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Macular Degeneration

Age-related macular degeneration (AMD) is visual impairment due to changes in the macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy, the area responsible for high-acuity vision Vision Ophthalmic Exam. It is marked by central vision Vision Ophthalmic Exam loss with peripheral vision Vision Ophthalmic Exam relatively spared. Risk factors include advanced age, smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases, family history Family History Adult Health Maintenance, and cardiovascular disease. The 2 types of AMD are exudative (wet) or non-exudative (dry). The difference between these 2 types is the presence of choroidal neovascularization in wet AMD, which manifests as visual distortion Distortion Defense Mechanisms or loss. The more frequently occurring dry AMD is usually asymptomatic but in a minority of cases leads to vision Vision Ophthalmic Exam loss. There is no treatment for early dry AMD but Age-Related Eye Disease Study 2 (AREDS 2) supplements are recommended for advanced disease. Inhibitors of vascular endothelial growth factor Vascular endothelial growth factor A family of angiogenic proteins that are closely-related to vascular endothelial growth factor a. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. Wound Healing are used for wet AMD.

Last updated: Jul 6, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Age-related macular degeneration (AMD):

  • Degenerative changes Degenerative Changes Spinal Stenosis involving the macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy, the central part of the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy, that cause central vision Vision Ophthalmic Exam impairment
  • Often affects bilateral vision Vision Ophthalmic Exam, but can be asymmetrical
  • Peripheral vision Vision Ophthalmic Exam is rarely lost.

Anatomy

  • Macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy
    • An oval area at the center of the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy, where light is focused by the lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy and cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy
    • Contains the fovea Fovea An area approximately 1. 5 millimeters in diameter within the macula lutea where the retina thins out greatly because of the oblique shifting of all layers except the pigment epithelium layer. It includes the sloping walls of the fovea (clivus) and contains a few rods in its periphery. In its center (foveola) are the cones most adapted to yield high visual acuity, each cone being connected to only one ganglion cell. Eye: Anatomy, which holds the highest density of cone cells (photoreceptors sensitive to colors under bright light conditions)
    • Function: 
      • Central, high-acuity, and color vision Color Vision Function of the human eye that is used in bright illumination or in daylight (at photopic intensities). Photopic vision is performed by the three types of retinal cone photoreceptors with varied peak absorption wavelengths in the color spectrum (from violet to red, 400 – 700 nm). Ophthalmic Exam
      • Provides the ability to read, drive, and see in great detail 
  • Other structures:
    • Photoreceptor cells in outer retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy: light-sensing rods and cones
    • Retinal pigment epithelium Retinal Pigment Epithelium The single layer of pigment-containing epithelial cells in the retina, situated closely to the tips (outer segments) of the retinal photoreceptor cells. These epithelial cells are macroglia that perform essential functions for the photoreceptor cells, such as in nutrient transport, phagocytosis of the shed photoreceptor membranes, and ensuring retinal attachment. Hypertensive Retinopathy (RPE)
      • Protects from damaging effects of sunlight
      • Eliminates waste products and damaged cells
      • Regulates transport of nutrients
    • Bruch’s membrane:
      • Barrier and filter separating the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy from blood vessels
      • A defect can be a site of blood vessel growth.
    • Capillary bed in the inner choroid Choroid The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. Eye: Anatomy (choriocapillaris): 
      • Nourishment and oxygen to RPE and outer layers of the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy 
      • Main blood supply for fovea Fovea An area approximately 1. 5 millimeters in diameter within the macula lutea where the retina thins out greatly because of the oblique shifting of all layers except the pigment epithelium layer. It includes the sloping walls of the fovea (clivus) and contains a few rods in its periphery. In its center (foveola) are the cones most adapted to yield high visual acuity, each cone being connected to only one ganglion cell. Eye: Anatomy

Classification

  • Dry AMD (non-exudative or atrophic)
    • 90% of all cases
    • Often asymptomatic with gradual onset of visual changes 
    • In a minority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: advances to central visual-field loss or wet AMD
    • Associated with drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome:
      • Deposits of extracellular material or waste beneath the RPE
      • Few are found in people > 50 years old as part of aging.
    • Increased size and/or number of drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome → AMD
  • Wet AMD (exudative or neovascular)
    • 10% of cases but accounts for majority of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with advanced AMD
    • Presents as insidious or rapid progression of central vision Vision Ophthalmic Exam loss
  • Caused by growth of abnormal blood vessels in the subretinal space Subretinal Space Retinal Detachment, frequently from the choroidal circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment (choroidal neovascularization (CNV))

