Intravitreal Dexamethasone Implant for the Management of Choroidal Neovascular Membrane in Pregnancy.

The management of choroidal neovascularization (CNVM) in pregnant young females has been a lacuna due to the rarity of the condition as well as the non-availability of comprehensive data to showcase the efficacy of currently available treatment regimes in order to achieve a positive outcome for both the growing fetus as well the patient herself. In a review of available literature, the condition has been treated with anti-vascular endothelial growth factors (anti-VEGF), laser photocoagulation, and intravitreal dexamethasone implants (IDI), with varied results ranging from the successful outcome in terms of pregnancy to abortions. When faced with such circumstances, healthcare professionals usually proceed cautiously, balancing the possible advantages against the hazards to the mother and the fetus. Here we present a case report of a young 30-year-old pregnant lady who developed idiopathic CNVM during her third month of gestation. Being a rare entity, CNVM in young pregnant women raises severe concerns due to potential consequences on the mother's and fetus's health. In certain previously documented cases, pregnant ladies with CNVM have been successfully treated with IDI. Hence, after much deliberation, we chose to go with IDI rather than anti-VEGF, which resulted in the successful management of her CNVM as well as achieving full-term normal delivery without any fetal anomalies. In this particular case, the pregnancy and the visual rehabilitation have both had favorable outcomes. There was no associated increased intraocular pressure (IOP) or changes to the lenticular structure. The literature review also suggests that IDI may still be as effective in managing CNVM during pregnancy, but at a lower risk than anti-VEGF drug. Even with the favorable outcomes revealed in case reports, larger-scale studies to properly examine IDI's safety profile would be required for regulatory clearance of its safety in pregnancy.

Double-dose investigation of aflibercept in neovascular age-related macular degeneration (DIANA): a real-world study.

BACKGROUND: To investigate the clinical effects of double-dose (4 mg) aflibercept treatment in neovascular age-related macular degeneration (nAMD), compared with the standard-dose (2 mg) treatment. METHODS: A total of 108 eyes from 97 patients with nAMD and received intravitreal aflibercept 2 mg and/or 4 mg treatment were retrospectively reviewed. The changes of central macular thickness (CMT)/ pigmental epithelium detachment height and the recurrence rate of exudation during the 12-month follow-up were compared between the 2 mg group and the 4 mg group. Self-control comparisons (2 mg switch to 4 mg) were also made between two regimens. RESULTS: Compared with the 2 mg group, tendencies of lower intraretinal fluid incidence and more CMT reduction were observed in the 4 mg group. The later one was also observed when eyes switching from 2 mg to 4 mg regimen. The median remission interval was 5 months in the 4 mg group, 2 months longer than the 3 months in the 2 mg group (P = 0.452). Injections needed in the 4 mg group were 3.644 ± 1.670, less than the 4.286 ± 2.334 injections in the 2 mg group within 12 months as well (P = 0.151). However, no associated vision benefits were gained from the double-douse regimen. No markedly increased-intraocular pressure events, or other adverse events were found in two groups. CONCLUSIONS: Compared to the aflibercept 2 mg treatment in nAMD, tendencies of anatomic gains and relieving treatment burden were brought by the aflibercept 4 mg treatment. This study may have additional importance, given the further application of high-dose aflibercept in real-world settings.

Treatment strategy for HER2-negative advanced gastric cancer: salvage-line strategy for advanced gastric cancer.

After immune checkpoint inhibitor (ICI) comes into third-line treatment of advanced gastric cancer, the therapeutic strategy has been dramatically changed. Recent first-line regimen, which consists of ICI and chemotherapeutic agents, prolonged progression-free survival, and subsequent treatment options enabled continuous treatment beyond second-line therapy. Moreover, the advent of vascular endothelial growth factor (VEGF)-targeted agents including angiogenesis inhibitors and TKIs provides an opportunity of considering the interaction between ICI and anti-VEGF agents, and facilitating novel treatment proposal. Although clinical benefit of prolonged VEGF blockade after disease progression has not been confirmed in gastric cancer, combination therapy of cytotoxic agents and anti-VEGF agent, such as irinotecan plus ramucirumab demonstrated favorable objective response rate and progression-free survival in third- or later-line setting. In this review, we discuss recent progress and future directions of later-line treatments of HER2-negative advancer gastric cancer.

