- Email: [email protected]
Diabetic Retinopathy Study
CORRESPONDENCE
VOL. 76, NO. 3
composition of the aqueous humour, hor monal and neuronal agents, etc., in influenc ing the morphogensis of the vacuoles re mains to be established." This subject has been discussed in greater depth more re cently.4 I have regarded the process of endothelial vacuolation as dynamic (which does not nec essarily imply that the driving force for this function can only be provided by the metab olism of the cell), (a) to distinguish it from the vacuoles that can be formed as a post mortem change or in a diseased condition, a subject fully discussed by Ashton,6 and (b) to indicate that the transcellular channels are regarded as transient stages in the develop ment of the vacuole during which it is open to both surfaces of the endothelial cell. Ramesh C. Tripathi, M.D., Ph.D., Institute of Ophthalmology, University of London Judd Street, London WC1H 9QS, England. REFERENCES
1. Tripathi, R. C. : Ultrastructure of Schlemm's canal in relation to aqueous outflow. Exp. Eye Res. 7:335,1968. 2. Tripathi, R. C : Mechanism of aqueous out flow across the trabecular wall of Schlemm's canal. Exp. Eye Res. 11:116, 1971. 3. Tripathi, R. C. : Aqueous outflow pathway in normal and glaucomatous eyes. Br. J. Ophthalmol. 56:157, 1972. 4. Tripathi, R. C. : Comparative physiology and anatomy of the outflow pathway. In Davson, H. (ed.) : The Eye, vol. 5. London, Academic Press. In press. 5. Cole, D. F., and Tripathi, R. C. : Theoretical consideration on the mechanism of aqueous outflow. Exp. Eye Res. 12:25, 1971. 6. Ashton, N. : The exit pathway of the aqueous. Trans. Ophthalmol. Soc. UK 80:397, 1960. REPLY
Editor, American Journal of Ophthalmology: We admire Dr. Tripathi's work, and ap preciate his pointing out that our interpreta tion of his concept was not exactly what he had in mind. His letter is helpful in making this clear. It is attractive to us to conceive of vital activity of the endothelial lining of
403
Schlemm's canal having some modulating in fluence on outflow of aqueous and not to postulate an active outward transport requir ing much energy from the metabolism of these cells. W. Morton Grant, M.D. Murray A. Johnston, M.D. Howe Laboratory of Ophthalmology Harvard University Medical School 243 Charles Street Boston, MA 02114 DIABETIC RETINOPATHY STUDY
To the Editor, American Journal of Ophthalmology: Diabetic retinopathy has become one of the four most common causes of blindness in the United States. 1 Although photocoagulation has been employed in its treatment for more than ten years, its true value remains controversial. In spite of the need for objec tive, definitive evidence, an adequately con trolled trial of photocoagulation in proliferative diabetic retinopathy has not been per formed. This is not surprising, considering the complexity and expense of large scale clinical trials in chronic disease. However, as Inglefinger2 has aptly stated, When serious diseases are treated by serious methods .. . then ethical as well as scientific con siderations require that medicine depend on the most reliable and the best controlled data avail able^—the kind of data that is sought by ran domized clinical study.
In keeping with this admonition, a ran domized clinical trial of photocoagulation in the treatment of proliferative diabetic reti nopathy has been designed and launched. The Diabetic Retinopathy Study (DRS) in volves 16 clinical centers in various parts of the United States, a coordinating center at the University of Maryland, and a fundus photograph reading center at the Univer sity of Wisconsin, all supported by contracts from the National Eye Institute, a part of the National Institutes of Health.
