Kendra J. Grande
LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Differentiate between the various ophthalmic disorders based on patient-specific information.
2. Choose an appropriate treatment regimen for an ophthalmic disorder.
3. Discuss the product differences that direct the selection of ophthalmic medications.
4. Assess when further treatment is required based on patient-specific information.
5. Recommend an ophthalmic monitoring plan given patient-specific information, a diagnosis, and a treatment regimen.
6. Educate patients about ophthalmic disease states and appropriate drug and nondrug therapies.
KEY CONCEPTS
The clinician must be able to distinguish ophthalmic conditions that lead to significant morbidity, including blindness.
The choice of topical antibiotic in patients who wear contact lenses must cover Pseudomonas aeruginosa.
Both acute and chronic bacterial conjunctivitis are self-limiting, except if caused by staphylococci.
Viral conjunctivitis is usually self-limiting, worsening after 4 to 7 days, but then resolving within 2 to 4 weeks.
Nonpharmacologic measures are critical to prevent the spread of viral conjunctivitis.
Use a step-care approach for treatment of allergic conjunctivitis.
Untreated bacterial keratitis is associated with corneal scarring and potential loss of vision. Corneal perforation may cause the loss of the eye.
There is no cure for age-related macular degeneration (AMD) and the efficacy of most treatments is low.
Dry eye is a chronic condition in which symptoms can be improved with treatment, but it is not usually curable. Patient education is critical.
INTRODUCTION
This chapter provides an overview of common ophthalmic disorders and their treatments. Many ophthalmic disorders are benign or self-limited, but the practitioner must be able to distinguish conditions that lead to serious morbidity, including blindness. Preserving both visual function and cosmetic appearance must be done whenever possible.1 The clinician must understand when referral is appropriate and the appropriate time frame for follow-up. These vary greatly by condition.
OCULAR EMERGENCIES
ETIOLOGY AND EPIDEMIOLOGY
Ophthalmic problems encompass 3% to 10% of all emergency department visits.1 Falls are a frequent cause of traumatic eye injury in the elderly.2 Corneal abrasions are the most common eye injury in children and are often due to fingernail scratches or objects swung near the eye. Even aggressive eye rubbing may damage the cornea. Accidental cigarette burns are common in children, but may be a sign of child abuse.3,4
Health care practitioners must know the proper treatment for ocular emergencies and the time frame for follow-up in order to prevent further morbidity (Table 63–1).
CORNEAL ABRASIONS
Treatment
Desired Outcomes
• Complete healing of the corneal abrasion with no scarring or vision impairment
• Prevent infection and pain
• Prevent corneal loss or corneal transplant
Clinical Presentation and Diagnosis of Corneal Abrasions3
Symptoms
• Photophobia
• Pain with extraocular muscle movement
• Foreign body sensation
• Recent ocular trauma
• Gritty feeling
• Headache
Signs
• Excessive tearing
• Blepharospasm
• Blurred vision
Diagnostic Test
Use sterile fluorescein dye strips and visualize the cornea under a cobalt-blue filtered light; abrasions appear green; ensure that no foreign body remains in the eye
Table 63–1 Ophthalmic Emergencies: Time to Follow-Up by Ophthalmologist
From Ref. 1.
General Approach to Treatment
The five layers of the cornea contain no blood vessels but are nourished by tears, oxygen, and aqueous humor. Minor corneal abrasions heal quickly. Moderate abrasions take 24 to 72 hours to heal. Deep scratches may scar the cornea and require corneal transplant if vision is impaired. Do not use eye patches to treat corneal abrasion, as they decrease oxygen delivery, increase pain, and increase the chance of infection.3
Corneal Abrasion Prevention3
• Wear eye protection during sports
• Wear industrial safety lenses
• Clip fingernails of infants and children
• Remove low-hanging branches and objects
Patient Encounter 1
A 12-year-old boy presents with a swollen, watery left eye that he cannot open. His mom says he was outside playing when it happened. You question the boy and he says he was sword-fighting with long sticks and was poked in the eye. He says it feels as though a piece of stick might still be in the eye. He rubbed it hard to try and improve it but now it hurts to even open the eye.
What is the proper time frame for follow-up for this injury?
What are the desired outcomes for this patient?
What pharmacologic therapy might be used after the foreign body is removed?
• Tape the eyelids closed or use gels or soft contacts during general anesthesia to prevent lag-ophthalmos
• Carefully fit and place contact lenses
Pharmacologic Therapy
Topical NSAIDs
Topical nonsteroidal anti-inflammatory drugs (NSAIDs) decrease pain from corneal abrasion. Available ocular NSAIDs are diclofenac 0.1%, ketorolac 0.5%, nepafenac 0.1%, and bromfenac 0.09%. The usual dose for diclofenac and ketorolac is one drop four times daily; nepafenac is dosed three times daily and bromfenac is dosed twice daily. Use topical NSAIDs with caution in patients with clotting disorders or those who are on systemic NSAIDs or warfarin therapy. Topical administration of NSAIDs may delay wound healing, especially with concurrent topical corticosteroid use.3,5 Oral analgesics are not well studied for use in corneal abrasion; they may have decreased efficacy. They are less expensive than topical NSAIDs and may be an option for some patients.3
Topical Antibiotics
Because an infection slows the healing of a corneal abrasion, prophylactic antibiotics are often used. Studies on the efficacy of this are mixed. Discontinue the use of contact lenses until the abrasion is healed and the antibiotic course complete.
