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Editorial
Early^Treatment Diabetic
Retinopathy Study: Good
News for Diabetic Patients
and Health Care Professionals
T
he recently published results of the Early-Treatment Diabetic Retinopathy Study (ETDRS) proved
the value of focal laser photocoagulation in nonproliferative diabetic retinopathy with macular
edema.' The study found that treated eyes were half as likely
to lose vision as were eyes in which treatment was deferred.
After 3 yr of follow-up, 12% of treated eyes, compared with
24% of eyes in which treatment was deferred, lost significant
vision. This finding underscores the importance of regular
ophthalmologic examinations for all patients with diabetes.
An earlier study, the Diabetic Retinopathy Study (DRS),
proved the benefit of laser photocoagulation in proliferative
diabetic retinopathy (PDR).2"4 This is the more severe of the
two types of retinopathy and carries a greater risk of significant
loss of vision. However, PDR accounts for <10% of diabetic
retinopathy; >90% of people with diabetic retinopathy have
the nonproliferative type. Although PDR causes more severe
loss, nonproliferative retinopathy causes visual loss in more
people. Although the visual loss usually is not severe, it can
still be of sufficient degree to alter the diabetic patient's lifestyle considerably. The ETDRS was done to determine whether
this large group of patients could benefit from laser therapy
in the macular region.
The Macular Photocoagulation Study is another clinical
trial of laser therapy that recently proved the efficacy of laser
treatment for certain abnormal vessels under the retina in the
macula in age-related macular degeneration and ocular histoplasmosis.5'6
All of these studies are randomized, multicenter, controlled
clinical trials. Because the randomized controlled trial greatly
reduces factors that might bias results, it is the best method
for establishing that a particular treatment is effective in a
particular condition. The findings of the ETDRS can be considered conclusive. They are based on data collected from 29
426
centers, including 23 clinical centers, nationwide. A Fundus
Photograph Reading Center graded stereophotographs in detail. A Coordinating Center maintained the communication
and flow of data among the centers. Several committees ensured strict adherence to the study protocol.
The study population consisted of patients with mild-tomoderate diabetic retinopathy. An eye was considered to have
"clinically significant macular edema" if it had at least one
of several characteristics: 1) thickening of the retina at or
within 500 \xm of the center of the macula (Fig. 1); 2) hard
exudates at or within 500 \xm of the center of the macula,
if associated with adjacent retinal thickening (Fig. 2); and
3) a zone of thickened retina, one disk diameter or larger,
within one disk diameter of the center of the macula (Fig.
3).
There were 1122 patients with bilateral involvement and
754 with unilateral involvement, for a total of 2998 eyes.
The eyes were first randomly assigned to one of two groups,
an immediate photocoagulation group (1508 eyes) or a deferred photocoagulation group (1490 eyes) in which treatment
was deferred until high-risk PDR developed. In the patients
with bilateral involvement, one eye was assigned to the immediate treatment group and the other to the deferred treatment group. The eyes with unilateral involvement were distributed about evenly in the two groups.
The eyes assigned to immediate treatment then were again
randomized into two treatment groups. Half of the eyes (754
eyes) were assigned to focal photocoagulation of leaking blood
vessels, and half were assigned to panretinal photocoagulation
with follow-up focal photocoagulation if macular edema persisted. The recent ETDRS publication reports on the outcome
in the focal-treatment group compared with the outcome in
the deferred-treatment group. The outcome in the panretinal
treatment group was not reported at this time.
Aspirin therapy (650 mg/day) was also given randomly to
half the patients. Compared with placebo, aspirin did not
affect the results of focal photocoagulation. The effect of
aspirin on the diabetic retinopathy is not reported here.
After 3 yr of follow-up, the treated eyes were half as likely
as the untreated eyes to lose significant visual acuity. Of the
treated eyes, 12% lost significant visual acuity, whereas 24%
DIABETES CARE, VOL. 9 NO. 4, JULY-AUGUST 1986
EDITORIAL
FIG. /. Thickening of retina at or within 500
|xm of center of macula.
of the eyes in which treatment was deferred lost vision. This
was true regardless of the baseline visual acuity. Even eyes
with excellent visual acuity benefited from treatment, because
they lost less vision over time than did eyes in the group in
which laser was deferred. The treated eyes also had a higher
rate of visual improvement and a lower rate of persistent
macular edema. The only noted adverse effect of treatment
was minor loss in central visual fields.
This study compared immediate treatment with treatment
deferred indefinitely. Clinically we have the option in many
cases of following an affected eye with good vision and treating
it if the eye becomes worse either in visual acuity or by clinical
appearance. This may be the best option in many cases.
The ETDRS research group recommended that focal photocoagulation treatment be considered for all eyes with retinopathy and "clinically significant macular edema" as defined by the study. For these eyes to receive the treatment
they should when they should, it is essential to educate health
care professionals and diabetic patients about diabetic eye
disease and the need for diabetic patients to have regular
ophthalmologic examinations.
