Wet Form Of Age-related Macular Degeneration Research Articles

Crocus sativus (saffron) and age-related macular degeneration.

Age-related macular degeneration (ARMD) leads to impaired vision and potential blindness. Globally, it accounts for approximately 9% of vision loss cases, and a projected 288 million individuals will be affected by 2040. Current treatments have limitations such as variable effectiveness, high costs, and potential side effects. Additionally, atrophic ARMD management remains challenging. As saffron has shown promising neuroprotective and antioxidant effects by potentially delaying disease progression, this study aims to review the mechanistic, pre-clinical, and clinical evidence of the effects, safety, and tolerability of saffron in ARMD treatment. The Scale for the Assessment of Narrative Review Articles was applied in this narrative review. To find relevant literature, the syntax "(saffron OR crocus) AND (retin* OR "geographic atrophy" OR "choroidal neovascular*" OR "macular degeneration")" was searched in PubMed/MEDLINE. Pre-clinical and clinical original investigations of the effects of saffron in ARMD along with the eligible studies cited in their reference lists were identified and included. Saffron and its active compounds, crocin and crocetin, have shown promising results in improving visual function and delaying ARMD progression. Several clinical studies have found that daily supplementation with 20-50 mg of saffron or 5-15 mg of crocin for 3-12 months significantly improved best-corrected visual acuity, contrast sensitivity, and retinal function as measured by electroretinogram and microperimetry, with benefits observed in both dry and wet forms of ARMD. The effects were independent of genetic risk factors and maintained during the follow-up periods, suggesting the potential role of saffron as a long-term treatment option. Saffron reduces ARMD progression via anti-angiogenic, neuroprotective, and antioxidant mechanisms. Moreover, saffron is safe and well tolerated. Although further research is needed to confirm long-term safety and efficacy, current evidence supports the use of saffron or crocin supplements as a safe and tolerable adjunct therapy for ARMD management.

Peptide Nanofiber System for Sustained Delivery of Anti-VEGF Proteins to the Eye Vitreous.

Ranibizumab is a recombinant VEGF-A antibody used to treat the wet form of age-related macular degeneration. It is intravitreally administered to ocular compartments, and the treatment requires frequent injections, which may cause complications and patient discomfort. To reduce the number of injections, alternative treatment strategies based on relatively non-invasive ranibizumab delivery are desired for more effective and sustained release in the eye vitreous than the current clinical practice. Here, we present self-assembled hydrogels composed of peptide amphiphile molecules for the sustained release of ranibizumab, enabling local high-dose treatment. Peptide amphiphile molecules self-assemble into biodegradable supramolecular filaments in the presence of electrolytes without the need for a curing agent and enable ease of use due to their injectable nature-a feature provided by shear thinning properties. In this study, the release profile of ranibizumab was evaluated by using different peptide-based hydrogels at varying concentrations for improved treatment of the wet form of age-related macular degeneration. We observed that the slow release of ranibizumab from the hydrogel system follows extended- and sustainable release patterns without any dose dumping. Moreover, the released drug was biologically functional and effective in blocking the angiogenesis of human endothelial cells in a dose-dependent manner. In addition, an in vivo study shows that the drug released from the hydrogel nanofiber system can stay in the rabbit eye's posterior chamber for longer than a control group that received only a drug injection. The tunable physiochemical characteristics, injectable nature, and biodegradable and biocompatible features of the peptide-based hydrogel nanofiber show that this delivery system has promising potential for intravitreal anti-VEGF drug delivery in clinics to treat the wet form age-related macular degeneration.

Наблюдательное несравнительное одноцентровое исследование эффективности и безопасности фиксированной комбинации Тобрамицин 0,3% + Фторметолон 0,1% (глазные капли) в качестве предоперационной подготовки и послеоперационного ведения пациентов с ВМД влажной формы после интравитреального введения ранибизумаба