In contact lens wearers, choose an antibiotic that covers Pseudomonas aeruginosa, like gentamicin ointment or solution or a fluoroquinolone.3 Antibiotic resistance is an increasing problem. Resistance occurs primarily with older antibiotics, but has been reported for fluoroquinolones as well. Two newer fluoroquinolones, gatifloxacin and moxifloxacin, do not yet have reports of resistance. These agents are more expensive.6
Outcome Evaluation
1. Reevaluate patients in 24 hours.
2. If symptoms worsen, recheck for foreign bodies.
3. If not fully healed, evaluate again in 3 to 4 days.
4. Refer to ophthalmologist if3 :
• No improvement in 3 days
• Worsening symptoms
• Symptoms do not improve daily
• Symptoms do not improve within a few hours of contact lens removal
OTHER OCULAR EMERGENCIES: TREATMENT
Traumatic Injuries
Attempt to remove loose foreign bodies by gentle irrigation with artificial tears or sterile saline. If removal is successful, a topical broad-spectrum antibiotic, such as erythromycin, will prevent infection. Some patients may need a short-acting cycloplegic mydriatic-like cyclopentolate or tropicamide to help with pain.7 Do not use cycloplegic mydriatics in children.8 If irrigation is unsuccessful, mechanical removal of foreign objects should be completed only by ophthalmologists using a slitlamp. Protect the eye with a metal eye shield or a paper cup taped over the eye while awaiting the ophthalmologist.7
Splash Injuries and Chemical Exposure
Instruct patients by phone to irrigate the eye immediately with water or saline continuously for at least 15 minutes before seeking a clinician. Irrigation dilutes and removes the chemical agent, and is the best way to decrease ocular tissue damage. Patients should then seek immediate care from an ophthalmologist or emergency facility.7
Loss of Vision
A variety of disorders may lead to rapid, painless, monocular or binocular vision loss. These include central retinal artery occlusion, acute narrow-angle glaucoma, trauma, and others. The differential diagnosis is complex and needs to be undertaken by an emergency department or ophthalmologist.9
CONJUNCTIVITIS
While no exact numbers are available, conjunctivitis, also known as red eye, is one of the most common ophthalmic complaints seen by general clinicians. An inflamed conjunctiva is the most common cause of red eye.10 Use the differential diagnosis algorithm shown in Figure 63–1 to determine the proper treatment or need for referral.
BACTERIAL CONJUNCTIVITIS
Etiology
The vast majority of conjunctivitis cases are viral in nature. For acute bacterial conjunctivitis, the cause is primarily gram-positive organisms.11 The primary pathogens in acute bacterial conjunctivitis are Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae.12
Staphylococcus, Moraxella, or other opportunistic bacteria typically cause chronic conjunctivitis.10 Moraxella infections may cluster in groups of women who share makeup.12 
Both acute and chronic bacterial conjunctivitis are self-limiting except if caused by staphylococci. 13 Because of this, the pathogens are rarely cultured unless the case is unresponsive to treatment. While infection typically begins in one eye, it will often spread to both within 48 hours.11
Hyperacute bacterial conjunctivitis is associated with gonococcal infections in sexually active patients. The causative agents are Neisseria gonorrhoeae or N. meningitidis. Prompt workup and treatment is required, as corneal perforation occurs in 10% of cases within 48 hours.12 An ophthalmologist should complete a conjunctival scraping and susceptibility testing.10
FIGURE 63–1. Differential diagnosis for red eye.
