Intravitreal Anti-vascular Endothelial Growth Factor Research Articles

BULBOSITIES AND INTERVORTEX VENOUS ANASTOMOSIS IN VENOUS OVERLOAD CHOROIDOPATHY MASQUERADING AS POLYPOIDAL CHOROIDAL VASCULOPATHY.

To describe a patient with venous overload choroidopathy in whom venous bulbosities masqueraded as polyps and intervortex venous anastomosis mimicked a branching vascular network, giving the appearance of polypoidal choroidal vasculopathy. The patient had complete ophthalmic examination including indocyanine green angiography and optical coherence tomography. Venous bulbosities were defined on indocyanine green angiography as focal dilations in which the diameter of the dilation is two times that of the host vessel. A 75-year-old woman presented with combined subretinal and subretinal pigment epithelium hemorrhages in the right eye. During indocyanine green angiography, focal nodular hyperfluorescent lesions connected to a network of vessels were observed, which looked like polyps and branching vascular network in polypoidal choroidal vasculopathy. In both eyes, the midphase angiogram had multifocal choroidal vascular hyperpermeability. There was late-phase placoid staining nasal to the nerve in the right eye. During enhanced depth imaging-optical coherence tomography evaluation, there were no retinal pigment epithelium elevations that would be expected with polyps or branching vascular network in the right eye. A double-layer sign was seen corresponding to the placoid area of staining. Diagnosis of venous overload choroidopathy and choroidal neovascularization membrane was made. She was treated with intravitreal antivascular endothelial growth factor injections for the choroidal neovascularization membrane. Indocyanine green angiography findings in venous overload choroidopathy may mimic polypoidal choroidal vasculopathy, but differentiation is essential because it has implications for treatment. Similar findings may have been misinterpreted in the past and may have previously contributed to conflicting clinical and histopathologic descriptions of polypoidal choroidal vasculopathy.

Risk of post-injection endophthalmitis peaks within the first three injections of anti-vascular endothelial growth factor therapy: A nationwide registry-based study.

To report the incidence of post-injection endophthalmitis (PIE) and the cumulative risk associated with repeated injections of intravitreal anti-vascular endothelial growth factor (anti-VEGF). We employed nationwide registries in Denmark to include all individuals aged ≥40 years who received at least one intravitreal anti-VEGF injection in 2007-2022. Our primary endpoint PIE was identified using specific diagnostic codes for endophthalmitis and procedure codes for vitreous biopsy within 10 days prior to and 120 days post-injection. Patients were stratified according to the underlying diagnoses for which they received the treatment. The relative risk (RR) for PIE was calculated between groups based on the number of injections received by the patients. We identified 60 825 patients who received intravitreal anti-VEGF treatment during study time, with a median age of 77.2 years and females constituting 58.1%. We identified 232 cases of PIE after 1 051 549 injections during follow-up, resulting in an incidence of 0.022% [95% CI 0.019%-0.025%]. Despite a linear growth in annual anti-VEGF use, the incidence remained stable at 0.020% [95% CI 0.017%-0.023%] from 2013 to 2022. Compared to patients receiving 1-3 injections, RR for patients receiving 4-20, 21-40, and >40 injections were 0.46 [95% CI 0.34-0.63], 0.32 [95% CI 0.21-0.50], and 0.54 [95% CI 0.36-0.81], respectively. Findings were similar across the different diagnoses. Based on 16 years of nationwide registry data, this study identified a low and stable incidence of PIE. Notably, the highest risk of endophthalmitis was within the first three anti-VEGF injections.

RETINAL VEIN OCCLUSIONS BEFORE AND DURING THE COVID-19 PANDEMIC: Visual Outcomes and Treatment Patterns in a Country with no Mandatory Lockdown.

