Risk of Intraocular Pressure Increase With Intravitreal Injections of Vascular Endothelial Growth Factor Inhibitors: A Cohort Study.

PURPOSE: Intraocular pressure increase (IOPi) after intravitreal injections of vascular endothelial growth factor inhibitors (VEGFis) might be different among different VEGFis (bevacizumab, aflibercept, ranibizumab). The purpose of this study was to evaluate the risk of IOPi among new users of bevacizumab, ranibizumab, and aflibercept in nondiabetic patients in Tuscany, Italy. DESIGN: Retrospective cohort study. METHODS: Tuscan regional administrative database was used to identify subjects with a first VEGFi intravitreal injection between 2011 and 2020, followed to first incidence of IOPi. Diabetic subjects, those with pre-existing IOPi, or previous use of dexamethasone implants were excluded. Multivariable Cox regression analyses (intention-to-treat and as treated) were conducted to evaluate risk of IOPi among aflibercept, bevacizumab, and ranibizumab, adjusting for potential confounding variables. IOPi was defined as the first record of International Classification of Diseases, Ninth Revision (ICD-9-CM) code 365 or use of 2 glaucoma drugs dispensations within 180 days of each other. RESULTS: We identified 6585 new users of VEGFis: 1749 aflibercept, 1112 bevacizumab, and 3724 ranibizumab. Women made up 60% of the cohort, with a mean age of 73.6 years. In the intention-to-treat analysis, the adjusted hazard ratio (HR) for incident IOPi, compared with aflibercept, was higher for bevacizumab (HR = 2.20, 95% CI = 1.64-2.95) and ranibizumab users (HR = 1.88, 95% CI = 1.46-2.42), respectively. The HRs remained robust after exclusion of patients with proxy of retinal vascular occlusion. As treated analysis confirmed such results (bevacizumab: HR = 3.76, 95% CI = 2.30-6.17; ranibizumab: HR = 2.49, 95% CI = 1.62-3.82). CONCLUSIONS: This study found an increased risk of IOPi among nondiabetic patients with ranibizumab and bevacizumab compared with aflibercept. Future studies are needed to validate these findings.

Hydrogels in Ophthalmology: Novel Strategies for Overcoming Therapeutic Challenges.

The human eye's intricate anatomical and physiological design necessitates tailored approaches for managing ocular diseases. Recent advancements in ophthalmology underscore the potential of hydrogels as a versatile therapeutic tool, owing to their biocompatibility, adaptability, and customizability. This review offers an exploration of hydrogel applications in ophthalmology over the past five years. Emphasis is placed on their role in optimized drug delivery for the posterior segment and advancements in intraocular lens technology. Hydrogels demonstrate the capacity for targeted, controlled, and sustained drug release in the posterior segment of the eye, potentially minimizing invasive interventions and enhancing patient outcomes. Furthermore, in intraocular lens domains, hydrogels showcase potential in post-operative drug delivery, disease sensing, and improved biocompatibility. However, while their promise is immense, most hydrogel-based studies remain preclinical, necessitating rigorous clinical evaluations. Patient-specific factors, potential complications, and the current nascent stage of research should inform their clinical application. In essence, the incorporation of hydrogels into ocular therapeutics represents a seminal convergence of material science and medicine, heralding advancements in patient-centric care within ophthalmology.

Clinical and visual outcomes following endogenous endophthalmitis: 175 consecutive cases from a tertiary referral center in Taiwan.

BACKGROUND: To elucidate the linkage between organisms and visual outcome in cases of endogenous endophthalmitis. METHODS: Patients who presented with signs of endogenous endophthalmitis between January 2008 and December 2015 and underwent a vitreous tapping were enrolled. The patients' demographics and clinical findings were recorded. The outcomes include visual acuity and enucleation. RESULTS: A total of 175 consecutive patients with endogenous endophthalmitis were enrolled. Forty-four percent of the patients had a known distal focus of infection. The most common focus was liver abscess (24.6%), and the major intravitreal isolate was Klebsiella pneumoniae (34.4%). In this series, 51.4% of the intravitreal cultures were positive. The visual acuity of fungal ophthalmitis were better than in bacterial ophthalmitis. Multivariate logistic regression showed that Gram negative vitreous isolates, compared with the negative vitreous culture, were associated with higher risk of enucleation (Odds ratio [OR]: 10.424, 95% confidence interval [95% CI]: 3.019-35.995). The use of intravitreal antibiotics, compared non-users, was associated with a reduced risk of enucleation (OR:0.084, 95% CI: 0.026-0.268). Trans pars plana vitrectomy was not associated with risk of enucleation (OR: 0.307, 95% CI: 0.035-2.693). The post-treatment VA was positively correlated with the presenting VA (r = 0.718, p = 0.0001). CONCLUSION: Our study demonstrated that liver abscess is the most common source of endogenous endophthalmitis in Taiwan. The visual outcome is good when the presenting visual acuity is relatively well preserved and when the infecting organism is fungus. The use of intra-vitreal antibiotics reduces the risk of enucleation.

