Anti-vascular Endothelial Growth Factor Agents Research Articles

Coenzyme Q10 eyedrops conjugated with vitamin E TPGS alleviate neurodegeneration and mitochondrial dysfunction in the diabetic mouse retina

Diabetic retinopathy (DR) is a leading cause of blindness and vision impairment worldwide and represents one of the most common complications among diabetic patients. Current treatment modalities for DR, including laser photocoagulation, intravitreal injection of corticosteroid, and anti-vascular endothelial growth factor (VEGF) agents, target primarily vascular lesions. However, these approaches are invasive and have several limitations, such as potential loss of visual function, retinal scars and cataract formation, and increased risk of ocular hypertension, vitreous hemorrhage, retinal detachment, and intraocular inflammation. Recent studies have suggested mitochondrial dysfunction as a pivotal factor leading to both the vascular and neural damage in DR. Given that Coenzyme Q10 (CoQ10) is a proven mitochondrial stabilizer with antioxidative properties, this study investigated the effect of CoQ10 eyedrops [in conjunction with vitamin E d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS)] on DR-induced neurodegeneration using a type 2 diabetes mouse model (C57BLKsJ-db/db mice). Utilizing a comprehensive electroretinography protocol, supported by immunohistochemistry, our results revealed that topical application of CoQ10 eyedrops conjugated with vitamin E TPGS produced a neuroprotective effect against diabetic-induced neurodegeneration by preserving the function and histology of various retinal neural cell types. Compared to the control group, mice treated with CoQ10 exhibited thicker outer and inner nuclear layers, higher densities of photoreceptor, cone cell, and rod-bipolar cell dendritic boutons, and reduced glial reactivity and microglial cell density. Additionally, the CoQ10 treatment significantly alleviated retinal levels of MMP-9 and enhanced mitochondrial function. These findings provide further insight into the role of mitochondrial dysfunction in the development of DR and suggest CoQ10 eyedrops, conjugated with vitamin E TPGS, as a potential complementary therapy for DR-related neuropathy.

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

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

Bilateral multiple recurrent branch retinal vein occlusions secondary to hypercoagulopathy associated with multiple mutations: A rare case report

Abstract: Retinal vein occlusions (RVOs) are relatively common vascular disorders, often resulting in significant visual impairment. We present an intriguing case of a 53-year-old male with recurrent bilateral branch RVOs stemming from underlying hypercoagulopathy. This complex scenario encompassed simultaneous bilateral RVO occurrences and subsequent unilateral recurrences. Despite the absence of systemic comorbidities or conventional risk factors, genetic assessment unveiled notable heterozygous mutations involving Factor V Leiden (G1691A) and Factor II (PT G20210A), along with a homozygous methylenetetrahydrofolate reductase A1298C mutation. While routine hematological indicators remained largely unremarkable, the marked efficacy of anti-vascular endothelial growth factor (anti-VEGF) agents, particularly when administered promptly, emerged as a noteworthy therapeutic avenue. This case underscores the imperative of scrutinizing thrombotic mutations in youthful patients with recurrent RVOs, accentuating the favorable retinal response to anti-VEGF interventions and emphasizing the rewards of timely clinical intervention.

Faricimab in Previously Treated Eyes With Neovascular Age-Related Macular Degeneration: An Assessment of Durability and Treatment Outcomes.

This study evaluated the efficacy and durability of faricimab in patients with neovascular age-related macular degeneration (nAMD) who were previously treated with anti-vascular endothelial growth factor (anti-VEGF) agents. This retrospective case series was conducted at a single tertiary center in the United States. It focused on nAMD patients who transitioned to faricimab after initial anti-VEGF therapy, with a follow-up period of at least 9 months. "Complete dryness" was defined as the absence of intra- and/or subretinal fluid on optical coherence tomography. Durability was gauged by the extension of treatment intervals relative to the injection frequency of the previous agent. Sixty-two eyes from 62 patients were included. Treatment interval ranged from 5 to 10 weeks; 10 (16%) patients were able to be extended by 2 or more weeks compared to their previous regimen. Median (interquartile range [IQR]) central field thickness was 310 μm (254, 376) on initiating faricimab and declined by the ninth month (P values at 3, 6, and 9 months were 0.01, 0.02, and 0.07, respectively). Median (IQR) visual acuity at initiation of faricimab was 0.4 (0.20, 0.50) and did not change by the ninth month. Complete anatomical dryness was present in 10 (16%) eyes before switching; 90% remained dry at 9 months. Of 52 (84%) incompletely dry eyes before switching, 15% achieved complete dryness by 9 months on faricimab. Faricimab modestly improved the treatment intervals for a small proportion of previously treated patients on anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Treatment Effects of Switching to Faricimab in Eyes with Diabetic Macular Edema Refractory to Aflibercept.

