Combination of STING agonist with anti-vascular RGD-(KLAKLAK)2 peptide as a novel anti-tumor therapy.

Immunotherapy is one of the most promising anti-cancer treatment. It involves activating the host's own immune system to eliminate cancer cells. Activation of cGAS-STING pathway is promising therapeutic approach for cancer immunotherapy. However, in human clinical trials, targeting cGAS-STING pathway results in insufficient or unsustainable anti-tumor response. To enhance its effectiveness, combination with other anti-cancer therapies seems essential to achieve synergistic systemic anti-tumor response.The aim of this study was to evaluate whether the combination of STING agonist-cGAMP with anti-vascular RGD-(KLAKLAK)2 peptide results in a better anti-tumor response in poorly immunogenic tumors with various STING protein and αvß3 integrin status.Combination therapy inhibited growth of murine breast carcinoma more effectively than melanoma. In melanoma, the administration of STING agonist alone was sufficient to obtain a satisfactory therapeutic effect. In both tumor models we have noted stimulation of innate immune response following cGAMP administration alone or in combination. The largest population of immune cells infiltrating the TME after therapy were activated NK cells. Increased infiltration of cytotoxic CD8+ T lymphocytes within the TME was only observed in melanoma tumors. However, they also expressed the "exhaustion" PD-1 receptor. In contrast, in breast carcinoma tumors each therapy caused the drop in the number of infiltrating CD8+ T cells.The obtained results indicate an additional therapeutic benefit from combining STING agonist with an anti-vascular agent. However, this effect depends on the type of tumor, the status of its microenvironment and the expression of specific proteins such as STING and αvß3 family integrin.

Acute kidney injury in cancer patients receiving anti-vascular endothelial growth factor monoclonal antibody vs. immune checkpoint inhibitors: a retrospective real-world study.

BACKGROUND: Anti-vascular endothelial growth factor monoclonal antibody (anti-VEGF) or immune checkpoint inhibitors (ICIs) combined with chemotherapy are commonly administered to cancer patients. Although cancer patients receiving anti-VEGF or ICIs have been reported to experience an increased risk of acute kidney injury (AKI), comparative studies on the AKI incidence have not been evaluated. METHODS: Cancer patients receiving anti-VEGF or ICIs were retrospectively selected from the hospital information system of the First Affiliated Hospital of Wenzhou Medical University between Jan, 2020 and Dec, 2022 and were divided into two groups according to the treatment regimen: anti-VEGF group and ICIs group. The baseline characteristics were propensity-score matched. The primary outcome was sustained AKI. A comparison of cumulative incidence of sustained AKI was performed by Kaplan-Meier curves and log-rank test. Risks for outcomes were assessed using Cox proportional regression. RESULTS: A total of 1581 cancer patients receiving anti-VEGF (n = 696) or ICIs (n = 885) were included in the primary analysis. The ICIs group had a higher cumulative incidence of sustained AKI within one year than the anti-VEGF group (26.8% vs. 17.8%, P < 0.001). Among 1392 propensity score matched patients, ICIs therapy (n = 696) was associated with an increased risk of sustained AKI events in the entire population (HR 2.0; 95%CI 1.3 to 2.5; P = 0.001) and especially in those with genitourinary cancer (HR 4.2; 95%CI 1.3 to 13.2; P = 0.015). Baseline serum albumin level (> 35 g/l) was an important risk factor for a lower incidence of sustained AKI in the anti-VEGF group (HR 0.5; 95%CI 0.3 to 0.9; P = 0.027) and the ICIs group (HR 0.3; 95%CI 0.2 to 0.5; P < 0.001). CONCLUSIONS: Among cancer patients in this real-world study, treatment with ICIs increased incidence of sustained AKI in one year. Baseline serum albumin level was an important risk factor for sustained AKI. The risk factors for sustained AKI differed between the anti-VEGF group and the ICIs group. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov (NCT06119347) on 11/06/2023.

Case report: heart failure related to intravitreal injection of anti-VEGF.

