Intravitreal Injections Of anti-VEGF Agents Research Articles

Sodium-glucose co-transporter 2 inhibitor therapy reduces the administration frequency of anti-vascular endothelial growth factor agents in patients with diabetic macular oedema with a history of anti-vascular endothelial growth factor agent use: A cohort study using the Japanese health insurance claims database.

We assessed the effectiveness of sodium-glucose co-transporter 2 inhibitors (SGLT2is) in reducing the administration frequency of anti-vascular endothelial growth factor (VEGF) agents in patients with diabetic macular oedema (DMO) using a health insurance claims database. This retrospective cohort study analysed health insurance claims data covering 11 million Japanese patients between 2005 and 2019. We analysed the frequency and duration of intravitreal injection of anti-VEGF agents after initiating SGLT2is or other antidiabetic drugs. Among 2412 matched patients with DMO, the incidence rates of anti-VEGF agent injections were 230.1 per 1000 person-year in SGLT2i users and 228.4 times per 1000 person-year in non-users, respectively, and the risk ratio for events was unchanged in both groups. Sub-analysis of each baseline characteristic of the patients showed that SGLT2is were particularly effective in patients with a history of anti-VEGF agent use [p = .027, hazard ratio (HR): 0.44, 95% confidence interval (CI): 0.22-0.91]. SGLT2is reduced the risk for the first (p = .023, HR: 0.45, 95% CI: 0.22-0.91) and second (p = .021, HR: 0.39, 95% CI: 0.17-0.89) anti-VEGF agent injections. There was no difference in the risk ratio for the addition of anti-VEGF therapy between the two treatment groups. However, the use of SGLT2is reduced the frequency of anti-VEGF agent administration in patients with DMO requiring anti-VEGF therapy. Therefore, SGLT2i therapy may be a novel, non-invasive, low-cost adjunctive therapy for DMO requiring anti-VEGF therapy.

Complications of Subconjunctival, Subtenon and Intravitreal Injections During the Procedure, Early and Late Post-procedure period

Intravitreal and periocular injections are increasingly applied for the treatment of a wide variety of retinal and uveal diseases, including age-related macular degeneration, diabetic retinopathy, retinal vascular occlusions, and uveitis. Despite promising results in stopping or slowing disease progression and improving visual acuity, intravitreal injection of anti-VEGF agents and corticosteroids may be associated with systemic side effects and serious ocular complications. In this review, we aim to provide an overview of the complications of intravitreal, subconjunctival and subtenon injection applications.

Preclinical evaluation of KH631, a novel rAAV8 gene therapy product for neovascular age-related macular degeneration

The upregulation of vascular endothelial growth factor (VEGF) is strongly associated with the development of choroidal neovascularization (CNV) in patients with neovascular age-related macular degeneration (nAMD). Currently, the standard treatment for nAMD involves frequent intravitreal injections of anti-VEGF agents, which inhibit the growth of new blood vessels and prevent leakage. However, this treatment regimen places a significant burden on patients, their families, and healthcare providers due to the need for repeated visits to the clinic for injections. Gene therapy, which enables the sustained expression of anti-VEGF proteins after a single injection, can dramatically reduce the treatment burden. KH631 is a recombinant adeno-associated virus 8 vector that encodes a human VEGF receptor fusion protein, and it is being developed as a long-term treatment for nAMD. In preclinical studies using non-human primates, subretinal administration of KH631 at a low dose of 3×108 vg/eye resulted in remarkable retention of the transgene product in the retina and prevented the formation and progression of grade IV CNV lesions. Furthermore, sustained transgene expression was observed for more than 96weeks. These findings suggest that a single subretinal injection of KH631 has the potential to offer a one-time, low-dose treatment for nAMD patients.

Short-Term Outcomes of Trabeculectomy With or Without Anti-VEGF in Patients With Neovascular Glaucoma: A Systematic Review and Meta-Analysis.

