Drugs for some common eye disorders

Adverse systemic effects can include fatigue, dizziness, bradycardia, respiratory depression, mask-ing of hypoglycemia, and blockmask-ing the effects of beta blockers should be used with

Treatment Guidelines

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Drugs for Some Common Eye Di sorders p 79

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Drugs for Some Common Eye Disorders

Tables

1 Some Topical Drugs for Glaucoma Page 80

2 VEGF Inhibitors for Neovascular AMD Page 82

3 Some Ophthalmic Antimicrobials Page 84

Treatment Guidelines

Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication

Volume 10 (Issue 123) November 2012

(supercedes vol 8 [Issue 89] January 2010)

www.medicalletter.org

Drugs for glaucoma, age-related macular

degenera-tion, bacterial conjunctivitis, and dry eyes are

reviewed here Drugs for the treatment of allergic

con-junctivitis will be reviewed in a future issue of

Treatment Guidelines on Drugs for Allergic Disorders.

In general, all eye drops should be given in doses of

only one drop The average volume of a single drop is

larger than the eyelid’s capacity to hold fluid; a second

drop only washes out the first, may increase systemic

absorption, and doubles the cost Ophthalmic drugs can

have local and systemic adverse effects In addition,

for some elderly patients, the complexity of

self-administering numerous ophthalmic drugs may be the

limiting factor in their ability to care for themselves

GLAUCOMA

Glaucoma is a progressive optic neuropathy that is

often associated with increased intraocular pressure

(IOP), which is the only disease-related variable that

ophthalmologists can modify Topical drugs for

glau-coma are listed in the table on page 80

PROSTAGLANDIN ANALOGS — Topical

prosta-glandin analogs (PAs) typically lower IOP by 25-30%

and stabilize it at a lower level throughout the day and

night Dosed once a day, usually at night, they increase

uveoscleral outflow PAs are now the drugs most

fre-quently used for the treatment of glaucoma

A new prostaglandin analog, tafluprost (Zioptan), was

as the first preservative-free topical prostaglandin

ana-log Tafluprost has not been shown to be tolerated

bet-ter than any other drug in this class

Adverse Effects – PAs can cause conjunctival

hyper-emia, and with long-term use, irreversible darkening

of the iris in people with multicolor irides

(green-brown, yellow-(green-brown, or blue/gray-brown), increases

in the length, thickness and number of eyelashes, and

an increase in periorbital (eyelid) skin pigmentation PAs may also cause local irritation, itching, dryness, blurred vision and periorbital fat atrophy, which leads

cause uveitis or cystoid macular edema, but have few,

if any, systemic effects

BETA BLOCKERS — Topical beta blockers

de-crease aqueous humor production They lower IOP by 20-25% with once- or twice-daily dosing The IOP-lowering effect of beta blockers is much less at night The selective beta1-blocker betaxolol (Betoptic S, and

generics) causes fewer systemic adverse effects than nonselective beta blockers, but it is not as effective in lowering IOP

Adverse Effects – Beta blockers are generally well

tolerated topically; rarely they may cause stinging, itching, redness and blurred vision Systemic effects, however, have limited their use as first-line therapy Adverse systemic effects can include fatigue, dizziness, bradycardia, respiratory depression, mask-ing of hypoglycemia, and blockmask-ing the effects of

beta blockers should be used with caution in patients with asthma, bradycardia, or chronic obstructive pul-monary disease

CARBONIC ANHYDRASE INHIBITORS —

Carbonic anhydrase inhibitors (CAIs), like beta block-ers, decrease IOP by decreasing production of aqueous humor CAIs are available in both oral and topical forms Oral CAIs include acetazolamide and methazo-lamide They can decrease IOP by 30-50%, but have many systemic adverse effects The topical CAIs

dor-zolamide (Trusopt, and generics) and brindor-zolamide (Azopt) typically decrease IOP by 15-20% throughout

the day and night Both are FDA-approved for use

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Related article(s) since publication

