age - related macular degeneration ( amd ) is subdivided into the dry form and the wet form . according to bressler et al .
the minimally classic / occult trial of the anti - vegf antibody ranibizumab in the treatment of neovascular age - related macular degeneration ( marina ) evaluated the benefit of ranibizumab in a dose of 0.5  mg  per month . at 12 months ,
95% of patients had lost < 15 early treatment diabetic retinopathy study ( etdrs ) letters from baseline and 34% of patients had a best corrected visual acuity ( bcva ) gain of 15 etdrs letters .
the study ranibizumab in patients with subfoveal choroidal neovascularization ( cnv ) secondary to age - related macular degeneration ( sustain study ) was designed to further evaluate the safety , tolerability , and efficacy of optical coherence tomography ( oct)/bcva - guided , individualized , and flexible pro re nata ( prn , as needed ) dosing regimen for ranibizumab . at 12 months ,
92.5% of patients had lost < 15 etdrs letters from baseline and 19.3% of patients had a bcva gain of 15 etdrs letters . whether the fixed or prn regimen was used in the treatment of wet amd , the therapeutic response of individual patients was not always the same .
current observations suggest that the factors which affect the response to the initial treatment with ranibizumab are individual .
the aim of this study was to assess the importance of various factors ( age , gender , baseline bcva , baseline macula thickness , and type and size of cnv ) for early morphological therapeutic response to ranibizumab in clinical practice .
the treatment of patients with wet amd is centralized into 9 tertiary referral centres in the czech republic ( see appendix ) .
anonymised data on treatment efficacy and safety have been consecutively entered into the czech national database amadeus ( age - related macular degeneration in patients in the czech republic ) since september 2008 .
the main aim of this registry is to collect basic epidemiologic data on patients diagnosed with wet amd in the czech republic , document standard diagnostic and therapeutic patterns , and assess treatment efficacy in standard clinical practice .
the data collection is independent of all treatment decisions ; it does not affect a patient 's access to treatment and fully complies with all ethical as well as legal requirements for noninterventional data collection in the czech republic .
all patients have given written informed consent to the treatment , as well as data collection .
the reported investigations were in accordance with the principles of the current version of the declaration of helsinki .
the data are recorded from the moment of diagnosis and start of treatment at regular 3-month intervals for half a year . in the following period , the record is completed every 6 months .
each record presumes biomicroscopic examination of the retina , determination of bcva using the etdrs chart , and an oct examination ( oct 3 stratus ) .
the first visit involves fluorescein angiography ( fa ) ; indocyanine green angiography ( icga ) is used only if it is necessary for determining a diagnosis .
the compulsory data always include bcva expressed by the number of etdrs letters , the central thickness of macula in 1  mm of macula in m , and volume in 6  mm of macula in mm .
the first visit also involves recording age and gender and measuring type and size of cnv using fa or icga .
patients with diagnosed wet form of amd who meet the czech society of ophthalmology criteria for initiation of treatment with the ranibizumab are entered into the registry .
ranibizumab therapy in the czech republic is indicated in patients with amd who are older than 50 years , with predominantly classic , minimally classic , or occult cnv in subfoveal localization , a bcva score between 70 and 35 letters ( 20/4020/200 snellen equivalent ) , total macular lesion area 8 disc area ( da ) , and submacular haemorrhage 25% of the total macular lesion area .
minimally classic and occult cnv must show signs of activity in the form of the presence of hard exudates , subretinal haemorrhages , or decrease in bcva within the last 3 months by 10 letters of the etdrs chart . in patients treated with ranibizumab in a dose of 0.5  mg , there are two separate phases : the loading phase , followed by a prn phase . in the loading phase ,
patients receive 3 consecutive monthly injections of ranibizumab ( months 02 ) , followed by a prn phase when further treatment is given between and including months 3 and 11 according to the retreatment criteria .
retreatment with ranibizumab is performed if the patient 's bcva worsened against bcva recorded in the previous visit and if there is a demonstrable macular edema on oct examination .
the prn method of application is also followed in the second year and all succeeding years of patient treatment .
