less commonly , this condition presents in teenagers and young adults often with less aggressive features.4 coats disease is a major simulator of retinoblastoma , a life - threatening pediatric ocular malignancy.14 in a study of angiographic findings of patients with coats disease , we noticed that occlusion of the retinal microvasculature with peripheral nonperfusion and shunt or microshunt formation between arterioles and venules in the retina was a prominent finding.5 this led to a speculation regarding serum factors that could lead to the microocclusions , such as a hypercoagulability state .
realizing that such a state would more likely lead to bilateral manifestations , we continued to explore serum features in coats disease . in 2012 , we found a significantly high level of anti - cytomegalovirus ( cmv ) immunoglobulin g ( igg ) in 92% of coats patients , higher serum proteins c and s , anti - herpes simplex virus ( hsv ) igg i / ii , alpha-2 globulin , and homocysteinemia in patients with coats disease.6 in the second step of the analysis , it was planned to compare these factors in patients with coats disease with a control group .
herein , we evaluated serum hypercoagulable factors and viral and protozoan diseases in patients with coats disease versus normal controls .
a prospective , single - center , comparative , consecutive cross - sectional study was conducted for evaluating blood hypercoagulability state and infectious diseases , including cmv , herpes simplex , epstein - barr virus ( ebv ) , toxoplasma and toxocara infections , in all patients with coats disease from february 2011 to december 2013 .
the research adhered to the tenets of the declaration of helsinki and the study was approved by tehran university of medical sciences institutional review board . each patient or parents
were carefully informed about the purpose of the research , and oral consent for laboratory examinations was obtained . each patient or
coats disease was defined as unilateral or bilateral retinal vasculopathy characterized by retinal telangiectasia , capillary non - perfusion , multiple aneurysmal formation , exudation , and exudative retinal detachment.19 patients with coats disease were grouped into those aged 10 years or less versus those older than 10 years .
clinical factors were compared to a control group , which consisted of patients with cataract undergoing lensectomy for congenital , traumatic , or senile cataract , with no evidence of retinal vascular disease .
patients were evaluated with best - corrected visual acuity , indirect ophthalmoscopy for fundus features and color fundus photography , fluorescein angiography , and b - scan echography as needed .
fluorescein angiography was performed using a scanning laser ophthalmoscope ( hra , heidelberg , germany ) or retcam 120 ( clarity medical systems , inc . ,
the blood sample for serum studies was obtained from patients immediately before the treatment of coats disease .
treatment options included cryotherapy , photocoagulation , and intravitreal antivascular endothelial growth factor and/or subtenon triamcinolone depending on the patient s condition .
serum studies included hemoglobinopathies by hemoglobin electrophoresis ; serum protein electrophoresis ; coagulable states by serum protein c , protein s level , antiphospholipid antibody , anticardiolipine antibody , antithrombin iii , homocysteine level , and lipid profile ; and infectious states by anti - hsv igg , anti - cmv igg , anti - epv , anti - toxoplasma and anti - toxocara serum antibodies were measured with a enzyme - linked immunosorbent assay ( elisa ) technique according to the manufacturer s protocol .
statistical analyses were performed using statistical package for social sciences ( v 17.0 ; spss , chicago , il , usa ) .
all data are presented as mean  standard deviation ( sd ) or median ( range of data ) .
a mann  whitney test was used for quantitative or skewed distributed parameters . to assess the relationship between the qualitative variable and coats diagnosis , fisher s exact test was applied .
logistic regression models were used to assess the relation of target exposure with coats diseases adjusting for possible confounding factors .
statistical analyses were performed using statistical package for social sciences ( v 17.0 ; spss , chicago , il , usa ) .
all data are presented as mean  standard deviation ( sd ) or median ( range of data ) .
a mann  whitney test was used for quantitative or skewed distributed parameters . to assess the relationship between the qualitative variable and coats diagnosis , fisher s exact test was applied .
logistic regression models were used to assess the relation of target exposure with coats diseases adjusting for possible confounding factors . a p - value of less than 0.05 was considered to be statistically significant .
during the study period , there were 22 patients with coats disease ( figure 1 ) and 19 control patients .
of those with coats disease , 13 were 10 years or younger and 9 were older .
