Major Review
 
Comitant Esodeviations An Update
 

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Geetha Srinivasan
Consultant Squint & Pediatric
Ophthalmology
ICARE Eye Hospital & Research Centre
NOIDA


Corresponding Author
: Geetha Srinivasan
E 104, AIIMS Quarters
Ansari Nagar (Eastern Campus)
New Delhi - 110029, India
Email: geethapsri@yahoo.com


Abstract

Comitant esodeviations are commonly encountered in clinical practice. While anatomical or innervational factors may be responsible for their occurrence, they could also be an indication of serious neurological disorders in some. It is extremely important to find out the cause of the esodeviation to manage them appropriately. There has been a lot of research in recent times to analyze optimal timing of surgery, assess the role of newer therapeutic agents like bupivacaine and also whether vision therapy is helpful in patients with amblyopia. This review looks at some of the relevant literature that would probably have a bearing on our management strategies.

Comitant esotropia is a common condition affecting all age groups. It is extremely important to evaluate the cause of the deviation, because the management would vary depending on the etiology. Further, unlike in most cases of exodeviation the propensity to develop amblyopia is much higher if esodeviations are not treated in time. An esodeviation that is not treated in a timely manner can adversely affect not just visual acuity; it can also impact stereopsis, loss of which is irreversible. While the goal of all corrective therapy is establishing or restoring binocular vision, the cosmetic aspect and quality of life changes that go hand in hand cannot be undervalued. The role of genetic factors in all types of squint including esodeviations and the changing profile of these squints are all being studied extensively.Some types of esotropia are amenable to optical therapy and others to surgery.

Comitant esodeviations are generally classified as follows:-
  1. Accommodative
    • Refractive accommodative
    • NonRefractive Accommodative
    • Partially accommodative
  2. NonAccommodative
    • Infantile esotropia
    • Nonaccommodative convergence excess
    • Acquired Basic esotropia
    • Divergence insufficiency or paralysis
    • Acute onset esotropia
    • Cyclic esotropia
    • Recurrent esotropia
  3. Microtropia
  4. Nystagmus Blockade Syndrome
There have been some significant advances and newer management strategies over the last decade. Further, the concomitant treatment of amblyopia is to be addressed for a favourable visual outcome. In the recent past, there has been a lot of discussion about the role of computerized vision therapy and television based therapy in amblyopia management.

Demographics

There is a difference in the reported prevalence of esodeviations and exodeviations in the West and in the Asian population. While some studies from the West1 have found that esodeviations are more prevalent, other large Asian studies report otherwise.[2,3] Chia et al reported that of 682 children < 16 years of age 72% (493) were exotropic. Esotropia was found in 191 (28%) children with majority being accommodative esotropes. Yu et al[3] reported that cases of esotropia have shown a decline over the past decade as opposed to cases of exotropia. They also reported that among esotropias, true infantile and accommodative esodeviations are showing a downtrend while those with nonaccommodative component and microesotropia are increasing due to the increasing prevalence of myopia.

Genetic Influence on Esodeviations

The suggestion that strabismus is heritable was made since the time of Hippocrates and recent genetic research has supported this view. (Figure 1a,1b)

When one considers all the different forms of strabismus, they are thought to be inherited in 30-70% of cases with the most likely mode of transmission being autosomal dominant with incomplete penetrance.[4] At present the STBMS1 locus is the only gene location that has been reported as being definitely responsible for the causation of strabismus. In fact what is thought to be heritable in esodeviations is not the strabismus per se, but the refractive status of hypermetropia. The present discussion aims to highlight some recent changes or suggested modalities in some of these types of esodeviations.

Refractive Accommodative Esotropia

It is the most common type of strabismus. The usual age of occurrence is around 2 1/2 years, though it can occur even during the first year of life (Figure 2) and rarely even in teenage (Figure 3).

