Intravitreal Drug Injections Research Articles

Effects on corneal endothelium of intravitreal injection of anti-VEGF drugs

Purpose Intravitreal drug administration has become the gold standard for the treatment of many retinal diseases, including age-related macular degeneration (AMD), diabetic retinopathy (DR) and retinal vein occlusion (RVO). The frequency of this procedure has increased significantly after the introduction of anti-VEGF drugs, since the rise in the average age of the population, which is closely correlated with these diseases. In order to ensure therapeutic success in these patients with chronic retinal diseases, intravitreal treatment with anti-VEGF requires a long-term maintenance regimen with repeated administrations. For this reason today, we must consider the risks linked to complications associated with the long-term application of this therapy. Our study aims to investigate whether the intravitreal injection of anti-VEGF may lead to damage to the corneal endothelium, either directly through the administration procedure or indirectly due to the drug’s toxicity. We aimed to establish a clear correlation between intravitreal drug administration and a statistically significant reduction in corneal endothelial cell count in the treated eye when compared to the untreated eye. The study also sought to assess whether different toxicities might be present between different types of drugs belonging to the same anti-VEGF family. Materials and Methods The study was conducted by examining a cohort of 133 patients suffering from different diseases: AMD, EMD and RVO. All patients underwent measurement of the endothelial count with CellChek® 20, considering the value measured at the first injection as time zero and reassessed at each subsequent treatment session. The measurement of the endothelial count was performed both on the eye under treatment (TE) and in the eye not undergoing intravitreal injection (NTE) with anti-VEGF drugs for each injection cycle. Different anti-VEGF drugs such as Bevacizumab, Ranibizumab, Aflibercept, Brolucizumab were used for intravitreal therapy. The test patients were included in a 12-month follow-up programme, in which the measurement intervals are dictated by the treatment plan. Results The statistical analysis performed on the corneal endothelial cell counts showed that the ECD (endothelial cell density) parameter decreases with each administration of the drug. The analysis of the difference in the mean endothelial cell counts of the TE reveals that the difference in the number of endothelial cells between the first and second counts in TE is 54.00; greater than the difference in the number of cells found in NTE, which was 13.42. Both the difference between the TE and NTE cell counts are statistically significant. In the case of the TE, the p-value is <0.001, while in the case of the NTE the p-value is still significant as <0.05. The hypothesis that the different types of anti-VEGF drugs could determine the decrease in endothelial cell count differently was also evaluated. No statistically significant data emerged from the analyses (p-value is >0.05). Conclusions The study demonstrated a statistically significant reduction of corneal endothelial cells in patients undergoing intravitreal injection treatment per number of injections with anti-VEGF, this reduction being independent of the type of anti-VEGF used (Bevacizumab, Ranibizumab, Aflibercept and Brolucizumab).

In Vitro Models of Diabetes: Focus on Diabetic Retinopathy.

Diabetic retinopathy is a major eye complication in patients with diabetes mellitus, and it is the leading cause of blindness and visual impairment in the world. Chronic hyperglycemia induces endothelial damage with consequent vascular lesions, resulting in global vasculitis, which affects the small vessels of the retina. These vascular lesions cause ischemic conditions in certain areas of the retina, with a consequent increase in the release of pro-angiogenic mediators. In addition to pharmacological interventions for controlling the blood glycaemic level, the main strategies for treating diabetic retinopathy are the intravitreal injections of drugs, surgical treatments, and vitrectomies. The complexity of diabetic retinopathy is due to its close interactions with different cell types (endothelial cells, astrocytes, and Müller cells). The evaluation of the efficacy of novel pharmacological strategies is mainly performed through in vivo models. However, the use of different animal species leads to heterogenic results and ethical concerns. For these reasons, the development of new and reliable in vitro models, such as cell co-cultures and eye organoids, represents an urgent need in this area of research. This review features an overview of the in vitro models used to date and highlights the advances in technology used to study this pathology.

Efficacy of anti-VEGF intravitreal injection in traumatic submacular hemorrhage: a retrospective study.

