April 2010, Issue 40
Vitreoretinal Adhesion and Age-Related Macular Degeneration
Charles C. Wykoff, MD, PhD
Harry W. Flynn, Jr., MD
Bascom Palmer Eye Institute
Age-related macular degeneration (AMD) is the leading cause of severe visual acuity (VA) loss in older adults in the developed world.1 While many risk factors for the development of AMD have been described including age, genetic predisposition, smoking and cardiovascular disease, the specific factors contributing to the pathogenesis and progression of AMD are incompletely understood.2 Clinically, AMD appears to involve primarily the retinal pigment epithelium (RPE) and outer retinal layers. Additionally, however, evidence suggests that the vitreous may also play a role in the pathogenesis and/or the progression of AMD.
A variable rate of posterior vitreous detachment (PVD) has been reported in older adults. In one study, approximately 25% of emmetropic eyes of people aged 80 years or more did not have a complete PVD.3 In another study, Lambert et al reported that 8 of 10 patients with neovascular AMD undergoing surgical excision of a subfoveal neovascular membrane had an attached posterior vitreous at the time of vitrectomy.4 Subsequently, studies employing echography have confirmed a lower rate of PVD in patients with AMD compared to patients without AMD.5, 6
More recently, ocular coherence tomography (OCT) has provided increased anatomic resolution. Subsequently, studies employing echography and OCT to study the vitreoretinal interface have reported a high coincidence of persistent macular vitreoretinal adhesion and AMD, particularly in the setting of exudative (wet) AMD.7, 8 For example, Robinson et al retrospectively analyzed 29 treatment naïve subjects with active wet AMD in one eye and dry AMD in the fellow eye with ultrasound and OCT.9-11 The incidence of PVD by echography was 6/29 (21%) in the eyes with wet AMD, compared with 20/29 (69%) in the eyes with dry AMD (P = .002). Additionally, vitreomacular adhesion (VMA) as detected by OCT was present in 11/29 (38%) eyes with wet AMD and in only 3/29 (10%) eyes with dry AMD (P = .008).
In another study, Mojana et al retrospectively evaluated 170 eyes with spectral domain OCT and scanning laser ophthalmoscopy, including 61 eyes with wet AMD, 59 eyes with dry AMD, and 50 control eyes.12 Eyes with AMD were more likely to have hyaloid adhesions (wet AMD, 27.8%, dry AMD, 25.4%) compared with control eyes (16%, P=0.002). Of the 40 eyes with hyaloid adhesion to the macula, 13 had evidence of tractional effects on the retina, a finding significantly associated with wet AMD (59%) vs. dry AMD (13%) vs. control eyes (12%; P=0.007). Furthermore, the anatomic location of the hyaloid adhesion to the macula correlated with the location of the choroidal neovascularization (P=0.48), a finding also reported by others.8 Of interest, 5 patients with vitreomacular traction underwent 25-gauge pars plana vitrectomy (PPV) with removal of the attached posterior hyaloid: 1 patient had dry AMD with a central drusenoid pigment epithelial detachment with decreased VA and 4 patients had wet AMD poorly responsive to aggressive anti-vascular endothelial growth factor (VEGF) therapy. While the clinical significance of PPV in these patients is unclear due to limited follow-up (6-36 weeks) and concurrent anti-VEGF therapy, 4 patients experienced improved VA and none lost VA. It is important to note that PPV in the setting of wet AMD may complicate pharmacologic treatments, as vitrectomy may shorten the half-life of intravitreal anti-VEGF medications, so that changes in the treatment regimen may be necessary.12, 13
Many lines of evidence suggest that vitreoretinal adherence and traction may have significant effects on the RPE and retinal morphology, function and metabolism.8, 12, 14, 15 Oxygenation of the retina can change significantly following vitrectomy and creation of a PVD.16 Traction may induce changes in RPE function and increase the secretion of certain growth factors including VEGF; for example, pulsatile stretching of cultured RPE cells can induce the transcription of VEGF.17 Despite these intriguing observations, however, whether vitreous adherence predisposes to AMD, and how it relates to other predisposing factors such as inflammation18 and genetic predisposition,19, 20 is yet to be clarified.