Purpose. To evaluate safety and efficacy of Floas-T ® (Tobramycin 0.3% + Fluormetholone 0.1%) as a preoperative preparation and postoperative management of patients with wet form of age-related macular degeneration (AMD) before and after intravitreal injection (IVI) of anti-VEGF drugs. Material and methods. 50 patients (50 eyes) with the wet form of AMD were examined and divided into two groups. The first group included 32 patients (32 eyes) with wet form of AMD. The second group consisted of 18 patients (18 eyes) with primary (11 eyes) and advanced (7 eyes) stages of primary open angle glaucoma with normalized IOP and wet form of AMD. Results. There were no significant changes in ВСVA and tonometric IOP values in the two groups before and within 7 days after IVI of ranibizumab and Floas-T ® instillations. Average value of individually tolerable true IOP in patients of the second group was 16,3±1,1 mm Hg, while average value of initial true IOP (14,7±2,56 mm Hg) pre-op was lower than tolerable pressure, indicating that individual norm of ophthalmotonus in glaucoma patients was reached. The difference between the mean values of ocular hydrodynamics in both groups before and 1 week after surgery was also statistically unsignificant (p>0.05). The difference between the mean values of the Schirmer I test was statistically unsignificant in patients in the two groups (p>0.05) before and after surgery, indicating the absence of Floas-T ® effect on tear production. There were no local and systemic side effects of Floas-T ® in 50 patients (50 eyes) during the observation period. Conclusion. Floas-T ® had an antiinflammatory effect without a decrease in the aqueous humor outflow, did not cause a significant increase in IOP in the early postoperative period, did not decrease tear production, and did not cause adverse local and systemic side effects. Floas-T ® can be used as a preoperative preparation and postoperative management drug in patients with wet type of AMD as well as in combination with primary open angle glaucoma when achieving an individual level of intraocular pressure. Key words: wet AMD, preoperative preparation, postoperative management, Floas-T® drug

An intelligent decision-making system for early diagnosis of macular pathology

Purpose: to develop a software technology based on artificial intelligence methods aimed at analyzing large volumes of optical coherent tomography (OCT) data in order to identify early symptoms of age-related macular degeneration (AMD) and the transition from dry AMD to neovascular AMD (nAMD).Material and methods. Patients with dry AMD (1125 eyes), wet nAMD (1200 eyes) and subjects without ophthalmic pathology (1205 eyes) underwent a standard ophthalmological examination and macular OCT (Cirrus HD-OCT 4000, Carl Zeiss Meditec AG, Germany) according to the MacularCube scanning protocol with a standard ETDRS macular map. The thickness of the retina from the inner limiting membrane to the retinal pigment epithelium and the presence and location of fovea configuration changes were determined.Results. Two ultra-precise artificial neural networks (ANN) were created: one intended to identify patients with early signs of dry AMD and the other to identify those with signs of nAMD. By the time when 1000 training images were processed, the image interpretation decision-making accuracy in the first ANN increased to reach 97.6%, in the second ANN, to 96.8%, which shows the high efficiency of this technology. The deep learning processes were run on an Amazon Web Service EC2 GPU. The trained ANN model was also tested on healthy eyes at each estimated probability value. The correspondence between the doctor's diagnosis and the decision taken by the ANN was assessed.Conclusions. A software technology based on artificial intelligence methods has been developed, which answered the need to process a large amount of OCT data. The technology proved effective in identifying early symptoms of dry and wet forms of AMD and in early diagnosis of the transition of the dry form of AMD into neovascular form, the latter requiring immediate treatment.

An integrated assessment of ophthalmogeriatric changes in patients with the wet form of agerelated macular degeneration

Purpose. Integrated assessment of ophthalmogeriatric changes in patients with the wet form of age-related macular degeneration (AMD) at the time of primary diagnosis.Material and methods. 200 senior and senile patients aged 60 or more (of which 43.5% were male) with the newly diagnosed wet AMD underwent a standard ophthalmological examination, took a survey aimed at identifying specific risk factors, and tested for Body Mass Index (BMI) and Charlson Comorbidity Index (CCI).Results. The BMI was 29.46 ± 4.1 kg/m2 and the CCI was 3.3 [2; 4]. The average number of disorders per patient with AMD was 4.0 [2; 6] (ranging from 1 to 7). Polypragmasia took place in 8% of cases. Degenerative changes in the conjunctiva were found in 11%, arcus senilis — in 34.55%, dystrophic changes of the iris — in 68%, pseudoexfoliation syndrome — in 17.5%, senile cataract — in 89.5%, degenerative changes of the vitreous — in 84.5%, primary open-angle glaucoma — in 2% of cases. No gender differences were revealed in these indicators. Among systemic diseases, the most frequent were cardiac and cerebrovascular pathologies (arterial hypertension — 74.5%, ischaemic heart disease — 40.5%, cerebrovascular pathology — 20.5%). Type 2 diabetes mellitus was found in 6.5% of AMD patients.Conclusion. The wet form of AMD is characterized by a wide range of comorbid disorders that can affect the development and progression of the main disease. Polypragmasia plays its own role in this progression.

