at the junction of vascular and avascular retina. Intravitreal anti-VEGF injection is one of promising management of ROP. The aim is to present the therapy outcomes of triplet babies with different severity and onset therapy.&#x0D; Case Illustration : This case shows ROP in triplets born at 25-26 weeks gestational age. First baby, weighed 630 g with Bilateral Stage 2 Zone II Posterior with Plus Disease treated with intravitreal ranibizumab injection at 11 weeks (PMA 36-37 weeks). Second baby, weighed 620 g and get bilateral intravitreal ranibizumab injection a week after first baby, left eye got worse on first week, but getting better on the last follow up. Third Baby, weighed 750 g with bilateral Stage 3 Zone I with Plus Disease (worst eye condition), but because he had worst general condition, so the latest got screening, got no intervention. Two babies were treated with anti-VEGF therapy – bevacizumab. All babies has outcome regression, no recurrence of ROP in those short term end point, and no adverse reactions were observed until the last follow up at 27 weeks old (PMA 52-53 weeks) recorded for all babies.&#x0D; Discussion : &#x0D; Conclusion : Primary prevention through well-managed screening programme for premature infants was the more effective way to manage the ROP. Intravitreal anti-VEGF treatment could be promising for management of ROP if it was given on the right time and early stadium.

When Retinal Vasculitis Wears a Mask: Unveiling Retinal Vasculitis Presented as Branch Retinal Vein Occlusion in a Young Male Patient

Introduction : Retinal vasculitis can present with a range of clinical features. Correct diagnosis and prompt treatment are essential to prevent permanent visual loss. We describe a case of retinal vasculitis with branch retinal vein occlusion (BRVO) as initial diagnosis, which is a rare manifestation in a young individual without any vascular risk factors.&#x0D; Case Illustration : A 24-year-old male was referred to our center with a sudden onset of blurry vision of his left eye. He was previously diagnosed with BRVO. The patient denied having any chronic diseases, fever, or sore throat. Visual acuity was 6/18 on the left eye and 6/6 on the right eye, respectively. The anterior segment showed no abnormalities. However, fundus examination revealed prominent retinal sheathing, retinal whitening at the inferior quadrant, and macular star. Systemic diseases, such as Bechet disease, sarcoidosis, and systemic lupus erythematosus were excluded by ancillary tests. One month after the initial examination, the patient reported worsening of vision. Funduscopic examination revealed preretinal hemorrhages and macular star. The patient then received intravitreal injection of anti-vascular endothelial growth factor (VEGF), which helped to resolve the hemorrhage and improve vision.&#x0D; Discussion : Further investigations, such as fundus fluorescein angiogram, may aid in the diagnosis and management of this condition. Anti-VEGF therapy may be a useful treatment option for retinal vasculitis-associated hemorrhages.&#x0D; Conclusion : Our case highlights the importance of considering retinal vasculitis as a differential diagnosis in young patients presenting with BRVO, even in the absence of traditional risk factors.

THE OUTCOME OF INTRAVITREAL BROLUCIZUMAB FOR NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TREATMENT

Introduction : Age-related macular degeneration (AMD) is a disease that results in irreversible severe loss of central vision in people over 50 years old. Hence, anti-VEGF therapy has become a standard treatment for neovascular AMD. Brolucizumab is a single-chain antibody fragment that inhibits VEGF-A binding to VEGF receptors. It has a higher molar concentration that allows a greater reduction in the central subfield thickness (CST)&#x0D; Case Illustration : A 59-year-old male with a chief complaint of gradually blurred vision in the left eye for 2 years. BCVA of the left eye was 0.3, OCT showed a hyperreflective band in the sub-neurosensory space with subretinal fluid in the left eye (Figure 1), and OCT-A revealed choroidal neovascularization (Figure 2). The patient was diagnosed with AMD AREDS IV in the left eye. He had undergone three monthly injections of brolucizumab. BCVA of the left eye after injection improved to 1.0 and OCT imaging showed no subretinal fluid, no intraretinal fluid, and no pigment epithelial detachment.&#x0D; Discussion : Brolucizumab has a greater reduction in CST because of its high molecular concentration. Results of HAWK and HARRIER concluded that brolucizumab was non-inferior towards aflibercept in BCVA change at week 48. According to the HAWK trial, a greater reduction of CST was seen in week 16 among eyes treated with brolucizumab. Brolucizumab was also well tolerated and adverse event rates were similar to aflibercept.&#x0D; Conclusion : Brolucizumab could be an alternative treatment option considering its efficacy in improving visual acuity and reducing CST.

