Nasolacrimal occlusion is effective and can maximize drug benefits because a
lower concentration of an ophthalmic formulation can be used and the dose can be
CASE 54-1, QUESTION 5: Two weeks after initiation of therapy, M.H. returns to clinic for a follow-up
evaluation. Her IOP measures 32 mm Hg in the right eye and 30 mm Hg in the left eye. She denies
alternative dosage forms or drugs that can be used?
Betaxolol may not be as effective as other ocular β-blockers. Therefore,
adjunctive therapy may be required. However, M.H. should be evaluated to
determine whether she has been using the technique of nasolacrimal occlusion. If not,
M.H. should be again instructed on the technique of nasolacrimal occlusion and the
importance of this technique in achieving the maximal therapeutic effect of her
therapy (see Case 54-1, Question 4).
After the initiation of therapy, patients should be seen for a follow-up evaluation
within about 2 weeks. If M.H. has been adherent to therapy and has been occluding
her nasolacrimal ducts, a new course of action is needed because her IOP still is
elevated. When the goal of therapy has not been achieved, the drug concentration of
the ophthalmic formulation can be increased, adjunctive therapy (e.g., brimonidine, a
topical CAI, a PGA) can be initiated, or an alternative first-line agent can be
selected. Patients who are experiencing unstable reductions of IOP should be
5 Stable patients usually are evaluated every 6 to 12
the left eye. What are the possible causes of her side effects and poor response to therapy?
The exposure of dorzolamide to the outside environment may result in the
aggregation of dry white granules on the tip of the dorzolamide bottle. These granules
can drop into a patient’s eyes when instilling the medication, leading to local side
effects, such as stinging and foreign body sensation. Such foreign bodies may cause
enough discomfort to induce nonadherence, resulting in a poor response to therapy.
These granules may be rinsed off of the tip with sterile water. M.H. should be
questioned about the presence of dry white granules on the tip of her dorzolamide
These complaints may also be a side effect from the medications, regardless of the
granule presence. Ocular burning, stinging, and discomfort were reported in one-third
of patients in dorzolamide clinical trials. M.H.’s administration technique should
also be assessed to determine whether she is administering the two drugs at least 5 to
10 minutes apart so that the first drug is not washed away by the second drug. This
should be a consideration when assessing her response to therapy.
CASE 54-1, QUESTION 7: After further discussions with M.H., it is determined that she has not been
especially appropriate for M.H.? What patient education information should be provided to M.H. about
Prostaglandin analogs are first-line agents and are appropriate in patients who are
not responding to or are having intolerable side effects from other medications.
Travoprost is an ideal choice for M.H., because African-Americans respond
especially well to travoprost.
also needs to be educated on the possibility of eyelid skin darkening and increased
thickness, length, and pigmentation of her eyelashes, which all may or may not be
reversible. These side effects might not be as cosmetically concerning to M.H.,
because she has brown eyes and will be instilling travoprost eyedrops into both eyes.
angle-closure glaucoma is made. How should D.H. be managed?
D.H. should be seen by an ophthalmologist because acute angle-closure glaucoma
is a medical emergency. Medical treatment usually consists of pilocarpine 2% to 4%,
one drop every 5 minutes for 4 to 6 administrations. It is recommended that the
puncta be covered during administration to decrease the possibility of systemic
absorption. Stronger miotic agents are contraindicated because they may potentiate
angle closure. Topical timolol also has been used in acute angle-closure glaucoma,
commonly in combination with pilocarpine. However, drugs that decrease aqueous
humor production may be ineffective in this situation because they have a decreased
ability to reduce aqueous production if the ciliary body is ischemic.
Hyperosmotic agents (Table 54-2) act by creating an osmotic gradient between the
79 Agents that are confined to the extracellular fluid space
(e.g., mannitol) provide a greater effect on blood osmolality at the same dosage than
do agents distributed in total body water.
Intravenously administered drugs provide
a faster, somewhat greater effect than oral agents. Palatability may be a problem with
oral agents and can be improved by serving these agents over crushed ice or with
lemon juice or cola flavoring.
Orally, 50% glycerin is the usual drug of choice and is administered in dosages of
Isosorbide is an alternative, especially in diabetic patients because it
is not metabolized to provide calories.
81 Parenterally, mannitol is the drug of choice.
It is administered in doses of 1 to 2 g/kg, is not metabolized to provide calories, and
may be used in patients with renal failure.