Study of the effect of RS1800629 TNF polymorphism on the course of age-related macular degeneration through the prism of ANTI-VEGF therapy

Annotation. Age-related macular degeneration (AMD) includes pathological changes in the deep layers of the retina, macula, and surrounding blood vessels, leading to loss of central vision. The wet form of nosology is the leading cause of irreversible blindness in developed countries among people over 60, where more than 30 million people suffer from the disease. The number of patients in the United States is expected to increase from 9.1 million in 2010 to 17.8 million in 2050. New therapeutic strategies and the development of new practical methods for identifying patients at high risk of treatment resistance are needed to reduce the prevalence of the disease. That is why the aim of the study was to shed light on the role of the rs1800629 polymorphism of the TNF gene as one of the prognostic factors in the effectiveness of treatment of the wet form of AMD. The study group consisted of 162 people diagnosed with a wet form of pathology, while the comparison group consisted of 105 people without a history of ophthalmic pathology. Optical coherence tomography of certain areas of the eye, including the retina, was used to confirm or rule out the diagnosis. To detect the polymorphism status of the TNF gene, the real-time polymerase chain reaction method was used on the BioRad CFX 96 thermocycler-amplifier, using “Litekh” (RF) reagent kits. Statistical processing of the results was performed by determining the Hardy-Weinberg equilibrium, Student’s and Wilcoxon’s criteria, logistic regression using OR values and 95% CI, and by subtracting RR and χ². The study found that the frequency of genotype distribution with mutant allele A was predominant among patients in the study group, and the G allele was determined predominantly in the control group and was associated with better results of anti-VEGF therapy. The results of OCT confirmed this information, because among carriers of genotypes GG and GA (p<0.05) visual acuity improved even after the first injection of the drug in most areas, while among carriers of homozygous genotype AA was not sufficient probability of biological effects, efficiency in the presence of this genotype was reduced (p<0,05). The results of treatment were most representative in the areas of OCT 4, OCT 8 and macula (OCT 3) – among carriers of allele A in the OCT 4 zone, the chance of resistance to treatment was 3.1 times (OR=3.1; 95% SI 1,686 - 5.7) higher than in carriers of the G allele, and in the zone of OCT 8 in patients from the study group the risk of ineffectiveness of therapy was 2.81 times (OR=2.81; 95% CI 1.56 - 5.059) higher than in the corresponding zone of the G allele carriers. This suggests a lack of clinical efficacy in individuals carrying the mutant A allele, and the need to identify the status of polymorphisms for prognostic assessment of treatment efficacy.

Screening of cytokines in blood serum and lacrimal liquid in wet and atrophic forms of age-related macular degeneration

Cytokines play an integral role in pathogenesis of age-related macular degeneration (AMD). Of particular interest are the late stages of this disease, which causes progressive visual impairment. Therapy-induced effects of post-treatment cytokine concentrations also need to be studied, both at long and short observation terms. These studies are of vital importance if the atrophy occurs during antiangiogenic therapy. Our purpose was to study an array of 45 cytokines, in blood serum (BS) and lacrimal liquid (LL) of the patients with wet and atrophic AMD.The study included 70 people (85 eyes) with stage 3-4 AMD according to AREDS. Depending on the form of AMD, 3 groups were discerned: I group (n = 24) included the patients with “geographic atrophy”; II group (n = 22), consisted of the patients with macular atrophy treated with antiangiogenic therapy of wet AMD; III group (n = 24), comprised the patients with a wet AMD who did not previously receive the treatment. Control group consisted of healthy volunteers (n = 25). All the groups were comparable for age and gender. The patients underwent a comprehensive ophthalmological examination to make a diagnosis. A multiplex study of the local (in the BS) and systemic (in the LL) cytokine status was carried out on a MAGPIX device (platform хMAP, Luminex Corporation, USA) in the Luminexx PONENT 3.1 software, using Procarta Plex kits (eBioscience, Austria). We determined 45 cytokines causing various biological effects, i.e., IL-1á, IL-1â, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, IFNá, IFNã, IL-8/CXCL8, IP-10/CXCL10, SDF-1á/CXCL12, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/ CCL4, RANTES/CCL5, Eotaxin/CCL11, TNFá, TNFâ, GM-CSF, VEGF-A, VEGF-D, FGF-2, EGF, PDGF-BB, HGF, SCF, GRO-á, NGF-â, BDNF, LIF, PIGF-1.Screening of a wide range of cytokines showing various biological effects was carried out in BS and LL of patients with atrophic and wet forms of AMD. It has been shown that the late stages of the disease are associated with local and systemic changes of pro / anti-inflammatory mediators (IL-1â, IL-1ra, IL-18, LIF), chemoattractant cytokines (IL-8/CXCL8, IP-10/CXCL10, MCP-1/CCL2, MIP-1á/CCL3, MIP-1â/ CCL4, RANTES/CCL5, Eotaxin/CCL11), hematopoietic regulators (IL-7), and growth factors with known angiogenic activity (EGF, HGF, PDGF-BB, VEGF-A). Altered concentrations of numerous chemokines, e.g., IP-10/CXCL10, SDF-1á/CXCL12, MIP-1á/CCL3, MIP-1â/CCL4, RANTES/CCL5 and Eotaxin/CCL11 (p < 0.05) in BS of the patients with atrophic and wet AMD may be of interest for the search of biomarkers associated with various clinical phenotypes of the disease and may be also helpful for development of new therapeutic strategies.

