Vitreoretinal Adhesion and Age-Related Macular Degeneration
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.
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About our author(s):
Charles C. Wykoff, MD, PhD
Harry W. Flynn, Jr., MD Bascom Palmer Eye Institute