A better understanding of a problem, its timely identification and quick action against it, always gives better results. Age-related macular degeneration (ARMD) is a condition that affects the macula. In the human eye, the retina is a light-sensitive layer and there is a small area in the centre which is the functional centre of the retina known as the macula, which has approximately 5 mm in diameter. A well functioning macular is basically required to clearly see the details of objects.
ARMD is a disease which is characterized by yellowish deposits called as drusen (build up of waste product of photoreceptor), Retinal Pigment epithelium (RPE) (outer most layer of retina) changes and new vessels formation termed as neovascular membranes. This disorder is most commonly present in elderly people and chances of occurring the same increases more in those 60 years or older. Various risk factors are there that change the tissue physiology of RPE and photoreceptor cells which leads to degeneration of retina and cause ARMD.
ARMD is a disease that is characterized by yellowish deposits called drusen (build-up of waste product of photoreceptor), Retinal Pigment epithelium (RPE) (outermost layer of the retina) changes and new vessels formation termed as neovascular membranes. This disorder is most commonly present in elderly people and chances of occurring the same increases more in those 60 years or older. Various risk factors are there that change the tissue physiology of RPE and photoreceptor cells which leads to degeneration of the retina and causes ARMD.
- Advancing age
- Family history
- Genetic association
- Female gender
- Cardiovascular disease
- Light skin pigmentation
Biochemical pathways and genetic association are the main possible factors in ARMD. Various biochemical pathways like complement activation pathways are involved in the pathogenesis of ARMD which caused oxidative damage, lipofuscin accumulation, and inflammation. When a series of such inflammatory events occur, the RPE layer gets weakened over a period of time. Alongside, due to inflammation and oxidative damage, there are new thin and fragile vessels that start forming below the RPE in the choroidal layers. When the RPE layer gets damaged, there is a breach in its continuity. From this breach or defect, these new vessels travel upwards and start entering the retinal tissue. Since these are fragile vessels, they begin to bleed and cause subsequent edema. Due to this, the macular architecture gets disturbed, and as a result of which the patient starts having blurry vision or distortion which is called metamorphopsia.
TYPES OF ARMD:–
- DRY ARMD: Although drusen are the hallmark of ARMD, most of the patients with drusen will not develop severe ARMD. In dry ARMD macula gets slowly damaged with gradual RPE and photoreceptor atrophy. Around 20 % of dry would progress to exudative form.
Patient with large drusen in one eye has 6.3 % chances and patient with bilateral large drusen has 26 % chances of progression to wet ARMD.
- EXUDATIVE OR WET ARMD: It is characterized by the presence of neovascular membrane which leaks fluid and blood and leads to RPE detachment, RPE tear, and scarring. This membrane was previously called the Choroidal neovascular membrane (CNVM). The new
consensus today terms it as macular neovascularization (MNV). If not treated on time, it can cause macular scarring and atrophy.
ARMD is a bilateral disorder but often asymmetrical. Some patients are asymptomatic and some patients themselves narrate a history of blurred vision, reduced contrast, mild metamorphopsia (distortion of visual images). Patients who develop atrophic ARMD see scotoma (blind spot)
which may enlarge slowly over the years. This mainly affects patients near vision. On physical examination, the doctor sees the dilated fundus and looks for drusen, geographical atrophy, subretinal fibrosis, RPE changes, subretinal fluid, hemorrhage, or exudation. Periodic fundus examinations are advised to identify new lesions.
Amsler grid test is used for screening purposes in people above the age of 60 years. Patients with ARMD might see wavy or bent lines, different sizes or shapes of boxes, missing, blur or discolored lines, and dark area at the center of the grid. Patients with abnormal Amsler grid charting should be further investigated. Stereo color photography of the fundus is done for documentation of the lesion and its extension.
Optical coherence tomography (OCT) is a simple, fast, and noninvasive investigation for detecting increased retinal thickness because of subretinal fluid accumulated due to leakage from the abnormal vessels. It also helps in monitoring the treatment and prognostication of the disease. With its current dye-free angiography advent, it is the gold standard investigation
Fundus fluorescein angiography is a highly accurate test for diagnosing choroidal new vessels due to ARMD. It is an invasive procedure where a specific dye is injected from the arm and photos of the retina are taken to detect leaks in the retina.
