- Email: [email protected]
National Eye Institute—Melanoma Conference
422
AMEPICAN JOURNAL OF OPHTHALMOLOGY
the fovea. Both lesions demonstrated subretinal neovascularization. Gail Tucker, described the developmental retinal anat omy in the kitten and an extensive histopathologic description of the maturational pattern of the cellular layers. She also correlated the development of late recep tor potentials to the presence of a surface photoreceptor membrane in the kitten. Jack Sipperley evaluated the efficacy of cryopexy vs diathermy in the treatment of giant retinal tears. Using a rabbit model, he found no histopathologic differences between the cryopexy and diathermy le sions when examined at ten, 30, and 60 minutes after treatment. Raymond Sever, described 14 patients with singular or multiple microdetachments of the retina following retinal detachment surgery. Most of the small areas of elevation re solved within seven months, and these elevations were attributed to accumula tions of viscous subretinal fluid. Jose Berrocal described two cases of traction retinal detachment in postoperative scleral buckling patients who showed "kiss ing choroidals." Adhesion of the retina to itself remained after the choroidals had resolved. Surgery was required to lyse these adhesions. Mary Szatkowski pre sented a comprehensive coding system for the External Disease Department based on an anatomic and pathologic classification. Donald Puro reported two cases of histopathologically confirmed or bital mucormycosis in apparently healthy diabetic adults. Both patients responded successfully to intervenous amphotericin therapy. Bernard Doft presented an intra venous drug user with endogeneous Aspergillus endophthalmitis. After treat ment with vitrectomy, amphoterecin and 5-flucytosine given intravitreally, periocularly and intravenously, the patient re tained ambulatory vision. Thomas J. Liesegang reported that of 663 cases of ulcerative keratitis, 251 were documented bacterial keratitis, 135 were fungal kerati
MARCH, 1979
tis, and the remaining 277 were culture negative. Steve Civiletto and Jerry Fisher used a rabbit model to evaluate the toxicity of intravitreal cefazolin. Using photo graphic, electroretinographic, and patho logic criteria, they found that up to 2.25 mg of cefazolin could be tolerated with out toxicity. Doses above 5 mg caused decreased b-waves in the electroretinogram and pigmentary disturbance was noted on photographic and pathologic examinations. JACK O. S I P P E R L E Y
NATIONAL EYE INSTITUTE—MELANOMA CONFERENCE A melanoma conference sponsored by the National Eye Institute was held in Bethesda July 14 and 15, 1978. The 29 participants included ophthalmologists working in the field of ocular malignancy, biometricians, and authorities in various aspects of oncology. The purpose of the meeting was to focus on problems of management of choroidal and ciliary body melanomas, and to define the infor mational gaps regarding the treatment of these lesions. Attention focused mainly on the recent reappraisal of survival data on patients with uveal melanomas carried out by Lorenz E. Zimmerman, Ian W. McLean, and Walter D. Foster, from the Armed Forces Institute of Pathology. These workers concluded from their study that (1) the mortality before enucleation is low, estimated at 1% per year; and (2) that the mortality rises abruptly after enucleation, reaching a peak of about 8% during the second year after enucleation, then drops off monotonically. Zimmer man and co-workers believe that about two thirds of the fatalities occurring after enucleation can be attributed to the dis semination of tumor emboli at the time of surgery. D. Jackson Coleman, Robert Ellsworth, and others offered an alterna-
VOL. 87, NO. 3
MEETINGS, CONFERENCES, SYMPOSIA
tive explanation: that the growth curve of ocular melanomas has an initial slow growth phase, which may last an unpre dictably long time. At some point, howev er, a rapidly accelerated growth phase is usually encountered which, clinically, may produce symptoms and may account for detection. Consequently, they attrib ute the rise in mortality resulting after enucleation to the phase of growth of the tumor at the time of detection and not to the therapy used (that is, enucleation). The ensuing discussion emphasized that there is a need for additional infor mation regarding the natural history and death rates of untreated melanomas of medium and large size. It was pointed out that our rationale for the treatment of melanomas was derived mainly from nu merous retrospective histologic reviews where, using materials and histories (of ten fragmentary and accumulated in pa thology laboratories), an attempt to corre late survival with factors such as cell type, tumor size, pigmentation, and scleral extension was made. It was pointed out that the major experimental defect in all such studies is that almost all the patients were treated by enucleation. We have learned from these studies that both cell type and tumor size at enucleation are major prognostic factors for survival after enucleation. Metastatic spread at the time of diagno sis of choroidal and ciliary body melano mas is apparently uncommon, the occur rence of metastases being less than 0.5% in the AFIP series. Participants stressed the need for more sensitive methods for detecting metastatic disease and better methods of informing ophthalmic pathologists and registries of such occurrence before or after enucleation. A survey of ophthalmologists, preferably carried out through the American Academy of Oph thalmology, to obtain more information on the presence of metastases at the time of diagnosis of melanoma was suggested.
