Ординатура / Офтальмология / Английские материалы / Strabismus Surgery and Its Complications_Coats, Olitsky_2007

References

1.Wutthiphan S, Vajaradul Y, Lerdvitayasakul R, Nimvorapun T, Koochingchai W (2002) Ocular fixation with quadriceps tendon allograft. Cell Tissue Bank 3:121–126

2.Salazar-Leon JA, Ramirez-Ortiz MA, Salas-Vargas M (1998) The surgical correction of paralytic strabismus using fascia lata. J Pediatr Ophthalmol Strabismus 35:27–32

3.Scott AB, Miller JM, Collins CC (1992) Eye muscle prosthesis. J Pediatr Ophthalmol Strabismus 29:216–218

4.Bicas HE (1991) A surgically implanted elastic band to restore paralyzed ocular rotations. J Pediatr Ophthalmol Strabismus 28:10–13

5.Goldberg RA, Rosenbaum AL, Tong JT (2000) Use of apically based periosteal flaps as globe tethers in severe paretic strabismus. Arch Ophthalmol 118:431–437

6.Kroczek SE, Heyde EL, Helveston EM (1970) Quantifying the marginal myotomy. Am J Ophthalmol 70:204–209

7.Bagolini B, Tamburrelli C, Dickmann A, Colosimo C (1990) Convergent strabismus fixus in high myopic patients. Doc Ophthalmol 74:309–320

Chapter 15

9.Aoki Y, Nishida Y, Hayashi O et al (2003) Magnetic resonance imaging measurements of extraocular muscle path shift and posterior eyeball prolapse from the muscle cone in acquired esotropia with high myopia. Am J Ophthalmol 136:482–489

10.Venkatesh CP, Gayathri N, Murthy KR (2003) Myopic strabismus fixus: a mitochondrial myopathy? Am J Ophthalmol 135:720–722

11.Krzizok TH, Kaufmann H, Traupe H (1997) New approach in strabismus surgery in high myopia. Br J Ophthalmol 81:625–630

12.Conrad HG, de Decker W (1978) Rotatorischer Kestenbaum

– Umalgerungshirurgie bei Kopfzwangshaltungen sur Schulter. Klin Monatsbl Augenkeilkd 173:681–690

13.von Noorden GK, Jenkins RH, Rosenbaum AL (1993) Horizontal transposition of the vertical rectus muscles for treatment of ocular torticollis. J Pediatr Ophthalmol Strabismus 30:8–14

14.Cuppers C (1976) The so-called “fadenoperation.” In Fells P (ed) Second Congress of the International Strabismological Association, p 395. Marseilles, Diffusion Generale de Librairie, France

15.Clark RA, Isenberg SJ, Rosenbaum AL, Demer JL (1999) Posterior fixation sutures: a revised mechanical explanation for the fadenoperation based on rectus extraocular muscle pulleys. Am J Ophthalmol 128:702–714

strictive motility in high myopia by magnetic resonance imaging. Arch Ophthalmol 115:1019–1027

accommodative esotropia with a high accommodative conver- gence-accommodation ratio. Arch Ophthalmol 105:815–818

16

Historically, methods to improve ocular alignment have involved surgery on the extraocular muscles. The most frequently utilized procedure to weaken an extraocular muscle is a surgical recession. Surgical recession has traditionally been favored due to its predictability and long history of known favorable outcomes. In the late 1970s and early 1980s, Alan Scott pioneered the use of botulinum for weakening one or more extraocular muscles in the treatment of strabismus [1–3].

16.1 Mechanism of Action

Botulinum is produced by the Gram-negative bacillus Clostri­ dium botulinum. It consists of several component proteins including both neurotoxic protein as well as associated nontoxic component proteins. Botulinum is initially produced as an inactive single chain molecule and becomes activated through a selective cleavage process yielding multiple protein chains. Seven different serotypes of botulinum toxin have been identified (A, B, C1, D, E, F, and G). Each of the serotypes is capable of producing a neurotoxic effect with a similar mechanism of action, but they differ in their relative potencies [4]. Type A botulinum toxin has been extensively studied and is the most commonly used serotype for the treatment of strabismus.

