Anti-vascular Endothelial Growth Factor Research Articles

Topical Dorzolamide as Adjunctive Treatment With Intravitreal Bevacizumab in Bilateral Diabetic Macular Edema.

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents is accepted as the gold standard treatment for center-involving diabetic macular edema (CI-DME). Adjunctive administration of topical dorzolamide may enhance the therapeutic effects of anti-VEGF agents. In this study, we compared the efficacy of topical dorzolamide plus intravitreal injection of bevacizumab (IVB) versus IVB alone in patients with bilateral DME. This prospective, randomized contralateral eye study was carried out in a tertiary referral ophthalmology center, Al-Zahra Eye Hospital, Zahedan, Iran, between April 2021 and April 2022. Thisstudy included 50 eyes of 25 patients with bilateral DME. All eyes received three consecutive monthly injections of IVB. For each patient, one eye was randomized to instill dorzolamide eye drops three times a day as an intervention, and the other received artificial tear drops as a placebo. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and intraocular pressure (IOP) were evaluated before starting treatment and then monthly for the first three months. Among 25 included patients, the average age was 56.64 ± 7.97 years, and 48% were female. BCVA did not improve significantly in any groups (P > 0.05). No significant difference was observed in terms of BCVA between the intervention and control groups (P > 0.05). The present study showed a decrease in CMT in both study groups (P < 0.05). At month 3, the decrease in mean CMT from baseline was significantly higher in eyes receiving topical dorzolamide compared to the control group (-88.92 ± 82.90 vs. -37.64 ± 86.16 µM, respectively; P = 0.037). IOP decreased significantly only in eyes receiving dorzolamide (P < 0.001). The results of the present study indicate that adjunctive administration of topical dorzolamide has a beneficial effect on CMT reduction from baseline, but it did not have an additive effect on BCVA improvement compared to IVB monotherapy.

Innovations in Diabetic Macular Edema Management: A Comprehensive Review of Automated Quantification and Anti-vascular Endothelial Growth Factor Intervention.

Diabetic macular edema (DME) poses a significant threat to the vision and quality of life of individuals with diabetes. This comprehensive review explores recent advancements in DME management, focusing on integrating automated quantification techniques and anti-vascular endothelial growth factor (anti-VEGF) interventions. The review begins with an overview of DME, emphasizing its prevalence, impact on diabetic patients, and current challenges in management. It then delves into the potential of automated quantification, leveraging machine learning and artificial intelligence to improve early detection and monitoring. Concurrently, the role of anti-VEGF therapies in addressing the underlying vascular abnormalities in DME is scrutinized. The review synthesizes vital findings, highlighting the implications for the future of DME management. Promising outcomes from recent clinical trials and case studies are discussed, providing insights into the evolving landscape of personalized medicine approaches. The conclusion underscores the transformative potential of these innovations, calling for continued research, collaboration, and integration of these advancements into clinical practice. This review aims to serve as a roadmap for researchers, clinicians, and industry stakeholders, fostering a collective effort to enhance the precision and efficacy of DME management.

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.

Acceleration of moyamoya disease after anti-vascular endothelial growth factor intravitreal injections

Abstract: Moyamoya disease (MMD) is a rare, progressive, irreversible vaso-occlusive disease affecting the cerebral vasculature. The progressive occlusion of blood vessels leads to the development of collateral vessels to compensate for the insufficient blood supply. Some growth factors such as vascular endothelial growth factor (VEGF) may cause excessive and aberrant angiogenesis in MMD. We report a case of a 55-year-old male, following up in retina clinics for diabetic retinopathy and macular edema who received anti-VEGF agents then he presented to the emergency room with left-sided face and body weakness, dysphagia, and dysarthria. Based on his clinical presentation and neuroimaging, he was diagnosed with moyamoya progression. We hypothesize that receiving anti-VEGF agents could have contributed to MMD progression in our patient and interfered with the collateral vessel development in a similar manner to their intended use in regressing neovascularization in diabetic retinopathy.

