Intravitreal Therapy Research Articles

Pegcetacoplan Treatment and Consensus Features of Geographic Atrophy Over 24 Months

Despite widespread availability and consensus on its advantages for detailed imaging of geographic atrophy (GA), spectral-domain optical coherence tomography (SD-OCT) might benefit from automated quantitative OCT analyses in GA diagnosis, monitoring, and reporting of its landmark clinical trials. To analyze the association between pegcetacoplan and consensus GA SD-OCT end points. This was a post hoc analysis of 11 614 SD-OCT volumes from 936 of the 1258 participants in 2 parallel phase 3 studies, the Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (OAKS) and Study to Compare the Efficacy and Safety of Intravitreal APL-2 Therapy With Sham Injections in Patients With Geographic Atrophy (GA) Secondary to Age-Related Macular Degeneration (DERBY). OAKS and DERBY were 24-month, multicenter, randomized, double-masked, sham-controlled studies conducted from August 2018 to July 2020 among adults with GA with total area 2.5 to 17.5 mm2 on fundus autofluorescence imaging (if multifocal, at least 1 lesion ≥1.25 mm2). This analysis was conducted from September to December 2023. Study participants received pegcetacoplan, 15 mg per 0.1-mL intravitreal injection, monthly or every other month, or sham injection monthly or every other month. The primary end point was the least squares mean change from baseline in area of retinal pigment epithelium and outer retinal atrophy in each of the 3 treatment arms (pegcetacoplan monthly, pegcetacoplan every other month, and pooled sham [sham monthly and sham every other month]) at 24 months. Feature-specific area analysis was conducted by Early Treatment Diabetic Retinopathy Study (ETDRS) regions of interest (ie, foveal, parafoveal, and perifoveal). Among 936 participants, the mean (SD) age was 78.5 (7.22) years, and 570 participants (60.9%) were female. Pegcetacoplan, but not sham treatment, was associated with reduced growth rates of SD-OCT biomarkers for GA for up to 24 months. Reductions vs sham in least squares mean (SE) change from baseline of retinal pigment epithelium and outer retinal atrophy area were detectable at every time point from 3 through 24 months (least squares mean difference vs pooled sham at month 24, pegcetacoplan monthly: -0.86 mm2; 95% CI, -1.15 to -0.57; P < .001; pegcetacoplan every other month: -0.69 mm2; 95% CI, -0.98 to -0.39; P < .001). This association was more pronounced with more frequent dosing (pegcetacoplan monthly vs pegcetacoplan every other month at month 24: -0.17 mm2; 95% CI, -0.43 to 0.08; P = .17). Stronger associations were observed in the parafoveal and perifoveal regions for both pegcetacoplan monthly and pegcetacoplan every other month. These findings offer additional insight into the potential effects of pegcetacoplan on the development of GA, including potential effects on the retinal pigment epithelium and photoreceptors. ClinicalTrials.gov Identifiers: NCT03525600 and NCT03525613.

SUCCESSFUL TREATMENT OF SEVERE PERIPAPILLARY PACHYCHOROID SYNDROME WITH ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY.

To describe two cases of severe peripapillary pachychoroid syndrome successfully managed with monthly intravitreal aflibercept therapy. Medical and imaging records were retrospectively reviewed. Patients were imaged with ultra-widefield fluorescein, indocyanine green angiography, and fundus autofluorescence. Spectral-domain optical coherence tomography was performed to evaluate macular edema and choroidal thickness. Optical coherence tomography angiography excluded macular neovascularization. This report summarizes two cases of peripapillary pachychoroid syndrome complicated by very severe bilateral macular edema. In all four eyes, the diffuse intraretinal and subretinal fluid remarkably improved or completely resolved after monthly intravitreal aflibercept injections with commensurate improvement of visual acuity. Multimodal imaging documented the significant improvement of fluid and the reduction in choroidal thickening in response to anti-vascular endothelial growth factor therapy in each case. Severe cases of peripapillary pachychoroid syndrome associated with vision loss can be successfully treated with intravitreal aflibercept therapy.

