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Abstract
To assess the prevalence and potential risk factors for late age-related macular degeneration (AMD) in three racially similar populations from North America, Europe, and AUSTRALIA:
Combined analysis of population-based eye disease prevalence data.
There were 14,752 participants with gradable photographs from the Beaver Dam Eye Study (n = 4756), Rotterdam Study (n = 6411), and Blue Mountains Eye Study (n = 3585).
AMD diagnosis was made from masked grading of stereo macular photographs. Final classification of AMD cases was agreed by consensus between study investigators.
AMD prevalence was strongly age related. Overall, AMD was present in 0.2% of the combined population aged 55 to 64 years, rising to 13% of the population older than 85 years. Prevalence of neovascular AMD (NV) increased from 0.17% among subjects aged 55 to 64 years to 5.8% for those older than 85 years. Prevalence of pure geographic atrophy (GA) increased from 0.04% to 4.2% for these age groups. There were no significant gender differences in the prevalence of NV or GA. Subjects in the Rotterdam population had a significantly lower age-adjusted and smoking-adjusted risk of NV than subjects in the Beaver Dam and Blue Mountains populations. Apart from age, tobacco smoking was the only risk factor consistently associated with any form of AMD in all sites separately and in pooled analyses over the three sites.
These combined data from racially similar communities across three continents provide strong and consistent evidence that tobacco smoking is the principal known preventable exposure associated with any form of AMD.
... При ВМД к факторам риска, наряду с возрастом, наследственностью, курением, артериальной гипертензией, сахарным диабетом, атеросклеротическим поражением сонных артерий, относят ожирение. Связь ожирения с повышением вероятности развития ранней или поздней ВМД отражена в различных популяционных исследованиях: Blue Mountains Eye Study [3][4][5][6], Rotterdam Eye study [7,8], POLA [9,10], Los Angeles Latinos Eye Study [11], Reykjavik Eye Study [12,13], Beijing eye study [14], Copenhagen City Eye Study [15,16], Andhra Pradesh Eye Disease Study [17], Hisayama [18,19] и др. [20,21]. ...
... Были определены положительные связи между высоким ИМТ и развитием ранней ВМД [37,39,40] или даже конкретной формой ВМД -географической атрофией и в других исследованиях [34,37,38]. Однако объединенные анализы 3 крупных популяционных продольных исследований опровергли связь между ИМТ и ВМД [3,6]. ...
... Таким образом, повышенный ИМТ фигурировал в тандеме с повышенной вероятностью развития ВМД практически в половине исследований [3,6,12,29,[36][37][38][39][40]. По сравнению с лицами с нормальным весом (ИМТ 20-25) у лиц с ожирением (ИМТ > 30) повышен также риск развития поздней ВМД (ОШ 1,2-2,2) [15,22]. ...
Purpose : evaluation of obesity as a risk factor for poor outcome (ineffectiveness) of antiangiogenic treatment of patients with neovascular AMD.
Patients and methods . Body mass index (BMI) was studied in 84 patients (92 eyes) with neovascular AMD who were treated with intravitreal injections of Eilea in a fixed mode.
Results . It was found that a poor treatment outcome in the subgroup with disease progression was associated with obesity of 1–2 degrees; the average BMI in this subgroup (with a deterioration in the morphostructural parameters of the retina) significantly exceeds the indicators of ideal respondents, for comparison: 31.5 ± 0.8 versus 28.6 ± 1.1 (p = 0.04); and the incidence of obese individuals is dominant: 72 %. At the same time, a moderate inverse reliable relationship of BMI with another risk factor — systolic blood pressure (SBP) was found. In this regard, we suggested that obesity indirectly affects the outcome of treatment, since it is “tied” to systolic blood pressure (p = 0.01). An argument in favor of this assumption is a higher correlation coefficient of SAD with the outcome of treatment. The authors hypothesized that obesity contributes to the development of hypertension by increasing the risk of poor outcome of nAMD treatment. The hypothesis explained the association of obesity with the progression of morphostructural changes in the retina in the group of non-responsents with nAMD.
Conclusion . Studies have demonstrated a causal relationship between obesity and the outcome of antiangiogenic treatment of patients with nAMD. The data obtained allow us to attribute OBESITY to moderate risk factors for a poor outcome of antiangiogenic treatment of patients with nAMD. Taking into account the fact that OBESITY is a modifiable factor that can be eliminated with certain efforts, opportunities are revealed to reduce the risk of an unfavorable outcome of treatment of patients with nAMD.
... Smith et al in their study of 14,752 patients by pooling ndings from three continents found no signicant gender difference in the prevalence of neovascular ARMD or geographic 11 atrophy . Owen et al in their study concluded that percentage 12 prevalence of ARMD were similar in males and females . ...
... Munoz et al in their study of population-based sample of Hispanic individuals aged 50 years and older observed that pigmentary abnormalities were 14 more likely to occur in men than women . 11,12 The present study correlates with the previous studies . Also ,prevalence of Intermediate and Exudative ARMD in males (21%) was more than females (15%). ...
The present study was aimed to study the gender and risk of age related macular degeneration. Agerelated macular degeneration(AMD) is one of the main socioeconomical health issues worldwide. This is prospective study include all patients of age related macular degeneration above 50 years of age presenting in the Department of Ophthalmology at Dr.RPGMC Tanda. Total 86 patients were examined. There were 41(47.67%) males patients while 45(52.33%) patients were females. Finding indicated that gender distribution of ARMD patients was almost equal. However, exudative ARMD was seen more in males.
... Age is by far the biggest risk factor. 1 Compared to those from other ethnic origins, Caucasians are more likely to be affected. 2 Family history and several genetic markers, specifically the complement factor H (CFH) gene, have been found to be important risk factors for AMD. 3 This report describes a patient who was diagnosed with dry AMD and had unilateral geographic atrophy. ...
... Since non-exudative AMD makes up to 90% of cases of AMD, there is currently no treatment at this time. 1,3 The ophthalmologist can assist these patients by providing visual rehabilitation, identifying treatable exudative manifestations, and lowering the risk of disease progression. There are clinical trials underway. ...
An advanced form of age-related macular degeneration (AMD) known as geographic atrophy (GA) is typified by atrophic lesions that begin in the outer retina and gradually enlarge, ultimately resulting in irreversible visual loss. We present the case of a 55-year-old male healthy patient who had dry AMD in one eye and unilateral geographic atrophy in the other eye. Clinical examination, optical coherence tomography (OCT), and OCT angiography were used to confirm the diagnosis. Growing older and family history are the two main risk factors for GA. Geographic atrophy can be prevented by managing modifiable risk factors such as smoking, controlling systemic disorders, and maintaining a balanced diet.
... Retinal degenerative diseases, such as Retinitis Pigmentosa and Age-related Macular Degeneration (AMD) are among the leading causes of incurable blindness today [1]. They result in a progressive loss of photoreceptors, but the inner retinal neurons largely survive, preserving many aspects of natural retinal signal processing [2][3][4][5][6]. ...
Objective. Clinical trials of the photovoltaic subretinal prosthesis PRIMA demonstrated feasibility of prosthetic central vision with resolution matching its 100 μm pixel size. To improve prosthetic acuity further, pixel size should be decreased. However, there are multiple challenges, one of which is related to accommodating a compact shunt resistor within each pixel that discharges the electrodes between stimulation pulses and helps increase the contrast of the electric field pattern. Unfortunately, standard materials used in integrated circuit resistors do not match the resistivity required for small photovoltaic pixels. Therefore, we used a novel material – doped amorphous silicon (a-Si) and integrated it into photovoltaic arrays with pixel sizes down to 20 μm.
Approach. To fit within a few μm2 area of the pixels and provide resistance in the MΩ range, the material should have sheet resistance of a few hundred kΩ/sq, which translates to resistivity of a few Ω*cm. The a-Si layer was deposited by low-pressure chemical vapor deposition (LPCVD) and its resistivity was adjusted by PH3 doping before encapsulating the resistors between SiO2 and SiC for stability in-vivo.
Main Results. High-resolution retinal implants with integrated shunt resistors were fabricated with values ranging from 0.75 to 4 MΩ on top of the photovoltaic pixels of 55, 40, 30 and 20 μm in size. Photoresponsivity with all pixel sizes was approximately 0.53 A/W, as high as in the arrays with no shunt resistor. The shunts shortened electrodes discharge time, with the average electric potential in electrolyte decreasing by only 21–31% when repetition rate increased from 2 to 30 Hz, as opposed to a 54–55% decrease without a shunt. Similarly, contrast of a Landolt C pattern increased from 16–22% with no shunt to 22–34% with a shunt. Further improvement in contrast is expected with pillar electrodes and local returns within each pixel.
Significance. Miniature shunt resistors in a MOhm range can be fabricated from doped a-Si in a process compatible with manufacturing of photovoltaic arrays. The shunt resistors improved current injection and spatial contrast at video frame rates, without compromising the photoresponsivity. These advances are critical for scaling pixel sizes below 100 μm to improve visual acuity of prosthetic vision.
... Retinal degenerative diseases resulting in the progressive loss of photoreceptors, such as Retinitis Pigmentosa, Stargardt Disease and Age-related Macular Degeneration (AMD), are among the leading causes of incurable blindness today [1]. While photoreceptors are lost in retinal degeneration, the inner retinal neurons survive to a large extent [2][3][4]. ...
... Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss in older adults in the developed world [1]. The prevalence of AMD is expected to rise with the increasing aging population worldwide [1][2][3], affecting up to 288 million adults in 2040 [1]. The neovascular form of AMD (nAMD) accounts for approximately 10-20% of the total cases of AMD and is responsible for nearly 90% of severe vision loss (20/200 or worse) from AMD [4]. ...
Purpose
To predict potential treatment need during treat-and-extend (T&E) anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (nAMD) using an artificial intelligence (AI) model trained using transfer learning.
Methods
ARIES and ALTAIR were randomized controlled Phase 3b/4 trials assessing intravitreal aflibercept (IVT-AFL) in patients with nAMD. Following treatment initiation with three monthly injections of IVT-AFL, treatment intervals were re-assessed continuously during the study based on prespecified criteria. In this post- hoc analysis, spectral domain optical coherence tomography (SD-OCT) scans from Week (Wk) 8 and Wk 16 visits from patients treated with T&E regimens of 2 mg IVT-AFL over 2 years were utilized to predict individual treatment intervals and frequency. Automated image segmentation of the SD-OCT scans was performed, predictive models of treatment intervals and frequency were developed using machine learning or logistic regression methods, and their performance was evaluated using a fivefold cross-validation. A transfer learning technique was used to adapt existing AI models previously trained on a pro-re-nata therapy regimen to the T&E dataset.
Results
In total, 205 ARIES and 112 ALTAIR patient datasets were used for training and evaluation. The following results were achieved with an AI model trained using transfer learning (for ARIES) and logistic regression (for ALTAIR). For prediction of the first treatment interval (short [< 12 weeks] or long [≥ 12 weeks]) following treatment initiation, at Visit 4 (Wk 16), the AI model achieved an area under the receiver operating characteristic curve (AUC) of 0.87 and 0.78 for ARIES and ALTAIR, respectively. For assessment of the individual frequency of IVT-AFL in the first and second study years, the model achieved an AUC of 0.84 and 0.79, respectively, for ARIES, and 0.79 and 0.78, respectively, for ALTAIR. For prediction of the last intended individual treatment interval at the end of Year 2, the AI model achieved an AUC of 0.74 and 0.77 for ARIES and ALTAIR, respectively.
