Wet-type Age-related Macular Degeneration Research Articles

Serum adropin level in wet-type age-related macular degeneration

PurposeOur objective was to compare the serum Adropin levels between patients with wet-type Age-Related Macular Degeneration (AMD) and otherwise healthy individuals.MethodThe study included 45 patients with wet-type AMD and 45 individuals without age-related macular degeneration. Patients with co-morbidities such as diabetes, hypertension, autoimmune diseases, and a previous history of visual impairment; were excluded. FBS, Hemoglobin A1C (HbA1C), lipid profile, and serum Adropin level were checked.ResultsThe mean serum Adropin level of patients with wet-type AMD was significantly lower than the control group (P-value < 0.001). Also, the mean High-sensitivity C-reactive protein ( hsCRP) level and High Density Lipoprotein (HDL) were significantly higher in wet-type AMD patients (P-value = 0.031 and < 0.001 respectively).ConclusionsIn our study, wet-type AMD was associated with a lower level of serum Adropin. Because of Adropin involvement in glucose metabolism and age-related changes, it may have a role in the pathogenesis of AMD, but it requires more investigations at the molecular level to elucidate its function.

Age-Related Macular Degeneration in Coastal Communities: Review Article

Background: Due to geographic conditions, Indonesia has gotten exposed to sun rays consistenly for the whole year. Besides, Many parts of the Indonesian coastline are open areas while at the same time there's not much place to take shelter caused exposure to sun rays become more frequent. This condition puts the people around coasts at high risk of Age-related macular degeneration (AMD).&#x0D; &#x0D; Content: AMD is a chronic eye disease that causes central vision impairment due to degeneration of retinal photoreceptor. 8 millions of people are enduring blindness due to retina complications not excluding AMD. Causes for AMD are ranging from sun exposure, smoking habit, diet, hypertency, and genetic factors. Blue light and ultraviolet light that is contained within sun rays are the main cause of harm to tissues in the retina and reduces vision function. In preventing AMD progression, photodynamic laser therapy, photocoagulation, and anti-vascular endothelial growth factor (anti-VEGF) therapy is highly recommended.&#x0D; &#x0D; Conclusion: Best action that can be done currently is preventing it by holding counseling sessions and increasing public awareness through education and therapies like laser therapy and anti-VEGF won't cure AMD but will slow down the progression, especially wet type AMD.

Evaluation of systemic immune-inflammatory index in patients with wet age-related macular degeneration

ABSTRACT Clinical relevance The systemic immune-inflammatory index is a relatively new parameter and has been shown to increase in inflammatory diseases. Background The primary aim of this study was to investigate the systemic immune-inflammatory index in patients with wet-type age-related macular degeneration. The secondary aim was to determine the relationship between best-corrected visual acuity, central macular thickness, subfoveal choroidal thickness, systemic immune-inflammatory index, platelet-to-lymphocyte ratio, and neutrophil-to-lymphocyte ratio. Methods This study retrospectively analysed patients with wet-type age-related macular degeneration between 2018 and 2022. Demographic data and peripheral complete blood count were obtained from the electronic medical record system. The most recent best-corrected visual acuity, central macular thickness, and subfoveal choroidal thickness values (within one month) for complete blood count were obtained from case sheets and the optical coherence tomography digital image database. The systemic immune-inflammatory index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio were calculated. Age- and sex-matched controls were also generated. Results Thirty-three patients (23 males, 10 females) with wet-type age-related macular degeneration and 43 controls (24 males, 19 females) were included. The groups were similar in terms of age and sex (78.0 ± 6.3 vs. 75.6 ± 6.6 years, p = 0.59; p = 0.38 for sex). The systemic immune-inflammatory index was higher in the wet-type age-related macular degeneration group (460.5 vs. 440.4); however, this difference was not statistically significant. When the correlations between the systemic immune-inflammatory index, platelet-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, best-corrected visual acuity (logMAR), central macular thickness, and subfoveal choroidal thickness were examined, there was only a moderate positive correlation between best-corrected visual acuity and platelet-to-lymphocyte ratio (r = 0.46, p = 0.007). Conclusion There were no differences in the systemic immune-inflammatory index, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio between the wet-type age-related macular degeneration and control groups. There was a positive correlation between the platelet-to-lymphocyte ratio and best-corrected visual acuity (logMAR). The systemic immune-inflammatory index was higher in patients with wet-type age-related macular degeneration than in the control group; however, this difference was not statistically significant.