Primary side effects of hyperosmotic agents include headache, nausea, vomiting,
diuresis, and dehydration. It is important that the patient not be allowed to drink
because this will counteract the osmotic effects of these agents.
Precipitation of pulmonary edema and CHF has been reported with hyperosmotic
agents, and an allergic reaction has been reported with mannitol.
Acetazolamide (Diamox) 500 mg intravenously may be administered in addition to
Administration Strength Onset Peak Duration Dose
E, extracellular water; IV, intravenous; PO, orally; TBW, total body water.
All the drugs that B.C. is taking have been associated with ocular side effects.
Thiazide diuretics have been associated with acute myopia that may last from 24 to
85,86 However, hydrochlorothiazide is an unlikely cause of B.C.’s blurred
vision considering its recent onset.
Amiodarone can cause keratopathy, but it is asymptomatic.
of patients who receive this drug exhibit microdeposits within the corneal epithelium
that resembles the verticillate keratopathy induced by chloroquine.
deposits are bilateral, dose- and duration-related, reversible, and unassociated with
Risperidone has been associated with disturbances of accommodation and blurred
B.C. may be in the approximately 1% of the population who experiences blurred
vision with chlorpheniramine. This effect has been seen in patients receiving 12 to 14
If an antihistamine is indicated, an agent such as cetirizine would be less
likely to cause such an effect. Sildenafil has been associated with change in color and
light perception as well as blurred vision.
90 These effects generally subside within 4
85–114 outlines some of the more common ocular side effects associated
with systemic medications. Each case should be evaluated individually and
alternative therapy considered in intolerant patients.
Ocular Side Effects of Systemic Medications
Drug Class Effect(s) Clinical Remarks
Ibuprofen Reduced vision Rare; blurred vision reported in patients taking from four 200-mg
tablets/week to six tablets/day; changes in color vision rarely
Miosis Miosis often with morphine in normal doses:slight with other
agents; effect secondary to CNS action on the pupillo-constrictor
Effects associated with narcotic withdrawal
Amiodarone Keratopathy Dose and duration related; resembles chloroquine keratopathy.
Corneal deposits are bilateral, reversible, and unassociated with
visualsymptoms. Patients taking 100–200 mg/day have only
minimal deposits. Deposits occur in almost 100% of patients
Cataracts Previously reported as insignificant, anterior subcapsular lens
opacities have been associated with amiodarone therapy. Rarely,
such opacities may progress, increasing in density and in the
diffuse distribution of the deposits, ultimately covering an area
somewhat larger than the undilated pupil’s aperture. The
mechanism for this effect is unclear, but like chlorpromazine,
amiodarone is a photosensitizing agent. Given that the lens changes
are limited largely to the pupillary aperture, light exposure may
Optic neuropathy Approximately 2% of patients experience optic neuropathy
Systemic and transdermal anticholinergic agents may cause
mydriasis and, less frequently, cycloplegia. Mydriasis may
precipitate angle-closure glaucoma. Photophobia is related to the
mydriasis. Accommodation for near objects
Ocular adverse reactions when dosage >1–2 g/day; disappear
Phenytoin Nystagmus cataracts Nystagmus in patients with high blood levels (>20 mcg/mL); rarely
occurs with other hydantoins. Cataracts may occur rarely with
secondary angleclosure glaucoma
Topiramate has been associated with angle-closure glaucoma.
Symptoms including ocular pain, headache, nausea, vomiting,
hyperemia, visual field defects, and blindness have been reported.
This process is usually bilateral, but if symptoms are recognized
and the drug is stopped in a timely manner, adverse outcomes may
Trimethadione Visual glares A prolonged glare or dazzle occurs when eyes are exposed to
light. The glare is reversible, occurs at the retinal level, and is more
common in adolescents and adults; rarely in young children
Visual field abnormalities including bilateral, symmetrical, and
irreversible peripheral constriction occur in up to 30% of patients.
Most patients are asymptomatic, and <0.1% of patients are
Propofol Inability to open eyes 6 of 50 patients undergoing ENT procedures using standardized
anesthesia with propofol were unable to open their eyes either
spontaneously or in response to verbal commands. This effect
lasted from 3 to 20 minutes after the end of anesthetic
administration. Two patients showed complete loss of ocular
motility. This was a transient, myasthenia-like weakness
Mydriasis is the most common ocular side effect of TCAs.
