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Active Pulley Hypothesis Withstands Challenge of Exenteration
Last Gasp of Oculomotor Fundamentalism?
Classical Histology and Physiology Leave APH Proponents Gasping for a Coherent Explanation
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Joseph Demer
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jld{at}ucla.edu Joseph Demer
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This letter comments on the paper of McClung, Allman, Dimitrova, and Goldberg, "Extraocular connective tissues: A role in human eye movements?,"1 a surgical case report that challenges modern anatomic concepts and the active pulley hypothesis (APH) of ocular kinematics.2 Inadequacy of the Specimen. McClung et al. examined two extraocular muscles (EOMs) obtained by surgical exenteration. Specimen integrity is key, since handling can distort tissue relationships.3 Since McClung et al. challenged claims based on studies of cadaveric orbits fixed, embedded, and serially sectioned whole without internal disturbance,2,4-12 the authors' description of their specimen as "undisturbed" is inconsistent with common meaning. The specimen could only have been harvested if the orbit had been severely traumatized or harbored malignancy. McClung et al. should specify the pre-existing pathology in their specimen, since such a mutilating extirpation of the orbit is not indicated for simple "reconstruction" as stated. McClung et al. acknowledge that the two EOMs were separately dissected. Later fixation would have permitted differential shrinkage artifacts that cannot be assessed. This issue is crucial because McClung et al. challenged prior anatomic studies that were based on serial sectioning of intact, whole, cadaveric orbits that were fixed with the bone intact, subjected to magnetic resonance imaging to detect subsequent distortions, and serially sectioned without dissection.9 Aging Degeneration. Aging and pathology compromise both pulley properties and ocular movements. Quantitative histological studies indicate that the pulley connective tissues degenerate markedly in elderly humans,9 correlating with sagging of horizontal rectus pulleys13 and version deficits.14 Since most MRI studies demonstrating rectus EOM path inflections were performed in young adults, as well as nearly all behavioral studies of Listing's Law, McClung et al. could not reasonably infer from a pathologically-damaged 78-year-old orbit that pulleys cannot underlie normal ocular motility in youth. That inference would be tantamount to denial of crystalline lens accommodation based on study of a 78-year-old man! Failure to Demonstrate Established Anatomy. McClung et al.'s failure to find smooth muscle in connective tissues suggests insensitive methodology. This should raise questions concerning remaining claims, for substantial smooth muscle in the involved region has been recognized since the classical anatomist Muller,15 and repeatedly confirmed by histochemical staining,5,16,17 electron microscopy,18 and immunohistochemistry.5,9,16 Failure to find smooth muscle near horizontal rectus pulleys suggests that the specimen was truncated. Figure 1C of McClung et al. appears to confirm the impression of tissue truncation, since the so-called "check ligament" terminates without insertion on the orbital wall. Kono et al.9 demonstrated that the region of the medial rectus pulley has a dense attachment on orbital bone. Dual Insertions. McClung et al. asserted, "Both the orbital and global portions of the muscle can be observed to course toward the single tendon of the muscle." This wording, of course, is not a statement that the orbital layer was observed to merge or insert into the scleral tendon, as the discussion of McClung et al. extrapolated. The authors did not even attempt to distinguish orbital from global layer fibers by histochemical staining, as others have done.2,12 McClung et al. have no basis for statements about termination of the orbital layer as a specific histological entity. Multiple classic19-21 and recent anatomic studies in rodents,22,23 monkeys,12 and humans2,12 have separately distinguished orbital and global layers, demonstrating that the orbital layer terminates posterior to the tendon and does not insert on sclera. McClung et al.'s claim that the orbital layers terminate in the scleral insertional tendons and therefore rotate the eye is contradicted by evidence from the Demer laboratory based on some 30 orbits, most embedded and serially sectioned whole.8-12 The findings were strongly supported by the study of 16 human and three monkey orbits by Ruskell et al.,17 who found: The present results confirm and extend the observation of Demer et al. (2000) that orbital fibres of rectus muscles separate from the global fibres and insert in the muscle sheath and that they are unlikely to contribute significantly to ocular rotation. No mechanism was proposed by McClung et al. to indicate how orbital layer fibers might transmit force to the global layer except