16.2 Effect on the Neuromuscular Junction

The extraocular muscles are striated muscles and are innervated by motor neurons. The motor neurons that innervate the extraocular muscles originate in the midbrain and brainstem and travel to the orbit to directly innervate individual extraocular muscles. The motor neuron branches into terminals that contact several muscle fibers, each of which forms a neuromuscular synapse. A motor unit consists of several striated muscle fibers each of which is innervated by a single motor neuron. The motor neuron signals the muscle to contract via an action potential. When the action potential reaches the neuromuscular synapse, the terminal motor neuron depolarizes which subsequently stimulates the release of acetylcholine into the synaptic cleft. The release of acetylcholine into the synaptic cleft is a multistage process, which is in part controlled by several proteins known as SNAREs (soluble N-ethylmaleimide-sensi-

tive factor attachment protein receptors). SNAREs modulate the fusion of the acetylcholine vesicle to the cell membrane, which allows its release into the synaptic cleft. After its release, acetylcholine travels across the synaptic cleft to bind with nicotinic cholinergic receptors on the muscle fiber motor end-plate. This produces an action potential in the muscle fiber that then eventually leads to muscle contraction.

Once injected, botulinum neurotoxin enters the presynaptic motor neuron through a process of endocytosis. This is a re- ceptor-mediated process during which the toxin is completely encapsulated within a vesicle. Once inside the cell, the toxin molecule passes through the vesicle wall. The toxin molecule then cleaves one of the proteins that is responsible for fusion and release of the acetylcholine vesicle. The various botulinum toxin serotypes act upon different SNARE proteins.

16.3 Other Actions of Botulinum Neurotoxin

Substance P is a neuropeptide that is involved in the genesis of pain. Like acetylcholine, substance P is released through a process requiring SNARE proteins. Botulinum has shown some clinical benefit in the relief of pain disorders mediated by substance P. Due to its large size, botulinum toxin is incapable of penetrating the blood–brain barrier. Therefore, direct effects of the neurotoxin on the central nervous system are not

aconcern.

16.4History of Botulinum Neurotoxin in the Treatment of Strabismus

In 1979, Alan Scott conducted an experiment on Rhesus monkeys in which he injected botulinum toxin into the horizontal rectus muscles. This initial research showed promise that botulinum toxin could be utilized to alter ocular realignment. Later experiments performed by Scott also showed efficacy of botulinum in the treatment of humans with strabismus. In these experiments, 42 patients with strabismus were injected with botulinum toxin [3]. The toxin was injected directly into extraocular muscles. The beneficial effect of the toxin injection lasted for a period of over 1 year in some patients. No systemic or local complications occurred. These encourag-

ing reports in humans were the foundation for a later clinical trial in which 677 patients underwent treatment of strabismus with botulinum toxin. In 55% of the treated patients, ocular realignment had been achieved to within 10 prism diopters of orthotropia when evaluated at 6 months following initial injection. Botulinum toxin was approved by the U.S. Food and Drug Administration for the treatment of strabismus in 1989. Since its approval, many forms of strabismus have been treated with the toxin. In addition, the use of botulinum toxin has enjoyed a more widespread treatment spectrum including many nonstrabismic disorders, such as cervical dystonia, blepharospasm, and more recently cosmetic use for the treatment of facial wrinkles. The use of this agent in the treatment of medical conditions has spread across multiple disciplines.

16.5 Injection Techniques

For botulinum toxin to achieve its desired effect, it must be directly injected into the belly of an extraocular muscle. This can be achieved in the operating room under direct visualization or through the use of electromyographic techniques, though some surgeons do not feel that electromyography use is critical to the success of the procedure [5]. When botulinum is injected at the same time that standard incisional strabismus surgery is being performed, the injection can be done under direct visualization. Generally, the conjunctiva is incised over the muscle and the agent is injected directly into the muscle belly. Botulinum toxin is commercially available under the trade name Botox® and is manufactured by Allergan. It is supplied in individual vials containing 100 units of freeze-dried toxin. Each unit contains approximately 0.25 ng of the protein. The toxin must be stored in a freezer until it is ready for use. Toxin is prepared for injection by reconstituting with nonpre-

Chapter 16

served normal saline. Reconstitution is based on the specific dilution required to achieve the desired concentration. Typically, for the treatment of strabismus, the desired concentration is 2.5 units/0.1 ml of solution.

The package insert states that Botox® must be used within several hours of reconstitution to maintain its therapeutic affect. However, one study indicated that botulinum toxin maintains its potency if it is refrozen or refrigerated for up to 2 weeks, though the manufacturer does not recommend reusing stored Botox®. In a study by Sloop and co-workers [6], eight volunteers had freshly reconstituted Botox® injected into the extensor digitorum brevis. They then underwent repeat injections of Botox® which was either refrozen or refrigerated for 2 weeks. Muscle paralysis was measured by performing electromyography and comparing the degree of decline in M-wave amplitude after each injection. No difference was found between fresh, frozen, or refrigerated Botox®. However, a study in the otolaryngology literature performed by Gartlan and Hoffman [7] demonstrated a 70% loss in potency when Botox® was reconstituted, refrozen, and then assayed 2 weeks later. Currently most ophthalmologists attempt to use the majority of the reconstituted Botox® within several hours of its dilution. In clinical practice this often translates to multiple patients being treated with a single vial of toxin on the same day.

