Diabetic retinopathy: early detection
DOI:
https://doi.org/10.22201/codeic.16076079e.2019.v20n3.a1Keywords:
diabetic retinopathy, vision, neurovascular unit, early functional endpoint, therapiesAbstract
Diabetic retinopathy (DR), commonly classified as a vascular complication of diabetes, is now recognized as a neurovascular affliction. A comprehensive set of evidence points to the fact that DR is a sensory neuropathy resulting from the neurovascular unit rupture, and that neuronal death is an early event in the pathogenesis of DR. However, current therapies for DR only focus on limiting the vascular alterations, including abnormal formation of new blood vessels and macular edema. Based on this information, much scientists’ efforts are about elucidating the mechanisms underlying both neurodegeneration and neurovascular unit rupture to develop new treatments for initial stages of DR. The identification and validation of early markers of visual function is also required to reduce the duration of clinical trials and to accelerate the delivery of new treatments for DR to the general population. In this article, we describe the neurovascular unit of the retina and examine how the retina is altered in early stages of diabetes. We also comment on how early functional endpoint of visual function would impact future clinical trials that aim to assess novel therapeutic options for DR.
References
Aiello, L. M. (2003). Perspectives on diabetic retinopathy. American Journal of Ophthalmology, 136(1), 122-135. doi: https://doi.org/10.1016/S0002-9394(03)00219-8.
Antonetti, D. A., Barber, A. J., Bronson, S. K., Freeman, W. M., Gardner, T. W., Jefferson, L. S., . . . Group, J. D. R. C. (2006). Diabetic retinopathy: seeing beyond glucose-induced microvascular disease. Diabetes, 55(9), 2401-2411. doi: https://doi.org/10.2337/db05-1635.
Antonetti, D. A., Klein, R. y Gardner, T. W. (2012). Diabetic retinopathy. New England Journal of Medecine, 366(13), 1227-1239. doi: https://doi.org/10.1056/NEJMra1005073.
Bek, T., Hajari, J. y Jeppesen, P. (2008). Interaction between flicker-induced vasodilatation and pressure autoregulation in early retinopathy of type 2 diabetes. Graefes Archive Clinical Experimental Ophthalmology, 246(5), 763-769. doi: https://doi.org/10.1007/s00417-008-0766-y.
Bloodworth, J. M. J. (1962). Diabetic retinopathy. Diabetes, 11, 1-22.
Cohen, S. R. y Gardner, T. W. (2016). Diabetic Retinopathy and Diabetic Macular Edema. Developemts in Ophthalmology, 55, 137-146. doi: https://doi.org/10.1159/000438970.
Cunha-Vaz, J. (2012). Neurodegeneration as an eraly event in the pathogenesis of Diabetic Retinopathy: A multicentric, prospective, phase ii-iii, randomised controlled trial to asses the efficacy of neuroprotective drugs administered topically to prevent or arrest Diabetic Retinopathy. eurocondor-eu fp7 Project. Acta Ophtalmologica, 90(249), 0.
Del Zoppo, G. J. (2010). The neurovascular unit in the setting of stroke. Journal of Internal Medecine, 267(2), 156-171. doi: https://doi.org/10.1111/j.1365-2796.2009.02199.x.
Doft, B. H. y Blankenship, G. W. (1982). Single versus multiple treatment sessions of argon laser panretinal photocoagulation for proliferative diabetic retinopathy. Ophthalmology, 89(7), 772-779.
Early Treatment Diabetic Retinopathy Study Research Group (1991). Early photocoagulation for diabetic retinopathy. etdrs report number 9. Ophthalmology, 98(5 Suppl), 766-785. doi: https://doi.org/10.1016/S0161-6420(13)38011-7.
Gardner, T. W., Abcouwer, S. F., Barber, A. J. y Jackson, G. R. (2011). An integrated approach to diabetic retinopathy research. Archive Ophthalmology, 129(2), 230-235. doi: https://doi.org/10.1001/archophthalmol.2010.362.
Garhofer, G., Zawinka, C., Resch, H., Kothy, P., Schmetterer, L. y Dorner, G. T. (2004). Reduced response of retinal vessel diameters to flicker stimulation in patients with diabetes. British Journal of Ophthalmology, 88(7), 887-891. doi: https://doi.org/10.1136/bjo.2003.033548.
Greenstein, V. C., Thomas, S. R., Blaustein, H., Koenig, K. y Carr, R. E. (1993). Effects of early diabetic retinopathy on rod system sensitivity. Optometry and Vision Science, 70(1), 18-23.
Group, T. D. R. S. R. (1976). Preliminary report on effects of photocoagulation therapy. American Journal of Ophtalmology, 81(4), 383-396.
