recent work. Fibrillin was identified as recently as 5 years ago as a significant connective tissue component
of the zonules and the cornea. The interval from identi¬ fication of a new connective tissue component to its molecular cloning, chromosomal assignment, and cor¬ relation with a disease thus was only about 5 years. Identification of a second fibrillin gene on chromosome 5 makes the existence of nonallelic heterogeneity likely. The first identified gene mutation was found in two of more than 100 patients tested, corresponding to a small proportion of patients with the Marfan syndrome. The association among zonular dehiscence, microspherophakia, and the altered fibrillin gene is obvious in these patients. In other patients with Marfan syndrome, however, the ocular abnormalities are characterized by excess stretching of the globe, flattening of the cornea, and stretching and partial dehiscence of the zonules. Patients with increased axial lengths are at risk for retinal detachment. This did not occur in the two pa¬ tients mentioned, nor was it a feature in the patient described by Marfan. Identification of a mutation in the fibrillin gene is a major breakthrough in this lethal disease. This disorder can now be removed from the list of syndromes and be called a disease, since a more detailed pathogenesis has been found. It has been speculated that patients with the severe neonatal form of the disease have an autoso¬ mal recessive subtype of the Marfan syndrome. Such an etiology is less likely since the mutation identified by Dietz et al codes for the most severe phenotype ob¬ served. The molecular diagnosis can now be confirmed in the laboratory in a definite, though small, proportion of patients. Indirect diagnosis, using probability esti-
Cataract Surgery After Uveal Melanoma melanoma of the posterior Malignant and choroid) is the body intraocular A most
(ciliary primary,
uvea
common
tumor. malignant, perplexing aspect of this neoplasm is its marked predisposition to eventually exhibit hepatic metastasis in spite of the fact that initial See also p 475.
liver enzyme levels and results of hepatic imaging studies are almost always normal when the eye tumor is treated by an ophthalmic oncologist.1 Some authors have proposed that manipulation of the eye by enucleation, radiotherapy, or other diagnostic or therapeutic
on linkage analysis, can be established in patients with a questionable diagnosis if they are mem¬ bers of a pedigree large enough to permit linkage as¬ signment. Treatment based on molecular diagnosis or linkage analysis may now be initiated early in an at¬ tempt to prevent or repair ocular or potentially lethal cardiovascular complications. Irene H. Maumenee, MD
mates based
Baltimore, Md
References 1. Marfan M. Un cas de d\l=e'\formationcong\l=e'\nitaledes quatre membres plus prononc\l=e'\eaux extr\l=e'\mit\l=e'\scharact\l=e'\ris\l=e'\epar l'allongement des os avec un certain degr\l=e'\d'amincissement. Bull Mem Soc Med Hop Paris. 1896;13:220-226. 2. Dietz HC, Cutting GR, Pyeritz RE, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352:337-339. 3. Sakai LY, Keene DR, Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol.
1986;103:2499-2509. 4. Hollister DW, Godfrey M, Sakai LY, Pyeritz RE. Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. N Engl J Med. 1990;323:152-159. 5. Kainulainen K, Pulkkinen L, Savolainen A, Kaitila I, Peltonen
L. Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med. 1990;323:935-939 6. Dietz HC, Pyeritz RE, Hall BD, et al. The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3. Genomics. 1991;9:335\x=req-\
361. 7. Maslen CL, Corson GM, Maddox BK, Glanville RW, Sakai LY. Partial sequence of a candidate gene for the Marfan syndrome. Nature. 1991;352:334-337. 8. Lee B, Godrey M, Vitale E, et al. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991;352:330-334.
