The complexities underlying age-related macular degeneration： could amyloid beta play an important role？

e-related macular degeneration （AMD） causes irreversible loss of central vision for which there is no effective treatment. Incipient pathology is thought to occur in the retina for many years before AMD manifests from midlife onwards to affect a large proportion of the elderly. Although genetic as well as non-genetic/environmental risks are recognized, its complex aetiology makes it difficult to identify susceptibility, or indeed what type of AMD develops or how quickly it progresses in different individuals. Here we summarize the literature describing how the Alzheimer＇s-linked amyloid beta （Aβ） group of misfolding proteins accumulate in the retina. The discovery of this key driver of Alzheimer＇s disease in the senescent retina was unexpected and surprising, enabling an altogether different perspective of AMD. We argue that Aβ fundamentally differs from other substances which accumulate in the ageing retina, and discuss our latest findings from a mouse model in which physiological amounts of Aβ were subretinally-injected to recapitulate salient features of early AMD within a short period. Our discoveries as well as those of others suggest the pattern of Aβ accumulation and pathology in donor aged/AMD tissues are closely reproduced in mice, including late-stage AMD phenotypes, which makes them highly attractive to study dynamic aspects of Aβ-mediated retinopathy. Furthermore, we discuss our findings revealing how Aβ behaves at single-cell resolution, and consider the long-term implications for neuroretinal function. We propose Aβ as a key element in switching to a diseased retinal phenotype, which is now being used as a biomarker for latestage AMD.

iTRAQ-based proteomics analysis of aqueous humor in patients with dry age-related macular degeneration

AIM: To preliminarily test proteomics in aqueous humor in patients with dry age-related macular degeneration(AMD) by using the proteomic technology.METHODS: Aqueous humor samples were collected from patients with or without dry AMD, who underwent cataract surgery. The aqueous samples were analyzed with isobaric tags for relative and absolute quantification(i TRAQ) combined with liquid chromatography tandem mass spectrometry(LC-MS/MS) technology. The differential expressed proteins were analyzed with gene ontology(GO) enrichment, Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein-protein interaction(PPI) network analysis. The data were partly validated by ELISA and Western blot. False discovery rate(FDR) was used for statistical analysis. RESULTS: A total of 244 proteins were detected, in which 38 proteins were up-regulated and 51 were down-regulated significantly in patients with dry AMD compared with that in control groups(FDR value <1.0%). Several proteins, e.g., protein S100-A8(S10 A8), dystroglycan(DAG1), Ig alpha-1 chain C region(IGHA1), carbonic anhydrase 3(CAH3) and alpha-1-acid glycoprotein(A1 AG1) were increased more than 5 times of that in control group. The bioinformatics analysis showed that dry AMD is closely associated with inflammation or immune reaction, oxidative stress, blood coagulation and remodeling of extracellular matrix.CONCLUSION: i TRAQ-based proteomic analysis of aqueous humor demonstrate the differential expressions of proteins between dry AMD and control groups, providing the clues to understand the mechanisms and possible treatments of dry AMD.

Risk Factors for Age-Related Macular Degeneration in Elderly Chinese Population in Shenyang of China

Objective The paper aims to evaluate the risk factors for age‐related macular degeneration （AMD） in elderly Chinese population in Shenyang,a northeast city of China.Methods A case‐control study was conducted to investigate the risk factors for the prevalence of AMD.Ninety three AMD patients diagnosed by a complete ophthalmic examination were recruited as cases from the outpatient departments of two eye hospitals in Shenyang,while 108 normal subjects of similar age and sex were recruited as controls.A questionnaire was administered among both cases and controls.Results AMD patients aged 60 years and older accounted for 75.3%.There were significantly higher educational levels,shorter smoking history,less sunlight exposure and cataract,and higher proportion of antioxidants intake in controls than in AMD patients.The frequency of intake of fruits,legumes,fish and shrimps was significantly higher in controls than in AMD patients.In a binary logistic regression analysis,smoking and cataract were the risk factors for AMD （OR：4.44,95% CI：2.27‐8.69;OR：4.47,95% CI：2.26‐8.85 respectively）.The high educational background was a protective factor for AMD （OR：0.761,95% CI：0.51‐0.98）.Conclusion A low educational background,smoking and cataract are associated with a higher prevalence of AMD.

