Exudative Age-related Macular Degeneration Patients Research Articles

Efficacy and safety of conbercept injection in the treatment of exudative senile macular degeneration

Objective To investigate the efficacy and safety of conbercept injection in the treatment of exudative age-related macular degeneration(AMD). Methods From October 2016 to October 2017, 300 patients(300 eyes) with exudative AMD in Linfen Central Hospital were divided into two groups according to the random number table method.The study group(150 cases and 150 eyes) received intravitreal injection of 0.05 mL of conbercept once a month for 3 months.The control group(150 cases and 150 eyes) received conservative treatment.All patients were followed up for 12 months after treatment.The differences of BCVA, CMT, QOL, clinical efficacy and complications between the two groups were compared. Results BCVA was significantly increased and CMT was significantly decreased in the two groups after treatment, and BCVA was higher in the study group at 9 months [(0.55±0.11) vs.(0.51±0.15)], 12 months [(0.59±0.21) vs.(0.53±0.11)] after treatment compared with the control group(t=2.634, 3.010, all P<0.05), and CMT was lower in the study group at 1-12 months after treatment(t=5.321, 20.035, 25.593, 22.456, 26.326, 27.005, all P<0.05). At the last follow-up, the distant vision, regulating ability, reading and fine work scores in the study group were (55.27±8.24)points, (30.21±5.20)points, (20.15±5.01)points, (47.02±12.34)points, respectively, which were better than those in the control group[(50.21±6.35)points, (25.34±4.17)points, (16.24±3.27)points, (40.25±9.25)points](t=6.352, 5.324, 6.392, 8.251, all P<0.05). The total effective rate of the study group[88.00%(132/150)] was higher than that of the control group[76.67%(115/150)](χ2=6.623, P<0.05). There were no serious complications in the two groups. Conclusion Conbercept injection can significantly improve the eyesight of exudative AMD patients, improve the quality of life, it is safe and reliable, and its treatment effect for AMD is better than traditional conservative treatment. Key words: Wet macular degeneration; Compaq sipper injection; Vision, ocular; Quality of life; Treatment outcome; Comparative effectiveness research; Aged

Genome-wide association study suggests four variants influencing outcomes with ranibizumab therapy in exudative age-related macular degeneration.

To identify factors associated with ranibizumab responses in patients with exudative age-related macular degeneration (AMD), we performed a genome-wide association study (GWAS) and a replication study using a total of 919 exudative AMD patients treated with intravitreal ranibizumab in a Japanese population. In the combined analysis of GWAS and the replication study, no loci reached genome-wide significant level; however, we found four variants showed suggestive level of associations with visual loss at month three (rs17822656, rs76150532, rs17296444, and rs75165563: Pcombined < 1.0 × 10-5). Of the candidate genes within these loci, three were relevant to VEGF-related pathway (KCNMA1, SOCS2, and OTX2). The proportions of patients who worsened visual acuity were 13.7%, 38.8%, 58.0%, and 80.0% in patients with 0, 1, 2, and 3 or more identified risk variants, respectively. Changes in visual acuity decreased linearly as the number of risk variants increased (P = 1.67 × 10-12). The area under the curve using age, baseline visual acuity, and history of previous treatment was 0.607, and improved significantly to 0.713 in combination with identified variants (P < 0.0001). Although further study is needed to confirm their associations, our results offer candidate variants influencing response to ranibizumab therapy.

The Association Between Variants of Receptor for Advanced Glycation End Products (RAGE) Gene Polymorphisms and Age-Related Macular Degeneration