Expert opinion on the management and follow-up of uveitis patients during SARS-CoV-2 outbreak.

INTRODUCTION: Routine medical and ophthalmic care is being drastically curtailed in the context of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. Uveitis patients require particular attention because of their theoretical risk of viral infection, in the context of therapeutic immunosuppression. AREAS COVERED: This collaborative work proposes practical management and follow-up criteria for uveitis patients in the context of the ongoing SARS-CoV-2 pandemic. EXPERT OPINION: Management should proceed as usual when access to health care possible in patients who do not belong to a group at high risk of severe SARS-CoV-2 infection, and in uncontrolled uveitis cases. In case of reduced access to eye clinics or high risk of SARS-CoV-2 infection, patients' management should be stratified based on their clinical presentation. In non-severe uveitis cases, the use of systemic steroids should be avoided, and local steroids preferred whenever possible. In uncontrolled situations where there is real risk of permanent visual loss, high-dose intravenous steroids and/or systemic immunosuppressants and/or biotherapies can be administered depending on the severity of eye disease. Immunosuppressive therapy should not be withheld, unless the patient develops SARS-CoV2 infection.

Ghost cell glaucoma after intravitreous injection of ranibizumab in proliferative diabetic retinopathy.

BACKGROUND: The development of ghost cell glaucoma in patients with proliferative diabetic retinopathy (PDR) after intravitreous injection (IV) was rare. Here we reported a series of patients with PDR who received Intravitreous Ranibizumab (IVR) and developed ghost cell glaucoma and analyzed the potential factors that might be related to the development of ghost cell glaucoma. METHODS: Retrospective case series study. The medical records of 71 consecutive eyes of 68 PDR patients who received vitrectomy after IVR from January 2015 to January 2017 were reviewed. The development of ghost cell glaucoma after IVR was recorded. Characteristics of enrolled patients were retrieved from their medical charts. Factors associated with ghost cell glaucoma were compared between eyes with the development of ghost cell glaucoma and eyes without the development of ghost cell glaucoma. Variables were further enrolled in a binary backward stepwise logistic regression model, and the model that had the lowest AIC was chosen. RESULTS: There were 8 out of 71 eyes of the PDR patients developed ghost cell glaucoma after they received IVR. The interval between detection of elevation of intraocular pressure (IOP) and IV ranged from 0 to 2 days. Among them, after IVR, there were two eyes had IOP greater than 30 mmHg within 30 min, four eyes showed normal IOP at 30 min, and then developed ghost cell glaucoma within 1 day, two eyes developed ghost cell glaucoma between 24 and 48 h. The mean IOP was 46.5 ± 8.0 mmHg. All patients gained normal IOP after vitrectomy without medicine for lowering IOP. The presence of ghost cell glaucoma was associated with tractional retinal detachment (RR = 4.60 [2.02 ~ 8.48], p = 0.004) and fibrovascular membrane involving disk (RR = -3.57 [- 7.59 ~ - 0.92], p = 0.03) (AIC = 39.23, AUC = 0.88) in a logistic regression model. CONCLUSION: Attention to postoperative IOP should be paid to patients with PDR undergoing vitrectomy who receive a preoperative IV of anti-VEGF agents. PDR patients with tractional retinal detachment or fibrovasucular membrane involving optic disc are more likely to develop ghost cell glaucoma after IV.

Prefilled syringes for intravitreal drug delivery.

