Advances in imaging technology assist in early detection of diabetic retinopathy

Earlier diagnosis leads to earlier treatment and better visual outcomes.

Diabetic retinopathy is a leading cause of preventable blindness in working-aged adults. Risk factors for visually significant DR include duration of disease, poor glycemic control and hypertension.

The American Diabetes Association recommends initial eye examinations for patients with diabetes as follows: for type 1 diabetes, initial dilated exam within 5 years of onset of diabetes; for type 2 diabetes, initial dilated exam at time of diagnosis; and for pregnant women with diabetes, a screening examination before or during the first trimester. Unfortunately, studies show that the rate of diabetic eye exams continues to be low.

Karen Jeng-Miller
Karen Jeng-Miller

Early detection of DR is important for prompt treatment and optimal visual outcomes. In cases of subclinical DR, neural retinal damage and microvascular changes may occur but be asymptomatic to patients. At the point of visible funduscopic diabetic changes, microvascular changes may have already resulted in irreversible structural damage.

Advancements

severe nonproliferative DR with many areas of microaneurysms and capillary dropout
Figure 1. Fluorescein angiography showing severe nonproliferative DR with many areas of microaneurysms and capillary dropout.

Source: Karen Jeng-Miller, MD

Advances in imaging technology have provided ophthalmologists with adjunctive diagnostic tools to better evaluate for the presence and extent of DR. Simple color fundus photography can be important in highlighting findings that may have been missed on slit lamp or indirect ophthalmoscopy examination. The development of ultra-widefield (UWF) retinal imaging allows glimpses into the far periphery with a single photograph.

As recently defined by the International Widefield Imaging Study Group, an UWF image is one showing retinal anatomy anterior to the vortex vein ampullae in all four quadrants in a single capture. As the need for DR screening increases without a corresponding increase in ophthalmology providers, UWF imaging is particularly important for the implementation of telemedicine models to improve screening rates. It can provide high-quality pictures to more accurately diagnose DR in a telemedicine model. In several published studies, including one by the Diabetic Retinopathy Clinical Research Network in JAMA Ophthalmology, UWF imaging has demonstrated moderate to substantial agreement when determining DR severity within the area covered by ETDRS seven standard fields. Many studies in other countries have demonstrated the cost-effectiveness of telemedicine programs for DR and even a significant decline in the rate of DR due to these screenings to the point where DR is no longer the leading cause of blindness in the working age group.

Fluorescein angiography is a standard tool for evaluating cases of severe nonproliferative DR and proliferative DR in order to determine the level of ischemia and any resulting pathology. Ultra-widefield fluorescein angiography (UWFA) is particularly important in assessing these changes as it provides views into the far periphery as well as posterior pole to provide a more comprehensive assessment of the degree of DR. In a 2015 study in Ophthalmology, the presence and increased extent of predominantly peripheral lesions in DR as identified by UWFA was associated with an increased risk for progression over 4 years. This association was independent of baseline DR severity and HbA1c levels.

OCT has been an important tool to evaluate for diabetic macular edema. Studies have shown that early changes on OCT, such as reduction of the inner neuroretinal layer thickness, can be seen in subclinical DR. OCT is helpful for identifying macular edema and often guides treatment decisions. OCT angiography (OCTA) is another imaging modality that is relatively new, providing noninvasive visualization of the retinal and choroidal vasculature. In cases of patients with diabetes with no evidence of clinical DR, OCTA can identify an increased size of the foveal avascular zone and capillary nonperfusion. Other forms of imaging not routinely used in clinical practice but that can possibly identify subclinical DR include reduced contrast sensitivity on contrast sensitivity testing, abnormal results in color vision and microperimetry testing, and a prolonged implicit time on multifocal electroretinography.

severe nonproliferative DR with extrafoveal intraretinal fluid and exudation
Figure 2. OCT of severe nonproliferative DR with extrafoveal intraretinal fluid and exudation.

Early treatment

Timely diagnosis of DR is critical because the importance of early treatment is becoming increasingly evident. Anti-VEGF therapy is a mainstay of treatment in cases of DME and proliferative DR. Current research seeks to determine its role in cases of nonproliferative DR without DME. Recent results of the phase 3 PANORAMA study presented by W. Lloyd Clark, MD, at the 2019 American Society of Retina Specialists annual meeting found that treatment with intravitreal Eylea (aflibercept, Regeneron) injections can reverse disease progression in patients with moderately severe to severe nonproliferative DR. In this study, patients were randomly assigned to receive aflibercept injections at intervals of every 8 weeks after receiving five monthly doses or aflibercept injections at intervals of every 16 weeks after receiving three monthly doses and aflibercept every 18 weeks or sham dosing. The study found that those in both arms of the aflibercept group had a lower proportion of patients developing vision-threatening complications than the sham group. Furthermore, the incidence of center-involving DME was lower in the aflibercept group.

In conclusion, our research to date demonstrates both the importance of early detection and treatment of DR, as well as the value of diagnostic imaging including UWF and OCT. Providers should be aware of these tools for DR detection and consider earlier, more aggressive treatments for high-risk individuals.