BACKGROUND: Intravitreal injection of anti-vascular endothelial growth factor is considered the first-line treatment for polypoidal choroidal vasculopathy. It has potential risks for circulatory system, which should be particularly carefully evaluated in older patients. In this case study, we aim to discuss the potential impact of this treatment regimen on cardiac health. CASE PRESENTATION: This case report describes an elderly patient with no prior history of heart disease who exhibited unexpected heart enlargement and dysfunction. Throughout the patient's hospital stay, various potential causes were investigated, leading to the hypothesis that a 10-year history of intravitreal injections of anti-vascular endothelial growth factor could be related to the observed clinical manifestations. The patient was advised to discontinue this treatment, and after a 2-month follow-up period, there was a gradual improvement in the patient's cardiac structure and function. CONCLUSION: This manuscript highlights the importance of conducting cardiac examinations before and after anti-vascular endothelial growth factor treatment, especially for individuals at risk of heart diseases like the elderly. It emphasizes the need to carefully weigh the benefits and risks of treatment regimens to ensure optimal therapeutic outcomes.

Self-delivery photothermal-boosted-nanobike multi-overcoming immune escape by photothermal/chemical/immune synergistic therapy against HCC.

Immune checkpoint inhibitors (ICIs) combined with antiangiogenic therapy have shown encouraging clinical benefits for the treatment of unresectable or metastatic hepatocellular carcinoma (HCC). Nevertheless, therapeutic efficacy and wide clinical applicability remain a challenge due to "cold" tumors' immunological characteristics. Tumor immunosuppressive microenvironment (TIME) continuously natural force for immune escape by extracellular matrix (ECM) infiltration, tumor angiogenesis, and tumor cell proliferation. Herein, we proposed a novel concept by multi-overcoming immune escape to maximize the ICIs combined with antiangiogenic therapy efficacy against HCC. A self-delivery photothermal-boosted-NanoBike (BPSP) composed of black phosphorus (BP) tandem-augmented anti-PD-L1 mAb plus sorafenib (SF) is meticulously constructed as a triple combination therapy strategy. The simplicity of BPSP's composition, with no additional ingredients added, makes it easy to prepare and presents promising marketing opportunities. (1) NIR-II-activated BPSP performs photothermal therapy (PTT) and remodels ECM by depleting collagen I, promoting deep penetration of therapeutics and immune cells. (2) PTT promotes SF release and SF exerts anti-vascular effects and down-regulates PD-L1 via RAS/RAF/ERK pathway inhibition, enhancing the efficacy of anti-PD-L1 mAb in overcoming immune evasion. (3) Anti-PD-L1 mAb block PD1/PD-L1 recognition and PTT-induced ICD initiates effector T cells and increases response rates of PD-L1 mAb. Highly-encapsulated BPSP converted 'cold' tumors into 'hot' ones, improved CTL/Treg ratio, and cured orthotopic HCC tumors in mice. Thus, multi-overcoming immune escape offers new possibilities for advancing immunotherapies, and photothermal/chemical/immune synergistic therapy shows promise in the clinical development of HCC.

Biomarkers determining treatment interval of diabetic macular edema after initial resolution by anti-vascular endothelial growth factor.

PURPOSE: To identify predictive factors that help determine the interval of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection after the initial resolution of diabetic macular edema (DME). METHODS: This retrospective case-control study enrolled treatment-naïve DME patients who had achieved DME resolution after intravitreal anti-VEGF injections. Patients were classified into the recurrence and no-recurrence groups, depending on the development of recurrent DME after deferring intravitreal anti-VEGF injection. The demographics and clinical features, including optical coherence tomography findings, were compared between the two groups. RESULTS: We enrolled 105 eyes. Sixty eyes (57.1%) belonged to the no-recurrence group, and 45 (42.9%), belonged to the recurrence group. The severity of diabetic retinopathy at baseline was related to early DME recurrence (P = 0.009). At the treatment deferring point, the non-recurrence group had both thinner central subfield thickness (289.5 ± 27.2 µm vs. 307.0 ± 38.2 µm, P = 0.011) and thinner central retinal thickness (214.9 ± 41.4 µm vs. 231.8 ± 41.2 µm, P = 0.043) compared to the recurrence group. Intraretinal cyst was observed in 34 eyes (56.7%) in the no-recurrence group and 42 eyes (93.3%) in the recurrence group at the deferring point (P < 0.001). CONCLUSION: A low risk of early DME recurrence is anticipated in the eyes with foveal thinning and no intraretinal cyst when anti-VEGF injection is deferred. These predictive biomarkers can be useful for patient monitoring and determining treatment strategies for DME patients.