Intravitreal injections of anti-vascular endothelial growth factor (VEGF) medications play an increasingly critical role in numerous retinal vascular diseases. Initially, anti-VEGF medications came in vials that had to be drawn up by the physician into a syringe for administration. In 2018, the US Food and Drug Administration (US FDA) approved the ranibizumab 0.3 mg prefilled syringe (PFS), and in October 2016, the US FDA approved the ranibizumab 0.5 mg PFS. This article discusses the advantages of the PFS, including reduced injection time, possible reduced risk of endophthalmitis, reduction in intraocular air bubbles and silicone oil droplets, and improved precision in the volume and dose of intravitreal ranibizumab administered, along with possible disadvantages. Implications of the innovation of the PFS on intravitreal injection technique and clinical practice pattern are discussed and reviewed.

Embryonic Intravitreous Injection in Mouse.

Axons of retinal ganglion cells (RGCs) relay visual information from the retina to lateral geniculate nucleus (LGN) and superior colliculus (SC), which are two major image-forming visual nuclei. Wiring of these retinal projections completes before vision begins. However, there are few studies on retinal axons at embryonic stage due to technical difficulty. We developed a method of embryonic intravitreous injection of dyes in mice to visualize retinal projections to LGN and SC. This study opens up the possibility of understanding early visual circuit wiring in mice embryos.

Effects of intravitreous sodium hydrosulfide on intraocular pressure and retinopathy in ocular hypertensive rats.

We investigated the possible neuroprotectant and intraocular pressure (IOP) lowering effects of intravitreous injection of sodium hydrosulfide (NaSH) in a rodent model of experimental glaucoma. Glaucoma currently is treated by controlling IOP using medications and/or surgery. These methods are not entirely adequate for all patients. We divided 24 rats into three groups. For the control group, the right eye was treated with intravitreous saline. For the glaucoma group, ocular hypertension was induced by photocoagulating three episcleral veins and the limbal plexus of the right eye using an argon laser, then saline was injected into the vitreous of these eyes during the third week. For the NaSH group, rats were treated with intravenous NaSH 3 weeks after photocoagulation. IOP was measured each week during the 6 week experimental period. Coagulating the episcleral veins rapidly increased the IOP of rat eyes. Intravitreous injection of NaSH significantly reduced IOP. Intravitreous NaSH prevented degeneration of the retina and decreased the number of apoptotic cells. Intravitreous NaSH appeared to reduce IOP and to prevent IOP induced retinopathy in rats.

Effects of retrobulbar or intravitreal injection of triamcinolone acetonide combined with laser photocoagulation for diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To investigate the clinical efficacy of retrobulbar or intravitreal injection of triamcinolone acetonide combined with 532nm laser photocoagulation in the treatment of diabetic macular edema(DME). <p>METHODS: Sixty-two eyes in 40 DME patients were divided into two groups(Group A and Group B)randomly. Thirty-one eyes in Group A were treated with retrobulbar injection of triamcinolone acetonide(RBTA)and 31 eyes in Group B were treated with intravitreous injection of triamcinolone acetonide(IVTA). Eyes with limited macular edema were treated by local direct retinal laser, those with diffuse and cystic macular edema were treated by grid retinal laser using Vitra 532nm fundus lasers at 1mo after injection. Visual acuity, intraocular pressure, fundus, macular edema and complications were recorded after 1wk, 1, 3 and 6mo in the follow-up study. <p>RESULTS: The mean best corrected visual acuity was improved and macular edema subsided after treatment in the two groups in the follow-up study at 1wk, 1, 3 and 6mo(<i>P</i><0.05), while there had no significant difference between groups(<i>P</i>>0.05). In Group A, significant efficiency rate was 39%(12/31), total effective rate was 90%(28/31). In Group B, significant efficiency rate was 39%(12/31), total effective rate was 94%(29/31). The follow-up study showed no retinal detachment, endophthalmitis, intraocular hemorrhage and other complications. <p>CONCLUSION: Triamcinolone acetonide injection combined with laser photocoagulation is an effective method for treatment of DME with significant effect, less adverse reactions, patient's vision improved effectively and macular edema reduced. No significant difference was noted in the treatment of DME between RBTA and IVTA.

Improved Intravitreal AAV-Mediated Inner Retinal Gene Transduction after Surgical Internal Limiting Membrane Peeling in Cynomolgus Monkeys.

