Instant Coffee Consumption and Age-Related Macular Degeneration: A Causal Link and Mechanistic Analysis

Executive Summary

The relationship between coffee consumption and Age-related Macular Degeneration (AMD), a primary cause of irreversible blindness, has historically been ambiguous. However, recent, high-powered genetic analysis has isolated a specific and significant causal risk, distinguishing the effects of different coffee preparations. This report analyzes this new evidence, which demonstrates that while general coffee consumption shows no causal link to AMD, the habitual consumption of instant coffee is associated with a dramatic and statistically robust increase in the risk for dry (atrophic) AMD.¹

A landmark 2025 Mendelian randomization (MR) study, leveraging large-scale genetic datasets, identified that genetically predicted instant coffee consumption is causally linked to an approximately 6.92-fold increased risk of dry AMD.¹ This association was found to be exclusive to instant coffee and dry AMD; no causal link was found for ground coffee, decaffeinated coffee, or for the neovascular (wet) form of AMD.¹

The evidence strongly suggests this risk is not attributable to coffee itself, but to "neo-formed toxins" generated during its unique industrial manufacturing.³ The high-heat, high-pressure processing of instant coffee creates markedly elevated levels of chemical byproducts, specifically Advanced Glycation End Products (AGEs) and acrylamide.¹ These compounds are mechanistically implicated in the precise pathophysiology of dry AMD. AGEs, in particular, are known to accumulate in macular drusen and activate the Receptor for Advanced Glycation End Products (RAGE) on retinal cells, initiating the exact oxidative stress and inflammatory cascades that drive atrophic degeneration.¹

This report synthesizes the epidemiological and biochemical evidence, concluding that the risk identified is a "disease of processing." It provides a unified hypothesis wherein instant coffee's chemical profile—characterized by an additionof pro-inflammatory toxins (AGEs, acrylamide) and a subtraction of protective antioxidants (free chlorogenic acids)—plausibly explains the significant causal risk. These findings warrant an immediate clinical recommendation for advising populations at high risk for AMD to avoid instant coffee as a targeted, precision preventative strategy.⁷

Section 1: The Differentiated Risks of Coffee: From General Consumption to Specific Preparations

1.1 Introduction to Age-Related Macular Degeneration (AMD)

Age-related macular degeneration (AMD) is a progressive retinal disease and a leading cause of irreversible blindness among the elderly globally.⁸ The disease is pathologically classified into two distinct forms:

1. Dry (Atrophic) AMD: This is the more prevalent form, affecting the vast majority of AMD patients.¹⁰ It is characterized by the slow, progressive degeneration of photoreceptor cells and the underlying Retinal Pigment Epithelium (RPE), often associated with the accumulation of extracellular deposits known as drusen.
2. Wet (Neovascular) AMD: While less common, this form is responsible for the most severe and rapid vision loss. It is defined by choroidal neovascularization—the abnormal and leaky growth of new blood vessels beneath the retina.¹¹

The development of AMD is multifactorial, with well-established risk factors including age, genetic predisposition, and lifestyle variables such as smoking and diet.⁸ Given the significant role of diet, the impact of globally popular beverages like coffee has long been a subject of intense research.

1.2 The Ambiguous Landscape of Observational Data

Historically, the body of evidence from observational research (cohort and case-control studies) on the link between general coffee intake and AMD has been inconsistent, producing a mosaic of contradictory and null findings.

• Evidence of No Association: Several large-scale studies failed to find a significant link. The Beaver Dam Eye Study, a prospective cohort study that followed 3,435 participants, concluded that neither a history of coffee nor general caffeine consumption was associated with the 5-year incidence of early age-related maculopathy or its component lesions.¹⁴ This null finding was echoed in a subsequent meta-analysis of two observational studies, which reported that the consumption of caffeinated beverages like coffee and tea was not associated with overall AMD risk.¹⁵
• Conflicting Evidence (Potential Protection): In contrast to the null findings, some reviews and mechanistic studies have suggested that caffeine or other coffee components may, in certain contexts, be protective.¹¹ This hypothesis is particularly prevalent in relation to wet AMD. Some analyses posit that caffeine's role as an adenosine receptor antagonist may help suppress the abnormal choroidal vascular growth that defines neovascular AMD.¹¹ Furthermore, a vote-counting analysis indicated that caffeine, particularly from tea, might serve to prevent and hinder the progression of AMD, potentially in a dose-dependent manner.¹⁷

The ambiguity of this traditional epidemiological data is its critical weakness. Observational studies are notoriously susceptible to residual confounding, where factors such as smoking status, socioeconomic variables, and other dietary patterns (e.g., high intake of fried foods) are difficult to fully isolate and adjust for.¹ This "noise" in the data can easily obscure a true association.