BackgroundAge-related macular degeneration (AMD) is the leading cause of blindness in people aged 65 years and older in developed countries. The pathogenesis of AMD has been linked to mechanisms involving inflammation, oxidative stress, and basal laminar deposit formation between retinal pigment epithelium (RPE) cells and the basal membrane, caused by advanced glycation end products (AGEs). AGEs are implicated in the pathogenesis of AMD through the AGE-and receptor for AGE (RAGE) interaction, which can be altered by polymorphisms of the RAGE gene. We examined RAGE rs1800624 and rs1800625 gene polymorphisms contributing to AMD development.Material/MethodsThe study enrolled 300 patients with early AMD, 300 patients with exudative AMD, and 800 healthy controls. The genotyping was carried out using the RT-PCR method.ResultsThe analysis of two single nucleotide polymorphisms (SNPs) in the RAGE gene showed that rs1800624 was associated with a 1.6-fold decreased risk for exudative AMD under the dominant model after adjustment for age (OR=0.616; 95% CI: 0.394–0.963; p=0.034) and each copy of allele T at rs1800624 was associated with a 1.4-fold decreased risk for exudative AMD development under the additive model after adjustment for age (OR=0.701; 95% CI: 0.510–0.962; p=0.028). Analysis revealed that the rs1800625 allele G at rs1800625 was associated with a 1.5-fold increased risk for exudative AMD after adjustment for age (OR=1.545; 95% CI: 1.003–2.379; p=0.048). These results suggested that the allele G at rs1800625 was a risk-allele for exudative AMD development. In haplotype analysis, A-G haplotype was significantly more frequently observed in exudative AMD patients compared to healthy controls (3.3% versus 1.4%, p=0.035).ConclusionsWe revealed a significant association between RAGE gene rs1800624 and rs1800625 polymorphisms and AMD risk. We considered T allele at rs1800624 to be protective against AMD development, while allele G at rs1800625 was considered to be a marker of poor prognosis in AMD development.

Chinese medicine formula HB01 for treating exudative age-related macular degeneration: a 6 consecutive months of clinical observation study

ObjectiveTo evaluate the clinical efficacy of Chinese medicine formula HB01 on exudative age-related macular degeneration (AMD) patients who received HB01 for 6 months by analyzing relative indexes. MethodsFrom July 2006 to August 2015, 139 eligible exudative AMD patients (183 eyes) were enrolled into this study and received aqueous extract from herbs of HB01 by oral twice a day (100 mL for once) for 6 months. The best corrected visual acuity, center macular thickness (CMT), hemorrhage area, fluorescein leakage area as the main outcomes were estimated and compared before and after treatment. ResultsAfter 3 and 6 months of treatment, visual acuity obtained a greater improvement (P < 0.01). After 1, 3 and 6 months of treatment, CMT obviously decreased (P < 0.05). After 3 and 6 months of treatment, the hemorrhage area and fluorescein leakage area also significantly narrowed (P < 0.01). During treatment, no significant adverse events relating to HB01 treatment were elucidated. ConclusionOn the basis of these results, HB01 could improve visual acuity, and reduce hemorrhage and fluorescein leakage of patients with exudative AMD, which may be an effective alternative and supportive treatment for exudative AMD.

Decreased Circulating Levels of Dickkopf-1 in Patients with Exudative Age-related Macular Degeneration

Aberrant activation of the Wnt/β-catenin signaling pathway plays a pathogenic role in retinal inflammation and neovascularization. Here, we investigated whether circulating levels of Dickkopf-1 (DKK-1), a specific inhibitor of this pathway, are altered in patients with exudative age-related macular degeneration (AMD). Plasma was obtained from 128 patients with exudative AMD, 46 patients with atrophic AMD and 111 healthy controls. DKK-1 levels in plasma were measured using ELISA, and data analyzed with one-way ANOVA, logistic regression analysis and receiver-operating characteristic analysis (ROC). We found that DKK-1 levels were decreased in exudative AMD patients, compared with healthy controls (P < 0.001) and atrophic AMD patients (P < 0.001). The decrease was more prominent in patients with classic choroidal neovascularization (CNV) than those with occult CNV (P < 0.001). The odds ratio (OR) of exudative AMD was 11.71 (95% CI; 5.24–6.13) for lowest versus upper quartile of DKK-1 levels. For discriminating exudative AMD patients, the optimum diagnostic cutoff of DKK-1 was 583.1 pg/mL with the area under curve (AUC) 0.76 (95% CI, 0.70–0.82; P < 0.001), sensitivity 78.1% and specificity 63.1%. These findings suggested that decreased circulating DKK-1 levels are associated with the development and severity of exudative AMD, and have potential to become a biomarker for exudative AMD.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY ASSESSMENT OF VASCULAR EFFECTS OCCURRING AFTER AFLIBERCEPT INTRAVITREAL INJECTIONS IN TREATMENT-NAIVE PATIENTS WITH WET AGE-RELATED MACULAR DEGENERATION.