Some Some Usual

Prostaglandin Analogs

Latanoprost – generic 0.005% soln* 2.5 mL 1 drop qPM $19.06

Bimatoprost – Lumigan (Allergan) 0.01%, 0.03% 2 soln* 2.5, 5, 7.5 mL 1 drop qPM 96.98 Travoprost – Travatan Z (Alcon) 0.004% soln 2.5, 5 mL 1 drop qPM 89.20 Tafluprost – Zioptan (Merck) 0.0015% soln 0.3 mL single-use 1 drop qPM 97.00 3

containers 4

Beta Blockers

Betaxolol – generic 0.5% soln* 5, 10, 15 mL 1 drop qAM or bid 50.86

Carteolol – generic 1% soln* 5, 10, 15 mL 1 drop qAM or bid 13.10 Levobunolol – generic 0.25%, 0.5% soln* 5, 10, 15 mL 5 1 drop qAM or bid 4.25

Metipranolol – generic 0.3% soln* 5, 10 mL 1 drop qAM or bid 16.48

Timolol – generic 0.25%, 0.5% soln* 6 5, 10, 15 mL 1 drop qAM or bid 2.67

Timoptic Ocudose (Valeant) 0.25%, 0.5% soln 0.2 mL individual units 8 1 drop bid 262.12 9 Timoptic (Merck) 0.25%, 0.5% soln* 6 5, 10 mL 7 1 drop bid 99.84

Carbonic Anhydrase Inhibitors

Brinzolamide – Azopt (Alcon) 1% susp* 10, 15 mL 1 drop tid 112.10

Alpha-2 Agonists

Apraclonidine – generic 0.5% soln* 5, 10 mL 1 drop tid 67.50

Brimonidine – generic 0.2%,* 0.15% soln 5, 10, 15 mL 1 drop tid 65.90

Cholinergic Agonists

Pilocarpine – generic 1%, 2%, 4% soln* 15 mL 1 drop qid 31.50

Carbachol –

Isopto Carbachol (Alcon) 1.5%, 3% soln* 15 mL 1 drop bid-tid 55.90 Echothiophate iodide –

Phospholine Iodide (Pfizer) 0.125% soln 11 5 mL 1 drop bid 77.10

Combinations

Brimonidine/timolol – Combigan 0.2%/0.5% soln* 5, 10 mL 1 drop bid 87.63 (Allergan)

Timolol/dorzolamide – generic 0.5%/2% soln* 10 mL 1 drop bid 60.47

containers 12

* Contains benzalkonium chloride, which may cause irritation.

soln = solution; susp = suspension

1 Wholesale acquisition cost (WAC) for the smallest size bottle available of the lowest strength Source: PricePointRx™ October 5, 2012 Reprinted with per-mission by FDB All rights reserved ©2012 http://www.firstdatabank.com/support/drug-pricing-policy.aspx Actual retail prices may vary.

2 The 0.03% formulation will no longer be produced in the US by the end of 2012.

3 Cost of 30 single-use containers.

4 Supplied in cartons of 30 or 90 0.3-mL single-use containers packaged in foil pouches (10 containers per pouch).

5 Only the 0.5% strength is available in a 15-mL bottle.

6 Also available as 0.25% and 0.5% ophthalmic gel-forming solution (generic and Timoptic XE).

7 0.25% solution is only available in 5-mL size.

8 Supplied in packages of 60 0.2-mL single-use containers.

9 Cost of 60 single-use containers.

10 The 1% solution is available in 0.1-mL individual dispensers.

11 Supplied as a powder for reconstitution (1 bottle of powder for solution + 5 mL diluent).

12 Supplied in packages of 60 or 180 0.2-mL single-use containers in foil pouches (15 containers per pouch).

Table 1 Some Topical Drugs for Glaucoma

Drugs for Some Common Eye Disorders

Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 123) • November 2012

three times daily, but they are often prescribed twice

daily and are most often used in patients already being

treated with a PA

Adverse Effects – Generally the only systemic

adverse effect of topical CAIs has been bitter taste;

