#90564: Disorders and Injuries of the Eye and Eyelid

The primary function of the external membrane is to protect the eye; other functions are filtration of ultraviolet light and refraction. The cornea comprises the anterior portion of the external membrane, and the sclera makes up the posterior portion [21,22]. The cornea has no lymphatic or blood vessels, is approximately 0.55 mm thick, and is made up of five layers. Anterior to posterior, these layers are the epithelium, Bowman's layer, corneal stoma, Descemet's membrane, and endothelium [21]. The epithelium, which is about five to six cells thick, covers the surface of the cornea. Bowman's layer is a strong, thick membrane made up of collagen fibrils arranged in a parallel pattern. This layer protects the cornea from injury. The corneal stroma is the thickest part of the cornea, comprising 90% of the total thickness. It consists primarily of lamellated connective tissue. Descemet's membrane is a layer of specialized basement membrane of endothelial cells that lies between the corneal stroma and the endothelium. A one-cell thick layer, the endothelium keeps the cornea clear by removing water from it.

The epithelium (i.e., the outer surface of the cornea) is coated with a multilayer tear film. The innermost layer of the tear film is the mucoid layer, which provides a hydrophilic layer of the cornea, allowing the tear film to remain on the corneal surface, which is naturally hydrophobic [23]. The mucoid layer is produced by goblet cells, which are found in the bulbar conjunctiva. The middle layer—the thickest layer—is produced by the lacrimal gland and sebaceous glands, primarily the meibomian glands (located in the tarsal plates along the margins of the eyelid) and the glands of Zeis (which open into the hair follicles of the eyelashes). The most external layer of the cornea, which is only a few molecules thick, is the lipid layer. This layer protects the lacrimal layer from evaporation and provides a smooth surface for the cornea.

The sclera, or "white" of the eye, is a dense membrane of collagen-elastic tissue. In the adult eye, the posterior portion of the sclera is approximately 1 mm thick, and it becomes thinner at the equator (a line that divides the eye into anterior and posterior halves). The sclera extends from the limbus at the margin of the cornea to the optic nerve, where it becomes fused with the dural and arachnoid sheaths of the optic nerve [21]. The most anterior portion of the sclera is coated with the bulbar conjunctiva, a thin transparent membrane.

The middle membrane of the eye is the uvea (i.e., uveal tract), a richly vascularized layer with pigmented tissue. The most anterior of the three components of the uvea is the iris, which surrounds the pupil, the black-looking aperture that determines the appropriate amount of light to enter the eye. Pigment in the iris gives the eye color and prevents light from passing through, thus protecting the retina from too much light. Intrinsic muscles on the pupil—the sphincter pupillae and the dilator pupillae—constrict and dilate the pupil, respectively, to allow the appropriate amount of light to enter the eye [24].

Behind the iris is the lens (i.e., the crystalline), a transparent body that is held in place by the suspensory ligaments attached to the anterior part of the ciliary body, a ring made up of epithelial, stromal, and ciliary muscle tissue. Intrinsic muscles on the ciliary body contract and relax to change the shape of the lens, a process referred to as accommodation. This process helps the eye to focus, allowing for a sharp image to form on the surface of the retina [24].

The posterior aspect of the ciliary body is attached to the choroid, a highly vascular layer that extends to the optic nerve. The choroid is thicker at the posterior pole (the area of the retina between the optic disc and the macula) and thinnest at the optic nerve head (optic disc) [22]. In the area of the optic nerve, the outer surface of the choroid is firmly attached to the sclera. The choroid consists of four layers, which are (from internal to external): Bruch's membrane, the choriocapillaris, the stroma, and the suprachoroid [21].

The innermost membrane of the eye is the retina, a thin (0.5 mm), transparent lining made up of several layers of nerve cells and photoreceptors (rods and cones) as well as a single layer of retinal pigment epithelium. The external surface of the retina is in contact with the choroid, and the internal surface is in contact with the vitreous. The center of the retina is the fovea, and the macula is a small area (representing approximately 5% of the retina) around the fovea. Approximately 3 mm to the nasal side of the fovea is the optic disc, where ganglion cell axons exit the eye to form the optic nerve [21]. A central depression in the optic disc is the optic cup. The area of the eye that includes the retina, optic disc, macula, and posterior pole is referred to as the fundus.

There are three fluid-filled structures of the eye: the anterior and posterior chambers and the vitreous body. The anterior chamber occupies the space between the cornea and the iris, and the posterior chamber lies between the iris, suspensory ligaments, and lens. Both of these chambers are filled with aqueous fluid (humor), which is produced in the posterior chamber by the ciliary body and circulates through the pupil into the anterior chamber, supplying oxygen and nutrients to the cornea and iris. Aqueous fluid also helps to maintain the pressure of the eye.

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 purpose of screening eye examinations is to detect occult disease and to identify individuals who are at high risk for such disease. Routine screening eye examinations include external assessment (orbit, lids, conjunctiva, cornea, iris, and pupil), evaluation of corneal reflexes, and assessment of red reflexes on funduscopy (Table 5)[8,25]. Visualization of the fundus with the use of a direct ophthalmoscope is essential for detecting occult eye disease. However, examination of other aspects of the eye can provide important information about the presence or risk of ocular disease. In addition, testing of vision is important, especially for patients with vision-related symptoms or diabetes. In general, a screening eye examination in the primary care setting includes the following components[8,25]:

As with the clinical evaluation for most disease settings, the patient's history provides details that are essential for making an accurate diagnosis. The history should include not only information specific to the eye but also details related to overall health, family eye health, systemic diseases, use of medications (including prescription and nonprescription drugs as well as herbal or vitamin supplements), and vocational and avocational vision requirements [8]. Eye health history should include the patient's self-assessment of his or her current visual function, including the use of corrective lenses; eye-related symptoms; and previous eye disease, injury, surgery, or medications. The family history as it relates to both ocular and systemic disease should be elicited. Because of the influence of lifestyle and environmental factors on the risk of many ocular diseases, the patient should also be asked about his or her occupation, smoking history, alcohol use, and living situation [8,25].

The external examination is directed at evaluating the eyebrows, eyelashes, orbital area, eyelids, lacrimal apparatus, and cornea and sclera [8]. The eyelids are evaluated to ensure that the upper eyelids overlap the iris but not the pupil, that they open and close completely, and that they move symmetrically. Signs of edema, sagging, or lesions in the orbital area should be noted. Retraction of the upper or lower eyelid and use of a penlight allows for examination of the conjunctiva and sclera.

To evaluate eye movement, the clinician should ask the patient to follow a target (light from a penlight) with both eyes into the cardinal fields of gaze. Normal movement is smooth, symmetric, and full [8]. Problems with eye movement may be a sign of systemic disease or a neurologic lesion. For example, poor abduction may be an indicator of Graves eye disease, myasthenia gravis, or palsy of the sixth cranial nerve.

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.

To assess pupillary reaction to light, a penlight is used while the patient fixates on a distant target; dim lighting in the room is best for the assessment. In individuals with normal pupils, there is consensual response to light; that is, both pupils will have equal constriction in response to light shined in one eye. Poor reaction of pupils is suggestive of many conditions, including diabetes, neurologic disease, optic nerve disease, or damage from trauma or surgery. In addition, abnormal reaction may be a sign of a serious ocular problem, such as acute angle-closure glaucoma or uveitis [39].

The size of the pupils can be affected by the use of systemic medications or drugs. Morphine, heroin, and parasympathetic agents (e.g., pilocarpine, demecarium bromide) cause constriction (miosis) of the pupils, and anticholinergic agents cause the pupils to dilate (mydriasis). When evaluation of the pupils demonstrates abnormality, examination with slit-lamp microscopy should be done to rule out causative factors, which may include an occult foreign body, intraocular inflammation or adhesions, a perforating injury, surgical trauma to the iris, and angle-closure glaucoma.

An integral component of all eye examinations is testing of visual acuity, or the quantitative measure of the ability of the eye to see an image in clear focus at a certain distance. Beyond assessing visual acuity in order to determine the need for correction of refractive errors, such testing is important because a loss of visual acuity is a sensitive indicator of occult eye disease [8,25].

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.

The term 20/20 vision applies to the ability to see an image at 20 feet that a person with "normal vision" can see at 20 feet. The ability to see an image at 20 feet that a person with normal vision can see at 40 feet is defined as 20/40 vision. When a patient has visual acuity that is worse than 20/20, the primary care clinician should provide a referral to an eye specialist for assessment of the refractive error and prescription of corrective lenses 8; 25].

In the primary care setting, the patient's visual field is usually assessed with the confrontation visual field exam. With this test, the patient is asked to cover one eye and fixate the contralateral eye on the clinician. The clinician holds up fingers in various quadrants of the field of vision to determine whether there is a deficiency in peripheral vision. Technology available in the specialty setting enables assessment of the visual field with use of the tangent screen exam or automated periphery (a computer program).

A deficiency in the visual field may indicate a lesion of the retina (macular degeneration), optic nerve (optic neuritis, glaucoma), or optic chiasm (tumors, stroke, trauma). The site of the lesion can be identified by mapping the visual field deficit.

The use of a direct ophthalmoscope enables visualization of the retina and the blood vessels of the eye. The fundus is best visualized after dilation of the pupil with eye drops, but a limited view can be achieved through an undilated pupil. In the latter situation, the room should be darkened and the patient should be asked to focus on a far corner of the room.

The red reflex is the term used to describe the reddish-orange reflection of the retina. This reflex can be found by looking through both pupils with the ophthalmoscope at a distance of about 2 feet and then moving to within a few inches of the patient. Evidence of decreased brightness, asymmetry, or the existence of a focal defect should prompt referral to an eye specialist for a comprehensive eye examination [40].

The primary objective of direct ophthalmoscopy is to evaluate the optic disc and the retinal vasculature. The outline of the disc should be clear, and the central area of the physiologic cup should be pale. The retina appears as reddish-orange, and the macula is dark. The retinal arteries should appear bright red, and veins should be slightly purple. It is vital to recognize swelling of the optic disc, as this is usually an indication of a serious condition.

A comprehensive eye examination for adults is done to detect ocular disease, visual dysfunction, or ocular signs of systemic disease [8]. This examination includes all of the components of a screening examination, as well as examination with slit-lamp microscopy and tonometry; other specialized tests may be warranted on the basis of symptoms or findings. A slit-lamp microscope allows for magnified viewing of the eye structures from the cornea to the vitreous. Fluorescein eye drops can be used to aid in the detection of tiny corneal tears or scrapes, foreign objects, or signs of infection.

Tonometry provides a measurement of intraocular pressure, a sign of glaucoma. Two methods are available to measure pressure. With contact applanation tonometry, fluorescein drops and anesthetic eye drops are used and the tonometer is slowly moved toward the eye and makes contact with the cornea. The amount of force needed to temporarily flatten a part of the cornea is measured. This method is preferred to noncontact tonometry (emitting a puff of air to test intraocular pressure) [8,25].

Other tests that may be incorporated into an eye examination include optical coherence tomography, central visual field testing (Amsler grid), gonioscopy, fundus photography, keratometry, pachymetry, glare testing, contrast sensitivity testing, and dry eye assessment [8,25].

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 typical characteristics of conjunctivitis are a red eye, blurred vision that can be cleared with a blink, purulent or watery discharge, and itching [10]. Primary care clinicians should promptly refer patients with conjunctivitis to an ophthalmologist if any of the following is present [10]:

Adenoviral Conjunctivitis

Adenoviral conjunctivitis can be difficult to distinguish from bacterial conjunctivitis. Adenoviral conjunctivitis is more likely to affect both eyes (often sequentially), and the eye discharge is either serous or clear [10]. Preauricular lymphadenopathy and petechial and subconjunctival hemorrhage are also distinctive signs. A rapid, in-office immunodiagnostic test is available to detect adenoviral antigen in specimens of conjunctival fluid [55].

Antimicrobial agents are not effective against adenoviruses, and corticosteroids should also be avoided, as they may actually prolong adenoviral infection [10]. The management of adenoviral conjunctivitis is directed toward symptom relief combined with scrupulous hygiene and other measures to prevent secondary spread of adenovirus conjunctivitis [10]. Artificial tears, cold compresses, and topical vasoconstrictors relieve symptoms. The AAO has noted that there is insufficient evidence to support the use of antiviral agents to treat adenoviral conjunctivitis [10]. Patients and caregivers should be told to wash their hands often, with soap and water rather than sanitizer only; to avoid touching their eyes; and to avoid close contact with others for at least seven days after the onset of symptoms [10].

Conjunctivitis related to herpes simplex or herpes zoster virus should be treated with topical and/or antiviral agents to prevent corneal infection [10]. Options include topical ganciclovir (0.15% gel) or trifluridine (1% solution), or oral acyclovir; oral valacyclovir and famciclovir may also be used [10]. Topical corticosteroids should be avoided. Herpes zoster vaccination should be strongly recommended in patients older than 50 years of age [10].

Bacterial Conjunctivitis

Bacterial conjunctivitis affects either one or both eyes, and eye drainage is either purulent or mucopurulent. Bacterial cultures of eye drainage may be helpful for recurrent, severe, or chronic purulent conjunctivitis [10]. Although bacterial conjunctivitis usually resolves spontaneously and does not cause any serious harm, a systematic review demonstrated that the use of antibiotic eye drops was associated with modest improvements in the rates of clinical and microbiologic remission [55]. No one broad-spectrum antibiotic covers all potential conjunctival bacterial pathogens, and the choice the antibiotic is usually empiric [10]. No specific antibiotic has been found to be superior to another, and factors for choosing may thus focus on convenience and cost [10].

Allergic Conjunctivitis

Primary itchiness is the hallmark of allergic conjunctivitis; drainage from the eye is usually serous or mucoid, and the condition is typically bilateral [10,56]. Allergic conjunctivitis may be treated with over-the-counter antihistamine/vasoconstrictor agent, second-generation topical histamine H1-receptor antagonists, mast-cell stabilizers, or medications that combine antihistamine activity with mast-cell inhibitors [10]. Second-generation topical histamine H1-receptor antagonists are more effective than vasoconstrictor agents [10]. Mast-cell inhibitors include cromolyn, lodoxamide, nedocromil, and pemirolast. Among the combination medications are azelastine, bepotastine, epinastine, ketotifen, and olopatadine. Ketorolac ophthalmic solution, a nonsteroidal anti-inflammatory drug, is also U.S. Food and Drug Administration (FDA) approved for the treatment of allergic conjunctivitis [10]. If such treatment does not adequately control symptoms, a short (one- to two-week) course of low-potency topical corticosteroids may be added to treatment [10]. Other measures to alleviate symptoms include cold compresses, artificial tears, and oral antihistamines, as well as allergen avoidance. If allergic conjunctivitis cannot be controlled with topical medications and oral antihistamines, consultation with an allergist or dermatologist may be helpful [10].

Keratitis is an inflammatory condition of the cornea caused by an adenovirus, herpes simplex virus, bacteria, or fungi[56]. Moderate-to-severe adenoviral keratitis presents with edema of the eyelid, preauricular lymphadenopathy, and chemosis; a punctate pattern is seen on fluorescein staining[56]. Keratitis caused by herpes simplex virus frequently occurs after conjunctivitis, usually involves only one eye, and is often associated with uveitis. Blisters may be present on the eyelid, and fluorescein staining shows classic dendritic corneal lesion[56].

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].

Ultraviolet radiation, as from tanning beds, welding, and photographic flood lamps, can burn the cornea, causing keratitis or keratoconjunctivitis [59]. Symptoms usually occur 8 to 12 hours after exposure [56]. The most common symptoms are pain, redness, swollen eyelids, photophobia, and headache. Treatment includes short-acting cycloplegic drugs, antibiotic solution or ointment, and a patch (over the more severely affected eye) [59]. Ultraviolet keratitis typically resolves within 24 to 48 hours without vision loss; and the eye should be rechecked in 24 hours [59].

Dacryocystitis is the acute or chronic inflammation/infection of the lacrimal sac and is usually accompanied by a blocked nasolacrimal passage [57]. Among adults, dacryocystitis is most often caused by chronic sinusitis or facial trauma; in infants, the most common cause is a nasolacrimal passage that has not formed or opened normally [57]. The medial lower lid location differentiates the swelling from styes and internal hordeolum. Typically, there is redness and swelling over the lacrimal sac and the surrounding lid tissue. An ophthalmologist should be consulted promptly [57].

In North America, the most common causative pathogen is S. aureus. Methicillin-resistant S. aureus (MRSA) is four times more likely to be associated with acute versus chronic dacryocystitis [63].

The most common therapies are oral cephalosporins and amoxicillin/clavulanic acid [63]. These antibiotics are useful against a spectrum of Gram-positive bacteria and some Gram-negative bacteria. Amoxicillin/clavulanic acid is also effective against anaerobes. As almost 30% of bacteria cultured from patients with dacryocystitis are resistant to these empiric antibiotics, further antibiotic therapy should be tailored to lacrimal sac culture results and sensitivity testing [63]. Lacrimal drainage surgery should be considered if nasolacrimal duct obstruction contributes to the patient's dacryocystitis, especially if MRSA is identified [63,64,65].

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).

Symptoms usually develop rapidly, in one or both eyes, and vary according to the location. Anterior uveitis is usually the most symptomatic, causing pain, redness, photophobia, and decreased vision. Intermediate and posterior uveitis are not usually associated with pain, but floaters may develop and vision may decrease. Panuveitis may be associated with all symptoms and signs [59]. The clinical evaluation to diagnose uveitis includes visual acuity testing, funduscopic examination, measurement of ocular pressure, and slit-lamp examination [59]. With anterior uveitis, cells and flare are found in the aqueous humor and keratic precipitates may be present. Features of intermediate uveitis include cells in the vitreous humor and aggregates and condensations of inflammatory cells over the pars plana. Posterior uveitis is also associated with cells in the vitreous humor, as well as with white or yellow-white lesions in the retina and/or choroid, retinal vasculitis, and optic disk edema [59]. Intraocular pressure may be substantially elevated or decreased [62].

Because uveitis is a leading cause of blindness in the United States, urgent referral to an ophthalmologist is recommended [62]. A cycloplegic-mydriatic drug and corticosteroids (given topically or by periocular injection) is the usual treatment, and an agent may be needed to lower intraocular pressure; immunosuppressants may also be part of therapy. Systemic corticosteroids are used for refractory uveitis [59,62]. Systemic treatment with corticosteroids and immunosuppressants was compared with local therapy with a fluocinolone acetonide implant for noninfectious intermediate and posterior uveitis and panuveitis. Compared with systemic therapy, implant therapy was associated with some benefits, including a lower rate of residual active uveitis and improved vision-related quality of life, but improvement in visual acuity did not significantly differ between the two groups, and higher rates of risk for cataract surgery, treatment for high intraocular pressure, and risk for glaucoma were associated with implant therapy [66]. The authors suggested that treatment be individualized according to a patient's specific circumstances. In a seven-year extended follow-up to the study, the authors found that participants randomized to receive systemic therapy had better visual acuity than those who received implant therapy [67].

Infection causes endophthalmitis, an acute, diffuse uveitis [59]. Localized endophthalmitis most commonly occurs as a complication several days after cataract surgery but may also be induced by ocular trauma or foreign bodies [50,62]. Additionally, bacterial endophthalmitis may be endogenous, with the liver, lung, endocardium, urinary tract, and meninges being the most common sources of infection [68]. Symptoms include periocular pain, vision loss, diffuse redness of the conjunctiva, and swollen eyelids [62]. The cornea is often hazy, and a layer of pus may occur on the meniscus (hypopyon).

Most cases are caused by Gram-positive bacteria (most frequently, Gram-positive coagulase-negative micrococci) as well as staphylococcal and streptococcal species [59,69]. Traumatic endophthalmitis occurs more frequently in rural areas than urban settings, as individuals are more likely to be exposed to contaminated soil and animal matter [70]. Staphylococcus and Bacillus cereus infection are usually associated with endophthalmitis following outdoor penetrating trauma to the eye [71].

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].

Scleritis defines focal or diffuse scleral inflammation. It is often linked to systemic autoimmune diseases such as rheumatoid arthritis, HLA-B27 spondyloarthropathy, relapsing polychondritis, systemic lupus erythematosus, rheumatoid arthritis, and necrotizing systemic vasculitis [59,62]. However, at least one-half of the cases are idiopathic. Scleritis usually involves the anterior segment and is defined as diffuse, nodular, or necrotizing [59].

According to the American College of Radiology, contrast-enhanced CT or contrast-enhanced MRI are both appropriate in evaluating orbital cellulitis, uveitis, or scleritis, with CT often performed first during the initial assessment.

(https://acsearch.acr.org/docs/69486/Narrative Last Accessed: November 29, 2023)

Level of Evidence: Expert Opinion/Consensus Statement

Scleritis causes severe pain, which is usually bilateral, and eye movement or palpation will exacerbate the pain [50]. The eye will appear red as a result of inflamed vessels, and symptoms may include tearing, photophobia, tenderness, and decreased visual acuity [59]. Mucopurulent discharge from the eye occurs in approximately 25% of cases [50].

Urgent referral to an ophthalmologist is recommended, as the diagnosis and treatment are challenging [62]. Initial treatment is a systemic corticosteroid. Nonsteroidal anti-inflammatory drugs may be given to manage the overall inflammatory response, and analgesic agents may be needed for pain [59]. Systemic immunosuppressant drugs may be used if there is no response from initial treatment; a rheumatologist should be consulted in such cases [59].

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].

The clinical features of optic neuritis have been thought to differ between adults and children. Among adults, optic neuritis usually involves only one eye, whereas children often have involvement of both eyes [59,77]. In addition, most pediatric cases follow a viral illness. Signs and symptoms among both children and adults include eye pain and vision loss (partial or complete) [59,76,78].

On funduscopy, the optic disk usually appears pale in late stages of optic neuritis; the disk appears normal in early stages of the condition. Magnetic resonance imaging (MRI) is a highly sensitive and specific tool for assessing changes in the optic nerves due to inflammation. Additionally, MRI may help predict the future development of multiple sclerosis in patients presenting for the first time with acute optic neuritis [79].

Treatment has typically involved oral or intravenous corticosteroids, but a systematic review demonstrated no conclusive evidence of benefit of corticosteroids with respect to recovery of normal visual acuity, visual field, or contrast sensitivity [80]. The AAO acknowledges this lack of benefit but notes that high-dose intravenous corticosteroids followed by oral corticosteroids may be appropriate in helping to achieve a shorter time to recovery of vision [13]. In addition, high-dose corticosteroids may also delay the onset of subsequent demyelination among patients with multiple sclerosis [13].

Prognosis regarding vision outcomes differs between adults and children, with the prognosis poorer for children [77]. Visual acuity among adults improves to at least 20/40 within a year in most cases (90% to 95%); 15-year follow-up of adults with optic neuritis demonstrated visual acuity of at least 20/20 in 72% of patients [76,81]. Among children, sustained vision impairment has been reported in 22% [82,83].

Blepharitis, or inflammation of the sebaceous glands or lash follicles of eyelids, affects both adults and children. The condition is categorized anatomically by anterior and posterior blepharitis and may be either acute or chronic. Typical diseases such as atopic allergies, seborrheic dermatitis, rosacea, HIV, and some inflammatory ocular conditions predispose individuals to blepharitis [15,84]. Bacterial infection (usually with staphylococci) is the most common cause of acute blepharitis, and infection may be caused by a virus, most notably herpes simplex or varicella zoster) [15,59]. Chronic blepharitis is usually noninfectious.

Signs and symptoms of blepharitis include redness, a gritty feeling, burning sensation, itchiness, loss of eyelashes, and crusting together of the eyelids during sleep [15]. Photophobia and blurred vision may also develop. Slit-lamp examination is used to diagnose the condition, but there are no specific clinical diagnostic tests to confirm blepharitis [15]. Cultures of the eyelid margin may be useful for patients who have recurrent anterior blepharitis with severe inflammation or for patients who do not have a response to therapy.

The treatment plan usually consists of eyelid margin hygiene (application of warm compresses to the eyes to drain the secretory glands and gentle cleaning of the eyelid margin with a wet then dry cotton-tipped applicator) [15]. If the condition does not resolve, nightly application of a topical antibiotic (e.g., bacitracin or erythromycin) to the eyelid margin may be prescribed [15]. Oral tetracycline or doxycycline is indicated for blepharitis that does not respond to topical antibiotics. Chronic blepharitis cannot be permanently cured; successful management is dependent on patient education and compliance [15]. A systematic review of treatment for chronic blepharitis demonstrated that eyelid margin hygiene often provided symptomatic relief in anterior and posterior blepharitis and that topical antibiotics provided some relief of symptoms and eradicated bacteria in cases of anterior blepharitis [84]. Data on the effectiveness of other treatments, such as topical steroids and oral antibiotics, were inconclusive [84].

A hordeolum, commonly known as a stye, is a focal inflammation of the eyelid, usually caused by bacterial infection [62,85]. An external hordeolum involves the eyelash follicles or accessory glands. A chalazion results from noninfectious occlusion of a meibomian gland [59]. It is difficult to distinguish the two conditions, as both cause swelling of the eyelid and pain. An internal hordeolum is rare and results from infection of a meibomian gland [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 syndrome—also known as keratoconjunctivitis sicca or tear film dysfunction—is a complex, multifactorial condition defined by clinical evidence of corneal and conjunctival dryness and reduced tear secretion [59]. Risk factors for chronic dry-eye syndrome include aging, female gender, cataract surgery, connective tissue disease, vitamin A deficiency, and androgen deficiency [19]. Prolonged use of antihistamines or estrogen replacement therapy is a reversible risk factor. In the United States, an estimated 3.2 million women and 1.7 million men older than 50 years of age are affected by dry-eye syndrome [5]. Approximately 10% of people with significant dry eye have primary Sjögren syndrome [19].

Most patients report feeling a gritty irritation or the sensation of a foreign body in the eye [19,59]. Other symptoms include itching, burning, and photophobia; blurred vision and sharp, stabbing pain may also occur [59]. Symptoms tend to worsen late in the day and after exposure to adverse environmental conditions [19]. No single test is adequate for diagnosing dry-eye syndrome; diagnosis is based on the characteristic symptoms and the clinical appearance [19]. The Schirmer test may also be useful; with this test, a strip of filter paper is placed at the junction of the middle and lateral third of the lower eyelid, and the wetness on the filter paper is measured [59].

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].

Although entropion is usually a result of advanced age, people of all ages can be affected [89]. Other risk factors are anatomical anomalies of the eye, chemical burn, trauma, scarring, and ocular surgeries. In determining the etiology, the clinician must distinguish entropion from other conditions that simulate it; appropriately classify it as congenital or acquired; and then subclassify it as involutional, cicatricial, or acute spastic; involutional entropion is the most common form [89]. Antibiotics, lubricating ointments, chemodenervation of the orbicularis muscle, or everting of the eyelid with adhesive tape may help to alleviate symptoms of involutional entropion, but only temporarily. The only effective treatment is surgery to repair or advance the lower eyelid retractors [89].

Ectropion is the abnormal outward turning of the eyelid margin (usually the lower lid) so that the inner surface is exposed. The primary morbidity is associated with corneal/conjunctival exposure. Other symptoms include excess tearing, redness of the lid and white part of the eye, and ocular irritation [59].

Although ectropion can occur at any age, it is most commonly seen in older adults. Other risk factors include a history of skin cancer removal, increased skin sun sensitivity, lighter iris color and presence of pinguecula, current smoking, hypertension, diabetes, and stroke [89]. Like entropion, treatment depends on the ectropion being properly classified as congenital/acquired and then as involutional, cicatricial, paralytic, or mechanical [89]. Involutional ectropion is the most common form of the condition.

Treatment consists of tear drops and lubricating ointment to provide symptomatic relief and prevent corneal complications; definitive treatment is surgery [89].

Dermatochalasis is a common, normal, physiologic condition clinically seen as the sagging of the upper and (to some degree) lower eyelids. Although it is most often seen in patients older than 65 years of age, the most frequently noted age of onset is between 40 and 50 years of age, and it may occur in younger adults as well [92]. The sagging is due to lax, redundant skin and fat with poor adhesion to the underlying connective tissue and muscle [92]. The major causes of dermatochalasis are, unsurprisingly, gravity and the loss of elastic tissue over many years. Other predisposing factors include heredity, some systemic diseases, trauma, and renal failure [92]. Dermatochalasis often results in ptosis.

In addition to being a cosmetic problem, dermatochalasis can result in a functional loss if the tissue obstructs the superior visual field by hanging over the eyelid margin into the visual axis [92]. Surgery is definitive treatment.

Ptosis (blepharoptosis) is drooping of the upper eyelid and is one of the most common involutional eyelid changes. The drooping is a result of underaction of the eyelid protractors relative to the eyelid retractors, which cause the eyelid to be lower than its normal position. Lowering of the upper eyelid obstructs the superior visual field, which may cause functional vision loss depending on the severity of the condition.

Etiology includes third cranial nerve palsy, age-related dehiscence of the levator muscle, Horner syndrome, or myasthenia gravis [93]. Injection of botulinum toxin (Botox) into the upper third of the face may also cause ptosis [94].

Patients with chronic ptosis can be referred to an ophthalmologist nonemergently, but patients with acute ptosis should be referred immediately, to rule out third cranial nerve palsy [93]. Although treatment is usually surgical, the many types of ptosis and the degree of levator function determine which of a variety of surgical interventions is most appropriate for a given patient.

Eyelid retraction is the shrinking or drawing back of the eyelid from its normal resting position. In the case of the upper lid, the normal resting position is 2 mm below the junction of the sclera and the superior cornea. Positioning is abnormal if a white band of sclera between the lid margin and the upper corneal limbus is exposed. Whereas the normal resting position of the lower lid is at the junction of the sclera and the inferior cornea, the retracted lower lid lies below the inferior corneal margin and is tethered to the orbital margin [95].

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.

Due to its multifactorial etiology, treatment is dependent on a differential diagnosis. Several surgical techniques and materials are available for the repair of eyelid retraction, and the patient should be referred to an ophthalmology specialist [96].

Blepharospasm is a focal dystonia characterized by involuntary chronic intermittent or persistent involuntary eyelid closure. Closure is due to spasmodic contractions of the orbicularis oculi muscles, and the spasms may be unilateral or bilateral [97]. Severity ranges from frequent blinking to forceful eyelid closure. Most cases are idiopathic [59]. Other facial and neck muscles are often involved. Nearly three-quarters of patients report that a stressful event occurred immediately prior to symptoms; photophobia may also precede the development of spasms [98]. The condition occurs more frequently in women than men, and approximately one-third of patients have a family history of blepharospasm [98]. Type A botulinum toxin injections is the treatment of choice, and surgery may be done if the injections fail [97].

Eye injuries in the home are caused by a wide variety of items, including chemicals, tools, outdoor equipment, paint, debris generated by power tools and lawn equipment, automobile mechanic materials, and toys. The most common cause overall is chemicals, with cleaning agents, personal care products, and automotive chemicals being the most common agents[101]. Across all ages, eye injuries related to consumer products are more common among male individuals than female individuals[100,101,103,105,108,109]. Among men, injuries attributable to hardware and lawn equipment have been found to be more common, whereas among women, more injuries are attributable to chemicals, housewares, storage and organization, and bed and bath items[110]. The cause of injury varies among age groups (Table 10)[100,103,105,108,109,112].

The most common consumer products causing eye injury among children 0 to 12 years of age are toys, pens and pencils, household cleaners and chemicals, adhesives, golf equipment, baseballs and basketballs, cigarettes/cigars/pipes/tobacco, furniture, and fireworks [105,109]. The rate of injury related to toys is proportionately higher among children 2 to 4 years of age and the rate of injury related to desk and school supplies is proportionately higher among children 5 to 8 years of age [105,109].

Chemicals are one of the most common causes of injury among individuals 10 to 24 years of age [103,108]. Aerosol cans have emerged as another cause of eye injury occurring at a high rate among children and adolescents. In one study, individuals younger than 18 years of age accounted for more than half of patients seen in the emergency department for eye injuries related to aerosol cans (5,927 of 10,765 patients) [111]. Spray paint was the most common product involved, and self-inflicted spray to the eye was the most common mechanism of injury [111]. Non-powder firearms (e.g., air, airsoft, paintball, pellet, BB guns) are an increasingly common cause of eye injury among children, adolescents, and young adults, having risen more than 50% since the 1990s, and are associated with a high risk of hospital admission, severe damage, and permanent vision impairment [105,112]. Nearly every eye injury with non-powder firearms (98%) occurs in individuals who are not wearing protective eyewear, highlighting the need for clinicians to emphasize the importance of preventing this type of injury [112].

Among individuals 25 to 64 years of age, cutting and construction tools are the most common causes of eye injury, and chemicals are the leading cause of injury among individuals 65 years of age and older; cutting and construction tools, furniture, and gardening are other common causes in this latter age group [106].An additional hazard to eyes for both adults and children is fireworks. Injuries related to fireworks have increased over the years, from 8,500 in 1998 to 11,500 in 2022; and the eye is the third leading affected part of the body (15%) [115]. Approximately 73% of these injuries occur during a one-month period from mid-June to mid-July [115]. Nearly one-half of the eye injuries were contusions or lacerations, with burns accounting for one-fifth of the injuries [115]. As with other causes of eye injuries, fireworks-related injuries occur much more frequently among male individuals (65%) [115]. Individuals 25 to 44 years of age account for 36% of the estimated injuries; 28% occur among children younger than 15 years of age [115].

Healthcare professionals should heighten awareness of the need for eye safety in the home. The AAO and the American Society of Ocular Trauma recommend that each home should have at least one pair of American National Standards Institute (ANSI)-approved protective eyewear, to be worn during activities related to a risk of eye injury [118]. Clinicians should also emphasize eye safety for children, specifically noting the following:

As stated, among children and adolescents, eye injuries are most often related to sports activities[100,107,108]. In a joint policy statement, the AAP and the AAO classified sports as eye safe, low-risk, moderate-risk, and high-risk in terms of the potential for eye injury (Table 11)[119]. Most sports are considered to be moderate risk when eye protection is not worn. Among athletes 5 to 24 years of age, baseball, basketball, and golf are the most common causes of eye injuries[105,119].

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:

Other types of eye injuries occur less frequently in sports. Penetrating injuries are less common than blunt trauma and range from mild (abrasions) to severe (serious lacerations). Such injuries can be caused by broken glass (including eyeglasses), a finger, or a fishing hook. Participants in snow skiing and water sports may be at some risk for radiation injuries because of exposure to ultraviolet light [50,120].

It has been shown that protective eyewear for athletes substantially reduces the number of eye injuries. While some sports mandate use of protective eyewear, rules and laws vary among sports and regions, so it is important for healthcare professionals (as well as coaches and athletic trainers) to know local mandates and ensure that athletes, especially those who are young, wear eye protection appropriate for the sport[122,123]. The proper eye protection for sports is made of polycarbonate, which is resistant to high impacts. According to the AAO/AAP statement, the types of eyewear that are satisfactory for eye-injury risk sports include [119]:

There are standard specifications for youth baseball batters and base runners, paintball, skiing, ice hockey, football, and men's lacrosse.

Eye injuries in the workplace range from minor, such as computer-related eyestrain and dry-eye syndrome, to severe injuries caused by flying objects. The overall lifetime prevalence of occupational eye injuries has been reported to be 4.4% [124]. In 2020, eye injuries accounted for 1.6% of the nearly 1.18 million occupational injuries involving days off from work [51,126]. The rate of eye injury varies according to many factors, including gender, age, socioeconomic status, and work setting. The rate of injury is more than three times higher among men than women and is highest (112.8 cases per 10,000 full-time workers) among individuals 45 to 54 years of age [51,125]. Individuals with less than a high school education and men in lower income brackets are more likely to have an eye injury [101]. These injuries are a substantial health and economic burden, with an estimated total cost of approximately $300 million annually [118].

Eye injuries occur in virtually every work setting. In 2020, the rates were highest among heavy and tractor-trailer truck drivers; laborers and freight, stock, and material movers; and nursing assistants [51]. Most workplace-related eye injuries are caused by flying objects (e.g., bits of metal or glass), tools, particles, and chemicals, resulting in corneal abrasion or burn. However, the type of injury ranges widely across work settings [118]. Approximately 64% to 90% of individuals who use a computer or digital screen devices have eye-related symptoms, particularly eyestrain, tired eyes, dry eye, blurred vision, and headache; this complex of symptoms has been termed computer vision syndrome or digital eye strain [127]. In addition, symptoms of dry eye have been associated with indoor office environments, and it has been postulated that the cause is dehydration of the corneal tear film as a result of low relative humidity and high room temperature, as well as decreased blinking during near-task activities [127]. Ergonomic adjustments, such as modification of lighting and glare, frequent breaks, eyeglasses specifically made for computer screen use, and lubricating eye drops can be helpful in reducing symptoms [127].

Allergic conjunctivitis can occur in food handlers and agriculture workers who are exposed to spices, fruits, and vegetables and in outdoor workers exposed to grass, ragweed, and rhus [51]. The absence of symptoms when the individual is not at work confirms the diagnosis. Outdoor workers are at increased risk for radiation injury and age-related macular degeneration, and sunglasses that provide protection from ultraviolet rays should be worn [51].

The Occupational Safety and Health Administration (OSHA) standards mandate that employers must provide suitable eye (and face) protection to all employees to protect against chemical, environmental, radiologic hazards, or mechanical irritants [131]. In addition, all employees must be trained to work safely. Safety spectacles (which may include side shields) or safety goggles should be worn when there is potential for impact injuries, as from flying/falling objects or heat hazards (e.g., high temperatures, splashes of molten metal, hot sparks). Safety goggles should fit tightly around the eyes, forming a protective seal to prevent objects from entering under or around the goggles [131]. Face shields should be used in conjunction with safety goggles when there is a high potential for exposure to impact injuries, heat hazards, or chemicals or when working with lasers and welding equipment [131]. Lenses for goggles and face shields may be specially filtered. Eyewashes should be readily available in occupational environments with risk for injuries from chemical exposure [131].

Approximately 90% of occupational eye injuries are preventable with protective eyewear [118]. As such, clinicians should help to reinforce the importance of eye safety in the workplace.

Corneal Abrasions and Removal of Foreign Bodies

A corneal abrasion is a defect in the corneal epithelial surface that is usually caused by trauma. A foreign body may or may not be in the eye at the time of examination. In diagnosing a corneal abrasion, the history is important in determining whether there has been recent trauma to the eye, bearing in mind that the cause can be as minor as aggressive eye rubbing or accidental scratching with a fingernail, or can be related to poor contact lens technique or overuse. If no clear history of trauma is present, infectious keratitis should be suspected [136]. Symptoms of corneal abrasion include sensation of a foreign body in the eye, photophobia, excessive tearing, and pain [137].

A topical anesthetic is helpful for pain-free examination of the eye and/or removal of a foreign body [136]. Visual acuity should be measured, and the cornea should be examined with use of a penlight and loupe or biomicroscope magnification [136]. The patient should be referred immediately to an ophthalmologist if any of the following is present [137]:

The diagnosis of abrasion is confirmed by applying fluorescein to the eye and examining the eye with use of cobalt-blue filtered light; the abrasion will appear green [136,137].

Examination of the eye should also be directed toward determining if there is a foreign body, even if the patient does not recall a foreign body entering the eye. The lower lid should be pulled down gently to allow for more complete examination of the eye, and the upper eyelid can be inverted to search for a subtarsal foreign body, but only if a penetrating injury is not suspected [136,137]. Vertical linear corneal abrasion on fluorescein staining may indicate a hidden foreign body, and the upper eyelid and lower fornix should be evaluated carefully [137].

Irrigation with saline can remove minor foreign bodies (e.g., soot particles). If the foreign body is larger, a moistened cotton-tipped applicator may be used to remove the foreign body [137]. A more deeply embedded (but nonperforating) foreign body can be removed with use of an eye spud or a 25-gauge needle, but primary care clinicians should attempt removal of such foreign bodies only if they are comfortable performing the procedure and if these instruments are available; otherwise, referral to an eye specialist should be made [137].

A metallic foreign body may be more difficult to remove because it can become "rusted" on the cornea. Rust residue may be present on the eye after removal of a metallic foreign body. This so-called rust ring can increase inflammation, prevent healing, and cause scarring. Patients should be referred to an ophthalmologist for removal of a rust ring within the next few days [137].

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].

For patients who wear contact lenses, a topical fluoroquinolone or aminoglycoside should be prescribed because of their antipseudomonal activity [137]. In addition, the contact lenses should be discarded, and new ones should not be worn until the abrasion has healed. All patients should be followed up in 24 hours; if symptoms have improved, no further follow-up is necessary. Patients should be referred to an ophthalmologist if symptoms do not improve, if the abrasion does not heal within three to four days, if the size of the abrasion increases, if a corneal infiltrate or ulcer develops, or if vision worsens [137].

Other Minor Injuries

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].

Eyelid lacerations may be sutured using 6-0 interrupted sutures, with nonabsorbable sutures used for adults and absorbable sutures used for children; if the laceration is small and the tissue edges are opposed, suturing is not necessary [148]. Patients with complicated eyelid lacerations should be referred to an ophthalmologist for repair [148].

Five eye injuries require urgent referral and immediate treatment to preserve vision [50]:

Chemical Injuries

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].

Signs and symptoms related to a chemical injury include pain or burning sensation, red eye, photophobia, blurred vision, and sensation of a foreign body in the eye[135,147,149]. Treatment begins with topical anesthetics to the eye and immediate copious irrigation of the eye with normal saline or lactated Ringer's solution (tap water may be used if necessary) for at least 15 minutes (at least 2 liters of fluid)[51,147,149]. The pH of the ocular surface should be checked periodically during irrigation. Once the physiologic pH has been restored (pH of 7.0–7.5), the clinician should refer the patient immediately to an ophthalmologist or an emergency department[147]. The next steps are a thorough medical history and a complete eye exam. The exam includes assessment of visual acuity, pupil symmetry, and pupillary light response; evaluation of extraocular muscles; slit lamp examination with fluorescein staining and cobalt blue light; measurement of intraocular pressure; and dilated funduscopic examination[149]. Some findings on examination include swelling and burns of the eyelid, a cloudy cornea, a corneal epithelial defect, conjunctival injection, or a white eye (indicating conjunctival ischemia[147]. The extent of injury can be defined with the Roper-Hall classification system (Table 12)[150].

The severity of a chemical injury dictates treatment. Topical antibiotics and artificial tears are usually sufficient for grade I and II burns; a topical steroid is added for grade II and IV burns [147]. There is no evidence to support the routine use of ascorbate in the treatment of alkali burns [151]. Patients should be referred to an ophthalmologist if visual acuity is abnormal, if intraocular pressure remains high, or if epithelial defects are present [149].

Mechanical Globe Injury

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].

Examination of the anterior segment with a slit lamp is preferred for diagnosing a globe injury; penlight examination may also be done. Indicators of a globe injury are subconjunctival hemorrhage, irregular pupil, and iris prolapse through a corneal or scleral wound [147,152]. If a diagnosis of globe injury is not clear, the Seidel test should be done. This test is performed by applying a moistened fluorescein dye strip to the area of possible injury and using a slit lamp and cobalt blue light to examine the site. The test is positive (presence of a globe injury) if the fluorescein is diluted by aqueous flow from the eye; if darker, diluted fluorescein dye streams from the injury site, or if bright-green concentrated dye surrounds the leak site [147,153]. Dilated pupil exam and tonometry are not recommended. Computed tomography (CT) (axial and coronal views) of the head and orbits is the preferred imaging modality and can be used to detect an intraocular foreign object or a fracture of the orbital wall [135,147,152]. If there is a protruding foreign body, the clinician should not attempt to remove it if a globe rupture is suspected [135,152].

If a globe injury is confirmed (or suspected), a metal shield should be placed over the eye and the patient should be referred immediately to an ophthalmologist [147,152]. The patient should be told to limit coughing or straining, and an antiemetic may be given to prevent the Valsalva maneuver. A tetanus booster should be given if tetanus immunization is not up to date [147,152].

The treatment of a globe injury consists of continued analgesic agents to maintain adequate pain relief and antibiotics to prevent endophthalmitis [135,147,152]. The preferred antibiotics are the fluoroquinolones levofloxacin and moxifloxacin, as they target the most common causes of post-traumatic endophthalmitis and have excellent vitreous penetration [147]. Another option is intravenous vancomycin or ceftazidime. If organic material (such as hay, grain, or leaves) was involved, an antibiotic to treat infection with Gram-negative bacteria or fungi should be chosen [135]. The risk of endophthalmitis is substantially reduced if surgical repair and/or removal of a foreign body is performed with 24 hours of the injury, further emphasizing the need for immediate referral to an ophthalmologist [147].

Retinal Detachment

Retinal detachment occurs when the neurosensory layer of the retina separates from the underlying choroid and retinal pigment epithelium. Retinal detachment can occur with a retinal tear (rhegmatogenous detachment) or without a retinal tear (nonrhegmatogenous). Rhegmatogenous detachment is most often associated with myopia, cataract surgery, and ocular trauma [59]. Nonrhegmatogenous detachment is caused by vitreoretinal traction or transudation of fluid into the subretinal space; detachment caused by traction is often associated with diabetic retinopathy, sickle cell disease, and advanced retinopathy of prematurity, whereas detachment caused by transudation of fluid is most often the result of inflammation, malignant effusions, or severe acute hypertension [59].

Retinal detachment is uncommon but can cause rapid degeneration of photoreceptors, and loss of vision can be permanent if diagnosis and treatment are not prompt. Signs and symptoms of retinal detachment include unilateral flashing lights, an increasing number of floaters, and blurred vision [59,147]. The patient may also note that it appears as if a dark curtain covers part of the visual field [154]. There is usually no pain. Involvement of the macula is associated with a substantial loss of central visual acuity [59,147,154]. Dilated funduscopic examination is used to diagnose retinal detachment; if the retina cannot be visualized because of vitreous hemorrhage, cataract, or corneal scar, B-scan ultrasonography should be done to identify a tear [59,147,154].

Patients who are suspected of having a retinal detachment should be referred urgently to an ophthalmologist [59,147]. If left untreated, a retinal detachment can result in permanent and severe vision loss; treatment with surgery is successful in approximately 90% to 95% of cases [59,147]. Patients should be followed up closely, as retinal detachment in the contralateral eye develops in about 25% of patients; in addition, monitoring for recurrent retinal detachment is necessary [147,154].

Central Retinal Artery Occlusion

Occlusion of the central retinal artery is usually caused by an embolism from atherosclerotic plaque, endocarditis, fat emboli, atrial myxoma, or thrombosis of a retinal artery [59]. Occlusion can also be caused by temporal arteritis. Immediate treatment of acute central retinal artery occlusion is needed, as complete loss of vision may develop as soon as 90 minutes after injury [50,135]. Older age, diabetes, atherosclerosis, hypercholesterolemia, hypertension, and hypercoagulable states are risk factors for central retinal artery occlusion [135,155]. Approximately 5% to 10% of cases are associated with giant cell arteritis [50,155]. Other diseases or disorders associated with central retinal artery occlusion include systemic lupus erythematosus, acute lymphoblastic leukemia, primary central nervous system vasculitis, iron deficiency anemia, and Wegener granulomatosis [50]. It may also result from blunt trauma to the eye or as a complication after coronary angiography, laryngectomy, or spinal surgery.

Central retinal artery occlusion is usually painless, with sudden blindness or visual field defect. In some cases, the patient may note a history of transient, painless loss of vision in one eye (amaurosis fugax) [135,155]. Transient, bilateral vision loss is usually caused by conditions other than central retinal artery occlusion, such as migraine auras, heart failure, and hypertensive emergencies [135].

During pupillary examination, the pupil may react slowly or poorly to light, but the pupil will constrict quickly when the contralateral eye is illuminated [59]. Findings on funduscopic examination that indicate central artery occlusion include a pale, opaque fundus and a cherry-red spot at the fovea; however, this spot may take hours to develop [59,155].

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.

Acute Angle-Closure Glaucoma

Acute angle-closure glaucoma is associated with a closed anterior chamber angle and may be caused by many mechanisms. With this type of glaucoma, the iris is pushed (or pulled) up into the angle, blocking the drainage of aqueous humor, which in turn increases the intraocular pressure [59]. Angle-closure glaucoma accounts for only 10% of glaucoma cases, but without treatment, angle-closure glaucoma can cause vision loss within several hours to days [34,59]. Thus, a suspected attack of acute angle-closure glaucoma requires emergent referral to an ophthalmologist.

A shallow anterior chamber and hyperopia are the ocular factors that most predispose individuals to primary angle-closure glaucoma; other factors include steep corneal curvature, thick crystalline lens, and a short axial length [34]. Demographic risk factors include advancing age, strong family history/heredity, and female gender [34]. The highest rates of primary angle-closure glaucoma have been found in Asian populations, especially Taiwanese; Inuit populations; and African or African-derived populations [34,59].

The signs and symptoms of acute angle-closure glaucoma are classic. The most common symptoms include [34,59]:

Patients usually have a mid-dilated pupil, which is fixed and reacts sluggishly to light. The conjunctiva may have signs of hyperemia, and corneal swelling may be present [34,59].

Treatment consists of decreasing intraocular pressure, reversing the angle closure, and preventing damage to the optic nerve [34]. Initial treatment usually involves medication to reduce intraocular pressure and reduce pain. The AAO recommended options include topical beta-adrenergic antagonists, topical alpha2-adrenergic agonists, topical or systemic carbonic anhydrase inhibitors, topical mitotics, and systemic hyperosmotic agents [34]. The preferred surgical treatment is laser peripheral iridotomy (LDI) because of its favorable risk-benefit ratio [34,59]. Because the chance of having an acute attack in the contralateral eye is 80%, LDI should be done on both eyes [59].

There are few risk factors for strabismus. Children are at risk for the condition if there is a family history of strabismus, if there is neurodevelopment impairment, if there was maternal exposure to smoking or alcohol during pregnancy, if the child was born prematurely, and if the child's birth weight was low [157]. A more recent study has indicated that very low birth weight may be more of a risk factor than gestational age [158].

Often, a parent's observation of deviation of one eye will prompt him or her to bring the child to the clinician for an eye examination. Children in whom strabismus is noted on screening eye examination in the primary care setting should be referred to an ophthalmologist for further evaluation and treatment [37].

The goals of treatment in young children with strabismus are good vision, correct alignment of the eyes, and the development of stereopsis (i.e., binocular depth perception) [156]. The AAO notes that the initial treatment for children with esotropia or exotropia is eyeglasses to correct any significant refractive error but emphasizes that restoration of good alignment does not ensure elimination of amblyopia; surgery may be indicated for some children [157]. The results of a Cochrane review (three studies) indicated that the true effect of correction of hyperopia on strabismus is uncertain [159]. Improved alignment may take several weeks. For children with intermittent exotropia, part-time patching therapy (two to six hours daily) may provide benefit [157]. If eyeglasses and treatment of amblyopia fail to align the eyes in children with esotropia, surgical realignment should be done. The AAO states that surgery is not needed for young children with intermittent exotropia and good fusional control [157].

Follow-up is essential after treatment for either esotropia or exotropia. If the eyes are well aligned and amblyopia is not present, children treated for esotropia should have follow-up visits every four to six months to monitor for amblyopia, loss of binocular vision, and recurrence of strabismus. Follow-up visits are recommended every 6 to 12 months for children with good fusional control of intermittent exotropia and no amblyopia [157].

When developing a treatment plan, the eye specialist will consider the goals and expectations of the parents and the child, when possible, and will emphasize the importance of compliance to treatment in order to achieve goals [157]. The primary care clinician should take advantage of the child's well-care visits to assess whether the child and parents are complying with the recommended treatment course as well as with follow-up examinations.

Prompt diagnosis and treatment of strabismus in children are crucial, as the condition can delay developmental milestones, adversely affect academic achievement, and have a lower psychosocial quality of life [157]. The AAPOS and AAO recommend that primary care clinicians screen for strabismus in children 3 to 5 years of age at all well-child visits; the USPSTF recommends screening for strabismus just once during these ages [26,157]. The USPSTF notes that the cover-uncover test and the Hirschberg light reflex text are feasible in primary care for assessing ocular alignment/strabismus [26].

The presence of strabismus increases the risk of amblyopia, with amblyopia occurring in approximately 50% of children with strabismus [160,163]. Significant refractive errors are risk factors for unilateral amblyopia, and bilateral astigmatism and bilateral hyperopia are risk factors for bilateral amblyopia [160,163]. Other identified risk factors include prematurity, low birth weight, developmental delay, and a first-degree relative with amblyopia [163]. As with strabismus, maternal smoking and use of drugs or alcohol have also been associated with an increased risk for amblyopia [163].

Amblyopia is suggested if a child has difficulty performing tasks that require binocular depth perception. Due to the high rate of amblyopia in association with strabismus, all children who have esotropia or exotropia should be evaluated closely for amblyopia. A cooperative child is necessary for reliable visual acuity testing, and the optimal tests vary according to age. The AAO notes that the optotypes on an eye chart can significantly affect the visual acuity score and recommends that optotypes be clear, standardized, have similar characteristics, and be free of cultural bias [163]. LEA Symbols (Good-Lite; Elgin, IL) are useful for young children, as is the HOTV chart [163]. Children who are too young to name the symbols on these charts may be able to match them to the symbols on a hand-held card. LEA numbers and Sloan letters are preferred for older children [163]. Children in whom amblyopia is noted on screening eye examination in the primary care setting should be referred to an ophthalmologist for further evaluation and treatment [163].

The goal of treatment is equal visual acuity in the two eyes [163]. Treatment of amblyopia is highly successful in approximately 75% of children who are younger than 7 years of age when treatment begins [161]. Although a younger age at the start of treatment is associated with better final visual acuity, treatment should be attempted in older children who have not been previously treated, as nearly half of such children have sustained improvement in visual acuity [161,162].

According to the American Academy of Ophthalmology, most children who have moderate amblyopia (20/40 to 20/80) respond to initial treatment consisting of two hours of daily patching or weekend atropine.

(https://www.aaojournal.org/article/S0161-6420(22)00865-X/fulltext Last Accessed: November 29, 2023)

Strength of Recommendation: Strong (The desirable effects of an intervention clearly outweigh the undesirable effects)

The treatment plan varies according to the type of amblyopia. Treatment of refractive error alone can improve visual acuity in children who have untreated strabismic or anisometropic amblyopia or bilateral refractive amblyopia [157,163]. Occlusion of the better eye to stimulate the amblyopic eye has been the cornerstone of treatment for amblyopia, and a systematic review demonstrated that occlusion in combination with refractive correction was more effective than refractive correction alone [164]. Occlusion is achieved with either patching or administration of 1% atropine drops (one drop daily); both have been found to be effective for children younger than 7 years of age, with one study showing that both treatment approaches led to good visual acuity up to at least 15 years of age in children with moderate amblyopia who were treated before the age of 7 [165,166]. Six hours of patching daily has been shown to be as effective as all-day patching (all but one waking hour), and initial treatment with two hours of daily patching has been as effective in improving visual acuity as six hours for children with moderate amblyopia [163]. A drawback of patching is compliance, with one study demonstrating a mean compliance of 44% [167]. The selection of a treatment approach should be discussed with the parents and the child, if feasible, to determine the best option.

Visual acuity (in both eyes) and treatment compliance should be assessed during follow-up, with the first follow-up visit within two to three months [163]. If visual acuity is unchanged, treatment intensity or modality should be considered.

As with strabismus, prompt diagnosis and treatment of amblyopia in children are crucial [163]. Screening to detect amblyopia among children younger than 5 years of age is recommended by the AAP, the AAO, and the USPSTF [26,163].

Advanced age is the most common cause of cataracts. As a person ages, the thickness and weight of the lens increase and nuclear sclerosis (hardening and compression of the nucleus) develops. Several risk factors have been evaluated, and overall, the most common factors are diabetes, smoking, use of inhaled or oral corticosteroids, and exposure to ultraviolet-B light [29]. Other potential risk factors vary according to the type of cataract. For example, a family history of cataracts and hypertension have been associated with an increased risk for nuclear and cortical cataracts; obesity has been associated with an increased risk for cortical and posterior subcapsular cataracts, and ocular trauma has been associated with posterior subcapsular cataracts [29].

The most common early symptoms associated with cataracts include loss of contrast, glare, the need for more light to see well, and decreased color perception. Blurring often occurs as the cataract progresses [59]. Primary care clinicians should refer patients suspected of having a cataract to an ophthalmologist for evaluation. According to the AAO, the ophthalmic evaluation for cataracts should include a complete history; measurement of visual acuity with current correction; examination of external aspects of the eye; examination of ocular alignment and motility; assessment of pupillary function; measurement of intraocular pressure; slit-lamp biomicroscopy of the anterior segment; and dilated examination of the lens, macular, peripheral retina, optic nerve, and vitreous [29].

The only effective treatment for cataracts is surgery; clinicians should emphasize to patients that no nutritional supplements (such as antioxidants), herbal medications, or pharmacologic agents have shown benefit in the treatment of cataracts [20,29]. Surgery involves replacement of the affected lens with an intraocular lens (artificial lens). In most cataract surgeries in the United States, the lens is removed by phacoemulsification, which has resulted in significantly better visual acuity and fewer postoperative complications [29]. A Cochrane review indicated that, compared with manual small incision cataract surgery, phacoemulsification was associated with better uncorrected visual acuity up to three months after surgery, but similar best-corrected visual acuity [174]. No data were available on long-term outcomes. The cost of manual small incision cataract surgery is lower than the cost of phacoemulsification, leading the authors to conclude that manual small incision cataract surgery may be a reasonable option for some patients. The AAO recommends joint decision-making regarding cataract surgery. Criteria typically considered during decision-making include the patient's visual acuity, the likelihood that surgery will improve vision, the effect of vision loss on the patient's lifestyle, and the patient's amenability to surgery [29].

When surgery is planned, the ophthalmologist is responsible for confirming the diagnosis and designing the treatment plan. The primary care clinician can play an important role in alleviating patient concerns preoperatively and monitoring improvement postoperatively. Cataract surgery leads to improved visual acuity in approximately 85% to 90% of patients [29]. Overall, cataract surgery is very cost-effective, with benefits in quality-adjusted life years [29].

Smoking cessation and protection from ultraviolet-B radiation have been shown to reduce the risk of cataracts, and the AAO notes that these are reasonable precautions to recommend to patients [29]. However, several randomized, long-term, clinical studies have demonstrated that using supplements such as multivitamins, vitamin C and E, beta carotene, or herbal medications does not prevent the incidence or progression of cataracts [20,29]. Prevention and appropriate treatment of type 2 diabetes can help to reduce the risk of cataract formation, as can avoidance of long-term use of oral or inhaled corticosteroids [29].

Elevated intraocular pressure is the most important—and only modifiable—risk factor for primary open-angle glaucoma [173]. Other strong risk factors include older age, family history of glaucoma, Black race, Latino/Hispanic ethnicity, thinner central cornea, myopia, and type 2 diabetes (and fasting glucose levels) [173,179]. Some studies have suggested that there may be gender differences in the prevalence and pathophysiology of glaucoma, with hormone therapy, oral contraceptive use, and menopausal status being associated with glaucoma [180]. A meta-analysis published in 2014 demonstrated that hypertension was associated with increased intraocular pressure, with a strong association between hypertension and primary open-angle glaucoma [181].

More than half of people with glaucoma have no symptoms; about 24% note ocular surface disease symptoms and 25% report visual problems [182]. Some people with glaucoma note vision difficulty while reading or driving [59]. The presence of symptoms has been associated with increased severity of glaucoma [182].

The AAO recommends prompt referral to an ophthalmologist for an abnormal intraocular pressure or a family history of glaucoma, especially in patients of Black or Hispanic race/ethnicity [40]. A diagnosis of glaucoma requires a complete history and an ophthalmic evaluation that includes measuring visual acuity and intraocular pressure and performing gonioscopy to rule out other causes of elevated intraocular pressure [173].

There are three types of computer-based optic nerve imaging devices that have been shown to be highly effective diagnostic tools, especially when coupled with functional tests: confocal scanning laser ophthalmoscopy, optical coherence tomography, and scanning laser polarimetry [173]. These devices have been found to be similar in their ability to distinguish between glaucoma and controls [173].

The goals of treating glaucoma are to control intraocular pressure, stabilize the status of the optic nerve/retinal nerve fiber layer, and stabilize visual fields [173]. Treatment options include medication, laser therapy, or incisional glaucoma surgery, all of which lower intraocular pressure. The choice of treatment depends on many factors, such as the effects of treatment, quality of life, and life expectancy, and the patient should be involved in the decision-making process [173].

Medical treatment is typically used initially, and prostaglandin analogs and beta-blockers are the eye drops most often prescribed; prostaglandin analogs have been the most effective at lowering intraocular pressure [173]. A comparative effectiveness study indicated that medical and surgical treatments for primary open-angle glaucoma reduce intraocular pressure and reduce the risk of damage to the optic nerve in the short- to medium-term setting [184]. However, the comparative effectiveness of different treatments is not clear. In addition, it is not clear which treatments are best in preventing visual disability and improving patient-reported outcomes [184]. Although marijuana has been shown to lower intraocular pressure, the American Glaucoma Society does not recommend the use of marijuana in any form to treat glaucoma because of the drug's side effects, short duration of action, and lack of evidence that it alters the course of glaucoma [185]. No data support the use of antioxidants or herbal supplements as treatment [20].

Primary care clinicians should ask their patients with glaucoma about adherence to medical treatment, as a high level of adherence is necessary for adequate treatment.

There is no agreed-on standard of diagnosis for glaucoma, and no single screening method can identify a significant number of patients with glaucoma [186]. The AAO notes that population-based screening is not practical or cost-effective and therefore does not recommend it [173]. Similarly, the USPSTF concluded that the evidence is insufficient to assess the balance of benefit and harms of screening for glaucoma [175]. Additionally, there is limited evidence that screening can reduce either intermediate or final health outcomes [186]. The AAO does note that screening may be useful for populations at high risk for glaucoma, including older adults, people with a family history of glaucoma, and people of Black or Latino/Hispanic race/ethnicity [173].

Several lifestyle risk factors have been explored as potential contributors to glaucoma, including consumption of dietary fat, cholesterol, and caffeine, but none of these has been found to be associated with the risk of glaucoma [187]. As a preventive measure, antioxidants or herbal supplements have shown no effect [20]. Early detection, through regular and complete eye exams, is the key to protecting vision from damage caused by glaucoma.

As noted, an eye examination should be completed every two to four years for patients younger than 40 years of age who have risk factors for glaucoma, with more frequent examinations as the patient ages [173].

The American Optometric Association asserts that cigarette smoking is a modifiable risk factor for age-related macular degeneration. Given the effect of smoking on overall health, and especially on vision, individuals should be advised by their healthcare providers of the risks of smoking and encouraged to quit smoking and/or seek smoking cessation assistance.

(https://aoa.uberflip.com/i/1183026-evidence-based-clinical-practice-guideline-eye-care-of-the-patient-with-diabetes-mellitus-second-edition/1?m4= Last Accessed: November 29, 2023)

Level of Evidence: A (Systematic reviews, cross-sectional study)

As with cataracts and glaucoma, increasing age is the primary risk factor for macular degeneration. A variety of other risk factors have been evaluated, but smoking and ethnicity are the only two that have been shown consistently to be risk factors for age-related macular degeneration[188]. The risk of age-related macular degeneration doubles with smoking, and the risk increases as the number of pack-years smoked increases[188]. Hypertension, other cardiovascular disease, low levels of antioxidants, and dietary fat have also been associated with advanced age-related macular degeneration, but the findings have been conflicting[188]. A meta-analysis identified several risk factors with varying levels of association with age-related macular degeneration (Table 14)[193].

The non-neovascular form of age-related macular degeneration is associated with a slow and painless loss of central visual acuity and central blind spots. With the neovascular form, the first sign is usually visual distortion in one eye, and vision loss is rapid[59]. Any signs of age-related macular degeneration should result in prompt referral to a specialist[188]. Although therapies can slow the visual deterioration associated with age-related macular degeneration, available treatments cannot restore vision lost to the condition. Drusen and/or pigmentary changes in the macula associated with early non-neovascular age-related macular degeneration can be identified using funduscopy (Image 2) [194]. In the neovascular form of macular degeneration, the earliest sign of choroidal neovascularization is the appearance of semi-translucent punctate dots in retroillumination (Image 3)[194]. Fluorescein angiography and optical coherence tomography are imaging modalities used to detect new or recurrent neovascular disease activity and guide therapy[188].

Fundus photo showing intermediate age-related macular degeneration.

Image 2

Source: National Eye Institute, National Institutes of Health

Fundus photo showing neovascular age-related macular degeneration.

Image 3

Source: National Eye Institute, National Institutes of Health

A combination of antioxidant vitamins (vitamin C, beta carotene, vitamin E), zinc oxide, and cupric oxide can slow the progression of intermediate age-related macular degeneration to the advanced form, but there is no evidence to support use of this combination for early age-related macular degeneration or prophylaxis in family members [188]. Evidence suggests that lutein supplementation is associated with a mild improvement in visual acuity and a significant improvement in macular pigment optical density [195].

The first-line treatment of neovascular macular degeneration is an antivascular endothelial growth factor (VEGF) agent, and three have been approved for use by the FDA: pegaptanib (Macugen), ranibizumab (Lucentis), and aflibercept (Eylea) [188]. All three drugs are administered by intravitreal injection. A biosimilar to ranibizumab (ranibizumab-nuna, Byooviz) was approved for the treatment of neovascular macular degeneration in 2021 [54]. Another anti-VEGF agent, bevacizumab (Avastin), has also been shown to be effective for neovascular age-related macular degeneration, but its use is off-label in this setting [188]. A Cochrane review and meta-analysis demonstrated that pegaptanib, ranibizumab, and bevacizumab are effective in maintaining visual acuity, with ranibizumab and bevacizumab also effective in improving visual acuity [196]. Aflibercept has been shown to be as effective as ranibizumab, with the need for fewer injections [197]. Thermal laser photocoagulation surgery and photodynamic therapy with verteporfin are approved treatments for subfoveal lesions [188]. Conbercept is a novel anti-VEGF approved for the treatment of neovascular macular degeneration in China. Its chemical structure differs slightly from the agents available in the United States, but the drug appears to have the same safety and efficacy profile, with reduced dosing frequency. The drug's developer is in discussions with the FDA about the possibility of introducing the drug into phase 3 testing in the United States [198,199].

Routine, comprehensive eye exams are critical for the early detection of age-related macular degeneration [188]. Smoking cessation reduces the risk of age-related macular degeneration, and clinicians should encourage their patients who are smokers to stop smoking and should provide resources on cessation options [188]. Early cessation is optimal; the risk of age-related macular degeneration in former smokers who have not smoked for more than 20 years is comparable to the risk in nonsmokers [188].

Diabetic retinopathy is a progressive vascular complication of diabetes mellitus and the leading cause of moderate-to-severe vision loss in working adults 20 to 65 years of age[212]. Globally, the prevalence of diabetes has been increasing, and with it the burden of diabetic retinopathy. In 2021, approximately 540 million people were living with diabetes; by 2045, this will rise to 783 million[211]. A meta-analysis of published population studies found that from 1990 to 2010, visual impairment caused by diabetic retinopathy increased by 64% and blindness by 27%[209]. By 2010, approximately 3.7 million cases of vision impairment and more than 800,000 cases of blindness worldwide were caused by diabetic retinopathy. In the United States and other countries with nationwide screening programs, advances in retinal imaging technologies and new therapies have improved the evaluation, treatment, and visual outcomes of patients with diabetic retinopathy[212].

Some degree of diabetic retinopathy develops in nearly all people with long-standing type 1 or type 2 diabetes. In general, the threat to vision arises from increased retinal vascular permeability, complications of retinal neovascularization, or vascular insufficiency in the central retina[212]. The underlying mechanisms for this retinal vasculopathy are unclear. Intravitreal glucocorticoids have been shown to reduce diabetic macular edema, suggesting that inflammation may be an important mechanism. Thinning of the inner retinal layers and abnormal neural function are known to precede clinical evidence of diabetic vascular lesions, indicating that diabetic neuropathy may be involved in pathogenesis of retinopathy[212]. Once retinopathy is established, the driver of disease progression is retinal ischemia and tissue hypoxia, potent inducers of vascular endothelial growth factor (VGEF). Elevated retinal concentrations of VEGF stimulate angiogenesis and promote vascular permeability, precursors to retinal neovascularization and macular edema, respectively[212].

Diabetic retinopathy is classified according to clinical stage of disease. The earliest stage, nonproliferative diabetic retinopathy (also known as background retinopathy), is characterized by retinal vascular abnormalities such as microaneurysms, intraretinal hemorrhages, and cotton-wool spots (white spots on the retinal surface, often having an irregular edge)[213]. Nonproliferative retinopathy is categorized as mild (microaneurysms only), moderate (more than microaneurysms but less than signs of severe retinopathy), and severe (severe intraretinal hemorrhages and microaneurysms in each of the four quadrants, definite venous beading in two or more quadrants, or moderate intraretinal microvascular abnormalities in one or more quadrants)[213]. An increase in vascular permeability can result in macular edema, which is characterized by retinal thickening and hard exudates (lipid deposits). Macular edema is the most common cause of vision loss associated with nonproliferative diabetic retinopathy[213]. As retinopathy progresses, retinal vessels gradually close, leading to impaired perfusion and retinal ischemia. Proliferative retinopathy, which poses the most threat to vision, is characterized by neovascularization on the retina and posterior surface of the vitreous[213]. The new blood vessels have weak walls, do not form in orderly branching, and bleed easily into the retina or vitreous cavity[201]. With advanced proliferative retinopathy, excess blood in the vitreous causes the retina to detach.

The prevalence of diabetic retinopathy in the United States has decreased since the early 2000s, from 40.3% reported in 2004 to 28.5% in the 2005–2008 NHANES; only a slight decline (26.4% in 2021) has been recorded in the decade between NHANES studies[43,176,177]. The prevalence is higher among non-Hispanic Black individuals (approximately 9%) compared with Mexican American and non-Hispanic White individuals (approximately 7% and 3%, respectively)[168,176]. Visual symptoms are rare with nonproliferative diabetic retinopathy; blurred vision and black spots or flashing lights in the field of vision are associated with proliferative retinopathy[59].

The primary risk factor for developing diabetic retinopathy is chronicity of disease coupled with sustained unsatisfactory control of metabolic derangements associated with diabetes. In short, the risk of retinopathy increases with duration of diabetes and poor glycemic control. In most patients, retinopathy develops 10 to 15 years after diabetes has been diagnosed[212,213].

Studies of individuals with type 1 diabetes have shown that the prevalence of diabetic retinopathy increases from 25% at 5 years to 60% at 10 years to 80% at 25 years[202,213]. The prevalence of retinopathy also increases with duration of type 2 diabetes, with rates that increase to 84% in patients who take insulin and 53% in patients who do not take insulin at 19 years[213]. These findings demonstrate a need to follow up patients more closely as the number of years with diabetes increases.

Studies have provided strong evidence that decreasing hemoglobin A1clevels in patients who have either type 1 or type 2 diabetes substantially reduces the development of new diabetic retinopathy or the progression of existing retinopathy[203,204]. Among people with type 2 diabetes, intensive glycemia treatment (target hemoglobin A1c level of less than 6.0%) was associated with a lower rate of progression of retinopathy than standard treatment (target hemoglobin A1c level of 7.0–7.9%)[203].

Hyperlipidemia has been associated with decreased visual acuity among patients with diabetic retinopathy. However, the benefit of treatment to decrease lipid levels has not been demonstrated[205].

As diabetes may go undiagnosed for many years, the American Optometric Association recommends that any individual with type 2 diabetes should have a comprehensive eye and vision examination soon after the diagnosis of diabetes, with follow-up examination, as directed by their eye doctor.

(https://aoa.uberflip.com/i/1183026-evidence-based-clinical-practice-guideline-eye-care-of-the-patient-with-diabetes-mellitus-second-edition/1?m4= Last Accessed: November 29, 2023)

Level of Evidence: B (Randomized clinical trial)

The AAO recommends that eye examinations should begin five years after the diagnosis of type 1 diabetes and at the time of diagnosis of type 2 diabetes; examinations should be yearly thereafter[213]. Pregnant women with pre-existing type 1 or type 2 diabetes should have examinations prior to conception, if possible, or early in the first trimester of pregnancy, as pregnancy can potentiate rapid progression of retinopathy[213]. If retinopathy is severe, follow-up examination should be done every 1 to 3 months; otherwise, follow-up examination should be done every 3 to 12 months[213]. The AOA also provides a guideline for the frequency of eye examinations, recommending yearly examinations for people with mild nonproliferative diabetic neuropathy (every four to six months if macular edema is also present); examinations every six to eight months for moderate nonproliferative retinopathy (every four to six months if macular edema is also present); examinations every three to four months for severe retinopathy (every two to three months if macular edema is also present); and examinations every two to three months for proliferative retinopathy[206]. All eye examinations in people with diabetic retinopathy should be carried out by an eye specialist.

Focal or panretinal photocoagulation is the recommended treatment for proliferative diabetic retinopathy[213,206,212]. While panretinal (scatter) laser photocoagulation is the preferred modality for high-risk proliferative retinopathy, it is sometimes used in patients with non-high risk disease and for cases of severe nonproliferative retinopathy[206]. With this technique, neovascularization is targeted, with delivery of laser in a scatter pattern, throughout the peripheral fundus, sparing the macula (Image 4).

Fundus photo showing scatter laser surgery for diabetic retinopathy.

Image 4

Source: National Eye Institute, National Institutes of Health

Although laser photocoagulation is effective for managing non-center involved macular edema, intravitreal anti-VEGF agents are standard of care for treatment of center-involved diabetic macular edema and accompanying vision loss [213,212]. Before the use of anti-VEGF agents, intravitreal sustained-release glucocorticoid therapy was shown to reduce retinal thickening and improve vision; however, treatment with glucocorticoids increases the risk of cataracts and other complications such as intraocular pressure elevation and glaucoma [212]. A systematic review demonstrated high-quality evidence of benefit for the use of intravitreal anti-VEGF agents for diabetic macular edema compared with grid laser photocoagulation, with improvement in visual acuity and patient-reported outcomes [214]. Most experts now recommend intravitreal anti-VEGF agents as standard of care for diabetic macular edema, and two such drugs—ranibizumab and aflibercept—are approved by the U.S. Food and Drug Administration [210,212]. Small studies have documented some efficacy of bevacizumab for treatment of diabetic macular edema; however, this is an off-label use [215,216]. There is no evidence to support the use of antioxidants or herbal medications for the prevention or treatment of diabetic retinopathy [20].

When baseline visual acuity in an eye with diabetic macular edema is 20/25 or better, initial management with observation is a reasonable strategy rather than immediate anti-VEGF therapy or laser treatment [212]. This strategy requires that patients are followed closely and anti-VEGF therapy is initiated promptly if vision worsens. In a randomized, controlled trial of initial management approaches, similar rates of vision loss at two years were observed with aflibercept (16%), laser treatment (17%), and clinical observation (19%) [208].

Despite the availability of treatment to prevent the progression of diabetic retinopathy, a large percentage of patients with diabetes have vision loss. A primary reason for this is poor patient compliance with eye examinations, with studies showing that 38% to 50% of people with diabetes do not adhere to the guidelines for eye examinations [213]. Lack of primary care physicians' referral for eye examinations is a contributing factor to low patient compliance, and a Canadian study demonstrated that printed educational messages for primary care physicians did not increase examination uptake [217]. Other strategies to enhance awareness of the need for close follow-up eye examinations for patients with diabetes are needed.

Over time, sustained hypertension is a risk factor for complications that threaten vision, including retinal vascular occlusion, retinal microaneurysm, and ischemic optic neuropathy [53,207]. In addition, hypertension exacerbates progression of diabetic retinopathy and the risk of developing glaucoma and age-related macular degeneration. The most common ocular presentation of hypertension is hypertensive retinopathy.

The eye is the one organ in the body where vascular changes of systemic hypertension can be observed and monitored. On visualization of the retina, an early sign of hypertension is generalized narrowing of arteriolar vessels due to vasospasm and increased vascular tone [207]. Intimal thickening of the vessel wall and hyaline degeneration are late changes of chronic hypertension. The combination of cotton-wool spots and optic disc edema is indicative of severe systemic hypertension [201]. Cotton-wool spots represent microinfarcts of the retinal nerve fiber layer, and optic disc edema is caused by leakage of optic disc arterioles [201]. Vision is usually not affected. When moderate hypertension (a systolic pressure higher than 160 mm Hg and a diastolic pressure higher than 100 mm Hg) is chronic (five years or more), the walls of retinal arterioles become stiff and the lumen narrows [201]. Arteriovenous nicking and an increase in light reflection from the vessel wall seen on ophthalmoscopic examination are signs of chronic hypertension in individuals younger than 70 years of age; these signs are not reliable indicators of chronic hypertension in older individuals, as these abnormalities may be caused by advanced age alone [59].

According to earlier population-based epidemiologic studies representing more than 26,000 participants, various signs of retinopathy occur in 2% to 15% of individuals older than 40 years of age, regardless of blood pressure status [218,219]. The prevalence of retinopathy has also been higher in the Black population than in the White population, which may be a reflection of higher blood pressure levels in the Black population [218]. No differences in the prevalence of hypertensive retinopathy have been found between men and women [218].

There are no specific treatments to reverse the retinal changes associated with systemic hypertension, but studies show that timely intervention and control of blood pressure can halt progression and reduce risk of ocular complications [53,218]. The evidence is insufficient to recommend routine ophthalmoscopic consultation for all patients with hypertension [218]. Referral to an eye specialist may be useful for patients who have borderline or inconsistent hypertension. Due to the association between retinopathy and stroke, it may be beneficial to closely monitor individuals with these signs for cerebrovascular risk and implement interventions to reduce the risk [218]. In addition, routine examination of the retina may be of particular value for risk stratification of Black individuals [218].

Several autoimmune disorders have ocular manifestations, primarily involving the cornea (Table 15) [201]. The conjunctiva, uvea, sclera, retina, and surrounding structures may also be affected. Individuals with such disorders as rheumatoid arthritis, systemic lupus erythematosus, seronegative spondyloarthropathy, multiple sclerosis, giant cell arteritis, or Graves disease should have routine ophthalmologic examination to prevent ocular impairment. The use of NSAIDs, corticosteroids, and immunosuppressive agents to treat the systemic effects of these diseases is usually sufficient in managing the ocular symptoms; but additional specific treatment may sometimes be necessary[201]. To ensure appropriate management of ocular symptoms, primary care physicians should make timely referrals to eye specialists.

Several ocular conditions have been associated with HIV infection. Retinopathy is the most common ocular condition in individuals with HIV or acquired immune deficiency syndrome (AIDS), and cytomegalovirus (CMV) retinitis is the most common HIV-associated retinopathy [222]. Since the advent of highly active antiretroviral therapy (HAART), the prevalence of CMV retinitis has decreased substantially, but the infection remains the leading cause of poor vision and a predictor of mortality [222,226]. CMV retinitis may be asymptomatic or be associated with floaters, scotomata, or peripheral visual field defects [228].

Non-CMV opportunistic infections of the eye are uncommon but may be associated with high rates of vision loss or mortality [74]. HIV retinal microangiopathy is another common HIV-related ocular disease and was significantly associated with mortality in one study [226]. Visual dysfunction (abnormal visual field, reduced contrast sensitivity, and altered color vision) is common among individuals with AIDS who do not have retinitis, with nearly 40% of such individuals having an abnormal visual field [75]. Retinal vasculopathy may contribute to vision dysfunction [90].

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 primary challenges in diagnosing skin cancers are to distinguish between benign and malignant lesions and to identify lesions with malignant potential. The first steps in diagnosing basal cell or squamous cell carcinoma involve obtaining a history and physical examination and evaluating the clinical features of the lesion [223]. Symptomatology does not play a large role in the detection and diagnosis, as early-stage lesions are usually asymptomatic. Advanced lesions may be associated with nonhealing ulceration, bleeding, or pain [31]. A sore that does not heal may be a sign of either basal cell or squamous cell carcinoma [31].

The classic appearance of basal cell carcinoma is a pearly, waxy, or translucent papule or nodule with small telangiectatic vessels on its surface (nodular type). This type occurs frequently in the periocular area [31,227]. Superficial basal cell carcinomas are thinner than nodular lesions and often appear as scaly erythematous patches or plaques that may slowly enlarge. Care should be taken to distinguish this type of lesion from a benign inflammatory skin disorder, such as psoriasis or nummular eczema [31]. Both the superficial and the nodular types may look brown, blue, or black as a result of the presence of melanin. The morpheaform type of basal cell carcinoma usually presents as a whitish or yellowish, indurated, scar-like plaque, usually with indistinct borders [31]. The clinical course of this type is aggressive, and left untreated, it can lead to extensive destruction of soft tissue [227].

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].

According to the National Comprehensive Cancer Network (NCCN), the goal of treatment is elimination of the tumor with maximal preservation of function and physical appearance. Treatment decisions should be individualized in accordance with the patient's particular risk factors and preferences [225]. The treatment of choice for periocular basal cell and squamous cell carcinomas is surgical excision, and biopsy should be done preoperatively to confirm the diagnosis and identify the histologic subtype [31]. Mohs microsurgery is preferred for high-risk lesions, such as recurrent tumors, larger lesions, lesions near the medial canthus, and morpheaform basal cell carcinomas, as these lesions are associated with incomplete resection, the primary risk factor for recurrence [227]. The American Academy of Dermatology, in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery, has developed appropriate use criteria for Mohs micrographic surgery [32]. Mohs surgery is associated with the lowest five-year recurrence rate of any of the treatment modalities (1% to 2% for primary tumors) [223].

Radiotherapy may be useful for patients who are not candidates for surgery or who have an unresectable lesion [31,227]. Cryotherapy for periocular basal cell or squamous cell carcinoma is not usually recommended because removal of the lesion cannot be confirmed. However, the findings of several studies have indicated that this approach can be effective, and it is best used to treat small lesions in patients who are not good candidates for surgery. Recurrence rates are high for curettage and laser removal and photodynamic therapy [227].