ANTERIOR SEGMENT ISCHEMIA AND STRABISMUS SURGERY : FROM THE ANATOMY TO THE CLINIC

Anterior segment ischemia is a serious complication that may occur after strabismus surgery, particularly after the deinsertion of three or four extraocular muscles, with transection of their anterior ciliary arteries. However, individual susceptibility and a considerable amount of risk factors also play an important role in the development of this condition, which endangers sight. A thorough evaluation is essential for each patient. Therefore, knowing the irrigation of the anterior segment along with the mechanisms that produce ischemia of the eye region is very important to assess patients, plan and decide which surgical procedure is best for each particular case, and to prevent the occurrence of this complication. Review of the descriptive anatomy and its subsequent combination with the clinical picture of this entity facilitates understanding of the pathogenesis of ischemia and raises awareness about the need to institute preventive measures.


INTRODUCTION
The anterior segment ischemia (ASI) is now a well-known clinical entity that is most frequently seen after strabismus surgical procedures.Given that, this complication may become a sightthreatening condition, a better understanding of ASI by researchers and clinicians is of vital importance to prevent this rare but serious disorder.In our article we review the descriptive and functional anatomy of the anterior segment of the eye, as well as the clinical features of the condition to highlight the importance of its recognition and prevention.

Vascular anatomy of the anterior segment
Three main arteries supply the anterior segment of the eye: the anterior ciliary arteries, the long posterior ciliary arteries and the conjunctival arteries.Seventy to eighty percent of the arterial blood flow to this region of the eye is supplied by the anterior ciliary arteries.The long posterior ciliary arteries irrigate the majority of the remaining territory, being the conjunctival arteries just a minor component of the blood supply to the aforementioned region (Olver and Lee, 1989;Skuta et al, 2011a;Bagheri et al, 2013).The muscular arteries, branches of the ophthalmic artery, supply the rectus muscles and after this has been achieved they divide into the anterior ciliary arteries.The anterior ciliary arteries travel within the rectus muscles and emerge on the surface at a short distance posterior to the transition from muscle to tendon.They advance anteriorly in a tortuous manner and give off the anterior conjunctival arteries just before they pierce the sclera to anastomose with the branches of the long posterior ciliary arteries.The anastomosis between the anterior ciliary arteries and the long posterior ciliary arteries forms the major arterial circle of the iris (MAC), which carries blood to the ciliary body, the ciliary processes and the iris.After palpebral branches of the lacrimal and nasal arteries have formed the palpebral arcades, ascending branches from the peripheral tarsal arcade advance into the superior fornix and continue to the bulbar conjunctiva as the posterior conjunctival arteries which anastomose with the corresponding anterior conjunctival arteries (Fig. 1) (Saunders et al, 1994;Hayreh, 2006).In his vascular anatomy of the eye, Leber (Graefe et al, 1916) described two anterior ciliary arteries for each of the rectus muscles, except for the lateral rectus, which has only one.Nevertheless, the number, caliber and location of the anterior ciliary vessels have been found to be variable in different studies (Heymann et al, 1985;Mckeown et al, 1989).The oblique muscles are not irrigated by muscular arteries and do not carry anterior ciliary arteries, as a consequence, they do not contribute to the anterior segment blood supply and the transection of these muscles should not produce ASI.The two long posterior ciliary arteries pierce the sclera at a short distance from the optic nerve and follow an anterior direction to the ciliary muscle in an intrascleral position, below the medial and lateral rectus muscles.The long posterior ciliary arteries form the intramuscular circle of the iris and its branches contribute to the formation of the usually discontinuous MAC (Skuta et al, 2011a).Anastomoses between the episcleral and subconjunctival tissue, the intramuscular circulation of the iris and the MAC provide a multichannel blood supply to the anterior segment that might prevent ASI after strabismus surgery (Fishman et al, 1990;Coats and Olitski, 2007).