Efficacy comparison of anti-vascular endothelial growth factor drugs for the treatment of type 1 retinopathy of prematurity: A network meta-analysis of randomised controlled trials.

PURPOSE: To compare the efficacy of different anti-vascular endothelial growth factor (VEGF) agents for the treatment of retinopathy of prematurity (ROP) in preterm infants. METHODS: Seven databases were searched for eligible literature up to February 22, 2023. Studies were included if they were randomised controlled trials (RCTs) investigating the efficacy of anti-VEGF agents for ROP in infants. A network meta-analysis (NMA) was performed. We also conducted subgroup analyses to determine the efficacy ranking of regimens used in different regions. The odds ratio (OR), standardised mean difference (SMD), and surface under the cumulative ranking curve (SUCRA) were calculated for each outcome. RESULTS: Thirteen RCTs of 10 different regimens, involving 1196 infants (2388 eyes), were identified. Bevacizumab (0.625 mg; OR = 0.16, 95% confidence interval [CI] 0.06-0.40, SUCRA = 80.6%) and conbercept (0.15 mg; OR = 0.08, 95% CI 0.02-0.30, SUCRA = 96.0%) were the most effective regimens in reducing the risk of ROP recurrence requiring retreatment in Western countries and China, respectively. Compared with laser therapy, bevacizumab (0.625 mg; SMD = 1.54, 95% CI 0.06-3.02) achieved significantly longer intervals between treatment and recurrence. No significant difference in the risk of retinal detachment was detected between any anti-VEGF agent and laser (p > 0.05). CONCLUSIONS: Bevacizumab (0.625 mg) and conbercept (0.15 mg) appeared to be the most effective therapies for ROP in Western countries and China, respectively. More high-quality RCTs are warranted to evaluate the efficacy and long-term safety of anti-VEGF drugs for the management of ROP.

Real-world experience with brolucizumab in neovascular age-related macular degeneration over 2 years: the REBA extension study.

BACKGROUND: To determine long-term efficacy and safety of intravitreal brolucizumab therapy for neovascular age-related macular degeneration (nAMD) in the real-world setting. METHODS: Retrospective, observational, multicentric study and an extension of the REBA study (Real-world Experience with Brolucizumab in nAMD) to 24 months. The study entailed follow-up of 91 consecutive eyes (67 patients) with nAMD who received brolucizumab therapy and completed 24 months of follow-up. Both treatment-naïve and switch therapy patients were included. All relevant data were collected. The primary outcome measure was changed in best-corrected visual acuity (BCVA) over time. Secondary outcome measures included change in central subfield thickness (CST) and complications. RESULTS: The mean (SD) baseline BCVA was 48.4 (3.5) letters and 36.2 (7.1) letters in treatment-naïve group and switch therapy group, respectively. BCVA gain was + 9.2 (3.7) letters (p = 0.01) and + 7.7 (3.4) letters (p = 0.011), respectively. The change in mean (SD) CST has shown a significant decrease in retinal thickness in treatment-naïve group (from 432.5 (68.4) to 283.0 (51.3) µm; p = 0.018) and in switch therapy group (from 452.5 (40.5) to 271.0 (43.4) µm; p = 0.011) group. One switch patient developed vascular occlusion and another a macular hole after the fifth brolucizumab injection as reported in the primary study. Both patients recovered uneventfully. Three patients demonstrated reversible intraocular inflammation between months 10 and 24. CONCLUSION: Patients showed a significant anatomical and functional response to brolucizumab therapy in the real world, regardless of prior treatment status, until the end of the follow-up period. Overall, 5 significant untoward events were noted.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Five-year outcomes of treat and extend regimen using intravitreal aflibercept injection for treatment-naïve age-related macular degeneration.