In this study we investigated the efficacy of short-term intravitreal injections of anti-vascular endothelial growth factors (anti-VEGF) in treating traumatic submacular hemorrhage. A total of 115 patients were diagnosed with submacular hemorrhage between 2018 and 2022 at Shenzhen Eye Hospital. In a retrospective analysis, we examined 13 of these patients who presented with submacular hemorrhage and choroidal rupture due to ocular trauma. Eight patients were treated with intravitreal anti-VEGF injection and 5 with oral drugs. We systematically analyzed changes in their ocular conditions pre and post-treatment. The evaluations encompassed best-corrected visual acuity (BCVA), optical coherence tomography, fundus fluorescein angiography, and retinal imaging. The 13 patients diagnosed with submacular hemorrhage comprised of 10 males and 3 female, with their age ranging between 27 and 64years, with an average age of 38.1years (standard deviation [SD]: 11.27). A statistically significant reduction in central foveal thickness (CFT) was observed following intravitreal injections of anti-VEGF drugs (P = 0.03). In control group, the CFT was reduced without statistical significance (P = 0.10). The BCVA of the patients in treatment group improved significantly from 1.15 (SD: 0.62. Range: 0.4-2) to 0.63 (SD: 0.59. Range: 0.1-1.6), indicating an average increase of 4.13 lines (SD: 3.36. Range: 0-9) as measured by the visual acuity test using an eye chart (P = 0.01). The difference between baseline visual acuity and final visual acuity was not statistically significant in control group (P = 0.51). Short-term administration of anti-VEGF drugs exhibited significant efficacy in reducing submacular hemorrhage following ocular trauma and enhancing visual acuity.

Anti-angiogenic and antioxidant effects of axitinib in human retinal endothelial cells: implications in diabetic retinopathy.

Diabetic retinopathy is a secondary microvascular complication of diabetes mellitus. This disease progresses from two stages, non-proliferative and proliferative diabetic retinopathy, the latter characterized by retinal abnormal angiogenesis. Pharmacological management of retinal angiogenesis employs expensive and invasive intravitreal injections of biologic drugs (anti-vascular endothelial growth factor agents). To search small molecules able to act as anti-angiogenic agents, we focused our study on axitinib, which is a tyrosine kinase inhibitor and represents the second line treatment for renal cell carcinoma. Axitinib is an inhibitor of vascular endothelial growth factor receptors, and among the others tyrosine kinase inhibitors (sunitinib and sorafenib) is the most selective towards vascular endothelial growth factor receptors 1 and 2. Besides the well-known anti-angiogenic and immune-modulatory functions, we hereby explored the polypharmacological profile of axitinib, through a bioinformatic/molecular modeling approach and in vitro models of diabetic retinopathy. We showed the anti-angiogenic activity of axitinib in two different in vitro models of diabetic retinopathy, by challenging retinal endothelial cells with high glucose concentration (fluctuating and non-fluctuating). We found that axitinib, along with inhibition of vascular endothelial growth factor receptors 1 (1.82 ± 0.10; 0.54 ± 0.13, phosphorylated protein levels in fluctuating high glucose vs . axitinib 1 µM, respectively) and vascular endothelial growth factor receptors 2 (2.38 ± 0.21; 0.98 ± 0.20, phosphorylated protein levels in fluctuating high glucose vs . axitinib 1 µM, respectively), was able to significantly reduce (p < 0.05) the expression of Nrf2 (1.43 ± 0.04; 0.85 ± 0.01, protein levels in fluctuating high glucose vs . axitinib 1 µM, respectively) in retinal endothelial cells exposed to high glucose, through predicted Keap1 interaction and activation of melanocortin receptor 1. Furthermore, axitinib treatment significantly (p < 0.05) decreased reactive oxygen species production (0.90 ± 0.10; 0.44 ± 0.06, fluorescence units in high glucose vs . axitinib 1 µM, respectively) and inhibited ERK pathway (1.64 ± 0.09; 0.73 ± 0.06, phosphorylated protein levels in fluctuating high glucose vs . axitinib 1 µM, respectively) in HRECs exposed to high glucose. The obtained results about the emerging polypharmacological profile support the hypothesis that axitinib could be a valid candidate to handle diabetic retinopathy, with ancillary mechanisms of action.

Long-term dynamic changes and influencing factors of corneal morphology after multiple intravitreal injections of anti-VEGF drugs.