Epidemiology

  • The leading cause of  irreversible blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity in developed countries
  • Worldwide prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of 8.7%
  • Women are affected more than men. 
  • Risk factors:
    • Advanced age: ↑ incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency in > 60 years of age
    • Caucasians Caucasians Esophageal Cancer > African Americans or Hispanics
    • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases 
    • Heavy alcohol use (> 3 drinks per day)
    • Family history Family History Adult Health Maintenance 
    • Genetic predisposition (complement H gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics)
    • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
    • Hypercholesterolemia Hypercholesterolemia A condition with abnormally high levels of cholesterol in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population. Lipid Disorders
    • Cardiovascular disease
    • HIV HIV Anti-HIV Drugs/ AIDS AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS
    • Chronic myeloproliferative disease
    • Cataract Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). Neurofibromatosis Type 2 surgery
  • Decrease the risk of AMD: ↑ fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing intake, ↑ omega-3, and omega-6 polyunsaturated fatty acids Fatty acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated. Fatty Acids and Lipids

Pathophysiology

Dry AMD

  • Exact mechanism is still unclear.
  • Known risk factors (such as aging and genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics), oxidative stress Oxidative stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products. Cell Injury and Death, and inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation lead to pathologic changes:
    • Aging Bruch’s membrane: membrane thickens and accumulates apolipoproteins → ↑ inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and debris  →  nodular basal deposits become soft drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome
    • RPE degeneration → dissociates from Bruch’s membrane → RPE dysfunction → photoreceptor loss
    • Loss of choriocapillaris:  
      • Correlates with ↑ size and number of soft drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome 
      • Precedes the damage of RPE (geographic atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation)

Wet AMD

  • Risk factors + oxidative stress Oxidative stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products. Cell Injury and Death + activated complement → inflammatory changes 
  • Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation → RPE and other retinal cells secrete vascular endothelial growth factor Vascular endothelial growth factor A family of angiogenic proteins that are closely-related to vascular endothelial growth factor a. They play an important role in the growth and differentiation of vascular as well as lymphatic endothelial cells. Wound Healing (VEGF)-A and vasculogenic molecules → CNV and RPE dysfunction
  • New immature blood vessels grow from the choroid Choroid The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. Eye: Anatomy → perforate Bruch’s membrane and extend toward the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy
  • These blood vessels leak fluid and blood below or within the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy → RPE detachment and hemorrhage

Related videos

Clinical Presentation

Dry AMD

  • Symptoms
    • Asymptomatic in most cases
    • As disease progresses:
      • Difficulty with night vision Vision Ophthalmic Exam
      • Visual fluctuation
      • Reading difficulty
      • Cannot make out faces
      • Prolonged time to adapt to low light levels
      • Metamorphopsia (distorted straight lines) in advanced disease
  • Signs (funduscopic examination and slit-lamp biomicroscopy)
    • Yellow-white deposits ( drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome) between Bruch’s membrane and RPE
    • RPE pigmentary mottling: increased pigmentation
    • Geographic (RPE) atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation
      • Seen in advanced dry AMD
      • Hypopigmentation Hypopigmentation A condition caused by a deficiency or a loss of melanin pigmentation in the epidermis, also known as hypomelanosis. Hypopigmentation can be localized or generalized, and may result from genetic defects, trauma, inflammation, or infections. Malassezia Fungi or depigmentation Depigmentation Vitiligo of the RPE
      • Represents cell death Cell death Injurious stimuli trigger the process of cellular adaptation, whereby cells respond to withstand the harmful changes in their environment. Overwhelmed adaptive mechanisms lead to cell injury. Mild stimuli produce reversible injury. If the stimulus is severe or persistent, injury becomes irreversible. Apoptosis is programmed cell death, a mechanism with both physiologic and pathologic effects. Cell Injury and Death in adjacent areas of RPE and photoreceptors 
  • Stages
    • Early stage: 
      • > 15 small drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome or < 20 medium-sized drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome
      • No vision Vision Ophthalmic Exam loss
    • Intermediate stage:
      •  At least 1 large druse, ≥ 20 drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome or non-central geographic atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation ( fovea Fovea An area approximately 1. 5 millimeters in diameter within the macula lutea where the retina thins out greatly because of the oblique shifting of all layers except the pigment epithelium layer. It includes the sloping walls of the fovea (clivus) and contains a few rods in its periphery. In its center (foveola) are the cones most adapted to yield high visual acuity, each cone being connected to only one ganglion cell. Eye: Anatomy not involved)
      • May have vision Vision Ophthalmic Exam loss
    • Advanced stage: 
      • Central geographic atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation ( fovea Fovea An area approximately 1. 5 millimeters in diameter within the macula lutea where the retina thins out greatly because of the oblique shifting of all layers except the pigment epithelium layer. It includes the sloping walls of the fovea (clivus) and contains a few rods in its periphery. In its center (foveola) are the cones most adapted to yield high visual acuity, each cone being connected to only one ganglion cell. Eye: Anatomy involved)
      • Noticeable vision Vision Ophthalmic Exam loss

