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OPHTHALMIC
DRUGS
21st Edition
A Supplement to
Disclosure: Drs. Melton and Thomas are consultants to, but have no financial
interests in, the following companies: Bausch + Lomb/Valeant and Icare. A PEER-REVIEWED
Dr. Vollmer has no financial interests in any company. SUPPLEMENT
Note: The authors present unapproved and “off-label” uses of specific drugs in this guide.
TAKE CONTROL OF
OCULAR ALLERGY
N
Atopic diseases early one-third of the popu-
IS IT ‘BURNING’ OR ‘ITCHING’?
lation is affected by allergic • Itching: If the patient tells you itch-
continue to disease, with an estimated ing is their primary concern, determine
40% to 80% of these people if it’s an isolated symptom or associat-
increase in manifesting ocular involve- ed with parallel signs of inflammation,
ment.1 Reports from studies around the and then treat accordingly. Remember:
prevalence. world indicate the prevalence of atopic Symptoms Only: Use an antihista-
Here’s how diseases is continuing to increase, which mine/mast cell stabilizer
has been well-documented over several Symptoms and Signs: Use a topical
to help your decades of research.2,3 At the same time, steroid (such as Alrex, Lotemax gel
ocular allergic disease is also on the rise. off-label or FML off-label)
patients So, we need to understand more about • Burning: If the main symptom is
the nature of the disease to better treat burning, consider dry eye as the foun-
with allergic and manage our patients. dational condition and treat accord-
ingly. A full dry eye workup is in order.
conjunctivitis. Allergic eye disease, an IgE-mediated
Of course, nothing in the rulebook
response and type I hypersensitivity reac-
tion, presents in numerous forms—from says a patient can’t have both of these
a persistent itch to a potentially sight- symptoms concomitantly. Due to the
threatening corneal ulcer (vernal kera- prevalence of dry eye across all ages,
toconjunctivitis). According to the most recognize and treat it whether or not it
is affiliated with allergic eye disease.
recent epidemiological data, as many as
two in five of your patients may have sea-
sonal or perennial allergic conjunctivitis.4 Though the treatment options are es-
sentially the same for perennial and sea-
sonal allergic conjunctivitis, perennial
allergic conjunctivitis follows a more in-
dolent course, often requiring greater
attention and persistent care by the at-
tending doctor. Treatment for seasonal
allergic conjunctivitis is more straightfor-
ward and includes antihistamines/mast
cell stabilizers or corticosteroids.
To find out whether your patients
are experiencing just symptoms or also
signs, first ask them: “Do your eyes burn
Determine signs and symptoms by first or itch?” Many patients will be able to
asking, “Do your eyes burn or itch?” provide an answer. For your patients
who are unable to decide which symptom
FROM THE
LITERATURE to these environmental changes.2 1. Björkstén B, Clayton T, Ellwood P, et al. Worldwide
time trends for symptoms of rhinitis and conjunctivitis:
More than 80% of patients who Phase III of the International Study of Asthma and
ALLERGIC suffer with allergies experience some Allergies in Childhood. Pediatr Allergy Immunol. 2008
Mar;19(2):110-24.
CONJUNCTIVITIS IS ON form of ocular symptomology (itch- 2. D’Amato G, Holgate ST, Pawankar R, et al. Meteo-
THE RISE WORLDWIDE ing, chemosis, redness).3,4 In addition, rological conditions, climate change, new emerging
factors, and asthma and related allergic disorders. A
According to the International Study various studies suggest that patients statement of the World Allergy Organization. World
of Asthma and Allergies in Childhood still vastly underreport the disease. Of Allergy Organ J. 2015; 8(1):25.
(ISAAC), allergic conjunctivitis has equal significance are studies estab- 3. Singh K, Axelrod S, Bielory L. The epidemiology of
ocular and nasal allergy in the United States, 1988-1994.
shown a worldwide trend in increas- lishing the impact of ocular allergies J Allergy Clin Immunol. 2010 Oct;126(4):778-83.e6.
ing prevalence.1 This has been attrib- on scholastic achievement, quality of 4. Blaiss MS. Allergic rhinoconjunctivitis: burden of dis-
life and behavior, which confirms the ease. Allergy Asthma Proc. 2007 Jul-Aug; 28(4):393-7.
uted to changing climate, pollution,
5. Bielory L, Katelaris CH, Lightman S, et al. Treating the
increased pollen and a heightened necessity of early therapeutic inter- ocular component of allergic rhinoconjunctivitis and re-
immunological sensitivity in response vention.5 lated eye disorders. MedGenMed. 2007 Aug 15;9(3):35.
Eye Allergies (Allergic Conjunctivitis). Asthma and Allergy Foundation of America. Available at: www.aafa.org/page/eye-allergy-conjunctivitis.aspx. Last accessed
Dec 16, 2016.
Severe itching of the eyelids can be caused by crab lice. Don’t miss these. Using your toothed, curved tip forceps, simply
remove them one by one. Slide one side of the forceps underneath the ventral aspect of the louse, gently close down on
the dorsal side and slowly pull the critter off the tissues. Repeat for each louse you can find. Then have the patient apply an
ophthalmic ointment at bedtime for a week, which will suffocate any juveniles you may have missed. Also have the patient
do lid scrubs each evening before applying the ointment. In a week, the eyelid tissue should be restored to normal. Explain
to the patient that these can be associated with sexual activity and any partner(s) should be examined by a physician.
EFFECTIVE USE OF
ANTIBIOTIC AGENTS
S
Increasing ince the early 1940s, the use timated. More recent medical literature
of antibiotics is well-docu- bemoans the egregious overprescribing of
antibiotic mented in reducing illnesses systemic antibiotics, and begs physicians
and fatalities attributed to and other health care providers to use
resistance many infections worldwide. great restraint in such prescribing.
sends many However, some bacteria are now resis- A recent report from the Centers for
tant to the antibiotics that were at one Disease Control and Prevention warns
clinicians time highly effective. This upward trend that antibiotic resistance causes two mil-
is causing concern throughout medical lion bacterial and fungal illnesses, and
scrambling for disciplines. Consequently, researchers are 23,000 deaths yearly. It also causes an
forced to find different, more effective annual increase in direct health care costs
more effective drugs to fight off bacterial infections. of $20 billion, plus $35 billion in lost pro-
therapy. The Antibiotic dosing is widespread and ductivity.1
overprescribed. These drugs are generally Bear in mind that most studies on anti-
key is to cheap and are offered as pills, liquids and biotic resistance have focused on systemic
injections, so dosing is inherently easy for antibiotics. But in the past few years, re-
select the patients of all ages. While antibiotics do searchers have begun to look at resistance
have a history of being remarkably effec- to topical ophthalmic antibiotics.
right medicine tive, drug resistance has been underes-
and dose it ANTIBIOTICS FOR
ACUTE ‘RED EYES’
WHY BACTERIAL DRUG
correctly. RESISTANCE? In the setting of an acute red eye, we have
- When a strain of bacteria becomes
found that the etiology is nearly always
Here’s how. resistant to an antibiotic, it becomes inflammatory, not infectious. An acute
the dominant organism, as bacteria red eye with no mucopurulent discharge
multiply quickly. is rarely the result of bacterial infection.