Анализ клинических случаев A-VEGF-терапии пациентов с разрывами пигментного эпителия, осложняющими влажную возрастную макулодистрофию

Purpose. Analysis A-VEGF therapy for wet form age-related macular degeneration (AMD) complicated by retinal pigment epithelium tear (RPET), different in involvement of macular zone (MZ), with different time of RPET regarding A-VEGF therapy. Material and methods. The results of treatment 18 patients with wet AMD complicated by RPET during monthly A-VEGF injection were analyzed. In first group (10 eyes) – RPET occurred before treatment, the second (8 eyes) – RPET arisen during A-VEGF. Visometry, ophthalmoscopy, fundus photoregistration, MZ OCT before and in month after each injection. Age – 65–83 years. Results. RPET (1,5 DD) captured fovea in 7 first group patients, in 3 patients RPET (0,5 DD) didn't affect fovea, In macula registered subretinal fluid (SRF) and hemorrhage (SRH). After 2 A-VEGF injections, resorption of SRF and SRH was observed. VA increased from 0,2 to 0,7 in cases RPET without capture of the fovea. RPET involving fovea occurred in 8 patients of the second group after the first A-VEGF injection. SRH and SRF resorbed. VA of patients decreased from 0,7 to 0,15. In both groups relapses of the SRF in macula after the development of RPET were not observed. Conclusion. Wet AMD complicated by RPET as a result of the pathological process and on the background of A-VEGF therapy. When RPET is involved fovea, VA decreases to 0.15. In case of preservation RPE in fovea – VA is high. A-VEGF therapy for wet AMD with RPET leads to resorption of SRH and SRF, to stop SRF for a long time. Key words: wet form macular degeneration, Anti-VEGF therapy, retinal pigment epithelium tear, macular zone

Management of wet AMD in an elderly patient - case report

Introduction: Age-related macular degeneration (AMD) is the most common cause of central vision loss in elderly people over 50 years of age. It is characterized by the presence of drusen on the fundus and may be associated with choroidal neovascularization (CNV) or geographic atrophy. AMD is a condition caused by many factors including environmental, genetic, and vascular. Currently, it affects over 25 million people worldwide, but with the progressive aging of the population, the incidence of the disease is increasing. Disease is therefore an important issue in geriatrics.Case report: A 75-year-old patient was referred to the General and Pediatric Ophthalmology Clinic of the Medical University of Lublin due to the three-week deterioration of visual acuity in the left eye. The visual acuity of the left eye was: counting fingers at a distance of 1.5 m. Initial cataracts of this eye and wet AMD were diagnosed. In July 2018. an injection of ranibizumab was administered into the vitreous humor of the left eye. After achieving an improvement in visual acuity to 0.2 (on Snellen charts), in September the patient was qualified to the Drug Program for the treatment of the wet form of AMD. From September to October 2019. the patient received 9 doses of ranibizumab. In October 2019. visual acuity improved to 0.4. In November, due to the unsatisfactory results of the therapy, the drug was changed to aflibercept. The patient received a total of 3 injections of this drug and his visual acuity improved to a value of 0.7. The last injection was given in July 2020 and the clinical condition and visual acuity stabilized. After the end of the drug program, the patient regularly shows up for checkups, and the visual acuity of the left eye has normalized since July 2020. and is now 0.4 (due in part to atrophic changes and scarring).Conclusions: Treatment of the wet form of AMD is a difficult and lengthy process. Early diagnosis of the disease, starting treatment as soon as possible, regular checkups and cooperation with the patient are very important for the success of the therapy. During 3 years of treatment, the patient experienced a significant improvement in visual acuity for one year. The treatment allowed the disease progression to slow down. The morphological condition of the retina improved. The applied treatment and management of the elderly patient turned out to be effective, and the achieved effects of the therapy are satisfactory.

