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To determine the correlation between the severity of chronic kidney disease (CKD) and treatment of diabetic macular edema (DME). The retrospective 2-year cohort study included eyes with DME confirmed using spectral-domain optical coherence tomography in Taipei Veterans General Hospital, Taiwan, between 2010 and 2020. All the eyes were treated with an intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) during regular follow-up around 2 years. They were categorized into 3 different groups: an estimated glomerular filtration rate ≥ 60 (mL/min per 1.73 m 2 ) (group A), < 60 (group B), and patients undergoing hemodialysis (group C). The main outcome measures were (1) visual improvement, (2) structural improvement, and (3) the injection frequency of anti-VEGF in the different groups. In this study, 167 eyes from 120 patients were enrolled. Compared with groups B and C, the eyes in group A experienced the only significant visual improvement at month 3, month 6, and month 12 (P = 0.0001, 0.0002, 0.0013, respectively). The presence of subretinal fluid and intraretinal cysts was significantly decreased in groups A and B. In the treatment frequency analysis, the number of injections was the highest in group A and lowest in group C during the study period (P = 0.04). The severity of CKD had an impact on the DME treatment. The less severe CKD was, the greater the visual improvement that could be achieved. In addition, relatively poor renal function required a lower anti-VEGF injection frequency. The active prevention of the progression of CKD may play a key role in DME treatment., (© 2024. The Author(s).)

Purpose: To compare 1-year outcomes of eyes with diabetic macular edema (DME) treated in routine clinical practice based on the proportion of visits where intravitreal VEGF inhibitor injections were delivered., Design: Cohort study., Participants: There were 2288 treatment-naive eyes with DME starting intravitreal VEGF inhibitor therapy from October 31, 2015 to October 31, 2021 from the Fight Retinal Blindness! international outcomes registry., Methods: Eyes 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 Measures: Mean visual acuity (VA) change after 12 months of treatment., Results: The 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 to -61) μm and -85 (-92 to -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., Conclusions: This 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., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. All rights reserved.)

Purpose: This study aims to examine and compare the effects of intravitreal bevacizumab injection (IVB) at subfoveal 1500 micron (μm) and submacular 6000 μm in patients with diabetic macular edema (DME)., Methods: Fifty eyes of 45 patients with DME who completed six doses of IVB were included in the study group, and 50 eyes of 42 patients who had diabetic retinopathy (DR) but did not receive any treatment were included in the control group. Central macular thickness (CMT), central choroidal thickness (CCT), subfoveal and total choroidal area (TCA), and choroidal vascular index (CVI) were calculated and their changes at zero, three and six months were evaluated., Results: At baseline, CVI was significantly lower in both the subfoveal and total macular areas in the study group ( p  = 0.004, p  = 0.003). In the study group, a significant decrease was observed in CVI between zero and six months in the subfoveal area ( p  = 0.001). In the submacular area, the decrease in CVI in the study group was significant between zero to three months and zero to six months. There was moderate correlation between measurements of CVI in the subfoveal and total macular areas ( r  = 0.66, p  < 0.001)., Conclusion: These findings indicate that intravitreal bevacizumab injection reduces the CVI and the effects of intravitreal anti-VEGF on CVI emerge earlier and more prominently in the submacular 6000 µm area.

Purpose: To evaluate the responses of different optical coherence tomography (OCT) patterns of diabetic macular edema (DME) to intravitreal injection therapy., Methods: In this retrospective, comparative, and multicenter study, patients who had previously untreated DME, who received intravitreal ranibizumab (IVR) or aflibercept (IVA) and/or steroid treatment with the pro re nata (PRN) treatment regimen after a 3-month loading dose, and had a 12-month follow-up in the MARMASIA Study Group were included. Morphological patterns of DME were divided into four groups based on OCT features diffuse/spongious edema (Group 1), cystoid edema (Group 2), diffuse/spongious edema+subretinal fluid (SRF) (Group 3), and cystoid edema+SRF (Group 4). Changes in central macular thickness (CMT) and best-corrected visual acuity (BCVA) at months 3, 6, and 12, and the number of injections at month 12 were compared between the DME groups., Results: 455 eyes of 299 patients were included in the study. The mean baseline BCVAs [Logarithm of the Minimum Angle of Resolution (logMAR)] in groups 1, 2, 3, and 4 were 0.54 ± 0.24, 0.52 ± 0.25, 0.55 ± 0.23, and 0.57 ± 0.27, respectively. There was no significant difference between the baseline mean BCVAs between the groups ( p  = .35). The mean BCVAs were significantly improved to 0,47 ± 0,33 in group 1, 0,42 ± 0,33 in group 2, 0,47 ± 0,31 in group 3, and 0,45 ± 0,43 at month 12. There was no significant difference between the groups in terms of BCVA change at month 12 ( p  = .71). The mean baseline CMTs in groups 1, 2, 3, and 4 were 387,19 ± 128,19, 447,02 ± 132,39, 449,12 ± 109,24, and 544,19 ± 178,61, respectively. At baseline, the mean CMT was significantly higher in Group 4 than in the other groups ( p  = .000). The mean CMTs were significantly decreased to 325,16 ± 97,55, 334,94 ± 115,99, 324,33 ± 79,20, and 332,08 ± 150,40 in four groups at month 12 respectively ( p  > .05). The groups had no significant difference in mean CMT at month 12 ( p  = .835). The change in CMT was significantly higher in Group 4 than in the other groups at month 12 ( p  = .000). The mean number of intravitreal anti-VEGF injections at month 12 was 4.51 ± 1.57 in Group 1, 4.63 ± 1.54 in Group 2, 4.88 ± 1.38 in Group 3, and 5.07 ± 1.49 in Group 4. The mean number of anti-VEGF injections in Group 1 and Group 2 was significantly lower than in Group 4 ( p  = 0,014 and p  = 0,017)., Conclusions: In real life, there was no significant difference between the DME groups in terms of visual improvement at month 12. However, better anatomical improvement was achieved in Group 4 than in the other DME groups.

Purpose: To identify factors for meeting prespecified criteria for switching from bevacizumab to aflibercept in eyes with center-involved diabetic macular edema (CI-DME) and moderate vision loss initially treated with bevacizumab in DRCR Retina Network protocol AC., Design: Post hoc analysis of data from a randomized clinical trial., Participants: Two hundred seventy participants with one or both eyes harboring CI-DME with visual acuity (VA) letter score of 69 to 24 (Snellen equivalent, 20/50-20/320)., Methods: Eligible eyes were assigned to receive intravitreal aflibercept monotherapy (n = 158) or bevacizumab followed by aflibercept if prespecified criteria for switching were met between 12 weeks and 2 years (n = 154)., Main Outcome Measures: Meeting switching criteria: (1) at any time, (2) at 12 weeks, and (3) after 12 weeks. Associations between meeting the criteria for switching and factors measured at baseline and 12 weeks were evaluated in univariable analyses. Stepwise procedures were used to select variables for multivariable models., Results: In the group receiving bevacizumab first, older participants showed a higher risk of meeting the switching criteria at any time, with a hazard ratio (HR) for a 10-year increase in age of 1.32 (95% confidence interval [CI], 1.11-1.58). Male participants or eyes with worse baseline VA were more likely to switch at 12 weeks (for male vs. female: odds ratio [OR], 4.84 [95% CI, 1.32-17.81]; 5-letter lower baseline VA: OR, 1.30 [95% CI, 1.03-1.63]). Worse 12-week central subfield thickness (CST; 10-μm greater: HR, 1.06 [95% CI, 1.04-1.07]) was associated with increased risk of switching after 12 weeks. The mean ± standard deviation improvement in visual acuity after completing the switch to aflibercept was 3.7 ± 4.9 letters compared with the day of switching., Conclusions: The identified factors can be used to refine expectations regarding the likelihood that an eye will meet protocol criteria to switch to aflibercept when treatment is initiated with bevacizumab. Older patients are more likely to be switched. At 12 weeks, thicker CST was predictive of eyes most likely to be switched in the future., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the management of diabetic macular oedema (DME) patients from the entire French population between 2012 and 2018., Methods: In this retrospective longitudinal study, we identified adults treated for DME from the French population using the exhaustive French National Health Information database (SNDS), and an algorithm based on diagnosis and procedure codes, and reimbursed treatments., Results: Between 2012 and 2018, we identified 53 584 treated DME patients, who were followed for up to 7 years from DME treatment initiation. Optical coherence tomography (OCT) became the predominant imaging tool to diagnose DME. Only 14% of patients consulted a diabetologist or endocrinologist in the 3 months prior to initiating DME treatment, whereas 84% consulted a general practitioner. The percentage of patients consulting an ophthalmologist declined over time, from 97% of patients in Year 1 (median of 9 consultations), to 46% in Year 7 (median of 7 consultations). The median DME treatment duration with an anti-VEGF and/or dexamethasone implant treatment was 9 months; 54% of patients had a treatment duration less than 1 year. First-line treatment was more common with ranibizumab (55% of patients) than with aflibercept (30%), or dexamethasone implant (15%). About 25% of patients who initiated anti-VEGF treatment switched treatment at least once, while 30% of patients who initiated dexamethasone implant switched to anti-VEGF treatment at least once., Conclusions: French DME patients seem well-monitored by their ophthalmologist, but median DME treatment duration was just 9 months. These results emphasise the challenge to manage and treat patients with DME over the long term., (© 2023 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Purpose: To investigate the efficacy and safety of brolucizumab in diabetic macular edema (DME) and diabetic retinopathy (DR)., Methods: In this systematic review and meta-analysis, an electronic search was done to acquire all articles describing brolucizumab use in patients with DME and DR. The review was prospectively registered on PROSPERO (CRD42022382625). Collected articles were filtered through two stages by independent reviewers. Data were extracted from the included articles and then analyzed accordingly., Results: Brolucizumab induced significant improvement in best-corrected visual acuity and was either better or non-inferior to other types of anti-VEGF (MD -0.64 mu, 95% CI [-1.15, -0.13], P  = .01); the same observation was noted with regards to central subfield macular thickness (CSMT) (MD -138.6 mu, 95% CI [-151.9, -125.3], P  = .00001). Brolucizumab was reported to be relatively safe for use in diabetic patients, with few adverse events observed, with a higher frequency of adverse events in relation to the 3 mg dose compared to the 6 mg dose., Conclusion: Brolucizumab is a new drug that has potential advantages in efficacy over other anti-VEGF agents in the treatment of DME and DR. It showed significant improvement in BCVA and CSMT with the possibility of a lower dosing schedule compared to other agents. Although observed in low frequency, sight-threatening adverse effects appear to occur more frequently compared to other anti-VEGF agents. The main observed adverse event was retinal vasculitis which was seen more commonly with the 3 mg dose versus the 6 mg dose.

