Eccentric Fixation and Inverse Occlusion: Renewing Our Interest?

ABSTRACT

The use of inverse occlusion and pleoptics came into favor in Europe and then in North America in the late 1940’s, and fell out of favor less than 25 years later. Introduced as a method of promoting foveal fixation, and improving binocularity and vision in cases of eccentric fixation, it did not outperform conventional occlusion prescribed at an earlier age.

In this issue, Godts and Mathysen provide a case series of 11 contemporary patients treated with inverse occlusion after patching failure. In response, this article reviews the procedures and goals of inverse occlusion and pleoptics using the historic information available, in attempt to ascertain whether there is an indication for renewing their use.

KEYWORDS:

• Eccentric fixation
• inverse occlusion
• amblyopia
• strabismic amblyopia

This article refers to:

Amblyopia with Eccentric Fixation: Is Inverse Occlusion Still an Option?

Buffon (1743) is credited as the first to treat amblyopia with occlusion of the stronger eye, and today conventional occlusion is widely used as the first line in amblyopia therapy. For a period beginning around 1945, practitioners shifted toward the use of inverse occlusion, pleoptics, and red filters in an attempt to increase treatment success rates. These therapies did not prove as useful as first expected, and by the 1970’s conventional occlusion was again the preferred management for all patients under 7 years of age.¹

In this issue, Godts and Mathysen² present eleven cases of mixed amblyopia with eccentric fixation that failed to get satisfactory results with conventional occlusion. The authors successfully treated these cases with inverse occlusion and red filters, followed by a second course of conventional occlusion. This presents some interesting food for thought. Did inverse occlusion play a part in treatment success? Did earlier investigations actually support the discontinuation of inverse occlusion? Should we re-examine its utility? To help answer these questions, it is important to understand the proposed mechanics of eccentric fixation, and, as there is no recent literature on the subject, how historical reports align with our current understanding of amblyopia. The practices of inverse occlusion and pleoptics were intertwined and grew and changed over time, and a full review of this is outside the scope of this paper which will focus on their link to eccentric fixation.

Finding primary sources of information from the period just prior to, and at the beginning of, the era of inverse occlusion and pleoptics is difficult, as much of it is from non-English publications, and most available publications are small, non-rigorous, case report series, which do not meet the current standard required of evidence based medicine.

Amblyopia treatment is most successful when implemented early in the visual development period³ and as soon after onset as possible.⁴ In the late 1800’s, amblyopia and strabismus were often left untreated until school age or later because some practitioners thought they were inherited and incurable conditions⁵, and others felt them to be inconsequential in the face of other health threats⁶ such as infection and influenza. The next century saw increased use of occlusion, but patching was often implemented after age 5^7–11 and so failed to increase vision in approximately half of strabismic amblyopia cases.^11,12 Even though authors noted better acuity outcomes with shorter duration of squint and earlier treatment,^9,13 the influence of these factors was not investigated until after Hubel and Wiesel’s work (late 1950s to early 1960s), and the search for the reason behind unsatisfactory results took a different course.