404
AMERICAN JOURNAL OF OPHTHALMOLOGY
The support of the medical and ophthalmological communities is needed to carry this study to a successful conclusion. The DRS investigators are, therefore, grateful to the JOURNAL for giving them this opportu nity to summarize the major features of the DRS and to appeal for the support of all physicians who care for diabetic patients. The principal eligibility criteria for the DRS are: 1. Visual acuity with best correction of 20/100 or better in each eye. 2. Diabetic retinopathy in each eye fulfill ing any one of the following conditions: (a) proliferative retinopathy in each eye; (b) proliferative retinopathy in one eye, nonproliferative retinopathy in the other eye; (c) severe nonproliferative retinopathy in each eye. 3. No prior treatment with photocoagulation or pituitary ablation. 4. Both eyes suitable for photocoagulation treatment. 5. Good prospects for survival and avail ability for five years of follow-up. (Patients 70 years of age or older are not eligible.) 6. Only patients willing and able to give their informed consent after thorough expla nation of all aspects of the study will be ad mitted. The basic question which the DRS has been designed to answer is: Can photocoagu lation help to prevent severe visual loss due to proliferative diabetic retinopathy? The chief criterion of success will be the degree to which visual acuity is maintained, al though visual fields and the morphologic ap pearance of the retina in stereoscopic color and fluorescein photographs will also be as sessed. In order to give all patients enrolled in the study the chance to benefit from pho tocoagulation, if it is helpful, while minimiz ing the risk of harm, if it proves deleterious, photocoagulation treatment will be limited to one eye of each patient. This arrangement gives each patient the best chance of retain ing vision in at least one eye, the goal of greatest importance to him.
SEPTEMBER, 1973
The eye to be treated and the treatment modality to be used (xenon arc or argon laser) will be selected by a random process. Treatment will be carried out meticulously according to a detailed protocol, with cen tral monitoring of posttreatment photo graphs. Each patient will be followed-up for a minimum of five years. The pooled results from all 16 centers will be followed closely by the Coordinating Center and presented at frequent intervals to a committee charged with the responsibility of monitoring the data for evidence of beneficial or harmful effects. If it becomes evident during the course of the study that photocoagulation is better than no treatment in a certain stage of diabetic retinopathy, patients with untreated eyes in that stage will be offered treatment. On the other hand, if any feature of either treatment technique proves harmful, this as pect of follow-up treatment will be discon tinued. Results of the study will be reported promptly to the scientific community. All 16 clinical centers are now enrolling patients and each is eager to fill its quota of 100 to 150 patients as rapidly as possible. The overall goal of the study is 1,800 pa tients enrolled and treated by July 1974. It is important to all ophthalmologists, as well as to the entire medical community, that this controlled study be successful in recruit ing the number of patients required to deter mine if and when photocoagulation therapy should be employed as a treatment of prolif erative diabetic retinopathy. It may be many years before facilities and funds will again be available if this opportunity is lost. The DRS investigators ask for the help of all physicians near DRS clinical centers in identifying and referring patients who may be eligible for participation in this study. The sooner we have solid information to guide our treatment of this distressing mani festation of diabetes, the better it will be for its unfortunate victims. Lloyd M. Aiello, M.D.—Joslin Clinic Jose Berrocal, M.D.—University of Puerto Rico Matthew D. Davis, M.D.—
BOOK REVIEWS
VOL: 76, NO. 3
University of Wisconsin Fred Ederer—National Eye Institute Morton F. Goldberg, M.D.— University of Illinois John E. Harris, M.D.— University of Minnesota Christian R. Klimt, M.D.— University of Maryland Genell L. Knatterud— University of Maryland Raymond R. Margherio, M.D.— Wayne State University Edward N. McClean, M.D.— University of Washington J. Wallace McMeel, M.D.— Massachusetts Eye and Ear Infirmary Frank L. Myers, M.D.— University of Wisconsin Edward W. D. Norton, M.D.— University of Miami Arnall Patz, M.D.— Johns Hopkins Hospital Thaddeus Prout, M.D.— Johns Hopkins Hospital F. Tempel Riekhof, M.D.— University of Utah Bradley R. Straatsma, M.D. UCLA Center for Health Sciences William Tasman, M.D.—Wills Eye Hospital W. A. J. van Heuven, M.D.— Albany Medical College Robert C. Watzke, M.D.— University of Iowa REFERENCES
1. Kahn, H. A., and Moorhead, H. B. : Statistics on Blindness in the Model Reporting Area, 1969-70. U.S. Department of Health, Education, and Wel fare, publication No. (NIH) 73-427. 2. Inglefinger, F. J. : The randomized clinical trial. New Engl. J. Med. 287:100, 1972.