Conclusion
AI trained using transfer learning can be used to predict potential treatment needs for anti-VEGF treatment in nAMD based on SD-OCT scans at Wk 8 and Wk 16, supporting medical decisions on interval adjustments and optimizing individualized IVT-AFL treatment regimens.
... A recent Finnish study of approximately 410,000 inhabitants demonstrated a constant 1.2-and 2.4-fold increase in the incidence of nAMD in the elderly population aged 75-84 and 85-96 years during the last 15 years, with a 3% prevalence of nAMD in 2020 [18]. The onset of nAMD is often rapid, and agerelated, with most patients being > 60 years of age and the incidence increasing rapidly thereafter [19]. Several studies have investigated the impact of nAMD on QoL [9,10,[20][21][22][23][24][25]. ...
Retinal diseases, such as neovascular age-related macular degeneration, diabetic retinopathy, and retinal vein occlusion, pose a significant global burden on individuals, families, and healthcare systems. Intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy has become the standard treatment for retinal diseases, improving clinical outcomes, while delaying disease progression. Although effective, biologics are associated with high costs, which can lead to underutilisation and, consequently, suboptimal patient treatment outcomes, further contributing to healthcare costs. Additionally, the expansion in the elderly population is predicted to significantly increase costs and burden on healthcare systems due to retinal diseases, requiring effective strategies and the utilisation of emerging technologies that are crucial public health priorities for tackling global vision impairment. Recently, anti-VEGF biosimilars have been approved and are expected to provide a cost-effective alternative, while providing equivalent efficacy and comparable safety, immunogenicity, and pharmacokinetic profiles as the reference product. The entry of biosimilars holds the promise of meeting some of these unmet needs, giving physicians and patients access to sustainable treatments that can provide cost-effective therapy, enabling savings to be reinvested into healthcare facilities. This article aims to review the impact of retinal diseases on clinical, social, and financial aspects of patient care, emphasising the potential value of biosimilars in ophthalmology.
... The pathology of AMD is a result of the interaction between metabolic, functional, genetic, and environmental factors, such as oxidative damage from light exposure and oxidative stress [1]. AMD is a major source of vision loss worldwide, accounting for vision loss in 10% of people older than 65 years and 25% of people older than 75 years [2]. In the UK alone, AMD cases were estimated to be 608,213 in 2010 and were expected to rise to 755,867 in 2020 [3]. ...
Background
Age-related macular degeneration (AMD) is a major cause of vision loss worldwide. This study aimed to assess risk factors for wet AMD by two methods: assessing risk factors measured in the Scottish Heart Health Extended Cohort (SHHEC), and to systematically review the literature.
Methods
Eighteen thousand one hundred seven volunteers were recruited to SHHEC between 1984–1995, with risk factor data collected on recruitment. Hospital records were linked to study data up to 2017 and survival analysis was used to analyse risk factors and wet AMD. Literature published between 2000–2023 was searched for studies assessing risk factors for wet AMD, resulting in 5,503 papers. Following review, 7 studies were included in the systematic review.
Results
Within the SHHEC data, 231 cases of wet AMD were reported. Increasing age (Hazard Ratio (HR) 10.51; 99% Confidence Interval (CI) 4.78–23.11) and smoking (HR 1.67; 99% CI 1.17–2.38) were significantly associated with an increased risk of wet AMD. Increased dietary intake of vitamin K (HR 0.56; 99% CI 0.34–0.94) was associated with a decreased risk of wet AMD.
According to a systematic review, smoking, high Body mass index, heavy alcohol intake, increased systolic blood pressure, increased pulse pressure, and high levels of C-reactive protein and serum triglycerides in the blood may be associated with an increased risk of wet AMD. However, the studies provide mixed evidence and no conclusive results.
Conclusion
We have demonstrated that increasing age and smoking are high-risk factors for the development of wet AMD, while vitamin K is associated with a reduced risk of wet AMD.
... AMD is considered to be caused by genetic and external factors [6]. Researchers have revealed many risk factors for AMD such as older age [7], tobacco smoking [8], diet [9], dyslipidemia [10], and cardiovascular diseases [11]. Currently, the effects of environmental pollutants exposure on AMD have become a research hotpot [12,13]. ...
Background
This study aims to investigate the connection between serum lipids, per- and polyfluoroalkyl substances (PFAS), and age-related macular degeneration (AMD) risk and assess whether serum lipids mediate the association between PFAS and AMD.
Methods
1605 participants were enrolled from NHANES 2005–2008. Four serum PFAS levels with high detective rates, including perfluorononanoic acid (PFNA), perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexane sulfonic acid (PFHxS) were examined. Restricted cubic spline analysis (RCS) and weighted quantile sum (WQS) analysis were employed to detect nonlinear and mixed exposure effects.
Results
PFOS level was associated with any AMD (OR, 1.54; 95% CI, 1.12 to 2.11; P = 0.011), early AMD (OR, 1.43; 95% CI, 1.06 to 1.95; P = 0.024), and late AMD (OR, 3.35; 95% CI, 1.55 to 7.23; P = 0.004) risk. PFHxS (OR, 1.72; 95% CI, 1.01 to 2.93; P = 0.045) and PFOA (OR, 2.10; 95% CI, 1.21 to 3.63; P = 0.011) levels were associated with late AMD risk. The RCS showed a nonlinear connection between PFOS exposure and AMD risk (P nonlinear = 0.006). WQS analysis indicated a positive relationship between mixed PFAS exposure and AMD risk (OR, 1.34; 95% CI, 1.03 to 1.75; P = 0.030). Serum total cholesterol (TC) and high-density lipoprotein (HDL) cholesterol were associated with AMD risk (ORTC, 1.005; 95% CI, 1.001 to 1.009; P = 0.026. ORHDL, 1.028; 95% CI, 1.014 to 1.042; P<0.001), and mediated the relationship of PFOS exposure and AMD risk, with mediation proportions of 5.73% (P = 0.020) and 7.27% (P = 0.032), respectively.
Conclusions
PFOS exposure was connected with AMD risk and serum TC and HDL mediated this relationship.
... exposición a la luz solar, consumo de alcohol y cerveza, ausencia de consumo de vino tinto (se ha observado el papel protector de un consumo moderado del mismo, relacionado con la presencia de un antioxidante), régimen pobre en oligoelementos o en vitaminas, obesidad (hasta el doble de mayor riesgo en personas con un IMC>30), tabaquismo (Smith W., 2001) (llega a duplicar el riesgo), cirugía de la catarata (existe una mayor progresión en paciente pseudofáquicos en comparación con los pacientes con cristalino intacto), postmenopausia y bajo nivel de estrógenos (incrementan el riesgo). ...
Resumen del proyecto
Objetivo: Evaluar la relación entre la agudeza visual (AV) y la calidad de vida en pacientes con degeneración macular asociada a la edad (DMAE) mediante el cuestionario Low Vision Quality of Life (LVQOL).
Resultados principales:
Existe una correlación significativa entre la AV de lejos y de cerca con algunos aspectos del cuestionario, como la visión de lejos, la movilidad, la lectura y los trabajos minuciosos.
No se encontró correlación entre la AV y el grado de adaptación a la patología, aunque sí con el tiempo desde el diagnóstico.
Introducción
La DMAE afecta gravemente la calidad de vida de los pacientes debido a la pérdida de visión central, dificultando actividades como la lectura y el reconocimiento de rostros.
El cuestionario LVQOL es una herramienta clave para medir la calidad de vida en personas con baja visión.
Metodología
Participantes: 20 pacientes con DMAE y 20 controles sanos.
Evaluación: Se midió la AV de lejos y de cerca, y se aplicó el cuestionario LVQOL.
Análisis: Se utilizó el software SPSS para analizar los datos, empleando pruebas estadísticas como Kolmogorov-Smirnov y Wilcoxon.
Resultados
Los pacientes con DMAE presentaron una calidad de vida significativamente más baja que el grupo control.
La AV del mejor ojo mostró una relación directa con la calidad de vida global y con subescalas específicas del cuestionario.
Los pacientes diagnosticados desde hace más tiempo mostraron una mejor adaptación psicológica y mayores puntuaciones en calidad de vida.
Conclusiones
El cuestionario LVQOL es fiable y útil para evaluar la calidad de vida en pacientes con DMAE.
Es importante implementar este tipo de evaluaciones en la práctica clínica para monitorizar la mejora tras la rehabilitación visual.
... The etiology of AMD, intricate in nature, involves environmental and genetic factors influencing susceptibility (1). While aging remains the chief risk factor for AMD, other contributors encompass family history, race, smoking, hypertension, and cataracts (5)(6)(7). Over the past two decades, mounting evidence has indicated a pivotal role for immune mechanisms in the pathobiology of AMD. ...
Objective
This study systematically investigates the causal relationships between 731 immune cell phenotypes and age-related macular degeneration (AMD) using comprehensive Mendelian randomization (MR) analyses. The goal is to identify immune cell factors that contribute to or protect against AMD, thereby clarifying the immunological mechanisms underlying AMD pathophysiology and informing prevention and treatment strategies.
Methods
Univariable, bidirectional, and multivariable MR analyses were conducted to evaluate the associations between immune cells and AMD. By utilizing publicly available GWAS datasets, we eliminated the need for individual consents. The large-scale MR approach adhered to STROBE-MR guidelines. Immune cell GWAS data were sourced from a study involving 3,757 Sardinians, encompassing a broad spectrum of immune phenotypes, while AMD summary statistics were derived from a GWAS with over 3,763 cases. Instrumental variables (IVs) were carefully selected to comply with MR assumptions, and multiple MR methods were employed to enhance the robustness of causal inferences. Additionally, we supplemented the data for dry AMD (2,469 cases and 206,221 controls) and wet AMD (2,114 cases and 206,601 controls) for validation purposes.
Results
Univariable MR analysis identified 17 immune cell phenotypes significantly associated with AMD, including 11 potential risk factors and 6 potential protective factors. Bidirectional MR analysis found no significant effects of AMD on the examined immune cell subsets. Multivariable MR analysis indicated that TD CD4+ %T cells and CD39+ CD8br %T cells likely inhibit AMD development, whereas CD39+ CD8br %CD8br cells and CD45RA on resting Treg cells appear to increase AMD risk. Validation of immune cell subsets in dry and wet AMD revealed significant associations between specific immune cells and both forms of AMD, with some subsets uniquely linked to wet AMD and others to dry AMD.
Conclusion
This study addresses a critical gap in understanding the causal relationship between immune cells and AMD, identifying immune cell subsets that may either mitigate or exacerbate AMD risk. Notably, it highlights the potential role of CD39+ CD8+ T cells as anti-inflammatory agents and potential targets for immunotherapy in AMD. The absence of bidirectional causality suggests a complex origin of immune dysregulation in AMD. The differential associations of immune cell subsets with AMD subtypes carry significant implications for precision medicine approaches in ophthalmology, laying a solid foundation for future research focused on understanding the immunological underpinnings of AMD and developing targeted therapeutic strategies.
... [8][9][10] However, epidemiologic data do not consistently support the association between serum and plasma lipid levels and AMD, indicating the hallmark change of extracellular lipid deposition on both apical and basolateral sides of the RPE in AMD patients may result from a local effect instead of systemic dyslipidemia. [11][12][13][14] The metabolic reprogramming and the resulting imbalance among the production, usage, and transport of lipids in local tissues, especially within the RPE, has emerged as a pivotal driving force of AMD pathogenesis. 15,16 The RPE normally takes up a large amount of lipids through phagocytosis of the photoreceptor outer segment (POS) and utilizes lipids as its major energy source through mitochondrial fatty acid oxidation (FAO) and, thus, spares glucose for photoreceptor cells. ...
