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Orbital Tumors
ORBITAL TUMORS DANIEL S I ,VA, M.D.
Mexico Cit;, Mexico Years ago I pointed out the need for an integrated study to establish the incidence and causes of ocular proptosis, and subse quently most of the orbital tumor cases in my country have been referred to me. I have always considered orbital tumors to be the field of the ophthalmic surgeon (as stated also by Birge 1 ), with, of course, the advice and technical assistance of the neurosurgeon, head and neck surgeon, or other specialist when necessary. However, at one time these tumors were generally referred to the neuro surgeon, due to the widespread acceptance of Dandy's 2 ideas. The refined diagnostic techniques in use today were lacking when I began my study, and inaccurate diagnoses were not uncom mon. Consequently, orbital surgery, like Pandora's box, was full of surprises. (I often recall an aphorism of my teacher Gonzalo Castaneda,3: "What is not known is not looked for, and what is not looked for is not found.") Initially, I analyzed data collected from a variety of sources, reviewing clinical histo ries and pathologic and radiologic findings in various large hospitals, and studying series of consecutive cases in the literature. Con siderable differences were apparent in the se ries of cases, due mainly to the origin of the material collected and to the specific interest of the investigator. Thus, in Forrest's se ries,4 hemangioma was the most common le sion; in Porterfield's,5 rhabdomyosarcoma; and in Reese and Jones', 6 endocrine exophthalmos. Differences in tumor incidence between Mexico and other countries were clearly eviFrom the Hospital de la Asociacioft para Evitar la Ceguera en Mexico and the Hospital de Oncologia del Instituto Mexicano del Seguro Social. Read before the Chicago Opthalmological Society May 20, 1967.
dent and I finally decided to include data only from Mexico. A new study was begun, using the criteria of Reese and Jones, and including only patients I saw personally, with diagnoses confirmed histologically. The patients were selected from the Hospital of the Association for the Prevention of Blind ness in Mexico, the Oncology Hospital of the Mexican Institute of Social Security, and from my private practice. (Portions of this study have been reported previously7-8). A year ago, I compared a series of 230 consecutive cases with Reese and Jones' series (table l ) . 9 Pseudotumor was found to be the commonest cause of unilateral exophthalmos in my series, whereas endocrine exophthalmos (mainly diagnosed clinically and confirmed in nine cases by orbital sur gery) was the most common in Reese and Jones' series. The series reported here includes 300 pa tients, all of whom underwent surgery, at least for biopsy (table 2). With broader knowledge of etiologic factors, improved techniques, and my own enlarged experience, initial clinical diagnoses were confirmed much more frequently than in previous studies. Table 1 shows the relative frequency and the histologic findings of orbital tumor in this series. FINDINGS
One in three cases was a pseudotumor, a mucocele, a dermoid cyst, or a soft tissue hyperplasia of endocrine origin, found with similar incidence in all age groups (table 3 ) . The unusually high incidence of retinoblastoma with orbital involvement (the tumor most common in the age group below 10 years) may be explained by the fact that at the Oncology Hospital we usually see only children referred for radiotherapy or chemo therapy.
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Table 4 shows the relative sex incidence of orbital tumor. Female predominance may be attributed to the higher proportion of women patients at the Hospital of the Asso ciation for the Prevention of Blindness, the source of most of the patients in this series. The ratio of unilateral to bilateral exophthalmos was approximately 15 to 1, even in cases of systemic disease such as leukemia, multiple myeloma, Hodgkin's disease, endo crine disturbance and reticulosarcoma. Many cases of bilateral retinoblastoma were far ad vanced when first seen. In these, orbital ex tension was usually found in the most se verely affected eye, which was subsequently removed. With orbital recurrence, optic nerve extension was often found in the fel low eye. Lymphangioma was usually found in both eyes. Pseudotumor was found, in one inTABLE 1
319 TABLE 2
HlSTOLOGIC NATURE OF 3 0 0 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias Rhabdomyosarcom as Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous Total
Number 31 30 21 21 20 18 16 16 15 14 13 13 10 8 7 7 7 6 5 4 3 3 3 3 6 300
ETIOLOGIC DIAGNOSIS OF 230 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis
Pseudotumors Mucoceles Dermoid cysts Meningiomas Orb. ext. of retinoblastoma Carcinomas of palpebral origin Hemangiomas Endocrine ophthalmopathy Malignant lymphomas and leukemias Rhinogenic carcinomas Lacrimal gland tumors Malignant melanomas Peripheral nerve tumors Undifferentiated sarcomas Carcinomas of epibulbar origin Osteomas Fibrosarcomas Rhabdomyosarcom as Osteosarcomas Gliomas of optic nerve Metastatic carcinomas Lymphangiomas Cysticercosis Miscellaneous Exophthalmos of unknown cause
Silva 1966 ,c • n (Surgical)
Reese & Jones 1962 (c,inical)
26 25 18 15 15
18 6 7 11
14 13 11
28 37
11 11 10 9 8 6 4 4 4 4 3 3 3 2 2 9
22 17 7 2 2 5 8 8 10 18 24
stance, to appear subsequently in the fellow eye. There was one case each of bilateral or bital varices and mucocele, although these are generally considered to occur only unilat erally (table 5). Histologically benign tumors were found in 58% in this series. However, some of these tumors led to serious consequences by their extension, causing damage to neighbor ing structures, visual disturbances, disfig urement, or poor general health, especially in cases of hemangioma, neurofibroma, and cystic tumor (mucocele and dermoid). One case of frontoethmoidal osteoma with deep extension into the orbit resulted in almost total blindness due to optic nerve compres sion. Malignancy was found in two out of every five cases of expanding orbital lesions. Although sufficient time has not elapsed for final evaluation, at present more than 60% of these patients have died. The number of recurrences is shown in Table 6. Again, there has not been sufficient
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TABLE 3 AGE DISTRIBUTION OF 300 CONSECUTIVE CASES OF ORBITAL TUMORS
Diagnosis
Number
Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis M iscellaneous
31 30 21 21 20 18 16 16 IS 14 13 13 10 8 7 7 7 6 5 4 3 3 3 3 6
Total
300
time to evaluate the incidence accurately, al though the number is expected to increase. A diagnosis of expanding orbital tumor was made in 48.6% of the cases in this se ries after complete clinical examination using routine techniques (table 7), later con firmed by histologic examination. Special ex ploratory techniques were used in some cases and the pathologic nature was correctly diag nosed in 64.3%. However, in 16.6% no tumor could be detected even with digital palpation through external canthotomy. A biopsy was then necessary to learn the etiol ogy of the exophthalmos. Biopsy at the time of surgery was often unsatisfactory, as the specimen was some times taken from a nonrepresentative por tion of the tumor, or the frozen sections did not permit accurate histologic diagnosis, as for instance, in diffuse infiltrating tumor or in endocrine exophthalmos and, more com monly, in undifferentiated sarcoma, lacrimal gland tumor, and orbital metastasis. After proper embedding and staining of the biopsy material, accurate diagnoses could be made.
0-9
10-29
30-49
50-69
11 6 1 5 11
7 10
4 13
1 1
2 1
9 1 8
2
1
7 3 1 4 11
1
1 4
2 6 6 5 1 4 3 1
8 20 3 7 6 2
1 2 3 1 1 2 3 3 1 65
1 4 3 2
1 1
70-<
10 1
5 8 2
3
6 5 1 5 1 1 1
2 2
1
2
2
1
78
56
72
3 1 1 2 4
1
29
SEX DISTRIBUTION OF 300 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis
Males
Females
Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous
11 14 9
20 16 12
7 9
14 11
7 7 3 8 7 5 7 4 6
11 9 13 7 7 8 6 6 2
4 2 3 5 2 2 2 1 1
3 5 4 1 3 2 1 2 3 3 5
129
171
Total
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ORBITAL TUMORS TABLE 5 SITE OF PRESENTATION OF 300 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias. Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous Total
Number
Right Eye
Left Eye
31 30 21 21 20 18 16 16 15 14 13 13 10 8 7 7 7 6 5 4 3 3 3 3 6
17 12 10 9 11 8 10 7 5 6 9 4 6 6 2 2 2 1 1 3 1 3
14 17 S 6 9 10 6 9 7 8 4 9 4 2 5 5 4 5 4 1 2
1 1
2 4
1
300
137
142
21
Bilateral 1 6 6
3
1
3
TABLE 6 CLINICAL EVOLUTION OF 300 CONSECUTIVE CASES OF ORBITAL TUMOR
Clinical Evolution
Cellular Character Diagnosis Benign Malignant Pseudotumors Mucoceles Orb. Ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasisas Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous
Total
31 29
1 21 21
20
Benign 30 28 1 19
18 16 16 15 8 13
6
10 15 14 8 10
13 10 8 7 7 7 6 5
6 6 1
1 6 3 13 10 8 7 7 1
1 2 11 2 10 7 1 1 3 3 6 1
16 6 9
5 4 6 5 3 4
I 2
4 4 3
5
3 3 3 1
5
1
2
125
158
137
51
71
3
175
2 20 21 1 18 3
Death
4 4 3
4 3 3 3 1
Malignant Recurred
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TABLE 7 DECISIVE FACTORS IN DIAGNOSIS OF 300 CONSECUTIVE CASES OF ORBITAL TUMOR Diagnosis Histologic Nature
No. Tumor
Pseudotumors M ucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous Total
31 30 21 21 20 18 16 16 15 14 13 13 10 8 7 7 7 6 5 4 3 3 3 3 6 300 100%
In a few cases, a definite diagnosis was es tablished only by careful follow-up. Exophthalmos can be categorized as fol lows: 1. Proptosis of less than 5 mm difference in the two eyes, no visual damage, no mass, and no measurable progress. In this cate gory, routine studies, including X-ray exam ination, are carried out and the patient is fol lowed closely for evidence of progression. 2. Proptosis of more than 5 mm differ ence in the two eyes, with signs suggestive of tumor behind the globe, visual impair ment, and definite expansion. Special radiographic techniques are used to determine the position of the tumor before entering the orbit for digital palpation. 3. A visible or palpable mass in unilateral exophthamos, with or without visual impair ment and expansion. Before attempting to remove the tumor, orbitographic techniques are used to earn the anatomotopographical characteristics.