Treatment Strategies for Anti-VEGF Resistance in Neovascular Age-Related Macular Degeneration by Targeting Arteriolar Choroidal Neovascularization.

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declining responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

Hydrogel-Based Therapy for Age-Related Macular Degeneration: Current Innovations, Impediments, and Future Perspectives.

Age-related macular degeneration (AMD) is an ocular disease that leads to progressive photoreceptor death and visual impairment. Currently, the most common therapeutic strategy is to deliver anti-vascular endothelial growth factor (anti-VEGF) agents into the eyes of patients with wet AMD. However, this treatment method requires repeated injections, which potentially results in surgical complications and unwanted side effects for patients. An effective therapeutic approach for dry AMD also remains elusive. Therefore, there is a surge of enthusiasm for the developing the biodegradable drug delivery systems with sustained release capability and develop a promising therapeutic strategy. Notably, the strides made in hydrogels which possess intricate three-dimensional polymer networks have profoundly facilitated the treatments of AMD. Researchers have established diverse hydrogel-based delivery systems with marvelous biocompatibility and efficacy. Advantageously, these hydrogel-based transplantation therapies provide promising opportunities for vision restoration. Herein, we provide an overview of the properties and potential of hydrogels for ocular delivery. We introduce recent advances in the utilization of hydrogels for the delivery of anti-VEGF and in cell implantation. Further refinements of these findings would lay the basis for developing more rational and curative therapies for AMD.

Changes in wider field swept-source OCT angiography vascular metrics with anti-vascular endothelial growth factor therapy in central retinal vein occlusion.

To investigate the impact of anti-VEGF therapy on vascular metrics in eyes with macular edema secondary to central retinal vein occlusion (CRVO) using wider field swept-source OCT angiography (WF SS-OCTA). We included 23 eyes with macular edema associated with non-ischemic CRVOfrom 22 patients treated with anti-VEGF therapy (median number of injections: 5 [2-9]). Changes in vessel density (VD), vessel skeletonized density (VSD), and foveal avascular zone (FAZ) parameters were measured using WF SS-OCTA. Visual acuity (VA) and central subfield thickness (CST) were also measured. Median CST decreased significantly from 369µm (305-531) to 267µm (243-300, p < 0.001). VD and VSD parameters in 12 × 12mm images showed significant reductions. For instance, VSD in the whole retina decreased from a median of 13.37 (11.22-13.74) to 11.29 (9.36-12.97, p = 0.013). Additionally, a significant increase in FAZ circularity was found, suggesting improved microvascular integrity. Significant inverse correlations were found between the number of anti-VEGF injections and all VSD and VD parameters on the 12 × 12mm images (p < 0.05). Notably, the reductions in VSD and VD on 12 × 12mm angiograms in the deep capillary plexus (DCP) after each injection significantly correlated with increased logMAR VA (worse VA). Anti-VEGF therapy in CRVO patients not only mitigates macular edema but also alters the overall microvascular morphology and functionality as revealed by WF SS-OCTA.

Prevalence and risk factors for impaired activities of daily living in patients with neo-vascular age-related macular degeneration who present for anti-VEGF treatment.