The retina is an ideal target for gene therapy because of its easy accessibility and limited immunological response. We previously reported that intravitreally injected adeno-associated virus (AAV) vector transduced the inner retina with high efficiency in a rodent model. In large animals, however, the efficiency of retinal transduction was low, because the vitreous and internal limiting membrane (ILM) acted as barriers to transduction. To overcome these barriers in cynomolgus monkeys, we performed vitrectomy (VIT) and ILM peeling before AAV vector injection. Following intravitreal injection of 50 µL triple-mutated self-complementary AAV serotype 2 vector encoding EGFP, transduction efficiency was analyzed. Little expression of GFP was detected in the control and VIT groups, but in the VIT+ILM group, strong GFP expression was detected within the peeled ILM area. To detect potential adverse effects, we monitored the retinas using color fundus photography, optical coherence tomography, and electroretinography. No serious side effects associated with the pretreatment were observed. These results indicate that surgical ILM peeling before AAV vector administration would be safe and useful for efficient transduction of the nonhuman primate retina and provide therapeutic benefits for the treatment of retinal diseases.

Prevalence of outer retinal tubulation in eyes with choroidal neovascularization.

BACKGROUND: Outer retinal tubulations (ORTs) are branching tubular structures located in the outer nuclear layer of the retina. The goal of this study is to determine the prevalence of ORTs observed in eyes with choroidal neovascularization (CNV) undergoing treatment with anti-angiogenic intravitreous injection (IVI) with anti-VEGF (vascular endothelial growth factor) at the Ophthalmology Department of a tertiary hospital in São Paulo, Brazil. METHODS: This is a descriptive study based on medical charts and Spectral-domain Optical Coherence Tomography (Sd-OCT) scans of 142 patients (158 eyes) treated between 2012 and 2014 with IVI of anti-VEGF for CNV. The patients' data was analysed according to age, gender, pathology, presence of ORTs, and best corrected visual acuity (BCVA). Patients with and without ORTs were compared according to the last BCVA obtained using Chi square corrected by the Yates factor. RESULTS: ORTs were found in a total of 40 out of 158 eyes (25.31 %) with CNV; in 33 out of 119 eyes (27.7 %) with neovascular age-related macular disease (AMD); in 5 out of 8 eyes (62.5 %) with neovascular angioid streaks; and in 2 out of 12 eyes (16.67 %) with myopic neovascular membranes. Most patients with ORTs had BCVA worse than 20/200, significantly worse BCVA than patients without ORTs. CONCLUSIONS: Recent studies have considered that the presence of ORTs is indicative of a photoreceptor degeneration process and may represent a final stage of multiple retinal degenerative pathologies. The prevalence of ORTs in eyes with CNV has not been well described, especially when considering the Brazilian population treated in a public health care system. In our study, ORTs were observed in only three different pathologies: neovascular AMD, neovascular angioid streaks and myopic neovascular membranes. The correct recognition of ORTs is fundamental for its differentiation from intraretinal cysts, for the latter is related to the activity of neovascular diseases, and usually guides anti-angiogenic therapy. We conclude that ORTs have a high prevalence in the population studied, and their correct identification presents relevant therapeutic implications.

Are you ready? The new era of targeted local chemotherapy for retinoblastoma is coming / 中华实验眼科杂志

Retinoblastoma (RB) therapy has evolved over decades.In the 1970s, enucleation was important for improving life prognosis.In the 1980s, external beam radiotherapy (EBRT) was popular.In the 1990s, systemic intravenous chemotherapy (IVC) was introduced and currently remains prevalent worldwide for intraocular RB control as well as prevention of systemic metastasis.However, RB seeds in vitreous and subretinal space are still the major obstacles for successful treatments.Advanced ophthalmic imaging technology promotes thorough and detailed description and observation of RB seeds.In the 2000s, interests in periocular chemotherapy (POC), intra-arterial chemotherapy (IAC) and intravitreous chemotherapy (IVitC) have been explored to overcome the low drug concentration around the seeds and to reduce the systemic side effects.This leads us into a new era of target local chemotherapy of RB.How to make the treatment decision based on biological behavior of RB seeds is a major task for us now.

