Geographic atrophy (GA) is a chronic disease, which leads to visual function loss. This often results in difficulties performing daily tasks such as reading, recognizing faces, and driving, and ultimately has severe consequences on independence.

Initially, patients often have good visual acuity if the GA lesions are not involved in the central macular, or foveal, region of the retina. As such, a standard vision test may underrepresent the visual deficit experienced by patients who report challenges reading, driving or seeing in low light conditions.

Drusen, from the German word for "node" or "geode" (singular, "Druse"), are tiny yellow or white accumulations of extracellular material that build up between Bruch's membrane and the retinal pigment epithelium of the eye. The presence of a few small ("hard") drusen is normal with advancing age, and most people over 40 have some hard drusen. However, the presence of larger and more numerous drusen in the macula is a common early sign of age-related macular degeneration (AMD).

Geographic Atrophy (GA), also known as atrophic age-related macular degeneration (AMD) or advanced dry AMD, is an advanced form of age-related macular degeneration that can result in the progressive and irreversible loss of retina (photoreceptors, retinal pigment epithelium, choriocappillaris) which can lead to a loss of visual function over time. It is estimated that GA affects >5 million people worldwide and approximately 1 million patients in the US, which is similar to the prevalence of neovascular (wet) AMD, the other advanced form of the disease.

The incidence of advanced AMD, both geographic atrophy and neovascular AMD, increases exponentially with age and while there are therapies for wet AMD, GA currently has no approved treatment options. The aim of most current clinical trials is to reduce the progression of GA lesion enlargement.

Drusen are associated with aging and macular degeneration are distinct from another clinical entity, optic disc drusen, which is present on the optic nerve head. Both age-related drusen and optic disc drusen can be observed by ophthalmoscopy. Optical coherence tomography scans of the orbits or head, calcification at the head of the optic nerve without change in size of globe strongly suggests drusen in a middle-age or elderly patient.

Whether drusen promote AMD or are symptomatic of an underlying process that causes both drusen and AMD is not known, but they are indicators of increased risk of the complications of AMD.

'Hard drusen' may coalesce into 'soft drusen' which is a manifestation of macular degeneration.

Signs and symptoms of macular degeneration include:

- Visual symptoms

- Distorted vision in the form of metamorphopsia, in which a grid of straight lines appears wavy and parts of the grid may appear blank: Patients often first notice this when looking at things like miniblinds in their home or telephone poles while driving. There may also be central scotomas, shadows or missing areas of vision

- Slow recovery of visual function after exposure to bright light (photostress test)

- Visual acuity drastically decreasing (two levels or more), e.g.: 20/20 to 20/80

- Blurred vision: Those with nonexudative macular degeneration may be asymptomatic or notice a gradual loss of central vision, whereas those with exudative macular degeneration often notice a rapid onset of vision loss (often caused by leakage and bleeding of abnormal blood vessels).

- Trouble discerning colors, specifically dark ones from dark ones and light ones from light ones

- A loss in contrast sensitivity

Macular degeneration by itself will not lead to total blindness. For that matter, only a very small number of people with visual impairment are totally blind. In almost all cases, some vision remains, mainly peripheral. Other complicating conditions may possibly lead to such an acute condition (severe stroke or trauma, untreated glaucoma, etc.), but few macular degeneration patients experience total visual loss.

The area of the macula comprises only about 2.1% of the retina, and the remaining 97.9% (the peripheral field) remains unaffected by the disease. Even though the macula provides such a small fraction of the visual field, almost half of the visual cortex is devoted to processing macular information.

The loss of central vision profoundly affects visual functioning. It is quite difficult, for example, to read without central vision. Pictures that attempt to depict the central visual loss of macular degeneration with a black spot do not really do justice to the devastating nature of the visual loss. This can be demonstrated by printing letters six inches high on a piece of paper and attempting to identify them while looking straight ahead and holding the paper slightly to the side. Most people find this difficult to do.

Dry (nonexudative, > 80%)—deposition of yellowish extracellular material in and between bruch membrane and retinal pigment epithelium (“drusen”) with gradual loss in vision.

Wet (exudative, 10–15%)—rapid loss of vision due to bleeding secondary to choroidal neovascularization.