Radiotherapy for maneuvers
tumor.2
may promote systemic dissemination of the
Consequently, emphasis has been placed on using "no touch" or "minimal manipulation" techniques at the time of enucleation or other procedures.1,3 In recent years, however, the "no touch" technique has become almost obsolete, although a minimal manipulation technique is still advocated.1,4 In view of these developments, is it not paradoxical that an ophthalmologist would purposely open a tumorcontaining eye, remove a cataract, and even insert an
intraocular lens? Should one conclude that this form of manipulation would promote extraocular extension and systemic dissemination of the tumor? In spite of these theoretical concerns, the study by
Downloaded From: http://archopht.jamanetwork.com/ by a University of Manitoba User on 06/14/2015
Gragoudas and associates5 reported
in this issue pro¬ vides statistical evidence that no additional risk of met¬ astatic disease is incurred by performing cataract sur¬ gery and intraocular lens implantation in patients who have undergone successful radiotherapy for posterior uveal melanoma. There are two reasons why cataract surgery is presumably safe in these patients. First, the uveal melanoma has received adequate irradiation to render it incapable or less capable of metastasis. Therefore, the minor manipulation in¬ volved in cataract surgery would not be likely to pro¬ mote metastasis. Second, there is increasing evidence that many pa¬ tients who have uveal melanoma have developed subclinical hepatic micrometastases prior to treatment of the primary uveal tumor and that these hepatic micro¬ metastases are being suppressed by host immunologie defense mechanisms.1,4 If that is the case, it seems unlikely that cataract surgery would have any adverse effect on these clinically dormant melanoma cells in the liver. Most nonneoplastic ophthalmic diseases are capable of producing visual loss but are not life-threatening. Therefore, the primary goal of the ophthalmologist is to preserve as much vision as possible. In contrast, uveal melanoma threatens the patient's life as well as the patient's vision. Hence, in cases of uveal melanoma, survival of the patient is the primary goal of treatment, and preservation of vision becomes a secondary goal. In addition to the observations of Gragoudas and asso¬ ciates, other studies have suggested that the patient's survival is not adversely affected by removing the cata¬ ract after successful clinical control of a tumor with radiotherapy.6 Another small nonstatistical study also suggested that patients who have undergone cataract surgery in eyes with unsuspected uveal melanoma may not have a worse prognosis.7 Therefore, it seems appro¬ priate to treat a visually disabling cataract with stan¬ dard methods if it appears that the tumor is adequately controlled.
Prior to undertaking cataract surgery in patients who have undergone radiotherapy for uveal melanoma, the ophthalmologist should be certain that the tumor shows excellent clinical regression, documented by in¬ direct ophthalmoscopy and ultrasonography. Further¬ more, the ophthalmologist should clearly determine that the visual loss is due primarily to the cataract and not to radiation maculopathy, in which case cataract surgery would be of little or no benefit. Based on my similar experience with a large number of cases, I currently recommend cataract removal and insertion of an intraocular lens in patients who have undergone successful radiotherapy for ciliary body or choroidal melanoma if evaluation suggests that it would benefit the patient visually. Jerry A. Shields, MD Philadelphia, Pa The author's research is supported by the Eye Tumor Research Foundation Ine, Philadelphia, Pa.
References 1. Shields JA, Shields CL. Management of posterior uveal melanoIn: Intraocular Tumors: A Text and Atlas. Philadelphia, Pa: WB Saunders Co Inc; 1992:171-205. 2. Zimmerman LE, McLean IE. An evaluation of enucleation in the management of uveal melanomas. Am J Ophthalmol. 1979; 87:741-760. 3. Fraunfelder FT, Boozman FW, Wilson RS, Thomas AH. Notouch technique for intraocular malignant tumors. Arch Ophthalmol. ma.
1977;95:1616-1620. 4. Shields JA, Shields CL, Donoso LA. Management of posterior uveal melanoma. Surv Ophthalmol. 1991;36:161-195. 5. Gragoudas ES, Egan KM, Arrigg PG, Seddon JM, Glynn RJ, Munzenrider JE. Cataract extraction after proton beam irradiation for malignant melanoma of the eye. Arch Ophthalmol. 1992;110:475\x=req-\
479. 6. Augsburger JJ, Shields JA. Cataract surgery following cobalt60 plaque radiotherapy for posterior uveal malignant melanoma.
Ophthalmology. 1985;92:815-822. 7. Shields JA, Augsburger JA. Cataract extraction and intraocular lenses in patients with malignant melanoma of the ciliary body and choroid. Ophthalmology. 1985;92:823-826.
