Age-related macular degeneration accounts for more than 54% of all vision loss in the white population in the USA. An estimated 8 million Americans are affected with early age-related macular degeneration, of whom over 1 million will develop advanced age-related macular degeneration within the next 5 years. In the UK, age-related macular degeneration is the cause of blindness in almost 42% of those who go blind aged 65–74 years, almost two-thirds of those aged 75–84 years, and almost three-quarters of those aged 85 years or older.

Macular degeneration is more likely to be found in Caucasians than in people of African descent.

Studies indicate drusen associated with AMD are similar in molecular composition to Beta-Amyloid (βA) plaques and deposits in other age-related diseases such as Alzheimer's disease and atherosclerosis. This suggests that similar pathways may be involved in the etiologies of AMD and other age-related diseases.

Optic disc drusen are found clinically in about 1% of the population but this increases to 3.4% in individuals with a family history of ODD. About two thirds to three quarters of clinical cases are bilateral. A necropsy study of 737 cases showed a 2.4% incidence with 2 out of 15 (13%) bilateral, perhaps indicating the insidious nature of many cases. An autosomal dominant inheritance pattern with incomplete penetrance and associated inherited dysplasia of the optic disc and its blood supply is suspected. Males and females are affected at equal rates. Caucasians are the most susceptible ethnic group. Certain conditions have been associated with disc drusen such as retinitis pigmentosa, angioid streaks, Usher syndrome, Noonan syndrome and Alagille syndrome. Optic disc drusen are not related to Bruch membrane drusen of the retina which have been associated with age-related macular degeneration.

Vision improves in almost all cases. In rare cases, a patient may suffer permanent visual loss associated with lesions on their optic nerve.

Rarely, coexisting vasculitis may cause neurological complications. These occurrences can start with mild headaches that steadily worsen in pain and onset, and can include attacks of dysesthesia. This type of deterioration happens usually if the lesions involve the fovea.

The most recognized cause of a toxic optic neuropathy is methanol intoxication. This can be a life-threatening event that normally accidentally occurs when the victim mistook, or substituted, methanol for ethyl alcohol. Blindness can occur with drinking as little as an ounce of methanol, but this can be counteracted by concurrent drinking of ethyl alcohol. The patient initially has nausea and vomiting, followed by respiratory distress, headache, and visual loss 18–48 hours after consumption. Without treatment, patients can go blind, and their pupils will dilate and stop reacting to light.

- Ethylene glycol, a component of automobile antifreeze, is a poison that is toxic to the whole body including the optic nerve. Consumption can be fatal, or recovery can occur with permanent neurologic and ophthalmologic deficits. While visual loss is not very common, increased intracranial pressure can cause bilateral optic disc swelling from cerebral edema. A clue to the cause of intoxication is the presence of oxalate crystals in the urine. Like methanol intoxication, treatment is ethanol consumption.

- Ethambutol, a drug commonly used to treat tuberculosis, is notorious for causing toxic optic neuropathy. Patients with vision loss from ethambutol toxicity lose vision in both eyes equally. This initially presents with problems with colors (dyschromatopsia) and can leave central visual deficits. If vision loss occurs while using ethambutol, it would be best to discontinue this medication under a doctor’s supervision. Vision can improve slowly after discontinuing ethambutol but rarely returns to baseline.

- Amiodarone is an antiarrhythmic medication commonly used for abnormal heart rhythms (atrial or ventricular tachyarrythmias). Most patients on this medication get corneal epithelial deposits, but this medication has also been controversially associated with NAION. Patients on amiodarone with new visual symptoms should be evaluated by an ophthalmologist.

- Tobacco exposure, most commonly through pipe and cigar smoking, can cause an optic neuropathy. Middle-aged or elderly men are often affected and present with painless, slowly progressive, color distortion and visual loss in both eyes. The mechanism is unclear, but this has been reported to be more common in individuals who are already suffering from malnutrition.

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.

In ischemic optic neuropathies, there is insufficient blood flow (ischemia) to the optic nerve. The anterior optic nerve is supplied by the short posterior ciliary artery and choroidal circulation, while the retrobulbar optic nerve is supplied intraorbitally by a pial plexus, which arises from the ophthalmic artery, internal carotid artery, anterior cerebral artery, and anterior communicating arteries. Ischemic optic neuropathies are classified based on the location of the damage and the cause of reduced blood flow, if known.

