Intravitreal anti-VEGF Injections Research Articles

The impact of Vitreo-Macular interface abnormalities on the response to Anti-VEGF therapy for centre involving diabetic macular oedema.

The influence of Vitreomacular Interface Abnormalities (VMIA) such as Epiretinal Membrane (ERM) and/or vitreomacular traction (VMT) on the response of patients with Centre Involving Diabetic Macular Edema (CIDME) to standard of care Anti-VEGF medications is under-researched. The aims of this study were: 1) To determine the incidence of VMIA at baseline and 12 months amongst treatment naive patients commencing anti-VEGF treatment 2) To compare the response to Anti-VEGF medications at 3 monthly intervals for 12 months in a large cohort of patients with and without VMIA on their baseline OCT scan. Response was determined in terms of: number of injections, central macular thickness and visual acuity. A retrospective case notes review of treatment naïve patients with newly diagnosed CIDME. Included patients had been commenced on intravitreal Anti-VEGF injections (ranibizumab or aflibercept) at a single centre. Inclusion criteria were: treatment naïve DME patients with a CMT of 400μ or more receiving anti-VEGF treatment with at least 12 months follow up and in whom macular OCT scans and visual acuity (VA) measurements were available within two weeks of baseline, 3, 6, 9 and 12 months. Exclusion criteria included: previous intravitreal therapy, previous vitrectomy, cataract surgery during the follow-up period, concurrent eye conditions affecting vision or CMT. 119 eyes met the inclusion criteria and underwent analysis. Groups were comparable in their baseline demographics. Baseline CMT measurements were comparable at baseline (417μ and 430μ in the No-VMIA and VMIA groups respectively) and improved to approximately 300μ in both groups. From 6 months CMT continued to improve in the no-VMIA while progressively deteriorating in the VMIA group. Change in CMT was statistically different at 12 months between the 2 groups (108μ and 79μ, p= 0.04). There was a mean of 7 injections after 12 months. Our study has shown a 46% incidence of VMIA amongst patients newly diagnosed with centre involving DME undergoing treatment with anti-VEGF injections. We have also demonstrated a significant difference in CMT and VA response to anti-VEGF treatment in patients with and without VMIA. Initial response was similar between the 2 groups up until 6 months. From 6 to 12 months significant differences in treatment response emerged. Differences in clinical response between patients with and without VMIA may help guide further prospective controlled studies and optimise treatment strategies.

Genetics in neovascular age-related macular degeneration susceptibility and treatment response to anti-VEGF intravitreal injection: A case series study.

To identify genotypes associated with neovascular age-related macular degeneration (nAMD) and investigate the associations between genotype variations and anti-vascular endothelial growth factor (VEGF) treatment response. This observational, retrospective, case series study enrolled patients diagnosed with nAMD who received anti-VEGF treatment in National Taiwan University Hospital with at least one-year follow-up between 2012 and 2020. A genome-wide association study (GWAS) was conducted on enrolled patients and controls. Correlations between the genotypes identified from GWAS and the treatment response of functional/anatomical biomarkers, including visual acuity (VA), presence of intraretinal or subretinal fluid (SRF), serous or fibrovascular pigmented epithelium detachment (PED), and disruption of the ellipsoid zone (EZ), were analysed. In total, 182 patients with nAMD and 1748 controls were enrolled. GWAS revealed 16 single nucleotide polymorphisms (SNPs) as risk loci for nAMD, including seven loci in CFH and ARMS2/HTRA1 and nine novel loci, including rs117517872 and rs79835234(COPB2-DT), rs7525578(RAP1A), rs2123738(LOC105376755), rs1374879(CNTN3), rs3812692(SAR1A), rs117501587(PRKCA), rs9965945(CNDP1), and rs189769231(MATK). Our study revealed rs800292(CFH), rs11200638(HTRA1), and rs2123738(LOC105376755) correlated with poor treatment response in VA (P = 0.005), SRF (P = 0.044), and fibrovascular PED (P = 0.007), respectively. Rs9965945(CNDP1) was correlated with poor response in disruption of EZ (P = 0.046) and serous PED (P = 0.049). Among the 16 SNPs found in the GWAS, four loci-CFH, ARMS2/HTRA1, and two novel loci-were correlated with the susceptibility of nAMD and anatomical/functional responses after anti-VEGF treatment.