Downloaded From: http://archopht.jamanetwork.com/ by a University of Manitoba User on 06/14/2015
of the zonules and the cornea. The interval from identi¬ fication of a new connective tissue component to its molecular cloning, chromosomal assignment, and cor¬ relation with a disease thus was only about 5 years. Identification of a second fibrillin gene on chromosome 5 makes the existence of nonallelic heterogeneity likely. The first identified gene mutation was found in two of more than 100 patients tested, corresponding to a small proportion of patients with the Marfan syndrome. The association among zonular dehiscence, microspherophakia, and the altered fibrillin gene is obvious in these patients. In other patients with Marfan syndrome, however, the ocular abnormalities are characterized by excess stretching of the globe, flattening of the cornea, and stretching and partial dehiscence of the zonules. Patients with increased axial lengths are at risk for retinal detachment. This did not occur in the two pa¬ tients mentioned, nor was it a feature in the patient described by Marfan. Identification of a mutation in the fibrillin gene is a major breakthrough in this lethal disease. This disorder can now be removed from the list of syndromes and be called a disease, since a more detailed pathogenesis has been found. It has been speculated that patients with the severe neonatal form of the disease have an autoso¬ mal recessive subtype of the Marfan syndrome. Such an etiology is less likely since the mutation identified by Dietz et al codes for the most severe phenotype ob¬ served. The molecular diagnosis can now be confirmed in the laboratory in a definite, though small, proportion of patients. Indirect diagnosis, using probability esti-
Cataract Surgery After Uveal Melanoma melanoma of the posterior Malignant and choroid) is the body intraocular A most
(ciliary primary,
uvea
common
tumor. malignant, perplexing aspect of this neoplasm is its marked predisposition to eventually exhibit hepatic metastasis in spite of the fact that initial See also p 475.
liver enzyme levels and results of hepatic imaging studies are almost always normal when the eye tumor is treated by an ophthalmic oncologist.1 Some authors have proposed that manipulation of the eye by enucleation, radiotherapy, or other diagnostic or therapeutic
on linkage analysis, can be established in patients with a questionable diagnosis if they are mem¬ bers of a pedigree large enough to permit linkage as¬ signment. Treatment based on molecular diagnosis or linkage analysis may now be initiated early in an at¬ tempt to prevent or repair ocular or potentially lethal cardiovascular complications. Irene H. Maumenee, MD
mates based
Baltimore, Md
References 1. Marfan M. Un cas de d\l=e'\formationcong\l=e'\nitaledes quatre membres plus prononc\l=e'\eaux extr\l=e'\mit\l=e'\scharact\l=e'\ris\l=e'\epar l'allongement des os avec un certain degr\l=e'\d'amincissement. Bull Mem Soc Med Hop Paris. 1896;13:220-226. 2. Dietz HC, Cutting GR, Pyeritz RE, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1991;352:337-339. 3. Sakai LY, Keene DR, Engvall E. Fibrillin, a new 350-kD glycoprotein, is a component of extracellular microfibrils. J Cell Biol.
1986;103:2499-2509. 4. Hollister DW, Godfrey M, Sakai LY, Pyeritz RE. Immunohistologic abnormalities of the microfibrillar-fiber system in the Marfan syndrome. N Engl J Med. 1990;323:152-159. 5. Kainulainen K, Pulkkinen L, Savolainen A, Kaitila I, Peltonen
L. Location on chromosome 15 of the gene defect causing Marfan syndrome. N Engl J Med. 1990;323:935-939 6. Dietz HC, Pyeritz RE, Hall BD, et al. The Marfan syndrome locus: confirmation of assignment to chromosome 15 and identification of tightly linked markers at 15q15-q21.3. Genomics. 1991;9:335\x=req-\
361. 7. Maslen CL, Corson GM, Maddox BK, Glanville RW, Sakai LY. Partial sequence of a candidate gene for the Marfan syndrome. Nature. 1991;352:334-337. 8. Lee B, Godrey M, Vitale E, et al. Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes. Nature. 1991;352:330-334.