Typical cytomegalovirus retinitis in non-human immunodeficiency virus partially immunosuppressed patients: A case series

Purpose: The purpose of the study was to analyze the occurrence of severe, typical cytomegalovirus (CMV) retinitis (CMVR) in human immunodeficiency virus (HIV) negative, partially immunosuppressed patients, emphasizing inconsistency in the clinical presentation of CMVR and to evaluate the role of combined anti-CMV therapy in the management of such patients. Materials and Methods: This study was a retrospective, observational, noncomparative case series. We examined and treated consecutive HIV-negative adult patients of CMVR. Blood-based polymerase chain reaction analysis of the CMV genome was done pre- and posttreatment. Details of underlying systemic conditions were collected. Patients were treated with simultaneous administration of intravitreal and intravenous (IV) anti-CMV therapy. Follow-up was for 1 year. All outcomes were determined retrospectively. Results: A total of 6 eyes of 4 consecutive patients were diagnosed with CMVR in HIV-negative patients. Patients were only partially immunosuppressed but revealed typical severe fulminant CMVR. Patients received a total of 2 intravitreal ganciclovir injections, and IV ganciclovir/oral valganciclovir was given. All patients achieved complete healing within the treatment period. Conclusion: As opposed to the general perception, typical, fulminant, severe CMVR may occur in patients with limited immune dysfunction. Our report underlines this inconsistency in the clinical presentation of CMVR in partially immunosuppressed patients. The immune status of the patients seems a significant factor in determining the clinical phenotypes of CMVR. Combined intravitreal and IV ganciclovir/oral valganciclovir therapy was successful in treating this group of CMVR patients.

Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity

Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Complications of ROP treated at investigator discretion (no study treatment). Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. ClinicalTrials.gov Identifier: NCT04015180.

Chronic Serous Chorioretinopathy: A Case Study

Introduction Chronic central serous chorioretinopathy (CSCR) is characterized by persistent subretinal fluid that disrupts the outer layers of the retina and may lead to complications such as: outer retinal atrophy, increased risk of choroidal neovascularization (CNVM) and the potential for permanent vision loss. This report describes the clinical features of chronic CSCR. Case Presentation A 73-year-old male with a history of systemic steroid and inhaler use presented for a routine eye exam without visual complaints. Examination findings included normal visual acuity in both eyes and multiple areas of retinal hyper and hypopigmentation along the arcades with no macular involvement in the right eye; the left eye was unremarkable. Fundus photography and optical coherence tomography showed localized areas of outer retinal disruption and thinning near the optic nerve head and along the corresponding retinal areas of irregular pigmentation in the right eye; the left eye was unremarkable. Discussion In chronic CSCR, structural changes in the retina can lead to retinal dysfunction and permanent vision loss. Treatment options for chronic CSCR include photodynamic therapy, intravitreal anti-vascular endothelial growth factor therapy, or systemic steroid receptor blockers. Visual prognosis varies depending on the severity of the disease, age of onset, risk of CNVM and the degree of outer retinal degeneration. Conclusion Patients with chronic CSCR are at risk for permanent vision loss. The structural changes in the outer retina also increase the risk for CNVM. Hence, it is important that patients with chronic CSR receive regular eye examinations and are educated on the role of regular Amsler grid testing.

Long-term dynamic changes and influencing factors of corneal morphology after multiple intravitreal injections of anti-VEGF drugs.

