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Vitreous and intraretinal macular changes in diabetic macular edema with and without tractional components

  • Mario R. Romano
  • Davide AllegriniEmail author
  • Chiara Della Guardia
  • Stefano Schiemer
  • Immacolata Baronissi
  • Mariantonia Ferrara
  • Gilda Cennamo
Review Article
  • 116 Downloads

Abstract

Diabetic macular edema (DME) is still one of the main causes of visual impairment. Repeated intravitreal injections of ranibizumab are considered the gold standard treatment, but the efficacy in patients with prominent cystic characteristics remains uncertain. In diabetic retinas, the identification of both antero-posterior and, particularly, tangential tractions is crucial to prevent misdiagnosis of tractional and refractory DME, and therefore to prevent poor treatment outcomes. The treatment of tractional DME with anti-VEGF injections could be poorly effective due to the influence of a tractional force. Pars plana vitrectomy (PPV) is a surgical procedure that has been widely used in the treatment of diffuse and refractory DME. Anatomical improvement, although stable and immediate, did not result in visual improvement. PPV with internal limiting membrane (ILM) peeling for the treatment of non-tractional DME in patients with prominent cysts (> 390 μm) causes subfoveal atrophy, defined as “floor effect”. Epiretinal tangential forces and intraretinal change evaluation by SD-OCT of non-tractional DME are essential for determining appropriate management.

Keywords

Diabetic macular edema Non-tractional macular edema Diabetic retinopathy 

Notes

Acknowledgments

The authors have no proprietary interest in any aspect of this study.

Authors’ contribution

MRR, DA, MF, CDG, SS contributed to conception and design; MRR, DA, IB, GC to acquisition of data, all authors contributed to interpretation of data; all authors drafted the article and approved its final version.

Compliance with ethical standards

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have conflict of interest.

