Optical coherence tomography angiography reveals progressive worsening of retinal vascular geometry in diabetic retinopathy and improved geometry after panretinal photocoagulation

English version

Autoři: Alaa E. Fayed ^aff001; Ahmed M. Abdelbaki ^aff002; Omar M. El Zawahry ^aff002; Amani A. Fawzi ^aff001
Působiště autorů: Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States of America ^aff001; Department of Ophthalmology, Kasr Al-Ainy School of Medicine, Cairo University, Cairo, Egypt ^aff002
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0226629

Souhrn

Purpose

To quantify vessel tortuosity and fractal dimension of the superficial capillary plexus (SCP) of the macula in different stages of diabetic retinopathy (DR), and following panretinal photocoagulation (PRP) using optical coherence tomography angiography (OCTA).

Methods

75 eyes of 75 subjects were divided into five groups; healthy controls, diabetes with no clinical DR, non-proliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR) and patients who received PRP for PDR (PDR+PRP).For vessel tortuosity, SCP slabs from 3x3 mm macular OCTA scans were processed using imageJ (NIH, USA), where large perifoveal vessels were traced and their length was measured with tortuosity calculated as the ratio between the actual length and the straight Euclidean length. For fractal dimension, SCP slabs were processed and imported to Fractalyse (ThéMA, France), where box-counting analyses produced fractal dimension values.

Results

We found a significant difference in vessel tortuosity and fractal dimension between the five groups (one-way ANOVA, p < 0.001both). NPDR and PDR had significantly more tortuous vessels and lower fractal dimension compared to healthy controls (Tukey HSD: p = 0.02, 0.015,0.015 and <0.001, respectively). Fractal dimension was also significantly lower in NPDR and PDR compared to eyes with no clinical DR (p <0.001 both), and in PDR compared to NPDR (p = 0.014). Following PRP, vessel tortuosity was significantly lower and fractal dimension was higher in PDR+PRP compared to PDR (p = 0.001 and 0.031, respectively).

Conclusions

We used macular OCTA scans to demonstrate significantly higher perifoveal large vessel tortuosity, and lower fractal dimension in NPDR and PDR compared to healthy controls. Vessel tortuosity shows more dramatic normalization than fractal dimension and could be explored as a sensitive marker for successful PRP.

Klíčová slova:

Eye diseases – Eyes – Diabetic retinopathy – Hydrostatic pressure – Retinal vessels – Capillaries – Fractals

Zdroje

1. Sasongko MB, Wang JJ, Donaghue KC, Cheung N, Benitez-Aguirre P, Jenkins A, et al. Alterations in retinal microvascular geometry in young type 1 diabetes. Diabetes care. 2010;33(6):1331–6. doi: 10.2337/dc10-0055 20299479

2. Kiely AE, Wallace DK, Freedman SF, Zhao Z. Computer-assisted measurement of retinal vascular width and tortuosity in retinopathy of prematurity. Archives of Ophthalmology. 2010;128(7):847–52. doi: 10.1001/archophthalmol.2010.133 20625044

3. Cheung N, Donaghue KC, Liew G, Rogers SL, Wang JJ, Lim S-W, et al. Quantitative assessment of early diabetic retinopathy using fractal analysis. Diabetes care. 2009;32(1):106–10. doi: 10.2337/dc08-1233 18835945

4. Hickam JB, Frayser R. Studies of the retinal circulation in man: observations on vessel diameter, arteriovenous oxygen difference, and mean circulation time. Circulation. 1966;33(2):302–16. doi: 10.1161/01.cir.33.2.302 25823104

5. Kristinsson JK, Gottfredsdóttir MS, Stefánsson E. Retinal vessel dilatation and elongation precedes diabetic macular oedema. Br J Ophthalmol. 1997;81(4):274–8. doi: 10.1136/bjo.81.4.274 9215053

6. Kylstra J, Wierzbicki T, Wolbarsht M, Landers M, Stefansson E. The relationship between retinal vessel tortuosity, diameter, and transmural pressure. Graefes Arch Clin Exp Ophthalmol. 1986;224(5):477–80. doi: 10.1007/bf02173368 3758696

7. Sasongko M, Wong T, Nguyen T, Cheung C, Shaw J, Wang J. Retinal vascular tortuosity in persons with diabetes and diabetic retinopathy. Diabetologia. 2011;54(9):2409–16. doi: 10.1007/s00125-011-2200-y 21625945