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&gt;0.05). The difference between the mean values of the Schirmer I test was statistically unsignificant in patients in the two groups (p&gt;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

Intraocular neutralizing antibodies against aflibercept in patients with age related macular degeneration

PurposeTo detect immunoglobulins in aqueous humour of AMD patients after repeated administration of intravitreal aflibercept.Patients and methodsTwenty-one patients (age: 77.85 ± 9.21 years) previously treated with intravitreal aflibercept due to wet type age-related macular degeneration (AMD group) and 18 age-matched control subjects (age: 69.75 ± 12.67 years) were included in this study. Patients in the AMD group received a mean of 5 intravitreal injections (min: 1 max: 17) prior to the cataract surgery. Samples of aqueous humour (50 μl) were obtained by anterior chamber paracentesis as the first step of routine cataract surgery. The IgG content of the samples was analysed by an in-house developed ELISA system.ResultsA significant increase in nonspecific IgG levels in the AMD group was detected compared to the control group (13.37 ± 6.65 vs. 9.44 ± 6.55 μg/ml; p = 0.03). In 11 patients, intraocular anti-aflibercept immunoglobulins could be detected (0.05 ± 0.01 μg/ml) which was significantly higher than the limit of detection for anti-aflibercept (0.04 μg/ml; p = 0.001). No correlation was found between the number of injections or the type of CNV and the aqueous level of anti-aflibercept (r = 0.02; p = 0.95).ConclusionAccording to our results, penetration of non-specific systemic antibodies through the impaired blood-retinal barrier is higher in patients with neovascular AMD than in subjects with an intact structural barrier. Evaluation of neutralizing antibodies to anti-VEGF agents in the aqueous humour can lead us to understanding tachyphylaxis and changes in intraocular immune mechanisms due to AMD.

Based on the Real-Life Data of Türkiye; Comparison of Anatomical and Functional Outcomes of Phakic and Pseudophakic Patients in Wet Type Age-Related Macular Degeneration.

The aim of the study was comparison of wet-type age-related macular degeneration in phakic and pseudophakic patients in terms of anatomical and functional success based on the real-life data of Türkiye. The multicenter retrospective real-life study data of the. retinal study group were used in this study. Among 867 eyes of 867 patients were included in the study. Patients were divided into two groups according to the status of the lens; phakic group and pseudophakic group. The follow-up period of the two groups, the number of injections at the 1st, 2nd, and 3rd years, and changes in the central macular thickness (CMT, μ) and visual acuity (VA, logMAR) of the patients at the beginning, 6th, 12th, 24th, and 36th months were examined. In our study, the number of injections in the 1st, 2nd, and 3rd years, respectively, was 4.2±2.0, 1.8±1.9, and 1.0±1.7 in the phakic group, and 3.9±2.0, 1.7±1.9, and 0.8±1.4 in the pseudophakic group. When the two groups were compared in terms of the number of injections, there was a statistically significant difference in the 1st year, but there was no significant difference in the 2nd and 3rd years (p=0.001, p=0.350, and p=0.288, respectively). There was no statistically significant difference between the groups in terms of CMT in the baseline, 6th, 12th, 24th, and 36th months (p=0.991, p=0.327, p=0.652, p=0.599, and p=0.873, respectively). Although there was no difference in VA between groups at the beginning (p=0.052), the phakic group showed statistically better VA in controls at 3rd, 6th, 12th, 24th, and 36th months (p=0.001, p=0.001, p=0.000, p=0.000, and p=0.003, respectively). Differences in the number of injections and visual results between phakic and pseudophakic patients in wet type AMD may necessitate the creation of different treatment and follow-up protocols.

