age - related macular degeneration ( amd ) is the most important cause of blindness in aged populations in developed countries . as the aging population and average life expectancy increase , the incidence of amd is growing in developing countries . the efficacy and safety of the anti - vegf medicine , ranibizumab ( lucentis ) , to treat wet age - related macular degeneration ( wamd ) have been demonstrated in many large samples , multicenter randomized clinical trials , and substantial clinical practice [ 2 , 3 ] . it is now one of the most widely used treatments for wamd and choroidal neovascularization ( cnv ) secondary to many other reasons [ 46 ] . we are the first to report the use of ranibizumab to treat wamd in chinese patients , and the aim of this study is to summarize the long - term effect of ranibizumab on wamd over a period of 5 years in chinese patients . thirty - seven eyes from 37 patients , who were treated with intravitreal ranibizumab injection in ophthalmology department of beijing hospital from june 2007 to june 2014 , were retrospectively analyzed . the inclusion criteria included ( 1 ) corresponding to the diagnostic standard of wamd , ( 2 ) being able to be followed up promptly according to the treatment protocol , ( 3 ) having a follow - up time of more than 60 months , and ( 4 ) no other anti - vegf drugs or other treatments during follow - up . at baseline , all eyes had an activating lesion , which presented with retinal edema , thickening , or patched retinal bleeding . all lesions were smaller than 4 da , 14 ( 37.8% ) of which were accompanied by ped . all patients were examined by the etdrs chart for visual acuity , ophthalmoscope , ffa , icga , and oct on their first visits . the etdrs visual acuity , ophthalmoscope , and oct were examined on every follow - up . the anterior segment , iop , and routine fundus test were examined within the first week after the injection to survey the operation - related complications . the treatment was injected monthly 3 times at the loading dose and then every month thereafter . in the recent 2 years , the follow - up was instructed by the t&e protocol , in which the follow - up time was gradually extended for 2 weeks up to more than 3 months if the lesion was stabilized . if the lesion relapsed , the follow - up went back to once a month again . in the first two years , according to the standard mentioned in the pronto study , we chose to retreat the patients when 2 of the following conditions were met : ( 1 ) the bcva decreased more than 5 letters or the va decreased subjectively ; ( 2 ) subretinal or intraretinal fluid accumulation on the macula area was measured by oct ; ( 3 ) there was a new hemorrhage lesion on the macula ; ( 4 ) cnv leakage increased or a new lesion developed according to ffa and/or icga . in the late stage , which was 2 years later , we choose to retreat the patients according to the activation of the lesion as follows : relapse or accumulation of intraretinal or subretinal fluid and new onset hemorrhage lesion related to the va decrease . we performed follow - up in the patients with stable ped or a prolonged intraretinal cyst . the follow - up time was 6097 months ( average 67.4 ) . during follow - up , 5 eyes were injected with a higher dose ( 1.0  mg , 0.1  ml ) for an increasingly shortened relapse interval . the retreatment criteria are patients with persistent recurrent macular intraretinal or subretinal fluid within 30 days . one - way analysis of variance was used to analyze the bcva at baseline and at every year after treatment . the relationship between the fibrosis / atrophy of the lesion in the 5th year after treatment and the injection times was analyzed by pearson correlation analysis . there were 22 male patients and 15 female patients , and there were 17 right eyes and 20 left eyes . the age of the patients ranged from 59 to 82 years , and the average age was 74.5  6.0 years . nine of the 37 eyes ( 24.3% ) had a pdt , avastin , or ta treatment history . the va of 37 patients before treatment ranged from 0.01 to 0.1 . among them , the va of 8 eyes ( 21.6% ) was 0.5 , the va of 21 eyes ( 56.8% ) was between 0.1 and 0.4 , and the va of 8 eyes ( 21.6% ) was 0.1 . five years after the treatment , the va of 6 eyes ( 16.2% ) was 0.5 , the va of 16 eyes ( 43.2% ) was between 0.1 and 0.4 , and the va of 15 eyes ( 40.5% ) was 0.1 ( figure 1 ) . the mean bcva examined by the etdrs chart was 34.89 letters ( table 1 ) . there was no statistically significant difference between the