Does addition of intravitreal bevacizumab confer additional benefit in management of proliferative diabetic retinopathy?

To evaluate visual outcome and complications of PDR after treatment with Intravitreal Bevacizumab followed by Pan Retinal Photocoagulation A hospital based retrospective study was done in the Department of Ophthalmology, to evaluate visual outcome and complications of PDR after treatment with intravitreal Bevacizumab followed by Pan Retinal Photocoagulation. Visual Acuity, Dilated fundus examination, OCT macula were done on subsequent follow ups 135 eyes of 133 patients were included in the study.The mean pre procedure visual acuity is 0.639±0.5327 which improved to 0.451±0.4089 post procedure. P value is <0.001 which is statistically significant.i.e, 94 (69.62%) eyes had improved vision, 21(15.55%) had stable vision and 20(14.81%) eyes had decreased vision. After injection followed by PRP out of 135 eyes,4(2.96%) eyes developed vitreous hemorrhage which resolved with repeat intravitreal anti-VEGF injection, 6(4.44%) eyes developed diabetic macular edema,3(2.2%) eyes developed Neovascularisation of iris and 4(2.96%)eyes developed vitreous hemorrhage with traction retinal detachment.From our study it appears that addition of intravitreal anti VEGF to Pan Retinal Photocoagulation for PDR confers the additional benefit of less incidence of vitreous hemorrhage and less incidence of traction retinal detachment requiring surgery in the 1 one year of follow up. This amounts to more compliance by the patient for taking the treatment as well as better visual outcome

The landscape of angiogenesis and inflammatory factors in eyes with myopic choroidal neovascularization before and after anti-VEGF injection

IntroductionTo investigate the levels of angiogenesis and inflammatory cytokines in individuals with myopic choroidal neovascularization (mCNV) and the changes in these factors following intravitreal anti-VEGF injection. MethodsAqueous humor samples were gathered from eyes with mCNV, those with single macular bleeding (SMB) without mCNV in highly myopic eyes, and those with age-related cataracts. Using a multiplex bead immunoassay, we analyzed 28 angiogenesis and inflammatory factors in the aqueous humor. Furthermore, clinical data were documented for correlation analysis. ResultsIn this study, the levels of vascular endothelial growth factor A (VEGF-A), interleukin 8 (IL-8), and fibroblast growth factors 1 (FGF-1) were significantly elevated in mCNV compared to SMB eyes (p < 0.05). Their odds ratios for mCNV occurrence were 1.05, 3.45, and 2.64, respectively. Hepatocyte growth factor (HGF) and VEGF-C were notably higher in mCNV than in cataract patients (p < 0.05), and VEGF-C correlated to the degree of myopic atrophic maculopathy (p = 0.024). Axial length exhibited a negative correlation with VEGF-A and positive correlations with VEGF-C, HGF, and MCP-1 (p < 0.01). Following anti-VEGF treatment, a reduction in VEGF-A, endothelin-1, and FGF-2 was noted in mCNV patients (p < 0.05), but MCP-1 levels increased. ConclusionOur findings highlight the predominant role of angiogenesis and inflammation factors in mCNV pathogenesis. VEGF-C’s correlation with axial length and atrophy suggests its involvement in the process of myopic atrophic maculopathy.

Suppression of retinal neovascularization by intravitreal injection of cryptotanshinone

Neovascular eye diseases, including proliferative diabetic retinopathy and retinopathy of prematurity, is a major cause of blindness. Laser ablation and intravitreal anti-VEGF injection have shown their limitations in treatment of retinal neovascularization. Identification of a new therapeutic strategies is in urgent need. Our study aims to assess the effects of Cryptotanshinone (CPT), a natural compound derived from Salvia miltiorrhiza Bunge, in retina neovascularization and explore its potential mechanism. Our study demonstrated that CPT did not cause retina tissue toxicity at the tested concentrations. Intravitreal injections of CPT reduced pathological angiogenesis and promoted physical angiogenesis in oxygen-induced retinopathy (OIR) model. CPT improve visual function in OIR mice and reduced cell apoptosis. Moreover, we also revealed that CPT diminishes the expression of inflammatory cytokines in the OIR retina. In vitro, the administration of CPT effectively inhibited endothelial cells proliferation, migration, sprouting, and tube formation induced by the stimulation of human retinal vascular endothelial cells (HRVECs) with VEGF165. Mechanistically, CPT blocking the phosphorylation of VEGFR2 and downstream targeting pathway. After all, the findings demonstrated that CPT exhibits potent anti-angiogenic and anti-inflammatory effects in OIR mice, and it has therapeutic potential for the treatment of neovascular retinal diseases.