Dysregulated lipid metabolism, characterized by the accumulation of lipid deposits on Bruch's membrane and in drusen, is considered a key pathogenic event in age‐related macular degeneration (AMD). The imbalance of lipid production, usage, and transport in local tissues, particularly in the retinal pigment epithelium (RPE), is increasingly recognized as crucial in AMD development. However, the molecular mechanisms governing lipid metabolism in the RPE remain elusive. LIPIN1, a multifunctional protein acting as both a modulator of transcription factors and a phosphatidate phosphatase (PAP1), is known to play important regulatory roles in lipid metabolism and related biological functions, such as inflammatory responses. While deficits in LIPIN1 have been linked to multiple diseases, its specific roles in the retina and RPE remain unclear. In this study, we investigated LIPIN1 in RPE integrity and function using a tissue‐specific knockout animal model. The clinical and histological examinations revealed age‐dependent degeneration in the RPE and the retina, along with impaired lipid metabolism. Bulk RNA sequencing indicated a disturbance in lipid metabolic pathways. Moreover, these animals exhibited inflammatory markers reminiscent of human AMD features, including deposition of IgG and C3d on Bruch's membrane. Collectively, our findings indicate that LIPIN1 is a critical component of the complex regulatory network of lipid homeostasis in the RPE. Disruption of LIPIN1‐mediated regulation impaired lipid balance and contributed to AMD‐related pathogenic changes.
... Smoking is a major modifiable risk factor related to AMD onset and development. Compared to non-smokers, ex-smokers and current smokers are two-to four-fold more likely to develop AMD [33,34]. Several studies investigated whether the risk of AMD is correlated to the dose of cigarette consumption, and there is evidence that smoking significantly increases the risk of developing AMD in a dose-dependent manner [35][36][37][38][39]. ...
Age-related macular degeneration (AMD) is the most common cause of irreversible loss of central vision in elderly subjects, affecting men and women equally. It is a degenerative pathology that causes progressive damage to the macula, the central and most vital part of the retina. There are two forms of AMD depending on how the macula is damaged, dry AMD and wet or neovascular AMD. Dry AMD is the most common form; waste materials accumulate under the retina as old cells die, not being replaced. Wet AMD is less common, but can lead to vision loss much more quickly. Wet AMD is characterized by new abnormal blood vessels developing under the macula, where they do not normally grow. This frequently occurs in patients who already have dry AMD, as new blood vessels are developed to try to solve the problem. It is not known what causes AMD to develop; however, certain risk factors (i.e., age, smoking, genetic factors) can increase the risk of developing AMD. There are currently no treatments for dry AMD. There is evidence that not smoking, exercising regularly, eating nutritious food, and taking certain supplements can reduce the risk of acquiring AMD or slow its development. The main treatment for wet AMD is inhibitors of VEGF (vascular endothelial growth factor), a protein that stimulates the growth of new blood vessels. VEGF inhibitors can stop the growth of new blood vessels, preventing further damage to the macula and vision loss. In most patients, VEGF inhibitors can improve vision if macular degeneration is diagnosed early and treated accordingly. However, VEGF inhibitors cannot repair damage that has already occurred. Current AMD research is trying to find treatments for dry AMD and other options for wet AMD. This review provides a summary of the current evidence regarding the different treatments aimed at both forms of AMD with particular and greater attention to the dry form.
... AMD stands as the leading cause of vision loss among individuals aged 50 and above in developed countries, underscoring the critical need for developing effective diagnostic methods [12,13]. Dry age-related macular degeneration (AMD) is characterized by the accumulation of drusen beneath the retinal pigment epithelium and the progressive thinning or atrophy of the retinal pigment epithelium and photoreceptors. ...
Introduction:
Recent advancements in imaging techniques, particularly optical coherence tomography angiography (OCTA), have transformed our understanding of retinal microvascular changes in various ocular diseases, including dry age-related macular degeneration (AMD). Our literature review summarizes key findings on retinal vascular alterations in dry AMD as observed with OCTA, highlighting their implications for disease progression and management.
Areas covered:
Studies reveal significant changes in dry AMD patients, affecting the superficial and deep capillary plexuses as well as the choroid. These alterations include decreased vascular and flow density, variations in the foveal avascular zone, reduced choriocapillaris perfusion, and alterations in choroidal vascularity and thickness. Such changes reflect the complex vascular pathology of dry AMD and serve as potential biomarkers for monitoring disease progression. Variability in study results underscores the importance of considering AMD stage, sample size, follow-up duration, imaging protocols, and standardization.
Expert opinion:
OCTA in dry AMD is primarily research-focused due to technical and methodological challenges. Its adoption in clinical practice requires standardized protocols and improved software. With future advancements and a better understanding of disease pathology, OCTA could become a routine part of dry AMD management, especially as new therapies emerge that utilize OCTA for assessing dry AMD progression.
... While in our elderly population, the AMD prevalence was not correlated with the prevalence and degree of arterial hypertension, there are conflicting reports of an association of arterial hypertension and age-related macular degeneration in the literature [27,28]. Neither was diet as assessed in the questionnaire correlated with the AMD prevalence in our elderly study population (Table 1). ...
Purpose
To assess the prevalence of age-related macular degeneration (AMD) and reticular pseudodrusen (RPD) in very old individuals.
Methods
The population-based Ural Very Old Study consisted of 1526 (81.1%) out of 1882 eligible individuals aged 85 + years. All individuals living in the study regions and having an age of 85 + years were eligible for the study. The presence of AMD and RPDs was assessed on color fundus photographs, red-free fundus images, and optical coherence tomographic images.
Results
The study included 932 (61.1% of 1526) individuals (age:88.6 ± 2.7 years) with available fundus images. Prevalence of any, early, intermediate and late AMD was 439/932 (47.1%; 95%CI:44.0,50.0), 126/932 (13.5%; 95% CI:11.0,16.0), 185/932 (19.8%; 95% CI:17.3,22.3) and 128/932 (13.7%; 95% CI:11.7,15.7), respectively. Neovascular AMD was present in 63 eyes (6.8%;95%CI:5.3,8.3) and geographic atrophy in 65 eyes (7.0%;95%CI:5.0,9.0). Higher prevalence of any AMD and late AMD was significantly correlated with urban region of habitation (OR:3.34; 95% CI:2.37,4.71; P < 0.001), and with older age (OR:1.12; 95% CI:1.04,1.19; P = 0.001), female sex (OR:1.63; 95%CI:1.02,2.60; P = 0.04), and urban region of habitation (OR:2.89; 95% CI:1.59,5.26; P < 0.001), respectively. RPDs (assessed in 889 (58.3%) study participants) were present in 220/889 participants (24.7%; 95%CI:21.7,27.7). Higher RPD prevalence was associated (multivariable analysis) with higher serum concentration of the rheumatoid factor (OR:1.15; 95% CI:1.04,1.28; P = 0.008), shorter axial length (OR:0.84;95%CI:0.71,0.00;P = 0.04), and higher degree of nuclear cataract (OR:1.06; 95% CI:1.01,1.12; P = 0.02). AMD was the main cause for vision impairment in 230 (24.7%) participants, for moderate-to-severe vision impairment in 75 (8.0%; 95% CI: 6.4, 10.0) individuals, and for blindness in 15 (1.6%; 95%CI: 0.8, 2.5) persons respectively.
Conclusions
In this ethnically mixed, very old population, AMD prevalence (any AMD:47.1%;late AMD:13.7%) was statistically independent of most systemic and ocular parameters. Higher RPD prevalence correlated with shorter axial length.
Key messages
What is knownThe prevalence of age-related macular degeneration (AMD) has been explored in many studies and societies. Information is missing about its prevalence and associations in very old individuals. The same holds true for reticular pseudodrusen of the macula.
What is newIn an ethnically mixed, very old population in Bashkortostan / Russia, the prevalence of AMD (any AMD: 47.1%; late AMD:13.7%) was statistically independent of most systemic and ocular parameters.
Higher prevalence of reticular pseudodrusen correlated with shorter axial length.
... Age-related macular degeneration (AMD) is a leading cause of central vision loss in the developed world, with 6-9% of legal blindness globally and an increasing prevalence (0.2% to 13%) related to the growing economic burden [1][2][3][4][5]. From 1990 to 2017, global disability-adjusted life years (DALYs) increased by 108.2% (2.5 million to 5.3 million) due to AMD [6]. ...
Introduction
Age-related macular degeneration (AMD) is a leading cause of central vision loss, with an increasing prevalence related to a growing economic burden. Understanding the epidemiological changes of AMD is essential for targeting the resource allocation of medicine, interventions, and the economy.
Material and methods
The global prevalence and years lived with disability of AMD by sociodemographic index (SDI), sex, and age groups from 1990 to 2019 based on the Global Burden of Disease Study 2019 were retrieved and utilized to estimate epidemiological changes.
Results
The global AMD population increased significantly from 3581.33 thousand in 1990 to 7792.53 thousand in 2019, and the years lived with disability significantly increased from 296.77 thousand years to 564.06 thousand years. The AMD burden was higher among females (57.77% to 59.20%), the elderly (65–74 years old), and individuals in high-middle and middle SDI regions from 1990 to 2019. The most significant increase in global burden occurred between 2014 and 2019. The age-standardized rate was predicted to remain stable, but the AMD case number was predicted to increase over the next 20 years. Tobacco use was the major diminishing risk factor.
Conclusions
The present study demonstrated the increasing AMD burden in the past 30 years and predicted the increasing change of AMD prevalence in the next 20 years in the context of the aging global population. Disease burdens, including case number and age-standardized rate, were higher among females, the elderly, and individuals in high-middle and middle SDI regions. The present findings will contribute to healthcare investment and policymaking.
... 1,3 In addition to aging, the impact of other environmental and nongenetic risk factors, such as smoking and diet, on the development of AMD has been indicated in previous studies. 1,3,4 According to previous reports, AMD has a high prevalence in different regions and is the third leading cause of visual impairment and blindness in the world. [5][6][7] The estimates indicate that about 200 million people around the world are affected by various types of this disease, and this number is projected to reach 300 million people by 2040. ...
Purpose
To estimate the prevalence of age-related macular degeneration (AMD) and determine its risk factors in Iran.
Methods
A comprehensive electronic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar, with no restrictions on time or language of publication. Eleven studies meeting the eligibility criteria were included. Six studies with a total sample size of 9930 were included in the meta-analysis to calculate the overall prevalence of AMD in Iran. Meta-analysis was performed using Stata/MP version 15.0. Risk of bias assessment was carried out based on the Newcastle–Ottawa Scale.
Results
All participants in the studies were over 40 years old. The pooled prevalence of AMD was estimated to be 9.9% (95% confidence interval [CI]: 6.3%–13.5%). After accounting for publication bias, this estimated decreased to 6.4% (95% CI: 4%–10.2%). Smoking (odds ratio [OR]: 1.781; 95% CI: 1.152–2.756), hypertension (HTN) (OR: 1.512; 95% CI: 1.119–2.044), diabetes mellitus (DM) (OR: 1.545; 95% CI: 1.088–2.194), and hyperlipidemia (OR: 1.512; 95% CI: 1.055–2.165) were identified as AMD risk factors.
Conclusion
Based on the results of the present review, the prevalence of AMD in the Iranian population over 40 years of age is estimated to be 6.4%, and having a history of smoking, HTN, DM, and hyperlipidemia are identified as risk factors of AMD in Iran. Further original studies are needed to draw more accurate conclusions.
