Macular Degeneration: What Causes It, and What Can Be Done About It
If you or a parent has just been told "there are changes in the macula," you probably want three answers quickly: why did this happen, how bad is it, and what can be done. This article covers all three.
The macula is the small central part of the retina responsible for sharp, detailed vision — reading, recognising faces, threading a needle. Age-related macular degeneration (AMD) damages this area while leaving peripheral vision intact. That is why AMD rarely causes total blindness, but it can make reading and driving impossible.
AMD is not rare in India. Population studies in south India found early AMD in roughly 21% of rural and 16% of urban residents aged 60 and above, with late AMD in about 2.3% of both groups.
What actually causes it: the risk factors worth knowing
Age is the single biggest factor. Risk rises steeply after 60 and very sharply after 80.
Smoking is the biggest modifiable factor, and the news is good. A large systematic review found current smoking to be one of the few risk factors with a strong, consistent association with late AMD. One British study found current smokers were roughly twice as likely to have vision-impairing AMD. A separate study found a clear dose relationship: those with over 40 pack-years had an odds ratio of 2.75 compared to non-smokers.
Here is the important part: quitting works. In both studies, people who had stopped smoking more than 20 years earlier had a risk comparable to those who had never smoked. If you smoke and have been diagnosed with AMD, stopping is the most powerful thing you can do yourself.
Genetics matter, and complement is the reason. Two gene variants dominate: CFH Y402H and ARMS2 A69S. Together with a third variant in C3, these account for roughly 76% of the population-attributable risk of developing AMD.
Complement factor H is a brake on the complement system, part of your innate immune defence. The Y402H variant makes that brake less effective, so complement activity stays switched on in the retina, driving chronic low-grade inflammation and damage to the retinal pigment epithelium. Carrying one copy raises risk roughly 2.2 to 4.6 times; two copies, 3.3 to 7.4 times, in white populations. CFH Y402H also appears strongly linked to AMD in Indian patients.
This matters for more than curiosity: every new dry AMD drug on the market works by targeting this pathway.
Other factors with reasonable evidence: family history of AMD, previous cataract surgery, higher body mass index, cardiovascular disease and hypertension. In the Indian population study above, smokeless tobacco emerged as a risk factor for both early and late disease, which is relevant given how common Khaini, Gutka and Jarda use is here.
Dry Age-related Macular Degeneration (dry AMD)
About 85 to 90% of AMD is "dry." Waste deposits called drusen build up under the retina. In early stages, vision may be entirely normal and the condition is picked up only on examination.
The advanced form is geographic atrophy (GA), which produces well-demarcated patches where the retinal pigment epithelium and photoreceptors have died. These patches enlarge slowly over years. When they reach the centre of the macula, central vision goes.
Dry AMD does not progress quickly, but it does progress. It also needs monitoring, because roughly 10 to 15% of dry AMD eyes convert to the wet form.
Wet Age-Related Macular Degeneration (wet AMD)
In wet AMD, abnormal new blood vessels grow under or into the retina. These vessels leak fluid and blood. Vision can drop over days to weeks, and straight lines appear bent or wavy.
Wet AMD is a medical urgency. Treated early, vision is usually preserved and often improved. Left for months, scar tissue forms and the damage is permanent. If you notice sudden distortion of straight lines, a grey patch in the centre of vision, or a drop in reading vision in one eye, get examined within days, not weeks.
Pachychoroid, PCV and PEHCR: why your diagnosis may not be "ordinary" AMD
This is where Indian and East Asian patients differ from Western textbook descriptions, and where getting the diagnosis right changes treatment.
Pachychoroid means "thick choroid," the vascular layer beneath the retina. A group of conditions shares this feature, including central serous chorioretinopathy (CSC), which many patients have had years earlier. Crucially, pachychoroid disease typically lacks the classic drusen of AMD. It is a different disease driven by abnormal choroidal circulation, not primarily by complement and drusen.