To assess the prevalence and correlates of impaired activities of daily living (ADLs) in patients with neovascular age-related macular degeneration (nAMD) who present for anti-vascular endothelial growth factor (VEGF) therapy. In a clinic-based cohort of 437 patients with nAMD who presented for anti-VEGF therapy, the Older American Resources and Services Scale (OARS) was administered to assess for impairments in basic, instrumental and total ADL. Logistic regression analyses were conducted to determine odds ratios (OR) and 95% confidence intervals (CI) for factors associated with ADL impairment. The prevalence of impaired basic, instrumental and total ADL was 37.76%, 67.82% and 39.59%, respectively. In multivariate-adjusted models, moderate visual impairment [OR 5.65, 95% CI (2.31-13.83) and blindness [OR 5.43, 95% CI (2.09-14.12)] were associated with greater odds of impaired total ADL. Depressive symptoms [OR 2.08, 95% CI (1.08-4.00)], the presence of any disability [OR 3.16, 95% CI (1.64-0.07)] and never driving [OR 4.00, 95% CI (1.60-10.00)] were also positively associated with total ADL impairment. Better vision-related quality of life (QoL) was inversely associated with impaired instrumental ADL whilst higher health-related QoL scores were associated with decreased odds of total ADL impairment. There is a high prevalence rate of ADL impairment among nAMD patients presenting for therapy. Visual impairment, never driving, poor physical and mental health increased the odds of experiencing ADL impairment whilst better VRQoL and HRQoL reduced the odds of impairment.

Disease quiescence in endophthalmitis patients treated with anti-VEGF injections for retinal pathologies

BackgroundThe most feared complication of intravitreal injections is the development of endophthalmitis, which could lead to irreversible visual loss. The aim of this study was to characterize the clinical profiles, causative pathogens, and clinical outcome of patients post-endophthalmitis.MethodsRetrospective, single center case series study. Clinical records, causative pathogens and management of all cases of endophthalmitis post intravitreal anti-vascular endothelial growth factor (VEGF) injections recorded between January 1st, 2006 and May 30th, 2022; were retrieved. The visual and anatomic changes prior to the episode of endophthalmitis and up to 2 years post-treatment were compared.ResultsEleven post-injection endophthalmitis eyes of 10 patients (n = 3 females; 30%) were recruited at mean age of 64.5 ± 20.4 years. The median last recorded BCVA, up to 3 months prior to the episode of endophthalmitis was 60 (Interquartile range (IQR) 55–75) ETDRS letters. Then, it dropped to 30 (IQR 0-57.5), 35 (IQR 0-52.5) and 35 (IQR 0-57.5) ETDRS letters at presentation, 6- and 12-months follow-up; respectively (p = 0.027, p = 0.017 and p = 0.012). However, at 24 months, the median BCVA returned to similar baseline values prior to the episode of endophthalmitis; BCVA 50 (IQR 0–60) ETDRS letters, p = 0.062. Interestingly, two eyes with neovascular age-related macular degeneration (NVAMD), 1 with myopic choroidal neovascularization (CNV) and 1 with retinal vein occlusion (RVO), experienced disease quiescence and did not require additional anti-VEGF injections up to 2 years of follow-up.ConclusionThis study demonstrates long-term recovery of vision loss due to endophthalmitis post anti-VEGF injections, regained up to 2 years later. It also indicates that disease quiescence post endophthalmitis may not only occur in eyes treated for NVAMD, but also with myopic CNV and RVO.

Comparison of pigment epithelium detachment composition indices between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy

PurposeTo compare changes in the fibrous component of pigment epithelium detachment composition indices (PEDCI-F) in neovascular age-related macular degeneration (n-AMD) and polypoidal choroidal vasculopathy (PCV) over 12 months.MethodsThis was a retrospective chart review of treatment-naïve n-AMD and PCV eyes treated with anti-vascular endothelial growth factor (anti-VEGF) agents. Optical coherence tomography (OCT) images were recorded at baseline and at 3, 6, and 12 months. OCT images were processed by filtering followed by pigment epithelium detachment (PED) segmentation and analysis of PED lesion heterogeneity based on the composition (PEDCI-F).ResultsA total of 74 eyes with n-AMD (36) and PCV (38) were included. Overall, PEDCI-F increased minimally in both n-AMD and PCV groups (both p > 0.05). The majority, i.e., 58.3% and 60.5%, of n-AMD and PCV eyes, respectively, showed an increase in PEDCI-F at 12 months. An increase in PEDCI-F was associated with improved BCVA logMAR (n-AMD, r = -0.79; p < 0.001 and PCV, r = − 0.06; p = 0.74) and the need for fewer anti-VEGF injections (n-AMD, r = − 0.53; p < 0.001 and PCV, r = − 0.09; p = 0.58).ConclusionPEDCI-F increases in the majority of eyes with n-AMD and PCV through 12 months following treatment with anti-VEGF injections. This group had better visual acuity compared to the other subset with reduction in PEDCI-F requiring more anti-VEGF injections and worse visual acuity, possibly due to fibrovascular PED (FVPED) collapse and atrophy or a relative increase in other PEDCI constituents at 12 months.

