Download a review of the current treatment modalities for diabetic retinopathy

CLINICIAN INTERVIEW
A REVIEW OF THE CURRENT TREATMENT MODALITIES
FOR DIABETIC RETINOPATHY
—
Interview with Emily Y. Chew, MD
Dr Chew is a medical officer at the Division of
Biometry and Epidemiology at the National Eye Institute,
the National Institutes of Health (Bethesda, MD). She
earned her Doctor of Medicine and completed her residency at the University of Toronto, Ontario, Canada. Dr
Chew obtained her postgraduate fellowship training at
the Johns Hopkins Hospital, Baltimore, MD. She currently sees patients with retinal disorders, including
patients with diabetes mellitus, at the Clinical Center of
the National Institutes of Health.
A senior clinical editor for Advanced Studies in
Medicine interviewed Dr Chew to discuss the importance of early diagnosis of diabetic retinopathy and the
current treatment modalities being used.
Diabetic retinopathy is one of the leading causes of
vision loss in the United States.1 There are approximately 4.1 million individuals aged 40 years and older
affected by diabetic retinopathy, and 1 in 12 persons
with diabetes has advanced vision-threatening
retinopathy.2 In the future, these numbers will likely
rise along with the expected increase in the incidence
of diabetes, resulting from the aging population and
the increase in obesity.3 Vision loss caused by diabetic
retinopathy is a significant and growing public health
problem. Early detection in persons with diabetes is
critical because timely treatment can reduce the rate of
severe vision loss by as much as 90%.4 However,
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despite the availability of effective treatment, many
patients with diabetic retinopathy are not adequately
screened so that timely intervention can be implemented. Intensive medical management of glycemia,
hypertension, and possibly dyslipidemia are important
and integral parts of the therapy for diabetic retinopathy. The ophthalmologists and the medical physicians
must adopt an interdisciplinary collaboration to care
optimally for patients with diabetes. In the following
interview, Emily Y. Chew, MD, discusses the importance of screening and early intervention in improving
the outcomes for diabetic retinopathy. She also
describes methods of diagnosis and assessment, treatment, and the disease rating scales that can facilitate
interdisciplinary and international collaborative treatment efforts.
ASiM: Early screening for diabetes and the
microvascular complications that often precede the
negative sequelae that occur as the disease progresses is an important determinant for patient outcomes. Please discuss the relationship of screening
to early diagnosis and the effect of early treatment
on outcomes.
Dr Chew: Early detection of diabetic retinopathy is
essential in preventing further progression and potential vision loss. Because the early stages and even the
more severe stages of diabetic retinopathy need not
produce symptoms, persons with diabetes must be
screened with periodic, thorough, dilated eye examinations to establish the presence and the severity of
diabetic retinopathy. The American Academy of
Ophthalmology, the American Diabetes Association,
and other organizations have provided guidelines for
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the frequency of these eye examinations. The recommendations for most individuals with diabetes include
an annual dilated eye examination with an eyecare
provider who is familiar with the course and the management of diabetic retinopathy. Currently, the adherence to the annual eye examination guidelines falls
short of the providers’ goals, with approximately 35%
to 65% of individuals with diabetes having an annual
eye examination.5-7 Early detection would lead to earlier and more appropriate and effective treatment.
Early detection is also important because the
physicians caring for patients with diabetes and diabetic retinopathy can appropriately counsel them
regarding the importance of medical management.
Recent improvements in diabetes care reflect the
general acceptance of the results of randomized controlled clinical trials demonstrating that good
glycemic control reduces the development and progression of diabetic retinopathy in individuals with
type 1 or type 2 diabetes.8-10 Management of hypertension is important in decreasing the progression of
diabetic retinopathy.11 Observational data suggest
management of dyslipidemia also may be beneficial
in preventing the progression of diabetic retinopathy.12 Screening for this disease is particularly important because there are effective treatments, such as
laser photocoagulation and vitrectomy, that can
reduce the risk of severe vision loss to less than
5%.13,14 Long-term follow-ups of these treatments
show promising results.13,14
ASiM: What is the status and the available methods
for a treatment team approach (primary care physicians, endocrinologists, and ophthalmologists) to
screening for retinopathy?
Dr Chew: There are many methods (with or without pharmacologic dilation of the pupils) available for
detecting diabetic retinopathy that can be conducted
by a variety of healthcare providers using a team
approach, including direct and indirect ophthalmoscopy (with or without stereoscopic viewing) and
fundus photography.
