Psychiatric disorders like depression and anxiety in age-related macular degeneration

Abstract

BACKGROUND

Age-related macular degeneration (AMD) is a major cause of central vision loss among older adults and is increasingly recognized as a condition with significant psychological consequences.

AIM

To synthesize current evidence on the prevalence, correlates, and management of depression and anxiety among individuals with AMD.

METHODS

A comprehensive literature search of PubMed, Scopus, and Web of Science (2000-2025) identified 33 relevant systematic reviews, observational studies, and interventional trials. Extracted data included study design, population characteristics, assessment tools, prevalence estimates, associated risk factors, and details of psychosocial or pharmacological interventions. Descriptive synthesis was performed because heterogeneity in study design and outcome measurement precluded meta-analysis. The synthesis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

RESULTS

Prevalence of depression in AMD ranges from 15.7% to 44%, with pooled estimates around 22%-25%, while anxiety affects 9.6%-30.1% of patients. Risk factors include severity of visual loss, type of AMD (wet or dry), female gender, and limited social support. These comorbidities exacerbate disability, impair quality of life, and reduce adherence to ophthalmologic treatment. Psychosocial interventions - particularly cognitive-behavioral therapy, self-management programs, and behavioral activation - are effective in reducing depression and improving coping. Pharmacologic options such as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors may also be beneficial, though evidence remains limited.

CONCLUSION

An integrated, multidisciplinary approach combining psychological, pharmacological, and rehabilitative strategies is recommended. Future research should focus on anxiety-specific interventions and long-term outcomes to optimize mental health and visual rehabilitation in AMD patients.

Key Words: Depression; Anxiety; Age-related macular degeneration; Quality of life; Cognitive behavioral therapy

Core Tip: Depression and anxiety are common but underrecognized in patients with age-related macular degeneration. Routine mental health screening, timely psychosocial interventions, and integration of psychiatric care within ophthalmology can improve overall patient outcomes and quality of life. This systematic review also synthesizes current evidence on the prevalence, correlates, and management of depression and anxiety among individuals with age-related macular degeneration.

INTRODUCTION

Age-related macular degeneration (AMD) is a leading cause of irreversible central vision loss in older adults worldwide[1]. It not only impairs visual function but also profoundly affects psychological well-being. The global burden of AMD-related vision impairment nearly doubled between 1990 and 2021, with corresponding increases in disability-adjusted life years[2]. Advanced AMD, encompassing neovascular AMD and geographic atrophy, leads to significant disability, dependence, and emotional distress. Studies report that AMD increases the risk of depression by approximately 15%, with up to 20% of patients exhibiting clinically relevant depressive symptoms[3-6]. Despite advances in ophthalmologic treatment, the mental health consequences of AMD remain underappreciated in clinical settings[7-10]. Major depressive symptoms are often compounded by factors such as high treatment costs, frequent hospital visits, reduced social participation, and dependence on caregivers[6,11,12].

Furthermore, variability in disease prognosis and treatment outcomes heightens psychological vulnerability, while anxiety can exacerbate perceived disability and promote functional decline[5,10,13]. Although literature increasingly recognizes the bidirectional relationship between visual impairment and mental health, psychological morbidity in AMD remains underdiagnosed and undertreated[5,9,10,14]. This review aims to consolidate existing evidence on the prevalence and impact of depression and anxiety in patients with advanced AMD, explore contributing risk factors, and evaluate current therapeutic strategies for addressing mental health needs in this vulnerable population.

MATERIALS AND METHODS

A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and Google Scholar between January 2000 and September 2025. Keywords included “age-related macular degeneration”, “depression”, “anxiety”, “mental health”, “psychological impact”, “retinal disorders”, “visual impairment”, and related thematic terms. Studies were included if they were published in English, involved adults aged ≥ 50 years, and evaluated depression or anxiety among patients diagnosed with AMD[4,9]. Thirty-three eligible publications were identified, comprising observational studies, randomized clinical trials, and systematic reviews (Figure 1). Case reports, commentaries, and studies lacking validated psychological assessment instruments were excluded[9].

Figure 1  Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) search methodology for the literature review.