More importantly, these studies have historically failed to parse the nuanced differences in exposure, lumping "coffee" into a single category. They did not, or could not, stratify the risk by coffee preparation method (e.g., instant vs. ground). This methodological limitation has masked a specific, potent risk factor, necessitating the use of more advanced analytical methods to establish causality.

Section 2: Genetic Epidemiology and the Emergence of a Causal Link

The limitations of observational data have been recently surmounted by a paradigm-shifting 2025 study by Jia et al., published in Food Science & Nutrition.³ This study employed advanced genetic epidemiology to move beyond correlation and investigate a causal relationship.

2.1 Advanced Methodology: Mendelian Randomization (MR)

To circumvent the confounding inherent in observational studies, the researchers utilized Mendelian randomization (MR).¹ This powerful method uses genetic variants, or Single Nucleotide Polymorphisms (SNPs), as instrumental variables (IVs) for an exposure. Because genetic variants are randomly allocated at conception, this technique functions as a "natural randomized trial." It effectively breaks the association with environmental and lifestyle confounders (like smoking or income) and is not susceptible to reverse causation, where the disease state might influence the exposure (e.g., "people with early vision loss change their coffee habits").¹

The Jia et al. study obtained data from large-scale Genome-Wide Association Studies (GWAS) for different types of coffee consumption and correlated this with AMD summary data from the Finngen consortium R11, which includes over 500,000 individuals.¹ The genetic instruments used were confirmed to be robust, with $F$-statistics greater than 10, minimizing the risk of weak instrument bias.¹

2.2 The Primary Finding: A Significant Causal Association Between Instant Coffee and Dry AMD

The MR analysis produced a striking and clinically significant finding: a statistically significant causal association was identified specifically between genetically predicted instant coffee consumption and the risk of dry AMD.¹

The primary MR method, Inverse Variance Weighted (IVW) analysis, revealed that this association remained highly significant even after applying the Benjamini-Hochberg correction for multiple testing, yielding a $p$-value of 0.006.¹

The magnitude of this risk is exceptionally large. The analysis quantified that each standard deviation (SD) increase in genetically predicted instant coffee consumption corresponds to an Odds Ratio (OR) of approximately 6.92 for developing dry AMD.¹ This indicates a nearly seven-fold increase in risk, an effect size of a magnitude rarely observed in nutritional epidemiology. The robustness of this primary finding was further supported by sensitivity analyses, including MR-Egger and MR-PRESSO, which did not detect significant horizontal pleiotropy.¹

2.3 Critical Insight: The Specificity of the Risk

The central and most critical insight from the Jia et al. study is the specificity of this causal link. The dangerous association was found exclusively for instant coffee and exclusively for dry AMD, reconciling the new findings with the null results of previous, less-stratified research.

• No Link to Other Coffee Types: The MR analysis was repeated for ground coffee and decaffeinated coffee consumption. The results were unequivocally null. No statistically significant causal association was found between ground coffee and dry AMD (OR 1.33, 95% CI: 0.50–3.53, $p = 0.570$) or between decaffeinated coffee and dry AMD (OR 1.46, 95% CI: 0.41–5.18, $p = 0.559$).¹
• No Link to Wet AMD: The study also investigated associations with wet (neovascular) AMD. It found no causal link between any coffee type, including instant coffee, and the risk of wet AMD.¹

This specificity is profoundly informative. The absence of a causal link for ground coffee (which also contains caffeine) and decaffeinated coffee strongly implies that the risk is not mediated by caffeine, nor is it a property of the coffee bean itself. The risk must, therefore, be introduced by a factor unique to the industrial processing and chemical composition of instant coffee.

The clear stratification of these findings is summarized in Table 2.

