Anti-vascular Endothelial Growth Factor Agents Research Articles

Antivascular Endothelial Growth Factor Dosing Frequency and Visual Outcomes in Macular Edema Following Central Retinal Vein Occlusion.

We evaluated the relationship between dosing frequency of intravitreal antivascular endothelial growth factor (anti-VEGF) agents and visual acuity (VA) outcomes over 2 years in eyes with macular edema (ME) secondary to central retinal vein occlusion (CRVO) in the US routine clinical practice setting. This retrospective analysis assessed electronic medical records of eyes with ME secondary to CRVO that received their first anti-VEGF injection January 1, 2012, to May 31, 2016, and were followed for 1 year or more in the US-based Vestrum Health Treatment and Outcomes database. Eyes were divided into 2 injection frequency subcohorts (≤6 or ≥7 injections/year). Overall, 851 (34.6%) of 2458 eyes with ME secondary to CRVO received 6 or fewer injections, and 1607 (65.4%) received 7 or more injections through 1 year. The mean number of injections in patients receiving 6 or fewer injections and 7 or more injections was 4.7 and 8.8, respectively, and baseline mean VA was 35 and 37 letters, respectively. At year 1, mean letter gain from baseline was less in eyes receiving 6 or fewer injections vs in those receiving 7 or more injections (7.0 vs 12.2, P < .001). Mean VA at year 2 was 50 letters in eyes receiving 6 or fewer injections (n = 50) and 55 letters in eyes receiving 7 or more injections (n = 157). In routine clinical practice, more frequent dosing with anti-VEGF agents was associated with greater visual benefits in eyes with ME secondary to CRVO.

Early Experience With Brolucizumab Treatment of Neovascular Age-Related Macular Degeneration

Outcome data are limited regarding early experience with brolucizumab, the most recently approved anti-vascular endothelial growth factor (VEGF) agent for the treatment of neovascular age-related macular degeneration (nAMD). To report clinical outcomes after intravitreous injection (IVI) of brolucizumab, 6 mg, for nAMD. This retrospective case series conducted at 15 private or academic ophthalmological centers in the United States included all consecutive patients with eyes treated with brolucizumab by 6 retina specialists between October 17, 2019, and April 1, 2020. Treatment with brolucizumab IVI, 6 mg. Change in mean visual acuity (VA) and optical coherence tomography parameters, including mean central subfield thickness and presence or absence of subretinal and/or intraretinal fluid. Secondary outcomes included ocular and systemic safety. A total of 172 eyes from 152 patients (87 women [57.2%]; mean [SD] age, 80.0 [8.0] years) were included. Most eyes (166 [96.5%]) were not treatment naive, and 65.7% of these eyes (109 of 166) were switched from the prior anti-VEGF agent because of persistent fluid detected on optical coherence tomography scans. Study eyes received a mean (SD) of 1.46 (0.62) brolucizumab IVIs. The mean (SD) VA prior to starting brolucizumab was a 64.1 (15.9) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score (Snellen equivalent, 20/50) and was a 63.3 (17.2) ETDRS letter score (Snellen equivalent, 20/63) at the last study evaluation (mean difference, 0.8; 95% CI, -2.7 to 4.3; P = .65). When analyzed by number of brolucizumab IVIs, the presence or absence of fluid prior to starting brolucizumab, or the presence or absence of intraocular inflammation after receiving brolucizumab, there was no difference in mean VA prior to starting brolucizumab compared with after brolucizumab IVIs or at the final study evaluation. The mean (SD) central subfield thickness in all eyes prior to starting brolucizumab was 296.7 (88.0) μm and was 269.8 (66.5) μm at the last study examination (mean difference, 26.9 µm; 95% CI, 9.0-44.7 µm; P = .003). Intraocular inflammation was reported in 14 eyes (8.1%) and was self-limited and resolved without treatment in almost half those eyes (n = 6). One previously reported eye (0.6%) had occlusive retinal vasculitis and severe loss of vision. In this analysis of brolucizumab IVI for nAMD, VA remained stable, with a reduction in central subfield thickness. Intraocular inflammation events ranged from mild with spontaneous resolution to severe occlusive retinal vasculitis in 1 eye.

