Ganglion Cell – Inner Plexiform Layer Damage in Diabetic Patients: 3-Year Prospective, Longitudinal, Observational Study

Abstract

Diabetes is expected to accelerate age-related ganglion cell-inner plexiform layer (GC-IPL) loss, but there is limited information on the rate of reduction in GC-IPL thicknesses. We aimed to evaluate the reduction rate of GC-IPL thickness in diabetic patients, and to compare the rates between patients without and with diabetic retinopathy (DR). We included 112 eyes of 112 patients with diabetes [49 eyes without DR (no-DR group) and 63 eyes with mild to moderate non-proliferative DR (NPDR group)] and 63 eyes of 63 normal controls (control group) in this study. Macular GC-IPL thickness in all participants was measured for 3 years at 1-year intervals. The reduction rates of GC-IPL thickness were determined by linear mixed models and compared among the three groups. The estimated reduction rates of the average GC-IPL thickness in the no-DR (−0.627 μm/year) and NPDR (−0.987 μm/year) groups were 2.26-fold (p = 0.010) and 3.56-fold (p = 0.001) faster, respectively, than the control group (−0.277 μm/year). Age, duration of diabetes, and baseline average GC-IPL thickness were associated with longitudinal changes in average GC-IPL thickness. The GC-IPL reduction rate was significantly faster in diabetic patients, with and without DR. Physicians should therefore be aware that GC-IPL damage continues even if there is no DR. Diabetic retinopathy (DR), the most common complication of diabetes, is the leading cause of preventable visual impairment 1,2. In general, DR is clinically defined based on the observation of abnormal fundus vascular lesions, such as microaneurysms, hemorrhages, hard exudates, and cotton wool spots. However, experimental and clinical studies have shown that neurodegenerative changes, including loss of ganglion cells and glial reactivity, are also early events in the pathogenesis of DR 3-5. The loss of ganglion cells affects retinal ganglion cell layer and retinal nerve fiber layer (RNFL) thickness, and reduced thickness of these layers has been detected in clinical and animal studies 3,6-8. Optical coherence tomography (OCT) is a reliable method for quantitative structural evaluation of inner retinal layers, including of the thickness of the peripapillary RNFL (pRNFL) and macular ganglion cell-inner plexiform layer (GC-IPL), where such parameters could be useful for evaluating various conditions, such as retinal neuro-ophthalmic disease and glaucoma 9-11. Progressive changes in GC-IPL thickness can be identified by serial analysis of OCT measurements, and this trend-based analysis could be useful to understand the pathogenesis of certain conditions. Although microvascular abnormalities represent the classic hallmarks of DR, recent studies have reported that diabetic retinal neurodegeneration (DRN) occurs in patients without DR and DRN, which antecedes DR 12-15. The presence of age-related loss of retinal ganglion cells has been demonstrated histologically, and a progressive reduction in GC-IPL thickness, as measured by OCT, has also been reported 16. Abnormal systemic and eye conditions may accelerate th...

Effects of Prolonged Type 2 Diabetes on the Inner Retinal Layer and Macular Microvasculature: An Optical Coherence Tomography Angiography Study

“…Previous studies have reported GC-IPL damage in patients with T2DM [ 22 , 23 , 24 ]. Ng et al [ 22 ] reported that subjects with T2DM but without DR had an average GC-IPL thinning of 4.37 μm, compared to controls.…”

“…Ng et al [ 22 ] reported that subjects with T2DM but without DR had an average GC-IPL thinning of 4.37 μm, compared to controls. Lim et al [ 23 ] found that the estimated reduction rate of the average GC-IPL thickness in T2DM patients without DR (−0.627 μm/year) was 2.26-fold faster than that in normal individuals (−0.277 μm/year). We obtained similar results: The GC-IPL was significantly thinner in T2DM patients than controls.…”

Characteristics of the inner retinal layer in the fellow eyes of patients with unilateral exudative age-related macular degeneration

“…Third, patients with comorbidities such as diabetes mellitus and hypertension were also included in the study. It has been reported that diabetes or hypertension affects GC-IPL and RNFL, and this change can occur even without retinopathy [21,22,51,52]. However, there were no statistically significant differences among the three groups concerning diabetes and hypertension, as presented in Table 1, so it is considered that the effect of diabetes and hypertension would be small.…”

“…Studies on GC-IPL thickness have reported observations of various ocular disorders, including glaucoma, neuro-ophthalmic diseases, and macular diseases [21][22][23][24]. Approximately half of the retinal ganglion cells are concentrated in the macula [25,26].…”

“…Approximately half of the retinal ganglion cells are concentrated in the macula [ 25 , 26 ]. Measurement of these large cell bodies in the macular ganglion cell complex has therefore been useful for the detection of many ocular disorders [ 21 – 24 , 27 , 28 ].…”