Harrison, W. W., Bearse, M. A., Jr., Ng, J. S., Jewell, N. P., Barez, S., Burger, D., . . . Adams, A. J. (2011). Multifocal electroretinograms predict onset of diabetic retinopathy in adult patients with diabetes. Investigation in Ophthalmology and Vision Science, 52(2), 772-777. doi: https://doi.org/10.1167/iovs.10-5931.
Jackson, G. R., Scott, I. U., Quillen, D. A., Walter, L. E. y Gardner, T. W. (2012). Inner retinal visual dysfunction is a sensitive marker of non-proliferative diabetic retinopathy. British Journal of Ophthalmology, 96(5), 699-703. doi: https://doi.org/10.1136/bjophthalmol-2011-300467.
Kristinsson, J. K., Gottfredsdottir, M. S. y Stefansson, E. (1997). Retinal vessel dilatation and elongation precedes diabetic macular oedema. British Journal of Ophthalmology, 81(4), 274-278.
Kur, J., Newman, E. A. y Chan-Ling, T. (2012). Cellular and physiological mechanisms underlying blood flow regulation in the retina and choroid in health and disease. Progress in Retina and Eye Research, 31(5), 377-406. doi: https://doi.org/10.1016/j.preteyeres.2012.04.004.
Kylstra, J. A., Wierzbicki, T., Wolbarsht, M. L., Landers, M. B., 3rd y Stefansson, E. (1986). The relationship between retinal vessel tortuosity, diameter, and transmural pressure. Graefes Archive Clinical and Experimental Ophthalmology, 224(5), 477-480.
Lasta, M., Pemp, B., Schmidl, D., Boltz, A., Kaya, S., Palkovits, S., . . . Schmetterer, L. (2013). Neurovascular dysfunction precedes neural dysfunction in the retina of patients with type 1 diabetes. Investigation in Ophthalmology and Vision Science, 54(1), 842-847. doi: https://doi.org/10.1167/iovs.12-10873.
Lott, M. E., Slocomb, J. E., Shivkumar, V., Smith, B., Gabbay, R. A., Quillen, D., . . . Bettermann, K. (2012). Comparison of retinal vasodilator and constrictor responses in type 2 diabetes. Acta Ophthalmologica, 90(6), e434-441. doi: https://doi.org/10.1111/j.1755-3768.2012.02445.x.
Metea, M. R. y Newman, E. A. (2007). Signalling within the neurovascular unit in the mammalian retina. Experimental Physiology, 92(4), 635-640. doi: https://doi.org/10.1113/expphysiol.2006.036376.
Mitchell, P., Bandello, F., Schmidt-Erfurth, U., Lang, G. E., Massin, P., Schlingemann, R. O., . . . restore study group (2011). The restore study: ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology, 118(4), 615-625. doi: https://doi.org/10.1016/j.ophtha.2011.01.031.
Ng, J. S., Bearse, M. A., Jr., Schneck, M. E., Barez, S. y Adams, A. J. (2008). Local diabetic retinopathy prediction by multifocal erg delays over 3 years. Investigation in Ophthalmology and Vision Science, 49(4), 1622-1628. doi: https://doi.org/10.1167/iovs.07-1157.
Nguyen, Q. D., Brown, D. M., Marcus, D. M., Boyer, D. S., Patel, S., Feiner, L., . . . Group, R. R. (2012). Ranibizumab for diabetic macular edema: results from 2 phase iii randomized trials: rise and ride. Ophthalmology, 119(4), 789-801. doi: https://doi.org/10.1016/j.ophtha.2011.12.039.
Nguyen, Q. D., Shah, S. M., Heier, J. S., Do, D. V., Lim, J., Boyer, D., . . . Group, R.-S. (2009). Primary End Point (Six Months) Results of the Ranibizumab for Edema of the mAcula in diabetes (read-2) study. Ophthalmology, 116(11), 2175-2181 e2171. doi: https://doi.org/10.1016/j.ophtha.2009.04.023.
Pahor, D. (1998). Visual field loss after argon laser panretinal photocoagulation in diabetic retinopathy: full- versus mild-scatter coagulation. International Ophthalmology, 22(5), 313-319.
Park, H. Y., Kim, I. T. y Park, C. K. (2011). Early diabetic changes in the nerve fibre layer at the macula detected by spectral domain optical coherence tomography. British Journal of Ophthalmology, 95(9), 1223-1228. doi: https://doi.org/10.1136/bjo.2010.191841.
Parravano, M., Oddone, F., Mineo, D., Centofanti, M., Borboni, P., Lauro, R., . . . Manni, G. (2008). The role of Humphrey Matrix testing in the early diagnosis of retinopathy in type 1 diabetes. British Journal of Ophthalmology, 92(12), 1656-1660. doi: https://doi.org/10.1136/bjo.2008.143057.
