|
|
 |
Vol. 27, Art. 19 (pp. 455-484) | 2026
Ischemic maculopathy at the preproliferative stage of diabetic retinopathy: epidemiology, clinical presentation, and diagnosis
Ogneva T.R.1, Tultseva S.N.1
1Federal State Budgetary Educational Institution of Higher Education “Academician I.P. Pavlov First St. Petersburg State Medical University” of the Ministry of Healthcare of Russian Federation
Brief summary
This literature review is devoted to one of the most challenging forms of retinal damage in diabetes mellitus—ischemic maculopathy. The article systematizes current data on the pathophysiological mechanisms underlying macular ischemia, including the role of microcirculatory disturbances, endothelial dysfunction, and neurodegeneration. Particular attention is given to the evolution of imaging methods, namely the transition from fluorescein angiography to optical coherence tomography angiography, which makes it possible to accurately delineate the foveal avascular zone and assess capillary density in the various retinal vascular plexuses. The paper reviews existing classifications of ischemic changes and discusses their prognostic significance for the preservation of visual function. It also addresses the challenges of diagnosing ischemic maculopathy in the presence of macular edema, as well as the limitations of current treatment options in cases of severe perfusion deficit. The review highlights the need to develop standardized criteria for the assessment of ischemic maculopathy to support a personalized approach to the management of patients with diabetic retinopathy. Key words Diabetic retinopathy, ischemic maculopathy, OCT-angiography, foveal avascular zone, pathogenesis (The article in PDF format. For preview need Adobe Acrobat Reader)  Open article in new window
Reference list 1. Teo Z.L., et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: Systematic review and meta-analysis. Ophthalmology. 2021;128(11):1580-1591. doi:10.1016/j.ophtha.2021.04.027 2. Tsai A.S.H., et al. Diabetic Macular Ischemia: Influence of Optical Coherence Tomography Angiography Parameters on Changes in Functional Outcomes Over One Year. Invest Ophthalmol Vis Sci. 2021;62(1):9. doi: 10.1167/iovs.62.1.9 3. Ashton N. Arteriolar involvement in diabetic retinopathy. Br J Ophthalmol. 1953;37(5):282-92. doi: 10.1136/bjo.37.5.282 4. Kohner E.M., Henkind P. Correlation of fluorescein angiogram and retinal digest in diabetic retinopathy. Am J Ophthalmol. 1970;69(3):403-14. doi: 10.1016/0002-9394(70)92273-7. 5. Arend O., et al. Macular microcirculation in cystoid maculopathy of diabetic patients. Br J Ophthalmol. 1995;79(7):628-32. doi: 10.1136/bjo.79.7.628. 6. Classification of diabetic retinopathy from fluorescein angiograms. ETDRS report number 11. Early Treatment Diabetic Retinopathy Study Research Group. Ophthalmology. 1991;98(5 Suppl):807-22. 7. Klein R., et al.The Wisconsin Epidemiologic Study of diabetic retinopathy. XIV. Ten-year incidence and progression of diabetic retinopathy. Arch Ophthalmol. 1994;112(9):1217-28. doi: 10.1001/archopht.1994.01090210105023 8. Klein R., et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. XV. The long-term incidence of macular edema. Ophthalmology. 1995;102(1):7-16. doi: 10.1016/s0161-6420(95)31052-4 9. Sim D.A., et al. The effects of macular ischemia on visual acuity in diabetic retinopathy. Invest Ophthalmol Vis Sci. 2013;54(3):2353-60. doi: 10.1167/iovs.12-11103 10. Sim D.A., et al. Predictive factors for the progression of diabetic macular ischemia. Am J Ophthalmol. 2013 Oct;156(4):684-92. doi: 10.1016/j.ajo.2013.05.033 11. Sim D.A., et al. Patterns of peripheral retinal and central macula ischemia in diabetic retinopathy as evaluated by ultra-widefield fluorescein angiography. Am J Ophthalmol. 2014;158(1):144-153.e1. doi: 10.1016/j.ajo.2014.03.009 12. Tadayoni R. Macular edema: drying is not repairing. J Ophthalmic Vis Res. 2013;8(2):97-8. PMID: 23943682; PMCID: PMC3740474 13. Waheed N.K., et al. Optical coherence tomography angiography in diabetic retinopathy. Prog Retin Eye Res. 2023;97:101206. doi: 10.1016/j.preteyeres.2023.101206 14. Spaide R.F., et al. Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol. 2015;133(1):45-50. doi: 10.1001/jamaophthalmol.2014.3616 15. Sun J.K., et al. Neural Retinal Disorganization as a Robust Marker of Visual Acuity in Current and Resolved Diabetic Macular Edema. Diabetes. 2015;64(7):2560-70. doi: 10.2337/db14-0782 16. Sun J.K., et al. Disorganization of the retinal inner layers as a predictor of visual acuity in eyes with center-involved diabetic macular edema. JAMA Ophthalmol. 2014;132(11):1309-16. doi: 10.1001/jamaophthalmol.2014.2350 17. Radwan S.H., et al. Association of Disorganization of Retinal Inner Layers With Vision After Resolution of Center-Involved Diabetic Macular Edema. JAMA Ophthalmol. 2015;133(7):820-5. doi: 10.1001/jamaophthalmol.2015.0972 18. Bolz M., et al. Diabetic Retinopathy Research Group Vienna. Optical coherence tomographic hyperreflective foci: a morphologic sign of lipid extravasation in diabetic macular edema. Ophthalmology. 2009 May;116(5):914-20. doi: 10.1016/j.ophtha.2008.12.039. 19. Nicholson L, Ramu J, Triantafyllopoulou I, Patrao NV, Comyn O, Hykin P, Sivaprasad S. Diagnostic accuracy of disorganization of the retinal inner layers in detecting macular capillary non-perfusion in diabetic retinopathy. Clin Exp Ophthalmol. 2015 Nov;43(8):735-41. doi: 10.1111/ceo.12557 20. Sen S., et al. Ultrastructural imaging biomarkers in diabetic macular edema: A major review. Indian J Ophthalmol. 2025;73(Suppl 1):S7-S23. doi: 10.4103/IJO.IJO_878_24 21. Muftuoglu I.K., et al. Integrity of outer retinal layers after resolution of central involved diabetic macular edema. Retina. 2017;37(11):2015-2024. doi: 10.1097/IAE.0000000000001459 22. Tokui S., et al. Paracentral Acute Middle Maculopathy in a Young-Onset Case Revealing Undiagnosed Hypertension. Cureus. 2025;17(10):e94903. doi: 10.7759/cureus.94903. 23. Abtahi S.H., et al. Retinal ischemic cascade: New insights into the pathophysiology and imaging findings. Surv Ophthalmol. 2023;68(3):380-387. doi: 10.1016/j.survophthal.2022.11.009 24. Bakhoum M.F., et al. Paracentral Acute Middle Maculopathy and the Ischemic Cascade Associated With Retinal Vascular Occlusion. Am J Ophthalmol. 2018;195:143-153. doi: 10.1016/j.ajo.2018.07.031. 25. Maltsev D.S., et al. Association of Resolved Paracentral Acute Middle Maculopathy Lesions with Diabetic Retinopathy. J Curr Ophthalmol. 2022;34(3):318-322. doi: 10.4103/joco.joco_91_22 26. Fumi D., et al. Paracentral Acute Middle Maculopathy (PAMM) in Ocular Vascular Diseases-What We Know and Future Perspectives. Vision (Basel). 2025;9(1):19. doi: 10.3390/vision9010019 27. Balaratnasingam C., et al.Visual Acuity Is Correlated with the Area of the Foveal Avascular Zone in Diabetic Retinopathy and Retinal Vein Occlusion. Ophthalmology. 2016;123(11):2352-2367. doi: 10.1016/j.ophtha.2016.07.008 28. Jia Y., et al. Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye. Proc Natl Acad Sci U S A. 2015;112(18):E2395-402. doi: 10.1073/pnas.1500185112 29. Spaide R.F. Volume-Rendered Optical Coherence Tomography of Diabetic Retinopathy Pilot Study. Am J Ophthalmol. 2015 Dec;160(6):1200-10. doi: 10.1016/j.ajo.2015.09.010. 30. Nesper P.L., et al. Correlating retinal perfusion with layer-by-layer proliferation of blood vessels in diabetic retinopathy using OCT angiography. Invest Ophthalmol Vis Sci. 2016;57(10):OCT549-OCT555. doi:10.1167/iovs.15-18879 31. Agemy S.A., et al. Retinal vascular perfusion density mapping using optical coherence tomography angiography in normals and diabetic retinopathy patients. Retina. 2015;35(11):2353-63. doi: 10.1097/IAE.0000000000000862 32. Nesper P.L., et al. Quantifying Microvascular Abnormalities With Increasing Severity of Diabetic Retinopathy Using Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci. 2017;58(6):BIO307-BIO315. doi: 10.1167/iovs.17-21787 33. Couturier A., et al. Capillary plexus anomalies in diabetic retinopathy on optical coherence tomography angiography. Retina. 2015;35(11):2384-91. doi: 10.1097/IAE.0000000000000859 34. Guo Y., et al. Quantification of Nonperfusion Area in Montaged Widefield OCT Angiography Using Deep Learning in Diabetic Retinopathy. Ophthalmol Sci. 2021;1(2):100027. doi: 10.1016/j.xops.2021.100027 35. Kong M., et al. Artificial Intelligence Applications in Diabetic Retinopathy: What We Have Now and What to Expect in the Future. Endocrinol Metab (Seoul). 