PURPOSE: This study evaluated the long-term outcomes of eyes with neovascular age-related macular degeneration (nAMD) treated with aflibercept according to a treat-and-extend (T&E) regimen for up to 5 years. Methods This retrospective study included 112 eyes of 111 patients with nAMD who received aflibercept according to the T&E regimen. The patients received 3 monthly injections of aflibercept followed by a T&E regimen for at least 12 months. Data, including best-corrected visual acuity (BCVA), treatment interval, presence of exudation, central retinal thickness, and central choroidal thickness were analyzed. RESULTS: Of the 112 consecutive eyes, 66 completed the 5-year follow-up. After 5 years of treatment, BCVA (logMAR) was significantly better than baseline (0.29 ± 0.31 at baseline and 0.18 ± 0.23 at 5 years, P < 0.01). A mean of 7.0 ± 1.5 injections in the first year and 4.9 ± 2.2 injections per year thereafter were required. In eyes with subretinal hyperreflective material (SHRM) at baseline, BCVA at baseline and 5 years were significantly worse than in eyes without SHRM at baseline and 5 years. However, the eyes with SHRM required fewer injections and exhibited greater BCVA improvement. CONCLUSION: This retrospective study demonstrated the effectiveness of the T&E regimen with aflibercept in managing nAMD over a 5-year period, maintaining significant improvements in BCVA.

Efficacy of anti-VEGF monotherapy versus anti-VEGF therapy with subthreshold micropulse laser (SML) in the management of diabetic macular oedema (DMO): a systematic review and meta-analysis.

BACKGROUND: Intravitreal injection anti-vascular endothelial growth factor (IVI anti-VEGF) therapy serves as the primary treatment for centre involving diabetic macular oedema (DMO). Conventional laser therapy (CLT) adjunct has proven beneficial; however, it is not widely used due to significant risks of retinal scarring. Subthreshold micropulse laser (SML) therapy has, however, emerged as a comparable alternative to combination therapy, offering a distinct advantage by mitigating the risk of retinal scarring. METHODS: A search of six databases was conducted. A meta-analysis of mean differences was performed including subgroup analyses where appropriate. Primary outcome was the number of injections at 12-14 months; secondary outcomes were changes in central macular thickness (CMT) and best corrected visual acuity (BCVA) at 6-8 months and 12-14 months. RESULTS: A total of ten papers including six randomised clinical trials and four retrospective clinical studies were included in our study, capturing 563 eyes of 478 patients. Overall, the risk of bias was moderate for these studies. Significantly fewer anti-VEGF therapy injections were administered in the combination therapy versus anti-VEGF monotherapy patients at 12-14 months who had poor visual acuity (6/18 Snellen or worse) at baseline, mean difference - 2.25 (95% CI; - 3.35, - 1.15; p < 0.05). Combination therapy was not associated with significantly fewer intravitreal injections in patients with a higher visual acuity (6/15 Snellen or better) at baseline. Our analysis also showed significant improvements to both BCVA and CMT were reached at 6 - 8 month post-baseline at the 95% confidence intervals: - 1.13 (- 2.09, - 0.16) and - 4.04 (- 7.59, - 0.50). These improvements remained statistically significant at 12-14 months: - 0.94 (- 1.67, - 0.20) and - 1.92 (- 3.52, - 0.32) respectively with combination therapy. CONCLUSION: Our findings demonstrate that combination therapy (SML + IVI anti-VEGF) is associated with fewer intravitreal injections. We report a better BCVA and a reduction in CMT at 6 and 12 months from baseline with combination treatment compared to the IVI anti-VEGF monotherapy comparator. SML is a proven non-scarring cost-effective therapy for DMO that should be readily available in the medical retinal therapy as it may reduce the burden of care.

Long-term outcomes of anti-vascular endothelial growth factor therapy with and without posterior scleral reinforcement on myopic maculopathy in myopic choroidal neovascularization eyes.

