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Management of vitreoretinal disorders (e.g., neovascular age-related macular degeneration [nAMD] and diabetic macular edema [DME]) have assumed the standard therapy of lifelong anti-VEGF injections with drugs like aflibercept, brolucizumab, ranibizumab and bevacizumab. However, the burden imposed on patients is a major deterrent for continual therapy and recovery. Faricimab, a bispecific antibody, blocking both VEGF-A and Ang-2 molecules, produces a comparable functional and anatomical results, with less injections, significantly reducing patient burden. Visual acuity, safety, adverse effects, and anatomical outcomes are discussed in the pivotal clinical trials (YOSEMITE/RHINE and TENAYA/LUCERNE), and early data from real-world studies (TRUCKEE, TAHOE, FARWIDE-DME, FARETINA and others). In YOSEMITE and RHINE, faricimab demonstrated non-inferior vision gains, better anatomical outcomes compared to aflibercept every 8 weeks. Faricimab in the personalized treatment interval (PTI), after week 96, achieved 12-week interval in 78.1% of the patients and 16-week interval in 62.3%. TENAYA and LUCERNE reported comparable best corrected visual acuity (BCVA) improvement and better anatomic outcomes during head-to-head phase, parallel to aflibercept, at its 8-week treatment schedule. Faricimab in the PTI regimen, after week 96 achieved 12-week interval in 77.8% of the patients and 16-week interval in 63.1%. Safety of faricimab has been comparable to aflibercept in these pivotal trials. Real-world data supports the data from the pivotal studies regarding the efficacy and safety profile of faricimab in heterogenous real world patient population. Moreover, in previously treated patients, it also demonstrated a faster fluid resolution, good safety profile. Considering faricimab has demonstrated anatomic and durability benefit in the treatment of nAMD and DME, additional data from ongoing extension clinical trials, AVONELLE-X and RHONE-X will help understand longer term outcomes for patients treated with faricimab as well as patients switching from aflibercept to faricimab after finishing the pivotal trials. Longer term data from the real-world studies will also continue to contribute to our understanding of long-term efficacy, safety and durability in the real world patient population.

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Recombinant adeno-associated viral vectors (rAAV) are the safest and most effective gene delivery platform to drive the treatment of many inherited eye disorders in well-characterized animal models. The use in rAAV of ubiquitous promoters derived from viral sequences such as CMV/CBA (chicken ß-actin promoter with cytomegalovirus enhancer) can lead to unwanted side effects such as pro-inflammatory immune responses and retinal cytotoxicity, thus reducing therapy efficacy. Thus, an advance in gene therapy is the availability of small promoters, that potentiate and direct gene expression to the cell type of interest, with higher safety and efficacy. In this study, we used six human mini-promoters packaged in rAAV2 quadruple mutant (Y-F) to test for transduction of the rat retina after intravitreal injection. After four weeks, immunohistochemical analysis detected GFP-labeled cells in the ganglion cell layer (GCL) for all constructs tested. Among them, Ple25sh1, Ple25sh2 and Ple53 promoted a widespread reporter-transgene expression in the GCL, with an increased number of GFP-expressing retinal ganglion cells when compared with the CMV/CBA vector. Moreover, Ple53 provided the strongest levels of GFP fluorescence in both cell soma and axons of retinal ganglion cells (RGCs) without any detectable adverse effects in retina function. Remarkably, a nearly 50-fold reduction in the number of intravitreally injected vector particles containing Ple53 promoter, still attained levels of transgene expression similar to CMV/CBA. Thus, the tested MiniPs show great potential for protocols of retinal gene therapy in therapeutic applications for retinal degenerations, especially those involving RGC-related disorders such as glaucoma.

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OBJECTIVE: To compare the anatomical results in patients with rhegmatogenous retinal detachment, at least grade B of proliferative vitreoretinopathy, and with a trans-surgical dexamethasone implant vs the control group. We also assessed the diminution of proliferative vitreoretinopathy and the final visual acuity (VA). METHOD: The patients were evaluated clinically and with optical coherence tomography for 10 months. Logistic regression analyses were performed to evaluate the effect of the dexamethasone implant on retinal detachment. Correlational analyses were explored depending on the variables' distribution, and an independent samples t-test was used to compare the VA in both groups. RESULTS: The study included 38 eyes of patients with proliferative vitreoretinopathy: 18 with the implant and 20 for the control group. The evaluation of the main objective showed significant differences (p < 0.05) in the anatomical success between the two groups (61.1% vs. 20%, treatment vs. control); odds ratio of 6.29; 95% confidence interval: 1.5- 26.8; p = 0.013; Nagelkerke's R2 = 0.225. The t-test showed a significant difference in the final VA of the patients (t = 2.047; df = 36; p = 0.048; Cohen's d = 0.66). CONCLUSIONS: Retinal redetachment was less frequent, and better VA was observed, in patients with the dexamethasone implant in comparison with the control group.

