Advanced Exudative Age-related Macular Degeneration Research Articles

Choriocapillaris Vascular Density Changes: Healthy vs. Advanced Exudative Age-Related Macular Degeneration Previously Treated with Multiple Anti-VEGF Intravitreal Injections

Purpose: To assess choriocapillaris vascular density (VD) in healthy and advanced exudative age-related macular degeneration (ae-AMD) patients by new full-range optical coherence tomography angiography (OCT-A). Method: In this observational, cross-sectional study, 21 healthy and 21 ae-AMD eyes, already treated with anti-VEGF, were enrolled. Angio-View retina patterns centered on fovea (6.4 × 6.4 mm) were acquired for all participants using Solix full-range OCT (Optovue Inc., Freemont, CA, USA). The main outcome was to compare choriocapillaris VD between healthy and ae-AMD eyes. Automated measurements of whole image choriocapillaris VD (%) and fovea grid-based (%) were collected for the analysis. Angio-View patterns were used to assess the flow area (mm2) of macular neovascularization (MNV) by contour flow measure algorithm. Best-corrected visual acuity (BCVA) of both groups was also used for the statistical analysis. Results: The mean age was 60.9 (±8.3) in healthy and 73.33 (±15.05) in ae-AMD eyes. The mean BCVA (ETDRS letters) was 98.47 (±1.50) in healthy and 7.04 (±5.96) in ae-AMD eyes. The Mann–Whitney test comparing choriocapillaries VD for whole and fovea healthy and ae-AMD eyes showed statistical significance (p < 0.0001 (t = 4.91; df = 40) and p < 0.0001 (t = 6.84; df = 40), respectively). Regarding, the correlation between MNV and VD of choriocapillaries, neither whole nor fovea areas were statistically significant (F = 0.38 (R2 = 0.01) and 1.68 (R2 = 0.08), respectively). Conclusions: Choriocapillaris VD showed a statistically significant reduction in comparison to healthy eyes in ae-AMD eyes. Choriocapillaris impairment can be seen in the early phase of MNV pathogenesis.

Absence of TGFβ signaling in retinal microglia induces retinal degeneration and exacerbates choroidal neovascularization.

Constitutive TGFβ signaling is important in maintaining retinal neurons and blood vessels and is a factor contributing to the risk for age-related macular degeneration (AMD), a retinal disease involving neurodegeneration and microglial activation. How TGFβ signaling to microglia influences pathological retinal neuroinflammation is unclear. We discovered that ablation of the TGFβ receptor, TGFBR2, in retinal microglia of adult mice induced abnormal microglial numbers, distribution, morphology, and activation status, and promoted a pathological microglial gene expression profile. TGFBR2-deficient retinal microglia induced secondary gliotic changes in Müller cells, neuronal apoptosis, and decreased light-evoked retinal function reflecting abnormal synaptic transmission. While retinal vasculature was unaffected, TGFBR2-deficient microglia demonstrated exaggerated responses to laser-induced injury that was associated with increased choroidal neovascularization, a hallmark of advanced exudative AMD. These findings demonstrate that deficiencies in TGFβ-mediated microglial regulation can drive neuroinflammatory contributions to AMD-related neurodegeneration and neovascularization, highlighting TGFβ signaling as a potential therapeutic target.

Ranibizumab combined with photodynamic therapy for the treatment of advanced-stage exudative age-related macular degeneration: Study protocol for a self-controlled trial and preliminary results