To observe alterations in corneal morphology caused by repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF). Prospective cohort study. Seventy-seven eyes were treated with intravitreal injection of anti-VEGF from June 2021 to March 2023. There were 25 eyes of neovascular age-related macular degeneration (nAMD), 24 eyes of diabetic macular edema (DME), and 28 eyes of retinal vein occlusion (RVO). Aflibercept was used in 37 eyes and Ranibizumab was used in 40 eyes. 3 + PRN was used. Corneal endothelium and corneal thickness were measured using a corneal endothelial microscope. The data related to central corneal thickness, corneal endothelial cell density (ECD), average cell size, coefficient of variation (CV), proportion of hexagonal cells (Hex%) was collected. A comparison was also made between baseline and the dynamic changes of all indexes 1 year following the last injection. It was observed that in comparison to baseline, ECD and Hex% decreased significantly after the 3rd injection of Aflibercept and Ranibizumab. However, ECD did not decrease further and remained at the same level as after the last injection. Hex% and average cell size increased to a certain extent in comparison to the last injection. All the changes were found to be statistically significant (P < .01). After 3 injections, ECD in DME group was markedly lower than that in nAMD and RVO group, but the CV in DME group was higher than that in nAMD as well as RVO groups, and all the differences were statistically significant (P < .05). Following intravitreal anti-VEGF therapy, DME is more likely than other disorders to result in a decrease in ECD. Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex% and ECD to a certain extent. After the last injection, Hex% can progressively recover, and ECD can remain stable without further declining. After injections, ECD in DME group was found to be significantly lower than that in nAMD and RVO groups, but CV in DME group was significantly higher in comparison to the other 2 groups. In patients with macular edema, repeated intravitreal injections of anti-VEGF may have certain effects on corneal morphology. Patients with diabetes mellitus in particular should pay special attention to corneal safety following repeated intravitreal injections if they have significantly reduced ECD at baseline.

Presumed macular toxicity of high-dose intravitreal ganciclovir

Abstract: A 56-year-old male with bilateral cytomegalovirus retinitis was initiated on oral valganciclovir and intravitreal ganciclovir injection twice a week in first 2 weeks and once a week in subsequent weeks. An intravitreal dose of 2 mg/0.08 mL was administered in the 1st week. Considering the suboptimal response, the dose of intravitreal ganciclovir was increased to 4 mg/0.08 mL. After 4 weeks of therapy (four doses of 4-mg ganciclovir), the patient complained of worsening of vision. Fundus examination showed resolving retinitis, but the optical coherence tomography (OCT) showed neurosensory detachment (NSD) at the fovea in both eyes with inner retinal hyperreflectivity in the right eye. Considering the possibility of retinitis involving fovea, a higher dose of intravitreal ganciclovir (6 mg/0.08 mL) was administered. The patient reported further worsening of vision immediately after removing the eye patch 2 hr following the injection. OCT showed a full-thickness hyperreflective vertical band with ellipsoid zone disruption at the fovea and inner retinal hyperreflectivity in the right eye. Hyperreflective vertical band with NSD was seen in the left eye. A possibility of macular toxicity due to intravitreal ganciclovir was considered. Intravitreal therapy was stopped and oral valganciclovir was continued. At 1-month follow-up, the patient reported improvement in vision. The hyperreflectivity and NSD were resolved at month follow-up. Although higher doses of ganciclovir up to 6 mg have been used in the past, it would be better to avoid higher doses considering the development of presumed drug toxicity in our case following the use of 4 mg and 6 mg.

Three-Year Outcomes of VEGF Inhibitors in Naive Branch Retinal Vein Occlusion: Fight Retinal Blindness!