Changes in ocular blood flow in patients with neovascular age-related macular degeneration after intravitreal injection of ranibizumab biosimilar and brolucizumab.

PURPOSE: To assess ocular blood flow (OBF) changes in patients with neovascular age-related macular degeneration (nAMD) treated with intravitreal injections of ranibizumab biosimilar (IVRbs) or brolucizumab (IVBr). METHODS: This retrospective longitudinal study included 43 eyes of 43 patients (74.5 ± 9.8 years old, male to female ratio 31:12) with nAMD treated with IVBr (29 eyes) or IVRbs (14 eyes). OBF in the optic nerve head (ONH) and choroid (Ch) was measured with laser speckle flowgraphy (Softcare Co., Ltd., Fukutsu, Japan) before and one month after treatment. Changes in mean blur rate (MBR) before and after each treatment were tested using Wilcoxon's signed-rank tests and mixed-effect models for repeated measures. RESULTS: In the IVBr group, MBR was significantly reduced in both the ONH and Ch (p < 0.01). In contrast, the IVRbs group showed no significant change in MBR in either the ONH or Ch (p = 0.56, p = 1). The linear mixed effect model showed a significant interaction between time and anti-VEGF drugs for MBR in both the ONH and Ch (ONH: p = 0.04; Ch: p = 0.002). A post hoc pairwise comparison of estimated marginal means showed that MBR decreased significantly only after IVBr (p < 0.001). CONCLUSION: Our findings suggest that the short-term impact on OBF varies depending on the drug used for nAMD.

Ranibizumab versus laser therapy for the treatment of very low birthweight infants with retinopathy of prematurity (RAINBOW): five-year outcomes of a randomised trial.

Background: Concerns remain over the long-term safety of vascular endothelial growth factor (VEGF) inhibitors to treat retinopathy of prematurity (ROP). RAINBOW is an open label randomised trial comparing intravitreal ranibizumab (in 0.2 mg and 0.1 mg doses) with laser therapy in very low birthweight infants (<1500 g) with ROP. Methods: Of 201 infants completing RAINBOW, 180 were enrolled in the RAINBOW Extension Study. At 5 years, children underwent ophthalmic, development and health assessments. The primary outcome was visual acuity in the better-seeing eye. The study is registered with ClinicalTrial.gov, NCT02640664. Findings: Between 16-6-2016 and 21-4-2022, 156 children (87%) were evaluated at 5 years. Of 32 children with no acuity test result, 25 had a preferential looking test, for 4 children investigators reported low vision for each eye, and in 3 further children no vision measurement was obtained. 124 children completed the acuity assessment, the least square mean (95% CI) letter score in the better seeing eye was similar in the three trial arms-66.8 (62.9-70.7) following ranibizumab 0.2 mg, 64.6 (60.6-68.5) following ranibizumab 0.1 mg and 62.1 (57.8-66.4) following laser therapy; differences in means: ranibizumab 0.2 mg v laser: 4.7 (95% CI: -1.1, 10.5); 0.1 mg v laser: 2.5 (-3.4, 8.3); 0.2 mg v 0.1 mg: 2.2 (-3.3, 7.8). High myopia (worse than -5 dioptres) in at least one eye occurred in 4/52 (8%) children following ranibizumab 0.2 mg, 8/55 (15%) following ranibizumab 0.1 mg and 11/45 (24%) following laser therapy (0.2 mg versus laser: odds ratio: 3.99 (1.16-13.72)). Ocular and systemic secondary outcomes and adverse events were distributed similarly in each trial arm. Interpretation: 5-year outcomes confirm the findings of the original RAINBOW trial and a planned interim analysis at 2 years, including a reduced frequency of high myopia following ranibizumab treatment. No effects of treatment on non-ocular outcomes were detected. Funding: Novartis Pharma AG.