OBJETIVO: Comparar los resultados anatómicos en pacientes con desprendimiento de retina regmatógeno, vitreorretinopatía proliferativa a partir de grado B y aplicación de implante de dexametasona transquirúrgico frente a un grupo control. También se valoraron la disminución de la vitreorretinopatía proliferativa y la agudeza visual (AV) final. MÉTODO: Los pacientes se evaluaron clínicamente y con tomografía de coherencia óptica por 10 meses. Se realizaron análisis de regresión logística para evaluar el efecto del implante en el redesprendimiento de retina. Se exploraron análisis correlacionales dependiendo de la distribución de variables y se aplicó la prueba t de muestras independientes para comparar la AV en ambos grupos. RESULTADOS: Se incluyeron 38 ojos de pacientes con vitreorretinopatía proliferativa: 18 con el implante y 20 del grupo control. La evaluación del objetivo principal mostró diferencias significativas (p < 0.05) en el éxito anatómico entre ambos grupos (61.1% en los ojos con tratamiento frente a 20% en el grupo control); razón de momios de 6.29; intervalo de confianza del 95%: 1.5- 26.8; p = 0.013; R2 de Nagelkerke = 0.225. La prueba t mostró una diferencia significativa entre la AV final de los pacientes (t = 2.047; gl = 36; p = 0.048; d de Cohen = 0.66). CONCLUSIONES: Se observó menor redesprendimiento, así como mejor AV, en los pacientes con el implante de dexametasona en comparación con el grupo control.

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Leukemia is a common neoplasia that, in its progress, can have ocular involvement due to direct infiltration or secondary to hematological alterations typical of the disease. These findings are consistent with an involvement of the central nervous system and are thus related to the prognosis. Despite the existing systemic therapies, there needs to be more literature that shows the treatment in the ocular involvement of this disease. A case report of a child with ocular involvement due to treatment-refractory acute lymphoblastic leukemia, successfully managed with intravitreal methotrexate, is presented.

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PRO-169 is an anti-VEGF monoclonal antibody developed by Laboratorios Sophia that shares its sequence with Bevacizumab (BVZ); though, PRO-169 is intended for intravitreal administration. In this study, analytical characterization showed that PRO-169 had glycosylation differences in comparison to BVZ reference product (RP); since it had more content of G1F, G2F, sialic acid and high mannose. Further investigation was performed to evaluate if differences between both products would affect the efficacy and safety profile of PRO-169. PRO-169 had no alteration in its in vitro biological activity; moreover, no cytotoxicity or immunogenicity concerns should be expected as demonstrated by different orthogonal methods at analytical, in vitro and in vivo assays. These results support moving to the clinical testing of PRO-169 since no major complications will be expected with its clinical use for the treatment of ophthalmic diseases.

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This review aimed to systematically compare the efficacy and safety of intravitreal aflibercept (IVA) and vitrectomy for treating severe vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR). The review was conducted in accordance with PRISMA guidelines. A search strategy, including the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and US National Library of Medicine databases, was developed to identify randomized controlled trials (RCTs) that compared vitrectomy and IVA for managing VH due to PDR (participant age ≥ 18 years). The primary outcome measure was the difference in the mean visual acuity between the two treatment groups at 1, 6, and 24 months. Outcome measures included clearance of VH (in weeks), the incidence of recurrent VH, and the rate of complications. The studies were evaluated using the Cochrane Bias (ROB) tool. We identified 774 articles; six articles met the inclusion criteria, and two were ultimately included (n = 239 eyes). With or without PRP, IVA injections and vitrectomy were performed in 117 and 122 eyes, respectively. The mean BCVA at one month was significantly better in the vitrectomy group (MD=0.22, CI:0.10-0.34, p=0.0003), but no difference was found at six months (MD=0.04, CI: -0.04-0.12, p=0.356). The incidence of recurrent VH was significantly higher in the IVA group (OR=5.05, CI:2.71-9.42, p<0.0001). The probability of recurrent VH was five times greater in the IVA group than that in the vitrectomy group. There were no significant differences in the overall proportions of intra- or postoperative complications (OR=0.64, CI: 0.09-4.85, p=0.669). None of the studies had a low ROB in any of the seven domains. We conclude that IVA can be considered a viable treatment modality for diabetic VH in patients with a good follow-up. Vitrectomy initially provides better visual effect, faster VH recovery, and lower VH recurrence than IVA injections.