Comparison of visual acuity outcomes between ranibizumab and bevacizumab treatment in neovascular age-related macular degeneration

AIM: To compare visual acuity (VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration (AMD). METHODS: We conducted a consecutive, retrospective case series study in patients with newly diagnosed all type choroidal neovascularization (CNV) secondary to AMD who received an intravitreal injection of bevacizumab (1.25mg) or ranibizumab (0.3mg) at Lions Eye Institute, Western Australia from Mar. 2006 to May 2008. All patients received injection at baseline with additional monthly injections given at the discretion of the treating physician. Main outcome measures were changes in VA. RESULTS: There were 371 consecutive patients received injection at least in one eye with at least 6 months of follow up (median of 12.0 months). Bevacizumab treatment prevented 221 out of 278 (79.5%) patient from losing < 15 letters in VA compared with 79 out of 93 (84.9%) of ranibizumab treated patients (P=0.25). While 68 (24.5%) of bevacizumab treated patients gained 15 letters of VA compared with 24 (25.8%) of ranibizumab treated patients (P=0.79). 75.3% and 66.2% patients benefited from ranibizumab and bevacizumab respectively with final VA better than 6/60 (P=0.10). Multivariate analysis showed that pre-treatment VA was negatively associated with benefit outcome. Assignment of injection was not associated with VA outcome of benefit after adjusting the covariate (P=0.857). CONCLUSION: There are no difference in treatment efficacy in terms of VA between bevacizumab and ranibizumab in routine clinical condition.

Bevacizumab vs ranibizumab for neovascular age-related macular degeneration in Chinese patients

AIM: To compare the clinical efficacy of intravitreal injections of bevacizumab and ranibizumab for treating Chinese patients with neovascular age-related macular degeneration (AMD).METHODS: Among 60 Chinese patients with exudative AMD (60 eyes), 28 received intravitreal bevacizumab injections (1.25mg) and 32 received intravitreal ranibizumab injections (0.5mg), once a month for 3 months and were followed for a total of 6 months. Monthly optical coherence tomography (OCT) was used to determine whether the patients received additional treatments during the follow-up. We compared the baseline and 6 -month follow-up values of mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) in both groups of patients. We also compared the occurrence of adverse events.RESULTS: At the 6-month follow-up, the mean BCVA (logMAR) of the bevacizumab and ranibizumab treatment groups improved from the baseline measurements of 0.72 ±0.23 and 0.73 ±0.22 to 0.47 ±0.14 and 0.45 ±0.20, respectively (P 【0.05 for both groups). However, the change was not significantly different between the two groups. As evaluated by OCT, CRT decreased from 366.71 ±34.72μm and 352 ±36.9μm at baseline to 250.86 ± 41.51μm and 243.22 ±41.38μm in the bevacizumab and ranibizumab groups, respectively (P 【0.05 for both groups). However, the change was not significantly different between the two groups. There were no severe local adverse reactions or systemic adverse events.CONCLUSION:Intravitreal bevacizumab and ranibizumab have equivalent effects on BCVA and CRT and appeare safe over the short-term.

Diabetic retinopathy and age-related macular degeneration: a survey of pharmacoutilization and cost in Calabria, Italy

The aged population is constantly growing, thus fostering an increase in age-dependent diseases. Among these, diabetic retinopathy (DR) along with age-related macular degeneration entails progressive vision loss. Since such conditions are associated with the proliferation of novel vessels, their pharmacotherapeutic management consists of the intravitreal injection of anti-vascular endothelial growth factor drugs, able to hinder the driving of vascular proliferation prompted by vascular endothelial growth factor. The humanized anti-vascular endothelial growth factor monoclonal antibody ranibizumab provided evidence for efficacy in several trials, hence earning approval by the US Food and Drug Administration for therapeutic use in all the stages of DR. Due to the lack of epidemiologic and pharmacoeconomic evaluation in the local Calabria Region context, the present retrospective observational study focused on prevalence of DR and age-related macular degeneration, treatment and cost of therapy with ranibizumab in 870 patients arriving to clinical observation at the "Mater Domini” University Hospital in Calabria, Italy from January 2014 to June 2017. Data were extracted from the database of ophthalmology ward and subjected to statistical analysis. The results suggest that the most frequent retinal diseases are age-related macular degeneration and DR and that the use of ranibizumab has been decreasing over the 4-year study period together with the associated cost per patient which was similar for both disorders. Therefore, appropriateness of treatment with drugs other than ranibizumab needs to be assessed in this setting and deep monitoring of pharmacologic treatment for retinal diseases is necessary to prevent or delay visual acuity decrease and complete vision loss. Study procedures were performed in accordance with the "Mater Domini” University Hospital ethical standards of the responsible committee on human experimentation.