To investigate the incidence, treatment patterns, and visual outcomes in patients with branch retinal vein occlusion (RVO) and central RVO before and during the COVID-19 pandemic in a country with no mandatory lockdown. This retrospective study included 788 patients presenting with a RVO during the years 2019 to 2022 at St. Erik Eye Hospital. The control group and study groups consisted of patients presenting before and during the pandemic, respectively. The incidence of diagnosed RVO cases decreased from 281 patients before the pandemic to 236 patients during the first year of the pandemic ( P < 0.05). In patients with branch RVO at the end of follow-up, the best-corrected visual acuity improved 10.3 letters (95% confidence intervals [CI] 7.6-12.9) in the control group compared with 14.3 letters (95% CI 12.6-16.0) in the study groups ( P < 0.05). In patients with central RVO, the best-corrected visual acuity improved 6.3 letters (95% CI 2.7-10.0) in the control group compared with 8.6 letters (95% CI 5.7-11.4) in the study groups (p = NS). Overall, the number of intravitreal anti-vascular endothelial growth factor injections increased from 7.0 (95% CI 6.6-7.3) in the control group to 7.6 (95% CI 7.4-7.8) in the study groups ( P < 0.05). Good visual and anatomical outcomes were sustained, and the number of intravitreal anti-vascular endothelial growth factor injections increased significantly in patients with RVO during the COVID-19 pandemic.

Gene Therapy for Non-Hereditary Retinal Disease: Age-Related Macular Degeneration, Diabetic Retinopathy, and Beyond.

Gene therapy holds promise as a transformative approach in the treatment landscape of age-related macular degeneration (AMD), diabetic retinopathy (DR), and diabetic macular edema (DME), aiming to address the challenges of frequent intravitreal anti-vascular endothelial growth factor (VEGF) injections. This manuscript reviews ongoing gene therapy clinical trials for these disorders, including ABBV-RGX-314, ixoberogene soroparvovec (ixo-vec), and 4D-150. ABBV-RGX-314 utilizes an adeno-associated virus (AAV) vector to deliver a transgene encoding a ranibizumab-like anti-VEGF antibody fragment, demonstrating promising results in Phase 1/2a and ongoing Phase 2b/3 trials. Ixo-vec employs an AAV2.7m8 capsid for intravitreal delivery of a transgene expressing aflibercept, showing encouraging outcomes in Phase 1 and ongoing Phase 2 trials. 4D-150 utilizes an evolved vector to express both aflibercept and a VEGF-C inhibitory RNAi, exhibiting positive interim results in Phase 1/2 studies. Other therapies reviewed include EXG102-031, FT-003, KH631, OLX10212, JNJ-1887, 4D-175, and OCU410. These therapies offer potential advantages of reduced treatment frequency and enhanced safety profiles, representing a paradigm shift in management towards durable and efficacious cellular-based biofactories. These advancements in gene therapy hold promise for improving outcomes in AMD and addressing the complex challenges of DME and DR, providing new avenues for the treatment of diabetic eye diseases.

Two-year Outcome of Intravitreal Anti-vascular Endothelial Growth Factor Therapy for Polypoidal Choroidal Vasculopathy

Two-year Outcome of Intravitreal Anti-vascular Endothelial Growth Factor Therapy for Polypoidal Choroidal Vasculopathy

Progression of macular retinoschisis following intravitreal aflibercept injection for myopic macular neovascularization—a case report and review of literature

BackgroundMacular retinoschisis (MRS) and myopic macular neovascularization (mMNV) are both potentially blinding complications of high myopia. In this case report, we highlight the progression of MRS after intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment for mMNV, as well as an extensive review of the literature on this topic.Case descriptionA 49-year-old woman presented with two weeks of recent onset blurring and metamorphopsia in her right eye. She had high myopia in both eyes (right eye − 20/60 with − 16D, left eye − 20/20 with − 13D). Slit-lamp ophthalmoscopy found a normal anterior segment in both eyes. On fundus examination, features of pathological myopia with posterior staphyloma and peripapillary atrophy were observed in both eyes. An active mMNV, as well as intraretinal fluid, minimal perifoveal inner and outer MRS, and focal posterior vitreous traction along the inferotemporal retinal arcade, were detected on optical coherence tomography (OCT) of the right eye. The patient received an intravitreal injection of Aflibercept (2 mg/0.05 ml).ResultsOCT scans at two- and four-month follow-up visits revealed regressed mMNV with a taut epiretinal membrane, progressive worsening of outer MRS, and the development of multiple perifoveal retinal detachment inferior to the fovea. Pars plana vitrectomy surgery was performed for the progressive MRS with good anatomical (resolved MRS) and functional outcome (maintained visual acuity at 20/60) at the last one-month post-surgery visit.ConclusionIntravitreal anti-VEGF injections for mMNV can cause vitreoretinal interface changes, exacerbating MRS and causing visual deterioration. Vitrectomy for MRS could be one of several treatment options.