- Anterior ischemic optic neuropathy (AION) includes diseases that affect the optic nerve head and cause swelling of the optic disc. These diseases often cause sudden rapid visual loss in one eye. Inflammatory diseases of the blood vessels, like giant cell arteritis, polyarteritis nodosa, Churg-Strauss syndrome, granulomatosis with polyangiitis, and rheumatoid arthritis can cause arteritic AIONs (AAION). The vast majority of AIONs are nonarteritic AIONs (NAION). The most common acute optic neuropathy in patients over 50 years of age, NAION has an annual incidence of 2.3-10.2/100,000. NAION presents as a painless loss of vision, often when awakening, that occurs over hours to days. Most patients lose the lower half of their visual field (an inferior altitudinal loss), though superior altitudinal loss is also common. The pathophysiology of NAION is unknown, but it is related to poor circulation in the optic nerve head. NAION is often associated with diabetes mellitus, elevated intraocular pressure (acute glaucoma, eye surgery), high cholesterol, hypercoagulable states, a drop in blood pressure (bleeding, cardiac arrest, peri-operative esp. cardiac and spine procedures), and sleep apnea. Rarely, amiodarone, interferon-alpha, and erectile dysfunction drugs have been associated with this disease.

- Posterior ischemic optic neuropathy is a syndrome of sudden visual loss with optic neuropathy without initial disc swelling with subsequent development of optic atrophy. This can occur in patients who are predisposed to AAION and NAION as described above as well as those who had cardiac and spine surgery or serious episodes of hypotension.

- Radiation optic neuropathy (RON) is also thought to be due to ischemia of the optic nerve that occurs 3 months to 8 or more years after radiation therapy to the brain and orbit. It occurs most often around 1.5 years after treatment and results in irreversible and severe vision loss, which may also be associated with damage to the retina (radiation retinopathy). This is thought to be due to damage to dividing glial and vascular endothelial cells. RON can present with transient visual loss followed by acute painless visual loss in one or both eyes several weeks later. The risk of RON is significantly increased with radiation doses over 50 Gy.

- There is also some evidence that interferon treatment (pegylated interferon with ribavirin) for hepatitis C virus can cause optic neuropathy.

The cause of the inflammation remains unknown, with various theories of it occurring as an autoimmune response to a mild infection, or the possibility of it being viral because of the preceding flu-like illness that generally accompanies it. It is usually associated with HLA-B7 and HLA-DR2.

Despite its name, the "presumed" relationship of POHS to "Histoplasma capsulatum" is controversial. The fungus has rarely been isolated from cases with POHS, the condition has also been found in locations where histoplasmosis is rare, and there appears to be a relationship with tobacco smoking.

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.

Risk factors for retinal detachment include severe myopia, retinal tears, trauma, family history, as well as complications from cataract surgery.

Retinal detachment can be mitigated in some cases when the warning signs are caught early. The most effective means of prevention and risk reduction is through education of the initial signs, and encouragement for people to seek ophthalmic medical attention if they have symptoms suggestive of a posterior vitreous detachment. Early examination allows detection of retinal tears which can be treated with laser or cryotherapy. This reduces the risk of retinal detachment in those who have tears from around 1:3 to 1:20. For this reason, the governing bodies in some sports require regular eye examination.

Trauma-related cases of retinal detachment can occur in high-impact sports or in high speed sports. Although some recommend avoiding activities that increase pressure in the eye, including diving and skydiving, there is little evidence to support this recommendation, especially in the general population. Nevertheless, ophthalmologists generally advise people with high degrees of myopia to try to avoid exposure to activities that have the potential for trauma, increase pressure on or within the eye itself, or include rapid acceleration and deceleration, such as bungee jumping or roller coaster rides.

Intraocular pressure spikes occur during any activity accompanied by the Valsalva maneuver, including weightlifting. An epidemiological study suggests that heavy manual lifting at work may be associated with increased risk of rhegmatogenous retinal detachment, but this relationship is not strong. In this study, obesity also appeared to increase the risk of retinal detachment. A high Body Mass Index (BMI) and elevated blood pressure have been identified as a risk factor in non-myopic individuals.

Genetic factors promoting local inflammation and photoreceptor degeneration may also be involved in the development of the disease.

Other risk factors include the following:

- Glaucoma

- AIDS

- Cataract surgery

- Diabetic retinopathy

- Eclampsia

- Family history of retinal detachment

- Homocysteinuria

- Malignant hypertension

- Metastatic cancer, which spreads to the eye (eye cancer)

- Retinoblastoma

- Severe myopia

- Smoking and passive smoking

- Stickler syndrome

- Von Hippel-Lindau disease

Retinal degeneration is the deterioration of the retina caused by the progressive and eventual death of the cells of the retina. There are several reasons for retinal degeneration, including artery or vein occlusion, diabetic retinopathy, R.L.F./R.O.P. (retrolental fibroplasia/ retinopathy of prematurity), or disease (usually hereditary). These may present in many different ways such as impaired vision, night blindness, retinal detachment, light sensitivity, tunnel vision, and loss of peripheral vision to total loss of vision. Of the retinal degenerative diseases retinitis pigmentosa (RP) is a very important example.