Autophagy Genes for Wet Age-Related Macular Degeneration in a Finnish Case-Control Study.

Age-related macular degeneration is an eye disease that is the main cause of legal blindness in the elderly in developed countries. Despite this, its pathogenesis is not completely known, and many genetic, epigenetic, environmental and lifestyle factors may be involved. Vision loss in age-related macular degeneration (AMD) is usually consequence of the occurrence of its wet (neovascular) form that is targeted in the clinic by anti-VEGF (vascular endothelial growth factor) treatment. The wet form of AMD is associated with the accumulation of cellular waste in the retinal pigment epithelium, which is removed by autophagy and the proteosomal degradation system. In the present work, we searched for the association between genotypes and alleles of single nucleotide polymorphisms (SNPs) of autophagy-related genes and wet AMD occurrence in a cohort of Finnish patients undergoing anti-VEGF therapy and controls. Additionally, the correlation between treatment efficacy and genotypes was investigated. Overall, 225 wet AMD patients and 161 controls were enrolled in this study. Ten SNPs (rs2295080, rs11121704, rs1057079, rs1064261, rs573775, rs11246867, rs3088051, rs10902469, rs73105013, rs10277) in the mTOR (Mechanistic Target of Rapamycin), ATG5 (Autophagy Related 5), ULK1 (Unc-51-Like Autophagy Activating Kinase 1), MAP1LC3A (Microtubule Associated Protein 1 Light Chain 3 α), SQSTM1 (Sequestosome 1) were analyzed with RT-PCR-based genotyping. The genotype/alleles rs2295080-G, rs11121704-C, rs1057079-C and rs73105013-T associated with an increased, whereas rs2295080-TT, rs2295080-T, rs11121704-TT, rs1057079-TT, rs1057079-T, rs573775-AA and rs73105013-C with a decreased occurrence of wet AMD. In addition, the rs2295080-GG, rs2295080-GT, rs1057079-TT, rs11246867-AG, rs3088051-CC and rs10277-CC genotypes were a positively correlated cumulative number of anti-VEGF injections in 2 years. Therefore, variability in autophagy genes may have an impact on the risk of wet AMD occurrence and the efficacy of anti-VEGF treatment.

EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration.

Epithelial–mesenchymal transition (EMT) and endothelial–mesenchymal transition (EndMT) are physiological processes required for normal embryogenesis. However, these processes can be hijacked in pathological conditions to facilitate tissue fibrosis and cancer metastasis. In the eye, EMT and EndMT play key roles in the pathogenesis of subretinal fibrosis, the end-stage of age-related macular degeneration (AMD) that leads to profound and permanent vision loss. Predominant in subretinal fibrotic lesions are matrix-producing mesenchymal cells believed to originate from the retinal pigment epithelium (RPE) and/or choroidal endothelial cells (CECs) through EMT and EndMT, respectively. Recent evidence suggests that EMT of RPE may also be implicated during the early stages of AMD. Transforming growth factor-beta (TGFβ) is a key cytokine orchestrating both EMT and EndMT. Investigations in the molecular mechanisms underpinning EMT and EndMT in AMD have implicated a myriad of contributing factors including signaling pathways, extracellular matrix remodelling, oxidative stress, inflammation, autophagy, metabolism and mitochondrial dysfunction. Questions arise as to differences in the mesenchymal cells derived from these two processes and their distinct mechanistic contributions to the pathogenesis of AMD. Detailed discussion on the AMD microenvironment highlights the synergistic interactions between RPE and CECs that may augment the EMT and EndMT processes in vivo. Understanding the differential regulatory networks of EMT and EndMT and their contributions to both the dry and wet forms of AMD can aid the development of therapeutic strategies targeting both RPE and CECs to potentially reverse the aberrant cellular transdifferentiation processes, regenerate the retina and thus restore vision.

EVALUATION OF THE DATA OF EFFECTIVENESS OF TREATMENT OF AGE-RELATED MACULAR DEGENERATION BY THE METHOD OF INTEGRATION OF ANGIOGENESIS INHIBITORS INTO THE BACK SUBTENON SPACE ON THE VISCOUS MEDIA