Pachychoroid neovasculopathy can mimic wet type age-related macular degeneration

Purposeto determine the percentage of patients with pachychoroid neovasculopathy (PNV) among patients who have been misdiagnosed and treated with wet age-related macular degeneration (AMD).MethodsIn this retrospective cross-sectional study, patients over 55 years old, who were diagnosed with wet AMD, were re-evaluated. All patients were recalled for examination and imaging. Patients with PNV were differentiated form wet AMD based on inclusion and exclusion criteria.ResultsOverall, 120 patients (137 eyes) were recorded with wet AMD in the clinic. Finally, after complete re-evaluation, 94 (106 eyes) and 26 patients (31 eyes) were assigned to the AMD and the PNV group, respectively. Thus, a total of 20% of patients with primary mistake diagnosis of wet AMD, actually had PNV. The mean sub field choroidal thickness (SFCT) in the AMD and PNV groups was 173.8 ± 69 μm and 342 ± 27 μm, respectively. Drusen and pachydrusen were found in 69.9% and 24% of the cases with AMD and PNV, respectively (P = 0.001). The average number of intravitreal injections of anti-VEGF (vascular endothelial growth factor) required in the AMD and PNV groups was about 5 and 3, respectively, which was statistically significant (P-value 0.02).ConclusionThis study revealed that about a one-fifth of wet AMD patients are actually pachychoroid neovasculopathy. These patients were younger and had thicker SFCT, and developed less subretinal scarring. Thus, the disorder must be considered as an important differential diagnosis of AMD-CNV.

PGE2 promotes macrophage recruitment and neovascularization in murine wet-type AMD models

Age-related macular degeneration (AMD), a progressive chronic disease of the central retina, is a leading cause of blindness worldwide. Activated macrophages recruited to the injured eyes greatly contribute to the pathogenesis of choroidal neovascularization (CNV) in exudative AMD (wet AMD). This study describes the effects of cyclooxygenase-2 (COX2)/prostaglandin E2 (PGE2) signalling on the macrophage activation and CNV formation of wet AMD. In a mouse model of laser-induced wet AMD, the mice received an intravitreal injection of celecoxib (a selective COX2 inhibitor). Optical coherence tomography (OCT), fundus fluorescein angiography (FFA), choroidal histology of the CNV lesions, and biochemical markers were assessed. The level of PGE2 expression was high in the laser-induced CNV lesions. Macrophage recruitment and CNV development were significantly less after celecoxib treatment. E-prostanoid1 receptor (EP1R)/protein kinase C (PKC) signalling was involved in M2 macrophage activation and interleukin-10 (IL-10) production of bone marrow-derived macrophages (BMDMs) in vitro. In addition, IL-10 was found to induce the proliferation and migration of human choroidal microvascular endothelial cells (HCECs). Thus, the PGE2/EP1R signalling network serves as a potential therapeutic target for CNV of the wet-type AMD.Graphical AXv86vuL_n_YsWmKFp4z_2Video abstract

Role of Adiponectin Peptide I (APNp1) in Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is an eye disease that can cause central vision loss, particularly in the elderly population. There are 2 classes of AMD, wet-type and dry-type. Wet-type involves excess angiogenesis around the macula, referred to as choroidal neovascularization (CNV). This can result in leaky vessels, often causing more severe vision loss than dry-type AMD. Adiponectin peptide 1 (APNp1) has been shown to slow the progression of CNV. Here, we used a mouse model and FITC-labeled APNp1 to determine if APNp1 could be delivered effectively as an eye drop. Our experiment revealed that topically applied FITC-APNp1 could reach the macula of the eye, which is crucial for treating wet-type AMD. We also tested delivery of APNp1 via injection of an adeno-associated virus (AAV) vector in a mouse model of CNV. AAV is a harmless virus easy to manipulate and is very often used for protein or peptide deliveries. Results revealed an increase in the expression of APNp1 in the retina and choroid over a 28-day period. Finally, we investigated the mechanism by which APNp1 affects CNV by examining the expression of adiponectin receptor 1 (AdipoR1) and proliferating cell nuclear antigen (PCNA) in the retinal and choroidal tissue of the mouse eyes. AdipoR1 and PCNA were overexpressed in these tissues in mice with laser-induced CNV compared to naïve mice. Based on our data shown here, we think it will enhance our understanding of APNp1 as a therapeutic agent for wet-type AMD and possible treatment alternatives that could be more beneficial for patients.