In 1905, Worth noted that a lack of foveal fixation may be found in strabismic amblyopia, and was most often associated with longstanding strabismus where the “macula has ceased to be the most sensitive part of the retina. This eye then wanders, without remaining steadily in any definite position (lost fixation). Or it may fix with some part of the paracentral region, … ”¹⁴ His work is often credited as one of the first to suggest the existence of eccentric fixation. Forty years later, clinicians linked eccentric fixation (EF) to occlusion failure, and it was speculated that in the presence of constant suppression for a prolonged period, the developing cortex could make a purposeful adaptation to using an eccentric fixation point, and create a new cortical pathway.^8,12,15 In these cases, reduced acuity was considered to be due to a combination of amblyopia, and the visual capability of the eccentric point,^16,17 therefore, the presence of well developed EF required that amblyopia treatments include efforts to reinforce the fovea as the primary fixation point. Identification of EF and classification of fixation patterns was advocated, as visual prognosis could be indicated by the degree of fixation eccentricity from the fovea,^17–19 and the completeness of cortical adaptation as shown by the tenacity with which the patient used this point for fixation prior to, and during treatment.^18,20,21 Early use of conventional occlusion could overcome EF if it was not well developed, but the presence of EF in cases with unsatisfactory outcomes proved conventional occlusion alone was not always sufficient.^15,22 Some believed that occlusion of the sound eye was of “doubtful value” when steady EF was present⁷, and was potentially harming the patient by providing continual stimulation to the abnormal cortical pathway. This was used to explain why some children did not respond adequately to conventional occlusion.^5,23,24 By 1955, fixation became a standard indicator when reporting amblyopia, and 22–44%^9,21,25 of all amblyopes were judged to have eccentric fixation. (Wybar and Thatcher¹⁵ give a synopsis of the trending doctrine circa 1960 for those who are interested in reading more.)

Two European physicians are named as instrumental in developing pleoptic treatment for EF. Bangerter (1947) began treatment with inverse occlusion (full time occlusion of the amblyopic eye) to remove the stimulus situation that required a suppression response,^10,22,26 and “break” the anomalous cortical pathway that had been created.²⁷ Inverse occlusion was complete when fixation was judged to become unsteady or wandering, which was important evidence that EF was disrupted. This was followed by in-office training aiming to eradicate the EF point by dazzling it with high intensity light, and then to promote foveal fixation through foveal stimulation with a flashing light. Between treatments, amblyopic pupil dilation and constant inverse occlusion were used to perpetuate the disruption.²²

Cuppers (1956) used inverse occlusion and equipment similar to Bangerter’s, but advanced from Bangerter’s treatment to encourage active participation from the patient by employing negative afterimages.^18,21 Cuppers felt that not only was the use of EF purposeful, but localization of the primary line of sight shifted to the eccentric fixation point, and active “relocation of the subjective visual direction” back to the fovea was an important part of treatment.¹² Better visual acuity was anticipated as a secondary outcome of shifting the fixation point,^15,21 and most papers reported improvement primarily in terms of a shift in fixation. After a course of inverse occlusion, pleoptics began by applying a small amount of light stimulation to the peripheral retina, following which the patient was trained to localize correctly with the macula by using the after image to encircle different objects. (see footnote¹ ). A full discussion of both methods can be found in the 1960 American Orthoptic Journal’s publication of the AAOT Pleoptic symposium.²⁸

Results of inverse occlusion and pleoptics together showed that as re-education moved fixation closer to the fovea, vision also improved.²² Originally, the conclusion of pleoptic treatment was the re-establishment of foveal fixation, which was followed by conventional occlusion to further improve vision.^20,29 Perhaps due to the exhaustive nature of the treatment, it later became acceptable to end pleoptic treatment when any shift of fixation toward the fovea was noted.

Over the next two decades, pleoptics spread through Europe and the UK, and slowly into North America,^9,28 requiring significant resources. Most European patients were hospitalized for several months to receive treatment,^17,30 and in North America patients were subject to frequent in-office visits. Requiring significant cooperation from the patient, pleoptics was most suitable for ages 5–15,¹⁸ and practitioners looked for ways to be more specific in case selection, and to lessen the burden of this rigorous treatment. Two of these ideas are of interest with regard to Godts and Mathysen’s report – the red filter, and the use of inverse occlusion without pleoptic treatment.