Two reviewers independently screened titles and abstracts; disagreements were resolved in consultation with a third reviewer. Extracted data included study design, population characteristics, assessment tools, prevalence estimates, associated risk factors, and details of psychosocial or pharmacological interventions[4,10]. Quality appraisal was undertaken using standardized checklists appropriate to each design, such as the Newcastle-Ottawa Scale for observational studies[10]. Descriptive synthesis was performed because heterogeneity in study design and outcome measurement precluded meta-analysis. The synthesis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (Figure 1).

RESULTS

Prevalence

Depression and anxiety, diagnosed according to various validated psychological scoring and assessment systems, are significantly more prevalent in AMD populations than in age-matched controls (Table 1). Prevalence of depression in AMD ranges from 15.7% to 44%, with pooled estimates around 22%-25% (Table 2). Rates are generally higher in patients with wet AMD compared to those with dry AMD, reflecting the greater visual loss, functional dependency, and treatment burden associated[12,15,16]. Systematic reviews and meta-analyses confirm that depression rates in AMD significantly exceed those observed in the general older population[4,9,10,12]. In one review, depression prevalence reached 56% among those with wet AMD, 27% among those with dry AMD, and 20% among control groups[12]. The prevalence of anxiety in AMD is less consistent but remains noteworthy, ranging from 9.6% to 30.1%, with pooled estimates between 14% and 18% (Table 2). Although less frequently studied than depression, several studies suggest that anxiety often coexists with depressive symptoms, forming a combined psychological burden that exacerbates functional limitations and reduces social engagement[5,7,9,11,17,18].

Table 1 Diagnostic basis of anxiety and depression used in included studies.

Diagnostic basis
Hospital Anxiety and Depression Scale
Centre for Epidemiological Studies - Depression scale
Structured Clinical Interview for DSM-IV
Geriatric Depression Scale
Goldberg Anxiety and Depression Scale
International Classification of Diseases
Patient Health Questionnaire

DSM: Diagnostic and Statistical Manual of Mental Disorders.

Table 2 Prevalence rates of depression and anxiety in patients with age-related macular degeneration.

Condition	Prevalence range	Pooled estimate	Ref.
Depression	15.7%-44%	22%-25%	Tran et al[4], 2025; Cimarolli et al[5], 2015; Senra et al[6], 2019; Dawson et al[9], 2014; Olson et al[13], 2019; Fernández-Vigo et al[16], 2021; Lee et al[17], 2021; Casten and Rovner[19], 2008
Anxiety	9.6%-30.1%	14%-18%	Tran et al[4], 2025; Cimarolli et al[5], 2015; Senra et al[6], 2019; Olson et al[13], 2019; Fernández-Vigo et al[16], 2021; Lee et al[17], 2021; Dawson et al[19], 2014

Thus, psychological morbidity is a substantial yet under-recognized component of AMD, particularly in advanced stages where vision loss is most disabling[6,7,9-12]. These comorbidities increase disability, impair quality of life, and complicate disease management, emphasizing the importance of incorporating routine psychological screening and multidisciplinary care into AMD management[6,7,10,12].

Risk factors

The severity of vision loss is one of the most consistent predictors of depression in AMD[5,8,9,12,16]. Patients with advanced or bilateral disease often experience greater dependence for daily tasks, loss of autonomy, and diminished self-esteem, all of which contribute to depressive symptoms. Although anxiety is less directly associated with the degree of visual impairment, individuals with more severe vision loss often report heightened emotional distress and uncertainty regarding disease progression[5,8,11,12]. Several studies have demonstrated that wet AMD is linked to higher rates of depression than dry AMD, likely due to its more aggressive course and the need for ongoing intravitreal therapy[6,9,12,16]. Sociodemographic variables play an important role as well. Female gender and advanced age have been independently associated with a higher likelihood of depressive or anxiety disorders in AMD[17,18]. These associations may reflect gender differences in emotional coping strategies and the cumulative psychological burden of age-related decline.