... [4][5][6] Environmental and lifestyle variables, such as smoking, hypertension, and body mass index, exert a significant influence on AMD risk. 7 Similarly, genetic factors play a crucial role, with individuals having a family history of AMD facing an elevated risk compared to those without such familial predisposition. 8 There is an increasing consensus suggesting that immunology also plays an important role. ...
Background
Age-related Macular Degeneration (AMD) poses a growing global health concern as the leading cause of central vision loss in elderly people.
Objection
This study focuses on unraveling the intricate involvement of Natural Killer (NK) cells in AMD, shedding light on their immune responses and cytokine regulatory roles.
Methods
Transcriptomic data from the Gene Expression Omnibus database were utilized, employing single-cell RNA-seq analysis. High-dimensional weighted gene co-expression network analysis (hdWGCNA) and single-cell regulatory network inference and clustering (SCENIC) analysis were applied to reveal the regulatory mechanisms of NK cells in early-stage AMD patients. Machine learning models, such as random forests and decision trees, were employed to screen hub genes and key transcription factors (TFs) associated with AMD.
Results
Distinct cell clusters were identified in the present study, especially the T/NK cluster, with a notable increase in NK cell abundance observed in AMD. Cell-cell communication analyses revealed altered interactions, particularly in NK cells, indicating their potential role in AMD pathogenesis. HdWGCNA highlighted the turquoise module, enriched in inflammation-related pathways, as significantly associated with AMD in NK cells. The SCENIC analysis identified key TFs in NK cell regulatory networks. The integration of hub genes and TFs identified CREM, FOXP1, IRF1, NFKB2, and USF2 as potential predictors for AMD through machine learning.
Conclusion
This comprehensive approach enhances our understanding of NK cell dynamics, signaling alterations, and potential predictive models for AMD. The identified TFs provide new avenues for molecular interventions and highlight the intricate relationship between NK cells and AMD pathogenesis. Overall, this study contributes valuable insights for advancing our understanding and management of AMD.
... Fatores como idade, histórico familiar de DMRI, tabagismo, dieta e exposição à luz ultravioleta são todos considerados na avaliação do risco do paciente (Mitchell et al., 1995). Estudos epidemiológicos demonstram que indivíduos com histórico familiar de DMRI têm um risco significativamente maior de desenvolver a doença (Smith et al., 2001). (Chew et al., 2013). ...
A Degeneração Macular Relacionada à Idade (DMRI) é uma condição degenerativa que afeta a mácula, a área central da retina responsável pela visão detalhada e central, essencial para atividades como leitura, reconhecimento de rostos e visão de detalhes finos. Realizar uma revisão é de extrema importância para aprimorar o manejo e a compreensão dessa condição ocular complexa. A DMRI está em constante evolução com novas descobertas sobre sua fisiopatologia, diagnóstico e tratamento. Uma revisão abrangente oferece uma oportunidade para consolidar e atualizar as informações mais recentes, proporcionando aos profissionais de saúde uma visão clara e atualizada das melhores práticas e inovações terapêuticas. Foi empregada uma abordagem quantitativa na pesquisa, complementada pela inclusão de estudos qualitativos relevantes para uma compreensão abrangente do tema. A revisão dos estudos demonstra que a DMRI seca apresenta uma evolução gradual e é caracterizada pelo acúmulo de drusas sob a retina, resultando em perda progressiva da visão central. Em contraste, a DMRI úmida é mais agressiva e está associada à formação de vasos sanguíneos anômalos na coroide, causando perda rápida e severa da visão central devido ao vazamento de fluido e sangue. Estudos mostram que a prevalência e a gravidade da doença podem variar de acordo com fatores genéticos, ambientais e de estilo de vida. Entre os fatores de risco identificados estão o tabagismo, a hipertensão e uma dieta pobre em antioxidantes. A realização de pesquisas contínuas e o desenvolvimento de novas terapias são essenciais para enfrentar os desafios impostos pela DMRI e melhorar os resultados para os pacientes.
... The intricate interaction of these elements contributes to the development and progression of AMD. [4][5][6][7][8][9] The relationship between diabetes mellitus (DM) and nAMD remains a topic of debate within the scientific community. Whereas some studies have reported a correlation between DM and nAMD, suggesting that DM may increase the risk of developing nAMD, other reports propose that diabetes could actually act as a protective factor against nAMD. ...
Purpose
To explore the long-term effect of diabetic retinopathy on response to anti-vascular endothelial growth factor (VEGF) treatment in age-related macular degeneration–associated type 1 macular neovascularization (MNV) using optical coherence tomography angiography (OCTA).
Methods
A total of 45 eyes with exudative neovascular age-related macular degeneration (nAMD) with type 1 MNV were included in the analysis. Among them, 24 eyes of 24 patients had no history of diabetes mellitus (DM) in their anamnesis and were assigned to the Not Diabetic group; 21 eyes of 21 patients had mild diabetic retinopathy and were included in the Diabetic group. We considered the following outcome measures: (1) best-corrected visual acuity changes; (2) central macular thickness; (3) MNV lesion area; and (4) MNV flow area. The OCTA acquisitions were performed at the following time points: (1) baseline visit, which corresponded to the day before the first injection; (2) post-loading phase (LP), which was scheduled at 1 month after the last LP injection; and (3) 12-month follow-up visit.
Results
All morphofunctional parameters showed a significant improvement after the LP and at the 12-month follow-up visit. Specifically, both the Diabetic group and the Not Diabetic group displayed a significant reduction of MNV lesion areas at both the post-LP assessment (P = 0.026 and P = 0.016, respectively) and the 12-month follow-up (P = 0.039 and P = 0.025, respectively). Similarly, the MNV flow area was significantly decreased in both the Diabetic group and the Not Diabetic group at the post-LP assessment (P < 0.001 and P = 0.012, respectively) and at the 12-month follow-up (P = 0.01 and P = 0.035, respectively) compared to baseline. A smaller reduction in the MNV lesion area was observed in the Diabetic group at both the post-LP evaluation (P = 0.015) and the 12-month follow-up (P = 0.032). No other significant differences were found between the groups for the other parameters (P > 0.05).
Conclusions
Our results indicated that the Diabetic group exhibited a smaller reduction in MNV lesion area after 12 months of anti-VEGF treatment. This highlights the importance of considering diabetic retinopathy as a potential modifier of treatment outcomes in nAMD management, with DM serving as a crucial risk factor during anti-angiogenic treatment.
... The demographic characteristics of the study population reveal a diverse representation across age groups, with a signicant proportion of older individuals and a male preponderance. This distribution is consistent with previous studies that have highlighted age-related changes in visual function and higher prevalence rates of certain eye conditions [10,11] in older age groups . The dominance of older participants in the study cohort underscores the importance of considering age-related factors in the evaluation of visual outcomes and treatment responses. ...
Background: Tuberculosis (TB) remains a global health challenge, with signicant morbidity and mortality rates worldwide. Ethambutol (E), a key component of TB treatment, is associated with ocular toxicity, particularly optic neuropathy, posing challenges in patient management. The National Tuberculosis Elimination Programme (NTEP) guidelines advocate for prolonged E therapy, raising concerns regarding ocular safety. Materials and Methods: This observational study aimed to evaluate visual function in newly diagnosed pulmonary tuberculosis patients receiving Ethambutol therapy in line with NTEP guidelines. Visual assessments included visual acuity, color vision, and visual elds. Data were collected from 122 patients over a one-year period and analyzed using appropriate statistical methods. Results: The study population exhibited a diverse age distribution, with a predominance of older individuals and a male preponderance. Visual acuity remained stable over the treatment period, with minimal changes observed in contrast sensitivity. Color vision outcomes uctuated slightly but did not show signicant differences between groups. However, visual eld defects increased over time, indicating potential treatment-related factors. Conclusion: Assessment of visual function is essential in monitoring Ethambutol-induced ocular toxicity. While visual acuity and color vision remained relatively stable, visual eld defects increased over time, highlighting the need for comprehensive monitoring during Ethambutol therapy. Incorporating objective assessments into routine practice can facilitate early detection and intervention, improving patient safety and treatment outcomes.
... This choice agreed with the copious evidence of the benefits accruing from the administration of nutraceutical medications, principally in the Age-Related Eye Disease Study (AREDS) 1 and 2, 18 which also recommends lifestyle changes, such as adopting a Mediterranean diet, 19 quitting smoking, losing excess weight, and reducing exposure to sunlight. [20][21][22] This study is limited by several limitations, especially the relatively small number of participants. The questionnaire has not been validated and some useful information is missing, for example infrared imaging for GA evaluation. ...
Purpose
Geographic atrophy (GA) is a severe complication of age-related macular degeneration (AMD) and leads to irreversible visual decline. To date, no effective treatment is available for GA patients. However, a number of new therapies have recently been approved and several others are in the pipeline. This rapid evolution of prospects for GA patients requires constant updating of ophthalmologists’ understanding of GA and its management so as to provide the appropriate treatment. For this reason, Società Italiana di Scienze Oftalmologiche (S.I.S.O.) has designed a specific survey to gauge the position of Italian ophthalmologists in this regard.
Methods
The three hundred and sixty-five Italian ophthalmologists who agreed to take part received a seventeen-part questionnaire guaranteeing privacy and anonymity. The survey was compiled through an online portal and the results were sent directly to S.I.S.O. ETS. Two graders analyzed the data and recorded the results.
Results
The results showed a high level of self-assessed awareness and understanding of GA, as well as considerable willingness to further improve knowledge of the disease. Most of the participants claimed to have effective rules of conduct in place for managing GA patients, including prompt response, involving a high prevalence of nutraceutical prescriptions and lifestyle recommendations.
Conclusions
This survey provided an overview of how GA patients are managed in Italy. The Italian ophthalmology community appears to be ready to adopt the upcoming treatments for GA.
... Kim et al. reported a high level of CLU in AH samples of neovascular AMD (nvAMD) patients compared to controls 54 . Smoking is the strongest modifiable risk factor for AMD 55,56 . The macular photocoagulation study 57 showed that individuals who pursued smoking were at increased risk of recurrent choroidal neovascularization in comparison to nonsmokers in the first year after successful photocoagulation. ...
The detrimental effects of smoking are multisystemic and its effects on the eye health are significant. Smoking is a strong risk factor for age-related nuclear cataract, age-related macular degeneration, glaucoma, delayed corneal epithelial healing and increased risk of cystoid macular edema in patients with intermediate uveitis among others. We aimed to characterize the aqueous humor (AH) proteome in chronic smokers to gain insight into its perturbations and to identify potential biomarkers for smoking-associated ocular pathologies. Compared to the control group, chronic smokers displayed 67 (37 upregulated, 30 downregulated) differentially expressed proteins (DEPs). Analysis of DEPs from the biological point of view revealed that they were proteins involved in complement activation, lymphocyte mediated immunity, innate immune response, cellular oxidant detoxification, bicarbonate transport and platelet degranulation. From the molecular function point of view, DEPs were involved in oxygen binding, oxygen carrier activity, hemoglobin binding, peptidase/endopeptidase/cysteine-type endopeptidase inhibitory activity. Several of the upregulated proteins were acute phase reactant proteins such as clusterin, alpha-2-HS-glycoprotein, fibrinogen, alpha-1-antitrypsin, C4b-binding protein and serum amyloid A-2. Further research should confirm if these proteins might serve as biomarkers or therapeutic target for smoking-associated ocular diseases.