Influence of CFH,HTRA1 and ARMS2 polymorphisms in the response to intravitreal ranibizumab treatment for wet age-related macular degeneration in a Spanish population

AIM：To determine whether gene polymorphisms of the major genetic risk loci for age-related macular degeneration（AMD）：ARMS2（rs10490923）,the complement factor H（CFH）（rs1410996） and HTRA1（rs11200638） influence the response to a treatment regimen with ranibizumab for exudative AMD.METHODS：This study included 100 patients（100 eyes）with exudative AMD.Patients underwent a treatment with ranibizumab injections monthly during three months.Reinjections were made when the best corrected visual acuity（BCVA） decrease five letters（ETDRS） or central subfield retinal thickness gained 100 pm in optical coherence tomography image.Genotypes（rs10490923,rs1410996 and rs11200638） were analyzed using TaqMan probes or polymerase chain reaction-restricted fragment length polymorphisms analysis.RESULTS：There were no statistically significant differences in allelic distribution of CFH（rs1410996）,ARMS2（rs10490923） and HTRA1（rs11200638）polymorphisms regarding to response to ranibizumab treatment.CONCLUSION：Ranibizumab treatment response is not related to CFH（rs1410996）,ARMS2（rs10490923） and HTRA1（rs11200638） poymorphisms.

Combination of ranibizumab with photodynamic therapy vs ranibizumab monotherapy in the treatment of age-related macular degeneration: a systematic review and meta-analysis of randomized controlled trials

AIM:To compare the efficacy and safety of combination of ranibizumab with photodynamic therapy(PDT)vs ranibizumab monotherapy in the treatment of age-related macular degeneration(AMD).METHODS:The Cochrane Central Register of Controlled Trials(CENTRAL)in the Cochrane Library,Pubmed,and Embase were searched.There were no language or data restrictions in the search for trials.Only randomized controlled trials(RCTs)were included.Methodological quality of the literatures was evaluated according to the Jadad Score.RevMan 5.2.6 software was used to do the meta-analysis.RESULTS:Seven studies were included in our systematic review,among which four of them were included in quantitative analysis.The result shows that the ranibizumab monotherapy group had a better mean best corrected visual acuity(BCVA)change vs baseline at month 12 compared with that of the combination treatment group,and the statistical difference was significant(WMD,-2.61;95%CI,-5.08 to-0.13;P=0.04).However,after the removal of one study,the difference between the two groups showed no significant difference(WMD,-2.29;95%CI,-4.81 to 0.23;P=0.07).Meanwhile,no significant central retinal thickness(CRT)reduction was found in the combination treatment group and the ranibizumab monotherapy group at 12 months follow-up.Nevertheless,the combination group tended to have a greater reduction in CRT(WMD,-4.13μm;95%CI,-25.88to 17.63,P=0.71).The proportion of patients gaining more than 3 lines at month 12 in the ranibizumab group was higher than in the combination group and there was a significant difference(RR,0.72;95%CI,0.54 to 0.95;P=0.02).Whereas there was no significant difference for the proportion of patients gaining more than 0 line at month12 between the two groups(RR,0.93;95%CI,0.76 to1.15;P=0.52).The general tendency shows a reduction in ranibizumab retreatment number in the combination treatment group compared with the ranibizumab monotherapy group.As major adverse events,the differences in the number of eye pain,endophthalmitis,hypertension and arterial thromboembolic events were not significant between the two groups,and the incidence of serious adverse events in the two groups was very low.CONCLUSION:For the maintenance of vision,the comparison of the combination of ranibizumab with PDT vs ranibizumab monotherapy shows no apparent difference.Compared with the combination of ranibizumab and PDT,patients treated with ranibizumab monothearpy may gain more visual acuity(VA)improvement.The combination treatment group had a tendency to reduce the number of ranibizumab retreatment.Both the two treatment strategies were well tolerated.