Intraocular inflammation with brolucizumab use : Patient management-diagnosis-therapy

Der VEGF(„vascular endothelial growth factor“)-Inhibitor Brolucizumab ist seit Oktober 2019 in den USA und seit Februar 2020 in Europa zur Behandlung der neovaskulären altersabhängigen Makuladegeneration (nAMD) zugelassen. Grundlage der Zulassung bildeten die randomisierten, doppel-blinden Phase-III-Studien HAWK und HARRIER mit insgesamt 1817 Patienten. Hierbei zeigte Brolucizumab 6 mg (je nach Krankheitsaktivität alle 12 oder alle 8 Wochen verabreicht) eine nichtunterlegene Wirksamkeit in Bezug auf den bestkorrigierten Visus gegenüber Aflibercept 2 mg (alle 8 Wochen verabreicht). Erste Rückmeldungen zum Einsatz von Brolucizumab nach der Marktzulassung in den USA haben einzelne, z. T. schwerwiegende Fälle behandlungsassoziierter intraokularer Entzündungen mit retinaler Vaskulitis und/oder retinaler, vaskulärer Okklusion beschrieben, die teilweise zu einem schweren Visusverlust führten. Die Daten der Zulassungsstudien wurden daraufhin durch ein Safety Review Committee (SRC) unabhängig retrospektiv analysiert. Ziel der vorliegenden Publikation ist es, Anwendern eine Orientierungshilfe aus Autorensicht bei der Therapie einer Brolucizumab-assoziierten intraokularen Entzündung zu bieten. Von zentraler Bedeutung ist hierbei auch eine erweiterte Aufklärung der Patienten über Symptome einer intraokularen Entzündung. Obwohl die Fallserien und die HAWK/HARRIER-Daten es nicht abschließend beantworten, bleiben eine zu späte Detektion, eine unterdosierte antientzündliche Therapie oder eine unbedachte Wiederbehandlung mit Brolucizumab dem Verdacht ausgesetzt, Komplikationen zu verstärken. Ein Stopp der Brolucizumab-Therapie sollte grundsätzlich erfolgen, sobald es nach Gabe des Medikaments zu intraokularen Entzündungen mit oder ohne retinalen Vaskulitiden und oder Gefäßverschluss kam. Abhängig vom Schwerpunkt der Entzündung werden dem Behandler an die Leitlinien und Stellungnahmen angelehnte Empfehlungen für Diagnostik und Therapie dargestellt. Diese Übersichtsarbeit ersetzt nicht die fachgesellschaftlichen Stellungnahmen.

Saudi Arabia Guidelines for diabetic macular edema: A consensus of the Saudi Retina Group.

ABSTRACTDiabetes mellitus (DM) and its complications are major public health burdens in Saudi Arabia. The prevalence of diabetic retinopathy (DR) is 19.7% and the prevalence of diabetic macular edema (DME) is 5.7% in Saudi Arabia. Diabetic macular edema is a vision-threatening complication of DR and a major cause of vision loss worldwide. Ocular treatments include retinal laser photocoagulation, anti-vascular endothelial growth factor (anti-VEGF) agents, intravitreal corticosteroids, and vitreoretinal surgery when necessary. The present consensus was developed as a part of the Saudi Retina Group’s efforts to generate Saudi guidelines and consensus for the management of DME, including recommendations for its diagnosis, treatment, and best practice. The experts’ panel stipulates that the treatment algorithm should be categorized according to the presence of central macula involvement. In patients with no central macular involvement, laser photocoagulation is recommended as the first-line option. Patients with central macular involvement and no recent history of cardiovascular (CVS) or cerebrovascular disorders can be offered anti-VEGF agents as the first-line option. In the case of non-responders (defined as an improvement of <20% in optical coherence tomography or a gain of fewer than 5 letters in vision), switching to another anti-VEGF agent or steroids should be considered after 3 injections. Within the class of steroids, dexamethasone implants are recommended as the first choice. In patients with a recent history of CVS events, the use of anti-VEGF agents is not recommended, regardless of their lens status. The experts’ panel recommends that a future study be conducted to provide a cut-off point for early switching to steroid implants in pseudo-phakic eyes.