In the early 1960’s, a red filter was added to treatment protocol in an effort to increase the benefit during the non-pleoptic intervals, and to remove the need for patient hospitalization.^19,31 Red wavelengths of light stimulate the fovea and are invisible to the eccentric point in photopic vision, thus were thought to encourage the use of the fovea.²⁴ The method of red filter treatment application varied widely. The filter could be used in conjunction with active pleoptics and inverse occlusion, or as a stand alone therapy. The duration of red filter wear varied from immediate use of full time wear, to starting with brief periods and increasing wearing time to several hours. The red filter was sometimes worn when both eyes were open,^19,31 however some advocated its use only during occlusion of the sound eye.²⁴ Reports of efficacy were contradictory.^13,19,26 Malik et al²⁶ studied the use of the red filter with occlusion of the sound eye 5 hours daily accompanied by inverse occlusion the remainder of the day, against 24 hour conventional occlusion, and inverse occlusion alone, in a group of eccentric fixators. While they reported that red filter treatment was encouraging, their charts show that it was less successful at changing fixation and improving acuity than conventional occlusion. This may be explained by the uneven age distribution between the two conditions, with the conventional occlusion group weighted to age 3, while the red filter group was more than 80% over age 12. Clements³² notes in his study that patients treated with occlusion alone had better results than occlusion combined with the red filter, although filtering this through our current amblyopia knowledge, these results are refutable as the average age of the occlusion only group was significantly younger, they had shorter duration of strabismus, and their initial vision was better. In short, the method of use of the red filter was never standardized, nor its use proven to be more effective than other treatments.

Two papers were often cited as proof that inverse occlusion alone is a viable treatment for changing the fixation pattern in EF. In 1963, Arruga²⁷ showed that inverse occlusion shifted fixation in 93% of his 40 cases. There is more information to be gleaned from this paper than he reports. Arruga divided his patients into 4 groups according to whether the onset of amblyopia was before or after age 2, and whether treatment was initiated before age 3 or after age 4, making it difficult to assess the effect of age in his cohort, but interesting to look at the role of duration. His tables show that in cases with the earliest onset and longest duration, acuity improvement after inverse occlusion and conventional occlusion was 57% compared to 73% in the rest of the group. Even though Arruga did not interpret his results this way, his study is relevant to today’s debate about onset vs duration in both binocular function repair⁴ and amblyopia treatment,³³ but does little to elucidate the role of inverse occlusion in amblyopia management as he did not report acuities after inverse occlusion alone. In 1967, Cibis and Windsor also advocated for the use of inverse occlusion³⁴, reporting that 70% of patients had a shift in fixation, and 40% in acuity, although only 18% improved more than 5 letters. Subsequent studies of inverse occlusion were unable to show comparative positive results. In the same study as the red filter results above, Malik et al found that only 25% of patients showed a change in vision and 25% in fixation with inverse occlusion alone.²⁶ No indication of the level of change was given. Von Noorden’s study¹³ of 29 patients with EF showed fixation improvement in 11 (38%) and vision improvement in 7 (24%), compared to 40/45 (89%) patients with fixation improvement and 42/45 (93%) vision improvement using conventional occlusion in the same study.

North American opinion on the treatment of EF was heavily influenced by Dr G. von Noorden, who used his clinical observations to help to flesh out the theory that an aberrant cortical pathway had been developed in these cases.¹² In 1970, von Noorden presented further clinical and experimental findings that refuted the “shift” of subjective visual localization to the EF point,^25,35–37 and suggested that EF in strabismic amblyopia was not purposeful use of eccentric retina, but a finding due to the depression of foveal receptor sensitivity and loss of its localizing value. Studies of efficacy showed that the results of inverse occlusion and pleoptics followed by conventional occlusion, were no better than conventional occlusion alone, leading ophthalmologists and orthoptists to advocate for a return to conventional occlusion in the 1970’s,^10,13,38,39 reserving pleoptics for use only in cases of occlusion failure.⁴⁰ By 1971, Wilson was advocating the use of inverse occlusion only to help the patient “become accustomed to a patch more readily since it is on the amblyopic eye (as) sometimes (the patient) responds better later when the dominant eye is covered”.⁴¹

Summary and conclusion

Early in the 20^th century, late treatment of amblyopia led to a significant number of cases deemed to be “incurable” with conventional occlusion, which was attributed to the presence of non-foveal fixation. Initially the treatment of EF was based on the premise that the eccentric point was purposefully used for vision and localization, rather than an associate of poor vision. Remediation required concerted effort to break the anomalous fixation pattern and encourage the use of the fovea through inverse occlusion, followed by pleoptics and conventional occlusion, with or without the use of red filters. Follow up studies comparing the results of these treatments to conventional occlusion showed they had no greater benefit, and they were abandoned in North America in the 1970’s in favor of the much easier and more economical, conventional occlusion.