Increased serum levels of soluble CD146 and vascular endothelial growth factor receptor 2 in patients with exudative age-related macular degeneration

AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent assay.RESULTS: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.

Correlation of neutrophil/lymphocyte and platelet/lymphocyte ratio with visual acuity and macular thickness in age-related macular degeneration

AIM：To investigate the place of neutrophil-to-lymphocyte ratio（NLR） and platelet-to-lymphocyte ratio（PLR） in the diagnosis of and prognosis for neovascular age-related macular degeneration（AMD）. METHODS：One hundred AMD patients and 100 healthy controls were included in the study. Blood samples were obtained from the venous blood, which is used for routine analysis, and these samples were subjected to complete blood count. NLR was defined as the neutrophil count divided by the number of lymphocytes, and PLR was defined as the platelet count divided by the number of lymphocytes. RESULTS：No statistically significant difference was observed between the two groups under consideration in terms of demographic features（P〉0.05）. The average NLR in the patient group was found to be significantly higher than that in the healthy control group（P〈0.05）. The average PLR was significantly higher in the patient group as compared to the control group（P〈0.05）. As best corrected visual acuity（BCVA） increased, both NLR and PLR decreased（significant negative correlations at 49.8% and 63.0%, respectively）, whereas as central macular thickness（CMT） increased, both NLR and PLR increased（significant positive correlations at 59.3% and 70.0%, respectively）.CONCLUSION：NLR and PLR levels are higher among neovascular AMD patients as compared to healthy control group. NLR and PLR levels were found to be inversely proportional to BCVA and directly proportional to CMT.

Temporal pattern of resolution/recurrence of choroidal neovascularization during bevacizumab therapy for wet age-related macular degeneration

AIMTo characterize temporal pattern of resolution and recurrence of naive choroidal neovascularization (CNV) secondary to wet age-related macular degeneration (AMD) treated with intravitreal bevacizumab on as needed regimen, and to analyze baseline risk factors for CNV resolution or recurrence.

Effect of Quercetin on Formation of Choroidal Neovascularization (CNV) in Age-related Macular Degeneration (AMD)

Purpose:Age-related macular degeneration(AMD)as a disease entity is "dry" at early stage and made up of two main components at late stage:atrophic AMD and exudative AMD.Quercetin acts as an anti-oxidant to protect retinal pigment epithelial cells(RPE)from damaged by oxidative stress,but its effect on formation of choroidal neovascularization(CNV)in AMD is unclear.The aim of this study is to investigate the effect of quercetin on the formation of CNV in AMD.Methods:The development of CNV induced by laser was detected.by fluorescein angiography(FA).Colored microsphere technique was used to determine the choroidal blood flow in ocular hypertensive rabbit eyes.In in vitro studies,HUVECs were treated with NaIO3,H2O2 and NaN3 to induce oxidative cell damages.The effect of quercetin on various oxidations-induced injuries in HUVECs was measured by MTT assay.HUVECs migration was assessed using a wound healing assay.Results:Quercetin significantly inhibited the formation of laser-induced CNV.The choroidal blood flow in rabbit eyes was significantly increased after quercetin instillation.In vitro results showed quercetin enhanced various oxidations-induced injuries in HUVECs and inhibited migration of HUVECs during wound healing.Conclusion:Quercetin inhibited the formation of CNV both in vivo and in vitro and increased choroidal blood flow.It could become a promising candidate for the treatment of AMD.

Association between complementary factor H Y402H polymorphisms and age-related macular degeneration in Chinese: Systematic review and meta-analysis