BACKGROUND: Anti-vascular endothelial growth factor (anti-VEGF) therapy is used for myopic choroidal neovascularization (mCNV). Patchy chorioretinal atrophy (pCRA) enlargement has been reported in mCNV cases associated with vision loss. Our aim was to compare the long-term effectiveness of anti-VEGF therapy alone versus anti-VEGF followed by posterior scleral reinforcement (PSR) in controlling myopic maculopathy in mCNV eyes. METHODS: We performed a retrospective review of the medical records of 95 high myopia patients (refractive error ≥ 6.00 diopters, axial length ≥ 26.0 mm) with mCNV. Patients were treated with anti-VEGF alone (group A) or anti-VEGF followed by PSR (group B). The following data were collected: refractive error, best corrected visual acuity (BCVA), ophthalmic fundus examination, ocular coherence tomography and ocular biometry at 12 and 24 months pre- and postoperatively. The primary outcomes were changes in pCRA and BCVA. RESULTS: In 26 eyes of 24 patients, the mean pCRA size significantly increased from baseline (0.88 ± 1.69 mm2) to 12 months (1.57 ± 2.32 mm2, t = 3.249, P = 0.003) and 24 months (2.17 ± 2.79 mm2, t = 3.965, P = 0.001) postoperatively. The increase in perilesional pCRA in group B (n = 12) was 98.2% and 94.2% smaller than that in group A (n = 14) at 12 and 24 months (Beta 0.57 [95% CI 0.01, 191 1.13], P = 0.048). In group B, 7 eyes (58.3%) gained more than 2 lines of BCVA compared with only 4 eyes (28.6%) in group A at 24 months. CONCLUSION: Anti-VEGF therapy followed by PSR achieved better outcomes than anti-VEGF therapy alone in controlling the development of myopic maculopathy in mCNV and may constitute a better treatment option by securing a better long-term VA outcome.

Non-surgical treatment of stage 4A retinopathy of prematurity.

BACKGROUND: Retinopathy of prematurity (ROP) is a major cause of visual impairment in premature infants, often requiring surgical interventions in advanced stages. This retrospective case series study investigates non-surgical management for Stage 4A ROP, specifically the use of combined laser therapy and intravitreal anti-vascular endothelial growth factor (VEGF) injections. METHODS: Ten eyes from five infants with Stage 4A ROP were treated with a combined laser and anti-VEGF approach. Comprehensive follow-up examinations were conducted to evaluate the treatment outcomes. RESULTS: The study demonstrated successful retinal attachment without complications, showcasing the efficacy and safety of this non-surgical method. A comparison with surgical interventions highlighted the potential benefits in terms of reduced adverse effects. DISCUSSION: This combined treatment emerges as a promising first-choice option for Stage 4A ROP, offering rapid regression without surgical intervention, particularly in early stages. However, larger randomized clinical trials are necessary to validate these findings and establish definitive guidelines for managing this complex condition. CONCLUSION: Combined laser and anti-VEGF therapy proved to be an effective and safe non-surgical approach for Stage 4A ROP, with the potential to reduce the need for surgery, especially in its early presentation. Further research is required to confirm these findings and provide comprehensive recommendations for clinical practice.

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

BACKGROUND: The 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. METHODS: Retrospective, 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. RESULTS: Eleven 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. CONCLUSION: This 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.