Observation and nursing of intravitreous injection of Avastin combined with laser photocoagulation for macular edema induced by vein occlusion / 中国实用护理杂志

Objective To investigate the treatment effect and nursing of intravitreous injection of Avastin combined with laser photocoagulation in macular edema caused by vein occlusion.Methods 38 patients(38 macular edema eyes)who had macular edema caused by retinal vein occlusion and accepted intravitreous injection of Avastin combined with laser photocoagulation were selected.Relevant nursing was given before and after the clinical treatment.The visual acuity and retinal thickness were observed and recorded.Results Visual acuity was improved in 36 eyes(94.7％),no change occurred in 2 eyes(5.3％).The thickness of macular was statistically significant compared with before treatment and 2,4,6 weeks after treatment.Conclusions Intravitreous injection of avastin combined with laser photocoagulation is effective on macular edema caused by vein occlusion.Successful treatment is guaranteed by psychological nursing,treatment guidance and health guidance.

The effect of triamcinolone acetonide by single intravitreous injection or repeatedly sub-Tenoninfusion on relieving diabetic macular oedema / 眼科

Objective To study the efficacy of intravitreous injection (IVI) or sub-Tenaninfusion (STi) of triamcinolone acetonide (TA) for diabetic macular oedema. Design Retrospective cases series. Participants 37 cases (37 eyes) with diabetic macular oedema confirmed by fundus fluorescence angiography (FFA) and optical coherence tomography (OCT). Methods Patients were received 4mg TA by single intravitreous injection or 40mg TA by three times sub-Tenoninfusion at 0d, 2w, 4w. The best corrected visual acuity, fundus examination, intraocular pressure, fundus fluorescence angiography were further analyzed, and the retinal thickness of macular fovea were measured by OCT. Main Outcome Measures The visual acuity, thickness of retinal macular fovea, ocular pressure was measured. Results 32 cases (32 eyes) completed the 24 week followed-up. In group IVI, the visual acuity before and after injection was 0.10±0. 03, 0.24±0.06(F=15.459, P=0.000) respectively; and retinal thickness of macular fovea is(460.73±46.33)μm,(394.53±41.43)μm (F=25. 282, P=0.0000) respectively. But in group STi, the visual acuity before and after injection is 0.11±0.04, 0.18±0.07(F=6.989, P=0.000) accordingly; and retinal thickness of maculur fovea is (454.76±56.28)μm,(424.94±42.69)μm (F=5.145, P=0.000) respectively. There was obvious statistical significance between two methods at same time point(all P<0.05). The serious, irreversible complications had not been found in all patients during follow-up. Conclusion Triamcinolone acetonide by single intravitreous injection or repeatedly sub-Tenoninfasion are good ways to relieve diabetic macular oederna, IVA-TA is more effective, and STi-TA safer. (Ophthaimol CHN, 2009, 18: 246-250)

Clinical Observation on Exogeneous Endophthalmitis

PURPOSE: To evaluate the effectiveness of intravitreous injection of Vancomycin and Amikacin in exogenous endophthalmitis (before culture results are obtained), and the relationship between such empirical therapy and results of culture, susceptibilities of cultured organism to antibiotics, and visual prognosis. METHODS: The authors conducted a retrospective study of 23 patients (23 eyes) who had been treated for endophthalmitis between May 1996 and November 2000. RESULTS: The final vision was 0.15 and better in 18 eyes out of 23 eyes, and 5 eyes reported vision worse than 0.1. Endophthalmitis was associated with cataract surgery in 15 eyes, ocular traumja in 7 eyes, filtration surgery in 1 eye. Eyes with posttraumatic endophthalmitis had worse visual prognosis. When smear and culture was performed, 14 out of 23 eyes were tested positive, and all the obtained microorganisms showed sensitivity to vancomycin and amikacin. The results were similar between Gram positive and negative bacteria. When the onset of symptoms was within 1 week after intraocular operation, and when the patients with ocular trauma reported to the hospital within two days, the prognosis was relatively better. The use of intravitreous antibiotics alone yielded similar results compared to the use of combined systemic antibiotics. Two out of 5 eyes which underwent vitrectomy and 16 out of 18 eyes which did not undergo vitrectomy reported final vision of 0.15 or better. CONCLUSIONS: When endophthalmitis is suspected, one should immediately perform diagnostic workup and the patient is immediately given intravitreous injection of vancomycin and amikacin. When smear and culture results are obtained later on, one can modify and improve the treatment modalities in an attempt to improve visual prognosis.