Burden of Disease Study of Patients with Diabetic Macular Oedema in Spain.

Diabetic macular oedema (DMO) is a complication of diabetic retinopathy that can result in vision loss. The disease can impact different spheres of a patient's life, including physical and psychological health, work, and activities of daily living, entailing an important use of healthcare and non-healthcare resources. This study aimed to estimate the socio-economic burden of DMO in Spain. The burden of DMO was estimated from a societal perspective, per patient, year of treatment since diagnosis, and type of treatment. Four categories were considered: direct healthcare costs (DHC), direct non-healthcare costs (DNHC), labour productivity losses (LPL), and intangible costs (IC) associated with loss of quality of life. Average annual costs were calculated by multiplying the resources used per patient by their corresponding unit price (or financial proxy). For a more accurate estimation, differences in resource use between treatments (intravitreal anti-vascular endothelial growth factor injections of ranibizumab or aflibercept, and intravitreal dexamethasone implants) and year since diagnosis (first, second, and third year or beyond) were considered and presented separately. The reference year for costs was 2021. The average annual costs of DMO in the first year of treatment after diagnosis was estimated at €18,774, €17,512, and €16,188 per patient treated with ranibizumab, aflibercept, and dexamethasone, respectively. This burden would be reduced to €15,783, €15,701, and €12,233 in the second year, and to €15,119, €15,043, and €12,790 in the third year, respectively. Diagnosis of DMO entails an additional one-off cost of €485. DHC accounted for the greatest proportion of total annual costs per patient, independent of the year, with LPL also making an important contribution to total costs. The socio-economic impact of DMO on patients, the healthcare system, and society at large is substantial. The constant increase in its prevalence accentuates the need for planning and implementation of healthcare strategies to prevent vision loss and reduce the socio-economic burden of the disease.

Posterior vitreous attachment as a risk factor for endophthalmitis following intravitreal antivascular endothelial growth factor injection.

To evaluate the importance of the status of posterior vitreous in eyes with endophthalmitis following intravitreal anti-vascular endothelial growth factor (anti-VEGF). The absence or existence of posterior vitreous detachment (PVD) was elicited in 23 eyes of 23 patients with injection related endophthalmitis, during pars plana vitrectomy (PPV) and compared with 24 control eyes of 24 patients who received intravitreal anti-VEGF without any complication. Thirtten (54.2%) out of 24 patients in the control group had full PVD, whereas only 2 (9.5%) out of 23 eyes in endophthalmitis group (p < 0.001) had full PVD. In all eyes without PVD, posterior vitreous was inducted to be detached at least from optic nerve and macular area without any iatrogenic tear. The absence of PVD is a factor that increases the risk of endophthalmitis after intravitreal injections. Uncomplicated separation of the posterior vitreous from the retina in PPV contributes to better prognosis.

Aflibercept to treat retinopathy of prematurity: need for more research.

Until recently, the standard care for retinopathy of prematurity (ROP) was destructive treatment of the peripheral avascular retina, most often using laser therapy. Now, intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents have been included in recommendations for treatment-warranted ROP. The three anti-VEGF agents used to treat ROP are bevacizumab, ranibizumab, and aflibercept and clinical trials using, a variety of treatment strategies, have shown all three are efficacious and easy to administer. Intravitreal Bevacizumab is most used in the US, and ranibizumab has been approved for ROP use in Europe. In 2023, the FDA approved aflibercept for treatment of severe ROP. We summarize the clinical trial results and provide a side-by-side comparisons of the three drugs. Despite FDA approval of the use of aflibercept to treat ROP, there is a need for more research as the body of knowledge regarding this agent to treat ROP is limited.