Prevention is always better than cure. Identification of modifiable risk factor and finding the measures to prevent further disease progression is the key to treat early ARMD. Nicotine and Tobacco are significant risk factors for ARMD, so smoking and tobacco cessation is a must for these patients to prevent further damage. Systemic factors such as hypertension and raised lipid profile should be urgently treated. Antioxidants are found to have a role in prevention of disease progression as light exposure,
inflammation and oxidative damage is found to be associated with ARMD. According to age related eye disease study (AREDS), daily dose of vitamin C (500 mg), vitamin E (400 IU), βcarotene (15 mg), zinc oxide (80 mg), and cupric oxide (2 mg) significantly reduced the chances OF developing advanced ARMD in individuals with high-risk characteristics. Although, few side effects due to these tablets can be constipation, gastric acidity and rarely lung cancer (specially due to beta carotene component). The AREDS 2 changed the formula of oral supplementation to doses of lutein, zeaxanthin, and omega-3 fatty acids (docosahexaenoic acid [DHA] and its precursor eicosapentaenoic acid [EPA]). The objective of the study was to assess the effects of eliminating beta-carotene and reducing the zinc dose from the original AREDS formula. Anti-vascular endothelium growth factor (Anti VEGF): Currently, it is the main stray of treatment today. The widely used intravitreal anti-VEGF agents are Bevacizumab, Ranibizumab,
Aflibercept and Brolucizumab, have proven to be highly effective and have given wonderful results in real-world scenario. A loading dose of 3 injections, one every month, is the followed
practice today. After that, various dosing regimens are present, which have to be tailored by
the retina specialist according to the patient’s condition.
The commonly used dosing regimens of Anti-VEGF treatment (after 3 loading doses) in
neovascular AMD in clinical practice are:
- Pro re nata (PRN) strategy- It basically means as and when required. The patient is called on follow up as per the doctor’s judgment, and if the clinical and OCT findings suggest that the disease is active, the patient receives an injection. It allows less number of injections and reduces the financial burden. A treat and extend regimen- It is more popular approach because it follows progressive lengthening of intervals between injections. After the 3 loading injections, the patient is called at 6 weeks instead of 4 weeks. At this time, the patient is given an injection, even if the disease is not active. Then the patient is called at 8 weeks, and injected. Thus, each visit is combined with an injection and subsequent intervals between the visits are increased.
- An observe and extend regimen- This regimen is the same as the treat and extend, the only difference is when patient comes for a follow up at 6 weeks, if the disease is inactive, no injection is given and patient is called again after 8 weeks. In case the disease is active, injection is given. Monitoring visits following each series of injections
aim to tune the interval in the subsequent injection series. This emerging regimen has achieved a favorable functional outcome with fewer clinic visits and less number of injections.
Laser photocoagulation is seldom used now a days. Previously it was considered to be the treatment of choice for extra foveal and parafoveal lesions. But since the advent of Anti VEGF injections, laser treatment is disappearing from the protocol due to high risk of recurrence, less
effectiveness and vision loss and scotoma due to scar expansion.
Photodynamic therapy (PDT) is a relatively expansive modality, which often given fantastic results, if used at the right time and place. A special dye is injected from the arm, which gets concentrated in the membranes/polyp, and these areas are lasered then. Sometimes, a PDT is combined with an Anti VEGF injection to yield better results. Patients who have a significantly low near vision can aid with a variety of low vision aids. Visual
rehabilitation in ARMD is a new turf, which needs to be ventured, studied and applied extensively.
Newer outlook in future is towards refillable injections, newer drug molecules that prevent ARMD and stem cell therapy. Submacular surgeries are being performed in a lot of centers around the world for scar removal and macular translocation. All these therapies are although under investigations and clinical trial at the moment, but they seem to be the future of ARMD therapy.
ARMD is a disease which can be treated with a od outcome, provided the treatment is given on time. Injections are the main stray of treatment today. The number of injections needed for complete resolution is still a question no one can answer. Some patients can get completely cured with 3 injections, and some might require 13. There is no fixed number, and it depends on type of disease and susceptibility of patient’s eye. But as long as the disease is active, the treatment is essential. Cessation of smoking/alcohol/tobacco and control of systemic factors plays a very important role in overall prognosis of disease. Amsler monitoring by patient at home is an extremely useful method to understand the course of disease. Visual rehab and low vision aids are always the backbone of atrophic stage of the disease. All in all, early identification and detection of ARMD with regular treatment and follow up is the key for a fine