To investigate vessel changes occurring after aflibercept injections in treatment-naive exudative age-related macular degeneration patients. Fifteen eyes of 15 patients affected by wet age-related macular degeneration were enrolled in the study. All the patients had a diagnosis of Type 1 choroidal neovascularization and were treated with 3 monthly aflibercept intravitreal injections (IVI). Subjects were evaluated by means of optical coherence tomography angiography at baseline, the day after the first injection and one month after both the first and the second IVI. At last, all the patients were followed up to 2 months after the third IVI. Foveal superficial vascular plexus flow density was 29.01% (21.13-37.32%) at baseline and was significantly reduced as soon as 1 month after the first IVI (median: 20.78%; interquartile range: 14.75-23.13%; P = 0.017). Parafoveal superficial vascular plexus flow density was 47.09% (44.91-51.72%) at baseline and significantly decreased as soon as 1 month after the second IVI (median: 44.40%; interquartile range: 41.59-49.29%; P = 0.034). Choroidal neovascularization lesion area remained stable throughout the follow-up. Nevertheless, interestingly, choroidal neovascularization flow area was significantly reduced as soon as the next day the first IVI (median: 0.37 mm and interquartile range: 0.27-0.72 mm at baseline; median: 0.30 mm and interquartile range: 0.24-0.64 mm at 1 day after the first IVI; P = 0.047). Intravitreal aflibercept injections are associated with a significant change in native retinal and choroidal vasculature. Moreover, the treatment did not cause a reduction in lesion area, but rather reduced the flow in the choroidal neovascularization.

Optical coherence tomography angiography and traditional multimodal fundus imaging in the diagnosis and activity evaluation of choroidal neovascularization in exudative age-related macular degeneration

Objective To compare the consistency and difference of optical coherence tomography angiography (OCTA) and traditional multimodal fundus imaging in the diagnosis and activity evaluation of choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). Methods A total of 112 exudative AMD patients (130 eyes) were included in this retrospective study, 62 were men (71 eyes) and 50 were women (59 eyes). The mean age was (68.250±9.789) years (range 50–91 years). All patients were underwent traditional multimodal fundus imaging including fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and spectral domain optical coherence tomography (OCT); OCTA was performed at the same time. The CNV type was divided into active and non-active according to the results of traditional multimodal fundus imaging. The vascular pattern was divided into active and non-active according to the results of OCTA. Using traditional multimodal fundus imaging as the standard, the sensitivity and specialty of OCTA was evaluated. Results In 130 eyes, CNV was visualized on traditional multimodal fundus imaging in 109 eyes (83.8%); CNV was visualized on OCTA in 103 eyes (79.2%), which including 7 eyes of false negative and 1 eye of false positive. The sensitivity of OCTA for CNV diagnosis was 93.6%, with specificity of 95.2%. The CNV detection rate between two methods had no significant difference (Youden index=0.89, Kappa value=0.796, P=0.07). In 109 eyes diagnosed with CNV by traditional multimodal fundus imaging, 73 eyes (67.0%) were active CNV and 36 eyes (33.0%) were non-active CNV; the vascular pattern was active in 60 eyes (55.0%) and non-active in 49 eyes (45.0%). The sensitivity of OCTA for the detection of active CNV was 82.2%, with specificity of 100.0%. The active CNV detection rate between two methods had no significant difference (Youden index=0.82, Kappa value=0.753, P=0.00). Conclusion In the diagnosis and activity evaluation of CNV in exudative AMD, there is remarkable consistency between OCTA and traditional multimodal fundus imaging. Key words: Choroidal neovascularization /diagnosis; Tomography, optical coherence; Fluorescein angiography; Indocyanine green/diagnostic use

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.