for their unsupported assertion of orbital layer continuity with the scleral tendon. McClung et al. have provided no evidence of myomyous junctions between fibers of the different layers and could not have done so given their inability to distinguish orbital from global layer fibers histologically. Even if correct, the major factual claim of McClung et al. does not contradict the APH. They acknowledge that the orbital layer connective tissue enveloping the rectus EOMs "also attaches onto the anterior third of the muscles by blending into the connective tissue of the muscle belly." McClung et al. further stated, "The posterior border of the sheath insinuates into the anterior third of the muscle belly and the anterior border of the sheath blends into the sides of the portal at Tenon's capsule." If individual orbital layer fibers become enveloped in connective tissue, how would this differ from the concept that they "insert" into the connective tissue? McClung et al. provide no criteria to distinguish an "attachment" from an "insertion." Their distinction is really a matter of nosology, not of anatomy. Misleading Citation. McClung et al. have misrepresented the findings of Ruskell et al. with their partial quotation and statement: In contrast with our present study, Ruskell et al. noted that by following muscle fibers through serial sections, "single muscle fibers, or sometimes two or three, continued for a short distance" (~1.0 mm) and could be observed to enter the orbital connective tissues (the CL). However, a small number of fibers that have a tight relationship with the orbital connective tissues (CL) in no way constitutes a "double insertion" or a separate orbital layer insertion. McClung et al.'s selective quotation of 13 words from Ruskell et al. is juxtaposed with McClung's own statement directly contradicting Ruskell et al.'s results as a whole, and misleadingly applicable only to the insertions of orbital fibers into discrete tendons that terminated into "sleeve tendons." Ruskell et al. actually indicated that orbital fibers insert into the connective tissues surrounding the rectus muscles in both humans and monkeys. In his section entitled "Results. Double Insertions," Ruskell et al.17 actually stated: In human preparations, slender groups of fibres extended from the orbital surface of muscles and passed forward towards the fascia bulbi. . . . fibres passed from the muscles at intervals, accumulating in stacks before merging into a compact collagenous mass of the muscle sleeve, continuous with the fascia bulbi. Occasionally clear evidence that the fibres were indeed muscle tendons became apparent and they will be referred to as sleeve tendons to distinguish them from the scleral tendons of the globe. Sleeve tendons were often followed through interrupted serial sections over a thickness of at least 500 mm, indicating that some arose as laminae rather than as discrete fibres. Single muscle fibres, or sometimes two or three, continued for a short distance into tendons as they left the surface of the muscle, confirming their identity, and significantly, putative tendons observed without a muscle fibre in a section were seen to contain one in the same tendon in another, indicating a common identity. Less frequently, thicker tendons carried bundles of muscle fibres. Where this occurred the muscle fibres persisted in the tendon for up to 1 mm and the generating muscle fibres sometimes could be traced back an equal distance into the fabric of the muscle itself. It is difficult to understand from examination of the work of Ruskell et al. how McClung et al. could reasonably maintain a "double insertion" was not found by Ruskell et al., nor that they were referring only to "a small number of fibers." Complete reading of Ruskell et al. makes it obvious that substantial "double insertion" is exactly what these authors described.17 McClung et al. have distorted the Ruskell citation17 in a way misleading to readers of IOVS. Physiology and the Active Pulley Hypothesis (APH). McClung et al. claimed the APH incorrect because a significant proportion of feline abducens motor neurons innervate both the orbital and global layers. This ignores the finding that 73% of abducens motor units project exclusively to either the orbital or the global layer of feline lateral rectus.24 Independence of EOM Layers? McClung et al. did not dispute existence of "pulleylike restraints on . . . eye movement[s]," but contended that constant distance between pulley and scleral insertion could be maintained without differences in activity of orbital and global layer fibers if the pulley were merely anchored to the surface of a homogeneous EOM. The argument for crude active shifting of pulley position by a homogeneous EOM ignores the fact that contraction of EOM fibers anterior to the pulley would diminish the distance between the pulley and the insertion, contravening the requirement of Listing's Law. Issues in Contention. McClung et al. acknowledged that EOM paths are inflected by connective