To evaluate the 3-year outcomes of VEGF inhibitors in the treatment of cystoid macular edema due to branch retinal vein occlusion (BRVO) in an international multicenter cohort of eyes. Multicenter, international, BRVO database study. Seven hundred forty-seven patients (760 eyes) undergoing intravitreal therapy for BRVO for 3 years in a multicenter international setting. Demographics, visual acuity (VA) in logarithm of the minimum angle of resolution letters, central subfield thickness (CST), treatments, number of injections, and visits data was collected using a validated web-based tool. Visual acuity gain at 3 years in logarithm of the minimum angle of resolution letters. Secondary outcome measures included anatomical results, treatment pattern, and percentage of completers. A subgroup analysis by study drug was conducted for clinical outcomes. Mean adjusted VA change was+11 letters (95% confidence interval 9-13), mean adjusted change in CST was-176 μm (-193,-159). Median number of injections/visits was 16 of 24 at 3 years of follow-up. Most eyes received VEGF inhibitors exclusively (89%, n= 677) and as a monotherapy in 71% (n= 538). Few eyes were switched to steroids (11%, n= 83). Suspensions in treatment >180 days occurred in 26% of study eyes. Aflibercept showed greater CST reductions (-147 vs.-128 vs.-114 μm; P < 0.001) and significantly lower switching rates (14% vs. 38% vs. 33%; P < 0.001) compared with ranibizumab and bevacizumab, respectively. This international study of 3-year BRVO outcomes after starting treatment with VEGF inhibitors found adequate visual and anatomical results in routine clinical care. Visual outcomes were similar among the different initiating VEGF inhibitors, although eyes starting with aflibercept had better anatomical outcomes and a lower switching rate. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

One-Year Anti-VEGF Therapy Outcomes in Diabetic Macular Edema Based on Treatment Intensity: Data from the Fight Retinal Blindness! Registry

PurposeTo compare one-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal vascular endothelial growth factor (VEGF) inhibitor injections were delivered. DesignCohort study ParticipantsThere were 2288 treatment-naïve eyes with DME starting intravitreal VEGF inhibitor therapy from 31 October 2015 to 31 October 2021 from the Fight Retinal Blindness! international outcomes registry. MethodsEyes were grouped according to the proportion of visits at which an injection was received, Group A with less than the median of 67% (n=1172) versus Group B with greater than the median (n=1116). Main Outcome MeasureMean visual acuity (VA) change after 12 months of treatment. ResultsThe mean (95% confidence interval [CI]) VA change after 12 months of treatment was 3.6 (2.8, 4.4) letters for eyes in Group A versus 5.2 (4.4, 5.9) letters for eyes in Group B (p=0.005). The mean (95% CI) central subfield thickness (CST) change was -69 (-76, -61) μm and -85 (-92, -78) μm for eyes in Group A versus Group B, respectively (p=0.002). A moderate positive correlation was observed between the number of injections received over 12 months of treatment and the change in VA (p<0.001). Additionally, eyes that received more injections had a moderately greater CST reduction. ConclusionsThis registry analysis found that overall VA and anatomic outcomes tended to be better in DME eyes treated at a greater proportion of visits in the first year of intravitreal VEGF inhibitor therapy.

Machine learning and optical coherence tomography-derived radiomics analysis to predict persistent diabetic macular edema in patients undergoing anti-VEGF intravitreal therapy

BackgroundDiabetic macular edema (DME) is a leading cause of vision loss in patients with diabetes. This study aimed to develop and evaluate an OCT-omics prediction model for assessing anti-vascular endothelial growth factor (VEGF) treatment response in patients with DME.MethodsA retrospective analysis of 113 eyes from 82 patients with DME was conducted. Comprehensive feature engineering was applied to clinical and optical coherence tomography (OCT) data. Logistic regression, support vector machine (SVM), and backpropagation neural network (BPNN) classifiers were trained using a training set of 79 eyes, and evaluated on a test set of 34 eyes. Clinical implications of the OCT-omics prediction model were assessed by decision curve analysis. Performance metrics (sensitivity, specificity, F1 score, and AUC) were calculated.ResultsThe logistic, SVM, and BPNN classifiers demonstrated robust discriminative abilities in both the training and test sets. In the training set, the logistic classifier achieved a sensitivity of 0.904, specificity of 0.741, F1 score of 0.887, and AUC of 0.910. The SVM classifier showed a sensitivity of 0.923, specificity of 0.667, F1 score of 0.881, and AUC of 0.897. The BPNN classifier exhibited a sensitivity of 0.962, specificity of 0.926, F1 score of 0.962, and AUC of 0.982. Similar discriminative capabilities were maintained in the test set. The OCT-omics scores were significantly higher in the non-persistent DME group than in the persistent DME group (p < 0.001). OCT-omics scores were also positively correlated with the rate of decline in central subfield thickness after treatment (Pearson’s R = 0.44, p < 0.001).ConclusionThe developed OCT-omics model accurately assesses anti-VEGF treatment response in DME patients. The model’s robust performance and clinical implications highlight its utility as a non-invasive tool for personalized treatment prediction and retinal pathology assessment.