Background and objectives: The lack of visual field in the visual center of older adults with age-related macular degeneration (AMD) has a serious impact on daily activities. AMD is subdivided into atrophic and exudative AMD according to pathology. Patients with advanced stage exudative AMD develop aged-related degeneration in the macular area. Ranibizumab combined with photodynamic therapy is mainly used for the treatment of early exudative AMD; however, treatment outcomes in advanced stage exudative AMD are not well documented. Therefore, we attempt to analyze vision recovery, retinal thickness, and leakage of choroidal neovascular lesions in patients with advanced stage exudative AMD after treatment with ranibizumab plus photodynamic therapy. We also further explore the therapeutic efficacy of the combined therapy. Design: A prospective self-controlled trial. Methods: The trial will be undertaken in the Department of Ophthalmology, Affiliated Hospital of Qinghai University, China. The study population will comprise 113 patients with advanced exudative AMD who are eligible for inclusion. Photodynamic therapy combined with intravitreal injection of ranibizumab will be given as the interventional therapy. Outcome measures and preliminary results: The primary outcome measure of the trial is visual improvement in patients 12 months after treatment. Secondary outcome measures include logarithmic visual acuity chart scores, retinal thickness, and leakage of choroidal neovascular lesions assessed monthly at 1-12 months after treatment. Adverse events are also recorded during follow-up. Pre-test results showed that at 12 months after treatment, visual acuity in 43 affected eyes was increased by ≥ 2 lines, and the average retinal thickness decreased by 111.21 μm compared with before treatment. Leakage of choroidal neovascular lesions in most affected eyes stopped or the lesions were contracted. Discussion: Findings from the trial are expected to provide reliable data on the efficacy of ranibizumab combined with photodynamic therapy in the treatment of advanced exudative AMD. This will provide a basis for the rational use of this combined therapy in the treatment of advanced exudative AMD. Ethics and dissemination: The study was designed in December 2017, and approved by the Ethics Committee of the Affiliated Hospital of Qinghai University (approval No. QHY001Y) in January 2018. The trial was registered with the Chinese Clinical Trial Registry in March 28, 2018. Participant recruitment was initialized in March 2018, and data analysis will be completed in December 2020. The results of this study will be disseminated by publications in peer-reviewed journals. Trial registration: This trial was registered in the Chinese Clinical Trial Registry with registration No. ChiCTR1800015410 (protocol version 1.0).

Next-generation sequencing analysis of the ARMS2 gene in Turkish exudative age-related macular degeneration patients.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. It is a complex disease with both genetic and environmental risk factors. To improve clinical management of this condition, it is important to develop risk assessment and prevention strategies for environmental influences, and establish a more effective treatment approach. The aim of the present study was to investigate age-related maculopathy susceptibility protein 2 (ARMS2) gene sequences among Turkish patients with exudative AMD. In addition to 39 advanced exudative AMD patients, 250 healthy individuals for whom exome sequencing data were available were included as a control group. Patients with a history of known environmental and systemic AMD risk factors were excluded. Genomic DNA was isolated from peripheral blood and analyzed using next-generation sequencing. All coding exons of the ARMS2 gene were assessed. Three different ARMS2 sequence variations (rs10490923, rs2736911, and rs10490924) were identified in both the patient and control group. Within the control group, two further ARMS2 gene variants (rs7088128 and rs36213074) were also detected. Logistic regression analysis revealed a relationship between the rs10490924 polymorphism and AMD in the Turkish population.

C-reactive protein and complement factor H polymorphism interaction in advanced exudative age-related macular degeneration.

To determine the association of C-reactive protein (CRP) and complement factor H (CFH) gene with exudative age-related macular degeneration (AMD) and any possible interaction among these factors. In this case-control study, 139 unrelated patients with exudative AMD and 123 non-AMD controls were recruited. Blood sample was taken for analysis of the CRP levels and DNA testing. DNA fragments of CFH gene variants containing 4 single nucleotide polymorphisms including rs800292, rs1061170, rs2274700, and rs3753395 were assessed. A CRP level of≥3mg/L was considered as elevated. The association of elevated CRP and CFH gene variants polymorphism with exudative AMD was compared between the groups. Mean age was 72.6±6.4 for controls and 74.9±7.4 for case group (P=0.006). The difference between CRP levels in cases and controls was not statistically significant (P=0.055). However, Y402H variant of CFH in both homozygous and heterozygous carriers C allele was significantly more frequent among exudative AMD patients than controls, 32.1 versus 6.5% (P<0.001). Evaluating various CRP levels in patients with CC and non-CC genotypes disclosed that in CC genotype group, higher CRP level (>3mg/L) was associated with higher risk of developing exudative AMD (OR=12.0, CI: 1.5-98.8) compared with the control group. This study disclosed no difference in CRP levels per se between exudative AMD patients with control group. However, higher levels of CRP in the presence of C allele of Y402H might confer more risk for the development of exudative AMD.

