Potential Risk Factors for Ocular Pain in Patients Undergoing Multiple Intravitreal Injections of Anti-Vascular Endothelial Growth Factor.

Purpose: To assess ocular pain in patients undergoing multiple intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) who have previous factors that may influence pain sensitivity. Methodology: This is a prospective, observational, case series study involving patients who underwent multiple (≥3) pro re nata intravitreal injections of ranibizumab or aflibercept to treat any cause of chorioretinal vascular disease. Ocular pain was assessed by the numerical analog scale during intravitreal injection. For this study, the main variable was ocular pain and the secondary variables included age, sex, previous history of glaucoma, primary retinal vascular disease, severe dry eye history, trigeminal pain, scleral buckle surgery, collagen diseases, fibromyalgia, severe migraine history, pars plana vitrectomy, scleral thickness measurements, and type of anti-VEGF. Results: In a total of 894 patients, 948 eyes (4822 intravitreal injections), 793 patients (88.6%) had ocular pain sensitivity between no pain to mild pain, 80 patients (8.9%) had moderate ocular pain, 15 patients (1.6%) had severe ocular pain, and 6 patients (0.7%) had extremely severe ocular pain. Patients with severe dry eye (p = 0.01) and previous history of scleral buckle surgery (p = 0.01) showed a significant correlation with ocular pain during intravitreal injection. Pars plana scleral thickness (>550 um) and diabetic neuropathy were associated with ocular pain but did not meet the criteria for statistical significance (p = 0.09 and p = 0.06, respectively). Conclusion: Dry eye and prior scleral buckle surgery may contribute to pain associated with intravitreal injection. These issues should be taken into consideration in patients undergoing multiple intravitreal injections.

Using 2% PVPI topical solution for serial intravitreous injections and ocular surface findings: a case control study.

BACKGROUND: The use of povidone-iodine for ocular surface asepsis is widespread for intravitreal injections. They became frequent procedures, leading to serial exposure of patients' eyes to iodinated solutions. In this study, we investigate the changes in the ocular surface in patients submitted to repeated use of povidine for intravitreal injection of anti-VEGF asepsis, analyzing Ocular Surface Disease Index, non-invasive break up time, blinking quality, lipid layer, meniscus height and osmolarity. METHODS: This case-control study included 34 individuals (68 eyes), 14 males, 20 females aged 48 to 94. Inclusion criteria were individuals who received application of 2% povidone-iodine eyedrops for intravitreal injections treatment with the non-treated contralateral eye used as control. Ocular surface examinations were performed at a single occasion. A pre-intravitreal injection asepsis protocol with povidone-iodine was applied. All statistical analysis was performed using the STATA® 18.0 Software and a p-value = 0.05 was considered as the statistical significance value in all tests. RESULTS: The median number of IVIs in treated eyes was 12 (range 6-20). The results in treated eyes compared with untreated eyes were respectively : median OSDI 16 (IQR 6-39) and 12.5 (IQR 8-39) (p = 0.380); mean NIBUT 10.30 (SD ± 2.62) and 10.78 (SD ± 2.92) ( s, p = 0.476); median blinking quality 100 (IQR 100) and 100 (IQR 100 ) (%, p = 0.188); median lipid layer 87 (IQR 77-90) and 86 (IQR 74-100) (nm, p = 0.451); median meniscus height 0.22 (IQR 0.19-0,31) and 0.24 (IQR 0.20-0.27) (mm, p = 0.862), median Meibomian gland atrophy 33 (IQR 24-45) and 31.5 (IQR 25-39) (%, p = 0.524); and mean osmolarity 306.6 (SD ± 21.13) and 313.8 (SD ± 29) (mOsm, p = 0.297). There was no statistically significant relationship between the repetitive use of 2% iodinated solution and signs or symptoms compatible with dry eye syndrome in this group of patients. CONCLUSIONS: The findings suggest that 2% povidone iodine is a safe and efficacious agent for ocular surface antisepsis during intravitreal injections, not leading to substantial ocular surface modifications. This conclusion supports the continued use of povidone iodine in routine ophthalmic procedures without increased risk of inducing dry eye syndrome.