To observe alterations in corneal morphology caused by repeated intravitreal injections of anti-vascular endothelial growth factor (VEGF). Prospective cohort study. Seventy-seven eyes were treated with intravitreal injection of anti-VEGF from June 2021 to March 2023. There were 25 eyes of neovascular age-related macular degeneration (nAMD), 24 eyes of diabetic macular edema (DME), and 28 eyes of retinal vein occlusion (RVO). Aflibercept was used in 37 eyes and Ranibizumab was used in 40 eyes. 3 + PRN was used. Corneal endothelium and corneal thickness were measured using a corneal endothelial microscope. The data related to central corneal thickness, corneal endothelial cell density (ECD), average cell size, coefficient of variation (CV), proportion of hexagonal cells (Hex%) was collected. A comparison was also made between baseline and the dynamic changes of all indexes 1 year following the last injection. It was observed that in comparison to baseline, ECD and Hex% decreased significantly after the 3rd injection of Aflibercept and Ranibizumab. However, ECD did not decrease further and remained at the same level as after the last injection. Hex% and average cell size increased to a certain extent in comparison to the last injection. All the changes were found to be statistically significant (P < .01). After 3 injections, ECD in DME group was markedly lower than that in nAMD and RVO group, but the CV in DME group was higher than that in nAMD as well as RVO groups, and all the differences were statistically significant (P < .05). Following intravitreal anti-VEGF therapy, DME is more likely than other disorders to result in a decrease in ECD. Repeated intravitreal injections of anti-VEGF drugs can reduce the Hex% and ECD to a certain extent. After the last injection, Hex% can progressively recover, and ECD can remain stable without further declining. After injections, ECD in DME group was found to be significantly lower than that in nAMD and RVO groups, but CV in DME group was significantly higher in comparison to the other 2 groups. In patients with macular edema, repeated intravitreal injections of anti-VEGF may have certain effects on corneal morphology. Patients with diabetes mellitus in particular should pay special attention to corneal safety following repeated intravitreal injections if they have significantly reduced ECD at baseline.

Drug Distribution After Intravitreal Injection: A Mathematical Model.

Intravitreal injection of drugs is commonly used for treatment of chorioretinal ocular pathologies, such as age-related macular degeneration. Injection causes a transient increase in the intraocular volume and, consequently, of the intraocular pressure (IOP). The aim of this work is to investigate how intravitreal flow patterns generated during the post-injection eye deflation influence the transport and distribution of the injected drug. We present mathematical and computational models of fluid motion and mass transport in the vitreous chamber during the transient phase after injection, including the previously unexplored effects of globe deflation as ocular volume decreases. During eye globe deflation, significant fluid velocities are generated within the vitreous chamber, which can possibly contribute to drug transport. Pressure variations within the eye globe are small compared to IOP. Even if significant fluid velocities are generated in the vitreous chamber after drug injection, these are found to have negligible overall effect on drug distribution.

Сравнительная оценка загрузочных инъекций анти-VEGF препаратов при васкулярных отслойках ретинального пигментного эпителия

Purpose. To compare of the effectiveness of anti-VEGF therapy in patients with exudative form of age-related macular degeneration (AMD). Material and methods. This study included 30 patients (30 eyes) with the exudative form of AMD. Standard ophthalmological examination methods and additional methods were carried out: optical coherence tomography (OCT) and OCT-angiography using the Spectralis HRA+OCT device “Heidelberg Engineering” (Germany) in standard mode. The patients were divided into two groups depending on the anti-VEGF drug: group I (15 eyes) — patients receiving aflibercept (Eylea, Bayer, Germany); group II (15 eyes) — patients who received faricimab (Vabismo, F. Hoffman-La Roche Ltd, Switzerland). All patients received loading intravitreal injections (IVI) of anti-VEGF drugs: 3 IVI of aflibercept or 4 IVI of faricimab. Data were assessed before the start of treatment, 1 month after the start of treatment and after loading injections. Results. In groups I and II, after the first intravitreal injection, there was a decrease in the height of the retinal pigment epithelium detachment and the central thickness of the retina, and an increase in visual acuity. In both groups, after loading injections, compared with the beginning of the study, the height of the retinal pigment epithelium detachment decreases and the thickness of the central zone of the retina decreases, and visual functions stabilize. Conclusions. Antiangiogenic therapy is an effective treatment for neovascular AMD. Despite the fact that intravitreal injections of anti-VEGF drugs stabilize visual acuity and improve morphological parameters, longer observation periods are required to further evaluate the effectiveness of anti-VEGF therapy. Keywords: retinal pigment epithelium detachment, age-related macular degeneration, antiVEGF therapy