Wet AMD

  • Symptoms
  • Signs (funduscopic examination and slit-lamp biomicroscopy)
    • Neovascularization in the macula Macula An oval area in the retina, 3 to 5 mm in diameter, usually located temporal to the posterior pole of the eye and slightly below the level of the optic disk. It is characterized by the presence of a yellow pigment diffusely permeating the inner layers, contains the fovea centralis in its center, and provides the best phototropic visual acuity. It is devoid of retinal blood vessels, except in its periphery, and receives nourishment from the choriocapillaris of the choroid. Eye: Anatomy: gray-green discoloration 
    • Subretinal hemorrhage
    • Retinal pigment epithelial detachments (PEDs): separation of RPE from Bruch’s membrane
    • Subretinal lipid deposits on occasions
    • Disciform scars

Diagnosis

  • Clinical findings, dilated funduscopic examination with slit-lamp biomicroscopy
  • Amsler grid Amsler Grid Ophthalmic Exam test: detects metamorphopsias and scotomas Scotomas A localized defect in the visual field bordered by an area of normal vision. This occurs with a variety of eye diseases (e.g., retinal diseases and glaucoma); optic nerve diseases, and other conditions. Chorioretinitis
  • Angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery
    • Fundus Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Stomach: Anatomy fluorescein Fluorescein A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor. Pseudomonas angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery (FFA):
      • IV injection of fluorescein Fluorescein A phthalic indicator dye that appears yellow-green in normal tear film and bright green in a more alkaline medium such as the aqueous humor. Pseudomonas dye, which follows the course of choroid Choroid The thin, highly vascular membrane covering most of the posterior of the eye between the retina and sclera. Eye: Anatomy and retinal vessels
      • Hypofluorescence: hemorrhage
      • Hyperfluorescence: drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome, RPE atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation, CNV membranes, serous PEDs 
    • Indocyanine green angiography Angiography Radiography of blood vessels after injection of a contrast medium. Cardiac Surgery
      • Uses a water-soluble tricarbocyanine dye
      • Detects choroidal neovascularization  and PEDs
  • Ocular coherence Coherence A view of the world and the individual’s environment as comprehensible, manageable, and meaningful, claiming that the way people view their life has a positive influence on their health. Neurological Examination tomography (OCT)
    • Non-invasive imaging test utilizing light waves
    • Produces high-resolution cross-sectional retinal images
    • Detection of:
      • Drusen Drusen Colloid or hyaline bodies lying beneath the retinal pigment epithelium. They may occur either secondary to changes in the choroid that affect the pigment epithelium or as an autosomal dominant disorder of the retinal pigment epithelium. Nephritic Syndrome as nodular elevation of RPE
      • Retinal edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and subretinal fluid
    • Monitors treatment response in wet AMD
  • Color fundus Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Stomach: Anatomy photography: used to monitor AMD
  • Fundus Fundus The superior portion of the body of the stomach above the level of the cardiac notch. Stomach: Anatomy autofluorescence Autofluorescence Cystoisospora/Cystoisosporiasis and Cyclospora/Cyclosporiasis
    • No contrast
    • Identifies lipofuscin accumulation (↑ in cellular aging)
    • Defines areas of geographic atrophy Atrophy Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. Cellular Adaptation
Amsler grid

1. Amsler grid Amsler Grid Ophthalmic Exam: normal vision Vision Ophthalmic Exam (left); 2. Amsler grid Amsler Grid Ophthalmic Exam: AMD with metamorphopsia (right). Note the distorted lines.