Intravitreal Anti-Vascular Endothelial Growth Factor Treatment in Patients with Neovascular Age-Related Macular Degeneration and Poor Visual Acuity

Purpose: To investigate the significance of intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with neovascular age-related macular degeneration (nAMD) and poor visual acuity (VA). Methods: Retrospective study of patients with nAMD with baseline best corrected VA of ≤ 20/200. Patients were divided into regular treatment (RT) and scarce treatment (ST) groups according to whether they underwent consecutive intravitreal anti-VEGF treatments at intervals of ≤ 4 months or not. Results: A total of 131 eyes were included: 87 and 44 eyes in the RT and ST groups, respectively. RT group showed significantly improved preservation of lesion size at both years 1 and 2, with significantly fewer incidences of new subretinal hemorrhage (SRH). Improvements in VA, reduction in central subfield macular thickness (CST), and maximal height of choroidal neovascularization were significantly favorable in RT group at year 1, and CST was significantly decreased at year 2. Survival analysis revealed that RT group had significantly greater preservation of VA and lesion size than that in ST group. Conclusion: Maintaining intravitreal anti-VEGF treatment for patients with nAMD and poor vision showed significant advantages in VA and lesion size stability and reduced the incidence of new SRH, which suggests preservation of paracentral vision.

Systemic Oxidative Stress Level as a Pathological and Prognostic Factor in Myopic Choroidal Neovascularization

PurposeTo investigate the association of oxidative stress level with myopic choroidal neovascularization (mCNV) and its clinical outcomes. DesignRetrospective case-control study. ParticipantsThis retrospective study included 52 eyes of 52 healthy participants (mean age 62.5 years), 30 eyes of 30 patients (mean age 59.6 years) with high myopia (HM) and no mCNV, and 23 eyes of 23 patients (mean age 61.8 years) with HM and mCNV who received intravitreal anti-vascular endothelial growth factor antibody injections (IVIs) with a pro re nata regimen for 6 months after an initial IVI. MethodsClinical findings, including oxidative stress parameters, such as diacron reactive oxygen metabolites (dROMs), biological antioxidant potential (BAP), and BAP/dROM ratio (B/d ratio), were analyzed. Main Outcome MeasuresClinical features and oxidative stress parameters. ResultsBoth BAP and B/d ratio were significantly lower in the HM/mCNV group than in the HM/no mCNV group (P=0.002 and P=0.012, respectively) or the control group (P=0.001 and P=0.026, respectively). In a multivariate logistic regression analysis (adjusted for age, gender, and axial length), B/d ratio (OR=0.47, P=0.026) was significantly associated with mCNV. Dividing the patients into high and low B/d ratio groups (with a cutoff of 5.2) showed that subfoveal choroidal thickness (SFCT) was lower (P=0.002) and the number of IVI treatments was higher (P=0.029) in eyes with a low B/d ratio than in eyes with a high B/d ratio. In a multiple regression analysis (adjusted for age, gender, and axial length), only B/d ratio was significantly associated with SFCT (β=0.68, P=0.006). ConclusionThe oxidative stress level in eyes with HM differed according to mCNV, SFCT, and the number of IVI treatments. Measuring oxidative stress parameters might be useful in eyes with HM both for assessing the risk of developing mCNV and determining disease activity.

Chronic Serous Chorioretinopathy: A Case Study

Introduction Chronic central serous chorioretinopathy (CSCR) is characterized by persistent subretinal fluid that disrupts the outer layers of the retina and may lead to complications such as: outer retinal atrophy, increased risk of choroidal neovascularization (CNVM) and the potential for permanent vision loss. This report describes the clinical features of chronic CSCR. Case Presentation A 73-year-old male with a history of systemic steroid and inhaler use presented for a routine eye exam without visual complaints. Examination findings included normal visual acuity in both eyes and multiple areas of retinal hyper and hypopigmentation along the arcades with no macular involvement in the right eye; the left eye was unremarkable. Fundus photography and optical coherence tomography showed localized areas of outer retinal disruption and thinning near the optic nerve head and along the corresponding retinal areas of irregular pigmentation in the right eye; the left eye was unremarkable. Discussion In chronic CSCR, structural changes in the retina can lead to retinal dysfunction and permanent vision loss. Treatment options for chronic CSCR include photodynamic therapy, intravitreal anti-vascular endothelial growth factor therapy, or systemic steroid receptor blockers. Visual prognosis varies depending on the severity of the disease, age of onset, risk of CNVM and the degree of outer retinal degeneration. Conclusion Patients with chronic CSCR are at risk for permanent vision loss. The structural changes in the outer retina also increase the risk for CNVM. Hence, it is important that patients with chronic CSR receive regular eye examinations and are educated on the role of regular Amsler grid testing.