they are better tolerated than beta blockers They can

cause stinging, redness, burning, conjunctivitis, dry

eyes and blurred vision CAIs should be used with

cau-tion after corneal transplantacau-tion because long-term

use may lead to graft decompensation They are

sul-fonamide derivatives, but topical CAIs have been

reported to be generally well tolerated in patients with

sulfonamide allergies

ALPHA AGONISTS — Like beta blockers and

CAIs, alpha agonists decrease IOP by decreasing

aqueous humor production, but they may also increase

uveoscleral outflow The selective alpha2-agonist

bri-monidine (Alphagan P, and generics) typically lowers

IOP by 15-20% during the day, but not during the

derivative of clonidine, is sometimes used for

prophy-laxis against acute increases in IOP after laser

proce-dures; tachyphylaxis and local allergic reactions have

The nonselective alpha agonists epinephrine and

dip-ivefrin are seldom used now because of local and

sys-temic side effects

Adverse Effects – Fatigue, somnolence (especially

in young children), and local allergic reactions occur

frequently with alpha agonists Topical effects

include dry eyes, stinging, conjunctival hyperemia

and foreign-body sensation A recent change in the

preservative used for brimonidine and a decrease in

its concentration from 0.15% to 0.1% may improve

the drug’s tolerability Brimonidine can cross the

blood-brain barrier and cause systemic hypotension

in infants and children; it has caused respiratory

depression in children <2 years old and should not be

used in this age group Alpha agonists are

contraindi-cated for use in patients taking a monoamine oxidase

(MAO) inhibitor

CHOLINERGIC AGONISTS — Stimulation of

parasympathetic receptors by cholinergic agonists

causes a contraction of muscle fibers in the ciliary

body that leads to an increase in outflow of aqueous

humor, decreasing IOP Pilocarpine mimics the effect

of acetylcholine Carbachol both mimics acetylcholine

and decreases its degradation These drugs have little

effect on aqueous humor formation

Adverse Effects – Topically applied cholinergic

ago-nists can cause local and systemic adverse effects that limit their use Contraction of the ciliary muscle leads

to ciliary spasm and resulting brow ache Corneal tox-icity, conjunctival inflammation, transient myopia and blurred vision can occur Retinal detachment can also occur, especially in high myopia Systemic effects are rare at recommended doses, but can include sweating, nausea, salivation and changes in blood pressure In cases of systemic toxicity, atropine can be used to reverse the symptoms

OSMOTIC AGENTS — Osmotic agents include oral

glycerol and IV mannitol These drugs act by increas-ing the osmotic gradient between the eye and circulat-ing blood, resultcirculat-ing in an efflux of fluid and a decrease

in IOP Both glycerol and mannitol are used for acute rises in IOP requiring rapid treatment Glycerol has an onset of action of 10 minutes and reaches maximal effect in 1-2 hours Mannitol’s onset of action is in

10-30 minutes, reaching peak effect by one hour

Adverse Effects – Osmotic agents can cause systemic

hyperosmolarity and electrolyte abnormalities that result in thirst, confusion, headache, diuresis, acute heart failure and, potentially, subdural hematoma Glycerol is gluconeogenic and can interfere with con-trol of diabetes Use of these drugs can also lead to rebound IOP spikes when the vitreous cavity becomes hyperosmolar compared to the circulating blood after the osmotic agent has been cleared from the circulation

COMBINATIONS — Combination products can

pro-duce a greater reduction in IOP than monotherapy, but their adverse effects are additive as well They may be

helpful in promoting adherence Cosopt, a

combina-tion of a beta blocker and a carbonic anhydrase

combi-nation with a beta blocker, are the only two combina-tion products available in the US for lowering IOP

CHOICE OF DRUGS — Topical drugs that lower

intraocular pressure (IOP) are still the mainstay of treatment for glaucoma For initial treatment, prostaglandin analog (PA) monotherapy is preferred If the PA lowers IOP into the target range, no additional treatment is necessary If it leads to a substantial decrease in IOP, but falls short of the target range, another agent such as a topical beta blocker, a topical

-agonist could be added If the PA fails to lower IOP substantially, it should be discontinued and another drug substituted Some patients who do not respond to