Macular Supplements Containing Zinc and Vitamin A Should Be Replaced with Meso-Zeaxanthin, Lutein and Zeaxanthin: An Ophthalmic Need for Pharmacovigilance

Objective: The objective of this paper is to report the importance of ophthalmic pharmacovigilance in AREDS macular formulations due to the potential toxicity of these macular vitamins with minimal benefit for patients with advanced exudative macular degeneration. Background: Age Related Eye Disease Studies macular formulations are currently treated as nutritional supplements and as such, do not undergo the required evaluation process for toxicity as pharmacologic agents. However, they more closely resemble a pharmacologic agent rather than a true nutritional supplement. Results: Macular formations have minimal benefit for patients with advanced exudative age-related macular degeneration and contain unsafe doses of substances like beta-carotene and zinc, which have the potential to cause cancer, Alzheimer’s disease, and worsen macular degeneration. This potential for toxicity necessitates pharmacovigilance for macular supplements to prevent exposure to harmful substances for negligible gain. Conclusion: These supplements should be replaced with other compounds that have both macular protective properties and an excellent safety profile such as Meso-Zeaxanthin, lutein and zeaxanthin.

Parafoveal contributions to retinal function during ranibizumab therapy for age-related macular degeneration

ObjectiveThe standard measure for the assessment of functional vision in the central retina is best corrected visual acuity (VA). Our aim was to investigate whether it is an advantage to include tests for functional changes in the near retinal periphery to monitor treatment effects in patients receiving multiple injections of anti–vascular endothelial growth factor (anti-VEGF) agents for advanced exudative age-related macular degeneration (AMD). DesignProspective pilot study. ParticipantsOur cohort consisted of 24 patients with exudative AMD (mean age ± SD: 77.46 ± 7.82 years) treated at an ophthalmology clinic. MethodsWe compared data from standard functional measurements, VA-near, and contrast sensitivity (CS), with results from the macular mapping test (MMT) at 10% and 100% contrast. Measurements of retinal thickness by optical coherence tomography (OCT) were used to document the morphologic efficacy of the anti-VEGF agent. Tests were performed at baseline and 4 weeks after 3 monthly ranibizumab injections. ResultsAll 4 functional tests yielded successes (equal or better visual performance after treatment) in 79.2% to 83.3% of cases. Including test locations in the near periphery yielded the highest success rate in the MMT at 10% contrast. Values for VA-near and CS also improved in a majority of cases. OCT measurements of retinal thickness indicated that the agent was effective in the fovea and near periphery. ConclusionsOur findings indicate that using the MMT adds information about functional changes in the near periphery of the retina and allows more sensitive assessment of treatment effects or disease progression without the high expense of other techniques.

Monotherapy or combination treatments of photodynamic therapy and intravitreal anti-vascular endothelial growth factor drugs for advanced exudative age-related macular degeneration

Objective To observe the efficacy of monotherapy and combination treatments of photodynamic therapy (PDT) and intravitreal anti- vascular endothelial growth factor (VEGF) drugs for advanced exudative age-related macular degeneration (EAMD).Methods Thirty-two eyes from 28 patients with EAMD were enrolled in this study.Fifteen eyes were treated with PDT or intravitreal anti-VEGF drugs (monotherapy group),while 17 eyes were treated with combination treatments of PDT and intravitreal anti-VEGF drugs (combination group).The follow-up was ranged from 5 to 28 months with a mean of 21 months.Vision and intraocular pressure were measured and optical coherence tomography (OCT) was performed every month after treatment.Fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) were performed every 3 months during follow-up period.The changes of visual acuity,leakage in macula lutea and central retinal thickness (CRT) before and after treatment,and adverse events during follow-up period were observed.The mean treatment times of monotherapy and combination group were compared and analyzed.Results Among 32 eyes,visual acuity improved in 20 eyes (62.5％),stabilized in 9 eyes (28.1％) and decreased in 3 eyes (9.4％).The leakage in macula lutea disappeared in 17 eyes (53.1％),decreased in 12 eyes (37.5％) and increased in 3 eyes (9.4％).CRT was reduced in 23 eyes (71.8％),increased in 9 eyes (28.2％).The mean treatment times of the combination group (2.3±0.2)was significantly less than that of monotherapy group (3.4 ± 0.5)(P＜0.05).No adverse events such as secondary retinal hemorrhage,vitreous hemorrhage or endoophthalmitis were found during the follow-up duration.Conclusions Both monotherapy and combination treatments of PDT and intravitreal anti-VEGF drugs for EAMD may improve visual acuity,exudation and macular edema.Combination of PDT and antiVEGF therapy decreases the frequency of retreatment. Key words: Macular degeneration/ therapy; Choroidal neovascularization/therapy; Antibodies,monoclonal/therapeutic use; Triamcinolone acetonide/therapeutic use; Photochemotherapy

