Injections Of anti-VEGF Agents Research Articles

Vitritis following intravitreal faricimab: a retrospective monocentric analysis.

Intravitreal injections of anti-VEGF agents are considered as safe, with a very low rate of intraocular inflammations (IOI). Faricimab is a novel intravitreal bispecific antibody targeting both VEGF-A and angiopoietin-Tie2 independently. Despite a safe profile in randomized clinical trials, several real-life studies have reported cases of IOI. The aim of this monocentric study was to report the incidence and clinical course of intraocular inflammation following intravitreal faricimab injections. A retrospective analysis was performed in our tertiary care center, based on the observation of cases between December 1, 2023 and April 30, 2024. The incidence of intraocular inflammation occurring following faricimab injections compared to other anti-VEGF agents and dexamethasone implants was assessed over the study period. Intraocular inflammation was observed in 11 eyes of seven patients, and presented as isolated, painless anterior uveitis with retrocorneal precipitates in three cases and vitritis associated with anterior uveitis in eight cases. The pattern of vitritis appeared distinctive, characterized by dense, grayish vitreous bands observed mainly in the peripheral fundus. The inflammatory phase persisted for 2-10 weeks, and regressed with steroid treatment. The overall incidence of IOI with faricimab was 0.87% (11 out of 1,271 injections), with vitritis specifically observed in 0.63% of cases (8 out of 1,271 injections). In contrast, of the 3,728 injections of other anti-VEGF agents administered (including 1,765 injections of aflibercept, 1,952 injections of ranibizumab) and 43 injections of dexamethasone implants, no cases of intraocular inflammation were reported. Our initial experience with faricimab indicates a potentially higher risk of intraocular inflammation, including a distinctive pattern of vitritis, compared to aflibercept and ranibizumab. The benefit/risk ratio should be carefully assessed, particularly in patients with monocular vision or who require simultaneous bilateral injections.

Randomized Clinical Trial of Intraocular Pressure-Lowering Medications on Preventing Spikes in Intraocular Pressure Following Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents are a primary management option for retinal diseases. Acute elevation of intraocular pressure (IOP) is a complication associated with these injections that should be considered. This study investigated and compared the prophylactic effects of fixed combination anti-glaucoma medication on IOP spikes following intravitreal anti-VEGF injections. This randomized double-blind clinical trial included one eye of each participant indicated for treatment with intravitreal injection of anti-VEGF agents (bevacizumab, aflibercept, and ranibizumab) and randomly allocated to one of the three prophylactic anti-glaucoma medications, with each drug further divided into one- and two-drop regimens before intravitreal injection. Participants with allergies or contraindications to medications were excluded from the pretreatment groups and were invited to participate in the control group. The study involved 308 participants: 89 in the dorzolamide/timolol group, 86 in the brimonidine/timolol group, 101 in the brinzolamide/brimonidine group, and 32 in the control group. Baseline characteristics and IOP were comparable across all groups. In the prophylactic premedication groups, mean IOP at 30min were within 21mmHg and returned to their baseline at 1h. Mean IOP measurements between baseline and 30min in the brimonidine/timolol two-drop regimen were not significantly different: 13.72 ± 4.63 vs 15.11 ± 4.39mmHg, p = 0.096. In the control group, IOP significantly increased from baseline at 30min and 1h post-injection: 14.31 ± 4.10, 22.15 ± 8.64, and 18.36 ± 7.52mmHg, respectively, p < 0.001. Topical fixed combination anti-glaucoma medication used as a prophylactic treatment before intravitreal anti-VEGF injections significantly prevented IOP spikes post-injection, with a comparable effect among three medications. Prophylactic treatment of IOP spikes should be considered as standard care to prevent further damage in patients with compromised retinal vascular and optic nerve perfusion. TCTR20241005001, retrospectively registered.

Development of axitinib-loaded polymeric ocular implants for the treatment of posterior ocular diseases.

Diabetic retinopathy (DR) and age-related macular degeneration (AMD) are the primary causes of vision impairment and blindness worldwide. The current treatment for these diseases is an intravitreal injection of anti-VEGF agents, which are costly and require frequent injections. Implants can be used to sustain the release of drugs and minimize side effects. Axitinib (AX) is a potent VEGF receptor inhibitor and a promising candidate for treating posterior ocular diseases, such as diabetic retinopathy (DR) and age-related macular degeneration (AMD). A sustained release of AX was successfully achieved from 3D-printed AX-loaded implants fabricated using the well-known 3D printing technique, semi-solid extrusion (SSE). AX at concentrations of 10% w/w and 20% w/w was incorporated within the polycaprolactone (PCL) and Precirol®-based matrix. The fabricated implants were characterized via FTIR spectroscopy, SEM imaging, and thermal analysis. The implants were also evaluated for their drug release and biocompatibility. The AX-loaded implants exhibited thermal stability, and no chemical interactions were found between AX and the matrix components. The release mechanism study of AX revealed that the concentration of drug loading influenced AX release from the implant, with a 10% w/w and 20 %w/w of AX showing first-order and Korsmeyer-Peppas mechanism, respectively. A biocompatibility study using ARPE-19 cells confirmed that AX-loaded implants are nontoxic and safe for ocular use.

