Ruedemann Lecture Good evening Dr. Tuck, Dr. Hawes, Mr. Acosta, members and fellows of the Academy and American Society of Ocularists, guests....friends. Thank you for the high honor you have bestowed upon me this evening in naming me the 21st Ruedemann Lecturer. I would like to first off thank my fellowship preceptors Dick Dortzbach and Brad Lemke for teaching me that the asking of “why” is the necessary first step in formulating “how”, the highly skilled ocularists I have had the pleasure of working with: Sue Alexander, Chuck Workman, Gene Fletecher and Carrie Messer, and, not the least, my wife, Sandy, and children, Julie, Scott and Steve, for having the patience to live with me in this pursuit called medicine. When I look at the roster of prior Ruedemann lecturers, I am humbled, indeed, but.... (Slide) Even a midget can expand the horizon by standing on the shoulders of a giant. (Slide) Dr. Albert Darwin Ruedemann, Sr., was such a giant. He was born in 1897, and died in 1971, when I was a freshman in medical school. He left his mark at the University of Michigan, the Cleveland Clinic and the Kresge Eye Institute in Detroit. Ruedemann 2 (Slide) He served as the secretary for instruction of the Academy from 1938 to 1962, and won numerous awards and accolades. In describing him, Dr. William Benedict said, “His thinking is clear, his learning is wide, his interest in instruction and education intense, and his tolerance of ignorance nil”. Quite an epitaph. (Slide) He had a long interest in anophthalmia, and it was through his effort that this joint meeting was established in 1957. He ushered in the era of the integrated implant with his description, in 1946, of a combination implant and prosthesis to be placed in the socket after enucleation. (Slide) We share Dr. Ruedemann’s enthusiasm, for we have a common interest in the restoration of as much function and cosmesis as possible following the loss of an eye. The problem we face is that seemingly consistent processes of enucleation and prosthesis fitting are met with confoundingly variable results. Tonight we will explore some possible reasons for this, and hopefully, formulate a clearer understanding of the pathophysiology of anophthalmia. The answers to these questions may both over- and underwhelm you, so hang on. (Slide) Ruedemann 3 First, lets be clear about what we actually do when we remove an eye. The eye is gone, unfortunately. We may, however, be guilty of concentrating too much on what was removed, and not enouth on what is left behind. (Slide) Secondly, let us make the general observation that, with certain exceptions, our goal of normal function and cosmesis is best served by performing the least amount of surgery. Again, leaving more behind seems to be correlated with a higher degree of “normalcy”. (Slide) For hundreds of years, it was enough that the patient survived the enucleation. This is a handout from an Academy instructional course in 1583. However, with the development of the Mules implant in the 1880’s, new possibilities developed. (Slide) Inquiring minds began to ask questions. George de Schweinitz remarked in 1900 that “An enucleation which pays no attention to the preservation of the relationship between the conjunctiva, ocular tendons and capsule of Tenon is a brutal operation.” A year later Jose Barraquer stated, “ What is necessary is to place Ruedemann 4 some soft tissue whose shape can easily adapt to the glass prosthesis and that can persist indefinitely in Tenon’s Capsule.” (Slide) In 1917, John Wheeler, the father of ophthalmic plastic surgery reflected on problems he identified in patients following enucleation. These same problems, with slightly different twists and emphases, have recurred throughout this century. (Slide) 65 years after Wheeler, Tyers and Collin coined the term “Postenucleation socket syndrome” to describe the constellation of enophthalmos, deep upper lid sulcus, ptosis and stretching of the lower lid. (Slide) In 1982, Lee Allen realized that the surgical practice of imbrication of muscles over a spherical implant invariably led to secondary changes in the muscle cone, and resulting iatrogenic ptosis. (Slide) pause (Slide) Ruedemann 5 In 1987, Dr. Lars Vistnes, a truely Renaisance reconstructive surgeon, recognized the same findings as Dr. Wheeler, with a slightly different twist, and termed this the “anophthalmic orbit syndrome”. We will revisit more of Dr. Vistnes’ thoughts later in this lecture. (Slide) To explain some of these problems, Henry Baylis and his co- authors, writing in Sonny McCord’s textbook of ophthalmic plastic surgery, made a statement profound with it’s simple truth. “The anophthalmic socket is a uniquely complex system of structural and functional elements in which a change in any single element profoundly affects the other elements.” The value of this statement was recognized by ______Willis, and could probably serve as a one-sentence text in socket surgery. (Slide) In 1988, Smerdon and Sutton attempted to delineate just what factors were involved in cosmetic failure in anophthalmia. 