Aim of the research. Study of clinical efficacy of treatment of wet form of age-related macular degeneration by using the method of introduction of the inhibitor of angiogenesis into the back s ubtenon s pace on the viscous media. Material and methods of the study. The first group (main group) included 41 patients (43 eyes) with wet form of age-related macular degeneration (AMD). All patients in this group were injected in the back subtenon space 7.5-12.5 mg of an angiogenesis inhibitor on a viscous medium (1.0 ml of 2% solution of hydroxypropylmethyl cellulose). The second group (control group) consisted of 30 patients (30 eyes) with wet form of AMD, for this group a retrospective analysis of dynamics of morpho-functional indices after intravitreal injections of angiogenesis inhibitors according to standard methods (1.25 mg) was carried out. The observance time period amounted to 12 months. Results. When comparing the effectiveness of treatment, the mean best-corrected visual acuity (BCVA) improved significantly in both groups after treatment. Also, according to data of the optical coherence tomography (OCT), the mean central retinal thickness (CRT), the extent, height of pathological changes, the area of the pathological focus and the relative volume of the pathological focus were significantly reduced as a result of treatment. No significant differences were found between the groups (all p>0.05). In accordance with results of the evaluation, the effect duration at subtenon method of administrations amounted to 2-2.5 months, at intravitreal method it amounted to 1-1.5 months. The number of administrations in the 12 months of observation in the main group amounted to 2.8 injections per patient on average, and in the control group it amounted to 4.2 injections. Conclusion: Subtenon injections of the inhibitor of angiogenesis into the back subtenon space gives the positive effect in the treatment of wet form of age-related macular degeneration, and its application on viscous medium has a prolonged effect.

Aster koraiensis Extract and Chlorogenic Acid Inhibit Retinal Angiogenesis in a Mouse Model of Oxygen-Induced Retinopathy.

Aster koraiensis extract (AKE) is a standard dietary herbal supplement. Chlorogenic acid (CA) is the major compound present in AKE. Retinal neovascularization is a common pathophysiology of retinopathy of prematurity, diabetic retinopathy, and wet form age-related macular degeneration. In this study, we aimed to evaluate the effects of AKE and CA on retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Vascular endothelial growth factor- (VEGF-) induced tube formation was assayed in human vascular endothelial cells. Experimental retinal neovascularization was induced by exposing C57BL/6 mice to 75% oxygen on postnatal day 7 (P7) and then returning them to normal oxygen pressure on P12. AKE (25 and 50 mg/kg/day) and CA (25 and 50 mg/kg/day) were administered intraperitoneally for 5 days (P12–P16). Retinal flat mounts were prepared to measure the extent of retinal neovascularization at P17. The incubation of human vascular endothelial cells with AKE and CA (1–10 μg/mL) resulted in the inhibition of VEGF-mediated tube formation in a dose-dependent manner. The neovascular area was significantly smaller in AKE or CA-treated mice than in the vehicle-treated mice. These results suggest that AKE is a potent antiangiogenic agent and that its antiangiogenic activity may, in part, be attributable to the bioactive component CA.

Evaluation pro/antioxidant balance in patients with wet form of age-related macular degeneration.

The aim of study was to evaluate the ability of the enzymatic antioxidant barrier to protect against peroxidation inpatients with wet age-related macular degeneration, as compared to healthy subjects. Hemolysate blood samples collected from 25 patients with wet form age-related macular degeneration and 25 healthy controls were analysed to determine the activity of superoxide dismutase (using Misra and Fridovich method), catalase (using Beers and Sizer method), glutathione peroxidase (using Sedlak and Lindsay method modified by Little andO’Brien), and malondialdehyde concentration (using Placer method). We observed a statistically significant decrease in the activity of following enzymes in patients with wet age-related macular degeneration, as compared to controls: superoxide dismutase (2086.3 vs. 2348.5 U/gHb/100 ml; p ≤ .05), catalase (6.9 vs. 7.6 BU/gHb, p ≤ .05) and glutathione peroxidase (36.3 vs. 45.8 U/gHb; p ≤ .05). At the same time, an increase in age-related macular degeneration thiobarbituric acid reactive substance concentration was demonstrated in patients with wet age-related macular degeneration, as compared to healthy subjects (.119 vs. .286 µmol/gHb; p ≤ .001). The obtained results indicate inefficient enzymatic antioxidant system which manifests as intense peroxidation inpatients with age-related macular degeneration.