Cycloplegia is rare. Reports of precipitation of angle-closure
Administration of fluoxetine 20–40 mg/day has been associated
with paroxysmal contractions of the muscles around the lateral
aspect of the eye. This effect occurred 3–4 weeks after initiation
of fluoxetine therapy and resolved within 2 weeks of
Chlorpheniramine Blurred vision
Blurred vision occurs rarely (about 1% of patients taking 12–14
Clonidine Miosis Miosis is seen in overdose
Diazoxide Lacrimation About 20% experience lacrimation, which may continue after drug
Guanethidine Miosis Sporadically documented. One study reported a 17% incidence of
blurred vision in patients taking guanethidine 70 mg/day
Reserpine Miosis Miosis is slight, but can last up to 1 week after a single dose
Conjunctivitis Common, secondary to dilation of conjunctival blood vessels
Amantadine Corneal lesions Diffuse, white punctate subepithelial corneal opacities have been
reported, occasionally associated with superficial punctate
keratitis. Onset has been 1–2 weeks after initiation of therapy with
dosages of 200–400 mg/day. Resolves with drug discontinuation
Chloramphenicol Optic neuritis Rare unless a total dose of 100 g and duration >6 weeks are
exceeded. Vision usually improves after the drug is discontinued
Chloroquine Corneal deposits Some patients using ordinary doses may develop corneal deposits
in a few months. The deposits are visible with use of a
biomicroscope and appear as white-yellow in color, but are of no
Serious retinopathy when total dose >100 g. Usually develops after
1–3 years; can occur in 6 months. Visual loss may be peripheral,
with progression to central vision loss and disturbance of color
vision. Rarely, effects such as blurred vision are seen earlier when
larger doses (500–700 mg/day) are used. Macular changes may
progress after drug is discontinued. These agents concentrate in
Ethambutol Retrobulbar neuritis At dosages of 15 mg/kg/day, virtually void of ocular side effects.
Such effects are rare at dosages of 25 mg/kg/day for a duration of
a few months. Patients treated for prolonged periods should have
routine visual examinations including visual fields. Most effects are
reversible after the drug is discontinued, but optic neuritis may
continue to progress for 1–2 months after the drug has been
Gentamicin Pseudotumor cerebri Rare, but has been well documented with secondary papilledema
Isoniazid Optic neuritis Prevalence not well defined, but appears to be significantly less
than peripheral neuritis. Evaluation difficult because most patients
are malnourished, chronic alcoholics, or receiving multiple
medications. Preexisting eye disease does not appear to be a
Nalidixic acid Visualsensations Most common ocular side effect. Main feature is a brightly colored
appearance of objects; occurs soon after the drug is taken.
Although quinolone antibiotics are nalidixic acid derivatives, they
have rarely been associated with these ocular side effects
Visual loss Temporary effect (30 minutes–3 days)
Papilledema Primarily in infants and young children and secondary to
intracranial pressure; reversible on withdrawal of the drug
Sulfonamides Myopia Acute and reversible; most common ocular side effect
Conjunctivitis Primarily with topicalsulfathiazole, 4% incidence between 5 and 9
Optic neuritis Even in low dosages. Usually reversible with complete recovery of
Photosensitivity Associated with use of sulfisoxazole lid margin therapy
Tetracyclines Myopia Appears to be acute, transient, and rare
Papilledema More common in children and infants than adults; rare
May be associated with higher doses or plasma concentrations
Anti-Inflammatory Agents (also see Analgesics; Corticosteroids)
Discontinuation of therapy leads to resolution without long-term
Deposition in the conjunctiva and superficial cornea more common
than in the lens or deep cornea. Incidence in cornea of 40%–80%
in total doses of 1.5 g; visual acuity is unaffected. One reported
Indomethacin Decreased vision Rare; also changes in color vision have been rarely reported.
Phenylbutazone Decreased vision Most common ocular side effect with this drug may be caused by
Occurs less often than vision. The conjunctivitis may be associated
with development of Stevens–Johnson syndrome or an allergic
Lovastatin Cataracts The crystalline lenses of hypercholesterolemic patients were
assessed before and after 48 weeks of treatment with lovastatin
20–80 mg/day. Statistical analyses of the distribution of cortical,
nuclear, and subcapsular opacities at 48 weeks showed no
significantly different among the groups
Busulfan Cataracts Reported with high dosages.
These ocular side effects are not well established. Evidence of
delayed bilateral ocular toxicity developed in 2 of 50 patients
treated with high-dose IV carmustine (800 mg/m
ocular toxicity became evident 4 weeks after IV treatment.
