Diabetic Retinopathy Vitrectomy Study (DRVS)

Purpose

To compare early vitrectomy versus conventional management for recent severe vitreous hemorrhage secondary to diabetic retinopathy. To compare early vitrectomy and conventional management in eyes that have good vision but a poor prognosis because they are threatened with hemorrhage or retinal detachment from very severe proliferative retinopathy. To study the natural history of severe proliferative diabetic retinopathy.

Study pattern Patient eligibility criteria was presence of recent severe vitreous hemorrhage (within 5 months) or very severe proliferative retinopathy with extensive active fibrovascular proliferations and useful vision in patients with Type 1 and Type 2 diabetes mellitus. Early vitrectomy 1-6 months after the onset of hemorrhage. Conventional management includes vitrectomy if hemorrhage fails to clear during a waiting period of 12 months or if retinal detachment involving the center of the macula develops at any time. Results

In the severe vitreous hemorrhage trial, 2-year results showed that recovery of good vision (10/20 or better) was more frequent in the early vitrectomy group (25 percent versus 15 percent in the conventional management group) and the advantage was more apparent in Type 1 diabetics who were younger and had more severe fibrovascular proliferations (36 percent with visual acuity of 10/20 or better in the early vitrectomy group versus 12 percent with conventional management). In Type 1 diabetics, the risk of loss of light perception was the same in two groups (28 percent and 26 percent, respectively) but in Type 2 diabetics, there was a trend toward more frequent loss of light perception in the early group (25 percent versus 19 percent).

Conclusion

For eyes with recent severe vitreous hemorrhage, early vitrectomy provided a greater chance of prompt recovery of visual acuity

although greater early risk of visual acuity of no light perception must be kept in mind. The benefit is more pronounced for patients with Type 1 diabetes, particularly for those in whom severe vitreous hemorrhage occurred after a shorter duration of diabetes. This benefit remained at least as great after 4 years of followup as it was at 2 years. The DRVS findings support early vitrectomy in eyes known or suspected to have very severe proliferative diabetic retinopathy as a means of increasing the chance of restoring or maintaining good vision.

Editors Note:At the present time, it should be noted that the results of DRVS were obtained before the development of modern vitrectomy instrumentation, techniques and endolaser photocoagulation. With these techniques, results are more favorable. Nowadays in general, the recommended timing of vitrectomy for severe diabetic vitreous hemorrhage is before 3 months for Type 1 diabetics and 6 months for Type 2 patients.

Diabetes Control and Complications Trial (DCCT)

Purpose: To assess the effect of tight glycemic control on complications of diabetes (nephropathy, neuropathy and diabetic retinopathy) for persons with Type 1 diabetes. Study Pattern Patients with IDDM with no retinopathy at base line (the primaryprevention cohort) and with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. Results In the primary-prevention cohort, intensive therapy (mean HbA1c 7.2%) reduced the risk for the development of retinopathy by 76 percent as compared with conventional therapy (mean HbA1c 9.0%). In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent. In the

two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of 40 mg per 24 hours) by 39 percent, that of albuminuria (urinary albumin excretion of 300 mg per 24 hours) by 54 percent and that of clinical neuropathy by 60 percent. The chief adverse event associated with intensive therapy was a two-tothreefold increase in severe hypoglycemia. Because of this risk, DCCT researchers do not recommend intensive therapy for children under age 13, people with heart disease or advanced complications, older adults, and people with a history of frequent severe hypoglycemia. Persons in the intensive management group also gained a modest amount of weight, suggesting that intensive treatment may not be appropriate for people with diabetes who are overweight. DCCT researchers estimate that intensive management doubles the cost of managing diabetes because of increased visits to a health care professional and the need for more frequent blood testing at home. However, this cost is offset by the reduction in medical expenses related to long-term complications and by the improved quality of life of people with diabetes. Conclusion Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

Early Treatment Diabetic Retinopathy Study (ETDRS)

Purpose

To evaluate the effectiveness of both argon laser photocoagulation and aspirin therapy in delaying or preventing progression of early diabetic retinopathy to more severe stages of visual loss and blindness. To help determine the best time to initiate photocoagulation treatment in diabetic retinopathy. To monitor closely the effects of diabetes mellitus and of photocoagulation on visual function. To produce natural history data that can be used to identify risk factors and test etiologic hypotheses in diabetic retinopathy.

