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Objective Evaluation of Improvement in Optic Neuropathy Following Radiation Therapy for Thyroid Eye Disease,
458
Surv Ophthalmol 45 (5) March–April 2001
CURRENT OPHTHALMOLOGY
Despite the above reservations about the current study, this is an interesting observation, and it will be interesting to see what further studies document in terms of the usefulness of OMT measurements in the clinical setting. Creig S. Hoyt, MD San Francisco, California, USA PII S0039-6257(01)00189-8
Objective Evaluation of Improvement in Optic Neuropathy Following Radiation Therapy for Thyroid Eye Disease, by S. Rush, J. M. Winterkorn, and R. Zak. Int J Radiat Oncol Biol Phys 47:191–4, 2000 Purpose: While the literature supports the use of radiation therapy for thyroid eye disease, it does not sufficiently describe in detail the results of radiation therapy for optic neuropathy associated with thyroid eye disease. The objective of this study is to quantify the changes in parameters of optic neuropathy after orbital irradiation for thyroid eye disease. Methods and Materials: Twelve consecutive patients with optic neuropathy from thyroid eye disease were followed by a single neuro-ophthalmology practice and treated by one radiation oncologist with radiation therapy from 1991 through 1995. All cases were prospectively followed for visual acuity, color vision, mean deviation, and/or foveal sensitivity and afferent pupillary defect. All patients received 2000 cGy in 10 fractions with megavoltage irradiation to the orbits. Results: Ten of 12 patients were evaluated for follow-up (one moved out of this country and one had a stroke, which confounded interpretation of examination results). An analysis was performed retrospectively while treatment and evaluation remained uniform. Five men and five women formed the basis of this study with a median age of 60 years (35–76 years). Nineteen eyes were evaluated for thyroid optic neuropathy. Improvement in optic nerve function occurred in eight of ten patients. Improvement was seen either during radiotherapy or within 2 weeks of completion. No longterm adverse effects were noted. Conclusion: This study objectively demonstrates improvement in optic neuropathy from radiation therapy for thyroid eye disease. (Authors’ address: Long Island Radiation Therapy, Manhasset, New York, USA.)
Comment Radiation therapy has been used to safely treat thyroid orbitopathy in over 1500 patients.1 Rush and coworkers describe 10 irradiated thyroid optic neuropathy patients with extensive neuro-ophthalmologic evaluations. Nine of these patients had failed a course of oral corticosteroids. Seven of 10 had an excellent response to radiation; one case required orbital decompression, one was stable and one had deterioration due to corneal exposure. The authors point out, as others have noted, that the radiation response is rapid.2 When should radiation be used to treat thyroid eye disease, what are the contraindications, and what are its limitations? Radiation is an excellent treatment in patients who develop moderate or severe inflammatory thyroid orbitopathy that does not respond (or responds, then re-exacerbates) to a short course of high dose oral prednisone. Radiation is lympholytic; its major effect is to ablate the inflammatory and immune cells in the orbit. Radiation is not effective in the fibrotic phase of the disease, and if there is uncertainty on the basis of a quiescent clinical appearance, orbital MRI or MRS should be performed. Sarah Donaldson and I recently reviewed the combined UCSF and Stanford radiation experience in thyroid eye disease. In over 600 cases, we observed no significant morbidity. There have been several reports of severe damage after radiation for thyroid orbitopathy, but all such cases we evaluated had sub-optimal treatment planning (unpublished data). Contraindications for radiation are lack of radiation expertise, noninflammatory disease, minimal eye disease and significant risk factors for vasculopathy (prior radiation to cranial structures or severe vascular disease). As pointed out by Rush and co-workers, patients often respond to a short course of high-dose oral prednisone, and I almost always try these medications before instituting radiation. One caveat not stressed in the article by Rush and associates is the incidence of late radiation treatment failure in thyroid optic neuropathy patients. In their study they noted one such case; unfortunately the overall length of post-treatment follow-up is not stated. In a 1985 report with long-term follow-up, we noted that as many as one-third of such patients
459
CURRENT OPHTHALMOLOGY
can develop recurrent compressive thyroid optic neuropathy after radiation. Occasionally, recurrence can be quite delayed and all treated patients require long-term monitoring. Devron H. Char, MD San Francisco, California, USA PII S0039-6257(01)00188-6 1. Char DH: Thyroid eye disease, 3rd edition. Boston, Butterworth, 1998 2. Hrubli T, Char DH, Harris J, et al: Radiation therapy for thyroid eye disease. Am J Ophthalmol 99:633–7, 1985
Retinopathy and Nephropathy in Patients with Type 1 Diabetes Four Years after A Trial of Intensive Insulin Therapy, by The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 342:381–9, 2000 Background: Among patients with type 1 diabetes mellitus, intensive therapy (with the aim of achieving nearnormal blood glucose and glycosylated hemoglobin concentrations [hemoglobin A1c]) markedly reduces the risk of microvascular complications as compared with conventional therapy. To assess whether these benefits persist, we compared the effects of former and intensive conventional therapy on the recurrence and severity of retinopathy and nephropathy for four years after the end of the Diabetes Control and Complications Trial (DCCT). Methods: At the end of the DCCT, the patients in the conventional-therapy group were offered intensive therapy, and the care of all patients was transferred to their own physicians. Retinopathy was evaluated on the basis of centrally graded fundus photographs in 1208 patients during the fourth year after the DCCT ended, and nephropathy was evaluated on the basis of urine specimens obtained from 1302 patients during the third or fourth year, approximately half of whom were from each treatment group. Results: The difference in the median glycosylated hemoglobin values between the conventional-therapy and intensive-therapy groups during the 6.5 years of the DCCT (average, 9.1% and 7.2%, respectively) narrowed during follow-up (median during 4 years, 8.2% and 7.9%, respectively, P ⬍ 0.001). Nevertheless, the proportion of patients who had worsening retinopathy, including proliferative retinopathy, macular edema, and the need for laser therapy, was lower in the intensive-therapy group than in the conventional-therapy group (odds reduction, 72% to 87%, P ⬍ 0.001). The proportion of patients with an increase in urinary albumin excretion was significantly lower in the intensive-therapy group. Conclusions: The reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persists for at least four years, despite increasing hyperglycemia.