Human retinal pigment epithelium (RPE) transplantation: outcome after autologous RPE-choroid sheet and RPE cell-suspension in a randomised clinical study

AimsTo evaluate the outcome after two types of retinal pigment epithelium (RPE) transplantation techniques.MethodsFourteen consecutive patients with advanced exudative age-related macular degeneration (AMD) were randomly assigned to RPE-choroid sheet transplantation...

Maculoplasty for age-related macular degeneration: Reengineering Bruch's membrane and the human macula

Age-related macular degeneration (AMD) is the leading cause of blindness in the western world. Over the last decade, there have been significant advances in the management of exudative AMD with the introduction of anti-VEGF drugs; however, many patients with exudative AMD continue to lose vision and there are no effective treatments for advanced exudative AMD or geographic atrophy. Initial attempts at macular reconstruction using cellular transplantation have not been effective in reversing vision loss. Herein we discuss the current status of surgical attempts to reconstruct damaged subretinal anatomy in advanced AMD. We reinforce the concept of maculoplasty for advanced AMD, which is defined as reconstruction of macular anatomy in patients with advanced vision loss. Successful maculoplasty is a three-step process that includes replacing or repairing damaged cells (using transplantation, translocation or stimulation of autologous cell proliferation); immune suppression (if allografts are used to replace damaged cells); and reconstruction or replacement of Bruch's membrane (to restore the integrity of the substrate for proper cell attachment). In the current article we will review the rationale for maculoplasty in advanced AMD, and discuss the results of initial clinical attempts at macular reconstruction. We will then discuss the role of Bruch's membrane damage in limiting transplant survival and visual recovery, and discuss the effects of age-related changes within human Bruch's membrane on the initial attachment and subsequent proliferation of transplanted cells. We will discuss attempts to repair Bruch's membrane by coating with extracellular matrix ligands, anatomic reconstitution of the inner collagen layer, and the effects of Bruch's membrane reconstruction of ultrastuctural anatomy and subsequent cell behavior. Lastly, we will emphasize the importance of continued efforts required for successful maculoplasty.

Heredity and Age-Related Macular Degeneration

To determine the concordance of age-related macular degenerative changes in monozygotic twins. Between 1984 and 1993, we examined a total of nine pairs of monozygotic twins with substantial age-related macular degenerative changes in at least one member of the pair, ranging from extensive large drusen to advanced atrophic and/or disciform scarring. Eight pairs were female and one pair was male. Ages ranged from 62 to 88 years. Monozygosity was confirmed by genetic testing in each of the seven twin pairs on whom it was performed. In eight of the nine twin pairs, the fundus appearance and the incidence of visual impairment were similar. In the ninth pair, one twin had advanced exudative age-related macular degeneration with vision loss in one eye, while the other had large, confluent drusen and good visual function in both eyes. Environmental factor, including diet, geographic background, and medical history, were essentially similar in the twin pairs. Although selection factors and similar environmental influences might impact our findings, the markedly similar incidence of macular degenerative changes in these monozygotic twins suggests that a substantial genetic component may exist in a potentially large proportion of patients with age-related macular degeneration. Further studies are warranted to define this hereditary influence.