Comparative regional pupillography as a noninvasive biosensor screening method for diabetic retinopathy

Maria Carolina Ortube, Alexander Kiderman, Yakov Eydelman, Fei Yu, Nelson Aguilar, Steven Nusinowitz, Michael B Gorin, Maria Carolina Ortube, Alexander Kiderman, Yakov Eydelman, Fei Yu, Nelson Aguilar, Steven Nusinowitz, Michael B Gorin

Abstract

Purpose: We describe infrared regional pupillometry as an objective comparative assessment of midperipheral to central retinal sensitivity and to correlate with midperipheral retinal ischemia in diabetic subjects.

Methods: We tested 12 normal and 17 diabetic subjects using bilateral infrared pupillometry. The diabetic cohort included seven subjects without, five with mild, three with moderate, and two with severe non-proliferative diabetic retinopathy (NPDR). Central and annular stimuli of varying intensity were presented to one eye, and pupillary amplitude and constriction velocity were measured from both eyes. Light stimulus of increasing intensity was presented as 20 consecutive trials (stimulus duration of 300 ms with 3000 ms intervals). The ratio of central to peripheral responses (Q values) was calculated for each stimulus configuration. Average responses with respect to the stimulus strength were regressed with Gompertz sigmoid function.

Results: Control and moderate/severe NPDR cases comparison showed statistically significant differences in amplitude (Q(A)) and constriction velocity (Q(CV)) (Wilcoxon rank sum test P = 0.002, respectively). Age difference for these groups was not statistically significant (Wilcoxon rank sum test P = 0.15). The comparison of control and diabetic subjects without NPDR/mild NPDR was statistically significant for Q(A) and Q(CV) (Wilcoxon rank sum test P = 0.0002 and P = 0.001, respectively). Q(A) and Q(CV) differences were statistically significant between moderate/severe NPDR cases and subjects without or mild NPDR cases (Wilcoxon rank sum test P = 0.013).

Conclusions: Q(A) and Q(CV) values correlated highly with the severity of diabetic retinopathy, but not with the duration of diabetes.

Trial registration: ClinicalTrials.gov NCT01546766.

Conflict of interest statement

Disclosure: M.C. Ortube, None; A. Kiderman, Neuro Kinetics, Inc. (F, I, E); Y. Eydelman, Neuro Kinetics, Inc. (E); F. Yu, None; N. Aguilar, None; S. Nusinowitz, None; M.B. Gorin, P

Figures

Figure 1.
Figure 1.
Pupillometer device and pupillometer functional diagram.
Figure 2.
Figure 2.
Static and dynamic pupillary measurements.
Figure 3.
Figure 3.
Q-Constriction velocity values versus age in control subjects.
Figure 4.
Figure 4.
Q-Amplitude values versus age in control subjects.
Figure 5.
Figure 5.
Q-Amplitude values for test versus re-test.
Figure 6.
Figure 6.
Q-Constriction velocity values for test versus re-test.
Figure 7.
Figure 7.
Q-Amplitude versus Q-Constriction velocity for all groups.
Figure 8.
Figure 8.
Q-Amplitude and Q-Constriction velocity versus diabetic condition (NPDR).

References

    1. Lee JM, Davis MM, Menon RK, Freed GL. Geographic distribution of childhood diabetes and obesity relative to the supply of pediatric endocrinologists in the United States. J Pediatr. 2008; 152: 331–336
    1. Tanne JH. Americans are living longer, but obesity and diabetes are rising. BMJ. 2011; 342:d1143
    1. Dea TL. Pediatric obesity & type 2 diabetes. MCN Am J Matern Child Nurs. 2011; 36: 42–48
    1. American Diabetes Association Economic costs of diabetes in the U.S. in 2007. Diabetes Care. 2008; 31: 596–615
    1. Zhang X, Saaddine JB, Chou CF, et al. Prevalence of diabetic retinopathy in the United States, 2005–2008. JAMA. 2010; 304: 649–656
    1. Center for Disease Control and Prevention (CDC) Preserving vision in patients with diabetes. 2012. Available at
    1. Oliver SC, Schwartz SD. Peripheral vessel leakage (PVL): a new angiographic finding in diabetic retinopathy identified with ultra wide-field fluorescein angiography. Semin Ophthalmol. 2010; 25: 27–33
    1. Niki T, Muraoka K, Shimizu K. Distribution of capillary nonperfusion in early-stage diabetic retinopathy. Ophthalmology. 1984; 91: 1431–1439
    1. Shimizu K, Kobayashi Y, Muraoka K. Midperipheral fundus involvement in diabetic retinopathy. Ophthalmology. 1981; 88: 601–612
    1. Sampson GP, Shahidi AM, Vagenas D, et al. Visual sensitivity loss in the central 30° of visual field is associated with diabetic peripheral neuropathy. Diabetologia 2012; 55: 1179–1185
    1. Fundus photographic risk factors for progression of diabetic retinopathy ETDRS report number 12. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991; 98 (5 Suppl): 823–833
    1. Spry PG, Johnson CA. Senescent changes of the normal visual field: an age-old problem. Optom Vis Sci. 2001; 78: 436–441
    1. Johnson CA, Adams AJ, Lewis RA. Evidence for a neural basis of age-related visual field loss in normal observers. Invest Ophthalmol Vis Sci. 1989; 30: 2056–2064
    1. Jaffe GJ, Alvarado JA, Juster RP. Age-related changes of the normal visual field. Arch Ophthalmol. 1986; 104: 1021–1025
    1. Klein R, Klein BE, Moss SE, et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. II. Prevalence and risk of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1984; 102: 520–526
    1. Klein R, Klein BE, Moss SE, et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years. Arch Ophthalmol. 1984; 102: 527–532

Source: PubMed

Sponsorer och medarbetare

Medicinska tillstånd

Läkemedelsinterventioner

3
Prenumerera