Perceived social support is another key determinant. Evidence suggests that low social support increases the risk of depression and anxiety independently of visual acuity[14]. The loss of social roles and limited engagement in meaningful activities may amplify loneliness and helplessness. Functional disability and treatment burden - including frequent hospital visits, uncertainty about treatment outcomes, and the financial costs of anti-vascular endothelial growth factor (VEGF) injections - are additional contributors to psychological distress[6,7,10,12,19]. These factors often interact to create a cycle of dependence, isolation, and emotional exhaustion that worsens the overall quality of life in AMD.

Consequences

The coexistence of depression and anxiety in patients with AMD has far-reaching implications for quality of life, treatment outcomes, and overall disease management[6,7,9,10,12,15,16,18,19].

Quality of life: Depression and anxiety are strongly associated with reduced vision-related quality of life and heightened disability. Difficulty in performing routine activities such as reading, driving, and recognizing faces contributes to frustration, social withdrawal, and feelings of dependency. The psychological comorbidities increase the risk of falls, exacerbate functional impairment, and elevate the likelihood of institutionalization among older adults[9,10,15,16,18]. The compounding effect of emotional distress and sensory loss also magnifies the perception of visual handicap and limits participation in previously valued social and recreational activities[7,12,16,18]. Concomitant effects of alcohol consumption, dietary patterns, and other environmental factors, such as active or passive smoking and drug abuse, also affect the quality of life and exacerbate psychological duress as well as worsen retinal health; however, the effect of these factors coexisting with AMD has not been studied well.

Treatment adherence: Emotional disorders can negatively affect adherence to anti-VEGF regimens and satisfaction with ophthalmic care[6,9,12,16]. Depressed patients are less likely to comply with follow-up schedules, adhere to self-management programs, or pursue vision rehabilitation services[6,9,19]. Reduced motivation and hopelessness often contribute to premature treatment discontinuation and poorer visual outcomes.

Comorbidity: Depression and anxiety in AMD patients often coexist with other chronic conditions, including cardiovascular disease, diabetes, and cognitive impairment[7,9,10,17]. The presence of these psychiatric disorders further increases healthcare utilization, lengthens recovery times, and impairs coping capacity[9,10,17]. The heightened risk of falls may also be associated with concurrent systemic comorbidities like neurological and cardiovascular disease, as well as the use of medication, thereby developing a vicious circle of psychological duress and increased hospitalization, amplifying the pressure on healthcare systems to cater to patients with these unique needs. Ultimately, these consequences underscore that AMD is not merely an ophthalmic condition but a multidimensional health disorder affecting emotional, social, and functional domains[7,9-11,15,16,18]. Recognition and early management of psychological distress are thus integral to optimizing patient outcomes and improving quality of life.

Psychosocial interventions

Psychosocial interventions play a central role in mitigating the emotional and functional burden associated with AMD[6,9,10,19-22]. Structured approaches such as cognitive-behavioral therapy (CBT), behavioral activation, and group self-management programs have demonstrated substantial efficacy in alleviating depressive symptoms and, to a lesser extent, anxiety[10,19,21,22].

CBT: CBT-based interventions aim to modify maladaptive beliefs and encourage adaptive coping behaviors. Studies show that CBT reduces depressive symptoms by enhancing patients’ sense of control and self-efficacy despite vision loss[10,19,22]. A stepped-care model incorporating self-help, problem-solving, and guided behavioral activation significantly lowered the incidence of depression and improved adjustment to vision impairment[21,22].

Behavioral activation and self-management: Behavioral activation, which encourages participation in meaningful daily activities, has been effective when combined with low vision rehabilitation[21,22]. Randomized controlled trials demonstrate that group self-management programs can both treat and prevent depression in AMD patients[21,22]. These programs typically include educational sessions, peer interaction, and coping-skills training to improve autonomy and emotional well-being[19,21].

Emotion-focused and self-help approaches: Non-randomized studies suggest that emotion-focused self-help interventions, including problem-solving therapy, can reduce depressive symptoms and enhance self-acceptance[10,19]. These approaches are valuable for individuals unable to access structured psychotherapy due to visual or logistical constraints.

Mindfulness-based stress reduction: Mindfulness interventions incorporating meditation and relaxation techniques improve resilience and emotional regulation. Mindfulness-based stress reduction, initially developed by Kabat-Zinn, has demonstrated benefits in anxiety and depression across various chronic illnesses[23,24]. In AMD, mindfulness may help patients reframe their emotional responses to visual decline and reduce anxiety related to disease uncertainty[24].