Godts and Mathysen state that inverse occlusion still has relevance as a treatment to be used as a last resort for patients who do not respond to conventional occlusion. There are five points that suggest that inverse occlusion may not be responsible for the improvement in their patients, but rather may be detrimental.

1. There is no proof that there is a difference in cortical pathways in presumed cases of EF. The argument for the role of EF in amblyopia is a bit like the chicken and egg argument – was EF causative or a result of, amblyopia⁴²? The foundation of EF treatment lies in the belief that EF is purposeful, and successful treatment must first disrupt the cortical conditions that support this fixation pattern. The link made between EF and amblyopia in 1945 was based on clinical observation. Worth noted the presence of EF in children with longstanding, deep amblyopia. Subsequent practitioners used their experiential knowledge to hypothesize that EF was causal, rather than secondary, to amblyopia. Based on today’s information, it is likely that EF is a characteristic of deep amblyopia and represents the random use of a non-specific point, marking a significant decrease in foveal sensitivity over time⁴³ that resulted in the inability to fixate with the fovea.^44,45

2. The determination of fixation is subjective and notoriously difficult. In the setting of the case reports of Godts and Mathysen, it is difficult to determine the reliability of the evidence given.

3. There is no proof that their patients had “good” or “moderate” compliance to the initial round of occlusion as reported. Parents over report treatment times even when they know that they are being objectively monitored.⁴⁶ It is possible that the patients included in their study improved because they were more compliant with the second round of conventional occlusion.

4. The use of inverse occlusion alone or prior to conventional occlusion in the 1960’s was not found to be any more effective than beginning with conventional occlusion, therefore not offering any proof that inverse occlusion is an important part of treatment in presumed cases of EF.

5. Inverse occlusion caused a further decrease in acuity of the amblyopic eye in 10 of 11 patients as seen in the results of Godts and Mathysen. Without proof that there will be compliance with subsequent conventional occlusion to recover this, it may be unethical to use inverse occlusion even as a last resort.

There are two points that leave this author with a niggling doubt and reluctance to suggest wholesale rejection of inverse occlusion.

1. It is possible that EF as an innate failure of the binocular system does exist. There are cases when even the most diligent and proven compliant application of conventional occlusion fails.³³

2. The reports from Cibis and Windsor³⁴ and Malik et al²⁶ show that for some patients acuity IMPROVED after inverse occlusion alone. Occlusion of the amblyopic eye 24 hours a day should have caused a further deprivational decrease in the acuity as was seen in Godts and Mathysen’s cohort.

While it seems that the disruption of EF played an essential role in the treatment of the patients presented, there is no evidence to support this. There are two considerations to control previously unacknowledged variables when undertaking further investigations to elucidate the role of EF and inverse occlusion in amblyopia.

1. Judgment of the state of fixation in an amblyopic eye is purely subjective and difficult to perform. Without validated testing methods, reporting of evidence is anecdotal. Reproducible and reliable methods must be used.

2. Consideration should be given to the use of occlusion dose monitors prior to using inverse occlusion to identify only those truly compliant patients who fail to improve.

Without evidence that proves the development of alternative cortical connections in the presence of a deviation, and rigorous investigation of inverse occlusion that excludes obvious sources of error, it is difficult to advocate for inverse occlusion as a last resort treatment when the potential for causing harm exists.

Notes

¹ It wasn’t until later that EF became associated with ARC and monofixation syndrome. In 1947, there was no connection between the use of EF and retinal disparity.²⁵ In 1951, Parks was still arguing that ARC and EF were distinct entities.^47.