Macular edema after rhegmatogenous retinal detachment repair: risk factors, OCT analysis, and treatment responses

PurposeTo investigate risk factors, imaging characteristics, and treatment responses of cystoid macular edema (CME) after rhegmatogenous retinal detachment (RRD) repair.MethodsConsecutive, retrospective case–control series of patients who underwent pars plana vitrectomy (PPV) and/or scleral buckling (SB) for RRD, with at least six months of follow-up. Clinical and surgical parameters of patients with and without CME (nCME), based on spectral-domain optical coherence tomography (OCT), were compared.ResultsOf 99 eyes enrolled, 25 had CME while 74 had nCME. Patients with CME underwent greater numbers of surgeries (P < 0.0001). After adjusting for number of surgeries, macula-off RRD (P = 0.06), proliferative vitreoretinopathy (PVR) (P = 0.09), surgical approach (PPV and/or SB, P = 0.21), and tamponade type (P = 0.10) were not statistically significant, although they all achieved significance on univariate analysis (P = 0.001 or less). Intraoperative retinectomy (P = 0.009) and postoperative pseudophakia or aphakia (P = 0.008) were more frequent in the CME group, even after adjustment. Characteristics of cCME on OCT included diffuse distribution, confluent cysts, and absence of subretinal fluid or intraretinal hyperreflective foci. Macular thickness improved significantly with intravitreal triamcinolone (P = 0.016), but not with anti-vascular endothelial growth factor agents (P = 0.828) or dexamethasone implant (P = 0.125). After adjusting for number of surgeries and macular detachment, final visual acuities remained significantly lower in the CME vs nCME group (P = 0.012).ConclusionRisk factors of CME include complex retinal detachment repairs requiring multiple surgeries, and pseudophakic or aphakic lens status. Although this cCME was associated with poor therapeutic response, corticosteroids were the most effective studied treatments.

OUTER RETINAL TUBULATION MAY RESULT FROM FIBROSED TYPE 2 NEOVASCULARIZATION: Clinical Observations and Model of Pathogenesis.

To investigate the role of Type 2 macular neovascularization with subsequent subretinal fibrosis in the pathogenesis of outer retinal tubulation (ORT). We conducted a retrospective cohort study of patients with stabilized inactive exudative macular degeneration who had been treated with intravitreal injections of antivascular endothelial growth factor agents. Baseline fluorescein and optical coherence tomography images were included. Macular neovascularizations (MNVs) were classified by type and size. Consecutive optical coherence tomography images analyzed for ORT development. One hundred forty-four eyes of 134 patients were included in this study. Sixty eyes presented with pure Type 1 MNV. Eighty-four eyes presented with some Type 2 component of MNV. In total, evidence of ORT is shown in 55 (38%) eyes. In the Type 1 group, 6.7% developed ORT. Outer retinal tubulation developed in 61% of eyes with some Type 2 component of the MNV. Among eyes that developed ORT, 92.7% presented with some Type 2 component. In a multivariate analysis, Type 2 membranes on optical coherence tomography (22.2 [6.1-80.8]; P < 0.001), larger MNV size {>1 DA (5.1 [1.1-24.2]; P = 0.041) and >1.5 DA (9.0 [1.8-44.0]; P = 0.007)}, and presence of subretinal fibrovascular material (3.1 [1.1-8.5]; P = < 0.03) are associated with higher odds of ORT formation. Once the ORT is formed, fibrosis was observed directly underlying the ORT on SD-optical coherence tomography in 70.9% of cases. Type 2 membranes at presentation predict ORT formation. Fibrosis often underlies ORT. This suggests that contraction of Type 2 MNV-derived fibrosis may be important in ORT formation.

Incidence and Factors of Postoperative Lens Opacity after Lens-Sparing Vitrectomy for Retinopathy of Prematurity