Interdisciplinary integration: The most successful psychosocial interventions combine psychological counseling with vision rehabilitation and social support frameworks, offering holistic management of both visual and emotional impairment[6,10,19-22]. However, despite robust evidence for depression reduction, anxiety outcomes remain underexplored, underscoring the need for targeted studies addressing anxiety in AMD[9,10,19,20].

Pharmacological interventions

Pharmacological management can complement psychosocial and rehabilitative interventions[6,7,9,10,19,25-28]. Although evidence remains limited, antidepressant therapy - particularly with selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) - has demonstrated potential benefits for mood stabilization, neuroprotection, and visual outcomes[25,26]. However, the use of SSRIs and SNRIs in the elderly is always a challenge, especially with other chronic medications, which can lead to electrolyte abnormalities and drug-drug interactions. Thus, it is pertinent to discuss in detail the current status of pharmacological therapy for anxiety and depression in AMD.

Antidepressants: Several studies report that the use of SSRIs (e.g., escitalopram) or SNRIs may improve depressive symptoms in patients with AMD, likely through mechanisms involving decreased inflammation, oxidative stress reduction, and upregulation of neurotrophic factors[25-27]. In a randomized clinical trial, escitalopram significantly alleviated depressive symptoms and improved quality of life, with minimal adverse effects[26]. Similarly, a pilot study of sertraline demonstrated safety and possible efficacy in reducing depression in AMD[27]. However, certain antidepressants may also affect ocular physiology. One observational study found that antidepressant use among patients with neovascular AMD was associated with an increased need for anti-VEGF retreatment, potentially due to medication-related upregulation of vascular endothelial growth factor or to the underlying depression itself[28]. Furthermore, isolated case reports have described cystoid macular edema associated with escitalopram use, emphasizing the importance of ophthalmic monitoring in patients receiving antidepressants[29]. Recent epidemiological analyses suggest that antidepressant exposure may be associated with a lower risk of AMD onset or progression, though causality remains uncertain[25]. These findings raise the possibility that certain antidepressants might exert neuroprotective effects within the retina, potentially by modulating oxidative and inflammatory pathways[25].

Anxiolytics: The role of anxiolytic medication in AMD remains less well defined. Benzodiazepines may provide short-term relief from severe anxiety or sleep disturbance, but their use in older adults carries risks of sedation, imbalance, and cognitive impairment[30]. Given the age profile of AMD patients, benzodiazepines should be prescribed cautiously and only for short durations[30]. Taken together, pharmacotherapy may be beneficial for selected patients with clinically significant depression or anxiety, but treatment decisions should consider the potential ocular and systemic risks. Close collaboration between psychiatrists and ophthalmologists is recommended to ensure safe and effective management[6,7,9,26-30].

Vision rehabilitation

Vision rehabilitation represents a critical component of AMD management, aimed at improving functional independence and emotional well-being in patients coping with central vision loss[6,9,10,19-22,31-33]. Rehabilitation strategies include the use of optical and electronic low-vision aids, occupational therapy, environmental modification, and training in adaptive behaviors to enhance daily functioning and quality of life[19-22,31,32].

Low-vision aids and assistive technology: Optical devices such as magnifiers, telescopic lenses, and electronic reading systems significantly enhance patients’ ability to perform routine activities, leading to reductions in frustration and depressive symptoms[21,31,32]. Recent advances in digital accessibility tools - including voice-assisted technology, contrast-enhancement software, and smartphone applications - have improved autonomy in such cases[32,33].

Occupational therapy: This includes activity modification, task adaptation, and environmental safety, enabling individuals to maintain independence despite central vision loss[21,31]. Incorporating psychosocial support into rehabilitation further strengthens outcomes by addressing emotional distress and enhancing motivation for therapy adherence[10,19,22,31].

Behavioral activation: Behavioral activation has shown measurable benefits for depression. Randomized controlled trials demonstrated that combined behavioral activation and low-vision rehabilitation can halve the incidence of depression compared with supportive therapy alone[21,22,31]. These effects are mediated through improved activity engagement, mastery experiences, and social re-engagement[19,21,22].