Treatment
General Approach to Treatment
• Complete resolution of the bacterial conjunctivitis
• Prevent adverse consequences of the infection
• Preserve functionality of the eye
General Approach to Treatment
Treat acute bacterial conjunctivitis with broad-spectrum antibiotics. Although the condition is usually self-limiting, antibiotic treatment decreases the spread of disease to other people and prevents extraocular infection. Additionally, treatment may help decrease the risk of corneal ulceration or other complications that affect sight. Finally, treatment speeds recovery.14
Pharmacologic Therapy
The choice of an antibiotic agent for acute bacterial conjunctivitis is largely empiric. The initial treatment needs to include Staphylococcus coverage, but also may be chosen on the basis of cost and side-effect profile.13,14 In general, ointments are a good dosage form for children. Adults may prefer drops because they do not interfere with vision.14
Many broad-spectrum topical antibiotics are approved to treat acute bacterial conjunctivitis (Tables 63–2 and 63–3). Polymyxin B/trimethoprim solution, polymyxin B with bacitracin ointment, or erythromycin ointment are cost-effective, first-line treatments. The aminoglycosides (tobramycin, neomycin, and gentamicin) are alternatives but have incomplete gram-positive coverage.14 The aminogly-cosides can cause corneal epithelial toxicity. Neomycin often causes allergic reactions. Tobramycin is the best tolerated of the class, but is also the most expensive. Sulfacetamide 10% shows increasing resistance. If infection recurs, use a topical fluoroquinolone like ofloxacin, ciprofloxacin, norfloxacin, gatifloxacin, moxifloxacin, or levofloxacin.12 Fluoroquinolones are not used first-line for conjunctivitis because they have poor Streptococcus coverage and are expensive. Development of resistance is also a concern with fluoroquinolones.14
Treat hyperacute bacterial conjunctivitis with a single dose of 1 g of intramuscular ceftriaxone in combination with topical antibiotics.11
Patients with chronic bacterial conjunctivitis often have a concurrent case of blepharitis. Add a lid hygiene regimen to topical antibiotic treatment.12
Outcome Evaluation
Significant improvement of acute bacterial conjunctivitis should be seen within 1 week.11 Terminate treatment with topical antibiotics when the inflammation is resolved.12
Table 63–2 Adult Bacterial Conjunctivitis Dosing Guidelines for Topical Ophthalmic Antibiotics
VIRAL CONJUNCTIVITIS
Etiology
The most common cause of viral conjunctivitis is adenovirus. It is often called “pink-eye.”10 Viral conjunctivitis infections are easily spread through swimming pools, camps, and contaminated fingers, and medical instruments.14Patients often present with an upper respiratory tract infection or recent exposure to viral conjunctivitis. While the infection begins in one eye, it will spread to both eyes 50% of the time. 
Viral conjunctivitis is usually self-limiting, worsening after 4 to 7 days but then resolving within 2 to 4 weeks.10 Five percentage of patients remain contagious 16 days after the appearance of symptoms.11
Table 63–3 Pediatric Dosing Guidelines for Bacterial Conjunctivitis for Topical Ophthalmic Antibiotics
Patient Encounter 2
A 40-year-old woman presents complaining of irritation, redness, and stickiness of the right eye for the past 48 hours. Today she woke up with the lids of the right eye stuck together and it took a warm washcloth to get her eye open. Examination reveals a whitish discharge from the right eye and a redness of the left eye. She has worn contact lenses for 6 years.
What is the probable diagnosis?
On physical assessment, how do you differentiate between bacterial, hyperacute bacterial, viral, and allergic causes?
What is a reasonable treatment regimen for her?
Treatment
Desired Outcomes
• Complete resolution of the viral conjunctivitis
• Prevent adverse consequences of the infection
• Avoid spreading infection to other patients
Nonpharmacologic Therapy
Nonpharmacologic measures are critical to prevent the spread of viral conjunctivitis. Patients should not share towels or other contaminated objects, should avoid close contact with other people, and avoid swimming for 2 weeks.10 The virus remains viable on dry surfaces for more than 2 weeks.13 Take care in the medical setting to thoroughly decontaminate instruments and wash hands.11
Patients may obtain symptomatic relief by using cold compresses and artificial tears.10 If artificial tear solutions sting, recommend a preservative-free formula.
Pharmacologic Therapy
Topical antivirals are not used to treat adenovirus conjunctivitis. Topical antibiotics are often prescribed for vira l conjunctivitis, ostensibly to prevent bacterial superinfection. In reality, this is a case of the patient insisting on a medication to speed healing.11 Avoid the use of antibiotics for a viral infection.12 Eliminating superfluous antibiotic use also helps prevent the development of antibiotic resistance.
If patients have a severe subepithelial infiltration, a topical steroid may be required. However, topical steroids may cause serious ocular complications and may worsen herpetic conjunctivitis, which has similar symptoms as viral conjunctivitis. Additionally, the period of virus shedding may be prolonged by up to 50% by topical prednisolone. Only ophthalmologists should prescribe topical steroids.10
Outcome Evaluation
Refer patients that do not see improvement within 7 to 10 days to an ophthalmologist to rule out herpetic and other infectious processes.11 If pain or photophobia occurs, suspect corneal involvement and refer the patient. This typically occurs 10 to 14 days after the onset of conjunctivitis.13
ALLERGIC CONJUNCTIVITIS
Etiology
Ocular allergy is a broad term that includes several diseases with the hallmark symptom of itching, often accompanied by tearing, conjunctival swelling, and nasal congestion.14 Seasonal ocular allergy is the most common type of allergic conjunctivitis. This is an IgE-mediated hypersensitivity to pollen or other airborne allergens.11 Often, the patient’s history is positive for atopic conditions such as allergic rhinitis, asthma, or eczema.14 Perennial allergic conjunctivitis has similar but less severe symptoms and may not be tied to a specific time of year. Finally, conjunctivitis medicamentosa is a contact allergy to a topical medication, often an antibiotic.11