Inherited retinal degenerative disorders in humans exhibit genetic and phenotypic heterogeneity in their underlying causes and clinical outcomes*. These retinopathies affect approximately one in 2000 individuals worldwide. A wide variety of causes have been attributed to retinal degeneration, such as disruption of genes that are involved in phototransduction, biosynthesis and folding of the rhodopsin molecule, and the structural support of the retina. Mutations in the rhodopsin gene account for 25% to 30% (30% to 40% according to) of all cases of autosomal dominant retinitis pigmentosa (adRP) in North America. There are many mechanisms of retinal degeneration attributed to rhodopsin mutations or mutations that involve or affect the function of rhodopsin. One mechanism of retinal degeneration is rhodopsin overexpression. Another mechanism, whereby a mutation caused a truncated rhodopsin, was found to affect rod function and increased the rate of photoreceptor degeneration.

- *For example, a single peripherin/RDS splice site mutation was identified as the cause of retinopathy in eight families; the phenotype in these families ranged from retinitis pigmentosa to macular degeneration.

All people with "diabetes mellitus" are at riskthose with Type I diabetes and those with Type II diabetes. The longer a person has diabetes, the higher their risk of developing some ocular problem. Between 40 and 45 percent of Americans diagnosed with diabetes have some stage of diabetic retinopathy. After 20 years of diabetes, nearly all patients with Type I diabetes and >60% of patients with Type II diabetes have some degree of retinopathy; however, these statistics were published in 2002 using data from four years earlier, limiting the usefulness of the research. The subjects would have been diagnosed with diabetes in the late 1970s, before modern fast acting insulin and home glucose testing.

Prior studies had also assumed a clear glycemic threshold between people at high and low risk of diabetic retinopathy.

However, it has been shown that the widely accepted WHO and American Diabetes Association diagnostic cutoff for diabetes of a fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl) does not accurately identify diabetic retinopathy among patients. The cohort study included a multi-ethnic, cross-sectional adult population sample in the US, as well as two cross-sectional adult populations in Australia. For the US-based component of the study, the sensitivity was 34.7% and specificity was 86.6%. For patients at similar risk to those in this study (15.8% had diabetic retinopathy), this leads to a positive predictive value of 32.7% and negative predictive value of 87.6%.

Published rates vary between trials, the proposed explanation being differences in study methods and reporting of prevalence rather than incidence values.

During pregnancy, diabetic retinopathy may also be a problem for women with diabetes.

It is recommended that all pregnant women with diabetes have dilated eye examinations each trimester to protect their vision.

People with Down's syndrome, who have extra chromosome 21 material, almost never acquire diabetic retinopathy. This protection appears to be due to the elevated levels of endostatin, an anti-angiogenic protein, derived from collagen XVIII. The collagen XVIII gene is located on chromosome 21.

Presumed ocular histoplasmosis syndrome (POHS) is a syndrome affecting the eye, which is characterized by peripheral atrophic chorioretinal scars, atrophy or scarring adjacent to the optic disc and maculopathy.

The loss of vision in POHS is caused by choroidal neovascularization.

Usually being asymptomatic, drusen are typically found during routine eye exams where the pupils have been dilated.

Familial exudative vitreoretinopathy (FEVR) ( ) is a genetic disorder affecting the growth and development of blood vessels in the retina of the eye. This disease can lead to visual impairment and sometimes complete blindness in one or both eyes. FEVR is characterized by exudative leakage and hemorrhage of the blood vessels in the retina, along with incomplete vascularization of the peripheral retina. The disease process can lead to retinal folds, tears, and detachments.

The prognosis for CSR is generally excellent. Whilst immediate vision loss may be as poor as 20/200 in the affected eye, clinically over 90% of patients regain 20/30 vision or better within 6 months.

Once the fluid has resolved, by itself or through treatment, visual acuity should continue to improve and distortion should reduce as the eye heals. However, some visual abnormalities can remain even if visual acuity is measured at 20/20, and lasting problems include decreased night vision, reduced color discrimination, and localized distortion caused by scarring of the sub-retinal layers.

Complications include subretinal neovascularization and pigment epithelial detachment.

The disease can re-occur causing progressive vision loss. There is also a chronic form, titled as type II central serous retinopathy, which occurs in approximately 5% of cases. This exhibits diffuse rather than focalized abnormality of the pigment epithelium, producing a persistent subretinal fluid. The serous fluid in these cases tends to be shallow rather than dome shaped. Prognosis for this condition is less favorable and continued clinical consultation is advised.

A cone dystrophy is an inherited ocular disorder characterized by the loss of cone cells, the photoreceptors responsible for both central and color vision.