Holistic outcomes: Vision rehabilitation also improves psychological resilience and life satisfaction[6,9,10,19,31-33]. This evidence supports the inclusion of psychological assessment and therapy as integral elements within low-vision rehabilitation services, ideally delivered through a multidisciplinary team involving ophthalmologists, psychologists, and occupational therapists[6,9,10,19,21,22,31-33].

Social and community support

Social and community support systems are fundamental to maintaining psychological resilience and functional independence in patients with AMD[6,9,10,12,14,18,19,31,34]. Social support mitigates loneliness, enhances coping capacity, and provides emotional stability, thereby reducing both depression and anxiety[12,14,18,19].

Peer and support groups: Peer-support groups foster a sense of belonging and mutual understanding, significantly decreasing perceived isolation and helplessness[9,12,14,18]. Group interventions also improve coping strategies by facilitating the exchange of adaptive experiences and problem-solving methods among participants[19,31]. Regular peer interaction helps in coping with vision loss and reinforces adherence to rehabilitation plans[9,10,12,31].

Family and caregiver involvement: Family support is a critical protective factor against depression and anxiety[14,18,19,34]. Educating caregivers about the nature and psychological impact of AMD improves empathy, communication, and emotional support within the household[14,19,34]. In turn, this enhances treatment adherence and patient well-being. However, caregivers themselves frequently experience burden, fatigue, and psychological distress, especially when the patient’s dependency is high or disease progression is unpredictable[14,34].

Community and social services: Community-based vision rehabilitation programs and volunteer-driven initiatives offer opportunities for social reintegration, reducing isolation and dependence[9,19,31,34]. Partnerships between ophthalmic clinics, mental health professionals, and social welfare organizations create a continuum of care, addressing both visual impairment and its emotional sequelae[6,9,10,19,31,34]. However, the incorporation of structured peer and community interventions into standard ophthalmologic care remains limited. Addressing this gap could substantially improve both psychological outcomes and treatment adherence in AMD populations[9,10,14,18,19,31,34].

Lifestyle and wellness interventions

Lifestyle modifications play an important adjunctive role[6,9,10,19,32,35]. Physical activity, nutrition, and overall wellness behaviors influence both visual and psychological outcomes[32,35].

Physical activity: Regular physical exercise has been associated with lower levels of depression and anxiety in older adults and may also slow AMD progression through improved vascular and metabolic health[9,10,32,35]. Studies indicate that moderate-intensity aerobic exercise enhances cerebral and retinal perfusion, improves mood-regulating neurotransmission, and supports functional independence[32,35]. Tailored exercise programs adapted to vision-impaired individuals can improve mobility, confidence, and social interaction while reducing fear of falls[9,19,32].

Nutrition: Nutritional interventions with antioxidant-rich foods - such as fruits, leafy greens, and omega-3 fatty acids - contribute to both ocular and psychological health[6,9,19,32,35]. Dietary supplementation with lutein, zeaxanthin, and vitamins C and E has been linked with a reduced risk of AMD progression and may indirectly enhance mood by improving overall health perception[35]. Adequate vitamin D intake has also been associated with lower depressive symptom severity in older adults, although this relationship has not been specifically validated in AMD populations[32,35].

Sleep and stress management: Good sleep hygiene and stress reduction techniques, such as meditation, breathing exercises, and mindfulness-based practices, may further alleviate anxiety and emotional fatigue, improving coping and reducing perceived stress in visually impaired populations[9,24,32,35].

Integrated wellness approaches: A comprehensive wellness model combining physical activity, balanced nutrition, stress management, and social engagement provides the best outcomes for mental and visual health[6,9,10,19,24,32,35]. Lifestyle optimization promotes psychological well-being and complements the effects of medical and psychosocial interventions, leading to improved overall functioning and quality of life.