our study assessed the influence of age , gender , baseline bcva , baseline macula thickness , and type and size of cnv on early morphological therapeutic response to ranibizumab in clinical practice .
we studied these factors in terms of anatomical changes in the macula after 3 consecutive monthly injections of ranibizumab in the loading phase ( months 02 ) .
the monitored factors : age , gender , baseline best corrected visual acuity , baseline macula thickness , and type and size of choroidal neovascularization nor any others parameters ( visual acuity , oct ) had no influence on the treatment scheme in the loading phase . from 01/09/2008 to 24/6/2013
, 1153 newly diagnosed , treatment - nave patients treated with ranibizumab were entered into the registry . following the 3 initial injections of ranibizumab
, the patients were divided into two groups based on the morphological findings in the macula : a group with active cnv and a group with inactive cnv . in the group with active cnv ,
oct screening revealed intraretinal macular edema , subretinal fluid accumulation , retinal pigment epithelium ( rpe ) detachment , fibrovascular rpe detachment , or the combination of all these findings .
oct screening revealed restored foveal depression and a scar at the site of cnv with no signs of exudation was apparent .
no intraretinal macular edema , subretinal fluid accumulation , rpe detachment , or fibrovascular rpe detachment was found . in both groups , we assessed the following parameters : gender and age of patients , type and size of cnv , baseline bcva on the etdrs chart , and baseline macular thickness .
standard descriptive statistics were applied in the analysis : absolute and relative frequencies for categorical variables and median supplemented with 5th95th percentiles and mean supplemented by 95% confidence interval for continuous variables .
the statistical significance of differences between groups was analyzed using pearson 's chi - square test for categorical variables and mann - whitney u test for continuous variables. = 0.05 was adopted as the level of statistical significance in all analyses .
( spss , inc . 2010 ) and performed by the institute of biostatistics and analyses at masaryk university , brno , operating independently of any amd treating centre in the czech republic .
the sample included 1092 patients , 38.6% men , average age 73.3 years ( sd : 8.4 ) , and 61.4% women , average age 74.2 years ( sd : 8.6 ) .
the analysis included 1153 treated eyes ; the right eye was treated 561 times , the left eye 592 times ( both eyes were treated 61 times ) . after the initial 3 injections ( day 0 , month 1 , and month 2 ) of ranibizumab , in month 3 we examined the sample of 1153 eyes .
of these there were 841 eyes with active cnv ( the active group ) and 312 eyes with inactive cnv ( the inactive group ) .
the sample in the inactive group included 41% of men and 59% of women ( p = 0.338 , pearson 's chi - square test ) .
the active and the inactive group included 29.3% and 27.9% of patients at the age < 70 years , 43.4% and 42.9% of patients aged 7080 years , and 27.3% and 29.2% of patients at the age > 80 years ( p = 0.237 , mann - whitney u tests ) , respectively .
the active and the inactive group included 31% and 20.2% of patients with predominantly classic cnv , 21% and 19.9% with minimally classic cnv , and 47.9% and 59.9% with occult cnv , respectively .
the inactive group showed statistically significantly higher presence of occult membranes and statistically significant lower presence of predominantly classic cnvs compared with the active group ( p < 0.001 , pearson 's chi - square test ) .
the active and the inactive group included 23.8% and 26.9% of patients with cnv < 2 disc areas ( da ) , 66.8% and 70.2% of patients with cnv 25  da , 9.4% and 2.9% of patients with cnv > 5  da , respectively .
the inactive group showed statistically significantly lower presence of cnv > 5  da compared with the active group ( p < 0.001 , pearson 's chi - square test ) .
the baseline bcva in the range of 1530 etdrs letters was shown in 10.2% of patients in the active group and 10.9% of patients in the inactive group .
the bcva in the range of 3160 etdrs letters was shown in 62.5% of patients in the active group and 55.1% of patients in the inactive group .
the baseline bcva of > 60 etdrs letters was shown in 27.2% of patients in the active group and 34% of patients in the inactive group .
the median of the baseline bcva was 54 ( 595 percentiles : 2273 ) and 55 ( 595 percentiles : 2375 ) in the active and inactive group , respectively .
we found no statistically significant difference in the value of the baseline bcva between the groups ( p = 0.066 , mann - whitney u test ) .