81

AGE-RELATED MACULAR DEGENERATION

Age-related macular degeneration (AMD) has two

major forms The “dry” or non-neovascular form is

characterized by abnormalities of the retinal pigment

epithelium with focal accumulation of metabolic

with AMD have the dry form; they may experience a

slow reduction in central vision About 10% of

patients have the “wet” exudative or neovascular

form, characterized by an often rapid decrease in

central visual acuity due to newly developed leaky

vessels growing from the choroid into the subretinal

space More than 90% of severe visual loss in the US

is caused by wet AMD

VEGF INHIBITORS — The principal mediator of

neovascularization in wet AMD is thought to be

vas-cular endothelial growth factor (VEGF), which

induces angiogenesis and increases vascular

perme-ability and inflammation Treatment of wet AMD with

VEGF inhibitors has reduced vision loss in many

patients and has led to the recovery of lost vision in

patients whose treatment began soon after the onset of

the leakage causing the vision loss These drugs are

given as periodic intravitreal injections with topical

anesthesia They can rarely cause serious

complica-tions such as retinal detachment and endophthalmitis,

leading to loss of vision.6

Pegaptanib sodium (Macugen) is FDA-approved for

treatment of wet AMD.7Given as an intravitreal

injec-tion, it binds to extracellular isoforms of VEGF that

are at least 165 amino acids long, preventing receptor

activation It appears to be less effective than

ranibizumab or bevacizumab, and has not been shown

to improve vision

Ranibizumab (Lucentis) is another VEGF inhibitor

approved for intravitreal injection in patients with wet

macular edema (DME) A recombinant, humanized

monoclonal antibody fragment (Fab) derived from the

same antibody as bevacizumab, it causes regression of

the abnormal vessels and reduction of leakage from

these vessels in wet AMD, improves visual acuity, and

decreases swelling of the retina In one controlled trial

(MARINA) in AMD patients with either minimally

classic or occult (no classic lesions) choroidal

neovas-cularization, 95% of patients injected monthly with

ranibizumab 0.3 or 0.5 mg for one year lost fewer than

15 letters of visual acuity, compared to 62% of those

who received sham injections Visual acuity improved

by 15 or more letters in 25% of patients injected with

ranibizumab 0.3 mg, in 34% of those who received 0.5

mg, and in 5% of the sham-injection group At 1 year,

patients injected with ranibizumab 0.3 mg had gained

an average of 6.5 letters from baseline, compared to a gain of 7.2 letters with 0.5 mg and a loss of 10.4 let-ters in the sham-injection group The average gain in visual acuity was maintained at 2 years with continued treatment: 6.6 letters gained (with 0.5 mg) vs 14.9 let-ters lost.9 Use of quarterly rather than monthly injec-tions of ranibizumab has not been successful in improving visual acuity.10

Bevacizumab (Avastin) – A systemic VEGF inhibitor

FDA-approved for treatment of colon cancer and non-small cell lung cancer, bevacizumab has also been used off-label as an intravitreal injection for treatment of wet AMD Divided into aliquots, it costs much less than pegaptanib or ranibizumab, but repackaging of the drug without proper aseptic technique has led to

NIH-sponsored trial (CATT) comparing monthly or as needed injections of bevacizumab with ranibizumab found that they had equivalent effects on visual acuity (8 letters gained with bevacizumab vs 8.5 letters

patients who continued treatment for an additional year and were randomized to monthly or as needed treatment with the same drug, ranibizumab and beva-cizumab had similar effects on visual acuity in the second year Patients who received bevacizumab had more systemic adverse events, but most of these had not previously been associated with VEGF treatment Patients who were randomized from monthly to as-needed treatment with either drug during the second year had a greater mean decrease in vision during the second year.13

Intravitreal

Aflibercept – 2 mg q4 wks x3 2 mg/0.05 $1850.00 Eylea (Regeneron) doses, then mL;

single-2 mg q8 wks use vial Pegaptanib sodium – 0.3 mg 0.3 mg/ 995.00 Macugen (Gilead q6 wks 0.09 mL;

syringe Ranibizumab – 0.5 mg 0.5 mg/ 1950.00 Lucentis once/mo 0.05 mL;

vial 2 Bevacizumab 3 – 1.25 mg 25 mg/mL; 75.00 4 Avastin once/mo 4-, 16-mL

1 Wholesale acquisition cost (WAC) for one intravitreal injection (administration cost not included) Source: PricePointRx™ (October 5, 2012) Reprinted with permis-sion by FDB All rights reserved ©2012 http://www.firstdatabank.com/support/ drug-pricing-policy.aspx Actual retail costs may vary.

2 Also available as 0.3 mg/0.05 mL vial.

3 Not FDA-approved for this indication.

4 Cost of a 4-mL single-use vial is $608.72 Actual retail prices may vary A com-pounding pharmacy can divide the vial into small aliquots Actual retail prices may vary.