IS 30 21 IS 19 18 13 13 11 14 13 11 S 4 7 4 7 6 4 4 3 3 3 3 3 250 83.3%
Clinical study
Path. Nature 9 30 21 11 19 18 10 9 5 12 11 11 3 7 4 7
1 2 2
193 64.3%
Routine
Special
Biopsy
6 30 21
9 30
17
15 11
2 2
7 1 3 7 7 8 2 2 2 5 8
4
4
5 3 4
6 5 4 2
8 15 5 5 7 3 7 11 3 1 7 1 7 1 2 1 1 2 2 1 146 48.6%
7 8 5 9 5
2 1 5 128 42.6%
1 3 6 100 33%
How can we be sure of the progression of the proptosis ? By and large, the instruments in common use for measuring exophthalmos have proved unreliable. Drews 10 has pointed out their inaccuracies, which are due mainly to facial assymmetry and parallax observa tion. Tengroth's 11 technique, however, re cords even very small changes of the posi tion of the eye in the orbit, independent of the investigator and even in the absence of the fellow eye. Since his technique was published, I have worked out a radiographic technique12 which I believe is simpler, as it eliminates the need for making a composite picture formed by superimposing the X-ray film, with the enlarged photograph being taken simultaneously. This technique has the sensitivity of Tengroth's and similarly elimi nates the sources of error—rotation of the head or eye (fig. 1). Following is a descrip tion : A contact lens with a central radio-opaque dot is placed on the eye close to the X-ray
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film making possible a comparison of the po sition of the cornea with the intracranial bony structures of the same side—the most important modification of Tengroth's proce dure. In his technique, the photographic pic ture of one side is superimposed on the radiographic image of the opposite side, the most clearly visible of the film. The technique is so simple it can be used routinely when lateral head X-rays are taken. The only modifications are the appli cation of the corneal-dotted contact lens, a fixation light directly in front of the patient, and steadying of the patient's head, with or without the aid of a cephalostat. With this technique one can determine with greater precision whether an exophthalmos of less than 5 mm or slightly larger is definitely progressive. If so, the case has ad vanced to the second category and the pa tient is reexamined ophthalmologically. Spe cial studies and orbitographic techniques are then carried out to learn if a tumor is pres ent. Radiographic studies are of utmost impor tance in detecting orbital tumors. 13 X-ray films of the orbit with the usual techniques (Watters, Caldwell, lateral, oblique for optic foramen, and Hirtz basal plates), may give sufficient information for location of the tumor or may suggest its existence by in creased density of soft tissue shadows. Rou tine pictures are often adequate for a correct
323
Fig. 1 (Silva). Radiographic exophthalmometry. Lateral radiograph showing the nasion-clinoid and cornea-clinoid distances. The first is used as a checkline to know if successive films have been properly taken. Changes on the cornea-clinoid distance show the progress of the exophthalmos.
diagnosis, or at least may give evidence suf ficient to justify exploratory surgical palpa tion. Knowledge of the size, shape, extension of the tumor, its location in the orbit, its re lation with important adjacent structures, encapsulation, consistency and, if possible,
Fig. 2 (Silva). Retrograde phlebography. Percutaneous injection of contrast into the angular vein gives a good view of this varicose aneurysm in the upper portion of the orbit. Visualization of the nu tritional vessels through retro grade phlebography is valuable for the surgical treatment.
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the nature of the tissue from which it origi nates, is important for carrying out an excisional biopsy. The purpose of orbitographic techniques is the visualization and differentiation of the soft tissues within the orbit. The use of con trast materials in radiographic examination helps in differentiation of various intraorbital structures.14 These materials can be in jected into the vascular network or directly into the loose, areolar fatty tissues surround ing these structures (fig. 2 ) . Arteriographic or phlebographic tech niques help in diagnosing vascular tumors of arterial or venous origin. The diagnosis is sometimes indicated by variations in the nor mal pattern of the vascular network, more specifically in the phlebogram than in the more variable arteriogram. In certain vascu lar tumors in which control of the main af ferent vessel is necessary before surgical re moval, a much better view of the vessels can be obtained by using the subtraction tech nique of Ziedses des Plantes 15 (fig. 3). The materials used in extravascular orbitographies can be less dense than the sur rounding soft tissues—that is, air, oxygen, carbonic dioxide, or some other gas. This technique, combined with tomography, is preferred in North America. I, personally, do not favor it, as it produces a painful em physema which reabsorbs slowly and, in ad dition to unfavorable results reported in the literature, I have known of sudden death from an air embolism in two patients. Positive contrast orbitographies have proved most effective in detecting a sus pected tumor, in studying the anatomotopographic characteristics of an already recog nized progressive lesion and, in some cases, in eliciting further data for establishing the pathologic nature of the tumor. Yoduron Cilag (a bivalent hydrosoluble iodine preparation) has proved satisfactory in concentrations from 30% to 70%, despite Groves and Cowie's16 statement that concen trations higher than 17% to 2 5 % are harm ful to orbital tissues. Trivalent hydrosoluble
MARCH, 1968
iodine preparations are irritating to the eye and retrobulbar tissues, but are preferred in intravascular or intracavity orbitographies. There are five variations of orbitographic technique, with usage depending on the clini cal findings.17 If tumor of the optic nerve is suspected, or there is orbital extension of an intraocular neoplasm, 1-3 cc of the material should be injected into Tenon's capsule just behind the globe, with a curved needle that skims over the sclera, close to the optic nerve (fig. 4). If the exophthalmos is direct and the tumor cannot be palpated, the material is in jected into the muscular cone in amounts varying from 2-5 cc. Care must be taken not to force the material outside the intermuscular fascia. The radiographic changes of the well-known four-leaf clover image in the anteroposterior view will help in locating the tumor; its position deep in the orbit will be
Fig. 3 (Silva). Retrograde phlebography with subtraction technique. The subtraction technique helps to visualize numerous vessels which are other wise hidden by bone shadows. This cavernous hemangioma could not be treated solely by ligature of the main nutritional vessels.
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325
Fig. 4 (Silva). Orbitography with intra-Tenon's capsule contrast injection. The material has filled Tenon's space, giving a clear view of the unfilled part which corresponds to the optic nerve. Its considerable enlarge ment suggests the existence of a nerve tumor. This is a glioma of the optic nerve. Routine oblique, simple X-ray did not show its presence. easily shown on the lateral radiograph (fig. 5). If marked displacement or limitation of
motility of the globe suggest the tumor to be outside the muscular cone, a retrobulbar forced injection is carried out, filling the or-
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Fig. S (Silva). Orbitography with contrast ma terial injected into the muscular cone. The fourleaf-clover image is formed if contrast in small amounts (3 to 6 cc) is injected into the muscular cone. This typical image will exist if the material has not been forced out laterally through the intermuscular fascia, or forward to the anterior Charpy's foramen. Note destruction of the portion corre sponding to the superonasal quadrant, where the tumor was located. It was diagnosed as a primary orbital meningioma.
bital tissues. The radiographic image will show the profile of the tumor in contrast to the injected tissues. The firmer and more en capsulated the tumor, the more apparent the contrast. A ragged profile or presence of the stained contrast material image indicates a
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diffuse tumor. In this variation, as in the previous one, use of a dispersing solution will speed up the diffusion of the contrast material; hence, radiographs will be more demonstrative (figs. 6 and 7). If there is clinical suspicion of cystic tumor or of liquid content, the cavity should be washed out and refilled with contrast material. Radiographs taken after this proce dure will give valuable information of the tumor characteristics, its relation to intraorbital structures, and its extension outside the bony orbit (figs. 8 and 9). In a few cases, particularly cavernous hemangiomas, lymphangiomas, and some cirsoid aneurysms, which biopsy has shown are formed of wide vascular or lymphovascular spaces or blood cysts, the material can be in jected directly into the tumor mass, thus al lowing the surgeon to see the extension of the tumor and to decide on the feasibility of excision (fig. 10). Ultrasonography 18 can yield useful infor mation as to the size and shape of a tumor located anteriorly in the orbit, and in some cases the exact nature of the tumor can be determined. This technique, however, is still limited to a few research institutions. Radioactive isotopes are valuable in de tecting intraocular solid tumors, 19 but have not proved particularly successful in detect-
Fig. 6 (Silva) Right, contrast orbitography with forced injection. A selected technique with forced injection (6 to 10 cc) is preferred when tumor is suspected outside the muscular cone. The material fills the orbital cavity, outlining an encapsulated solid tumor located in the upper portion, as shown in the figure. Its morphologic characteristics are clearly seen. Compare with X-ray film on left. The tumor proved to be a malignant Schwannoma.
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327
Fig. 7 (Silva). The accuracy of this technique is clearly seen in this sequence. Left, a routine lateral X-ray film; center, the orbitographic lateral view, outlines the shadow of the tumor. (Sec arrows) Right, the resected tumor is placed over the orbitographic film. Note the correlation of size and shape of tumor, with its orbitographic image. This is a mixed benign lacrimal gland tumor.
Fig. 8 (Silva). Intracavity orbitography. In cystic tumors or those with liquid content the sac must be emptied and washed out before injecting the contrast material. An air bubble must finish the injec tion, to clean out the needle and so avoid dripping which may be confused with a fistula. It also improves the outline of the cystic image. These pictures correspond to a very large fronto-ethmoidal mucocele whose anatomic characteristics are clearly seen, thus greatly facilitating the surgical procedure.
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Fig. 9 (Silva). Intracavity orbitography. Important orbital structures must be clearly identified before surgery. The reflected tendon of the superior oblique muscle may be enclosed by the sac. Intracavity orbitog raphy indicates its position in relation to the cyst, and its orbital attachment. This helps avoid damage during surgical maneuvers. ing orbital tumors. Although I personally have had no experience with this method, it is promising.
Exhaustive clinical examinations, routine laboratory tests, simple radiographic studies and orbitographic techniques with positive
Fig. 10 (Silva). Orbitography with direct injection into the tumor mass. The technique must be reserved for diffuse recognized hemangiomas or cases with large vascular spaces in which extension into the orbit must be known for surgical evaluation. This case of a relapsing cavernous hemangioma was easily removed in toto after orbitographic information.
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ORBITAL TUMORS TABLE 8
THERAPEUTIC PROCEDURES IN 300 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis
B iopsy
Ant. Orbit
Lat. Orbit
13 30
2 3
1 1
65
90
61
Total
19 7 1 12
5
7 4 4 3 3
6 8 5D 8 7
1
1 2
7 5
4
1
Radio therapy 27 1 21 21
Chemo therapy
17 14
18 2
7
8
9 8 6 7 2
13
4 1 1
5 4
1
2
86
144
1 8 7 7
7
1
2 2
contrast media, as described above, are most helpful in making a presumptive diagnosis. Once the presumptive diagnosis of exophthalmos due to orbital tumor is made, a biopsy should be done. Treatment must be in direct relationship to the increase of the exophthalmos, which parallels the growth of the tumor mass and endangers the visual func tions and the eye itself. Accurate diagnosis at an early stage is essential. Following are suggestions for treatment: 1. All benign expanding orbital lesions should be handled conservatively, without disturbance of function, eye or lid motility, or esthetic aspect. 2. In-block resections, with wide safety margins, should be carried out and lymphatic drainage areas radically excised if spread of the tumor to the local lymph nodes is sus pected. 3. In inoperable tumors with orbital in volvement of systemic disease, and in meta static tumors to the orbit, radiotherapy or chemotherapy, or both, should be carried out.
Radical Exent.
14
16 Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias 13 3 Dermoid cysts 3 Carcinomas of palpebral origin 3 Hemangiomas Meningiomas Endocrine ophthalmopathy 6 Lacrimal gland tumors 1 Peripheral nerve tumors 2 Rhinogenic carcinomas 4 Malignant melanomas Undifferentiated sarcomas 5 Carcinomas of epibulbar origin Metastatic carcinomas 2 Osteomas Fibrous dysplasias Rhabdomyosarcomas 1 Fibrosarcomas 1 Osteosarcomas 2 Gliomas of optic nerve Lymphangiomas 3 Cysticercosis Miscellaneous
11
Transcranial
2
1
6
40
4. Radical surgery of the orbit should be done only in cases of malignant tumor. Immediate plastic repair of radical surgery should not be done as it may interfere with early detection of relapses in situ. We have applied these rules in treating the 300 cases in this series, as shown in Table 8. Biopsy was the sole surgical proce dure in 65 of the 300 cases in this series, mainly for pseudotumors, orbital manifesta tions of systemic disease, and endocrine ophthalmopathies. Anterior orbitotomies were done in 90 cases. We found the superointernal approach to be the most satisfactory in resecting mucoceles, osteomas, and many dermoid cysts of the superointernal orbital angle. The Benedict incision over the exter nal orbital rim was also used successfully to resect dermoid cysts, benign lacrimal tu mors, hemangiomas, and some meningiomas and neurilemmomas. The Davis inferior ap proach was used in the resection of two gliomas and two meningiomas of the optic nerve.