Photocoagulation or sham laser in addition to conventional anti-VEGF therapy in macular edema associated with TelCaps due to diabetic macular edema or retinal vein occlusion (TalaDME): a study protocol for a multicentric, French, two-group, non-commercial, active-control, observer-masked, non-inferiority, randomized controlled clinical trial

BackgroundMacular edema (ME) results from hyperpermeability of retinal vessels, leading to chronic extravasation of plasma components into the retina and hence potentially severe visual acuity loss. Current standard of care consists in using intravitreal injections (IVI), which results in a significant medical and economic burden. During diabetic retinopathy (DR) or retinal vein occlusion (RVO), it has recently been shown that focal vascular anomalies (capillary macro-aneurysms, also termed TelCaps) for telangiectatic capillaries may play a central role in the onset, early recurrence, and/or persistence of ME. Since targeted photocoagulation of TelCaps may improve vision, identification, and photocoagulation of TelCaps, it may represent a way to improve management of ME.ObjectiveThe Targeted Laser in (Diabetic) Macular Edema (TalaDME) study aims to evaluate whether ICG-guided targeted laser (IGTL), in association with standard of care by IVI, allows reducing the number of injections during the first year of treatment compared with IVI only, while remaining non-inferior for visual acuity.MethodsTalaDME is a French, multicentric, two-arms, randomized, sham laser-controlled, double-masked trial evaluating the effect of photocoagulation of TelCaps combined to IVI in patients with ME associated with TelCaps. Patients with vision loss related to center involved ME secondary to RVO or DR and presenting TelCaps are eligible. Two hundred and seventy eyes of 270 patients are randomized in a 1:1 ratio to standard care, i.e., IVI of anti-VEGF solely (control group) or combined with IGTL therapy (experimental group). Stratification is done on the cause of ME (i.e., RVO versus diabetes). Anti-VEGF IVI are administered to both groups monthly for 3 months (loading dose) and then with a pro re nata regimen with a monthly follow-up for 12 months. The primary endpoint will be the number of IVI and the change in visual acuity from baseline to 12 months. Secondary endpoints will be the changes in central macular thickness, impact on quality of life, cost of treatment, and incremental cost-utility ratio in each groups.Key safetyRare but severe AE linked to the use of IVI and laser, and previously described, are expected. In the sham group, rescue laser photocoagulation may be administered by the unmasked investigator if deemed necessary at month 3.DiscussionThe best management of ME associated with TelCaps is debated, and there have been no randomized study designed to answer this question. Given the fact that TelCaps may affect 30 to 60% of patients with chronic ME due to DR or RVO, a large number of patients could benefit from a specific management of TelCaps. TalaDME aims to establish the clinical and medico-economic benefits of additional targeted laser. The results of TalaDME may raise new recommendations for managing ME and impact healthcare costs.Trial registrationEudraCT: 2018-A00800-55/ NCT03751501. Registration date: Nov. 23, 2018.

Effect of Pro Re Nata regimen with anti-VEGF on Type 3 Macular Neovascularization - Long term outcomes.

This retrospective study included 19 eyes of 17 patients with nAMD and type 3 MNV treated with anti-VEGF IVI with a loading dose and PRN regimen. Best corrected visual acuity (BCVA), central macular thickness (CMT), presence of macular intraretinal fluid (IRF) and subretinal fluid (SRF), flow area (FA), subfoveal choroidal thickness (CT) and macular atrophy (MA) were assessed at baseline (T0) and during follow up (T1, post loading phase; T2, one year; T3, two years, T4>2 years). The correlations between MA at the last follow-up and standard deviation (SD) values of CMT and CT during follow-up were assessed. The influence of the number of injections on the change in MA over time was also analysed. MA differences at T4 were assessed for pseudodrusen presence. BCVA improved significantly during follow-up (p=0.013) particularly increasing from baseline to post loading phase and then did not modify significantly thereafter. CMT significantly reduced from T0 to T1 and remained stable during follow-up (p = <0.001). MNV flow area showed a trend toward increase in the post loading phase that was not statistically significant (p=0.082) and CT decreased significantly during follow-up (p<0.001). MA changed significantly during follow-up (p<0.001) with significant increase from T0 to T3 and from T0 to T4 (p < 0.010). Cochrane Armitage test for trend showed a significant reduction (p=0.001) of macular IRF and SRF during follow-up. MA at T4 showed a significant positive correlation with SD (standard deviation) values of CMT (p=0.040) and CT (p=0.020). Indeed, the number of injections did not influence the change over time of MA (p=0.709). MA at T4 was not statistically significantly different between patients with pseudodrusen at baseline (p=0.497). Intravitreal anti-VEGF injections with PRN regimen in MNV type 3 showed functional and anatomical benefits. Variations of retinal thickness and choroidal thickness during treatment were related to MA modification over time.