... Выявлены различия между влиянием повышенного систолического (САД) и диастолического артериального давления (ДАД) на течение ВМД: САД показало положительную связь как с нВМД, так и с сухой ВМД [13], в то время как ДАД обратно коррелировало с развитием ранней сухой ВМД [12]. Исследования «случай-контроль» и популяционные исследования, напротив, не подтвердили статистически значимую взаимосвязь между ВМД и гипертонией [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. При этом если связь между системной артериальной гипертонией и ВМД изучали, то связь артериальной гипертонии с ответом на лечение нВМД осталась вне фокуса внимания офтальмологического сообщества. ...
Purpose : to assess hypertension as a risk factor for a poor response to antiangiogenic therapy.
Patients and methods . Systemic blood pressure was studied in 84 patients (92 eyes) with age-related macular degeneration who were treated with intravitreal injections of Eilea in a fixed mode.
Results . It was found that significantly more often a poor response to treatment in the form of partial non-resposing or progression of the disease, despite treatment, is associated with elevated diastolic blood pressure (DBP, p = 0.01). An increase in systolic (SBP) blood pressure in patients with arterial hypertension and AMD is accompanied by an increase in eye perfusion pressure (p < 0.01), which apparently worsens the absorption of angiostatics and causes a poor response to treatment. According to the results of the study, the most favorable corridor of SBP values associated with ideal response is in the range of values of 104–140 mm Hg, and DBP is in the range of 68–80 mm Hg st., which should be taken as the recommended parameters of blood pressure in patients with nVMD receiving a course of treatment for Eylea. Intraocular pressure (IOP) has demonstrated itself as a second modifiable independent and independent risk factor for poor response to treatment with nVMD with line 1 anti-VEGF therapy drugs. Intraocular pressure (IOP) has demonstrated itself as a second modifiable independent and independent risk factor for poor response to nVMD treatment with line 1 anti-VEGF therapy drugs. The biomarker associated with the ideal response was — 12.6 mm Hg, and the corridor of recommended values — 11–21 mm Hg. An increase in ophthalmotonus with the output of personalized values beyond this corridor seems to worsen the outcome of treatment.
Conclusion . The identification of modifiable risk factors is extremely important in practical ophthalmology, as it opens up the possibility of increasing the patient’s chances of a better treatment outcome. Modifiable risk factors are valuable and powerful tools that replenish our arsenal. Information about them is important not only in the treatment of AMD, but can also be the patient’s motivation for switching to a healthy lifestyle and reducing the risk of developing the disease.
... AMD impacts both developed and developing countries with more than 170 million individuals affected globally [1]. In developed countries, AMD affects nearly 10% of those people older than 65 years and 25% of those older than 75 years [46]. In the USA, the total economic impact of late-stage AMD was estimated at USD 49.1 billion in 2022 [47]. ...
Purpose
To compare diagnostic power for different severities of age-related macular degeneration (AMD) of two-dimensional macular pigment optical densities (2D-MPOD) and spatially matched objective perimetry, with standard perimetry and best-corrected visual acuity (BCVA).
Methods
The ObjectiveField Analyser (OFA) provided objective perimetry, and a Heidelberg Spectralis optical coherence tomography (OCT) measured 2D-MPOD in AMD patients, both completed twice over 0.99 ± 0.16 years. From each 2D-MPOD image, we extracted 20 regions/macula, matched to the 20 OFA stimuli/macula. For each region, we calculated 7 measures from the 2D-MPOD pixel values and correlated those with OFA sensitivities and delays. We quantified 2D-MPOD changes, the ability of 2D-MPOD and OFA to discriminate AMD stages, and the discriminatory power of Matrix perimetry and BCVA using percentage area under receiver operator characteristic plots (%AUROC).
Results
In 58 eyes of 29 subjects (71.6 ± 6.3 years, 22 females), we found significant correlations between 2D-MPOD and OFA sensitivities for Age-Related Eye Disease Studies (AREDS)-3 and AREDS-4 severities. Delays showed significant correlations with AREDS-2. For AREDS-4, correlations extended across all eccentricities. Regression associated with the Bland–Altman plots showed significant changes in 2D-MPOD over the study period, especially variability measures. MPOD per-region medians discriminated AREDS-1 from AREDS-3 eyes at a %AUROC of 80.0 ± 6.3%, outperforming OFA, Matrix perimetry, and BCVA.
Conclusions
MPOD changes correlated with central functional changes and significant correlations extended peripherally in later-stage AMD. Good diagnostic power for earlier-stage AMD and significant change over the study suggest that 2D-MPOD and OFA may provide effective biomarkers.
... Aging is the main and most important risk factor for AMD. The relevance between AMD and female sex as a risk factor has shown inconsistent findings in various research [5]. ...
Purpose
Our objective was to compare the serum Adropin levels between patients with wet-type Age-Related Macular Degeneration (AMD) and otherwise healthy individuals.
Method
The study included 45 patients with wet-type AMD and 45 individuals without age-related macular degeneration. Patients with co-morbidities such as diabetes, hypertension, autoimmune diseases, and a previous history of visual impairment; were excluded. FBS, Hemoglobin A1C (HbA1C), lipid profile, and serum Adropin level were checked.
Results
The mean serum Adropin level of patients with wet-type AMD was significantly lower than the control group (P-value < 0.001). Also, the mean High-sensitivity C-reactive protein ( hsCRP) level and High Density Lipoprotein (HDL) were significantly higher in wet-type AMD patients (P-value = 0.031 and < 0.001 respectively).
Conclusions
In our study, wet-type AMD was associated with a lower level of serum Adropin. Because of Adropin involvement in glucose metabolism and age-related changes, it may have a role in the pathogenesis of AMD, but it requires more investigations at the molecular level to elucidate its function.
... 90 Smoking confers progression risk with an odds ratio of 3.1 (2.1-4.6). 91 Low risk in the outer ring (odds ratio for progression 1.2, 0.3-4.3) separated central soft drusen from the many other drusen in peripheral retina. ...
A progression sequence for age-related macular degeneration onset may be determinable with consensus neuroanatomical nomenclature augmented by drusen biology and eye-tracked clinical imaging. This narrative review proposes to supplement the Early Treatment of Diabetic Retinopathy Study (sETDRS) grid with a ring to capture high rod densities. Published photoreceptor and retinal pigment epithelium (RPE) densities in flat mounted aged-normal donor eyes were recomputed for sETDRS rings including near-periphery rich in rods and cumulatively for circular fovea-centered regions. Literature was reviewed for tissue-level studies of aging outer retina, population-level epidemiology studies regionally assessing risk, vision studies regionally assessing rod-mediated dark adaptation (RMDA), and impact of atrophy on photopic visual acuity. The 3 mm-diameter xanthophyll-rich macula lutea is rod-dominant and loses rods in aging whereas cone and RPE numbers are relatively stable. Across layers, the largest aging effects are accumulation of lipids prominent in drusen, loss of choriocapillary coverage of Bruch's membrane, and loss of rods. Epidemiology shows maximal risk for drusen-related progression in the central subfield with only one third of this risk level in the inner ring. RMDA studies report greatest slowing at the perimeter of this high-risk area. Vision declines precipitously when the cone-rich central subfield is invaded by geographic atrophy. Lifelong sustenance of foveal cone vision within the macula lutea leads to vulnerability in late adulthood that especially impacts rods at its perimeter. Adherence to an sETDRS grid and outer retinal cell populations within it will help dissect mechanisms, prioritize research, and assist in selecting patients for emerging treatments.
In the 21st century, the demographic shift toward an aging population has posed a significant challenge, particularly with respect to age-related diseases, which constitute a major threat to human health. Accordingly, the detection, prevention, and treatment of aging and age-related diseases have become critical issues, and the introduction of novel molecular recognition elements, called aptamers, has been considered. Aptamers, a class of oligonucleotides, can bind to target molecules with high specificity. In addition, aptamers exhibit superior stability, biocompatibility, and applicability, rendering them promising tools for the diagnosis and treatment of human diseases. In this paper, we present a comprehensive overview of aptamers, systematic evolution of ligands by exponential enrichment (SELEX), biomarkers associated with aging, as well as aptamer-based diagnostic and therapeutic platforms. Finally, the limitations associated with predicting and preventing age-related conditions are discussed, along with potential solutions based on advanced technologies and theoretical approaches.
Objective. Patients implanted with the PRIMA photovoltaic subretinal prosthesis in geographic atrophy report form vision with the average acuity matching the 100um pixel size. Although this remarkable outcome enables them to read and write, they report difficulty with perceiving faces. This paper provides a novel, non-pixelated algorithm for simulating prosthetic vision the way it is experienced by PRIMA patients, compares the algorithm's predictions to clinical perceptual outcomes, and offers computer vision and machine learning (ML) methods to improve face representation. Approach. Our simulation algorithm integrates a grayscale filter, spatial resolution filter, and contrast filter. This accounts for the limited sampling density of the retinal implant, as well as the reduced contrast sensitivity of prosthetic vision. Patterns of Landolt C and faces created using this simulation algorithm are compared to reports from actual PRIMA users. To recover the facial features lost in prosthetic vision, we apply an ML facial landmarking model as well as contrast adjusting tone curves to the face image prior to its projection onto the implant. Main results. Simulated prosthetic vision matches the maximum letter acuity observed in clinical studies as well as patients' subjective descriptions. Application of the inversed contrast filter helps preserve the contrast in prosthetic vision. Identification of the facial features using an ML facial landmarking model and accentuating them further improve face representation. Significance. Spatial and contrast constraints of prosthetic vision limit resolvable features and degrade natural images. ML based methods and contrast adjustments mitigate some limitations and improve face representation. Even though higher spatial resolution can be expected with implants having smaller pixels, contrast enhancement still remains essential for face recognition.
The present study was aimed to study the age and risk of age related macular degeneration. Age-related macular degeneration(AMD) is one of the main socioeconomical health issues worldwide. This is prospective study include all patients of age related macular degeneration above 50 years of age presenting in the Department of Ophthalmology at Dr.RPGMC Tanda. There were total 86 patients with age ranging from 50 to 90 years.Most of the patients were in early ARMD group(n=55) and maximum were in the age group of 61-70 years(n=37).Finding showed that with increasing age number of patients with intermediate/exudative form of ARMD also increases.
Age-related macular degeneration (AMD) continues to be the most common hereditary disease among older people in the western world. In addition to the clinical examination, multimodal imaging with fluorescein angiography, optical coherence tomography, fundus autofluorescence and fundus photography are crucial for the correct diagnosis and classification. This is particularly important with regard to risk assessment for the development of a late form of the disease. Since the introduction of intravitreal therapy against vascular endothelial growth factor (VEGF), the treatment options for neovascular AMD have increased significantly and the prognosis for patients in terms of maintaining their vision has improved. The hope is to develop stronger and longer-lasting drugs and also to obtain approval for drugs to treat geographic atrophy. It is therefore of great importance to be able to make a quick and correct diagnosis for patients. In this paper we want to present an overview of the pathophysiology, classification and diagnosis of AMD.
Age-related macular degeneration (AMD) continues to be the most common hereditary disease among older people in the western world. In addition to the clinical examination, multimodal imaging with fluorescein angiography, optical coherence tomography, fundus autofluorescence and fundus photography are crucial for the correct diagnosis and classification. This is particularly important with regard to risk assessment for the development of a late form of the disease. Since the introduction of intravitreal therapy against vascular endothelial growth factor (VEGF), the treatment options for neovascular AMD have increased significantly and the prognosis for patients in terms of maintaining their vision has improved. The hope is to develop stronger and longer-lasting drugs and also to obtain approval for drugs to treat geographic atrophy. It is therefore of great importance to be able to make a quick and correct diagnosis for patients. In this paper we want to present an overview of the pathophysiology, classification and diagnosis of AMD.
