Wet AMD: A Brief Overview

Ali Adel Ne’ma Abdullah Contact

University Hospital of Wales, UK

Introduction

Age-related macular degeneration (AMD) is a well-characterised disease responsible for being the principal cause of visual impairment in elderly patients (1). Generally, it is subdivided into two categories: ‘dry’ and ‘wet’. Dry AMD is more common than wet AMD, accounting for more than 85% of AMD cases (2). However, the severity of wet AMD is such that it is responsible for 80% of cases with severe visual impairment (2).

This article will focus on wet AMD and its aetiology, pathogenesis and treatment.

Epidemiology

Wet AMD has a greater incidence among the elderly and has been reported in many different populations. One UK study calculated a prevalence of 4.8% and 12.2% for individuals ≥65 years and ≥80 years, respectively (3). A US/Europe/Australian study calculated a prevalence of 0.0%, 0.2%, 0.9%, 4.6% and 13.1% for individuals aged <55, 55-64, 65-74, 75-84 and >84, respectively (4).

Risk factors

Age is one of the most important risk factors, as alluded to in the aforementioned epidemiology statistics. Regarding ethnicity, it appears to affect Caucasians the most, with an intermediate prevalence in Hispanics and Chinese and a lower prevalence in Africans (5-6). Smoking has been shown to increase AMD risk, with one study showing a 1.9-fold increased risk for current smokers and 1.7-fold increased risk for past smokers (7). Alcohol is also thought to be a risk factor, with heavy alcohol consumption causing a 1.47 odds ratio in one study (8). Genetics, especially the Y402H polymorphism of the complement factor H gene, is a well-established risk factor for AMD progression, given the plethora of evidence implicating inflammation and the complement cascade in AMD (9).

Pathogenesis

The hallmark of wet AMD pathogenesis is choroidal neovascularisation. New blood vessels grow from the choroid into the subretinal pigment epithelium as a response to hypoxia (10). Whilst many pro-angiogenic factors have been demonstrated to play a role in this response, the two factors that are most important are vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) (10-11). This angiogenesis leads to the accumulation of subretinal fluid, haemorrhage (as the new vessels formed are friable), exudation, RPE detachment, and scarring (12).

Clinical presentation

In the absence of investigations and treatment, wet AMD often results in rapid central visual loss over months. Earlier symptoms include metamorphopsia, the perception of straight edges being distorted (13).

Diagnosis

Ophthalmoscopy and/or retinal photographs will demonstrate subretinal fluid and/or haemorrhage in the macular area (14). Fluorescein dye retinal angiography will show leakage of fluorescein from the friable, newly formed choroidal vessels (14). Optical coherence tomography will produce detailed retinal reconstructions that show subretinal fluid (14).

Treatment

Wet AMD treatment aims to halt the neovascularisation process. The most successful method of achieving this is through using intravitreal VEGF inhibitors such as bevacizumab and ranibizumab. These agents revolutionised the treatment of wet AMD and improved visual prognosis from almost-certain blindness to high levels (>90%) of three-line visual improvement after two years of treatment (15-16). Treatment is initially monthly for the first 3 months. Thereafter, frequency of injections depends on how quickly deterioration occurs.

Conclusion

Wet AMD is a potentially blinding disorder affecting the central vision that increases in incidence with age. In the current time, treatment has come a long way and we are able to diagnose and treat this disorder more successfully than ever before. It is important to raise awareness amongst our elderly patients to seek prompt evaluation if they notice metamorphopsia or central visual field disturbances that could signal AMD, before it is too late.

References

  1. Zeng S, Hernández J, Mullins RF. Effects of antioxidant components of AREDS vitamins and zinc ions on endothelial cell activation: implications for macular degeneration. Invest Ophthalmol Vis Sci. 2012;53(2):1041-1047.
  2. Jager RD, Mieler WF and Miller JW. Age-related macular degeneration. N Engl J Med. 2008 Jun 12;358(24):2606-17.
  3. Owen CG, Jarrar Z, Wormald R, Cook DG, Fletcher AE, Rudnicka AR. The estimated prevalence and incidence of late stage age related macular degeneration in the UK. Br J Ophthalmol. 2012 May;96(5):752-6.
  4. Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, Hofman A, Jensen S, Wang JJ, de Jong PT. Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology. 2001 Apr;108(4):697-704.
  5. Bressler SB, Muñoz B, Solomon SD, West SK; Salisbury Eye Evaluation (SEE) Study Team. Racial differences in the prevalence of age-related macular degeneration: the Salisbury Eye Evaluation (SEE) Project. Arch Ophthalmol. 2008 Feb;126(2):241-5.
  6. Klein R, Rowland ML, Harris MI. Racial/ethnic differences in age-related maculopathy. Third National Health and Nutrition Examination Survey. Ophthalmology. 1995 Mar;102(3):371-81. Erratum in: Ophthalmology 1995 Aug;102(8):1126.
  7. Seddon JM, George S, Rosner B. Cigarette smoking, fish consumption, omega-3 fatty acid intake, and associations with age-related macular degeneration: the US Twin Study of Age-Related Macular Degeneration. Arch Ophthalmol. 2006 Jul;124(7):995-1001.
  8. Chong EW, Kreis AJ, Wong TY, Simpson JA, Guymer RH. Alcohol consumption and the risk of age-related macular degeneration: a systematic review and meta-analysis. Am J Ophthalmol. 2008 Apr;145(4):707-715.
  9. Schaumberg DA, Hankinson SE, Guo Q, Rimm E, Hunter DJ. A prospective study of 2 major age-related macular degeneration susceptibility alleles and interactions with modifiable risk factors. Arch Ophthalmol. 2007 Jan;125(1):55-62.
  10. Bressler SB. Introduction: understanding the role of angiogenesis and antiangiogenic agents in age-related macular degeneration. Ophthalmology 2009;116:1–7.
  11. Crawford Y, Ferrara N. VEGF inhibition: insights from preclinical and clinical studies. Cell Tissue Res 2009;335:261–9.
  12. Ambati J, Fowler BJ. Mechanisms of age-related macular degeneration. Neuron. 2012;75(1):26-39.
  13. Xu K, Gupta V, Bae S, Sharma S. Metamorphopsia and vision-related quality of life among patients with age-related macular degeneration. Can J Ophthalmol. 2018 Apr;53(2):168-172.
  14. Hernández-Zimbrón LF, Zamora-Alvarado R, Ochoa-De la Paz L, Velez-Montoya R, Zenteno E, Gulias-Cañizo R, Quiroz-Mercado H, Gonzalez-Salinas R. Age-Related Macular Degeneration: New Paradigms for Treatment and Management of AMD. Oxid Med Cell Longev. 2018 Feb 1;2018:8374647.
  15. Velez-Montoya R, Oliver SC, Olson JL, Fine SL, Mandava N, Quiroz-Mercado H. Current knowledge and trends in age-related macular degeneration: today’s and future treatments. Retina. 2013;33(8):1487-1502.
  16. Velez-Montoya R, Oliver SC, Olson JL, Fine SL, Quiroz-Mercado H, Mandava N. Current knowledge and trends in age-related macular degeneration: genetics, epidemiology, and prevention. Retina. 2014;34(3):423-441.
Tags: , ,

Leave a Reply