The aim of this study was to compare the safety and efficacy of trabeculectomy alone or combined with intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents for the treatment of neovascular glaucoma. We conducted a systematic review and meta-analysis to compare the effects of trabeculectomy alone or combined with intravitreal injections of anti-VEGF agents for the treatment of neovascular glaucoma. We searched four databases (PubMed, Cochrane Library, Embase, and Web of Science) up to January 2023 and extracted data on three surgical outcomes: postoperative intraocular pressure, success rate and complications. We used a random-effects model to calculate pooled relative risk (RR) or standardized mean difference (SMD) estimates and 95% confidence intervals (CIs). We assessed publication bias using Begg and Egger tests. We included seven studies with 353 eyes. Compared to trabeculectomy alone, trabeculectomy with anti-VEGF had a lower risk of postoperative complications (RR, 0.60; 95% CI, 0.41-0.89) and higher success rate (RR, 1.19; 95% CI, 1.02-1.40). The intraocular pressure reduction was significantly greater in the trabeculectomy with anti-VEGF augmentation group than the trabeculectomy group from 1 week (SMD, -1.36; 95% CI, -2.76 to 0.04) to 6months (SMD, -0.79; 95% CI, -1.50 to -0.07) after surgery. According to current evidence, adding intravitreal injection of anti-VEGF agents to trabeculectomy may improve the short time outcomes of patients with neovascular glaucoma.

Effects of Topical or Intravitreal Application of Anti-Vascular Endothelial Growth Factor on Density of Intestinal Blood Vessels of Mice.

Background and Objectives: Anti-vascular endothelial growth factor (anti-VEGF) therapy has become the first-line treatment for diabetic macular edema. However, it is still not clear whether anti-VEGF agents act on systemic blood vessels. The aim of this study is to determine whether a direct topical application or intravitreal injection of anti-VEGF will change the intestinal blood vessels of mice. Materials and Methods: C57BL/6 mice were laparotomied under deep anesthesia, and the blood vessels on the surface of the intestines were exposed, examined, and photographed through a dissecting microscope. Vascular changes were evaluated before and at 1, 5, and 15 min after the topical application of 50 µL of the different anti-VEGF agents onto the surface of the intestine (group S) or after the intravitreal injection (group V). The vascular density (VD) was determined for five mice in each group before and after 40 μg/μL of aflibercept (Af), or 25 μg/μL of bevacizumab (Be), or 10 μg/μL of ranibizumab (Ra) were applied. Endothelin-1 (ET1), a potent vasoconstrictor, was used as a positive control, and phosphate-buffered saline (PBS) was used as a control. Results: For group S, no significant changes were observed after PBS (baseline, 1, 5, and 15 min: 46.3, 44.5, 44.8, and 43.2%), Be (46.1, 46.7, 46.7, and 46.3%), Ra (44.7, 45.0, 44.7, and 45.6%), and Af (46.5, 46.2, 45.9, and 46.1%, repeated ANOVA) were applied topically. Significant decreases in the VD were observed after ET1 (46.7, 28.1, 32.1, and 34.0%, p < 0.05) was topically applied. For group V, no significant differences were observed for all anti-VEGF agents. Conclusions: The topical application or intravitreal injections of anti-VEGF agents do not cause a change in the VD of the intestinal vessels, which may be related to its safety.

Optical coherence tomography and Scheimpflug imaging of the iridocorneal angle following intravitreal injection of different medications: A longitudinal analysis.

Intravitreal injection of medications induces a sudden increase in posterior segment volume and pushes iris plane anteriorly to narrow iridocorneal angle. The aim of this study to follow and define longitudinal course of these changes following intravitreal injection of 3 different anti-vascular endothelial growth factor (VEGF) medications or dexamethasone implant. This prospective, longitudinal study included 89 eyes of 89 patients that had an intravitreal injection of bevacizumab (n=20) or ranibizumab (n=26) or aflibercept (n=22) or dexamethasone implant (n=21). All the participants had a detailed ophthalmological examination including anterior segment optical coherence tomography (AS-OCT) and Scheimpflug imaging of the iridocorneal angle, evaluation of anterior chamber depth (ACD), axial length with optical biometry and endothelial cell counts with specular microscopy just before the injection, at post-injection day 1, and post-injection 1st month. Iridocorneal angle became significantly wider following intravitreal injection of dexamethasone implant at nasal and temporal quadrants at the post-injection 1st month both in AS-OCT (p=0.006, p=0.002, respectively) and Scheimpflug imaging (p=0.003, p=0.004, respectively). Small changes were observed in iridocorneal angle following anti-VEGF injections but these small could not be confirmed in both imaging techniques. There were also no changes in ACD, axial length and endothelial counts in all groups. Dexamethasone implants induced widening of iridocorneal angle that persisted at the post-injection 1st month both at nasal and temporal quadrants. However, intravitreal injection of anti-VEGF agents did not have a comparable effect on iridocorneal angle.