Background and Objectives: Faricimab is a vascular endothelial growth factor A and angiopoietin-2 bispecific antibody. It is a novel therapeutic approach distinct from previous anti-vascular endothelial growth factor agents. This study aimed to evaluate the efficacy of switching from aflibercept to faricimab in the treatment of diabetic macular edema (DME) refractory to aflibercept, with a specific focus on the resolution of macular edema. Materials and Methods: The medical records of 29 eyes of 21 patients with DME that were refractory to intravitreal injections of aflibercept (IVAs) and who had completed the clinical follow-up of at least four intravitreal injections of faricimab (IVFs) were reviewed. The central retinal thickness (CRT), best-corrected visual acuity (BCVA), and the mean period (weeks) until the next injection were measured after the second-to-last IVA, first-to-last IVA, last IVA, and first to fourth IVFs following the transition to IVF. Results: The mean time from the first IVF to the assessment of effectiveness was significantly shorter than the time to the last IVA; however, no significant difference was found in the time from the second, third, and fourth IVFs to the assessment. The mean CRTs after the first and second IVFs were not significantly different from the CRT after the last IVA, but the mean CRT after the third and fourth IVFs was significantly thinner than that after the last IVA (p = 0.0025 and p = 0.0076, respectively). The mean BCVAs after the third and fourth IVFs significantly improved compared with that after the last IVA (p = 0.0050 and p = 0.0052, respectively). Conclusions: When switching the treatment to IVF for eyes with IVA-resistant DME, better treatment outcomes are achieved if IVF is performed three or more times.

The efficacy of adjunctive mitomycin C and/or anti-VEGF agents on glaucoma tube shunt drainage device surgeries: a systematic review.

The effectiveness of mitomycin C (MMC) in trabeculectomy has long been established. The aim of this review is to evaluate the efficacy and safety of adjunctive agents in tube shunt drainage device surgery for glaucoma or ocular hypertension, since controversy still exists regarding their benefit. We searched CENTRAL, PubMed, Embase, Web of Science, Scopus, and BASE for RCTs, which have used adjuvant antimetabolites-either MMC or 5-Fluorouracil (5-FU)-and/or anti-vascular endothelial growth factors (anti-VEGF) agents. The main outcome was IOP reduction at 12 months. Ten studies met our inclusion criteria. Nine used the Ahmed Glaucoma Valve (AGV) implant, while the double-plate Molteno implant was used in one study. Four studies used MMC. The remaining six studies used an anti-VEGF drug - either bevacizumab, ranibizumab or conbercept. Only one MMC-study reported a significant difference in the IOP reduction between groups at 12 months, favouring the MMC group (55% and 51%; p < 0.01). A significant difference was also reported by two out of five bevacizumab-studies, both favouring the bevacizumab group (55% and 51%, p < 0.05; 58% and 27%, p < 0.05), with the highest benefit seen in neovascular glaucoma cases, especially when panretinal photocoagulation (PRP) was also used. Neither ranibizumab nor conbercept were found to produce significant differences between groups regarding IOP reduction. There is no high-quality evidence to support the use of MMC in tube shunt surgery. As for anti-VEGF agents, specifically bevacizumab, significant benefit seems to exist in neovascular glaucoma patients, especially if combined with PRP.

Visual outcomes of intraocular inflammation after brolucizumab injection in Japanese patients with neovascular age-related macular degeneration.