2024;39(3):416-424. doi: 10.3803/EnM.2023.1913 36. Mutua E.N., et al. Deep learning applications for diabetic retinopathy and retinopathy of prematurity diseases diagnosis: a systematic review. Int J Ophthalmol. 2025;18(8):1594-1602. doi: 10.18240/ijo.2025.08.23 37. Mysataeva H. T., s soavt. Iskysstvennii intellekt v oftalmologii: obzor sovremennih dostijenii i perspektiv. Aktyalnie issledovaniya. 2026. №6 (292). Ch.I. S. 64-69 38. Qian H.Y., et al. Inflammatory mechanisms in diabetic retinopathy: pathogenic roles and therapeutic perspectives. Am J Transl Res. 2025;17(8):6262-6274. doi: 10.62347/GBFO5856 39. van der Wijk A.E., et al. Is leukostasis a crucial step or epiphenomenon in the pathogenesis of diabetic retinopathy? J Leukoc Biol. 2017;102(4):993-1001. doi: 10.1189/jlb.3RU0417-139 40. Agrawal R., et al. Assessment of red blood cell deformability in type 2 diabetes mellitus and diabetic retinopathy by dual optical tweezers stretching technique. Sci Rep. 2016;6:15873. doi: 10.1038/srep15873 41. Pfister F., et al. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes. 2008 Sep;57(9):2495-502. doi: 10.2337/db08-0325 42. Gardner T.W., et al. The neurovascular unit and the pathophysiologic basis of diabetic retinopathy. Graefes Arch Clin Exp Ophthalmol. 2017;255(1):1-6. doi: 10.1007/s00417-016-3548-y 43. Miyamoto K., et al. Prevention of leukostasis and vascular leakage in streptozotocin-induced diabetic retinopathy via intercellular adhesion molecule-1 inhibition. Proc Natl Acad Sci U S A. 1999;96(19):10836-41. doi: 10.1073/pnas.96.19.10836 44. Cheung N., et al. Diabetic retinopathy. Lancet. 2010;376(9735):124-136. doi:10.1016/S0140-6736(09)62124-3 45. Lee M.W., et al. Impacts of Systemic Hypertension on the Macular Microvasculature in Diabetic Patients Without Clinical Diabetic Retinopathy. Invest Ophthalmol Vis Sci. 2021;62(12):21. doi: 10.1167/iovs.62.12.21 46. Wang X.F., et al. The causal effect of hypertension, intraocular pressure, and diabetic retinopathy: a Mendelian randomization study. Front Endocrinol (Lausanne). 2024;15:1304512. doi: 10.3389/fendo.2024.1304512 47. Sperling S., et al. Bidirectional 5-year risks of diabetic retinopathy, glaucoma and/or ocular hypertension: Results from a national screening programme. Acta Ophthalmol (2023) 101:384-91. doi: 10.1111/aos.15300 48. Joussen A.M., et al. A central role for inflammation in the pathogenesis of diabetic retinopathy. FASEB J. 2004;18(12):1450-1452. doi:10.1096/fj.03-1476fje 49. Antropoli A., et al. Peripheral and central capillary non-perfusion in diabetic retinopathy: An updated overview. Front Med (Lausanne). 2023;10:1125062. doi: 10.3389/fmed.2023.1125062 50. Cheung C.M.G., et al. Diabetic macular ischaemia- a new therapeutic target? Prog Retin Eye Res. 2022;89:101033. doi: 10.1016/j.preteyeres.2021.101033 51. Neroev V. V., Lipatov D. V., Zaiceva O. V., Bragin A. A. Sovremennie vozmojnosti iskysstvennogo intellekta v diagnostike i lechenii glaznih oslojnenii saharnogo diabeta. Rossiiskii oftalmologicheskii jyrnal. - 2026. - T. 19, № 1. - S. 185-190. - doi 10.21516/2072-0076-2026-19-1-185-190 52. Usef N.U., Dyrjinskaya M.H., Pavlov V. G. i dr. Avtomatizirovannii analiz retinalnoi mikrocirkylyacii pri saharnom diabete 1 tipa. Saharnii diabet. - 2024. - T. 27, № 1. - S. 41-49. - doi 10.14341/DM12931 53. Usef N.U., Dyrjinskaya M.H., Pavlov V.G. i dr. Vzaimovliyanie biomarkerov OKT i OKTA pri diabeticheskoi retinopatii na fone saharnogo diabeta 1 tipa. Proliferativnii sindrom v biologii i medicine: Materiali II Rossiiskogo foryma s mejdynarodnim ychastiem, Moskva, 29-30 noyabrya 2022 goda. - Moskva: Obshestvo s ogranichennoi otvetstvennostu "Izdatelstvo GEOS", 2022. - S. 110-114. - doi 10.34756/GEOS.2023.17.38612 54. Filippov V.M., Petrachkov D.V., Bydzinskaya M.V., Matushenko A.G. Rol biomarkerov neirodegeneracii pri diabeticheskoi retinopatii. Vestnik oftalmologii. - 2021. - T. 137, № 5-2. - S. 314-322. - doi 10.17116/oftalma2021137052314 55. Filippov V.M., Petrachkov D.V., Bydzinskaya M.V., Sidamonidze A.L. Sovremennie koncepcii patogeneza diabeticheskoi retinopatii. Vestnik oftalmologii. - 2021. - T. 137, № 5-2. - S. 306-313. - doi 10.17116/oftalma2021137052306 |
|||||||||
Articles
| Размещение рекламы | |
|
| |
 |