AIM: Age-related macular degeneration (AMD) is the leading cause of blindness in the developed world and complement factor H (CFH) polymorphism has been found to associate with the AMD. To investigate whether the Y402H variant in CFH is associated with AMD in Chinese populations, a systematic review and meta-analysis were performed to estimate the magnitude of the gene effect and the possible mode of action. METHODS: A meta-analysis was performed using data available from ten case-control studies assessing association between the CFH Y402H polymorphism and AMD in Chinese populations involving 1538 AMD. Data extraction and study quality assessment were performed in duplicate. Summary odds ratios (ORs) and 95% confidence intervals (CIs) an allele contrast and genotype contrast were estimated usingfixed- effects models. The Q-statistic test was used to assess heterogeneity, and Funnel plot was used to evaluate publication bias. RESULTS: Seven of ten case-control studies were neovascular AMD, and few studies came from west and north of China. There was strong evidence for association between CFH and AMD in Chinese population, with those having risk allele C 2.35 times more likely to have AMD than subjects with T allele. Evidence of publication bias was not observed in our meta-analysis. CONCLUSION: This meta-analysis summarizes the strong evidence for an association between CFH and AMD in Chinese and indicates each C allele increasing the odds of AMD by 2.33-fold. But more evidences about the relation between CFH polymorphism and different type of Chinese AMD from various district were needed.

TNF-α gene polymorphisms: association with age-related macular degeneration in Russian population

AIM: To study polymorphisms in promotor regions of tumor necrosis factor(TNF)-α TNF-863 A/C(rs1800630), TNF-308 A/G(rs1800629), and TNF-238 A/G(rs361525) in patients with age-related macular degeneration(AMD) and associations of complex TNF-α genotypes with AMD. METHODS: One hundred and two patients(82 women, 20 men; mean age 64.2±1.2 y) with AMD and 100 healthy age-and sex-matched controls(82 women, 18 men; 60±1.4 y) were included in the study. All subjects were Caucasian, all subjects and their parents were inhabitants of Russia. Genomic DNA was obtained from EDTA-preserved blood using the standard phenol-chloroform method. Polymorphisms were detected by polymerase chain reaction followed by the restriction fragment length polymorphism method. The following TNF-α genotypes were studied: TNF-α-238 AA, GA, GG, TNF-α-308 AA, GA, GG, TNF-α-863 AA, CA, CC. RESULTS: Differences in TNF-α-863 and TNF-α-238 genotypes frequencies in patients with AMD and healthy controls were not found. The distribution of TNF-α-308 AA and TNF-α-308 GA genotypes was significantly different between the studied group and the controls [odds ratios(OR) =0.22, P=0.0287 and OR=2.91, P=0.0063, respectively]. TNF-863 CC/TNF-308 GA and TNF-308 GA/TNF-238 GG genotypes were associated with the increased risk of AMD(OR=2.48, P=0.0332 and OR=2.51, P=0.0187, respectively). Five genotypes combinations appeared to be protective. CONCLUSION: In the present study, single nucleotide polymorphisms and complex polymorphisms of one of the key inflammatory cytokines TNF-α, and a number of significant associations of these polymorphisms with AMD in Russian population have been shown. Complexanalysis of genotypes could be important in AMD risk factors detection and studying pathogenesis.

Six-year outcomes in neovascular age-related macular degeneration with ranibizumab

AIM： To evaluate the outcomes of （6y ranibizumab therapy in neovascular age-related macular degeneration （AMD）.METHODS： HELIX was a retrospective, observational effectiveness study using medical records of patients treated in three clinics in Belgium. Patients had neovascular AMD and were initially treated with intravitreal ranibizumab （0.5 mg） between November 1, 2007 and October 31, 2008, had （6y of data available, and were treated on an ongoing, as-needed basis. Outcomes included best-corrected visual acuity （BCVA） and central retinal thickness （CRT）.RESULTS： The sample consisted of 88 eyes from 69 patients. Mean age was 76.4±6.5y, most patients were female （62.3%）. Most eyes （62.5%） were treatment-naive, 33 previously treated eyes had received predominantly other anti-vascular endothelial growth factor agents and verteporfin. Mean baseline BCVA was 57.4±12.7 ETDRS letters and CRT was 291.5±86.1 （m. On average, patients received 20.6±11.9 ranibizumab injections over the （6y. Intervals between injections were on average 12.7±16.1wk. Mean change in BCVA from baseline to last observation for the sample was less than one letter （-0.9±17.3 letters）, with an average loss of -3.2±15.6 letters in previously treated eyes versus a gain of 0.6±18.4 letters in treatment-na？ve eyes. When considering a loss of 〈15 letters over 6y as stabilization of disease, 75.9% of all eyes showed a positive （improvement or stabilization） outcome. Mean change in CRT from baseline to last observation for the sample was -26.9±148.4 （m with the greatest reduction observed in treatment-naive eyes.CONCLUSION： This retrospective study of 69 neovascular AMD patients treated for （6y with ranibizumab demonstrates long-term visual stabilization. In light of the natural evolution of the disease, these data confirm that ranibizumab is effective long-term under real-world conditions of heterogeneity of patients, clinicians, and centers.