Pathophysiology
The conjunctiva of the eye is often the first site of contact with an environmental allergen. Mast cell degranulation occurs, resulting in the release of mediators. The earliest mediator is histamine, which causes itching, redness, and swelling. Leukotrienes and prostaglandins cause increased mucus secretion and cellular infiltration along with chemosis, resulting in conjunctival vasodilation. The mast cells also release cytokines, chemokines, and growth factors which trigger inflammatory processes.17
Treatment of ocular allergy is aimed at slowing or stopping these processes. Antihistamines block the histamine receptors and some prevent histamine production and/or inhibit mediator release from the mast cells.17 Mast cell stabilizers inhibit the degranulation of mast cells, preventing mediator release. Some topical agents have multiple mechanisms of action, combining antihistaminic, mast cell stabilization, and anti-inflammatory properties (Tables 63–4, 63–5, and 63–6).18
Treatment
Desired Outcomes
• Relief of current allergic symptoms
• Prevention of future allergic symptoms
• No adverse effects from treatment
Nonpharmacologic Therapy
The primary treatment for ocular allergy is removal and avoidance of the allergen.19 For conjunctivitis medicamentosa, discontinue the offending medication.11 Apply cold compresses three to four times daily to reduce redness and itching and to provide symptomatic relief.20
Pharmacologic Therapy
Use a step-care approach for the treatment of allergic conjunctivitis. The first step is a nonmedicated, artificial tears solution. The solution dilutes or removes the allergen, providing relief while lubricating the eye. Solutions are applied two to four times daily as needed. Ointments may be used in the evenings to further moisturize the surface of the eye.19 There are many products on the market. Try a preservative-free formulation if other products sting or burn. Unit-dose preservative-free products are more expensive. Some newer multidose products, such as sodium perborate (Purite), have rapidly dissociating preservatives and are more cost-effective.
Table 63–4 Mechanisms of Action of Ocular Allergy Drugs
Table 63–5 Adult Dosing and Common Side Effects of Ocular Allergy Drugs
Table 63–6 Pediatric Dosing of Ocular Allergy Drugs
If artificial tears are insufficient, the second treatment step is a topical antihistamine or antihistamine/decongestant combination. The antihistamine/decongestant combination is more effective than either agent alone. Decongestants are vasoconstrictors that reduce redness and seem to have a small synergistic effect with the antihistamine. The only topical decongestant used in combination products is naphazoline. Topical decongestants burn and sting on instillation and commonly cause mydriasis, especially in patients with lightercolored eyes. Long-term use leads to rebound congestion. Topical decongestant use should be limited to less than 10 days.19
There is still debate whether oral antihistamines control ocular allergy as well as topical antihistamines. Topical antihistamines are recommended before oral agents in step therapy because of the increased risk of systemic side effects with oral drugs. Additionally, topical antihistamines provide faster relief of ocular symptoms. Consider oral antihistamines when systemic symptoms are present.17
If insufficient relief is obtained from these products, either a mast cell stabilizer or a multiple-action agent is appropriate.19 Use mast cell stabilizers prophylactically throughout the allergy season. Full response may take 4 to 6 weeks.
If mast cell stabilizers or multiple-action agents are not successful, a trial of a topical NSAID is appropriate. Ketorolac is the only approved topical agent for ocular itching. NSAIDs do not mask ocular infections, affect wound healing, increase intraocular pressure, or contribute to cataract formation like the topical corticosteroids. However, in clinical trials, for allergic conjunctivitis topical ketorolac was not as effective as olopatadine or emedastine.17 Full efficacy of ketorolac may take up to 2 weeks.19
If all these avenues are ineffective, short-term topical corticosteroids and immunotherapy are the third-line treatments for ocular allergy.19
Outcome Evaluation
Monitor patients for relief of symptoms. Ensure an adequate trial of the agent. If no improvement is seen, follow a stepped-care approach to treatment. Refer severe cases that do not respond to an ophthalmologist for short-term topical corticosteroids.
BACTERIAL KERATITIS
EPIDEMIOLOGY
Thirty thousand cases of microbial keratitis occur annually in the United States.21 Microbial keratitis encompasses bacterial, fungal, and Acanthamoeba keratitis.21 Only bacterial keratitis, the most common form, is discussed here.
PATHOPHYSIOLOGY
Bacterial keratitis is a broad term for a bacterial infection of the cornea. This includes corneal ulcers and corneal abscesses. The cornea in a healthy eye has natural resistance to infection, making bacterial keratitis rare. However, many factors may predispose a patient to bacterial infection by compromising the defense mechanisms of the eye (Table 63-7).21
Clinical Presentation and Diagnosis of Bacterial Keratitis10,21
General
The rate of progression of signs and symptoms varies depending on the infecting organism. A differential diagnosis for keratitis must include viral, fungal, and nematodal infections in addition to bacterial causes.
Symptoms
• Photophobia
• Rapid onset of ocular pain
Signs
• Red eye
• Conjunctival discharge
• Decreased vision
Laboratory Tests
Culture if keratitis is severe or sight-threatening. Otherwise, culture or smear only if the corneal infiltrate is chronic or unresponsive to broad-spectrum antimicrobial therapy.