Effect of anti-vascular endothelial growth factor on early-stage post-vitrectomy macular edema in patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the effectiveness of anti-vascular endothelial growth factor (VEGF) therapy on post-vitrectomy macular edema (PVME) and determine the risk factors for PVME recovery. METHODS: This retrospective study included 179 eyes of 179 patients who underwent pars plana vitrectomy for proliferative diabetic retinopathy and developed PVME within 3 months after surgery. Eyes were grouped according to postoperative anti-VEGF treatment. RESULTS: Central retinal thickness (CRT) decreased significantly from baseline to 3-month follow-up in groups with (509.9 ± 157.2 µm vs. 401.2 ± 172.1 µm, P < 0.001) or without (406.1 ± 96.1 µm vs. 355.1 ± 126.0 µm, P = 0.008) postoperative anti-VEGF treatment. Best-corrected visual acuity (BCVA) did not differ between the two groups during follow-up. In the group not receiving anti-VEGF therapy, BCVA was significantly improved at 1, 2, and 3 months (P = 0.007, P < 0.001, and P < 0.001, respectively), while in the anti-VEGF group, BCVA was significantly improved at 1 and 3 months (P = 0.03 and P < 0.001). A thicker baseline CRT (ß = 0.44; 95% confidence interval, 0.26-0.61; P < 0.001) was significantly associated with decreasing CRT. CONCLUSION: PVME tends to spontaneously resolve in the early postoperative period. The effect of anti-VEGF therapy in the first 3 months after diagnosis appears to be limited.

Characteristics of macular edema associated with retinal vein occlusion showing poor anatomic response to three loading anti-vascular endothelial growth factor injections: an optical coherence tomography analysis.

PURPOSE: To analyze the clinical features of refractory cystoid macular edema related to retinal vein occlusion associated with the response to three consecutive loading doses of anti-vascular endothelial growth factor. METHODS: A retrospective chart review was performed on retinal vein occlusion patients treated by three anti-vascular endothelial growth factor injections. They were divided into a group according to resolution of macular edema in optical coherence tomography (Group 1) and with persistent macular edema (Group 2). We analyzed qualitative and quantitative morphologic features of optical coherence tomography. RESULTS: We enrolled a total of 120 eyes from 120 patients (Group 1: n = 54, Group 2: n = 66). The baseline choroidal thickness differed significantly between groups 1 and 2 (290.70 ± 19.58 µm and 311.06 ± 17.87 µm P < 0.001). The presence of Hyperreflective foci (16.70% vs. 36.40% P < 0.001), Disorganization of the retinal inner layers (14.80% vs. 87.90%) and external limiting membrane disruption (16.60% vs. 39.3% P < 0.001) differed significantly. Logistic regression analysis showed that the initial central macular thickness (B = 0.012; P = 0.006), baseline choroidal thickness (B = 0.232; P = 0.016) and presence of hyperreflective foci (B = 1.050; P = 0.019), disorganization of the retinal inner layers (B = 1.132; P = 0.001) and external limiting membrane disruption (B = 1.575; P = 0.012) significantly affected the anti-vascular endothelial growth factor treatment response. CONCLUSION: A thicker sub-fovea choroid and the presence of hyperreflective foci, disruption of the external limiting membrane and disorganization of the retinal inner layers associated with a poorer response to three loading anti-vascular endothelial growth factor injections in macular edema associated retinal vein occlusion.

Impact of anti-VEGF treatment on development of proliferative diabetic retinopathy in routine clinical practice.

BACKGROUND: This study evaluated impact of anti-vascular endothelial growth factor (VEGF) treatment on proliferative diabetic retinopathy (PDR) development among patients with non-proliferative diabetic retinopathy (NPDR) in US real-world clinical practice. METHODS: This was a retrospective analysis of electronic medical records (Vestrum Health; January 2013 to June 2019) of eyes with baseline NPDR, without DME, and naïve to anti-VEGF treatment at index DR diagnosis. Eyes that received anti-VEGF and/or laser treatment over the course of study before development of PDR constituted the treated cohort while the remaining including those treated with laser constituted the anti-VEGF naïve cohort. Survival analysis via Kaplan-Meier method evaluated time to DME and PDR development by baseline NPDR severity, with anti-VEGF treatment as censoring variable. Baseline factors affecting PDR development were analyzed using Cox multivariable regression, censoring for anti-VEGF treatment. RESULTS: Among anti-VEGF-naive eyes, cumulative incidence of DME in eyes with mild (n = 70,050), moderate (n = 39,116), and severe NPDR (n = 10,692) at baseline was 27.1%, 51.2%, and 60.6%. Multivariable regression analysis identified baseline NPDR severity as the most significant predictor of PDR development over 48 months (hazard ratio [HR] [95% confidence interval {CI}] of 2.69 (2.65-2.72) for moderate vs mild NPDR and 6.51 (6.47-6.55) for severe vs mild NPDR). Cumulative incidence (95% CI) of PDR was 7.9% (7.4%-8.3%), 20.9%, (20.0%-21.7%) and 46.8% (44.4%-49.2%) over 48 months in eyes with mild, moderate, and severe NPDR at baseline, respectively. Among treated eyes with baseline severe NPDR, cumulative incidence of PDR at 48 months was 50.1% in eyes treated with laser (n = 546; HR [95% CI] vs no treatment: 0.8 [0.7-1.0]), 27.4% in eyes treated with anti-VEGF (n = 923; HR [95% CI]: 0.4 [0.4-0.5]), and 25.6% in eyes treated with anti-VEGF plus laser (n = 293; HR [95% CI]: 0.5 [0.4-0.7]) compared with 49.9% in eyes with no treatment (n = 8930). CONCLUSIONS: DME and PDR development rates increased with increasing baseline NPDR severity. Approximately half of anti-VEGF‒naive eyes with severe NPDR progressed to PDR within 4 years in US clinical practice. The progression rate from severe NPDR to PDR was approximately halved with anti-VEGF versus no treatment.