References

  1. 1.
    Ciulla TA, Amador AG, Zinman B (2003) Diabetic retinopathy and diabetic macular edema: pathophysiology, screening, and novel therapies. Diabetes Care 26:2653–2664CrossRefGoogle Scholar
  2. 2.
    Early Treatment Diabetic Retinopathy Study research group (1985) Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report number 1. Arch Ophthalmol (Chicago, Ill 1960) 103:1796–1806CrossRefGoogle Scholar
  3. 3.
    Dowler JGF (2003) Laser management of diabetic retinopathy. J R Soc Med 96:277–279CrossRefGoogle Scholar
  4. 4.
    Ferrara N, Damico L, Shams N et al (2006) Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration. Retina 26:859–870.  https://doi.org/10.1097/01.iae.0000242842.14624.e7 CrossRefGoogle Scholar
  5. 5.
    Mitchell P, Bandello F, Schmidt-Erfurth U et al (2011) The RESTORE study. Ophthalmology 118:615–625.  https://doi.org/10.1016/j.ophtha.2011.01.031 CrossRefGoogle Scholar
  6. 6.
    Nguyen QD, Brown DM, Marcus DM et al (2012) Ranibizumab for diabetic macular edema: results from 2 phase III randomized trials: RISE and RIDE. Ophthalmology 119:789–801.  https://doi.org/10.1016/j.ophtha.2011.12.039 CrossRefGoogle Scholar
  7. 7.
    Diabetic Retinopathy Clinical Research Network MJ, Elman MJ, Qin H, et al (2012) Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trial results. Ophthalmology 119:2312–2318.  https://doi.org/10.1016/j.ophtha.2012.08.022 CrossRefGoogle Scholar
  8. 8.
    Do DV, Nguyen QD, Khwaja AA et al (2013) Ranibizumab for edema of the macula in diabetes study: 3-year outcomes and the need for prolonged frequent treatment. JAMA Ophthalmol 131:139–145.  https://doi.org/10.1001/2013.jamaophthalmol.91 CrossRefGoogle Scholar
  9. 9.
    Schmidt-Erfurth U, Lang GE, Holz FG et al (2014) Three-year outcomes of individualized ranibizumab treatment in patients with diabetic macular edema: the RESTORE extension study. Ophthalmology 121:1045–1053.  https://doi.org/10.1016/j.ophtha.2013.11.041 CrossRefGoogle Scholar
  10. 10.
    Brown DM, Nguyen QD, Marcus DM et al (2013) Long-term outcomes of ranibizumab therapy for diabetic macular edema: the 36-month results from two phase III trials: RISE and RIDE. Ophthalmology 120:2013–2022.  https://doi.org/10.1016/j.ophtha.2013.02.034 CrossRefGoogle Scholar
  11. 11.
    Comyn O, Sivaprasad S, Peto T et al (2014) A randomized trial to assess functional and structural effects of ranibizumab versus laser in diabetic macular edema (the LUCIDATE study). Am J Ophthalmol 157:960–970.  https://doi.org/10.1016/j.ajo.2014.02.019 CrossRefGoogle Scholar
  12. 12.
    Browning DJ (2010) Interpreting thickness changes in the diabetic macula: the problem of short-term variation in optical coherence tomography-measured macular thickening (an american ophthalmological society thesis). Trans Am Ophthalmol Soc 108:62–76Google Scholar
  13. 13.
    Massin P, Duguid G, Erginay A et al (2003) Optical coherence tomography for evaluating diabetic macular edema before and after vitrectomy. Am J Ophthalmol 135:169–177CrossRefGoogle Scholar
  14. 14.
    Sebag J (1987) Age-related changes in human vitreous structure. Graefes Arch Clin Exp Ophthalmol 225:89–93CrossRefGoogle Scholar
  15. 15.
    Sebag J (2004) Anomalous posterior vitreous detachment: a unifying concept in vitreo-retinal disease. Graefes Arch Clin Exp Ophthalmol 242:690–698.  https://doi.org/10.1007/s00417-004-0980-1 CrossRefGoogle Scholar
  16. 16.
    Lundquist O, Osterlin S (1994) Glucose concentration in the vitreous of nondiabetic and diabetic human eyes. Graefes Arch Clin Exp Ophthalmol 232:71–74CrossRefGoogle Scholar
  17. 17.
    Sebag J, Buckingham B, Charles MA, Reiser K (1992) Biochemical abnormalities in vitreous of humans with proliferative diabetic retinopathy. Arch Ophthalmol (Chicago, Ill 1960) 110:1472–1476CrossRefGoogle Scholar
  18. 18.
    Stitt AW (2001) Advanced glycation: an important pathological event in diabetic and age related ocular disease. Br J Ophthalmol 85:746–753CrossRefGoogle Scholar
  19. 19.
    Gella L, Raman R, Kulothungan V, Sharma T (2012) Prevalence of posterior vitreous detachment in the population with type II diabetes mellitus and its effect on diabetic retinopathy: Sankara Nethralaya diabetic retinopathy epidemiology and molecular genetic study SN-DREAMS report no. 23. Jpn J Ophthalmol 56:262–267.  https://doi.org/10.1007/s10384-012-0134-7 CrossRefGoogle Scholar