Photodynamic Therapy for Age-related Macular Degeneration

Purpose: To evaluate short-term effects of single photodynamic therapy (PDT) for age-related macular degeneration (AMD) accompanied with choroidal neovascularization (CNV).Methods: We analyzed retrospectively the effects of single PDT for 20 patients (20 eyes) with CNV caused by AMD. Corrected visual acuity, fluorescein angiography (FA) and optic coherence tomography (OCT) were examined before and after PDT. All patients were followed up at least 3 months. Results: At the end of 3-month follow-up, 5 eyes had vision progress, 15 eyes had vision stable and no eye had vision deterioration. Fluorescein angiography one week post PDT showed cessation of fluorescein leakage in 8 eyes with predominant classic CNV, and reduction of fluorescein leakage in 12 eyes with minimal classic CNV or occult CNV without classic component. At the 3-month following PDT fluorescein angiography showed fluorescein leakage reappeared in 4 of 8 eyes with predominant classic CNV. Among 12 eyes with minimal classic CNV or occult CNV without classic component, 9 eyes showed decreased or unchanged fluorescein leakage, 3 eyes had a progression of fluorescein leakage. Optic coherence tomography showed obvious recovery of serous sensory retinal detachment after PDT. Conclusion: PDT may occlude or inhibit CNV caused by AMD in short term. No obvious side effects were noticed.

Spontaneous or secondary to intravitreal injections of anti-angiogenic agents retinal pigment epithelial tears in age-related macular degeneration

·AIM:Toevaluatethevisualfunctionevolutionofretinal pigment epithelial(RPE) tears in patients with age-related macular degeneration(AMD) according to type of occurrence [spontaneous or secondary to anti-vascular endothelial growth factor(anti-VEGF) injection] and the topographic location of the tear after a two-year followup period.·METHODS: A total of 15 eyes of 14 patients with RPE tears in exudative AMD were analyzed retrospectively at the University Eye Clinic of Trieste. Inclusion criteria were: patient age of 50 or older with AMD and RPE tears both spontaneous occurring or post anti-VEGF treatment. Screening included: careful medical history,complete ophthalmological examination, fluorescein angiography(FA), indocyanine green angiography(ICG),autofluorescence and infrared imaging and optical coherence tomography(OCT). Patients were evaluated every month for visual acuity(VA), fundus examination and OCT. Other data reported were: presence of PED,number of injections before the tear, location of the lesion.·RESULTS:Meanfollow-up was24wk(SD±4wk). Atotal of 15 eyes were studied for RPE tear. In 6 cases(40%),the RPE tears occurred within two years of anti-VEGF injections the others occurred spontaneously. In 13cases(86.6%), the RPE tear was associated with pigment epithelial detachment(PED). In 7 cases(46.6%), the RPE tear occurred in the central area of the retina and involved the fovea. Two lesions were found in the parafoveal region, six in the extra-macular area. In all cases visual acuity decreased at the end of the follow-up period(P <0.01) independently of the type or the topographical location of the lesion.·CONCLUSION: RPE tear occurs in exudative AMD as a spontaneous complication or in relation to anti-VEGF injections. Visual acuity decreased significantly and gradually in the follow-up period in all cases. No correlation was found between visual loss and the type of onset or the topographic location of the tears.

Comparative proteomic analysis of plasma proteins in patients with age-related macular degeneration

AIM:To find the significant altered proteins in agerelated macular degeneration(AMD)patients as potential biomarkers of AMD.METHODS:A comparative analysis of the protein pattern of AMD patients versus healthy controls was performed by means of proteomic analysis using twodimensional gel electrophoresis followed by protein identification with MALDI TOF/TOF mass spectrometry.RESULTS:We identified 28 proteins that were significantly altered with clinical relevance in AMD patients.These proteins were involved in a wide range of biological functions including immune responses,growth cytokines,cell fate determination,wound healing,metabolism,and anti-oxidance.CONCLUSION:These results demonstrate the capacity of proteomic analysis of AMD patient plasma.In addition to the utility of this approach for biomarker discovery,identification of alterations in endogenous proteins in the plasma of AMD patient could improve our understanding of the disease pathogenesis.