Non-Neovascular Subretinal Fluid with Serous Retinal Pigment Epithelial Detachment: Wait or Treat

Introduction: To describe the course of subretinal fluid (SRF) in eye with serous pigment epithelial detachment (serous PED) in the absence of macular neovascularization (non-neovascular AMD). Method: This is a retrospective case study included one eye with non-neovascular SRF associated with serous PED. Swept source optical coherence tomography (SS-OCT) and optical coherence angiography (OCTA) were obtained at baseline and follow up with qualitative and quantitative analysis of macula, pigment epithelial detachment (PED), subretinal fluid (SRF) and the presence or absence of macular neovascular membrane (MNV) in addition to other multimodal imaging modalities like fluorescein angiography (FA) and fundus auto fluorescence (FAF). Results: Our 66-year-old female has presented with left serous (PED) with apical (SRF) and no MNV on OCTA with baseline best corrected vision (BCVA) in Log MAR = 0.5. The SS-OCT, OCTA, and BCVA were stable over the initial five-month follow-up observation period with no MNV (non-neovascular SRF). One month later, the patient received an intravitreal anti-VEGF injection outside our clinic. 1-month post-outside clinic anti-VEGF injection, SS-OCT showed a small RPE tear with flattening of RPE detachment and preservation of BCVA =0.5. In the 3rd month post-outside clinic anti-VEGF injection, the SS-OCT showed slight flattening of RPE detachment with an obvious increase in SRF, still negative MNV on the OCTA associated with a drop in BCVA to 0.3. The decision was made to give the patient an initial three loading doses of aflibercept injections .The SS-OCT post 2nd aflibercept injection showed complete resolution and drying out of SRF, with an improvement of BCVA to 0.5. we continue completing the loading phase and then the patient was placed on treat and extend regimen (T&amp;E). After the fifth aflibercept injection, the PED was completely flattened with appearance of MNV on OCTA after resolution of SRF. Conclusion: Many published studies provide preliminary data about non-neovascular AMD with SRF. SRF could be present in the absence of MNV due to RPE decompensation or RPE pump failure. However, the non-neovascular SRF could be transformed with time into a neovascular one with the presence of MNV. Multimodal imaging approach is essential in differentiating non-neovascular versus neovascular SRF and avoiding unnecessary antiVEGF injections.

Short-Term Effects of Adding Topical Ketorolac to Intravitreal Bevacizumab in Diabetic Macular Edema: A Crossover Randomized Clinical Trial.

To evaluate the short-term additive effects of topical ketorolac to intravitreal bevacizumab (IVB) in the management of center-involved diabetic macular edema (CI-DME). In a randomized double-masked placebo-controlled crossover clinical trial, eyes with CI-DME and the best-corrected visual acuity (BCVA) between (20/40) and (20/400) were included. These eyes should have had at least one intravitreal anti-VEGF injection in the preceding two months. They were randomized into two groups; while both groups received two IVB injections with a six-week interval, one group received topical ketorolac every 6 hr in the first interval and artificial tears every 6 hr as a placebo in the second interval and the other group received the same medications using a crossover method. The main outcome measures were changes in BCVA and central macular thickness (CMT). Fifty-seven eyes of 35 patients with CI-DME were included in the study. The mean BCVA improvement was -0.09 0.47 logMAR in the periods of receiving ketorolac and -0.03 0.12 logMAR in the periods of placebo treatment, respectively (P = 0.99). Corresponding changes in CMT were -13.1 170.1 and +11.7 157.7 µm in the ketorolac and placebo periods, respectively (P = 0.322). The treatment effect was not statistically significant regarding both BCVA and CMT changes. Statistical analysis also disclosed that the carryover effect was insignificant for BCVA and CMT. Although the period effect was not significant for BCVA, it was at a meaningful level for CMT changes (P = 0.012). This crossover clinical trial demonstrated that in the course of DME treatment with IVB injections, topical ketorolac did not have any additive beneficial effect at least during a six-week period.