Reduced Size of Telangiectatic Capillaries After Intravitreal Injection of Anti-Vascular Endothelial Growth Factor Agents in Diabetic Macular Edema

Intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) agents reduces microaneurysms in patients with diabetic macular edema (DME). However, residual anti-VEGF-resistant telangiectatic capillaries (TelCaps) have been reported. In this study, we investigated changes in the size of TelCaps after intravitreal injection of anti-VEGF agents in DME. Indocyanine green angiography (IA) and optical coherence tomography were performed before and 3 months after the intravitreal injection of anti-VEGF agents (pro re nata regimen after three monthly loading doses) in 12 eyes of 12 patients (7 males and 5 females, mean age 65.2 ± 8.8 years) with DME. The number and size of TelCaps within a 6-mm diameter macular region of the edema were measured using optical coherence tomography B-scan images overlaid on IA images. There were significant reductions in the number and size of TelCaps between the baseline and 3 months after anti-VEGF agent administration (P < 0.05 and P < 0.0001, respectively). The maximum corrected visual acuity (logMAR visual acuity) and the central macular thickness after anti-VEGF therapy were significantly improved (P < 0.01 and P < 0.02, respectively). The TelCaps remaining after loading three consecutive anti-VEGF agents had a significantly larger mean size at baseline than the TelCaps that resolved after the treatment (P < 0.03). Our study demonstrated that intravitreal injection of anti-VEGF agents could reduce TelCap size in patients with DME. We propose that larger-sized TelCaps detected by IA might be useful predictors of refractory DME, which could thus be principal targets of laser photocoagulation.

Assessment of retinal ganglion cell complex thickness in diabetic patients before and after intravitreal injection of anti-VEGF agents by OCT

Assessment of retinal ganglion cell complex thickness in diabetic patients before and after intravitreal injection of anti-VEGF agents by OCT

Novel episcleral implants of sunitinib can depress ocular neovascularization under ex‐vivo conditions

AbstractBackground: Current management of posterior segment disease such as Age‐related Macular degeneration (AMD) and Diabetic Macular Edema (DME) is by monthly Intravitreal injections of Anti‐VEGF agents (IVT). IVT therapy suffers from various serious drawbacks such as highly invasive procedure and risk of ocular tissue damage. Moreover, Lower response rate of Anti‐VEGF agents in patients also demands development of novel alternative therapies. One of the major challenge of posterior segment drug delivery is selection of suitable in‐vivo models for pharmacokinetic and therapeutic screening due to highly localized nature of eye leading limited choices animals that resemble human ocular anatomy. Hence we aim to novel episcleral implant platform for posterior segment drug delivery along with using suitable ex‐vivo assays for therapeutic estimation of developed drug delivery systems.Methods: The Implants loaded with sunitinib malate were fabricated using a polymeric blend of gelatin and polyglycerol sebacate (PGS) by electrospinning technique. The effect of polymer blending and drug loading on morphology and in‐vitro drug release profile by scanning electron microscopy and shaking incubator drug release method. Further, the effect of electrospinning and polymer blending on mucoadhesion was studied by mucin agar plate method. Transscleral drug permeation and the secondary depot formation of sunitinib following episcleral application were studies Franz diffusion cell experiment. The biocompatibility of implant was tested on ARPE‐19 cells and the effect of treatment on cell morphology was studied by crystal violet staining. The therapeutic efficacy of episcleral implants was tested by ex‐vivo choroidal angiogenesis assay.Results: The electrospinning process lead to development of highly porous and flexible implants. It was found that polymer blending has profound effect on the morphology as well as in vitro drug release of implants. The addition of PGS lead to thinner fibres within implant and it also lead to sustained release of sunitinib over the period of one week. The drug loading did not has proficient effect on the morphology of implants; however, higher loading lead to sustained release of sunitinib over the release period. The electrospinning process lead to enhanced mucoadhesion that could possibly due to increased surface area and improved contact angle. The implants were found to be biocompatible and did not alter the morphology of ARPE‐19 cells upon treatment as observed by crystal violet staining. The drug release samples of implants in cell culture media were tested upon ex‐vivo rat choroidal angiogenesis assay where it was observed that the release samples were able to suppress the ocular neovascularization significantly when compared with untreated samples.Conclusions: We can conclude that sunitinib loaded episcleral implants could be a promising alternative for management of disease with posterior segment neovascularization such as AMD and DME. The polymer blending of different polymers along with electrospinning technique could aid in development of novel episcleral implants with sustained release of medicinal agents. The electrospun implant platform could also be used for anterior segment drug delivery as well. Finally ex‐vivo rat choroidal angiogenesis assay could be a great tool for therapeutic screening of ocular drug delivery systems.