423
The question of whether the traditional management of melanomas of medium to large size should be modified and, if so, how, was discussed. Frederick T. Fraunfelder reviewed his "no touch" technique of enucleation to prevent tumor spread from occurring secondary to ocular ma nipulation during enucleation. This tech nique avoids intraocular pressure in crease above 15 mm/Hg before freezing completely around the tumor, thereby preventing flow of fluid and blood to or from the tumor before the manipulation necessary for enucleation. Francis LaPiana reviewed an alternative method of surgery aimed at minimizing the dissemi nation of tumor cells utilizing a pressure stabilizing device. The use of adjunctive therapy, including radiation, chemothera py, and immunotherapy, was discussed by Marvin Rotman, David Berd, Devron Char, and others. Overall, there was little enthusiasm for replacement of enuclea tion for tumors of medium to large size by other therapeutic modalities. With regard to poor prognosis cases (those cases in which the expected tumor death rate exceeds 50% as determined after pathologic study of size, cell type, mitotic activity, extraocular extension, vascular invasion, and the like), the role of adjunctive therapy, particularly preoperative or postoperative radiation, or both, was raised. While having the enthusiastic endorsement of radiotherapists such as Dr. Rotman, there appears little hard data to evaluate the usefulness of these modal ities. This lack of such information seems to make difficult the establishment of ran domized clinical trials at the present time for the purpose of evaluating adjunctive therapy in poor prognosis cases. Victor Curtin, Jerry Shields, and Fred erick Davidorff presented their ongoing evaluation of series of patients with small melanomas, defined as those 10 mm or less in their largest diameter and 2 mm or less in elevation. William R. Green re-
424
AMERICAN JOURNAL OF OPHTHALMOLOGY
viewed the results of cases on file in the Wilmer Pathology collection, including 70 cases that have been followed up for over five years. These studies appeared to confirm the existing impression that the results with regard to prognosis are excel lent, regardless of how these tumors are treated or not treated. In the ensuing discussion, the need to learn more from collaborative prospective studies regard ing the natural history and death rate of untreated small melanomas was empha sized. Most physicians present opted for observation rather than enucleation in most cases of these tumors. For this rea son, and because of a reluctance to turn to alternative methods of treatment other than nontreatment or enucleation in this group, the design of randomized clinical trials may be difficult, and participation by clinicians may be limited. A review of registries as a source of information to fill gaps in our knowledge regarding the management of melanomas followed. Ian W. McLean described the AFIP's melanoma collection, which in cludes 6,000 cases on file, and to which approximately 120 additional cases are added each year. Max Myer discussed the Cancer Surveillance, Epidemiology and End Results (SEER) program, sponsored by the Biometry Branch of the National Cancer Institute. This study, which re cords data from five states and four metro politan areas, collected a total of 103 choroidal melanomas between 1973 and 1976, but is, unfortunately, not geared to investigate the unique problems pertinent to this tumor. Daniel Albert described a proposal which has been submitted to the Division of Research Grants of the Na tional Institutes of Health for a collabora tive prospective study of uveal melano mas as presently treated, which would involve collaboration effort of centers in Boston, Miami, Cleveland, Iowa City, Madison, Los Angeles, Seattle, and the AFIP. The goal of this study on the course
MARCH, 1979
of choroidal melanomas, both treated and untreated, is to provide a scientifically sound basis for the diagnosis and treat ment of these tumors. Paul Henkind and others called for the establishment, through the American Academy of Oph thalmology and American Registry of Pa thology, of a registry of all untreated cases of melanoma. Next, a review of studies in progress or planned pertinent to the melanoma prob lem was explored. The first of these de scribed was the Wills Eye Hospital-Ohio State-Oncologic Hospital-AFIP study, which focused on a subgroup of patients with choroidal melanoma having a poor prognosis. The study is intended to evalu ate the efficacy of a methanol-extraction residue of BCG, examine histopathologic characteristics relating to metastasis, and explore the sensitivity of various tests for detecting metastatic melanoma. Jerry Shields presented a summary of his on going study of ocular melanomas based on the experience of the Oncology Unit at the Wills Eye Hospital which he began in 1974 and which presently includes close to 400 patients. In the final portion of the