Anterior segment ischemia
Due to the multilevel blood supply of the anterior segment, ASI is a rare, but potentially serious complication that threatens vision.The first clinical descriptions of the anterior segment changes due to ischemia made by Schmidt in 1874 (Schmidt, 1874), the studies in animal models (Chamberlain Jr, 1954;Laatikainen, 1971) and the analysis of pathological specimens (Sharp et al, 1982;Apple et al, 1984) provided a background that allowed to associate and recognize the clinical syndrome of ASI with extensive surgery of the rectus muscles in the late 1950's and early 1960's (Wilson and Irvine, 1955;Forbes, 1959;Girard and Beltranena, 1960;Nauheim, 1962;Orzalesi and Saba, 1966).

Incidence
A survey of the members of the American Association of Pediatric Ophthalmology and Strabismus estimated an incidence of ischemia, for all age groups after strabismus surgery of 1 in 13,333.In this study, 400 000 surgical procedures were documented and only 30 cases were found (France and Simon, 1986).Nevertheless, the reported incidence might underestimate its true occurrence given the lack of clinical manifestations of mild cases.The ASI is most frequently seen after transection of three or four rectus muscles and their respective anterior ciliary arteries during strabismus surgery (Bagheri et al, 2013).It is almost exclusively found in adults and particularly in those with circulatory problems (Jacobs et al, 1976;Cullis et al, 1979;Fells, 1980;Saunders and Sandall, 1982;Wagner and Nelson, 1985;France and Simon, 1986).Yet, cases of clinically significant ASI in children who went through strabismus surgery can be found in the literature (France and Simon, 1986;Elsas and Witherspoon, 1987).

Anterior segment perfusion after strabismus surgery
Hypoperfusion of the anterior segment after strabismus surgery can be demonstrated by iris fluorescein angiography (IFA) (Hayreh and Scott, 1978a;b;Virdi and Hayreh, 1987;Chan et al, 2001).IFA is a valuable diagnostic technique that can be used to determine the etiology of different disorders that affect the anterior segment structures and their vasculature.To perform IFA, the examiner needs a fundus camera or any other specialized camera used for this purpose.After the injection into a peripheral vein of sodium fluorescein, a hydrocarbon that reacts with wavelengths of 465 to 490 nm and that fluoresces at 520-530 nm, two fluorescein matched filters of the camera (exciter and barrier) allow the blue absorbed excitation wavelength to be changed to a resultant green-yellow fluorescence.A consecutive series of pictures are taken during time to document the filling patterns of the vasculature of the anterior segment structures (Brancato et al, 1997).If a single rectus muscle is detached from the sclera, a filling delay adjacent to the disinserted muscle will ensue.A sectorial filling delay after surgery of the vertical rectus muscles is greater than when horizontal rectus muscles are operated.In a clinical and angiographic assessment of the anterior segment circulation made in 35 patients, Olver (Olver and Lee, 1989) demonstrated that on postoperative day one, detachment of the inferior rectus muscle resulted in a larger defect of perfusion than superior rectus muscle tenotomy.Because of the transection of the anterior ciliary arteries following procedures on the rectus muscles, compensatory blood flow to the anterior segment increases in the long posterior ciliary arteries, particularly in the medial one (Hayreh and Scott, 1978b;Prakash et al, 1986;Olver and Lee, 1989).Despite this useful contribution, an experimental study showed that disruption of the blood supply of only the long posterior ciliary arteries does not lead to ASI (Virdi and Hayreh, 1987).Within the first few weeks after surgery the filling delay rapidly decreases, suggesting an increase in the collateral circulation.Nevertheless, the filling pattern remains the same and the last sector to fill will still correspond to the hypoperfused area.In spite of anecdotal evidence, reestablishment of the circulation of a transected anterior ciliary vessel does not occur (Olver and Lee, 1992).