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INTRODUCTION: Diabetic retinopathy is a major cause of visual loss worldwide. The most important clinical findings include diabetic macular edema (DME) and proliferative diabetic retinopathy (PDR). AREAS COVERED: PubMed was used for our literature review. Articles from 1995 to 2023 were included. Pharmacologic treatment of diabetic retinopathy generally involves the use of intravitreal anti-vascular endothelial growth factor (VEGF) therapy for DME and PDR. Corticosteroids remain important second-line therapies for patients with DME. Most emerging therapies focus on newly identified inflammatory mediators and biochemical signaling pathways involved in disease pathogenesis. EXPERT OPINION: Emerging anti-VEGF modalities, integrin antagonists, and anti-inflammatory agents have the potential to improve outcomes with reduced treatment burdens.

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PURPOSE: To compare accuracy, precision, and residual volume of commonly used syringes for intravitreal injections (IVIs) and to assess the intraocular pressure (IOP) rise by variations in volumes delivered. DESIGN: Experimental laboratory study. SUBJECTS: No subjects were involved in this study. METHODS: We tested 8 syringe models with 2 different needle setups, with 2 different solutions (distilled water or glycerin) and target volumes (50 and 70 µL). To obtain the delivered and residual volumes, we weighed the syringe-needle setups with scale before liquid withdrawal, with liquid, and after liquid release. We also created an experimental eye model to determine the transient rise in IOP following stepwise 10-µL increases in injection volumes. MAIN OUTCOME MEASURES: Delivered and residual volumes, IOP rise. RESULTS: We tested a total of 600 syringe-needle setups. Becton Dickinson (BD) Ultra-Fine (0.34 ± 0.28 µL), Zero Residual (1.53 ± 1.15 µL), and Zero Residual Silicone Oil-free (1.40 ± 1.16 µL) syringes showed the lowest residual volume (P < 0.001) in comparison with the others (range: 24.86 ± 1.78 µL for Injekt-F to 51.97 ± 3.37 µL for Omnifix-F). The most accurate setups were (percentage deviation from target volume): Zero Residual Silicone Oil-free (+ 0.70%), Zero Residual 0.3 ml (+ 4.49%), BD Ultra-Fine (+ 7.83%), Injekt-F (9.42%), Norm-Ject (+ 15.88%), Omnifix-F (+ 16.96%), BD Plastipak Brazil (+17.96%), and BD Plastipak Spain syringes (+ 19.41%). There was a statistically significant difference between the Zero Residual Silicone Oil-free syringe and all other syringes (P < 0.0001), except for the Zero Residual 0.3-ml syringe (P = 0.029). The coefficient of variation was low for all syringes. The modeled IOP rise ranged from 32.3 (standard deviation [SD], 1.4) mmHg for 20-µL injection volume to 76.5 (SD, 1.0) mmHg for 80-µL injection volume. For the standard 50-µL injection volume, the peak pressure was 50.7 (SD, 0.1) mmHg, and the pressure rise duration was 28 (SD, 2) minutes. CONCLUSIONS: There were significant differences in accuracy and residual volume between syringes, whereas they showed a high precision. Volume excess results in a considerable increase in IOP rise after injection. These findings may provide a relevant overview to clinicians and to both device and drug manufacturers regarding pharmacoeconomic, safety, and efficacy issues. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

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ABSTRACT Staphylococcus hominis (S. hominis) is a coagulase-negative Staphylococci and an infrequent cause of endophthalmitis. Due to its ability to produce biofilm, especially in diabetic patients, strains may acquire antibiotic resistance. We present two cases of S. hominis endophthalmitis, one with acute endophthalmitis after intravitreal bevacizumab injection and one with chronic endophthalmitis following undiagnosed penetrating ocular trauma. Although there are only four published S. hominis endophthalmitis cases in the literature, to the best of our knowledge, there has been no previously published case after intravitreal bevacizumab.