BOOK R E V I E W S Trans actions of the New Orleans Academy of Ophthalmology. St. Louis, C. V. Mosby, 1973. Clothbound, 296 pages, 165 illustra tions, two color plates. $29.50 The 21st annual session of the New Or
SYMPOSIUM ON CONTACT LENSES.
405
leans Academy of Ophthalmology was de voted to contact lenses and maintained the traditional excellence the symposia have es tablished over the years. The publisher has successfully completed the rather herculean task of publishing the text within one year of the symposium. The reader is thus as sured of most recent material. Eight men of vast contact lens experience contribute sound chapters on the history, optics, use of contact lenses in aphakia and corneal pathol ogy, etc. Most revealing, however, is the dis cussion emanating from the round tables. There are five panel discussions and it is here that one best sees that contact lens work is still more art than science. Differences of opinion abound in a most healthy manner although sometimes perhaps to an extreme. The opinions on fenestration ranged from no holes to several holes and from center holes to peripheral holes. Much to-do about nothing, but it is important to re mind us that the cornea needs oxygen and that it comes from the air and that tears must thus carry it under the contact lens, even though the lens is soft and semipermeable. There is relatively little new information on the soft lenses although their use as cor neal bandages is well documented. The many uses of the flush-fitting scierai contact lens is discussed, although they require no small de gree of expertise. This is important because it points up the obvious personal involve ment in time and energy these contact lens men have invested to master their art. The diseases amenable to contact lens therapy range from aphakia and keratoconus to keratitis and Stevens-Johnson syndrome. This book contains adequate material on the con tributors' successes as well as discussion of the many complications of contact lens wear. Contact lenses, whether they are large and soft, medium and fenestrated, or little and hard, have definitely earned a place in the ophthalmologist's armamentarium. This book is an admirable addition to contact lens information and can be a most valuable aid to the clinician. J. Terry Ernest
VOL. 76, NO. 3
composition of the aqueous humour, hor monal and neuronal agents, etc., in influenc ing the morphogensis of the vacuoles re mains to be established." This subject has been discussed in greater depth more re cently.4 I have regarded the process of endothelial vacuolation as dynamic (which does not nec essarily imply that the driving force for this function can only be provided by the metab olism of the cell), (a) to distinguish it from the vacuoles that can be formed as a post mortem change or in a diseased condition, a subject fully discussed by Ashton,6 and (b) to indicate that the transcellular channels are regarded as transient stages in the develop ment of the vacuole during which it is open to both surfaces of the endothelial cell. Ramesh C. Tripathi, M.D., Ph.D., Institute of Ophthalmology, University of London Judd Street, London WC1H 9QS, England. REFERENCES
1. Tripathi, R. C. : Ultrastructure of Schlemm's canal in relation to aqueous outflow. Exp. Eye Res. 7:335,1968. 2. Tripathi, R. C : Mechanism of aqueous out flow across the trabecular wall of Schlemm's canal. Exp. Eye Res. 11:116, 1971. 3. Tripathi, R. C. : Aqueous outflow pathway in normal and glaucomatous eyes. Br. J. Ophthalmol. 56:157, 1972. 4. Tripathi, R. C. : Comparative physiology and anatomy of the outflow pathway. In Davson, H. (ed.) : The Eye, vol. 5. London, Academic Press. In press. 5. Cole, D. F., and Tripathi, R. C. : Theoretical consideration on the mechanism of aqueous outflow. Exp. Eye Res. 12:25, 1971. 6. Ashton, N. : The exit pathway of the aqueous. Trans. Ophthalmol. Soc. UK 80:397, 1960. REPLY
Editor, American Journal of Ophthalmology: We admire Dr. Tripathi's work, and ap preciate his pointing out that our interpreta tion of his concept was not exactly what he had in mind. His letter is helpful in making this clear. It is attractive to us to conceive of vital activity of the endothelial lining of
403
Schlemm's canal having some modulating in fluence on outflow of aqueous and not to postulate an active outward transport requir ing much energy from the metabolism of these cells. W. Morton Grant, M.D. Murray A. Johnston, M.D. Howe Laboratory of Ophthalmology Harvard University Medical School 243 Charles Street Boston, MA 02114 DIABETIC RETINOPATHY STUDY
To the Editor, American Journal of Ophthalmology: Diabetic retinopathy has become one of the four most common causes of blindness in the United States. 1 Although photocoagulation has been employed in its treatment for more than ten years, its true value remains controversial. In spite of the need for objec tive, definitive evidence, an adequately con trolled trial of photocoagulation in proliferative diabetic retinopathy has not been per formed. This is not surprising, considering the complexity and expense of large scale clinical trials in chronic disease. However, as Inglefinger2 has aptly stated, When serious diseases are treated by serious methods .. . then ethical as well as scientific con siderations require that medicine depend on the most reliable and the best controlled data avail able^—the kind of data that is sought by ran domized clinical study.