tissue pulleys attached to the orbital surfaces of the rectus EOMs. This issue is a central feature of the APH. McClung et al. have argued that the orbital fibers of rectus EOMs do not travel along paths substantially diverging from those of global layer fibers, misunderstanding that the APH never stated that orbital layer fibers must have widely divergent paths. The diagrammatic summary in the proposal of the APH depicts orbital fibers paralleling global fibers, with the orbital fibers attached to the inside of the pulley of each rectus EOM.2 McClung et al.'s confusion may have arisen from a cartoon-like exaggeration of the splitting of orbital from global layers in a publication emphasizing innervation of the two layers25 or perhaps misinterpretation of MRI images of the pulley suspensions. We have published detailed histological examinations of the tissues forming the connective tissue band suspending the medial rectus pulley and that McClung et al. term the "check ligament." These include staining for collagen and elastin content (Fig. 12 of Ref. 6), longitudinal2 and transverse2,12 micrographs stained for collagen, elastin, and smooth muscle, and quantitative analyses of these connective tissues in humans of a wide range of ages.9 We have never suggested wide separation of orbital from global layers. McClung et al.'s position appears fundamentally incorrect regarding separate insertional tendons for the orbital layer. Figure 3 of the original presentation of the APH illustrated several fine tendons in a gross photograph, and Figure 6 illustrated one in sequential serial sections stained for collagen and elastin.2 In his paper on "Double Insertions," Ruskell et al. explicitly confirmed these small tendons.17 McClung et al. have emphasized existence of attachments of global as well as orbital fibers to connective tissue. This confuses thin connective tissue sheathes of the global layer and its classic tendon with a terminal insertion. Although anatomy clearly favors transmission of rectus EOM orbital layer force mainly to the pulley, and global layer force mainly to the sclera, the APH anticipated that laminar forces would be mutually coupled to some degree.2 Summary. McClung et al.'s case of a presumably disturbed, partial pathologic specimen is inadequate for general anatomical conclusions; the functional implications are overinterpreted. McClung et al.'s overall claim is inconsistent with larger studies employing superior methods, multiple species, and correlative evidence. McClung et al.'s report represents neither a serious challenge to modern descriptions of orbital anatomy, nor to any implications of the APH. Contemporary reviews of the APH are available to interested readers.3,26 Joseph L. Demer Jules Stein Eye Institute, UCLA References 1. McClung JR, Allman BL, Dimitrova DM, Goldberg SJ. Extraocular connective tissues: A role in human eye movements? Invest Ophthalmol Vis Sci. 2006;47:202-205. |
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Joel Miller
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jmm{at}eidactics.com Joel Miller
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The recent IOVS paper by McClung, Allman, Dimitrova, and Goldberg,1 "Extraocular connective tissues: a role in human eye movements?" makes it clear that concepts introduced by Demer and myself are widely misunderstood and that fascination with our apparently exotic notions has given way to backlash. However, neither credulity nor uncomprehending denial is an appropriate response to evidence-based proposals, and a didactic review is clearly indicated. The present letter, however, must be a more focused critique. Based on gross misunderstandings of Demer, Oh, and Poukens,2 in a report of a single surgical pathology sample, McClung, Allman, Dimitrova, and Goldberg1 ask us to reconsider years of careful and innovative work by many investigators, insisting that extraocular mechanics remains as it was "described in classic anatomic studies and books for over 70 years." First, I offer a guess about the line of thought that McClung et al. followed into error regarding Demer et al.'s proposal of "dual EOM insertions" and show that this error makes their critique irrelevant. It is easily seen that Demer's proposal is quite different from what McClung et al. suppose and that the histological data presented by McClung et al. actually supports Demer's hypothesis. Next, I try to account for McClung et al.'s focus on a bit of connective tissue (the "CL") that likely has nothing to do with pulley function. Finally, I show that McClung et al. have overlooked the basic, well-supported assertions of the "active pulley hypothesis" (APH), misdirecting their critique at a hypothesis abandoned in 2002. What is an insertion? Demer, Oh, and Poukens2 report: [T]he orbital layer of each rectus EOM inserts on its corresponding pulley, rather than on the globe. Only the global layer of the EOM inserts on the sclera. This dual insertion was visualized in vivo by MRI in human horizontal rectus