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The lateral approach with Kronlein's op eration (Berke's modification), was used in more than 50 cases. Guillaume procedures to ensure a wider opening when resecting some meningiomas of the lesser wing of the sphenoid are grouped here also, as are some cases of lateral orbital decompression. The transcranial approach to the orbit was used in only six cases in this series, two with unsatisfactory results (one, a resection of a glioma of the optic nerve, resulting in palpebral ptosis and flaccid proptosis with neuroparalytic keratitis; the other, an intratecal psammomatous meningioma that could not be resected in toto through the orbit, or transcranially). Radical surgery was carried out in 86 cases, 61 of which required orbital exenteration. Other radical procedures, including ethmoid resection, sinus curettage and par tial or total resection of the superior maxilla, were done in epithelial lacrimal gland tumors and in invading carcinomas of palpebral or rhinogenic origin. There was one far-ad vanced case of osteosarcoma and one of a mucocele with all the periorbital sinuses af fected. Opening of the optic canal to resect the nerve invaded with retinoblastoma, re section of bone adjacent to the temporal fos sae in other cases, and large resections of frontal bone in orbital reproductions of lac rimal gland tumors are also included in this group. Radiotherapy combined with corticosteroids was indicated in most of the pseudotumor cases and the results were gratifying. This treatment was also beneficial in dimin ishing the residual proptosis after de compression surgery in cases of endocrine ophthalmopathy, often with dramatic results.20 The synergic action of radiotherapy and selective chemotherapy proved useful in treating certain malignant orbital tumors. In one case of rhabdomyosarcoma, this therapy, combined with Actinomycin D, seemed to hold out hope of a complete cure, but unfor tunately this did not materialize.21 Proptosis
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from multiple myelomas of the orbit disap peared with radiotherapy combined with Melfalan22 (fig. 11), as it did also in two cases of Hodgkin's lymphoma in which alkylating agents were administered, and in sev eral cases of leukemia with primary orbital localization in which synergic action of methotrexate-purinetol-prednisone and ra diation restored the eye (if not the patient) to normal condition. Thio-TEPA was used in all retinoblastoma cases when TEM was no longer available.23 Oncovin (Vincristine) was used in transoperative parenteral perfusion in all melanotic tumors, 24 most of which were orbital extensions of uveal melanoma or invasions from conjunctival foci. ThioT E P A has not proved effective in melanotic tumors. 25 A comparison of opinions might be inter esting. Reese26 believes that mucoceles should be removed by the otolaryngologist; however, I feel that after intracavity orbitography, removal of mucoceles by anterior orbitotomy ensures the functional preserva tion of the superior oblique muscle which is visualized with this technique. It is also helpful in learning when a bony erosion of the orbital roof can be expected, thus ena bling the eye surgeon to protect the dura when dissecting the mucocele walls adherent to it. Dyeing the cavity before emptying it is a useful surgical maneuver to ease total re section, as the entire mucocele wall is more easily seen. Recurrence due to incomplete re section is more likely with the intranasal curettage technique than with the direct vi sual control obtained by anterior orbitotomy. It has been claimed that more satisfactory cosmetic results are achieved by the transcranial approach (Ray 2 7 ). However, to ex pose a patient to neurosurgical intervention in order to resect a benign expanding orbital lesion does not seem very advantageous (fig. 12). The results in the 30 cases of mucoceles in this series could not be more gratifying.28 In 29 patients the frontoethmoidal mucoceles were totally removed without damage to eye
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331
Fig. 11 (Silva). Orbital localization of multiple myeloma. This patient had a bone inolvement of cranium and both humeri. Diplopia preceded the development of right exophthalmos. Orbitography revealed presence of a mass in upper part of right orbit going deeply below orbital roof (see arrows). Biopsy showed fibrous mass impregnated with myeloma cells. Radiotherapy, combined with Melphalan, reduced the proptosis, with disappearance of diplopia. motility and with practically no disfigure ment, except in very advanced cases. In one patient with carcinomatous degeneration, suspected after orbitography and confirmed by histologic study, the tumor was controlled with postoperative radiotherapy. In an ad vanced case with mucoceles filling all the periorbital sinuses and the eye lost from corneal perforation and endophthalmitis, an orbital exenteration was immediately closed with a large skin flap. Although Reese29 believes that most or bital meningiomas are the bailiwick of the neurosurgeon, in this series, 12 out of 16 meningiomas were removed easily using ei ther the anterior or lateral approach. Those of primary origin in the orbit were easily enu
cleated by digital dissection. In one case or bital exenteration was done because of comitant endophthalmitis (which can lead to er roneous diagnosis). Four cases are grouped with transcranial procedures because of a further attempt to remove the intracranial extension of the meningioma, although this proved to have been necessary in only two cases. I agree wholeheartedly with Reese in op posing the transcranial approach for lacrimal gland tumors, systemic orbital manifesta tions and diffuse orbital neoplasms, and also when, in a discussion with Poppen,30 he in sisted that diagnosis of orbital lesions be made by the eye surgeon. For biopsy pur poses, there is undoubtedly less risk for the
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Fig. 12 (Silva). Enormous fronto-ethmoidal mucocele. The anterior approach was used in this patient. The mucocele was resected after freeing the reflex portion of the superior oblique muscle, previously iden tified by the orbitography. The immediate postoperative result shows the good cosmetic appearance and the restoration of the eye to its normal position.
patient in transconjunctival orbitotomy than in trans frontal craniotomy. To avoid the transcranial approach, I try not to com pletely remove a meningioma of the optic nerve near the optic foramen, thus, as with Stallard's 31 procedure, eliminating the risk of exposing the nerve supply of the eye and lids to injury during surgery, which might result in a cosmetic defect. Further growth in the remaining benign tumor is so negligi ble that the patient can be considered cured without postoperative disfigurement. This applies also to a glioma of the optic nerve (not included in this series) in which I fol lowed Hogan's procedure: resecting, for biopsy, a mass sufficiently large to restore the normal position of the eye. The proptosis was reduced and no further growth of the tumor was apparent (fig. 13).
Orbital neurofibromas truly are a thera peutic problem. Excision of a solitary tumor of the orbit is simple and the results satis factory, but in the plexiform variety (the commonest) there is no end to palliative op erations to reduce the proptosis, improve the cosmetic aspect of the affected eyelid, or correct the ptosis. If the tumor erodes the bony orbit, penetrating to the cranium or ex tending backward by way of the temporal fossae, the eye surgeon is relieved in refer ring the patient to someone else. Fibrous dysplasias originate mainly around the maxillary antrum. Spreading out ward, they reach the orbit and produce exophthalmos. I have been consulted by head and neck surgeons in a number of these cases and in all I performed wide anterior orbitotomies of almost all the medial half of the
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Fig. 13 (Silva). (A) Meningioma of the optic nerve removed by lateral orbitotomy using Berke's modification of the Kronlein tech nique. (B) Postoperative appear ance of patient proves that transcranial approach cannot be justified on grounds of better cosmetic end results. (C) Pathologic specimen.
orbit. Spreading the orbital tissues outward exposed the intraorbital portion of these tumors without damage to the lacrimal passages, the superior oblique muscle, or the internal palpebral ligament. After complete removal
of the tumor, the orbital tissues were placed in their original position (fig. 14). This technique was followed also in managing secondary orbital tumors, such as osteomas, in the internal portion of the orbit.
Fig. 14 (Silva). Ossifying fibroma removed by anterior orbitotomy. The incision followed half of the interior orbital rim. It was necessary to separate the inferior oblique muscle and the lacrimal ducts which were both replaced at the end of surgical extraction of a highly vascularized tumor which filled the inner orbit, the entire right nostril and the maxillary antrum. The patient retained his ocular motility and visual acuity. X-ray films show the restoration of air passages and re-establishment of radiographic bone density on right side.
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Their resection is simple: After a wide in ternal orbitotomy, the tumor is exposed and dissected from the periorbita; its base is then separated with a chisel and the f rontoethmoidal cells are curetted (fig. 15). Soft tissues are replaced and the skin is sutured without drains. In one case however, com plete removal of a gigantic osteoma was not possible. At the suggestion of Byron Smith (New York), because it filled and over flowed the entire orbit of the only useful eye, I drilled out only the portion invading the orbital cavity, in order to get the eye back in place and liberate the compressed optic nerve. Smith and I were highly satis fied with the final result32 (fig. 16).
MARCH, 1968
In this series, infiltration of the retrobulbar region occurred most frequently with pseudotumors. It is not possible, with orbitography, to differentiate an infiltrating tumor such as reticulosarcoma, which commonly occurs unilaterally, or orbital myositis of endocrine origin, if thyroid tests are nega tive. Orbital fibrositis, the flat variety of pseudotumor, might be mistaken for the fi brous infiltration of inferior rectus and oblique muscles in endocrine ophthalmopathy if palpebral retraction is not present. Be cause of the unreliability of thyroid tests, biopsy is therefore the most reliable test for making a differential diagnosis.33 In pseudotumor, surgery is done only for
Fig. 15 (Silva). Nasal osteoma invading the orbit. This patient complained of marked diplopia with history of long-standing nasal obstruction. X-rays showed existence of very large osteoma whose extension can be seen. Removed through anterior internal orbitotomy. Incision extended to lateral side of nose. Macroscopic aspect of operative specimen.
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biopsy. Once a correct diagnosis is made, treatment with corticosteroids and radiother apy is indicated. Satisfactory results were obtained in all 31 cases of pseudotumor in this series. In one case, however, a pseudotu mor reappeared in the fellow eye. Primary benign lesions sometimes present a surgical problem. Dermoid cysts may grow deep in the orbital apex. Resection can be difficult and, if incomplete, recurrence can be expected. In dermoids of the eyebrow it is necessary to resect both the intra- and extraorbital portions, together with the bony area from which they originate. Dermolipomas of the outer canthus often grow deep. They must be dissected from the external muscle and, because conjuctiva adheres to their surface, the wound should be closed with a mucous membrane graft. In pseudocholesteatomas, curettage is the procedure of rhnire fnr rpmnvincr the raraffinlike material
Fig. 17 (Silva). Enormous congenital hemangioma involving entire right side of face. Syndactyly is also seen. In cases such as this, the surgeon is helpless.
