Diabetic retinopathy (DR) stands as a prevalent complication in the eye resulting from diabetes mellitus, predominantly associated with high blood sugar levels and hypertension as individuals age. DR is a severe microvascular complication of both type I and type II diabetes mellitus and the leading cause of vision impairment. The critical approach to combatting and halting the advancement of DR lies in effectively managing blood glucose and blood pressure levels in diabetic patients; however, this is seldom achieved. Both human and animal studies have revealed the intricate nature of this condition involving various cell types and molecules. Aside from photocoagulation, the sole therapy targeting VEGF molecules in the retina to prevent abnormal blood vessel growth is intravitreal anti-VEGF therapy. However, a substantial portion of cases, approximately 30-40%, do not respond to this treatment. This review explores distinctive pathophysiological phenomena of DR and identifiable cell types and molecules that could be targeted to mitigate the chronic changes occurring in the retina due to diabetes mellitus. Addressing the significant research gap in this domain is imperative to broaden the treatment options available for managing DR effectively.

Corneal neovascularization can impair vision and result in a poor quality of life. The pathogenesis involves a complex interplay of angiogenic factors, notably vascular endothelial growth factor (VEGF). This review provides a comprehensive overview of potential therapies for corneal neovascularization, covering tissue inhibitors of metalloproteinases (TIMPs), transforming growth factor beta (TGF-β) inhibitors, interleukin-1L receptor antagonist (IL-1 Ra), nitric oxide synthase (NOS) isoforms, galectin-3 inhibitors, retinal pigment epithelium-derived factor (PEDF), platelet-derived growth factor (PDGF) receptor inhibitors, and surgical treatments. Conventional treatments include anti-VEGF therapy and laser interventions, while emerging therapies such as immunosuppressive drugs (cyclosporine and rapamycin) have been explored. Losartan and decorin are potential antifibrotic agents that mitigate TGF-β-induced fibrosis. Ocular nanosystems are innovative drug-delivery platforms that facilitate the targeted release of therapeutic agents. Gene therapies, such as small interfering RNA and antisense oligonucleotides, are promising approaches for selectively inhibiting angiogenesis-related gene expression. Aganirsen is efficacious in reducing the corneal neovascularization area without significant adverse effects. These multifaceted approaches underscore the corneal neovascularization management complexity and highlight ideas for enhancing therapeutic outcomes. Furthermore, the importance of combination therapies and the need for further research to develop specific inhibitors while considering their therapeutic efficacy and potential adverse effects are discussed.

Diabetic retinopathy (DR) represents a severe complication of diabetes mellitus, characterized by irreversible visual impairment resulting from microvascular abnormalities. Since the global prevalence of diabetes continues to escalate, DR has emerged as a prominent area of research interest. The development and progression of DR encompass a complex interplay of pathological and physiological mechanisms, such as high glucose-induced oxidative stress, immune responses, vascular endothelial dysfunction, as well as damage to retinal neurons. Recent years have unveiled the involvement of genomic and epigenetic factors in the formation of DR mechanisms. At present, extensive research explores the potential of biomarkers such as cytokines, molecular and cell therapies, antioxidant interventions, and gene therapy for DR treatment. Notably, certain drugs, such as anti-VEGF agents, antioxidants, inhibitors of inflammatory responses, and protein kinase C (PKC)-β inhibitors, have demonstrated promising outcomes in clinical trials. Within this context, this review article aims to introduce the recent molecular research on DR and highlight the current progress in the field, with a particular focus on the emerging and experimental treatment strategies targeting the immune and redox signaling pathways.