EOMs. It is possible to read this discussion of "insertions," carelessly think of a long, discrete musculo-tendonous extension, and imagine rectus muscle orbital fibers coursing anteriorly alongside global fibers, turning orbitally to depart from those global fibers, becoming tendinous, and finally inserting some distance away in a pulley. One might then glance at Demer et al.'s2 MR images (his Figs. 1, 2), where this "dual insertion was visualized" to see dark tissue projections from the orbital side of the anterior recti (McClung et al. refer to them by their archaic designation, "check ligaments"), and imagine that Demer is proposing that the CL contains the departing orbital fibers and their tendons, en route to a distant connective tissue pulley. This appears to capture McClung et al.'s1 misunderstanding of Demer's proposal, of which they write: The CL is the band of tissue present on the MRI images, but was previously described as the orbital layer insertion for the active pulley hypothesis . . . . Their misunderstanding leads McClung et al. to look for orbital fibers in the CL, and failing to find them, to mistakenly believe they have refuted Demer's notion of dual insertions: The CL can be seen coursing away from the orbital side of the muscle. . . . Note that no muscle fibers can be observed following the CL along its orbitally directed course. Pulley sleeves and pulley suspensions McClung et al. reasonably describe the pulley sleeve (or ring) as a "tubelike sheath," Tenon's capsule "reflect[ed] back as a sleeve around the muscle." The pulley suspension, in contrast, is the complex of connective tissues that suspend the pulley sleeve from the orbital wall, from the pulleys of other EOMs, and from other extraocular tissues. The "classical" description of this suspensory complex was given by Koornneef,3 for example. Our abstraction of this anatomy, with specification of constituent tissues based on immunohistochemistry, is given in Demer, Miller et al.4 Anatomically, the CL may be considered part of the pulley suspension (see below for caveats concerning functionality).
McClung et al. have confused pulley sleeves with pulley suspensions. Demer et al.'s proposal is actually that terminal orbital fibers insert in the overlying tissues of the pulley sleeve. McClung et al. misunderstand them to mean that the pulley suspension, part of which is the tissue band they call the CL, contains these orbital fibers and their tendons en route to inserting in some more distant pulley. It is senseless on its face to think that the CLs mediate the proposed insertions of orbital fibers in pulleys, because CLs do not terminate in connective tissue at all, pulley or otherwise. McClung et al. would presumably agree with Demer et al.'s description of them as "dark bands running anteriorly and peripherally toward the orbital rim." In most of Demer et al.'s MR images, arrows point to the pulley sleeve at the base of the CL, proximal to the orbital surface of the EOM, but unfortunately, in some images the arrow is not carefully drawn and points to the CL generally. There can be no doubt that the orbital fiber insertion Demer et al. intend is in the pulley sleeve (or ring), not the suspension. Referring to a gross anatomic sample, in which the pulley sleeve is stretched away from the orbital surface of its muscle, Demer et al.2 write: Figure 3 shows a surgical exposure of the MR, and illustrates multiple dense, white fibrous bands extending from the orbital surface of the MR muscle and inserting into the glistening white tissue on its nasal [orbital] side. This adjacent connective tissue was confirmed in cadaveric material to form the pulley ring encircling the MR [emphasis added]. It is also shown schematically in Demer et al.2 (Fig. 8, upper left panel) that, according to the APH, the orbital layer inserts in the pulley sleeve, whereas the global layer passes through the sleeve to insert in the sclera. In contrast, regarding the part of the pulley suspension that McClung et al. call the CL, Demer2 writes: Favorable image planes . . . consistently demonstrated the presence of one or more dark bands running anteriorly and peripherally toward the orbital rim. . . . Histologic evidence indicates that this dark band represents the connective tissue suspension of the corresponding EOM pulley [emphasis added] . . . . Again, because both the authors and the IOVS expert reviewers got it wrong: the proposed insertion of orbital fibers is in the pulley sleeve (or ring) and does not involve the pulley suspension (and, so, does not involve the CL, which is anatomically part of the suspension). It is interesting to compare the high magnification histology presented by McClung et al.4 (Fig. 1D) with that presented by Demer2 (Fig. 7B). The former are described by McClung et al. as "demonstrating the CL blending into the orbital side of the muscle by investing collagen filaments around the peripheral (orbital) muscle fibers," the latter by Demer2 as the "insertion of rectus orbital layer fibers