Short-term effect of intravitreal dexamethasone implant in refractory diabetic macular edema.

PURPOSE: To evaluate the short-term effects (hours-days) of intravitreal dexamethasone implant (IDI) in eyes with diabetic macular edema (DME) refractory to anti-vascular endothelial growth factor (VEGF) injections. METHODS: This was a prospective, single-arm, interventional clinical series. Eyes with DME and 3-9 injections of ranibizumab without a good response were included. Patients underwent a single IDI. Best-corrected visual acuity (BCVA) measurement, complete ophthalmic evaluation, and spectral-domain optical coherence tomography (SD-OCT) were performed at baseline, 2 h, 3 h, 24 h, 7 days, and 1 month. The main outcomes were change in central retinal thickness (CRT) on SD-OCT and BCVA. RESULTS: Fifteen eyes of 15 patients were included. Mean CRT decreased after treatment from 515.87 µm ± 220.00 µm at baseline to 489.60 µm ± 176.53 µm after 2 h (p = 0.126), and 450.13 µm ± 163.43 at 24 h (p = 0.006). Change in BCVA was from 0.85 ± 0.44 logMAR baseline to 0.58 ± 0.37 log MAR at 1 month (p = 0.003). CONCLUSIONS: Eyes treated with IDI showed significant decrease in CRT detectable 1 day after injection. In some patients, the effect could be observed 3 h post-implantation. TRIAL REGISTRATION: Clinicaltrials.gov NCT05736081 . Registered 20 February 2023, Retrospectively registered.

Primary Vitrectomy versus Tap and Inject for Fungal Endophthalmitis: Meta-Analysis and Comparison with Data from a Reference Centre.

PURPOSE: We aimed to compare the visual outcomes after pars plana vitrectomy (PPV) versus tap and inject (T&I) in fungal endophthalmitis (FE) reported in the literature and to compare the findings from the literature with data from a reference centre. METHODS: We performed a systematic review and meta-analysis of studies reporting the use of PPV versus T&I in FE. We also performed a retrospective review of the clinical records of patients with endophthalmitis from a reference centre in Colombia. RESULTS: We included 13 studies with 334 eyes; 53.59% received PPV and 46.4% received T&I. The overall relative risk of improving ≥ 2 lines in PPV versus T&I was 0.98 (95% confidence interval [CI] 0.80-1.22; p = 0.88) with a mean difference of final visual acuity of 0.26 (95% CI 0.12-0.63; p = 0.18). There were no significant differences in subgroup analysis. Data from the reference centre included 32 endophthalmitis cases, 15.6% of which had a fungal aetiology (80% received PPV and 20% T&I). There were no significant differences in the subgroup analysis. CONCLUSIONS: Based on the findings from the literature and the reference centre, T&I is noninferior to PPV. This is the first meta-analysis in the literature evaluating these effects in FE. It is necessary to execute new prospective randomised controlled studies in patients with endophthalmitis.

Review of real-world evidence of dual inhibition of VEGF-A and ANG-2 with faricimab in NAMD and DME.

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.

rAAV-compatible human mini promoters enhance transgene expression in rat retinal ganglion cells.

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.