Purpose: To compare the outcomes of early or late switching from intravitreal (IV) anti-vascular endothelial growth factor (anti-VEGF) injection to IV Dexamethasone (DEX) implant injection in treatment-naïve patients with macular edema secondary to branch retinal vein occlusion., Methods: This study included 68 eyes of 68 treatment-naïve BRVO patients who started anti-VEGF treatment. After the loading dose, the patients were divided into two groups: Early DEX group (n:34) (DEX implant treatment started after 3 loading doses) and Late DEX group (n:34) (DEX implant treatment started after 6 months). Visual acuity and examination findings were recorded at baseline, 3rd, 6th, and 12th month follow-ups. Optical coherence tomography data were recorded for central macular subfield thickness assessment., Results: A total of 30 (44.1%) women and 38 (55.9%) men participated, and the average age was 67.6 ± 6.4 years. The mean letter gains at week 52 was 15.1 and 20.9 in the Early DEX and Late DEX groups, respectively. The group with the highest gain of ≥15 letters was the Late DEX group (26/34 patients) and the gain of ≥15 letters was 14/34 in the Early DEX group (p: 0.006). At week 52, the anatomical gain was 115.3 µm and 136.9 µm in the Early DEX and Late DEX groups, respectively., Conclusions: A gain of 15 or more letters was demonstrated to be higher in patients who switched to DEX implant late after anti-VEGF treatment. If it is necessary to switch, the late switch may be more effective for more visual gain at the end of the first year.

Purpose: The purpose of this study was to determine whether specific genetic polymorphisms affect the response to intravitreal anti-vascular endothelial growth factor (anti-VEGF) treatment in patients with macular oedema secondary to retinal vein occlusion (RVO)., Methods: Participants in this prospective study were 50 patients with macular oedema secondary to RVO, who were treated with intravitreal ranibizumab or aflibercept, and were followed-up for 12 months after initiation of treatment. Five single nucleotide polymorphisms (SNPs) from three different genes ( APOE , PON1 , SDF-1 ) were examined as potential predictors for treatment response to intravitreal anti-VEGF agents., Results: Patients with the LL genotype of the PON1 L55M SNP had significantly higher reduction in central subfield thickness (CST) at month 12 after initiation of intravitreal anti-VEGF treatment (101.63 ± 56.80 μm in LL vs. 72.44 ± 39.41 μm in LM vs. 40.25 ± 19.33 μm in MM, p  = .026). Patients with the M allele of the PON1 L55M SNP were significantly associated with lower reduction in CST compared to non-carriers (68.29 ± 38.77 μm in LM + MM vs. 101.63 ± 56.80 μm in LL, p  = .032)., Conclusion: PON1 L55M SNP may serve as a promising genetic biomarker for predicting response to intravitreal anti-VEGF treatment in patients with macular oedema due to RVO.

Purpose: To introduce the treatment of diabetic macular edema (DME) with subthreshold micropulse diode laser (SMPL), to summarize the biological impact, therapeutic effects, and safety of this treatment, and to discuss the response to DME when SMPL is combined with anti-vascular endothelial growth factor (anti-VEGF) or steroid., Methods: The literature search was performed on the PubMed database, with a selection of English-language articles published from 2000 to 2023 with the following combinations of search terms: diabetes macular (o) edema, micropulse laser or subthreshold micropulse laser, anti-vascular endothelial growth factor, and steroid., Results: SMPL is a popular, invisible retinal laser phototherapy that is inexpensive, safe, and effective in the treatment of DME. It can selectively target the retinal pigment epithelium, reduce the expression of pro-inflammatory factors, promote the absorption of macular edema, and exert a similar and lasting clinical effect to traditional lasers. No significant difference was found in the therapeutic effects of SMPL between different wavelengths. However, HbA1c level and pretreatment central macular thickness (CMT) may affect the therapeutic outcomes of SMPL., Conclusion: SMPL has a slow onset and produces lasting clinical effects similar to conventional photocoagulation. It has been reported that SMPL combined with the intravitreal anti-VEGF injection can significantly reduce the number of injections without influencing the therapeutic effect, which is essential for clinical applications and research. Although 577 nm SMPL is widely used clinically, there are no standardized protocols for SMPL. Additionally, some important problems regarding the treatment of SMPL require further discussion and exploration., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose: We quantify the association between visit adherence and visual acuity (VA) in retinal vein occlusions (CRVO)., Methods: The SCORE2 protocol included a visit every 4 weeks (every 28-35 days) during the first year. Visit adherence was measured as follows: number of missed visits, average and longest (avg and max days) visit interval, and average and longest (avg and max missed days) and unintended visit interval. Avg and max missed days were categorized as on time (0 days), late (>0-60 days), and very late (>60 days). The primary outcome was a change in the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity letter score (VALS) between baseline study visit and last attended visit during Year 1, using multivariate linear regression models controlling for numerous demographic and clinical factors., Results: After adjustment, for each visit missed, patients lost 3.0 letters (95% CI: -6.2, 0.2) of vision ( p  = .07). On average, the 48 patients who missed at least 1 visit lost 9.4 letters (95% CI: -14.4, -4.3, p  < .001) of vision after adjustment. Average days and maximal intervals between visits were not associated with changes in VALS ( p  > .22) for both comparisons. However, when a visit was missed, the average missed days between missed visits and the max missed interval were both associated with loss of VALS (both variables: 0 days missed as reference, late [1-60 days] -10.8 letters [95% CI: -16.9, -4.7], very late [>60 days] -7.3 letters [95% CI: -14.5, -0.2]; p  = .003 for both)., Conclusions: Visit adherence is associated with VALS outcomes in CRVO patients.

Objectives: This study aimed to report the demographic and clinical characteristics of diabetic macular edema (DME) patients treated with intravitreal injection (IVI) of anti-vascular endothelial growth factors (anti-VEGF) and provide an overview of outcomes during routine clinical practice in Türkiye., Materials and Methods: This retrospective, real-world study included 1,372 eyes (854 patients) treated with a pro re nata protocol by 21 ophthalmologists from 8 tertiary clinics on the Asian side of the Marmara region of Türkiye (MARMASIA Study Group). Five cohort groups were established by collecting the patients' baseline and 3, 6, 12, 24, and 36-month follow-up data, where each subsequent cohort may include the previous. Changes in best-corrected visual acuity (BCVA, approximate ETDRS letters) and central macular thickness (CMT, μm), number of visits and IVI, and rates of anti-VEGF switch and intravitreal dexamethasone implant (IDI) combination were evaluated., Results: The 3, 6, 12, 24, and 36-month cohorts included 1372 (854), 1352 (838), 1185 (722), 972 (581), and 623 (361) eyes (patients), respectively. The mean baseline BCVA and CMT were 51.4±21.4 letters and 482.6±180.3 μm. The mean changes from baseline in BCVA were +7.6, +9.1, +8.0, +8.6, and +8.4 letters, and in CMT were -115.4, -140.0, -147.9, -167.3, and -215.4 μm at the 3, 6, 12, 24, and 36-month visits (p<0.001 for all). The median cumulative number of anti-VEGF IVI was 3.0, 3.0, 5.0, 7.0, and 9.0, respectively. The overall anti-VEGF switch and IDI combination rates were 18.5% (253/1372 eyes) and 35.0% (480/1372 eyes), respectively., Conclusion: This largest real-life study of DME from Türkiye demonstrated BCVA gains inferior to randomized controlled trials, mainly due to the lower number of IVI. However, with the lower baseline BCVA and higher IDI combination rates in our cohorts, these gains were relatively superior to other real-life study counterparts., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by the Turkish Ophthalmological Association / Turkish Journal of Ophthalmology published by Galenos Publishing House.)