Metamorphopsia is a type of distorted vision in which a grid of straight lines appears wavy and parts of the grid may appear blank. People with this condition often first notice this when looking at mini-blinds in their home.

It is mainly associated with macular degeneration, particularly age-related macular degeneration with choroidal neovascularization. Other conditions that can present with complaints of metamorphopsia include pathological myopia, presumed ocular histoplasmosis syndrome, choroidal rupture and multifocal choroiditis.

Intermediate AMD is diagnosed by large drusen and/or any retinal pigment abnormalities. Intermediate AMD may cause some vision loss, however, like Early AMD, it is usually asymptomatic.

Optic disc drusen (ODD) or optic nerve head drusen (ONHD) are globules of mucoproteins and mucopolysaccharides that progressively calcify in the optic disc. They are thought to be the remnants of the axonal transport system of degenerated retinal ganglion cells.

ODD have also been referred to as congenitally elevated or anomalous discs, pseudopapilledema, pseudoneuritis, buried disc drusen, and disc hyaline bodies. They may be associated with vision loss of varying degree occasionally resulting in blindness.

Optic nerve damage is progressive and insidious. Eventually 75% of patients will develop some peripheral field defects. These can include nasal step defects, enlarged blind spots, arcuate scotomas, sectoral field loss and altitudinal defects. Clinical symptoms correlate to visibility of the drusen. Central vision loss is a rare complication of bleeding from peripapillar choroidal neovascular membranes. Anterior ischemic optic neuropathy (AION) is a potential complication.

CNV can create a sudden deterioration of central vision, noticeable within a few weeks. Other symptoms which can occur include colour disturbances, and metamorphopsia (distortions in which straight lines appears wavy). Hemorrhaging of the new blood vessels can accelerate the onset of symptoms of CNV. CNV may also include the feeling of pressure behind your eye.

Cornea verticillata, also called Fleischer vortex, vortex keratopathy or whorl keratopathy, is a condition characterised by corneal deposits at the level of the basal epithelium forming a faint golden-brown whorl pattern. It is seen in Fabry disease or in case of prolonged amiodarone intake.

Choroidal neovascularization (CNV) is the creation of new blood vessels in the choroid layer of the eye. Choroidal neovascularization is a common cause of neovascular degenerative maculopathy (i.e. 'wet' macular degeneration) commonly exacerbated by extreme myopia, malignant myopic degeneration, or age-related developments.

Onset : Early childhood

Progression: Chronic progressive

Clinical: Cerebellar ataxia plus syndrome / Optic Atrophy Plus Syndrome

Ocular: Optic atrophy, nystagmus, scotoma, and bilateral retrobulbar neuritis.

Other: Mental retardation, myoclonic epilepsy, spasticity, and posterior column sensory loss. Tremor in some cases.

Musculoskeletal

Contractures, lower limbs, Achilles tendon contractures, Hamstring contractures, Adductor longus contractures

Systemic

Hypogonadotrophic hypogonadism.

Macular edema occurs when fluid and protein deposits collect on or under the macula of the eye (a yellow central area of the retina) and causes it to thicken and swell (edema). The swelling may distort a person's central vision, because the macula holds tightly packed cones that provide sharp, clear, central vision to enable a person to see detail, form, and color that is directly in the centre of the field of view.

Fleischer rings are pigmented rings in the peripheral cornea, resulting from iron deposition in basal epithelial cells, in the form of hemosiderin. They are usually yellowish to dark-brown, and may be complete or broken.

They are named for Bruno Fleischer.

Fleischer rings are indicative of keratoconus, a degenerative corneal condition that causes the cornea to thin and change to a conic shape.

Cystoid macular edema (CME) involves fluid accumulation in the outer plexiform layer secondary to abnormal perifoveal retinal capillary permeability. The edema is termed "cystoid" as it appears cystic; however, lacking an epithelial coating, it is not truly cystic. The cause for CME can be remembered with the mnemonic "DEPRIVEN" (diabetes, epinepherine, pars planitis, retinitis pigmentosa, Irvine-Gass syndrome, venous occlusion, E2-prostaglandin analogues, nicotinic acid/niacin).