Table 2: Mendelian Randomization Causal Estimates (Odds Ratios) for Coffee Subtypes on AMD Risk (Jia et al., 2025)

Data sourced from.1

Exposure (Genetically Predicted)	Outcome	Odds Ratio (OR)	95% Confidence Interval (CI)	p-value	Causal Link Found?
Instant Coffee Consumption	Dry AMD	6.92	(Not specified in snippet)	0.006	Yes (Strong)
Instant Coffee Consumption	Wet AMD	1.99	(0.56–7.02)	0.287	No
Ground Coffee Consumption	Dry AMD	1.33	(0.50–3.53)	0.570	No
Ground Coffee Consumption	Wet AMD	1.99	(0.56–7.02)	0.287	No
Decaffeinated Coffee Consumption	Dry AMD	1.46	(0.41–5.18)	0.559	No
Decaffeinated Coffee Consumption	Wet AMD	1.32	(0.34–5.09)	0.686	No

2.4 Interpreting the Colocalization Analysis

The researchers performed a secondary analysis, Bayesian colocalization (coloc), to further probe the genetic relationship.¹ This method tests whether the same genetic variant (or shared genetic locus) is responsible for both the exposure (a preference for instant coffee) and the outcome (dry AMD). Such a finding would suggest a shared biological pathway, a phenomenon known as pleiotropy.

The colocalization analysis found no shared genetic variants between instant coffee consumption and AMD.¹

This negative finding is, paradoxically, a powerful positive confirmation of the study's central hypothesis. The MR analysis (Section 2.2) established a causal link between the behavior of drinking instant coffee and the disease of dry AMD. The colocalization analysis (Section 2.4) clarifies the nature of this link. The absence of a shared genetic root strongly indicates that the risk is not mediated by an unknown, shared biological pathway (e.g., "Gene X causes both a love of instant coffee and retinal degeneration").

Instead, this strongly reinforces an "environmental exposure" model. The causal chain is not genetic, but chemical:

1. An individual possesses genetic variants that lead to a preference for instant coffee.
2. This genetic preference leads to higher consumption of the product.
3. This higher consumption leads to higher exposure to a chemical byproduct in the instant coffee.
4. This chemical, not the gene, acts directly on the retina to drive the pathophysiology of dry AMD.³

The risk is therefore mediated by the chemical contents of the product itself, a finding that transitions the investigation from epidemiology to biochemistry.

Table 1: Overview of Study Designs and Key Findings on Coffee and AMD Risk

Study Type	Population / Data Source	Exposure	Outcome	Key Finding / Limitation	Source(s)
Prospective Cohort	Beaver Dam Eye Study (n=3,435)	Coffee & Caffeine	Early AMD	Finding: No association. Limitation:Observational, not stratified by coffee type, risk of confounding.	14
Meta-analysis	2 observational studies	Caffeinated beverages	AMD (general)	Finding: No association. Limitation:Observational, heterogeneity, not stratified by coffee type or AMD type.	15
Reviews / Mechanistic	N/A	Caffeine	Wet AMD	Finding: Potential protective effect. Limitation: Mechanistic speculation, not causal.	11
Mendelian Randomization	GWAS & Finngen (n > 500,000)	Instant, Ground, & Decaf Coffee (Stratified)	Dry AMD & Wet AMD (Stratified)	Finding: Causal OR 6.92 for Instant Coffee & Dry AMD. No other associations. Strength: Causal inference, avoids confounding.	1

Section 3: The Chemical Profile of Instant Coffee: A Mechanistic Investigation

The genetic evidence, by isolating the risk to instant coffee, poses a critical question: What is in instant coffee, and not other preparations, that causes dry AMD? The answer lies in the byproducts of its industrial manufacturing.

3.1 The "Disease of Processing": How Instant Coffee is Made

Instant coffee is not simply ground coffee. Its production involves brewing a highly concentrated coffee extract, which is then dehydrated into a soluble powder or crystal.¹⁹ This dehydration is typically achieved through one of two methods:

1. Spray-drying: The concentrate is sprayed into a current of very hot gas (up to 347°F or 175°C).¹⁹
2. Freeze-drying: The concentrate is frozen and then dehydrated under a vacuum.

This intense heat and concentration, particularly in spray-drying, is a chemically aggressive process.³ It is known to generate "markedly elevated 'neo-formed' toxins" ³ and "high levels of Maillard reaction byproducts".¹ This is a distinct chemical transformation that simple brewing, which produces "relatively few" of these byproducts, does not.³Two of these byproducts, acrylamide and Advanced Glycation End Products (AGEs), are the primary suspects for the retinotoxicity identified in the MR study.