Once the toxin is reconstituted, it is important to handle the vial carefully. Botulinum protein is delicate and is susceptible to destruction if the vial is shaken too aggressively. The diluted toxin is drawn into a tuberculin syringe using a disposable needle. A Teflon-coated needle is then placed on the syringe. The base of the needle is connected to a portable EMG machine. An EMG lead is attached to the patient’s forehead to complete the electrical circuit (>Fig. 16.1). After the conjunctiva is anesthetized with topical anesthetic, the needle is passed through the conjunctiva just posterior to the muscle insertion site on the sclera. While the needle is being passed into the orbit, the

patient is asked to look in the direction opposite the muscle to be injected. Stabilization of the eye with forceps as the needle penetrates the conjunctiva is often helpful. As the needle is advanced into the orbit, the ophthalmologist listens carefully for EMG evidence of needle entry into the muscle belly. Once the muscle belly has been penetrated, the patient is asked to look slowly toward the needle. An increase in the EMG signal verifies that the needle is indeed in the muscle. An alternative approach is to pass the needle between the orbital wall and the extraocular muscle to be treated. The needle is angled slightly toward the orbital wall. When the needle makes contact with orbital wall, it is redirected to enter the muscle belly (>Fig. 16.2). This technique can facilitate the use of botulinum by the less experienced ophthalmologist, by easing placement of the needle into the muscle and reducing the risk of globe perforation. Because the orbital wall has not been anesthetized, the patient may experience discomfort or pain when the needle touches the orbital wall. After the needle has entered the extraocular muscle, the botulinum is slowly injected. The sound emitted from the EMG recorder will be reduced as the injected fluid buffers contact between the needle and the muscle. The needle is then withdrawn from the orbit and topical antibiotics often administered before sending the patient home.

Fig. 16.2. Injection of botulinum toxin using the orbital wall for reference. The needle is directed toward the orbital wall until contact with bone is made, and then redirected into the muscle

16.6Treatment of Strabismus with Botulinum Toxin

Following his initial human study, Scott performed additional studies using botulinum toxin in the treatment of strabismus. These studies continued to show a beneficial effect from botulinum toxin injection. Initial studies were conducted on adult patients with various forms of strabismus. No systemic or local complications occurred in these studies, except for the unwanted effect of the toxin on adjacent extraocular muscles [1, 2]. Later, Magoon and Scott [8] utilized botulinum toxin chemodenervation in infants and young children. In their study, 82 children 13 years of age or younger were injected with botulinum toxin for treatment of horizontal strabismus. All but one child achieved an improvement in ocular alignment. They were able to inject all children younger than 1 year of age and older than 6 years of age using only topical anesthesia and did not require sedation. Reinjection of botulinum toxin was required in 85% of the patients treated. Long-term follow-up of these same patients demonstrated stable ocular alignment over a 5-year period [9].

Later, in 1990, a larger study involving the use of botulinum in childhood strabismus was published by a group of strabismus surgeons. In this study, 413 children ranging in age from 2 months to 12 years were treated with botulinum toxin. Treatment averaged 1.7 injections per child with an average followup of 26 months after the last injection. Of the 362 patients who were available for follow-up, successful alignment, defined as correction to within 10 prism diopters of orthotropia, was achieved in 61% of the patients as a whole. The success rate varied depending on the condition being treated. Sixtysix percent of children with all forms of esotropia were successfully aligned compared with 65% of children with infantile esotropia, and 45% of children with exotropia. Patients with smaller deviations (10–20 prism diopters) were more likely to achieve successful alignment, with a success rate of 73%. In comparison, those with larger deviations (21–110 prism diopters) achieved success 54% of the time. No complications were reported in this study [10].

Early sensory data from children treated for infantile esotropia demonstrated results that compared unfavorably with historical data for standard incisional surgery. In a study by Ing [11] only 6 of 12 children demonstrated optimum motor alignment to within 10 prism diopters of orthotropia and only 3 of these patients demonstrated gross stereopsis. However, the sample size in Ing’s study was small and these results were considered preliminary. Further studies suggested that the motor results were comparable to incisional surgery. In 76 children ranging in age from 4 to 48 months, successful alignment was achieved in 68 (89%) children with esotropia. Forty achieved successful alignment with a single bilateral injection of Botox® and 36 required multiple bilateral injections to achieve successful alignment [12]. In a more uniform group of younger patients, Campos and coworkers [13] achieved successful alignment in 88% of children initially treated between the ages of 5 and 8 months with follow-up averaging 5 years. No variation of the angle of strabismus was observed after 6 months from the injection date. McNeer and coworkers [14] reported long-term

sensory data on a group of 41 children treated with botulinum toxin prior to the age of 6 months. In this study, two-thirds of the children achieved some degree of stereopsis.