Комбинированный метод лечения рефрактерного диабетического макулярного отека

Purpose. To determine the effectiveness of the anatomical and functional results of treatment of refractory diabetic macular edema after removal of the inner limiting membrane using the latest generation anti-VEGF drug. Material and methods. We examined 6 patients with 1st type and 2nd type diabetes mellitus. The average age of the subjects was 47.45 ± 27.15 years. Of these, there were 4 women and 2 men. 1st type diabetes mellitus was detected in 2 people, in other patients — 2nd type. 3 patients had previously undergone pan-retinal photocoagulation (from 1st to 2nd stages). All patients received intravitreal injections (anti-VEGF) of Eylea (4–5 injections) during the last year. According to the optical coherence tomogram (OCT), macular edema was recorded, recurring on average after 1.36 ± 0.85 months. All patients underwent surgical treatment. In the presence of lens opacity, surgical treatment was started with phacoemulsification of cataracts. A microinvasive subtotal vitrectomy was performed with the removal of the posterior layers of the vitreous body and proliferative membranes fixed to the retina. The removal of the inner boundary membrane was performed after its staining in the size of two to three diameters of the optic disc without any tamponade. After 2 months, two patients had an increase in retinal thickness in the fovea. These patients received one injection of Vabismo. Results. The compared groups did not differ in morphofunctional characteristics. In the postoperative period, there was a tendency to increase visual acuity and decrease retinal thickness, regression of hard exudates in 4 patients. In 2 patients, an increase in retinal thickness in the fovea was noted after 2 months. After intravitreal injection of the latest generation anti-VEGF drug (Vabismo), these patients also showed an increase in visual acuity, regression of solid exudates and a decrease in retinal thickness. Conclusion. Microinvasive subtotal vitrectomy with removal of the inner limiting membrane in combination with intravitreal injection of the latest generation anti-VEGF drug (Vabismo) is an effective method of treating refractory diabetic macular edema. Keywords: anti-VEGF, Vabismo, diabetic macular edema, intravitreal injections, optical coherence tomogram, subtotal vitrectomy, inner boundary membrane

Potential Mechanism of Platelet GPIIb/IIIa and Fibrinogen on Retinal Vein Occlusion

Purpose To explore the role of coagulation and fibrinolytic factors, and the potential mechanism of platelet aggregation in the pathogenesis of retinal vein occlusion. Methods Coagulation and fibrinolytic parameters in patients with retinal vein occlusion were determined using hemagglutinin and HISCL-5000. Relationships between these elevated parameters and factors representing typical clinical manifestations of retinal vein occlusion were examined, and these parameters were analyzed using a STRING database to indicate the potential role of platelet aggregation. Platelet glycoprotein IIb/IIIa (GPIIb/IIIa) levels were evaluated by flow cytometry after antiplatelet treatment in patients and mouse models. Furthermore, the GPIIb/IIIa ligand fibrinogen in peripheral blood and retina of mouse models was assessed by the turbidimetric method and real-time PCR, respectively. Results In patients, significant increases in peripheral blood fibrinogen and GPIIb/IIIa levels were observed (p = 0.0040, p < 0.0001, respectively). A positive correlation was observed between macular thickness (MT) and both fibrinogen and GPIIb/IIIa (r = 0.4528, p = 0.0063; r = 0.3789, p = 0.0427, respectively). After intravitreal injections of anti-vascular endothelial growth factor drugs, a significant reduction in fibrinogen levels was observed (p = 0.0072). In addition, the use of antiplatelet drugs resulted in a significant decrease in GPIIb/IIIa (p < 0.0001). In a mouse model, antiplatelet therapy significantly reduced both peripheral blood and retina fibrinogen levels and the overall rate of vein occlusion 3 days after occlusion (p < 0.0005). In addition, the reduction in GPIIb/IIIa levels after antiplatelet therapy was remarkable. Conclusion Fibrinogen and GPIIb/IIIa may be involved in retinal vein occlusion and blocking platelet aggregation may be a new therapeutic approach for retinal vein occlusion.