- Animals raised for dietary consump- These inflammatory conditions require
tion are often fed antibiotics, thus steroids, not antibiotics; yet time and time
potentially increasing resistance that again clinicians prescribe an antibiotic
can affect humans. drug that does not improve the patient’s
- Antibiotics have been and continue condition. Generally speaking, infectious
to be considerably overprescribed diseases produce a discharge whereas in-
throughout the last 70 years. flammatory diseases do not. However,
- Antibiotics continue to be prescribed the hesitancy to prescribe a steroid and
inappropriately, such as in the setting uncertainty of diagnosis continues to set
of a virus or inflammation. the stage for antibiotics to be inappropri-
ately prescribed in optometric practice.
Aminoglycosides
Tobrex tobramycin 0.3% Alcon, and generic sol./oint. > 2 mos. 5ml/3.5g
Garamycin gentamicin 0.3% Perrigo, and generic sol./oint. N/A 5ml/3.5g
Polymyxin B Combinations
Polytrim polymyxin B/trimethoprim Allergan, and generic solution > 2 mos. 10ml
Polysporin polymyxin B/bacitracin generic ointment N/A 3.5g
Neosporin polymyxin B/neomycin/ generic solution N/A 10ml
gramicidin
polymyxin B/neomycin/ generic ointment N/A 3.5g
bacitracin
Other Antibiotics
AzaSite azithromycin 1% Akorn solution > 1 yr. 2.5ml
Ilotycin erythromycin 0.5% Perrigo, and generic ointment > 2 mos. 3.5g
Bacitracin bacitracin 500u/g Perrigo ointment N/A 3.5g
Accurate diagnosis and drug se- the frequency for eye drop adminis- (tobramycin, Alcon) or Besivance
lection are paramount in patients tration depends almost exclusively (besifloxacin, Bausch + Lomb).
presenting with red eyes. We have on the severity of the infectious ex- Now, let’s take a more in-depth
seen hundreds of patients who were pression. look at this class of medicines. There
treated elsewhere with topical antibi- In the setting of ocular infections, are many antibiotics; however, only
otics and presented to us for a second antibiotics are prescribed almost a few should have widespread use.
opinion when their condition did not exclusively in topical or oral form.
resolve. We recognized the condition With the exception of besifloxacin— ANTIBIOTICS AND
as inflammatory and initiated topical a suspension—all other antibiotic PREGNANCY
steroids; the patient improved in sev- drops are solutions. Oral antibiotics Clinicians are almost inherently
eral days. are most commonly prescribed as a overcautious when prescribing oral
Thankfully, most of the com- tablet, capsule or liquid (the latter drugs for patients who are pregnant
monly used antibiotic drops are used mostly in children). or breastfeeding. But like everyone
broad-spectrum, and are generally In our practices, we prescribe else, pregnant women are just as sus-
effective against many common bac- oral antibiotics more commonly ceptible to infections and should be
terial pathogens. We have found than topical ones simply because treated appropriately.
frequency of administration—rather we encounter more patients need- Generally speaking, in a review
than particular drug selection—to be ing oral antibiotic therapy, such as of FDA categories (A-X), only cat-
the key determining factor of clini- those with meibomian gland disease egory A and B drugs are considered
cal outcome. Because most (but not (doxycycline), rosacea blepharitis safe for administration in pregnancy.
all) of the currently approved topical (doxycycline) and internal hordeola While antibiotic usage in pregnancy
antibiotics possess reasonable anti- (cephalexin). For uncommon acute is guarded due to ethical and legal is-
microbial abilities, the more frequent bacterial conjunctivitis, we typically sues, obstetricians use several classes
the administration of these drops, the prescribe generic Polytrim (polymyx- of drugs routinely with no harmful
greater the clinical result. However, in B/trimethoprim, Allergan), Tobrex effects to the mother or baby.
The three main drug classes that is the oldest macrolide and is FDA- This dosing is more sensible, as an
are safe in pregnancy are: penicillins, classified as category B. ointment will blur the patient’s vi-
cephalosporins and macrolides— One eye disease that must be treat- sion if dosed during waking hours. If
with penicillins, by far, the most pre- ed with an oral medication (azithro- there is significant concurrent eyelid
scribed antibiotic for pregnant wom- mycin) is adult chlamydial conjunc- margin inflammation, then perhaps
en, based on our experience. All of tivitis. In one study comparing the an antibiotic-steroid combination
these drugs are category B, with the efficacy of azithromycin and erythro- ointment such as generic Maxitrol
exception of two macrolide drugs: mycin, 15 pregnant women took 1g (dexamethasone/neomycin/polymyx-
clarithromycin and telithromycin of azithromycin during gestation for in B) would better serve the patient
(category C). a chlamydial infection.1 Azithromy- than just an antibiotic ointment.
Penicillins and cephalosporins cin was found to be better tolerated Additionally, bacitracin can be
are considered category B due to a than erythromycin, and no adverse used at bedtime to provide overnight
higher selective toxicity. This is be- affects to the baby were reported.2 coverage for moderate to severe ul-
cause these drugs cause alterations Keep in mind that the more com- cerative keratitis. Be advised that for
of the beta-lactam ring, a structure monly prescribed antibiotic drugs true bacterial corneal infections, a
that is unique to bacteria. Spanning such as fluoroquinolones, amino- broad-spectrum antibiotic is always
from first (more gram-positive cover- glycosides and tetracyclines are not preferred. In such cases, we dose
age) to fourth (more gram-negative) safe in any stage of pregnancy due to besifloxacin ophthalmic suspension
generation classes, cephalosporins documented harm to the fetus. As al- with Polysporin ophthalmic oint-
are commonly used in eye care. First- ways, be mindful to comanage your ment (bacitracin/polymyxin B) be-
generation drugs are especially com- pregnant patients with bacterial in- cause the polymyxin B is bactericidal
mon; cephalexin (e.g., Keflex) is rou- fections with their obstetrician when against gram-negative pathogens.
tinely used to treat internal hordeola prescribing oral therapy.
and mild cases of preseptal cellulitis. THE AMINOGLYCOSIDES
These drugs are perfectly fine to use BACITRACIN While these drugs do (quite unfairly)
during pregnancy and can prevent Available since 1948, bacitracin, a carry a reputation for being poten-
more serious disease sequelae. strictly gram-positive antibiotic, is of- tially corneotoxic, aminoglycosides
Macrolides were first isolated in ten employed in the clinical setting of are relatively protected from bacteri-
1952, and quickly gained ground as staphylococcal blepharitis. It is only al resistance that comes from prima-
a first choice of therapy for patients available in ointment form, which ry care use. Why? Due to ototoxicity
allergic to penicillin. Bacterial pro- somewhat limits its practicality out- issues, they are not used systemical-
tein synthesis is inhibited by linking side of bedtime dosing. After warm ly, thereby considerably lowering the
to the 50S sub-unit of the bacterial compresses and lid scrubs, bacitracin potential for antibiotic resistance.
ribosome, which is different from can be applied to the lid margins at Remember, it is the widespread sys-
the human ribosome. Erythromycin night before the patient goes to bed. temic use of antibiotics that tends
to promote resistance. In fact, these
older generic aminoglycosides are
some of the most highly efficacious
antibiotic eye drops available.