Association between the response of intravitreal antivascular endothelial growth factor injection and systemic factors of diabetic macular edema

BackgroundThis study investigated the effects of systemic factors in response to intravitreal injections in patients with macular edema due to non-proliferative diabetic retinopathy (NPDR).MethodsWe retrospectively reviewed the medical records of patients treated with intravitreal injections for macular edema secondary to NPDR between January 2018 and January 2021. The patients were divided into three groups according to the injection response. When patients with diabetic macular edema showed 20µ or more reduction in central retinal thickness compared to baseline, they were classified as responsive group, and if not, they were classified as refractory group. The responsive group was further divided into the complete and incomplete response groups. Patients with complete disappearance of edema at seven months were classified as the complete response group, whereas those in which edema did not disappear were classified as the incomplete response group. The clinical characteristics of each group, including medical history, ophthalmic examination results, and laboratory examination results at the time of diagnosis, were analyzed.ResultsOf the 112 eyes (91 patients) that satisfied the inclusion criteria, 89 (77 patients) in the responsive group and 23 (14 patients) in the refractory group were included in the analysis. The responsive group was further divided into the complete (51 eyes) and incomplete (38 eyes) response groups. The refractory group had significantly higher glycated hemoglobin levels and significantly lower estimated glomerular filtration rates than the responsive group (p = 0.026 and p = 0.012, respectively). In the multivariate logistic regression analysis, both factors were found to be significant in predicting the degree of response (all p < 0.05). No factor showed a significant difference between the incomplete and complete response groups(all p > 0.05).ConclusionsIn macular edema caused by NPDR, low glomerular filtration rates and high glycated hemoglobin levels may be used as predictors of poor response to intravitreal injection therapy. In addition to blood glucose control, education should be provided regarding the need for the continuous monitoring of renal function.

Comparative Study on Anti-VEGF in Wet Age-Related Macular Degeneration in the Setting Based on Lean Methodology from the Bari Intravitreal Injection Registry (BIVIR).

Optimizing treatment protocols for wet age-related macular degeneration (wAMD) is an ongoing challenge, as it involves a delicate balance between achieving therapeutic efficacy and minimizing invasive procedures' frequency. This study aimed to apply the Lean methodology and evaluate the effectiveness of this new setting on intravitreal therapy for wAMD, employing different anti-vascular endothelial growth factors (VEGF) drugs (bevacizumab, brolucizumab, aflibercept, ranibizumab), drawing data from the Bari Intravitreal Injections Registry (BIVIR). This was a retrospective, monocentric, nonrandomized, comparative study. Lean methodology was employed to design the new setting and the BIVIR collected information from electronic medical records. Clinical data of four groups, stratified based on the first-line anti-VEGF agents used, were compared. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) changes were compared between the four groups at 3 and 12 months. Out of 4990 eyes and 41,323 intravitreal injections (IVs) recorded in BIVIR, 1421 eyes of 1182 patients were included. The mean number of IVs in first year was 6.1 ± 2.5, with no significant differences among the four subgroups. The mean change in BCVA was + 6.2 letters [95% confidence interval (CI) 5.6-6.8] after two IVs, and + 5.9 (95% CI 5.1-6.8) letters after three IVs; at three months, brolucizumab was associated with a greater mean increase in BCVA than bevacizumab (p = 0.050); aflibercept (p = 0.044) and ranibizumab p = 0.047). At the 1-year follow-up, the mean change was + 6.3 letters (95% CI 5.4-7.2), brolucizumab and ranibizumab were associated with a superior improvement in BCVA compared to aflibercept (p = 0.033). Regarding the CRT, a significant reduction was observed in the subgroup treated with brolucizumab at the 3-month follow-up, compared to bevacizumab (p = 0.003), aflibercept (p = 0.015), and ranibizumab (p < 0.001); Aflibercept exhibited a superior effect than ranibizumab (p = 0.001). At 1-year follow-up, aflibercept resulted in a more significant reduction of macular thickness compared to ranibizumab (p = 0.016) while no significant differences were observed among the other drugs. Our practical experience showed the effectiveness of the new setting in the treatment of wAMD. This comparative study at 1year suggested a predominant brolucizumab efficacy on functional outcomes. In addition, brolucizumab and aflibercept appeared to have similar efficacy in fluid control.