Recent Advances in Nanomedicine for Ocular Fundus Neovascularization Disease Management.

As an indispensable part of the human sensory system, visual acuity may be impaired and even develop into irreversible blindness due to various ocular pathologies. Among ocular diseases, fundus neovascularization diseases (FNDs) are prominent etiologies of visual impairment worldwide. Intravitreal injection of anti-vascular endothelial growth factor drugs remains the primary therapy but is hurdled by common complications and incomplete potency. To renovate the current therapeutic modalities, nanomedicine emerged as the times required, which is endowed with advanced capabilities, able to fulfill the effective ocular fundus drug delivery and achieve precise drug release control, thus further improving the therapeutic effect. This review provides a comprehensive summary of advances in nanomedicine for FND management from state-of-the-art studies. First, the current therapeutic modalities for FNDs are thoroughly introduced, focusing on the key challenges of ocular fundus drug delivery. Second, nanocarriers are comprehensively reviewed for ocular posterior drug delivery based on the nanostructures: polymer-based nanocarriers, lipid-based nanocarriers, and inorganic nanoparticles. Thirdly, the characteristics of the fundus microenvironment, their pathological changes during FNDs, and corresponding strategies for constructing smart nanocarriers are elaborated. Furthermore, the challenges and prospects of nanomedicine for FND management are thoroughly discussed.

Comparative study of the three-dimensional perception of videos recorded on a "Do it yourself" three-dimensional recording assembly versus the conventional recording system.

To develop an indigenous "Do it yourself" (DIY) three-dimensional (3D) ophthalmic surgery recording system and validate the perception of stereopsis using it. A cross-sectional survey of practicing ophthalmologists with post-postgraduation experience of at least 5 years for perception of stereopsis for three different surgeries was performed; cataract, retinal detachment, and intravitreal drug injection were recorded on DIY assembly, viewed on VRBOX and using laptop videos and pseudo 3 d videos as control. The laptop videos and 3D VR Box videos received higher ratings for stereopsis than the pseudo 3D videos. The parameters that received significantly higher ratings on the 3D VR Box viewing were instrument's position relative to the ocular surface in cataract surgery, anterior chamber depth during capsular staining, ophthalmic visco-surgical device injection, capsulorhexis, phaco tunnel depth, movement of nuclear fragments in the anterior chamber, and intra-ocular lens tilt in the capsular bag during cataract surgery ( P < 0.05). In scleral buckling surgery, the parameters that were significantly rated higher on VR Box were globe contour, separation of the scleral plane from muscle, and explant plane ( P < 0.05). Furthermore, the depth of the needle in the vitreous cavity while administering intravitreal drug injection was also rated significantly higher on VR Box ( P < 0.05). However, the ratings for the depth of corneal incision, depth of scleral incision, overall color, and overall quality were not different statistically when compared between laptop and VR Box viewing. DIY 3D recording assembly offers a superior means of appreciating depth at various stages of cataract surgery, scleral buckling, and intravitreal drug injection when compared to laptop viewing and can serve as an effective tool for skill transfer.

Fungal Endophthalmitis: Clinical Characteristics, Pathogens, and Factors Affecting Visual Outcome.

The aims of this study are to investigate the etiology, microbiological spectrum, and risk factors associated with visual outcomes of fungal endophthalmitis (FE) in a tertiary eye specialty hospital in Shanghai, China. This was a retrospective, single-center case series. The clinical characteristics, etiology, microbiological spectrum, and management, as well as the visual outcomes, were analyzed. Logistic regression was used to analyze the factors related to visual outcomes. This study involved 102 eyes of 92 patients with FE, including 63 males (66.3%). The mean age was 44.4 ± 19.8 years. The most common etiology of FE was trauma (56.5%). The predominant fungal species isolated were Aspergillus spp. (31/93, 33.3%). Pars plana vitrectomy (PPV) and intravitreal antifungal agents was performed initially in 86 (84.3%) and 83 (81.4%) eyes, respectively. Only 35 (34.3%) eyes achieved final best corrected visual acuity (BCVA) of 20/400 or better. Ten (9.8%) eyes had a final BCVA of light perception or worse, and five (4.9%) had to be enucleated. The factors determining better visual outcomes included initial visual acuity better than finger-counting (FC) (odds ratio (OR) 5.811, p = 0.036), the absence of corneal infiltrate (OR 10.131, p = 0.002), and Candida species infection (OR 6.325, p = 0.011). Early diagnosis of FE and a timely vitrectomy, combined with an intravitreal injection of an antifungal drug, can mitigate the devastating results of intraocular fungal infection. Not being infected by Aspergillus spp., an initial BCVA that was no worse than FC, and the absence of corneal involvement were related to better visual prognosis.

