...little has been written on the mechanism of divergence insufficiency or frank paralysis... The two prevalent hypotheses...include altered cerebrospinal fluid flow in the posterior cranial fossa, and involvement of the abducens nucleus or infranuclear portion.

Divergence insufficiency is a rare ophthalmologic disorder manifesting itself among older adults. Primary and secondary forms exist, with the latter more urgently addressed due to neurologic comorbidities. Ultimately, the diagnosis of DI, particularly in the primary form, tends to be elusive. This article will review the typical presentation, diagnosis and treatment options, and report a case of primary DI, along with the often complex consideration leading to this diagnosis.

Divergence insufficiency can vary in severity, from minor deficits to complete divergence paralysis. Similarly, the theories on mechanism of divergence itself have varied. Drs. Bielchovsky and Duane favored the presence of a dedicated active divergence center, while Drs. Bergman, Pugh and Duke-Elder favored the view of divergence as a passive result of relaxation of convergence.¹ The existing literature on DI is sparse, with a keyword search in PubMed producing 18 references ranging from 1937 to 2010.^1,2 Upon review of the literature, Alexander Duane can be credited with the first comprehensive description of this entity.³ Dr. Duane suggested this diagnosis required 2 to 8 degrees of esophoria at distance and only slight esophoria or even exophoria at near. In a 1971 study, authors reported on the magnitude of misalignment, ranging from 8 to 30 prism diopters at distance, but only 4 to 18 prism diopters at near.⁴ The importance of measuring the magnitude of alignment defect in different directions of gaze was underscored in a 1947 study,⁵ allowing clinicians to distinguish between external rectus paresis/paralysis and DI due to other causes. Among patients with high myopia the presence of a long axis has been associated with development of DI,² likely due to altered angles at which the extraocular muscles insert and exert their force on the globe.

Another historically reported feature of DI is significantly decreased negative fusional vergence (fusional divergence), along with the deficit’s direct relationship to distance of gaze.³ This is a feature useful in differential diagnosis of DI particularly from other, more ominous conditions like divergence paralysis.⁶ The decrease in fusional divergence, with sparing of fusional convergence, was subsequently corroborated.⁴ A 2005 study, however, did not find a difference in fusional divergence among primary and secondary DI cases.⁷ Similarly, A-pattern defects need to be considered in the workup of these patients. Here a methodical, complete examination of eye alignment in nine cardinal positions of gaze comes in useful.

Table 1. Evolution of Diagnostic Criteria for Divergence Insufficiency  Author   Diagnostic Criteria   Comments Duane, A (1937)   ET 2-8 Δ at distance Slight ET or XT at near Significantly decreased fusional divergence   Magnitude of deviation depends on distance of gaze Moore, S (1971)   ET 8-30 Δ at distance ET 4-18 Δ at near     Scheiman, M (1988)   Fusional divergence   Good for differentiating DI from other conditions Berscheid C (2005)   Fusional divergence   Not helpful in differentiating primary from secondary DI

Patients with DI typically complain of gradual onset, variable frequency, homonymous diplopia, which is worse at distance. Sometimes it is exacerbated by fatigue and improves with rest. Other associated symptoms can include asthenopia of panoramic type,⁵ motion sickness, headaches or sensitivity to light.^3,6 Early presbyopia is also a frequent comorbidity. Nausea and headaches are reported to be uncommon among patients with the primary form of DI, as are any history of head trauma or intracranial pathology.⁸ The pattern of gradual onset is an important distinction from usually more sudden sixth-nerve palsy, a common item in the differential of DI, as is the absence of papilledema or endpoint nystagmus—a finding easily missed with cursory motility examination.⁶ Evidence of sudden onset or rapid progression should also point the clinician towards secondary DI and re-doubled efforts to find the underlying neurologic abnormality. 

The association with refractive errors (and high myopia in particular) has been a point of contention for some time,⁶ with most recent experiments attributing this association to specific anatomic differences among high myopes with DI and high myopes without diplopia.² Specifically, the former group had the superior rectus shifted nasally, lateral rectus-inferiorly, in the setting of normal orbital lengths. The extraocular muscle angles were 112.9 ±9.7 degrees for the former, and 99.2 ±2.8 degrees for the latter. The anatomic differences may be entirely due to increased axial length, a question requiring further investigation. At present, these differences are not routinely utilized in preoperative planning.