Aminoglycosides are often hesi-
tantly prescribed due to their poten-
tial to cause a type IV hypersensitivity
useful at night for sustained antibac- THE EFFICIENT RED EYE EVALUATION
terial coverage. KEEP
IN MIND Each of these procedures generally takes about
Neosporin. This triple-antibiotic
two to three minutes in most cases.
comprised of neomycin, bacitracin
and polymyxin B is conveniently • Assess visual acuity (pinhole if indicated)
available generically as an ophthal- • Note the degree of conjunctival injection
mic ointment and solution (the solu- Mild: dry eyes, allergy, chlamydia, mild bacterial infections
tion contains gramicidin, not baci- Marked: acute viral or non-specific bacterial infection, acute iritis
tracin). Remember, both bacitracin • Note the degree of conjunctival injection pattern
and Polysporin are available only as Sector injection: corneal infiltrate, episcleritis, phlyctenule, inflamed
ointments. pinguecula
We rarely use Neosporin in eye Global injection: uniform—bacterial or viral infection, or uveitis
drop form, as we prefer generic Poly- More pronounced in fornices: bacterial infection
trim (trimethoprim/polymyxin B), More pronounced paralimbally: uveitis
tobramycin or Besivance, depending • Quality and quantity of discharge if any
on the nature and severity of the in- Watery: viral
fectious condition. However, we use Mucoid: dry eyes, allergy, chlamydia
Neosporin ointment without hesita- Mucopurulent: bacteria
tion for those rare occasions when
• Preauricular lymphadenopathy (not grossly visible)
overnight antibiosis is deemed neces- Most commonly, adenoviral
sary to enhance a clinical cure. Less commonly, chlamydial
To be clear, neomycin is an ef- Rarely, hyperacute conjunctivitis
ficacious drug that can occasionally If grossly visible: Parinaud’s oculoglandular syndrome (cat-scratch disease)
cause a delayed type IV hypersensitiv-
• Follicles vs. papillae: clinically virtually meaningless
ity reaction. Given that we have three
Exception: Giant follicles in the inferior forniceal conjunctiva are highly
alternatives (generic Polytrim, generic
indicative of chlamydial infection
tobramycin and Besivance) that are
much less prone to cause any sort of • Character of cornea: Examine without, then with, fluorescein dye to rule
allergic response, we prefer to follow out herpes keratitis, subtle abrasions, ulceration, through-and-through
this simpler path for most patients perforation (Seidel’s sign)
most of the time. • Measure the IOP if no contraindications exist
• Evert the eyelid to rule out conjunctival foreign material or pathology
THE FLUOROQUINOLONES • Examine the anterior chamber for cells/flare
The options in this class have some
notable differences. • Quick ophthalmoscopy to rule out concurrent intraocular disease
Besifloxacin. Besivance, a unique,
dual-halogenated fluoroquinolone, est concentration of an antibiotic at (up to more than 70% by day five)
is the only topical ophthalmic antibi- which 90% of isolates are inhibited.) and bacterial eradication (more than
otic that comes as a suspension. As As a suspension, this thick eye drop 90% by day five), and a low incidence
with all fluoroquinolones, Besivance must be shaken prior to each use, and of adverse effects.”4
provides activity against DNA gyrase has been shown to maintain high con- For severe infectious processes such
and topoisomerase IV. Its broad-spec- centrations on the ocular surface after as microbial keratitis, we dose Besiv-
trum coverage combats gram-positive, instillation, with minimal systemic ex- ance hourly (while awake) for one
gram-negative (including Pseudomo- posure. to three days, then taper the dose to
nas), and anaerobic organisms, as well A study in the Journal of Oph- every two hours for a few more days,
as methicillin-resistant Staphylococcus thalmology and Therapy concludes: then to four times a day for a few
aureus (MRSA) and Staphylococcus “Large randomized, controlled clini- more days. Depending upon the sever-
epidermis (MRSE). The latest research cal trials have established the efficacy ity and character of the infectious pro-
(ARMOR) has demonstrated in vi- and safety of besifloxacin adminis- cess, we may adjunctively prescribe
tro that besifloxacin and vancomycin tered three times daily for five days for Polysporin or Neosporin ointment at
share very low MIC90 levels against the treatment of acute bacterial con- bedtime.
the common gram-positive ocular junctivitis in both adults and children, Ciprofloxacin. Ciloxan, a second-
pathogens.3 (MIC90 indicates the low- with high rates of clinical resolution generation fluoroquinolone, remains
infection is typically secondary to an of drugs. Always take a careful medi- tients who need antibiotic treatment
overproduction of bacteria on their cal history to avoid the risk of an al- for chronic conditions such as mei-
lids, and that continued warm com- lergic reaction. If a patient has a true bomian gland disease or rosacea
presses and lid scrubs daily will help anaphylactic reaction to penicillin or blepharitis. We prescribe doxycycline
reduce the risk of recurrences. penicillin-like drugs such as cephalo- at 50mg daily for three to six months.
Patients tend to have allergies to sporin, we opt for Levaquin (500mg The dichotomous nature of doxycy-
antibiotics more than other classes QD) or doxycycline (200mg QD), or cline (anti-infective at high dosage and
Bactrim DS or Septra DS (both com- anti-inflammatory at low dosage) re-
CUT THE PILL—AND THE mon brand names of trimethoprim quires different dosing based on clini-
COST—IN HALF with sulfamethoxazole) prescribed as cal intent.
The cost of brand name and two double-strength tablets BID for While both doxycycline hyclate and
generic drugs is continually one week, which is the standard, com- doxycycline monohydrate are well-
changing, and clinicians are con- monly prescribed dosage. tolerated, the monohydrate form ap-
stantly faced with dynamic and If the patient is truly allergic to pen- pears to be a bit better tolerated. DG
ever-changing pricing structures. icillin and sulfa, consider oral doxy-
Regarding doxycycline, we have cycline 100mg BID for one week, or
1. Centers for Disease Control and Prevention. Anti-
biotic Resistance Threats in the United States, 2013.
found in several instances that the oral fluoroquinolone levofloxacin Available at: www.cdc.gov/drugresistance/pdf/ar-
threats-2013-508.pdf (last accessed March 24, 2017).
the 100mg units are cheaper than
500mg once daily for one week. For 2. Bush MR, Rosa C. Azithromycin and erythromycin in
the 50mg units. To be more cost- the treatment of cervical chlamydial infection during
perspective, the risk of a cross-sensi-
effective for the patient, we occa- pregnancy. Obstet Gynecol. 1994 Jul;84(1):61-3.
tivity reaction of a cephalosporin in a 3. Asbell PA, Sanfilippo CM, Pillar CM, et al. Anti-
sionally prescribe 100mg doxy- biotic resistance among ocular pathogens in the
patient who is truly allergic to penicil-
cycline monohydrate tablets that United States: Five-Year results from the antibiotic
can be split in half. (Patients can lin is about 0.1%—but why ever take resistance monitoring in ocular microorganisms (AR-
MOR) surveillance study. JAMA Ophthalmol. 2015
purchase affordable pill-splitters the miniscule risk? Just prescribe an Dec;133(12):1445-54.
at most drug stores.) alternative class. 4. Mah FS, Sanfilippo CM. Besifloxacin: Efficacy and
safety in treatment and prevention of ocular bacterial
Occasionally, we encounter pa- infections. Ophthalmol Ther. 2016 Jun; 5(1): 1-20.