Table 2 VEGF Inhibitors for Neovascular AMD

Drugs for Some Common Eye Disorders

Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 123) • November 2012

Aflibercept (Eylea) is a fusion protein FDA-approved

for treatment of wet AMD It acts as a decoy VEGF

receptor, competing for binding of VEGF In 2

con-trolled trials, it appeared to be similar to ranibizumab

directly to bevacizumab

Adverse Effects – The adverse effects of all of these

agents have been largely related to the injection

procedure rather than the drug itself; they include

con-junctival hemorrhage, acute IOP rise after injection,

traumatic cataract, uveitis, and retinal detachment, all

occurring in less than 2% of patients Intravitreal

injec-tion of VEGF inhibitors carries a risk of intraocular

infection or endophthalmitis In one study,

endoph-thalmitis developed after 2 of 5449 injections (0.04%)

with ranibizumab and after 4 of 5508 injections

injections would be equally effective and safer remains

to be established.16

PHOTODYNAMIC THERAPY — Verteporfin

(Visudyne) is a benzoporphyrin derivative that, when

infused intravenously and activated in the eye by

low-intensity infrared light 15 minutes following

infusion, occludes abnormal blood vessels found in

the eye while (relatively) sparing normal vessels and

over 10 minutes and repeated as often as every 3

months (if leakage persists), this form of therapy has

been shown to reduce the risk of severe vision loss

and slow the progression of AMD In one 2-year

study, 213 (53%) of 402 treated patients lost fewer

than 15 letters (3 lines) of vision, compared to 78

(38%) of 207 placebo-treated patients A sub-group

analysis showed that the treatment benefit occurred in

patients with predominantly classic choroidal

neovas-cularization; the benefit was significant for 2 years.18

The results of other similar studies indicate that

patients with minimally classic or occult lesions may

the visual outcome in eyes treated with

photodynam-ic therapy is generally not as good as in eyes treated

with VEGF inhibitors

Adverse Effects – A sudden severe decrease in visual

acuity, usually transient and probably caused by

post-treatment swelling, has been reported in <5% of

patients after photodynamic therapy Transient back

pain occurs in about 2% of patients during the

infu-sion The skin and eyes of patients who receive

verteporfin may be sensitive to sunlight and

high-intensity halogen lights for up to 5 days after the

infusion Patients with porphyria should not receive

this form of treatment

INTRAVITREALTRIAMCINOLONE ACETONIDE —

Intravitreal triamcinolone acetonide (IVTA) has been

approved for intravitreal injection (Trivaris) for the

treatment of sympathetic ophthalmia, temporal arteritis, uveitis, and ocular inflammatory conditions unrespon-sive to topical corticosteroids, it may be effective in decreasing retinal edema and improving visual function

in some patients with wet AMD; an improvement in visual acuity (up to 2-3 lines) can be seen on Snellen eye chart examination after a single injection, but this effect often wanes 6-9 months later Re-injection may

be required every 3-4 months

Adverse Effects – IVTA has many adverse effects that

make it undesirable for long-term use It causes an acceleration of cataract formation and a high incidence

of ocular hypertension that may be refractory to topi-cal ocular hypotensive therapy In addition, IVTA is injected through the sclera into the vitreous cavity, which may lead to hemorrhage, endophthalmitis, and retinal detachment

ANTIOXIDANTS AND ZINC — Various oral

vita-min supplements are advertised for ocular health and specifically for AMD Antioxidants have been theo-rized to decrease inflammation and perhaps reduce oxidative stress produced from metabolic byproducts

in and around the retina A large prospective study, sponsored by the National Eye Institute and Bausch and Lomb, known as the Age-Related Eye Disease Study (AREDS), analyzed 3640 patients 55-80 years old who had AMD at various stages Patients were ran-domized (double-masked) to: (1) antioxidants at doses 5-15 times higher than the RDA (vitamin C 500 mg, vitamin E 400 IU and beta carotene 15 mg), (2) zinc oxide 80 mg plus cupric oxide 2 mg, (3) antioxidants plus zinc and copper, or (4) placebo The primary end-points were progression to advanced AMD (choroidal neo-vascularization or geographic atrophy including the center of the macula) and moderate loss of visual acuity (3 or more lines of vision)

After 5 years of treatment, no benefit was seen in 1063 patients who joined the study with only multiple small

or a few medium drusen and good vision in the eye with more advanced disease When these patients were excluded from the analysis (a predefined design vari-able), the estimated probability of progression to advanced AMD among the remaining patients was 28% with placebo, 23% with antioxidants alone, 22% with zinc alone, and 20% with both zinc and antioxi-dants The estimated probability that at least 3 lines of vision would be lost at 5 years in at least one eye was 29% with placebo, 26% with antioxidants, 25% with zinc and 23% with both zinc and antioxidants Only the