Real-world experience of using stereotactic radiotherapy combined with anti-vascular endothelial growth factor to treat neovascular AMD.

Adjunctive treatment or longer-acting drugs are required to treat nAMD to help ease burdens for patients and hospital clinics alike. Stereotactic therapy is one such option, providing a reduction in the number of injections over time. To determine the clinical outcomes in a cohort of patients with nAMD receiving a combination therapy of stereotactic radiotherapy (SRT) with intravitreal anti-VEGF injections (IVI). A retrospective analysis of 74 patients with nAMD, who had received IVI and SRT (16 Gray maximum dose to the macula) at a large tertiary university eye hospital, between March 2018 and September 2019 was performed. The number of IVIs, visual acuity (VA), and central retinal thickness (CRT) were evaluated at 12, 24, and 36months after patients received SRT and compared to the same time interval prior to SRT. Follow-up data at 12, 24, and 36months following and prior to SRT was available for 74, 48, and 22 patients respectively. Overall there was a significant reduction in the number of injections post-SRT. Twelve months following SRT, the median number of IVI was reduced by 1 (p < 0.05). The reduction in the median number of IVI was significantly reduced by 3 and 6 injections at 24- and 36-month follow-up respectively (p < 0.05). The CRT was significantly reduced post-SRT compared to the baseline values at all time periods. There was no statistically significant difference in VA at 12-month follow-up compared to baseline. The VA, however, significantly decreased at 24- and 36-month follow-up (p < 0.05). A therapy combining SRT with IVI has shown an overall reduction in the number of injections required in nAMD patients at 12, 24, and 36months following SRT compared to IVI treatment alone. These real-world outcomes are comparable to other studies while also confirming the maintenance of the reduced frequency of required IVI for patients with nAMD.

Clinical and Imaging Biomarkers Associated with Outer Retinal Atrophy Onset in Exudative Age-Related Macular Degeneration: A Real-Word Prospective Study.

Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting. This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points. We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79 ± 8years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p > 0.05). We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.

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.

Outcomes of intravitreal anti-VEGF injections and panretinal photocoagulation in preretinal hemorrhage secondary to proliferative diabetic retinopathy involving the fovea.

To evaluate the outcome of intravitreal anti-vascular endothelial growth factor (VEGF) injections and panretinal photocoagulation (PRP) in fovea involving preretinal hemorrhage (PRH) secondary to proliferative diabetic retinopathy (PDR). Retrospective non-comparative cross-sectional series of patients diagnosed with fovea involving PRH secondary to PDR at our institute from March 2019 to October 2021 who were treated with combination treatments of intravitreal anti-VEGF and PRP and have completed a minimum 6-month follow-up. The primary outcome measure was serial changes in the visual acuity (VA) and PRH regression from the fovea. Secondary outcome measures were the quantitative assessment of the size of PRH, its association with VA improvement and time to regression, and the proportion of patients who underwent surgery for poor response. In total, 22 eyes of 21 patients showed regression of PRH from the foveal center at 33.6 days, and complete regression was seen at 140.7 days. The average number of anti-VEGF injections required for clearance of PRH from the fovea was 1.6. Mean LogMAR visual acuity improved from 0.54 at baseline to 0.32 at 4 weeks and 0.18 at 6 months ( P < 0.01). Three eyes (13.6%) required vitrectomy surgery during follow-up. The mean area of PRH as measured by Image J analysis was 14.78 mm 2 at baseline, 8.97 mm 2 at 4 weeks, and 1.25 mm 2 at 3 months ( P < 0.01). No statistically significant difference was seen between the size of PRH and PRH clearance time and VA improvement. No systemic side effects were observed following the intravitreal injections during follow-up. Intravitreal anti-VEGF injections and PRP were found to be effective and safe treatment methods for fovea involving PRH secondary to PDR. Long-term studies are warranted to assess the long-term efficacy.