Development and characterization of injectable depot forming thermoresponsive hydrogel for the sustained intrascleral delivery of Sunitinib

Age-related macular degeneration (AMD) is a potentially blinding posterior segment disease; inflammatory responses and subretinal drusen formation lead to leaky blood vessels. The current treatment method involves intravitreal injections of anti-VEGF agents, which is highly invasive and requires frequent injections administered by trained personnel. Periocular injections such as trans-/intra-scleral injections would provide a minimally invasive treatment option. The sclera is the outermost protective layer occupying 5/6th of the ocular globe. Owing to its avascular nature and self-healing ability, sclera could be the potential space for the delivery of depot forming long-acting formulations. This project focuses on the development of chitosan grafted poly(n-isopropylacrylamide) (Cs-g-PNIPAAm) gel for the sustained intrascleral delivery of small molecular weight, multiple tyrosine kinase inhibitor Sunitinib malate.

Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications.

Diabetic retinopathy (DR), with increasing incidence, is the major cause of vision loss and blindness worldwide in working-age adults. Diabetic macular edema (DME) remains the main cause of vision impairment in diabetic patients, with its pathogenesis still not completely elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of DR and DME. Currently, intravitreal injection of anti-VEGF agents remains as the first-line therapy in DME treatment due to the superior anatomic and functional outcomes. However, some patients do not respond satisfactorily to anti-VEGF injections. More than 30% patients still exist with persistent DME even after regular intravitreal injection for at least 4 injections within 24 weeks, suggesting other pathogenic factors, beyond VEGF, might contribute to the pathogenesis of DME. Recent advances showed nearly all the retinal cells are involved in DR and DME, including breakdown of blood-retinal barrier (BRB), drainage dysfunction of Müller glia and retinal pigment epithelium (RPE), involvement of inflammation, oxidative stress, and neurodegeneration, all complicating the pathogenesis of DME. The profound understanding of the changes in proteomics and metabolomics helps improve the elucidation of the pathogenesis of DR and DME and leads to the identification of novel targets, biomarkers and potential therapeutic strategies for DME treatment. The present review aimed to summarize the current understanding of DME, the involved molecular mechanisms, and the changes in proteomics and metabolomics, thus to propose the potential therapeutic recommendations for personalized treatment of DME.

Safety of simultaneous bilateral intravitreal versus unilateral anti-vasculo-endothelial growth factors injection in an operating room setting.

Chorioretinal diseases requiring the use of anti-vascular endothelial growth (anti-VEGF) injections often occur in both eyes simultaneously. This can necessitate injecting both eyes together rather than one eye at a time. The purpose of the study was to determine whether simultaneous bilateral intravitreal injections of anti-VEGF agents are safe when administered in an operation theatre setting. Retrospective review of data was conducted. Single center study conducted in a tertiary care hospital in Karachi Pakistan. Approximately 30,000 eyes that received anti-VEGF injection during a 10-year study period were included (March 2008-February 2018). Patients who were lost to follow up prior to completion of treatment were excluded. Consecutive sampling technique was employed. The patients who received bilateral anti-VEGF injections were analysed separately from the ones who received unilateral injections. All injections were administered in operating theatre setting. The rate of endophthalmitis was measured in each group. A total of 30,258 injections were administered of which 15,338 were bilateral injections. Four cases (4/30,258, 0.013%) of endophthalmitis occurred during the study period. Only one case (1/15,338, 0.0065%) of endophthalmitis occurred after the administration of simultaneous bilateral anti-VEGF injections. Administration of simultaneous bilateral anti-VEGF injections was safe in our population.

Risk factors for myopic choroidal neovascularization-related macular atrophy after anti-VEGF treatment.