Ophthalmoscopy. Physicians in general practice,
endocrinologists, and ophthalmologists can use an
ophthalmoscope to perform fundus examinations
within their own practices. Ophthalmoscopy is a useful screening procedure, relatively easy to use, and
accessible for all physicians. Examination of the eyes
through dilated pupils provides the physician with an
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optimal view of the fundus. However, the sensitivity
and specificity or the ability of each of these groups of
healthcare workers to diagnose diabetic retinopathy
will vary greatly. Studies conducted among different
groups of healthcare providers clearly show that ophthalmologists, specifically retinal specialists, are most
likely to detect the presence of diabetic retinopathy
requiring laser photocoagulation or other treatments.
Assessment from simple ophthalmoscopy through
dilated fundus by an experienced examiner was found
to agree with results obtained by fundus photography
85% of the time.15 The diagnosis of diabetic macular
edema, an important cause of vision loss, often
requires stereoscopic evaluation that may only be
performed effectively by an ophthalmologist.
Ophthalmoscopy is less sensitive than fundus photography for detecting some of the earliest lesions of diabetic retinopathy.16
Fundus photography. Several forms of retinal
screening with standard fundus photography or digital imaging (with and without pupil dilation) are
being investigated as a means of detecting retinopathy early; these methods warrant further evaluation.17 Some studies have shown that screening
patients with diabetes to identify sight-threatening
retinopathy with photography is more sensitive
compared to a clinical examination using an ophthalmoscope.13,18,19 It is unclear whether the new digital photography techniques (eg, single-field 45°
photograph) are as sensitive and specific as traditional standard 7-field stereoscopic 30° fundus photography for determining the level of diabetic
retinopathy.20 Most digital nonmydriatic cameras
lack stereoscopic capability that is useful for identifying subtle neovascularization and macular edema.
However, there are digital nonmydriatic cameras
that are used in a stereoscopic manner and have been
validated against fundus photography. Future studies may eventually show that these cameras are useful tools.
Whether photographic screening programs achieve a
greater reduction in vision loss compared to routine
community care in areas with unrestricted access to ophthalmologists has not been proven.21 These screening
programs have great value in circumstances in which
access to ophthalmic care is limited.13 Currently, these
technologies are not considered as a replacement for a
comprehensive eye examination by an ophthalmologist
experienced in managing diabetic retinopathy.
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ASiM: Please discuss the importance of early diagnosis in more detail.
Dr Chew: Early detection of diabetic retinopathy is
essential because diabetic retinopathy can progress to
irreversible stages with relatively few symptoms,22 and the
optimal time for treatment is before visual acuity is
impaired. Treatment will often stabilize vision, but it
improves vision less frequently. Studies have confirmed
that the clinical outcome is better if patients are screened
and treated early.23
The 2 main causes of vision loss in patients with
diabetic retinopathy include proliferative retinopathy
and diabetic macular edema; both conditions can be
asymptomatic initially. Patients with proliferative
retinopathy may have excellent vision until the neovascularization leads to a vitreous hemorrhage or to the
more severe stage with tractional retinal detachment
involving the center of the macula. Patients with severe
nonproliferative diabetic retinopathy also are asymptomatic but are at a high risk for developing proliferative
disease within 1 year after initial onset of the disease.
Patients with an early or even more moderate stage of
diabetic macular edema may maintain reasonable
vision, but they may suffer a threat to central vision
when thickening of the retina occurs close to the fovea.
The standard treatments for eyes approaching or
classified as showing proliferative diabetic retinopathy
and diabetic macular edema include laser photocoagulation (occasionally combined with vitrectomy).
Neither laser photocoagulation nor vitrectomy is likely to result in a complete reversal of any vision loss;
however, if the treatment is performed in a timely fashion, the long-term results show that a large proportion
of patients can maintain “driving” vision. This important result underscores the significance of treating diabetic retinopathy when the visual acuity is still good,
which requires regular dilated eye examinations by an
eyecare provider who is familiar with diabetic
retinopathy and can diagnose diabetic retinopathy
requiring treatment.
area and to guide laser treatment for diabetic macular
edema. These angiograms can also be transmitted to
reading centers for evaluations in clinical studies.
Fluorescein angiography requires specialized and expensive equipment and personnel. It is not a useful screening procedure because of its invasiveness, time demands,
and possible adverse reactions from allergy to the sodium
fluorescein dye. Serious complications are rare.
Optical coherence tomography. OCT, using laser light,
provides high-resolution (eg, 10 µm) imaging of the retina and its surrounding structures. OCT can be useful for
quantifying retinal thickness, monitoring partial resolution of macular edema, and identifying abnormalities in
the vitreous and retinal junction. OCT is becoming an
important tool to assess diabetic macular edema for clinical trials and in clinical practice.
ASiM: What are the other methods or tools available for diagnosing diabetic retinopathy?