Clinical investigations and technological advances allowing visualization of incredible retinal and vitreous detail have revealed that the vitreous may play a significant role in a variety of retinal diseases including proliferative diabetic retinopathy, vitreomacular traction syndrome, epiretinal membrane, macular hole, optic pit and macular edema associated with retinal vein occlusion.14 Certainly, more work is needed to better understand the role of the vitreous in AMD.
- Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med 2008;358(24):2606-17.
- Spaide RF, Armstrong D, Browne R. Continuing medical education review: choroidal neovascularization in age-related macular degeneration--what is the cause? Retina 2003;23(5):595-614
- Perichon JY, Brasseur G, Uzzan J. [Ultrasonographic study of posterior vitreous detachment in emmetropic eyes]. J Fr Ophtalmol 1993;16(10):538-44.
- Lambert HM, Capone A, Jr., Aaberg TM, et al. Surgical excision of subfoveal neovascular membranes in age-related macular degeneration. Am J Ophthalmol 1992;113(3):257-62
- Weber-Krause B, Eckardt U. [Incidence of posterior vitreous detachment in eyes with and without age-related macular degeneration. An ultrasonic study]. Ophthalmologe 1996;93(6):660-5.
- Ondes F, Yilmaz G, Acar MA, et al. Role of the vitreous in age-related macular degeneration. Jpn J Ophthalmol 2000;44(1):91-3.
- Krebs I, Brannath W, Glittenberg C, et al. Posterior vitreomacular adhesion: a potential risk factor for exudative age-related macular degeneration? Am J Ophthalmol 2007;144(5):741-6.
- Lee SJ, Lee CS, Koh HJ. Posterior vitreomacular adhesion and risk of exudative age-related macular degeneration: paired eye study. Am J Ophthalmol 2009;147(4):621-6 e1.
- Robison CD, Krebs I, Binder S, et al. Vitreomacular adhesion in active and end-stage age-related macular degeneration. Am J Ophthalmol 2009;148(1):79-82 e2.
- Wheatley HM. Posterior vitreomacular adhesion and exudative age-related macular degeneration. Am J Ophthalmol 2008;145(4):765; author reply -6.
- Schmidt JC, Mennel S, Meyer CH, Kroll P. Posterior vitreomacular adhesion: a potential risk factor for exudative age-related macular degeneration. Am J Ophthalmol 2008;145(6):1107; author reply -8.
- Mojana F, Cheng L, Bartsch DU, et al. The role of abnormal vitreomacular adhesion in age-related macular degeneration: spectral optical coherence tomography and surgical results. Am J Ophthalmol 2008;146(2):218-27.
- Freeman WR, Falkenstein I. Avastin and new treatments for AMD: where are we? Retina 2006;26(8):853-8.
- Schulze S, Hoerle S, Mennel S, Kroll P. Vitreomacular traction and exudative age-related macular degeneration. Acta Ophthalmol 2008;86(5):470-81.
- Gross-Jendroska M, Flaxel CJ, Schwartz SD, et al. Treatment of pigment epithelial detachments due to age-related macular degeneration with intra-ocular C3F8 injection. Aust N Z J Ophthalmol 1998;26(4):311-7.
- Stefansson E, Loftsson T. The Stokes-Einstein equation and the physiological effects of vitreous surgery. Acta Ophthalmol Scand 2006;84(6):718-9.
- Seko Y, Fujikura H, Pang J, et al. Induction of vascular endothelial growth factor after application of mechanical stress to retinal pigment epithelium of the rat in vitro. Invest Ophthalmol Vis Sci 1999;40(13):3287-91.
- Anderson DH, Mullins RF, Hageman GS, Johnson LV. A role for local inflammation in the formation of drusen in the aging eye. Am J Ophthalmol 2002;134(3):411-31
- Maller J, George S, Purcell S, et al. Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nat Genet 2006;38(9):1055-9.
- Seddon JM, Reynolds R, Maller J, et al. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci 2009;50(5):2044-53.
Ingrid U. Scott,
MD, MPH, Editor
Professor of Ophthalmology and
Public Health Sciences,
Penn State College of Medicine