Study Pattern Patient eligibility criteria was presence of mild to very severe NPDR

and/or non high risk PDR with or without macular oedema in both eyes. One eye of each patient was assigned randomly to immediate photocoagulation and the other eye to deferral of photocoagulation (careful follow up) until high-risk PDR developed. Eyes with diabetic macular edema were assigned to immediate or deferred focal photocoagulation (direct laser for focal leaks and grid laser for diffuse leaks). Patients were assigned randomly to aspirin or placebo. The term "clinically significant macular oedema" was coined to designate this level of severity. Results

Focal photocoagulation reduced the risk of moderate vision loss (defined as doubling of visual angle) by 50% or more and increased the chance of a small improvement in visual acuity. Both early scatter and deferral were followed by low rates of severe visual loss (5 year rates in deferral subgroups were 2-10%; in early photocoagulation groups these rates were 2-6%.groupsstatistically significant reduction in severe visual loss for those eyes with early treatment, especially for those patients with non-insulin-dependent diabetes mellitus (NIDDM). However, the reduction was small and the risk was low in the deferral group. Aspirin use did not affect the progression of retinopathy to the highrisk proliferative stage but aspirin also did not increase the risk of vitreous hemorrhage, did not affect vision, and was associated with a decreased risk of cardiovascular disease.

Conclusion

Focal photocoagulation should be considered for eyes with CSME. Scatter treatment is not indicated for eyes with mild to moderate non proliferative diabetic retinopathy. As the retinopathy progresses to the severe non proliferative or early proliferative stage, scatter treatment should be considered, especially for patients with Type 2 diabetes and it should be performed without delay for virtually all eyes with high-risk proliferative retinopathy. Aspirin has no clinically important beneficial effect on the progression of retinopathy. However, since aspirin also has no clinically important harmful effects for diabetic patients with retinopathy therefore there is no ocular contraindications to aspirin use when required for cardiovascular disease or other medical indications.

Diabetic Retinopathy Vitrectomy Study (DRVS)

Purpose

To compare early vitrectomy versus conventional management for recent severe vitreous hemorrhage secondary to diabetic retinopathy. To compare early vitrectomy and conventional management in eyes that have good vision but a poor prognosis because they are threatened with hemorrhage or retinal detachment from very severe proliferative retinopathy. To study the natural history of severe proliferative diabetic retinopathy.

Study pattern Patient eligibility criteria was presence of recent severe vitreous hemorrhage (within 5 months) or very severe proliferative retinopathy with extensive active fibrovascular proliferations and useful vision in patients with Type 1 and Type 2 diabetes mellitus. Early vitrectomy 1-6 months after the onset of hemorrhage. Conventional management includes vitrectomy if hemorrhage fails to clear during a waiting period of 12 months or if retinal detachment involving the center of the macula develops at any time. Results

In the severe vitreous hemorrhage trial, 2-year results showed that recovery of good vision (10/20 or better) was more frequent in the early vitrectomy group (25 percent versus 15 percent in the conventional management group) and the advantage was more apparent in Type 1 diabetics who were younger and had more severe fibrovascular proliferations (36 percent with visual acuity of 10/20 or better in the early vitrectomy group versus 12 percent with conventional management). In Type 1 diabetics, the risk of loss of light perception was the same in two groups (28 percent and 26 percent, respectively) but in Type 2 diabetics, there was a trend toward more frequent loss of light perception in the early group (25 percent versus 19 percent).

Conclusion

For eyes with recent severe vitreous hemorrhage, early vitrectomy provided a greater chance of prompt recovery of visual acuity although greater early risk of visual acuity of no light perception must be kept in mind. The benefit is more pronounced for patients with Type 1 diabetes, particularly for those in whom severe vitreous hemorrhage occurred after a shorter duration of diabetes. This

benefit remained at least as great after 4 years of followup as it was at 2 years. The DRVS findings support early vitrectomy in eyes known or suspected to have very severe proliferative diabetic retinopathy as a means of increasing the chance of restoring or maintaining good vision.

Editors Note:At the present time, it should be noted that the results of DRVS were obtained before the development of modern vitrectomy instrumentation, techniques and endolaser photocoagulation. With these techniques, results are more favorable. Nowadays in general, the recommended timing of vitrectomy for severe diabetic vitreous hemorrhage is before 3 months for Type 1 diabetics and 6 months for Type 2 patients.