Infection with Toxoplasma gondii (T. gondii) protozoan can lead to toxoplasmosis and has high seroprevalence in the human population. T. gondii can cross the Blood-retinal barrier, leading to ocular toxoplasmosis (OT), which can severely impair vision. Our group demonstrated microcirculatory alterations and reduced angiogenesis in mouse brains after acquired T. gondii infection, suggesting that such alterations may also occur in OT. This work aims to analyze the effects of acquired T. gondii in vivo infection on the retina and its vasculature. For the acquired OT model, C57BL/6 mice were intragastrically inoculated with two ME49 strain cysts and analyzed 10, 20, and 30 days post-infection (dpi). Clinical parameters, parasitic load, cytokine pro les, retinal vasculature, endothelial activation, vascular function, and glial activation were assessed. Infected mice exhibited significant weight loss and reduced chow consumption. Tachyzoites were detected by RT-qPCR at 10 dpi, while bradyzoites' signal appeared at 20 and 30 dpi. Infected mice had elevated serum pro-inflammatory cytokines TNF-α, IFN-γ, and IL-6 at 10 dpi, transitioning to increased IL-4 and IL-10 at 20 dpi, returning to basal levels at 30 dpi. Retinal blood ow and functional capillary density were increased, while structural changes in the vasculature, such as vessel length and area, varied over time. Collagen IV expression increased at 20 and 30 dpi, indicating vascular remodeling. Angiogenic markers VEGFR1 and Notch1 expression were consistently downregulated, and Delta-like4 expression decreased at 20 and 30 dpi. Endothelium-leukocyte interaction, as assessed by rolling and adherent leukocytes, was increased in infected retinal venules. Retinal endothelial function was impaired, with reduced vasodilation response to acetylcholine and alterations in tight junction markers ZO-1, claudin5 and occludin. Increased glial activation was observed, with elevated GFAP immunoreactivity and expression at 20 and 30 dpi. CX3CR1 expression was elevated at all times studied, indicative of microglial activation, accompanied with Arg1 and iNOS upregulation and STAT3 phosphorylation, corroborating neuroinflammatory responses. T. gondii infection in mice induces systemic and retinal inflammation, leading to significant changes in the retinal vasculature and impaired endothelial function. These findings contribute to a better understanding of OT pathophysiology, enabling the design of future therapeutic strategies.
Purpose: The primary aim of this paper is to design, create, and improve functional and artificial Bruch's membranes (BM) using bioengineering techniques, which can be applied in the treatment of maculopathies by supporting the growth and maintenance of retinal pigment epithelium (RPE) cells, thereby potentially enabling subretinal implantation in patients. Methods: We fabricated by electrospinning ultrathin 3D nanofibrous membranes from Poly-caprolactone (PCL), and different concentrations of gelatin (5%, 15% and 30%). ARPE-19 cells were seeded onto these artificial membranes. MTT assays were performed in order to evaluate ARPE-19 cell viability and cytotoxicity. IF assays were realized to observe the ARPE-19 cells onto each membrane. Ultrastructure of the modified Bruch's membrane and ARPE-19 morphology after 25 days of
Purpose
The aim of this study was to investigate the role of −1154 guanine (G)>adenine (A) and +405 G>cytosine (C) vascular endothelial growth factor (VEGF) gene polymorphisms as possible risk factors for neovascular age-related macular degeneration (nAMD) and to evaluate their role in patients’ response to anti-VEGF therapy.
Patients and methods
The study included 50 nAMD patients and 64 age and sex-matched healthy volunteers. Polymerase chain reaction-restriction fragment length polymorphism was performed to assess the VEGF −1154 G>A and +405 G>C polymorphisms in relation to AMD.
Results
Hypertension was reported in 40 (80%) cases compared to 14 (21.9%) of the controls, with a statistically significant difference ( P < 0.001). Heart disease was also reported more significantly in patients (13 = 26%) than in controls (7 = 10.9%), P = 0.036. In addition, smoking was detected in 39 cases (78%) compared to 10 (15.6%) controls, a statistically significant difference ( P < 0.001). Molecular analysis of VEGF −1154 G>A and VEGF +405 G>C gene polymorphisms yielded nonstatistically significant difference between cases and control groups. Assessment of genotype frequency of VEGF −1154 among responders and nonresponders yielded nonstatistically significant difference. However, genotype frequency of VEGF +405 among responders and nonresponders revealed a statistically significant difference, with the GG genotype associated with better response to anti-VEGF therapy (61.1% responders versus 28.6% nonresponders according to visual acuity and optical coherence tomography parameters, P = 0.037).
Conclusion
Smoking, hypertension, and heart disease were critical risk factors for the development of AMD. The VEGF +405 G>C genotype was found to be an important predictor for response to anti-VEGF therapy.
Age-related macular degeneration (AMD) is a major source of vision loss worldwide. This study aims to assess risk factors for wet AMD by two methods: assessing risk factors measured in the Scottish Heart Health Extended Cohort (SHHEC), and to systematically review the literature.
Methods: 18,107 volunteers were recruited to SHHEC between 1984-1995, with risk factor data collected on recruitment. Hospital records were linked to study data up to 2017 and survival analysis used to analyse risk factors and wet AMD. Literature published between 2000-2023 was searched for studies assessing risk factors for wet AMD, resulting in 5503 papers. Following review, 7 studies were included in the systematic review.
Results: Within the SHHEC data, 231 cases of wet AMD are reported. Age (Hazard Ratio (HR) 10.74; 95% Confidence Interval (CI) 5.90-19.56), being female (HR 1.37; 95% CI 1.02-1.84), smoking (HR 1.67; 95% CI 1.28-2.18), and a serum glucose > 5.32mmol/l (HR 1.62; 95% CI 1.09-2.42) were significantly associated with an increased risk of wet AMD. Vitamin K (HR 0.56; 95% CI 0.38-0.83), and Apolipoprotein B (HR 0.65; 95% CI 0.43-0.99) were associated with a decreased risk of wet AMD.
Within the systematic review, there was evidence that systolic blood pressure, pulse pressure, high BMI, alcohol intake, high C-reactive protein, high serum triglycerides and smoking may be associated with an increased risk of wet AMD; however the studies provide mixed evidence and no conclusive results can be drawn.
Purpose:
No large-mammal surgical models exist for geographic atrophy (GA), choroidal neovascularization (CNV), and pachychoroidal vascular remodeling. Our goal was to develop a porcine RPE debridement model of advanced macular degeneration to study photoreceptor cell loss and choroidal remodeling.
Methods:
Seven 2-month-old female domestic pigs were used for this study. After 25G vitrectomy, the area centralis was detached via subretinal bleb. A nitinol wire (Finesse Flex Loop) was used to debride RPE cells across a 3- to 5-mm diameter region. Fluid-air exchange was performed, and 20% SF6 gas injected. Animals underwent fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT-angiography (OCTA) at 2 weeks, 1 month, 2 months, 3 months, and 6 months postoperatively. Retinal histology was obtained at euthanasia, 2 months (n = 3), 3 months (n = 2), or 6 months (n = 2) after surgery.
Results:
RPE debridement resulted in GA with rapid loss of choriocapillaris, progressive loss of photoreceptors, and pachychoroidal changes in Sattler's and Haller's layers in all seven eyes undergoing debridement within 2 months. OCT and histological findings included subretinal disciform scar with overlying outer retinal atrophy; outer retinal tubulations and subretinal hyper-reflective material. OCTA revealed type 2 CNV (n = 4) at the edges of the debridement zone by 2 months, but there was no significant exudation noted at any time point.
Conclusions:
Surgical debridement of the RPE results in GA, CNV, and pachychoroid and reproduced all forms of advanced macular degeneration. This surgical model may be useful in examining the role of RPE and other cell replacement in treating advanced macular disease.
To investigate to what extent age-related maculopathy (ARM) is genetically determined.
Familial aggregation study based on probands derived from the population-based Rotterdam Study.
First-degree relatives of 87 patients with late ARM, i.e., atrophic or neovascular macular degeneration, were compared with first-degree relatives of 135 control subjects without ARM.
Presence and stage of ARM as diagnosed on fundus transparencies, odds ratio, lifetime risk, risk ratio, and population-attributable risk.
Independent of other risk factors, the prevalence of early (odds ratio = 4.8, 95% confidence interval [CI] = 1.8-12.2) and late (odds ratio = 19.8, 95% CI = 3.1-126.0) ARM was significantly higher in relatives of patients with late ARM. The lifetime risk estimate of late ARM was 50% (95% CI = 26%-73%) for relatives of patients vs 12% (95% CI = 2%-16%) for relatives of controls (P < .001), yielding a risk ratio of 4.2 (95% CI = 2.6-6.8). Relatives of patients expressed the various features of ARM at a younger age. The population-attributable risk related to genetic factors was 23%.
First-degree relatives of patients with late ARM developed ARM at an increased rate at a relatively young age. Our findings indicate that approximately one fourth of all late ARM is genetically determined and suggest that genetic susceptibility may play an important role in determining the onset of disease.
This paper reports the annual blind certification by the Association for the Blind, Western Australia, for five consecutive years, to December 1988. The data are analysed with a view to obtaining minimum figures for incidence of the major causes of blindness in this state.
Hyman, L. G. (School of Medicine, SUNY, Stony Brook, NY 11794), A.M. Lilienfetd, F. L. Ferris III and S. L. Fine. Senile macular degeneration: a case-control study. Am J Epidemiol 1983; 118: 213–27.
Senile macular degeneration, although a leading cause of visual loss in the United States, remains a poorly understood disease. To assess the effects of host and environmental factors on this condition, a study of 228 cases and 237 controls matched by age and sex, who had visited any of 34 Baltimore ophthalmologists between September 1, 1978 and March 31, 1980, was conducted. Study participants were interviewed for past medical, residential, occupational, smoking and family histories, as well as social and demographic factors. Diagnoses were validated by means of fundus photographs. The 162 cases and 175 controls who met the study diagnostic criteria for cases and controls were included in the analysis. Statistically significant associations were demonstrated between senile macular degeneration and family history of macular disease (odds ratio (OR) = 2.9), chemical work exposures (OR = 4.2), blue or medium pigmented eyes (OR = 3.5), history of one or more cardiovascular diseases (OR = 1.7), decreased hand grip strength, and hyperopia. The risk of macular degeneration in cigarette smokers was significant for males only (OR = 2.6). The study results suggest that the development of macular degeneration is mainly influenced by familial, genetic, and personal characteristics, rather than by the few environmental factors studied. Additional studies are needed to further evaluate the role of environmental factors.
We studied the smoking habits of 114 patients with senile disciform degeneration of the macula. The mean age at onset of blindness in the first eye was 64 years in those currently smoking; this was significantly less than the mean age in those who had never smoked (71 years). We advise all patients with disciform degeneration to stop smoking.
The relationships of retinal drusen, retinal pigmentary abnormalities, and macular degeneration to age and sex were studied in 4926 people between the ages of 43 and 86 years who participated in the Beaver Dam Eye Study.
The presence and severity of various characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System.
One or more drusen were present in the macular area of at least 1 eye in 95.5% of the population. People 75 years of age or older had significantly higher frequencies (P less than 0.01) of the following characteristics than people 43 to 54 years of age: larger sized drusen (greater than or equal to 125 microns, 24.0% versus 1.9%), soft indistinct drusen (23.0% versus 2.1%), retinal pigment abnormalities (26.6% versus 7.3%), exudative macular degeneration (5.2% versus 0.1%), and geographic atrophy (2.0% versus 0%).
These data indicate signs of age-related maculopathy are common in people 75 years of age or older and may pose a substantial public health problem.