Clinical effects of atorvastatin combined with conbercept in the treatment of patients with macular edema secondary to retinal vein occlusion and carotid plaque: study protocol for a prospective randomized controlled trial.

Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) drugs have been widely used in patients with macular edema (ME) secondary to retinal vein occlusion (RVO); however, recurrence is a major concern. This study aims to observe the clinical effects of atorvastatin and intravitreal therapy in the treatment of patients with branch or central RVO-ME and coexistent carotid plaques (CP). A prospective randomized controlled clinical trial will be conducted. Sixty-four patients diagnosed with branch or central RVO-ME and coexistent CP will be enrolled and randomly allocated in a 1:1 ratio to the control and experimental groups. The control group will be treated with intravitreal conbercept monthly for 3 months, followed by monthly evaluation and injection of pro re nata (PRN) for 12 months, while the experimental group will be treated with oral atorvastatin 20 mg daily combined with the control group treatment. If a drop of best-corrected visual acuity (BCVA) is more than five Early Treatment Diabetic Retinopathy Study (ETDRS) letters (one line) or an increment in central subfield thickness (CSFT) of 100 μm (or a 10% increment from the previous visit), intravitreal re-treatment will be performed. Outcome measurements include CSFT, BCVA, number of injections, and incidence of adverse events during the 12-month follow-up period. Differences between groups will be evaluated using Student's t-test, and comparisons between groups will be evaluated using repeated-measures analysis of variance. The study has been approved by the Institutional Review Board of Nanjing Lishui People's Hospital, Nanjing, China (approval number 2023KY0418-12, dated 18 April 2023), and has been registered on chictr.org.cn. Written informed consent will be collected from each patient and the results of this trial will be submitted to a peer-reviewed journal. Chinese Clinical Trial Registry ChiCTR2300071359. Registered on 12 May 2023.

Nanostructured Lipid Carriers Mediated Drug Delivery to Posterior Segment of Eye and their In-vivo Successes.

The disease of the posterior segment of the eye is a major concern worldwide, and it affects more than 300 million people and leads to serious visual deterioration. The current treatment available is invasive and leads to serious eye complications. These shortcomings and patient discomfort lead to poor patient compliance. In the last decade, Nanostructured lipid carriers (NLC) have established a remarkable milestone in the delivery of drug substances to the posterior segment of the eye. Additionally, NLC can reduce the clearance due to adhesive properties which are imparted due to nano-metric size. This attribute might reduce the adverse effects associated with intravitreal therapy and thus enhance therapeutic efficacy, eventually raising patient adherence to therapy. The current review provides an inclusive account of NLC as a carrier to target diseases of the posterior segment of the eye. The review focuses on the various barrier encountered in the delivery of drugs to the posterior segment of the eye and the detail about the physicochemical property of drug substances that are considered to be suitable candidates for encapsulation to lipid carriers. Therefore, a plethora of literature has been included in this review. The review is an attempt to describe methods adopted for assessing the in-vivo behavior that strengthens the potential of NLC to treat the disease of the posterior segment of the eye. These NLC-based systems have proven to be a promising alternative in place of invasive intravitreal injections with improved patient compliance.