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

BACKGROUND: Diabetic 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. METHODS: A 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. RESULTS: The 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). CONCLUSION: The 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.

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

BACKGROUND:  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. METHODS: 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. This study 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. RESULTS: 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). CONCLUSIONS: 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.

Spontaneous Massive Retinal Pigment Epithelium Tear: A Case Report of a Dramatic Complication of Age-Related Macular Degeneration.

Retinal pigment epithelium (RPE) tears occur when the RPE acutely breaks and retracts, leaving the underlying Bruch's membrane and choroid exposed. They usually happen in areas of previous pigment epithelial detachments and are generally associated with age-related macular degeneration (AMD). The purpose of this report is to describe a case of a spontaneous massive central RPE tear in a patient with untreated AMD. A 67-year-old female patient presented with complaints of sudden decreased vision in her right eye. Her best-corrected visual acuity was 2/20, and fundoscopy revealed a massive central retinal hemorrhage with intraretinal, subretinal, and sub-RPE blood. The patient started anti-vascular endothelial growth factor (VEGF) treatment, and after the blood was reabsorbed, a very large central tear of the RPE involving the central macula was evident, with a layer of detached retina folded on itself. She received continuous anti-VEGF therapy, and the final measurement of her visual acuity was 2/200, despite the complete reabsorption of the hemorrhage. RPE tears may occur spontaneously as part of the natural history of AMD or be triggered by the initiation of anti-VEGF treatment in the presence of large pigment epithelium detachments. There are currently no strategies to prevent their spontaneous development, and they constitute a dramatic complication of AMD. The prognosis is dependent on the size and location of the lesion, and the visual loss is irreversible.

Ranibizumab Modifies the Expression of Metalloproteinases and Their Tissue Inhibitors in Peripheral Blood Mononuclear Cells in Patients with Exudative Age-Related Macular Degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of vision loss in people over 60 years of age. Despite research, the causes of AMD remain unclear. Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) are known to be involved in AMD development, and anti-vascular endothelial growth factor therapy has revolutionized its treatment. This study aims to analyze the changes in gene expression in MMPs and TIMPS in patients with neovascular AMD before and after three doses of ranibizumab. METHODS: The study involved 29 patients with neovascular AMD treated with ranibizumab. Peripheral blood mononuclear cells were collected before treatment and 24 h after the third dose of ranibizumab. We assessed MMP and TIMP gene expression profiles through oligonucleotide microarrays and validated selected differential genes using RT-qPCR. RESULTS: A statistically significant change in the expression of six MMP- and TIMP-related genes was observed using oligonucleotide microarray. The mRNA levels of the two genes with the most significant fold changes, MMP15 and TIMP2, were then quantified using RT-qPCR. The results confirmed a statistically significant increase in MMP15 expression and a decrease in TIMP2 levels, although this change was not statistically significant in the group before and after the third dose of ranibizumab. CONCLUSION: Ranibizumab affects the systemic expression of MMP and TIMP-related genes in patients with neovascular AMD. Results from our exploratory study suggest that MMP15, in particular, may play a role in the treatment response, but further research is necessary.

Bioinformatics and Network Pharmacology Explore the Role of Immune Cells in the Occurrence of Anti-Vascular Endothelial Growth Factor (VEGF) Resistance in Patients with Neovascular Age-Related Macular Degeneration(nAMD) and the Application of Complementary Medicine Treatment.