  20. 20.
    Duker JS, Kaiser PK, Binder S et al (2013) The international Vitreomacular traction study group classification of vitreomacular adhesion, traction, and macular hole. Ophthalmology 120:2611–2619.  https://doi.org/10.1016/j.ophtha.2013.07.042 CrossRefGoogle Scholar
  21. 21.
    Sebag J (2008) Vitreoschisis. Graefes Arch Clin Exp Ophthalmol 246:329–332.  https://doi.org/10.1007/s00417-007-0743-x CrossRefGoogle Scholar
  22. 22.
    Qiao H, Hisatomi T, Sonoda K-H et al (2005) The characterisation of hyalocytes: the origin, phenotype, and turnover. Br J Ophthalmol 89:513–517.  https://doi.org/10.1136/bjo.2004.050658 CrossRefGoogle Scholar
  23. 23.
    Sebag J, Gupta P, Rosen RR et al (2007) Macular holes and macular pucker: the role of vitreoschisis as imaged by optical coherence tomography/scanning laser ophthalmoscopy. Trans Am Ophthalmol Soc 105:121–129 discusion 129–31Google Scholar
  24. 24.
    Romano MR, Vallejo-Garcia JL, Camesasca FI et al (2012) Vitreo-papillary adhesion as a prognostic factor in pseudo- and lamellar macular holes. Eye 26:810–815.  https://doi.org/10.1038/eye.2012.43 CrossRefGoogle Scholar
  25. 25.
    Abe S, Yamamoto T, Kashiwagi Y et al (2013) Three-dimensional imaging of the inner limiting membrane folding on the vitreomacular interface in diabetic macular edema. Jpn J Ophthalmol 57:553–562.  https://doi.org/10.1007/s10384-013-0275-3 CrossRefGoogle Scholar
  26. 26.
    Bringmann A, Wiedemann P (2009) Involvement of Müller glial cells in epiretinal membrane formation. Graefes Arch Clin Exp Ophthalmol 247:865–883.  https://doi.org/10.1007/s00417-009-1082-x CrossRefGoogle Scholar
  27. 27.
    Bu S-C, Kuijer R, Li X-R et al (2014) Idiopathic epiretinal membrane. Retina 34:2317–2335.  https://doi.org/10.1097/IAE.0000000000000349 CrossRefGoogle Scholar
  28. 28.
    Govetto A, Lalane RA, Sarraf D et al (2017) Insights into Epiretinal membranes: presence of ectopic inner foveal layers and a new optical coherence tomography staging scheme. Am J Ophthalmol 175:99–113.  https://doi.org/10.1016/j.ajo.2016.12.006 CrossRefGoogle Scholar
  29. 29.
    Erickson PA, Fisher SK, Guérin CJ et al (1987) Glial fibrillary acidic protein increases in Müller cells after retinal detachment. Exp Eye Res 44:37–48CrossRefGoogle Scholar
  30. 30.
    Lewis GP, Fisher SK (2003) Up-regulation of glial fibrillary acidic protein in response to retinal injury: its potential role in glial remodeling and a comparison to vimentin expression. Int Rev Cytol 230:263–290CrossRefGoogle Scholar
  31. 31.
    Lewis GP, Guérin CJ, Anderson DH et al (1994) Rapid changes in the expression of glial cell proteins caused by experimental retinal detachment. Am J Ophthalmol 118:368–376CrossRefGoogle Scholar
  32. 32.
    Rutka JT, Murakami M, Dirks PB et al (1997) Role of glial filaments in cells and tumors of glial origin: a review. J Neurosurg 87:420–430.  https://doi.org/10.3171/jns.1997.87.3.0420 CrossRefGoogle Scholar
  33. 33.
    Charteris DG, Downie J, Aylward GW et al (2007) Intraretinal and periretinal pathology in anterior proliferative vitreoretinopathy. Graefes Arch Clin Exp Ophthalmol 245:93–100.  https://doi.org/10.1007/s00417-006-0323-5 CrossRefGoogle Scholar
  34. 34.
    Antonetti DA, Klein R, Gardner TW (2012) Diabetic retinopathy. N Engl J Med 366:1227–1239.  https://doi.org/10.1056/NEJMra1005073 CrossRefGoogle Scholar
  35. 35.
    Sohn EH, van Dijk HW, Jiao C et al (2016) Retinal neurodegeneration may precede microvascular changes characteristic of diabetic retinopathy in diabetes mellitus. Proc Natl Acad Sci U S A 113:E2655–E2664.  https://doi.org/10.1073/pnas.1522014113 CrossRefGoogle Scholar
  36. 36.
    Tien T, Zhang J, Muto T et al (2017) High glucose induces mitochondrial dysfunction in retinal Müller cells: implications for diabetic retinopathy. Invest Opthalmol Vis Sci 58:2915.  https://doi.org/10.1167/iovs.16-21355 CrossRefGoogle Scholar
  37. 37.