An Experimental and Clinical Justification for Prolongation of Action of Anti-VEGF Drug in the “Wet” Form Age-related Macular Degeneration by the Introduction in the Back Subtenon Space on the Basis of Viscous Media

Purpose. Experimental-clinical substantiation of the effectiveness of subtenon injection of anti-VEGF drug on the viscous media with the purpose of strengthening and prolong of therapeutic effect in the treatment of wet form of age-related macular degeneration (AMD). Material and methods. The experimental part of the work was carried out on 10 rabbits (20 eyes). The main group of rabbits (10 eyes) were injected into the back subtenon space 0,5 ml of a 10% solution of fluorescein on the viscous mediа, which was used as a 2% solution of hydroxypropylmethylcellulose; a control (10 eyes) — without the viscous medium. After enucleation and isolation of ocular tissues in the posterior pole was performed water extraction of the dye determined the intensity of fluorescence after 3, 7, 10, 14 and 16 days after injection. In the clinical part of the work included 32 patients (34 eyes) with the wet form of AMD, to be administered anti-VEGF drug at a dose of 12,5 mg (0,5 ml) into the back subtenon space аt the same viscous media. The efficacy and safety were evaluated for 6 months. Results. As a result of the experimental study found that the length of stay in the back subtenon space of fluorescein solution of rabbit’s eye, introduced in the viscous medium to 2 times longer than without it. In a clinical study of stabilization was observed in 52,9 % of cases, improved visual function in 35,3 % of cases. Deterioration in visual functions noted in 11,8 % of cases. It was also noted improvement in photo-stress test. According OCT showed a decrease in central retinal thickness 2 times by reducing the size and volume of lesions by 30%, a significant decrease transsudativ processes in the retina in all patients, indicating that suppression of choroidal neovascularization. Conclusion: Subtenon injections of anti-VEGF drug is safe and has a positive effect in wet AMD, and its application to a viscous media has a prolonged action or property interest in any material or method mentioned.

Novel association of FCGR2A polymorphism with age-related macular degeneration (AMD) and development of a novel CFH real-time genotyping method.

Age-related macular degeneration (AMD) is a degenerative ocular disease, which may lead to loss of central vision. In Caucasian populations, a strong correlation has been established with polymorphism Y402H (rs1061170) in the complement factor H gene (CFH). The H131R polymorphism (rs1801274) in the FCGR2A gene has been associated with many inflammatory diseases, but has not been investigated in relation to AMD. The goal of our study was the development of a novel method for Y402H (g.43097C>T) genotyping, the confirmation of its association with AMD in the Greek population and the investigation of the H131R polymorphism in AMD. DNAs were extracted from blood samples of 120 patients with the severe wet form of AMD and 103 age- and sex-matched controls, all of whom were clinically evaluated. A real-time PCR and melting curve analysis method for Y402H genotyping was developed in the LightCycler platform, after in silico design of appropriate primers and probes. Genotyping for H131R was performed using a real-time PCR method previously described by our group. The novel genotyping method for Y402H in the CFH gene is fast, reproducible (Efficiency=1.79, reproducibility CVCq=3.33%, Tm C allele 53.36 °C and T allele 61.91 °C, ΔTm=8.55) and accurate as results were confirmed with the gold standard DNA Sequencing method. The present study confirmed the association between CFH Y402H SNP and wet AMD in the Greek population (OR=1.77, p=0.002). FCGR2A H131R polymorphism was investigated for the first time in this present study for possible correlation with wet AMD and a statistically significant association was detected (OR=1.74, p=0.006), that awaits further confirmation in a larger set of samples.

Stereo imaging in ophthalmology

Stereo imaging in ophthalmology is an important diagnostic modality and a task not often undertaken in many ophthalmic photography departments. Origins of retinal stereo imaging date back to over 100 years ago. Stereo imaging is recommended, for example, for all photographs of the optic nerve head and for ocular angiography intended to determine clinically significant macular oedema. It is also useful in determining sub types of wet-form age-related macular degeneration. Stereo fundus photography and angiography facilitate the diagnostic process by clearly defining retinal structure and elevation. This allows the clinician to assess the patient's retina, presenting a 3D image that does not move and is not light sensitive. Stereo imaging of the fundus is useful for follow-up management of the patient, and is used extensively in clinical trials. This article will look at the history of stereo photography, its application and rationale to ophthalmology, and the different methods of attaining stereo images of the retina.