Fig. 16 (Silva). Large fronto-ethmoidal osteoma in a patient whose opposite eye was blind. As the vision in the right eye was being impaired by the optic nerve distention due to the forward displace ment of the eye ball, because of the growth of the osteoma, a partial removal was made. Through an anterior internal orbitotomy a new orbital cav ity was formed by drilling out the part of the oste oma which filled the orbit. The eye ball was then put back in its proper position. This partial opera tion proved very successful as the benign tumor has not regrown since surgery. Dotted lines show amount of resection and arrow points to the nar row optic foramen.
which fills them. The capsule must be re sected completely to prevent recurrences. Teratomas require exenteration in most cases. The treatment of orbital hemangiomas is controversial. The congenital type is the most difficult to manage, as the surgeon faces two problems: the tumor itself, and the family's pressure upon him. The surgeon may choose to temporize rather than use freezing or sclerosing injections, or perform even partial resection. Radiation may not reduce the size of the tumor and may endan ger future growth of the orbit. One may hope for spontaneous regression as the child becomes older. However, the surgeon is helpless in advanced cases (fig. 17). A capillary hemangioma can be resected partially, as it too may regress. Orbitography with positive contrast material injected
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Fig. 18 (Silva). Cavernous hemangioma treated by transconjunctival approach. (A and B) This 4year-old girl had a cavernous hemangioma which developed an acute exophthalmos during an attack of whooping cough. (C) Microscopic aspect of the tumor. (D) Prompt surgical treatment led to an excellent and rapid recovery. directly into the tumor may be helpful in de termining the feasibility of total resection. This is true also of hemolymphangioma, in which partial resection is sometimes difficult. One has to control profuse bleeding from thinly walled vessels or blood lacunes which are prone to break easily. On the other hand, encapsulated cavernous hemangiomas in the adult are easily removed by digital dissection through direct approach (fig. 18). A tumor of the lacrimal gland is difficult to manage. When clinical exploration and orbitography have shown its location in the lacrimal fossae, removal is indicated if it is found to be encapsulated, as this type is gen erally a benign mixed tumor. However, if the tumor is diffuse, orbital exenteration is indicated without the generally advised deep bite for biopsy which may result in cellular dissemination. Because of the problems faced in surgery of this type of tumor, at Limon's suggestion (Dr. Noriega Limon) I order a short course of prophylactic radia tion before surgery, not only for prevention
of cellular dissemination but also for ruling out an inflammatory lesion of the lacrimal gland. Although with this procedure there is risk of excising a pseudotumor or benign lacrimal gland lesion, so far this has not hap pened. After histologic study we proceed as fol lows: Orbital exenteration is done if malig nancy is found, care being taken to perform a sufficiently wide resection of the adjacent bone if it is infiltrated. The exenterated orbit is gauze-packed or, at most, covered with a split-thickness skin graft. Immediate plastic repair is not advisable. In this series, there have been three recurrences out of 14 cases of lacrimal gland tumor. Orbital melanoma also requires early radi cal surgery—formerly exenteration, but now, at Hogan's 34 suggestion, enucleation of the eye with exteriorized melanoma. Vincristine is administered transoperatively and in week ly doses as tolerated. Thio-TEPA has proved to be ineffective. Orbital carcinomas of palpebral, epibulbar
Fig. 19 (Silva). Upper left, rhabdomyosarcoma of left orbit in a 9-year-old girl. Upper right, after tumor was removed by orbital exenteration, with split thickness skin graft. Lower left, pathologic speci men. Lower right, microscopic aspect shows embryonal type with very few striated cells. This is the only patient with rhabdomyosarcoma surviving five years after surgery and radiation therapy.
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9. Silva, D.: Incidencia y Diagnostico en Patologia Tumoral Orbitaria. Gac. Med. Mexico 97:604, 1967. 10. Drews, L. C.: Exophthalmometry. Am. J. Ophth. 43 :37,1957. 11. Tengroth, B., Bogren, H., and Zackrisson, U.: Human exophthalmometry. Acta Ophth. 42:864, 1964. 12. Silva, D., and Acosta Ruiz, R.: Exof talmometria Radiografica. Arch. As. p. e. Ceguera en Mex. II Serie9:18, 1967. 13. Silva, D.: Tumores Orbitarios: Metodos Radiologicos. Arch. As. p. e. Ceguera en Mex. II Serie 4:9, 1962. 14. Silva, D., and Arribas Aveleyra, E.: Exploracion Radiologica de los Tumores de la Orbita con Medios de Contraste. El Medico 12 :35, 1962. 15. Ziedses des Plantes, B. C.: Substraktion. Stuttgart, Thieme, 1961. 16. Cowie, J. W., and Groves, J. S.: Preliminary CONCLUSION report on the use of contrast media in orbital radi There are endless aspects of this discus ography. Brit. J. Ophth. 39:283,1955. 17. Silva, D.: Diagnostico Radiografico de los Tu sion. I must say, however, that the practice mores Orbitarios. In: Troutmann, R. C, Converse, of this not-very-favored sector of ophthal J. M., and Smith, B.: Plastic and Reconstructive mology has given me the satisfaction of sav Surgery of the Eye and Adnexa. Washington, Buting many eyes which otherwise might have terworth, 1962, p. 71. 18. Baum, G., and Greenwood, I.: Orbital lesion been enucleated, with benign tumors held in localization by three dimensional ultrasonography. the orbit, and preservation of ocular func New York J. Med. 61:4149, 1961. 19. Newel'l, F. W., Goren, S. B., Brizel, H. E., and tion that could have been damaged by other Harper, P. V.: The use of Iodine-125 as a diagnos methods of surgery. tic agent in ophthalmology. Tr. Am. Acad. Ophth. Otolaryng. 67:177, 1963. I firmly believe that the responsibility of 20. Werner, S. C.: Prednisone in emergency treat managing orbital tumors must rest, in almost ment of malignant exophthalmos. Lancet 1:1004, 1966. every case, with the eye surgeon. 21. Pinkel, D., and Pickren, T-: RhabdomyosarHamburgo 203 coma in children. JAMA 175:293, 1961. 22. Brook, J., Bateman, J. R., and Steinfeld, J. REFERENCES L.: Evaluation of melphaian (NSC-8806) in treat 1. Birge, H. L.: Meningiomas: An ophthalmic ment of multiple myeloma. Cancer Chemother. Rep. 36:25,1964. problem. Am. J. Ophth. 31:828, 1951. 23. Chapman, R. B.: Retinoblastoma. Clin. Pediat. 2. Dandy, W. E.: Orbital Tumors; Results Fol lowing the Transcranial Operative Attack. New 5 :86,1966. 24. Reitemeier, R. J., Moertel, C. G., and Black York, Oskar Piest, 1941. 3. Castaneda, G.: Ideario Clinico en Aforismos y burn, C. M.: Vincristine (NSC-67574) therapy of Frases Breves. Edit, e Impres. Ciceron. Mexico, adult patients with solid tumors. Cancer Chemother. 1946. Rep. 34:21,1964. 25. Stehlin, J. S., Jr., Smith, J. L., Jr., and 4. Forrest, A. W.: Intraorbital tumors. Arch. Clark, R. L., Jr.: The present status of chemother Ophth. 41:198,1949. 5. Porterfield, J. F . : Orbital tumors in children: apy for malignant melanoma. Proc. Natl. Cancer a report on 214 cases. Internat. Ophth. Clin. 2 :319, Conf. 4:625,1960. 1962. 26. Reese, A. B.: Incidence and management of 6. Reese, A. B. and Jones, I. S. In Moss, H. M. : unilateral proptosis. In: Boniuk, M.: Ocular and Expanding lesions of the orbit. A clinical study of Adnexal Tumors. New and Controversial Aspects. 230 consecutive cases. Am. J. Ophth. 54:761, 1962. St. Louis, Mosby, 1964, p. 389. 7. Silva, D.: Consideraciones sobre el Diagnostico 27. Ray, B. S.: Intracranial operations for dis y Tratamiento de los Tumores de la Orbita. Cir. eases of the orbit and adjacent structures. Am. J. Cir. 30:93,1962. Ophth. 54:581,1962. 8. Silva, D.: El Manejo Clinico de los Tumores 28. Silva, D., and Gomez Leal, A.: Mucoceles y Orbitarios. Analisis de 185 casos consecutivos opera- Dermoides orbitarios. An. Soc. Mex. Oftal. 37:104, dos. IV Gradle Lecture. Arch. As. p. e. Ceguera en 1964. Mex. IISerie7:3, 1965. 29. Reese, A. B.: The role of the neurosurgeon in
or rhinogenic origin, require early radical surgery. If bone invasion or lymphatic infil tration is found, surgery must be considered palliative, and radiotherapy and chemother apy used to control painful episodes. In mesenquimal tumors such as rhabdomyosarcoma, fibrosarcoma, osteosarcoma, undifferentiated sarcoma, etc, biopsy is fol lowed by exenteration which, if done in the early stage, may increase the life expectancy of such patients. Radiotherapy and chemo therapy are of little value if early radical surgery does not control the disease, as shown in 18 cases in this series (fig. 19).
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the treatment of orbital tumors. Am. J. Ophth. 58:140,1964. 30. Poppen, J. L.: Neurosurgical approach to the orbit. In Boniuk, M.: Ocular and Adnexal Tumors. New and Controversial Aspects. St. Louis, Mosby, 1964, pp. 466 and 491. 31. Stallard, H. B.: A plea for lateral orbitotomy with certain modifications. Brit. J. Ophth. 44:718, 1960. 32. Silva, D. and Plascencia, J. A.: Osteoma gi-
339
gante del hueso frontal con invasion orbitaria masiva. Arch. As. p. e. Ceguera en Mex. 6:41,1964. 33. Silva, D.: Exof talmos endocrino unilateral. Su diagnostico diferencial Gac. Med. Mex. 97 :27, 1967. 34. Hogan, M. J.: Clinical aspects, management, and prognosis of melanomas of the uvea and optic nerve. In Boniuk, M.: Ocular and Adnexal Tumors. New and Controversial Aspects. St. Louis, Mosby, 1964, p. 203.
ADHESION O F REGENERATING CORNEAL E P I T H E L I U M T H E ROLE OF BASEMENT MEMBRANE A L I A. KHODADOUST, M.D.,
ARTHUR M.
SILVERSTEIN,
PH.D.,
K E N N E T H R. KENYON,* AND J O H N E. DOWLING, P H . D .
Baltimore, Maryland The corneal epithelium, consisting of a layer five to six cells thick that rests on a basement membrane, provides the main pro tective barrier for the underlying cornea. For this protective barrier to maintain its in tegrity and thereby function efficiently, it must fulfill two important requirements: the maintenance of an unbroken layer of cells over the entire corneal surface, and the tight adhesion of this layer to Bowman's mem brane in some species, or directly to the cor neal stroma in others. When the corneal epithelium is subjected to physical or chemical injury, the woundhealing process is directed primarily toward reestablishing the continuity of the epithelial covering of the cornea, and only later toward developing tight adhesion to the underlying tissue. This study is primarily concerned with the latter aspect of corneal wound healing. To provide a proper context for the ex periments reported here, we briefly review
From The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine. These investigations were supported in part by USPHS Research Grants NB-03040 and NB-05336 from the National Institute of Neurological Dis eases and Blindness, by an unrestricted grant from the Alcon Laboratories, Inc., and by an Independent Order of Odd Fellows Research Professorship. * Alfred P. Sloan Foundation Fellow.
what is known about the healing process of corneal epithelium. Many investigators have shown that two phenomena are involved in the repair of superficial corneal injuries.1-3 There is first the epithelial "slide," by which the cells surrounding the denuded area im migrate rapidly to cover the site of injury. This is followed some time later by a burst of mitotic activity, assisted by a temporary pause in the natural process of exfoliation, and resulting in reconstitution of the normal number of epithelial cells and a normal epi thelial thickness. The sliding process com mences as early as one hour after injury, and continues until the denuded area is com pletely covered by a monolayer of epithelial cells. Each cell, by spreading and flattening, can cover several times its normal area, so that a small defect may be repaired rapidly even without multiplication of cells. The proliferative phase starts several hours later, when the inhibitory effect of the mechanical insult has subsided. Mitotic activity gener ally starts in the two deepest layers of the epithelium, and even at some distance from the site of the defect. We can thus see how the damaged cornea re-covers itself with epithelium, a step which is important not only in restoration of the protective barrier, but also as an important contribution to the underlying stromal heal-
Mexico Cit;, Mexico Years ago I pointed out the need for an integrated study to establish the incidence and causes of ocular proptosis, and subse quently most of the orbital tumor cases in my country have been referred to me. I have always considered orbital tumors to be the field of the ophthalmic surgeon (as stated also by Birge 1 ), with, of course, the advice and technical assistance of the neurosurgeon, head and neck surgeon, or other specialist when necessary. However, at one time these tumors were generally referred to the neuro surgeon, due to the widespread acceptance of Dandy's 2 ideas. The refined diagnostic techniques in use today were lacking when I began my study, and inaccurate diagnoses were not uncom mon. Consequently, orbital surgery, like Pandora's box, was full of surprises. (I often recall an aphorism of my teacher Gonzalo Castaneda,3: "What is not known is not looked for, and what is not looked for is not found.") Initially, I analyzed data collected from a variety of sources, reviewing clinical histo ries and pathologic and radiologic findings in various large hospitals, and studying series of consecutive cases in the literature. Con siderable differences were apparent in the se ries of cases, due mainly to the origin of the material collected and to the specific interest of the investigator. Thus, in Forrest's se ries,4 hemangioma was the most common le sion; in Porterfield's,5 rhabdomyosarcoma; and in Reese and Jones', 6 endocrine exophthalmos. Differences in tumor incidence between Mexico and other countries were clearly eviFrom the Hospital de la Asociacioft para Evitar la Ceguera en Mexico and the Hospital de Oncologia del Instituto Mexicano del Seguro Social. Read before the Chicago Opthalmological Society May 20, 1967.