ERG and OCT abnormalities in retinoblastoma after melphalan intravitreous injection / Anormalidades do ERG e OCT em um caso de retinoblastoma após injeção intravítrea de melfalan

ABSTRACT The authors report full-field electroretinogram and optical coherence tomography findings of intravitreal melphalan retinal toxicity. An 18-month-old girl with unilateral group D retinoblastoma was evaluated with light-adapted 3 full-field electroretinogram protocol and optical coherence tomography (I-Stand optical coherence tomography, Optovue) after treatment with intravitreal melphalan for active vitreous seeds. After the third injection, the child developed retinal pigment epithelial changes near the injection site. The photopic response of the full-field electroretinogram standard flash cones showed a decrease in amplitude responses of waves a and b in the affected eye compared to the contralateral eye. Optical coherence tomography showed loss of photoreceptors and outer nuclear layers in the affected eye. Melphalan toxicity is dose-dependent, and despite its treatment benefits, it can affect vision. Our case shows an updated, in-depth retinal toxicity assessment of intravitreal melphalan in the human retina with optical coherence tomography and its correlation with electroretinogram changes.

RESUMO Os autores relatam os achados de eletrorretinograma de campo total e tomografia de coerência óptica (OCT) da toxicidade retiniana ao melfalan intravítreo. Menina de 18 meses com retinoblastoma foi avaliada com fases fotópicas do eletrorretinograma de campo total e tomografia de coerência óptica após o tratamento com melfalan intravítreo. Após a terceira injeção, a criança desenvolveu alterações do epitélio pigmentar da retina próximo ao local da injeção. A resposta fotópica do eletrorretinograma de campo total mostrou diminuição da amplitude das respostas das ondas a e b no olho afetado comparado com o olho sadio. A tomografia de coerência óptica mostrou alterações significativas nas camadas retinianas externas no olho comprometido. A toxicidade do melfalan é dose dependente e, apesar dos benefícios terapêuticos, podem causar alterações retinianas significativas. Este caso demonstra uma avaliação atual e aprofundada da toxicidade retiniana do melfalan intravítreo na retina humana através da tomografia de coerência óptica e sua correlação com as alterações no eletrorretinograma.

Vitreous metastasis from cutaneous melanoma: diagnosis and management / Metástase vítrea de melanoma cutâneo: diagnóstico e tratamento

ABSTRACT Purpose: To report the clinical findings, treatments, and outcomes in a series of patients with vitreous metastasis from cutaneous melanoma. Methods: This single-center, retrospective, interventional case series included patients with biopsy-confirmed vitreous metastasis from cutaneous melanoma diagnosed between 1997 and 2020. Standard 23- or 25-gauge pars plana vitrectomy was performed for diagnostic sampling. Sclerotomies were treated with double or triple freeze-thaw cryotherapy. Perioperative intravitreal injections of melphalan (32 µg/0.075 mL) were administered, when indicated. Visual acuity, intraocular pressure, and systemic and ocular treatment responses were reported. Results: Five eyes of five patients with unilateral vitreous metastasis from cutaneous melanoma were identified. The median age at diagnosis was 84 (range, 37-88) years. The median follow-up after ophthalmic diagnosis was 28 (8.5-36) months; one patient did not have a follow-up. The initial visual acuity ranged from 20/30 to hand motions. Baseline clinical findings included pigmented or non-pigmented cellular infiltration of the vitreous (5/5), anterior segment (4/5), and retina (3/5). Four patients had secondary glaucoma. Systemic therapy included checkpoint inhibitor immunotherapy (n=3, all with partial/complete response), systemic chemotherapy (n=2), surgical resection (n=3), and radiation (n=2). The median time from primary diagnosis to vitreous metastasis was 2 (2-15) years. One patient had an active systemic disease at the time of vitreous metastasis. The final visual acuity ranged from 20/40 to no light perception. Ophthalmic treatment included vitrectomy in all five patients, intravitreal administration of melphalan in three, and intravitreal administration of methotrexate in one. One patient required enucleation, and histopathology revealed extensive invasion by melanoma cells. Conclusions: Vitreous metastasis from cutaneous melanoma can present as a diffuse infiltration of pigmented or non-pigmented cells into the vitreous and may be misdiagnosed as uveitis. Diagnostic pars plana vitrectomy and periodic intravitreal chemotherapy may be indicated.