This study investigates the visual outcomes of neovascular age-related macular degeneration (nAMD) patients who developed intraocular inflammation (IOI) after intravitreal brolucizumab injection (IVBr). We studied 285 eyes of 279 cases diagnosed with nAMD and focused on 18 eyes (6.3%) of 17 cases which developed IOI after IVBr. IVBr was performed either on the initial treatment or for switching of other anti-vascular endothelial growth factor agents during January 2020 to December 2021. We evaluated clinical features and the course of treatment of a 6-month follow-up after IOI occurred. Of 17 cases, 9 cases were male, 8 cases were female. Baseline logarithm of the minimum angle of resolution(logMAR) best-corrected visual acuity (BCVA) was 0.36, BCVA before IOI occurred was 0.30, and BCVA when IOI occurred was 0.43. 16 eyes (88.9%) had symptoms such as visual loss or floaters when IOI occurred. On the other hand, the remaining 2 eyes (11.1%) had no symptoms. 11 eyes (61.1%) had only IOI, while the remaining 7 eyes (38.9%) had IOI and perivascular sheathing. Steroid sub-tenon injection was performed on 1 eye (5.6%), steroid eye drops were used in 11 eyes (61.1%), and 6 eyes (33.3%) were followed-up without treatment. Neovascular AMD recurred in 16 eyes (88.9%) after IOI occurred and were treated with aflibercept. VA at 3 and 6 months after IOI occurred were significantly improved to 0.34 and 0.30, respectively (P = 0.09 at 3 months and P = 0.02 at 6 months). The symptoms of patients were improved in all cases. We were able to stop steroid treatment in all cases. IOI occurred in 6.3% of nAMD patients after IVBr treatment. All of which showed significant improvement from logMAR of 0.43 to 0.30 with steroid treatment or without any treatment. We should consider the possibility of IOI after IVBr as a complication, however, they have a relatively good prognosis if treated at an early stage.

Exploring Current Molecular Targets in the Treatment of Neovascular Age-Related Macular Degeneration toward the Perspective of Long-Term Agents.

Long-lasting anti-vascular endothelial growth factor (anti-VEGF) agents have become an option to reduce treatment frequency, with ongoing research exploring optimal responses and safety profiles. This review delves into molecular targets, pharmacological aspects, and strategies for achieving effective and enduring disease control in neovascular age-related macular degeneration (AMD). The molecular pathways involved in macular neovascularization, including angiogenesis and arteriogenesis, are explored. VEGF, PlGF, Ang-1, and Ang-2 play crucial roles in regulating angiogenesis, influencing vessel growth, maturation, and stability. The complex interplay of these factors, along with growth factors like TGFβ and bFGF, contributes to the pathogenesis of neovascular membranes. Current anti-VEGF therapies, including bevacizumab, ranibizumab, aflibercept, brolucizumab, and faricimab, are discussed with a focus on their pharmacokinetics and clinical applications. Strategies to achieve sustained disease control in AMD involve smaller molecules, increased drug dosages, and novel formulations. This narrative review provides a comprehensive overview of the molecular targets and pharmacological aspects of neovascular AMD treatment.

Deep learning assisted fluid volume calculation for assessing anti-vascular endothelial growth factor effect in diabetic macular edema

ObjectiveTo develop an algorithm using deep learning methods to calculate the volume of intraretinal and subretinal fluid in optical coherence tomography (OCT) images for assessing diabetic macular edema (DME) patients’ condition changes. DesignCross-sectional study. ParticipantsTreatment-naive patients diagnosed with DME recruited from April 2020 to November 2021. MethodsThe deep learning network, which was built for autonomous segmentation utilizing an encoder-decoder network based on the U-Net architecture, was used to calculate the volume of intraretinal fluid (IRF) and subretinal fluid (SRF). The alterations of retinal vessel density and thickness, and the correlation between best-corrected visual acuity (BCVA) and OCT parameters were analyzed. Results2,955 OCT images of fourteen eyes from DME patients with IRF and SRF who received anti-vascular endothelial growth factor (VEGF) agents were obtained. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve of the algorithm was 0.993 for IRF and 0.998 for SRF. The volumes of IRF and SRF were significantly decreased from 1.93 ± 0.58 /1.14 ± 0.25 mm3 (baseline) to 0.26 ± 0.13 /0.26 ± 0.18 mm3 (post-injection), respectively (p = 0.0170 for IRF, and p = 0.0004 for SRF). The Spearman correlation demonstrated that the reduction of IRF volume was negatively correlated with age (coefficient = −0.698, p = 0.006). ConclusionWe developed a deep learning assisted fluid volume calculation algorithm with high sensitivity and specificity for assessing the volume of IRF and SRF in DME patients. Key words: deep learning; diabetic macular edema; optical coherence tomography.

