corneal neovascularization is defined as the occurrence of neovessels developed from preexisting vascular structures in the limbus , invading areas of the cornea initially not vascularized . the avascular character results from a balance between angiogenic and antiangiogenic factors . in pathological conditions such as inflammatory , infectious , degenerative , or traumatic ones , this homeostasis can be broken and can be responsible for the occurrence of corneal neovessels .
several therapeutic modalities have been proposed : steroids , physical therapy by superficial keratectomy or argon laser , cauterization , and local   and subconjunctival application of anti - vegf ( bevacizumab , ranibizumab ) ; but there is so far no consensus in the therapeutic management of corneal neovessels .
the aim of our study is to report the efficiency and safety of bevacizumab in intrastromal injection in the treatment of corneal neovascularization .
this is a prospective , noncomparative study , conducted at the university hospital mohammed vi of marrakech , between september 2013 and december 2015 , and it included 25 eyes of 23 patients with deep predescemetic corneal neovessels who received intrastromal injections of bevacizumab .
all patients underwent an eye examination with a measurement of best corrected visual acuity , examination at the slit lamp with photographs of the cornea , intraocular pressure measurement , and examination of the eye fundus with an ocular ultrasound in the absence of a refractive medium of the eye .
the severity was assessed using a clinical grading scale ; this method aims to analyze directly photographs of the cornea ( table 1 ) .
patients had to have a minimum setback of six months to be included in the study .
all patients received initially a topical corticosteroid to reduce their diameter and act on their effects ( edema and inflammation ) .
the bevacizumab at 25  mg / ml was prepared sterilely into a syringe with a needle of 30 gauge .
an injection of about 0.01  ml was performed under topical anesthesia with instillation of oxybuprocaine hydrochloride 0.4% .
the product was administered in the corneal stroma next to neovessels ; the exact location depends on the location of the neovessels compared to the limbus , their number , and their extension according to the quadrants .
the intrastromal injections were spaced by a month and were continued until the stagnation of the regression of neovascularization .
patients who received intrastromal injections of bevacizumab were monitored at day 7 , day 30 , and day 120 .
patients received blood pressure test , visual acuity , intraocular pressure measurement , and the slit lamp exam with photographs .
the photographs on photographic slit lamp were taken in the inclusion visit then monthly until the end of the treatment .
the primary evaluation criterion was the corneal surface covered with neovessels before and after treatment .
the analysis was performed by clinical grading scale and photoshop software ( adobe systems , inc .
the second criterion for efficacy was the variation in visual acuity before and after treatment .
twenty - five eyes of twenty - three patients ( 15 men and 8 women ) with nine months of setback after the beginning of bevacizumab therapy were included in the study .
the average age of patients at the time of treatment with bevacizumab was 31 years ( between 16 and 44 years ) .
the etiologies of corneal neovascularization were scars of herpetic keratitis in 10 patients ( 43.4% ) , ocular trauma in 6 patients ( 26.1% ) , postinfectious keratitis in 3 patients ( 13% ) , chemical burns in 2 patients ( 8.7% ) , and toxic epidermal necrolysis in 2 patients ( 8.7% ) .
10 patients received 3 intrastromal injections of bevacizumab , 9 received four injections , and 4 had 5 injections .
the evolution was marked by the total regress in 15 patients ( figures 1 , 2 , and 3 ) , partial in 5 .
overall , the percentage of corneal neovascularization is reduced by 43  19% ( between 14 and 70% ) at 18  16% ( between 0 and 39% ) in day 120 ( p < 0.001 ) . later on ,
intraoperatively , 6 patients received subconjunctival corticoids injections , and 2 were injected with subconjunctival bevacizumab .
postoperatively , there was recurrence of neovessels at the collar of the receiver in 3 patients , which was well controlled under topical corticosteroids , and a backlash in 3 patients .
there was also a recurrence of neovascularization in 2 patients after an average of five months .
our study seems to suggest the efficacy of bevacizumab in the treatment of deep corneal neovascularization .
the development of corneal neovessels occurs in several phases : a perivascular latency phase , a second active neovascularization , and finally a maturation phase of new vessels .
the first two phases will be a potential target for angioregressive therapy by blocking angiogenic factors .
classical treatment modalities include corticoids , nonsteroidal anti - inflammatory drugs , laser photocoagulation , and reconstruction of the ocular surface . however , these treatments have demonstrated limited therapeutic effect with considerable complications [ 710 ] .
the development of inhibitors of vegf , a humanized monoclonal antibody bound to isoforms of vegf - a , introduced a new perspective in the treatment of various ophthalmic disorders , including damage to the ocular surface such as corneal neovascularization .
the efficiency of bevacizumab in intrastromal injection has been reported ; the dose of 25  mg / ml appears to be effective and well tolerated in several studies [ 1215 ] ( table 2 ) .
several hypotheses can be made to explain this variability in response to bevacizumab as the different etiologies of neovascularization are involved : the extension of the neovascularization , the state of limbo , and the delay between the appearance of neovessels and the beginning of treatment .
indeed , in these patients , the decline was not only due to corneal neovascularization , but also due to corneal scars . compared to other forms of administration , the intrastromal injection allows greater exposure to bevacizumab and delivery of a known concentration of the drug .
the penetration of the topical form of this drug may be limited by an intact epithelium because of the high molecular weight of bevacizumab .
the intrastromal administration also ensures less risk of failure due to lack of patient compliance .
patients may sometimes forget to install the medication at home , when using a topical preparation .
the subconjunctival injection of bevacizumab allows better diffusion compared to topical instillation ; several studies have shown its effectiveness in the treatment of superficial and average depth neovessels [ 17 , 18 ] , and others have proved that subconjunctival injection of bevacizumab allows only partial reduction of deep neovessels [ 1921 ] .
a recent study showed that the subconjunctival injection has no effect on mature neovessels ; it is quite effective in the active phase of the process of angiogenesis .
used a ranibizumab having a lower molecular weight than subconjunctival topical instillation and found satisfactory results .
the intrastromal injection of bevacizumab increases the concentration and duration of exposure ; in addition , it is also very effective in mature neovessels [ 13 , 14 ] .
the intrastromal injection of bevacizumab might be a useful option in the management of corneal neovascularization .
. however , further studies are needed to determine the optimum dosage and to define the indications , the frequency , and risk factors for developing possible side effects .
 
 introduction . 
 corneal neovessels are a major risk factor for corneal graft rejection , due to the loss of the immune privilege . 
 the purpose of this study is to evaluate the effectiveness of intrastromal injection of bevacizumab in the treatment of corneal neovascularization . 
 material and methods . 
 this is a prospective study that included 25 eyes of 22 patients with deep corneal neovessels , treated with intrastromal injections of bevacizumab 
 . results . 
 the average age of patients was 31 years ranging from 16 to 44 years . 
 the causes of neovascularization were dominated by herpetic keratitis ( 10 cases ) . 
 the evolution was marked by complete regress of neovessels in 16 patients , partial regress in 6 cases , and reduced opacity and improved visual acuity in 5 patients . 
 no side effects were noted . 
 discussion . 
 short - term results demonstrated the effectiveness of intrastromal injection of bevacizumab in the treatment of corneal neovessels . 
 it may be an option or a complement to other useful treatments in stabilizing or improving vision . 
 conclusion . 
 bevacizumab is an effective additional treatment for the improvement of corneal transplants prognosis with preoperative corneal neovascularization . 
1. Introduction
2. Material and Methods
3. Results
4. Discussion
5. Conclusion