Purpose: To evaluate the effect of intravitreal injection of ranibizumab (IVR) on subfoveal choroidal thickness (SFCT) and its relationship with central macular thickness (CMT) and best-corrected visual acuity (BCVA) changes in eyes with center-involving DME (CI-DME) using a deep learning-based auto-segmentation., Methods: This prospective interventional case series included 68 eyes of 68 patients with CI-DME naive to treatment. Morphological optical coherence tomography (OCT) findings of DME were classified into three patterns of structural change: (i) diffuse retinal thickening (DRT), (ii) cystoid macular edema (CME), and (iii) serous retinal detachment (SRD). All patients underwent 3+prorenata IVR. The treated eyes underwent BCVA evaluation and OCT scanning at baseline and months 1, 3, and 6 after the first injection. Then, the choroid layer was measured using a deep learning-based auto-segmentation., Results: At baseline, the mean SFCT and CMT for SRD, DRT, and CME groups were 324.68 ± 65.58 μm and 624.37 ± 77.92 μm, 348.91 ± 45.81 μm and 443.5 ± 78.33 μm, 361.4 ± 64.62 μm, and 536.5 ± 66.02 μm, respectively. After anti-VEGF treatment, the SFCT and CMT have decreased by varying degrees. At 3 and 6 months of treatment, there were no significant changes among these groups. There was no correlation between baseline SFCT and the resulting BCVA (P = 0.670, P = 0.584). There was also no correlation between changes in SFCT and BCVA, CMT (P = 0.344, P = 0.336)., Conclusion: After treating CI-DME with IVR, SFCT and CMT significantly decreased. However, there were no significant changes among the SRD, DRT, and CME groups., Trial Registration: Trial registration: ChiCTR, ChiCTR-ROC-17013360. Registered 13 November 2017, http://www.chictr.org.cn/ChiCTR-ROC-17013360 ., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Intravitreal injection of anti- Vascular Endothelial Growth Factor (VEGF)is commonly used to treat patients with diabetic macular edema (DME). However, the injection alone requires high cost and compliance. Combining micropulse subthreshold laser (MPSL) and anti-VEGF is a new approach to treating DME. This study intended to answer the question of whether MPSL plus anti-VEGF is effective compared to anti-VEGF alone. The following terms were used in PubMed, clinicaltrial.gov, and Google Scholar: anti-VEGF, DME, MPSL, and diabetic retinopathy. All studies of DME comparing the intervention of MPSL plus anti-VEGF and VEGF alone between the years 2017-2021 were included. Studies with no comparison between the intervention and control group, abstract-only papers, case reports, case series, and systematic review studies were excluded. Five Randomized Controlled Trial (RCTs) and three retrospective studies were analyzed. Four studies found that best-corrected visual acuity (BCVA) improved in both therapies. Central macular thickness in six studies was also improved. The improvement differences between both therapies were insignificant and the number of anti-VEGF injections was significantly lower in combination therapy. These studies show equal outcomes of both therapies. The reduced number of anti-VEGF injections of the combination therapy could improve the management of DME in terms of cost-effectiveness. Further analysis should be conducted to pool the data from the studies and evaluate the overall outcome., Competing Interests: None

Background: Diabetic macular edema (DME) is the main cause of vision loss in diabetic patients. Currently, anti-vascular endothelial growth factor (VEGF) intravitreal injection stands as the first-line therapy for DME. However, some patients exhibit insufficient response to anti-VEGF agents and often require multiple injections, imposing psychological and economic burdens. While microinvasive pars plana vitrectomy (PPV) has been shown to be safe and effective in treating refractory DME, scant research has explored its application to treatment-naïve DME. The purpose of this study is to determine whether early PPV combined with internal limiting membrane (ILM) peeling can lessen the therapeutic burden of DME patients, prevent vision loss, and maintain long-term stabilization of diabetic retinopathy., Methods: This is a single-center, prospective, parallel-group, non-inferiority randomized controlled trial involving 102 DME participants. Participants will be randomly assigned to either the study group (PPV combined with ILM peeling) or the control group (conbercept intravitreal injection (IVC)) at a 1:1 ratio, with a scheduled follow-up at 12 months post-operation. Comparative analysis of results between the two groups will be conducted at months 1, 3, 6, and 12 after the intervention. The primary outcomes involve evaluating the changes in central subfield thickness (CST) and best corrected visual acuity (BCVA). The secondary outcomes include assessment of optical coherence tomography (OCT) and OCT angiography (OCTA) biomarkers, re-treatment and adverse events rates, diabetic retinopathy (DR) development, cost-effectiveness analysis, and vision-related quality of life (VRQL)., Discussion: Some patients do not respond well to anti-VEGF drugs and repeated intravitreal injections increase the treatment burden for patients. The VVV study aims to explore whether PPV combined with ILM peeling could become an initial treatment option for treatment-naïve DME patients., Trial Registration: ClinicalTrials.gov NCT05728476. Registered on 15 February 2023., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Anti-vascular endothelial growth factor (VEGF) drugs are widely used in modern ophthalmology, especially in treating macular disorders like age-related macular degeneration or diabetic macular edema. Protocols for such treatments include repeated administration of intravitreal injections, with the volume of drug injected into the vitreous chamber seemingly high enough to cause an increase in intraocular pressure. Hence, questions might arise if such therapeutic approaches are safe for ocular tissue. Moreover, anti-VEGF compounds may theoretically harm the retinal nerve fibers due to the inhibition of VEGF and its neuroprotective effects. Thus, this manuscript aims to review the literature regarding studies evaluating the retinal nerve fiber layer (RNFL) in eyes receiving anti-VEGF treatment due to age-related macular degeneration. The RNFL was chosen as a subject of this review, as it is the innermost retinal layer exposed to the direct action of intravitreally administered drugs. The results of the available studies remain inconclusive. Most researchers seem to confirm the safety of the anti-VEGF treatment in wet age-related macular degeneration, at least regarding the retinal nerve fiber layer. However, some authors noticed that the influence of anti-VEGFs on RNFL could become apparent after more than thirty injections. Nonetheless, the authors of all studies agree that further, long-term observations are needed to help clinicians understand the effect of anti-VEGF treatment on the dynamics of changes in the thickness of retinal nerve fibers in patients with the wet form of age-related macular degeneration., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Degenerative eye conditions such as age-related macular degeneration (AMD), diabetic retinopathy, and retinal vein occlusion are major contributors to significant vision loss in developed nations. The primary therapeutic approach for managing complications linked to these diseases involves the intravitreal delivery of anti-vascular endothelial growth factor (VEGF) treatments. Faricimab is a novel, humanised, bispecific antibody that simultaneously binds all VEGF-A isoforms and Angiopoietin-2, which has been approved by regulatory agencies, such as the US Food and Drug Administration (FDA), the UK Medicines and Healthcare products Regulatory Agency (MHRA) and the European Medicines Agency (EMA), for the treatment of neovascular AMD and diabetic macular oedema (DMO). Intravitreal faricimab holds the promise of reducing the treatment burden for patients with these conditions by achieving comparable or superior therapeutic outcomes with fewer clinic visits. The scope of faricimab's application includes addressing complex macular conditions such as DMO. This review intends to elucidate the distinctive pharmacological characteristics of faricimab and provide an overview of the key clinical trials and real-world studies that assess its effectiveness and safety in treating degenerative macular diseases., Competing Interests: Winfried M Amoaku has provided consultancy services to Alcon, Alimera, Allergan (AbbVie), Bayer, Novartis and Roche. The other authors report no conflicts of interest in this work., (© 2023 Panos et al.)

Background: Retinal diseases, including wet or dry age-related macular degeneration, diabetic macular edema, and diabetic retinopathy (DR), are underdiagnosed and undertreated in the United States. Clinical trials support the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) therapies for several retinal conditions, but real-world data suggest underuse by clinicians, resulting in patients experiencing poorer visual outcomes over time. Continuing education (CE) has demonstrated effectiveness at changing practice behaviors, but more research is needed to understand whether CE can help address diagnostic and treatment gaps., Methods: This test and control matched pair analysis examined pre-/post-test knowledge of retinal diseases and guideline-based screening and intervention among 10,786 healthcare practitioners (i.e., retina specialists, ophthalmologists, optometrists, primary care providers, diabetes educators, pharmacists/managed care specialists, and other healthcare providers, such as registered nurses, nurse practitioners, and physician assistants) who participated in a modular, interactive CE initiative. An additional medical claims analysis provided data on practice change, evaluating use of VEGF-A inhibitors among retina specialist and ophthalmologist learners (n = 7,827) pre-/post-education, compared to a matched control group of non-learners. Outcomes were pre-/post-test change in knowledge/competence and clinical change in application of anti-VEGF therapy, as identified by the medical claims analysis., Results: Learners significantly improved knowledge/competence scores on early identification and treatment, identifying patients who could benefit from anti-VEGF agents, using guideline-recommended care, recognizing the importance of screening and referral, and recognizing the importance of early detection and care for DR (all P-values = 0.003 to 0.004). Compared with matched controls, learners' incremental total injections for anti-VEGF agents for retinal conditions increased more after the CE intervention (P < 0.001); specifically, there were 18,513 more (new) anti-VEGF injections prescribed versus non-learners (P < 0.001)., Conclusions: This modular, interactive, immersive CE initiative resulted in significant knowledge/competence gains among retinal disease care providers and changes in practice-related treatment behaviors (i.e., appropriate consideration and greater incorporation of guideline-recommended anti-VEGF therapies) among participating ophthalmologists and retina specialists compared to matched controls. Future studies will utilize medical claims data to show longitudinal impact of this CE initiative on treatment behavior among specialists and impact on diagnosis and referral rates among optometrists and primary care providers who participate in future programming., (© 2023. The Author(s).)