Utility of multicolor imaging in endogenous endophthalmitis

The utility of multicolor imaging (MCI) has been well evaluated for various retinal disorders like age-related macular degeneration, retinal vascular occlusions, and central serous chorioretinopathy. However, the utility of MCI in endogenous endophthalmitis is very limited. We report a unique case of endogenous endophthalmitis showcasing the utility of MCI in monitoring the response of bacterial colonies to intravitreal antibiotic therapy.

Exploring the Impact of Saccharin on Neovascular Age-Related Macular Degeneration: A Comprehensive Study in Patients and Mice.

We aimed to determine the impact of artificial sweeteners (AS), especially saccharin, on the progression and treatment efficacy of patients with neovascular age-related macular degeneration (nAMD) under anti-vascular endothelial growth factor (anti-VEGF-A) treatment. In a cross-sectional study involving 46 patients with nAMD undergoing intravitreal anti-VEGF therapy, 6 AS metabolites were detected in peripheral blood using liquid chromatography - tandem mass spectrometry (LC-MS/MS). Disease features were statistically tested against these metabolite levels. Additionally, a murine choroidal neovascularization (CNV) model, induced by laser, was used to evaluate the effects of orally administered saccharin, assessing both imaging outcomes and gene expression patterns. Polymerase chain reaction (PCR) methods were used to evaluate functional expression of sweet taste receptors in a retinal pigment epithelium (RPE) cell line. Saccharin levels in blood were significantly higher in patients with well-controlled CNV activity (P = 0.004) and those without subretinal hyper-reflective material (P = 0.015). In the murine model, saccharin-treated mice exhibited fewer leaking laser scars, lesser occurrence of bleeding, smaller fibrotic areas (P < 0.05), and a 40% decrease in mononuclear phagocyte accumulation (P = 0.06). Gene analysis indicated downregulation of inflammatory and VEGFR-1 response genes in the treated animals. Human RPE cells expressed taste receptor type 1 member 3 (TAS1R3) mRNA and reacted to saccharin stimulation with changes in mRNA expression. Saccharin appears to play a protective role in patients with nAMD undergoing intravitreal anti-VEGF treatment, aiding in better pathological lesion control and scar reduction. The murine study supports this observation, proposing saccharin's potential in mitigating pathological VEGFR-1-induced immune responses potentially via the RPE sensing saccharin in the blood stream.

Clinical Features of Patients with Penetrating Eye Injury and Foreign Body Complicated by Endophthalmitis

Purpose: to study the clinical features of patients with penetrating eye injury and foreign body, complicated by endophthalmitis.Methods. 68 patients (68 eyes) with penetrating injury and ocular foreign body were included in the retrospective study, including 91.2 % males and 8.8 % females. The mean age was 50.00 [32.00; 60.00] years. The patients were divided into 2 groups: with endophthalmitis — 24 patients, without inflammation — 44 patients. All patients underwent standard ophthalmologic methods of examination.Results. The age of patients with endophthalmitis was significantly greater compared to patients without inflammation — 51.50 [46.25; 63.25] years and 36.50 [31.25; 58.50] years, respectively (p = 0.0446). In the first day after injury, only 25 % of patients asked for medical care (p = 0.0071). In patients with endophthalmitis according to biomicroscopy data on admission the following were significantly more frequent: eyelid edema (p &lt; 0.0001), purulent discharge (p &lt; 0.0001), total hyphema (p = 0.029), hypopyon (p &lt; 0.0001), iris edema (p &lt; 0.0001), fibrin in vitreous body (p = 0.0014), as well as its destruction (p = 0.0005). 87.5 % of patients with endophthalmitis showed absence of fundus reflex (p = 0.0105), and 25 % of patients with inflammation showed increased intraocular pressure (p = 0.0019). In patients with endophthalmitis, surgical treatment was performed: cataract phacoemulsification in 91.7 % of patients (p &lt; 0.0001), vitreoectomy in 87.5 % (p = 0.0098), enucleation of the eye in 12.5 % (p = 0.0165) and evisceration in 12.5 % (p = 0.0165). Bacterial culture in patients with endophthalmitis revealed Gram-positive microflora in 100 % of cases. There were also significant differences between the groups in the intravitreal, systemic and subconjunctival antibiotic therapy used.Conclusion. Patients with penetrating eye injury and foreign body, complicated by endophthalmitis, are characterized by more signs of inflammation, pronounced damage to the eye and its structures.