We examined 20 patients (24 eyes) who had refractive errors of -8 diopters or more and subretinal hemorrhages at the initial visit. They were divided into two groups according to fluorescein angiographic findings: 15 eyes without choroidal neovascularization (CNV) and 9 eyes with CNV. Subretinal hemorrhage without CNV was frequent in patients aged 20-39 years (mean, 36.8 years). CNV was common in patients aged 60-79 years (mean, 61.0 years). No relationship was noted between refractive error and type of hemorrhage. In the eyes without CNV, the subretinal hemorrhages disappeared spontaneously after a few months. The visual acuity of these patients was variable at the initial visit (range, 0.01-0.8), and was unchanged or improved during the follow-up period. In the eyes with CNV, the visual acuity was less than 0.1 at the initial visit and was unchanged or worse during the follow-up period.
The relationship between exposure to sunlight and senile cataract, age-related macular degeneration, pterygium, and climatic droplet keratopathy was examined in 838 watermen who work on the Chesapeake Bay. The presence and severity of lenticular, corneal, and macular changes were assessed by either clinical examination or from stereo macular photographs. From detailed exposure histories, ocular exposure was estimated for three bands of visible radiation-violet (400 to 450 nm), blue (400 to 500 nm), or all visible (400 to 700 nm)-as well as for UV-A (320 to 340 nm) and UV-B (290 to 320 nm). The results with each band of visible radiation were similar. Neither cortical nor nuclear cataract was associated with ocular exposure to blue or all visible radiation, but pterygium and climatic droplet keratopathy were more common with higher exposures. Compared with age-matched controls, patients with advanced age-related macular degeneration (geographic atrophy or disciform scarring) had significantly higher exposure to blue or visible light over the preceding 20 years (odds ratio, 1.36 [1.00 to 1.85]) but were not different in respect to exposure to UV-A or UV-B. These data suggest that high levels of exposure to blue or visible light may cause ocular damage, especially later in life, and may be related to the development of age-related macular degeneration.
Visual disability in individuals aged 50 years and over seeking services of the Royal Blind Society in the years 1984 to 1989, was studied with respect to changes in frequency of major causes together with age and sex of those affected.
The results mirror statistics in the UK. Age-related macular degeneration (AMD) accounts for an increasing proportion of visual disability (34% in 1984 to 43% in 1989). Of particular interest was the frequency of disability attributed to cataract. While decreasing (24% in 1984 to 19% in 1989), cataract still represents a significant cause of potentially treatable disability.
The authors conclude that there is a changing prevalence of visual disability caused mainly by an increase in AMD and a subgroup of patients attending for services who appear to have a potentially remediable disability. These conclusions affirm the need for close liaison between ophthalmological practitioners and agencies for the blind.
A new system for grading age-related maculopathy is described and measures of reliability are reported. A number of characteristics of age-related maculopathy are graded in a semiquantitative fashion from stereoscopic 30 degrees color fundus photographs, using a grid to define subfields, standard circles printed on plastic to assess size and area, and a specially designed lightbox to allow better discrimination of subtle drusen. The degree of exact agreement achieved between two trained graders across a variety of lesions ranged from 67.1% for drusen size to 99.6% for geographic atrophy. Kappa scores ranged from 0.55 (for drusen confluence) to 0.95 for geographic atrophy. This system will be useful in epidemiologic studies and clinical trials.
Follow up studies on 200 patients who had macular drusen were done for an average of four years. Loss of central vision was caused by disciform detachment of the pigment epithelium and retina, or less often by geographic atrophy of the pigment epithelium and retina. The average age of onset of loss of central vision in the first eye was 66 years and in the second eye 70 years. No clinical fluorescein angiographic or electrophysiologic criteria were found to differentiate patients with familial from those with so called senile drusen. Probably all patients with macular drusen have the same autosomal dominant heredodegenerative disease, which rarely causes significant loss of central vision prior to the sixth and seventh decades of life. Fifty three patients were treated with photocoagulation, the value of which is still uncertain.
An analysis of blind registration forms was made to determine the commonest causes of blindness in the west of Scotland. It was found that the leading causes of blindness in order of frequency of incidence were senile macular degeneration, glaucoma, cataract, diabetic retinopathy, and myopic degeneration. Diabetic retinopathy was the leading cause of blindness among persons of working age.
True vitelliform dystrophy rarely appears in the adult population. We describe 10 cases in adults of bilateral vitelliform lesions clinically mistaken for Best's disease. Fluorescein angiography is a useful tool in distinguishing this dystrophy from Best's disease or other diseases. The angiographic findings suggest pigment epithelial disease. Adult vitelliform degeneration may lead to dry atrophic macular degeneration in a similar fashion as macular drusen. Symptoms and visual findings in these patients are fairly stable, and may be only slowly progressive in spite of ophthalmoscopic and fluorescein angiographic changes over a period of years. The electro-oculogram is useful in separating adult vitelliform macular degeneration from true vitelliform dystrophy.
To determine the prevalence of age-related maculopathy in an elderly population in The Netherlands.
Fundus photographs of 6251 participants of the Rotterdam Study, a single-center prospective follow-up study in persons 55 to 98 years of age, were reviewed for the presence of drusen, pigmentary abnormalities, and atrophic or neovascular age-related macular degeneration.
The prevalence of at least one drusen of 63 microns or larger increased from 40.8% in persons 55 to 64 years of age to 52.6% in those 85 years of age or older. Similarly, the prevalence of the following abnormalities increased significantly in these age categories: drusen of 125 microns or larger from 4.8% to 17.5%, retinal pigment epithelial hypopigmentations from 3.5% to 9.0%, and increased retinal pigment from 3.7% to 15.3%. Atrophic or neovascular age-related macular degeneration was present in 1.7% of the total population. Atrophic age-related macular degeneration increased from 0.1% in persons 55 to 64 years of age to 3.7% in those 85 years of age or older. Neovascular age-related macular degeneration increased from 0.1% to 7.4% in these age groups. No sex differences were observed for these lesions.
The prevalence of atrophic or neovascular age-related macular degeneration is 1.7%. In those 55 years of age or older, the prevalence increases strongly with age and it is similar in men and women. Neovascular age-related macular degeneration was twice as common as atrophic age-related macular degeneration. These findings suggest that age-related maculopathy may be less common in this European population than in similar populations in the United States.
Sibling correlations were evaluated and segregation analysis was performed on age-dependent maculopathy scores of the right and left eyes of individuals from 564 families in the Beaver Dam Eye study. There is evidence of significant sibling correlations. The data fit a mixture of two normal distributions, especially after undergoing the Box and Cox power transformation. In each eye, the hypothesis of mendelian transmission of a major effect cannot be rejected under the tau AB free model, but is rejected under the tau's free model. The hypothesis of a random environmental major effect is rejected. Similar major gene parameter estimates are found for both eyes. The results are consistent with a major effect accounting for 62% and 59%, in the right and left eyes, respectively, of the determination of age-related maculopathy scores. A single major gene can account for about 89% and 97% of this variability due to a major effect, or for about 55% and 57% of the total variability, in the right and left eyes, respectively.
There are conflicting reports regarding the relation of cigarette smoking to age-related maculopathy, a major cause of blindness in the United States. In this report, the authors examined this association in people aged 43-86 years (n = 4,771) who participated in the Beaver Dam Eye Study, Beaver Dam, Wisconsin (1988-1990). Exposure data on cigarette smoking were derived from questions about present and past smoking, duration of smoking, and the number of cigarettes smoked per day. Age-related maculopathy status was determined by grading stereoscopic color fundus photographs using the Wisconsin Age-related Maculopathy Grading System. Smoking status, pack-years smoked, and current exposure to passive smoking were not associated with drusen characteristics (type, area, and confluence) or signs of early age-related maculopathy in any age-sex group studied, except for a higher frequency of increased retinal pigment in males who had ever smoked compared with those who had never smoked. The relative odds for exudative macular degeneration, one form of late age-related maculopathy, in females who were current smokers was 2.50 (95% confidence interval 1.01-6.20) compared with those who were ex-smokers or never smokers; for males, it was 3.29 (95% confidence interval 1.03-10.50). There was no significant relation between smoking status and pure geographic atrophy, another form of late age-related maculopathy. These results suggest that exudative macular degeneration is associated with cigarette smoking and that different forms of macular degeneration may have different etiologies.
Choroidal neovascularization (CNV) is a common cause of legal blindness in developed countries. In patients younger than 50 years of age, CNV can be due to various causes, but to the authors' knowledge there has been no large epidemiologic study to compare the relative incidence of the various causes of CNV in this younger-aged group.
A retrospective study was performed of patients seen over a 30-month period to precisely define the relative incidence of the various etiologies of CNV in patients younger than 50 years of age who had been referred to a tertiary care ophthalmology department in western Europe.
Clinical charts and angiograms of 363 patients were reviewed. The etiology of CNV was high myopia in 225 (62%) patients, pseudo-presumed ocular histoplasmosis syndrome in 42 (12%), angioid streaks in 17 (5%), and miscellaneous hereditary or traumatic or inflammatory disorders in 16 (4%). Choroidal neovascularization could not be related to any etiology in 63 (17%) patients, and was considered to be idiopathic lesions. Choroidal neovascularization was subfoveal in 62% of the patients due to myopia versus 30% to 36% in patients due to other etiologies. Laser photocoagulation was applied in the majority of patients due to all etiologies except myopia.
These data provide the relative incidence of the various etiologies of CNV in young patients and emphasize the importance of myopia as an etiology of CNV in such patients. In addition, an apparent preferential localization of CNV to the subfoveal region in myopic eyes precludes its treatment with photocoagulation.
To examine the association between cigarette smoking and the incidence of age-related macular degeneration (AMD) in men.
Prospective cohort study with average person-years of follow-up for AMD of 12.2 years.
A total of 21 157 US male physicians participating in the Physicians' Health Study who did not have a diagnosis of AMD at baseline, were followed for at least 7 years, and had known levels of baseline smoking. Based on information reported at baseline, 11% were current smokers, 39% were past smokers, and 50% were never smokers.
Incident AMD, defined as a self-report that was confirmed by medical record, review, first diagnosed after randomization, and responsible for vision loss to 20/30 or worse.
A total of 268 incident cases of AMD with vision loss were confirmed. In multivariate analysis, current smokers of 20 or more cigarettes per day, compared with never smokers, had an increased risk of AMD (relative risk [RR], 2.46; 95% confidence interval [CI], 1.60-3.79). Past smokers had a modest elevation in risk of AMD (RR, 1.30; 95% CI, 0.99-1.70). For current smokers of fewer than 20 cigarettes per day, there was a nonsignificant 26% increased risk of AMD (RR, 1.26; 95% CI, 0.61-2.59).
These prospective data provide support for the hypothesis that cigarette smoking increases the risk of developing AMD.
To evaluate the relationship between cigarette smoking and incidence of age-related macular degeneration (AMD) among women.
Prospective cohort study with 12 years of follow-up (1980 to 1992), in which information on smoking habits was updated every 2 years.
Eleven states throughout the United States.
A total of 31 843 registered nurses enrolled in the Nurses' Health Study who were aged 50 to 59 years in 1980 and did not report a diagnosis of cancer or AMD at the beginning of the study. Additional women entered the analytic cohort as they reached 50 years of age.
Incidence of AMD with visual loss.