Clinical evaluation of tear substitute utility after anti-VEGF intravitreal injection.

The purpose of this study is to evaluate the role of a polyethylene glycol 400 - propylene glycol - hydroxypropyl guar - hyaluronic acid eye drops in relieving the symptoms of dry eye syndrome after anti-VEGF intravitreal injection. In this randomized, parallel-group study, patients were randomized to receive standard therapy alone or study eye drops plus standard therapy. Patients enrolled were older than 50 with exudative age-related macular degeneration, who have never had intravitreal injections, and without severe dry eye condition or severe ocular or systemic conditions. Patients had baseline preoperative evaluation (V0), and successively after 15 (V1) and 30 (V2) days. At VO and V1 T-BUT, Schirmer's test, fluorescein staining, DEQ5 and OSDI questionnaires were performed and at V2 (30) the OSDI questionnaire was administered. 80 patients were included in the study, of them 40 received standard therapy plus study eye drops. DEQ5 questionnaire showed an increase in the control group between the values at V0 and V1, while in the study group a decrease was observed. No changes in T-BUT, Schirmer, and fluorescein staining values between V0 and V1 were observed in both groups. OSDI data in the control group showed no statistically significant differences, while in the study group they showed a statistically significant difference. In our study patients undergoing for the first time intravitreal treatment presented dry eye symptoms in the postoperative period: in this group of patients the use of a tears substitute reduces postoperative ocular discomfort.

Emerging Co-Assembled and Sustained Released Natural Medicinal Nanoparticles for Multitarget Therapy of Choroidal Neovascularization.

Age-related macular degeneration (AMD) disease has become a worldwide senile disease, and frequent intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) is the mainstream treatment in the clinic, which is associated with sight-threatening complications. Herein, nintedanib, an inhibitor of angiogenesis, and lutein, a potent antioxidant, can co-assemble into nanoparticles through multiple noncovalent interactions. Interestingly, the co-assembled lutein/nintedanib nanoparticles (L/N NPs) exhibit significantly improved stability and achieve long-term sustained release of two drugs for at least two months in mice. Interestingly, in rabbit eyeball with a more complete barrier system, the L/N NPs still successfully distribute in the retina and choroid for a month. In the laser-induced mouse choroidal neovascularization model, the L/N NPs after a minimally invasive subconjunctival administration can successfully inhibit angiogenesis and achieve comparable and even better therapeutic results to that of standard intravitreal injection of anti-VEGF. Therefore, the subconjunctival injection of L/N NPs with long-term sustained drug release behavior represents a promising and innovative strategy for AMD treatment. Such minimally invasive administration together with the ability to effectively inhibit angiogenesis reduce inflammation and counteract oxidative stress and holds great potential for improving patient outcomes and quality of life in those suffering from this debilitating eye condition.

Increasing trends in the use of the Precivia® intravitreal injection assist device across the UK.

Intravitreal anti-VEGF injections are the most frequently performed outpatient procedure in the UK, the need for which continues to rise. To meet this demand, injection assist devices such as Precivia® are increasingly adopted to aid in their prompt and safe delivery. We present data on the usage of Precivia® intravitreal injection assist device across two district general hospitals and its distribution across the UK over five years. A retrospective review was undertaken of all Precivia® assisted intravitreal injections delivered at Great Western Hospitals NHS Trust (GWH), and Gloucestershire and Cheltenham Hospitals NHS Trust (GCH) between 2015-2020. Data were also obtained from the Precivia® device UK distributor; Veni Vidi Medical. In GCH, 47,968 intravitreal injections were administered with Precivia®: 5947 in year 1; 7058 in year 2; 9893 in year 3; 11,503 in year 4 and 13,567 injections in year 5, observing a 128.13% increase in the use of Precivia® over the five-year-period. In GWH, 26,923 injections were administered with Precivia®: 4232 in year 1; 5117 in year 2; 5437 in year 3; 5878 in year 4 and 6259 in year 5, observing a 47.89% increase in Precivia® injections over a five-year study period. The number of Precivia® devices distributed across the UK similarly increased including 42,150 devices sold in 2015; 68,125 in 2016; 72,575 in 2017; 88,325 in 2018; 112,850 in 2019 and 115,125 in 2020 observing a 173.31% increase in five years. An increasing trend in the use of the Precivia® intravitreal injection assist device was observed across the UK.