PurposeThe study aimed to evaluate risk factors for macular atrophy (MA) associated with myopic choroidal neovascularization (mCNV) during long-term follow-up after intravitreal anti-vascular endothelial growth factor (VEGF) treatment in highly myopic eyes.MethodsThe medical records of patients who received intravitreal injection of anti-VEGF agents as mCNV treatment and were followed-up for more than 36 months were retrospectively reviewed. The risk factors for the development of mCNV-MA, which is the fovea-involving patchy atrophy lesion adjacent to mCNV, were investigated using the Cox proportional hazard model.ResultsA total of 82 eyes (74 patients) were included in the study. The mean age at anti-VEGF treatment was 56.3 ± 12.5 years (range, 26–77), and the mean follow-up period was 76.3 ± 33.5 months (range, 36–154). During follow-up, mCNV-MA developed in 27 eyes (32.9%), and its occurrence was estimated to be 24.5% at 3 years and 37.3% at 5 years after the first anti-VEGF treatment. Old age (hazard ratio [HR] = 1.054, 95% confidence interval [CI]: 1.018–1.091; P = 0.003) and greater CNV size at baseline (HR = 2.396, CI: 1.043–5.504; P = 0.040) were significant factors for mCNV-MA development. Eyes with a thinner subfoveal choroid were more likely to show faster enlargement of the mCNV-MA during follow-up.ConclusionsIn mCNV eyes treated with intravitreal anti-VEGF agents, older age and greater mCNV size at baseline were risk factors for the development of MA during long-term follow-up, which was associated with a poor visual prognosis.

New Insights into Treating Early and Advanced Stage Diabetic Retinopathy.

Diabetic retinopathy (DR) is the leading cause of preventable blindness in the working-age population. The disease progresses slowly, and we can roughly differentiate two stages: early-stage (ESDR), in which there are mild retinal lesions and visual acuity is generally preserved, and advanced-stage (ASDR), in which the structural lesions are significant and visual acuity is compromised. At present, there are no specific treatments for ESDR and the current recommended action is to optimize metabolic control and maintain close control of blood pressure. However, in the coming years, it is foreseeable that therapeutic strategies based in neuroprotection will be introduced in the clinical arena. This means that screening aimed at identifying patients in whom neuroprotective treatment might be beneficial will be crucial. Regarding the treatment of ASDR, the current primary course is based on laser photocoagulation and intravitreal injections of anti-angiogenic factors or corticosteroids. Repeated intravitreal injections of anti-VEGF agents as the first-line treatment would be replaced by more cost-effective and personalized treatments based on the results of “liquid biopsies” of aqueous humor. Finally, topical administration (i.e., eye drops) of neuroprotective, anti-inflammatory and anti-angiogenic agents will represent a revolution in the treatment of DR in the coming decade. In this article, all these approaches and others will be critically discussed from a holistic perspective.

Regional Variety of Reduction in Retinal Thickness of Diabetic Macular Edema after Anti-VEGF Treatment.

Background and Objectives: The presence of refractory cases resistant to anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME) is a problem in clinical practice. This study aimed to explore the less responsive area of optical coherence tomography (OCT) 3D map the characteristics of naïve DME cases after their first anti-VEGF. Materials and Methods: In 46 patients with DME who received an intravitreal injection of anti-VEGF agents, retinal thickness in 100 sections of the macular area was measured by 3D-mapping mode using OCT before and 1 month after injection. The density of the microaneurysm (MA) was calculated using merged images of the OCT map and fluorescein angiography. Results: One month after injection, the central retinal thickness significantly decreased (p < 0.0001). In severe edema (retinal thickness more than 500 µm), the area percentages with a reduction rate of the retinal thickness greater than 30% and less than 5% were 6.4 ± 6.6% and 10.1 ± 4.6%, respectively. The reduction rate of the retinal thickness varied from section to section. The mutual distance between the areas of maximum thickness before and after the injection averaged 1.22 ± 0.62 mm apart. The reduction rate of retinal thickness in the thickest region before injection was significantly higher (p = 0.02), and that in the thickest region after injection was lower (p = 0.001) than in the other regions. MA density in the residual edema was significantly higher than in the edema-absorbed area (p = 0.03). Conclusion: DME has areas that show low response to the reduction in retinal thickness with anti-VEGF therapy. A high density of MA may be associated with this pathogenesis.

Treatment for Retinopathy of Prematurity in Twins: The Small Twin without High Birth Weight Discordant Is Not at Increased Risk.