Diabetes Control and Complications Trial (DCCT)

Purpose: To assess the effect of tight glycemic control on complications of diabetes (nephropathy, neuropathy and diabetic retinopathy) for persons with Type 1 diabetes. Study Pattern Patients with IDDM with no retinopathy at base line (the primaryprevention cohort) and with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. Results In the primary-prevention cohort, intensive therapy (mean HbA1c 7.2%) reduced the risk for the development of retinopathy by 76 percent as compared with conventional therapy (mean HbA1c 9.0%). In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent. In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of 40 mg per 24 hours) by 39 percent, that of albuminuria (urinary albumin excretion of 300 mg per 24 hours) by 54 percent and that of clinical neuropathy by 60 percent.

The chief adverse event associated with intensive therapy was a two-tothreefold increase in severe hypoglycemia. Because of this risk, DCCT researchers do not recommend intensive therapy for children under age 13, people with heart disease or advanced complications, older adults, and people with a history of frequent severe hypoglycemia. Persons in the intensive management group also gained a modest amount of weight, suggesting that intensive treatment may not be appropriate for people with diabetes who are overweight. DCCT researchers estimate that intensive management doubles the cost of managing diabetes because of increased visits to a health care professional and the need for more frequent blood testing at home. However, this cost is offset by the reduction in medical expenses related to long-term complications and by the improved quality of life of people with diabetes. Conclusion Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.

Diabetic Retinopathy Study (DRS)

Purpose

To determine whether laser photocoagulation helps to prevent severe visual loss from proliferative diabetic retinopathy. To determine whether a difference exists in the efficacy and safety of argon versus xenon photocoagulation for proliferative diabetic retinopathy

Study Pattern Patient eligibility criteria was presence of proliferative diabetic retinopathy in at least one eye or severe non proliferative retinopathy in both eyes. One eye of each patient was assigned randomly to immediate photocoagulation (scatter panretinal treatment, direct local treatment to new vessels and focal treatment for macular edema). The other eye was assigned to follow up without photocoagulation. The eye chosen for treatment was then randomly assigned to either argon laser or xenon arc photocoagulation. Results

Both argon and xenon photocoagulation reduced the risk of severe visual loss by 50 percent or more compared with no treatment

(Severe vision loss was defined as visual acuity <5/200 at two consecutively completed 4 monthly follow up visits). The study identified a stage of retinopathy, termed high-risk proliferative diabetic retinopathy, where the benefits of photocoagulation definitely outweighed the risks (5 year rate of SVL in such eyes was reduced from 50% without treatment to 20% with treatment). There was modest risk of decrease in visual acuity (usually only one line) and visual field (risk greater with xenon than argon photocoagulation).

Conclusion Early PRP is recommended for high-risk proliferative diabetic retinopathy.

Early Treatment Diabetic Retinopathy Study (ETDRS)

Purpose

To evaluate the effectiveness of both argon laser photocoagulation and aspirin therapy in delaying or preventing progression of early diabetic retinopathy to more severe stages of visual loss and blindness. To help determine the best time to initiate photocoagulation treatment in diabetic retinopathy. To monitor closely the effects of diabetes mellitus and of photocoagulation on visual function. To produce natural history data that can be used to identify risk factors and test etiologic hypotheses in diabetic retinopathy.

Study Pattern Patient eligibility criteria was presence of mild to very severe NPDR and/or non high risk PDR with or without macular oedema in both eyes. One eye of each patient was assigned randomly to immediate photocoagulation and the other eye to deferral of photocoagulation (careful follow up) until high-risk PDR developed. Eyes with diabetic macular edema were assigned to immediate or deferred focal photocoagulation (direct laser for focal leaks and grid laser for diffuse leaks). Patients were assigned randomly to aspirin or placebo. The term "clinically significant macular oedema" was coined to designate this level of severity.

Results

Focal photocoagulation reduced the risk of moderate vision loss (defined as doubling of visual angle) by 50% or more and increased the chance of a small improvement in visual acuity. Both early scatter and deferral were followed by low rates of severe visual loss (5 year rates in deferral subgroups were 2-10%; in early photocoagulation groups these rates were 2-6%.groupsstatistically significant reduction in severe visual loss for those eyes with early treatment, especially for those patients with non-insulin-dependent diabetes mellitus (NIDDM). However, the reduction was small and the risk was low in the deferral group. Aspirin use did not affect the progression of retinopathy to the highrisk proliferative stage but aspirin also did not increase the risk of vitreous hemorrhage, did not affect vision, and was associated with a decreased risk of cardiovascular disease.