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

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

Assessment of intraocular pressure changes following intravitreal injections of three anti-VEGF agents

PurposeIntravitreal injection (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents has emerged as the primary treatment for prevalent retinal diseases. Despite its efficacy, IVI may induce intraocular pressure elevation due to vitreous fluid shifts. This study aims to compare the effects of three distinct anti-VEGF agents on intraocular pressure (IOP) elevation within a single clinic setting. DesignA prospective study, conducted at a single retinal clinic in a tertiary medical center (Tel Aviv Sourasky Medical Centre, Tel-Aviv, Israel). MethodsPatients receiving 3 different anti VEGF medications; bevacizumab, aflibercept, and ranibizumab, were examined. IOP was measured pre- and post-injection using an iCare Pro-tonometer. Demographic parameters and ocular characteristics were collected. ResultsThe study included 195 patients (average age 76.13 years; 100 males, 95 females). The medications administered were aflibercept (N = 70, 35 %), bevacizumab (N = 73, 37.4 %), and ranibizumab (N = 52, 26.7 %). In patients with a normal baseline intraocular pressure, no significant variance was observed in the post-injection versus pre-injection pressure change (delta) across medications. Conversely, in patients with higher pressure (>20 mmHg), aflibercept incited a more substantial increase than bevacizumab or ranibizumab. No correlation emerged between the pressure rise and age or lens status. ConclusionsNo significant difference was found in the increase of intraocular pressure following injection among different medications in patients with low-normal intraocular pressure. However, for patients prone to higher baseline pressure, caution is recommended with aflibercept due to a more pronounced increase. Further research is essential to comprehend the factors influencing pressure increase and their associated clinical implications.

A prospective comparative study of conjunctival autograft (CAG) with dry amniotic membrane graft (AMG) transplantation in pterygium excision surgery

: Pterygium is a wing-shaped, fibrovascular proliferation of the bulbar conjunctiva which crosses the limbus and causes encroachment over the cornea. It is mainly treated by surgical excision. Management options for pterygium include conjunctival autografting, and the use mitomycin C, amniotic membrane graft, 5-fluorouracil, anti-vascular endothelial growth factor (anti-VEGF) agents, and β-irradiation along with excision, to avoid recurrence.: To compare the efficacy and safety of conjunctival autograft (CAG) transplantation and dry amniotic membrane graft (AMG) transplantation in pterygium excision surgery.: Prospective comparative study.: The study was done on 43 eyes of 43 patients. CAG was transplanted on 23 patients &amp; dry AMG was transplanted on 20 patients. All patients were followed up on day 1, day 7, 1 month and 6 months post operatively. On each visit pterygium recurrence, graft retraction, necrosis and visual outcomes were noted from all the patients.: Fisher exact test.: 28(65%) were males while 15(35%) were females. Most of the patients were &amp;#60;40 years of age. During the follow up period, best corrected visual acuity of 3(7%) patients remained same and improved in 40(93%) patients. CAG group had 2(8.69%) while dry AMG group had 4(20%) recurrences (p value = 0.39, non-significant).: Although both the groups showed low recurrence rate but recurrence rate was more in dry AMG group as compared to conjunctival autograft group.: AMG is not always the best option for treating pterygium, but in some situations—such as those with extensive pterygium, conjunctival scarring etc.—it may be more advantageous for the patient.

GCN-assisted attention-guided UNet for automated retinal OCT segmentation

With the increase in the aging population of many countries, the prevalence of neovascular age-related macular degeneration (nAMD) is expected to increase. Morphological parameters such as intraretinal fluid (IRF), subretinal fluid (SRF), subretinal hyperreflective material (SHRM), and pigment epithelium detachment (PED) of spectral-domain optical coherence tomography (SD-OCT) images are vital markers for proper treatment of nAMD, especially to get the information of treatment response to determine the proper treatment interval and switching of anti-vascular endothelial growth factor (VEGF) agents. For the precise evaluation of the change in nAMD lesions and patient-specific treatment, quantitative evaluation of the lesions in the OCT volume scans is necessary. However, manual segmentation requires many resources, and the number of studies of automatic segmentation is increasing rapidly. Improving automated segmentation performance in SD-OCT visual results requires long-range contextual inference of spatial information between retinal lesions and layers. This paper proposes a GAGUNet (graph convolution network (GCN)-assisted attention-guided UNet) model with a novel global reasoning module considering these points. The dataset used in the main experiment of this study underwent rigorous review by a retinal specialist from Konkuk University Hospital in Korea, contributing to both data preprocessing and validation to ensure a qualitative assessment. We conducted experiments on the RETOUCH dataset as well to demonstrate the scalability of the proposed model. Overall, our model demonstrates superior performance over the baseline models in both quantitative and qualitative evaluations.

METHOD OF POVIDONE-IODINE APPLICATION AND ENDOPHTHALMITIS RISK.