In keeping with this admonition, a ran domized clinical trial of photocoagulation in the treatment of proliferative diabetic reti nopathy has been designed and launched. The Diabetic Retinopathy Study (DRS) in volves 16 clinical centers in various parts of the United States, a coordinating center at the University of Maryland, and a fundus photograph reading center at the Univer sity of Wisconsin, all supported by contracts from the National Eye Institute, a part of the National Institutes of Health.
404
AMERICAN JOURNAL OF OPHTHALMOLOGY
The support of the medical and ophthalmological communities is needed to carry this study to a successful conclusion. The DRS investigators are, therefore, grateful to the JOURNAL for giving them this opportu nity to summarize the major features of the DRS and to appeal for the support of all physicians who care for diabetic patients. The principal eligibility criteria for the DRS are: 1. Visual acuity with best correction of 20/100 or better in each eye. 2. Diabetic retinopathy in each eye fulfill ing any one of the following conditions: (a) proliferative retinopathy in each eye; (b) proliferative retinopathy in one eye, nonproliferative retinopathy in the other eye; (c) severe nonproliferative retinopathy in each eye. 3. No prior treatment with photocoagulation or pituitary ablation. 4. Both eyes suitable for photocoagulation treatment. 5. Good prospects for survival and avail ability for five years of follow-up. (Patients 70 years of age or older are not eligible.) 6. Only patients willing and able to give their informed consent after thorough expla nation of all aspects of the study will be ad mitted. The basic question which the DRS has been designed to answer is: Can photocoagu lation help to prevent severe visual loss due to proliferative diabetic retinopathy? The chief criterion of success will be the degree to which visual acuity is maintained, al though visual fields and the morphologic ap pearance of the retina in stereoscopic color and fluorescein photographs will also be as sessed. In order to give all patients enrolled in the study the chance to benefit from pho tocoagulation, if it is helpful, while minimiz ing the risk of harm, if it proves deleterious, photocoagulation treatment will be limited to one eye of each patient. This arrangement gives each patient the best chance of retain ing vision in at least one eye, the goal of greatest importance to him.