PURPOSE: This study explores the immune cells' role in anti-VEGF resistance in nAMD patients, and the potential of Zi-Yin-Jiang-Huo-Tang (ZYJHT), a Traditional Chinese Medicine formula, as complementary therapy. METHODS: Aqueous humor proteomics data from 10 nAMD patients with anti-VEGF resistance and 10 nAMD patients without anti-VEGF resistance were analyzed, investigating immune cells's role in anti-VEGF resistance and its underlying mechanism. Network pharmacology methods are employed to analyze the active ingredients in ZYJHT that contribute to therapeutic effects and their mechanisms. Real-time PCR (polymerase chain reaction) was used to detect changes in the expression of SOD1 (superoxide dismutase 1) after treatment with compounds targeting SOD1 in ARPE-19 cells. RESULTS: nAMD patients with anti-VEGF resistance showed enhancement of biological processes linked to the positive regulation of immune function, along with decreased cellular resistance to oxidative stress. Infiltration of B cells memory, plasma cells, CD8+and γδ-T cells were higher in nAMD patients with anti-VEGF resistance. SOD1 was identified as a hub gene in the occurrence of anti-VEGF resistance and a core therapeutic target of ZYJHT, negatively correlated with B and T cell infiltration. Compounds diosgenin, naringenin, and liquiritin in ZYJHT can bind to SOD1 and upregulating SOD1 expression in ARPE-19 cells.

Diabetic Macular Edema Management: A Review of Anti-Vascular Endothelial Growth Factor (VEGF) Therapies.

Diabetic macular edema (DME) is a major cause of vision impairment in diabetic individuals, characterized by fluid accumulation in the macula due to a breakdown of the blood-retinal barrier (BRB). This review article explores the role of anti-vascular endothelial growth factor (anti-VEGF) therapies in the management of DME. Anti-VEGF treatments, including ranibizumab, bevacizumab, and aflibercept, have revolutionized DME management by targeting VEGF, a key mediator in DME pathogenesis. We critically examined the efficacy of these therapies in reducing macular edema and improving visual acuity, assessed their safety and tolerability, and explored the variability in treatment response. The review highlights the latest advancements and future directions in anti-VEGF therapy, including novel drug delivery systems and emerging treatment paradigms. By providing a comprehensive overview of current anti-VEGF therapies, this review seeks to inform clinical practice, guide future research, and contribute to improved patient outcomes in DME management.

The role of blood neutrophil lymphocyte ratio in predicting the initial response to anti-VEGF treatment in neovascular AMD patients.

PURPOSE: Vascular endothelial growth factor (VEGF) has a critical role in age-related macular degeneration (AMD), and intravitreal injection of anti-VEGF drugs is the mainstay of neovascular AMD treatment. Blood neutrophil-to-lymphocyte ratio (NLR) is shown to be a biomarker of inflammation in AMD. We aimed to investigate the role of NLR in predicting favorable short-term anti-VEGF treatment results in neovascular AMD patients. METHODS: A total of 112 patients diagnosed with exudative AMD and had taken 3 monthly intravitreal bevacizumab injections were analyzed retrospectively. Medical records were reached to obtain neutrophil and lymphocyte values to calculate NLR. Best-corrected visual acuity and central macular thickness (CMT) measurements were recorded at each visit. T test or Mann-Whitney U test was used to compare continuous variables, and chi-square test was used to compare categorical variables. Receiver operating characteristics curve (ROC) analysis was performed to determine cut-off, sensitivity, and specificity values. P value of ≤ 0.05 was considered statistically significant. RESULTS: The mean age was 68.1 ± 7.2 years, and the mean NLR was 2.11 ± 0.81. The ROC analysis revealed a cut off value of 2.0 for NLR to predict at least 100 µm CMT change (sensitivity 87.1%; specificity 87.8%) and a cut off value of 2.4 for NLR to predict at least 0.1 logMAR visual improvement (sensitivity 77.2%; specificity 64.8%) after 3 monthly IVT bevacizumab injections. CONCLUSION: NLR can provide additional prognostic information for the identification of patients with a good initial response to anti-VEGF therapy.