Management of Wet Age-Related Macular Degeneration: A Case Report

Introduction: Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of the photoreceptors and retinal pigment epithelium (RPE). It is a leading cause of blindness and visual impairment in the elderly population, despite recent advances in treatment. We reported a case of wet AMD and its management.&#x0D; Case Presentation: A 69 years old woman complained of blurred vision, especially in the left eye, which she had experienced since 3 years ago, progressively worsen since the last 3 months. Fundoscopy and OCT examination was done. Fundoscopy found no foveal reflex with a drusen and perifoveal haemorrhage found on left eye. She was diagnosed with wet age-related macular degeneration type II of left eye. She had done intravitreal anti-VEGF injection with local anaesthesia.&#x0D; Conclusion: AMD management relies heavily on observation, lifestyle changes, frequent follow-up evaluations, early recognition of visual impairment and detection of CNV. Meanwhile, the current modality for wet AMD therapy is intravitreal anti-VEGF injection to preserve patient’s visual acuity and improve quality of life.

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.

Classic Choroidal Neovascularization in Young Man

Introduction : Classic choroidal neovascularization (CNV 2) represent a pathological growth of blood vessels and can result in loss of visual function. The most common cause of CNV 2 in elderly patients is age- related macular degeneration, meanwhile in young age it is frequently due to inflammation, high myopia, angioid disks and hereditary disorders. Hence, the presented case reports the characteristic findings as well the management of the disease.&#x0D; Case Illustration : A 37-year-old man had two weeks history of metamorphopsia on both eyes. The left eye (LE) had a worse visual acuity, macular fibrosis with pigment epithelial detachment in funduscopy and Optical Coherence Tomography (OCT). A submacular hemorrhage and exudative lesion were recognized on the right eye (RE) with type 2 choroidal neovascularization. Fundus Fluorescence Angiography (FFA) was also performed. Systemic conditions were unremarkable. Intravitreal anti-VEGF injections on RE were given for three consecutive months and showed significant improvement.&#x0D; Discussion : The etiology of CNV 2 includes high myopia, and inflammation. However, none was found in this patient. Nonetheless, CNV type 2 is still uncommon in young age without predisposing conditions. As most common lesions involve the macula, symptoms shown include metamorphopsia, central scotoma and floaters. FFA is still considered to be the gold standard to differentiate the types of choroidal vascularization. Neovascularization and submacular hemorrhage can be treated with intravitreal injection of anti-VEGF, as previous studies reported significant improvement.&#x0D; Conclusion : This was a case of bilateral CNV type 2 in a young man without any previous predisposing conditions. Three monthly injections of anti-VEGF showed significant improvement.

UNRESOLVED QUESTIONS ABOUT COATS DISEASE: A CASE REPORT

Introduction : Coats disease (CD) is an idiopathic retinal vascular disorder accompanied by retinal telangiectasia with intraretinal and/or subretinal exudation without appreciable retinal or vitreal traction. The disease most common in young males and unilateral involvement. The etiopathogenesis of CD is unclear. However, previous studies have reported changes in inflammatory cytokines, and levels of VEGF in aqueous humor are also higher in patients with CD.&#x0D; Case Illustration : We reported a 19-year-old man with complaints of decreased vision, floaters, and uncomfortable feelings in his RE, since one year before presentation. Initial examination showed visual acuity of the RE was 0.5F2 and the LE was 1.0. Examination of posterior segment showed irregularly-dilated telangiectatic vessels and exudative RD. We performed an OCT examination in both eyes and the results showed extensive cystoid macular edema in the RE. Ultrasonography of the RE also showed an exudative RD. The patient was diagnosed with Coats disease grade 3 and planned to receive intravitreal anti-VEGF injection in RE. After the second injection, OCT examination results showed no improvement in the patient's eye condition. Until now, we’re still trying to find a suitable therapy and considering laser photocoagulation.&#x0D; Discussion : Previous studies showed that there was an improvement in some CD patients only with anti-VEGF injections, but some other patients didn’t improve and had to get other additional therapy with laser photocoagulation/cryotherapy. It’s related to the severity of the disease, where a disease with grade ?3, tends to require combination therapy with laser photocoagulation/cryotherapy.&#x0D; Conclusion : Intravitreal anti-VEGF injections alone don’t show improvement in CD grade?3.