Silent Information Regulator T1 in Aqueous Humor of Patients with Age-Related Macular Degeneration

Purpose: The purpose of this study is to compare the aqueous humor level of Silent Information Regulator T1 (SIRT1) between patients with Age-related Macular Degeneration (AMD) and cataract patients. Materials and Methods: Aqueous humor level of SIRT1 was measured by enzyme-linked immunosorbent assay in 13 patients with wet-type AMD (n=13, AMD group) and 13 patients with cataracts (cataract group). In addition, the thickness of each retinal layer was determined by optical coherence tomography. Results: The aqueous humor level of SIRT1 was significantly lower in the AMD group than in the cataract group (p=0.007). In the AMD group, the SIRT1 level was positively correlated with the thickness of the retinal ganglion cell layer (r=0.31) and the inner nuclear layer (r=0.76). Conclusion: The aqueous level of SIRT1 decreased as the ganglion cell layer and inner nuclear layer became thinner, suggesting that reduction of SIRT1 activity might be involved in the pathogenesis of this disease.

Thyroid Dysfunction as a Modifiable Risk Factor for Wet Type Age-Related Macular Degeneration: A Case-Control Study.

Purpose:To investigate possible links between thyroid dysfunction and prevalence of wet age-related macular degeneration (AMD).Methods:The present case–control study enrolled a total number of 90 patients with wet AMD and 90 sex-, and age-matched controls through a convenient sequential sampling method. Thyroid hormones were profiled in serum assay. Statistical measures were done to compare means between groups.Results:Our findings showed a significant difference in free T4 levels between wet AMD and control groups (P = 0.002), but the mean values of total T3 and Thyroid-stimulating hormone levels were similar between the two groups. In addition, there were no differences in serum lipid profile between groups. Although no significant difference in the history of hypertension and hyperlipidemia between wet AMD and control groups was found, the history of smoking was higher in controls (P = 0.039).Conclusion:Thyroid hormone abnormalities may be associated with wet AMD.

Sustained-Release Microspheres of Rivoceranib for the Treatment of Subfoveal Choroidal Neovascularization.

The wet type of age-related macular degeneration (AMD) accompanies the subfoveal choroidal neovascularization (CNV) caused by the abnormal extension or remodeling of blood vessels to the macula and retinal pigment epithelium (RPE). Vascular endothelial growth factor (VEGF) is known to play a crucial role in the pathogenesis of the disease. In this study, we tried to repurpose an investigational anticancer drug, rivoceranib, which is a selective inhibitor of VEGF receptor-2 (VEGFR2), and evaluate the therapeutic potential of the drug for the treatment of wet-type AMD in a laser-induced CNV mouse model using microsphere-based sustained drug release formulations. The PLGA-based rivoceranib microsphere can carry out a sustained delivery of rivoceranib for 50 days. When administered intravitreally, the sustained microsphere formulation of rivoceranib effectively inhibited the formation of subfoveal neovascular lesions in mice.

Evaluation of oxidative stress, 3-Nitrotyrosine, and HMGB-1 levels in patients with wet type Age-Related Macular Degeneration.