RESUMO Objetivo: Descrever os achados clínicos, tratamentos, e desfechos em uma série de pacientes com me tástases vítreas de melanoma cutâneo. Métodos: Série retrospectiva de casos de único centro com intervenção. Pacientes incluídos tiveram seu diagnóstico de MVMC confirmado por biópsia entre 1997 e 2020. Vitrectomia via pars plana com 23 ou 25 gauge foram realizadas para obter espécimens. Esclerotomias foram tratadas com crioterapia em duplo ou triplo congelamento. Injeção intravítrea perioperatória de melfalano (32 ug/0,075 mL) foi administrada quando necessário. Foram relatados acuidade visual, pressão intraocular, resposta terapêutica sistêmica e ocular. Resultados: Cinco olhos de 5 pacientes com metástases vítreas de melanoma cutâneo unilateral foram identificados. Idade média de diagnóstico foi 84 anos (variando de 37-88). Seguimento médio após diagnóstico oftalmológico foi 28 (8,5-36) meses; 1 paciente não teve acompanhamento. Acuidade visual inicial variou de 20/30 a movimentos de mão. Achados clínicos iniciais incluíram infiltração de células pigmentadas e não-pigmentadas no vítreo (5/5), segmento anterior (4/5), e retina (3/5). Quatro pacientes tiveram glaucoma secundário. Tratamento sistêmico incluiu imunoterapia com inibidores da via de sinalização (3 - todos com resposta parcial/completa), quimioterapia sistêmica (2), ressecção cirúrgica (3), e irradiação (2). Intervalo médio entre diagnóstico primário e metástases vítreas foi 2 (2-15) anos. Um paciente teve doença sistêmica ativa simultânea as metástases vítreas. Acuidade visual final variou entre 20/40 e SPL. Tratamento oftalmológico incluiu vitrectomia nos 5 pacientes, melfalano intravítreo em 3 e metotrexato intravítreo em 1. Um paciente precisou de enucleação. A histopatologia revelou invasão celular extensa de melanoma. Conclusões: Metástases vítreas de melanoma cutâneo pode se manifestar como uma infiltração difusa de células pigmentadas e não-pigmentadas no vítreo e erroneamente diagnosticada como uveites. Vitrectomia diagnóstica e quimioterapia intravítrea periódica podem estar indicadas.

Profile of patients treated with intravitreal antiangiogenics in a Brazilian public service with high level of complexity / Perfil de pacientes tratados com antiangiogênicos intravítreo em serviço público brasileiro de alto nível de complexidade

ABSTRACT Purpose: Intravitreal antiangiogenic therapy is currently the most invasive ophthalmic procedure performed worldwide. This study aimed to describe the clinical and epidemiological profile of patients undergoing intravitreal antiangiogenic therapy in a tertiary referral hospital in Brazil. Methods: This cross-sectional, retrospective, and observational study analyzed medical records of patients who received intravitreal injections of antiangiogenic agents for the treatment of retinal diseases at the ophthalmology outpatient clinic in the Hospital das Clínicas at Unicamp between January and December 2020. Results: The study included 429 patients and 514 eyes. The study population was predominantly male (51.28%), white (80.89%), between 50 and 80 years old (mean age, 60.92 years), had complete or incomplete first-grade education (56.88%), and did not belong to the Regional Health Department of which Campinas is a part (78.55%). Bevacizumab was the most commonly used intravitreal injectable medicine (79.38%), pro re nata was the most commonly used treatment regimen (90.27%), and macular edema was the most prevalent pathology indicative of treatment (60.12%), with diabetes etiology accounting for 48.25%. The average number of injections per patient was 3.83, with the macular neovascularization group and the pro re nata group having the highest and lowest with five and three injections, respectively. Treatment adherence was associated with the patient's pathology, and the macular edema (52.24%) and macular neovascularization (49.48%) groups had the lowest adherence rates. Conclusions: This study evaluated the epidemiological and clinical profile of patients undergoing antiangiogenic therapy in a high-complexity public hospital, which is fundamental for a better understanding of the demand for ophthalmic reference service in Brazil, and the analysis of functional results and user adherence profile promotes optimization of indications and leverages the benefits of intravitreal therapy.