Successful treatment of retinopathy of prematurity in oculocutaneous albinism with OCA2 variants: a case report and review of literature.

BACKGROUND: Oculocutaneous albinism (OCA) is a group of autosomal recessive hereditary disorders that affect melanin biosynthesis, resulting in abnormalities in hair, skin, and eyes. Retinopathy of prematurity (ROP) is a proliferative retinopathy mainly observed in premature infants with low birth weight and early gestational age, but it can also affect full-term infants or children with normal weight, particularly in developing countries. The coexistence of ROP and OCA is rare. There is limited documentation regarding treatment approaches, with few studies reporting positive outcomes with laser treatment due to the absence of melanin pigment. This study discusses the treatment challenges in a female infant diagnosed with ROP and OCA, and underscores the importance of genetic analysis in guiding therapeutic decisions for this rare comorbid condition. CASE PRESENTATION: The study presents a case of ROP occurring concurrently with OCA. Genetic testing revealed two variants, c.727C > T (p.R243C) and c.1832 T > C (p.L611P), in the OCA2 gene, inherited from the patient's mother and father, respectively. The identified mutations were consistent with a diagnosis of OCA2, classified as a subtype of OCA. The patient initially received intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection, followed by laser photocoagulation therapy for a recurrent event. A favorable outcome was observed during the 2-month follow-up period. CONCLUSIONS: The co-occurrence of ROP and OCA is a rare phenomenon, and this is the first recorded case in the Chinese population. The current case supports the use of laser as the primary treatment modality for ROP in OCA2 patients with partial pigmentation impairment. Furthermore, genetic analysis can aid in predicting the effectiveness of laser photocoagulation in this patient population.

Visual Outcome after Anti-Vascular Epithelial Growth Factor Therapy Using New Classification of Diabetic Macular Edema by Optical Coherence Tomography.

INTRODUCTION: The aim of the study was to examine alterations in visual acuity in patients with diabetic macular edema (DME), classified according to the TCED-HFV optical coherence tomography (OCT) system, following anti-vascular epithelial growth factor (VEGF) therapy. METHODS: The medical records of patients with DME receiving anti-VEGF therapy were retrospectively reviewed. Patients were divided into four groups according to the TCED-HFV OCT classification. Patient demographic and clinical characteristics and best-corrected visual acuity (BCVA) before and after treatment were compared among the groups. RESULTS: The BCVA before treatment was 0.49 ± 0.18, 0.81 ± 0.41, 0.83 ± 0.41, and 0.82 ± 0.49 in the early DME, advanced DME, severe DME, and atrophic maculopathy groups, respectively. The BCVA in the early DME group was therefore significantly lower than that in the other three groups (p = 0.042). After treatment, the BCVA improved to 0.15 ± 0.17, 0.52 ± 0.31, 0.62 ± 0.32, and 0.69 ± 0.47 in the early DME, advanced DME, severe DME, and atrophic maculopathy groups, respectively (p < 0.005). There were some differences among patients in the four groups in terms of the duration of diabetes, percentage of hemoglobin A1c, and duration of hypertension. CONCLUSION: The TCED-HFV OCT classification of patients with DME is exact and functional and can allow the severity of DME, and its response to anti-VEGF therapy, to be estimated.