Optical coherence tomography-derived texture-based radiomics features identify eyes with intraocular inflammation in the HAWK clinical trial

Background and objectiveIntravitreal injection of anti-VEGF agents is the first-line treatment for patients with neovascular-age related macular degeneration (nAMD). One unique serious adverse event that may be associated with these agents is intraocular inflammation (IOI). The main purpose of this analysis was to evaluate the potential presence of texture-based radiomics features characterizing heterogeneity within the vitreous compartment of spectral domain optical coherence tomography (SD-OCT) images that may precede or develop in association with IOI and might serve as OCT biomarkers for IOI. MethodsThis is a post-hoc analysis of a subset of cases (N = 67) involving IOI, endophthalmitis, and/or retinal vascular occlusion in the phase 3 HAWK trial. These were investigator determined diagnoses that were also confirmed by the safety review committee. Intraocular inflammation was any signs of inflammation within the eye, endophthalmitis was inflammation associated with presumed infection, and retinal vascular occlusions consisted of intraocular inflammation with concurrent vascular occlusions/vasculitis. Out of 67 eyes, 34 belonged to the Safety group with an IOI event and 33 were propensity-matched Controls. A total of 481 texture-based radiomics features were extracted from the vitreous compartment of the SD-OCT scans at pre-IOI time point (i.e., much earlier than the actual event). Most discriminating five features, selected by the Wilcoxon Rank Sum feature selection were evaluated using Random Forest (RF) classifier on the training set (Str, N = 47) to differentiate between the two patient groups. Classifier performance was subsequently validated on the independent test set (St, N = 20). Additionally, the classifier performance in discriminating the Control and Safety group was also validated on St at the IOI event timepoint. ResultsThe RF classifier yielded area under the Receiver Operating Characteristics curve (AUC) of 0.76 and 0.81 on St using texture-based radiomics features at pre-IOI and event time-point, respectively. ConclusionsIn this analysis, the presence of a pre-IOI safety signal was detected in the form of textural heterogeneity within the vitreous compartment even prior to the actual event being identified by the investigator. This finding may help the clinicians to assess for underlying posterior inflammation.

Current perspectives in the management of diabetic macular edema

Diabetic macular edema (DME) is the leading cause of vision impairment in diabetic patients and is a major cause of blindness worldwide in the working age adults. The pathogenesis is still not well understood. Vascular endothelial growth factor (VEGF) is known to play a major role in the pathogenesis of DME. Currently, intravitreal injection of anti-VEGF agents remains as the first-line therapy in DME treatment due to the favorable anatomic and functional outcomes. Despite this, around 30% of the patients have persistent DME even after multiple anti-VEGF injections. This suggests that various other pathogenetic mechanisms such as inflammatory marker upregulation and oxidative stress are in play, so there is a need to look into intravitreal steroids and other modalities to tackle DME. Multimodal imaging using Optical coherence tomography (OCT)/OCT-angiography (OCT-A)/Fluocinolone acetonide (FA) gives insights into the DME subtypes and biomarkers which guide the diagnosis, optimal treatment, and monitoring. The present review aims to summarize the current understanding of DME and explore the modalities for personalized treatment protocols in patients with DME.

Sustained elevation of intraocular pressure after multiple intravitreal injections of anti-VEGF agents

Sustained elevation of intraocular pressure after multiple intravitreal injections of anti-VEGF agents

Response of Diabetic Macular Edema to Anti-VEGF Medications Correlates with Improvement in Macular Vessel Architecture Measured with OCT Angiography