Background: To evaluate the predictive effect of TCED-HFV grading and imaging biomarkers on anti-vascular endothelial growth factor (anti-VEGF) treatment in diabetic macular edema (DME)., Methods: 81 eyes of 81 DME patients who were treated with anti-VEGF were included in this retrospective cohort study. All patients underwent a comprehensive ophthalmic examination at baseline and follow-up, including best-corrected visual acuity (BCVA), fundus photography, and spectral domain-optical coherence tomography (SD-OCT). Baseline imaging biomarkers were qualitatively and quantitatively graded according to the TCED-HFV classification protocol, and DME was divided into early stage, advanced stage, severe stage, and atrophy stage., Results: Six months post treatment, central subfield thickness (CST) in 49 eyes (60.5%) had decreased by 10% from baseline, 30 eyes (37.0%) had achieved CST < 300 μm, and 45 eyes (55.6%) had BCVA improved by more than five letters. Multivariate regression analysis revealed that eyes with baseline CST ≥ 390 μm had a higher probability of ≥ 10% reduction in CST from baseline, and eyes with abundant hyperreflective dots (HRD) had a lower probability of 10% reduction in CST (all P < 0.05). Eyes with vitreomacular traction (VMT) or epiretinal membrane (ERM) at baseline were less likely to reach the end point of CST < 300 μm (P < 0.05). BCVA increases of more than five letters were less likely in eyes with baseline BCVA ≥ 69 letters, complete or partial destruction of ellipsoid zone (EZ) at baseline (all P < 0.05). TCED-HFV staging was negatively correlated with BCVA at both baseline and 6 months (Kendall's tau-b=-0.39 and - 0.55, all P < 0.01). TCED-HFV staging was positively correlated with CST at 6 months (Kendall's tau-b = 0.19, P = 0.049) and negatively correlated with the reduction of CST (Kendall's tau-b=-0.32, P < 0.01)., Conclusion: The TCED-HFV grading protocol facilitates a comprehensive assessment of DME severity, standardizes the grading of multiple imaging biomarkers, and predicts the anatomical and functional outcomes of anti-VEGF treatment., (© 2023. The Author(s).)

Background and Objectives : The main cause of the vision loss in diabetics is the development of diabetic macular edema, regardless of the stage of diabetic retinopathy. The paper aimed to examine whether the additional intravitreal application of triamcinolone acetonide to continuous anti-vascular endothelial growth factor therapy could improve therapeutic outcomes for pseudophakic eyes with persistent diabetic macular edema. Materials and Methods : twenty-four pseudophakic eyes with refractory diabetic macular edema, that had appeared despite three previously administered intravitreal injections of aflibercept, were divided into two groups (twelve eyes in each group). The first group continued to have aflibercept administered according to a fixed dosing regimen (once in two months). Triamcinolone acetonide 10 mg/0.1 mL (administered once per four months) was included for the second group, i.e., their treatment continued with a combination of aflibercept + triamcinolone acetonide. Results : The reduction in central macular thickness was higher in the eyes treated with combined therapy (aflibercept + triamcinolone acetonide) compared with the use of aflibercept alone during the entire 12-month follow-up period (3rd month p = 0.019; 6th month p = 0.023; 9th month p = 0.027; 12th month p = 0.031). As was evident from the p -values, the differences were statistically significant. No statistically significant difference was recorded for visual acuity: 3rd month p = 0.423; 6th month p = 0.392; 9th month p = 0.413; 12th month p = 0.418. Conclusions : Combined anti-vascular endothelial growth factor and steroid therapy leads to a better anatomical outcome of persistent diabetic macular edema in pseudophakic eyes, but does not lead to a more significant improvement in visual acuity than continuous anti-VEGF therapy alone.

Background: Early Identifying and characterizing patients with diabetic macular edema (DME) is essential for individualized treatment and outcome optimization. This study aimed to timely investigate optical coherence tomography (OCT) biomarkers of DME refractory to intravitreal anti-vascular endothelial growth factor (VEGF) therapy., Methods: We retrospective reviewed 72 eyes from 44 treatment-naïve patients who were treated with intravitreal anti-VEGF for DME. OCT scans prior to anti-VEGF were evaluated for serous retinal detachment (SRD), size of outer nuclear layer cystoid changes, diffuse retinal thickening, integrity of the inner segment-outer segment (IS-OS) junction, quantity and location of hyperreflective foci, vitreomacular interface abnormalities, and epiretinal membrane (ERM). The Baseline best-corrected visual acuity (BCVA) and central macular thickness was recorded at baseline and 4 months after treatment with anti-VEGF. The main outcome measure was the correlation between spectral-domain OCT measurements and BCVA response at baseline and after anti-VEGF treatment (mean change from baseline; ≥ 10 Early Treatment Diabetic Retinopathy Study letters in BCVA)., Results: Partially continuous IS-OS layers (partially vs. completely continuous: β, -0.138; Wald chi-square, 16.392; P<0.001) was predictor of better response to anti-VEGF treatment. In contrast, ERM (present vs. absent ERM: β, 0.215; Wald chi-square, 5.921; P=0.015) and vitreomacular traction (vitreomacular traction vs. posterior vitreous detachment: β=0.259; Wald chi-square=5.938; P=0.015) were the predictors of poor response. The improvement of BCVA trended toward the OCT predictive value of central macular thickness reduction; however, this was not significant., Conclusion: Partially continuous IS-OS layers is predictive of better response to anti-VEGF therapy in DME. Meanwhile, ERM is a significant predictor of poor response., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hsieh, Deng, Chang, Chang and He.)

Purpose: The purpose of this study was to evaluate retrospectively the efficacy and safety profile of intravitreal injection of bevacizumab bio-similar product Zybev(Z) for macular edema because of retinal diseases., Methods: A retrospective analysis was conducted on patients with macular edema because of retinal diseases, who had been administered intravitreal injections of bio-similar bevacizumab at a tertiary eye care center. Changes in the retinal thickness and visual acuity were evaluated to judge the efficacy, and adverse events were noted for the safety profile over a period of 6 weeks., Results: A total of 104 patients were included in the study. The mean age of the patients was 53 ± 13.5 years. The mean pre-injection best corrected visual acuity (BCVA) was 1.32 ± 0.70 log minimum angle of resolution (logMAR) with a central subfield thickness (CST) of 429.26 ± 204.30 μm, and the post-injection BCVA at 6 weeks was 1.13 ± 0.71 logMAR with a CST of 302.26 ± 104.50 μm; this change was statistically significant (P < 0.05) for all groups. The mean average cube thickness (μm) decreased from 11.85 ± 1.96 pre-injection to 10.52 ± 1.75 post-injection, and the mean average cube volume (mm 3 ) decreased from 329.30 ± 54.35 to 302.23 ± 49.56 (P < 0.05). During the follow-up period after injection, no patient had inflammation, endophthalmitis, an increase in intra-ocular pressure, or systemic side effects., Conclusion: This short-term retrospective analysis provides evidence regarding the efficacy and safety of intravitreal injection of bio-similar products of bevacizumab for the treatment of macular edema because of retinal diseases., Competing Interests: None

Objective: Intravitreal ranibizumab is one of the anti-vascular endothelial growth factors used for the treatment of diabetic macular oedema, not always successfully. We aimed to identify the factors affecting the changes of central macular thickness after induction treatment with intravitreal ranibizumab, to predict the treatment effect and facilitate early treatment decisions., Methods: Cross-sectional study involving a retrospective record review of diabetic macular oedema patients who received an induction treatment of three monthly 0.5 mg intravitreal ranibizumab injections between 2016 and 2019. Central macular thickness was measured at baseline and 3 months post-treatment. Linear regression was applied to identify the factors associated with the changes of central macular thickness., Results: A total of 153 diabetic macular oedema patients were involved in this study. Their mean age was 57.5 ± 7.7 years, 54.9% were female. The mean change of central macular thickness from baseline to 3 months after completed induction treatment of intravitreal ranibizumab was 155.5 ± 137.8 μm. Factors significantly associated with changes of central macular thickness were baseline central macular thickness [b = 0.73; 95% (CI): 0.63, 0.84; p = <0.001] and presence of subretinal fluid [b = 35.43; 95% CI: 3.70, 67.16; p = 0.029]., Conclusion: Thicker baseline central macular thickness and presence of subretinal fluid were the factors significantly associated with greater changes of central macular thickness in diabetic macular oedema patients after receiving three injections of intravitreal ranibizumab., (© 2023 John Wiley & Sons Ltd.)