In a Wisconsin study, 62% of a group of diabetic patients
FIG. 2. Hard exudates at or within 500 [Lm of
center of macula with associated thickening of adjacent retina.
DIABETES CARE, VOL. 9 NO. 4, JULY-AUGUST 1986
427
EDITORIAL
L'i;,\
never had an eye exam.7 A study in Michigan found that 2
yr after the DRS findings were made public, two-thirds of the
family practice physicians and half of the internists surveyed
were unaware of the study and its implications for prevention
of visual loss secondary to severe diabetic retinopathy.8
Another study evaluated the ability of different types of
physicians to diagnose diabetic retinopathy. The serious error
rates for diagnosing PDR were 52% for internists, 50% for
medical residents, 33% for diabetologists, 9% for general
ophthalmologists, and 0% for retinal specialists.9 Retinopathy
FIG- 3. Zone of thickened retina within I disk
diameter of center of macula.
must be diagnosed before it can be treated. Because the physicians who provide primary care to diabetic patients have a
significant probability of missing the diagnosis of PDR, it is
clear that referral to an ophthalmologist or retinal specialist
should be a routine part of management of the diabetic patient.
The same study also found that even ophthalmologists may
err in the clinical classification of diabetic retinopathy. The
study suggested the use of fluorescein angiography and/or
fundus photographs to elucidate the extent of diabetic reti-
FIG. 4. Treatable lesions: microaneurysms (open
arrow) and intraretinal microvascular abnormal-
ities (solid arrow).
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DIABETES CARE, VOL. 9 NO. 4, JULY-AUGUST 1986
EDITORIAL
nopathy before performing laser photocoagulation. Furthermore, the definitive treatment benefit demonstrated by the
ETDRS applies only to patients evaluated and managed according to the technical protocol of the study. This protocol
includes fluorescein angiography, which is projected for study
during the laser treatment. The angiogram helps identify
treatable lesions, which include microaneurysms, intraretinal
microvascular abnormalities, avascular zones, and leaking
capillaries (Fig. 4).
In addition to potential confusion about diagnosis, the
treatment, which includes focal whitening or darkening of
individual microaneurysms, requires considerable technical
skill. Where possible, optimal patient care will be expedited
if the diabetic patient is referred directly to an ophthalmologist who is very experienced in managing diabetic retinopathy. Retinal specialists and other ophthalmologists with particular interest and training in diabetic retinopathy should
have the necessary facilities readily available. This includes
in-office or nearby fluorescein angiography and its developing
capabilities, as well as ready access to an argon laser and
possibly other laser photocoagulators.
To ensure the best visual prognosis for the diabetic patient,
it is essential to educate health care professionals and patients
with diabetes about the need for regular ophthalmologic examination. Examination by an ophthalmologist or retinal specialist with the necessary experience and equipment for the
diagnosis and management of diabetic retinopathy provides
the best chance for preservation of vision in patients with
diabetes.
LAWRENCE J. SINGERMAN, MD, FACS
From the Retinal Service, Mount Sinai, St. Luke's, and Case
Western Reserve University Hospitals, Cleveland, Ohio.
Send reprint requests to Lawrence J. Singerman, M.D., Retina
Associates of Cleveland, Retinal Laboratories, 26900 Cedar Road,
Suite 323, Cleveland, OH 44122.
REFERENCES
1
Early Treatment Diabetic Retinopathy Study Research Group:
Photocoagulation for diabetic macular edema. Arch. Ophthalmol.
1985; 103:1796-806.
2
The Diabetic Retinopathy Study Research Group: Preliminary
report on effects of photocoagulation therapy. Am. J. Ophthalmol.
1976; 81:3383-96.
3
The Diabetic Retinopathy Study Research Group: Four risk factors for severe visual loss in diabetic retinopathy. The third report
from the diabetic retinopathy study. Arch. Ophthalmol. 1979; 97:65455.
4
The Diabetic Retinopathy Study Research Group: Photocoagulation treatment of proliferative diabetic retinopathy. Clinical application of Diabetic Retinopathy Study (DRS) findings, report number
8. Ophthalmology 1981; 88:583-600.
5
The Macular Photocoagulation Study Group: Argon laser photocoagulation for senile macular degeneration. Results of a randomized clinical trial. Arch. Ophthalmol. 1982; 100:912-18.
6
The Macular Photocoagulation Study Group: Argon laser photocoagulation for ocular histoplasmosis. Results of a randomized
clinical trial. Arch. Ophthalmol. 1983; 101:1347-57.
7
Witkin, S. R., and Klein, R.: Ophthalmologic care for persons
with diabetes. JAMA 1984; 251:2534-37.
8
Stross, J. K., and Harlan, W. R.: The dissemination of new
medical information. JAMA 1979; 241:2622-24.
9
Sussman, E. J., Tsiaras, W. G., and Soper, K. A.: Diagnosis of
diabetic eye disease. JAMA 1982; 247:3231-34.
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