Image: “ Amsler Grid Amsler Grid Ophthalmic Exam” by Africa Regional Medical Advisor: Fred Hollows Foundation, Kigali, Rwanda. License: CC BY 2.0

Management

Dry AMD

  • For all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship: smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation
  • Monitoring of progression with regular Regular Insulin follow-up
  • For intermediate AMD and advanced AMD: AREDS 2 (Age-Related Eye Disease Study 2) supplement daily
    • Vitamin C Vitamin C A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. Water-soluble Vitamins and their Deficiencies 500 mg
    • Vitamin E Vitamin E A generic descriptor for all tocopherols and tocotrienols that exhibit alpha-tocopherol activity. By virtue of the phenolic hydrogen on the 2h-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of isoprenoids. Fat-soluble Vitamins and their Deficiencies 400 international units (IU)
    • Zinc Zinc A metallic element of atomic number 30 and atomic weight 65. 38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with anemia, short stature, hypogonadism, impaired wound healing, and geophagia. It is known by the symbol zn. Trace Elements oxide 80 mg
    • Cupric oxide 2 mg
    • Lutein 10 mg
    • Zeaxanthin 2 mg

Wet AMD

  • AREDS 2
  • Intravitreal anti-VEGF 
    • First-line therapy; antiangiogenic
    • Ranibizumab: 
      • Recombinant humanized antibody fragment ( Fab Fab Univalent antigen-binding fragments composed of one entire immunoglobulin light chain and the amino terminal end of one of the immunoglobulin heavy chains from the hinge region, linked to each other by disulfide bonds. Fab contains the immunoglobulin variable regions, which are part of the antigen-binding site, and the first immunoglobulin constant regions. This fragment can be obtained by digestion of immunoglobulins with the proteolytic enzyme papain. Immunoglobulins: Types and Functions) that binds VEGF
      • 0.5 mg monthly for 3 months
    • Bevacizumab Bevacizumab An anti-vegf humanized murine monoclonal antibody. It inhibits vegf receptors and helps to prevent pathologic angiogenesis. Targeted and Other Nontraditional Antineoplastic Therapy
      • Monoclonal antibody against VEGF
      • 1.25 mg monthly for 3 months
      • Lower cost than ranibizumab
    • Aflibercept: 
      • Recombinant fusion protein Fusion protein Proteins that catalyze membrane fusion. Measles Virus that acts as a VEGF receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors decoy
      • 2 mg every month for 3 months then every 2 months
    • Adverse effects: 
      • Endophthalmitis Endophthalmitis Endophthalmitis is an inflammatory process of the inner layers of the eye, which may be either infectious or sterile. Infectious endophthalmitis can lead to irreversible vision loss if not treated quickly. Based on the entry mode of the infectious source, endophthalmitis is divided into endogenous and exogenous types. Endophthalmitis
      • Increased intraocular pressure Increased intraocular pressure An ocular disease, occurring in many forms, having as its primary characteristics an unstable or a sustained increase in the intraocular pressure which the eye cannot withstand without damage to its structure or impairment of its function. The consequences of the increased pressure may be manifested in a variety of symptoms, depending upon type and severity, such as excavation of the optic disk, hardness of the eyeball, corneal anesthesia, reduced visual acuity, seeing of colored halos around lights, disturbed dark adaptation, visual field defects, and headaches. Osmotic Diuretics 
      • Retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment
      • Thrombotic events reported
    • Thermal laser photocoagulation
      • Rarely used due to recurrence of disease and poor visual outcomes
    • Photodynamic therapy Photodynamic Therapy Actinic Keratosis
      • Application of light of specific wavelength and IV administration of verteporfin
      • Results in slowed CNV progression
      • Rarely used but an option in cases of failed anti-VEGF treatment
    • Surgery
      • Intravitreal tissue plasminogen Plasminogen Precursor of plasmin (fibrinolysin). It is a single-chain beta-globulin of molecular weight 80-90, 000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. Hemostasis activator with pneumatic displacement Displacement The process by which an emotional or behavioral response that is appropriate for one situation appears in another situation for which it is inappropriate. Defense Mechanisms
      • Required in rare cases of submacular hemorrhage