RESUMO Staphylococcus hominis (S. hominis) é um estafilococo coagulase-negativo e uma causa pouco frequente de endoftalmite. Devido à sua capacidade de produzir biofilme, especialmente em pacientes diabéticos, cepas dessa bactéria podem adquirir resistência a antibióticos. Este relato apresenta dois casos de endoftalmite por S. hominis: um de endoftalmite aguda após injeção intravítrea de bevacizumabe e outro de endoftalmite crônica após trauma ocular penetrante não diagnosticado. Embora existam apenas quatro casos de endoftalmite por S. hominis publicados na literatura, até onde sabemos não houve nenhum caso publicado anteriormente após bevacizumabe intravítreo.

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ABSTRACT Purpose: To compare viscotrabeculotomy with anterior chamber irrigation to Ahmed glaucoma valve implantation for secondary glaucoma following silicone oil removal. Methods: A prospective study was conducted on 43 vitrectomized pseudophakic eyes with persistent glaucoma after silicone oil removal. Patients were randomized to either viscotrabeculotomy with anterior chamber irrigation or Ahmed glaucoma valve implantation. All patients were examined on day 1, week 1, and months 1, 3, 6, 9, 12, 18, and 24 postoperatively. Postoperative complications were noted. Success was defined as an intraocular pressure between 6 and 20 mmHg and with an intraocular pressure reduction of >30% compared with the preoperative intraocular pressure. Results: There were 22 eyes in the viscotrabeculotomy with anterior chamber irrigation and 21 eyes in the Ahmed glaucoma valve implantation group. The mean preoperative and postoperative intraocular pressure in the viscotrabeculotomy with anterior chamber irrigation and Ahmed glaucoma valve implantation groups were 35.5 ± 2.6 mmHg and 35.5 ± 2.4 mmHg and 16.9 ± 0.7 mmHg and 17.9 ± 0.9 mmHg respectively (p˂0.0001). There was a statistically significant intraocular pressure reduction at all follow-up time points compared to preoperative values (p˂0.0001) in both groups. The unqualified success rate in the viscotrabeculotomy with anterior chamber irrigation and Ahmed glaucoma valve implantation groups were 72.73% and 61.9%, respectively. A minimal self-limited hyphema was the most common complication. Conclusions: Both viscotrabeculotomy with anterior chamber irrigation and Ahmed glaucoma valve implantation are effective in lowering the intraocular pressure in glaucoma after silicone oil removal with viscotrabeculotomy with anterior chamber irrigation providing greater reduction, higher success rates, and minimal complications.

RESUMO Objetivo: Comparar a viscotrabeculotomia com irrigação da câmara anterior com o implante de válvula de glaucoma de Ahmed para glaucoma secundário após remoção de óleo de silicone. Métodos: Foi realizado um estudo prospectivo de 43 olhos pseudofácicos vitrectomizados com glaucoma persistente após a remoção de óleo de silicone. Os pacientes foram randomizados para viscotrabeculotomia com irrigação da câmara anterior ou implante de válvula de Ahmed. Todos os pacientes foram examinados no primeiro dia, na primeira semana e 1, 3, 6, 9, 12, 18 e 24 meses após a cirurgia. Observaram-se complicações pós-operatórias. O sucesso foi definido como uma pressão intraocular entre 6 e 20 mmHg e uma redução da pressão intraocular >30% em comparação com a pressão intraocular pré-operatória. Resultados: Foram designados 22 olhos para o grupo da viscotrabeculotomia com irrigação da câmara anterior e 21 olhos para o grupo do implante de válvula de Ahmed. A pressão intraocular média pré-operatória foi de 35,5 ± 2,6 mmHg para o grupo da viscotrabeculotomia com irrigação da câmara anterior e pós- e de 35,5 ± 2,4 mmHg no grupo do implante de válvula de Ahmed. e Os valores pós-ope­ratórios foram de 16,9 ± 0,7 mmHg e 17,9 ± 0,9 mmHg para esses mesmos grupos, respectivamente (p<0,0001). Ambos os grupos tiveram uma redução estatisticamente significativa da pressão intraocular em relação aos valores pré-operatórios (p<0,0001) em todos os momentos do acompanhamento. A taxa de sucesso não qualificado nos grupos da viscotrabeculotomia com irrigação da câmara anterior e do implante de válvula de Ahmed foi de 72,73% e 61,9%, respectivamente. A complicação mais comum foi o hifema, autolimitado e mínimo. Conclusões: Tanto a viscotrabeculotomia com irrigação da câmara anterior quanto o implante de válvula de Ahmed são eficazes na redução da pressão intraocular no glaucoma após injeção de óleo de silicone, mas a viscotrabeculotomia com irrigação em câmara anterior proporcionou maior redução da pressão intraocular e maiores taxas de sucesso, com complicações mínimas.