[Three-year follow-up study of clinical effectiveness of antiangiogenic therapy for neovascular age-related macular degeneration]. / Klinicheskaya effektivnost' antiangiogennoi terapii neovaskulyarnoi vozrastnoi makulyarnoi degeneratsii po rezul'tatam trekhletnego nablyudeniya.

PURPOSE: The study analyzes long-term (three years) clinical effectiveness of anti-VEGF treatment of neovascular age-related macular degeneration (nAMD) and attempts to identify the most clinically significant associations between the functional and structural parameters. MATERIAL AND METHODS: The study included 122 patients (122 eyes) diagnosed with nAMD, mean age -73.4±6.6 years old. Prospective follow-up lasted 144 weeks. All patients were treated with angiogenesis inhibitor (aflibercept 2 mg), and most of them (72.9%) - according to the Treat-and-Extend protocol. RESULTS: The average number of injections was 7.39±1.28, 4.63±0.97 and 4.06±0.81 during the first, second and third years of the follow-up, respectively. The mean baseline best-corrected visual acuity (BCVA) was 0.24±0.21. After three loading doses, BCVA increased to 0.33±0.26 (+0.09; 37.5%), by the end of follow-up BCVA was 0.35±0.27 (+0.11; 45.8%). Central retinal thickness (CRT) decreased from 314.89±88.07 µm to 234.4±42.8 µm (a 25.5% decrease) by the end of the follow-up. After three loading injections baseline functional and anatomical parameters had the most significant correlations (r≥0.7, p<0.05) with intraretinal fluid, ellipsoid zone integrity and the area of macular atrophy. CONCLUSIONS: Analysis of the morphological and functional outcomes by the end of the first year demonstrates the feasibility of preserving the results while reducing the number of visits and injections according to the Treat-and-Extend protocol. Achieving maximum improvement of functional parameters most significantly correlated with changes in such biomarkers as central retinal thickness, area of macular atrophy and integrity of the ellipsoid zone.

Treatment strategy for BVO-ME based on long-term outcomes correlating retinal structure by OCT image and visual acuity.

BACKGROUND: Intravitreal anti-vascular endothelial growth factor (VEGF) is a mainstream treatment for reducing ME secondary to BRVO (BVO-ME). Regrettably, most reports of intravitreal anti-VEGF for BVO-ME have disclosed only short-term outcomes. Here, we characterized long-term indicators for the visual prognosis of patients with BVO-ME, including the correlation between retinal structure by OCT and visual acuity. METHODS: Patients with BVO-ME were retrospectively recruited based on clinical records in Kansai Medical University Hospital from June 2012 to March 2022. This study enrolled patients with vision loss who received intravitreal injection of anti-VEGF for BVO-ME. Inclusion criteria were that patients received intravitreal injection of anti-VEGF as their first treatment and were followed for at least 36 months. Exclusion criteria were those patients with ocular disease other than BRVO or who had been previously treated for BVO-ME. Patients were divided into two groups according to BCVA at the final visit: Group A (≥ 0.7) and Group B (< 0.7). RESULTS: Forty-seven eyes from 45 patients were assessed. The mean follow-up period from initial to final visit was 64.38 ± 15.07 (range, 38-100) months. BCVA in Group A (n = 32) was significantly greater than in Group B (n = 15) at all timepoints. The ratio that the number of eyes which the EZ band and the foveal bulge were intact in Group A was higher than in Group B (p = 0.0004 and p = 0.0002, respectively). The ratio that the number of eyes which recurrence SRD was observed by the final visit in Group A was lower than in Group B (p = 0.0485). CONCLUSIONS: The integrity of the EZ band and an intact foveal bulge were significant predictors for visual acuity. In contrast, recurrent SRD led to poor visual acuity in the long term, even if BCVA was good in the short term.