Polypoidal choroidal vasculopathy (PCV) sits at the severe end of this spectrum. Instead of a diffuse vascular membrane, PCV forms grape-like aneurysmal dilatations ("polyps") at the edge of a branching network. It is now understood as a variant of type 1 neovascularisation, sometimes called aneurysmal type 1 MNV.
Why this matters enormously in India: a south Indian hospital study found that of patients presenting with clinical features of wet AMD, roughly half (49.7%) actually had PCV. In Asian series generally, PCV accounts for 22 to 62% of presumed wet AMD, against only 4 to 14% in white patients.
PCV behaves differently. Some patients respond poorly to anti-VEGF injections alone and do better with photodynamic therapy (PDT) added. Suspect it if there are reddish-orange subretinal nodules, heavy bleeding relative to lesion size, a haemorrhagic pigment epithelial detachment, or poor response to injections.
The practical conclusion: anyone presenting with suspected wet AMD in India should have proper multimodal imaging, including ICG angiography where indicated, not just an OCT and a treatment plan.
Peripheral exudative haemorrhagic chorioretinopathy (PEHCR) is the same process occurring in the far periphery rather than the macula. It produces bleeding and exudation outside the macula, often with no symptoms at all, and is frequently mistaken for a choroidal melanoma. It is the second most common lesion simulating melanoma. Most PEHCR lesions can simply be observed, with around 89% stabilising or regressing. Treatment is reserved for lesions threatening the macula or causing vitreous haemorrhage.
So the picture is a family of related conditions: drusen-driven AMD at one end, pachychoroid-driven disease at the other, PCV straddling both, and PEHCR as the peripheral expression.
Treatment: What Works Today
For dry AMD: AREDS2 supplements
"AREDS2" refers to the Age-Related Eye Disease Study 2, a large trial run by the US National Eye Institute. The formulation is set out below.
Component | Daily dose |
Vitamin C | 500 mg |
Vitamin E | 400 IU |
Lutein | 10 mg |
Zeaxanthin | 2 mg |
Zinc (as zinc oxide) | 80 mg |
Copper (as cupric oxide) | 2 mg |
The original AREDS formula reduced progression from intermediate to advanced AMD by about 25%. AREDS2 replaced beta-carotene with lutein and zeaxanthin, because beta-carotene increased lung cancer risk in current and former smokers. Copper is included to prevent zinc-induced copper deficiency. Adding omega-3 fatty acids gave no additional benefit.
Two things to understand: this is for intermediate AMD or advanced AMD in one eye, not for everyone with a few drusen, and not a preventive for people with healthy retinas. And it slows progression; it does not reverse damage.
For wet AMD: anti-VEGF injections
How they work: Wet AMD is driven by vascular endothelial growth factor, or VEGF, a signal that tells new blood vessels to grow. In wet AMD these vessels sprout from the choroid, the vascular layer underneath the retina, and push through into or under the retina, where they leak fluid and blood. Anti-VEGF drugs block that signal. The abnormal vessels shrink back and stop leaking, the retina dries out, and vision recovers as the swelling settles. The injection itself is given in the clinic under anaesthetic drops and takes a few minutes.
The loading dose, and what happens after it: Treatment begins with three injections, one a month apart. In a good number of patients the abnormal vessels stay shrunken once that loading phase is complete, and no further injections are needed for a considerable time. In others the vessels reopen and begin leaking again, and injections have to be repeated. How often depends partly on the disease itself and partly on which drug is used, because they differ in how long they hold the eye dry.
The drugs, and how long each one lasts. The agents in use in India are set out below.
Drug | Brand names in India | Typical duration in the eye |
Ranibizumab | Accentrix, Razumab, Lucentis | About 1 month |
Bevacizumab | Avastin (used off-label) | About 1 month |
Aflibercept 2 mg | Eylea, Anyra | About 2 months |
Brolucizumab | Pagenax | About 3 months |
Aflibercept 8 mg | Eylea 8 mg (being introduced) | About 4 months |
Faricimab | Vabysmo | About 4 months |
Ranibizumab, aflibercept and brolucizumab all block VEGF-A alone. Faricimab works on two pathways: it blocks VEGF-A and also angiopoietin-2, which is involved in blood vessel instability and leakage, and that dual action is part of why it can hold longer intervals. Aflibercept 8 mg is the same molecule as the 2 mg dose at a higher concentration, so it extends the interval rather than changing the mechanism.
