Journal of Neuro-Ophthalmology, June 1999, Volume 19, Issue 2

Letter to the Editor

Journal of Neuro- Ophthalmology 19( 2): 120- 121, 1999. © 1999 Lippincott Williams & Wilkins, Inc., Philadelphia Letters to the Editor To the Editor: On a personal note, I ( J. D. B.) have had a long­standing interest in mucormycosis beginning 25 years ago when I diagnosed my first case while I was a resident ( 1). That patient and one other from the Yale- New Ha­ven Medical Center were described in a 1974 publication in the American Journal of Ophthalmology ( 2). Those two patients were cited by Kohn and Hepler ( 3) in their 1985 article as early examples of the successful manage­ment of rhino- orbital mucormycosis without exentera­tion. Since then, I have had clinical experience with six additional patients treated without exenteration, two of whom died ( 4,5). Additionally, in the past 2 years I have been a forensic medical- legal defense expert in two other cases of mucormycosis. In the first case the phy­sicians were sued because they performed an exentera­tion, and the patient survived; in the second case the physicians were sued because they did not perform an exenteration, and the patient died. Of these 10 patients, 9 were treated without exenteration; 6 of these survived, and 3 died. The patient treated with exenteration survived. Kohn and Hepler ( 3) reported survival of eight pa­tients treated without exenteration over a 12- year period. However, they provided no survival or management de­tails of the other patients with mucormycosis seen and treated during that same period. Ochi et al. ( 6) reported 8 of 11 patients treated without exenteration: One sur­vived, and seven died. Of the three patients treated with exenteration, one survived and two died. These data from different series clearly demonstrate a marked variability in the survival of patients with mucormycosis. Outcomes vary because of the number and severity of the patients' risk factors; the number and virulence of the invading organisms; the extent of involvement at the time treat­ment is sought; the speed and accuracy of the diagnosis; the rapidity, effectiveness, dosage, and methods of insti­tuting appropriate antifungal agents and other treatment methods, such as hyperbaric oxygen; the correction of underlying metabolic defects and/ or disease states; and the rapidity, effectiveness, and extent of surgical de­bridement ( 7). Avet et al. describe three patients with presumed rhino- orbital- cerebral mucormycosis treated by endo­scopic sinus surgery and intravenous amphotericin B without exenteration. We would be interested to know whether they have treated other patients less successfully by similar means. One feature unusual to mucormycosis in their series was edema of the optic disc ( 4) in case 1. In only one ( case 3) of their three cases was the diagnosis supported by culture. Without identification by culture, we cannot be certain that the involved fungi were mu-cormycosis- type organisms. Avet et al. extol the advantages of endoscopic sinus surgery allowing a resection of the nasal turbinates, sinus mucosa, and lamina papyracea, and examination and bi­opsy of the medial orbital fat. In their three cases they did not report performing frozen sections, but they state that they could " selectively remove necrotic tissue and spare healthy structures." However, as they stated, this tech­nique does not allow adequate examination of the supe­rior, posterior, lateral, or inferior orbit, and merely in­specting the orbital fat without frozen section analysis does not assure the surgeon that the tissue is not infected ( 10,11). In cases 1 and 2, we think there was most cer­tainly infection of the posterior orbit ( rather than " spill­over" inflammation, as the authors suggested) because there was optic neuropathy and total ophthalmoplegia. However, surgical debridement of orbital tissues was not performed. Therefore, the resolution of the presumed or­bital infection and the absence of detectable intracranial spread was most likely a result of the medical manage­ment and less likely a result of the endoscopic sinus surgery. Thus, orbital infection was clinically apparent but not recognized surgically by means of endoscopic examination of the medial orbital fat. In addition, the authors suggest that there is no " detrimental effect to delaying ( surgery)." In Table 7 of our article in Survey of Ophthalmology ( 4) we clearly showed a decrease in sur­vival with delayed surgical therapy. Although it is important for ophthalmologists to rec­ognize the possible value of endoscopic sinus surgery in the management of early mucormycosis without orbital necrosis in patients with limited risk factors, others may attempt the same treatment in different subsets of pa­tients with disastrous results ( 12). A legitimate change in the conventional management of this life- threatening dis­ease requires therapy and recommendations based on air­tight logic, sound clinical principles, and rock- solid documentation of the disease entity itself. We recommend surgical excision and culture of all grossly necrotic and infected tissues when possible. In­volved nasal turbinates and paranasal sinuses should un­dergo debridement and drainage, with daily packing and irrigation with 1 mg/ ml amphotericin B. The extent of orbital surgical debridement to be performed must be decided on a case- by- case basis. An actively inflamed orbit with an immobile, blind eye should be considered for exenteration. A more difficult decision is how to manage an infected orbit with an unaffected or partially affected eye. A limited orbital debridement guided by frozen section analysis with medical treatment or medi­cal treatment alone may, in some cases, be curative. The mainstay of medical management is intravenous amphotericin B. It may also include local infusion of 120 LETTERS TO THE EDITOR 121 amphotericin B through a catheter directly into the or­bital space ( 13) and possibly hyperbaric oxygen ( 