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

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