Purpose: As common retinopathy is observed in low-birth infants, the characteristics of ROP in twins are worth exploring. The present study tried to demonstrate the risk factors of treatment for retinopathy of prematurity (ROP) in twins both diagnosed with ROP. Methods: A retrospective, institution-based cohort study of 62 premature ROP twin pairs with a mean gestational age (GA) younger than 35 weeks and a birth weight (BW) lower than 2500 g. Only infants with a follow-up period longer than 6 months and complete treatment records were included. The demographic data, treatment requirements and further rescue treatments were all collected and analyzed for all infants according to whether they accepted treatments. Moreover, all twin infants were divided into small and large twin groups according to birth weight, and they were also categorized as three groups according to the treatment requirement including both twins receiving treatment (BT group), one of the twins receiving treatment (ST group) and none of the twins receiving treatment (NT group). Comparisons of demographic data, treatment requirements and further rescue treatments were all conducted according to the different grouping methods. Results: The mean GA of the enrolled infants was (29.29 ± 2.45) weeks with a mean BW of (1335.77 ± 390.36) grams. Among them, 110 infants were mechanically ventilated. Fifty-one of the infants did not receive any treatment and 73 infants received laser or intravitreal injection of anti-VEGF agents. In total, 64 infants only underwent intravitreal injection of anti-VEGF agents or laser treatment, while the other nine infants received scleral buckling or vitrectomy as a necessary treatment when the retinal detachment was observed. No significantly different mechanical ventilation or treatment requirements could be observed between the small twin group and the large twin group (p = 0.73, 0.94). The twins in the BT groups showed the lowest BW, while the NT group infants had the highest BW. The GA for the BT, ST and NT groups were (27.86 ± 1.87) weeks, (29.60 ± 1.52) weeks and (31.33 ± 2.39) weeks, respectively, and showed significant differences as well (p < 0.001). Conclusion: Being a small twin in twin-paired ROP without a high BW discordant will not increase the risk for treatment requirement or additional surgery necessity with a much more severe stage of ROP.

469-P: Sodium–Glucose Cotransporter 2 Inhibitors Decrease the Frequency of Antivascular Endothelial Growth Factor Agent Injection in Patients with Type 2 Diabetes Complicated by Diabetic Macular Edema

Aims: Diabetic macular edema (DME) leads to impaired vision. The first line of treatment is intravitreal injection of anti-vascular endothelial growth factor (VEGF) agent. However, there are patients who are refractory to this. We reported patients whose DME were refractory to anti-VEGF agents and showed improvement by using sodium glucose cotransporter 2 inhibitors (SGLT2is) . The effectiveness of SGLT2is for DME was assessed using a health insurance claim database. Methods: The JMDC inc. database covering million Japanese patients between 2005-20was used for analysis. Patients with type 2 diabetes (T2D) with DME were included, and those who were undergo dialysis, had other ocular diseases that may be treated by anti-VEGF agents, or were not on treatment with any antidiabetic drug introduced after 2014 were excluded. Propensity score matching was performed between SGLT2i users and non-users. The frequency and the duration of intravitreal injection of anti-VEGF agent after the period from the start of SGLT2is or other antidiabetic drugs were analyzed. Results: In this study, 340 matched patients with T2D were analyzed. Initiation of SGLT2is revealed a decrease in the frequency of anti-VEGF agent injection (2.7 ± 4.1 vs. 3.8 ± 4.6 times, p &amp;lt; 0.001; the Wilcoxon signed rank test, p &amp;lt; 0.001, 95%CI -0.25 to -0.085; the Poisson regression, p &amp;lt; 0.001, HR 0.80, 95% CI 0.73 to 0.87; the recurrent event analysis) and an extension in the duration for the requirement of the first injection of anti-VEGF agent (the number of patients who received no anti-VEGF agents, 96 vs. 32, p &amp;lt; 0.001; the log-rank test) . Conclusion: Using SGLT2is for patients with T2D complicated by DME extended the duration for the requirement of the first anti-VEGF agent injection and decreased the frequency of anti-VEGF agent injection. SGLT2is may be an option for DME treatment. Disclosure R.Ishibashi: Research Support; Astellas Pharma Inc., Boehringer Ingelheim International GmbH, Daiichi Sankyo, Mitsubishi Tanabe Pharma Corporation, Taiho Pharmaceutical Co. Ltd., YL Biologics, ZERIA Pharmaceutical Co.,Ltd. E.Kawakami: None. M.Koshizaka: None. Y.Maezawa: None. K.Yokote: None. Y.Takatsuna: None. T.Tatsumi: None. S.Yamamoto: None. Y.Inaba: None. Y.Shiko: None.