THE EFFECTIVENESS OF INTRAVITREAL ANTI-VEGF INJECTION IN EALES' DISEASE: A CASE REPORT

Introduction : Eales’ Disease (ED) is an idiopathic inflammatory retinal vasculitis, affecting retinal veins of small and large caliber that results in extraretinal neovascularization with vitreous hemorrhage. The etiopathogenesis of ED is poorly understood. However, many studies have attributed inflammation as a response to mycobacterium tuberculosis. Treatment of this disease can be done with corticosteroids, anti-VEGF therapy, laser photocoagulation, and vitreoretinal surgery.&#x0D; Case Illustration : We reported a patient, a 31-year-old woman with complaints of blurred vision and floaters in both eyes. An initial examination showed the visual acuity of the RE was 0,1F1 and the LE was 0,1. Examination of the posterior segment found perivascular exudate and peripheral retinal neovascularization. We performed an OCT examination on both eyes and found that there was extensive macular edema, especially in the RE. Patient was diagnosed with ED and received steroidsas an initial treatment. But there was no improvement in both eyes. In addition, patient received two anti-VEGF injections in the RE and one injection in the LE and showed good improvement. After that injection, the posterior segment showed very minimal lesions on the macula and repeated OCT results showed normal central macular thickness.&#x0D; Discussion : Anti-VEGF may also play a role in the treatment and management of ED. This is because, besides inflammation, there is an increased expression of VEGF in vitreous patients with ED. Several case reported there is significant improvement in anti-VEGF injection in the management of patients with ED.&#x0D; Conclusion : Intravitreal anti-VEGF injection shows good results in ED that did not improve with steroid treatment.

Comparation of Bevacizumab Intravitreal Injection Effects with and without Yellow Subthreshold Micropulse Laser (577-nm) Combination on Central Macular Thickness and Best Corrected Visual Acuity of Mild-Moderate Diabetic Macular Edema Patients

Introduction &amp; ObjectivesThe management of macular edema is constantly evaluated, with anti-VEGF therapy being the firstline. Subthreshold micropulse laser (SML) has been proposed as alternative adjuvant. Previousretrospective studies demonstrated the effectiveness of 577-nm SML as monotherapy in macularedema with CMT below 400 ?m. However, prospective data on the effectiveness of SML as adjuvantis lacking. The aim is to assess the effect of the combination of bevacizumab and 577-nm SML lasercompared to bevacizumab monotherapy on central macular thickness and visual acuity in mildmoderatediabetic macular edema patients.&#x0D; MethodsA prospective randomized clinical trial was performed on diabetic macular edema patients withmacular thickness range of 300-600 ?m. Subjects are divided into two groups. The control groupreceived a standard protocol and the study group received a yellow SML laser adjuvant one weekafter injection. Patients underwent follow-up assessment of visual acuity and central macularthickness at 28 and 35 days post-injection.&#x0D; Results26 subjects were equally divided into study and control groups. Significant decrease in CMT werefound in study group (p=0.011 and 0.014) and the control group (p=0.006 and p=0.001). However,there was no significant difference in ?CMT values between the two groups in the 28-day (p=0.317)and 35-day controls (p=0.84). There was no difference in ?BCVA ETDRS between the study andcontrol groups at 28 days (p=0.568) and 35 days (p=0.128) after injection.&#x0D; ConclusionThe combination of SML and intravitreal bevacizumab can reduce central macular thickness andimprove visual acuity but there was no significant difference with standard monotherapy.