The most common pathogens in bacterial keratitis are Pseudomonas (including Pseudomonas aeruginosa) and other gram-negative rods, Staphylococci, and Streptococci.21 If the keratitis is related to the use of contacts, Pseudomonas and Serratia marcescens are the most common pathogens.21 For hospitalized infants and adults on respirators, Pseudomonas is the most common.21
Untreated bacterial keratitis is associated with corneal scarring and potential loss of vision.21 Corneal perforation may occur and the patient may lose the eye. 21 In virulent organisms, this destruction may occur within 24 hours.21 Central corneal scarring may result in vision loss even after successful eradication of the organism.21
TREATMENT
Desired Outcomes21
• Resolution of infection
• Resolution of corneal inflammation
Table 63–7 Risk Factors for Bacterial Keratitis
Exogenous Factors
Contact lenses
Loose sutures
Previous corneal surgery
Previous ocular or eyelid surgery
Trauma
Ocular Surface Disease
Abnormal lid anatomy or function
Misdirection of eyelashes
Ocular infection (e.g., conjunctivitis, blepharitis)
Tear film deficiencies
Systemic Conditions
Atopic dermatitis
Connective tissue disease
Debilitating illness (e.g., malnourishment or respirator dependence)
Diabetes mellitus
Factitious disease (including anesthetic abuse)
Gonococcal infection
Immunocompromised
Stevens-Johnson syndrome
Substance abuse
Vitamin A deficiency
Medications
Anesthetics
Antimicrobials
Contaminated ocular medications
Glaucoma medications
Preservatives
Steroids
Topical NSAIDs
Corneal Epithelial Abnormalities
Corneal epithelial edema
Predisposition to recurrent erosion of the cornea
Viral keratitis (e.g., herpes simplex or zoster keratitis)
From Ref. 21.
• Reduced corneal pain
• Restored corneal integrity with minimal scarring
• Restored visual function
General Approach to Treatment
All cases of suspected bacterial keratitis require prompt ophthalmology consultation to prevent permanent vision loss.10
Pharmacologic Therapy
Dosage Considerations
Topical antibiotic drops are preferred. Consider subconj-unctival antibiotics if compliance is a concern. Systemic therapy is useful in cases of systemic infection (e.g., gonorrhea) or if the sclera is infected. Reserve ointments for minor cases or adjunctive nighttime therapy.21
Drug Choice
Start topical broad-spectrum antibiotics empirically. Use a loading dose for severe keratitis (Table 63–8). Single-drug therapy with a fluoroquinolone is as effective as combination therapy. Resistance is seen with some fluoroquinolones. Because of this, choose a newer fluoroquinolone such as moxifloxacin or gatifloxacin in severe keratitis cases.6,21 Fortified antibiotic therapy is an option for severe or unresponsive infections, but may increase toxicity to the cornea and surrounding tissues. Fortified antibiotics must be compounded.21 All compounded formulations must comply with governmental 797 regulations concerning compounding of drug preparations.
Table 63–8 Pharmacologic Therapies for Bacterial Keratitis Organism
Topical corticosteroids are employed in some cases of bacterial keratitis. The suppression of inflammation may reduce corneal scarring. However, local immunosuppression, increased ocular pressure, and reappearance of the infection are disadvantages to their use. There is no conclusive evidence that they alter clinical outcomes. If the patient is already on topical corticosteroids when the keratitis occurs, discontinue use until the infection is eliminated.21
Outcome Evaluation 21
• Monitor patient symptoms for improvement to determine therapeutic efficacy
• Modify treatment regimen based on results of culture and sensitivity testing, if necessary
• Modify the treatment regimen if the patient does not show improvement within 48 hours
• Gram-negative keratitis will have increased inflammation in the first 24 to 48 hours, even on appropriate therapy
• Taper therapy based on clinical response
• Reculture or biopsy if negative clinical response; to improve culture results, discontinue antibiotics for 12 to 24 hours before culturing.
MACULAR DEGENERATION
EPIDEMIOLOGY AND ETIOLOGY
Age-related macular degeneration (AMD) is the primary cause of severe, irreversible vision impairment in developed countries (Figs. 63–2 and 63–3). The prevalence increases with age.22 In the United States, 1.75 million people age 40 or older have advanced AMD, and another 7 million people may have intermediate AMD.22 Because of the rapid aging of the U.S. population, it is projected that almost 3 million people will develop AMD by 2020.23 The causes of AMD are not completely known (Table 63–9).22
PATHOPHYSIOLOGY
AMD is a deterioration of the macula, the central portion of the retina. The macula facilitates central vision and highresolution visual acuity because it has the highest concentration of photoreceptors in the retina. The loss of central vision leads to irreversible loss of the ability to drive, read, and perform other fine visual tasks like recognize faces.25 Peripheral vision is preserved, allowing mobility.22 AMD is characterized by one or more of the following: drusen formation, retinal pigment abnormalities (e.g., hypo- or hyperpigmentation), geographic atrophy, and neovascular maculopathy.20
FIGURE 63–2. Normal vision. (From the National Eye Institute, National Institutes of Health Ref. No. EDS01. Accessed online at: http://www.nei.nih.gov/photo/)
FIGURE 63–3. The scene in Figure 63–2 as it might be viewed by a person with age-related macular degeneration. (From the National Eye Institute, National Institutes of Health Ref. No. EDS05. Accessed online at: http://www.nei.nih.gov/photo/)
Table 63–9 Risk Factors for AMD
Clinical Presentation and Diagnosis of AMD 20,23
Symptoms
• Mild blurry central vision
• Difficulty reading
• Trouble with color and contrast
• Painless, progressive, moderate to severe blurring of central vision
• Sudden loss or distortion of vision possible
Signs
• Drusen
• Retinal pigment epithelial mottling
Other Diagnostic Tests
• Amsler’s grid abnormalities indicate fluid in subretinal space (Figs. 63–4 and 63–5)
• Dilated fundus examination shows drusen and pigmentary abnormalities in the macula
• Rapid sequence fluorescein angiography shows leakage in the neovascular form
Patient Encounter 3, Part 1
ET, a 60-year-old white male, presents with difficulty reading and says he is having trouble differentiating between red and orange.