Comment Diabetic retinopathy remains the third leading cause of permanent blindness in the United States. All ophthalmologists must be familiar with the diagnosis of this disorder and know that prevention of visual loss is achieved with appropriate laser treatment. Ophthalmologists should also be aware that appropriate control of blood glucose has an important influence on the development and progression of diabetic retinopathy. The Diabetes Complications and Control Trial (DCCT) was a multicenter clinical trial in which 1441 type 1 insulin dependent diabetics were randomized to either conventional insulin therapy, consisting of one or two injections of insulin and one blood or urine test per day, or intensive therapy, consisting of at least three injections of insulin or an insulin pump and at least four blood glucose measurements per day. The study group found that after an average of 6.5 years, the severity of retinopathy (graded as none, mild, moderate/severe, or proliferative) was less in the intensive therapy group. The risk of progression from lower to higher grades was reduced from 30% to 10% by intensive insulin therapy. Following the conclusion of the DCCT, all patients in the conventional treatment group were offered intensive insulin therapy, and all patients in both groups were followed by their own physicians. The Epidemiology of Diabetes Interventions and Complications (EDIC) research group reassessed 1208 of the original 1441 DCCT patients four years after the close of the original study. They found that while less than half of the patients in both the original intensive group and the original conventional group monitored their blood glucose more than three times a day, and that while hemoglobin AlC levels in both groups tended to converge, there
Surv Ophthalmol 45 (5) March–April 2001
CURRENT OPHTHALMOLOGY
Despite the above reservations about the current study, this is an interesting observation, and it will be interesting to see what further studies document in terms of the usefulness of OMT measurements in the clinical setting. Creig S. Hoyt, MD San Francisco, California, USA PII S0039-6257(01)00189-8
Objective Evaluation of Improvement in Optic Neuropathy Following Radiation Therapy for Thyroid Eye Disease, by S. Rush, J. M. Winterkorn, and R. Zak. Int J Radiat Oncol Biol Phys 47:191–4, 2000 Purpose: While the literature supports the use of radiation therapy for thyroid eye disease, it does not sufficiently describe in detail the results of radiation therapy for optic neuropathy associated with thyroid eye disease. The objective of this study is to quantify the changes in parameters of optic neuropathy after orbital irradiation for thyroid eye disease. Methods and Materials: Twelve consecutive patients with optic neuropathy from thyroid eye disease were followed by a single neuro-ophthalmology practice and treated by one radiation oncologist with radiation therapy from 1991 through 1995. All cases were prospectively followed for visual acuity, color vision, mean deviation, and/or foveal sensitivity and afferent pupillary defect. All patients received 2000 cGy in 10 fractions with megavoltage irradiation to the orbits. Results: Ten of 12 patients were evaluated for follow-up (one moved out of this country and one had a stroke, which confounded interpretation of examination results). An analysis was performed retrospectively while treatment and evaluation remained uniform. Five men and five women formed the basis of this study with a median age of 60 years (35–76 years). Nineteen eyes were evaluated for thyroid optic neuropathy. Improvement in optic nerve function occurred in eight of ten patients. Improvement was seen either during radiotherapy or within 2 weeks of completion. No longterm adverse effects were noted. Conclusion: This study objectively demonstrates improvement in optic neuropathy from radiation therapy for thyroid eye disease. (Authors’ address: Long Island Radiation Therapy, Manhasset, New York, USA.)