on their respective pulleys." The sections are actually very similar, with McClung's clearly showing orbital fiber termination short of the sclera, near the pulleys, and interdigitation of terminal orbital fibers with overlying connective tissue. Whether orbital fibers insert in pulley tissues (Demer) or pulley tissues invest orbital fibers (McClung) is, as the lawyers say, "a distinction without a difference." The interdigitation, clearly shown in McClung et al.'s histology, is precisely the insertion of orbital fibers in pulley connective tissues proposed by Demer. Is the CL an effective part of the pulley suspension? Although it extends from the pulley sleeve to the orbital wall, the CL is unlikely to be involved in pulley stabilization. The attention given by McClung et al. to this structure may be the result of confusing the 19th century notions of Tenon5 and Sappey6 with the modern notion of pulleys. The 19th century notion of "poulies"6 addressed the bowing of muscle paths away from the orbital axis. Bowing would be observed, e.g., in a horizontal section of the eye that included the lateral and medial recti and might be mediated by connective tissue bands that, like the CLs, lay in that horizontal plane, and which couple the LR and MR sleeves to the orbital wall. In contrast, the modern notion of pulleys accounts for the stability of posterior muscle paths during ductions that rotate the eye out of the muscle's plane of action. With elevation and depression, for example, the posterior segments of the LR and MR remain in approximately the same horizontal plane because they are restrained by pulleys from following the vertical movements of their insertions. It should be appreciated that the plane in which poulies were supposed to act to produce bowing is orthogonal to the plane in which pulleys act to impose stability. The notion that eye position contingent kinematics could be implemented by stabilizing posterior muscle paths relative to the orbit is the essence of the modern notion of pulleys.7 The 19th century notion of poulies has no such implication. Further, van den Bedem et al.8 show that the CLs (which they call faisseaux tendineux) have very low stiffnesses within the normal oculomotor range. CLs, therefore, would not have suitable mechanical properties to stabilize pulleys, even if they had the necessary orientation. (Their mechanical properties also make CLs unsuitable for bowing rectus muscles). It might have been reasonable to focus attention on the CLs tissue structures, but this is far from being the case. As can be seen from the figure above, there are substantial connections among pulleys, as well as connections to the orbit, other than the CLs. There is no reason to think that in order to be stabilized relative to the orbital wall, a pulley must be directly connected to the nearby orbital wall. Additionally, it seems likely, although it has not yet been convincingly demonstrated, that orbital fat filling spaces between connective tissue septa helps stabilize posterior muscle paths.9 What is an active pulley? Mathematically-oriented neurophysiologists observed that EOM pulleys finally provided a plausible explanation for how the brain controls the non-commutative 3D rotations of the globe10,11 and does so with separate horizontal and vertical gaze centers.12 However, the notion of pulleys presented in my early papers7,13 did not consider that they might move, except "passively," due to the transverse force component produced by deflection of the EOM sliding freely through it. Demer et al.2 provided the important insight that pulleys could only perform their essential kinematic functions in tertiary gazes (gazes with both horizontal and vertical coordinates non-zero) if they moved anteriorly and posteriorly in particular ways (e.g., in abduction, the LR pulley would have to move posteriorly and the MR pulley anteriorly). Kono, Clark, and Demer14 then demonstrated by MRI that horizontal rectus pulleys actually moved as required. They move because they are attached to the EOMs (to striated, not smooth muscle, as McClung et al. mistakenly suggest, as well as being stabilized to resist movement in other directions. There was clear evidence then15 and there is more now16 that orbital layer fibers terminating in the pulley sleeve couple it to the EOM. This is the notion of active pulleys. Again, McClung et al. agree on the anatomy, and on the essential point that each EOM moves its pulley, and again, McClung et al. misunderstand Demer's proposal and consequently offer a misdirected critique. They fail to recognize that the APH consists of two separate proposals. This distinction was implicit in Demer et al.,2 and explicit in Kono, Clark, and Demer14 who named the two versions of the APH: one in which orbital and global fiber movement was coordinated, and the other in which differential contraction was possible: (1) Coordinated active pulleys: Pulleys move (roughly) anteriorly and posteriorly ("longitudinally" with respect to the EOM), while