A Case Report Intravitreal Anti VEGF Bevacizumab on Patient with Hypertension Retinopathy and Exudative Retinal Detachment

Introduction : To present a case of intravitreal anti VEGF bevacizumab function on patient with hypertension retinopathy and exudative retinal detachment.&#x0D; Case Illustration : A 29 years old man presented with chief complaint blurry vision with visual acuity 1/60 on both eyes. History of hypertension sinced one year ago and already got hemodialisa treatment twice a week sinced 6 months ago. Ophthalmic examination showed decreased vision on both eyes and posterior segment both eyes we can find macular star and papil edema. Patient had diagnosed with hypertension retinopathy scheie 4 and exudative retinal detachment both eyes.&#x0D; Discussion : Hypertension will cause blood vessels to become damage in the form of sclerosis, thickening of blood vessel walls, and plasma leakage. Hypertension retinopathy acts as predictor of systemic morbidity and mortality due to organ target damage. Regulating systemic disease like blood pressure to become normal will improve clinical signs of hypertension retinopathy. Administration of anti-VEGF intravitreal injection therapy like bevacizumab can improve permeability of blood vessels in retina and decreased volume of exudate in retina. Visual acuity for this patient will improve to become 4/60 for both eyes.&#x0D; Conclusion : Uncontrolled hypertension can lead to organ target damage, which one of that was eyes. Hypertension retinopathy can make complications like exudative retinal detachment if the blood pressure still uncontrolled. Management of exudative retinal detachment caused by hypertension retinopathy was giving intravitreal anti VEGF injection in eyes to repair breakdown of blood retinal barrier, and the blood pressure must be well controlled to maintain permeability of blood retinal barrier.

Initial Outcome of Subconjunctival Bevacizumab for Corneal Neovascularization - a Case Series

Introduction : Corneal neovascularization (CNV) has a variety of causes and threatens corneal clarity, thus optimal visual acuity. Conventional medical management includes topical steroids and matrix metalloproteinase inhibitors like doxycycline. Anti-vascular endothelial growth factor (anti-VEGF) agents have demonstrated promise but remain off-label for this indication.&#x0D; Case Illustration : We present three patients with corneal neovascularization varied in etiology who underwent subconjunctival injection of Bevacizumab . Case 1: a-female-69 years old came with blurred vision after had Stephen Johnson Syndrome which affect her cornea. The examination revealed opacification of cornea accompanied by neovascularization at 5 until 9 o’clock position up to edge of pupil in the left. Case 2: a-male-47 years old presented corneal haze with neovascularization almostin all corneal region on background of fungal keratitis. Case 3: a-male-63 years old who underwent penetrating keratoplasty of indication corneal lekoma following an episode of fungal keratitis. There was opacity in all corneal region and neovascularization in 360 degree of limbus. All of these patients showed regression of neovessel after first injection of bevacizumab.&#x0D; Discussion : Corneal neovascularization is a condition caused by disruption homeostasis in which proangiogenic balanced by antiangiogenic, thereby maintaining avascularity. Bevacizumab as VEGF-A-binding proteins could prevent VEGF-A from binding cell surface receptors.&#x0D; Conclusion : Subconjunctival injection of Bevacizumab can be considered as a treatment for corneal neovascularization. It has shown promising effects in recess neovascularization in cornea regardlessthe etiology.

Advances in Research Related to MicroRNA for Diabetic Retinopathy.

Diabetic retinopathy (DR) is a severe microvascular complication of diabetes and is one of the primary causes of blindness in the working-age population in Europe and the United States. At present, no cure is available for DR, but early detection and timely intervention can prevent the rapid progression of the disease. Several treatments for DR are known, primarily ophthalmic treatment based on glycemia, blood pressure, and lipid control, which includes laser photocoagulation, glucocorticoids, vitrectomy, and antivascular endothelial growth factor (anti-VEGF) medications. Despite the clinical efficacy of the aforementioned therapies, none of them can entirely shorten the clinical course of DR or reverse retinopathy. MicroRNAs (miRNAs) are vital regulators of gene expression and participate in cell growth, differentiation, development, and apoptosis. MicroRNAs have been shown to play a significant role in DR, particularly in the molecular mechanisms of inflammation, oxidative stress, and neurodegeneration. The aim of this review is to systematically summarize the signaling pathways and molecular mechanisms of miRNAs involved in the occurrence and development of DR, mainly from the pathogenesis of oxidative stress, inflammation, and neovascularization. Meanwhile, this article also discusses the research progress and application of miRNA-specific therapies for DR.