3.2 Suspect 1: The Acrylamide Hypothesis

Acrylamide is a "potential carcinogen" ¹⁹ and "neurotoxin" ²¹ formed during high-temperature cooking of starchy foods.

• Elevated Levels: Multiple sources confirm that instant coffee contains significantly higher concentrations of acrylamide than its brewed counterpart. Analyses show that instant coffee can contain twice, or 100% more, acrylamide than regular roasted coffee.²⁰ A 2013 study reported average levels of 358 mcg/kg in instant coffee, compared to 179 mcg/kg in fresh roasted coffee.²²
• Plausible Retinotoxic Mechanism: The mechanism of acrylamide toxicity provides a plausible pathway for dry AMD. Acrylamide is known to induce significant oxidative stress.²⁴ A 2018 study on zebrafish embryos, a common model for retinal research, found that acrylamide exposure:
• Significantly increased reactive oxygen species (ROS).²¹
• Decreased the expression of critical endogenous antioxidant genes (Sod1, Sod2, Catalase) and reduced the activity of their corresponding enzymes.²¹
• Led directly to the "loss of both rod and cone photoreceptor cells through Caspase-3-dependent apoptotis".²¹

Another study specifically identified acrylamide-induced "retinal lesions" and a significant decrease in glutathione, a primary antioxidant in the retina.²⁶

This mechanism—initiating oxidative stress, depleting the RPE's antioxidant defenses, and triggering photoreceptor apoptosis—is a near-perfect mimic of the known cellular-level pathogenesis of atrophic (dry) AMD. While most human epidemiological research on dietary acrylamide has focused on cancer (and has largely produced null findings ²⁷), the new MR study ¹ suggests the research priority may have been misguided. The primary risk of dietary acrylamide, at least from this source, may not be carcinogenic but specifically retinotoxic.²¹

3.3 Suspect 2: The Advanced Glycation End Products (AGEs) Hypothesis

An even more compelling suspect, specifically implicated by the Jia et al. study authors, is the class of compounds known as Advanced Glycation End Products (AGEs).¹

• Formation and Elevated Levels: AGEs are "Maillard reaction byproducts" ¹ formed non-enzymatically when sugars react with proteins or lipids during high-heat processing.³ The production process for instant coffee creates these in high concentrations.³ One specific AGE, N(ε)-carboxymethyl-lysine (CML), has been quantified in commercial instant coffee samples.³¹
• Established Role of AGEs in AMD Pathophysiology: This is the most critical link. The role of AGEs in driving AMD is not speculative; it is a well-established field of ophthalmic research.⁶
• Accumulation: AGEs, and CML specifically, have been localized via immunohistochemistry directly within the soft macular drusen and in the cytoplasm of RPE cells in aged eyes and those with AMD.⁵ Their accumulation is directly linked to AMD pathogenesis.⁵
• Mechanism of Damage (RAGE Pathway): This is the core biochemical mechanism. Extracellular AGEs (from sources like diet) bind to their specific receptor, the Receptor for Advanced Glycation End Products (RAGE), which is expressed on retinal cells.¹
• The Downstream Cascade: The binding of AGEs to RAGE is known to initiate the following pathogenic cascade:
1. Induces the production of Reactive Oxygen Species (ROS), "exacerbating oxidative stress and inflammatory responses".¹
2. Activates multiple pro-inflammatory signaling pathways, most notably nuclear factor-κB (NF-κB).¹
3. Promotes apoptosis (photoreceptor cell death) and angiogenesis.¹
4. Increases expression of adhesion molecules, promoting leukocyte adhesion to retinal endothelial cells and leading to the "disruption of the blood-retinal barrier".¹

The Jia et al. MR study ¹ effectively provides the missing piece of the puzzle. A large body of literature had already established that AGEs are a primary driver of dry AMD pathogenesis via the RAGE pathway.⁵ The MR study now causally links a major dietary source of these AGEs (instant coffee) to the very disease (dry AMD) that they are known to cause.