dent and I finally decided to include data only from Mexico. A new study was begun, using the criteria of Reese and Jones, and including only patients I saw personally, with diagnoses confirmed histologically. The patients were selected from the Hospital of the Association for the Prevention of Blind ness in Mexico, the Oncology Hospital of the Mexican Institute of Social Security, and from my private practice. (Portions of this study have been reported previously7-8). A year ago, I compared a series of 230 consecutive cases with Reese and Jones' series (table l ) . 9 Pseudotumor was found to be the commonest cause of unilateral exophthalmos in my series, whereas endocrine exophthalmos (mainly diagnosed clinically and confirmed in nine cases by orbital sur gery) was the most common in Reese and Jones' series. The series reported here includes 300 pa tients, all of whom underwent surgery, at least for biopsy (table 2). With broader knowledge of etiologic factors, improved techniques, and my own enlarged experience, initial clinical diagnoses were confirmed much more frequently than in previous studies. Table 1 shows the relative frequency and the histologic findings of orbital tumor in this series. FINDINGS
One in three cases was a pseudotumor, a mucocele, a dermoid cyst, or a soft tissue hyperplasia of endocrine origin, found with similar incidence in all age groups (table 3 ) . The unusually high incidence of retinoblastoma with orbital involvement (the tumor most common in the age group below 10 years) may be explained by the fact that at the Oncology Hospital we usually see only children referred for radiotherapy or chemo therapy.
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Table 4 shows the relative sex incidence of orbital tumor. Female predominance may be attributed to the higher proportion of women patients at the Hospital of the Asso ciation for the Prevention of Blindness, the source of most of the patients in this series. The ratio of unilateral to bilateral exophthalmos was approximately 15 to 1, even in cases of systemic disease such as leukemia, multiple myeloma, Hodgkin's disease, endo crine disturbance and reticulosarcoma. Many cases of bilateral retinoblastoma were far ad vanced when first seen. In these, orbital ex tension was usually found in the most se verely affected eye, which was subsequently removed. With orbital recurrence, optic nerve extension was often found in the fel low eye. Lymphangioma was usually found in both eyes. Pseudotumor was found, in one inTABLE 1
319 TABLE 2
HlSTOLOGIC NATURE OF 3 0 0 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias Rhabdomyosarcom as Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous Total
Number 31 30 21 21 20 18 16 16 15 14 13 13 10 8 7 7 7 6 5 4 3 3 3 3 6 300
ETIOLOGIC DIAGNOSIS OF 230 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis
Pseudotumors Mucoceles Dermoid cysts Meningiomas Orb. ext. of retinoblastoma Carcinomas of palpebral origin Hemangiomas Endocrine ophthalmopathy Malignant lymphomas and leukemias Rhinogenic carcinomas Lacrimal gland tumors Malignant melanomas Peripheral nerve tumors Undifferentiated sarcomas Carcinomas of epibulbar origin Osteomas Fibrosarcomas Rhabdomyosarcom as Osteosarcomas Gliomas of optic nerve Metastatic carcinomas Lymphangiomas Cysticercosis Miscellaneous Exophthalmos of unknown cause
Silva 1966 ,c • n (Surgical)
Reese & Jones 1962 (c,inical)
26 25 18 15 15
18 6 7 11
14 13 11
28 37
11 11 10 9 8 6 4 4 4 4 3 3 3 2 2 9
22 17 7 2 2 5 8 8 10 18 24
stance, to appear subsequently in the fellow eye. There was one case each of bilateral or bital varices and mucocele, although these are generally considered to occur only unilat erally (table 5). Histologically benign tumors were found in 58% in this series. However, some of these tumors led to serious consequences by their extension, causing damage to neighbor ing structures, visual disturbances, disfig urement, or poor general health, especially in cases of hemangioma, neurofibroma, and cystic tumor (mucocele and dermoid). One case of frontoethmoidal osteoma with deep extension into the orbit resulted in almost total blindness due to optic nerve compres sion. Malignancy was found in two out of every five cases of expanding orbital lesions. Although sufficient time has not elapsed for final evaluation, at present more than 60% of these patients have died. The number of recurrences is shown in Table 6. Again, there has not been sufficient
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TABLE 3 AGE DISTRIBUTION OF 300 CONSECUTIVE CASES OF ORBITAL TUMORS
Diagnosis
Number
Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis M iscellaneous
31 30 21 21 20 18 16 16 IS 14 13 13 10 8 7 7 7 6 5 4 3 3 3 3 6
Total
300
time to evaluate the incidence accurately, al though the number is expected to increase. A diagnosis of expanding orbital tumor was made in 48.6% of the cases in this se ries after complete clinical examination using routine techniques (table 7), later con firmed by histologic examination. Special ex ploratory techniques were used in some cases and the pathologic nature was correctly diag nosed in 64.3%. However, in 16.6% no tumor could be detected even with digital palpation through external canthotomy. A biopsy was then necessary to learn the etiol ogy of the exophthalmos. Biopsy at the time of surgery was often unsatisfactory, as the specimen was some times taken from a nonrepresentative por tion of the tumor, or the frozen sections did not permit accurate histologic diagnosis, as for instance, in diffuse infiltrating tumor or in endocrine exophthalmos and, more com monly, in undifferentiated sarcoma, lacrimal gland tumor, and orbital metastasis. After proper embedding and staining of the biopsy material, accurate diagnoses could be made.
0-9
10-29
30-49
50-69
11 6 1 5 11
7 10
4 13
1 1
2 1
9 1 8
2
1
7 3 1 4 11
1
1 4
2 6 6 5 1 4 3 1
8 20 3 7 6 2
1 2 3 1 1 2 3 3 1 65
1 4 3 2
1 1
70-<
10 1
5 8 2
3
6 5 1 5 1 1 1
2 2
1
2
2
1
78
56
72
3 1 1 2 4
1
29
SEX DISTRIBUTION OF 300 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis
Males
Females
Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous
11 14 9
20 16 12
7 9
14 11
7 7 3 8 7 5 7 4 6
11 9 13 7 7 8 6 6 2
4 2 3 5 2 2 2 1 1
3 5 4 1 3 2 1 2 3 3 5
129
171
Total
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321
ORBITAL TUMORS TABLE 5 SITE OF PRESENTATION OF 300 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias. Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous Total
Number
Right Eye
Left Eye
31 30 21 21 20 18 16 16 15 14 13 13 10 8 7 7 7 6 5 4 3 3 3 3 6
17 12 10 9 11 8 10 7 5 6 9 4 6 6 2 2 2 1 1 3 1 3
14 17 S 6 9 10 6 9 7 8 4 9 4 2 5 5 4 5 4 1 2
1 1
2 4
1
300
137
142
21
Bilateral 1 6 6
3
1
3
TABLE 6 CLINICAL EVOLUTION OF 300 CONSECUTIVE CASES OF ORBITAL TUMOR
Clinical Evolution
Cellular Character Diagnosis Benign Malignant Pseudotumors Mucoceles Orb. Ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasisas Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous
Total
31 29
1 21 21
20
Benign 30 28 1 19
18 16 16 15 8 13
6
10 15 14 8 10
13 10 8 7 7 7 6 5
6 6 1
1 6 3 13 10 8 7 7 1
1 2 11 2 10 7 1 1 3 3 6 1
16 6 9
5 4 6 5 3 4
I 2
4 4 3
5
3 3 3 1
5
1
2
125
158
137
51
71
3
175
2 20 21 1 18 3
Death
4 4 3
4 3 3 3 1
Malignant Recurred
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TABLE 7 DECISIVE FACTORS IN DIAGNOSIS OF 300 CONSECUTIVE CASES OF ORBITAL TUMOR Diagnosis Histologic Nature
No. Tumor
Pseudotumors M ucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias Dermoid cysts Carcinomas of palpebral origin Hemangiomas Meningiomas Endocrine ophthalmopathy Lacrimal gland tumors Peripheral nerve tumors Rhinogenic carcinomas Malignant melanomas Undifferentiated sarcomas Carcinomas of epibulbar origin Metastatic carcinomas Osteomas Fibrous dysplasias Rhabdomyosarcomas Fibrosarcomas Osteosarcomas Gliomas of optic nerve Lymphangiomas Cysticercosis Miscellaneous Total
31 30 21 21 20 18 16 16 15 14 13 13 10 8 7 7 7 6 5 4 3 3 3 3 6 300 100%
In a few cases, a definite diagnosis was es tablished only by careful follow-up. Exophthalmos can be categorized as fol lows: 1. Proptosis of less than 5 mm difference in the two eyes, no visual damage, no mass, and no measurable progress. In this cate gory, routine studies, including X-ray exam ination, are carried out and the patient is fol lowed closely for evidence of progression. 2. Proptosis of more than 5 mm differ ence in the two eyes, with signs suggestive of tumor behind the globe, visual impair ment, and definite expansion. Special radiographic techniques are used to determine the position of the tumor before entering the orbit for digital palpation. 3. A visible or palpable mass in unilateral exophthamos, with or without visual impair ment and expansion. Before attempting to remove the tumor, orbitographic techniques are used to earn the anatomotopographical characteristics.