Evidence of delayed ocular toxicity (mean onset 6 weeks)
ipsilateral to the site of infusion developed in 7 of 10 patients
treated with intra-arterial carotid doses of carmustine to a
cumulative minimum of 450 mg/m
Cytarabine Keratoconjunctivitis
Corneal toxicity and conjunctivitis have been reported with highdose (3 g/m
Doxorubicin Conjunctivitis May last for several days after treatment
Fluorouracil Ocular irritation Reversible and seldom interfere with continued therapy
Generally occurs in patients receiving more than 1 year of
treatment when a total dose exceeding 100 g has been taken
The onset of EMP or paralysis may be seen as early as 2 weeks.
Dose related. Most recover fully when drug is discontinued
Most significant ocular side effects occur in chronic users or in
toxic states. Pupillary responses are variable; miosis seen most
frequently except in toxicity when mydriasis predominates.
Nystagmus and weakness in extraocular muscles may be seen.
Chronic abusers have a characteristic ptosis
Bisphosphonates (Alendronate, Etidronate, Pamidronate, Risedronate)
Adverse events more common with pamidronate. Scleritis and
uveitis are of greatest concern. After persistent reduction in vision
of sustained ocular pain, refer patient to an ophthalmologist. Ocular
NSAID treatment may be of symptomatic benefit
Primarily blurred vision; transient blindness at peak concentrations
has been observed in several patients
Cataracts Posterior subcapsular cataracts have been associated with
systemic corticosteroids in patients who have received >15 mg/day
of prednisone or its equivalent daily for periods >1 year.
Rare reports of bilateral posterior subcapsular cataracts associated
with nasal aerosol or inhalation of beclomethasone dipropionate
have been received. Most patients had received therapy for >5
years, often in higher than the recommended dosage.
Approximately 40% of patients also were receiving systemic
(Also see Case 54-8, Question 1.)
More common with topical corticosteroids than with systemic
therapy. Of little consequence in patients without preexisting
glaucoma. Glaucoma patients should be monitored routinely if
receiving systemic corticosteroids.
Papilledema Intracranial hypertension or pseudotumor cerebri from systemic
corticosteroids has been well documented. The incidence appears
to be greater in children than in adults; primarily associated with
Altered color vision, Changes in color vision. A glare phenomenon and a snowy
visual acuity appearance in objects have been associated primarily with digitalis
intoxication. In a small number of cases, reversible reduction in
visual acuity has been noted. Also associated with changes in the
Decreased IOP Digitalis derivatives can decrease IOP, but clinical use for
glaucoma is not practical because the therapeutic systemic dose
for this effect is very near the toxic dose
Myopia Acute myopia that may last from 24 to 48 hours. Probably caused
by an increase in the anteroposterior diameter of the lens, which
may be reversible even if drug use is continued
Thiazides Myopia Thiazide diuretics have been associated with acute myopia that
may last from 24 to 48 hours.85,86
5%–10% experience ocular side effects. Blurred vision is the most
common effect, although visualsensations such as flashing lights,
distortion of images, and various colored lights (primarily silver)
Quite rare. In patients with retinal vascular abnormalities, use of
OCs is questionable. Numerous other possible ocular side effects
are associated with these agents, and further documentation is
Allopurinol Cataracts Conflicting reports have suggested allopurinol may be associated
with anterior and posterior lens capsule changes and with anterior
subcapsular vacuoles; 42 cases of cataracts have been reported;
these have been observed primarily in age groups in whom normal
lens aging changes would not be expected. No cause-and-effect
Imatinib Visual deficits Ocular symptoms include blurred vision, conjunctivitis, dry eyes,
epiphora, and periorbital edema. The latter occurs in up to 74% of
Interleukin 2 Visual deficits Interleukin 2 visual complications have occurred during the first or
second treatment cycle, usually within 5–6 days of initiation of
therapy. Ocular symptoms included diplopia, binocular negative
scotomas (isolated areas of varying size and shape in which vision
is absent or depressed; these are not perceived ordinarily, but
would be apparent on completion of a visual field examination),
and palinopsia (abnormal recurring visual imagery). In most cases,
treatment was continued for the entire planned duration of therapy.