    Zhang Z-H, Liu H-Y, Hernandez-Da Mota SE et al (2013) Vitrectomy with or without preoperative intravitreal bevacizumab for proliferative diabetic retinopathy: a meta-analysis of randomized controlled trials. Am J Ophthalmol 156:106–115.e2.  https://doi.org/10.1016/j.ajo.2013.02.008 CrossRefGoogle Scholar
  38. 38.
    El-Sabagh HA, Abdelghaffar W, Labib AM et al (2011) Preoperative intravitreal bevacizumab use as an adjuvant to diabetic vitrectomy: histopathologic findings and clinical implications. Ophthalmology 118:636–641.  https://doi.org/10.1016/j.ophtha.2010.08.038 CrossRefGoogle Scholar
  39. 39.
    Walshe R, Esser P, Wiedemann P, Heimann K (1992) Proliferative retinal diseases: myofibroblasts cause chronic vitreoretinal traction. Br J Ophthalmol 76:550–552CrossRefGoogle Scholar
  40. 40.
    Erdurman FC, Pellumbi A, Durukan AH (2012) Lamellar macular hole formation in a patient with diabetic CME treated by intravitreal bevacizumab injections. Ophthalmic Surg Lasers Imaging 43 Online:e87–e89.  https://doi.org/10.3928/15428877-20120823-05 Google Scholar
  41. 41.
    Van Geest RJ, Lesnik-Oberstein SY, Tan HS et al (2012) A shift in the balance of vascular endothelial growth factor and connective tissue growth factor by bevacizumab causes the angiofibrotic switch in proliferative diabetic retinopathy. Br J Ophthalmol 96:587–590.  https://doi.org/10.1136/bjophthalmol-2011-301005 CrossRefGoogle Scholar
  42. 42.
    Diabetic Retinopathy Clinical Research Network Writing Committee, Haller JA, Qin H et al (2010) Vitrectomy outcomes in eyes with diabetic macular edema and vitreomacular traction. Ophthalmology 117:1087–1093.e3.  https://doi.org/10.1016/j.ophtha.2009.10.040 CrossRefGoogle Scholar
  43. 43.
    Navarrete-Sanchis J, Zarco-Bosquets J, Tomas-Torrent JM et al (2015) Long-term effectiveness of vitrectomy in diabetic cystoid macular edema. Graefes Arch Clin Exp Ophthalmol 253:713–719.  https://doi.org/10.1007/s00417-014-2745-9 CrossRefGoogle Scholar
  44. 44.
    Romano MR, Romano V, Vallejo-Garcia JL et al (2014) MACULAR HYPOTROPHY AFTER INTERNAL LIMITING MEMBRANE REMOVAL FOR DIABETIC MACULAR EDEMA. Retina 34:1182–1189.  https://doi.org/10.1097/IAE.0000000000000076 CrossRefGoogle Scholar
  45. 45.
    Patel JI, Hykin PG, Schadt M et al (2006) Pars plana vitrectomy with and without peeling of the inner limiting membrane for diabetic macular edema. Retina 26:5–13CrossRefGoogle Scholar
  46. 46.
    Kamura Y, Sato Y, Isomae T, Shimada H (2005) Effects of internal limiting membrane peeling in vitrectomy on diabetic cystoid macular edema patients. Jpn J Ophthalmol 49:297–300.  https://doi.org/10.1007/s10384-005-0199-7 CrossRefGoogle Scholar
  47. 47.
    Wolf S, Schnurbusch U, Wiedemann P et al (2004) Peeling of the basal membrane in the human retina: ultrastructural effects. Ophthalmology 111:238–243.  https://doi.org/10.1016/j.ophtha.2003.05.022 CrossRefGoogle Scholar
  48. 48.
    Pichi F, Lembo A, Morara M et al (2014) Early and late inner retinal changes after inner limiting membrane peeling. Int Ophthalmol 34:437–446.  https://doi.org/10.1007/s10792-013-9831-6 CrossRefGoogle Scholar
  49. 49.
    Clark A, Balducci N, Pichi F et al (2012) Swelling of the arcuate nerve fiber layer after internal limiting membrane peeling. Retina 32:1608–1613.  https://doi.org/10.1097/IAE.0b013e3182437e86 CrossRefGoogle Scholar
  50. 50.
    Tadayoni R, Paques M, Massin P et al (2001) Dissociated optic nerve fiber layer appearance of the fundus after idiopathic epiretinal membrane removal. Ophthalmology 108:2279–2283CrossRefGoogle Scholar
  51. 51.
    Spaide RF (2012) Dissociated optic nerve fiber layer appearance" after internal limiting membrane removal is inner retinal dimpling. Retina 32:1719–1726.  https://doi.org/10.1097/IAE.0b013e3182671191 CrossRefGoogle Scholar
  52. 52.
    Alkabes M, Salinas C, Vitale L et al (2011) En face optical coherence tomography of inner retinal defects after internal limiting membrane peeling for idiopathic macular hole. Invest Opthalmol Vis Sci 52:8349.  https://doi.org/10.1167/iovs.11-8043 CrossRefGoogle Scholar
  53. 53.
    Tamura K, Yokoyama T, Ebihara N, Murakami A (2012) Histopathologic analysis of the internal limiting membrane surgically peeled from eyes with diffuse diabetic macular edema. Jpn J Ophthalmol 56:280–287.  https://doi.org/10.1007/s10384-012-0130-y CrossRefGoogle Scholar