8. Gardner TW, Antonetti DA, Barber AJ, LaNoue KF, Levison SW. Diabetic retinopathy: more than meets the eye. Survey of ophthalmology. 2002;47:S253–S62. doi: 10.1016/s0039-6257(02)00387-9 12507627

9. Weiler DL, Engelke CB, Moore AL, Harrison WW. Arteriole tortuosity associated with diabetic retinopathy and cholesterol. Optometry and Vision Science. 2015;92(3):384–91. doi: 10.1097/OPX.0000000000000484 25525892

10. Cheung CY-l, Sabanayagam C, Law AK-p, Kumari N, Ting DS-w, Tan G, et al. Retinal vascular geometry and 6 year incidence and progression of diabetic retinopathy. Diabetologia. 2017;60(9):1770–81. doi: 10.1007/s00125-017-4333-0 28623387

11. Sasongko MB, Wong TY, Donaghue KC, Cheung N, Jenkins AJ, Benitez-Aguirre P, et al. Retinal arteriolar tortuosity is associated with retinopathy and early kidney dysfunction in type 1 diabetes. Am J Ophthalmol. 2012;153(1):176–83 e1. doi: 10.1016/j.ajo.2011.06.005 21907319

12. Sasongko M, Wong T, Nguyen T, Shaw J, Jenkins A, Wang J. Novel versus traditional risk markers for diabetic retinopathy. Diabetologia. 2012;55(3):666–70. doi: 10.1007/s00125-011-2424-x 22198262

13. Tam J, Dhamdhere KP, Tiruveedhula P, Manzanera S, Barez S, Bearse MA, et al. Disruption of the retinal parafoveal capillary network in type 2 diabetes before the onset of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2011;52(12):9257–66. doi: 10.1167/iovs.11-8481 22039250

14. Lim SW, Cheung N, Wang JJ, Donaghue KC, Liew G, Islam FA, et al. Retinal vascular fractal dimension and risk of early diabetic retinopathy: a prospective study of children and adolescents with type 1 diabetes. Diabetes care. 2009;32(11):2081–3. doi: 10.2337/dc09-0719 19690082

15. Cogan DG, Toussaint D, Kuwabara T. Retinal vascular patterns: IV. Diabetic retinopathy. Archives of Ophthalmology. 1961;66(3):366–78.

16. Ţălu Ş, Călugăru DM, Lupaşcu CA. Characterisation of human non-proliferative diabetic retinopathy using the fractal analysis. International journal of ophthalmology. 2015;8(4):770. doi: 10.3980/j.issn.2222-3959.2015.04.23 26309878

17. Avakian A, Kalina RE, Helene Sage E, Rambhia AH, Elliott KE, Chuang EL, et al. Fractal analysis of region-based vascular change in the normal and non-proliferative diabetic retina. Current eye research. 2002;24(4):274–80. doi: 10.1076/ceyr.24.4.274.8411 12324866

18. Landini G, Misson GP, Murray PI. Fractal analysis of the normal human retinal fluorescein angiogram. Current eye research. 1993;12(1):23–7. doi: 10.3109/02713689308999492 8436007

19. Li X, Wong WL, Cheung CY-l, Cheng C-Y, Ikram MK, Li J, et al. Racial differences in retinal vessel geometric characteristics: a multiethnic study in healthy Asians. Invest Ophthalmol Vis Sci. 2013;54(5):3650–6. doi: 10.1167/iovs.12-11126 23652487

20. Zahid S, Dolz-Marco R, Freund KB, Balaratnasingam C, Dansingani K, Gilani F, et al. Fractal dimensional analysis of optical coherence tomography angiography in eyes with diabetic retinopathy. Invest Ophthalmol Vis Sci. 2016;57(11):4940–7. doi: 10.1167/iovs.16-19656 27654421

21. Chen Q, Ma Q, Wu C, Tan F, Chen F, Wu Q, et al. Macular Vascular Fractal Dimension in the Deep Capillary Layer as an Early Indicator of Microvascular Loss for Retinopathy in Type 2 Diabetic Patients. Invest Ophthalmol Vis Sci. 2017;58(9):3785–94. doi: 10.1167/iovs.17-21461 28744552

22. Lee H, Lee M, Chung H, Kim HC. QUANTIFICATION OF RETINAL VESSEL TORTUOSITY IN DIABETIC RETINOPATHY USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY. Retina (Philadelphia, Pa). 2017.