Protective effects of an HTRA1 insertion–deletion variant against age-related macular degeneration in the Chinese populations

Age-related macular degeneration (AMD) is a leading cause of visual impairment and irreversible blindness in most developed countries, affecting about 50 million elderly people worldwide. Retinal pigment epithelial (RPE) cell degeneration is the pathophysiological cause of AMD, leading to geographic atrophy and choroidal neovascularization. We and others have previously identified several polymorphisms on chromosome 10q26 (HTRA1 rs11200638 as well as LOC387715 rs10490924 and c.372_815del443ins54) associated with AMD. In this study, we confirmed the association of our previously identified HTRA1 insertion–deletion (indel) variant (c.34delCinsTCCT) in 195 exudative AMD patients and 390 controls from the Hong Kong Chinese cohort with additional 168 patients and 210 controls from the Chengdu Chinese cohort and followed by studying its biological functions in RPE cells. Genetic analysis verified the higher prevalence of c.34delCinsTCCT allele in control subjects (8.0%) than in AMD patients (1.9%; P=7.87 × 10−5, odds ratio=0.229). This protective effect was validated as the haplotype of the c.34delCinsTCCT allele existed independent of the risk haplotype (P=1.17 × 10−5). In vitro studies showed that recombinant HTRA1 c.34delCinsTCCT variant protein was more localized in the endoplasmic reticulum of RPE cells compared with the wild-type protein, and its secretion was delayed. Moreover, ARPE-19 cells expressing HTRA1 c.34delCinsTCCT variant had higher cell viability, lower cell apoptosis and were less responsive to anoikis, supporting its protective role. We revealed a protective AMD-associated HTRA1 variant in Chinese populations and the biological role of HTRA1 in RPE cell degeneration, indicating its involvement in AMD pathogenesis.

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.

Gas-mediated vitreomacular adhesion release with intravitral ranibizumab injections for exudative age-related macular degeneration.

To evaluate the efficiency of gas-assisted vitreomacular adhesion (VMA) release combined with intravitreal ranibizumab injections for exudative age-related macular degeneration (AMD) patients. This prospective, interventional case series included a total of 23 eyes of 22 patients. The eyes were treated with intravitreal injection of 0.3mL of perfluoropropane (C3F8) gas and concomitant intravitreal ranibizumab injection to stimulate VMA release. After three initial loading injections, additional intravitreal ranibizumab injections were performed pro re nata. Over a 12-month period, monthly examinations were performed for best-corrected visual acuity (BCVA, logMAR; logarithm of the minimum angle resolution), optical coherence tomography, and dilated fundus examinations. After gas injection, 22 eyes (95.7%) showed complete VMA release at 1week. Complete VMA was achieved in all eyes at 2months after VMA release, without serious ocular adverse events except one patient who developed a retinal tear. Mean BCVA was 0.61 ± 0.37 logMAR (20/81 Snellen equivalents) at baseline and 0.46 ± 0.30 logMAR (20/57 Snellen equivalents) at 12months (P = 0.135). Mean central macular thickness was 357.9 ± 128.6μm at baseline and 245.6 ± 60.0μm at 12months (P = 0.188). Mean numbers of intravitreal ranibizumab injections were 4.8 ± 2.4 times during 12months (4 to 8 injections). Gas-assisted VMA release can be used as an efficient alternative for exudative AMD patients with obvious VMA.

Plasmatic Ganglioside Profile and Age-Related Macular Degeneration: A Case-Control Study

Purpose: Gangliosides are glycosphingolipids that are particularly abundant in the nervous system, including the retina. However, their precise role in this tissue and its pathologies remain poorly understood. The objective of the present study was to characterize the ganglioside profile of human plasma and to determine whether it is affected in age-related macular degeneration (AMD). Methods: Eighty-three subjects were included: control subjects (n = 25), atrophic AMD patients (n = 27) and exudative AMD patients (n = 31). For each subject, gangliosides were extracted from plasma and analyzed by liquid chromatography coupled to mass spectrometry. Results: GM3 appeared to be by far the major ganglioside of human plasma, associated with GD3. No specific ganglioside class was detected in the plasma of AMD patients. Fourteen molecular species of GM3 and 9 species of GD3, accounting for the variability of the ceramide moiety of the ganglioside molecule, were identified and characterized. Analyses revealed no significant differences in the proportion of these species between control, atrophic and exudative AMD patient groups. Total GM3 levels did not differ either. Conclusion: Although gangliosides are considered important for the retina's structure and function, it seems that circulating gangliosides are not associated with the retinal damage occurring during the course of AMD.