1. Vehof J, Sillevis Smitt-Kamminga N, Kozareva D, et al. Clinical characteristics of dry eye patients with chronic pain syndromes. Am J Ophthalmol. 2016;Feb;162:59-65.e2.
always the case. Once patients de- manage the manifest symptoms. question. We see no reason to have
scribe the hallmark complaints, some To quantify the symptoms, Dr. patients complete any questionnaire
clinicians choose to use a variety of Melton has developed an approach when we use this straightforward and
in-office assessments beyond slit-lamp that is simply to ask the patient: “On practical approach.
examination of the lacrimal lake and a scale from one to 10, how badly do
measuring tear film break-up time, your eyes bother you?” TREATING AND MANAGING
although we have found these evalua- The success of your therapeutic THE DRY EYE PATIENT
tions to be superfluous. Our next step strategy in addressing symptoms can Besides capturing symptoms, how do
is to develop an interventional plan to be ascertained by re-asking the same we best care for this population? It’s
nuanced and can be quite complex. open the meibomian gland orifices and This is quite helpful and should be per-
Not all patients need all of the follow- improves what meibum flow is there. formed on every dry eye disease patient
ing interventions. As with any chronic,
progressive disease, care must be indi- NEUROPATHIC EYE PAIN AND IDIOPATHIC DRY EYE
vidualized based on the time of diag- Thankfully, most dry eye patients can be helped with the myriad therapeutic
nosis and specific patient characteris- approaches available. However, a small subset of patients remains symp-
tics. What is common to all patients tomatic, no matter what is done. Their eyes appear healthy. That is, there is
is the need for tear film stability to be no superficial punctate keratopathy; they also have good tear lake volume,
restored. Beyond this, given that MGD normal tear film break-up time and so on, yet their eyes are uncomfortable.
is one major driver of dry eye, mei- What’s going on?
bomian gland rehabilitation and the Many of these patients have what is called somatosensory dysfunction,
management of inflammation are key which accompanies such neuropathic eye pain. A yet-to-be-understood
approaches. defect in the nociceptive system may be driving ocular pain in some patients
with idiopathic dry eye disease.
• The goal in treating meibomian
As optometric clinicians, all this sounds pretty esoteric and daunting. Let
gland obstruction is to evacuate the
us share a few direct quotes from the expert literature to try to wrap our
gland contents. This is not done by
heads around this relatively newly appreciated somatosensory dysfunction.
pressing the lower eyelid against the • Pain does not exist in isolation, and individuals experiencing one form of
globe without protecting the globe chronic pain often have other chronic pain conditions—a concept termed
from pressure, as that maneuver would chronic overlapping pain conditions. Dry eye symptoms may represent a
require the intraocular pressure to be peripheral manifestation of a chronic overlapping pain condition.1
very high for it to be effective. Rather, • For a significant number of patients, there is a discordance between the
use the Mastrota Meibomian Paddle signs seen on physical exam and the sensory symptoms these patients feel.
(OcuSoft), a cotton swab, the butt end Nerve sensitization, genetic susceptibility to pain, neuropathic pain mecha-
of your jeweler’s forceps, or other ap- nisms and psychological status have been proposed as mechanisms for this
propriate instrument as a backstop (af- incongruity between signs and symptoms of dry eye disease.2
ter proparacaine instillation). Then ap- • Dry eye symptoms are not only manifestations of a local disorder, but also
ply sufficient (uncomfortable) pressure involve somatosensory dysfunction beyond the trigeminal system.2
for 15 seconds in an attempt to express • Dry eye is also strongly associated with depression, post-traumatic stress
the glandular contents. (Expression syndrome and anxiety, providing further evidence of centralized pain dis-
can be enhanced by aggressively pre- order.1
heating the eyelids, but this is rarely • Quantitative sensory testing at a site remote from the eye, mainly at the
practical in a busy office setting.) This forearm, implicates central sensitization as a mechanism modulating aber-
procedure can be effective and usually rant sensations in a subset of patients with ocular neuropathic pain.2
lasts two to four months. These patients may best be served by neurologists or pain management
• Clean the keratinized lid margins clinics. Of course, we need to exhaust all reasonable, prudent therapeutic
interventions before defaulting to such tertiary measures.
by gently removing debris from the
margin and mucocutaneous junction 1. Galor A, Levitt RC, McManus KT, et al. Assessment of somatosensory function in patients with idiopathic
with a golf club spud (no topical an- dry eye symptoms. JAMA Ophthalmol. 2016 Nov 1;134(11):1290-8.
2. Rosenblatt MI. Remote quantitative sensory testing and neuropathic ocular pain. JAMA Ophthalmol. 2016
esthesia is needed for debridement). Nov 1;134(11):1298.
It feels good to the patient, serves to
at every visit. There is no CPT code for troesophageal reflux. Bear in mind that to doxycycline, perhaps a trial of oral
this maneuver, but it only takes about some women rapidly develop vaginal azithromycin could be initiated.
10 to 15 seconds per eyelid. yeast infections when on antibiotics, so • Start every dry eye disease patient
• Place all of your dry eye patients be sure to discuss this possibility with on a lipid-based artificial tear and in-
on a premium-quality omega-3 fish your female patients. And patients struct them to use it as often as they
oil supplement at 2,000mg per day. should be warned about photosensitiv- care to, up to four to six times a day
Let them know it can take four to six ity, which can occur at this low dose. initially. We prefer either Soothe XP
months to slowly build up to a mean- The monohydrate salt is slightly more (Bausch + Lomb) or Systane Balance
ingful degree. For the subset of patients patient-friendly than the hyclate salt (Alcon) because our mentor and friend,
who have difficulty swallowing these form, but this is rarely a big deal. For Donald Korb, OD, a world-recognized
relatively large capsules, two good liq- the patient who is allergic or intolerant expert in the area of meibomian gland
uid (and quite palatable) supplements Photo: Allergan
that can be used are Coromega Orange In our 2016 Guide, we introduced a new
Squeeze (coromega.com) and Nordic technology then in development called
Naturals (nordicnaturals.com). We intranasal lacrimal neurostimulation (ILN), a
recommend these be taken with break- battery-powered, handheld device used to
fast, or certainly by lunch. stimulate lacrimation. The device, now called
For those patients with advanced TrueTear, was recently FDA approved and is
meibomian gland disease, with or marketed by Allergan. We are intrigued with
without advanced rosacea blepharitis, this novel approach, and are hopeful it will be
it may be that concurrent use of 50mg beneficial. We look forward to using TrueTear
of doxycycline daily for about three to in the care of some of our dry eye patients.
four months would more effectively As the tear film is essentially three-layered,
jump-start the fatty acid metabolism and lacrimal stimulation is thought to enhance
enhancement within the meibomian the watery layer, it will be critical to protect
glands. Doxycycline needs to be taken this augmented aqueous layer with a robust
with breakfast or lunch, not near bed- lipid layer.
time, to reduce the small risk of gas-
1. White, DE. Pediatric dry eye disease: The next generation of dry eye patients is already here. Ocular Surgery News U.S. Edition, January 25, 2017.
2. Moon JH, Kim KW, Moon NJ, et al. Smartphone use is a risk factor for pediatric dry eye disease according to region and age: a case control study. BMC Ophthalmol. 2016
Oct 28;16(1):188.