The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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).
CONCLUSIONS: 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.
Протокол ведения пациентов с неоваскулярной формой возрастной макулярной дегенерации (нВМД) подразумевает многократные интравитреальные инъекции (ИВИ) анти-VEGF-препарата, возможность уменьшить пик повышения уровня внутриглазного давления (ВГД), имеет высокую значимость в клинической практике.
UNASSIGNED: Оценить влияние местного применения гипотензивных препаратов на кратковременное повышение уровня ВГД после ИВИ анти-VEGF-препарата у пациентов с нВМД.
UNASSIGNED: В проспективное исследование были включены 80 пациентов с впервые выявленной нВМД. Перед началом лечения пациенты были разделены на 4 группы по 20 человек в каждой: 1-я — контрольная, препараты с профилактической целью не применялись, во 2, 3 и 4-й группах местно проводились инстилляции одной капли в конъюнктивальную полость гипотензивных препаратов бринзоламида 1%, бринзоламид–тимолола, бримонидин–тимолола дважды: за 1 день до инъекции (в 20 ч) и в день инъекции за 2 ч до манипуляции (в 8 ч) соответственно. У каждого пациента измеряли уровень ВГД с помощью точечного контактного тонометра ICare Pro до инъекции, через 1, 30 и 60 мин после инъекции.
UNASSIGNED: Применение гипотензивных препаратов с профилактической целью ассоциировалось со значимым снижением уровня ВГД сразу после ИВИ по сравнению с аналогичным показателем в 1-й группе (p<0,001), максимальное снижение значений ВГД наблюдалось при использовании фиксированной комбинации бримонидин–тимолол на 12,1 мм рт.ст. по сравнению с данными контрольной группы (p<0,001), комбинация бринзоламид–тимолол снижала уровень ВГД на 8,5 мм рт.ст. (p<0,001), бринзоламид 1% приводил к наименьшему снижению показателей ВГД — на 5,1 мм рт.ст. (p<0,001).
UNASSIGNED: При применении инстилляций одной капли в конъюнктивальную полость за 1 день до инъекции и в день инъекции в группе, где применялась комбинация бримонидин–тимолол, наблюдалось максимальное снижение уровня ВГД в сравнении с данными других групп.

Intravitreal injection (IVI) of anti-angiogenic drugs is one of the most common therapeutic procedures in ophthalmology. In recent years, a new non-contact study method has been developed - anterior segment optical coherence tomography (AS-OCT), which allows the formation of three-dimensional images of the lens and provides more detailed information about its structure and morphology.
OBJECTIVE: This study uses optical coherence tomography method to analyze the risks of developing changes in the posterior lens capsule in patients after IVI of an anti-angiogenic drug.
METHODS: The study involved 100 people (14 men and 86 women) with a natural lens and neovascular age-related macular degeneration (nAMD). The average age was 70.57±7.98 years. During the study (12 months), all patients underwent IVI of an anti-angiogenic drug aflibercept in the treat-and-extend (T&E) mode. All subjects were divided into 2 groups: with a total number of IVI less than 10 - group 1 (50 patients), and more than 10 IVI - group 2 (50 patients, of which 49 were included in the study). All patients underwent OCT using the Optopol REVO NX device (Poland) with the Anterior B-scan Wide protocol before inclusion in the study, as well as after 3, 6 and 12 months.
RESULTS: It was found that the risk of developing a posterior lens capsule rupture, visualized using OCT, depends on the total number of IVI (correlation coefficient 0.473 p=0.001): the more IVI, the higher the probability that damage to the posterior capsule will occur after the next IVI, and after the 15th injection the risk of developing damage to the posterior capsule increases sharply.
CONCLUSIONS: The astudy analyzed the risk factors for the development of posterior lens capsule damage that can be detected using OCT, and presented three risk groups for the development of rupture (or damage) of the posterior lens capsule depending on the number of intravitreal injections performed.
Интравитреальное введение (ИВВ) антиангиогенных препаратов — одна из самых распространенных терапевтических процедур в офтальмологии. В последние годы получил развитие новый, бесконтактный метод исследования — оптическая когерентная томография (ОКТ) переднего отрезка глаза (AS-OCT), позволяющий формировать трехмерные изображения хрусталика и дающий более подробную информацию о его структуре и морфологии.
UNASSIGNED: Изучить с помощью ОКТ риски развития изменений задней капсулы хрусталика у пациентов после ИВВ афлиберцепта.
UNASSIGNED: В исследовании участвовало 100 человек (14 мужчин и 86 женщин) с нативным хрусталиком и неоваскулярной формой возрастной макулярной дегенерации (ВМД). Средний возраст составил 70,57±7,98 года. Во время исследования (12 мес) всем пациентам выполняли ИВВ афлиберцепта в режиме T&Е (TREAT&EXTEND). Все испытуемые были разделены на 2 группы: с общим количеством ИВВ меньше 10 — 1-я группа (50 пациентов) и больше 10 — 2-я группа (50 пациентов, из которых в исследование было включено 49). Всем пациентам проводилась ОКТ с использованием прибора Optopol REVO NX (Польша) и протокола Anterior B-scan Wide перед включением в исследование, через 3, 6 и 12 мес.
UNASSIGNED: Таким образом мы выявили, что риск развития надрыва задней капсулы хрусталика, визуализируемый при помощи ОКТ, зависит от общего числа ИВВ (коэффициент корреляции 0, 473 p=0,001): чем больше ИВВ, тем выше вероятность того, что после следующей ИВВ произойдет повреждение задней капсулы, причем после 15-й инъекции риск развития повреждения задней капсулы резко возрастает.
UNASSIGNED: В статье проанализированы факторы риска развития повреждений задней капсулы хрусталика, выявляемые на ОКТ. Представлены 3 группы риска развития надрыва (или повреждения) задней капсулы хрусталика в зависимости от количества проведенных интравитреальных инъекций.