Comparison of two different treatment regimens’ efficacy in neovascular age-related macular degeneration in Turkish population—based on real life data-Bosphorus RWE Study Group

AIM: To compare two different anti-vascular endothelial growth factor(anti-VEGF) treatment regimens'-a priori pro re nata(PRN) and PRN regimen following^(th)e loading phaseanatomical and functional results in neovascular agerelated macular degeneration(n AMD) patients. METHODS: Totally 544 n AMD patients followed and treated with aflibercept(n=135) and ranibizumab(n=409)at 9 different centers between 2013 and 2015 were enrolled into^(th)is retrospective multicenter study. Patients with initial best corrected visual acuity(BCVA) interval of 1.3-0.3(log MAR) and a minimum follow-up of 12 mo were included. Patients under two different regimens-a priori pro re nata(1+PRN) or 3 consecutive intravitreal injections followed by a PRN regimen(3+PRN)-were compared in BCVA at 3^(th), 6^(th) and 12^(th) months, and in central macular^(th)ickness(CMT) at 6^(th) and 12^(th) months. The total study group, intravitreal ranibizumab(IVR) and intravitreal aflibercept(IVA) groups were evaluated separately. RESULTS: The mean CMT decreased in^(th)e 1+PRN(n=101) regimen from 407 to 358 and 340 μm and in^(th)e 3+PRN(n=443) group from 398 to 318 and finally to 310 μm at months 6 and 12, respectively. Anatomically,^(th)e CMT reduction at 6^(th) month(48.5 vs 76.4;P<0.05) was statistically significant in favor of 3+PRN group. BCVA changed in 1+PRN group from 0.77 to 0.78, 0.75 and 0.75;in 3+PRN group from 0.81 to 0.69, 0.72, and 0.76 at months 3, 6, and 12, respectively. Visual gain was statistically better in 3+PRN group at 3^(th) month(-0.01 vs 0.12;P<0.001). In IVR group, CMT reduction was in greater in 3+PRN at 6^(th)(44 vs 72) and 12^(th) month(61 vs 84), but statistically insignificant. The 3+PRN group revealed statistically better visual results at 3^(th) month(-0.02 vs 0.11, P<0.05). In IVA group, although statistically insignificant, CMT reduction(61 vs 89, 6^(th) month;85 vs 97, 12^(th) month) and visual gain(0.02 vs 0.16;0.02 vs 0.14;0.05 vs 0.11) was found in favor of 3+PRN group at all visits.CONCLUSION: The loading dose of anti-VEGF treatments in n AMD leads to significantly better anatomical and functional results, regardless of the agent, specially in early follow-up interval.

Assessment of the long-term visual and anatomical outcomes of ranibizumab to treat neovascular age-related macular degeneration

AIM： To investigate the long-term visual and anatomical outcomes of patients who underwent intravitreal ranibizumab monotherapy to treat neovascular age-related macular degeneration（AMD） and followed-up for at least 2 y.METHODS： A total of 74 eyes of 74 patients who underwent ranibizumab monotherapy for neovascular AMD were included in this retrospective study.RESULTS： The average patient age was 72.1±6.5（range, 57-85）y, the average follow-up time 46.2±13.1（range, 24-75）mo, and the average number of visits 24.1±9.5（range, 8-48）. The mean number of injections in year 1 was 4.5, 1.6 in year 2, 0.9 in year 3, 0.4 on year 4, and 0.1 in the following years. Within the entire follow-up period, the mean number of injections was 7.6±4.4（range, 2-21）. The mean visual acuity was 48.1±15（range, 15-76） letters at baseline and 45.7±19（range, 7-75） at year 5. The mean central macular thickness was 303±78（range, 178-552） μm at baseline and 251±51（range, 138-359） μm at year 5. Scars developed in 47（63.5%） eyes at the end of the follow-up period, and atrophy was evident in 6（8.1%） eyes.CONCLUSION： Ranibizumab monotherapy can stabilize visual acuity for a mean period of 4 y in patients with neovascular AMD.