23. Tang FY, Ng DS, Lam A, Luk F, Wong R, Chan C, et al. Determinants of Quantitative Optical Coherence Tomography Angiography Metrics in Patients with Diabetes. Sci Rep. 2017;7(1):2575. doi: 10.1038/s41598-017-02767-0 28566760

24. Spaide RF, Fujimoto JG, Waheed NK. Image Artifacts in Optical Coherence Angiography. Retina (Philadelphia, Pa). 2015;35(11):2163.

25. Gao SS, Jia Y, Zhang M, Su JP, Liu G, Hwang TS, et al. Optical coherence tomography angiography. Invest Ophthalmol Vis Sci. 2016;57(9):OCT27–OCT36. doi: 10.1167/iovs.15-19043 27409483

26. Fayed AE, Fawzi AA. Projection resolved optical coherence tomography angiography to distinguish flow signal in retinal angiomatous proliferation from flow artifact. PLoS One. 2019;14(5):e0217109. doi: 10.1371/journal.pone.0217109 31091288

27. Fawzi AA, Fayed AE, Linsenmeier RA, Gao J, Yu F. IMPROVED MACULAR CAPILLARY FLOW ON OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY AFTER PANRETINAL PHOTOCOAGULATION FOR PROLIFERATIVE DIABETIC RETINOPATHY. Am J Ophthalmol. 2019.

28. Wilkinson C, Ferris FL, Klein RE, Lee PP, Agardh CD, Davis M, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110(9):1677–82. doi: 10.1016/S0161-6420(03)00475-5 13129861

29. Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, Liu JJ, et al. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Opt Express. 2012;20(4):4710–25. doi: 10.1364/OE.20.004710 22418228

30. Campbell J, Zhang M, Hwang T, Bailey S, Wilson D, Jia Y, et al. Detailed vascular anatomy of the human retina by projection-resolved optical coherence tomography angiography. Sci Rep. 2017;7:42201. doi: 10.1038/srep42201 28186181

31. Rasband WS. Imagej, us national institutes of health, bethesda, maryland, usa. http://imagej.nih.gov/ij/. 2011.

32. Witt N, Wong TY, Hughes AD, Chaturvedi N, Klein BE, Evans R, et al. Abnormalities of retinal microvascular structure and risk of mortality from ischemic heart disease and stroke. Hypertension. 2006;47(5):975–81. doi: 10.1161/01.HYP.0000216717.72048.6c 16585415

33. Rasmussen M, Broe R, Frydkjaer-Olsen U, Olsen BS, Mortensen H, Peto T, et al. Retinal vascular geometry and its association to microvascular complications in patients with type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987). Graefes Arch Clin Exp Ophthalmol. 2017;255(2):293–9. doi: 10.1007/s00417-016-3454-3 27520462

34. Owen CG, Newsom RS, Rudnicka AR, Barman SA, Woodward EG, Ellis TJ. Diabetes and the tortuosity of vessels of the bulbar conjunctiva. Ophthalmology. 2008;115(6):e27–e32. doi: 10.1016/j.ophtha.2008.02.009 18423868

35. Alam M, Thapa D, Lim JI, Cao D, Yao X. Quantitative characteristics of sickle cell retinopathy in optical coherence tomography angiography. Biomed Opt Express. 2017;8(3):1741–53. doi: 10.1364/BOE.8.001741 28663862

36. Saraf SS, Tyring AJ, Chen C-L, Le TP, Kalina RE, Wang RK, et al. Familial retinal arteriolar tortuosity and quantification of vascular tortuosity using swept-source optical coherence tomography angiography. Am J Ophthalmol. 2019;14:74–8.

37. Ataer-Cansizoglu E, You S, Kalpathy-Cramer J, Keck K, Chiang MF, Erdogmus D, editors. Observer and feature analysis on diagnosis of retinopathy of prematurity. 2012 IEEE International Workshop on Machine Learning for Signal Processing; 2012: IEEE.

38. Ataer-Cansizoglu E, Kalpathy-Cramer J, You S, Keck K, Erdogmus D, Chiang M. Analysis of underlying causes of inter-expert disagreement in retinopathy of prematurity diagnosis. Methods of information in medicine. 2015;54(01):93–102.

39. TheMa. Fractalyse 2.4. Théoriser et Modéliser pour Aménager. CNRS–Universités de Franche-Comité et de Bourgagne. 2012.

40. Karperien A, Jelinek HF, Leandro JJ, Soares JV, Cesar RM Jr, Luckie A. Automated detection of proliferative retinopathy in clinical practice. Clinical ophthalmology (Auckland, NZ). 2008;2(1):109.