BackgroundThis study aims to compare serum HMGB-1, 3-nitrotyrosine (3-NT), TAS, TOS, and OSI levels in Wettype Age-Related Macular Degeneration (wAMD) patients and healthy controls to determine the correlation of these parameters with each other.MethodsThirty patients with Wet-type Age-Related Macular Degeneration (wAMD) and 27 healthy adults, as controls were enrolled in the study. We determined the TAS and TOS levels in serum samples of both groups using commercial kits on a microplate reader. Serum HMGB-1 and 3-NT levels were measured with the enzyme-linked immunosorbent assay method.ResultsHMGB-1 levels were significantly higher in the patient group (137.51 pg/mL, p=0.001), while there was no difference between the two groups in serum 3-NT levels (p=0.428). A statistically significant difference found in the levels of TOS and OSI (p=0.001 and p=0.045, respectively) between the patients and controls, however, no significant difference was observed between the groups in terms of TAS levels (p=0.228).ConclusionsOxidative stress and HMGB-1 levels were increased in wAMD patients and enhanced oxidative stress may be associated with increased tissue necrosis and inflammation. Thus administration of antioxidant treatment in addition to routine therapy should be considered in wAMD.

The impact of glucosamine on age-related macular degeneration in patients: A nationwide, population-based cohort study.

PurposeTo analyze the association between glucosamine (GlcN) use and the risk of age-related macular degeneration (AMD) using claims data from the National Health Insurance Research Database (NHIRD).MethodsA retrospective, population-based study was conducted with NHIRD data from a 14-year period (2000–2013). Chi-squared and Student’s t-tests were used to evaluate differences between the study and comparison cohorts for categorical and continuous variables, respectively. Risk factors for disease development were examined by the adjusted hazard ratio (aHR) with 95% confidence interval. Kaplan-Meier analysis was performed to compare the cumulative risk of AMD between the two cohorts.ResultsIn total, 1,344 patients with GlcN treatment were enrolled in the study cohort and 5,376 patients without GlcN use were enrolled in the comparison cohort. The incidence rate of AMD was lower with GlcN use (3.65%) than without GlcN use (5.26%) (P = 0.014). GlcN use was associated with a lower risk of developing AMD among patients with hyperlipidemia, coronary artery disease, chronic obstructive pulmonary disease, stroke, other neurological disorders, or degenerative arthritis. Although the incidence of wet type AMD did not significantly differ (P = 0.91), the incidence of dry type AMD was lower in patients with GlcN use (2.9%) than those without GlcN use (4.84%) (P = 0.003). Kaplan-Meier analysis similarly revealed a lower rate of dry type AMD in patients with GlcN use compared to those without GlcN use (log-rank P = 0.004).ConclusionsGlcN treatment can decrease the risk of developing dry type AMD. Further prospective controlled studies are needed to determine the effectiveness of GlcN treatment in patients with AMD and the associated mechanism.

Is there a relationship between hematological inflammatory parameters and age-related macular degeneration?

Purpose:We aimed to analyze blood inflammation parameters in patients with age-related macular degeneration (AMD).Methods:In this retrospective study, patients were divided into three groups: wet-type AMD (n = 60), dry-type AMD (n = 60), and healthy controls (n = 71). The laboratory and demographic data of the patients were analyzed. Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) were calculated manually.Results:The mean NLR was 2.26 ± 1.42 in the dry-type AMD group, 3.90 ± 1.65 in the wet-type AMD group, and 1.84 ± 0.61 in the control group (p < 0.001). The mean MLR was 0.30 ± 0.20 in the dry-type AMD group, 0.47 ± 0.31 in the wet-type AMD group, and 0.28 ± 0.14 in the control group (p < 0.001). The mean PLR was 129.31 ± 79.82 in the dry-type AMD group, 156.67 ± 83.99 in the wet-type AMD group, and 135.59 ± 58.68 in the control group (p = 0.101). Receiver operating characteristic (ROC) curve analyses revealed that the area under the curve (AUC) for NLR and MLR was 0.920 and 0.717, respectively, for wet-type AMD. The sensitivity and specificity of NLR for wet-type AMD were 64% and 93%, respectively, whereas MLR was 63% and 75%, respectively.Conclusion:Simple blood tests revealed that NLR and MLR were significantly higher in patients with wet-type AMD than in patients with dry-type AMD and healthy controls, which implies low-grade inflammation.