Conclusion

Focal photocoagulation should be considered for eyes with CSME. Scatter treatment is not indicated for eyes with mild to moderate non proliferative diabetic retinopathy. As the retinopathy progresses to the severe non proliferative or early proliferative stage, scatter treatment should be considered, especially for patients with Type 2 diabetes and it should be performed without delay for virtually all eyes with high-risk proliferative retinopathy. Aspirin has no clinically important beneficial effect on the progression of retinopathy. However, since aspirin also has no clinically important harmful effects for diabetic patients with retinopathy therefore there is no ocular contraindications to aspirin use when required for cardiovascular disease or other medical indications.

Diabetic Retinopathy Vitrectomy Study (DRVS)

Purpose

To compare early vitrectomy versus conventional management for recent severe vitreous hemorrhage secondary to diabetic retinopathy. To compare early vitrectomy and conventional management in eyes that have good vision but a poor prognosis because they are threatened with hemorrhage or retinal detachment from very severe proliferative retinopathy. To study the natural history of severe proliferative diabetic retinopathy.

Study pattern Patient eligibility criteria was presence of recent severe vitreous hemorrhage (within 5 months) or very severe proliferative retinopathy with extensive active fibrovascular proliferations and useful vision in patients with Type 1 and Type 2 diabetes mellitus. Early vitrectomy 1-6 months after the onset of hemorrhage. Conventional management includes vitrectomy if hemorrhage fails to clear during a waiting period of 12 months or if retinal detachment involving the center of the macula develops at any time. Results

In the severe vitreous hemorrhage trial, 2-year results showed that recovery of good vision (10/20 or better) was more frequent in the early vitrectomy group (25 percent versus 15 percent in the conventional management group) and the advantage was more apparent in Type 1 diabetics who were younger and had more severe fibrovascular proliferations (36 percent with visual acuity of 10/20 or better in the early vitrectomy group versus 12 percent with conventional management). In Type 1 diabetics, the risk of loss of light perception was the same in two groups (28 percent and 26 percent, respectively) but in Type 2 diabetics, there was a trend toward more frequent loss of light perception in the early group (25 percent versus 19 percent).

Conclusion

For eyes with recent severe vitreous hemorrhage, early vitrectomy provided a greater chance of prompt recovery of visual acuity although greater early risk of visual acuity of no light perception must be kept in mind. The benefit is more pronounced for patients with Type 1 diabetes, particularly for those in whom severe vitreous hemorrhage occurred after a shorter duration of diabetes. This benefit remained at least as great after 4 years of followup as it was at 2 years. The DRVS findings support early vitrectomy in eyes known or suspected to have very severe proliferative diabetic retinopathy as a means of increasing the chance of restoring or maintaining good vision.

Editors Note:At the present time, it should be noted that the results of DRVS were obtained before the development of modern vitrectomy instrumentation, techniques and endolaser photocoagulation. With these techniques, results are more favorable. Nowadays in general, the

recommended timing of vitrectomy for severe diabetic vitreous hemorrhage is before 3 months for Type 1 diabetics and 6 months for Type 2 patients.

Diabetes Control and Complications Trial (DCCT)

Purpose: To assess the effect of tight glycemic control on complications of diabetes (nephropathy, neuropathy and diabetic retinopathy) for persons with Type 1 diabetes. Study Pattern Patients with IDDM with no retinopathy at base line (the primaryprevention cohort) and with mild retinopathy (the secondary-intervention cohort) were randomly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections. Results In the primary-prevention cohort, intensive therapy (mean HbA1c 7.2%) reduced the risk for the development of retinopathy by 76 percent as compared with conventional therapy (mean HbA1c 9.0%). In the secondary-intervention cohort, intensive therapy slowed the progression of retinopathy by 54 percent and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent. In the two cohorts combined, intensive therapy reduced the occurrence of microalbuminuria (urinary albumin excretion of 40 mg per 24 hours) by 39 percent, that of albuminuria (urinary albumin excretion of 300 mg per 24 hours) by 54 percent and that of clinical neuropathy by 60 percent. The chief adverse event associated with intensive therapy was a two-tothreefold increase in severe hypoglycemia. Because of this risk, DCCT researchers do not recommend intensive therapy for children under age 13, people with heart disease or advanced complications, older adults, and people with a history of frequent severe hypoglycemia. Persons in the intensive management group also gained a modest amount of weight, suggesting that intensive treatment may not be appropriate for people with diabetes who are overweight. DCCT researchers estimate that intensive management doubles the cost of managing diabetes because of increased visits to a health care professional and the need for more frequent blood testing at home. However, this cost is offset by the

reduction in medical expenses related to long-term complications and by the improved quality of life of people with diabetes. Conclusion Intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy, nephropathy, and neuropathy in patients with IDDM.