19.3% of patients in the active group and 15.6% of patients in the inactive group had a baseline macular thickness of < 250  m .
the baseline macular thickness in the range of 250400  m was shown in 51.7% of patients and 58.5% of patients , respectively , and baseline macular thickness of > 400  m was shown in 29% and 25.9% of patients , respectively .
the median of the baseline macular thickness was 330  m ( 595 percentiles : 190600 ) and 337  m ( 595 percentiles : 201535 ) in the active and inactive group , respectively .
there was no statistically significant difference in the value of the baseline macular thickness between groups ( p = 0.663 , mann - whitney u test ) .
in the literature , we found no publications describing prognostic factors for early morphological therapeutic response to treatment with ranibizumab in patients with wet amd .
sarks , killingsworth , and gonzales noted that occult cnv may have a good functional treatment response .
and killingsworth   demonstrated histologically that the onset of cnv is characterized by intrachoroidal neovascularization followed by sub - rpe fibrovascular proliferation .
occult cnv which is fibrovascular tissue in the sub - rpe space may in part represent an earlier stage of cnv because it is in the same tissue plane . up to 50% of occult cnv
occult cnv as an earlier stage of the disease is assumed to be associated with less damage to photoreceptors in macula and successful treatment has a better prognosis . in our study
, we evaluated the impact of gender , age , baseline bcva , baseline macular thickness , and type and size of cnv on early morphological therapeutic response following the 3 initial injections of ranibizumab . in the inactive group of 312 patients with complete regression of cnv activity after the initial 3 injections of ranibizumab
, we found a statistically significantly higher proportion of occult membranes , statistically significant lower presence of predominantly classic cnv ( p < 0.001 ) , and statistically significantly lower incidence of cnv > 5  da ( p < 0.001 ) compared with the active group .
we observed that smaller and occult cnv lesions have potentially better morphological therapeutic response with the disappearance of the cnv activity and resorption of the macular edema .
we found no significant impact of gender , age , value of baseline bcva , or baseline macular thickness on early morphological therapeutic response after the initial 3 injections of ranibizumab .
additional studies are needed to further clarify the relationship of morphological and functional results in ranibizumab treated patients with wet age - related macular degeneration .
the results showed positive early morphological therapeutic response with restored foveal depression and no signs of exudation on oct in patients with higher incidence of occult cnv , lower incidence of predominantly classic cnv , and lower incidence of cnv > 5  da .
there was no evidence of any effect of age , gender , baseline best corrected visual acuity , or baseline macula thickness on the early anatomical restoration of the macula .
we believe that occult cnv and a cnv smaller than 5  da are optimistic for better morphological therapeutic response at the beginning of ranibizumab therapy . to determine
if other factors influence the morphological response to ranibizumab treatment in patients with wet amd , further clinical studies are needed .
 
 aim . to assess the significance of age , gender , baseline 
 best corrected visual acuity , baseline macula thickness , and type and size of choroidal neovascularization in early morphological therapeutic response to ranibizumab treatment in patients with the wet form of age - related macular degeneration . 
 methods . from 09/2008 to 
 06/2013 we evaluated 1153 newly diagnosed , treatment - nave patients treated with ranibizumab . 
 based on the morphological findings in the macula following the initial 3 injections of ranibizumab , the patients were divided into two groups based on active and inactive choroidal neovascularization . results . 
 after the initial 3 injections of ranibizumab , we examined the sample of 841 eyes with active cnv and 312 eyes with inactive cnv . in the inactive group 
 , we found a statistically higher proportion of occult cnv ( p < 0.001 ) and lower incidence of cnv greater than 5da ( p < 0.001 ) compared with the active group . 
 we found no statistically significant difference in age , gender , baseline best corrected visual acuity , or baseline macula thickness between the inactive and active groups . 
 conclusion . 
 occult cnv and cnv smaller than 5da are optimistic factors for a better morphological therapeutic response at the beginning of ranibizumab treatment . 
1. Introduction
2. The Population and Methodology
3. Results
4. Discussion
5. Conclusion