RESUMO Objetivo: A terapia antiangiogênica intravítrea revolucionou o tratamento de inúmeras patologias de relevância global, sendo atualmente o procedimento oftalmológico invasivo mais realizado no mundo. Objetiva-se no presente estudo descrever o perfil clínico e epidemiológico dos pacientes submetidos a terapia intravítrea com antiangiogênicos em hospital terciário de referência no Brasil. Métodos: Trata-se de um estudo transversal, retrospectivo e observacional que foi realizado através da análise de prontuários de pacientes submetidos a injeção intravítrea de antiangiogênicos para tratamento de doenças retinianas no ambulatório de oftalmologia do Hospital das Clínicas da Unicamp no período de janeiro a dezembro de 2020. Resultados: O estudo analisou 429 pacientes e 514 olhos. A maioria pertencia ao sexo masculino (51,28%), raça branca (80,89%), possuía entre 50-80 anos com idade média de 60,92 anos e escolaridade de 1º grau completo ou incompleto (56,88%) e não pertenciam (78,55%) a área de abrangência do Departamento Regional de Saúde do qual Campinas faz parte. O fármaco mais utilizado nas injeções intravítreas foi o bevacizumabe (79,38%), o principal regime de tratamento foi o pro re nata (90,27%) e a principal grupo de patologia indicativa de tratamento foi o edema macular (60,12%), sendo 48,25% desses de etiologia diabética. A média de injeções foi de 3,83/paciente, sendo o grupo de neovascularização macular o de maior mediana com 5 injeções/paciente e o esquema pro re nata o regime de tratamento com menor mediana, 3 injeções/paciente. A adesão ao tratamento associou-se a patologia do paciente, sendo as menores taxas de adesão as dos grupos com edema macular (52,24%) e neovascularização macular (49,48%). Conclusões: O presente estudo avaliou o perfil epidemiológico e clínico dos pacientes submetidos a terapia antiangiogênica em hospital público de alta complexidade, o que é fundamental para melhor conhecimento da demanda de serviço oftalmológico de referência no Brasil e possibilita, a partir da análise dos resultados funcionais e perfil de adesão dos usuários, otimizar as indicações e alavancar os benefícios de terapia intravítrea.

Transoperative intravitreal dexamethasone implantation in patients with proliferative vitreoretinopathy.

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.

Glycosylation differences of an anti-VEGF monoclonal antibody (PRO-169) and its extensive comparison with Bevacizumab.

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.

Bacterial endophthalmitis following anti-VEGF intravitreal injections: a retrospective case series.