Effects of Repeated Intravitreal Injections of Dexamethasone Implants on Intraocular Pressure: A 4-Year Study.

PurposeDexamethasone and other corticosteroids are administered intravitreally to treat a variety of retinal diseases. As a side effect, they can alter intraocular pressure (IOP). The purpose of this study is to describe the incidence, severity, and management of ocular hypertension following the administration of multiple intravitreal injections of dexamethasone implants.Materials and MethodsA total of 78 eyes of 78 subjects (males 62%; females 38%; mean age 67 ± 13 years SD) received a total of 152 intravitreal injections of 0.7 mg dexamethasone implants over 4 years. Indications included retinal vein occlusion (87%), diabetic macular edema (9%), wet-type age-related macular degeneration (4%). Ocular hypertension was defined as intraocular pressure above 23 mmHg or any pressure increase of 10 mmHg or more from baseline values. IOP was measured by applanation tonometry before the injection (T0), as well as one week (T1), one month (T2), and three months (T3) afterwards.ResultsFive percent (4/78) of subjects developed ocular hypertension after the 1st injection. On the second and third rounds, additional 7.2% (3/42) and 4.2% (1/24) of subjects developed the same side effect. Among the 8 subjects who received a fourth injection, none was found with OHT. Pressure elevations were detected at T2 and T3. In all patients, topical medical therapy was sufficient to lower the IOP below threshold. Mean pressure variations following the first injection as compared to previous recorded values were +0.97 mmHg (T1), +0.92 mmHg (T2), and −0.41 mmHg (T3) (p < 0.05). Mean pressure variations following the second injection were +0.54 mmHg (T1), +0.23 mmHg (T2) and −0.66 mmHg (T3) (p < 0.05).ConclusionOcular hypertension is a recognized side effect of intravitreal dexamethasone. Some patients develop it right after the first injection, while others develop it subsequently, on the 2nd or 3rd round. This side effect becomes most apparent 30–90 days following the implantation procedure and responds well to topical pressure-lowering medications.

Serum malondialdehyde, monocyte chemoattractant protein-1, and vitamin C levels in wet type age-related macular degeneration patients.

Purpose:The purpose of this study was to investigate the serum levels of malondialdehyde (MDA) which is a marker of oxidative stress, monocyte chemoattractant protein-1 (MCP-1) which has an important role in inflammation, and vitamin C which has antioxidant properties in patients with wet age-related macular degeneration (wAMD).Methods:Thirty patients with wAMD were included in the study and serum levels of MDA, MCP-1, and vitamin C were compared with healthy participants (n = 30). Serum vitamin C and MDA levels were measured using a spectrophotometric method. Serum MCP-1 levels were determined by the ELISA method.Results:MCP-1 and MDA levels were higher in patients with wAMD compared with the control group (p < 0.05). Serum vitamin C levels were lower in patients with wAMD compared with the control group (p < 0.05).Conclusions:The increase in the MCP-1 levels in patients with wAMD may be associated with increased inflammation in wAMD. Decreased serum vitamin C and elevated MDA levels in patients with wAMD suggest increased oxidative stress in wAMD patients. These results indicate that the increased oxidative stress and inflammation can play a role in the pathogenesis of wAMD.

Is age-related macular degeneration a local manifestation of systemic disorder? Changes in nailfold capillaries at age-related macular degeneration.