Diabetic macular edema (DME) is similarly caused by leaking macular capillaries. DME is the most common cause of visual loss in both proliferative, and non-proliferative diabetic retinopathy.

The experience of amaurosis fugax is classically described as a temporary loss of vision in one or both eyes that appears as a black "curtain coming down vertically into the field of vision in one eye;" however, this altitudinal visual loss is relatively uncommon. In one study, only 23.8 percent of patients with transient monocular vision loss experienced the classic "curtain" or "shade" descending over their vision. Other descriptions of this experience include a monocular blindness, dimming, fogging, or blurring. Total or sectorial vision loss typically lasts only a few seconds, but may last minutes or even hours. Duration depends on the cause of the vision loss. Obscured vision due to papilledema may last only seconds, while a severely atherosclerotic carotid artery may be associated with a duration of one to ten minutes. Certainly, additional symptoms may be present with the amaurosis fugax, and those findings will depend on the cause of the transient monocular vision loss.

Behr syndrome is characterized by the association of early-onset optic atrophy with spinocerebellar degeneration resulting in ataxia, pyramidal signs, peripheral neuropathy and developmental delay.

Although it is an autosomal recessive disorder, heterozygotes may still manifest much attenuated symptoms. Autosomal dominant inheritance also being reported in a family. Recently a variant of OPA1 mutation with phenotypic presentation like Behr syndrome is also described. Some reported cases have been found to carry mutations in the OPA1, OPA3 or C12ORF65 genes which are known causes of pure optic atrophy or optic atrophy complicated by movement disorder.

Some confusion exists between Fleischer rings and Kayser-Fleischer rings. Kayser-Fleischer rings are caused by copper deposits, and are indicative of Wilson's disease, whereas Fleischer rings are caused by iron deposits. One example of a medical condition that can present with Fleischer rings is Keratoconus.

Ocular causes include:

- Iritis

- Keratitis

- Blepharitis

- Optic disc drusen

- Posterior vitreous detachment

- Closed-angle glaucoma

- Transient elevation of intraocular pressure

- Intraocular hemorrhage

- Coloboma

- Myopia

- Orbital hemangioma

- Orbital osteoma

- Keratoconjunctivitis sicca

The preferred name is "dense deposit disease". Most cases of dense deposit disease do not show a membranoproliferative pattern, A 2012 review considers DDD to be in a continuum with C3 glomerulonephritis, one reason the use of type I to type III classification system is falling out of favour.

Most cases are associated with the dysregulation of the alternative complement pathway.

Spontaneous remissions of MPGN II are rare, approximately half of those affected with MPGN II will progress to end stage renal disease within 10 years.

In many cases, people with MPGN II can develop drusen which is caused by same deposits within the Bruch's membrane beneath the retinal pigment epithelium (RPE) layer of the eye. Over time vision can deteriorate and subretinal neovascular membranes, macular detachment, and central serous retinopathy develop.

Membranoproliferative glomerulonephritis ("MPGN"), also known as mesangiocapillary glomerulonephritis, is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating complement and damaging the glomeruli.

MPGN accounts for approximately 4% of primary renal causes of nephrotic syndrome in children and 7% in adults.

It should not be confused with membranous glomerulonephritis, a condition in which the basement membrane is thickened, but the mesangium is not.

Phakomatoses are inconsistently defined, and there is a lack of consensus about what conditions are included in this category.

Conditions included are:

- Ataxia telangiectasia

- Incontinentia pigmenti

- Neurofibromatosis

- Nevoid basal cell carcinoma syndrome

- Sturge-Weber syndrome

- Tuberous sclerosis

- Wyburn-Mason syndrome (Bonnet–Dechaume–Blanc syndrome)

- von Hippel-Lindau disease

Phakomatoses refers to a group of neuro-oculo-cutaneous syndromes or neurocutaneous disorders involving structures arising from the embryonic ectoderm. These multisystem disorders involve the ectodermal structures like central nervous system, skin and eyes. The lesions have a variable severity. However, it has been subsequently noted that mesodermal and endodermal tissues too are involved.

A number of genetic and acquired diseases come in this category and may affect one or more of these tissues. However, in some conditions, such as von Hippel-Lindau disease, ectodermal presentation is minimal.