BACKGROUND: To describe the incidence of endophthalmitis and the treatment outcomes of acute bacterial endophthalmitis following intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in a Brazilian hospital. The analysis was based on the timing of infection after intravitreal injection, culture results, visual acuity, and the presence of epiretinal membrane after a 1-year follow-up period, spanning nine years. METHODS: This retrospective case series, conducted over a 9-year period, aimed to evaluate the treatment outcomes of acute endophthalmitis following intravitreal Bevacizumab injections. The inclusion criteria involved a chart review of 25 patients who presented clinical signs of acute endophthalmitis out of a total of 12,441 injections administered between January 2011 and December 2019. Negative culture results of vitreous samples or incomplete data were excluded. Ultimately, 23 patients were enrolled in the study. Eight patients were treated with intravitreal antibiotic injections (IVAI) using vancomycin 1.0 mg/0.05mL and ceftazidime 2.25 mg/0.05mL, while 15 patients underwent pars plana vitrectomy (PPV) followed by intravitreal antibiotic injections at the end of surgery (IVAIES). The main outcome measures were the efficacy of controlling the infection with IVAI as a standalone therapy compared to early PPV followed by IVAIES. Data collected included pre-infection and one-year post-treatment best corrected visual acuity (BCVA), optical coherence tomography (OCT) abnormalities, and enucleation/evisceration rates. To compare groups, Mann-Whitney and ANOVA tests were employed for statistical analysis. RESULTS: The incidence rate of bacterial endophthalmitis was 0.185% (1/541 anti-VEGF injections), with the highest infection rates observed in 2014 and 2017. Patients presented clinical symptoms between 2 and 7 days after injection. The most common isolated organisms were coagulase-negative Staphylococci and Streptococci spp. Treatment outcomes showed that both IVAI and PPV + IVAIES effectively controlled the infection and prevented globe atrophy. After one year, the PPV group with BCVA better than Light Perception had a significantly better BCVA compared to the IVAI group (p 0.003). However, PPV group had higher incidence of epiretinal membranes formation compared to the IVAI group. (P 0.035) CONCLUSION: Anti-VEGF injections carry a risk of developing acute bacterial endophthalmitis. Isolated antibiotic therapy could be an effective treatment to control the infection, but performing PPV + IVAIES as a primary treatment showed promising results in terms of improving BCVA after one year, despite a higher rate of epiretinal membrane formation. Further studies are needed to confirm these findings.

Intravitreal methotrexate in type B lymphoblastic leukemia-Case Report.

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.

Pseudophakic macular edema in nondiabetic and diabetic patients without diabetic retinopathy treated with intravitreal dexamethasone implant.

BACKGROUND: The purpose of this study was to compare the impact of intravitreal dexamethasone (DEX) implant during a 12-month period in nondiabetic and diabetic patients without diabetic retinopathy (DR) as a treatment for refractory pseudophakic cystoid macular edema (PCME) following prior treatment with topical nepafenac 0.1% and prednisolone 1%. METHODS: Forty-two consecutive medical records of patients diagnosed with PCME after uneventful cataract surgery were included. The outcomes measured included best corrected visual acuity (BCVA) and central foveal thickness (CFT). Linear regression analysis was statistically applied. RESULTS: Following topical treatment, nondiabetic and diabetic subjects presented a mean ± SD gain of - 0.11 ± 0.11 and - 0.18 ± 0.11 BCVA logMAR and a CFT reduction of - 43.42 ± 53.66 µm and - 58.76 ± 36.28 µm, respectively. The mean BCVA gain at month 12 subsequent to DEX implantation was - 0.35 ± 0.17 in nondiabetic (p < 0.001) and - 0.55 ± 0.26 in diabetic patients (p < 0.001), with CFT reductions of - 195.71 ± 93.23 µm (p < 0.001) and - 260.81 ± 198.69 µm (p < 0.001), respectively. Patients who responded with better VA after topical treatment presented better visual outcomes at month 12 following DEX implantation (r2 = 0.46; rho = - 0.71, p < 0.01). CONCLUSION: Nondiabetic and diabetic patients without DR demonstrated similar results after DEX implant after combined topical therapy, suggesting that selected diabetic patients may have a response comparable to that of nondiabetic patients with PCME.

Alternativas de tratamiento de la obstrucción venosa retiniana: terapias combinadas y vitrectomía pars plana / Treatment Alternatives for Retinal Venous Obstruction: Combined Therapies and Pars Plana Vitrectomy