Variability in the deviation is a hallmark of this condition. (Figure 4) It is standard procedure to prescribe the full cycloplegic correction either with atropine or cyclopentolate in all cases of esotropia. In fact if this treatment is initiated at an early stage the visual outcome is very favourable. In some cases there is a significant decrease in the hyperopia and the child can be weaned off the glasses. The initial amount of hyperopia i.e baseline hyperopia appears to predict this. However, on follow up some children develop a nonaccommodative component in the deviation, necessitating surgery. In partially accommodative esotropia the nonaccommodative part of the deviation requires surgical correction. (Figure 5)

The role of keratorefractive surgery, both photorefractive keratectomy (PRK) and LASIK are being evaluated as therapy for accommodative and partially accommodative esotropia. LASIK is more preferred because of its ability to correct larger deviations with lower incidence of complications. Studies have reported good results with LASIK and PRK in fully refractive accommodative esotropia as well as the accommodative component of partially accommodative esotropia.[5,6,7] Magli et al[5] did a retrospective study on 20 adoloscent and adult patients with refractive accommodative esotropia and found that over a follow up of 30.2 months, 40% were orthophoric for distance and near and the remaining were well within acceptable limits of residual deviation. Their mean correction was +4.62D (Range +2.25-+7.75DS SD 4.52). Polat et al[6] shared their favourable experience with their patients of accommodative esotropia including partially accommodative esotropia, in whom the accommodative component was satisfactorily treated with keratorefractive surgery. They studied 42 eyes of 21 patients with esotropia , with a mean age of 19.00+/-4.51 months. They reported a final deviation of less than 5 degrees at the final follow up of 12.19+/-4.51 months. They also found that 1 eye lost 1 line BCVA and 3 gained 1 line. The procedure of LASIK was corroborated to be effective and safe in accommodative esotropes. While these studies focussed on the role of keratorefractive procedures in adults/adolescents, there have been reports of similar procedures even in children.[8] One study evaluated LASIK in 20 eyes of children between 5.1-9.2 years, with a hyperopia of +3.5D to 6.75D and anisometropia of 2D or less. All patients had good fusion and all achieved orthophoria after surgery. At the final follow up at 9 months none of these children needed enhancements.













Though longer and larger studies are needed before considering these procedures in young eyes which are yet to complete their development anatomically, these authors claim that it could be considered as an alternative in children who are not compliant with glasses. Another issue is the corneal aberrations reported with keratorefractive procedures.[9] As of now, keratorefractive procedures in children with accommodative esotropia are not the preferred practice pattern.

Infantile Esotropia

Infantile esotropia (IE) is defined as an esotropia before the age of 6 months, with a large angle, latent nystagmus, dissociated vertical deviation, limitation of abduction, and reduced binocular vision, without any neurological disorder. In the US the standard age of first surgery is 12-18 months and in Europe 2-3 years. While there has been a lot of discussion about the terminology of infantile esotropia and congenital esotropia, the nomenclature does not preclude any change in the management options. Whether the misalignment causes the lack of fusion or vice versa is not very clear yet. Worth believed it to be a problem primarily in the fusion faculty while Chavasse attributed the squint to be the primary cause of the poor sensory status. It is logical to assume that the earlier the ocular alignment is restored, the more beneficial is the visual outcome mainly the sensory outcome.

Early surgery has been the standard accepted modality of treatment, with the predominant question being-How early is early? Several recent studies[10,11,12] have evaluated the outcome of surgery with respect to the timing of surgery. Birch et al 10 compared the results of surgery in such infants less than 6 months and between 6-12 months and found that while there was no significant difference in the motor outcomes or the need for additional surgery, what was striking was the difference in central fusion 15% versus 2% respectively (p<0.01%) and randot stereopsis (38% versus 16%) p <0.003 between the groups. However ,one of the largest studies that analyzed congenital esotropia (ELISSS study) 11 reported that though the sensory outcome was better in infants operated between 6-24 months of age (n=231), they needed repeat surgeries for alignment much more as compared to children operated between 32-60 months (n=301). This is in contrast to another report 12 which concluded that earlier surgery before 6 months of age results not only in better stereopsis but also less need for resurgery. An important observation of this latter study was that the duration of misalignment was responsible for the decrease in stereopsis and not the visual impact of the misalignment in the early critical period of visual maturation. They believed that the role of the critical period is not as important as the duration of the misalignment. Infantile esotropia is known to be associated with dissociated vertical deviation (DVD). While the DVD may coexist, it can also occur at a later stage. In fact it has been an accepted fact the DVD is infrequently found in children less than one year of age.[13,14] It is often thought to emerge only after the horizontal deviation has been surgically corrected, though Campos [15] observed that the DVD present before surgery may actually resolve after early horizontal alignment with chemodenervation. Various studies have looked into whether surgery as well as its timing has an impact on this association. The issue is yet to be set to rest. There is a differing consensus. While Neely et al[16] found that 92% of their patients developed DVD by 6 years of age, despite surgery to restore horizontal alignment; the timing of surgery did not influence the occurrence. This was supported by a study in a Japanese population.[17] However they came up with an interesting observation that early surgery is associated with less severe i.e. latent rather than manifest DVD, which indicates that a surgery for DVD could be avoided.