Brolucizumab for Wet Aged-Related Macular Degeneration Patients : too Good to be True

Introduction &amp; ObjectivesBrolucizumab is the newest anti-vascular endothelial growth factor (anti-VEGF). It showed superioranatomic outcomes and noninferiority best corrected visual acuity (BCVA) results for Wet Aged-Related Macular Degeneration (Wet-AMD) compared to other anti-VEGF. In Yogyakarta, it's beenonly used in a few patients and we want to report the effectiveness and safety of brolucizumab inWetAMD&#x0D; MethodsIn this retrospective study, all wetAMD patients who underwent Brolucizuab intravitreal injectionsbetween December 2021 and January 2023 at Dr YAP Eye Hospital were studied. Patient’sdemographic data, before and after intravitreal brolucizumab injections (central macular thickness,intraocular pressure, and BCVA) were assessed.&#x0D; ResultsThis study included 6 eyes of 6 patients (3 women) with a mean age of 69.5 years old. The meanfollow-up period was 27 ± 10.1 weeks after the first injection of brolucizumab. Three patients werenaïve wetAMD patients, three anti-VEGF experienced wetAMD patients. The mean BCVA at baseline(before brolucizumab injection) was 0.12 decimal (6/48) and 0.29 decimal (6/20) at the last followup.Five out of six patients' visual acuity were improved. In four out of six patient central macularthickness were reduced (mean difference 29,2 um). None of the patient's intraocular pressureincreased over 21 mmHg. None of the patients reported any signs of inflammation, vasculitis, ocularor systemic adverse effects.&#x0D; ConclusionThis limited data demonstrated that brolucizumab was relatively safe and effective in stabilizingBCVA for both WetAMD patients who had previous treatment with other anti-VEGF agents andnaive. Larger sample sizes studies &amp; future multicenter collaborative are warranted

The Effects of Bevacizumab in Augmenting Trabeculectomy for Glaucoma : Systematic Review and Meta-Analysis

Introduction &amp; Objectives : Anti-vascular endothelial growth factor (VEGF) agents have been used to slow the healing response and postoperative scar tissue formation. To determine the effectiveness of adding Anti VEGF bevacizumab to the results of trabeculectomy in glaucoma.&#x0D; Methods : Searches were conducted in a structured way using keywords across several data sources, including Pubmed, Proquest and Cochrane library. The keywords used for searching were “Bevacizumab”, “Trabeculectomy” and “Glaucoma”. The reviewed articles are Randomized Control Trial in english, conducted on humans in the last 15 years. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.&#x0D; Results : From a total of 353 articles, there were 6 studies with 362 eyes of 352 patients been evaluated for the effectiveness of bevacizumab addition to trabeculectomy. The primary outcome of all articles was the assessment of Intra Ocular Pressure (IOP). No significant difference in IOP was found between the subconjunctival bevacizumab + Mytomycin-c group and mytomycin-c alone group (MD 0.11 ; 95% CI -0.10 to 0.33), as well as subconjunctival comparison with mytomycin-c (MD 0.11 ; 95% CI -0.29 to 0.50). Similar results were also found in the intracameral and placebo groups (MD 0.08 ; -0.22 to 0.38). However, 3 articles reported significant differences in peripheral vascularity of the bleb both by the Moorfields Bleb Grading System and by the Indiana Bleb Appearance System.&#x0D; Conclusion : The addition of bevacizumab to trabeculectomy did not show any benefit in reducing IOP when compared with MMC. But it gives better peripheral vascularity of the bleb.