Pender, P. M., Benson, W. E., Compton, H. y Cox, G. B. (1981). The effects of panretinal photocoagulation on dark adaptation in diabetics with proliferative retinopathy. Ophthalmology, 88(7), 635-638.
Petzold, G. C. y Murthy, V. N. (2011). Role of astrocytes in neurovascular coupling. Neuron, 71(5), 782-797. doi: https://doi.org/10.1016/j.neuron.2011.08.009.
Reijmer, Y. D., Brundel, M., de Bresser, J., Kappelle, L. J., Leemans, A., Biessels, G. J. y Utrecht Vascular Cognitive Impairment Study, G. (2013). Microstructural white matter abnormalities and cognitive functioning in type 2 diabetes: a diffusion tensor imaging study. Diabetes Care, 36(1), 137-144. doi: https://doi.org/10.2337/dc12-0493.
Runkle, E. A. y Antonetti, D. A. (2011). The blood-retinal barrier: structure and functional significance. Methods in Molecular Biology, 686, 133-148. doi: https://doi.org/10.1007/978-1-60761-938-3_5.
Russell, P. W., Sekuler, R. y Fetkenhour, C. (1985). Visual function after pan-retinal photocoagulation: a survey. Diabetes Care, 8(1), 57-63.
Saydah, S. H., Fradkin, J. y Cowie, C. C. (2004). Poor control of risk factors for vascular disease among adults with previously diagnosed diabetes. jama, 291(3), 335-342. doi: https://doi.org/10.1001/jama.291.3.335.
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., . . . Stevens, B. (2012). Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron, 74(4), 691-705. doi: https://doi.org/10.1016/j.neuron.2012.03.026.
Seiberth, V., Alexandridis, E. y Feng, W. (1987). Function of the diabetic retina after panretinal argon laser coagulation. Graefes Archive Clinical and Experimental Ophthalmology, 225(6), 385-390.
Simo, R., Hernandez, C. y European Consortium for the Early Treatment of Diabetic, R. (2012). Neurodegeneration is an early event in diabetic retinopathy: therapeutic implications. British Journal of Ophthalmology, 96(10), 1285-1290. doi: https://doi.org/10.1136/bjophthalmol-2012-302005.
Sinclair, S. H., Grunwald, J. E., Riva, C. E., Braunstein, S. N., Nichols, C. W. y Schwartz, S. S. (1982). Retinal vascular autoregulation in diabetes mellitus. Ophthalmology, 89(7), 748-750.
Stem, M. S. y Gardner, T. W. (2013). Neurodegeneration in the pathogenesis of diabetic retinopathy: molecular mechanisms and therapeutic implications. Current Medical Chemistry, 20(26), 3241-3250.
Umegaki, H. (2012). Neurodegeneration in diabetes mellitus. Advance in Experimental Medical Biology, 724, 258-265. doi: https://doi.org/10.1007/978-1-4614-0653-2_19.
Van Dijk, H. W., Verbraak, F. D., Kok, P. H., Garvin, M. K., Sonka, M., Lee, K., . . . Abramoff, M. D. (2010). Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes. Investigation in Ophthalmology and Vision Science, 51(7), 3660-3665. doi: https://doi.org/10.1167/iovs.09-5041.
Volgyi, B., Kovacs-Oller, T., Atlasz, T., Wilhelm, M. y Gabriel, R. (2013). Gap junctional coupling in the vertebrate retina: variations on one theme? Progress in Retina and Eye Research, 34, 1-18. doi: https://doi.org/10.1016/j.preteyeres.2012.12.002.
Wilkinson, C. P., Ferris, F. L., 3rd, Klein, R. E., Lee, P. P., Agardh, C. D., Davis, M., . . . Global Diabetic Retinopathy Project, G. (2003). Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology, 110(9), 1677-1682. doi: https://doi.org/10.1016/S0161-6420(03)00475-5.
Wolter, J. R. (1961). Diabetic retinopathy. American Journal of Ophtalmology, 51, 1123-1141.
Wood, J. R., Miller, K. M., Maahs, D. M., Beck, R. W., Dimeglio, L. A., Libman, I. M., . . . Woerner, S. E. (2013). Most Youth With Type 2 Diabetes in the T1D Exchange Clinic Registry Do Not Meet American Diabetes Association or International Society for Pediatric and Adolescent Diabetes Clinical Guidelines. Diabetes Care, 36(7): 2035–2037. doi: https://doi.org/10.2337/dc12-1959.
Zlokovic, B. V. (2008). The blood-brain barrier in health and chronic neurodegenerative disorders. Neuron, 57(2), 178-201. doi: https://doi.org/10.1016/j.neuron.2008.01.003.
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