Intravitreal antivascular endothelial growth factor (anti-VEGF) treatment has drastically improved the visual and anatomical outcomes in patients with diabetic macular edema (DME); however, success is not always guaranteed, and a proportion of these eyes demonstrate persistent DME (pDME) despite intensive treatment. While standardized criteria to define these treatment-resistant eyes have not yet been established, many studies refer to eyes with no clinical response or an unsatisfactory partial response as having pDME. A patient is considered to have pDME if the retinal thickness improves less than 10-25% after 6 months of treatment. A range of treatment options have been recommended for eyes with pDME, including switching anti-VEGF agents, using corticosteroids and/or antioxidant drugs in adjunct with anti-VEGF therapy, and vitrectomy. In addition, multimodal imaging of DME eyes may be advantageous in predicting the responsiveness to treatment; this is beneficial when initiating alternative therapies. We explore the literature on persistent DME regarding its defining criteria, incidence, the baseline biological markers that may be useful in anticipating the response to treatment, and the available treatment options., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: This study examines the efficacy and safety of brolucizumab in the treatment of diabetic macular edema (DME) in real clinical practice in the Russian Federation., Material and Methods: The study included 14 consecutive treatment-naïve DME patients, among them 7 males and 7 females (21 eyes in total) with mean age of 65.1±8.0 years. Patients underwent standard ophthalmological examination and multimodal imaging, including optical coherence tomography. All patients received intravitreal injections of brolucizumab every 6 weeks. A total of 73 injections were performed. A data analysis was performed for 10 eyes of 10 patients 6 months after initiation of the treatment., Results: After 4 injections of brolucizumab, best-corrected visual acuity (BCVA) increased statistically significantly from 35.8±13.7 to 41.5±11.9 ETDRS letters ( p =0.03), central retinal thickness (CRT) and macular volume (MV) decreased from 411.5±107.4 to 280.2±64.6 microns ( p =0.014) and from 7.39±0.92 to 6.16±7.37 mm 3 ( p =0.0006), respectively. The average gain of visual acuity was 5.7±7.0 letters, average decrease of CRT was -131.3±91.2, and average decrease of MV was -1.21±0.75 mm 3 . There were no adverse events associated with intraocular inflammation., Conclusion: Intravitreal injections of brolucizumab provide significant anatomical and functional improvement to DME patients in real clinical practice with results comparable to that of randomized clinical trials.

Introduction: The objective of this study was to evaluate the impact of unplanned treatment gap, secondary to COVID-19 pandemic lockdowns, on visual acuity in previously treated diabetic macular edema (DME) patients., Methods: A multicenter, retrospective study of DME patients, previously treated with anti-VEGF injections, who were followed up during COVID-19 pandemic (2020) compared to pre-CO-VID-19 period (2019)., Results: A total of 634 DME patients with a mean age of 68.4 years met the inclusion criteria, 385 were assessed in 2019 (pre-COVID-19) and 239 patients assessed in 2020 (COVID-19). Baseline best corrected visual acuity (BCVA) among patients in 2019 and 2020 was 0.52 ± 0.44, 0.45 ± 0.43 (logarithm of the minimal angle of resolution, respectively). There was no significant difference between the years 2020 and 2019 in baseline BCVA (p = 0.07). Mean number of anti-VEGF injections was significantly lower (5 vs. 6, p < 0.01), with a major lower ratio of injections per patient in the COVID-19 first lockdown period (March-June 2020) in the COVID-19 group. Baseline BCVA (p < 0.01) was the only significant predictor of final BCVA. Number of injections, age, gender, and the year were not found as predictors of final BCVA., Conclusions: In a large cohort of DME patients, an unplanned delay in treatment with anti-VEGF injections for 2-3 months, due to COVID-19 pandemic lockdown, had no significance impact on visual acuity. For most patients, returning to routine treatment regimen was sufficient for maintaining BCVA., (© 2022 S. Karger AG, Basel.)

Purpose: The aim of this study was to compare the results of vitrectomy performed in patients' worse eyes with diabetic macular edema to the results of continuous anti-VEGF treatment performed in patients' fellow eyes., Methods: A retrospective interventional study of 14 patients with diabetic macular edema in both eyes. The better eye was always qualified for aflibercept injections (group 1), and the worse eye was scheduled for vitrectomy (group 2). The follow-up lasted 12 months. The following parameters were measured: visual acuity (V), central retinal thickness (CRT), maximum retinal thickness (MRT), central choroidal thickness (CCT), superficial fovea avascular zone (sFAZ) and deep fovea avascular zone (dFAZ), and vessel density at the level of superficial (sVD) and deep (dVD) retinal vessels., Results: None of the analyzed factors differed between groups with statistical significance at any timepoint. The time of recovery of vision was identical in both eyes (F = 0.91, p = 0.449). The final sFAZ was significantly smaller for group 2 (median 196 μm) than for group 1 (median 375 μm; U = 101.0; p = 0.022; r = 0.44)., Conclusion: Both techniques resulted in similar improvements in visual acuity and decreases in CRT after 1 year. sFAZ decreased in all eyes, with a higher extent after vitrectomy., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To determine clinical effectiveness, safety, and cost-effectiveness of subthreshold micropulse laser (SML), compared with standard laser (SL), for diabetic macular edema (DME) with central retinal thickness (CRT) < 400 μm., Design: Pragmatic, multicenter, allocation-concealed, double-masked, randomized, noninferiority trial., Participants: Adults with center-involved DME < 400 μm and best-corrected visual acuity (BCVA) of > 24 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in one/both eyes., Methods: Randomization 1:1 to 577 nm SML or SL treatment. Retreatments were allowed. Rescue with intravitreal anti-vascular endothelial growth factor therapies or steroids was permitted if 10 or more ETDRS letter loss occurred, CRT increased > 400 μm, or both., Main Outcome Measures: Primary outcome was mean change in BCVA in the study eye at 24 months (noninferiority margin 5 ETDRS letters). Secondary outcomes were mean change from baseline to month 24 in binocular BCVA; CRT and mean deviation of Humphrey 10-2 visual field in the study eye; percentage meeting driving standards; EuroQoL EQ-5D-5L, 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), and Vision and Quality of Life Index (VisQoL) scores; cost per quality-adjusted life-years (QALYs) gained; adverse effects; and number of laser and rescue treatments., Results: The study recruited fully (n = 266); 87% of SML-treated and 86% of SL-treated patients had primary outcome data. Mean ± standard deviation BCVA change from baseline to month 24 was -2.43 ± 8.20 letters and -0.45 ± 6.72 letters in the SML and SL groups, respectively. Subthreshold micropulse laser therapy was deemed not only noninferior but also equivalent to SL therapy because the 95% confidence interval (CI; -3.9 to -0.04 letters) lay wholly within both upper and lower margins of the permitted maximum difference (5 ETDRS letters). No statistically significant difference was found in binocular BCVA (0.32 ETDRS letters; 95% CI, -0.99 to 1.64 ETDRS letters; P = 0.63); CRT (-0.64 μm; 95% CI, -14.25 to 12.98 μm; P = 0.93); mean deviation of the visual field (0.39 decibels (dB); 95% CI, -0.23 to 1.02 dB; P = 0.21); meeting driving standards (percentage point difference, 1.6%; 95% CI, -25.3% to 28.5%; P = 0.91); adverse effects (risk ratio, 0.28; 95% CI, 0.06-1.34; P = 0.11); rescue treatments (percentage point difference, -2.8%; 95% CI, -13.1% to 7.5%; P = 0.59); or EQ-5D, NEI-VFQ-25, or VisQoL scores. Number of laser treatments was higher in the SML group (0.48; 95% CI, 0.18-0.79; P = 0.002). Base-case analysis indicated no differences in costs or QALYs., Conclusions: Subthreshold micropulse laser therapy was equivalent to SL therapy, requiring slightly higher laser treatments., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: Retinal vein occlusion (RVO) is the main cause of retinal vascular blindness. Laser photocoagulation therapy is the regarded as the standard treatment for branch retinal vein occlusion (BRVO) in the guidelines, but it is not effective for macular edema (ME) secondary to central retinal vein occlusion (CRVO). As anti-VEGF (vascular endothelial growth factor) or steroids monotherapy has been used to treat RVO, but each has its advantages and disadvantages. Our purpose was to evaluate the efficacy and safety of intraocular injection of anti-VEGF combined with steroids versus anti-VEGF or steroids monotherapy for ME secondary to RVO., Methods: We systematically searched trials on Pubmed, Embase, Cochrane Library, Web of Science and China National Knowledge Infrastructure (CNKI) for RCTs (random clinical trials) or non-RCTs, comparing anti-VEGF or steroids monotherapy to their combination. The primary outcomes were changes in best-corrected visual acuity (BCVA), central macular thickness (CMT) and intraocular pressure (IOP). The pooled data was analyzed by random effects model., Findings: A total of 10 studies selected from 366 studies were included in this meta-analysis. Our results favored anti-VEGF with steroids combination therapy in comparison with anti-VEGF {pooled SMD (standardized mean difference), 95% CI, -0.16 [-0.28, -0.04], P = 0.01} or steroids (pooled SMD, 95% CI, -0.56 [-0.73, -0.40], P < 0.00001) alone on changes of BCVA. Compared with anti-VEGF monotherapy group, the combination therapy also had a better effect {pooled MD (mean difference), 95% CI, -9.62 [-17.31, -1.93], P = 0.01)} at improvements on CMT. On the changes of IOP, assessment favored that combination therapy was associated with a better relief of IOP compared to steroids monotherapy group (pooled MD, 95% CI, -5.93 [-7.87, -3.99],P < 0.00001). What's more, the incidence of ocular hypertension was lower in the combined treatment group compared with control group treated with steroids alone (Odds Ratio, 95% CI, 0.21 [0.06, 0.77], P = 0.02). Results also showed that the combination group can prolong the average time to first anti-VEGF reinjection (MD, 95% CI, 1.74 [0.57, 2.90], P = 0.003) compared to control group treated with anti-VEGF alone., Conclusion: Anti-VEGF with steroids combination treatment can enable a better achievement of improving BCVA, CMT, reducing the risk of increased IOP and improving patient prognosis compared to anti-VEGF or steroids therapy alone, lengthening the average time to anti-VEGF reinjection with reducing the injections during follow-up., (© 2022. The Author(s).)