83

combination of zinc and antioxidants had a statistically

significant treatment effect compared to placebo.21

A prospective, randomized trial (AREDS 2) is in

progress Even though no results are expected before

2013, an AREDS 2 formula (PreserVision Eye Vitamin

AREDS 2 Formula – Bausch & Lomb) has already

been marketed as the only formula proven to slow the

new formula differs from the original AREDS formula

in substituting lutein and zeaxanthin for beta carotene

and adding omega-3 fatty acids

Adverse Effects – In 2 prospective double-blind trials,

long-term use (5-8 years) of a high dose (20 mg) of

beta carotene in male smokers was associated after 18

months with an increased incidence of lung cancer and

death.23,24Some studies have suggested that vitamin E,

particularly in doses >400 mg/day, may increase

antioxi-dants to prevent AMD may be taking other

multivita-min preparations as well

CHOICE OF DRUGS — Whether any drug can slow

the progression of dry AMD is unclear; the positive results reported with antioxidant vitamins and zinc are modest at best For wet AMD, ranibizumab, beva-cizumab and aflibercept have all been shown in ran-domized trials to maintain vision in a large majority of patients and improve it in a significant minority

BACTERIAL CONJUNCTIVITIS

The most common bacterial pathogens associated with

acute conjunctivitis in adults are Staphylococcus

aureus, Streptococcus pneumoniae and Haemophilus influenzae.27In children, Moraxella catarrhalis is also

common Ophthalmic use of antibacterials is much less likely to cause adverse effects than systemic use

OPHTHALMIC ANTIBACTERIALS — Sulfa-cetamide is not highly effective, can be sensitizing and

rarely has caused Stevens-Johnson syndrome

Neomycin causes sensitization and other local

reac-tions in about 5-10% of patients Most streptococci are

resistant in vitro to gentamicin and tobramycin.

Fluoroquinolones

Gatifloxacin –

Other Single Agents

Mixtures

Polymyxin B/Neomycin/Gramicidin –

susp = suspension; soln = solution; oint = ointment

1 Wholesale acquisition cost (WAC) for the smallest size tube or bottle available Source: PricePointRx™ (October 5, 2012) Reprinted with permission by FDB All rights reserved ©2012 http://www.firstdatabank.com/support/drug-pricing-policy.aspx Actual retail prices may be higher.

2 Contains the same active agent as Vigamox, but has a different vehicle (Xanthum gum).

3 Retail cost according to a local CVS pharmacy.

Table 3 Some Ophthalmic Antimicrobials

Drugs for Some Common Eye Disorders

Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 123) • November 2012

Bacitracin and erythromycin are not active against

the gram-negative organisms that cause a small

per-centage of these infections Trimethoprim has a broad

spectrum of activity, often including

methicillin-resistant staphylococci Polymyxin B has only a

macrolide antibiotic with activity primarily against

gram-positive microbes, but also against H influenzae.

All fluoroquinolones are active against most bacteria

associated with conjunctivitis In vitro, S aureus and

some anaerobes resistant to older fluoroquinolones

such as ciprofloxacin (Ciloxan, and others) and

ofloxacin (Ocuflox, and others) may be susceptible to

(Zymar, Zymaxid), and besifloxacin (Besivance).29

CHOICE OF DRUGS — Moxifloxacin, gatifloxacin

and besifloxacin have better activity in vitro against

the most common ocular pathogens than other

ophthalmic antimicrobials However, ophthalmic

for-mulations of other antibacterial drugs can achieve

high concentrations on the surface of the eye and may

be effective clinically in treating surface ocular

infec-tions, even when the organisms are reported to be

resistant in vitro Topical antibiotic drops are used

off-label in prophylactic regimens and postoperatively to

prevent infection after ocular surgeries such as

cataract surgery No randomized trials have

estab-lished that any drugs or dosage regimens are effective

for such use

DRY EYES

Dry eyes can be caused by altered tear-film

composi-tion, reduced tear produccomposi-tion, poor lid funccomposi-tion,

envi-ronmental conditions, or diseases such as Sjögren’s

syndrome Medications, including anticholinergics,

estrogens and selective serotonin receptor antagonists

artificial tears, topical drugs, or use of an ocular insert

device.31

ARTIFICIAL TEARS — Many artificial tear

prepa-rations are available and are administered every 4-6

hours, but can be used as often as hourly, depending on

symptoms They generally include cellulose to

main-tain viscosity, a spreading agent such as polyethylene

glycol or oil emulsions to prevent evaporation, and a

preservative to prevent contamination Preservatives

may be irritating and aggravate ocular surface disease;