PMH: Hypertension, diabetes mellitus for 12 years, congestive heart failure
SH: Smokes half a pack daily; denies any alcohol or drug use; married, one adult child who lives nearby
FH: Father died at age 57 from heart failure; mother blind from age 50, died at 62 from breast cancer
PE:
BP 140/98, ht 6’ 0” (182 cm), wt 120 kg (264 lb)
What risk factors and potential risk factors for age-related macular degeneration does the patient have?
Based on clinical presentation, AMD is classified as early, intermediate, or advanced.20 Early AMD is characterized by small or intermediate drusen and minimal macular pigment abnormalities.20 These patients generally have normal central vision.20 Intermediate AMD patients have medium or large drusen in one or both eyes.20 Approximately 18% of these patients will progress to advanced AMD within 5 years.20
Advanced AMD is classified as non-neovascular (also called the atropic, nonexudative, or dry form) or neovascular (the exudative or wet form).22,25 In the non-neovascular form, the retina and other layers atrophy.25 In the neovascular form, new blood vessels appear.22,25 Generally, vision is already affected when patients progress to advanced AMD; vision loss is seen in both forms.22 Ten to twenty percentage of patients with the non-neovascular form will progress to the neovascular form.26 Once one eye develops advanced AMD, 43% of patients will develop neovascular changes or atrophy in the other eye within 5 years.22
TREATMENT
Desired Outcomes
The primary goal of treatment for AMD is to slow the disease progression. Th is includes slowing the loss of visual acuity and the progression to legal blindness, along with maintaining contrast sensitivity and slowing the rate of progression to late AMD. The secondary goals are maintaining quality of life for the patient and minimizing the adverse effects of treatment.25
General Approach to Treatment
There is no cure for AMD and the efficacy of most treatments is low. Newer drug developments show promise but no treatment can reverse damage that has already occurred. 26 Early diagnosis is critical. High-risk patients need periodic eye examinations because some patients do not notice any changes, even when neovascularization has occurred.22
Nonpharmacologic Therapy
Non-neovascular AMD
Advise patients to stop smoking as observational data support a causal relationship between smoking and AMD.22
Drusen ablation by laser has been used in non-neovascular AMD. However, it is not clear if the treatment reduces progression to neovascular AMD.26 There is a possibility that the treatments may induce neovascularization and retinal atrophy.25 Other nonpharmacologic therapies are in trials but there is insufficient evidence for experts to recommend these procedures at this time.22
Neovascular AMD
Thermal laser photocoagulation reduces severe visual loss 2 to 5 years after the procedure, but leads to an immediate and permanent reduction in central vision. There is a 50% chance that leakage will recur in the next 2 years after the procedure.25
Photodynamic therapy uses nonthermal red light to activate verteporfin, which produces reactive oxygen species that locally damage the neovascular endothelium.27 Verteporfin treatment reduces the risk of loss of visual acuity and legal blindness over 1 to 2 years. Long-term results are not yet available. Severe photosensitivity for 3 to 5 days after the procedure is common and some patients experience a severe loss of vision. Eventually, most patients have some visual recovery. This procedure requires multiple treatments over time.25 Other nonpharmacologic therapies are in trials but there is insufficient evidence for experts to recommend these procedures at this time.22
Pharmacologic Therapy
There are no approved pharmacologic treatments for nonneovascular AMD.28 The Age-Related Eye Disease Study showed that a supplement containing ascorbic acid 500 mg, vitamin E 400 IU, β-carotene 15 mg, zinc oxide 80 mg, and cupric oxide 2 mg reduced the rate of clinical progression of all types of AMD by 28% in patients with at least intermediate macular degeneration.28 No benefit was seen in patients with earlier stages of AMD; however, the duration of the study may have been insufficient to detect this benefit.28 Currently, experts recommend antioxidant supplementation for intermediate AMD or advanced AMD in one eye.22 Supplementation is not without risk.26 For example, β-carotene supplementation in smokers may increase the risk of developing lung cancer.22,26 At this time, it is not clear from the evidence if a patient at a high risk but without symptoms of AMD would benefit from supplementation.29
Vascular endothelial growth factor induces angiogenesis, increases vascular permeability, and increases inflammation, all of which are thought to contribute to neovascular AMD. 30 Pegaptanib, a vascular endothelial growth factor antagonist, binds to these growth factors in an attempt to suppress neovascularization.22,30 In clinical studies, patients treated with pegaptanib experienced a slower rate of visual decline than patients treated with a sham injection.31 Vision loss continued to occur in patients and the drug was less effective in the second year of treatment.30 Long-term efficacy studies are not available yet.30
Patient Encounter 3, Part 2
ET is diagnosed with non-neovascular intermediate AMD.