To evaluate the proportion of patients developing endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor agents according to the mode of povidone-iodine (PI) antisepsis. A retrospective review of the anti-vascular endothelial growth factor injections given in a 7-year period at a community-based retinal practice. Endophthalmitis was diagnosed to have occurred if an eye developed intraocular inflammation and was given antibiotics with or without supportive culture identification of an organism. As part of their habitual clinical practice, component physicians used 5% PI as two drops, one drop, or just a dot of PI administered with a cotton-tipped applicator to the site before injection. There were 113,610 intravitreal injections administered and 23 cases were diagnosed with endophthalmitis over the 7-year period, for a rate of 1 case per 4,940 injections. The mode of PI antisepsis showed no significant relation to the rate of endophthalmitis ( P = 0.55, chi-square test). The proportion of endophthalmitis by physician demonstrated no significant difference ( P = 0.39, chi-square test). The use of PI has been associated with decreased incidence of endophthalmitis, but the mode of application has not been standardized. The results of this study suggest that "more is not better" in PI antisepsis in endophthalmitis. Moreover, the toxicity of PI on the ocular surface is known to be dose-related.

Comparative efficacy and safety of different anti-VEGF agents combined with different delivery methods for neovascular glaucoma: a systematic review and Bayesian network meta-analysis

ObjectiveTo compare the efficacy and safety of different anti-vascular endothelial growth factor (VEGF) agents combined with different delivery methods for neovascular glaucoma (NVG).DesignSystematic review and Bayesian network meta-analysis (NMA).Data sourcesPubMed,...

Genetics and Age-Related Macular Degeneration: A Practical Review for Clinicians.

Age-related macular degeneration (AMD) is a multifactorial genetic disease, with at least 52 identifiable associated gene variants at 34 loci, including variants in complement factor H (CFH) and age-related maculopathy susceptibility 2/high-temperature requirement A serine peptidase-1 (ARMS2/HTRA1). Genetic factors account for up to 70% of disease variability. However, population-based genetic risk scores are generally more helpful for clinical trial design and stratification of risk groups than for individual patient counseling. There is some evidence of pharmacogenetic influences on various treatment modalities used in AMD patients, including Age-Related Eye Disease Study (AREDS) supplements, photodynamic therapy (PDT), and anti-vascular endothelial growth factor (anti-VEGF) agents. However, there is currently no convincing evidence that genetic information plays a role in routine clinical care.

Displacement of Submacular Hemorrhage Using Subretinal Cocktail Injection versus Pneumatic Displacement: A Real-World Comparative Study

Introduction: The objective of this study was to compare the outcome of submacular hemorrhage (SMH) displacement using pneumatic displacement with intravitreal expansile gas versus pars plana vitrectomy (PPV) with subretinal injection of tissue plasminogen activator (tPA), anti-vascular endothelial growth factor (VEGF) agent, and air as primary surgery. Methods: Retrospective interventional case series of 63 patients who underwent surgical displacement of SMH secondary to neovascular age-related macular degeneration (nAMD) or polypoidal choroidal vasculopathy (PCV) from May 1, 2015, to October 31, 2022. Medical records were reviewed for diagnosis, logMAR visual acuity (VA), central subfield thickness (CST), and postoperative displacement rates and complications up to 12 months after operation. Results: The diagnosis was nAMD in 24 (38.1%) and PCV in 39 (61.9%) eyes. There were 40 (63.5%) eyes in the pneumatic displacement group (38 received C3F8, 2 received SF6) and 23 (36.5%) eyes in the subretinal cocktail injection. Mean baseline VA was 1.46 and 1.62, respectively (p = 0.404). The subretinal injection group had more extensive SMH (p = 0.005), thicker CST (1,006.6 μm vs. 780.2 μm, p = 0.012), and longer interval between symptom and operation (10.65 vs. 5.53 days, p p = 0.180) for pneumatic displacement and subretinal injection groups, respectively, though VA was significantly better in the pneumatic group at 12-month visit (0.64 vs. 1.03, p = 0.040). At least 10 mean change in VA were >10 letters gain in both groups up to 12 months. Postoperative CST reduction was greater (625.1 μm vs. 326.5 μm, p = 0.008) and complete foveal displacement (87.0% vs. 37.5%), p p = 0.009, OR = 5.15) were more frequent in the subretinal injection group. Two patients with failed pneumatic displacement were successfully treated with subretinal cocktail injection as a second operation. Conclusion: Surgical displacement of SMH leads to clinically meaningful improvement in VA. PPV with subretinal cocktail injection is more effective than pneumatic displacement in displacing SMH with similar safety profile despite longer interval before operation, higher CST, and more extensive SMH at baseline. Retinal surgeons could consider this novel technique in cases with thick and extensive SMH or as a rescue secondary operation in selected cases.

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.

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.

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.