Diabetic retinopathy is a leading cause of irreversible blindness in developed countries. Diabetes and diabetic retinopathy have been shown to negatively impact almost every aspect of visual function from letter acuity to night vision. Although numerous studies have been published, few studies have described the natural history of the visual function abnormalities associated with this disease. In this issue, Hellgren et al. (1) provide one of the first natural history descriptions of early visual function abnormalities in patients with early-stage diabetic retinopathy. The investigators measured the visual field sensitivity of patients with diabetes both with and without mild to moderate diabetic retinopathy, as defined by retinal vascular lesions. The visual field technique used in this study is the standard method for quantification of visual field sensitivity. It is routinely used for detection of defects from glaucoma or neurologic disease. Moreover, it is widely available in clinicians’ offices, so the data are immediately applicable to practice.

Visual field sensitivity is the ability to detect a dim white spot presented at various locations on a white background and has important functional implications: It is important for mobility, driving, and other important tasks of daily living. It has been shown that patients with good visual acuity (e.g., 20/20) but poor visual fields have diminished quality of life (2).

The major strengths of the study by Hellgren et al. are that the authors enrolled 81 well-characterized patients and measured visual fields over 5 years: every 6 months during the first 3 years and annually during the final 2 years. Notably, 91% of subjects were retained during follow-up. Study participants had fairly well-controlled diabetes (mean HbA1c 7.6%) and an average diabetes duration of 13 years at baseline. The severity of retinopathy, as defined by vascular features, remained stable in 68 subjects and changed in only 6 subjects (2 worsened and 4 improved) during follow-up. At study end, 22% of patients exhibited significant worsening of the visual field, defined by standard criteria from glaucoma studies. However, the magnitude of reduced visual field sensitivity was modest, ranging from –0.19 dB to –1.26 dB, a change similar to that noted by Scott et al. (3) in patients with severe nonproliferative or non-high-risk proliferative retinopathy who were observed over 2 years using frequency doubling perimetry. Interestingly, worsening of the visual field occurred in patients with and without changes in vascular lesions associated with diabetic retinopathy. Further, visual field changes were not correlated with duration of diabetes, HbA1c levels, or diastolic blood pressure. One limitation of the study is that 20 of the final 74 subjects lost one or more lines of visual acuity, some of which was due to clinically significant macular edema or cataract; but in 18 cases, the cause of visual loss was not determined.

The study by Hellgren et al. suggests that diabetes has a direct and pronounced effect on the neural retina, and this impact may be independent from the microvascular lesions that are typically used to classify disease severity. It is notable that deterioration of the neural retina may occur for years without a clinically detectable change in the microvasculature using traditional imaging tools. It also may be the case that neural retinal changes precede microvascular changes or that we currently lack the advanced imaging technology necessary to detect subclinical changes in the microvasculature. This question deserves further investigation because the answer will direct the search for therapeutic targets aimed at preserving vision. Indeed, although the entire neurovascular unit is disrupted in diabetes, specific cellular targets remain unclear (4). Because the early visual field deficits in the current study were not correlated with typical risk factors such as blood glucose control or retinal appearance, the clinical assessment of vision beyond the standard letter chart should be investigated for detection of patients at risk for diabetic retinopathy. An obvious question is whether the 20% of patients with worsening visual fields are at higher risk of progression to advanced disease.

Hellgren et al. (1) show that diabetic retinopathy progresses slowly and insidiously early in its evolution, during a period when visual acuity is still intact and patients are free of symptoms (Fig. 1). Therefore, additional longitudinal studies of markers of retinal functional and structural integrity are needed to better define the course of retinopathy with the goal of preserving vision in people with diabetes. This information is essential to better understand the relationship between neural and vascular lesions and to define novel approaches to develop nondestructive therapies. The potential application of this work is suggested by recent studies showing that the neural defects in diabetic retinopathy are responsive to intervention (3,5). Thus, the potential to reduce the progression of retinopathy is substantial and hinges on the use of clinically practical tests.

Figure 1

Both retinal and vascular dysfunction have been linked to vision loss. The temporal and possible causal relationship between the two insults are largely unknown.

Figure 1

Both retinal and vascular dysfunction have been linked to vision loss. The temporal and possible causal relationship between the two insults are largely unknown.

Close modal

See accompanying article, p. 3104.

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

1.
Hellgren
K-J
,
Agardh
E
,
Bengtsson
B
.
Progression of early retinal dysfunction in diabetes over time: results of a long-term prospective clinical study
.
Diabetes
2014;63:3104–3111
[PubMed]
2.
Qiu
M
,
Wang
SY
,
Singh
K
,
Lin
SC
.
Association between visual field defects and quality of life in the United States
.
Ophthalmology
2014;121:733–740
[PubMed]
3.
Scott IU, Jackson GR, Quillen DA, et al. Effect of doxycycline vs placebo on retinal function and diabetic retinopathy progression in patients with severe nonproliferative or non-high-risk proliferative diabetic retinopathy: a randomized clinical trial. JAMA Ophthalmol 2014;132:535–543
4.
Antonetti
DA
,
Klein
R
,
Gardner
TW
.
Diabetic retinopathy
.
N Engl J Med
2012
;
366
:
1227
1239
[PubMed]
5.
Holfort
SK
,
Nørgaard
K
,
Jackson
GR
, et al
.
Retinal function in relation to improved glycaemic control in type 1 diabetes
.
Diabetologia
2011
;
54
:
1853
1861
[PubMed]