Choroidal neovascularization associated with butterfly-shaped pattern dystrophy - a case report.

The pattern dystrophies (PDs) are a group of primarily autosomal dominant inherited macular diseases that cause the deposition of lipofuscin in retinal pigment epithelium (RPE) and may lead to significant vision loss in later life. Patients can develop choroidal neovascularization (CNV) and/ or geographic atrophy (GA) and for this reason they are often misdiagnosed as age-related macular degeneration (AMD). We presented a case of a 66-year-old patient complaining of vision loss in the right eye (RE) for 8 months. At the initial examination, his best corrected visual acuity (BCVA) was 0.6 in the RE. Optical coherence tomography angiography (OCTA), fundus autofluorescence (FAF) and fundus fluorescein angiography (FFA) allowed to diagnose butterfly-shaped PD in both eyes with choroidal neovascularization (CNV) in the RE. The patient was treated with three intravitreal anti-vascular epithelial growth factor (anti-VEGF, ranibizumab) injections during six weeks intervals, which improved and stabilized the BCVA of the RE to 0.7 during the over two-year observation period. Our report contributes to the still limited data regarding CNV associated with butterfly-shaped PDs and the results of treatment with ranibizumab. Abbreviations: AMD = age-related macular degeneration, anti-VEGF = anti-vascular epithelial growth factor, AOFVD = adult-onset foveomacular vitelliform dystrophy, BCVA = best corrected visual acuity, CNV = choroidal neovascularization, FAF = fundus autofluorescence, FFA = fundus fluorescein angiography, GA = geographic atrophy, LE = left eye, MIDD = maternally inherited diabetes and deafness, OCT = optical coherence tomography, OCTA = optical coherence tomography angiography, OU = oculus uterque, both eyes, PD = pattern dystrophy, PDSFF = pattern dystrophy simulating fundus flavimaculatus, PDT = photodynamic therapy, PRPH2 = peripherine-2, RE = right eye, RPE = retinal pigment epithelium, VA = visual acuity.

Cataract surgery in neovascular AMD: impact on visual acuity and disease activity.

BACKGROUND: Cataract and neovascular age-related macular degeneration (nAMD) often co-exist and both contribute to impaired vision. It has been debated whether cataract surgery can increase nAMD activity. The purpose of this retrospective study was to investigate the impact of cataract surgery on visual acuity, treatment intensity for nAMD and macular morphology in patients with on-going treatment for nAMD. METHODS: Data was obtained from the Swedish Macular Register, the Swedish National Cataract Register, optical coherence tomography (OCT) images and patient charts. All eyes were treated at the Department of Ophthalmology at the County Hospital of Västmanland, Västerås, Sweden. Follow-up was 6 months after surgery. The study was approved by the Swedish Ethical Review Authority. RESULTS: In total, 156 patients (168 eyes) were included. The mean age at cataract surgery was 82 (standard deviation, SD 6) years. Both distance and near visual acuity improved after surgery. Distance visual acuity increased from 59 (SD 12) to 66 (SD 15) letters ETDRS (P < 0.001). Proportion of eyes with normal near visual acuity increased from 12 to 41%. The anti-vascular endothelial growth factor (VEGF) treatment intensity remained unchanged: mean of 3.4 (SD 1.9) and 3.3 (SD 1.7) treatments were given 6 months pre- and postoperatively, respectively. The prevalence of intraretinal fluid (IRF) in the macula increased from 22 to 31% postoperatively, while subretinal fluid, fluid under the pigment epithelium (sub-RPE fluid) and central retinal thickness were unaltered. In eyes with new IRF, improvement in visual acuity and number of anti-VEGF treatments were similar to eyes without new IRF. CONCLUSION: Cataract surgery improved visual acuity in patients with on-going treatment for nAMD and did not affect anti-VEGF treatment intensity. Macular morphology remained unchanged. The slight increase in intraretinal fluid after surgery was not found to affect visual acuity or anti-VEGF treatment intensity. It is hypothesized that this might indicate that it represents degenerative intraretinal cystic fluid.