some patients may tolerate one, but not another

Preservative-free tears are available, but only in

rela-tively expensive single-use formulations; some

clini-cians recommend them particularly for patients who

need drops >4 times a day Ointment formulations can

be used at night and during the day in severe cases

Lacrisert (Valeant) is an insert that gradually releases

hydroxypropylcellulose after placement into the

inferi-or conjunctival sac It should be used daily in patients with moderate to severe dry eyes who remain sympto-matic after therapy with artificial tears

TOPICAL CYCLOSPORINE — A 0.05% emulsion

of cyclosporine (Restasis) has been approved by the

FDA for treatment of dry eye disease.32 It has been effective in moderate to moderately severe tear dys-function, producing statistically significant improve-ment in Schirmer tear test results and other measures

of dryness in many patients, and has been remarkably safe, but may take 4-6 weeks to achieve results.33

Serum cyclosporine concentrations have been unde-tectable or negligible, and no systemic or topical toxi-city has been reported The mechanism of action is unknown, but is thought to be immunomodulating or anti-inflammatory Transient burning and stinging may occur in the treated eye; addition of topical corticos-teroids in the first month may be helpful

OTHER DRUGS — Topical corticosteroids are

effec-tive for treatment of dry eyes, but can cause cataracts and increase intraocular pressure with continued use

Tacrolimus (Protopic), another immunosuppressant,

has been effective in clinical trials, but is not available

in an ophthalmic formulation in the US

1 Tafluprost (Zioptan) - a new topical prostaglandin for glaucoma Med Lett Drugs Ther 2012; 54:31.

2 K Inoue et al Deepening of the upper eyelid sulcus caused by 5 types

of prostaglandin analogs J Glaucoma 2012; August 29 (epub).

3 JH Liu et al Diurnal and nocturnal effects of brimonidine

monothera-py on intraocular pressure Ophthalmology 2010; 117:2075.

4 S Arthur and LB Cantor Update on the role of alpha-agonists in glau-coma management Exp Eye Res 2011; 93:271.

5 RJ Casson et al Efficacy and safety of bimatoprost as replacement for latanoprost in patients with glaucoma or ocular hypertension: a unioc-ular switch study J Glaucoma 2009; 18:582.

6 LP Aiello Targeting intraocular neovascularization and edema – one drop at a time N Engl J Med 2008; 359:967.

7 Pegaptanib sodium (Macugen) for macular degeneration Med Lett Drugs Ther 2005; 47:55.

8 Ranibizumab (Lucentis) for macular degeneration Med Lett Drugs Ther 2006; 48:85.

9 PJ Rosenfeld et al Ranibizumab for neovascular age-related macular degeneration N Engl J Med 2006; 355:1419.

10 CD Regillo et al Randomized, double-masked, sham-controlled trial

of ranibizumab for neovascular age-related macular degeneration: PIER Study year 1 Am J Ophthalmol 2008; 145:239.

11 BA Frost and MA Kainer Safe preparation and administration of intravitreal bevacizumab injections N Engl J Med 2011; 365:2238.

12 CATT Research Group Ranibizumab and bevacizumab for neovas-cular age-related maneovas-cular degeneration N Engl J Med 2011; 364:1897.

13 CATT Research Group Ranibizumab and bevacizumab for treatment

of neovascular age-related macular degeneration: two-year results Ophthalmology 2012; 119:1388.

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16 FG Holz et al Safety and efficacy of a flexible dosing regimen of

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17 Photodynamic therapy with verteporfin (Visudyne) for macular

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18 NM Bressler Treatment of Age-Related Macular Degeneration with

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19 M Azab et al Verteporfin therapy of subfoveal minimally classic

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Copyright 2012 ISSN 1541-2792

Treatment Guidelines

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Hans Meinertz, M.D., University Hospital, Copenhagen Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine Dan M Roden, M.D., Vanderbilt University School of Medicine Esperance A K Schaefer, M.D., M.P.H., Harvard Medical School

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