Short Term Effect of Pre-Operative Anti-VEGF on Angiogenic and Fibrotic Profile of Fibrovascular Membranes of Proliferative Diabetic Retinopathy.

Adjuvant, pre-operative intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have been used to reduce peri-operative bleeding in eyes undergoing pars-plana vitrectomy for complications of proliferative diabetic retinopathy (PDR). To address the concern over their potential off-target effects of progressive fibrous contraction, we sought to dissect the transcriptional changes in the surgically extracted fibrovascular membranes (FVMs). We analyzed surgically extracted FVMs from 10 eyes: 4 eyes pretreated with intravitreal bevacizumab (IVB) and 6 untreated eyes. FVMs were digested into single cells, mRNA was extracted from endothelial cell-enriched (microbead selection with CD31) and non-endothelial cell compartments, followed by RT-qPCR quantification. We then compared the relative expression of genes involved in angiogenesis, endothelial cell integrity, and myofibroblastic processes between treated and untreated FVMs. Endothelial cells from IVB pretreated FVMs showed significant reduction of VEGFA, VEGF receptors (FLT1 and KDR), and angiopoietin 2 expression as well as increased vascular endothelial cadherin and endothelin, suggesting reduced angiogenesis and enhanced vascular integrity. The non-endothelial cell fraction showed decreased expression of VEGFA and fibronectin, without significant difference in the expression of other profibrotic factors. Our findings confirm that adjuvant pre-operative IVB decreased fibronectin and increase endothelin-1 expression without affecting other profibrotic gene expression, uncovering an important interaction between IVB and endothelin-1 that deserves further study.

Non-surgical treatment of stage 4A retinopathy of prematurity

BackgroundRetinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants, often requiring surgical interventions in advanced stages. This retrospective case series study investigates non-surgical management for Stage 4A ROP, specifically the use of combined laser therapy and intravitreal anti-vascular endothelial growth factor (VEGF) injections.MethodsTen eyes from five infants with Stage 4A ROP were treated with a combined laser and anti-VEGF approach. Comprehensive follow-up examinations were conducted to evaluate the treatment outcomes.ResultsThe study demonstrated successful retinal attachment without complications, showcasing the efficacy and safety of this non-surgical method. A comparison with surgical interventions highlighted the potential benefits in terms of reduced adverse effects.DiscussionThis combined treatment emerges as a promising first-choice option for Stage 4A ROP, offering rapid regression without surgical intervention, particularly in early stages. However, larger randomized clinical trials are necessary to validate these findings and establish definitive guidelines for managing this complex condition.ConclusionCombined laser and anti-VEGF therapy proved to be an effective and safe non-surgical approach for Stage 4A ROP, with the potential to reduce the need for surgery, especially in its early presentation. Further research is required to confirm these findings and provide comprehensive recommendations for clinical practice.

Association between the response of intravitreal antivascular endothelial growth factor injection and systemic factors of diabetic macular edema

BackgroundThis study investigated the effects of systemic factors in response to intravitreal injections in patients with macular edema due to non-proliferative diabetic retinopathy (NPDR).MethodsWe retrospectively reviewed the medical records of patients treated with intravitreal injections for macular edema secondary to NPDR between January 2018 and January 2021. The patients were divided into three groups according to the injection response. When patients with diabetic macular edema showed 20µ or more reduction in central retinal thickness compared to baseline, they were classified as responsive group, and if not, they were classified as refractory group. The responsive group was further divided into the complete and incomplete response groups. Patients with complete disappearance of edema at seven months were classified as the complete response group, whereas those in which edema did not disappear were classified as the incomplete response group. The clinical characteristics of each group, including medical history, ophthalmic examination results, and laboratory examination results at the time of diagnosis, were analyzed.ResultsOf the 112 eyes (91 patients) that satisfied the inclusion criteria, 89 (77 patients) in the responsive group and 23 (14 patients) in the refractory group were included in the analysis. The responsive group was further divided into the complete (51 eyes) and incomplete (38 eyes) response groups. The refractory group had significantly higher glycated hemoglobin levels and significantly lower estimated glomerular filtration rates than the responsive group (p = 0.026 and p = 0.012, respectively). In the multivariate logistic regression analysis, both factors were found to be significant in predicting the degree of response (all p < 0.05). No factor showed a significant difference between the incomplete and complete response groups(all p > 0.05).ConclusionsIn macular edema caused by NPDR, low glomerular filtration rates and high glycated hemoglobin levels may be used as predictors of poor response to intravitreal injection therapy. In addition to blood glucose control, education should be provided regarding the need for the continuous monitoring of renal function.