During 556 338 person-years of follow-up, 215 women were newly diagnosed as having AMD. After adjusting for other risk factors for AMD, women who currently smoked 25 or more cigarettes per day had a relative risk (RR) of AMD of 2.4 (95% confidence interval [CI], 1.4-4.0) compared with women who never smoked. Past smokers of this amount also had a 2-fold increased risk (RR=2.0; 95% CI, 1.2-3.4) relative to never smokers. Compared with current smokers, little reduction in risk was suggested even after quitting smoking for 15 or more years. Risk of AMD also increased with an increasing number of pack-years smoked (P for trend <.001); among women who smoked for 65 or more pack-years, the risk was 2.4 times the risk of never smokers (95% CI, 1.5-3.8). Analyses of dry and exudative types of AMD and other alternative definitions of AMD revealed similar results.
Cigarette smoking is an independent and avoidable risk factor for AMD among women. Because AMD is the most common cause of severe visual impairment among the elderly and treatment is not available or is ineffective for most patients, reducing the risk of this disease is another important reason to avoid smoking.
To assess the relation between cigarette smoking and age-related macular degeneration (AMD) in a population of elderly persons.
A cross-sectional, community-based study.
City district of Rotterdam, the Netherlands.
A total of 6174 persons 55 years and older who participated in the Rotterdam Study. In 36 persons atrophic AMD and in 65 persons neovascular AMD were diagnosed.
Age-related macular degeneration was diagnosed by evaluating fundus transparencies, smoking behavior was identified by interviewing subjects, and the presence of atherosclerosis was assessed by the ankle-arm systolic blood pressure index. Relative risks and 95% confidence intervals (CIs) were calculated using multivariate logistic regression analysis.
In subjects younger than 85 years, current smokers had a 6.6-fold increased risk of neovascular AMD vs those who had never smoked (95% CI, 2.8-15.9). Former smokers had a 3.2-fold increased risk of neovascular AMD vs nonsmokers in this age group (95% CI, 1.4-7.4). These associations were not observed in subjects 85 years or older. Smoking was not associated with atrophic AMD. A strong increased risk of neovascular AMD was present in those who had smoked more than 10 pack-years (relative risk, 6.5; 95% CI, 2.9-14.8). Adjusting the results for atherosclerosis did not change the association. Persons who had quit smoking 20 or more years before the eye examination had no increased risk.
The results provide evidence for a dose-response relationship between smoking and AMD, particularly in persons with the neovascular form of the disease.
To assess the associations between stage of age-related maculopathy (ARM) and current, past, and passive smoking.
A cross-sectional study of 3654 subjects from a defined geographic area west of Sydney, Australia, identified subjects with late age-related macular degeneration (AMD) and early ARM by ocular examination and detailed grading of retinal photographs. Interviewer-administered questionnaires provided data about smoking history for subjects and spouses. Logistic regression, adjusting for age and sex, and 2-way analysis of variance were used to assess associations.
Current tobacco smoking was significantly associated with late AMD (odds ratio [OR], 3.92), including neovascular AMD (OR, 3.20) and geographic atrophy (OR, 4.54), and early ARM (OR, 1.75). Having ever smoked was significantly associated with late AMD (OR, 1.83) but not early ARM. Passive smoking was associated with increased but insignificant odds for late AMD. The risk was slightly higher among women compared with men for most exposure categories.
These findings provide convincing evidence that smoking may be causally associated with ARM. The strongest risk was found for current smokers, suggesting potential benefits of targeting education to older people who are current smokers and have signs of early ARM.
The aim of the study was to describe the incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy. Population: A population of 3583 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied during a 5-year period.
Characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System.
There was a statistically significant increased incidence of age-related maculopathy lesions with age (P < 0.05). Individuals 75 years of age or older had a significantly (P < 0.01) higher 5-year incidence of the following characteristics than people 43 to 54 years of age: larger sized drusen (125-249 microm, 17.6% vs. 2.1%; > or = 250 microm, 6.5% vs. 0.2%), soft indistinct drusen (16.3% vs. 1.8%), retinal pigment abnormalities (12.9% vs. 0.9%), exudative macular degeneration (1.8% vs. 0%), and pure geographic atrophy (1.7% vs. 0%). After adjusting for age, the incidence of early age-related maculopathy was 2.2 times (95% confidence interval 1.6, 3.2) as likely in women 75 years of age or older compared with men this age. At follow-up, late age-related macular degeneration was more likely to develop in eyes with soft indistinct drusen (6.5% vs. 0.1%) or retinal pigmentary abnormalities (7.1% vs. 0.1%) at baseline than in eyes without these lesions. Conclusions: These population-based estimates document the high incidence of signs of age-related maculopathy in people 75 years of age or older, and in women compared with men that age. The findings demonstrate that the presence of soft drusen and pigmentary abnormalities significantly increases the risk for the development of geographic atrophy and exudative macular degeneration.
To examine the prevalence of age-related maculopathy (drusen and retinal pigmentary abnormalities) and end-stage age-related macular degeneration lesions (neovascular maculopathy or geographic atrophy) in a defined older Australian urban population.
All noninstitutionalized residents 49 years of age or older who were identified in a door-to-door census of two postcode areas west of Sydney, Australia.
All participants received a detailed eye examination, including stereoscopic photographs of each macula. Two trained graders used the Wisconsin Age-related Maculopathy Grading System to assess the presence and severity of typical lesions.
A marked age-related increase in all typical lesions of age-related maculopathy and macular degeneration was observed. End-stage age-related macular degeneration was present in 1.9% of the population, rising from 0% among people younger than 55 years of age to 18.5% among those 85 years of age or older. Soft drusen were found in 13.3% of people, with distinct drusen more frequent than indistinct soft drusen. Retinal pigmentary abnormalities were found in 12.6% of people. For end-stage lesions and soft drusen, females had higher age-specific prevalence rates than males, whereas retinal pigmentary abnormalities were more frequent in males, although most of these differences were not significant. Prevalence rates for all lesions were lower (statistically significant for retinal pigmentary abnormalities and soft drusen) than for the United States Beaver Dam Eye Study which examined a similar population.
These data provide detailed prevalence rates for most components of ARM in an Australian population and reinforce the Beaver Dam Eye Study findings for the relative age-specific frequency of age-related macular degeneration components.
The notion that sun exposure is a risk factor for age-related macular degeneration (AMD) is widespread, but studies have not shown this conclusively.
To test the hypothesis that AMD cases have greater ocular sun exposure than control subjects, the authors compared 409 cases with 286 control subjects resident in Newcastle, Australia. Sensitivity to sun and glare of the participants was characterized. Sun exposure was estimated from detailed histories and was validated against sun-seeking or avoidance behavior expected, given sun sensitivity and history of treatment for skin neoplasia.
Contrary to the authors' hypothesis, control subjects had greater median annual ocular sun exposure (865 hours) than cases (723 hours), Mann-Whitney U (U) = 45704, z = -4.9, P > 0.0001. Cases had poorer tanning than did control subjects (mean 2 = 18.2, 4 df, P = 0.001) and as young adults were more sensitive to glare, odds ratio (OR), 2.5; 95% confidence intervals (CIs), 1.8 to 3.5. After stratifying by tanning ability, in the poor-tanning group, the median annual sun exposure of control subjects (685 hours) exceeded that of cases (619 hours), U = 6556, z = -1.9, P = 0.06. Among people who tanned well, control subjects also had significantly greater annual sun exposure than did cases (940 vs. 770 hours), U = 16263, z = -3.7, P = 0.0002.
Sensitivity to glare and poor tanning ability are markers of increased AMD risk. Sun sensitivity confounds study of the postulated AMD-sunlight link. Despite analyses stratified by sun sensitivity, sun exposure was greater in control subjects than in cases with AMD.
To determine whether age-related maculopathy aggregates in families by evaluating whether its prevalence is higher among relatives of case subjects with age-related maculopathy compared with relatives of control subjects without age-related maculopathy.
Individuals with (n = 119) and without (n = 72) age-related maculopathy were identified. First-degree relatives of case and control probands (parents, siblings, or offspring) 40 years of age or older were asked whether they had ever been diagnosed with macular degeneration. Medical records of 177 case and 146 control relatives confirmed the presence or absence of age-related maculopathy.
The prevalence of medical-record confirmed age-related maculopathy was significantly higher among first-degree relatives of case probands (23.7%) compared with first-degree relatives of control probands (11.6%) with an age- and sex-adjusted odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2 to 4.7; P = .013. Relatives of 78 case probands with exudative disease had a significantly higher prevalence of maculopathy (26.9%) compared with relatives of the 72 unaffected control probands (11.6%) (adjusted OR, 3.1; 95% CI, 1.5 to 6.7; P = .003), whereas the prevalence of age-related maculopathy among relatives of 41 probands with dry maculopathy (19.2%) was slightly but not significantly higher (adjusted OR, 1.5; 95% CI, 0.6 to 3.7; P = .36).
The prevalence of age-related maculopathy among first-degree relatives of subjects with age-related maculopathy, particularly with exudative disease, is greater than among first-degree relatives of subjects without this disease. Results suggest that macular degeneration has a familial component and that genetic or shared environmental factors, or both, contribute to its development.
To date, a number of reports have been published on the relation of cigarette smoking to age-related maculopathy, an important cause of blindness in the United States. However, few studies have examined the relation between smoking and the incidence of age-related maculopathy. In this report, the authors examine this association in persons aged 43-86 years (n = 3,583) at baseline who were participants in the baseline examination and 5-year follow-up of the Beaver Dam Eye Study, Beaver Dam, Wisconsin (1988-1990 and 1993-1995). Exposure data on cigarette smoking were obtained from questions about present and past smoking, duration of smoking, and the number of cigarettes smoked per day. Age-related maculopathy status was determined by grading stereoscopic color fundus photographs using the Wisconsin Age-related Maculopathy Grading System. After controlling for age, sex, vitamin supplement use, and beer consumption, men who smoked greater amounts of cigarettes were more likely to develop early age-related maculopathy (odds ratio (OR) per 10 pack-years smoked = 1.06, 95% confidence interval (CI) 1.00-1.13, p = 0.06) than men who had smoked less. This association was not observed in women. Men (OR = 3.21, 95% CI 1.09-9.45) and women (OR = 2.20, 95% CI 1.04-4.66) who were current smokers at the time of the baseline examination had significantly higher odds of developing large drusen (> or = 250 microns in diameter) after 5 years than those who had never smoked or who quit before the baseline study. Current or past history of cigarette smoking was not related to the incidence of retinal pigment epithelial depigmentation. The authors conclude that smoking appears to be related to the incidence of some lesions associated with early age-related maculopathy.
To assess the associations between age-related macular degeneration (ARMD) and smoking.
The POLA study is a population-based study taking place in the town of Sète, located on the French Mediterranean Sea border. The presence of early and late ARMD was assessed in 2196 participants on the basis of 50 degrees color fundus photographs using an international classification system.
After adjustment for age and sex, current and former smokers showed an increased prevalence of late ARMD (odds ratio [OR] = 3.6, 95% confidence interval [CI] = 1.1-12.4; OR = 3.2, 95% CI = 1.3-7.7, respectively). An increased risk was present in participants who smoked more than 20 pack-years (OR = 3.0, 95% CI = 0.9-9.5 for 20-39 pack-years; OR = 5.2, 95% CI = 2.0-13.6 for 40 pack-years and more). In addition, the risk of late ARMD remained increased until 20 years after cessation of smoking (OR = 9.0, 95% CI = 3.0-27.0 for 1-9 years; OR = 4.0, 95% CI = 1.3-12.0 for 10-19 years; OR = 1.3, 95% CI = 0.4-4.3 for 20 years and more). Smoking was not significantly associated with early signs of ARMD.
This study further confirms the adverse effect of tobacco on late ARMD. Former smokers seem to remain at high risk for ARMD.