Table 3: Comparative Analysis of Key Chemical Constituents in Instant vs. Ground Coffee

Chemical Constituent	Ground (Brewed) Coffee	Instant Coffee	Significance for AMD Risk	Supporting Source(s)
Acrylamide	Baseline (e.g., ~179 mcg/kg)	Significantly Elevated(e.g., ~358 mcg/kg, 100-200% higher)	Plausible retinotoxin; causes oxidative stress & photoreceptor apoptosis in animal models.	[20, 21, 22, 23, 26]
Advanced Glycation End Products (AGEs)	"Relatively few"	Markedly Elevated("High levels of Maillard reaction byproducts")	Primary Suspect: Directly activates the RAGE pathway, driving the known inflammation & oxidative stress cascade of dry AMD.	[1, 3, 4, 5, 6, 18]
Free Chlorogenic Acids (CGAs)	High	Low / Degraded	Protective Antioxidant: Levels are reduced by high-heat processing and incorporation into melanoidins.	[19, 35, 36, 37, 38, 39]
Melanoidins	Present	High	Complex Maillard products; possess some in vitro antioxidant activity but also bind/sequester protective CGAs.	[37, 39, 40, 41, 42]

Section 4: The Antioxidant Paradox: Reconciling Conflicting Data

A key contradiction in the literature is the antioxidant status of instant coffee. While the MR study implies a net toxic effect, some chemical analyses report that instant coffee possesses a high antioxidant capacity. Resolving this paradox is essential to understanding the net biological effect.

4.1 The Protective Case: Chlorogenic Acid (CGA) and Retinal Health

First, it is established that key antioxidants in coffee, primarily Chlorogenic Acid (CGA), are retinoprotective. A Cornell University study identified CGA as a powerful antioxidant that may protect against retinal degeneration from sources like hypoxia and oxidative stress.³⁶ Mechanistic studies have further shown that CGA can protect retinal ganglion cells (RGCs) from oxidative damage ³⁵ and may even suppress laser-induced choroidal neovascularization, a model for wet AMD.³⁵

This existing evidence likely explains the ambiguous findings from the observational studies discussed in Section 1.2. Any slight protective signal detected in those studies was likely driven by high-CGA ground coffee and may be specific to wet AMD, which aligns perfectly with the anti-neovascularization mechanism of CGA.³⁵ This observation only strengthens the specificity of the instant coffee/dry AMD link.

4.2 The "Missing" Compound: CGA Degradation in Instant Coffee

The protective effect of CGA is absent in instant coffee because the manufacturing process either destroys it or renders it non-bioavailable. The intense heat of roasting and processing is known to degrade CGAs.¹¹

Critically, CGAs are also incorporated into the high-molecular-weight melanoidin structures formed during the Maillard reaction.³⁷ A 2014 study on dark-roasted instant coffees found that these incorporated CGAs are covalently linked to the melanoidin polymers. Upon in-vitro gastrointestinal digestion, these CGAs were not freed, leading the researchers to conclude they are not bioavailable.³⁷ This finding is supported by other analyses concluding that instant coffee has, on average, lower levels of chlorogenic acid and other key phenolic compounds than regular brewed coffee.¹⁹

4.3 Resolving the Paradox: Melanoidins and "Total Antioxidant Capacity"

This leads to the central paradox: some studies, such as one analyzing antioxidant capacity by Jeszka-Skowron et al. (2017), found that instant coffee brews had the highest Total Phenolic Content (TPC) and Relative Antioxidant Capacity Index (RACI).⁴⁰

The resolution to this paradox is that the chemical assays used in those studies are measuring the total antioxidant capacity of all compounds in the brew. The melanoidins—the large polymers created during processing, which are also Maillard byproducts—themselves possess antioxidant properties in vitro.⁴¹

Therefore, the manufacturing of instant coffee enacts a critical trade-off:

1. It destroys or sequesters the primary, bioavailable retinoprotective antioxidants (free CGAs).¹⁹
2. It creates a new, different class of "antioxidants" (melanoidins).⁴¹
3. Simultaneously, it also creates massive quantities of pro-inflammatory, pro-oxidant toxins (AGEs and acrylamide).¹

The central hypothesis of this report is that the "antioxidant" capacity of the melanoidins, while measurable in a test tube, is biologically insufficient to offset the potent, targeted, and receptor-mediated retinotoxic damage initiated by the co-generation of AGEs and acrylamide. The net effect of the instant coffee chemical profile, despite testing as "high antioxidant" in some assays, is powerfully pro-inflammatory and pro-oxidant within the sensitive microenvironment of the human retina.