Ocular blood flow in preterm neonates

Retinopathy of prematurity (ROP) is a disorder affecting low birthweight, preterm neonates. In the preterm eye, the retina is not fully developed and neovascularization may occur at the margin between the developed vascular retina and undeveloped avascular retina. Without timely treatment by laser or intravitreal anti-vascular endothelial growth factor (VEGF) therapy, this can lead to tractional retinal detachment and blindness. Visualization of the retina in regular examinations by indirect ophthalmoscopy is hence the current standard of care, but the exams are stressful and interpretation of images is subjective. The upregulation of VEGF in ROP would suggest an increase in ocular blood flow. In this report, we evaluate the potential of ultrafast plane-wave Doppler ultrasound (PWU) to detect increased flow velocities in the orbital vessels supplying the eye in a gentle exam with objective findings. We imaged both eyes of 50 low-birthweight preterm neonates using 18 MHz PWU. Flow velocity in the central retinal artery (CRA) and vein (CRV), and the short posterior ciliary arteries were determined and values at each ROP Stage compared. We found significantly increased velocities in the CRA and CRV in Stage 3 ROP eyes, where intervention would be considered. We compared multivariate models for identifying Stage 3 eyes comprised solely of clinical factors, solely of Doppler parameters, and clinical plus Doppler parameters. The respective models provided areas under their respective ROC curves of 0.760, 0.812, and 0.904. PWU Doppler represents a gentle, objective means for identifying neonates at risk for ROP that could complement ophthalmoscopy.

CENTRAL BOUQUET HEMORRHAGE: Clinical and Multimodal Imaging Features.

To describe the clinical characteristics, multimodal imaging features, and anatomic basis of a distinctive pattern of deep retinal hemorrhages located in the central fovea, a presentation referred to as "central bouquet hemorrhage." Retrospective, observational, multicenter case series of eyes with central bouquet hemorrhage. Multimodal imaging features were reviewed and analyzed. Ten eyes from 10 patients (4 women and 6 men), with a mean age of 55.6 ± 21.7 years (range 25-84 years) were included. Underlying etiologies were neovascular age-related macular degeneration (40%), lacquer cracks in pathological myopia (30%), macular telangiectasia Type 2 (10%), proliferative diabetic retinopathy (10%), and ocular trauma associated with angioid streaks (10%). On ophthalmoscopy, all eyes with central bouquet hemorrhage displayed a deep retinal hemorrhage with round margins in the central fovea and associated with petaloid hemorrhages radiating in the surrounding Henle fiber layer. Cross-sectional optical coherence tomography showed a well-delineated round hyperreflective lesion involving the central foveal Henle fiber layer/outer nuclear layer in all cases. Accompanying hyperreflective hemorrhages tracking along the obliquely oriented Henle fiber layer were present in all eyes. Resolution occurred in all patients, either spontaneously (30%) or after treatment with intravitreal anti-vascular endothelial growth factor injections (70%), and was associated with partial visual acuity improvement (from 20/113 to 20/36). "Central bouquet hemorrhage" is a novel descriptive term describing a characteristic round pattern of intraretinal blood in the fovea associated with Henle fiber layer hemorrhage and encountered in a spectrum of macular disease.

Enhancing Diabetic Macular Edema Treatment Outcomes: Exploring the ESASO Classification and Structural OCT Biomarkers.