56 enucleation patients were subjected to quantitative measurements of sulcus depth and socket volume and qualitative assessment of cosmetic appearance. Somewhat surprizingly, cosmetic failure was not correlated with volume loss, but with superior sulcus formation. Sulcus formation itself was not correlated with volume loss. Younger patients were found to have better cosmetic results. Ruedemann 6 (Slide) The decade of the 1990’s has seen the rapid presentation of additional observations which have significantly increased our knowledge of what clinical factors are responsible for cosmetic failure in anophthalmia. ____Willis described the “post- enucleation” syndrome and.... (Slide) Emphasized that these factors are interdependent and self- perpetuating over time if left untreated. (Slide) Neuhaus and Hawes pointed out that the loss of the inferior fornix can be present even with adequate conjunctiva, and is due to loss of the attachments of the lower eyelid retractors to the conjunctival fornix. (Slide) Smit, Koornneef and the talented investigators in Amsterdam presented perhaps the most important series of articles explaining, anatomically, what is happening in those patients who develop this post-enucleation constellation of pathological changes. They observed the following abnormalities: enophthalmos, retraction, not ptosis, of the upper eyelid, deepening of the superior sulcus, backwards tilt of the prosthesis Ruedemann 7 and stretching of the lower eyelid. This almost constant correlation of deep upper eyelid sulcus with deep superior fornix is, I think, a key element. (Slide) To analyse these patients, they performed sagital CT imaging, superimposed the normal orbit on the anopthalmic orbit, and noted the difference in key measurements. (Slide) They found: an anterior displacement of posterior Tenons, as their implants were placed behind posterior Tenons, a rotatory displacement of orbital contents, superior to posterior and posterior to inferior and a retraction and apical displacement of the vertical recti muscles. (Slide) pause (Slide) These anatomic findings, and their resolution after implant placement, are even more dramatically represented in sagital MRI imaging of an anophthalmic orbit before and after secondary implant placement. (Slide) Ruedemann 8 Certainly, enucleation has the potential to cause changes in a number of orbital and periorbital tissues. Smit’s observations are pointing us towards the connective tissue component of the orbit. Let’s dig a little deeper. (Slide) Tenon’s Fascia--everyone talks about it, but what is it? Is it important? Why ask why? Well, it is extremely important in the understanding of the pathophysiology of anophthalmia, but, as Dwight stated in 1900, “The complications of this membrane are limited only by the perverted ingenuity of those who describe it.” How is it described? Is it Tenon’s Capsule, indicating it to be a structure more closely related to the globe, or is it Tenon’s Fascia, indicating a structure perhaps more related to the extraocular muscles. The Motais school views Tenon’s as an extention of the rectus muscle sheaths, while the view of Testut, Charpy and Virchow was that the rectus muscle sheaths are formed from Tenon’s . (Slide) Anatomic dissections do not always help, and yet, our understanding of the teleologic significance of Tenons...”whatever”, seems to be at the root of understanding the changes in the anophthalmic orbit. (Slide) Ruedemann 9 Lester Jones can be credited, I think, with acting as a referee in this debate. His classic descriptions of the levator muscle involved a comparative anatomic study of mammals. He found in marine mammals, a most convincing arguement. The primitive rectus muscle divides into an ocular and palpebral head. The palpebral head in turn divides into a true palpebral head, and a capsular head, which corresponds to the human anterior Tenon’s ...FASCIA. The finding of smooth muscle cells in Tenon’s further supports it’s close relationship to the ocular muscles, rather than to the globe. (Slide) This view is further supported by the elegant and seminal work of Koornneef in his description of the unity of the “musculo-fibrous apparatus of the orbit”. (Slide) Pause (Slide) Pause (Slide) Henry Baylis, thank you again. (Slide) Ruedemann 10 It has been one of my pleasures to work with a number of fellows in the basic science investigation into pathophysiologic changes in the anophthalmic orbit. I would like to review the results of two such investigations, as I think we are getting someplace now. Sara Kaltreider studied the production of socket contraction in the monkey orbit, and its correlation with myofibroblast induction. (Slide) With our model, we could reliably produce socket contraction, with resulting loss of socket volume and depth. (Slide) Cells consistent with myofibroblasts were found, with severe anterior disruption of orbital anatomy and the formation of dense scar bands from the optic nerve and recti muscles to the fundus of the socket. What tissue unites the conjuctiva, rectus muscles and optic nerve? Tenon’s fascia. Proliferation of contractile scar tissue along this tissue plane will produce the contracted socket.... (Slide) As evidenced in this sagital MRI. (Slide) It had been hypothesized that altered blood flow in anophthalmia may contribute to fat atrophy and loss of socket volume with the Ruedemann 11 production of the constellation of findings of the anophthalmic socket syndrome. To investigate this, Jan Kronish investigated, with arteriography and labeled microspheres, the blood supply of the