Comment Radiation therapy has been used to safely treat thyroid orbitopathy in over 1500 patients.1 Rush and coworkers describe 10 irradiated thyroid optic neuropathy patients with extensive neuro-ophthalmologic evaluations. Nine of these patients had failed a course of oral corticosteroids. Seven of 10 had an excellent response to radiation; one case required orbital decompression, one was stable and one had deterioration due to corneal exposure. The authors point out, as others have noted, that the radiation response is rapid.2 When should radiation be used to treat thyroid eye disease, what are the contraindications, and what are its limitations? Radiation is an excellent treatment in patients who develop moderate or severe inflammatory thyroid orbitopathy that does not respond (or responds, then re-exacerbates) to a short course of high dose oral prednisone. Radiation is lympholytic; its major effect is to ablate the inflammatory and immune cells in the orbit. Radiation is not effective in the fibrotic phase of the disease, and if there is uncertainty on the basis of a quiescent clinical appearance, orbital MRI or MRS should be performed. Sarah Donaldson and I recently reviewed the combined UCSF and Stanford radiation experience in thyroid eye disease. In over 600 cases, we observed no significant morbidity. There have been several reports of severe damage after radiation for thyroid orbitopathy, but all such cases we evaluated had sub-optimal treatment planning (unpublished data). Contraindications for radiation are lack of radiation expertise, noninflammatory disease, minimal eye disease and significant risk factors for vasculopathy (prior radiation to cranial structures or severe vascular disease). As pointed out by Rush and co-workers, patients often respond to a short course of high-dose oral prednisone, and I almost always try these medications before instituting radiation. One caveat not stressed in the article by Rush and associates is the incidence of late radiation treatment failure in thyroid optic neuropathy patients. In their study they noted one such case; unfortunately the overall length of post-treatment follow-up is not stated. In a 1985 report with long-term follow-up, we noted that as many as one-third of such patients
459
CURRENT OPHTHALMOLOGY
can develop recurrent compressive thyroid optic neuropathy after radiation. Occasionally, recurrence can be quite delayed and all treated patients require long-term monitoring. Devron H. Char, MD San Francisco, California, USA PII S0039-6257(01)00188-6 1. Char DH: Thyroid eye disease, 3rd edition. Boston, Butterworth, 1998 2. Hrubli T, Char DH, Harris J, et al: Radiation therapy for thyroid eye disease. Am J Ophthalmol 99:633–7, 1985
Retinopathy and Nephropathy in Patients with Type 1 Diabetes Four Years after A Trial of Intensive Insulin Therapy, by The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group. N Engl J Med 342:381–9, 2000 Background: Among patients with type 1 diabetes mellitus, intensive therapy (with the aim of achieving nearnormal blood glucose and glycosylated hemoglobin concentrations [hemoglobin A1c]) markedly reduces the risk of microvascular complications as compared with conventional therapy. To assess whether these benefits persist, we compared the effects of former and intensive conventional therapy on the recurrence and severity of retinopathy and nephropathy for four years after the end of the Diabetes Control and Complications Trial (DCCT). Methods: At the end of the DCCT, the patients in the conventional-therapy group were offered intensive therapy, and the care of all patients was transferred to their own physicians. Retinopathy was evaluated on the basis of centrally graded fundus photographs in 1208 patients during the fourth year after the DCCT ended, and nephropathy was evaluated on the basis of urine specimens obtained from 1302 patients during the third or fourth year, approximately half of whom were from each treatment group. Results: The difference in the median glycosylated hemoglobin values between the conventional-therapy and intensive-therapy groups during the 6.5 years of the DCCT (average, 9.1% and 7.2%, respectively) narrowed during follow-up (median during 4 years, 8.2% and 7.9%, respectively, P ⬍ 0.001). Nevertheless, the proportion of patients who had worsening retinopathy, including proliferative retinopathy, macular edema, and the need for laser therapy, was lower in the intensive-therapy group than in the conventional-therapy group (odds reduction, 72% to 87%, P ⬍ 0.001). The proportion of patients with an increase in urinary albumin excretion was significantly lower in the intensive-therapy group. Conclusions: The reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persists for at least four years, despite increasing hyperglycemia.
Comment Diabetic retinopathy remains the third leading cause of permanent blindness in the United States. All ophthalmologists must be familiar with the diagnosis of this disorder and know that prevention of visual loss is achieved with appropriate laser treatment. Ophthalmologists should also be aware that appropriate control of blood glucose has an important influence on the development and progression of diabetic retinopathy. The Diabetes Complications and Control Trial (DCCT) was a multicenter clinical trial in which 1441 type 1 insulin dependent diabetics were randomized to either conventional insulin therapy, consisting of one or two injections of insulin and one blood or urine test per day, or intensive therapy, consisting of at least three injections of insulin or an insulin pump and at least four blood glucose measurements per day. The study group found that after an average of 6.5 years, the severity of retinopathy (graded as none, mild, moderate/severe, or proliferative) was less in the intensive therapy group. The risk of progression from lower to higher grades was reduced from 30% to 10% by intensive insulin therapy. Following the conclusion of the DCCT, all patients in the conventional treatment group were offered intensive insulin therapy, and all patients in both groups were followed by their own physicians. The Epidemiology of Diabetes Interventions and Complications (EDIC) research group reassessed 1208 of the original 1441 DCCT patients four years after the close of the original study. They found that while less than half of the patients in both the original intensive group and the original conventional group monitored their blood glucose more than three times a day, and that while hemoglobin AlC levels in both groups tended to converge, there