The view of some other researchers[18] differs in that they found that almost 50% of such infants developed DVD at an average age of 3.2 years whether treated or not. However they found that not only surgery but also the timing of surgery could have a bearing on development of DVD. In those treated surgically a lesser number (37.5%) developed a DVD as opposed to 80.5% in unoperated cases. In children operated after 2 years of age, almost double the number developed DVD (52% versus 24.1%) as compared to those operated between 6 months to 2 years. Further in cases that are undercorrected and need resurgery the incidence of DVD was reportedly higher. In a metaregression analysis done by Simonsz HJ[19] analyzing ELISSS study and 12 others, the authors found that reoperation rates were 60-80% for children first operated around 1 year of age and 25% for children operated around 4 years. Another point of interest is the role of botulinum toxin A in infantile esotropia. Gursoy and co authors have reported that injections are as effective as incisional surgery in treating this condition (68% versus 77% respectively in restoring binocularity) , while others have not found the injections to be as effective. So the debate of how early is early is yet to be set to rest. Suffice it to conclude that once the angle of deviation is reproducibly stable, one should consider surgery in these cases.

Role of Bupivacaine In Esotropia

The concept of chemodenervation by dilute injections of botulinum A toxin to alter ocular muscle alignment has been in vogue for about 3 decades now. While some authors like Scott and associates reported that 2/3 of patients of infantile esotropia were satisfactorily aligned over a 2 year follow up, others reported that incisional surgery was more effective.[20] The larger the deviation the longer it took to achieve the desired effect. In fact Couser et al[21] have recently tried this therapy in children with consecutive esotropia within a year of occurrence of the esotropia and reported an excellent outcome. Transient ptosis and vertical deviations were an accompaniment in almost 1/3rd of patients in their series, which corroborated with older reports. Thouvenin D[22] reported that with early treatment with botulinum toxin 82.4% of infantile esotropes showed improvement.

Alan Scott and associates[23] injected Bupivacaine into the agonist and botulinum toxin into the antagonist to treat horizontal strabismus. Bupivacaine (BUP), the aminoglycoside anaesthetic injected into the fast muscle fibres like the extraocular muscles damages the muscle fibres in minutes, probably by allowing the excess calcium ions to enter the cytoplasm from the sarcoplasmic reticulum. This is said to result in the separation of the muscle fibre at the sarcomeres at the Z band. Within a few hours autocrine growth factor molecules such as insulin like growth factor and mechano growth factor are released from the damaged sites. These molecules then activate satellite cells that proliferate over the next 10-20 days to form new muscle fibres and myocytes to replace the damaged muscle. This proliferation leads to a muscle with greater contractile strength, intrinsic elastic stiffness and size than before and this is said to cause the change in alignment.[24] They attributed the increased size of the muscles to intracellular deposition of noncontractile molecules. They did report orbital inflammation as a side effect in one case, postulating that the possible cause could be inflammation from muscle damage. In a recent study[25] they injected bupivacaine with botulinum toxin A in cases of large angle deviation in cases of concomitant esotropia and exotropia. Over a follow up of 3 years they found that the alignments obtained were maintained over a 3 year follow up. More than half of their patients had a residual deviation of less than 5 degrees. They did have to repeat the injections in some patients. Further studies would clarify the role of bupivacaine in restoring ocular alignment.