CFH Y402H and VEGF Polymorphisms and Anti-VEGF Treatment Response in Exudative Age-Related Macular Degeneration

Purpose: The aim of this study was to evaluate the prevalence of single nucleotide polymorphisms (SNPs) in complement factor H (CFH) Y402H and VEGF rs2146323 and rs699947 in exudative age-related macular degeneration (AMD) and their relationship with intravitreal anti-VEGF treatment response. Methods: A total of 109 exudative AMD patients and 70 controls were included. Patients were classified as ‘good responders' and ‘nonresponders' based on the changes in best corrected visual acuity, central foveal thickness, lesion size, and the persistence of retinal hemorrhage after three dosages of anti-VEGF. We examined CFH, VEGF rs2146323 and rs699947 SNPs, and plasma interleukin-6 (IL-6) levels in both groups. Results: In total, 42 patients (38.5%) and 11 controls (15.7%) had homozygote wild genotype TT (p = 0.002). The variant C allele frequency was 45% in controls and 31.7% in patients (p = 0.011). A and C allele frequencies for VEGF rs699947 and rs2416323 were similar between the control and patient groups (p = 0.947, p = 0.378). Both SNPs were similar in responders and nonresponders. No significant difference was detected between plasma IL-6 levels of the control and AMD groups (p = 0.594), but the levels were higher in good responders than nonresponders (p < 0.001). Conclusion: CFH Y402H SNP might be protective for AMD in the Turkish population. VEGF rs2146323 and rs699947 SNPs have no relationship to exudative AMD formation, and none of these seem to have any effect on anti-VEGF response.

Aflibercept administration in neovascular age-related macular degeneration refractory to previous anti-vascular endothelial growth factor drugs: a critical review and new possible approaches to move forward.

The recent introduction of anti-VEGF drugs has widely changed the prognosis of exudative age-related macular degeneration (AMD), even if a variable percentage of patients showed an insufficient response. Aflibercept is a new anti-VEGF drug approved by FDA for the treatment of exudative AMD with a wider binding capacity than either bevacizumab or ranibizumab. Therefore, the purposes were as follows: (i) to report anatomical and functional outcomes of switching from bevacizumab/ranibizumab to aflibercept previously described in the scientific literature, (ii) to hypothesize the possible pathophysiological mechanisms of the resistance and tachyphylaxis to anti-VEGF drugs, and (iii) to suggest possible clinical actions to increase the chances of success for such difficult cases. We reviewed the available scientific literature in Medline, Cochrane database, Current Contents, PubMed, and cross-referencing from identified articles, regarding the treatment of exudative AMD patients refractory to bevacizumab and/or ranibizumab and switched to aflibercept monotherapy. We included in this review all the cases in which the diagnosis of refractory or resistant exudative AMD was properly made, and the results of at least one aflibercept injection were described. We reported the outcomes of 21 papers for a total of 1066 eyes affected by exudative AMD resistant to previous anti-VEGF drug injections and switched to aflibercept. Enrolled reports were divided into two groups: 5 prospective reports and 16 retrospective reports. All the reported papers conclude their analysis, stating that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. Analysis of the papers reported in this review demonstrates that switching from bevacizumab/ranibizumab to aflibercept injections can improve outcomes successfully in refractory neovascular AMD patients. The mechanism for these effects is not yet completely understood.

EFFECT OF PEGAPTANIB AND RANIBIZUMAB ON PLASMA AND VITREOUS HOMOCYSTEINE IN PATIENTS WITH EXUDATIVE AGE-RELATED MACULAR DEGENERATION.

To investigate homocysteine (Hcy) concentration in the blood plasma and the vitreous in patients with exudative age-related macular degeneration receiving intravitreal anti-vascular endothelial growth factor therapy. Plasma Hcy and vitreous Hcy levels were analyzed in 73 exudative age-related macular degeneration patients (50.7% received pegaptanib 0.3 mg and 50.3% received ranibizumab 0.5 mg) and compared with 80 controls and 40 patients with idiopathic epiretinal membranes, respectively. Homocysteine concentration was measured by immunonephelometric particle test, and it was determined before and after antiangiogenic therapy. The mean Hcy concentrations (± SD) of blood plasma and vitreous were 13.0 ± 4.2 μmol/L and 1.00 ± 0.3 μmol/L in patients treated with pegaptanib; in ranibizumab group, they were 12.8 ± 2.5 μmol/L and 1.4 ± 0.6 μmol/L, respectively. The results of plasma and vitreous Hcy indicated statistically significant differences between exudative age-related macular degeneration patients and control groups (P = 0.03 and P = 0.02). After 6 months with both intravitreal therapies, the plasma and vitreous Hcy concentrations did not change significantly (P = 0.1). Pegaptanib and ranibizumab did not increase the plasma or vitreous Hcy concentrations.