meeting, the members explored the implications of Zimmerman and co-workers' new find ings on our management of melanoma. The majority thought that it would not be advisable at the present time for clini cians to change the type of management routinely recommended for patients with malignant melanoma. In cases in which enucleation was undertaken, the need for an experienced surgeon using maximum care and minimal manipulation of the eye was stressed. The need for prospective collaborative studies of uveal melanomas was emphasized; a long-term follow-up study of untreated patients with melano mas of the choroid and ciliary body was cited as being extremely important. The biometricians at the conference were unanimous, however, in their opinion
VOL. 87, NO. 3
MEETINGS, CONFERENCES, SYMPOSIA
that a nonrandomized study would not be able to resolve the controversy dealing with the hazards or benefits of enucleation. The consensus of the members at the meeting was summarized by Matthew Davis, who stated that, eventually, it will be desirable to develop a randomized clinical trial to test the hypotheses of Dr. Zimmerman and his associates. Further examination of alternative explanations for the high frequency of deaths observed soon after enucleation, other than the suggestion that it represents an adverse effect of enucleation, needs to be carried out by specialists in the field of cancer research and biostatistics. Dr. Davis noted that the eventual randomized'clini cal trial may support the clinician in following currently accepted clinical practice, or may provide substantial evi dence that this is not in the patient's best interest. D A N I E L M. A L B E R T
T H E FIRST PAN AFRICAN CONGRESS O F OPHTHALMOLOGY The First Pan African Congress of Oph thalmology was held in Dakar, Senegal, at a modern, beautifully designed, well equipped International Pavillion, from Nov. 21-24, 1978. It had the blessings of the International Council of Ophthalmol ogy. Professor Jules Francois attended and received a decoration. Professor Paul Bregeat, dean of French ophthalmologists also attended, as did half a dozen French ophthalmologists. Approximately 200 ophthalmologists from North, East, West, and Central Afri ca and Madagascar were present. South Africa and Rhodesia were not represent ed. The scientific papers were of high cali ber. The majority were presented in French with simultaneous translation into English. Glaucoma, detachment of the retina, onchocerciasis, fungus infec
425
tions of the eye, corneal transplantation were on the scientific agenda. The full morning's session was devoted to the prevention of blindness. The con sensus was that 10% of all patients seen in African countries consulted medical fa cilities because of eye diseases. Accord ing to M.S. Quaraishy: "Blindness in Af rica causes a colossal loss and waste in manpower and costs as much in terms of money as many development projects." E. O. Akinsete of Lagos, Nigeria, estimat ed 500,000 blind people in his country. The main causes of blindness were tra choma, onchocerciasis, measles, glauco ma, cataract, and ocular trauma. The is sues raised in conjunction with preven tion of blindness included the establish ment of priorities in each country, their prevention.through the use of the mass media and mass eye examinations, train ing of auxiliary ophthalmic-trained per sonnel, improved health education of the public and the Ministries of Health, Fi nance, Labor Welfare and Agriculture. Professor Joseph Salla Diallo, of Dakar, Senegal, was the Congress president. The Minister of Health of Senegal and the President of the Municipal Council of Dakar spoke at the opening ceremonies. The principal aims and purposes of the Pan African Society of Ophthalmology are as follows: Promoting research work in ophthalmology in Africa; convening periodic congresses every four years, in alternance with the International Con gress of Ophthalmology; strengthening interdisciplinary exchange with practi tioners in fields such as epidemiology, parasitology, hygiene, health administra tion, biostatistics, including Public Health ophthalmology, on the occasions of national, regional and international so ciety meetings. T. M. Otiti,. of Kampala, Uganda, was elected secretary. The next congress is scheduled to take place in Nigeria in November or Decem-
AMEPICAN JOURNAL OF OPHTHALMOLOGY