( table 1 ) . the mean age for coats patients was 14.5 years ( median 8 years , range : 2 month to 59 years ) , and for the control group it was 30 years ( median 17 years , range : 282 years ) ( table 2 ) .
for those 22 patients with coats disease , the mean time from the first notice of the disease by patients ( or parents ) to diagnosis was 7.15.4 months in the younger age group ( 10 years old ) and 7.89.9 months in the older age group ( > 10 years old ) . there were three ( 13.6% ) with bilateral involvement . using the coats disease
classification,4 the conditions of the eyes were classified as stage 1 ( n=0 ) , stage 2 ( n=7 ) , stage 3 ( n=12 ) , stage 4 ( n=3 ) , and stage 5 ( n=0 ) .
total retinal detachment was seen in six ( 28% ) cases , whereas macular detachment was seen only in three ( 14% ) cases . in two
using fluorescein angiography , avascular non - perfused areas were found in 18 ( 82% ) cases , located in the periphery region in 10 ( 46% ) and in the macular region in 2 ( 9% ) ( table 1 ) .
the first step of analysis was a comparison of the two age groups of coats disease ( 10 years vs > 10 years ) .
this revealed no significant difference in the lipid profile , serum antithrombin iii , anticardiolipine and antiphospholipid antibody serum antibody titer as well as polymerase chain reaction test for toxoplasma , toxocara , or ebv in the two groups .
there was statistical difference ( mann  whitney test - skewed deviation ) in the two groups with regard to hemoglobin ( p=0.02 ) , serum anti - hsv igg ( p=0.05 ) , anti - cmv igg ( p=0.05 ) , protein c ( p=0.07 ) , homocysteine ( p<0.01 ) , serum alpha-2 globulin ( p<0.01 ) , and serum gamma globulin ( p=0.05 ) . due to
the small sample size in each age group , the logistic regression analysis was inconclusive .
the second step of analysis involved comparison of laboratory findings in coats disease versus the normal control group ( table 2 ) .
there was no significant difference in the lipid profile , serum antithrombin iii , anticardiolipine , and antiphospholipid antibody serum antibody titer as well as polymerase chain reaction for toxoplasma , toxocara , or ebv .
however , in the control group , the serum titer of anti - hsv igg was higher and that of anti - cmv igg was lower . in coats group ,
serum beta globulin was significantly higher in both young ( 10 years , p<0.001 ) and old ( > 10 years , p=0.05 ) subgroups compared to controls . applying bonferroni correction
did not change the results of serum beta globulin in the group less than 10 years old .
logistic regression analysis for the main serologic findings in coats patients ( irrespective of age ) and control group was performed .
after adjustment for age and sex , a significant association persisted for the presence of higher titer of serum beta globulin in coats disease compared to controls ( odds ratio [ or ] : 1.8 , 95% confidence interval [ ci ] : 1.03.1 , p=0.02 ) ( table 3 ) .
anti - hsv showed a mild negative impact ( p=0.01 , or = 0.94 ) on the diagnosis of coats disease . after adjusting for age and sex , in those less than 10 years
, the serum beta globulin was found to be significantly associated with the diagnosis of coats disease ( or : 6.3 , 95% ci : 1.232.6 , p=0.02 ) . in patients greater than 10 years with coats disease , there was a non - significant association with the diagnosis of coats disease ( or : 1.3 , 95% ci : 0.82.0 , p=0.24 ) .
for the older age , anti - hsv antibody was borderline significant ( or : 0.98 , 95% ci : 0.971.00 , p=0.05 ) .
the small sample size precluded more conclusive results in the logistic regression analysis , adjusting for all other covariates .
in this study , we could not find any association between hypercoagulability state and coats disease ( compared to controls ) .
the only factor associated with coats disease was elevated serum beta globulin mainly in the younger age group .
we also recognized the negative impact of anti - hsv antibody on coats disease in the older age group .