What nonpharmacologic treatment options does this patient have?
What pharmacologic treatment options does this patient have? What are the risks and benefits of each option?
What monitoring is appropriate for this patient?
Patient Encounter 3, Part 3
Two years have passed. ET (now 62 years of age) has progressed to advanced neovascular AMD. His central vision continues to deteriorate and he recently gave up driving after several near-accidents. His wife and son help him with his daily routine now.
What treatment options does this patient have? What are the risks and benefits of each option?
Another drug, ranibizumab, binds to and inhibits the activity of VEGF-A, a critical protein in angiogenesis.22 In one clinical study, 95% of patients treated with ranibizumab maintained visual acuity after 12 months compared with 62% of control patients.22 Both pegaptanib and ranibizumab are administered by intravitreous injection.22,30
Outcome Evaluation
Monitor patients for acute and chronic vision changes or loss. The Amsler’s grid (Figs. 63–4 and 63–5) and frequent eye examinations may detect changes more quickly. The long-term prognosis for AMD is poor. Monitor patients for inability to drive and remove driving privileges as appropriate. Work with patients and family members to plan for lifestyle changes as vision decreases.22
DRY EYE
EPIDEMIOLOGY
Dry eye is a frequent cause of eye irritation. A lack of a single diagnostic test for the condition limits the available epidemiologic data. One study estimated the prevalence of dry eye in the U.S. population age 65 and older at 14.6%, which is approximately 4.3 million Americans.32
FIGURE 63–4. Amsler’s grid distortions in the lines of the grid may be caused by subtle changes in central vision due to fluid in the subretinal space. This is the Amsler’s grid as it appears to someone with normal vision. (From the National Eye Institute, National Institutes of Health Ref. No. EC03. Accessed online at: http://www.nei.nih.gov/photo/)
FIGURE 63–5. Amsler’s grid as it might appear to someone with AMD. (From the National Eye Institute, National Institutes of Health Ref. No. EC04. Accessed online at: http://www.nei.nih.gov/photo/)
The risk factors for dry eye are listed in Table 63–10. Of interest, the use of caffeine is associated with a decreased risk of dry eye. Dry eye that is left untreated can cause loss of vision or other morbidities over time.33
PATHOPHYSIOLOGY
The ocular surface and the tear-secreting glands of the eye function as an integrated unit. This unit refreshes the tear supply and clears away used tears. An autonomic neural reflex loop stimulates secretion of tear fluid and proteins by the lacrimal glands. The sensitivity of the ocular surface decreases with the decrease of aqueous tear production and tear clearance. This results in a decrease in sensory-stimulated reflex tearing which exacerbates dry eye.32,33Over time, wearing contact lenses also desensitizes the cornea by constant stimulation.12
Table 63–10 Risk Factors for Dry Eye
Older age
Female gender
Arthritis
Smoking
Multivitamin use
Estrogen replacement therapy
From Ref. 33.
Table 63–11 Associated Conditions That Cause or Worsen Dry Eye
Dysfunction may be caused by aging, systemic inflammatory diseases, a decrease in androgen hormones, surgery, ocular surface diseases (such as herpes zoster), systemic diseases, or medications that affect the efferent cholinergic nerves. Decreased tear secretion produces an inflammatory response on the ocular surface called keratoconjunctivitis sicca. This inflammation is a target for new medications that treat dry eye.32,33
Conditions that increase the evaporative loss of tears also worsen dry eye. In addition to environmental causes (Table 63–11), an abnormal blink reflex is a common cause of increased evaporative loss.33
TREATMENT
Desired Outcomes
• Relief of the symptoms of dry eye
• Prevention of recurrence
• Prevention of long-term adverse effects from dry eye
General Approach to Treatment
Dry eye is a chronic condition. Symptoms can be improved with treatment but unless dry eye is secondary to a disease, it is not usually curable. Because of this, patient education is critical and a periodic reassessment of the efficacy of the treatment is appropriate. If the patient is unresponsive to treatment, refer to an ophthalmologist for additional options. If the dry eye is secondary to a systemic disease, the disease should be managed by the appropriate medical specialist.33
Clinical Presentation and Diagnosis of Dry Eye 33
General
Many other ocular diseases have similar symptoms. Patients with suggestive symptoms without signs should be placed on a treatment trial. Repeated observations over time may be required for a clinical diagnosis.