To determine the incidence and factors associated with lens opacity after lens-sparing vitrectomy (LSV) for retinopathy of prematurity (ROP). Retrospective, comparative case series. Among the 141 eyes of 94 patients who underwent LSV for ROP between 2006 and 2019, 108 eyes of 71 patients with a minimum follow-up of 12 months after LSV were investigated. Data were collected from patients' charts, including gender, gestational age at birth, birth weight, stage of ROP, postmenstrual age (PMA) at LSV, surgical procedure, preoperative injection of anti-vascular endothelial growth factor (VEGF) agents, subsequent retinal surgeries, and lensectomy during follow-up. Lens status at last visit, incidence and timing of lensectomy, and risk factors for lens opacity requiring lensectomy. Stages of ROP at LSV were 4A, 4B, and 5 in 92 eyes, 13 eyes, and 3 eyes, respectively. The median PMA at LSV was 40.6 weeks. Thirty-two eyes received anti-VEGF therapy before LSV. Lens opacity was found in 17 eyes (15.7%), of which 10 eyes (9.3%) underwent lensectomy. The period between LSV and lensectomy ranged from 21 days to 131.9 months (median, 21.1 months). Eleven other eyes (10.2%) underwent lensectomy as part of a reoperation for worsening of ROP. A total of 80 eyes (74.1%) preserved clear lenses at the latest follow-up examination after surgery (median, 6.8 years; range, 1-14 years). The Kaplan-Meier estimate showed that the proportion of patients with phakia at 5 and 10 years was 92.4% and 89.0%, respectively. Multivariate Cox regression analysis revealed that eyes with the use of tamponade at LSV (P= 0.005; odds ratio [OR], 25.68; 95% confidence interval [CI], 4.187-157.5) and young PMA at LSV (P= 0.033; OR, 1.047; 95% CI, 1.012-1.099) were associated significantly with lens opacity requiring lensectomy. However, anti-VEGF therapy was not associated with lens opacity requiring lensectomy. Nearly 10% of eyes required lensectomy because of lens opacity after LSV for ROP. The development of lens opacity requiring lensectomy seems to be associated with the use of tamponade and young PMA at LSV.

Translational Research in Retinopathy of Prematurity: From Bedside to Bench and Back Again.

Retinopathy of prematurity (ROP), a vascular proliferative disease affecting preterm infants, is a leading cause of childhood blindness. Various studies have investigated the pathogenesis of ROP. Clinical experience indicates that oxygen levels are strongly correlated with ROP development, which led to the development of oxygen-induced retinopathy (OIR) as an animal model of ROP. OIR has been used extensively to investigate the molecular mechanisms underlying ROP and to evaluate the efficacy of new drug candidates. Large clinical trials have demonstrated the efficacy of anti-vascular endothelial growth factor (VEGF) agents to treat ROP, and anti-VEGF therapy is presently becoming the first-line treatment worldwide. Anti-VEGF therapy has advantages over conventional treatments, including being minimally invasive with a low risk of refractive error. However, long-term safety concerns and the risk of late recurrence limit this treatment. There is an unmet medical need for novel ROP therapies, which need to be addressed by safe and minimally invasive therapies. The recent progress in biotechnology has contributed greatly to translational research. In this review, we outline how basic ROP research has evolved with clinical experience and the subsequent emergence of new drugs. We discuss previous and ongoing trials and present the candidate molecules expected to become novel targets.

Retinal venous pressure is decreased after anti-VEGF therapy in patients with retinal vein occlusion\u2013related macular edema

PurposeThe pathomechanism leading to retinal vein occlusion (RVO) is unclear. Mechanical compression, thrombosis, and functional contractions of veins are discussed as the reasons for the increased resistance of venous outflow. We evaluated changes in the retinal venous pressure (RVP) following intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent to determine the effect on RVO-related macular edema.MethodsTwenty-six patients with RVO-related macular edema (16 branch RVOs [BRVOs] and 10 central RVOs [CRVOs], age 72.5 ± 8.8 years) who visited our hospital were included in this prospective study. Visual acuity (VA), intraocular pressure (IOP), central retinal thickness (CRT) determined by macular optical coherence tomography, and RVP measured using an ophthalmodynamometer were obtained before intravitreal injection of ranibizumab (IVR) and 1 month later.ResultsComparison of the BRVOs and CRVOs showed that VA was significantly improved by a single injection in BRVOs (P < 0.0001; P = 0.1087 for CRVOs), but CRT and RVP were significantly decreased without significant difference in IOP after the treatment in both groups (P < 0.0001).ConclusionThe anti-VEGF treatment resulted in a significant decrease in the RVP, but the RVP remained significantly higher than the IOP. An increased RVP plays a decisive role in the formation of macula edema, and reducing it is desirable.

How do alternative regimens compare with monthly injection of anti-vascular endothelial growth factor agents for treating neovascular age-related macular degeneration (ARMD)?