Although the use of botulinum toxin in infantile esotropia has now been shown to be favorable in several studies, both from a motor and a sensory stand point, its use has not gained wide popularity. Reasons for this lack of popularity are uncertain, but several theories have been proposed. Most surgeons do not see an advantage to botulinum toxin injection if anesthesia or sedation is required for the procedure in younger patients. Additionally, side-effects such as ptosis, involvement of adjacent extraocular muscles, temporary exotropia and the need for more than one injection in many patients make the technique cumbersome and unsatisfactory for many patients, parents, and strabismus surgeons alike. Although serious complications have not been reported in previous studies, this may nevertheless be a concern to some strabismus surgeons, particularly those who are not experienced or comfortable with the technique. Finally, it may be that the historical tradition of a titrated medial rectus muscle recession and its well known risks and benefits is more familiar and more comfortable for the vast majority of surgeons treating infantile esotropia.

While botulinum toxin has not been widely accepted by the strabismus surgical community for the treatment of young children with strabismus, it has achieved popularity among many ophthalmic surgeons for treatment of certain forms of strabismus in adults. It is most commonly used for the treatment of sensory strabismus and acute paralytic strabismus in the adult population. Metz and Dickey [15] treated 29 patients with acute unilateral sixth nerve palsy with botulinum toxin injection to the antagonist medial rectus muscle. Seventy-six percent of the patients had complete resolution of their sixth nerve palsy with follow-up Other authors also reported successful treatment in patients with sixth nerve palsy using botulinum toxin [16–18]. Theoretically, toxin injection into the antagonist medial rectus muscle during the acute stage of the palsy should prevent or reduce contracture of the medial rectus muscle and improve the chance of total recovery. However, a multicenter, nonrandomized study failed to demonstrate this [19]. In this multicenter study, 84 patients were enrolled by 46 different investigators. Sixty-two patients (74%) were treated conservatively and 22 patients (26%) were treated with botulinum injection. Recovery rates were similar between the two groups. Eighty-one percent of the patients managed conservatively and 83% of the patients treated with botulinum toxin recovered. Although botulinum toxin injections may not increase the recovery rates in patients with acute sixth nerve palsy, its use continues to be popular among some ophthalmologists. The use of botulinum toxin has also been reported for the treatment of fourth nerve and third nerve palsies, with variable success [20, 21].

Botulinum toxin injection is used in the treatment of comitant forms of strabismus in adults by some ophthalmologists. Dawson and coworkers [22] reported on their extensive experience with the use of botulinum toxin in patients with strabismus secondary to sensory deprivation. In their series, 503 patients were treated with botulinum toxin. Seventy-six percent of the patients had exotropia, 22.5% had esotropia, and 1.5% had a vertical strabismus. A total of 1457 injections were given,

Chapter 16

with a range of 1–50 injections per patient. Twenty percent of the patients continued to be managed successfully with toxin treatment, 43% eventually required surgery and 8% required no further treatment. Only 3% of their patients failed to obtain a reduction in their angle of deviation. The large number of re-treatments needed and the eventual need for surgery in a large proportion of patients may explain why most surgeons infrequently offer botulinum toxin injection to patients with strabismus.

Another potential use for botulinum toxin has been for the treatment of small angle strabismus, including surgical underand overcorrections. Dawson and coworkers [23] injected 60 patients for the treatment of surgically overcorrected exotropia. The mean distance deviation was 17 prism diopters and the time from the last operation to botulinum toxin injection averaged 28 months. In the 36 patients with fusion potential, 15 achieved and maintained good ocular alignment with resolution of their diplopia following injection. In the 24 patients with poor fusion potential, only 4 patients achieved the same success. In a group of 68 patients with a small angle esotropia of less than 20 prism diopters, Dawson and Lee [24] performed a total of 434 injections, with an average of 6 injections per patient. Sixty-six percent of these patients underwent continued treatment and 19% achieved long-term benefit from a single injection. These studies demonstrated the potential benefits of botulinum toxin injection. However, the rate of success with a single injection is relatively low compared to conventional surgery. The convenience of in-office injection may be outweighed by the frequent need for multiple injections.