Dentro de las enfermedades vasculares de la retina, la oclusión venosa retiniana es relativamente frecuente y debido a sus complicaciones afecta de forma moderada o grave la visión. Las opciones terapéuticas aplicadas en el edema macular y los desprendimientos de retina traccionales causados por las oclusiones venosas son varias. Se realizó una revisión en la literatura científica para valorar la eficacia y seguridad del uso combinado de diferentes terapias que incluye los antiangiogénicos y esteroides intravítreos con o sin aplicación de láser, así como la vitrectomía pars plana como alternativas de tratamiento de las complicaciones de la enfermedad oclusiva venosa retiniana. Aun cuando los antiangiogénicos se consideren como primera línea de tratamiento en la oclusión venosa retiniana, en varios casos hay mejor respuesta en sus combinaciones y de los esteroides con láser. Para resolver el desprendimiento de retina traccional y hemorragia vítrea, debidas a las oclusiones venosas, se requiere, mayormente, operación de vitrectomía pars plana. Se realizó una búsqueda en bases de datos electrónicas como PubMed, Cochrane y otras publicaciones relacionadas con las alternativas de tratamiento de la obstrucción venosa retiniana en los últimos años.

Among retinal vascular diseases, retinal venous occlusion is relatively frequent and due to its complications, it moderately or severely affects vision. The therapeutic options applied in macular edema and tractional retinal detachments caused by venous occlusions are several. A review of the scientific literature was performed to assess the efficacy and safety of the combined use of different therapies including intravitreal antiangiogenics and steroids with or without laser application, as well as pars plana vitrectomy as treatment alternatives for the complications of retinal venous occlusive disease. Even when antiangiogenics are considered as first line of treatment in retinal venous occlusion, in several cases there is better response in their combinations and steroids with laser. To resolve tractional retinal detachment and vitreous hemorrhage due to venous occlusions, a pars plana vitrectomy operation is mostly required. A search was made in electronic databases such as PubMed, Cochrane and other publications related to treatment alternatives for retinal venous obstruction in recent years.

Determining the Superiority of Vitrectomy vs Aflibercept for Treating Dense Diabetic Vitreous Hemorrhage: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

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.

Update on current pharmacologic therapies for diabetic retinopathy.

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.

The Evolution of Triamcinolone Acetonide Therapeutic Use in Retinal Diseases: From Off-Label Intravitreal Injection to Advanced Nano-Drug Delivery Systems.

Ophthalmic drug delivery to the posterior segment of the eye has been challenging due to the complex ocular anatomy. Intravitreal injection of drugs was introduced to deliver therapeutic doses in the posterior segment. Different posterior segment diseases including age-related macular degeneration, diabetic macular edema, retinal vein occlusions, uveitis, and cystoid macular edema, among others, have been historically treated with intravitreal corticosteroids injections, and more recently with intravitreal corticosteroids drug implants. Triamcinolone acetonide (TA) is the most frequently used intraocular synthetic corticosteroid. Using nanoparticle-based TA delivery systems has been proposed as an alternative to intravitreal injections in the treatment of posterior segment diseases. From these novel delivery systems, topical liposomes have been the most promising strategy. This review is oriented to exhibit triamcinolone acetonide drug evolution and its results in treating posterior segment diseases using diverse delivery platforms.

Ocular Syphilis with Retinal and Disc Neovascularization Treated with Bevacizumab: A Case Report.

We report the findings observed in a young woman with ocular syphilis complicated with retinal and disc neovascularization successfully treated with intravitreal bevacizumab. Fluorescein angiography revealed in both eyes intense hyperfluorescence at the level of the disc, multifocal venous wall staining, multifocal paravenous leakage, multiple peripheral saccular venular dilations, diffuse retinal and macular edema, and retinal and disc neovascularization. There was no evidence of retinal ischemia in both eyes. After antibiotic and corticosteroid treatment, the neovascularization persisted in both eyes. Three consecutive doses of intravitreal bevacizumab were administered, with total regression of the retinal and disc neovascularization. Disc and retinal neovascularization along with nonocclusive retinal vasculitis may be a form of presentation of ocular syphilis. Combination of specific treatment, oral corticosteroids, and intravitreal bevacizumab may be useful for treating this clinical manifestation.

Accuracy, Precision, and Residual Volume of Commonly Used Syringes for Intravitreal Injections and the Impact on Intraocular Pressure.

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.