anophthalmic orbit. (Slide) No change in size of blood vessels was found, although their course was somewhat more tortuous. Microsphere analysis showed no difference in blood flow to the fat, muscles, connective tissue or eyelids following enucleation. (Slide) Far from fat atrophy, a statistically significant 13% increase was seen in fat and connective tissue, excluding muscle mass, following enucleation. This is consistent with a similar increase in soft-tissue orbital volume found by Manson and associates in their investigation into orbital volumes following orbital floor fracture. (Slide) Moreover, no difference in adipocyte morphophometry was found. (Slide) Our conclusions were that there was primarily a disturbance in spatial architecture in anophthalmia with a redistribution of soft tissue and contractile scar formation. The volume of the globe Ruedemann 12 was lost, to be sure, but there was an actual increase in connective tissue mass. (Slide) Remember this (Slide) Sooner or later, we must address the volume question. The volume of the globe is 6.5-7.0 cc. The volume of the average prosthesis is 2.5 cc. In order to match the volume lost in an enucleation, an implant of @ 21 mm would be needed. (Slide) Pause (Slide) However, this may be overly simplistic. The ocularists point out that fitting a prosthesis over a 21 mm implant would usually be difficult. There is little room for building adequate chamber depth. Remember too the finding of Smerdon and Sutton: cosmetic failure was correlated not with volume loss, but with superior sulcus formation. Our volume augmentation must be directed, and, to counter the effects described by Smit, should be intra-Tenons. (Slide) Ruedemann 13 Pause (Slide) Can we summarize these findings? The main problem in anophthalmia is a rotational volume displacement, probably caused by changes in Tenon’s fascia. This produces an apical collapse of the muscle cone, with resulting deep superior fornix and superior sulcus formation. Further rotational changes flatten the inferior fornix with resulting pressure and secondary changes on the lower eyelid. It is unclear whether there is ptosis or retraction of the upper eyelid, but there is most certainly altered rectus and probably levator function, with alterations in the length/tension curve of the muscles. (Slide) There are no alterations in muscle mass or blood flow. The fat/connective tissue compartment undergoes a significant increase in mass, and there are varying degrees of myofibroblast induction. (Slide) Let’s return to our enucleation, concentrating this time on what is left behind, rather than on what is removed. It is clear, that to block the changes which occur following enucleation, the ideal orbital implant would duplicate the eye as closely as possible. (Slide) Ruedemann 14 The genius of Dr. Ruedemann is now even more apparent, as that is what his plastic eye was designed to do. The theory was, and is, sound. Technology and engineering are needed to make it workable. (Slide) What are our requirements? Ideally, to solve the problems of Dr. Ruedemann’s implant, the implant should be autogenous, or able to be vascularized. The total volume and size of implant and prosthesis should equal that of the globe. It should duplicate the influence of the globe on Tenon’s fascia, recti muscles and conjunctiva, and integration of the prosthesis and implant should be possible. Judged by this strict criteria, in 1994 the ideal implant from the pathophysiologic perspective would be an evisceration, Vistnes’ eviscero-enucleation or a dermis fat graft. (Slide) Evisceration, especially with retention of the cornea, offers the least pathophysiologic alteration in the orbit, and, not surprizingly... (Slide) Gives excellent cosmesis and motility. (Slide) Ruedemann 15 The eviscero-enucleation of Vistnes, basically leaving the muscles attached to a rim of sclera and placement of an implant behind this, seems to be exceedingly difficult. (Slide) Dermis fat grafts can provide an excellent socket. Their resorption is unpredictable, however. (Slide) The long and short of it is that all of these implant choices have disadvantages. Hydroxyapatite and porous polyethylene, and Allen and Universal implants also have their advantages and disadvantages. How lucky we are that the ideal implant is yet to be found. Perhaps a young investigator in the audience tonight will be challenged enough to find it. (Slide) It may be quite different that we expect. We should not limit our horizon to restoration only of cosmesis and motility. A number of laboratories are actively investigating direct cortical stimulation which may lead to a truely functioning artificial eye. I wish I could say that in 5 or 10 years, “I’ll be back” to report on this, but 20/20 by 2020 is not beyond reason. (Slide) Ruedemann 16 At the beginning of this lecture, I said I thought you may be both over and underwhelmed by its content. Such simple concepts, really, yet so simple that they are easily invisible. Orbital physiology is minimally altered by enucleation. The best results can be expected when the underlying architecture, especially that of Tenon’s Fascia, is minimally altered. Our technology can do little to improve on the underlying basic design of the orbit, only duplicate it as closely as possible. I thank you for your kind attention.