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
UNASSIGNED: Сравнить с использованием оптической когерентной томографии переднего отрезка глаза (AS-OCT) изменения параметров передней камеры глаза у пациентов с собственным и искусственным хрусталиком на фоне многократных интравитреальных введений (ИВВ) анти-VEGF-препарата при лечении неоваскулярной формы возрастной малекулярной дегенерации (нВМД).
UNASSIGNED: Пациенты были разделены на 2 группы: 1-я группа (контроля) включала 30 пациентов (30 глаз) — пациенты с собственным хрусталиком, 2-я группа — 30 пациентов (30 глаз) с наличием интраокулярной линзы (ИОЛ). При помощи томографа Revo NX (Optopol, Польша) проводили AS-OCT, исследовали глубину передней камеры (ГПК), параметры угла передней камеры (УПК). Уровень внутриглазного давления (ВГД) измеряли контактным тонометром ICare Pro.
UNASSIGNED: У пациентов с наличием ИОЛ уровень ВГД через 1 мин после интавитреальной инъекции (ИВИ) анти-VEGF-препарата был статистически ниже, чем в контрольной группе, в среднем на 17,8% во время первой ИВИ и на 28,7% через 1 год наблюдения (p<0,001). ГПК до лечения была статистически значимо глубже у пациентов с наличием ИОЛ по сравнению с аналогичным показателем пациентов 1-й группы в среднем на 39,3% (p<0,001). УПК с носовой и височной стороны в меридиане 0º—180º до начала лечения был статистически значимо шире у пациентов с артифакией, чем в группе контроля, в среднем на 15,9±9,3° (p<0,001) и 16,9±8,2 ° (p<0,001) соответственно. По результатам AS-OCT, у пациентов с наличием ИОЛ не наблюдалось сдвига иридохрусталиковой диафрагмы на фоне многократных ИВИ анти-VEGF-препарата в отличие от данных контрольной группы.
UNASSIGNED: При помощи AS-OCT впервые были определены изменения параметров передней камеры глаза у пациентов с собственным и искусственным хрусталиком на фоне многократных инъекций анти-VEGF-препарата при лечении нВМД.

Diabetic retinopathy (DR) is a highly tissue-specific neurovascular complication of type 1 and type 2 diabetes mellitus and is among the leading causes of blindness worldwide. Pathophysiological changes in DR encompass neurodegeneration, inflammation, and oxidative stress. Current treatments for DR, including anti-vascular endothelial growth factor, steroids, laser photocoagulation, and vitrectomy have limitations and adverse reactions, necessitating the exploration of novel treatment strategies. This review aims to summarize the current pathophysiology, therapeutic approaches, and available drug-delivery methods for treating DR, and discuss their respective development potentials. Recent research indicates the efficacy of novel receptor inhibitors and agonists, such as aldose reductase inhibitors, angiotensin-converting enzyme inhibitors, peroxisome proliferator-activated receptor alpha agonists, and novel drugs in delaying DR. Furthermore, with continuous advancements in nanotechnology, a new form of drug delivery has been developed that can address certain limitations of clinical drug therapy, such as low solubility and poor penetration. This review serves as a theoretical foundation for future research on DR treatment. While highlighting promising therapeutic targets, it underscores the need for continuous exploration to enhance our understanding of DR pathogenesis. The limitations of current treatments and the potential for future advancements emphasize the importance of ongoing research in this field.