16.7Botulinum Toxin in the Treatment of Nystagmus

Adult patients with acquired nystagmus are generally bothered by both a reduction in visual acuity as well as oscillopsia. Botulinum toxin has been used in the treatment of acquired nystagmus. Crone and coworkers [25] first reported injecting botulinum toxin directly into the extraocular muscles for this purpose. Leigh and coworkers [26] also injected toxin directly into the muscles. In their report, two patients with multiplanar nystagmus underwent injection of the horizontal rectus muscles in one eye. Both patients demonstrated resolution of the horizontal component of their nystagmus as well as a small improvement in their visual acuity. Helveston and Pogrebniak [27] injected 25 units of botulinum toxin into the retrobulbar space of two patients. Both patients showed an improvement in their functional vision and one patient achieved an improvement in visual acuity from 20/80 to 20/30. The effect of the injection lasted from 5 to 13 weeks. Repka and coworkers [28] treated nine eyes of six patients with acquired nystagmus. They injected 25–30 units of botulinum toxin into the retrobulbar space. All patients demonstrated both subjective and objective improvement in their vision. Eye movement recordings showed a reduction of the amplitude of the nystagmus following the injection but the frequency was generally unchanged. The effect of the injection lasted no more than 8 weeks in most cases. We have found the use of retrobulbar botulinum toxin

to be helpful in these patients. Although it may induce strabismus, and occlusion of one eye may be needed, the reduction in nystagmus intensity achieved is often functionally beneficial.

16.8 Complications

Serious complications associated with botulinum toxin injection are rare. Globe perforation with the risk of endophthalmitis or retinal detachment is uncommon in the hands of an experienced ophthalmologist. Liu and coworkers [29] reported a case of inadvertent intraocular injection of botulinum. Their patient did develop a retinal tear and retinal detachment though had a good visual outcome. The toxin itself did not appear harmful to the intraocular structures. Hoffman and coworkers [30] injected botulinum toxin into the vitreous of rabbit eyes and demonstrated no toxic affects to the retina. The most frequent side effect of botulinum toxin injection is unanticipated changes in alignment due to migration of the toxin to other extraocular muscles and the development of ptosis if the toxin migrates to the levator palpebrae superioris muscle of the upper eyelid. These potential side-effects are temporary and increase in frequency as the dose of toxin injected is increased [31]. We have had one patient treated with unilateral injection of 25 units of botulinum into the retrobulbar space to develop permanent horizontal diplopia, requiring the prescription of prism in her glasses.

References

1.Scott AB (1980) Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. J Pediatr Ophthalmol Strabismus 17:21–25

2.Scott AB (1980) Botulinum toxin injection into extraocular muscles as an alternative to strabismus surgery. Ophthalmology 87:1044–1049

10.Scott AB, Magoon EH, McNeer KW, Stager DR (1990) Botulinum treatment of childhood strabismus. Ophthalmology 97:1434–1438

11.Ing MR (1993) Botulinum alignment for congenital esotropia. Ophthalmology 100:318–322

12.McNeer KW, Tucker MG, Spencer RF (1997) Botulinum toxin management of essential infantile esotropia in children. Arch Ophthalmol 115:1411–1418

13.Campos EC, Schiavi C, Bellusci C (2000) Critical age of botulinum toxin treatment in essential infantile esotropia. J Pediatr Ophthalmol Strabismus 37:328–332; quiz 354–355

14.McNeer KW, Tucker MG, Guerry CH, Spencer RF (2003) Incidence of stereopsis after treatment of infantile esotropia with botulinum toxin A. J Pediatr Ophthalmol Strabismus 40:288–292

15.Metz HS, Dickey CF (1991) Treatment of unilateral acute sixthnerve palsy with botulinum toxin. Am J Ophthalmol 112:381–384

16.Elston JS, Lee JP (1985) Paralytic strabismus: the role of botulinum toxin. Br J Ophthalmol 69:891–896

17.Wagner RS, Frohman LP (1989) Long-term results: botulinum for sixth nerve palsy. J Pediatr Ophthalmol Strabismus 26:106–108

18.Quah BL, Ling YL, Cheong PY, Balakrishnan V (1999) A review of 5 years’ experience in the use of botulinum toxin A in the treatment of sixth cranial nerve palsy at the Singapore National Eye Centre. Singapore Med J 40:405–409

19.Holmes JM, Beck RW, Kip KE, Droste PJ, Leske DA (2000) Botulinum toxin treatment versus conservative management in acute traumatic sixth nerve palsy or paresis. J AAPOS 4:145–149

20.Metz HS, Mazow M (1988) Botulinum toxin treatment of acute sixth and third nerve palsy. Graefes Arch Clin Exp Ophthalmol 226:141–144

21.Garnham L, Lawson JM, O’Neill D, Lee JP (1997) Botulinum toxin in fourth nerve palsies. Aust N Z J Ophthalmol 25:31–35