Association between polymorphisms of the DNA base excision repair genes MUTYH and hOGG1 and age-related macular degeneration

Age-Related Macular Degeneration (AMD) is an eye disease that results in progressive and irreversible loss of central vision and is considered as the primary cause of visual impairment, including blindness, in the elderly in industrialized countries. Oxidative stress has been implicated in the pathogenesis of AMD. The hOGG1 and the MUTYH genes play an important role in the repair of oxidatively damaged DNA in the base excision repair pathway. The DNA glycosylases encoded by the hOGG1 and MUTYH genes initiate this pathway by recognizing and removing 8-oxoguanine and adenine paired with 8-oxoguanine, respectively. Our study was designed to examine the association between the c.977C>G polymorphism (rs1052133) of the hOGG1 gene and the c.972G>C polymorphism (rs3219489) of the MUTYH gene and AMD as well as the modulation of this association by some clinical and lifestyle factors. Genotypes were determined in DNA from blood of 271 AMD patients, including 101 with wet and 170 with dry form of the disease and 105 sex- and age-matched individuals without AMD. We observed an association between AMD, dry and wet forms of AMD and the C/G genotype and the G allele of the c.977C>G-hOGG1 polymorphism (p 0.006; 0.009; 0.021 and 0.004; 0.005; 0.016 respectively). On the other hand, the C/C genotype and the C allele reduced the risk of AMD as well as of its dry form or wet form (p 0.002; 0.003; 0.010 and 0.004; 0.005; 0.016, respectively). Therefore, the associations we detected were driven by the dry AMD. We observed some statistically significant association between the occurrence of AMD and its dry and wet forms and genotypes of the other polymorphism, the c.972G>C-MUTYH polymorphism, but due to borderline character of all this association we do not consider them as medically relevant. Our findings suggest that the c.977C>G-hOGG1 polymorphism may be associated with dry AMD. Further studies are needed to determine possible association between AMD and the c.972G>C-MUTYH polymorphism.

Ranibizumab for age-related macular degeneration

Introduction: Age-related macular degeneration (AMD) is the leading cause of blindness in patients over 50 years in the developed world. The wet form of AMD is responsible for the majority of severe vision loss. VEGF-A is a key component in the development of wet AMD. Ranibizumab is an anti-VEGF agent that has established itself as the gold standard in the treatment of neovascular AMD. Herein, we review the pharmacology, pharmacokinetics, efficacy and safety of ranibizumab.Areas covered: Since its approval in 2006, ranibizumab has revolutionized the treatment of wet AMD. In two pivotal Phase III trials, MARINA and ANCHOR, ranibizumab (0.5 mg) prevented moderate visual loss in 90 and 96% of patients, respectively, and improved vision by 15 letters or more in 33 and 40% of patients, respectively. Fixed monthly dosing regimens were compared with quarterly dosing regimens in PIER and EXCITE studies and support the superiority of fixed monthly dosing. The CATT trial revealed that bevacizumab was not inferior to ranibizumab when dosed monthly. As-needed treatment regimens of ranibizumab were also found to be non-inferior to monthly ranibizumab after 1 year of follow-up.Expert opinion: Ranibizumab has positively altered the treatment of wet AMD and offers hope for millions of patients.

INNER SEGMENT–OUTER SEGMENT JUNCTIONAL LAYER INTEGRITY AND CORRESPONDING RETINAL SENSITIVITY IN DRY AND WET FORMS OF AGE-RELATED MACULAR DEGENERATION

To investigate a relationship between the inner segment-outer segment (IS-OS) junctional layer integrity and the overlying retinal sensitivity assessed by Spectral OCT/SLO (spectral-domain optical coherence tomography) and microperimetry testing in patients with dry and wet forms of age-related macular degeneration (AMD). Spectral-domain optical coherence tomography examination and microperimetry testing were performed in 55 eyes of 43 consecutive patients with AMD. Microperimetry maps were registered onto three-dimensional retinal topography maps, and point-to-point analysis of correlation between microperimetric retinal sensitivities and corresponding status of the underlying IS-OS junctional layer was performed. In addition, the analysis of correlation between the best-corrected visual acuity and the integrity of IS-OS layer in the center of the fovea also was performed. Retinal sensitivity was inversely and strongly correlated with the integrity of IS-OS layer in both dry and wet forms of AMD (correlation coefficient [r] = -0.75 [95% confidence interval, 0.49-0.88], P < 0.001, and -0.79 [95% confidence interval, 0.61-0.89], P < 0.001, respectively). The correlation between the best-corrected visual acuity and the integrity of IS-OS layer in the center of fovea was less significant (r = -0.58 [95% confidence interval, 0.19-0.79], P = 0.02, for dry AMD, and r = -0.6 [95% confidence interval, 0.32-0.78], P = 0.015, for wet AMD). Retinal sensitivity consistently correlated with the status of underlying IS-OS junctional layer in both dry and wet forms of AMD. Loss of IS-OS layer is significantly associated with poor retinal sensitivity, assessed by microperimetry. Compared with visual acuity, functional testing with microperimetry appears to more consistently correlate with changes in the outer retina, such as IS-OS junctional integrity, especially, in patients with wet AMD.