Quality of Life in Patients Suffering from Active Exudative Age-Related Macular Degeneration: The EQUADE Study

Purpose: Age-related macular degeneration (AMD) is the main cause of visual loss in the elderly population. With the use of anti-vascular endothelial growth factor, the visual outcomes of exudative AMD patients have been improved. This study was aimed at assessing the quality of life (QoL) of exudative AMD patients treated with ranibizumab and at determining its drivers in a real-life setting. Methods: We performed a national, cross-sectional, observational survey based on questionnaires sent to members of French associations relative to AMD between December 2012 and March 2013. Patients suffering from exudative AMD with at least one intravitreal injection of ranibizumab within the last 6 months were included. Demographics, AMD characteristics, visual acuity (VA) and past and ongoing treatments were collected. The 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) was self-administered. A multivariate model was used to identify QoL drivers. Results: 416 questionnaires fulfilled the complete criteria for both QoL and cost analyses. The mean age of exudative AMD patients was 78.0 years and bilateral involvement was reported in 60.4%. The overall mean QoL score was 53.4. Mental health, driving and role difficulties were the most widely affected domains. After bivariate analyses, long-term illness status, worse VA and higher number of unpaid aids were associated with worse QoL, with odds ratios of 2.4, 5.2 and 11.6, respectively. The mean cost per year and per patient was 1,741 EUR. The main components of costs were aids and services and the purchase of visual equipment. Conclusions: The main predictors of QoL in exudative AMD patients treated with ranibizumab are VA outcomes, home healthcare and social services provided to the patients.

Prevalence and Incidence of Exudative Age-Related Macular Degeneration in South Korea: A Nationwide Population-Based Study

To determine the prevalence and incidence of exudative age-related macular degeneration (AMD) in South Korea. Nationwide population-based retrospective study using data from the Korean national health claims database from 2008 through 2012. Entire South Korean population 40 years of age or older (n = 22,376,510). We accessed the national health claims database to identify exudative AMD patients using the registration program database for rare intractable diseases, which included ophthalmologist-confirmed exudative AMD, for copayment reduction. Prevalence and incidence rates of exudative AMD. During the 5-year study period, 81 513 patients had exudative AMD (48.2% men) and were included in the prevalence estimates. The prevalence in the general population 40 years of age or older was 36.43 (95% confidence interval [CI], 36.18-36.68) per 10,000 people, that in men was 37.01 (95% CI, 36.65-37.38) per 10,000 people, and that in women was 35.90 (95% CI, 35.56-36.24) per 10,000 people. After excluding prevalent cases during the initial 2-year washout period, 20,196 cases were identified with incident exudative AMD during the final 3-year study period (2010-2012). The incidence in the general population 40 years of age or older was 3.02 (95% CI, 2.98-3.06) per 10,000 person-years, that in men was 3.76 (95% CI, 3.69-3.83) per 10,000 person-years, and that in women was 2.34 (95% CI, 2.29-2.39) per 10,000 person-years. The prevalence and incidence increased with advancing age and peaked at approximately 80 years of age. Both the prevalence and incidence were higher in men than in women in all age groups. These detailed estimates of the nationwide, population-based prevalence and incidence of exudative AMD in an Asian population may help to understand the disease pathophysiology and to plan accordingly within the healthcare system.

Analysis of Genetic and Environmental Risk Factors and Their Interactions in Korean Patients with Age-Related Macular Degeneration.