Effect of Intravitreal Anti-Endothelial Growth Factor Agents on Renal Function in Patients With Diabetes Mellitus

BackgroundIntravitreal administration of vascular endothelial growth factor inhibitors (anti-VEGF) is the treatment of choice in retinal pathology associated with type 2 diabetes mellitus (DM2). We aimed to analyze the effect on renal function in patients with DM2 after intravitreal anti-VEGF administration. MethodsSingle-center retrospective and observational study of patients with DM2 with and without chronic kidney disease (CKD). We analyzed the evolution of renal function after anti-VEGF onset, compared with a control group. ResultsWe included 45 patients (55.6% male) who received anti-VEGF therapy. Mean age was 74.4±11.5 (50-91) years. These were compared with 45 patients with similar characteristics. After 12-months, 76.3% had CKD with a mean reduction in estimate glomerular filtration rate (eGFR) of 19.4%. Nine patients (20%) had a >25% reduction in eGFR, and three patients (6.7%) had a >50% reduction in GFR. At 24-months, 80% of patients had CKD with a mean eGFR drop of 28%. The mean eGRF slope of patients who had received anti-VEGF treatment was 10 ml/min/year compared to 1,5 ml/min/year in the control group (p<0.05). After the first administration, five patients (17.2%) in the CKD group required renal replacement therapy during follow-up (mean time 22±12 months). Main risk factors for need of dialysis were age, presence of previous CKD, and baseline proteinuria. ConclusionIntravitreal anti-VEGF administration is a risk factor for CKD and rapid progression to end-stage kidney disease in patients with previous CKD. Knowing these drugs' implications is crucial to avoid CKD progression and opportunely limit their use in certain patients.

Advancements in the treatment of age-related macular degeneration: a comprehensive review

Abstract Age-related macular degeneration (AMD) stands as a leading cause of irreversible blindness, particularly affecting central vision and impeding daily tasks. This paper provides a thorough exploration of AMD, distinguishing between its two main subtypes—Wet and Dry AMD—while shedding light on the prevalence and risk factors, including age, genetics, and smoking. The focus shifts to the current and future treatment landscape, examining both Dry and Wet AMD. Regarding Dry AMD, interventions such as antioxidant supplementation and ongoing clinical trials offer hope. Notable among these is Pegcetacoplan which is the only Food and Drug Administration (FDA)-approved medication, displaying promising results in reducing geographic atrophy lesions. For Wet AMD, anti-Vascular Endothelial Growth Factor therapies like Ranibizumab (Lucentis®) have been instrumental, and newer drugs like Faricimab and OPT-302 show comparable efficacy with extended dosing intervals. Additionally, gene therapies such as RGX-314 present a potential paradigm shift, reducing or eliminating the need for frequent injections. Biosimilars offer cost-effective alternatives. The paper also delves into the integration of technology and artificial intelligence in AMD management, highlighting the role of smartphone apps for patient monitoring and artificial intelligence algorithms for diagnosis and surveillance. Furthermore, patient perspectives on artificial intelligence demonstrate a positive correlation between understanding and trust. The narrative concludes with a glimpse into ground-breaking technologies, including retinal implants and bionic chips, offering hope for vision restoration. Overall, this paper underscores the multifaceted approach in addressing AMD, combining traditional and innovative strategies, paving the way for a more promising future in AMD treatment.

Targeting adenosine A2A receptors for early intervention of retinopathy of prematurity.

Retinopathy of prematurity (ROP) continues to pose a significant threat to the vision of numerous children worldwide, primarily owing to the increased survival rates of premature infants. The pathologies of ROP are mainly linked to impaired vascularization as a result of hyperoxia, leading to subsequent neovascularization. Existing treatments, including anti-vascular endothelial growth factor(VEGF) therapies, have thus far been limited to addressing pathological angiogenesis at advanced ROP stages, inevitably leading to adverse side effects. Intervention to promote physiological angiogenesis during the initial stages could hold the potential to prevent ROP. Adenosine A2A receptors (A2AR) have been identified in various ocular cell types, exhibiting distinct densities and functionally intricate connections with oxygen metabolism. In this review, we discuss experimental evidence that strongly underscores the pivotal role of A2AR in ROP. In particular, A2AR blockade may represent an effective treatment strategy, mitigating retinal vascular loss by reversing hyperoxia-mediated cellular proliferation inhibition and curtailing hypoxia-mediated neovascularization in oxygen-induced retinopathy (OIR). These effects stem from the interplay of endothelium, neuronal and glial cells, and novel molecular pathways (notably promoting TGF-β signaling) at the hyperoxia phase. We propose that pharmacological targeting of A2AR signaling may confer an early intervention for ROP with distinct therapeutic benefits and mechanisms than the anti-VEGF therapy.