41. Cheung N, Rogers SL, Donaghue KC, Jenkins AJ, Tikellis G, Wong TY. Retinal arteriolar dilation predicts retinopathy in adolescents with type 1 diabetes. Diabetes care. 2008;31(9):1842–6. doi: 10.2337/dc08-0189 18523143

42. Wong TY, Shankar A, Klein R, Klein BE. Retinal vessel diameters and the incidence of gross proteinuria and renal insufficiency in people with type 1 diabetes. Diabetes. 2004;53(1):179–84. doi: 10.2337/diabetes.53.1.179 14693713

43. Grauslund J, Hodgson L, Kawasaki R, Green A, Sjølie A, Wong T. Retinal vessel calibre and micro-and macrovascular complications in type 1 diabetes. Diabetologia. 2009;52(10):2213–7. doi: 10.1007/s00125-009-1459-8 19618163

44. Bedell AJ. Retinal vessel proliferation in diabetes. Transactions of the American Ophthalmological Society. 1945;43:271. 16693381

45. Daxer A. Characterisation of the neovascularisation process in diabetic retinopathy by means of fractal geometry: diagnostic implications. Graefes Arch Clin Exp Ophthalmol. 1993;231(12):681–6. doi: 10.1007/bf00919281 8299974

46. Family F, Masters BR, Platt DE. Fractal pattern formation in human retinal vessels. Physica D: Nonlinear Phenomena. 1989;38(1–3):98–103.

47. Cheung CY-l, Lamoureux E, Ikram MK, Sasongko MB, Ding J, Zheng Y, et al. Retinal vascular geometry in Asian persons with diabetes and retinopathy. Journal of diabetes science and technology. 2012;6(3):595–605. doi: 10.1177/193229681200600315 22768891

48. Bracher D. Changes in peripapillary tortuosity of the central retinal arteries in newborns. Graefes Arch Clin Exp Ophthalmol. 1982;218(4):211–7. doi: 10.1007/bf02150097 7200930

49. Ashraf M, Nesper PL, Jampol LM, Yu F, Fawzi AA. Statistical model of optical coherence tomography angiography parameters that correlate with severity of diabetic retinopathy. Invest Ophthalmol Vis Sci. 2018;59(10):4292–8. doi: 10.1167/iovs.18-24142 30167660

50. Group ETDRSR. Early photocoagulation for diabetic retinopathy: ETDRS report number 9. Ophthalmology. 1991;98(5):766–85.

51. Molnar I, Poitry S, Tsacopoulos M, Gilodi N, Leuenberger PM. Effect of laser photocoagulation on oxygenation of the retina in miniature pigs. Invest Ophthalmol Vis Sci. 1985;26(10):1410–4. 4044168

52. Budzynski E, Smith JH, Bryar P, Birol G, Linsenmeier RA. Effects of photocoagulation on intraretinal PO2 in cat. Invest Ophthalmol Vis Sci. 2008;49(1):380–9. doi: 10.1167/iovs.07-0065 18172116

53. Grunwald JE, Riva CE, Brucker AJ, Sinclair SH, Petrig BL. Effect of panretinal photocoagulation on retinal blood flow in proliferative diabetic retinopathy. Ophthalmology. 1986;93(5):590–5. doi: 10.1016/s0161-6420(86)33691-1 3725318

54. Grunwald JE, Brucker AJ, Petrig BL, Riva CE. Retinal blood flow regulation and the clinical response to panretinal photocoagulation in proliferative diabetic retinopathy. Ophthalmology. 1989;96(10):1518–22. doi: 10.1016/s0161-6420(89)32697-2 2587047

55. Hartnett ME, Martiniuk D, Byfield G, Geisen P, Zeng G, Bautch VL. Neutralizing VEGF decreases tortuosity and alters endothelial cell division orientation in arterioles and veins in a rat model of ROP: relevance to plus disease. Invest Ophthalmol Vis Sci. 2008;49(7):3107–14. doi: 10.1167/iovs.08-1780 18378573

56. Paques M, Krivosic V, Girmens J-f, Giraud C, Sahel J, Gaudric A. Decreased venous tortuosity associated with resolution of macular edema after intravitreal injection of triamcinolone. Retina. 2005;25(8):1099–101. doi: 10.1097/00006982-200512000-00022 16340544

57. Torp TL, Kawasaki R, Wong TY, Peto T, Grauslund J. Temporal changes in retinal vascular parameters associated with successful panretinal photocoagulation in proliferative diabetic retinopathy: A prospective clinical interventional study. Acta ophthalmologica. 2017.