Non Refractive Accommodative Esotropia

This condition is diagnosed when an emmetropically corrected patient with a high accommodative convergence to accommodation (AC/A) ratio shows orthotropia at distance fixation but displays more than 5 degrees of esotropia at near fixation which can be corrected with a +3.00 dioptre add lens. (Figure 6) Bifocals are the mainstay of treatment (Figure 7), though miotics have also been used as a short term measure. Progressive addition lenses have also been tried by some with an average of +3.0D add.[26] Timely treatment prevents amblyopia. As the patients grow older, some (1/3-2/3) are able to do away with the bifocals. Some of them need the continuance of glasses or surgery. The AC/A ratio at presentation is said to be one of the determining factors in predicting which child would probably be weaned off glasses.[26] Obviously the higher the ratio the lesser the probability. In fact the average age at bifocal discontinuation has been about 10 years.[26,27] Besides some children needing a surgery due to the natural course of the disease, children in whom prescription of bifocals has been delayed tend to need surgery. The standard surgical treatment options in those in whom it is indicated is bimedial recession, augmented/slanted recessions and posterior fixation sutures.[28] In general, the younger the age at surgery the higher the requirement of a second surgery. Faden followed by slanted recessions are said to be effective in correcting the deviation for near.[29]





Nonaccommodative Convergence Excess Esotropia

It is similar in presentation to a nonaccommodative esotropia with high AC/A ratio. However the esodeviation for near does not respond to addition of plus lenses. Surgery is the mainstay of treatment. Hence it is important to differentiate between the two conditions.

Acute Acquired Esotropia

As the name suggests, it is an acute onset esotropia which generally occurs after occlusion and disruption of fusion or sometimes even in the absence of occlusion. In these two types binocular potential is excellent. Treatment is by bimedial recession. Schoffler et al[30] suggest that since in the long term all patients regain high grade stereopsis, even multiple surgeries if indicated are worth the effort in these cases. However another type of acute esotropia is a sign of some serious intracranial life threatening problem like hydrocephalus, Arnold Chiari malformation, tumors etc. Unlike in the other two types, surgical alignment is not always favourable in this type. Some have tried botulinum toxin in these situations with favourable results.

Acquired Basic Esotropia

This condition manifests after 6 months of age, with the deviation for distance and near being equal. There is no role of accommodation and hence refractive correction in these cases. Surgery is the mainstay in management. (Figure 8)





While the basic aim of surgery is to restore alignment, some have stressed on the fact that in the immediate postoperative period minimal esotropia or orthotropia is preferred. This is because overcorrection in the early postoperative period has the propensity to develop consecutive exotropia later.[31] There are some nonaccommodative early onset esotropias like those associated with cerebral palsy, in which botulinum toxin has been tried with relative success [32] It is an established fact that surgery in these cases has unpredictable results. So considering botulinum toxin as a viable alternative may not be another option.

Cyclic Esotropia

This uncommon variety of esodeviation shows periods of orthotropia alternating with esotropia. The cycles can vary between 1-4 days. While it is usually seen in children, it can occur very rarely in adults also. The treatment is surgery. However botulinum toxin has also been tried with mixed results.[33]

Divergence Paralysis Esotropia

This is an acquired comitant strabismus in adults characterised by esotropia and diplopia at distance. Occlusion, base out prisms and Lateral rectus resection are the standard treatment options. There have been a few[34,35] who have reported that medial rectus recession is also an effective surgical option.