Aim: To evaluate, on the basis of two-year observations, the effectiveness of intravitreal treatment with Ranibizumab in patients with diabetic macular edema (DME) unresponsive to the previous laser treatment. Cohort and Methods: A retrospective study evaluates 29 eyes of 29 patients with diffuse DME unresponsive to their previous laser treatment. The group of the patients consisted of 16 males (55.1%) and 13 females (44.8%); their mean age was 71.3. The mean duration of diabetes mellitus was 13 years (3-20). 19 patients (65.5%) were treated with insulin, 10 patients (34.4%) were treated with peroral antidiabetics (PAD); the mean HbA1c value was 52 mmol/l. The treatment was started with 3 initial doses of intravitreal injections of Ranibizumab 0.5 mg. There was a one- -month interval between the applications. Subsequent evaluations and administrations of the following injections were made in the pro re nata (PRN) mode; the check-ups were carried out every month during the first year and on average every 3 months in the second year. The monitored parameters: the best corrected visual acuity (BCVA) measured on ETRDS (Early Treatment Diabetic Retinopathy Study) optotypes, the central retinal thickness (CRT). These parameters were monitored prior to the treatment and then in the 3rd, 6th, 9th, 12th, 18th and 24th months., Results: A statistically significant improvement in the mean value of BCVA was detected. From the initial 65.4 ±10.61 letters it improved by 11.2 letters (p.

Purpose: To report the estimated incidence, probability, risk factors, and 1-year outcomes of rhegmatogenous retinal detachment (RRD) in eyes receiving intravitreal injections (IVTs) of VEGF inhibitors for various retinal conditions in routine clinical practice., Design: Retrospective analysis of data from a prospectively designed observational outcomes registry: the Fight Retinal Blindness!, Participants: Eyes of patients starting IVTs of VEGF inhibitors (ranibizumab, aflibercept, or bevacizumab) for neovascular age-related macular degeneration, diabetic macular edema, or retinal vein occlusion from January 1, 2006, to December 31, 2020. All eyes that developed RRD within 90 days of IVTs were defined as cases with RRD and were matched with control eyes., Methods: Estimated incidence, probability, and hazard ratios (HRs) of RRD were measured using Poisson regression, Kaplan-Meier survival curve, and Cox proportional hazards models. Locally weighted scatterplot smoothing curves were used to compare visual acuity (VA) between cases and matched controls., Main Outcome Measures: Estimated incidence of RRD., Results: We identified 16 915 eyes of 13 792 patients who collectively received 265 781 IVTs over 14 years. Thirty-six eyes were reported to develop RRD over the study period. The estimated incidence (95% confidence interval [CI]) per year per 1000 patients and per 10 000 injections was 0.77 (0.54-1.07) and 1.36 (0.95-1.89), respectively. The probability of RRD did not significantly increase at each successive injection (P = 0.95) with the time of follow-up. Older patients (HR [95% CI] = 1.81 [1.21-3.62] for every decade increase in age, P < 0.01) were at a higher risk of RRD, whereas patients with good presenting VA (HR [95% CI] = 0.85 [0.70-0.98] for every 10-letter increase in VA, P = 0.02) were at a lower risk. Neither the type of retinal disease (P = 0.52) nor the VEGF inhibitor (P = 0.09) was significantly associated with RRD risk. Cases with RRD lost 3 lines of vision on average compared with the prior RRD VA and had significantly fewer injections than matched controls over the year after the RRD., Conclusions: Rhegmatogenous retinal detachment is a rare complication of VEGF inhibitor IVT in routine clinical practice with poor visual outcomes at 1 year., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Aims: To investigate potential laboratory and imaging biomarkers as treatment response predictors to intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in patients with retinal vein occlusion (RVO)., Methods: Participants in this prospective study were 53 patients with treatment naïve macular edema secondary to RVO, treated with intravitreal anti-VEGF agents and followed-up for 12 months. At baseline, all participants underwent best-corrected visual acuity measurement, dilated fundoscopy, optical coherence tomography and fluorescein angiography (FFA), while full blood count and biochemical analysis of various parameters was also performed. At month 12, treatment response was examined and classified as "favorable" or "non-response". Potential associations between laboratory/imaging biomarkers and treatment response were assessed., Results: Univariate analysis showed that "favorable" response at month 12 after initiation of anti-VEGF treatment was correlated with baseline central subfield thickness (CST) < 464 μm (p < 0.001), absence of subretinal fluid (p = 0.004), absence of hyperreflective foci (HF) (p = 0.004), intact ellipsoid zone (EZ) and external limiting membrane (ELM) (p < 0.001 and p = 0.001, respectively), absence of epiretinal membrane (ERM) (p = 0.020) and absence of macular ischemia on FFA (p < 0.001), while increased monocytes-to-lymphocytes ratio was also associated with "favorable" treatment response (p = 0.010). All other laboratory parameters did not reach statistical significance. However, at the multivariate analysis, EZ and ELM status, HF, macular ischemia and monocytes-to-lymphocytes ratio were found to be independent predictors of treatment response., Conclusions: Intact EZ and ELM, absence of HF, absence of macular ischemia and increased monocytes-to-lymphocytes ratio at baseline can predict "favorable" treatment response in patients with treatment naïve macular edema secondary to RVO., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Intravitreal injection treatment for the management of macular edema as an expression of increased capillary permeability and leakage constitute the mainstay of treatment in retinal vein occlusion. In contrast to diabetic retinopathy or neovascular age-related macular degeneration, permanent and complete functional and morphological restoration can be achieved, as retinal vein occlusions are usually associated with risk factors, but do not represent the manifestation form of an underlying systemic or degenerative chronic disorder; however, successful long-term management of retinal vein occlusion -associated macular edema usually requires intensive and also long-term continued treatment with vascular endothelial growth factor (VEGF) inhibitors or with a less favorable side effect profile, dexamethasone. A functional treatment success can be maintained over the long term by both pro re nata (PRN) or treat and extend (T&E) regimens. In contrast, according to the currently available data, the combination of anti-VEGF administration and grid laser treatment has no additional benefit compared to monotherapy. In patients with recalcitrant macular edema, switching to another intravitreal agent may be considered during the course of treatment, although a true therapeutic benefit with respect to the development of visual acuity has not yet been proven. The current review summarizes the relevant aspects in the management of RVO-associated macular edema and provides the foundations for the application of successful treatment strategies., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose: To investigate the efficacy and safety of dexamethasone (DEX) implant in eyes with diabetic macular edema (DME) over 12-months., Methods: In this retrospective study charts from a single center were analysed, including naïve and pre-treated patients. Best corrected visual acuity (BCVA) and central retinal thickness (CRT) were evaluated at baseline, months 1-2, 3-4, 5-6 and 7-12., Results: Data of 77 eyes were analysed (58.4% were pre-treated with anti-VEGF inhibitors). Mean baseline BCVA values for the whole sample, pre-treated and naïve patients, were 60.94 (SD 13.74), 60.85 (SD 13.80) and 61.01 (SD 13.86) letters, respectively. In the whole sample BCVA changes against baseline were significant (p < 0.05) at months 1-2, 3-4 and 7-12. In the pre-treated group changes were statistically significant at months 1-2 and 7-12. No statistically significant differences were found in the naïve group and between subgroups.In the whole group and the pre-treated group, CRT changes against baseline were significant (p < 0.05) at all time points, while in the naïve group changes were only significant at time point months 3-4. No statistically significant differences were found between subgroups.IOP increases were moderate and successfully managed with topical medication., Conclusion: After treatment with DEX implant, BCVA increased and CRT decreased significantly in the whole population at all time points. No significant differences were found between naïve and pre-treated patients. Changes in BCVA and CRT in the naïve group were not statistically significant. This was most likely attributable to the small sample size. The data underlines the importance of DEX implant as an efficacious and safe alternative to VEGF- inhibitors in real world practice.

Diabetic retinopathy (DR), with increasing incidence, is the major cause of vision loss and blindness worldwide in working-age adults. Diabetic macular edema (DME) remains the main cause of vision impairment in diabetic patients, with its pathogenesis still not completely elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of DR and DME. Currently, intravitreal injection of anti-VEGF agents remains as the first-line therapy in DME treatment due to the superior anatomic and functional outcomes. However, some patients do not respond satisfactorily to anti-VEGF injections. More than 30% patients still exist with persistent DME even after regular intravitreal injection for at least 4 injections within 24 weeks, suggesting other pathogenic factors, beyond VEGF, might contribute to the pathogenesis of DME. Recent advances showed nearly all the retinal cells are involved in DR and DME, including breakdown of blood-retinal barrier (BRB), drainage dysfunction of Müller glia and retinal pigment epithelium (RPE), involvement of inflammation, oxidative stress, and neurodegeneration, all complicating the pathogenesis of DME. The profound understanding of the changes in proteomics and metabolomics helps improve the elucidation of the pathogenesis of DR and DME and leads to the identification of novel targets, biomarkers and potential therapeutic strategies for DME treatment. The present review aimed to summarize the current understanding of DME, the involved molecular mechanisms, and the changes in proteomics and metabolomics, thus to propose the potential therapeutic recommendations for personalized treatment of DME.