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.

Cataract surgery in patients with diabetes mellitus. Prevention and optimisation of the diabetic macular edema therapy

Diabetes mellitus (DM) is a major public health problem, with approximately one third having signs of diabetic retinopathy (DR). In such patients, cataracts develop at an earlier age and 2–5 times more frequently. The incidence of macular edema (ME) after phacoemulsification of cataracts (FEC) in patients with diabetes has been shown to increase by 1.80 times and, in the presence of DR by 6.23. The critical period for retinal deterioration is 2 months after FEC, which requires an active therapy and monitoring. For patients with pre-existing diabetic macular edema (DME), If the cataract does not affect daily activities of patients with a pre-existing DME and the optical clarity is adequate, it is preferable to postpone surgical treatment in order to maximize retinal stabilization on OCT at two consecutive visits with a month’s interval between. In the case of severe impairment of lens transparency, FEC with an intravitreal injection of anti-VEGF 28 days or steroids 1 month before surgery under strict monitoring of the retinal condition using OCT is recommended. If macular changes are absent and there is a risk of developing DME, the use of nonsteroid anti-inflammatory drugs is necessary. Prophylactic intravitreal therapy is unacceptable in the absence of MO.

Comparative quantitative analysis of optical coherence tomography angiography in varied morphologies of macular neovascularization following intravitreal conbercept and ranibizumab treatments for neovascular age‑related macular degeneration.

The present study aimed to examine the optical coherence tomography angiography (OCTA) parameters associated with macular neovascularization (MNV) in patients diagnosed with neovascular age-related macular degeneration (nAMD) and treated with either intravitreal conbercept (IVC) or ranibizumab (IVR). It enrolled 39 nAMD patients presenting with MNV, including 23 in the IVC group and 16 in the IVR group. All participants were treatment-naïve with intravitreal therapy and they underwent treatment following a '3+PRN' regimen. The MNV patterns identified through OCTA were categorized as Medusa, tangled, seafan and other variations. Key outcome measures encompassed best-corrected visual acuity (BCVA), MNV vascular area (MNV-VA), MNV vascular density (MNV-VD) ratio and central macular thickness (CMT). In the present study, 44 eyes were included, with 28 eyes undergoing treatment with IVC and 18 eyes with IVR. On day 90, there was a statistically significant improvement in mean BCVA from baseline among all patients treated with IVC (P=0.002). Notably, improved outcomes were observed in those with the 'tangled' pattern compared with the other three patterns (P=0.007). CMT exhibited a significant decrease from baseline (P=0.007), with consistent improvement observed across all four patterns (P=0.052) on day 90. The mean MNV-VA decreased in all patients, reaching statistical significance for the Medusa pattern (P=0.008), although the improvement in visual acuity was deemed unsatisfactory. Patients with the seafan pattern treated with IVR improved significantly in BCVA (P=0.042). The mean CMT significantly improved from baseline (P=0.001), consistent across the four patterns (P=0.114). Significant improvements were noted in the mean MNV-VA for the seafan pattern and in the mean MNV-VD ratio for the other patterns. The two regimens had no significant differences regarding BCVA, CMT, and MNV parameters. Conbercept emerged as a viable treatment option for patients presenting with tangled MNV patterns. On the other hand, ranibizumab might be considered an effective intervention for individuals with seafan MNV patterns. Notably, the Medusa MNV pattern was associated with a morphologic configuration indicative of a poor prognosis.