Современный подход к хирургическому лечению травматических субретинальных макулярных кровоизлияний с разрывом хориоидеи (серия наблюдений)

The selection of management strategy for closed globe injury with massive submacular hemorrhage (SMH) remains a pertinent issue, particularly in the context of the advent and improvement of surgical techniques. These patients typically maintain an active lifestyle and are highly demanding with regard to vision. Moreover, existing observational approaches and passive management of SMH are unacceptable for them. This paper describes two patients with closed globe injuries accompanied by SMH and significant vision loss. The active management strategy employed for these patients (pneumodislocation plus enzymatic lysis) was analyzed based on the results of optical coherence tomography, eye fundus photography, and visual acuity measurement. The intravitreal injection of drugs and a gas-air mixture resulted in a significant improvement of visual acuity due to the displacement of the subretinal blood clot to the extramacular area, reduction in the height and area of hemorrhage, and elimination of the toxic effect of blood elements on the retinal pigment epithelium and photoreceptors. This management strategy for SMH helps improve vision in a short time interval and to reduce potential negative effects of this condition. KEYWORDS: subretinal hemorrhage, closed globe injury, choroidal rupture, intravitreal injection, tissue plasminogen activator, commotio retinae. FOR CITATION: Seleznev A.V., Amashova U.L., Brezhnev A.Yu., Nagornova Z.M., Egorova A.C., Kuroyedov A.V. Contemporary approach to the surgical management of traumatic submacular hemorrhage with choroidal rupture (case series). Russian Journal of Clinical Ophthalmology. 2024;24(2):94–100 (in Russ.). DOI: 10.32364/2311-7729-2024-24-2-9.

Topical application of hypotensive drugs for the prevention of intraocular pressure elevation after intravitreal injections of anti-VEGF drugs

This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD. The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection. Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001). Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.

Treatment of neovascular age-related macular degeneration with anti-vascular endothelial growth factor drugs: progress from mechanisms to clinical applications.

Neovascular age-related macular degeneration (nARMD) is an important cause of visual impairment and blindness in the elderly, with choroidal neovascularization in the macula as the main pathological feature. The onset of nARMD is closely related to factors including age, oxidative stress, and lipid metabolism. Vascular endothelial growth factor (VEGF) is an important factor contributing to nARMD as well as choroidal neovascularization and retinal leakage formation. At present, anti-VEGF therapy is the only treatment that improves vision and halts disease progression in most patients, making anti-VEGF drugs a landmark development for nARMD treatment. Although intravitreal injection of anti-VEGF drugs has become the first-line treatment for nARMD, this treatment has many shortcomings including repeated injections, poor or no response in some patients, and complications such as retinal fibrosis. As a result, several new anti-VEGF drugs are being developed. This review provides a discussion of these new anti-VEGF drugs for the treatment of nARMD.

Changes in intraocular pressure and biometric parameters of the anterior segment of the eye after intravitreal injections

This study compares the changes in the parameters of the anterior chamber of the eye using anterior segment optical coherence tomography (AS-OCT) in patients with a natural and artificial lens after treatment of neovascular age-related macular degeneration (nAMD) by multiple intravitreal injections (IVI) of anti-VEGF drugs. The patients were divided into 2 groups: group 1 (control) included 30 patients (30 eyes) with a natural lens, group 2 - 30 patients (30 eyes) with an intraocular lens (IOL). AS-OCT was performed using the Revo NX tomograph (Optopol, Poland) to analyze anterior chamber depth (ACD) and the parameters of anterior chamber angle (ACA). Intraocular pressure (IOP) was measured with a contact tonometer ICare Pro. In patients with an IOL, the IOP level 1 minute after intravitreal injection (IVI) of an anti-VEGF drug was statistically lower than in the control group, on average by 17.8% during the first IVI and by 28.7% after 1 year of observation (p<0.001). ACD before treatment was statistically significantly higher in patients with IOL compared to patients of group 1 by an average of 39.3% (p<0.001). ACA from the nasal and temporal sides in the meridian 0°-180° before the start of treatment was statistically significantly wider in phakic patients than in the control group, by an average of 15.9±9.3° (p<0.001) and 16.9±8.2° (p<0.001), respectively. According to AS-OCT, there was no shift of the iris-lens diaphragm in patients with an IOL after multiple IVI of an anti-VEGF drug, in contrast to the control group. AS-OCT was used to determine for the first time the changes in the parameters of the anterior chamber of the eye in patients with a natural and artificial lens after multiple injections of an anti-VEGF drug in the treatment of nAMD.