Symptoms
• Dry or foreign body sensation
• Mild itching
• Burning
• Stinging
• Photophobia
• Ocular irritation or soreness
• Blurry vision
• Contact lens intolerance
• Diurnal fluctuation
• Symptoms that worsen later in the day
Signs
• Redness
• Mucus discharge
• Increased blink frequency
• Tearing
Other Diagnostic Tests
• The tear break-up time test assesses the stability of precorneal tear film. Break-up times of less than 10 seconds are considered abnormal.
• Ocular surface dye staining assesses the ocular surface and will show blotchy or exposure-zone punctate areas in the dry eye.
• Schirmer’s test evaluates aqueous tear production but is not diagnostic for dry eye. Results of 5 mm or less are considered abnormal.
• Assess corneal sensation if trigeminal nerve dysfunction is suspected.
• Evaluate for an autoimmune disorder if significant dry eyes or other signs and symptoms or family history are present.
Nonpharmacologic Therapy
Behavioral and environmental modifications may significantly improve dry eye, especially in mild cases. Evaluate the patient’s environment for air drafts. Consider adding a humidifier in low-humidity areas. Schedule regular breaks from computer work or reading. Lower the computer screen to below eye level to decrease lid aperture. Evaluate medication profile and therapeutically substitute medications that do not exacerbate dry eye. Spectacle sideshields or goggles may reduce tear evaporation.33
If pharmacologic and other therapies are not sufficient, punctal occlusion or lateral tarsorrhaphy may be an option. Punctal occlusion is the plugging of the punctal drainage sites with collagen (temporary) or Silastic (permanent) plugs. Lateral tarsorrhaphy sutures portions of the lid margins together to decrease evaporative tear loss. These procedures are reserved for severe cases of dry eye secondary to other diseases.12
Pharmacologic Therapy
Regardless of the cause, the mainstay of treatment for dry eye is artificial tears. Artificial tears augment the tear film topically and provide relief. If a patient uses artificial tears more than four times daily, recommend a preservative-free formulation. Preservative-free formulations are also appropriate if the patient develops an allergy to ophthalmic preservatives. Artificial tears are available in gel, ointment, and emulsion forms that provide a longer duration of relief and may allow for less frequent instillation. Ointment use is appropriate at bedtime.33
Anti-inflammatory agents may be used in conjunction with artificial tears. The only approved agent is cyclosporine emulsion. Administered topically, the exact mechanism is unknown but it is thought to act as a partial immunomodulator suppressing ocular inflammation. Cyclosporine emulsion increases tear production in some patients. Fifteen minutes should elapse after instillation of cyclosporine before artificial tears are instilled.34 Use of topical corticosteroids for short periods (e.g., 2 weeks) may suppress inflammation and ocular irritation symptoms. No topical corticosteroid is approved for this indication, however.33
The oral cholinergic agonists pilocarpine and cevimeline are used for patients with combined dry eye and dry mouth (e.g., Sjögren’s syndrome) or severe dry eye. By binding to muscarinic receptors, the cholinergic agonists may increase tear production. Excessive sweating is a common side effect with pilocarpine and may limit its use (Table 63–12).
Outcome Evaluation 32
• Monitor patient for relief of symptoms
• Periodically reassess the patient’s compliance and understanding of the disease
• It may take 6 weeks before improvement is seen with pilocarpine therapy
• Cyclosporine therapy may take up to 6 months for full efficacy
• If a patient presents with visual loss, moderate or severe pain, corneal ulceration, or a lack of response to therapy, refer the patient to an ophthalmologist for prompt evaluation.
Patient Encounter 4
A 60-year-old woman presents with complaints of redness, burning, and watering of both eyes, which worsen as the day progresses. She does not have any itching of the eyes or other visible discharge. She has had the symptoms for several years but the symptoms have worsened recently. Your physical examination reveals red and teary eyes.
Her medical history includes osteoarthritis, mild osteoporosis, and hypertension. She also has recurrent sinus infections associated with seasonal allergic rhinitis. She has a new job as a medical transcriptionist.
Meds: Metoprolol 100 mg daily; conjugated estrogens 0.3 mg daily; calcium carbonate tablets 1,200 mg daily; ibuprofen 600 mg as needed for joint pain; loratadine 10 mg as needed for allergies; senior nonprescribed multivitamin daily
What is the probable diagnosis?
What are the other contributing factors that may be worsening her condition?
What nonpharmacologic interventions might she benefit from?
What pharmacologic treatment option is best for her?
Table 63–12 Pharmacologic Therapies for Dry Eye
Patient Care and Monitoring: Nasolacrimal Occlusion 36
Use of nasolacrimal occlusion decreases systemic absorption up to 60% and may increase ocular bioavailability of the drug. After instilling the eye drop, the patient should close the eye and press a finger gently against the nasolacrimal duct (tear duct) for 2 to 3 minutes.
Table 63–13 Selected Drug-Induced Ocular Changes
DRUG-INDUCED OCULAR DISORDERS
Table 63–13 shows some ocular changes due to the use of certain drugs.
Abbreviations Introduced in This Chapter
Self-assessment questions and answers are available at http://www.mhpharmacotherapy.com/pp.html.
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