Table 4: Summary of Plausible Pathophysiological Mechanisms

Compound (Altered in Instant Coffee)	Biological Target / Receptor	Pathophysiological Effect in Retina	Relevance to Dry AMD
Acrylamide(Elevated)	Glutathione (GSH), Caspase-3	Depletes endogenous antioxidants (GSH); induces high oxidative stress; triggers photoreceptor apoptosis (cell death).	Direct mechanism for RPE and photoreceptor degeneration (atrophy).
Advanced Glycation End Products (AGEs)(Elevated)	RAGE Receptor(on RPE cells)	RAGE activation $\rightarrow$ Triggers NF-κB; induces massive ROS production; promotes chronic inflammation, apoptosis; disrupts blood-retinal barrier.	The central, established pathway for drusen-associated inflammation and RPE degeneration.
Free Chlorogenic Acids (CGAs)(Diminished)	N/A (Absence of effect)	N/A	Loss of a known retinoprotective, anti-oxidant, and anti-neovascularization compound.

Section 5: Synthesis, Clinical Guidance, and Future Research Directives

5.1 A Unified Hypothesis of Instant Coffee-Mediated Retinopathy

The synthesis of the available evidence points to a clear and compelling conclusion. The 2025 Mendelian randomization study by Jia et al. has, for the first time, provided robust causal evidence identifying a potent and specific risk factor for dry AMD.¹ This finding resolves the long-standing ambiguity in observational literature by demonstrating that the risk is not from "coffee" but is a "disease of processing."

The industrial manufacturing of instant coffee creates a unique and uniquely toxic chemical profile defined by a "dual-hit" mechanism:

1. Addition of Toxins: The high-heat, high-pressure process generates significant concentrations of potent retinotoxins, primarily Advanced Glycation End Products (AGEs) and acrylamide.¹
2. Subtraction of Protectors: The same process degrades and sequesters the primary retinoprotective compounds in coffee, namely free chlorogenic acids (CGAs), rendering them non-bioavailable.¹⁹

These toxins then activate the precise, established pathogenic pathways (RAGE activation, oxidative stress, depletion of glutathione, photoreceptor apoptosis) that are the known cellular hallmarks of dry AMD.¹ This unified mechanism plausibly explains the massive 6.92-fold increased risk for dry AMD causally linked to instant coffee consumption.

5.2 Clinical Implications and Precision Nutrition Recommendations

These findings have immediate and significant clinical implications. The Jia et al. study provides, for the first time, genetically-based causal evidence to support targeted dietary recommendations for AMD prevention.¹

• Primary Recommendation: Clinicians, particularly ophthalmologists, optometrists, and general practitioners, should be advised to include coffee type as a standard part of patient history, especially when assessing lifestyle risks for ocular disease.
• Precision Prevention: For patients identified as being at high risk for AMD—such as those with a strong family history, individuals with known genetic risk factors (e.g., Complement Factor H (CFH) polymorphisms ³), or patients already exhibiting early macular changes (e.g., soft drusen)—clinicians should now specifically advise the reduction or avoidance of instant coffee.¹
• Patient Reassurance: This advice must be specific. The evidence does not support a recommendation against coffee consumption broadly. The MR analysis found no causal evidence of harm from ground coffee or decaffeinated coffee, which may be considered safe alternatives in this context.¹

5.3 Unanswered Questions and Future Research Directives

While the MR study provides powerful causal evidence, it is a single study. This new finding opens several critical avenues for future research.

1. Replication: The most immediate need is the independent replication of the MR analysis in different, large-scale populations to confirm the finding and the precise magnitude of the effect size.²
2. Mechanistic Confirmation: Animal models (e.g., murine models) fed instant coffee itself, rather than its isolated components, are necessary to observe the in-vivo development of atrophic retinal lesions and confirm the activation of the AGE-RAGE and oxidative stress pathways in the retina.¹
3. Chemical Isolation: Further analytical chemistry and toxicology studies are needed to isolate the most harmful component. While AGEs and acrylamide are the primary suspects, other "neo-formed toxins" or oxidized lipids may also contribute to the risk.¹ Identifying the specific agent could inform manufacturing process improvements.
4. Observational Re-evaluation: New, large-scale observational studies are warranted. Existing cohorts, such as the UK Biobank ⁴⁹, should be re-analyzed to specifically investigate the observational (non-genetic) link between instant coffee consumption and the incidence and progression of dry AMD. This signal was likely missed in the past due to a lack of stratification by both coffee type and AMD type.

 

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