Bibliometric and visualized analysis of diabetic macular edema.

Our aim was to identify recent research trends on diabetic macular edema (DME) and focus on publications from different countries, institutions, and authors. We retrieved and analyzed data from January 1, 2003 to December 31, 2022 on the DME research field from the Web of Science Core Collection (WoSCC) database. Microsoft Excel and VOSviewer were applied to perform visualization analysis and evaluate the trends. A total of 4482 publications were identified, and the annual global publications increased steadily, from 36 to 390, during this period. The United States (1339 publications, 71,754 citations), Johns Hopkins University (176 publications, 17,015 citations), and Bressler NM (76 publications, 9621 citations) were the most influential and productive countries, institutions, and authors, respectively. The top 100 keywords were classified into five clusters: (1) therapy and adverse effects of DME; (2) clinical biomarkers of DME; (3) mechanistic research on DME; (4) improving bioavailability and efficacy; and (5) early diagnosis of diabetic complications. "Diabetic macular edema," "retinopathy," "ranibizumab," and "optical coherence tomography angiography" were the most frequent keywords. Regarding the average appearing years (AAYs) of the keywords, "deep learning" (AAY:2020.83), "optical coherence tomography angiography" (AAY:2019.59), "intravitreal Aflibercept" (AAY:2019.29), and "dexamethasone implant" (AAY:2019.20) were recognized as the hotspots of the DME research area in the short run. In the past two decades, the United States was in master status in DME research. Although intravitreal drug injection has been the mainstream therapy for a long time, the effectiveness of different drugs, such as dexamethasone, new solutions for drug delivery, such as intravitreal implantation, and more accurate tools for the classification and follow-up of DME patients, such as deep learning systems, are still research hotspots.

A comprehensive overview of diagnosis, imaging and treatment of vitreoretinal lymphoma.

Vitreoretinal lymphoma (VRL) is a rare B-cell intraocular neoplasia characterized by poor long-term prognosis and lack of effective therapies. It mainly involves the vitreous humor, the retina, and the retinal pigment epithelium (RPE), although anterior segment involvement can occur. VRL is classified as a lymphoma of immune privileged sites, along with testis lymphoma and primary central nervous system lymphoma (PCNSL). VRL and PCNSL are strictly connected indeed: 80% of VRL develop PCNSL, while 20% of patients with PCNSL present VRL during natural history of lymphoma. Due to the lack of worldwide consensus about diagnosis, therapy, and follow-up timing, VRL represents one of the most challenging ocular affections.VRL commonly masquerades as a posterior uveitis, and misdiagnosis often occurs because of partial response to topical steroids. Gold standard for diagnosis is cytological analysis of vitreous humor. However, this technique lacks sensitivity and supplemental molecular analyses can improve the diagnostic process. Multimodal imaging allows ophthalmologists to empower their clinical suspicion and a comprehensive examination can highlight typical features of VRL and justify further invasive procedures.There is no consensus about VRL therapy, and none of the therapeutical scheme has demonstrated to prevent cerebral involvement and improve patient's overall survival. Intravitreal injections of chemotherapeutics drugs, ocular radiation therapy and systemic chemotherapy can be considered in the treatment of VRL. Once cerebral involvement occurs, systemic chemotherapy must be included in the treatment as a life-saving therapy. Further multicentric studies are required to find out the best treatment of patients with VRL.

Immediate effect of anti-VEGF injections on optic nerve head: Correlation between intraocular pressure and anatomical peripapillary changes.