FROM THE
LITERATURE • The ben-
eficial effects of
UPDATE ON OMEGA-3 ESSENTIAL FATTY omega-3 EFAs
ACIDS AND DRY EYE DISEASE on reducing bul-
Any ambiguity about the benefits of omega-3 essential bar hyperemia
fatty acids (EFAs) in the care of patients with dry eye dis- were first appar-
ease is put to rest with an excellent article in the January ent at day 30
2017 issue of Ophthalmology. Here are the highlights: and were main-
• A 30% reduction in the risk of dry eye disease was tained at day 90.
found for each additional gram of omega-3 essential fatty • Bulbar
acids consumed per day. hyperemia was
• In fish oil, the omega-3 EFAs are stored as triacylg- the first clinical
lycerides. But in krill oil, a major component of the EPA sign to demonstrate improvement with omega-3 EFA
and DHA are esterified in phospholipid form; this poten- supplementation, with a significant reduction evident at
tially influences their tissue distribution and bioavailability. day 30 compared with placebo. The observed decrease
Krill oil also contains the carotenoid antioxidant astaxan- in ocular redness may relate to omega-3 EFA supplemen-
thin, which improves its stability. tation imparting ocular anti-inflammatory effects. Indeed,
• The fish oil used in this study supplied 1,000mg/day topical loteprednol 0.5%, a corticosteroid with potent
of EPA and 500mg/day of DHA. The krill oil supplied anti-inflammatory properties, reduced clinical markers of
945mg/day of EPA and 510mg/day of DHA. These were inflammation, including conjunctival injection, in patients
from commercially available sources. with DED over a two-week treatment period.
• Study authors reported they • This study demonstrated the beneficial effect of long-
previously found tear film break-up chain omega-3 EFA supplementation for reducing key
time to be highly sensitive (82%) and clinical signs and symptoms of mild to moderate DED
specific (94%) for diagnosing dry eye over a three-month treatment duration.
disease. Our take is that probably all patients with dry eye dis-
• Krill oil slightly outperformed ease should be taking a premium quality fish oil or krill oil
fish oil in ameliorating the signs and supplement. If the dry eye disease expression is moder-
symptoms of dry eye disease. ate to severe, consider off-label loteprednol 0.5% QID
• Moderate (roughly 1,000mg EPA for two weeks, then BID for two more weeks to suppress
and roughly 500mg DHA) daily doses the inflammatory component. Do this concurrent with
of both forms of long-chain omega- the fish/krill oil, since it may take a month or two for the
3 EFAs were found to significantly omega-3 essential fatty acids to build up in the tissues.
reduce tear osmolarity, improve tear
stability and reduce ocular bulbar Deinema LA, Vingrys AJ, Wong CY, et al. A randomized, double-masked,
placebo-controlled clinical trial of two forms of omega-3 supplements for treat-
redness. ing dry eye disease. Ophthalmology. 2017 Jan;124(1):43-52.
The eye drop solution is to be instilled twice daily, about 12 hours apart, and can be used indef-
initely to keep your eyes comfortable.
As with most drugs, some patients experience one or more side effects with Xiidra, the most
common of which are:
• Blurred vision
For most all people, these side effects tend to go away within two to three weeks of consistent
use, and do not cause any permanent damage.
Relief from burning, scratchy, gritty, sandy, itchy, dry eye symptoms generally takes four to six
weeks to occur.
CAPITALIZE ON
CORTICOSTEROIDS
The extensive The eye is vulnerable to damage from intraocular inflammation. If left untreated, inflam-
mation may lead to temporary or even permanent vision loss. Steroids suppress cellular
benefits of infiltration, collagen deposition, fibroblast proliferation and scar formation. They stabi-
lize cell membranes and block phospholipase A2—a critical initial step in the inflamma-
these drugs tory cascade of the arachidonic acid pathway.
Topical corticosteroids are based on two different molecular classes: ketones and
considerably esters. Ketone-based steroids (e.g., dexamethasone, prednisolone, fluorometholone)
outweigh their have a higher propensity over time for unwanted side effects, compared to ester-based
steroids (e.g., loteprednol). Why? Our bodies have limited means to actively degrade
potential, the ketone molecules, whereas esters are rapidly broken down by physiological ester-
ases into inert substances shortly after providing effective anti-inflammatory effects.
but rare and This greatly lowers the risk for increased intraocular pressure, and there have been no
reports of cataract formation with the use of loteprednol. For either category, the risks
manageable, associated with short-term topical use are minimal.
Remember: Suppressing ocular inflammation early in the process substantially
side effects, decreases the potential for tissue damage. Uncontrolled intraocular inflammation is
yet these much more dangerous than a steroid eye drop.
R
epeat aloud: “I will not be antibiotic/steroid—could cause the condi-
afraid to prescribe my patient tion to worsen; however, these are exceed-
prescribed with a topical steroid.” Year after ingly rare presentations with clinically dis-
unwarranted year, antiquated teaching strat- tinct features.
egies focusing more on the pos- In all cases of disease management, prop-
apprehension. sible side effects of oral and topical cortico- er follow-up and careful patient education
steroids continue to trump the far-reaching are vital. After explaining the condition
benefits of these important drugs. In the and plan of action to the patient, always
setting of acute red eyes, we have always ask, “Do you have any more questions for
been strong advocates for the use of topi- me?” By doing so, the patient will have the
cal ophthalmic steroids, either alone or in opportunity to eliminate any misconcep-
combination with an antibiotic. tions or worries about their disease or the
While there are plenty of clinical indica- selected therapy. Also, open discussion in-
tions for topical steroids, the only contra- creases the paramount doctor-patient trust
indication is active epithelial herpetic infec- and minimizes a second opinion that can
tion.1 In addition, the only precaution for potentially further delay care.
using these drugs bears explanation. With a
difficult-to-diagnose Acanthamoeba or fun- NEED FOR FOLLOW-UP
gal keratitis, especially in the early stages, When prescribing topical steroids, having
the use of a steroid—even a combination the patient return to you in a judicious
and timely manner will illuminate in- treatment, but to the treatment of any Durezol. Introduced in 2008, Du-
effective treatments or misdiagnosed eye condition.) rezol is often used as the “big gun” of
conditions. By seeing the patient back topical corticosteroids (but don’t shy
sooner rather than later, you will be away from it). Because of its potency,
able to refine the diagnosis and alter it is typically prescribed when inflam-
the therapy, if necessary. If you are mation needs to be rapidly brought
truly concerned, get the patient’s pre- under control. Durezol is an emulsion
ferred telephone number and call the and does not need to be shaken before
patient in a couple of days to check on use.
their progress. (Patients love having The drug has a long history of use in
their doctors call to check on them.) the setting of severe or non-resolving
For example, let’s say you see a pa- anterior uveitis, and more recently is
tient with a typical lesion that could This inflamed pingueculum should be
gaining recognition as a popular post-
be Thygeson’s or herpetic. Since most operative drug. Clinically, we prefer
treated with a topical steroid. Once
red eyes are inflammatory in nature, it over Pred Forte for several reasons:
the inflammation is under control,
we are inclined to initiate therapy we have found it to be more effective,
the ocular surface must be kept
with a steroid. However, in the uncer- it does not need to be shaken prior to
properly lubricated to prevent further
tainty of the diagnosis, we would tell instillation and it does not need to be
inflammatory expression.
the patient something like this: “This dosed as often as Pred Forte, thereby
medicine should help your eye get increasing patient compliance.