Using capillary electrophoresis sodium dodecyl sulfate (CE-SDS) and liquid chromatograph mass spectrometry (LC-MS) to identify glycosylated heavy chain heterogeneity in the anti-VEGFR-2 monoclonal antibody.

The size variant, which can be measured by capillary electrophoresis sodium dodecyl sulfate (CE-SDS), is a critical quality attribute of monoclonal antibodies (mAbs). The CE-SDS size heterogeneity can hardly be identified by tandem mass spectrometry, which is an intractable obstacle of mAb development and quality control across the industry. We analyzed the purity of an anti-vascular endothelial growth factor receptor 2 (VEGFR-2) mAb, an antagonist of the human VEGFR-2, through reduced CE-SDS and observed glycosylated heavy chain heterogeneity. The heterogeneity has potential impact on safety, efficacy, and stability of drugs for clinical use. Therefore, it should be characterized so as to evaluate its potential risk. In order to identify the heterogeneity, we used mass spectrometry to confirm that the molecular size heterogeneity was not due to peptide bond cleavage in the heavy chain. Subsequently, we employed mass-spectrometry-glycosylation profiling and CE-SDS analysis of various glycosidase-treated samples, in addition to the preparation of mAb references with different glycoforms. Ultimately, we demonstrated that the heavy chain heterogeneity was induced by different levels of galactosylation modifications which will potentially impact the efficacy of antibody drugs (i.e., complement-dependent cytotoxicity). In this study, potential risk caused by heavy chain size heterogeneity was evaluated, which addressed the obstacle of mAb development and quality control. Therefore, this study offers a feasible approach for the investigation and identification of heavy chain heterogeneity in reduced CE-SDS, providing a novel strategy for mAb quality control and evaluation.

Injection Frequency and Differences in Visual Outcomes based on Diagnosis Year in Neovascular Age-related Macular Degeneration

Purpose: To evaluate the changes in injection frequency based on the diagnosis year in neovascular age-related macular degeneration (AMD) and the differences in visual outcomes associated with these changes.Methods: This retrospective study included 667 patients (667 eyes) diagnosed with treatment-naïve neovascular AMD and polypoidal choroidal vasculopathy in 2013, 2015, 2017, and 2019. The number of anti-vascular endothelial growth factor (VEGF) injections and degree of changes in visual acuity during the first 24 months after diagnosis were compared among the 4 years.Results: The 2013, 2015, 2017, and 2019 groups had a mean of 5.7 ± 2.7, 6.0 ± 2.8, 6.6 ± 3.0, and 6.9 ± 3.3 anti-VEGF injections, respectively. The number of injections was significantly higher in 2019 than in 2013 and 2015 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). The mean degree of visual change during the 24-month follow-up period was 0.07 ± 0.55, 0.01 ± 0.51, 0.08 ± 0.50, and 0.04 ± 0.48 in 2013, 2015, 2017, and 2019, respectively. There was a significant difference in the degree of visual change among the four groups (&lt;i&gt;p&lt;/i&gt; = 0.020).Conclusions: Patients diagnosed more recently tend to receive more injections and have better visual outcomes. We speculate that more injections contributed to these results. This trend should be considered when predicting the future socioeconomic burden of neovascular AMD.

Recent advances in the treatment and delivery system of diabetic retinopathy.