Risk factors
Thanks to the anatomical and functional studies regarding anterior segment irrigation and the changes that strabismus surgery produces in this region of the eye, it has become evident that individual susceptibility and the type of surgery are important factors that condition the occurrence of ASI (Saunders et al, 1994).Several risk factors for the development of ASI have been identified.Advanced age, surgery on the vertical rectus muscles, previous rectus muscle surgery, atherosclerosis, diabetes, hypertension, blood dyscrasias, dysthyroid ophthalmopathy, simultaneous surgery on three or four rectus muscles of the same eye, simultaneous surgery on adjacent rectus muscles and the use of a limbal incision are all determinants that place patients at risk for ischemia (Jacobs et al, 1976;Von Noorden, 1976;Hayreh and Scott, 1978b;Cullis et al, 1979;Fells, 1980;Saunders and Sandall, 1982;Simon et al, 1984;Wagner and Nelson, 1985;Fishman et al, 1990;Murdock and Kushner, 2001).Of those mentioned, the most important risk factor is the patient's age (France and Simon, 1986).In children, several rectus muscles can be detached from the sclera and it will be very rare that they develop ASI (Berens and Girard, 1950).It is therefore presumed that adults lack a sufficiently adaptable vascular system.The coexistence of two or more of the aforementioned risk factors puts the patient at greater risk and demands a careful surgical planning along with appropriate patient counseling.Another risk factor taken into account is the fact that vortex vein occlusion could lead to the development of ASI (Hayreh and Baines, 1973;Robertson, 1975).Procedures during which vortex veins are at greater risk of lesion are recessions or resections of the superior or inferior rectus muscles, exposition of the superior oblique muscle tendon and weakening of the inferior oblique muscle (Skuta et al, 2011b).

Classification Clinical manifestations Grade I
Asymptomatic patient with reduced iris perfusion Grade II Asymptomatic patient with reduced iris perfusion associated with transient findings on the slit lamp examination consisting in corectopia, irregular pupil reaction and flattening of the pupil margin.

Grade III
Photophobic patient with postoperative uveitis and marked pupil signs.

Grade IV
Patient with pain and reduced vision.Keratopathy, uveitis and decreased intraocular pressure present on examination.

Clinical manifestations
In early stages, the most common clinical findings include anterior chamber flare (visualization of the slit-lamp light beam as it passes through the anterior chamber because of an increase in the protein content of the aqueous humor) and cells (inflammatory cells visualized as white dots in the slit-lamp light beam that move along the convection currents of the aqueous humor (Wilson and Blomquist, 2009), corectopia (a pupil that is not localized in its normal central location) and a sluggish pupillary reaction to light (Bagheri et al, 2013).Olver and Lee have classified ASI into four grades of severity, representing grade I a sector filling delay in an asymptomatic patient, and grade IV as an infarction in a patient with reduced vision and pain (Olver and Lee, 1989) (Table 1).Patients with grade IV ASI can loose their vision and, in rare cases, phthisis bulbi can ensue (Girard and Beltranena, 1960).As previously stated, the collateral blood flow to the hypoperfused areas increases in the following weeks after surgery, therefore, most of the cases will improve during this period of time.Nevertheless, if significant ischemia develops, atrophy of the iris, a sluggish pupil and corectopia may remain permanently.

Treatment
Because the predominant manifestations of ASI are those of an inflammatory process, treatment consists of topic, subconjunctival and/or systemic steroids.However, there are no data about the benefits of treatment of ASI and no universal consensus about this treatment strategy exists.In a survey of the members of the American Association for Pediatric Ophthalmology and Strabismus, it was found that 21.4% of the ophthalmologists that detected a case of ASI did not use any medical treatment (France and Simon, 1986).