This study assessed the European School of Advanced Studies in Ophthalmology (ESASO) classification's prognostic value for diabetic macular edema (DME) in predicting intravitreal therapy outcomes. In this retrospective, multicenter study, patients aged > 50years with type 1 or 2 diabetes and DME received intravitreal antivascular endothelial growth factor (anti-VEGF) agents (ranibizumab, bevacizumab, and aflibercept) or steroids (dexamethasone). The primary outcome was visual acuity (VA) change post-treatment, termed as functional response, measured 4-6weeks post-third anti-VEGF or 12-16weeks post-steroid injection, stratified by initial DME stage. Of the 560 eyes studied (62% male, mean age 66.7years), 31% were classified as stage 1 (early), 50% stage 2 (advanced), 17% stage 3 (severe), and 2% stage 4 (atrophic). Visual acuity (VA; decimal) improved by 0.12-0.15 decimals in stages 1-2 but only 0.03 decimal in stage 3 (all p < 0.0001) and 0.01 in stage 4 (p = 0.38). Even in eyes with low baseline VA ≤ 0.3, improvements were significant only in stages 1 and 2 (0.12 and 0.17 decimals, respectively). Central subfield thickness (CST) improvement was greatest in stage 3 (-229µm, 37.6%, p < 0.0001), but uncorrelated with VA gains, unlike stages 1 and 2 (respectively: -142µm, 27.4%; - 5µm, 12%; both p < 0.0001). Stage 4 showed no significant CST change. Baseline disorganization of retinal inner layers and focal damage of the ellipsoid zone/external limiting membrane did not influence VA improvement in stages 1 and 2. Treatment patterns varied, with 61% receiving anti-VEGF and 39% dexamethasone, influenced by DME stage, with no significant differences between therapeutic agents. The ESASO classification, which views the retina as a neurovascular unit and integrates multiple biomarkers, surpasses single biomarkers in predicting visual outcomes. Significant functional improvement occurred only in stages 1 and 2, suggesting reversible damage, whereas stages 3 and 4 likely reflect irreversible damage.

Incidence of Blepharoptosis Following Intravitreal Anti–Vascular Endothelial Growth Factor Injections

PurposeWe aimed to determine the incidence of blepharoptosis following intravitreal anti-vascular endothelial growth factor (VEGF) injections and compare the rates of blepharoptosis between patients injected with an eyelid speculum and those injected without a speculum. DesignRetrospective cohort study MethodsInternational Classification of Diseases (ICD-10) was used to identify patients with exudative age-related macular degeneration (AMD) and those who developed ptosis following intravitreal injections. Patients with nonexudative AMD who did not receive intravitreal injections served as control. The outcomes were the incidence of ptosis in the injection group compared to the non-injection group and incidence of ptosis in patients whose injections were performed with an eyelid speculum as compared to those whose injections were performed without specula. ResultsWe recruited 1,100 exudative AMD patients who received at least one intravitreal anti-VEGF injection and 2,258 nonexudative AMD patients who had not received an injection. In the injection group, 18 out of 1100 patients (1.6%) developed ptosis, compared to 52 out of 2258 patients (2.3%) in the non-injection group (p=0.25). Within the injection group, ptosis was mostly bilateral, diagnosed on average 22.4 months following the initial injection, and following more than a one-year injection-free period. 11 out of 537 patients (2.0%) injected without a speculum developed ptosis, compared to 8 out of 444 patients (1.8%) injected with a speculum (p= 0.82). ConclusionsNo statistically significant differences in incidence rates of ptosis were observed. In this analysis, neither intravitreal anti-VEGF injections nor speculum use during injections appears to increase the risk of ptosis.

Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study

Objective or PurposeA) To characterize the incidence of kidney failure associated with intravitreal anti-vascular endothelial growth factor (VEGF) exposure, and B) compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DesignRetrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. Subjects, Participants, and/or ControlsSubjects aged ≥18 years with ≥3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). Methods, Intervention, or TestingA) The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. B) For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random-effects meta-analysis was performed to combine each database’s hazard ratio (HR) estimate into a single network-wide estimate. Main Outcome MeasuresIncidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. ResultsOf the 6.1 million patients with blinding diseases, 37,189 who received ranibizumab, 39,447 aflibercept, and 163,611 bevacizumab were included; the total treatment exposure time was 161,724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100,000 persons (range 0 to 2389), and incidence rate 743 per 100,000 person-years (0 to 2661). The meta-analysis HR of kidney failure comparing aflibercept to ranibizumab was 1.01 (95% confidence interval (CI) 0.70, 1.47, p=0.45), ranibizumab to bevacizumab 0.95 (95% CI 0.68, 1.32, p=0.62), and aflibercept to bevacizumab 0.95 (95% CI 0.65, 1.39, p=0.60). ConclusionsThere was no substantially different relative risk for kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk for kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents.