Each eye has three primary membranes: the cornea and sclera (external membrane), the uvea (middle membrane), and the retina (innermost membrane).

The vitreous is attached to the lens and occupies the space between the lens and the retina; the attachment is firm in young individuals and becomes weaker with age. This structure represents two-thirds of the volume of the eye and is filled with vitreous fluid, a clear, jelly-like substance made up primarily of water, with approximately 1% to 2% of the components being soluble proteins, salts, and hyaluronic acid [22]. Vitreous fluid has many functions: it transmits light, supports the posterior surface of the lens, helps to hold the retina against the retinal pigment epithelium, and transports nutrients to the cornea. During natural aging, vitreous fluid may shrink or thicken, causing tiny strands or clumps to form, the cause of muscae volitantes or so-called floaters (small spots or threads that appear in the field of vision).

The act of vision is made possible by a process that is similar to the function of a camera. The cornea transmits and focuses light into the eye, and the intrinsic muscles of the iris constrict and expand to control the size of the pupil, allowing the appropriate amount of light to enter the eye. The contraction and relaxation of the muscles of the ciliary body change the shape of the lens, helping the eye to focus and allowing for a sharp image to form on the surface of the retina. The central point for focusing of the image (the visual axis) is the fovea.

The human retina contains approximately 100 million rods and 5 million cones. Rods allow vision in dim light, and cones facilitate vision in bright light (daylight). Cones also provide color perception and high spatial resolution. Rods are responsible for peripheral vision, and the macula provides the central 10 degrees of vision. Most cones are located within the macula. The fovea is made up exclusively of cones and provides for the best visual acuity. In contrast, there are no rods or cones in the area of the retina where the optic nerve leaves the eye; as such, this area is known as the eye's blind spot.

Among children, the rate of appropriate eye examinations is also low, as is the rate of follow-up examinations for children who failed visual acuity screening[33]. For example, a survey of pediatricians showed that preschool vision screening was done on 36% of children 3 years of age, 58% of children 4 years of age, and 73% of children 5 years of age[33]. Respondents gave many reasons for the lack of screening, with the most common reasons being that children were not cooperative (39%) and that testing is time-consuming (21%)[33].

Pupils should be equal, round, and reactive to light (which is documented as the acronym PERRL). It is fairly common for there to be subtle inequalities (up to 0.4 mm) in the size of the two pupils, but this inequality is normal only if the asymmetry remains constant during changes in ambient light [39]. In assessing anisocoria (unequal pupils), the first two questions should be: Is there a normal light reaction? Is anisocoria worse in darkness or light? If the light reaction is poor in the eye with a larger pupil, the pupillary constrictor of that eye is abnormal; if the light reaction is good in both eyes, the pupillary dilator of the eye with smaller pupil is abnormal [39]. Anisocoria that is worse in light and accompanied by ptosis and paresis of extraocular muscles may be indicative of intracranial aneurysm. Anisocoria may indicate Horner syndrome if ipsilateral ptosis and anhidrosis are also present. Other possible causes of unequal pupils include trauma-related damage to the iris and pupil and palsy of the third cranial nerve. Irregularly shaped pupils are most commonly related to an intraocular problem, such as congenital anomaly, inflammation, or trauma.

Visual acuity is usually measured with a wall-mounted Snellen chart. Patients are asked to cover one eye and read the line of the smallest letters they can at a distance of 20 feet; the test is then repeated with the other eye covered. The lines of letters on the chart correspond to specified visual acuity based on what a person with "normal vision" can see at various distances. A smaller version (to scale) of the Snellen chart is the Rosenbaum card, which can be held 14 inches away from the patient.

Testing of visual acuity in children who cannot communicate verbally is done by evaluating the ability to fix and follow an object (cross-cover test), and this may be carried out binocularly and monocularly[27,37]. For older children, visual acuity can be assessed with vision testing machines or a variety of picture cards and wall charts (e.g., LEA symbols, Snellen letters or numbers, tumbling E test, or HOTV test)[27,37]. The guideline developed by the AAP in conjunction with other organizations includes detailed information on these tests and how to perform and interpret them[41].

Approximately 75% of adults older than 40 years of age have ametropia requiring refraction correction [8,43]. However, many refractive errors are not sufficiently corrected and are, as such, the leading cause of mild visual impairment [43]. Among all adults, myopia occurs more frequently than hyperopia (25% vs. 10%), and hyperopia is more common in women than men; both myopia and hyperopia have been found to be more common in White adults than in Hispanic or Black adults [43]. A high degree of myopia has been associated with a higher risk of ocular diseases that may lead to vision loss (e.g., glaucoma, cataract, retinal detachment).

Conjunctivitis is inflammation of the membrane that lines the underneath surface of the eyelids and the exposed surface of the sclera. Of the so-called red-eye-associated conditions, conjunctivitis is encountered most often by primary care clinicians and is one of the most common diagnoses in family practice [52]. One study found that more than 80% of all cases of acute conjunctivitis are diagnosed by non-ophthalmologists [52]. The condition is most often caused by the highly contagious adenoviruses; other causes include infectious micro-organisms, chemicals, mechanical eye irritation, allergies, immune-mediated factors, and neoplastic diseases [10]. In general, bacterial conjunctivitis is uncommon, and fungal or parasitic cases are rare. Any ocular chemical irritants, foreign bodies, or trauma can introduce conjunctivitis. These noninfectious agents cause inflammation in only the affected eye. The features and treatment differ according to the type of conjunctivitis. Conjunctivitis rarely causes permanent vision loss or structural damage but is a socioeconomic burden because of lost work or school time and the cost of medical visits and treatment [10].

Conjunctivitis is inflammation of the membrane that lines the underneath surface of the eyelids and the exposed surface of the sclera. Of the so-called red-eye-associated conditions, conjunctivitis is encountered most often by primary care clinicians and is one of the most common diagnoses in family practice [52]. One study found that more than 80% of all cases of acute conjunctivitis are diagnosed by non-ophthalmologists [52]. The condition is most often caused by the highly contagious adenoviruses; other causes include infectious micro-organisms, chemicals, mechanical eye irritation, allergies, immune-mediated factors, and neoplastic diseases [10]. In general, bacterial conjunctivitis is uncommon, and fungal or parasitic cases are rare. Any ocular chemical irritants, foreign bodies, or trauma can introduce conjunctivitis. These noninfectious agents cause inflammation in only the affected eye. The features and treatment differ according to the type of conjunctivitis. Conjunctivitis rarely causes permanent vision loss or structural damage but is a socioeconomic burden because of lost work or school time and the cost of medical visits and treatment [10].

The primary risk factor for bacterial and fungal keratitis is contact lens use; other common risk factors are pre-existing ocular disease and ocular trauma[55,58].Pseudomonas aeruginosa,Staphylococcus aureus, and other coagulase-negative staphylococci are the most common causative micro-organisms[58]. Treatment with topical antibiotic should be empiric, and the eye should not be patched[10,59]. Bacterial keratitis carries a heavy burden: in 2010, 930,000 physician office and outpatient clinic visits and 58,000 emergency department visits were for bacterial keratitis or contact lens disorders[60]. The estimated cost was $175 million in direct healthcare expenditures annually[60]. This burden calls for clinicians to heighten awareness of proper hygiene among their patients who wear contact lenses, emphasizing several points (Table 9) [61].

Uveitis is inflammation of the uvea, or the iris, ciliary body, and choroid; the condition is categorized by site: anterior, intermediate, and posterior uveitis and panuveitis [59]. The cause of uveitis is usually unclear. It may follow certain acute infections, toxin exposures, or bruising of the eye. Cytomegalovirus (CMV), herpes viruses, Pneumocystis jiroveci, and toxoplasmosis are the most common causes of infectious uveitis [59]. On occasion, uveitis is a "herald sign" of an unrecognized autoimmune disorder or granulomatous disease (e.g., sarcoidosis, tuberculosis, histoplasmosis).

Patients with endophthalmitis should be referred to an ophthalmologist immediately, as prompt treatment is crucial to preserving vision [62]. Cultures of aspirate from the aqueous and vitreous should be done to determine the causative organism [62]. Treatment of endophthalmitis after cataract surgery usually consists of intravitreal injection of antibiotics, and primary vitrectomy may be done, although its benefit is unclear [69]. Treatment outcomes depend on the causative organism, with outcomes best for cases of Gram-positive coagulase-negative infections, followed by Gram-negative and S. aureus infections [69]. Endogenous endophthalmitis is most often treated with both systemic and intravitreal antibiotics, and vitrectomy is sometimes done [68]. The most commonly used intravitreal antibiotics are vancomycin (for Gram-positive infections) and ceftazidime (for Gram-negative infections) [59,68]. Other potential treatments being investigated for the management of endophthalmitis include perioperative prophylaxis with antibiotics and adjunctive steroid therapy [72,73].

Inflammation of the optic nerve is most often associated with a demyelinating disease, especially multiple sclerosis. In fact, optic neuritis is considered to be an early indicator of multiple sclerosis, with the disease subsequently developing in more than 50% of individuals [76]. Other possible causes include infection (e.g., meningitis, Lyme disease, syphilis, viral infection), tumor metastasis, and chemicals or medications; the cause is often unknown [59]. Optic neuritis occurs most often in individuals 20 to 40 years of age [59].

Treatment with warm compresses will help alleviate the symptoms of an external hordeolum, and the condition usually resolves spontaneously within a few days [62]. No treatment has been found to shorten the time to resolution. An external hordeolum does not grow; if the mass becomes enlarged, the patient should be evaluated for a neoplasm [62]. A systematic review of treatments for acute internal hordeolum showed no evidence for or against a variety of treatments that included warm (or hot) compresses, lid scrubs, antibiotics, or glucocorticoids [85].

Dry eye is classified as mild, moderate, severe, and severe and/or disabling, according to several factors, including severity and frequency of discomfort, visual symptoms, conjunctival injection and staining, corneal staining, corneal/tear signs, and lid/meibomian gland abnormalities, as well as the fluorescein tear break-up time and the Schirmer score [19]. The AAO recommends treatment according to the severity of the condition. For mild dry eye, recommendations include environmental modifications (avoidance of dry, drafty environments; use of a humidifier; and avoidance of secondary smoke), discontinuation of offending topical or systemic medications, artificial tears, warm compresses and eyelid scrubs, treatment of contributing ocular conditions (such as blepharitis), and correction of eyelid abnormalities [19]. In addition to these treatments, anti-inflammatory agents, such as topical cyclosporine, lifitegrast, and corticosteroids; systemic omega-3 fatty acids supplements and punctal plugs are options for moderate dry eye [86]. Although omega-3 fatty acid products have been used for treatment of dry eye, a prospective randomized 12-month trial of 3,000 mg omega-3 fatty acids failed to show any clinical benefit over placebo [19]. Punctal occlusion, with either silicone or collagen plugs, may provide relief for severe dry eye [87]. However, in its Choosing Wisely campaign, the AAO notes that punctal plugs should not be used until other options (artificial tears, lubricants, and compresses) have been used [88] Additional options for severe dry eye include systemic cholinergic agonists, systemic anti-inflammatory agents, mucolytic agents, autologous serum tears, contact lenses, and tarsorrhaphy [19].

Entropion is a condition in which the eyelid margin (usually the lower lid) turns inward so that the eyelashes rub against the cornea and conjunctiva. The primary symptom is irritation of the ocular surface; other signs and symptoms may include redness, excessive tearing, eye discomfort or pain, photophobia, and stringy white mucoid discharge [59].

Eyelid retraction is symptomatic of many congenital and acquired diseases, and its multifactorial etiology includes neurogenic, myogenic, mechanical, and miscellaneous causes [95]. As the most common cause is thyroid ophthalmopathy, the patient's thyroid status should be evaluated.

Eye injuries cover a spectrum of severity, from corneal abrasions caused by minor trauma (e.g., vigorous rubbing or fingernails) to high-velocity penetrating injuries and injuries that cause sudden loss of vision. Corneal abrasions are the most common eye injury treated in the emergency department, followed by foreign body in the external eye. Other injuries include laceration of skin of the eyelid and around the eye, unspecified bruise of the eye, bruise of orbital tissues, and other specified open wound of the ocular adnexa) [101]. The rates of eye injury, as well as the causes of injury, vary according to patient demographics. Understanding the populations at greatest risk of injury and the types of injuries incurred in distinct populations can help clinicians and other healthcare professionals to better target education and prevention strategies.

Several causes of eye injury have been identified as occurring most frequently, and the causes vary according to age and the site of injury. Many consumer products cause eye injuries in the home, sports and recreation also cause a large proportion of eye injuries, and occupational hazards cause eye injuries in the workplace. The home is the most common setting for eye injuries among adults and children, accounting for approximately 69% to 78% of all eye injuries [100,103,105,106]. Among children and adolescents, close to 50% of eye injuries occur in sports and recreational activities [107].

The most common mechanism of eye injury in sports is blunt trauma, which is defined as an injury that occurs when a blunt object that is larger than the orbital opening exerts force on the floor of the orbit or the medial wall, with resultant fractures of the thin bones [120]. Blunt trauma can cause several different types of injury, such as:

The treatment of corneal abrasions (with or without a foreign body) has simplified over the past several years, with adequate healing achieved with minimal treatment. Most corneal abrasions heal without complications, and relieving pain is the primary concern. Oral analgesics and topical nonsteroidal anti-inflammatory drugs (NSAIDs) may be used, but oral analgesics are more cost-effective [137]. One 2017 systematic review of five topical NSAIDs (i.e., 0.1% indomethacin, 0.03% flurbiprofen, 0.5% ketorolac, 1% indomethacin, 0.1% diclofenac) found no strong evidence to support their use [138]. However, other studies indicate that diclofenac 0.1% is effective [137]. Topical NSAIDs should be used for no more than one or two days [137]. Topical mydriatics and cycloplegics were once used to relieve pain, but they are no longer recommended, as evidence has shown no benefit in cases of uncomplicated corneal abrasion [139,140]. Evidence for the use of topical antibiotics is lacking, but they are often prescribed to prevent infection [137,141,142]. If a topical antibiotic is used, an ointment is preferred to drops because it is more lubricating and soothing; erythromycin 0.5% ophthalmic ointment and sulfacetamide 10% ophthalmic ointment are two recommended options [137]. A systematic review found that patching does not reduce pain; in addition, the use of a patch results in a loss of binocular vision [143]. A tetanus booster is not needed for patients with a superficial corneal abrasion when there is no evidence of perforation, infection, or devitalized tissue [144].

Other minor injuries that are encountered in the primary care setting are subconjunctival hemorrhage, small conjunctival lacerations, and minor eyelid lacerations. Subconjunctival hemorrhage is typically a focal, bright red lesion in the underlying white of the sclera. It is usually related to minor trauma or to a contact lens-induced injury [145]. In evaluating the eye, a globe rupture should be ruled out; subconjunctival hemorrhage in the area surrounding the cornea is a sign of globe rupture [135]. In older patients, spontaneous subconjunctival hemorrhage is often associated with hypertension [145]. The condition usually resolves on its own in a few days to a few weeks, and patients should be reassured that the condition is not serious. In infants and children with subconjunctival hemorrhage, nonaccidental trauma should be considered [146].

Primary care clinicians can treat small conjunctival lacerations (less than 1 cm) that do not involve the underlying sclera with a topical antibiotic and close follow-up [147]. Patients with larger lacerations should be referred to an eye specialist, as sutures may be necessary. Examination with a slit-lamp microscope can help to distinguish a conjunctival laceration from a globe rupture [135].

Exposure of an eye to chemicals (liquid, powder, or gas) represents a true ocular emergency, and it is the only injury for which treatment should not be delayed until visual acuity is tested. The eye should be treated immediately on the basis of the history alone, if necessary[50,135]. The severity of an injury caused by exposure to a chemical can range from reversible edema to stromal scarring, calcific band keratopathy, and fibrosis of the iris or ciliary body. Severity will depend on the pH concentration of the chemical, the nature of the chemical, the volume of direct exposure, and the duration of exposure[50,135,149]. An alkali (pH of more than 10) can penetrate the cornea more readily than an acid (pH of less than 4) and thus presents the greater danger; alkali burns are also more common[147,149]. Determining the type of chemical is important, as the mechanism of injury differs between acidic and alkali agents. Examples of alkalis are household cleaning fluids, fertilizer, pesticides, and sparklers and firecrackers[135]. Hydrofluoric acid is the most common cause of acid burns[50,135]. When possible, the patient should be asked to bring in the container or a sample of the chemical. Identification of the chemical can also be obtained from Material Safety Data Sheets, which are required for some occupational sites[51].

Blunt trauma or a high-velocity injury can cause a full-thickness rupture or laceration through the cornea and/or sclera. Because of the high risk of infection and vision loss associated with a mechanical globe injury, it should be considered in every case of eye trauma [51,135]. Blunt trauma to the eye, as from a thrown ball, motor vehicle accident, or assault, can cause a globe rupture, whereas penetrating injury, as from a knife or a small high-velocity projectile, can cause a globe laceration [147]. The most common signs/symptoms are eye pain, redness, tearing, and decreased vision, but a globe injury should be suspected after blunt trauma or a penetrating injury even if these symptoms are absent [147].

Immediate treatment should be given if the occlusion occurred within the past 24 hours. Because of the need for immediate restoration of blood flow to the retina in order to preserve vision, interventions should be implemented before the patient can be seen by an eye specialist. Digital massage of the closed eyelid should be done immediately (for 15 minutes), as it may dislodge an embolus, allowing it to move to a smaller branch of the artery [59]. In addition, the intraocular pressure should be lowered with either a topical hypotensive drug, such as timolol 0.5%, or acetazolamide (oral or intravenous) [59,155]. However, treatment rarely improves visual acuity, and treatment given 72 hours or more after occlusion is unlikely to improve vision [59]. Systemic corticosteroids should be given to patients who have central retinal artery occlusion caused by temporal arteritis.

In MEPEDS, which included children 6 to 72 months of age in Los Angeles County, the prevalence of strabismus was highest for Asian children (3.6%) and lowest for Hispanic/Latino children (2.4%) (Table 13)[48,49]. Different rates were found in the Vision in Preschoolers (VIP) Study, which included children 3 to 5 years of age in five geographically diverse locations. In this older population, the prevalence of strabismus was highest among non-Hispanic White (4.6%) and lowest among Asian children (1.0%)[46].

Cataracts—opacifications of the eye's crystalline lens—are the leading cause of blindness among adults worldwide and are the second leading cause in North America; they are also the overall leading cause of moderate and severe vision impairment[14]. Cataracts affect more than 24 million people older than 40 years of age in the United States, and by 75 years of age, half of all people have cataracts[5,14]. Slow, painless vision loss occurs over years in the eye with a cataract. Due to the cataract's opacity, the patient's pupil may appear gray. The different types of adult-onset cataracts are nuclear, cortical, and subcapsular (posterior and anterior), and mixed. Of the three types, nuclear cataracts develop most frequently in older adults[29]. With nuclear cataracts, central opacification and coloration interfere with visual function. Nuclear cataracts affect distance vision more often than near vision[29]. Cortical cataracts are characterized by light-blocking spokes extending from the outer rim of the lens to its center (Image 1), and patients most often report glare. Posterior subcapsular cataracts, granular opacities in the posterior pole of the cortex that develop under the capsule, cause visual impairment in bright light and glare. With posterior subcapsular cataracts, near vision is affected more often than distance vision[29].

Glaucoma is the fourth leading cause of blindness and moderate and severe vision impairment in the United States and worldwide [14]. An estimated 2.7 million people older than 40 years of age in the United States have glaucoma, and the number is expected to reach 7.3 million by the year 2050. The prevalence of glaucoma is highest among people 70 to 79 years of age (32%), women (50%), and Hispanics (50%) [7,14]. It has been estimated that an additional 2.4 million people in the United States have undetected (and untreated) glaucoma [14]. The prevalence of glaucoma increases with age and occurs twice as frequently in the non-Hispanic Black population (the highest prevalence) than in the non-Hispanic White population [176]. The rate of undiagnosed glaucoma is higher among minority populations compared with the non-Hispanic White population [14].

Age-related macular degeneration, the leading cause of blindness in North America, is a degenerative disease that causes loss of central visual acuity by its effects on the Bruch's membrane, choroid, outer neural retina, and retinal pigment epithelium [188]. Age-related macular degeneration is classified into two forms: neovascular (otherwise known as wet or exudative) and non-neovascular (otherwise known as dry or nonexudative). The slowly progressing, atrophic non-neovascular form is more common than the wet form, affecting approximately 80% of people with age-related macular degeneration; however, the neovascular form is responsible for almost 90% of the severe vision loss due to age-related macular degeneration [188]. Age-related macular degeneration is classified as early, intermediate, and advanced, based on the size and extent of drusen (small yellow deposits that form under the macula) [188].

HIV-related CMV retinitis is treated with anti-CMV agents, such as valganciclovir (oral), ganciclovir (intravenous), ganciclovir followed by valganciclovir, foscarnet (intravenous), or cidofovir (intravenous) [228]. In a guideline on the prevention and treatment of HIV-related opportunistic infections, the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America recommend that the choice of treatment should be individualized, based on the location and severity of the lesions and the level of immunosuppression [228]. Ophthalmologic examination is recommended every three months for individuals with CMV retinitis in whom maintenance therapy has been discontinued; examinations may be done annually after immune reconstitution [228].

The diagnosis of primary vitreoretinal lymphoma includes examination with direct ophthalmoscopy and slit-lamp microscopy. Ancillary studies such as fluorescein angiography and ultrasonography are often useful [221]. Cytologic analysis is the criterion standard for diagnosis, and other tests such as immunocytochemistry, flow cytometry, and polymerase chain reaction testing are also useful [221]. A complete medical and neurologic examination should be carried out to determine the presence of central nervous system lymphoma and to rule out other causes of uveitis, such as sarcoidosis, toxoplasmosis, and tuberculosis. Diagnostic testing should include a chest x-ray, laboratory studies (complete blood count, erythrocyte sedimentation, chemistry levels), neuroimaging of the brain and orbits, vitreous testing, and a lumbar puncture [221].

The various clinical presentations of basal cell carcinoma make diagnosis a challenge, with the lesion being undetected or misidentified in 20% to 40% of cases [227]. The lesions that are most often confused with basal cell carcinoma include papilloma, nevus, hidrocystoma, epidermal inclusion cyst, and squamous cell carcinoma [31]. The clinical features of squamous cell carcinoma also vary widely [223]. Squamous cell carcinoma usually presents as an ulcerated erythematous nodule or superficial erosion on the skin but can also appear as a verrucous papule or plaque. Color also varies, and the lesions may be reddish-brown, pink, or flesh-colored. They typically present as exophytic tumors, ranging in size from a few millimeters to centimeters. Larger lesions may appear crusted, erythematous, or eroded. In contrast to basal cell carcinoma, overlying telangiectasias are uncommon. The margins may be ill defined or well circumscribed [223].