Evidence-based strategies for prevention of ASI
In the interest of preventing cases of ASI, patients who are at risk of developing the condition should be identified and an individualized plan for the patient's surgery should be designed.In order to reach the episcleral space and to operate on the extraocular muscles an incision in the conjunctiva and in Tenon's fascia is required.The two most common techniques that are used are the fornix conjunctival incision (Parks, 1968) and the limbal conjunctival incision (Von Noorden, 1968).Of these two, the limbal conjunctival incision disrupts the circulation of the episcleral arterial circle and reduces, though in a minor percentage, blood flow to the multichannel level of the anterior segment of the eye.Fishman (Fishman et al, 1990) reported less events of ischemia with the fornix conjunctival incision in animal models.Therefore, when possible, a fornix conjunctival incision should be preferred in at-risk patients.Although some authors have described the possibility to detach the four rectus muscles in children or a young adult (Girard and Beltranena, 1960;Uribe, 1968), the number of rectus muscles that are to be operated is an important determinant for the appearance of ischemic changes.In addition to the number, the combination of rectus muscles that are going to be operated is also important.An operation of the two horizontal rectus muscles in a healthy patient with a previously unoperated eye represents no risk because of the compensatory flow of the long posterior ciliary arteries and the fact that the lateral anterior ciliary artery does not contribute to the supply of the intramuscular arterial circle (Woodlief, 1980;Morrison and Van Buskirk, 1983).Whenever possible, no more than three rectus muscles should be simultaneously operated on the same eye and if extensive surgery is needed, a staged procedure appears to be beneficial when trying to prevent ASI (Harley, 1971;Hiatt, 1978;Simon et al, 1984;Wagner and Nelson, 1985;Prakash et al, 1986;Olver and Lee, 1992); this presumably is because the interval of time between the operations allows for the collateral blood flow to increase.The procedures that most frequently require simultaneous detachment of three rectus muscles in an eye are those that treat paralytic strabismus (strabismus due to paralysis or weakness of one or several rectus muscles where the deviation of the affected eye varies with the different gaze positions (Harper, 2010).Several techniques to preserve the anterior ciliary arteries during extensive strabismus surgeries have been developed.For example, in the treatment of paralytic strabismus, splitting and/or transposition of the muscle insertion sites have been the essence of some operations like the Hummelsheim (Hummelsheim, 1908) and the Jensen (Jensen, 1964) procedures.During these procedures and their further modifications, it is sought to preserve one anterior ciliary artery in each muscle.Combining different techniques can also reduce the number of muscles that have to be operated in one eye.For example, vertical rectus muscle transposition in the paretic eye and rectus muscle recession or resection in the contralateral eye on patients with sixth cranial nerve palsy, or combinations of rectus muscle recession or resection with vertical or horizontal transposition in complicated incomitant strabismus (Buckley and Townshend, 1991).The toxin produced by the gram-negative bacteria Clostridium botulinum presents as an important alternative in patients who require rectus muscle recession in complex strabismus surgeries.The botulinum toxin has seven serotypes (A, B, C1, D, E, F, G), form which the type A botulinum toxin is the most studied and therefore, the most used (Aoki and Guyer, 2001).The most common indication to use botulinum toxin in strabismus patients is acute sixth cranial nerve palsy (Fitzsimons et al, 1988;Biglan et al, 1989;Fitzsimons et al, 1989).Even though the paralytic effect of the toxin ranges from 1 to 2 months, the results are good and complications are rare.Though more complicated and time demanding, dissection of the anterior ciliary vessels prior to muscle tenotomy emerges as a relevant alternative for patients who are at risk.This technique was first described by McKeown (Mckeown et al, 1989) and adaptations to use magnifying glasses instead of the dissecting microscope have been suggested (Freedman et al, 1992).The importance of these anterior ciliary arteries preservation techniques is that no cases of ASI have been reported when implementing these procedures and postoperative evaluations with IFA have demonstrated normal filling patterns (Mckeown et al, 1989;Aguirre Vila-Coro, 1990;Wright and Lanier, 1991).
The anterior segment of the eye is provided with a rich blood supply deriving mainly from the anterior ciliary arteries system and receiving contribution, in order of importance, from the long posterior ciliary arteries and the conjunctival arteries.Because of anastomotic rings that occur in this region, ASI may be rare but when present, represents a serious complication that can lead to blindness.Though the patients that are at greater risk are those of advanced age and those who submit to procedures in which three or four rectus muscles have to be operated simultaneously, individual susceptibility plays an important role in the occurrence of this condition.There are different strabismus surgery techniques that can be used to treat a specific type of strabismus.Therefore, careful evaluation with identification and stratification of risk factors in each patient should be done in order to perform the surgical procedure that represents the best option for the patient, a "made-tomeasure-suit" surgery.

Figure 1 .
Figure 1.Schematic three-dimensional representation of the vascular anatomy of the anterior segment of the eye.Superficial vessels are represented with dark lines, whereas clear lines illustrate deeper arteries.ACA= Anterior ciliary artery; LPCA= Long posterior ciliary artery; AcA= Anterior conjunctival artery; PcA= Posterior conjunctival artery; IMC= Intramuscular circle; MAC= Major arterial circle; RCA= Recurrent ciliary artery.

Table 1 .
Classification of anterior segment ischemia severity