Diabetic retinopathy (DR) is a highly tissue-specific neurovascular complication of type 1 and type 2 diabetes mellitus and is among the leading causes of blindness worldwide. Pathophysiological changes in DR encompass neurodegeneration, inflammation, and oxidative stress. Current treatments for DR, including anti-vascular endothelial growth factor, steroids, laser photocoagulation, and vitrectomy have limitations and adverse reactions, necessitating the exploration of novel treatment strategies. This review aims to summarize the current pathophysiology, therapeutic approaches, and available drug-delivery methods for treating DR, and discuss their respective development potentials. Recent research indicates the efficacy of novel receptor inhibitors and agonists, such as aldose reductase inhibitors, angiotensin-converting enzyme inhibitors, peroxisome proliferator-activated receptor alpha agonists, and novel drugs in delaying DR. Furthermore, with continuous advancements in nanotechnology, a new form of drug delivery has been developed that can address certain limitations of clinical drug therapy, such as low solubility and poor penetration. This review serves as a theoretical foundation for future research on DR treatment. While highlighting promising therapeutic targets, it underscores the need for continuous exploration to enhance our understanding of DR pathogenesis. The limitations of current treatments and the potential for future advancements emphasize the importance of ongoing research in this field.

Subjective Visual Floaters after Intravitreal Injection and Effect of the Inverse Tapping Technique

Purpose: To analyze the incidence of vitreous floaters after intravitreal antivascular endothelial growth factor injection and the effectiveness of the inverse tapping technique, which involves tapping the syringe with the needle downwards to prevent the entry of air bubbles during injection.Methods: The study enrolled patients undergoing their first intravitreal injection for exudative age-related macular degeneration or diabetic macular edema. The patients were divided into two groups: those who received an injection after inverse tapping (IT group) and controls who received the injection without tapping. Patients who consented to the study were randomly assigned to the IT group and the control group through block randomization. One week after injection, a questionnaire was used to assess the presence of vitreous floaters; those who reported them were examined via optical coherence tomography and wide fundus photography.Results: Of the 39 patients in the IT group, two (5.1%) reported floaters 1 week after injection. By contrast, eight (20.5%) of the 39 controls reported them, with a significant difference (&lt;i&gt;p&lt;/i&gt; = 0.042). Patients with floaters were significantly younger. Posterior vitreous detachment, as evaluated by pre-injection optical coherence tomography, was observed in 10.0% of those with floaters and 76.5% of those without them.Conclusions: The occurrence of vitreous floaters after intravitreal injection is related to age and the presence of posterior vitreous detachment. The use of the inverse tapping technique may help reduce these after intravitreal injection.

Comparison Between Results of Trabeculectomy With or Without Anti- Vascular Endothelilal Growth Factor in Patients With Neovascular Glaucoma at Undaan Eye Hospital Surabaya, Indonesia

Introduction &amp; ObjectivesNew intraocular medication, Anti-vascular endothelial growth factor (Anti-VEGF) agents has beendeveloped in the management of neovascular glaucoma and in glaucoma surgery. But there are nostudies comparing trabeculectomy with Anti-VEGF to no Anti-VEGF treatment in patients withneovascular glaucoma. This study aims to compare decrease of intraocular pressure (IOP) betweentrabeculectomy with Anti-VEGF and without Anti-VEGF in neovascular glaucoma.&#x0D; MethodsThis observational retrospective study comprised 30 medical records of neovascular glaucoma,divided to 15 medical records of patients with anti-VEGF before trabeculectomy and medical recordsof patients operated with trabeculectomy without anti-VEGF, monitored between January 2021 toDecember 2021. Patients with incomplete medical records were excluded. Data collected are age,gender, risk factor, intraocular pressure pre operative, and during 6 months follow-up IOP postoperative. Data analysis uses an Independent T test.&#x0D; ResultsFrom 30 samples, mean IOP in trabeculectomy with anti-VEGF group generally is 12,26 mmHg.Meanwhile, mean IOP in trabeculectomy without anti-VEGF group generally is 16,74 mmHg. Tindependent test between 2 groups shows that there are significant mean difference between themduring 1-5 months follow-up (1 month: p = 0,022; 2 months: p = 0,007; 3 months: p = 0,007; 4months: p = 0,042; 5 months: p = 0,029).&#x0D; ConclusionTrabeculectomy with prior administration of intravitreal anti-VEGF shows good IOP reduction andcan be implemented in NVG patients.