better quickly; however, at this time Durezol’s glucocorticoid bind-
the diagnosis of your condition is not MAXIMUM EFFICACY ing affinity for the active metabolite
completely clear, and there is a chance STEROIDS difluprednate was found to be 56
your eye could actually worsen on this Don’t let ocular inflammation linger times stronger than prednisolone.2
medicine. It is important that you let by hesitantly prescribing topical ste- A derivative of prednisolone, diflu-
me see you again in a couple of days. I roids. Rather, dose the corticosteroid prednate’s structural modifications
will be glad to work you in any time.” frequently until the inflammation has enable it to have a stronger affin-
As previously mentioned, this truly subsided before electing to taper the ity and a more consistent potency
caring conversation is crucial for opti- medication if necessary. compared with its counterpart. As a
mum patient care and rapport. Clinically, we have found the two general rule, the more powerful the
All of this is called “patient man- most efficacious topical ophthalmic drug, the more potential for adverse
agement,” and is far more than just steroids in the last several years to side effects. Durezol is no exception,
disease management alone. Trying to be Durezol emulsion (difluprednate as it can be associated with an elevat-
manage the disease without managing 0.05%, Alcon) and Pred Forte sus- ed IOP. Thus, standard of care prac-
the patient often results in frustration pension (prednisolone acetate 1%, Al- tices must be engaged, with frequent
for the doctor and the patient. (This lergan)—but not generic prednisolone follow-ups to monitor the condition
not only applies to corticosteroid acetate. (More on this below.) and check IOP.
THOUGHTFUL PRESCRIBING FOR Now, if—and that is a strong if—patients faithfully use
CONTROLLING INFLAMMATION their lipid-based artificial tears and omega-3 supplements,
When we encounter anterior uveitis, we know it is an ocular surface inflammation should remain subclinical.
inflammatory condition. Certainly, there are various Scientifically, this all makes perfectly good sense. For
expressions of the disease, but for most patients most of most patients, there is
the time, we use Durezol initially every two hours while no reason to use any
awake. Had we used the traditional prednisolone acetate eye drop once or twice
suspension, we would have to dose the patient hourly a day forever. Control
while awake, at least initially. So, we choose Durezol for the inflammation
two reasons: it has a more powerful molecule in a more upfront, and keep it
elegant emulsion vehicle that requires no shaking, mini- controlled with omega-
mizes dosing frequency, and provides a protracted ocular 3 supplementation and
surface residency time. Another attribute: It’s BAK-free. proper ocular surface
Does every uveitis patient require such aggressive dos- lubrication. Punctal
ing, or could a more conservative dosing schedule be plugs can enhance the efficacy if needed after a month of
used while increasing patient compliance? The answer is steroid therapy to quiet the surface inflammation.
that there are likely cases in which a less aggressive dos- • Other considerations. Cost is also a significant deter-
ing schedule would be appropriate, but since this cannot rent to compliance. Simple arithmetic shows that one
be fully known, we use a therapeutic approach shown to or two bottles of loteprednol is vastly less expensive
be highly effective in virtually all cases. (especially with the “pay no more than $35” coupons with
• Inflammation in different settings. Let’s compare the most commercial insurances) than any of the protracted,
suppression of inflammation in anterior uveitis to that of enduring, twice-daily therapies. Additionally, the patient
dry eye. A question arises: How aggressive do we need to may appreciate the short and effective therapy with
be to suppress the inflammatory component? pulse-dosing as needed, as opposed to indefinite therapy
Given that inflammation in the setting of dry eye dis- with other agents.
ease is quantitatively less than that seen in more severe • A final note. Some patients do not properly adhere to
diseases such as anterior uveitis, a drug such as Durezol their omega-3 and/or artificial tear protocols, and other
would be overkill—but would most certainly do the job. patients’ inflammation simply “breaks through.” In these
So, should we prescribe loteprednol 0.5%, loteprednol cases, we perform the time-honored maneuver of pulse-
0.2%, a topical NSAID, lifitegrast 5.0% or cyclosporine dosing. In our practices, such symptomatic breakthroughs
0.05%? There are some patients in whom any of these are controlled by off-label use of loteprednol QID for one
would suffice—but the clinical dilemma is that we have no week, then we stop (no taper is needed). A few patients
way of knowing which patients those are, and our primary will need such a “booster shot” once or twice a year. This
job at this point is to adequately suppress inflammation. is a safe, effective and cost-saving maneuver to help keep
Therefore, it stands to reason that prescribing lotepred- patients with dry eye well controlled and comfortable.
nol (a safety profile-enhanced, ester-based topical steroid As in all clinical circumstances, thoughtful prescribing is
that does not require shaking) would be rational initia- virtuous and merits enthusiastic embrace.
tion of therapy. Sound, scientific articles in peer-reviewed
1. Sy A, O’Brien KS, Liu MP, et al. Expert opinion in the management of aque-
journals have firmly established the efficacy and safety of ous Deficient Dry Eye Disease (DED). BMC Ophthalmol. 2015 Oct 13;15:133.
such a clinical approach.1,2 Following the consensus in the 2. Pflugfelder SC, Maskin SL, Anderson B, et al. A randomized, double-masked,
expert literature, we prescribe loteprednol 0.5% QID for placebo-controlled, multicenter comparison of loteprednol etabonate
ophthalmic suspension, 0.5%, and placebo for treatment of keratoconjunc-
two weeks, and then BID for two more weeks. At the end tivitis sicca in patients with delayed tear clearance. Am J Ophthalmol. 2004
of a month, the inflammatory component is controlled. Sep;138(3):444-57.
NSAIDs:
WHAT’S NEW & WHAT’S PRUDENT
B
All topical ecause of the rare, but real, po- (77% to 82%) were pain-free at one day
tential for corneal toxicity and post-op compared with those given only
NSAIDs are melting, use nonsteroidal anti- vehicle (48% to 62%). Also, more patients
inflammatory drugs (NSAIDs) given BromSite were free of inflammation
generally cautiously when there is preex- at 15 days post-cataract surgery compared
isting corneal epithelial compromise. As a with patients given only the vehicle.1
approved general rule, we never prescribe any topi- BromSite is dosed BID, preserved with
for treating cal NSAID for use beyond two weeks—ex- benzalkonium chloride (BAK) 0.005%,
cept for a case of cystoid macular edema, and comes in a 5ml supply.
postoperative which we treat with a topical NSAID for a • Prolensa. This NSAID, Prolensa
month concurrently with a potent steroid. (bromfenac 0.07%, Bausch + Lomb),
inflammation, While steroids are often initially dosed potentiates penetration of the bromfenac
as frequently as hourly for a few days, we molecule thereby allowing for a slightly
and as such recommend that NSAID use not exceed the lower concentration (0.07%) than Brom-
they are used FDA-approved dosing frequency. Always Site, yet providing once-daily dosing.
remember that steroids reign supreme in Also, Prolensa has pH of 7.8 vs. the 8.3
much more for inflammation control; topical NSAIDs are pH of generic bromfenac 0.09% (formerly
never an appropriate substitute when the brand-name Bromday). This pH modifica-
perioperative condition merits a topical corticosteroid. tion enables the lower 0.07% concentra-
care than for In recent years, the following NSAIDs tion of Prolensa to clinically perform as
have come to market: well as the generic 0.09% concentration.
primary eye • BromSite. Approved by the FDA in Prolensa is preserved with BAK 0.005%
April 2016, BromSite (bromfenac 0.075%, and comes in two quantities: 1.6ml and
care. Sun Pharma) is the first NSAID specifical- 3ml (both in 7.5ml bottles).
ly indicated for preventing ocular pain in Because BromSite and Prolensa are so-
patients undergoing cataract surgery. Like lutions, not suspensions, shaking the bot-
other NSAIDs, it’s also indicated for treat- tle before use is not required.
ing postoperative inflammation. • Ilevro. The other topical NSAID
BromSite achieves its low with once-daily dosing, Ilevro (nepafenac
0.075% concentration due 0.3%, Alcon) achieves this by increasing
to its DuraSite delivery ve- the concentration from the earlier-gener-
hicle (developed by InSite ation Nevanac (nepafenac 0.1%, Alcon).