Purpose: To compare clinical manifestations and disease outcomes in Epidemic Retinitis (ER) with positive or negative Weil Felix Test (WFT)., Methods: Retrospective, observational, comparative study. WFT positive or negative patients formed Group 1 and 2, respectively. Patients receiving oral doxycycline monotherapy formed subgroup A and B. Duration of resolution of macular edema and retinitis was compared., Results: Novel finding of "ring retinitis" was observed equally in group 1 and 2. Complete resolution of macular edema took 41.3 days (range: 30-60 days) and 43.68 days (range: 20-105 days) ( p = .668) and retinitis lesions resolved in 34.3 days (range: 14-65 days) and 34 days (range: 12-60 days) ( p = .875) in group A and B, respectively. All (n = 14) eyes with retinitis within 1 disc diameter of fovea improved better than 20/80 except 1., Conclusion: No significant difference with respect to clinical, imaging findings and the treatment outcome was observed in WFT positive or negative cases.

Purpose of Review: Intravitreal anti-vascular endothelial growth factor (VEGF) agents are used routinely in the management of neovascular conditions including proliferative diabetic retinopathy and diabetic macular edema. While the efficacy of anti-VEGF agents has been well-validated, their ocular and systemic adverse events should always be considered and discussed with patients. The aim of this review is to discuss the most recent literature reports regarding the various ocular and systemic adverse events associated with intravitreal anti-VEGF treatment in diabetic retinopathy., Recent Findings: The most frequently reported adverse ocular events include subconjunctival hemorrhage, vitreous hemorrhage, increased intraocular pressure, uveitis, endophthalmitis, ocular surface disease, and traumatic cataract. Subconjunctival hemorrhage and vitreous hemorrhage are the most common ocular adverse events reported with intravitreal anti-VEGF treatment. The most serious (though rare) ocular adverse events include endophthalmitis and rhegmatogenous retinal detachment. A consensus regarding the association of systemic adverse events (such as myocardial infarction, stroke, and death) with intravitreal anti-VEGF treatments has not been established. Intravitreal anti-VEGF therapy is used in the treatment of diabetic retinopathy, macular degeneration, and other diseases. These agents are associated with a variety of ocular and systemic adverse events that ophthalmologists should always consider., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The advent of anti-vascular endothelial growth factor (VEGF) agents has revolutionized the treatment of retinal neovascular diseases including neovascular age-related macular degeneration (nAMD), a leading cause of irreversible blindness. Multiple agents and methods for drug delivery are emerging to increase the duration of treatment effect and treatment interval, reducing the overall treatment burden on patients and clinicians. The newest agent on the market is faricimab. This medication targets two distinct pathways in retinal angiogenesis, VEGF-A and Ang-2, to create a more durable effect. Phase 3 trials for this drug compared treatment intervals up to 16 weeks against aflibercept dosed at 8-week intervals for both nAMD and diabetic macular edema (DME). While the drug shows similar functional and anatomic outcomes with a low adverse effect profile and trial data demonstrating increased treatment duration, its exact place in the VEGF marketplace is yet to be determined. In this article, we discuss the mechanism of action, pivotal clinical trials leading to approval, and the anticipated role for faricimab in the treatment of retinal neovascular disease., Competing Interests: Dr Archana A Nair participated on an advisory board for Eyepoint, outside the submitted work. Dr Avni P Finn is a member of the advisory board for Genentech, Allergan, Eyepoint, and Alimera, outside the submitted work. Dr Paul Sternberg Jr reports personal fees from and a consultant for Novartis; personal fees from Outlook Therapeutics and DRCR network, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Nair et al.)

Purpose: The clinical practice visual acuity (VA) outcomes of anti-VEGF therapy for up to 5 years were assessed in patients with neovascular age-related macular degeneration (nAMD), diabetic macular edema (DME), branch retinal vein occlusion-related macular edema (BRVO-ME), and central retinal vein occlusion-related macular edema (CRVO-ME)., Design: A retrospective analysis was performed using the Vestrum Health Retina Database., Participants: Treatment-naive patients with nAMD, DME, BRVO-ME, or CRVO-ME who received anti-VEGF injections between 2014 and 2019 and had follow-up data for ≥12 months., Methods: Data on age, sex, the number of anti-VEGF treatments, and VA were analyzed., Main Outcome Measures: Mean VA change up to 3 years (BRVO-ME and CRVO-ME) and 5 years (nAMD and DME)., Results: At 1, 3, and 5 years, in 67 666, 21 305, and 5208 eyes with nAMD, after a mean of 7.6, 19.5, and 32 injections, there was a mean change of +3.1, -0.2, and -2.2 letters, respectively. At 1, 3, and 5 years, in 40 832, 7728, and 1192 eyes with DME, after a mean of 6.2, 15.4, and 26.0 injections, there was a mean change of +4.7, +3.3, and +3.1 letters, respectively. At 1 and 3 years, in 12 451 and 3027 eyes with BRVO-ME, after a mean of 7.1 and 18.2 injections, there was a mean change of +9.5 and +7.7 letters, respectively. At 1 and 3 years, in 9298 and 2264 eyes with CRVO-ME, after a mean of 7.3 and 18.8 injections, there was a mean change of +8.3 and +6.0 letters, respectively (P < 0.01 for all VA changes of > 1 letter). In all 4 conditions, the mean VA increased with the mean number of anti-VEGF injections, eyes with a baseline VA of 20/40 or better tended to lose VA, and eyes with progressively worse baseline VA experienced a progressively greater VA gain at 3 years., Conclusions: In practice, patients with nAMD, DME, BRVO-ME, and CRVO-ME showed limited visual outcomes, with patients with nAMD tending to lose VA at 3 and 5 years. Across all 4 disorders, the mean change in VA correlated with treatment intensity at 1, 3, and 5 years. Patients with better baseline VA are more vulnerable to vision loss., (Copyright © 2022 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD) are common retinal vascular diseases responsible for most blindness in the working-age and older population in developed countries. Currently, anti-VEGF agents that block VEGF family ligands, including ranibizumab, bevacizumab (off-label use), brolucizumab, and aflibercept, are the first-line treatment for nAMD and DME. However, due to the complex pathophysiological background of nAMD and DME, non-response, resistance during anti-VEGF therapy, and relapses of the disease are still observed. Moreover, frequent injections are a psychological and economic burden for patients, leading to inadequate adhesion to therapy and a higher risk of complications. Therefore, therapeutic methods are strongly needed to develop and improve, allowing for more satisfactory disease management and lower treatment burden. Currently, the Ang/Tie-2 pathway is a promising therapeutic target for retinal vascular diseases. Faricimab is the first bispecific monoclonal antibody for intravitreal use that can neutralize VEGF and Ang-2. Due to the prolonged activity, faricimab allows extending the interval between successive injections up to three or four months in nAMD and DME patients, which can be a significant benefit for patients and an alternative to implanted drug delivery systems.

Background and Objectives: Intravitreal injections (IVI) of vascular endothelial growth factor (VEGF) inhibitors are guideline-indicated treatments for diabetic macular edema (DME). However, some recent data have suggested that IVI VEGF inhibitors might, through systemic absorption, lead to a reduction in renal function. Our study aims to compare changes in glycated hemoglobin A1c (HbA1c) and estimated glomerular filtration rate (eGFR) between patients who received IVI ranibizumab and aflibercept treatment and patients who have not received IVI treatments. Materials and Methods: There were 17,165 DME patients with documented ophthalmology visits in the China Medical University Hospital-Clinical Research Data Repository. Those with a history of ESRD or bevacizumab treatment history, and those with missing information on HbA1c or eGFR, were excluded. After matching by age (±2 years), gender, and the year of clinical visit, 154 patients with medical treatment (including ranibizumab and aflibercept) and 154 patients without medical treatment were included in the study. The difference between HbA1c and eGFR at baseline and 3 and 12 months after the index date between the two groups was assessed. Results: Mean HbA1c and eGFR decreased between baseline and 12 months after the index date in both groups (p < 0.05). Compared with the non-treatment group, the treatment group had significantly lower HbA1c 3 and 12 months after the index date. There was no significant difference in eGFR between the two groups. In the generalized estimating equations (GEE) model, HbA1c in the treatment group was lower than the non-treatment group (−0.44%, 95% CI = −0.75, −0.14), but eGFR was similar after adjusting for age, gender, and index-year. HbA1c and eGFR decreased with the time in the adjusted GEE model (p < 0.0001) in both groups. Conclusions: This study showed that eGFR decreased with age and time and was not related to IVI anti-VEGF treatments in our tertiary referral hospital. IVI anti-VEGF therapy was also associated with better HbA1c control. It is suggested that DME patients can receive intravitreal VEGF inhibitors without inducing more renal impairment.

This work aims to summarize predictive biomarkers to guide treatment choice in DME. Intravitreal anti-VEGF is considered the gold standard treatment for centers involving DME, while intravitreal steroid treatment has been established as a second-line treatment in DME. However, more than 1/3 of the patients do not adequately respond to anti-VEGF treatment despite up to 4-weekly injections. Not surprisingly, insufficient response to anti-VEGF therapy has been linked to low-normal VEGF levels in the serum and aqueous humor. These patients may well benefit from an early switch to intravitreal steroid treatment. In these patients, morphological biomarkers visible in OCT may predict treatment response and guide treatment decisions. Namely, the presence of a large amount of retinal and choroidal hyperreflective foci, disruption of the outer retinal layers and other signs of chronicity such as intraretinal cysts extending into the outer retina and a lower choroidal vascular index are all signs suggestive of a favorable treatment response of steroids compared to anti-VEGF. This paper summarizes predictive biomarkers in DME in order to assist individual treatment decisions in DME. These markers will help to identify DME patients who may benefit from primary dexamethasone treatment or an early switch.