Association of the Complement Factor H Y402H Polymorphism and Response to Anti-Vascular Endothelial Growth Factor Treatment in Age-Related Macular Degeneration: An Updated Meta-Analysis.

INTRODUCTION: Anti-vascular endothelial growth factor (anti-VEGF) agents have a variable effect on patients with age-related macular degeneration (AMD) that has been attributed to several causes, including genetic factors. We evaluated the effects of Complement Factor H (CFH) rs1061170/Y402H polymorphism on the response to anti-VEGF therapy among AMD patients. METHODS: PubMed, Scopus, EMBASE, Web of Science, and Google Scholar were used for a literature search. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated to assess the effects of CFH Y402H polymorphism on the response to anti-VEGF therapy in AMD. I2 was used to present the amount of heterogeneity. We used STATA version 14.0 software. RESULTS: Twenty-five papers reporting data for 4,681 patients were included in this study. Better response to anti-VEGF therapy was seen in T over C (OR = 1.25, 95% CI = 1.04-1.50), TT over CC (OR = 1.60, 95% CI = 1.06-2.4), and TT + TC over CC (OR = 1.68, 95% CI = 1.23-2.28) genotypes. There was no significant difference in the three other genetic models (TT vs. TC, TT vs. TC + CC, TC vs. TT + CC). In Asians, no significant difference was observed in all six genetic models. Ranibizumab and bevacizumab had similar efficacy; however, conbercept was more effective in homozygous genotypes. The literature indicated that TT and TC genotypes and T allele were associated with a better functional response, while the CC genotype and C alleles had a better anatomical response. The combination of risk alleles in ARMS2 A69S (rs10490924), VEGF-A (rs699947), and VEGF-A (rs833069) with Y420H is a predictor of non-respondents. CONCLUSION: In patients with AMD, the CFH Y402H is a predictor of the response to anti-VEGF agents and should be considered in the treatment plan.

The Association between Retinal Thickness Fluctuations and Visual Outcomes under Anti-Vascular Endothelial Growth Factor Therapy: A Systematic Review and Meta-Analysis.

INTRODUCTION: The objective of this study was to examine the association between retinal thickness (RT) fluctuations and best corrected visual acuity (BCVA) in eyes with neovascular AMD, macular edema secondary to RVO, and DME treated with anti-VEGF therapy. METHODS: A systematic search of Ovid MEDLINE, EMBASE, and the Cochrane Library was performed from January 2006 to March 2024. Studies comparing visual or anatomic outcomes of patients treated with anti-VEGF therapy, stratified by magnitudes of RT fluctuation, were included. ROBINS-I and Cochrane RoB 2 tools were used to assess risk of bias, and certainty of evidence was evaluated with GRADE criteria. Meta-analysis was performed with a random-effects model. Primary outcomes were final BCVA and change in BCVA relative to baseline. RESULTS: 15,725 articles were screened; 15 studies were identified in the systematic review and 5 studies were included in the meta-analysis. Final ETDRS VA was significantly worse in eyes with the highest level of RT fluctuation (weighted mean difference [WMD] = 7.86 letters; 95% CI, 4.97, 10.74; p < 0.00001; I2 = 81%; 3,136 eyes). RT at last observation was significantly greater in eyes with high RT fluctuations (WMD = -27.35 µm; 95% CI, -0.04, 54.75; p = 0.05; I2 = 88%; 962 eyes). CONCLUSIONS: Final visual outcome is associated with magnitude of RT fluctuation over the course of therapy. It is unclear whether minimizing RT fluctuations would help optimize visual outcomes in patients treated with anti-VEGF therapy. These findings are limited by a small set of studies, risk of bias, and considerable heterogeneity.