4). However, the life- threatening nature of the disease must be considered, and the fact that the globe and apical structures are spared does not necessarily indicate that the intracranial structures are entirely safe. For example, a patient with rhino- orbital- cerebral mucormycosis, or­bital involvement with proptosis, and normal visual acu­ity who did not undergo orbital exenteration but was treated with medical therapy and an external sphenoeth-moidectomy died of a sudden massive cerebral infarction on hospital day 30 ( 6). Thus, the patient, family members, and all involved health care personnel must understand that the physical and psychological morbidity of disfiguring wide surgical d6bridement must be weighed against the potential life- threatening risks of medical management alone or minimally aggressive surgical management ( 7). In conclusion, it is important to be open to the ideas of others; that is the only way in which we can learn. At the same time, it is essential to exercise appropriate caution and skepticism in evaluating new methods of treatment, particularly when sight and life- threatening diseases are involved. John D. Bullock, M. D., M. S., F. A. C. S. Ronald E. Warwar, M. D. Department of Ophthalmology Wright State University School of Medicine Dayton, Ohio REFERENCES 1. Bullock JD. Mucormycosis following cataract extraction. In: Em­ery JM, Paton D, eds. Current concepts in cataract surgery. St. Louis: C. V. Mosby, 1976: 349- 55. 2. Bullock JD, Jampol LM, Fezza AJ. Two cases of orbital phyco-mycosis with recovery. Am J Ophthalmol 1974; 78: 811- 15. 3. Kohn R, Hepler R. Management of limited rhino- orbital mucor­mycosis without exenteration. Ophthalmology 1985; 92: 1440- 3. 4. Yohai RA, Bullock JD, Aziz AA, Market RJ. Survival factors in rhino- orbital- cerebral mucormycosis. Surv Ophthalmol 1994; 39: 3- 22. 5. Bullock JD. Orbital infections in the immunocompromised patient. Ophthal Plast Reconstr Surg 1986; 2: 189- 96. 6. Ochi JW, Harris JP, Feldman JI, Press GA. Rhino- cerebral mucor­mycosis: Results of aggressive surgical debridement and amphot­ericin B. Laryngoscope 1988; 98: 1339^ t2. 7. Warwar RE, Bullock JD. Rhino- orbital- cerebral mucormycosis: a review. Orbit 1998; 17: 237^ 15. 8. Gamba JL, Woodruff WW, Djang WT, Yeates AE. Craniofacial mucormycosis: assessment with CT. Radiology 1986; 160: 207- 12. 9. Schwartz JN, Donnelly EH, Klintworth GK. Ocular and orbital phycomycosis. Surv Ophthalmol 1977; 22: 3- 28. 10. Langford JD, McCartney DL, Wang RC. Frozen section- guided surgical debridement for management of rhino- orbital mucormy­cosis. Am J Ophthalmol 1997; 124: 265- 7. 11. Ferry AP. Discussion of management of limited rhino- orbital mu­cormycosis without exenteration. Ophthalmology 1985; 92: 1443^ 1. 12. Sponsler TA, Sassani JW, Johnson LN, Towfighi J. Ocular inva­sion in mucormycosis. Surv Ophthalmol 1992; 36: 345- 50. 13. Luna JD, Ponssa XS, Rodriguez SD, et al. Intraconal amphotericin B for the treatment of rhino- orbital mucormycosis. Ophthalmic Surg Lasers 1996; 27: 706- 8. Authors' Reply To the Editor: We appreciate Drs. Bullock and Warwar's comments and offer the following response. It is clear from the literature that " identification by culture" is not necessary to establish the diagnosis of mucormycosis. In at least three major publications ( 1- 3) ( one of which Dr. Bullock coauthored), the diagnosis was established by recognition of pathogenetic fungi by microscopic examination of either fresh tissue scrapings or fixed paraffin- embedded tissue. We agree that in cases 1 and 2 there may have been active infection in the posterior orbit. Yet the decision to spare the orbital contents was prompted by the absence of orbital tissue necrosis seen with endoscopy. Both pa­tients responded to medical therapy and avoided exentera­tion. Even if a traditional surgical approach to the orbit had been used in these two patients, there is no way to perform debridement of the orbital apex short of exenteration! We are not suggesting that surgery should be delayed in patients with mucormycosis. Indeed, with the low morbidity of endoscopy, surgery can be performed early in the clinical course and repeated as often as deemed necessary. The reports by Blitzer et al. ( 4) and Peterson et al. ( 5) indicate that the difficult decision to proceed with exenteration need not be made on an immediate basis. We are not advocating a radical change in the " con­ventional management" of mucormycosis. Urgent in­spection of the paranasal sinuses and periorbita, control of medical risk factors, and intravenous antifungal therapy are still the mainstays of therapy. However, en­doscopic surgery provides a safe and effective surgical option in disease management. We trust that our study has not led the reader to con­clude that a less aggressive approach is required in pa­tients with mucormycosis. Rather, our goal is to increase awareness of endoscopy as an alternative to transcutane­ous surgery and to demonstrate that not all patients with mucormycosis of the orbital apex will die if exenteration is not performed. Patrick P. Avet, M. D. Lanning B. Kline, M. D. Department of Ophthalmology Michael J. Sillers, M. D. Division of Otolaryngology University of Alabama, School of Medicine Birmingham, Alabama REFERENCES 1. Schwartz JN, Donelly EH, Klintworth GK. Ocular and orbital phy­comycosis. Surv Ophthalmol 1977; 22: 2- 28. 2. Ferry AP, Abedi S. Diagnosis and management of rhino- orbito-cerebral mucormycosis ( phycomycosis). Ophthalmology 1983; 90: 1096- 1104. 3. Yohai RA, Bullock JD, Aziz AA, et al. Survival factors in rhino-orbital- cerebral mucormycosis. Surv Ophthalmol 1994; 39: 3- 22. 4. Blitzer A, Lawson W, Meyers BR. Patient survival factors in para­nasal sinus mucormycosis. Laryngoscope 1980; 90: 635^ t8. 5. Peterson KL, Wang M, Canalis RF et al. Rhinocerebral mucormy­cosis: Evolution of the disease and treatment options. Laryngo­scope 1997; 107: 855- 62. J Neuro- Ophthalmol, Vol. 19, No. 2, 1999