Vision), which is believed to Ilevro comes in a 1.7ml quantity, whereas
extend the drug’s residence Nevanac is dispensed as 3ml. Because Il-
time on the ocular surface. evro is a suspension, the bottle must be
In Phase III trials, a greater shaken before the drop is instilled. DG
number of patients treated
1. BromSite [prescribing information]; Cranbury NJ: Sun
with twice-daily BromSite Pharma Industries, Inc; Apr 2016.
EFFECTIVE
ANTIVIRAL THERAPY
T
Herpetic he herpes virus (HSV) can similar presentation as seen in dry eye. Re-
manifest in a wide range of member that in early HSV, corneal lesions
eye disease ocular conditions—from a may not present in their classic dendrite
mild vesicular lid lesion to an formation. Document the corneal staining
remains the aggressive retinitis. Clinicians pattern carefully and monitor closely if
leading cause should be aware that the virus has the you suspect a possible HSV infection.
ability to affect every ocular tissue, and Clinical pearl: Limbal dendrites are
of corneal treat the patient accordingly. typically more recalcitrant to treatment
than central dendrites because the im-
blindness HERPES SIMPLEX munological armamentarium (antibodies
The herpes simplex virus is a DNA virus and leukocytes) is abundantly present in
worldwide. primarily spread by close personal con- the limbal microvasculature.2
Early diagnosis tact. Usually seen in children and young Recurrent infections may occur at any
adults, the disease can be broken down age. Up to 25% of patients with a primary
and treatment into two types: herpes simplex-1 (oral/ infection will have a recurrence of the dis-
facial/ocular) or herpes simplex-2 (geni- ease later in life. Additionally, up to 50%
can help tal), although HSV can also cross infect with a recurrent infection will have an-
between type 1 and type 2.1 other outbreak within two to five years.3
dampen the Disease expression often occurs in two Neurotrophic keratitis is a much more
impact of this phases—prodromal and outbreak. In the serious complication of herpes simplex
setting of periocular skin disease, the pa- keratitis (HSK) and may occur secondari-
disease. tient may have confined prodromal symp- ly to previous keratitis outbreaks where
toms consisting of mild pain, tingling, the basement membrane was damaged.
itching or burning before the lesion po- These patients are often in minimal or no
tentially progresses through the following pain due to the widespread damage of the
stages: macule, papule, vesicle, encrusta- corneal nerves. In essence, their corneas
tion and healing (without scarring). Only are now “permanently anesthetized.”
after the skin lesions are crusted over is Neurotrophic keratitis is clinically seen
the primary disease no longer contagious. as round defects with rolled edges, and
In secondary ocular disease expression, the potential for stromal thinning and
the patient presents with a unilateral in- subsequent perforation is increased. It is
jected eye with a mild, watery discharge. especially important to evaluate the ante-
(This is in contrast with epidemic kera- rior chamber in these patients, as there is
toconjunctivitis, where profuse tearing is often a mild anterior iritis that accompa-
commonly observed in a much more in- nies the keratitis.
jected eye.) A staining pattern on the cor- Because there is no active viral repli-
nea (early microdendrites) may resemble a cation seen in neurotrophic keratitis, the
disease is treated with a different ap- examination. The need to culture is FROM CHICKEN POX
proach. A bland antibiotic ointment exceedingly rare, but when in doubt, TO SHINGLES
can be instilled BID-QID alongside the virus can be cultured by lifting The varicella virus (chicken pox) is the
a cycloplegic agent BID. Culturing and swabbing the base of the lesion. initial or primary infection of the her-
should be considered, and the poten- While the disease process is self-lim- pes zoster disease process. Herpes zos-
tial for corneal perforation should iting, treatment should be initiated ter (shingles) is the reactivation of the
be monitored daily. For non-healing to decrease the likelihood of corneal varicella virus most commonly seen
lesions, consider consultation with a scarring and subsequent vision com- in the sixth to seventh decade of life.
corneal specialist. promise. When a patient is initially exposed
Other serious complications of to chicken pox, the virus becomes
HSK consist of a necrotizing stromal HERPES ZOSTER latent in the sensory ganglion
keratitis and necrotizing interstitial Up to 30% of patients will of the trigeminal nerve. If the
keratitis. Both can rapidly lead to develop a herpes zoster out- disease is reactivated, the virus
stromal scarring and perforation if break in their lifetime. Better travels down the ganglion to its
not treated quickly with cycloplegics, known as “shingles” to the respective afferent peripheral
antivirals and topical steroids. Refer general public, the preva- nerves and dermatome (an
patients with these conditions to a lence is well-documented area of skin that is mainly
corneal specialist for evaluation. to be increasing over the supplied by a single spinal
Fortunately, diagnosis of herpetic past decade.4 Nearly one nerve).
eye disease is nearly always made million Americans develop A shingles outbreak is al-
with a careful history and clinical shingles every year, with ways unilateral, and will not
The study concluded that: • Additionally, oral acyclovir did dosed BID for one year resulted in a
• Epithelial disease alone did not not improve outcomes in stromal 45% decrease in the chance of recur-
make future recurrences more keratitis cases, nor did it prevent rence for all forms of ocular involve-
likely, but stromal disease defi- stromal involvement. ment; however, the effect was stopped
nitely did. • Stromal disease was best man- upon discontinuation of the drug.9 So,
• With regards to patients who aged with topical steroids, which strongly consider lifetime treatment
had epithelial dendrites, oral acy- did not increase recurrence rate. with oral acyclovir in patients who
clovir did not reduce the rate of As revealed in the Acyclovir Pre- have two or more outbreaks in a year,
stromal disease. vention Trial, oral acyclovir 400mg or a recurrent disciform keratitis.
Prostaglandin Analogs
Bimatoprost bimatoprost generic 0.03% 2.5ml, 5ml, 7.5ml
Lumigan bimatoprost Allergan 0.01% 2.5ml, 5ml, 7.5ml
Travatan Z travoprost Alcon 0.004% 2.5ml, 5ml
Travoprost travoprost generic 0.004% 2.5ml, 5ml
Xalatan latanoprost Pfizer, + generic 0.005% 2.5ml
Zioptan tafluprost Akorn 0.0015% unit-dose
Alpha Agonists
Alphagan P brimonidine Allergan 0.1%, 0.15% 5ml, 10ml, 15ml
Brimonidine brimonidine generic 0.15%, 0.2% 5ml, 10ml, 15ml
FROM THE
LITERATURE
TIMOLOL EYE DROPS FOR MIGRAINE HEADACHE?