elastically resisting movements in other directions. Translational forces are applied by orbital fibers inserting into their pulley sleeve, whereas oculorotary forces are applied by global fibers inserting into the sclera. Note that there is nothing in this basic notion of active pulleys about independent control or differential motion of orbital and global lamina. Laminar distinctions are merely the specifics of anatomic implementation. Nothing about the kinematic proposal would change if all fibers were coupled to both the pulley sleeve and the sclera. Coordinated active pulleys are sufficient to explain half-angle Listing's law behavior during fixation, saccadic, and pursuit eye movements. Additionally, the histological and electrophysiological laminar specializations that were found to exist suggested the following hypothesis2: (2) Differentially controlled pulleys: Orbital and global fiber contractions are mechanically independent (the two layers can slide relative to each other), and are independently controlled by the brainstem. Demer et al.2 initially proposed that differentially controlled pulleys capable of large relative laminar movements could explain the "quarter-angle" behavior of the vestibuloocular (VOR) response. This theory, which we will term the strong differential APH, was abandoned soon after it was proposed14 as having unsuitable kinematics and being anatomically implausible. As with their confusion about orbital fiber "insertions," the objections of McClung et al. to active pulleys appear rooted in a careless supposition that all "pulleys" are prototypical. Whereas passive pulleys are pulleys in the ordinary sense of the term, coordinated active pulleys, because there is no free movement of the muscle with respect to the pulley sleeve, are more like "tethers" than pulleys. Nevertheless, the term "pulley" is appropriate, because both passive pulleys and coordinated active pulleys implement the critical pulley-like kinematic property of tilting the muscle's action vector as a function of eye rotation. In contrast to coordinated active pulleys, differentially controlled pulleys are typical pulleys in that their global fibers slide freely through the pulley sleeve (even if their orbital fibers do not). It appears that McClung et al. overlooked the proposal of (less pulley-like) coordinated active pulleys, and recognized only the (prototypical) differentially controlled pulleys. Thus, they cite evidence that connective tissue insinuates global as well as orbital fibers and wrongly suppose that it disproves the APH. It should be understood that "differential control" does not necessarily imply unrestricted relative movement of EOM layers, but only that functionally significant shear can occur through the depth of the muscle. We term this notion the weak differential APH. The existence of significant laminar shear remains an empirical question, which is currently under investigation.17 Neurophysiologists have generally maintained that the solution to the problem of noncommutativity, and the implementation of Listing's Law, must lie in the brainstem. Recently, however, Ghasia and Angelaki18 have shown that cyclovertical motoneurons do not modulate their firing during pursuit, which would be required if the brainstem implemented these kinematic functions. Subsequently, Klier, Meng, and Angelaki19 stimulated the abducens nerve and nucleus, bypassing all neural circuits that might contribute to the implementation of Listing's law, and found that eye movements nevertheless obeyed Listing's law, proving that ocular plant mechanics are capable of implementing Listing's law in the absence of neural commands. Given these compelling findings, the mechanism underlying the eye's fundamental kinematics would now seem to be either (a) pulleys or (b) magic. Conclusion We have shown that McClung et al. challenged only the differential APH (the strong form of which is long abandoned; the weak form of which is admittedly conjectural), overlooking the well-supported coordinated APH, which is the basis of the modern theory. We agree with McClung et al. that the CLs are unsuitable as functional components of pulley suspensions but wonder why they ignored other, more suitable, extraocular connective tissues. We have also shown that their arguments against separate orbital fiber insertions are as irrelevant to the APH as their histological data are supportive. Joel M. Miller References 1. McClung JR, Allman BL, Dimitrova DM, Goldberg SJ. Extraocular connective tissues: a role in human eye movements? Invest Ophthalmol Vis Sci. 2006;47:202-205. |
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Stephen J. Goldberg
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sgoldber{at}hsc.vcu.edu Stephen J. Goldberg