Disclosure: Jeng-Miller reports no relevant financial disclosures.

Diabetic retinopathy is a leading cause of preventable blindness in working-aged adults. Risk factors for visually significant DR include duration of disease, poor glycemic control and hypertension.

The American Diabetes Association recommends initial eye examinations for patients with diabetes as follows: for type 1 diabetes, initial dilated exam within 5 years of onset of diabetes; for type 2 diabetes, initial dilated exam at time of diagnosis; and for pregnant women with diabetes, a screening examination before or during the first trimester. Unfortunately, studies show that the rate of diabetic eye exams continues to be low.

Karen Jeng-Miller
Karen Jeng-Miller

Early detection of DR is important for prompt treatment and optimal visual outcomes. In cases of subclinical DR, neural retinal damage and microvascular changes may occur but be asymptomatic to patients. At the point of visible funduscopic diabetic changes, microvascular changes may have already resulted in irreversible structural damage.

Advancements

severe nonproliferative DR with many areas of microaneurysms and capillary dropout
Figure 1. Fluorescein angiography showing severe nonproliferative DR with many areas of microaneurysms and capillary dropout.

Source: Karen Jeng-Miller, MD

Advances in imaging technology have provided ophthalmologists with adjunctive diagnostic tools to better evaluate for the presence and extent of DR. Simple color fundus photography can be important in highlighting findings that may have been missed on slit lamp or indirect ophthalmoscopy examination. The development of ultra-widefield (UWF) retinal imaging allows glimpses into the far periphery with a single photograph.

As recently defined by the International Widefield Imaging Study Group, an UWF image is one showing retinal anatomy anterior to the vortex vein ampullae in all four quadrants in a single capture. As the need for DR screening increases without a corresponding increase in ophthalmology providers, UWF imaging is particularly important for the implementation of telemedicine models to improve screening rates. It can provide high-quality pictures to more accurately diagnose DR in a telemedicine model. In several published studies, including one by the Diabetic Retinopathy Clinical Research Network in JAMA Ophthalmology, UWF imaging has demonstrated moderate to substantial agreement when determining DR severity within the area covered by ETDRS seven standard fields. Many studies in other countries have demonstrated the cost-effectiveness of telemedicine programs for DR and even a significant decline in the rate of DR due to these screenings to the point where DR is no longer the leading cause of blindness in the working age group.

Fluorescein angiography is a standard tool for evaluating cases of severe nonproliferative DR and proliferative DR in order to determine the level of ischemia and any resulting pathology. Ultra-widefield fluorescein angiography (UWFA) is particularly important in assessing these changes as it provides views into the far periphery as well as posterior pole to provide a more comprehensive assessment of the degree of DR. In a 2015 study in Ophthalmology, the presence and increased extent of predominantly peripheral lesions in DR as identified by UWFA was associated with an increased risk for progression over 4 years. This association was independent of baseline DR severity and HbA1c levels.

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OCT has been an important tool to evaluate for diabetic macular edema. Studies have shown that early changes on OCT, such as reduction of the inner neuroretinal layer thickness, can be seen in subclinical DR. OCT is helpful for identifying macular edema and often guides treatment decisions. OCT angiography (OCTA) is another imaging modality that is relatively new, providing noninvasive visualization of the retinal and choroidal vasculature. In cases of patients with diabetes with no evidence of clinical DR, OCTA can identify an increased size of the foveal avascular zone and capillary nonperfusion. Other forms of imaging not routinely used in clinical practice but that can possibly identify subclinical DR include reduced contrast sensitivity on contrast sensitivity testing, abnormal results in color vision and microperimetry testing, and a prolonged implicit time on multifocal electroretinography.

severe nonproliferative DR with extrafoveal intraretinal fluid and exudation
Figure 2. OCT of severe nonproliferative DR with extrafoveal intraretinal fluid and exudation.

Early treatment

Timely diagnosis of DR is critical because the importance of early treatment is becoming increasingly evident. Anti-VEGF therapy is a mainstay of treatment in cases of DME and proliferative DR. Current research seeks to determine its role in cases of nonproliferative DR without DME. Recent results of the phase 3 PANORAMA study presented by W. Lloyd Clark, MD, at the 2019 American Society of Retina Specialists annual meeting found that treatment with intravitreal Eylea (aflibercept, Regeneron) injections can reverse disease progression in patients with moderately severe to severe nonproliferative DR. In this study, patients were randomly assigned to receive aflibercept injections at intervals of every 8 weeks after receiving five monthly doses or aflibercept injections at intervals of every 16 weeks after receiving three monthly doses and aflibercept every 18 weeks or sham dosing. The study found that those in both arms of the aflibercept group had a lower proportion of patients developing vision-threatening complications than the sham group. Furthermore, the incidence of center-involving DME was lower in the aflibercept group.

In conclusion, our research to date demonstrates both the importance of early detection and treatment of DR, as well as the value of diagnostic imaging including UWF and OCT. Providers should be aware of these tools for DR detection and consider earlier, more aggressive treatments for high-risk individuals.

Disclosure: Jeng-Miller reports no relevant financial disclosures.