PurposeImprovement in best corrected visual acuity (BCVA) and central subfield thickness (CST) have been well documented after intravitreal injection of anti-VEGF medications in diabetic macular edema (DME), however their effect on the vasculature of the macula in diabetic retinopathy (DR) remains poorly understood. Our aim was to explore the effect of intravitreal injection of anti-VEGF on parameters of retinal vascular microstructure in DR with optical-coherence tomography angiography (OCT-A). DesignRetrospective study of adult patients with DME that were treated with anti-VEGF intravitreal injections at the University of Illinois at Chicago between 2017-2022. Subjects, Participants, and/or Controls41 eyes from 30 patients with non-proliferative or proliferative DR with a mean age of 58.83 ± 11.71years, mean number of intravitreal injections of 2.8 ± 1.4, and mean follow up of 6.5 ± 1.7 months. Methods, Intervention, or TestingImageJ was employed to measure parameters of retinal vascular microstructure in OCT-A images, which included perfusion density, vessel length-density (VLD), vessel diameter, and FAZ characteristics (area, perimeter, circularity). Student’s T-tests and ANOVA were used to determine statistical significance. Main Outcome MeasuresA primary analysis was performed comparing the mean of each parameter of all patients as a single group at the beginning and end of the study period. A subgroup analysis was then performed after stratifying patients based on visual improvement, change in CST, prior injection history, and number of injections. ResultsEyes demonstrated statistical improvement in BCVA logMAR score and CST after anti-VEGF treatment. Primary analysis showed a reduction in the vessel diameter of the superficial and deep retinal vasculature as well as an increase in the circularity of the FAZ within the superficial retinal vasculature after anti-VEGF treatment. Subgroup analysis revealed that eyes with improvement in BCVA exhibited reduced vessel diameter in the superficial retinal vasculature and that eyes with the largest decrease in CST displayed increased perfusion density and VLD in the deep retinal vasculature. ConclusionsIntravitreal injection of anti-VEGF agents to treat DME improved parameters of retinal vascular microstructure on OCT-A over a period of 3-9 months, and this effect was most pronounced in eyes that experienced improvement in BCVA and CST.

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.

Changing Reimbursement Criteria on Anti-VEGF Treatment Patterns Among Wet Age-Related Macular Degeneration and Diabetic Macular Edema Patients: An Interrupted Time Series Analysis.

To evaluate the impact of reimbursement criteria change on the utilization pattern of anti-vascular endothelial growth factor (anti-VEGF) among patients with wet age-related macular degeneration (wAMD) and diabetic macular edema (DME) separately in Taiwan. An interrupted time series analysis (ITSA) was performed using Taiwan's National Health Insurance (NHI) database, and patients with wAMD or DME diagnosis at the first injection of anti-VEGF agents was identified from 2011 to 2019. The outcome of interest was treatment gaps between injections of anti-VEGF. This outcome was retrieved quarterly, and the study period was divided into three phases in wAMD (two criteria changed in August 2014 [intervention] and December 2016 [intervention]) and two phases in DME (three consecutive criteria changed in 2016 [intervention]). Segmented regression models adjusted for autocorrelation were used to estimate the change in level and the change in slope of the treatment gaps between each anti-VEGF injection. The treatment gaps between each anti-VEGF injection decreased from 2011 to 2019. The cancellation of the annual three needles limitation was associated with significantly shortened treatment gaps between the third and fourth needles (wAMD change in level: -228 days [95% CI -282, -173], DME change in level: -110 days [95% CI -141, -79]). The treatment gap between the fifth and sixth needles revealed a similar pattern but without significant change in DME patients. Other treatment gaps revealed considerable change in slopes in accordance with criteria changes. This is the first nationwide study using ITSA to demonstrate the impact of reimbursement policy on treatment gaps between each anti-VEGF injection. After canceling the annual limitation, we found that the treatment gaps significantly decreased among wAMD and DME patients. The shortened treatment gaps might further link to better visual outcomes according to previous studies. The different impacts from criteria changes can assist future policy shaping. Future studies were warranted to explore whether such changes are associated with the benefits of visual effects.

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.

Aflibercept Versus Bevacizumab as First-Line Therapy in Age-Related Macular Degeneration.

AMD (age-related macular degeneration) is the main cause of central vision loss in the population over 60 years old. AMD does not affect peripheral vision and complete blindness does not occur, instead, central vision is affected both for distance and for near. The purpose of this study is to evaluate the neovascular form of AMD treatment and compare ocular and systemic effects after intravitreal injection of aflibercept, respectively after bevacizumab when administered in comparable dosages and regimens. We conducted a retrospective, single-center study from June 2021 to December 2022 and enrolled 20 patients with neovascular AMD who had not received any prior treatment for this condition. We randomly assigned them to two groups of 10: group one received aflibercept and group two received bevacizumab as intravitreal injections under aseptic conditions. We excluded 2 patients who did not meet the criteria and ended up with two groups of 9 patients who received monocular treatment. We gave the patients 3 monthly injections of anti-VEGF agent and followed them up at 1 month, 3 months, and 9 months after the treatment. We assessed their visual acuity, intraocular pressure and OCT appearance at each follow-up visit. The primary outcome was visual acuity. All 18 patients included in the study reported an improvement in visual acuity after the intervention. When comparing the two anti-VEGF agents, data revealed the effect of aflibercept was prompter and more long-lasting. Areas of retinal ischemia appeared in both cases. However, they were observed faster in the case of patients treated with aflibercept. Thus, neovascular AMD is a disease that occurs with age, it can be early detected by OCT and slowed the progression to central blindness with intravitreal treatment.

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

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.