UNASSIGNED: The association between anti-vascular endothelial growth factor (VEGF) drugs and ocular adverse events (AEs) has been reported, but large real-world studies of their association with systemic AEs are still lacking.
UNASSIGNED: A disproportionality analysis of reports from the FDA Adverse Event Reporting System from January 2004 to September 2021 was conducted to detect the significant ADR signals with anti-VEGF drugs (including aflibercept, bevacizumab, brolucizumab, pegaptanib, and ranibizumab).
UNASSIGNED: A total of 2980 reported cases with 7125 drug-AEs were included. Five drugs were all associated with eye disorders, and pegaptanib and ranibizumab were also associated with cardiac disorders. For ranibizumab, pegaptanib, bevacizumab and aflibercept, the proportions of cardiac AEs were 8.57%, 5.62%, 3.43% and 3.20%, respectively, and the proportions of central nervous AEs were 8.81%, 7.41, 5.86% and 5.68%, respectively. In multiple comparisons, ranibizumab was significantly higher than bevacizumab and aflibercept in the proportion of cardiac AEs (P < 0.001), and ranibizumab was significantly higher than aflibercept in central nervous AEs (P < 0.001).
UNASSIGNED: Our findings support the associations between anti-VEGF drugs and ocular AEs, cardiac AEs, and central nervous AEs. After intravitreal injection, attention should not only be paid to ocular symptoms, but also to systemic symptoms.

Purpose: The efficacy and safety of anti-vascular endothelial growth factor (anti-VEGF) treatment for Coats\' disease remains controversial. This study was designed to evaluate the efficacy and safety of anti-VEGF treatment for Coats\' disease. Methods: PubMed, Embase, The Cochrane Library, Clinical Trials, CNKI, and WanFang databases were systematically searched for clinical efficacy and safety studies on anti-VEGF treatment for Coats\' disease through June 2021. Study selection, data extraction, and quality assessment were independently performed by 2 reviewers. Quality assessments were performed using the Joanna Briggs Institute Critical Appraisal tools and GRADE-CERQual. Results: A total of 1,501 articles were retrieved and reviewed, of which 24 case series involving 378 patients (range: 3-67 patients each with 3-71 eyes) were included in the analysis. No randomized controlled trials, case-controlled studies, or cohort studies were available for analysis. Most patients were male (60.0%-92.9%), aged 1.35-42.3 years, with a median follow-up time ranging from 3 to 63 months. Among the 24 case series, 22 reported changes in the visual acuity (VA) after anti-VEGF treatment and 21 reported safety outcomes. The results showed that VA improved in 73 patients (37.63%), was stable in 89 (45.87%), and worsening VA was observed in 12 cases (6.19%). The most common adverse event was fibrotic changes (n = 35). Systemic complications were not observed. Conclusions: The results of this study indicate that anti-VEGF drugs provide an effective and relatively safe treatment strategy for Coats\' disease. However, conducting well-designed, prospective, randomized clinical trials are necessary to confirm our findings.

Nowadays; intravitreal anti-vascular endothelial growth factor (VEGF) drugs are considered the first-line therapeutic strategy for treating macular exudative diseases; including wet age-related macular degeneration (w-AMD) and diabetic macular edema (DME). Despite the important clinical achievements obtained by anti-VEGF drugs in the management of w-AMD and DME; some limits still remain; including high treatment burden; the presence of unsatisfactory results in a certain percentage of patients and long-term visual acuity decline due to complications such as macular atrophy and fibrosis. Targeting the angiopoietin/Tie (Ang/Tie) pathway beyond the VEGF pathway may be a possible therapeutic strategy; which may has the potential to solve some of the previous mentioned challenges. Faricimab is a new; bispecific antibody targeting both VEGF-A and the Ang-Tie/pathway. It was approved by FDA and; more recently; by EMA for treating w-AMD and DME. Results from phase III trials TENAYA and LUCERNE (w-AMD) and RHINE and YOSEMITE (DME) have shown the potential of faricimab to maintain clinical efficacy with more prolonged treatment regimens compared to aflibercept (12 or 16 weeks) with a a good safety profile.