Treat-and-extend versus PRN. Two protocols are in common use. Treat-and-extend means giving an injection at every visit and gradually stretching the gap between visits, so the patient is injected whether or not the disease is active on that day. PRN, meaning as and when needed, means examining and imaging the eye at each visit and injecting only when there are signs of activity.
At Claritas, Dr Mayank Bansal works towards a PRN approach for most patients. The aim is that each patient receives as few injections as the disease genuinely requires, rather than being committed to a fixed schedule. That judgement is made on imaging at every follow-up visit.
Why OCT angiography matters here. A standard OCT scan shows the structure of the retina: whether fluid is present, how much of it, and exactly where. OCT angiography goes further. It maps blood flow through the retinal and choroidal vessels without any dye injection, so the abnormal vessel network itself can be seen, along with whether it is still active or has gone quiet. Being able to look at the vessels rather than only at the fluid they produce makes it considerably easier to judge whether an injection is actually needed on a given day. Claritas has OCT angiography on site, and it is a large part of how a retina-focused practice keeps the number of injections down.
Costs have fallen substantially in India. An indigenously developed aflibercept biosimilar launched in February 2026, and the originator responded by cutting its price by about 44%.
For geographic atrophy: Complement Inhibitors
Two drugs are approved in the US: pegcetacoplan (a C3 inhibitor, approved February 2023) and avacincaptad pegol (a C5 inhibitor, approved August 2023). Both slow lesion growth by roughly 20 to 30%. Five-year extension data for pegcetacoplan showed it delayed progression by approximately 1.5 years versus modelled natural history, with greater benefit from earlier treatment.
An honest caveat: these drugs slow the lesion. They do not restore vision, and they require ongoing injections. They are also not yet routinely available in India. This is the direct therapeutic payoff of the CFH complement biology described earlier.
Frequently Asked Questions
Can stem cells cure macular degeneration?
Not yet, but this is genuinely active research, not hype. The logic is sound: replace the dead retinal pigment epithelium cells with healthy ones.
The programme furthest along is OpRegen, developed by Lineage with Roche and Genentech. It reported three-year results in 2026 showing gains of +9 letters among patients whose cells covered the atrophy area extensively, after a single treatment. A Phase 2a study is enrolling.
A related therapy, jCyte's jCell, is sometimes mentioned in this context but is being tested for retinitis pigmentosa, not AMD.
This is early-phase work in small numbers of patients, and it is promising. But no stem cell therapy is approved for AMD anywhere in the world today. Be cautious of any clinic offering "stem cell treatment" for macular degeneration commercially, because that is not an approved treatment.
What about gene therapy?
The idea is to make the eye produce its own anti-VEGF protein continuously after a single treatment, instead of repeated injections. The furthest advanced is RGX-314 (surabgene lomparvovec), developed by REGENXBIO with AbbVie. Two pivotal trials, ATMOSPHERE and ASCENT, have enrolled over 1,200 patients between them, with topline results expected in late 2026. Early patients have maintained stable or improved vision through five years after a single dose. Other programmes, including 4D-150, have Phase 3 results expected in 2027.
If these succeed, the treatment burden of wet AMD could change substantially. It will take several years to reach Indian clinics, but the direction is clear.
Can I just have an eye transplant?
This is the most common question patients ask, and the answer surprises most people. What is routinely called an "eye transplant" is a corneal transplant, replacing the clear front window of the eye. That is a well-established, successful operation.
The retina cannot be transplanted. The reason is the optic nerve: a cable of roughly one million nerve fibres connecting eye to brain. Once cut, it does not regrow, and surgeons cannot currently reconnect it.