bcva at baseline and that in the first 3 years after treatment ( p = 1.314 , 0.595 , and 0.148 ) . the bcva at baseline and in the 5th year after the treatment had statistically significant difference ( p = 0.013 ) . the bcva in the 5th year after the treatment was significantly different ( p = 0.024 ) from that in the first 2 years after the treatment ( p = 0.03 and 0.025 ) ( figure 2 ) . the lesions were estimated by fundus image and oct 5 years after the treatment to check the formation of geographic atrophy and/or fibrotic scar . the lesion was stable at the first year after the treatment in 5 of the 36 patients ; the va increased and there was no recurrence . twenty - six eyes ( 70.3% ) had no treatment after 3 years because the lesion was stable or became a fibrous scar . four eyes ( 10.8% ) still needed uninterruptible treatment because of activation of the lesion after 5 years . five years after the treatment , 17 eyes ( 47.22% ) had fibrosis , and 2 eyes ( 5.4% ) had an atrophic change . the fibrosis / atrophy of the cnv lesion 5 years after the treatment was significantly correlated with the intravitreal injection times ( pearson , r = 0.663 , and p = 0.000 ) . the number of injections ranged from 3 to 31 in 5 years , and the average number was 11.53 . the injection was concentrated in the first 2 years , and , from the third year on , the injection number was gradually reduced ( table 2 ) . five patients ( 13.5% ) underwent more than 20 injections , 18 ( 48.6% ) patients underwent 1019 injections , and 14 ( 37.8% ) patients underwent fewer than 10 injections . our previous reports showed that the use of ranibizumab to treat wamd in chinese people has clear short - term efficacy and safety [ 79 ] . the long - term follow - up results of this study demonstrate that although the average bcva decreased by 13 letters compared with the bcva at baseline after 5-year treatment with ranibizumab , 37.8% of the patients had improved vision and 13.5% among whom gain 15 letters or more , indicating that the long - term efficacy of ranibizumab to treat wamd in chinese people is clear and definite . we found that the average bcva in the first , second , and third years had no significant difference compared with that at baseline , indicating that most of the patients can maintain their visual function in the first three years , results which are similar to other reports . in the late stage , the average bcva significantly decreased , which coincided with the change in the cnv lesion . the proportion and extent of fibrosis of the cnv lesion increased with prolonged follow - up . the cnv lesion in 46% of the patients in this study showed fibrosis , while only 5.4% had atrophy . the proportion and extent of fibrosis in chinese people are much higher than those in other reports [ 13 , 14 ] , whether because some patients had previously undergone pdt treatment or because the different pathophysiological changes in chinese people are not yet clear . eyes that received monthly ranibizumab had a higher incidence of geographic atrophy when compared with prn treatment . this was similar to the results of our prn treatment , in which the geographic atrophy was less than the fibrosis . this decrease in vision was accompanied by expansion of the size of the total neovascular complex comprising neovascularization , scarring , and atrophy and by persistence of fluid on oct . fibrosis may be due to multiple factors , and the exact cause has yet to be studied . fibrous scar is the major reason for a decline of vision in wamd patients , and reducing or avoiding fibrosis is an effective approach to improving vision , suggesting that combined therapy with antifibrosis might be the new trend for cnv treatment . our results demonstrate that the average injection time is nearly 12 , and 13.5% of patients were injected more than 12 times , while 37.2% were injected fewer than 10 times . our average injection time was less than that of catt study , in which the number was 15.4 . patients who undergo fewer injections can be classified into 2 subtypes according to the cnv features . first , when the lesion is small , treatment is effective , and patients rarely relapse . second , when the lesion becomes a fibrous scar , the treatment is stopped . from a statistical point of view , most injections occur during the first year and second year , which is related to the increase in cnv fibrosis in some of the patients . our results show that 10% of patients need treatment after 5 years due to lesion activation , indicating that some wamd patients require long - term , continuous treatment . in some patients , the repetitive injection interval is shorter with increases in the injection times , and we increased ranibizumab dose to 1.0  mg , which can extend the efficacy period , suggesting that some patients may be resistant to anti - vegf medicine after long - term application . another study from our group indicates that the probable anti - vegf antibody can affect the efficacy [ 1618 ] . during treatment , an individualized regime that is based on the patient 's reaction is needed [ 19 , 20 ] . for anti - vegf drugs that have poor outcome , increasing the dosage , changing the drug , and combined treatment can be applied . in the wamd treatment guidelines , the follow - up time for patients is recommended as once per month . in clinical practice , especially during long - term follow - up , once per month is a high burden for both patients and doctors . in the early stage , the patients are followed up once a month , for those whose cnv lesion is relatively steady and who can use the amsler grid by themselves , so the t&e follow - up program is adopted . in the cases where there are stable visual acuity , an absence of macular hemorrhage , and a dry oct , the follow - up intervals increase to 6 weeks without treatment . if there are no changes , the next visit is scheduled for 8 weeks later . if there is a change , the patient comes for injection and examination after 4 weeks . practice shows that this program not only reduces the number of follow - up visits but also can promptly detect the change in the cnv , suggesting that it can be used in clinical practice . wamd patients commonly have age - related cataracts . with the increase in the number of injections or prolonged follow - up time patients and doctors should be concerned about whether cataract surgery can improve the vision of wamd patients , whether the surgery can influence the cnv lesion , and when to perform the surgery . in our study , 7 cases underwent cataract surgery combined with iol implantation during the 5 years of follow - up , and most of the patients had improved visual function or visual clarity . another study of ours demonstrated that half of the wamd patients have improved visual acuity after cataract surgery , and 70% of the patients have improved visual clarity or visual field vision . for some patients , the anti - vegf drug injection and cataract surgery were performed simultaneously , and there was no interaction between them . in wamd patients , if a significant cataract develops , surgery can be performed even if the cnv lesion is active . however , because of the uncertainty of improved visual acuity after cataract surgery , a preoperative visual prognosis and sufficient explanation are needed . although the impact on visual acuity is multifactorial during long - term follow - up and the implementation of the treatment program is not uniform because different doctors and patients can affect the results of this study , our data reflects clinical treatment and can provide a reference for clinical use .
purpose . to observe the effect of intravitreal ranibizumab injection on wet age - related macular degeneration ( wamd ) over 5 years in chinese patients 
 . methods . 
 thirty - seven patients who were diagnosed with wamd in our hospital from june 2007 to june 2014 were retrospectively reviewed . 
 the prn regimen and the treatment and extend regimen were applied . 
 best corrected visual acuity ( bcva ) , number of ranibizumab injections , and changes in the choroidal neovascularization ( cnv ) lesion over 5 years were analyzed . 
 results . 
 the mean bcva measured by the etdrs chart at baseline was 47.4 and 5 years after the treatment it was 34.89 letters , which was significantly different ( p = 0.013 ) . 
 fourteen eyes ( 37.8% ) had improved visual acuity after 5 years . 
 the number of injections in 5 years was 11.53 , and most of the injections were in the first two years . 
 seventeen ( 45.9% ) cases developed fibrous lesions , and 2 ( 5.4% ) cases had atrophic lesions after 5 years . 
 the fibrosis / atrophy was significantly correlated with the injection numbers ( pearson , r = 0.663 , and p = 0.000 ) . 
 conclusion . 
 most of the patients can maintain visual acuity treated by ranibizumab in the first 3 years . 
 after 5 years , some patients can still improve or maintain visual acuity . 
 fibrous scarring of the lesion is the main reason for a decrease in vision of wamd patients .