IS 30 21 IS 19 18 13 13 11 14 13 11 S 4 7 4 7 6 4 4 3 3 3 3 3 250 83.3%
Clinical study
Path. Nature 9 30 21 11 19 18 10 9 5 12 11 11 3 7 4 7
1 2 2
193 64.3%
Routine
Special
Biopsy
6 30 21
9 30
17
15 11
2 2
7 1 3 7 7 8 2 2 2 5 8
4
4
5 3 4
6 5 4 2
8 15 5 5 7 3 7 11 3 1 7 1 7 1 2 1 1 2 2 1 146 48.6%
7 8 5 9 5
2 1 5 128 42.6%
1 3 6 100 33%
How can we be sure of the progression of the proptosis ? By and large, the instruments in common use for measuring exophthalmos have proved unreliable. Drews 10 has pointed out their inaccuracies, which are due mainly to facial assymmetry and parallax observa tion. Tengroth's 11 technique, however, re cords even very small changes of the posi tion of the eye in the orbit, independent of the investigator and even in the absence of the fellow eye. Since his technique was published, I have worked out a radiographic technique12 which I believe is simpler, as it eliminates the need for making a composite picture formed by superimposing the X-ray film, with the enlarged photograph being taken simultaneously. This technique has the sensitivity of Tengroth's and similarly elimi nates the sources of error—rotation of the head or eye (fig. 1). Following is a descrip tion : A contact lens with a central radio-opaque dot is placed on the eye close to the X-ray
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film making possible a comparison of the po sition of the cornea with the intracranial bony structures of the same side—the most important modification of Tengroth's proce dure. In his technique, the photographic pic ture of one side is superimposed on the radiographic image of the opposite side, the most clearly visible of the film. The technique is so simple it can be used routinely when lateral head X-rays are taken. The only modifications are the appli cation of the corneal-dotted contact lens, a fixation light directly in front of the patient, and steadying of the patient's head, with or without the aid of a cephalostat. With this technique one can determine with greater precision whether an exophthalmos of less than 5 mm or slightly larger is definitely progressive. If so, the case has ad vanced to the second category and the pa tient is reexamined ophthalmologically. Spe cial studies and orbitographic techniques are then carried out to learn if a tumor is pres ent. Radiographic studies are of utmost impor tance in detecting orbital tumors. 13 X-ray films of the orbit with the usual techniques (Watters, Caldwell, lateral, oblique for optic foramen, and Hirtz basal plates), may give sufficient information for location of the tumor or may suggest its existence by in creased density of soft tissue shadows. Rou tine pictures are often adequate for a correct
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Fig. 1 (Silva). Radiographic exophthalmometry. Lateral radiograph showing the nasion-clinoid and cornea-clinoid distances. The first is used as a checkline to know if successive films have been properly taken. Changes on the cornea-clinoid distance show the progress of the exophthalmos.
diagnosis, or at least may give evidence suf ficient to justify exploratory surgical palpa tion. Knowledge of the size, shape, extension of the tumor, its location in the orbit, its re lation with important adjacent structures, encapsulation, consistency and, if possible,
Fig. 2 (Silva). Retrograde phlebography. Percutaneous injection of contrast into the angular vein gives a good view of this varicose aneurysm in the upper portion of the orbit. Visualization of the nu tritional vessels through retro grade phlebography is valuable for the surgical treatment.
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the nature of the tissue from which it origi nates, is important for carrying out an excisional biopsy. The purpose of orbitographic techniques is the visualization and differentiation of the soft tissues within the orbit. The use of con trast materials in radiographic examination helps in differentiation of various intraorbital structures.14 These materials can be in jected into the vascular network or directly into the loose, areolar fatty tissues surround ing these structures (fig. 2 ) . Arteriographic or phlebographic tech niques help in diagnosing vascular tumors of arterial or venous origin. The diagnosis is sometimes indicated by variations in the nor mal pattern of the vascular network, more specifically in the phlebogram than in the more variable arteriogram. In certain vascu lar tumors in which control of the main af ferent vessel is necessary before surgical re moval, a much better view of the vessels can be obtained by using the subtraction tech nique of Ziedses des Plantes 15 (fig. 3). The materials used in extravascular orbitographies can be less dense than the sur rounding soft tissues—that is, air, oxygen, carbonic dioxide, or some other gas. This technique, combined with tomography, is preferred in North America. I, personally, do not favor it, as it produces a painful em physema which reabsorbs slowly and, in ad dition to unfavorable results reported in the literature, I have known of sudden death from an air embolism in two patients. Positive contrast orbitographies have proved most effective in detecting a sus pected tumor, in studying the anatomotopographic characteristics of an already recog nized progressive lesion and, in some cases, in eliciting further data for establishing the pathologic nature of the tumor. Yoduron Cilag (a bivalent hydrosoluble iodine preparation) has proved satisfactory in concentrations from 30% to 70%, despite Groves and Cowie's16 statement that concen trations higher than 17% to 2 5 % are harm ful to orbital tissues. Trivalent hydrosoluble
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iodine preparations are irritating to the eye and retrobulbar tissues, but are preferred in intravascular or intracavity orbitographies. There are five variations of orbitographic technique, with usage depending on the clini cal findings.17 If tumor of the optic nerve is suspected, or there is orbital extension of an intraocular neoplasm, 1-3 cc of the material should be injected into Tenon's capsule just behind the globe, with a curved needle that skims over the sclera, close to the optic nerve (fig. 4). If the exophthalmos is direct and the tumor cannot be palpated, the material is in jected into the muscular cone in amounts varying from 2-5 cc. Care must be taken not to force the material outside the intermuscular fascia. The radiographic changes of the well-known four-leaf clover image in the anteroposterior view will help in locating the tumor; its position deep in the orbit will be
Fig. 3 (Silva). Retrograde phlebography with subtraction technique. The subtraction technique helps to visualize numerous vessels which are other wise hidden by bone shadows. This cavernous hemangioma could not be treated solely by ligature of the main nutritional vessels.
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Fig. 4 (Silva). Orbitography with intra-Tenon's capsule contrast injection. The material has filled Tenon's space, giving a clear view of the unfilled part which corresponds to the optic nerve. Its considerable enlarge ment suggests the existence of a nerve tumor. This is a glioma of the optic nerve. Routine oblique, simple X-ray did not show its presence. easily shown on the lateral radiograph (fig. 5). If marked displacement or limitation of
motility of the globe suggest the tumor to be outside the muscular cone, a retrobulbar forced injection is carried out, filling the or-
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Fig. S (Silva). Orbitography with contrast ma terial injected into the muscular cone. The fourleaf-clover image is formed if contrast in small amounts (3 to 6 cc) is injected into the muscular cone. This typical image will exist if the material has not been forced out laterally through the intermuscular fascia, or forward to the anterior Charpy's foramen. Note destruction of the portion corre sponding to the superonasal quadrant, where the tumor was located. It was diagnosed as a primary orbital meningioma.
bital tissues. The radiographic image will show the profile of the tumor in contrast to the injected tissues. The firmer and more en capsulated the tumor, the more apparent the contrast. A ragged profile or presence of the stained contrast material image indicates a
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diffuse tumor. In this variation, as in the previous one, use of a dispersing solution will speed up the diffusion of the contrast material; hence, radiographs will be more demonstrative (figs. 6 and 7). If there is clinical suspicion of cystic tumor or of liquid content, the cavity should be washed out and refilled with contrast material. Radiographs taken after this proce dure will give valuable information of the tumor characteristics, its relation to intraorbital structures, and its extension outside the bony orbit (figs. 8 and 9). In a few cases, particularly cavernous hemangiomas, lymphangiomas, and some cirsoid aneurysms, which biopsy has shown are formed of wide vascular or lymphovascular spaces or blood cysts, the material can be in jected directly into the tumor mass, thus al lowing the surgeon to see the extension of the tumor and to decide on the feasibility of excision (fig. 10). Ultrasonography 18 can yield useful infor mation as to the size and shape of a tumor located anteriorly in the orbit, and in some cases the exact nature of the tumor can be determined. This technique, however, is still limited to a few research institutions. Radioactive isotopes are valuable in de tecting intraocular solid tumors, 19 but have not proved particularly successful in detect-
Fig. 6 (Silva) Right, contrast orbitography with forced injection. A selected technique with forced injection (6 to 10 cc) is preferred when tumor is suspected outside the muscular cone. The material fills the orbital cavity, outlining an encapsulated solid tumor located in the upper portion, as shown in the figure. Its morphologic characteristics are clearly seen. Compare with X-ray film on left. The tumor proved to be a malignant Schwannoma.
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Fig. 7 (Silva). The accuracy of this technique is clearly seen in this sequence. Left, a routine lateral X-ray film; center, the orbitographic lateral view, outlines the shadow of the tumor. (Sec arrows) Right, the resected tumor is placed over the orbitographic film. Note the correlation of size and shape of tumor, with its orbitographic image. This is a mixed benign lacrimal gland tumor.
Fig. 8 (Silva). Intracavity orbitography. In cystic tumors or those with liquid content the sac must be emptied and washed out before injecting the contrast material. An air bubble must finish the injec tion, to clean out the needle and so avoid dripping which may be confused with a fistula. It also improves the outline of the cystic image. These pictures correspond to a very large fronto-ethmoidal mucocele whose anatomic characteristics are clearly seen, thus greatly facilitating the surgical procedure.
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Fig. 9 (Silva). Intracavity orbitography. Important orbital structures must be clearly identified before surgery. The reflected tendon of the superior oblique muscle may be enclosed by the sac. Intracavity orbitog raphy indicates its position in relation to the cyst, and its orbital attachment. This helps avoid damage during surgical maneuvers. ing orbital tumors. Although I personally have had no experience with this method, it is promising.
Exhaustive clinical examinations, routine laboratory tests, simple radiographic studies and orbitographic techniques with positive
Fig. 10 (Silva). Orbitography with direct injection into the tumor mass. The technique must be reserved for diffuse recognized hemangiomas or cases with large vascular spaces in which extension into the orbit must be known for surgical evaluation. This case of a relapsing cavernous hemangioma was easily removed in toto after orbitographic information.
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ORBITAL TUMORS TABLE 8
THERAPEUTIC PROCEDURES IN 300 CONSECUTIVE CASES OF ORBITAL TUMOR
Diagnosis
B iopsy
Ant. Orbit
Lat. Orbit
13 30
2 3
1 1
65
90
61
Total
19 7 1 12
5
7 4 4 3 3
6 8 5D 8 7
1
1 2
7 5
4
1
Radio therapy 27 1 21 21
Chemo therapy
17 14
18 2
7
8
9 8 6 7 2
13
4 1 1
5 4
1
2
86
144
1 8 7 7
7
1
2 2
contrast media, as described above, are most helpful in making a presumptive diagnosis. Once the presumptive diagnosis of exophthalmos due to orbital tumor is made, a biopsy should be done. Treatment must be in direct relationship to the increase of the exophthalmos, which parallels the growth of the tumor mass and endangers the visual func tions and the eye itself. Accurate diagnosis at an early stage is essential. Following are suggestions for treatment: 1. All benign expanding orbital lesions should be handled conservatively, without disturbance of function, eye or lid motility, or esthetic aspect. 2. In-block resections, with wide safety margins, should be carried out and lymphatic drainage areas radically excised if spread of the tumor to the local lymph nodes is sus pected. 3. In inoperable tumors with orbital in volvement of systemic disease, and in meta static tumors to the orbit, radiotherapy or chemotherapy, or both, should be carried out.
Radical Exent.
14
16 Pseudotumors Mucoceles Orb. ext. of retinoblastoma Malignant lymphomas and leukemias 13 3 Dermoid cysts 3 Carcinomas of palpebral origin 3 Hemangiomas Meningiomas Endocrine ophthalmopathy 6 Lacrimal gland tumors 1 Peripheral nerve tumors 2 Rhinogenic carcinomas 4 Malignant melanomas Undifferentiated sarcomas 5 Carcinomas of epibulbar origin Metastatic carcinomas 2 Osteomas Fibrous dysplasias Rhabdomyosarcomas 1 Fibrosarcomas 1 Osteosarcomas 2 Gliomas of optic nerve Lymphangiomas 3 Cysticercosis Miscellaneous
11
Transcranial
2
1
6
40
4. Radical surgery of the orbit should be done only in cases of malignant tumor. Immediate plastic repair of radical surgery should not be done as it may interfere with early detection of relapses in situ. We have applied these rules in treating the 300 cases in this series, as shown in Table 8. Biopsy was the sole surgical proce dure in 65 of the 300 cases in this series, mainly for pseudotumors, orbital manifesta tions of systemic disease, and endocrine ophthalmopathies. Anterior orbitotomies were done in 90 cases. We found the superointernal approach to be the most satisfactory in resecting mucoceles, osteomas, and many dermoid cysts of the superointernal orbital angle. The Benedict incision over the exter nal orbital rim was also used successfully to resect dermoid cysts, benign lacrimal tu mors, hemangiomas, and some meningiomas and neurilemmomas. The Davis inferior ap proach was used in the resection of two gliomas and two meningiomas of the optic nerve.