22.Dawson EL, Sainani A, Lee JP (2005) Does botulinum toxin have a role in the treatment of secondary strabismus? Strabismus 13:71–73

23.Dawson EL, Marshman WE, Lee JP (1999) Role of botulinum toxin A in surgically overcorrected exotropia. J AAPOS 3:269–271

24.Dawson EL, Lee JP (2004) Does Botulinum toxin have a role in the treatment of small-angle esotropia? Strabismus 12:257–260

rect strabismus. Trans Am Ophthalmol Soc 79:734–770

4.Aoki KR, Guyer B (2001) Botulinum toxin type A and other botulinum toxin serotypes: a comparative review of biochemical and pharmacological actions. Eur J Neurol 8 [Suppl 5]:21–29

5.Benabent EC, Garcia Hermosa P, Arrazola MT, Alio y Sanz JL (2002) Botulinum toxin injection without electromyographic assistance. J Pediatr Ophthalmol Strabismus 39:231–234

6.Sloop RR, Cole BA, Escutin RO (1997) Reconstituted botulinum toxin type A does not lose potency in humans if it is refrozen or refrigerated for 2 weeks before use. Neurology 48:249–253

7.Gartlan MG, Hoffman HT (1993) Crystalline preparation of botulinum toxin type A (Botox): degradation in potency with storage. Otolaryngol Head Neck Surg 108:135–140

8.Magoon E, Scott AB (1987) Botulinum toxin chemodenervation in infants and children: an alternative to incisional strabismus surgery. J Pediatr 110:719–722

9.Magoon EH (1989) Chemodenervation of strabismic children. A 2- to 5-year follow-up study compared with shorter follow-up. Ophthalmology 96:931–934

tagmus using injections of botulinum toxins into the eye muscles.] Klin Monatsbl Augenheilkd 184:216–217

26.Leigh RJ, Tomsak RL, Grant MP et al (1992) Effectiveness of bo­ tulinum toxin administered to abolish acquired nystagmus. Ann Neurol 32:633–642

27.Helveston EM, Pogrebniak AE (1988) Treatment of acquired nystagmus with botulinum A toxin. Am J Ophthalmol 106:584–586

28.Repka MX, Savino PJ, Reinecke RD (1994) Treatment of acquired nystagmus with botulinum neurotoxin A. Arch Ophthalmol 112:1320–1324

29.Liu M, Lee HC, Hertle RW, Ho AC (2004) Retinal detachment from inadvertent intraocular injection of botulinum toxin A. Am J Ophthalmol 137:201–202

30.Hoffman RO, Archer SM, Zirkelbach SL, Helveston EM (1987) The effect of intravitreal botulinum toxin on rabbit visual evoked potential. Ophthalmic Surg 18:118–119

31.Sener EC, Sanac AS (2000) Efficacy and complications of dose increments of botulinum toxin-A in the treatment of horizontal comitant strabismus. Eye 14:873–878

Not every disorder of ocular alignment requires treatment with surgery. Even practitioners with large surgical practices probably treat many more patients with strabismus using nonsurgical modalities than they do using surgical intervention. This chapter will review some of the most important nonsurgical treatment options for common forms of strabismus. For some conditions, surgery is rarely considered an option, while for others, surgery is often clearly the best treatment option.

Before reviewing these issues in detail, it may be pertinent to briefly discuss the role of surgery in the strabismus patient. Many patients, and even some eye care professionals, erroneously regard surgery as a treatment of “last resort” for all patients with strabismus. Not only is this myth incorrect, it is also misleading and unfair to affected patients. In most cases where surgery is offered, far from being the “last resort,” it is often the optimal or only option to properly treat the disorder.

Patients should understand that treatment is not based upon a step-wise protocol from the least invasive modality to most invasive modality. Rather, treatment recommendations are based on what the ophthalmologist feels is in the best interests of the patient overall. Although surgery may have more potential risks than other treatment options, it generally also has more potential benefit when offered. In many, if not most, cases where surgery is indicated, a decision to choose a nonsurgical treatment over a surgical one often means an outcome with fewer overall benefits. Although this does not mean that every patient should opt for surgical intervention when possible, it does suggest that patients should be aware of the alternatives and likely outcomes of treatment, both surgical and nonsurgical.

17.1 Spectacles

17.1.1 Accommodative Esotropia

Spectacles are the mainstay of treatment for accommodative esotropia. Accommodative esotropia generally occurs in a child between 2 and 3 years of age, though it can be diagnosed at any age. Patients typically present with a history of an acquired intermittent or constant esotropia. The treatment of accommodative esotropia includes a prescription of the full

hyperopic correction as determined by cycloplegic refraction (>Fig. 17.1).