Initial Outcome of Subconjunctival Bevacizumab for Corneal Neovascularization - a Case Series

Introduction : Corneal neovascularization (CNV) has a variety of causes and threatens corneal clarity, thus optimal visual acuity. Conventional medical management includes topical steroids and matrix metalloproteinase inhibitors like doxycycline. Anti-vascular endothelial growth factor (anti-VEGF) agents have demonstrated promise but remain off-label for this indication.&#x0D; Case Illustration : We present three patients with corneal neovascularization varied in etiology who underwent subconjunctival injection of Bevacizumab . Case 1: a-female-69 years old came with blurred vision after had Stephen Johnson Syndrome which affect her cornea. The examination revealed opacification of cornea accompanied by neovascularization at 5 until 9 o’clock position up to edge of pupil in the left. Case 2: a-male-47 years old presented corneal haze with neovascularization almostin all corneal region on background of fungal keratitis. Case 3: a-male-63 years old who underwent penetrating keratoplasty of indication corneal lekoma following an episode of fungal keratitis. There was opacity in all corneal region and neovascularization in 360 degree of limbus. All of these patients showed regression of neovessel after first injection of bevacizumab.&#x0D; Discussion : Corneal neovascularization is a condition caused by disruption homeostasis in which proangiogenic balanced by antiangiogenic, thereby maintaining avascularity. Bevacizumab as VEGF-A-binding proteins could prevent VEGF-A from binding cell surface receptors.&#x0D; Conclusion : Subconjunctival injection of Bevacizumab can be considered as a treatment for corneal neovascularization. It has shown promising effects in recess neovascularization in cornea regardlessthe etiology.

Steroidal nanoformulations for the treatment of uveitis: potential, promises and future perspectives.

Intraocular inflammation, commonly referred to as uveitis, is a prevalent ocular disease. The categorization of uveitis may be based on the prevailing anatomical site, which includes anterior, intermediate, and posterior uveitis. There exists a significant body of evidence indicating that T cells play a pivotal role in the pathogenesis of autoimmune uveitis. In addition to the presence of T cells, an elevation in levels of inflammatory cytokines and a reduction in regulatory cytokines were also noted. The primary pharmacological interventions for uveitis comprise of corticosteroids, methotrexate, anti-vascular endothelial growth factor (VEGF) agents, anti-tumor necrosis factor-alpha (TNF-α) antibodies, and sirolimus. These medications offer prompt alleviation for inflammation. Nevertheless, prolonged administration of corticosteroids invariably leads to unfavorable adverse reactions. The traditional topical corticosteroids exhibit certain limitations, including inadequate transcorneal permeation and low corneal retention, leading to reduced ocular bioavailability. Consequently, there is a growing inclination towards the creation of innovative steroid drug delivery systems with the aim of reducing the potential for adverse effects, while simultaneously enhancing the drug's corneal permeation and retention. This review is an attempt to compile all the research work done so far in this field and provides a brief overview of the global efforts to develop innovative nanocarrier-based systems for corticosteroids.

Advances in Research Related to MicroRNA for Diabetic Retinopathy.