A systematic review of clinical practice guidelines for myopic macular degeneration.

BackgroundMyopic macular degeneration (MMD) is a primary cause of blindness and visual impairment in many parts of the world. A review of clinical practice guidelines (CPGs) for intervention selection are required with the increasing demand for MMD management in clinical practice as well as in national health services. Therefore, we aim to systematically review CPGs for MMD and assist the recommendations development of the Package of Eye Care Interventions (PECI) program of the World Health Organization.MethodsA systematic review of CPGs published on MMD between 2010 and April 2020 was conducted. Guidelines were evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. Cochrane systematic reviews were also included when the evidence from included CPGs were inadequate or contradict.ResultsAfter applying exclusion criteria and conducting the quality appraisal, two CPGs were finally included. The average of the AGREE II ratings for the identified Guidelines were 56 and 63 respectively (7 for each item). To provide further information on interventions for MMD, one Cochrane review on MMD was additionally identified and included in the study. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) drugs were recommended for patients with myopic choroidal neovascularization (mCNV) as first-line therapy to improve vision and reduce central macular thickness, and ranibizumab showed significant effectiveness compared to photodynamic therapy (PDT). PDT was recommended to be performed in those resistant to the treatment by one CPG but lacked of adequate description and support. Data extracted from the Cochrane systematic reviews indicated that anti-VEGF therapy for mCNV had significant effectiveness in improving visual acuity and reducing CMT compared to PDT with moderate to low certainty of evidence. Ranibizumab and bevacizumab were considered as equally effective with moderate certainty.ConclusionsThe outcomes of this review suggest that high quality clinical practice guidelines for MMD management are limited. Intravitreal injection of anti-VEGF agents was recommended as an effective intervention to treat myopic CNV as the first-line treatment, while there was inadequate guidance for the application of PDT in myopic CNV management. The use of other interventions for MMD were not recommended at this time and additional evidence is called for.

Safety Measures for Maintaining Low Endophthalmitis Rate after Intravitreal Anti-Vascular Endothelial Growth Factor Injection before and during the COVID-19 Pandemic.

During the COVID-19 pandemic, intravitreal injections are performed with patients wearing masks. The risk of endophthalmitis after intravitreal injection is reported to increase due to an influx of exhaled air containing oral bacteria from the upper part of the mask onto the ocular surface. We retrospectively investigated the incidence of endophthalmitis when intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections were performed using the same infection control measures before and during the pandemic. Vitreoretinal specialists performed intravitreal injections of anti-VEGF agents in the outpatient room of a university hospital. Infection control measures before and during the pandemic included covering the patient’s eye with adhesive face drape and irrigating the ocular surface with 0.25% povidone-iodine before draping, and immediately before and after injection. Before the COVID-19 pandemic (February 2016 to December 2019), one case of endophthalmitis occurred among 31,173 injections performed (0.0032%; 95% confidence interval (CI), 0.000008–0.017872%). During the COVID-19 pandemic (January 2020 to August 2021), one case of endophthalmitis occurred among 14,725 injections performed (0.0068%; 95% CI, 0.000017–0.037832%). There was no significant difference between the two periods (Fisher’s exact test: p = 0.5387). Even during the COVID-19 pandemic, very low incidence of endophthalmitis after intravitreal injection can be maintained by implementing basic infection prophylactic measures, including face draping and 0.25% povidone-iodine irrigation, established before COVID-19 pandemic.

Prevention of intraocular pressure elevation following intravitreal injections

Determining the role of vascular endothelial growth factor (VEGF) in the pathogenesis of intraocular neovascularization prompted the development of anti-VEGF therapy. In general, these intravitreal injections (IVI) are considered relatively safe. One of the side effects that can occur after IVI of anti-VEGF agents is ocular hypertension, it can be acute or persistent. Numerous studies investigating the prevention of ophthalmic hypertension have been carried out in connection with the proven risk of short-term intraocular pressure (IOP) elevation after anti-VEGF injections. Scientific literature describes several methods of preventing intraocular pressure spikes after IVI: prophylactic medications, anterior chamber paracentesis, scleral decompression. Despite the significant number of publications, there is no universal consensus on the necessity of prevention measures for IVI of anti-VEGF drugs since the clinical benefits of slightly reducing the short-term IOP spikes remain unclear. This literature review analyzes the prospects of preventing ocular hypertension after IVI of anti-VEGF agents.