There is no absolute rule as to how much hyperopia must be present to justify an attempt to correct a patient’s esotropia with spectacles. Most ophthalmologists will generally correct children who present with a new-onset esotropia with a hyperopic refractive error greater than +2.50 to +3.00 diopters. Spectacles may also be considered for smaller levels of hyperopia, especially when the esotropia is intermittent, significantly worse with near effort, and/or when it significantly worsens following cycloplegia. However, it is also useful to compare the esotropic deviation with the level of hyperopia before prescribing glasses. A very large deviation in the presence of a small to moderate amount of hyperopia is not likely to respond to spectacle correction, and a trial of spectacles is usually not warranted in such cases.

Strabismus surgery is generally not indicated in patients who respond to their full hyperopic correction by re-establish- ing excellent ocular alignment. In an older child with a very small degree of hyperopia, surgery may be indicated to allow the child to maintain binocularity without the need for a pair of glasses that does not significantly improve visual acuity.

17.1.2Poor Uncorrected Visual Acuity

Spectacles are often useful in the treatment of strabismus in patients with poor uncorrected visual acuity. Patients with reduced vision due to uncorrected refractive errors may present with horizontal or vertical strabismus. Correction of the patient’s refractive error may improve vision resulting in an increase of “fusable” material in the patient’s visual space, which in turn can result in improvement of or control of the patient’s ocular motility disturbance. Correction of any significant refractive error, whether hyperopic, myopic, or astigmatic, can result in improvement of ocular alignment. Thus it is important to consider a trial of spectacle correction in all patients with poor vision and large uncorrected refractive errors prior to considering surgery.

This scenario may be more common for patients with exotropia. The patient with an intermittent exotropia and a moderate to large degree of myopia may become aware of diplopia once their visual acuity is improved with a new prescription.

Once this occurs a greater effort will be made to fuse. We prescribe any significant level of myopic correction to patients with an intermittent exotropia and then reevaluate alignment once their new glasses have been worn for a period of time. Occasional patients with intermittent, or even constant, exotropia may be found to have a large degree of hyperopia on cycloplegic refraction. If the hyperopic refractive error is large, the patient may not exhibit the level of accommodative effort required to see clearly, and thus vision remains constantly blurred. Prescribing glasses to treat the hyperopic refractive error can improve visual acuity and may allow for better control of the deviation, much like that seen in patients with myopia [1]. However, we also warn parents that the reduced need to accommodate that results from correcting their hyperopia may result in worsening exotropia in some patients. In these cases it is important to maximize the visual acuity and treat the strabismus later, if necessary.

17.1.3 Over Minus Lens Therapy

Over correcting minus lens therapy is used to stimulate accommodative convergence in patients with intermittent exotropia. Caltrider and Jampolsky [2] and Reynolds and co-workers [3] found that over minus lens therapy could be used to help improve fusional control in some patients with moderate angles of intermittent exotropia. However, in one study only 12% of patients treated in this manner were able to eventually discontinue use of their glasses. An important limitation of over minus lens therapy is accommodative asthenopia, restricting use of this treatment to young patients with large accommodative amplitudes. In addition, patients who do not require optical correction for improvement of their visual acuity are generally

less enthusiastic about this treatment and tend to be less compliant with this form of therapy.

17.1.4 Bifocal Lenses

Many ophthalmologists correct accommodative esotropia with a high accommodative convergence to accommodation (AC/A) ratio with bifocals. Most ophthalmologists initially employ the use of +2.50 executive-type bifocal with the top of the lower segment intersecting the lower pupillary border, or titrate the bifocal to the minimum power that will allow the patient to achieve fusion at near. Although this is the most common form of treatment for accommodative esotropia with a high AC/A, other treatment options are available, including pharmacolo­ gic therapy with miotics, and strabismus surgery targeting the near deviation angle. Treatment of the distance deviation with single vision spectacles based on the cycloplegic refraction and observation of the near deviation may also be reasonable, as the high AC/A will often normalize with time [4, 5].

17.2 Occlusion Therapy

17.2.1 Part-Time Occlusion

Part-time monocular occlusion therapy is used by some ophthalmologists in the treatment of intermittent exotropia. The objective of occlusion therapy is to eliminate the need for suppression which usually first begins to develop during the transition phase between an intermittent deviation and a constant

deviation. Occlusion is generally recommended late in the day when the deviation is most likely to be manifest. Occlusion during this time permits the deviation to occur (under the occlusive patch) while avoiding the need for active cortical suppression of the deviating eye to avoid diplopia. In a sense, this therapy can be thought of as a means to help the patient unlearn how to use suppression as an adaptive mechanism. This breakdown of the suppression mechanism may allow normal alignment and normal binocular vision during the remainder of the day.