Diabetic retinopathy (DR) is a severe microvascular complication of diabetes and is one of the primary causes of blindness in the working-age population in Europe and the United States. At present, no cure is available for DR, but early detection and timely intervention can prevent the rapid progression of the disease. Several treatments for DR are known, primarily ophthalmic treatment based on glycemia, blood pressure, and lipid control, which includes laser photocoagulation, glucocorticoids, vitrectomy, and antivascular endothelial growth factor (anti-VEGF) medications. Despite the clinical efficacy of the aforementioned therapies, none of them can entirely shorten the clinical course of DR or reverse retinopathy. MicroRNAs (miRNAs) are vital regulators of gene expression and participate in cell growth, differentiation, development, and apoptosis. MicroRNAs have been shown to play a significant role in DR, particularly in the molecular mechanisms of inflammation, oxidative stress, and neurodegeneration. The aim of this review is to systematically summarize the signaling pathways and molecular mechanisms of miRNAs involved in the occurrence and development of DR, mainly from the pathogenesis of oxidative stress, inflammation, and neovascularization. Meanwhile, this article also discusses the research progress and application of miRNA-specific therapies for DR.

Intermittent Topical Bevacizumab for Treatment of Pediatric Corneal Neovascularization after Keratitis

Introduction : Corneal neovascularization imposes pediatric patients to risk of amblyopia. Current treatment of corneal neovascularization consists of topical steroids, nonsteroidal anti-inflammatory medications, immunomodulatory agents, anti-Vascular Endothelial Growth Factor (anti-VEGF) and few surgical procedures. Anti-VEGF shows promising results in treating corneal neovascularization but is difficultto obtain in developing countries such as Indonesia. We report intermittent topical use of Bevacizumab as antiVEGF in a child experiencing corneal neovascularization in the settings of limited antiVEGF availability.&#x0D; Case Illustration : A 5-year-old girl presented with corneal neovascularization after keratitis. Topical fluorometholone 4 times a day for 3 weeks was given with no clinical improvement. An intermittent topical Bevacizumab was started, each episode of treatment lasted 4 days. Corneal neovascularization regressed after 1 episode of treatment and thus continued until a total of 2 treatment episodes. She improved clinically on treatment, with some residual corneal scarring. Visual acuity improved from logMar 0.5 to logMar 0.2 following treatment.&#x0D; Discussion : Bevacizumab regresses corneal neovascularization by inhibiting proangiogenic factor VEGF which is upregulated in neovascularization. Topical Bevacizumab ability to penetrate cornea was contributed by defective corneal epithelial overlying neovascularization. Long-term use of antiVEGF may hinder VEGF beneficial role on wound recovery and trigger unwanted side effects.&#x0D; Conclusion : Intermittent short-term use of topical bevacizumab may be effective to treat corneal neovascularization during acute period in pediatric patient and is safely tolera

OUTCOME OF EYES TREATED FOR RETINOPATHY OF PREMATURITY IN POSTERIOR ZONE I: An Eastern India Study.

To analyze the outcomes of eyes treated for retinopathy of prematurity in posterior Zone I. In a part retrospective (9 years) and part prospective (1 year) interventional study, we analyzed eyes treated for retinopathy of prematurity in posterior Zone I with a minimum follow-up for 6 months. This study included 109 eyes of 56 infants; mean gestational age and birth weights were 29.3 (±2.1) weeks and 1112.5 (±381.9) g, respectively. The treatment included intravitreal anti-vascular endothelial growth factor as the initial treatment modality in 101 eyes (92.6%), either alone (27 eyes) or combined with laser or vitreous surgery (73 eyes). Laser was the initial treatment modality in eight eyes, either alone (n = 3) or in combination with surgery (n = 5). With anti-vascular endothelial growth factor alone, 30.68% (n = 27) eyes responded favorably, and the remaining 69.32% (n = 59) eyes needed retreatment (laser in the majority). At the final follow-up, 89.9% (out of 109) of eyes did well anatomically. Good outcome was significantly linked to no detachment at presentation ( P < 0.0001) and the presence of well-defined central vascular trunks ( P = 0.001). Treating the eyes before retinal detachment with bevacizumab followed by laser (and surgery, if needed) results in a favorable outcome in babies with posterior Zone I retinopathy of prematurity.