the fovea. Both lesions demonstrated subretinal neovascularization. Gail Tucker, described the developmental retinal anat omy in the kitten and an extensive histopathologic description of the maturational pattern of the cellular layers. She also correlated the development of late recep tor potentials to the presence of a surface photoreceptor membrane in the kitten. Jack Sipperley evaluated the efficacy of cryopexy vs diathermy in the treatment of giant retinal tears. Using a rabbit model, he found no histopathologic differences between the cryopexy and diathermy le sions when examined at ten, 30, and 60 minutes after treatment. Raymond Sever, described 14 patients with singular or multiple microdetachments of the retina following retinal detachment surgery. Most of the small areas of elevation re solved within seven months, and these elevations were attributed to accumula tions of viscous subretinal fluid. Jose Berrocal described two cases of traction retinal detachment in postoperative scleral buckling patients who showed "kiss ing choroidals." Adhesion of the retina to itself remained after the choroidals had resolved. Surgery was required to lyse these adhesions. Mary Szatkowski pre sented a comprehensive coding system for the External Disease Department based on an anatomic and pathologic classification. Donald Puro reported two cases of histopathologically confirmed or bital mucormycosis in apparently healthy diabetic adults. Both patients responded successfully to intervenous amphotericin therapy. Bernard Doft presented an intra venous drug user with endogeneous Aspergillus endophthalmitis. After treat ment with vitrectomy, amphoterecin and 5-flucytosine given intravitreally, periocularly and intravenously, the patient re tained ambulatory vision. Thomas J. Liesegang reported that of 663 cases of ulcerative keratitis, 251 were documented bacterial keratitis, 135 were fungal kerati
MARCH, 1979
tis, and the remaining 277 were culture negative. Steve Civiletto and Jerry Fisher used a rabbit model to evaluate the toxicity of intravitreal cefazolin. Using photo graphic, electroretinographic, and patho logic criteria, they found that up to 2.25 mg of cefazolin could be tolerated with out toxicity. Doses above 5 mg caused decreased b-waves in the electroretinogram and pigmentary disturbance was noted on photographic and pathologic examinations. JACK O. S I P P E R L E Y
NATIONAL EYE INSTITUTE—MELANOMA CONFERENCE A melanoma conference sponsored by the National Eye Institute was held in Bethesda July 14 and 15, 1978. The 29 participants included ophthalmologists working in the field of ocular malignancy, biometricians, and authorities in various aspects of oncology. The purpose of the meeting was to focus on problems of management of choroidal and ciliary body melanomas, and to define the infor mational gaps regarding the treatment of these lesions. Attention focused mainly on the recent reappraisal of survival data on patients with uveal melanomas carried out by Lorenz E. Zimmerman, Ian W. McLean, and Walter D. Foster, from the Armed Forces Institute of Pathology. These workers concluded from their study that (1) the mortality before enucleation is low, estimated at 1% per year; and (2) that the mortality rises abruptly after enucleation, reaching a peak of about 8% during the second year after enucleation, then drops off monotonically. Zimmer man and co-workers believe that about two thirds of the fatalities occurring after enucleation can be attributed to the dis semination of tumor emboli at the time of surgery. D. Jackson Coleman, Robert Ellsworth, and others offered an alterna-
VOL. 87, NO. 3
MEETINGS, CONFERENCES, SYMPOSIA
tive explanation: that the growth curve of ocular melanomas has an initial slow growth phase, which may last an unpre dictably long time. At some point, howev er, a rapidly accelerated growth phase is usually encountered which, clinically, may produce symptoms and may account for detection. Consequently, they attrib ute the rise in mortality resulting after enucleation to the phase of growth of the tumor at the time of detection and not to the therapy used (that is, enucleation). The ensuing discussion emphasized that there is a need for additional infor mation regarding the natural history and death rates of untreated melanomas of medium and large size. It was pointed out that our rationale for the treatment of melanomas was derived mainly from nu merous retrospective histologic reviews where, using materials and histories (of ten fragmentary and accumulated in pa thology laboratories), an attempt to corre late survival with factors such as cell type, tumor size, pigmentation, and scleral extension was made. It was pointed out that the major experimental defect in all such studies is that almost all the patients were treated by enucleation. We have learned from these studies that both cell type and tumor size at enucleation are major prognostic factors for survival after enucleation. Metastatic spread at the time of diagno sis of choroidal and ciliary body melano mas is apparently uncommon, the occur rence of metastases being less than 0.5% in the AFIP series. Participants stressed the need for more sensitive methods for detecting metastatic disease and better methods of informing ophthalmic pathologists and registries of such occurrence before or after enucleation. A survey of ophthalmologists, preferably carried out through the American Academy of Oph thalmology, to obtain more information on the presence of metastases at the time of diagnosis of melanoma was suggested.