How do alternative regimens compare with monthly injection of anti-vascular endothelial growth factor agents for treating neovascular age-related macular degeneration (ARMD)?

The HIF-1α/p53/miRNA-34a/Klotho axis in retinal pigment epithelial cells promotes subretinal fibrosis and exacerbates choroidal neovascularization.

Wet age‐related macular degeneration (wAMD), characterized by choroidal neovascularization (CNV), is a leading cause of irreversible vision loss among elderly people in developed nations. Subretinal fibrosis, mediated by epithelial‐mesenchymal transition (EMT) of retinal pigment epithelium (RPE) cells, leads to unsuccessful anti‐vascular endothelial growth factor (VEGF) agent treatments in CNV patients. Under hypoxic conditions, hypoxia‐inducible factor‐1α (HIF‐1α) increases the stability and activation of p53, which activates microRNA‐34a (miRNA‐34a) transcription to promote fibrosis. Additionally, Klotho is a target gene of miRNA‐34a that inhibits fibrosis. This study aimed to explore the role of the HIF‐1α/p53/miRNA‐34a/Klotho axis in subretinal fibrosis and CNV. Hypoxia‐induced HIF‐1α promoted p53 stability, phosphorylation and nuclear translocation in ARPE‐19 cells (a human RPE cell line). HIF‐1α‐dependent p53 activation up‐regulated miRNA‐34a expression in ARPE‐19 cells following hypoxia. Moreover, hypoxia‐induced p53‐dependent miRNA‐34a inhibited the expression of Klotho in ARPE‐19 cells. Additionally, the HIF‐1α/p53/miRNA‐34a/Klotho axis facilitated hypoxia‐induced EMT in ARPE‐19 cells. In vivo, blockade of the HIF‐1α/p53/miRNA‐34a/Klotho axis alleviated the formation of mouse laser‐induced CNV and subretinal fibrosis. In short, the HIF‐1α/p53/miRNA‐34a/Klotho axis in RPE cells promoted subretinal fibrosis, thus aggravating the formation of CNV.

Longer-acting treatments for neovascular age-related macular degeneration-present and future.

The treatment of neovascular AMD (nAMD) has been revolutionized by the introduction of anti-vascular endothelial growth factor (VEGF) agents. Though, there is a tremendous gap between the outcomes in randomized clinical trials and real-world settings, where long-term outcomes are not as good as expected. This is due to undertreatment, i.e., fewer injection and low monitoring frequency. Treatment burden due to frequent injections remains a major limitation. Long-lasting treatments provide promising solutions for this unmet need by achieving better results with less mandatory injections. This review aims to cover the current state in this field and also discuss the mechanism of action, data from pivotal trials, and safety profile of long-acting treatments in present and future, going into details about the following agents: Brolucizumab, Faricimab, Abipicar, and Conbercept.

Treatment patterns for retinal diseases in patients newly-treated with anti-VEGF agents: A retrospective analysis of claims data from the Japan Medical Data Center database.

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. This non-interventional, descriptive, retrospective, observational cohort study included insured Japanese patients aged ≥ 21 and ≤ 75years at index date (anti-VEGF treatment initiation). 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 12months post-index date. The median (interquartile range) number of claims for anti-VEGF injections during 12months 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 12months pre-index date and 21 (8.24%), 85 (38.12%) and 62 (49.60%) in the 12months post-index date, respectively. 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.

Increased expression of adenosine 2A receptors in metastatic renal cell carcinoma is associated with poorer response to anti-vascular endothelial growth factor agents and anti-PD-1/Anti-CTLA4 antibodies and shorter survival