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In the following we will respond to the major points made in two letters to the editor, by Dr. Demer and Dr. Miller, regarding our recent publication1 in IOVS. We thank them both for their letters wherein they, of course, defend their versions of the active pulley hypothesis (APH). It is clear to anyone who has read their letters that they are often contradictory, the major contradiction being that Dr. Demer strongly defends the dual insertions of the APH while Dr. Miller maintains that at least one version of the hypothesis was abandoned in 2002. But for reasons of clarity, we will address the letters sequentially. Dr. Demer's review and bibliography clearly document that he is, personally, quite prolific concerning the APH, but not necessarily correct. He criticizes what is obvious and clearly stated in our paper. We report on one specimen and we interpret our findings without reference to his biases on the anatomy and physiology of the orbit. What he calls "modern anatomic concepts" are only the interpretations that his papers have proposed. Dr. Demer challenges the adequacy of our specimen, but the quality of the histology we present speaks for itself -- as accurately observed by the original reviewers of the manuscript and the journal editors. We felt fortunate to get a human specimen that we could subject to appropriate histological preparation and staining. The specimen was from a patient following "craniofacial reconstruction; excision" (quote from pathology report) and consists of a craniofacial resection specimen following recurrent, squamous cell carcinoma of the eyelid and surrounding tissues. The bones of the orbit and optic nerve were reported to be "negative for tumor." It is obvious that the orbit, muscles, and their surrounding connective tissues were unaffected by this disease process. It is also important to note that one of the MRI images Dr. Demer refers to, in proposing the APH,2 is from a subject that was 6 years older that the one we used (84 years old vs. our 78-year-old). It is, therefore, quite surprising that Dr. Demer would imply that all senior orbits are functionally abnormal. Dr. Demer continues by questioning our interpretation of a manuscript by Ruskell et al.,3 even though we clearly state that Ruskell's findings are "in contrast with our present study."1 We agree with Dr. Demer when he encourages a "complete reading of Ruskell et al." but we think it is informative to quote their concluding sentences.3 If independent adjustment of sleeves does not occur then the determination of ocular kinematics in terms of the active pulley theory appears invalid. The logic of pulley theory as first stated is compelling, proposing a rational application of the peculiar arrangement of muscle inflections but, again, the present findings raise some questions regarding its validity and further examination of the hypothesis is indicated. We chose, by accurately citing the data presented by Ruskell et al.,3 to be somewhat less critical of the hypothesis and suggested, only, that the "APH should now be questioned."1 We did not state in our paper that the hypothesis could be "invalid," but we certainly think it might be. What Dr. Demer refers to as overinterpretation, by us, actually becomes presentation of hard evidence that the anatomy of the orbit is very similar to what has been reported for over 70 years. It seems to us that there is no reason to change the terminology from fascia bulbi with "muscle sleeves" and "check ligaments" to "pulley rings" and "pulley suspensions" with orbital layer insertions.2,4 His hypothesis (the APH) still is in dire need of experimental clarification anatomically, as well as physiologically (Lennerstrand G, et al. IOVS 2003;44:ARVO E-Abstract 2735).5-9 Dr. Demer's letter does not address the issue of which motoneurons might independently control the tension on the "pulley" as opposed to those motoneurons that control the tendon's insertion to the globe. He did, however, acknowledge the significance of motoneuron firing in 2004.4 "Even during coordinated movements, however, ocular rotation by the GL [global layer] and pulley translation by the OL [orbital layer] require fundamentally different EOM actions and neural commands."4 In our manuscript1 we reasserted this very important issue and point out the shortcomings of the APH in that regard. That is, no motoneurons have ever been found to satisfy the requirement that the orbital muscle layer controls the "pulley" while the global muscle layer, alone, moves the eye. All EOM motoneurons show similar firing patterns during eye movements.10 In addition, Dr. Demer accurately reports that 73% of cat motor units are exclusively restricted to either the global (globe controlling according to Demer?) or orbital (pulley controlling according to Demer?) muscle layers. But he misses the point that at least the purely orbital (≈20%) and purely global (≈54%) units11 should be innervated by neurons with different firing patterns since they have different roles according to the APH. We look forward to the elucidation of such independent EOM motoneuron firing patterns in the future, but until then we will maintain, again, that the "APH should now be questioned."1 Next, Dr. Miller's letter