PurposeTo investigate the association of genetic and environmental factors, and their interactions in Korean patients with exudative age-related macular degeneration (AMD).MethodsA total of 314 robustly characterized exudative AMD patients, including 111 PCV (polypoidal choroidal vasculopathy) and 154 typical choroidal neovascularization (CNV), and 395 control subjects without any evidence of AMD were enrolled. Full ophthalmologic examinations including fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were done, according to which patients were divided into either PCV or typical CNV. Standardized questionnaires were used to collect information regarding underlying systemic diseases, dietary habits, smoking history and body mass index (BMI). A total of 86 SNPs from 31 candidate genes were analyzed. Genotype association and logistic regression analyses were done and stepwise regression models to best predict disease for each AMD subtype were constructed.ResultsAge, spherical equivalent, myopia, and ever smoking were associated with exudative AMD. Age, hypertension, hyperlipidemia, spherical equivalent, and myopia were risk factors for typical CNV, while increased education and ever smoking were significantly associated with PCV (p<.05 for all). Four SNPs, ARMS2/HTRA1 rs10490924, rs11200638, and rs2736911, and CFH rs800292, showed association with exudative AMD. Two of these SNPs, ARMS2/HTRA1 rs10490924 and rs11200638, showed significant association with typical CNV and PCV specifically. There were no significant interactions between environmental and genetic factors. The most predictive disease model for exudative AMD included age, spherical equivalent, smoking, CFH rs800292, and ARMS2 rs10490924 while that for typical CNV included age, hyperlipidemia, spherical equivalent, and ARMS2 rs10490924. Smoking, spherical equivalent, and ARMS2 rs10490924 were the most predictive variables for PCV. When comparing PCV cases to CNV cases, age, BMI, and education were the most predictive risk factors of PCV.ConclusionsOnly one locus, the ARMS2/HTRA1 was a significant genetic risk factor for Korean exudative AMD, including its subtypes, PCV and typical CNV. Stepwise regression revealed that CFH was important to risk of exudative AMD in general but not to any specific subtype. While increased education was a unique risk factor to PCV when compared to CNV, this association was independent of refractive error in this homogenous population from South Korea. No significant interactions between environmental and genetic risk factors were observed.

Macular Atrophy Progression and 7-Year Vision Outcomes in Subjects From the ANCHOR, MARINA, and HORIZON Studies: the SEVEN-UP Study

To assess the incidence and progression of macular atrophy and other key anatomic outcomes over 7 to 8 years in an early cohort of ranibizumab-treated exudative age-related macular degeneration patients. Follow-up analysis of long-term outcomes in a multicenter treatment cohort. Fourteen study sites enrolled 65 previous subjects from the ranibizumab treatment arms of the ANCHOR, MARINA, and HORIZON trials. In a single update visit, clinical assessment and retinal imaging studies were performed, with comparison with each subject's prior results from the previous trials. Early Treatment Diabetic Retinopathy Study visual acuity was the primary outcome. Secondary outcomes, including area of macular atrophy and selected anatomic factors, were analyzed for associations with long-term vision outcomes. At a mean 7.3 years after ANCHOR or MARINA enrollment, mean visual acuity was 54 letters, study eyes having received a mean 1.6 injections per year since the HORIZON study. Macular atrophy was present in 98% of study eyes, the mean area increasing from 0.83± 0.96mm(2) at the ANCHOR or MARINA year 2 exit to 2.22 ± 1.6mm(2) at the SEVEN-UP visit, a growth rate of 0.28mm(2)/year. Progression of macular atrophy was associated significantly with visual decline over this 5-year period (P < .001), and final macular atrophy lesion size was related significantly to final vision (P < .001). Other key anatomic outcomes (macular thickening, thinning, or fluid and submacular fibrosis) did not have significant effects on vision outcomes. Seven years after initiation of intensive ranibizumab therapy for exudative age-related macular degeneration, macular atrophy progression and severity were the primary anatomic determinants of visual outcomes.

Alteration of cytokine expression in exudative age-related macular degeneration and its targeting therapy

Exudative age-related macular degeneration (AMD) is the leading cause of central vision loss in elderly population, and its primary pathological mechanism is the formation of choroidal neovascularization (CNV). Recently, it is found that the balance of angiogenesis and antiangiogenic factors plays an important role in the formation of CNV, and the main factors are vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF). The targeting therapy for these cytokines provides a new approach to the treatment of exudative AMD. Anti-VEGF therapy is of great effect on controlling CNV and improving visual acuity in exudative AMD patients. The purpose of this review was to summarize current advance in the study of cytokines associated with the pathogenesis of exudative AMD and its targeting therapy. Key words: Aging; Macular degeneration/drug therapy; Choroidal neovascularization; Cytokine; Vascular endothelial growth factor; Pigment epithelium-derived factor