There are several small series reporting on the use of parttime occlusion in such patients. Freeman and Isenberg [6] reported on the use of part-time occlusion for early-onset exotropia. Eleven children with intermittent or constant exotropia were treated with part-time patching of the nondeviating eye from four to six hours a day. All patients initially demonstrated improved fusional control of their strabismus. After a mean follow-up of 22 months three patients (27%) became orthotropic and did not require further therapy. An equal number of patients later developed a constant exotropia and required strabismus surgery. This study suggests that part-time occlusion may postpone surgical intervention in some patients and possibly convert a small percentage of patients to orthotropia or exophoria, avoiding the need for surgery. Most ophthalmologists consider part-time occlusion therapy a temporizing measure which may allow improvement of the fusional control but which does not generally lead to tangible long-term benefits. It may be helpful in postponing surgery in some younger patients until they reach an age when amblyopia, disruption of stereopsis, or other problems following surgery are less likely to occur should an over correction take place.

17.2.2 Full-Time Occlusion

Full-time occlusion is a reasonable treatment option in a small number of patients with chronic diplopia. Full-time occlusion of the nonfavored eye is an excellent option for the relief of diplopia in a selected minority of patients. For example, patients suffering from an acute cranial nerve palsy often benefit from occlusion of the nonfavored eye to eliminate diplopia while awaiting spontaneous recovery. Unfortunately, most patients will not tolerate full-time occlusion for an extended period of time. The visual discomfort, physical discomfort, and reduction of visual field associated with the use of an occlusive patch make this option viable for long-term treatment in relatively few patients. Full-time occlusion can also be used in the treatment of intractable diplopia either before or after strabismus surgery for nonparalytic strabismus.

There are several methods available to occlude the visual axis for the relief of diplopia. The simplest method is the use of a patch. A patch can be either an adhesive patch or a tradition “pirate’s patch.” This form of occlusion allows for a simple placement and removal as desired by the patient. However, patients often consider this option cosmetically unacceptable and not usually a good option for use on a long-term basis. Occlusive material may also be placed on spectacle lenses and may

consist of an opaque material or plastic tape. Bangerter foils are commercially available and can be used to degrade the visual acuity in one eye until bothersome diplopia is eliminated. A trial set of these foils may be used in the office to determine the foil that results in the least degradation of visual acuity, while eliminating bothersome diplopia. The foil is selected by the patient and placed on the spectacle lens of the nonfavored eye. Bangerter foils are less noticeable than traditional occlusive patches and are often better tolerated than standard patches.

Contact lenses can be used in some patients who suffer from constant diplopia. The use of contact lenses is generally limited to patients who are able to properly handle and care for the contact lens as well as those patients without ophthalmic conditions in whom the use of a contact lens poses a significant risk, such as the patient with advance dry eye syndrome. A contact lens with an opaque center may be used to completely occlude the visual axis. Alternatively, the use of a high power plus contact lens may result in degradation of vision to the point that diplopia is no longer bothersome while allowing the patient to maintain use of their peripheral visual.. We have successfully used these therapies in patients for whom strabismus surgery was not felt to be a good treatment option.

17.3 Orthoptic Therapy

Historically, orthoptic therapy has been used in the treatment of strabismus when surgical intervention has been thought to be too risky or unnecessary. However, with improvement in surgical techniques, improved safety of general anesthesia for young children and improved surgical outcomes, the role of orthoptic therapy has diminished with time. Currently, most ophthalmologists reserve orthoptic therapy for the treatment of intermittent exotropia where the angle of deviation is relatively small, perhaps 20 prism diopters or less. Even in these cases, orthoptic therapy often merely delays the need for surgery.

Hiles and co-workers [7] reported on the long-term observation of 48 patients with intermittent exotropia who were followed for up to 22 years. Forty patients (83%) remained within 10 prism diopters of their original measurement by the end of the observation period. However, the study was retrospective and included selective instead of consecutive patients with intermittent exotropia. Their patients had either refused surgery or had fusional control that was thought to be too good to require surgical intervention. For most patients, orthoptic therapy consists of diplopia awareness training and improvement of fusional vergence amplitudes. Many patients with intermittent exotropia already experience diplopia consciously or subconsciously, as evidenced by their closing of one eye or the fact that the deviation is intermittent. In many patients with intermittent exotropia, fusional convergence amplitudes are already abnormally large. Therefore, many ophthalmologists limit the use of orthoptic therapy to increasing fusional convergence in patients with convergence insufficiency.

In the past, orthoptic therapy was also used for the treatment of small angle esodeviations. Some esotropic patients who underwent diplopia awareness training as a child may