This study was designed to investigate retinal nerve fiber layer (RNFL) and radial peripapillary capillaries (RPC) changes on optical coherence tomography (OCT) angiography and OCT thickness alterations associated with acutely increased intraocular pressure after intravitreal injections. This observational clinical study was conducted on 35 eyes (35 patients) with treatment-naïve age-related macular degeneration (AMD) and type 1 or type 2 MNV were enrolled. All patients underwent anti-vascular endothelial grow factor (VEGF) intravitreal injections with 0.05-mL aflibercept (2 mg) between January 2022 and October 2022. Peripapillary OCT angiography perfusion density, retinal nerve fiber layer thickness, and intraocular pressure (IOP) were measured before and immediately after intravitreal injections. In particular, the analysis was performed at the following visits: (T0) 5 to 15 min before the injection of aflibercept; (T1) 2 to 5 min after the injection of aflibercept. Paired t-test was used to compare pre-injection and post-injection values. The mean baseline IOP (T0) value was 17.26 ± 2.4 mmHg and the immediate post-injection IOP (T1) mean value was 34.7 ± 11.50 mmHg (P < 0.01). The mean global RNFL thickness before and immediately after the injection was 100.9 ± 18.8 m and 98.6 ± 17.4 m (P = 0.001). Furthermore, the topographical RNFL analysis showed significant thickness reduction of the nasal and inferior sectors after the procedure when compared to T0 (P = 0.046 and P = 0.001). On the contrary, the mean RCP density changes at T1 did not reach statistically significant (P = 0.636). Furthermore, we found a significant negative correlation between the retinal nerve fiber layer global thickness and the IOP changes (Pearson's correlation = -0.126; P = 0.031). In particular, the nasal RNFL region showed a significant negative correlations with IOP values (Pearson's correlation = -0.198, P = 0,046). We reported acute IOP changes that are associated with reduced RNFL thickness in a group of patients undergoing intravitreal injections of anti-VEGF drugs for neovascular age-related macular degeneration. Moreover, topographical sub-analysis revealed that the nasal RNFL region is most prone to IOP fluctuations. This finding may explain the sudden visual acuity change in patients immediately after injection and may sustain injuries to optic nerve head structures producing glaucomatous damage.

Антиангиогенная терапия в сочетании с ферментным тромболизисом – новый перспективный способ лечения тромбоза вен сетчатки

Сentral retinal vein occlusion (CRVO), the first mention of which was made more than 200 years ago, today is characterized by a sufficiently fully and in detail studied pathogenesis and a detailed clinical picture [1]. It should be noted that currently, when studying certain aspects of the pathogenesis of this disease, preference is given to studying the role of various angiogenic factors, in particular, vascular endothelial growth factor (VEGF) [2, 3]. At the same time, the assessment of the influence of coagulation, hemodynamic and immune-inflammatory factors of retinal vein occlusion to a certain extent fades into the background. However, it is a holistic understanding of the pathogenesis of CRVO based on the principles of systemic methodology that is the basis for the development of effective, pathogenetically substantiated methods of treating this disease. Purpose. To study the effectiveness of anti-angiogenic therapy in combination with epiretinal thrombolysis in the treatment of «fresh» CRVO. Methods. A clinical study was conducted among 106 patients with retinal vein occlusion with a disease development period up to 7 days, divided depending on the method of treatment into 2 groups: the main one – 56 patients (56 eyes), who were intravitreally injected with the anti-VEGF drug aflibercept with simultaneous epiretinal injection of recombinant prourokinase, and a comparison group – 50 patients (50 eyes) who received monotherapy with an angiogenesis inhibitor. All patients were matched for age and gender. Ophthalmological examination included: visometry, pneumotonometry, ophthalmoscopy, optical coherence tomography of the macular retina. Statistical processing of the obtained results was carried out using the IBM SPSS Statistics 27 program. Differences were considered statistically significant at p&lt;0.05. Results. The use of a new combined method for thrombosis treatment, including intravitreal injection of an antiVEGF drug in combination with epiretinal injection of prourokinase, provides high and stable clinical and functional results in the postoperative period with an increase in visual acuity by 1.8 times, as well as an acceleration of hemorrhage lysis and resorption of macular edema by 2.0 times. Key words: central retinal vein occlusion; branch central retinal vein occlusion; anti-VEGF therapy; thrombolytics; prourokinase.