The Responses of Different Types of Diabetic Macular Edema after Three Loading Doses of Anti-vascular Growth Factor: Outcomes in Two Medical Centers

Background: Diabetic macular edema (DME) is currently treated by anti-vascular endothelial growth factor (anti-VEGF). Aim: The aim of this study was to evaluate the effect of intravitreal anti-VEGF in different types of DME classified by optical coherence tomography (OCT). Methods: This retrospective study included 161 treatment-naive eyes (116 patients) diagnosed with DME in two tertiary medical centers, which were classified into three groups according to initial OCT finding: diffuse retinal thickening (DRT), cystoid macular edema (CME), and serous retinal detachment (SRD). All eyes received three monthly loading doses of anti-VEGF. Primary and secondary outcomes were the improvement of best-corrected visual acuity (BCVA) and the decrease of central foveal thickness (CFT) on OCT, respectively. Results: Among the three groups, there was no significant difference in baseline BCVA (P = 0.137); however, the SRD group had the thickest baseline CFT (P &lt; 0.001). After three loading doses of anti-VEGF, the BCVA of all three groups improved from baseline (DRT vs. CME vs. SRD, P = 0.0002, P &lt; 0.0001, and P &lt; 0.0001, respectively), while the SRD group seemed to have relatively better improvement among three groups although not significant (P = 0.051). The CFTs of all three groups significantly decreased from baseline (P &lt; 0.0001 in all three groups). The CFT decreased the most in the SRD group, followed by the CME group, and the least in the DRT group (P &lt; 0.001). Conclusion: Anti-VEGF therapy improved the anatomical structure and function in all types of DME; SRD responded the best.

Myopic choroidal neovascularization with neovascular signal around perforating scleral vessel prone to recur after anti-VEGF therapy

BackgroundTo compare the recurrence of myopic choroidal neovascularization (mCNV) based on the neovascular signal of mCNV around the perforating scleral vessel (PSV).MethodsA consecutive series of naïve patients with mCNV accepted anti-VEGF therapy with a minimum 12-month follow-up period. The neovascular signal relationship between PSV and mCNV were classified into the presence of neovascular signal of CNV around PSV or not. The recurrence of mCNV, best-corrected visual acuity (BCVA), hyperreflective foci height, CNV area and CNV flow area were analyzed between two groups.ResultsNeovascular signal of CNV around PSV was detected in 20 eyes (39.2%). The one-year recurrence rate in the group with neovascular signal of CNV around PSV was significantly higher than that in the group without neovascular signal of CNV around PSV (P = 0.045). The recurrence time in the group with neovascular signal around PSV was shorter than that in the group without neovascular signal around PSV (P = 0.030). Cox proportional hazard model showed that the presence of neovascular signal of CNV around PSV [hazard ratio (HR): 2.904] and subfoveal choroidal thickness ≤ 50 μm (HR: 0.368) were risk factors for recurrence of mCNV. In the group with neovascular signal around PSV, the BCVA was worse (P = 0.024) and the CNV flow area was more unstable (P = 0.027) after therapy.ConclusionsPSV was commonly detected in patients with mCNV. The presence of neovascular signal of CNV around PSV was prone to recur with a shorter time in mCNV patients.

Frequency and distribution of the active agent of intravitreal injections in German centers 2015-2021-An oregis study