DISCUSSION

The available literature consistently indicates that depression and anxiety are highly prevalent yet underrecognized comorbidities among patients with AMD[4-7,9-12,14-16,18,19]. Prevalence estimates for depression range between 15% and 44%, and anxiety occurs in approximately 10%-30% of patients[4,9-12,16,18]. These rates exceed those in the general elderly population, suggesting that the psychological burden of AMD is comparable to that of other chronic disabling conditions such as stroke or Parkinson’s disease[6,9,12,15,17].

Determinants of psychological distress

Emotional morbidity in AMD is multifactorial. Severity of vision loss, functional dependence, female gender, and limited social support are independent predictors of depression and anxiety[5,6,9,12,14,16-18]. Need for recurrent visits, intravitreal therapy, uncertainty about prognosis, and the financial burden of long-term care further exacerbate distress[6,7,10,12,19]. These stressors often lead to maladaptive coping behaviors and social withdrawal, reinforcing the cycle of depression and anxiety[9,14,18,19].

Clinical implications

Psychological distress significantly affects treatment adherence, visual rehabilitation outcomes, and quality of life[6,9,10,12,16,18,19]. Depression is associated with poorer compliance to anti-VEGF therapy, reduced motivation for self-care, and lower engagement in vision rehabilitation[6,9,16,19]. Conversely, psychological interventions - particularly CBT, behavioral activation, and structured self-management programs - demonstrate substantial benefits in reducing depressive symptoms and improving adjustment to vision loss[10,19-22,31]. However, anxiety-focused interventions remain underrepresented in current research[9,10,19,20].

Pharmacologic considerations

Although antidepressants such as SSRIs and SNRIs may offer benefits, their use requires caution due to age-related risks and possible systemic and ocular side effects in the elderly[26-30]. Evidence supporting pharmacotherapy is encouraging but limited, emphasizing the need for integrated psychiatric-systemic-ophthalmologic monitoring[6,9,10,19,26-30].

Rehabilitation and psychosocial care

Vision rehabilitation, including low-vision aids, occupational therapy, and digital assistive technologies, has proven effective in improving autonomy and reducing psychological distress[19,21,22,31-33]. Incorporating psychosocial components such as group support and behavioral activation into these programs doubles their effectiveness in mitigating depression[21,22,31]. Likewise, community engagement, family education, and caregiver support play pivotal roles in maintaining mental health and social functioning[9,10,12,14,18,19,31,35-39].

Lifestyle and preventive strategies

Regular physical activity, a nutrient-rich diet, and mindfulness-based stress reduction appear to buffer against depression and anxiety while complementing medical and rehabilitative treatments[9,19,24,32,35,38,39].

Future directions

Future research should focus on anxiety-specific interventions, longitudinal outcomes, and cost-effectiveness analyses of integrated care models[9,10,19,20,24,31]. Large-scale, multicenter studies are warranted to establish evidence-based protocols that combine ophthalmologic, psychiatric, and rehabilitative management. Incorporating validated mental health screening tools into routine ophthalmic assessments could also improve early detection and treatment of depression and anxiety[6,9,10,12,19].

Routine screening for depression and anxiety using validated tools should become standard practice in ophthalmologic clinics[6,9,10,12,19]. Early detection and prompt intervention can prevent deterioration in both mental health and visual functioning, ultimately improving long-term outcomes. By viewing AMD as both a visual and psychological disorder, clinicians can offer more holistic, patient-centered care that enhances recovery, preserves independence, and restores quality of life[9,10,12,19,31,35-39].

CONCLUSION

Depression and anxiety are common, clinically significant, and often underrecognized comorbidities among patients with AMD[4-7,9-12,14-16,18,19]. These disorders profoundly affect quality of life, treatment adherence, and visual rehabilitation outcomes[6,7,9,10,12,39]. An integrated, multidisciplinary approach - involving ophthalmologists, psychiatrists, psychologists, rehabilitation specialists, and social workers - is essential to address the complex interplay between vision loss and mental health[6,9,10,12,19,21,22,31-34]. CBT, behavioral activation, and structured self-management programs in reducing depression and improving coping[10,19-22,31]. Complementary strategies, including lifestyle optimization, community engagement, and family support, further enhance resilience and emotional well-being[9,14,18,19,24,32,35-39].

ACKNOWLEDGEMENTS

My teachers, family, and friends.