serum protein electrophoresis is a technique to assess the two major fractions of protein in blood , including albumin and globulins.10 albumin is a transport protein that plays a significant role in fat solubility.11 the globulin fraction of blood includes hundreds of serum proteins , including carrier proteins , enzymes , complement , and immunoglobulins .
globulins are divided into four groups by electrophoresis : alpha , alpha-2 , beta , and gamma , depending on their migratory pattern between the anode and the cathode of the electrophoresis test.11 the beta fraction of serum globulins is known to have two peaks , named as beta 1 and beta 2 .
beta 1 is composed of mostly transferrin , and beta 2 contains beta - lipoprotein.12 iga , igm , and sometimes igg , along with complement proteins ( c3 ) , beta-2 microglobulin , plasminogen , angiostatins , properdin , sex hormone - binding globulin , transferrin , hemopexin , and factor h , can also be identified in the beta fraction.1012 these proteins carry out numerous biological functions in the human body , including iron transport and monitoring immune response.10,11 beta globulin protein can be elevated or depressed in various diseases .
beta globulin is found to be elevated in iron deficiency anemia , hypercholesterolemia , pregnancy , estrogen therapy , and also substantially increased in liver disease.9,10,13,14 it is found to be decreased in malnutrition , cirrhosis , and immune deficiency due to decreased synthesis , and in nephrotic syndrome due to protein loss in the kidney.11 in this series of coats disease , the beta globulin fraction was elevated , which is particularly evident in patients lesser than 10 years . this age - related difference could correlate with milder manifestations of coats disease in older patients .
the relationship of this fraction with coats disease is unclear , but could correlate to higher c3 ( complement protein 3 ) level or other factors .
complement 3 is an important protein in the immune system , which plays a vital role in the acute phase response .
it controls several biological processes , including cell lysis , chemotaxis , anaphylaxis , vascular permeability , and cellular membrane adhesion .
this protein is categorized as a beta globulin and might represent the elevation of beta globulin in coats disease in this report.12,1518 chronic low - grade inflammation has been correlated with elevated c - reactive protein , as well as complement c3 plasma levels , and these can be predictive of arterial thrombotic events.1620 elevated c3 is also associated with prolonged fibrinolysis.18,2123 both of these roles could relate to the vascular pathology of coats disease .
the discrepancy found in the younger and older age groups could suggest a difference in the main pathophysiological basis of coats disease in children and adults .
there are limitations of this study , including the small sample size and unclear relevance of beta - globulin relationship to the condition studied .
this relationship could be further explored with larger cohort and more precise fractionation of the beta - globulin subgroup to better understand the exact protein(s ) that contribute to this finding and its relationship to coats disease .
this analysis demonstrated that children with coats disease showed elevated serum levels of beta globulin . we speculate that this finding could reflect the known fluorescein angiographic - evident ischemic component and possibly now a low - grade inflammatory component .
 purposethe purpose of this study was to investigate the serum hypercoagulability state and common viral and protozoan infections in coats disease versus a normal control group.materials and methodsin this comparative case series , 22 consecutive patients with coats disease and 19 non - coats patients undergoing lensectomy for congenital , traumatic , or senile cataract between january 2011 and june 2014 were included . 
 laboratory data for hypercoagulability states and common viral and protozoan infections were investigated.resultsthe mean age for the coats group was 14.5 years ( median 8 years , range : 2 months to 59 years ) , and for the control group it was 30.6 years ( median 17 years , range : 282 years ) . in patients aged 10 years or younger , anticytomegalovirus immunoglobulin g ( igg ) ( p0.01 ) , homocysteine ( p=0.03 ) , and serum beta globulin ( p<0.001 ) were associated with coats disease . in those older than 10 years , higher serum protein s ( p=0.04 ) , beta globulin ( p=0.05 ) , and gamma globulin ( p=0.04 ) were related to coats diagnosis . after adjusting for sex and age as confounding factors , 
 only beta globulin was found to be associated with coats disease in logistic regression analysis ( odds ratio : 1.8 , 95% confidence interval : 1.03.1 , p=0.02).conclusionserum beta globulin levels appear to be elevated in patients with coats disease . 
Introduction
Materials and methods
Statistical analysis
Results
Discussion
Conclusion