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The lateral approach with Kronlein's op eration (Berke's modification), was used in more than 50 cases. Guillaume procedures to ensure a wider opening when resecting some meningiomas of the lesser wing of the sphenoid are grouped here also, as are some cases of lateral orbital decompression. The transcranial approach to the orbit was used in only six cases in this series, two with unsatisfactory results (one, a resection of a glioma of the optic nerve, resulting in palpebral ptosis and flaccid proptosis with neuroparalytic keratitis; the other, an intratecal psammomatous meningioma that could not be resected in toto through the orbit, or transcranially). Radical surgery was carried out in 86 cases, 61 of which required orbital exenteration. Other radical procedures, including ethmoid resection, sinus curettage and par tial or total resection of the superior maxilla, were done in epithelial lacrimal gland tumors and in invading carcinomas of palpebral or rhinogenic origin. There was one far-ad vanced case of osteosarcoma and one of a mucocele with all the periorbital sinuses af fected. Opening of the optic canal to resect the nerve invaded with retinoblastoma, re section of bone adjacent to the temporal fos sae in other cases, and large resections of frontal bone in orbital reproductions of lac rimal gland tumors are also included in this group. Radiotherapy combined with corticosteroids was indicated in most of the pseudotumor cases and the results were gratifying. This treatment was also beneficial in dimin ishing the residual proptosis after de compression surgery in cases of endocrine ophthalmopathy, often with dramatic results.20 The synergic action of radiotherapy and selective chemotherapy proved useful in treating certain malignant orbital tumors. In one case of rhabdomyosarcoma, this therapy, combined with Actinomycin D, seemed to hold out hope of a complete cure, but unfor tunately this did not materialize.21 Proptosis
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from multiple myelomas of the orbit disap peared with radiotherapy combined with Melfalan22 (fig. 11), as it did also in two cases of Hodgkin's lymphoma in which alkylating agents were administered, and in sev eral cases of leukemia with primary orbital localization in which synergic action of methotrexate-purinetol-prednisone and ra diation restored the eye (if not the patient) to normal condition. Thio-TEPA was used in all retinoblastoma cases when TEM was no longer available.23 Oncovin (Vincristine) was used in transoperative parenteral perfusion in all melanotic tumors, 24 most of which were orbital extensions of uveal melanoma or invasions from conjunctival foci. ThioT E P A has not proved effective in melanotic tumors. 25 A comparison of opinions might be inter esting. Reese26 believes that mucoceles should be removed by the otolaryngologist; however, I feel that after intracavity orbitography, removal of mucoceles by anterior orbitotomy ensures the functional preserva tion of the superior oblique muscle which is visualized with this technique. It is also helpful in learning when a bony erosion of the orbital roof can be expected, thus ena bling the eye surgeon to protect the dura when dissecting the mucocele walls adherent to it. Dyeing the cavity before emptying it is a useful surgical maneuver to ease total re section, as the entire mucocele wall is more easily seen. Recurrence due to incomplete re section is more likely with the intranasal curettage technique than with the direct vi sual control obtained by anterior orbitotomy. It has been claimed that more satisfactory cosmetic results are achieved by the transcranial approach (Ray 2 7 ). However, to ex pose a patient to neurosurgical intervention in order to resect a benign expanding orbital lesion does not seem very advantageous (fig. 12). The results in the 30 cases of mucoceles in this series could not be more gratifying.28 In 29 patients the frontoethmoidal mucoceles were totally removed without damage to eye
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Fig. 11 (Silva). Orbital localization of multiple myeloma. This patient had a bone inolvement of cranium and both humeri. Diplopia preceded the development of right exophthalmos. Orbitography revealed presence of a mass in upper part of right orbit going deeply below orbital roof (see arrows). Biopsy showed fibrous mass impregnated with myeloma cells. Radiotherapy, combined with Melphalan, reduced the proptosis, with disappearance of diplopia. motility and with practically no disfigure ment, except in very advanced cases. In one patient with carcinomatous degeneration, suspected after orbitography and confirmed by histologic study, the tumor was controlled with postoperative radiotherapy. In an ad vanced case with mucoceles filling all the periorbital sinuses and the eye lost from corneal perforation and endophthalmitis, an orbital exenteration was immediately closed with a large skin flap. Although Reese29 believes that most or bital meningiomas are the bailiwick of the neurosurgeon, in this series, 12 out of 16 meningiomas were removed easily using ei ther the anterior or lateral approach. Those of primary origin in the orbit were easily enu
cleated by digital dissection. In one case or bital exenteration was done because of comitant endophthalmitis (which can lead to er roneous diagnosis). Four cases are grouped with transcranial procedures because of a further attempt to remove the intracranial extension of the meningioma, although this proved to have been necessary in only two cases. I agree wholeheartedly with Reese in op posing the transcranial approach for lacrimal gland tumors, systemic orbital manifesta tions and diffuse orbital neoplasms, and also when, in a discussion with Poppen,30 he in sisted that diagnosis of orbital lesions be made by the eye surgeon. For biopsy pur poses, there is undoubtedly less risk for the
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Fig. 12 (Silva). Enormous fronto-ethmoidal mucocele. The anterior approach was used in this patient. The mucocele was resected after freeing the reflex portion of the superior oblique muscle, previously iden tified by the orbitography. The immediate postoperative result shows the good cosmetic appearance and the restoration of the eye to its normal position.
patient in transconjunctival orbitotomy than in trans frontal craniotomy. To avoid the transcranial approach, I try not to com pletely remove a meningioma of the optic nerve near the optic foramen, thus, as with Stallard's 31 procedure, eliminating the risk of exposing the nerve supply of the eye and lids to injury during surgery, which might result in a cosmetic defect. Further growth in the remaining benign tumor is so negligi ble that the patient can be considered cured without postoperative disfigurement. This applies also to a glioma of the optic nerve (not included in this series) in which I fol lowed Hogan's procedure: resecting, for biopsy, a mass sufficiently large to restore the normal position of the eye. The proptosis was reduced and no further growth of the tumor was apparent (fig. 13).
Orbital neurofibromas truly are a thera peutic problem. Excision of a solitary tumor of the orbit is simple and the results satis factory, but in the plexiform variety (the commonest) there is no end to palliative op erations to reduce the proptosis, improve the cosmetic aspect of the affected eyelid, or correct the ptosis. If the tumor erodes the bony orbit, penetrating to the cranium or ex tending backward by way of the temporal fossae, the eye surgeon is relieved in refer ring the patient to someone else. Fibrous dysplasias originate mainly around the maxillary antrum. Spreading out ward, they reach the orbit and produce exophthalmos. I have been consulted by head and neck surgeons in a number of these cases and in all I performed wide anterior orbitotomies of almost all the medial half of the
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Fig. 13 (Silva). (A) Meningioma of the optic nerve removed by lateral orbitotomy using Berke's modification of the Kronlein tech nique. (B) Postoperative appear ance of patient proves that transcranial approach cannot be justified on grounds of better cosmetic end results. (C) Pathologic specimen.
orbit. Spreading the orbital tissues outward exposed the intraorbital portion of these tumors without damage to the lacrimal passages, the superior oblique muscle, or the internal palpebral ligament. After complete removal
of the tumor, the orbital tissues were placed in their original position (fig. 14). This technique was followed also in managing secondary orbital tumors, such as osteomas, in the internal portion of the orbit.
Fig. 14 (Silva). Ossifying fibroma removed by anterior orbitotomy. The incision followed half of the interior orbital rim. It was necessary to separate the inferior oblique muscle and the lacrimal ducts which were both replaced at the end of surgical extraction of a highly vascularized tumor which filled the inner orbit, the entire right nostril and the maxillary antrum. The patient retained his ocular motility and visual acuity. X-ray films show the restoration of air passages and re-establishment of radiographic bone density on right side.
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Their resection is simple: After a wide in ternal orbitotomy, the tumor is exposed and dissected from the periorbita; its base is then separated with a chisel and the f rontoethmoidal cells are curetted (fig. 15). Soft tissues are replaced and the skin is sutured without drains. In one case however, com plete removal of a gigantic osteoma was not possible. At the suggestion of Byron Smith (New York), because it filled and over flowed the entire orbit of the only useful eye, I drilled out only the portion invading the orbital cavity, in order to get the eye back in place and liberate the compressed optic nerve. Smith and I were highly satis fied with the final result32 (fig. 16).
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In this series, infiltration of the retrobulbar region occurred most frequently with pseudotumors. It is not possible, with orbitography, to differentiate an infiltrating tumor such as reticulosarcoma, which commonly occurs unilaterally, or orbital myositis of endocrine origin, if thyroid tests are nega tive. Orbital fibrositis, the flat variety of pseudotumor, might be mistaken for the fi brous infiltration of inferior rectus and oblique muscles in endocrine ophthalmopathy if palpebral retraction is not present. Be cause of the unreliability of thyroid tests, biopsy is therefore the most reliable test for making a differential diagnosis.33 In pseudotumor, surgery is done only for
Fig. 15 (Silva). Nasal osteoma invading the orbit. This patient complained of marked diplopia with history of long-standing nasal obstruction. X-rays showed existence of very large osteoma whose extension can be seen. Removed through anterior internal orbitotomy. Incision extended to lateral side of nose. Macroscopic aspect of operative specimen.
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biopsy. Once a correct diagnosis is made, treatment with corticosteroids and radiother apy is indicated. Satisfactory results were obtained in all 31 cases of pseudotumor in this series. In one case, however, a pseudotu mor reappeared in the fellow eye. Primary benign lesions sometimes present a surgical problem. Dermoid cysts may grow deep in the orbital apex. Resection can be difficult and, if incomplete, recurrence can be expected. In dermoids of the eyebrow it is necessary to resect both the intra- and extraorbital portions, together with the bony area from which they originate. Dermolipomas of the outer canthus often grow deep. They must be dissected from the external muscle and, because conjuctiva adheres to their surface, the wound should be closed with a mucous membrane graft. In pseudocholesteatomas, curettage is the procedure of rhnire fnr rpmnvincr the raraffinlike material
Fig. 17 (Silva). Enormous congenital hemangioma involving entire right side of face. Syndactyly is also seen. In cases such as this, the surgeon is helpless.
