Retinal layers changes in human preclinical and early clinical diabetic retinopathy support early retinal neuronal and Müller cells alterations

Stela Vujosevic, Edoardo Midena, Stela Vujosevic, Edoardo Midena

Abstract

Purpose: To evaluate the changes in thickness of individual inner and outer macular and peripapillary retinal layers in diabetes.

Methods: 124 subjects (124 eyes) were enrolled: 74 diabetics and 50 controls. Macular edema, proliferative diabetic retinopathy (DR), any intraocular treatment and refractive error >6 diopters were the main exclusion criteria. Full ophthalmic examination, stereoscopic fundus photography, and spectral domain-OCT were performed. After automatic retinal segmentation (layering) in 5 layers, the thickness of each layer was calculated, and values compared among groups.

Results: Thirty patients had no DR, 44 patients had non proliferative DR. A significant increase of inner plexiform and nuclear layers was found in DR eyes versus controls (P < 0.001). A significant decrease (P < 0.01) of retinal nerve fiber layer (RNFL) and at specific sites of retinal ganglion cell layer (P = 0.02) was documented in the macula. In the peripapillary area there were no differences between diabetics and controls.

Conclusions: Decreased RNFL thickness and increased INL/OPL thickness in diabetics without DR or with initial DR suggest early alterations in the inner retina. On the contrary, the outer retina seems not to be affected at early stages of DM. Automatic intraretinal layering by SD-OCT may be a useful tool to diagnose and monitor early intraretinal changes in DR.

Figures

Figure 1
Figure 1
Spectral domain OCT automatic segmentation of retinal layers in the macula ((a) and (b)) and in the peripapillary area (c). In the macula the segmentation is performed on the linear scan (b) and in the peripapillary area on the circular scan around the optic disc (c). Six lines determine 5 retinal layers which from inside out are as follows: inner limiting membrane + nerve fibre layer (ILM + RNFL); ganglion cell layer + inner plexiform layer (GCL + IPL); inner nuclear layer + outer plexiform layer (INL + OPL); outer nuclear layer + external limiting membrane (ONL + ELM); and inner segment/outer segment photoreceptor layer + retinal pigment epithelium (IS/OS + RPE) (a).
Figure 2
Figure 2
Graphs showing specific retinal layer thickness in normal subjects (control), diabetics without retinopathy (no DR), and diabetics with nonproliferative diabetic retinopathy (NPDR) determined automatically by spectral domain OCT in 9 ETDRS areas in the macula. (a) Inner limiting membrane + nerve fibre layer (ILM + RNFL); (b) ganglion cell layer + inner plexiform layer (GCL + IPL); (c) inner nuclear layer + outer plexiform layer (INL + OPL); (d) outer nuclear layer + external limiting membrane (ONL + ELM); and (e) inner segment/outer segment photoreceptor layer + retinal pigment epithelium (IS/OS + RPE). (∗) indicates statistically significant values; CSF: central subfield thickness; SIM: superior inner quadrant in the macula; NIM: nasal inner quadrant; IIM: inferior inner quadrant; TIM: temporal inner quadrant; SOM: superior outer quadrant in the macula; NOM: nasal outer quadrant; IOM: inferior outer quadrant; TOM: temporal outer quadrant.
Figure 3
Figure 3
Graphs showing specific retinal layer thickness in normal subjects (control), diabetics without retinopathy (no DR), and diabetics with nonproliferative diabetic retinopathy (NPDR) determined automatically by spectral domain OCT in 4 peripapillary areas (temporal, superior, nasal, and inferior). (a) Inner limiting membrane + nerve fibre layer (ILM + RNFL); (b) ganglion cell layer + inner plexiform layer (GCL + IPL); (c) inner nuclear layer + outer plexiform layer (INL + OPL); (d) outer nuclear layer + external limiting membrane (ONL + ELM); and (e) inner segment/outer segment photoreceptor layer + retinal pigment epithelium (IS/OS + RPE). There is no significant difference in the retinal layer thickness among the controls, no DR, and NPDR groups.
Figure 4
Figure 4
Spectral domain OCT linear scans in the macula of (a) normal subject, (b) diabetic patient without retinopathy, and (c) diabetic patient with mild nonproliferative diabetic retinopathy. The arrows indicate a progressive thinning of the retinal nerve fiber layer in diabetics (without and with retinopathy) versus normal subjects.

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