BackgroundAdenosine and its adenosine 2A receptors (A2AR) mediate the immunosuppressive mechanism by which tumors escape immunosurveillance and impede anti-tumor immunity within the tumor microenvironment. However, we do not know whether the adenosine pathway (CD39/CD73/A2AR) plays a role in renal cell carcinoma (RCC). Therefore, we studied the role of immunosuppression in RCC by assessing the adenosine pathway in patients with RCC treated with anti-vascular endothelial growth factor (anti-VEGF) agents or immune checkpoints inhibitors (ICIs) or both.MethodsIn 60 patients with metastatic RCC, we examined the expression of CD39, CD73, A2AR, and programmed cell death 1 ligand 1 (PD-L1) immunohistochemically in surgically resected tumor tissues and studied the clinicopathological characteristics of these patients. Patients were treated by cytoreductive nephrectomy with systemic therapy with anti-VEGF agent or a combination of the ICIs anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibody and programmed cell death 1 (PD-1) antibody.ResultsIncreased expression of A2AR in the primary tumors was associated with metastatic profiles. Patients treated with anti–PD-1 antibody in monotherapy, a combination of anti-PD-1 and anti-CTLA4 antibodies, or anti-VEGF agents showed better response and longer overall survival if the primary tumor had higher PD-L1 expression and lower A2AR expression. In Cox multivariate regression analysis, higher expression of A2AR was associated with shorter overall survival.ConclusionsOur findings suggest that the expression of A2AR and PD-L1 in the primary tumors in RCC might predict the outcomes of treatment with anti-VEGF agents and ICIs and that the A2AR pathway might be a molecular target for immunotherapy.

One year outcomes of eyes with polypoidal choroidal vasculopathy with ≥20/40 visual acuity treated with anti-vascular endothelial growth factor agents.

PURPOSE:To report the 12 months outcomes of treatment naïve polypoidal choroidal vasculopathy (PCV) in patients with ≥20/40 Snellen's best-corrected visual acuity (BCVA).METHODS:This was a retrospective study including eyes treated with monotherapy of anti-vascular endothelial growth factors (VEGF) agents (bevacizumab, ranibizumab, aflibercept, and ziv-aflibercept) on a pro-re-nata (PRN) protocol. Photodynamic therapy using verteporfin (vPDT) was used as rescue therapy. The primary study objective was change in BCVA at 12 months. Secondary objectives included change in optical coherence tomography parameters: central macular thickness (CMT) and pigment epithelial detachment (PED) height, the mean number of injections, and treatment-free interval at 12 months.RESULTS:A total of 18 eyes of 18 patients (7 males, 11 females) were included. The mean age was 58.0 ± 12.0 years. BCVA at baseline and 12 months were 0.16 ± 0.08 (Snellen equivalent 20/30) and 0.15 ± 0.15 logarithm of the minimum angle of resolution (20/30), respectively. Twelve (66.6%) eyes either improved or maintained BCVA. Mean (±standard deviation [SD]) CMT at baseline and 12 months were 188.2 ± 61.1 μ and 161.7 ± 47.4 μ (P = 0.15), respectively. PED height improved to 236.4 ± 208.7 μ at 12 months (P = 0.05). The mean (±SD) number of injections was 3.28 ± 1.96 with a treatment-free period of 6.83 ± 3.63 months. Three eyes required vPDT (4 treatment sessions; mean: 1.33) as a rescue therapy through 12 months.CONCLUSION:PRN anti-VEGF monotherapy in real-life situations for the treatment of naïve PCV eyes with good visual acuity (≥20/40) achieves maintenance or improvement of visual acuity through 12 months follow-up.

Multifocal Choroiditis: Clinic, Diagnosis, and Treatment

Multifocal choroiditis is a posterior chorioretinal inflammatory disease of unknown etiology. The acute chorioretinal lesions subsequently scar with the proliferation of retinal pigment epithelium and fibrosis, which may, in turn, lead to the occurrence of choroidal neovascular membranes and irreversible visual loss. Although there is no generally accepted standard treatment, anti‑inflammatory and anti-vascular endothelial growth factor agents are necessary for the acute stage to control the inflammation and choroidal neovascularization.

Active concurrent central serous chorioretinopathy and pachychoroid neovasculopathy managed with combination therapy of photodynamic therapy and anti-vascular endothelial growth factor agent

Pachychoroid disease spectrum includes central serous chorioretinopathy (CSR) and pachychoroid neovasculopathy (PNV). Pachychoroid phenotype is characterized by choroidal hyperpermeability, dilated choroidal vessels (pachyvessels), and focal or diffuse increase in choroidal thickness. Newer imaging modalities have aided in the diagnosis of choroidal diseases. Herein, we present a case of active concurrent CSR with PNV in a middle-aged patient with successful treatment by photodynamic therapy and intravitreal anti-vascular endothelial growth factor (VEGF) (ranibizumab) injection.