Radiotherapy for maneuvers
tumor.2
may promote systemic dissemination of the
Consequently, emphasis has been placed on using "no touch" or "minimal manipulation" techniques at the time of enucleation or other procedures.1,3 In recent years, however, the "no touch" technique has become almost obsolete, although a minimal manipulation technique is still advocated.1,4 In view of these developments, is it not paradoxical that an ophthalmologist would purposely open a tumorcontaining eye, remove a cataract, and even insert an
intraocular lens? Should one conclude that this form of manipulation would promote extraocular extension and systemic dissemination of the tumor? In spite of these theoretical concerns, the study by
Downloaded From: http://archopht.jamanetwork.com/ by a University of Manitoba User on 06/14/2015
Gragoudas and associates5 reported
in this issue pro¬ vides statistical evidence that no additional risk of met¬ astatic disease is incurred by performing cataract sur¬ gery and intraocular lens implantation in patients who have undergone successful radiotherapy for posterior uveal melanoma. There are two reasons why cataract surgery is presumably safe in these patients. First, the uveal melanoma has received adequate irradiation to render it incapable or less capable of metastasis. Therefore, the minor manipulation in¬ volved in cataract surgery would not be likely to pro¬ mote metastasis. Second, there is increasing evidence that many pa¬ tients who have uveal melanoma have developed subclinical hepatic micrometastases prior to treatment of the primary uveal tumor and that these hepatic micro¬ metastases are being suppressed by host immunologie defense mechanisms.1,4 If that is the case, it seems unlikely that cataract surgery would have any adverse effect on these clinically dormant melanoma cells in the liver. Most nonneoplastic ophthalmic diseases are capable of producing visual loss but are not life-threatening. Therefore, the primary goal of the ophthalmologist is to preserve as much vision as possible. In contrast, uveal melanoma threatens the patient's life as well as the patient's vision. Hence, in cases of uveal melanoma, survival of the patient is the primary goal of treatment, and preservation of vision becomes a secondary goal. In addition to the observations of Gragoudas and asso¬ ciates, other studies have suggested that the patient's survival is not adversely affected by removing the cata¬ ract after successful clinical control of a tumor with radiotherapy.6 Another small nonstatistical study also suggested that patients who have undergone cataract surgery in eyes with unsuspected uveal melanoma may not have a worse prognosis.7 Therefore, it seems appro¬ priate to treat a visually disabling cataract with stan¬ dard methods if it appears that the tumor is adequately controlled.
Prior to undertaking cataract surgery in patients who have undergone radiotherapy for uveal melanoma, the ophthalmologist should be certain that the tumor shows excellent clinical regression, documented by in¬ direct ophthalmoscopy and ultrasonography. Further¬ more, the ophthalmologist should clearly determine that the visual loss is due primarily to the cataract and not to radiation maculopathy, in which case cataract surgery would be of little or no benefit. Based on my similar experience with a large number of cases, I currently recommend cataract removal and insertion of an intraocular lens in patients who have undergone successful radiotherapy for ciliary body or choroidal melanoma if evaluation suggests that it would benefit the patient visually. Jerry A. Shields, MD Philadelphia, Pa The author's research is supported by the Eye Tumor Research Foundation Ine, Philadelphia, Pa.
References 1. Shields JA, Shields CL. Management of posterior uveal melanoIn: Intraocular Tumors: A Text and Atlas. Philadelphia, Pa: WB Saunders Co Inc; 1992:171-205. 2. Zimmerman LE, McLean IE. An evaluation of enucleation in the management of uveal melanomas. Am J Ophthalmol. 1979; 87:741-760. 3. Fraunfelder FT, Boozman FW, Wilson RS, Thomas AH. Notouch technique for intraocular malignant tumors. Arch Ophthalmol. ma.
1977;95:1616-1620. 4. Shields JA, Shields CL, Donoso LA. Management of posterior uveal melanoma. Surv Ophthalmol. 1991;36:161-195. 5. Gragoudas ES, Egan KM, Arrigg PG, Seddon JM, Glynn RJ, Munzenrider JE. Cataract extraction after proton beam irradiation for malignant melanoma of the eye. Arch Ophthalmol. 1992;110:475\x=req-\
479. 6. Augsburger JJ, Shields JA. Cataract surgery following cobalt60 plaque radiotherapy for posterior uveal malignant melanoma.
Ophthalmology. 1985;92:815-822. 7. Shields JA, Augsburger JA. Cataract extraction and intraocular lenses in patients with malignant melanoma of the ciliary body and choroid. Ophthalmology. 1985;92:823-826.
Downloaded From: http://archopht.jamanetwork.com/ by a University of Manitoba User on 06/14/2015