takes a somewhat different approach than Dr. Demer's in his critique of our paper. Dr. Miller implies, in his opening statement, that many have been uncritical in their acceptance of the APH and others, through lack of comprehension, have denied it. Neither of these responses, he argues, is appropriate. We agree and thought that we had taken the middle ground in our manuscript by suggesting (as stated earlier) that the "APH should now be questioned."1 Dr. Miller continues by questioning our interpretation of orbit anatomy while explaining Dr. Demer's use of "pulley sleeve" and "pulley suspension" terminology. Even though he is incorrect in thinking we are confused by the distinctions between these two, it seems appropriate to ask the reader to refer to our response (above) to Dr. Demer regarding this issue. It is also interesting to read both letters in sequential order for they refute each other on several points. Dr. Demer defends the APH, which requires differential control of the orbital and global layers of the muscle to work properly, as he described it in 2004.4 Dr. Miller spends several paragraphs trying to convince us that they abandoned some version of this in 2002. Dr Miller now introduces, in heretofore unknown terminology, the strong differential APH in contrast to the weak differential APH. He refers to Kono et al.12 regarding this abandonment. But in our view, those investigators do not appear to "abandon" anything. We suggest that interested clinicians and investigators read that paper.12 First, the following sentence is the last one of the Kono et al.12 introduction: "The current experiment did not address the differential control postulate." That seems clear and is certainly okay with us. Later, there is a paragraph on "Differential Control" in the discussion of this paper12 that is, in our view, quite difficult to decipher. But the first sentences of that "differential control" paragraph are as follows. As pointed out earlier, even coordinated control of pulley movement requires differential EOM effort because of different static and dynamic loadings on pulley and globe. This implies a requirement for at least some differential neural commands to the OL and GL of each EOM, even during coordinated control.12 Therefore, our response to Dr. Demer's letter regarding different firing patterns by EOM motoneurons is an appropriate response to both of their positions on neural control of EOMs. Dr. Miller and Dr. Demer both state that there is no difference between a band of connective tissue attaching to the side of a muscle and muscle fibers making an insertion onto its site of action (e.g., the globe). Miller calls it "a distinction without a difference" while Demer claims, "their distinction is really a matter of nosology." On the contrary, connective tissue surrounds and attaches to all muscles, but those attachments do not constitute functional insertions. Therefore, the connective tissue ligament we describe (CL) should not be considered a functional insertion of the rectus muscles. We have challenged some of the new anatomical terminology as well as the APH premise that the orbital muscle layer actively and independently controls the pulley tissue. However, we did state, clearly, in our paper1 that "our findings do not challenge the idea that there are pulleylike restraints on the dynamics of eye movement [emphasis added]." Therefore, we don't necessarily disagree with Dr. Miller's summation (in his penultimate paragraph) that the eye's kinematics involve connective tissue restraints (pulleys). But Ghasia and Angelaki13 (a reference cited in this regard by Dr. Miller) do include the following disclaimer in their paper on the noncommutativity of ocular rotations: "Neither can these experiments directly support nor contradict the pulley hypothesis." In a more recent paper Klier et al.14 present results that are consistent with the idea that "pulleys change the effective pulling direction of the eye muscles." And, this is not inconsistent with our statement quoted earlier in this paragraph. Even though Dr. Miller and Dr. Demer conclude that our arguments are irrelevant to the APH (Miller) or represent no serious challenge to the APH (Demer), we think these two pointed Letters to the Editor indicate that they know this is not the case. It seems that they "protest too much, methinks."15 We have explicated on what we have observed in human tissue and cited other lines of experimental evidence as well. And therefore we ask again, quite reasonably, that the scientific and clinical ophthalmologic communities question the active pulley hypothesis before it has an even more damaging effect on the field. J. Ross McClung and Stephen J. Goldberg Department of Anatomy and Neurobiology, Virginia Commonwealth University, Richmond, Virginia References 1. McClung JR, Allman BL, Dimitrova DM, Goldberg SJ. Extraocular connective tissues: a role in human eye movements? Invest Ophthalmol Visual Sci. 2006;47:202-205. |
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