Digitalization in medicine, especially the electronic documentation of patient data, is revolutionizing healthcare systems worldwide. The evaluation of real-world data collected under everyday conditions presents opportunities but also challenges. Electronic medical registries provide ameans to compile extensive patient data for scientific inquiries. Oregis is the first nationwide digital registry for health services research established by the German Ophthalmological Society (DOG). Intravitreal operative medicinal injections (IVOM) are among the most frequently performed procedures in ophthalmology. Data on injection numbers and injection frequencies with anti-vascular endothelial growth factor (VEGF) are already available from other countries, whereas data at a national level are not yet available in Germany due to the lack of anationwide register. It is known that the treatment success of anti-VEGF IVOMs depends largely on the adherence to treatment and thus on the number of injections. There are also differences in cost. In the context of this study, real-world data on the frequency and distribution of intravitreal injections in German centers from 2015 to 2021 were compiled for the first time since the introduction of oregis. The aim of this study is to collect data on the use of anti-VEGF IVOMs in Germany from oregis for the first time and to show the development of injection numbers and anti-VEGF drugs used. At the same time, the possibilities of data retrieval from oregis are demonstrated using aconcrete example from daily ophthalmological practice. An automated query of records was performed for all patients who received IVOM at oregis-affiliated healthcare facilities between 2015 and 2021. The number of treated patients and the use of anti-VEGF medications, including aflibercept, bevacizumab, brolucizumab, and ranibizumab, were determined. The data were collected in apseudonymized and anonymized manner. At the time of data collection, 9German ophthalmological healthcare facilities were affiliated with oregis. In total, 309,152 patients were registered during the observation period, with 8474 receiving IVOMs. Over the observation period, the number of participating centers, patients, and intravitreal injections increased. The proportional share of anti-VEGF agents among the total number of injections varied during the observation period. Real-world data captured in oregis offer significant potential for enhancing healthcare provision. Oregis enables the depiction of ophthalmological care conditions in Germany and contributes to research and quality assurance. The ability to query the presented data exemplifies the multitude of inquiries through which oregis can contribute to the representation of ophthalmological care in Germany.

The Efficacy of Immune Checkpoint Inhibitors in Microsatellite Stable Colorectal Cancer: A Systematic Review.

The use of immune checkpoint inhibitors (ICIs) has revolutionized cancer care, particularly in immune-inflamed tumors and tumors with a high mutational burden, like microsatellite instable colorectal cancer (CRC). However, their effectiveness in microsatellite stable (MSS) CRC is limited. This systematic review aims to evaluate the efficacy of ICIs in MSS CRC and explore promising combination strategies. A comprehensive search from the Web of Science, Medline, and Embase databases, for studies published until 14 November 2022, identified 53 clinical trials included in the review. ICI monotherapy or ICI-ICI combinations demonstrated limited clinical activity for patients with MSS CRC, with overall response rates below (ORR) 10% in most studies. The ICI and tyrosine kinase inhibitor (TKI) garnered ORRs ranging from 10% to 40% and indicated a higher benefit for patients, particularly those without active liver metastases. The combination of ICIs with anti-VEGF agents showed modest ORRs, especially in the earlier treatment lines and in combination with chemotherapy. While these combinations could lead to modest improvements, well-defined biomarkers for long-term benefit are yet to be delineated. Combinations involving BRAF inhibitors with ICIs were studied, showing promising responses with combination approaches in molecularly defined subgroups. In conclusion, while ICI monotherapy has limited efficacy in MSS CRC, combination strategies hold promise to enhance survival outcomes. Further research is necessary to identify optimal combination approaches, predictive biomarkers for treatment response, as well as enrollment according to tumor molecular characteristics.

Trends in Anti-Vascular Endothelial Growth Factor Original Medicare Part B Claims in the United States, 2014–2019

ABSTRACT Purpose To characterize trends in use of and expenditure for the intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents aflibercept, ranibizumab, and bevacizumab among the population enrolled in Original Medicare from 2014 to 2019. Methods The Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File was used to extract Medicare Part B fee-for-service outpatient injection claims data submitted by ophthalmologists. Multivariable linear regression models were used to evaluate the association between reimbursement, ophthalmologist availability, and agent administration rate. Results Between 2014 and 2019, 17,588,995 intravitreal injection claims were filed by 4218 US ophthalmologists. Medicare costs for anti-VEGF injections increased from 2.51 B USD in 2014 to 4.02 B USD in 2019. Increased state-level ophthalmologist availability and incremental increases in average reimbursement amounts were found to be significantly associated with a 6.8-fold variation in 2019 overall anti-VEGF injection rates across states. Conclusions Medicare injection rates and costs for anti-VEGF injections have both increased between 2014 and 2019, largely driven by increased aflibercept use. There is a significant association between ophthalmologist availability and anti-VEGF injection rate on the state level, suggesting access to care may contribute to the observed state-level disparities in intravitreal injection rates. Further characterization of factors contributing to the state-level variation in injection rates of individual anti-VEGF agents may help inform interventions promoting equitable access to and use of these drugs.