Opportunities and Challenges in Translational Research: The Development of Photodynamic Therapy and Anti-Vascular Endothelial Growth Factor Drugs

The development of photodynamic therapy and anti-vascular endothelial growth factor agents have revolutionized the treatment of retinal diseases, transforming the retina subspecialty by ushering in an age of pharmacological treatments for a wide range of diseases, including age-related macular degeneration (AMD).

Efficacy and safety of Ziv-aflibercept in patients with central retinal vein occlusion

Background Retinal vein occlusion is one of the most common vascular disorders that can cause visual loss. It is classified into central retinal vein occlusion (CRVO) and branch retinal vein occlusion. The most common cause of visual loss in CRVO is cystoid macular edema. Intravitreal injection of many antivascular endothelial growth factor agents can treat cystoid macular edema that occur owing to CRVO.Purpose The aim of the present study was to evaluate the efficacy of a new drug (Ziv-aflibercept) in the management of patients with CRVO.Patients and methods This is a prospective interventional study that was conducted on 15 eyes of 15 patients of recently diagnosed nonischemic CRVO of less than 2-month duration. Three loading doses of 1.25 mg of Ziv-aflibercept were given 1 month apart for each patient and then continued as needed in a pro re nata regimen. Complete ophthalmic evaluation was done at the Ophthalmology Department of Tanta University, including best-corrected visual acuity (BCVA), fundus examination, intraocular pressure measurement, and anterior segment examination. Optical coherence tomography (TOPCON 3D optical coherence tomography machine) was done for all patients at presentation and 1 month after each injection and then monthly during the follow-up period, which persisted for 6 months.Results The intraocular pressure did not show a statistically significant increase after intravitreal injection of Ziv-aflibercept. The BCVA improved significantly from 0.87±0.10 to 0.32±0.12 LogMAR after injection (P=0.001). The central macular thickness decreased significantly from a baseline value of 771±141.87 μm before injection to 306.67±91.51 μm after the three loading doses and to 208.07±12.97 μm after 6 months (P=0.001). There was no statistically significant correlation between the final BCVA and the final central macular thickness after 6 months (r=0.054, P=0.848). No serious complications were reported, such as endophthalmitis, vitreous hemorrhage, retinal detachment, or stroke.Conclusion Ziv-aflibercept is a highly effective drug in cases of nonischemic CRVO with a high safety profile and a relatively low cost.

Experience with Intravitreal Ranibizumab as an Adjunct to Ablation Therapy in Eyes with Exudative Coats' Disease.

BackgroundCoats’ disease is a rare entity with retinal vascular telangiectasia that can progress to exudative retinal detachment, neovascular glaucoma, and a blind painful eye requiring enucleation. Despite recent therapeutic advances decreasing the need for enucleation, no consensus exists about the optimum management of exudative Coats’ disease. The use of intravitreal anti-vascular endothelial growth factor agents as an adjunct to ablation therapy has been shown to achieve favorable outcomes, but some reports suggest an increased incidence of vitreoretinal (VR) fibrosis and tractional retinal detachment (TRD).MethodsWe retrospectively reviewed records of patients presenting with exudative Coats’ disease (stages 2 and 3) from April 2016 till November 2020. Extracted data included clinical and radiological assessment, stage (Shields’ classification), interventions, and follow-up.ResultsSixteen eyes were included in the final analysis, of which 4 (25%) were stage 2 and 12 (75%) were stage 3. All eyes underwent intravitreal ranibizumab injection combined with ablation therapy, 14 (87.5%) underwent cryotherapy, 4 (25%) underwent laser ablation, 3 (18.75%) underwent external subretinal fluid drainage, and 3 (18.75%) underwent buckle or vitrectomy surgery. After a median follow-up of 16 months, 11 eyes (68.75%) had complete resolution, 4 (25%) had incomplete resolution, and only one (6.25%) progressed but did not require enucleation. Three eyes (18.75%) developed VR fibrosis, but none progressed to TRD.ConclusionCombining intravitreal ranibizumab injection with ablation therapy is effective in managing exudative Coats’ disease. External drainage should be preserved for when ablation therapy is not feasible. Future prospective trials with pre-defined outcomes are required.