Differential Diagnosis

  • Cataracts: a decrease in vision Vision Ophthalmic Exam due to clouding of the lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy, which presents as painless, blurry vision Vision Ophthalmic Exam and glare problems. Cataracts are the leading cause of blindness Blindness The inability to see or the loss or absence of perception of visual stimuli. This condition may be the result of eye diseases; optic nerve diseases; optic chiasm diseases; or brain diseases affecting the visual pathways or occipital lobe. Retinopathy of Prematurity worldwide. The condition can occur at any age, but most cases affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment those > 60 years old.
  • Diabetic retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome: a visual impairment due to microvascular end-organ damage from diabetes mellitus Diabetes mellitus Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus. Diabetic retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome is classified as non-proliferative Non-Proliferative Fibrocystic Change and proliferative retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome. Non-proliferative Non-Proliferative Fibrocystic Change retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome is characterized by microaneurysms, intraretinal hemorrhages, exudates, and macular edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. The distinguishing feature of the proliferative type is the presence of retinal or optic disc Optic disc The portion of the optic nerve seen in the fundus with the ophthalmoscope. It is formed by the meeting of all the retinal ganglion cell axons as they enter the optic nerve. Eye: Anatomy neovascularization. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are initially asymptomatic but in the late stages present with decreased or fluctuating vision Vision Ophthalmic Exam, possibly with floaters Floaters Chorioretinitis.
  • Retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment: separation of the retina Retina The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outermost layer is pigmented, whereas the inner nine layers are transparent. Eye: Anatomy from the retinal pigment epithelium Retinal Pigment Epithelium The single layer of pigment-containing epithelial cells in the retina, situated closely to the tips (outer segments) of the retinal photoreceptor cells. These epithelial cells are macroglia that perform essential functions for the photoreceptor cells, such as in nutrient transport, phagocytosis of the shed photoreceptor membranes, and ensuring retinal attachment. Hypertensive Retinopathy. This results in rapid photoreceptor damage. Symptoms include painless vision Vision Ophthalmic Exam changes such as sudden flashes of light, floaters Floaters Chorioretinitis, worsening peripheral vision Vision Ophthalmic Exam, or having a shadow in the field of vision Vision Ophthalmic Exam. Retinal detachment Retinal detachment Retinal detachment is the separation of the neurosensory retina from the retinal pigmented epithelium and choroid. Rhegmatogenous retinal detachment, the most common type, stems from a break in the retina, allowing fluid to accumulate in the subretinal space. Retinal Detachment is a medical emergency requiring corrective surgery.

References

  1. Ambati, J., Fowler, B. (2012 ) Mechanism of age-related Macular Degeneration. https://pubmed.ncbi.nlm.nih.gov/22794258/
  2. Arroyo, J., Gardiner, M., Schmader, K., Givens, J. (2020). Age-related macular degeneration: Treatment and prevention. UpToDate. Retrieved September 18, 2020, from https://www.uptodate.com/contents/age-related-macular-degeneration-treatment-and-prevention?search=macular%20degeneration&source=search_result&selectedTitle=1~66&usage_type=default&display_rank=1
  3. Arroyo, J., Gardiner, M., Schmader, K., Givens, J. (2020). Age-related macular degeneration: Clinical presentation, etiology, and diagnosis. UpToDate. Retrieved September 18, 2020, from https://www.uptodate.com/contents/age-related-macular-degeneration-clinical-presentation-etiology-and-diagnosis?search=macular%20degeneration&source=search_result&selectedTitle=2~66&usage_type=default&display_rank=2
  4. Handa, J., Rickman, C., Dick, A., Gorin, M., Miller, J., Toth, C.,Ueffing, M., Zarbin, M., Farrer, L. (2019). A systems biology approach towards understanding and treating non-neovascular age-related macular degeneration. Nature 10, 3347. https://doi.org/10.1038/s41467-019-11262-1
  5. Jonas, JB, Cheung, C., Panda-Jonas, S. (2017). Updates on the Epidemiology of Age-related Macular Degeneration. Asia Pacific J Ophthalmol 6 (6):493-497. doi: 10.22608/APO.2017251
  6. Maturi, R., Franklin, A. (2018). Nonexudative (Dry) Age-Related Macular Degeneration. Medscape. Retrieved September 19, 2020, from https://emedicine.medscape.com/article/1223154-overview
  7. Prall, F.R., Ciulla, T.,  Dahl, A. (2019). Exudative (Wet) Age-Related Macular Degeneration. Medscape. Retrieved September 19, 2020, from https://emedicine.medscape.com/article/1226030-overview

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