Symptoms resolved after discontinuation
most cases; incidence may increase to 90% after ≥2.5 kg. Usually,
deposits do not affect vision appreciably. The cornea and
conjunctiva may be affected after the lens shows pigment
The number of reported cases is small; further documentation is
Primarily associated with maximal daily dosages or average doses
>1,000 mg. Daily dosages up to 600 mg are relatively safe; 600–
800 mg is uncertain, but rarely suspect. If >800 mg/day is used,
periodic ophthalmoscopic examinations may uncover problems
before visual acuity is compromised
Therapy for Erectile Dysfunction
Color vision alterations are mild to moderate. Blurred vision does
not impair visual acuity. Visual alterations usually subside within 4
110–112 Ocular adverse effects are
uncommon, dose dependent, and fully reversible to date. Incidence
is not related to age, but is related to blood concentration. Peak
visual effects usually occur within 60 minutes after ingestion
Alfuzosin Visual defects Amblyopia, blurred vision, and floppy iris have been reported
Tamsulosin Floppy iris Approximately 3% of patients taking tamsulosin for benign
prostatic hyperplasia (BPH) experience floppy iris during cataract
surgery. Modification of the surgical procedure usually results in
CNS, central nervous system; ENT, ear, nose, and throat; NSAID, nonsteroidal anti-inflammatory drug.
refer him to the emergency department?
Chemical burns require immediate attention. The immediate treatment is copious
irrigation using the most accessible source of water (e.g., shower, faucet, drinking
fountain, hose, bathtub). After at least 5 minutes of initial irrigation, S.J. should be
taken immediately to the emergency department. A water-soaked towel or cloth
should be kept on his eyes during transport.
When healthcare professionals are approached by patients with acute ocular
ophthalmologist if the practitioner has even the slightest doubt about appropriate
therapy. It is difficult to effectively evaluate the severity of ocular disorders without
the benefit of a thorough ophthalmologic workup and specialized training. In
situations of corneal trauma from abrasion or foreign bodies, the patient often
complains of a gritty, scratchy feeling and can be aware of a foreign body’s presence.
The corneal tissue is an excellent culture medium for bacteria (e.g., Pseudomonas
aeruginosa), and therapy should be initiated as soon as possible to avoid corneal
perforation and possible blindness.
1 Signs and symptoms of acute angle-closure
glaucoma are reviewed in Case 54-2, Question 1.
Gonococcal conjunctivitis is an ocular emergency, and patients should be referred
immediately to an ophthalmologist to minimize the potential of corneal perforation.
These patients, who can present with symptoms of red, tender, swollen eyelids with
exophthalmos and mild pain, may be suffering from orbital cellulitis or
endophthalmitis, which require immediate treatment with systemic antibiotics.
Conjunctivitis of other origins (see Acute Bacterial Conjunctivitis [Pinkeye] and
Allergic Conjunctivitis sections) generally is not an ocular emergency.
Any loss of vision (whether sudden, complete, or transient), flashes of light, pain,
or photophobia can signify potentially damaging ocular disorders (e.g., retinal artery
occlusion, optic neuritis, amaurosis fugax, retinal detachment), and an
ophthalmologist should evaluate the patient as soon as possible. Referral also is
recommended for patients with blurred vision, pupil disorders, diplopia, nystagmus,
Sties are infections of the hair follicles or sebaceous glands of the eyelids. The most
common infecting organism is Staphylococcus aureus. Treatment consists of hot,
moist compresses and topical antibiotics (e.g., sulfacetamide). Over-the-counter
products should not be recommended. An ophthalmologist should evaluate sties that
do not respond to warm compresses within a few days.
Conjunctivitis, a common external eye problem that involves inflammation of the
conjunctiva, usually is associated with symptoms of a diffusely reddened eye with
purulent or serous discharge accompanied by itching, smarting, stinging, or a
scratching foreign-body sensation. Patients with pain, decreased vision, unequal
distribution of redness, irregular pupils, or opacity should be referred immediately to
an ophthalmologist because these are signs of more serious eye disease.
Conjunctivitis can be bacterial, fungal, parasitic, viral, or allergic in origin. Most
cases of bacterial conjunctivitis are caused by Staphylococcus. aureus, Streptococcus
pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, although a number
of other organisms may be responsible. The infection usually starts in one eye and is
spread to the other by the hands. It also may be spread to other persons. Unlike
bacterial conjunctivitis, corneal infections can obliterate vision rapidly; therefore,
accurate diagnosis is important.
ACUTE BACTERIAL CONJUNCTIVITIS (PINKEYE)
10% ophthalmic drops, two drops in both eyes every 2 hours while awake, are prescribed. What other
measures should be used? What instructions should his caregivers receive?
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