Amblyopia Management

Management of amblyopia is as important as correcting the misalignment in visual axes to get the optimal visual outcome. Occlusion has been the mainstay and continues to be the gold standard of treatment. The mainstay of amblyopia therapy is occlusion of the sound eye with either an opaque patch which can be prescribed either full time or for part of the day. Penalization is another method of treating amblyopia. To further improve visual acuity and binocularity in children with amblyopia, traditional therapies may be augmented with vision therapy, with some claiming good results and others questioning its efficacy. Vision therapy has been used as a modality of treatment in amblyopia since the last 4 decades in the West. It is traditionally done in the form of synoptophore exercises, Haidinger Brushes, After Images, stimulation with Euthyscope, etc. More recently computerized vision therapy using specifically designed software has come into vogue for the treatment of amblyopia, vergence disorders and perceptual disorders. The use of Computerized Vision Therapy is still controversial. In Computerized Home Vision Therapy, a sequence of prescribed activities is typically performed on a daily basis at home and weekly in-office and is directed towards an individual patient’s deficient skills. Visual skills are practiced under conditions that provide the patient with feedback. The feedback, along with a gradual increase in the demand of the activities as improvement occurs, enables the patient to improve visual functions such as visual acuity, fixation, accommodation, and vergence skills depending on the deficiency it has been advised for. Thus, the therapy works on the concept of operant conditioning, which is a form of psychological learning during which an individual modifies the occurrence and form of its own behavior due to the association of the behaviour with a stimulus. Most therapy procedures are designed to take care of specific deficiencies in five main areas: fixation, spatial perception, accommodative efficiency, binocular function and oculomotor control. Computerized Vision Therapy (Figure 9) is prescribed in cases of mild to moderate amblyopia with adequate stereopsis. This modality can be added to the treatment regimen once the patient has reached atleast moderate levels of amblyopia not responding further to the occlusion treatment. It has also been tried as a primary modality of treatment. It is thought that the best candidates for this type of therapy are those children with a minimum level of stereopsis (at least 800”) and without constant strabismus.Polat et al.36 tested the results of perceptual training in cases of conventional occlusion failures and reported an improvement of 1.5 Snellen’s lines in the whole group. They also reported that about 40 hours of perceptual training might be even more effective than patching per se, which faced the problem of compliance.

To evaluate the efficacy of Computerized Vision Therapy in cases of failure of standard occlusion therapy in amblyopia, we conducted a study in our hospital. 15 patients of mild to moderate amblyopia with previous history of occlusion therapy failure were given computerized vision therapy with HTS Amblyopia Therapy VTS3 for 150 sessions, each comprising of 30 minutes of therapy. Improvement in visual acuity, contrast sensitivity, and stereopsis was noted and results were analyzed with improvement in visual acuity against age of onset of therapy, type of amblyopia, depth of amblyopia, compliance, and degree of anispmetropia as variables. Mean logMAR visual acuity improved by 0.22 (equivalent to 1.5 Snellen’s lines of acuity) (p=0.001) at final outcome visit (6 months). 9 patients (60%) improved by = 1 Snellen’s acuity lines after 6 months. Mean contrast sensitivity improved from 30% (SD=36.33) to 14% (SD= 24.11) from baseline to final outcome (p=0.072). Mean stereopsis improved from a baseline of 152.57 seconds of an arc (SD=136.98) to 81.85 (SD=93.61) at 6 months (p=0.05). 8 patients (53.33%) improved by =2 levels of Randot stereoacuity at 6 months (p=0.004). The average compliance was good (51-75%) in 5 (33.33%) and excellent (76-100%) in 10 (66.67%) of patients. The improvement in discussed parameters in our study could probably be attributed to the fact that Computerized HVT exercises are assigned to improve smooth eye movements, saccadic eye movements, crowding phenomenon & hand eye coordination, which are all variably impaired in amblyopic eyes, and to near vision stimulation, which is an inherent part of this treatment. We concluded that Computerized vision therapy can be tried as an alternative modality of amblyopia treatment, especially in cases of occlusion failure. However, longer followup is indicated to assess regression of improved visual acuity.

Conclusion

Treatment for each type of esotropia needs to be individualized. Whether keratorefractive procedures are the modality to treat accommodative esotropia needs further larger studies over a longer timeframe. The role of monovision glasses in nonrefractive accommodative esotropia is a concept that is showing promise. Infantile esotropia needs to be operated at the earliest, once the magnitude of the deviation is stable. Computerized vision therapy can be offered as complementary or supplementary treatment to occlusion in amblyopia management.

Financial & competing interest disclosure

The authors do not have any competing interests in any product/procedure mentioned in this study. The authors do not have any financial interests in any product / procedure mentioned in this study.

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