Purpose: To investigate potential laboratory and imaging biomarkers as treatment response predictors to intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents in patients with diabetic macular edema (DME)., Methods: The study included 36 treatment naïve patients with DME, treated with intravitreal anti-VEGF agents and followed-up for 12 months. At baseline, all participants underwent best-corrected visual acuity (BCVA) measurement, dilated fundoscopy, optical coherence tomography, color fundus photography and fluorescein angiography, while full blood count and biochemical analysis of various parameters was also performed. At month 12, treatment response was examined and classified as "favorable" or "non-response". Potential associations between laboratory/imaging biomarkers and treatment response were assessed., Results: Univariate analysis showed that favorable response at month 12 after initiation of anti-VEGF treatment was correlated with baseline central subfield thickness (CST)≤405 μm ( p < .001), absence of subretinal fluid ( p = .034), absence of exudates ( p = .041), absence of disorganization of the inner retinal layers ( p = .037), intact ellipsoid zone (EZ) and external limiting membrane (ELM) ( p < .001 and p = .002, respectively), absence of epiretinal membrane (ERM) ( p = .040) and absence of macular ischemia ( p = .042), while increased lipoprotein(a) was associated with no treatment response ( p = .025). At the multivariate analysis, CST was found to be independent predictor of treatment response, while EZ, ELM and ERM were found to predict treatment response perfectly and they could not be entered in the model., Conclusion: Intact EZ and ELM, absence of ERM and CST≤405 μm at baseline can predict favorable treatment response in patients with treatment naïve DME, while no correlation with baseline laboratory parameters was found.

Purpose: To investigate the incidence, characteristics, and baseline predictors of poor visual outcomes in eyes with diabetic macular edema (DME) receiving intravitreal therapy in routine clinical practice., Design: Observational study., Participants: Treatment-naïve eyes starting intravitreal therapy for DME between 2014 and 2018 tracked in the Fight Retinal Blindness! registry. We examined 2 groups with poor visual outcomes: (1) those with sustained vision loss of > 10 letters from baseline without recovery of visual acuity (VA); and (2) those with a VA of < 55 letters at 2 years. Respective controls were eyes that did not experience poor visual outcomes., Methods: Kaplan-Meier curves analyzed the proportion of eyes that experienced poor outcomes. Cox proportional hazards models evaluated the potential baseline predictors of poor outcomes., Main Outcome Measures: The proportion of eyes that experienced poor visual outcomes within 2 years of treatment initiation and its baseline predictors., Results: The proportion of eyes with sustained VA of ≥ 10 letter loss was 14% at 2 years; 16% of eyes had VA of ≤ 55 letters 2 years after starting intravitreal therapy. Initial treatment with intravitreal corticosteroid was independently associated with a higher incidence of ≥ 10 letter loss (hazard ratio [HR], 3.21; 95% confidence interval [CI], 1.60-6.44; P < 0.01). No improvement in the VA at 3 months after starting treatment was associated with ≥ 10 letter loss (HR, 6.81; 95% CI, 4.11-11.27; P < 0.01) and VA of ≤ 55 letters at 2 years (HR, 4.28; 95% CI, 2.66-6.89; P < 0.01). The other factors related to higher risk of VA of ≤ 55 letters were older age (HR, 1.02 per year; 95% CI, 1-1.04; P = 0.04) and poor baseline VA (HR, 0.68 per 5 letters; 95% CI, 0.65-0.72, P < 0.001)., Conclusions: Fourteen percent of eyes managed with intravitreal therapy in routine clinical care experienced ≥ 10 letter loss and 16% had VA of ≤55 letters 2 years after starting the treatment for DME. The identification of the incidence and predictors of poor outcomes provides a more accurate assessment of the potential benefit from intravitreal therapy., (Copyright © 2022 American Academy of Ophthalmology. All rights reserved.)

Objectives: To analyze the current preferences of ophthalmologists for the treatment of macular edema and age-related macular degeneration (AMD) and to evaluate off-label use of bevacizumab in Turkey., Materials and Methods: All members of the Turkish Ophthalmological Association were contacted by e-mail to complete an anonymous, 47-question internet-based survey. The second part of the survey (questions 36-47) was evaluated., Results: When current legal regulations were considered, ophthalmologists used bevacizumab as the first-line agent in patients with diabetic macular edema (DME), AMD, and retinal vein occlusion (RVO) (58.25%, 55.89%, and 52.29%, respectively). When economic and legal constraints were disregarded, the participants' preference for bevacizumab in the treatment of DME, AMD, and RVO decreased (11.64%, 10.58%, and 10.93%, respectively). Approximately three-quarters (75.75%) of ophthalmologists stated that dispensing multiple syringes from a single bevacizumab bottle could increase the risk of endophthalmitis. Most participants (93.68%) did not feel legally safe from harm caused by off-label bevacizumab use. However, 66.43% of ophthalmologists stated that bevacizumab is as effective as other anti-vascular endothelial growth factor (anti-VEGF) drugs., Conclusion: Bevacizumab is widely used as a first-line treatment for all indications of anti-VEGF use in the current reimbursement conditions, which preclude the right of ophthalmologists to treat according to their own preferences., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2022 by Turkish Ophthalmological Association, Turkish Journal of Ophthalmology, published by Galenos Publishing House.)

Purpose: In eyes with diabetic macular oedema (DME), aqueous humour (AH) cytokine levels before and after anti-vascular endothelial growth factor (VEGF) treatment were compared and correlated with optical coherence tomography structural parameters., Methods: This prospective study included 56 control patients with cataracts and 83 patients with DME manifesting as diffuse retinal thickening (DRT), cystoid macular oedema and serous retinal detachment (SRD). AH samples were obtained before intravitreal injection of anti-VEGF or cataract surgery. VEGF, interleukin (IL)-6, IL-8, IL-10, interferon-inducible protein 10 (IP-10) and monocyte chemotactic protein 1 (MCP-1) levels were measured by multiplex bead assay. AH cytokine levels, central macular thickness (CMT), number of hyper-reflective foci (HF), continuity of external limiting membrane and ellipsoid zone (EZ) and best-corrected visual acuity were evaluated., Results: In SRD, IL-6 and MCP-1 levels and HF were increased (all p < 0.05) compared to DRT. At baseline, the number of HF was correlated with VEGF, IL-6, IL-8, IP-10 and MCP-1 (all p < 0.05). Eyes sensitive to anti-VEGF treatment had high baseline levels of VEGF, MCP-1, HF and many EZ disruptions (all p < 0.05). DME patients with normal VEGF levels but with high levels of IL-8, IP-10 and MCP-1 (all p < 0.05) had little change in CMT after anti-VEGF treatment (p = 0.678)., Conclusions: AH concentrations of some inflammatory cytokines in DME were differentially expressed among the three DME morphologies. HF was associated with VEGF and other inflammatory cytokine levels. Multiple HF at baseline predicted a significant decrease in CMT, and eyes with normal VEGF but increased inflammatory cytokines may be insensitive to anti-VEGF treatment., (© 2021 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Introduction: KSI-301 is an intravitreal anti-vascular endothelial growth factor (VEGF) agent in clinical trials for the treatment of neovascular age-related macular degeneration (nAMD), diabetic retinopathy, diabetic macular edema (DME), and retinal vein occlusion (RVO). Its antibody-biopolymer conjugate structure is designed to decrease clearance from the eye and increase the duration of the effect., Areas Covered: This article briefly discusses the impact and mechanisms of nAMD, DME, and RVO and evaluates currently approved anti-VEGF therapies. It progresses to examine a new agent, KSI-301 and the results from numerous clinical trials in these disease areas., Expert Opinion: Despite varied results in the phase 2b/3 study for nAMD, there is potential for KSI-301 to serve as a durable therapy for VEGF-mediated retinal disorders. Ongoing phase 3 trials for nAMD, DME, and RVO will provide additional evidence on its efficacy, duration, and safety profiles.

Purpose: INVICOST, a medico-economic analysis, compared costs of managing treatment-naive patients with diabetic macular edema (DME) receiving intravitreal injections (IVIs) of aflibercept (AFL), dexamethasone implant (DXI) or ranibizumab (RAN) over 1 year., Methods: Healthcare resource use and associated costs were estimated using individual patient data from INVICTUS, a prospective, open-label, monocentric study. Healthcare costs comprised direct medical costs such as drug acquisition and administration, consultations and ophthalmological procedures. Costs were assessed from the French National Health Insurance perspective using published national tariffs expressed in 2019 euros., Results: Of the 60 treated eyes, 48 had no treatment switch; 14 received AFL, 19 received DXI and 15 received RAN. AFL-treated eyes received an average of 6.5 IVIs, DXI-treated patients received 2 IVIs and RAN-treated received 6.8 IVIs. All treated eyes received an initial prescription for adjunctive ocular medications and 349 follow-up procedures were performed including an average of 3.9 optical coherence tomography and 3.2 retinography procedures per eye. Average total direct cost of per-eye treatment was €4516 (€1128-€8257). Average cost was €5782 for eyes treated with AFL, €2779 with DXI and €5536 with RAN. Drug therapy was the cost driver: €4394 (76%) for AFL, €1915 for DXI (69%) and €4268 (77%) for RAN., Conclusion: The difference in total treatment cost is largely explained by the significantly lower frequency of IVI and annual cost of therapy with DXI, compared with AFL and RAN. INVICOST is the first study comparing treatment costs with AFL, DXI and RAN in France in current clinical practice.