SCORE2 Report 24: Nonlinear Relationship of Retinal Thickness and Visual Acuity in Central Retinal and Hemiretinal Vein Occlusion.

PURPOSE: To investigate whether a nonlinear association between central subfield thickness (CST) on spectral-domain OCT and concurrent visual acuity letter score (VALS) exists in eyes treated initially with aflibercept or bevacizumab for macular edema associated with central retinal vein occlusion (CRVO) or hemiretinal vein occlusion (HRVO) in the Study of Comparative Treatments for Retinal Vein Occlusion 2 (SCORE2). DESIGN: Long-term follow-up after a randomized clinical trial from 64 centers in the United States. PARTICIPANTS: Participants were followed up to 60 months and treated at investigator discretion after completing the 12-month treatment protocol. METHODS: Two-segment linear regression models were compared with simple linear regression models of VALS on CST. Pearson correlation coefficients were calculated to assess strength of CST and VALS associations. MAIN OUTCOME MEASURES: Central subfield thickness was measured by OCT and VALS by the electronic Early Treatment Diabetic Retinopathy Study methodology. RESULTS: Estimated inflection points, reflecting turning points at which the CST and VALS association changes from positive to negative, calculated at 7 postbaseline visits, range from 217 to 256 µm. A strongly positive correlation exists to the left of each estimated inflection point, ranging from 0.29 (P < 0.01 at month 60) to 0.50 (P < 0.01 at month 12), and a strongly negative correlation exists to the right of each estimated inflection point, ranging from -0.43 (P < 0.01 at month 1) to -0.74 (P < 0.01 at month 24). Randomization statistical tests showed that 2-segment models are favored over 1-segment models for all postbaseline months (P < 0.001 for all tests performed). CONCLUSIONS: The relationship between CST and VALS in eyes with CRVO or HRVO after treatment with anti-vascular endothelial growth factor (VEGF) therapy is not simply linear. The usually modest correlations between OCT-measured CST and visual acuity belie strong left and right correlations present in 2-segment models. Post-treatment CST close to the estimated inflection points showed the best expected VALS. The SCORE2 participants with a post-treatment CST after treatment close to the estimated inflection points of 217 to 256 µm showed the best VALS. In patients treated with anti-VEGF for macular edema associated with CRVO or HRVO, a thinner retina is not always associated with better VALS. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

[Late sequelae of retinopathy of prematurity in infancy]. / Spätfolgen der Frühgeborenenretinopathie im Kindesalter.

BACKGROUND: Retinopathy of prematurity (ROP) is one of the most frequent causes of severe visual impairment or blindness in childhood and can lead to severe late complications in children even after the initial disease has resolved. PURPOSE: The present study summarizes possible late effects in childhood after treated and untreated ROP. A special focus is on the development of myopia, retinal detachment, as well as neurological and pulmonary development after anti-vascular endothelial growth factor (VEGF) treatment. MATERIAL AND METHODS: This work is based on a selective literature search on late effects in childhood of treated or untreated ROP. RESULTS: Preterm infants have an increased risk of developing high-grade myopia. Interestingly, several studies indicate that the risk of myopia is reduced following anti-VEGF treatment. With anti-VEGF treatment, however, late recurrences after initial response are possible even after several months, making long-term and frequent follow-up examinations essential. Controversy exists regarding the possible negative effects of anti-VEGF treatment on neurological and pulmonary development. After both treated and untreated ROP, rhegmatogenous, tractional or exudative retinal detachment, vitreous hemorrhage, high myopia and strabismus are possible late complications. DISCUSSION: Children with a history of ROP with or without treatment have an increased risk for late ocular sequelae, such as high myopia, retinal detachment, vitreous hemorrhage and strabismus. A seamless transition from ROP screening to pediatric and ophthalmological follow-up care is therefore essential for timely detection and treatment of possible refractive errors, strabismus, or other amblyogenic changes.