Acute migraine headaches may be reduced in intensity or
stopped altogether with beta blocker eye drops. While the
NEW PERSPECTIVES daily use of beta-blocker pills has proved effective in
ON TARGET IOP preventing chronic migraine headaches, they have been
“Meta-analysis shows mean IOP unsuccessful in treating acute, sudden-onset migraines.
reduction with prostaglandin Beta-blocker eye drops, however, are absorbed more
analogues ranges from 28-33%. quickly than pills by tear duct drainage onto the nasal
Slightly smaller IOP reduction mucosa, achieving therapeutic plasma levels “within min-
is typically achieved with beta- utes.”
blockers whereas alpha-agonists
Migliazzo CV, Hagan JC. Beta-blocker eyedrops for treatment of acute mi-
and carbonic anhydrase inhibitors graine. Missouri Medicine. 2014; 111(4):283-8.
will usually reduce IOP by 15-20%.”
combined therapy usually achieves One drop is instilled within 20 to In our experience, the addition
target IOP. 30 minutes after waking, followed of 0.2% brimonidine has two main
If the beta-blocker is contraindi- by a second drop of brimonidine be- limitations. The first is that the drop
cated (as in a patient with asthma), tween 4pm and 5pm in the afternoon. is dosed BID as adjunctive therapy—
our next preferred drop is the alpha-2 Though FDA-approved dosing for the the patient will now be instilling a to-
selective adrenergic agonist 0.2% bri- medication is TID, the use of brimo- tal of three drops in the affected eye
monidine. (For some unexplained rea- nidine off-label BID as an adjunctive per day. The second potential setback
son, 0.2% brimonidine is less costly therapy tends to work well for about is the possibility of ocular surface al-
than 0.15%, although we would pre- eight hours, and does very little dur- lergic disease. We have found this
fer the latter; both are generic.) While ing the sleep cycle; thus, the late after- type IV conjunctival hypersensitivity
1% apraclonidine does demonstrate noon instillation of the drop provides response in about 30% of patients
a much more rapid decrease in IOP, maximum therapeutic benefit. after six to 12 months.
the drop is reserved for short-term
adjunctive use due to a slight propen-
sity to cause tachyphylaxis (i.e., rapid
decrease in response to a given drug
after repeated administration) when
used longer than one month.
Alpha-2 adrenergic agonists exert
their effects by decreasing aqueous
humor production and increasing
uveoscleral outflow. The average IOP
reduction is around 26%.5
CREATIVE USE OF COMBINATION DRUGS generic dorzolamide suspension (replacing the brand
Treating glaucoma is like a chess game: every move has name-protected brinzolamide [Azopt]) with a clinically
consequences. The goal for all treatment is efficacy; but equivalent topical carbonic anhydrase inhibitor solu-
cost and convenience must also be considered, because tion twice daily. No shaking is required and this option
they affect compliance. provides a cost savings from using two generics over
We appreciate the convenience of combination one brand name-protected combination drug. Again,
therapy and the reduction of preservative exposure, but have the patient use the second set of drops about eight
combination medicines can also be more costly. So, if the hours after the morning instillation and wait five to 10
patient has limited financial resources and simply can’t minutes between drops.
afford the cost of brand name products, then judicious, Last, and perhaps most important in our experience,
critical thinking skills have to come into play to do the just a single generic drug, usually added to a prostaglan-
best we can to care for these patients. din, will sufficiently achieve target IOP. This means we
As such, doctors sometimes have to get creative in can use one of the following as an additive option: 0.25%
their prescribing to finesse the best solution for the or 0.5% timolol as a once-daily add-on (our preferred
individual patient. For example, if you’re considering choice because it’s a once-daily drug and by far the least
Combigan but the patient is concerned about cost, pre- expensive), 0.2% brimonidine used twice daily, or 0.2%
scribe 0.5% timolol to be used once daily in the morning, dorzolamide used twice daily.
and 0.2% brimonidine to be used every morning and Remember, a small percentage of patients are non-
again in the late afternoon. Not as convenient, but less responders, so to blindly use a combination drug may be
expensive for the patient and equally effective. entirely unnecessary if one of the ingredient drugs brings
Two things to remember: (1) Neither timolol nor brimo- nothing to the table. So, the intelligent use of any combi-
nidine do much (if anything) to reduce intraocular pres- nation drug requires a therapeutic trial of the component
sure during the sleep cycle; (2) the effect of brimonidine drugs to first establish efficacy prior to even thinking of
is about eight hours, so using the second drop around using them in a combination product.
4pm captures the maximum efficacy of the drug. We wish such combination drugs offered two key
Likewise, when cost is of paramount importance with components: guaranteed efficacy of both ingredient
Simbrinza, a brand name-protected drug, prescribe drugs, and more affordable pricing. If they did, we would
generic 0.2% brimonidine to be used twice daily and use them much more often.
FROM THE
LITERATURE when indicated and always a close
observation of the optic nerves at ev-
ery follow-up to prevent vision loss.
THE MONOCULAR TRIAL: IS IT VALUABLE? As medical practitioners of the eye, it
We have always embraced the value of a therapeutic monocular trial in the care seems appropriate that we should be
of patients for whom we contemplate therapeutic intervention. Some dismiss the first-line providers for the major-
this approach; some advocate for it. Here’s some wisdom from the literature.
ity of glaucoma patients. DG
If a prostaglandin has a therapeutic effect on the first eye, then it almost
certainly will have a therapeutic effect on the second eye, and the magnitude 1. Tham Y-C, Li X, Wong TY, et al. Global prevalence
of this response will be similar in both eyes. This finding argues against the of glaucoma and projections of glaucoma burden
through 2040. Ophthalmology. Nov 2014;121(11):
requirement of additional clinic visits to assess the response of treatment in the 2081–90.
second eye. 2. U.S. Department of Health and Human Services
Health Resources and Services Administration Bureau
The monocular trial of therapy is effective in accurately predicting the of Health Professions October 2006. Physician Supply
response of an untreated eye to monotherapy with a prostaglandin analogue and Demand: Projections to 2020. Available at: bhw.
hrsa.gov/sites/default/files/bhw/nchwa/projections/
at all daytime points measured. There is no requirement for patients to be seen physician2020projections.pdf. Last accessed March
at the same time of day after treatment has commenced. The effect in the first 7, 2017.
eye predicts both the likelihood and magnitude of an effect in the second eye 3. U.S. Department of Health and Human Services
Health Resources and Services Administration Bureau
at all time points during office hours, and negates the requirement for an addi- of Health Professions December 2008. The Physician
tional visit to check the therapeutic effect when commencing therapy in the Workforce: Projections and Research into Current Is-
sues Affecting Supply and Demand. Available at: bhw.
second eye. hrsa.gov/sites/default/files/bhw/nchwa/projections/
Our take: This is in keeping with our 70-plus combined years of glaucoma physiciansupplyissues.pdf. Last accessed March 7,
2017.
patient care, and we commonly embrace the monocular therapeutic trial in 4. De Moraes CG. NTG: The Nocturnal Blood Pressure
most of our patients most of the time. Factor. Rev Ophthalmol. 2014; 24(2):54-57.
5. Mishra D, Sinha BP, Kumar MS, et al. Comparing
King AJ, Rotchford AP. Validity of the monocular trial of intraocular pressure-lowering at differ- the efficacy of latanoprost (0.005%), bimatoprost
ent time points in patients starting topical glaucoma medication. JAMA Ophthalmol. 2016; Jul (0.03%), travoprost (0.004%), and timolol (0.5%) in
1;134(7):742-7. the treatment of primary open angle glaucoma. Ko-
rean J Ophthalmol. 2014 Oct; 28(5): 399–407.