Determining whether nailfold capillary involvement is present in patients with Age-related macular degeneration (AMD) and whether there are different nailfold capillaroscopy findings between wet and dry types. From January 2016 to December 2017, with an initial diagnosis of AMD, 53 consecutive adult patients (AMD group) and 91 age- and sex-matched healthy individuals were studied prospectively. There was no history of any other ocular disease and other disease affecting nailfold capillaries. All subjects underwent a complete ophthalmic examination. The classified and advanced stages of wet and dry types were not included. All nailfold capillaroscopy examinations were performed by the same rheumatologist. It was found that the frequency of major capillaroscopic findings such as capillary ectasia, micro-hemorrhage, tortuosity, neo-formation, bizarre capillary, and bushy capillaries increased in the AMD group according to the normal group, but no significant relationship was found for capillary aneurysm. In dry or wet type of AMD in terms of ectasia, micro-hemorrhage, tortuosity, neo-formation, bizarre structure, bushy structure, or aneurism of nailfold capillaries, no significant correlation was found. Nailfold capillaroscopy can detect microvascular changes in the nailfold capillary, in early and late stages of AMD. There were morphological changes in the nailfold capillaries of AMD patients, suggesting that there are systemic superficial microvascular changes that may be due to the systemic nature of the disease.

Dysregulations of follicular helper T cells through IL-21 pathway in age-related macular degeneration

Age-related macular degeneration (AMD) is the most common cause of vision loss in the aged population. Aging and inflammation are thought to promote AMD pathogenesis in people with genetic predisposition. Follicular helper T (Tfh) cells play critical roles in inflammatory responses. Here, we investigated circulating Tfh cells in AMD patients. Circulating Tfh cells were defined as CXCR5+ CD4 T cells. Data showed that patients with the wet-type AMD presented significantly higher levels of Tfh cells than non-AMD controls. Interestingly, the Tfh cells from dry and wet AMD patients also presented significantly higher ICOS and PD-1 expression, together with higher IL-17 and IL-21 expression directly ex vivo and following PMA/ionomycin stimulation. The expression of IFNg and IL-10, on the other hand, was not different between Tfh cells from AMD patients and their counterparts in non-AMD controls. Functional analysis revealed that Tfh cells from AMD patients were better at inducing the production of IgG and IgA, and this effect was in an IL-21-dependent manner. Together, we demonstrated that the circulating Tfh cell responses were dysregulated in AMD patients.

Establishing Liposome-Immobilized Dexamethasone-Releasing PDMS Membrane for the Cultivation of Retinal Pigment Epithelial Cells and Suppression of Neovascularization.

Age-related macular degeneration (AMD) is the eye disease with the highest epidemic incidence, and has great impact on the aged population. Wet-type AMD commonly has the feature of neovascularization, which destroys the normal retinal structure and visual function. So far, effective therapy options for rescuing visual function in advanced AMD patients are highly limited, especially in wet-type AMD, in which the retinal pigmented epithelium and Bruch’s membrane structure (RPE-BM) are destroyed by abnormal angiogenesis. Anti-VEGF treatment is an effective remedy for the latter type of AMD; however, it is not a curative therapy. Therefore, reconstruction of the complex structure of RPE-BM and controlled release of angiogenesis inhibitors are strongly required for sustained therapy. The major purpose of this study was to develop a dual function biomimetic material, which could mimic the RPE-BM structure and ensure slow release of angiogenesis inhibitor as a novel therapeutic strategy for wet AMD. We herein utilized plasma-modified polydimethylsiloxane (PDMS) sheet to create a biomimetic scaffold mimicking subretinal BM. This dual-surface biomimetic scaffold was coated with laminin and dexamethasone-loaded liposomes. The top surface of PDMS was covalently grafted with laminin and used for cultivation of the retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSC-RPE). To reach the objective of inhibiting angiogenesis required for treatment of wet AMD, the bottom surface of modified PDMS membrane was further loaded with dexamethasone-containing liposomes via biotin-streptavidin linkage. We demonstrated that hiPSC-RPE cells could proliferate, express normal RPE-specific genes and maintain their phenotype on laminin-coated PDMS membrane, including phagocytosis ability, and secretion of anti-angiogenesis factor PEDF. By using in vitro HUVEC angiogenesis assay, we showed that application of our membrane could suppress oxidative stress-induced angiogenesis, which was manifested in decreased secretion of VEGF by RPE cells and suppression of vascularization. In conclusion, we propose modified biomimetic material for dual delivery of RPE cells and liposome-enveloped dexamethasone, which can be potentially applied for AMD therapy.