The role of serum metrics in anti- VEGF treatment for macular edema induced by retinal vein occlusion.

AIM: To evaluate association between pretreatment serum metrics and best corrected visual acuity ( BCVA) of patients with macular edema secondary to retinal vein occlusion and its subtypes after intravitreal ranibizumab or conbercept implant. METHODS: This prospective research included 201 patients(201 eyes) who were diagnosed with macular edema secondary to retinal vein occlusion at Heibei Eye Hospital between January 2020 and January 2021, who all received intravitreal anti- vascular endothelial growth factor treatment. Serum metrics were measured before the first treatment, and correlations between BCVA and each of four parameters- platelets, neutrophil- to- lymphocyte ratio(NLR), platelet- to- lymphocyte ratio(PLR) and monocyte- to- lymphocyte ratio(MLR)- were analyzed to identify predictors of effective intravitreal injection treatment outcomes. RESULTS: The mean platelets was significantly different in the effective and ineffective group for RVO-ME (273.02 ± 41.49 × 109/L,214.54 ± 44.08 × 109/L P < 0.01),BRVO-ME (269.43 ± 49.52 × 109/L,214.72 ± 40.42 × 109/L P < 0.01), and CRVO-ME (262.32 ± 32.41 × 109/L,209.27 ± 42 0.91 × 109/L P < 0.01). The cutoff value of the platelets was 266.500, the area under the curve was 0.857,and the sensitivity and specificity were 59.8% and 93.6%, respectively. The mean PLR was significantly different in the effective and ineffective group for RVO-ME (154.66 ± 49.60, 122.77± 44.63 P < 0.01),BRVO-ME (152.24 ± 54.99, 124.72 ± 41.46 P = 0.003), and CRVO-ME (152.06±44.23, 118.67 ± 41.80 P = 0.001). The cutoff value of the platelets was 126.734, the area under the curve was 0.699, and the sensitivity and specificity were 70.7% and 63.3%, respectively. There were no statistical differencies between the effective and ineffective group(RVO- ME and its subtypes) in NLR and MLR. CONCLUSION: Higher pretreatment platelets and PLR were associated with BCVA in patients with RVO- ME and its subtypes who were treated with anti- VEGF drugs. The platelets and PLR may be used as predictive and prognostic tools for effective intravitreal injection treatment outcomes.

[Prospective noninterventional BLUE SKY study evaluating the efficacy of brolucizumab in treatment-naïve and previously treated patients with neovascular AMD]. / Prospektive nichtinterventionelle BLUE SKY-Studie zur Beurteilung der Wirksamkeit von Brolucizumab bei unbehandelten und vorbehandelten Patienten mit neovaskulärer AMD.

Intravitreal injection of anti-vascular endothelial growth factor (VEGF) is the standard treatment for patients with neovascular age-related macular degeneration (nAMD). In addition to the approved substances ranibizumab (Lucentis®, Novartis) and aflibercept (Eylea®, Bayer), bevacizumab (Avastin®, Roche) is also available. Furthermore, brolucizumab (Beovu®, Novartis) has been approved and has been available in Germany since April 2020. The multicenter, noninterventional prospective BLUE SKY study investigates brolucizumab treatment with different schemes in 600 treatment-naive and pretreated nAMD patients in routine clinical practice over a 24-month period. Besides general patient data, visual acuity and treatment data will be documented. Fluorescein angiography, fundus photography, spectral domain optical coherence tomography and swept-source optical coherence tomography angiography will be performed and analyzed by reading centers. The focus of the analysis will be on the intraretinal and subretinal fluid distribution as well as morphological MNV changes and injection frequency. Also, safety and adverse drug effects of brolucizumab, with a specific focus on inflammatory complications, particularly retinal (occlusive) vasculitis will be evaluated.