Dr Chew: In addition to ophthalmoscopy and
fundus photography, other techniques include fluorescein angiography and optical coherence tomography (OCT).
Fluorescein angiography. Fluorescein angiography is
used mainly to evaluate the blood flow in the macular
ASiM: What are some of the issues and considerations in terms of classifying diabetic retinopathy to
standardize care?
Dr Chew: For decades, the gold standard for grading the severity of diabetic retinopathy was stereoscopic fundus photography of 7 standard fields through
dilated pupils. These fields were graded using the Early
Treatment Diabetic Retinopathy Study (ETDRS) clas-
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ASiM: Please discuss in greater detail how the primary care physician, endocrinologist, and ophthalmologist can work together effectively in a
treatment team approach to improve early detection and diagnosis of diabetic retinopathy.
Dr Chew: Clearly, the ophthalmologist should
manage eye disease and ensure that patients with diabetes are referred for appropriate management of their
systemic condition. The patient’s family physician, primary care physician, internist, or endocrinologist
should manage the systemic condition of the patient
with diabetes. The ophthalmologist should communicate with the attending physician. An ongoing dialogue must occur between the members of the
interdisciplinary team who are treating the patient.
Development of educational material regarding the
importance of good glycemic control and tight control
of hypertension in the role of diabetic retinopathy is
important for the physicians and the patients. Education
regarding the need of a regular dilated eye examination
for all patients (at least annually) should also be directed
toward the physicians, the patients, and their families
who would benefit from this knowledge.
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sification,24 a classification used in research studies.
Use of the ETDRS classification in everyday clinical
practice was not easy or practical. The photographic
grading system has more levels than are necessary for
clinical use and the specific definitions of the levels are
detailed, often requiring comparisons with standard
photographs. This system was too complex for clinicians to use in their offices. In addition, development
of a common practical standard terminology that
would be acceptable for worldwide exchange of information was needed.
The need to provide a framework for improved
communication and transfer of information among
primary care physicians, endocrinologists, ophthalmologists, and other eyecare providers has been the
major drive to develop simplified clinical disease severity scales that could be used internationally. The
International Summary Severity Scale was developed
for diabetic retinopathy and diabetic macular edema25
as an attempt to improve communication between
ophthalmologists and primary care physicians,
endocrinologists, and other healthcare providers who
are caring for diabetic patients and among clinicians
worldwide. This scale is based on the data collected in
clinical trials26 and epidemiologic studies of diabetic
retinopathy.27,28 It simplifies the ETDRS classification
of diabetic retinopathy for clinical use.
One of the criteria for the development of this classification system was its usefulness for a broad range of
providers with varying skills and diagnostic equipment
(ie, ranging from retinal specialists with contemporary
equipment to trained physician assistants with only
direct ophthalmoscopes). This criterion required a
simpler classification because all lesions described
must be detected by the personnel with the least level
of training who are using the direct ophthalmoscope.
This staging system is intended primarily for comprehensive ophthalmologists and others with skills necessary for evaluating the retina and also should allow
better communication regarding diabetic retinopathy
severity to all physicians and care providers for patients
with diabetes. The improved communication should
lead to more effective and consistent follow-up of diabetic retinopathy and diabetic macular edema cases.
ASiM: Please discuss the use of any disease rating
scales and their applicability and use across the
span of healthcare providers.
Dr Chew: The diabetic retinopathy severity scale
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(see “International Classification of Diabetic
Retinopathy Disease Severity Scale” table on page 697)
can be easily translated into field work with minimal
training of the clinician because of the simplicity of the
lesions. The level of severe nonproliferative diabetic
retinopathy, although somewhat difficult to diagnose, is
essential because treatment with scatter laser photocoagulation is initiated at this stage, allowing for worldwide
communication as to the severity of the retinopathy.
The scale used for diabetic macular edema (see
“International Classification of Diabetic Macular
Edema Disease Severity Scale” table on page 697) is
more difficult to use compared to the scale for diabetic retinopathy because without stereoscopic viewing,
retinal thickening in the absence of retinal hard exudates may be difficult to recognize; however, this presentation may be less common. Diabetic macular
edema is a prevalent cause of vision loss, thus it is
important to have a classification that can be easily
used by clinicians worldwide.
In the classification system, the most important
groups indicate patients at risk for vision loss from
diabetic retinopathy. Patients who have severe nonproliferative diabetic retinopathy are at high risk for developing proliferative retinopathy associated with risk of
severe vision loss. Diabetic macular edema is another
important cause of vision loss that is evaluated with
this simple scale. This international collaboration will
hopefully initiate studies to improve the ocular health
and quality of life for all patients with diabetes.
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