The epidemiology of primary and secondary form appears similar, with highest incidence among adults, but pediatric cases are reported sporadically as well. No clear sex predilection has been identified for the primary form of the condition.⁸ In a recent review of 251 cases, the patients with primary DI were older (61 vs. 52 years old on average) than those with the secondary form.⁷ Importantly, only the absence of neurologic comorbidities (e.g., epidemic encephalitis,⁹ intracranial hypertension,^9,10 Miller-Fisher syndrome,¹¹ or intracranial mass lesions) differentiates primary from secondary cases of DI.^12,13

Interestingly very little has been written on the mechanism of divergence insufficiency or frank paralysis in the above settings. The two prevalent hypotheses put forth so far include altered cerebrospinal fluid flow in the posterior cranial fossa, and involvement of the abducens nucleus or infranuclear portion.

Treatment options include correction with base-out prisms for distance,^5,8 and orthoptic exercises, but surgical options (e.g., medial rectus recession) have also been put forth.¹⁴ Naturally, all of the above rely on a manifest refraction, particularly to identify high myopes, as well as a meticulously performed measurement of lateral vergence at distance and at near to serve as a starting point.¹⁵

Divergence Insufficiency Case Report  A 59-year-old, otherwise healthy woman presented to our clinic with a chief complaint of being non-tolerant to glasses at distance. In the past four years she had been to many eye doctors and several different glasses prescriptions were subsequently tried, including single vision and bifocal progressive lenses, none able to produce adequate binocular vision. She also complained of loss of depth perception and said that her monocular vision was good, but she could not focus binocularly. The patient denied any ocular trauma or ophthalmic operations. She did report a possible remote history of strabismus treated in early childhood with occlusion of the right eye, subsequently asymptomatic until the current episode.  The patient reported allergies to penicillin and tetracycline. Her past medical history was negative for any neurologic problems. Her family and social history did not reveal anything concerning. On examination her entering vision was found to be 20/25- in the right eye and 20/60 in the left eye. Manifest refraction was -0.25 +1.00 x 175 right eye and +1.25+0.50 x 005 left eye, with VA corrected to 20/20 OD and 20/25 OS with near a add power of +2.50. Extraocular muscle movements were normal and eyes looked fairly aligned. Cover-uncover test revealed 4 prism diopters of alternating esotropia at near and 7 prism diopters at distance. The patient revealed anisometropia and divergence insufficiency more so at distance. Treatment Our patient received a prescription for distance glasses including 6 prism diopters base-out, split evenly, and reported marked improvement of vision at distance with resolution of symptoms.

Historically, the amount of base- out prism to be prescribed should be either the minimum to maintain single vision, or that required for correction of esophoria at near.¹ The time-proven success of therapy with base-out prisms does not alleviate the difficulty some patients have tolerating the treatment. As a result, compliance with prismatic correction has remained suboptimal. Therefore a trial of Fresnel prisms is indicated before committing the patient to ground-in ones. Orthoptic exercises have been proposed in classic literature (Maddox, Pugh), but the success of these strategies has been varied. 

 • Recess vs Resect. The utility of medial rectus recession surgery in management of patients with slowly progressive DI was found in one study to be most suitable for reducing the difference in defect magnitudes for near and distance, particularly in elderly patients.¹⁴ In cases of rapidly progressive DI, the focus should be on ruling out the secondary form of the condition. The optimal timing of surgical correction has not been clearly established to date. One exception is conversion from esophoria at distance to esotropia. This condition has been identified as an indication for urgent surgical correction via lateral rectus resection.8 Others have proposed unilateral medial rectus recession in young DI patients with smaller (<17 prism diopter) deviations, reserving bilateral procedures for cases with larger defects.¹³ Whether anatomic differences in muscle angles in high myopes should be incorporated in the choice of surgery, and if so, in what way, remains unclear. Failure of surgical repair of DI in pediatric patients may require the clinician to reconsider its secondary form, especially in the background of rare malformations,¹⁶ as well as acquired neurologic conditions, e.g. pseudotumor cerebri.⁹ Clinically, primary and secondary forms of divergence deficiency need to be distinguished on the basis of the presence of neurologic comorbidities¹⁷ or their absence, as in our case report. Meticulous history and review of systems, along with a careful examination, allows this. Particular vigilance for end-gaze nystagmus and the role of neuro-imaging remain vital,¹² even with subtle focal findings on neurologic examination, with MRI the preferred study in such cases.¹⁸   REVIEW