CSR is a fluid detachment of macula layers from their supporting tissue. This allows choroidal fluid to leak beneath the retina. The buildup of fluid seems to occur because of small breaks in the retinal pigment epithelium.

CSR is sometimes called "idiopathic CSR" which means that its cause is unknown. Nevertheless, stress appears to play an important role. An oft-cited but potentially inaccurate conclusion is that persons in stressful occupations, such as airplane pilots, have a higher incidence of CSR.

CSR has also been associated with cortisol and corticosteroids. Persons with CSR have higher levels of cortisol. Cortisol is a hormone secreted by the adrenal cortex which allows the body to deal with stress, which may explain the CSR-stress association. There is extensive evidence to the effect that corticosteroids (e.g. cortisone), commonly used to treat inflammations, allergies, skin conditions and even certain eye conditions, can trigger CSR, aggravate it and cause relapses. In a study documented by Indian Journal of Pharmacology, a young male was using Prednisolone and began to display subretinal fluid indicative of CSR. With the discontinuation of the steroid drop the subretinal fluid resolved and did not show any sign of recurrence. Thus indicating the steroid was the probable cause of the CSR. A study of 60 persons with Cushing's syndrome found CSR in 3 (5%). Cushing's syndrome is characterized by very high cortisol levels. Certain sympathomimetic drugs have also been associated with causing the disease.

Evidence has also implicated helicobacter pylori (see gastritis) as playing a role. It would appear that the presence of the bacteria is well correlated with visual acuity and other retinal findings following an attack.

Evidence also shows that sufferers of MPGN type II kidney disease can develop retinal abnormalities including CSR caused by deposits of the same material that originally damaged the glomerular basement membrane in the kidneys.

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE) primarily occurs in adults (with a mean age of 27). Symptoms include blurred vision in both eyes, but the onset may occur at a different time in each eye. There are yellow-white placoid lesions in the posterior pole at the level of the RPE. Some suggest a genetic predisposition to the disease, while others postulate an abnormal immune response to a virus.

Specific characteristics regarding the white dots and predicted etiology are presented of selected diseases.

Treatment is based

on the stage of the disease. Stage 1 does not

require treatment and

should be observed. 4

Neovascularization

(stage 2) responds well

to laser ablation or

cryotherapy.2,4 Eyes

with retinal detachments (stages

3 through 5) require surgery, with

earlier stages requiring scleral

buckles and later stages ultimately

needing vitrectomy. 2,4

More recently, the efficacy of

anti-VEGF intravitreal injections

has been studied. In one study,

these injections, as an in adjunct

with laser, helped early stages

achieve stabilization, but further

investigation is needed.6

Angioid streaks are often associated with pseudoxanthoma elasticum (PXE), but have been found to occur in conjunction with other disorders, including Paget's disease, Sickle cell disease and Ehlers-Danlos Syndrome. These streaks can have a negative impact on vision due to choroidal neovascularization or choroidal rupture. Also, vision can be impaired if the streaks progress to the fovea and damage the retinal pigment epithelium.

At least one type of autosomal dominant cone-rod dystrophy is caused by mutations in the guanylate cyclase 2D gene (GUCY2D) on chromosome 17.

The incidence of retinal detachment in otherwise normal eyes is around 5 new cases in 100,000 persons per year. Detachment is more frequent in middle-aged or elderly populations, with rates of around 20 in 100,000 per year. The lifetime risk in normal individuals is about 1 in 300. Asymptomatic retinal breaks are present in about 6% of eyes in both clinical and autopsy studies.

- Retinal detachment is more common in people with severe myopia (above 5–6 diopters), in whom the retina is more thinly stretched. In such patients, lifetime risk rises to 1 in 20. About two-thirds of cases of retinal detachment occur in myopics. Myopic retinal detachment patients tend to be younger than non-myopic ones.

- Retinal detachment is more frequent after surgery for cataracts. The estimated long-term prevalence of retinal detachment after cataract surgery is in the range of 5 to 16 per 1000 cataract operations, but is much higher in patients who are highly myopic, with a prevalence of up to 7% being reported in one study. One study found that the probability of experiencing retinal detachment within 10 years of cataract surgery may be about 5 times higher than in the absence of treatment.

- Tractional retinal detachments can also occur in patients with proliferative diabetic retinopathy or those with proliferative retinopathy of sickle cell disease. In proliferative retinopathy, abnormal blood vessels (neovascularization) grow within the retina and extend into the vitreous. In advanced disease, the vessels can pull the retina away from the back wall of the eye, leading to tractional retinal detachment.

Although retinal detachment usually occurs in just one eye, there is a 15% chance of it developing in the other eye, and this risk increases to 25–30% in patients who have had a retinal detachment and cataracts extracted from both eyes.