423
The question of whether the traditional management of melanomas of medium to large size should be modified and, if so, how, was discussed. Frederick T. Fraunfelder reviewed his "no touch" technique of enucleation to prevent tumor spread from occurring secondary to ocular ma nipulation during enucleation. This tech nique avoids intraocular pressure in crease above 15 mm/Hg before freezing completely around the tumor, thereby preventing flow of fluid and blood to or from the tumor before the manipulation necessary for enucleation. Francis LaPiana reviewed an alternative method of surgery aimed at minimizing the dissemi nation of tumor cells utilizing a pressure stabilizing device. The use of adjunctive therapy, including radiation, chemothera py, and immunotherapy, was discussed by Marvin Rotman, David Berd, Devron Char, and others. Overall, there was little enthusiasm for replacement of enuclea tion for tumors of medium to large size by other therapeutic modalities. With regard to poor prognosis cases (those cases in which the expected tumor death rate exceeds 50% as determined after pathologic study of size, cell type, mitotic activity, extraocular extension, vascular invasion, and the like), the role of adjunctive therapy, particularly preoperative or postoperative radiation, or both, was raised. While having the enthusiastic endorsement of radiotherapists such as Dr. Rotman, there appears little hard data to evaluate the usefulness of these modal ities. This lack of such information seems to make difficult the establishment of ran domized clinical trials at the present time for the purpose of evaluating adjunctive therapy in poor prognosis cases. Victor Curtin, Jerry Shields, and Fred erick Davidorff presented their ongoing evaluation of series of patients with small melanomas, defined as those 10 mm or less in their largest diameter and 2 mm or less in elevation. William R. Green re-
424
AMERICAN JOURNAL OF OPHTHALMOLOGY
viewed the results of cases on file in the Wilmer Pathology collection, including 70 cases that have been followed up for over five years. These studies appeared to confirm the existing impression that the results with regard to prognosis are excel lent, regardless of how these tumors are treated or not treated. In the ensuing discussion, the need to learn more from collaborative prospective studies regard ing the natural history and death rate of untreated small melanomas was empha sized. Most physicians present opted for observation rather than enucleation in most cases of these tumors. For this rea son, and because of a reluctance to turn to alternative methods of treatment other than nontreatment or enucleation in this group, the design of randomized clinical trials may be difficult, and participation by clinicians may be limited. A review of registries as a source of information to fill gaps in our knowledge regarding the management of melanomas followed. Ian W. McLean described the AFIP's melanoma collection, which in cludes 6,000 cases on file, and to which approximately 120 additional cases are added each year. Max Myer discussed the Cancer Surveillance, Epidemiology and End Results (SEER) program, sponsored by the Biometry Branch of the National Cancer Institute. This study, which re cords data from five states and four metro politan areas, collected a total of 103 choroidal melanomas between 1973 and 1976, but is, unfortunately, not geared to investigate the unique problems pertinent to this tumor. Daniel Albert described a proposal which has been submitted to the Division of Research Grants of the Na tional Institutes of Health for a collabora tive prospective study of uveal melano mas as presently treated, which would involve collaboration effort of centers in Boston, Miami, Cleveland, Iowa City, Madison, Los Angeles, Seattle, and the AFIP. The goal of this study on the course
MARCH, 1979
of choroidal melanomas, both treated and untreated, is to provide a scientifically sound basis for the diagnosis and treat ment of these tumors. Paul Henkind and others called for the establishment, through the American Academy of Oph thalmology and American Registry of Pa thology, of a registry of all untreated cases of melanoma. Next, a review of studies in progress or planned pertinent to the melanoma prob lem was explored. The first of these de scribed was the Wills Eye Hospital-Ohio State-Oncologic Hospital-AFIP study, which focused on a subgroup of patients with choroidal melanoma having a poor prognosis. The study is intended to evalu ate the efficacy of a methanol-extraction residue of BCG, examine histopathologic characteristics relating to metastasis, and explore