Fig. 16 (Silva). Large fronto-ethmoidal osteoma in a patient whose opposite eye was blind. As the vision in the right eye was being impaired by the optic nerve distention due to the forward displace ment of the eye ball, because of the growth of the osteoma, a partial removal was made. Through an anterior internal orbitotomy a new orbital cav ity was formed by drilling out the part of the oste oma which filled the orbit. The eye ball was then put back in its proper position. This partial opera tion proved very successful as the benign tumor has not regrown since surgery. Dotted lines show amount of resection and arrow points to the nar row optic foramen.
which fills them. The capsule must be re sected completely to prevent recurrences. Teratomas require exenteration in most cases. The treatment of orbital hemangiomas is controversial. The congenital type is the most difficult to manage, as the surgeon faces two problems: the tumor itself, and the family's pressure upon him. The surgeon may choose to temporize rather than use freezing or sclerosing injections, or perform even partial resection. Radiation may not reduce the size of the tumor and may endan ger future growth of the orbit. One may hope for spontaneous regression as the child becomes older. However, the surgeon is helpless in advanced cases (fig. 17). A capillary hemangioma can be resected partially, as it too may regress. Orbitography with positive contrast material injected
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Fig. 18 (Silva). Cavernous hemangioma treated by transconjunctival approach. (A and B) This 4year-old girl had a cavernous hemangioma which developed an acute exophthalmos during an attack of whooping cough. (C) Microscopic aspect of the tumor. (D) Prompt surgical treatment led to an excellent and rapid recovery. directly into the tumor may be helpful in de termining the feasibility of total resection. This is true also of hemolymphangioma, in which partial resection is sometimes difficult. One has to control profuse bleeding from thinly walled vessels or blood lacunes which are prone to break easily. On the other hand, encapsulated cavernous hemangiomas in the adult are easily removed by digital dissection through direct approach (fig. 18). A tumor of the lacrimal gland is difficult to manage. When clinical exploration and orbitography have shown its location in the lacrimal fossae, removal is indicated if it is found to be encapsulated, as this type is gen erally a benign mixed tumor. However, if the tumor is diffuse, orbital exenteration is indicated without the generally advised deep bite for biopsy which may result in cellular dissemination. Because of the problems faced in surgery of this type of tumor, at Limon's suggestion (Dr. Noriega Limon) I order a short course of prophylactic radia tion before surgery, not only for prevention
of cellular dissemination but also for ruling out an inflammatory lesion of the lacrimal gland. Although with this procedure there is risk of excising a pseudotumor or benign lacrimal gland lesion, so far this has not hap pened. After histologic study we proceed as fol lows: Orbital exenteration is done if malig nancy is found, care being taken to perform a sufficiently wide resection of the adjacent bone if it is infiltrated. The exenterated orbit is gauze-packed or, at most, covered with a split-thickness skin graft. Immediate plastic repair is not advisable. In this series, there have been three recurrences out of 14 cases of lacrimal gland tumor. Orbital melanoma also requires early radi cal surgery—formerly exenteration, but now, at Hogan's 34 suggestion, enucleation of the eye with exteriorized melanoma. Vincristine is administered transoperatively and in week ly doses as tolerated. Thio-TEPA has proved to be ineffective. Orbital carcinomas of palpebral, epibulbar
Fig. 19 (Silva). Upper left, rhabdomyosarcoma of left orbit in a 9-year-old girl. Upper right, after tumor was removed by orbital exenteration, with split thickness skin graft. Lower left, pathologic speci men. Lower right, microscopic aspect shows embryonal type with very few striated cells. This is the only patient with rhabdomyosarcoma surviving five years after surgery and radiation therapy.
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9. Silva, D.: Incidencia y Diagnostico en Patologia Tumoral Orbitaria. Gac. Med. Mexico 97:604, 1967. 10. Drews, L. C.: Exophthalmometry. Am. J. Ophth. 43 :37,1957. 11. Tengroth, B., Bogren, H., and Zackrisson, U.: Human exophthalmometry. Acta Ophth. 42:864, 1964. 12. Silva, D., and Acosta Ruiz, R.: Exof talmometria Radiografica. Arch. As. p. e. Ceguera en Mex. II Serie9:18, 1967. 13. Silva, D.: Tumores Orbitarios: Metodos Radiologicos. Arch. As. p. e. Ceguera en Mex. II Serie 4:9, 1962. 14. Silva, D., and Arribas Aveleyra, E.: Exploracion Radiologica de los Tumores de la Orbita con Medios de Contraste. El Medico 12 :35, 1962. 15. Ziedses des Plantes, B. C.: Substraktion. Stuttgart, Thieme, 1961. 16. Cowie, J. W., and Groves, J. S.: Preliminary CONCLUSION report on the use of contrast media in orbital radi There are endless aspects of this discus ography. Brit. J. Ophth. 39:283,1955. 17. Silva, D.: Diagnostico Radiografico de los Tu sion. I must say, however, that the practice mores Orbitarios. In: Troutmann, R. C, Converse, of this not-very-favored sector of ophthal J. M., and Smith, B.: Plastic and Reconstructive mology has given me the satisfaction of sav Surgery of the Eye and Adnexa. Washington, Buting many eyes which otherwise might have terworth, 1962, p. 71. 18. Baum, G., and Greenwood, I.: Orbital lesion been enucleated, with benign tumors held in localization by three dimensional ultrasonography. the orbit, and preservation of ocular func New York J. Med. 61:4149, 1961. 19. Newel'l, F. W., Goren, S. B., Brizel, H. E., and tion that could have been damaged by other Harper, P. V.: The use of Iodine-125 as a diagnos methods of surgery. tic agent in ophthalmology. Tr. Am. Acad. Ophth. Otolaryng. 67:177, 1963. I firmly believe that the responsibility of 20. Werner, S. C.: Prednisone in emergency treat managing orbital tumors must rest, in almost ment of malignant exophthalmos. Lancet 1:1004, 1966. every case, with the eye surgeon. 21. Pinkel, D., and Pickren, T-: RhabdomyosarHamburgo 203 coma in children. JAMA 175:293, 1961. 22. Brook, J., Bateman, J. R., and Steinfeld, J. REFERENCES L.: Evaluation of melphaian (NSC-8806) in treat 1. Birge, H. L.: Meningiomas: An ophthalmic ment of multiple myeloma. Cancer Chemother. Rep. 36:25,1964. problem. Am. J. Ophth. 31:828, 1951. 23. Chapman, R. B.: Retinoblastoma. Clin. Pediat. 2. Dandy, W. E.: Orbital Tumors; Results Fol lowing the Transcranial Operative Attack. New 5 :86,1966. 24. Reitemeier, R. J., Moertel, C. G., and Black York, Oskar Piest, 1941. 3. Castaneda, G.: Ideario Clinico en Aforismos y burn, C. M.: Vincristine (NSC-67574) therapy of Frases Breves. Edit, e Impres. Ciceron. Mexico, adult patients with solid tumors. Cancer Chemother. 1946. Rep. 34:21,1964. 25. Stehlin, J. S., Jr., Smith, J. L., Jr., and 4. Forrest, A. W.: Intraorbital tumors. Arch. Clark, R. L., Jr.: The present status of chemother Ophth. 41:198,1949. 5. Porterfield, J. F . : Orbital tumors in children: apy for malignant melanoma. Proc. Natl. Cancer a report on 214 cases. Internat. Ophth. Clin. 2 :319, Conf. 4:625,1960. 1962. 26. Reese, A. B.: Incidence and management of 6. Reese, A. B. and Jones, I. S. In Moss, H. M. : unilateral proptosis. In: Boniuk, M.: Ocular and Expanding lesions of the orbit. A clinical study of Adnexal Tumors. New and Controversial Aspects. 230 consecutive cases. Am. J. Ophth. 54:761, 1962. St. Louis, Mosby, 1964, p. 389. 7. Silva, D.: Consideraciones sobre el Diagnostico 27. Ray, B. S.: Intracranial operations for dis y Tratamiento de los Tumores de la Orbita. Cir. eases of the orbit and adjacent structures. Am. J. Cir. 30:93,1962. Ophth. 54:581,1962. 8. Silva, D.: El Manejo Clinico de los Tumores 28. Silva, D., and Gomez Leal, A.: Mucoceles y Orbitarios. Analisis de 185 casos consecutivos opera- Dermoides orbitarios. An. Soc. Mex. Oftal. 37:104, dos. IV Gradle Lecture. Arch. As. p. e. Ceguera en 1964. Mex. IISerie7:3, 1965. 29. Reese, A. B.: The role of the neurosurgeon in
or rhinogenic origin, require early radical surgery. If bone invasion or lymphatic infil tration is found, surgery must be considered palliative, and radiotherapy and chemother apy used to control painful episodes. In mesenquimal tumors such as rhabdomyosarcoma, fibrosarcoma, osteosarcoma, undifferentiated sarcoma, etc, biopsy is fol lowed by exenteration which, if done in the early stage, may increase the life expectancy of such patients. Radiotherapy and chemo therapy are of little value if early radical surgery does not control the disease, as shown in 18 cases in this series (fig. 19).
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the treatment of orbital tumors. Am. J. Ophth. 58:140,1964. 30. Poppen, J. L.: Neurosurgical approach to the orbit. In Boniuk, M.: Ocular and Adnexal Tumors. New and Controversial Aspects. St. Louis, Mosby, 1964, pp. 466 and 491. 31. Stallard, H. B.: A plea for lateral orbitotomy with certain modifications. Brit. J. Ophth. 44:718, 1960. 32. Silva, D. and Plascencia, J. A.: Osteoma gi-
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gante del hueso frontal con invasion orbitaria masiva. Arch. As. p. e. Ceguera en Mex. 6:41,1964. 33. Silva, D.: Exof talmos endocrino unilateral. Su diagnostico diferencial Gac. Med. Mex. 97 :27, 1967. 34. Hogan, M. J.: Clinical aspects, management, and prognosis of melanomas of the uvea and optic nerve. In Boniuk, M.: Ocular and Adnexal Tumors. New and Controversial Aspects. St. Louis, Mosby, 1964, p. 203.
ADHESION O F REGENERATING CORNEAL E P I T H E L I U M T H E ROLE OF BASEMENT MEMBRANE A L I A. KHODADOUST, M.D.,
ARTHUR M.
SILVERSTEIN,
PH.D.,
K E N N E T H R. KENYON,* AND J O H N E. DOWLING, P H . D .
Baltimore, Maryland The corneal epithelium, consisting of a layer five to six cells thick that rests on a basement membrane, provides the main pro tective barrier for the underlying cornea. For this protective barrier to maintain its in tegrity and thereby function efficiently, it must fulfill two important requirements: the maintenance of an unbroken layer of cells over the entire corneal surface, and the tight adhesion of this layer to Bowman's mem brane in some species, or directly to the cor neal stroma in others. When the corneal epithelium is subjected to physical or chemical injury, the woundhealing process is directed primarily toward reestablishing the continuity of the epithelial covering of the cornea, and only later toward developing tight adhesion to the underlying tissue. This study is primarily concerned with the latter aspect of corneal wound healing. To provide a proper context for the ex periments reported here, we briefly review
From The Wilmer Ophthalmological Institute, The Johns Hopkins University School of Medicine. These investigations were supported in part by USPHS Research Grants NB-03040 and NB-05336 from the National Institute of Neurological Dis eases and Blindness, by an unrestricted grant from the Alcon Laboratories, Inc., and by an Independent Order of Odd Fellows Research Professorship. * Alfred P. Sloan Foundation Fellow.
what is known about the healing process of corneal epithelium. Many investigators have shown that two phenomena are involved in the repair of superficial corneal injuries.1-3 There is first the epithelial "slide," by which the cells surrounding the denuded area im migrate rapidly to cover the site of injury. This is followed some time later by a burst of mitotic activity, assisted by a temporary pause in the natural process of exfoliation, and resulting in reconstitution of the normal number of epithelial cells and a normal epi thelial thickness. The sliding process com mences as early as one hour after injury, and continues until the denuded area is com pletely covered by a monolayer of epithelial cells. Each cell, by spreading and flattening, can cover several times its normal area, so that a small defect may be repaired rapidly even without multiplication of cells. The proliferative phase starts several hours later, when the inhibitory effect of the mechanical insult has subsided. Mitotic activity gener ally starts in the two deepest layers of the epithelium, and even at some distance from the site of the defect. We can thus see how the damaged cornea re-covers itself with epithelium, a step which is important not only in restoration of the protective barrier, but also as an important contribution to the underlying stromal heal-