SEPTEMBER, 1973
The eye to be treated and the treatment modality to be used (xenon arc or argon laser) will be selected by a random process. Treatment will be carried out meticulously according to a detailed protocol, with cen tral monitoring of posttreatment photo graphs. Each patient will be followed-up for a minimum of five years. The pooled results from all 16 centers will be followed closely by the Coordinating Center and presented at frequent intervals to a committee charged with the responsibility of monitoring the data for evidence of beneficial or harmful effects. If it becomes evident during the course of the study that photocoagulation is better than no treatment in a certain stage of diabetic retinopathy, patients with untreated eyes in that stage will be offered treatment. On the other hand, if any feature of either treatment technique proves harmful, this as pect of follow-up treatment will be discon tinued. Results of the study will be reported promptly to the scientific community. All 16 clinical centers are now enrolling patients and each is eager to fill its quota of 100 to 150 patients as rapidly as possible. The overall goal of the study is 1,800 pa tients enrolled and treated by July 1974. It is important to all ophthalmologists, as well as to the entire medical community, that this controlled study be successful in recruit ing the number of patients required to deter mine if and when photocoagulation therapy should be employed as a treatment of prolif erative diabetic retinopathy. It may be many years before facilities and funds will again be available if this opportunity is lost. The DRS investigators ask for the help of all physicians near DRS clinical centers in identifying and referring patients who may be eligible for participation in this study. The sooner we have solid information to guide our treatment of this distressing mani festation of diabetes, the better it will be for its unfortunate victims. Lloyd M. Aiello, M.D.—Joslin Clinic Jose Berrocal, M.D.—University of Puerto Rico Matthew D. Davis, M.D.—
BOOK REVIEWS
VOL: 76, NO. 3
University of Wisconsin Fred Ederer—National Eye Institute Morton F. Goldberg, M.D.— University of Illinois John E. Harris, M.D.— University of Minnesota Christian R. Klimt, M.D.— University of Maryland Genell L. Knatterud— University of Maryland Raymond R. Margherio, M.D.— Wayne State University Edward N. McClean, M.D.— University of Washington J. Wallace McMeel, M.D.— Massachusetts Eye and Ear Infirmary Frank L. Myers, M.D.— University of Wisconsin Edward W. D. Norton, M.D.— University of Miami Arnall Patz, M.D.— Johns Hopkins Hospital Thaddeus Prout, M.D.— Johns Hopkins Hospital F. Tempel Riekhof, M.D.— University of Utah Bradley R. Straatsma, M.D. UCLA Center for Health Sciences William Tasman, M.D.—Wills Eye Hospital W. A. J. van Heuven, M.D.— Albany Medical College Robert C. Watzke, M.D.— University of Iowa REFERENCES
1. Kahn, H. A., and Moorhead, H. B. : Statistics on Blindness in the Model Reporting Area, 1969-70. U.S. Department of Health, Education, and Wel fare, publication No. (NIH) 73-427. 2. Inglefinger, F. J. : The randomized clinical trial. New Engl. J. Med. 287:100, 1972.
BOOK R E V I E W S Trans actions of the New Orleans Academy of Ophthalmology. St. Louis, C. V. Mosby, 1973. Clothbound, 296 pages, 165 illustra tions, two color plates. $29.50 The 21st annual session of the New Or
SYMPOSIUM ON CONTACT LENSES.
405
leans Academy of Ophthalmology was de voted to contact lenses and maintained the traditional excellence the symposia have es tablished over the years. The publisher has successfully completed the rather herculean task of publishing the text within one year of the symposium. The reader is thus as sured of most recent material. Eight men of vast contact lens experience contribute sound chapters on the history, optics, use of contact lenses in aphakia and corneal pathol ogy, etc. Most revealing, however, is the dis cussion emanating from the round tables. There are five panel discussions and it is here that one best sees that contact lens work is still more art than science. Differences of opinion abound in a most healthy manner although sometimes perhaps to an extreme. The opinions on fenestration ranged from no holes to several holes and from center holes to peripheral holes. Much to-do about nothing, but it is important to re mind us that the cornea needs oxygen and that it comes from the air and that tears must thus carry it under the contact lens, even though the lens is soft and semipermeable. There is relatively little new information on the soft lenses although their use as cor neal bandages is well documented. The many uses of the flush-fitting scierai contact lens is discussed, although they require no small de gree of expertise. This is important because it points up the obvious personal involve ment in time and energy these contact lens men have invested to master their art. The diseases amenable to contact lens therapy range from aphakia and keratoconus to keratitis and Stevens-Johnson syndrome. This book contains adequate material on the con tributors' successes as well as discussion of the many complications of contact lens wear. Contact lenses, whether they are large and soft, medium and fenestrated, or little and hard, have definitely earned a place in the ophthalmologist's armamentarium. This book is an admirable addition to contact lens information and can be a most valuable aid to the clinician. J. Terry Ernest