the sensitivity of various tests for detecting metastatic melanoma. Jerry Shields presented a summary of his on going study of ocular melanomas based on the experience of the Oncology Unit at the Wills Eye Hospital which he began in 1974 and which presently includes close to 400 patients. In the final portion of the meeting, the members explored the implications of Zimmerman and co-workers' new find ings on our management of melanoma. The majority thought that it would not be advisable at the present time for clini cians to change the type of management routinely recommended for patients with malignant melanoma. In cases in which enucleation was undertaken, the need for an experienced surgeon using maximum care and minimal manipulation of the eye was stressed. The need for prospective collaborative studies of uveal melanomas was emphasized; a long-term follow-up study of untreated patients with melano mas of the choroid and ciliary body was cited as being extremely important. The biometricians at the conference were unanimous, however, in their opinion
VOL. 87, NO. 3
MEETINGS, CONFERENCES, SYMPOSIA
that a nonrandomized study would not be able to resolve the controversy dealing with the hazards or benefits of enucleation. The consensus of the members at the meeting was summarized by Matthew Davis, who stated that, eventually, it will be desirable to develop a randomized clinical trial to test the hypotheses of Dr. Zimmerman and his associates. Further examination of alternative explanations for the high frequency of deaths observed soon after enucleation, other than the suggestion that it represents an adverse effect of enucleation, needs to be carried out by specialists in the field of cancer research and biostatistics. Dr. Davis noted that the eventual randomized'clini cal trial may support the clinician in following currently accepted clinical practice, or may provide substantial evi dence that this is not in the patient's best interest. D A N I E L M. A L B E R T
T H E FIRST PAN AFRICAN CONGRESS O F OPHTHALMOLOGY The First Pan African Congress of Oph thalmology was held in Dakar, Senegal, at a modern, beautifully designed, well equipped International Pavillion, from Nov. 21-24, 1978. It had the blessings of the International Council of Ophthalmol ogy. Professor Jules Francois attended and received a decoration. Professor Paul Bregeat, dean of French ophthalmologists also attended, as did half a dozen French ophthalmologists. Approximately 200 ophthalmologists from North, East, West, and Central Afri ca and Madagascar were present. South Africa and Rhodesia were not represent ed. The scientific papers were of high cali ber. The majority were presented in French with simultaneous translation into English. Glaucoma, detachment of the retina, onchocerciasis, fungus infec
425
tions of the eye, corneal transplantation were on the scientific agenda. The full morning's session was devoted to the prevention of blindness. The con sensus was that 10% of all patients seen in African countries consulted medical fa cilities because of eye diseases. Accord ing to M.S. Quaraishy: "Blindness in Af rica causes a colossal loss and waste in manpower and costs as much in terms of money as many development projects." E. O. Akinsete of Lagos, Nigeria, estimat ed 500,000 blind people in his country. The main causes of blindness were tra choma, onchocerciasis, measles, glauco ma, cataract, and ocular trauma. The is sues raised in conjunction with preven tion of blindness included the establish ment of priorities in each country, their prevention.through the use of the mass media and mass eye examinations, train ing of auxiliary ophthalmic-trained per sonnel, improved health education of the public and the Ministries of Health, Fi nance, Labor Welfare and Agriculture. Professor Joseph Salla Diallo, of Dakar, Senegal, was the Congress president. The Minister of Health of Senegal and the President of the Municipal Council of Dakar spoke at the opening ceremonies. The principal aims and purposes of the Pan African Society of Ophthalmology are as follows: Promoting research work in ophthalmology in Africa; convening periodic congresses every four years, in alternance with the International Con gress of Ophthalmology; strengthening interdisciplinary exchange with practi tioners in fields such as epidemiology, parasitology, hygiene, health administra tion, biostatistics, including Public Health ophthalmology, on the occasions of national, regional and international so ciety meetings. T. M. Otiti,. of Kampala, Uganda, was elected secretary. The next congress is scheduled to take place in Nigeria in November or Decem-