  54. 54.
    Kenawy N, Wong D, Stappler T et al (2010) Does the presence of an Epiretinal membrane Alter the cleavage plane during internal limiting membrane peeling? Ophthalmology 117:320–323.e1.  https://doi.org/10.1016/j.ophtha.2009.07.024 CrossRefGoogle Scholar
  55. 55.
    Romano MR, Ilardi G, Ferrara M et al (2018) Intraretinal changes in idiopathic versus diabetic epiretinal membranes after macular peeling. PLoS One 13.  https://doi.org/10.1371/journal.pone.0197065
  56. 56.
    Romano MR, Cennamo G, Montorio D et al (2018) Correlation between various trace elements and ultramicroscopic structure of epiretinal macular membranes and glial cells. PLoS One 13:e0204497.  https://doi.org/10.1371/journal.pone.0204497 CrossRefGoogle Scholar
  57. 57.
    Das A, McGuire PG, Rangasamy S (2015) Diabetic macular edema: pathophysiology and novel therapeutic targets. Ophthalmology 122:1375–1394.  https://doi.org/10.1016/j.ophtha.2015.03.024 CrossRefGoogle Scholar
  58. 58.
    Rabbani H, Allingham MJ, Mettu PS et al (2015) Fully automatic segmentation of fluorescein leakage in subjects with diabetic macular edema. Invest Ophthalmol Vis Sci 56:1482–1492.  https://doi.org/10.1167/iovs.14-15457 CrossRefGoogle Scholar
  59. 59.
    Spaide RF, Klancnik JM, Cooney MJ (2015) Retinal vascular layers imaged by fluorescein angiography and optical coherence tomography angiography. JAMA Ophthalmol 133:45–50.  https://doi.org/10.1001/jamaophthalmol.2014.3616 CrossRefGoogle Scholar
  60. 60.
    Feng Y, Wang Y, Stock O et al (2009) Vasoregression linked to neuronal damage in the rat with defect of polycystin-2. PLoS One 4:e7328.  https://doi.org/10.1371/journal.pone.0007328 CrossRefGoogle Scholar
  61. 61.
    Lecleire-Collet A, Audo I, Aout M et al (2011) Evaluation of retinal function and flicker light-induced retinal vascular response in normotensive patients with diabetes without retinopathy. Invest Ophthalmol Vis Sci 52:2861–2867.  https://doi.org/10.1167/iovs.10-5960 CrossRefGoogle Scholar
  62. 62.
    Silva KC, Rosales MAB, Biswas SK et al (2009) Diabetic retinal neurodegeneration is associated with mitochondrial oxidative stress and is improved by an angiotensin receptor blocker in a model combining hypertension and diabetes. Diabetes 58:1382–1390.  https://doi.org/10.2337/db09-0166 CrossRefGoogle Scholar
  63. 63.
    Hammes H-P, Feng Y, Pfister F, Brownlee M (2011) Diabetic retinopathy: targeting vasoregression. Diabetes 60:9–16.  https://doi.org/10.2337/db10-0454 CrossRefGoogle Scholar
  64. 64.
    Yamana Y, Oka Y, Ohnishi Y et al (1988) Reflow of obstructed capillaries in the maculae of humans with diabetic retinopathy, observed by fluorescein angiography. Br J Ophthalmol 72:660–665CrossRefGoogle Scholar
  65. 65.
    Takase N, Nozaki M, Kato A et al (2015) Enlargement of foveal avascular zone in diabetic eyes evaluated by EN face optical coherence tomography angiography. Retina 35:2377–2383.  https://doi.org/10.1097/IAE.0000000000000849 CrossRefGoogle Scholar
  66. 66.
    Romano MR, Cennamo G, Schiemer S et al (2017) Deep and superficial OCT angiography changes after macular peeling: idiopathic vs diabetic epiretinal membranes. Graefes Arch Clin Exp Ophthalmol 255:681–689.  https://doi.org/10.1007/s00417-016-3534-4 CrossRefGoogle Scholar
  67. 67.
    Liu L, Wu X, Geng J et al (2012) IVTA as adjunctive treatment to PRP and MPC for PDR and macular edema: a meta-analysis. PLoS One 7:e44683.  https://doi.org/10.1371/journal.pone.0044683 CrossRefGoogle Scholar
  68. 68.
    Kim YT, Kang SW, Kim SJ et al (2012) Combination of vitrectomy, IVTA, and laser photocoagulation for diabetic macular edema unresponsive to prior treatments; 3-year results. Graefes Arch Clin Exp Ophthalmol 250:679–684.  https://doi.org/10.1007/s00417-011-1888-1 CrossRefGoogle Scholar
  69. 69.
    Boyer DS, Faber D, Gupta S et al (2011) Dexamethasone intravitreal implant for treatment of diabetic macular edema in VITRECTOMIZED patients. Retina 31:915–923.  https://doi.org/10.1097/IAE.0b013e318206d18c CrossRefGoogle Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Biomedical SciencesHumanitas UniversityMilanItaly
  2. 2.Federico II UniversityNaplesItaly

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