A surgical team at NYU Langone Health performed the world's first whole-eye transplant in 2023. Three years on, the transplanted eye is alive, well perfused and its photoreceptors survived, but the patient cannot see through it. Keeping the eye healthy turned out to be the easier half of the problem.
So when someone offers to donate an eye to a relative with AMD, the honest answer is that it would not help. Research into optic nerve regeneration continues, but it is a long way off.
I have lost central vision. What can help me read?
A great deal, and this is underused. Peripheral vision is preserved in AMD, which is exactly what low vision aids exploit. Options include:
Optical magnifiers, which may be hand-held, stand-mounted, or spectacle-mounted, in a range of strengths
Electronic video magnifiers (CCTV), a camera and screen allowing very high magnification with adjustable contrast, in desktop and portable versions
Telescopic spectacles for distance tasks
Smartphone and tablet accessibility features, which are free and genuinely powerful: text enlargement, high contrast modes, screen readers, and camera-magnifier apps
AI-based smart vision glasses, which work by voice rather than by magnification. The Smart Vision Glasses made by SHG Technologies in Bengaluru read printed text aloud in several Indian languages, identify faces, detect obstacles and give spoken navigation cues through an earpiece. They were developed for severe visual impairment in general rather than for AMD specifically, but where central vision is too poor for any magnifier to help, having text read aloud is often the most practical route back to reading. They are distributed in India through eye hospitals and NGO programmes.
Non-optical aids, including good task lighting (often the single most effective change), reading stands, bold-line notebooks, and large-print or audiobooks
A formal low vision assessment is worth doing. Most patients are given far less help than is actually available to them.
How often should I be checked?
If you have dry AMD, typically every 6 to 12 months, more often if there are high-risk features. Use an Amsler grid at home, one eye at a time, and come in immediately if lines look wavy or a patch appears. If you have wet AMD on treatment, follow the schedule your retina specialist sets, because gaps in treatment are the commonest reason for avoidable vision loss.
When to see a retina specialist urgently?
Straight lines suddenly appearing bent or wavy
A new grey or dark patch in central vision
Sudden drop in reading vision in one eye
A rapid change in an eye already diagnosed with AMD
About the author
Dr Mayank Bansal is a vitreoretinal surgeon and Director of Claritas Eye & Retina Institute, New Delhi, and Senior Consultant in Vitreo-Retinal Surgery at Fortis Memorial Research Institute. He trained at AIIMS, holds FRCS (Glasgow) and FACS (USA), and completed a fellowship at UCLA's Stein Eye Institute. He has performed over 20,000 retina and cataract surgeries.
References
Chakravarthy U et al. Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol. 2010;10:31.
Khan JC et al. Smoking and age related macular degeneration: the number of pack years of cigarette smoking is a major determinant of risk. Br J Ophthalmol. 2006;90:75.
Evans JR et al. 28,000 cases of age related macular degeneration causing visual loss in the UK may be attributable to smoking. Br J Ophthalmol. 2005;89:550-553.
CFH Y402H, ARMS2 A69S and C3 R102G account for approximately 76% of population-attributable AMD risk (see review literature on AMD genetics).
Sankara Nethralaya Rural-Urban Age-related Macular Degeneration Study (SN-RAM), Report No. 1. Br J Ophthalmol.
Kumar M et al. Prevalence of polypoidal choroidal vasculopathy in Indian population. PLoS ONE. 2020;15(4).
Chaikitmongkol V et al. Latest developments in polypoidal choroidal vasculopathy. Asia Pac J Ophthalmol.
AREDS2 Research Group. Ophthalmology. 2012;119(11):2282-9; and NEI AREDS/AREDS2 results.
Shields CL et al. Peripheral exudative hemorrhagic chorioretinopathy simulating choroidal melanoma in 173 eyes. Ophthalmology. 2009;116(3):529-535.
Dhoot DS et al. Five-year GALE extension data, Macula Society 49th Annual Meeting, February 2026.
Comments