anterior segment disclosure statement grand rounds · headache, malaise, fever, chills followed in...
TRANSCRIPT
3/6/2015
1
Anterior Segment
Grand RoundsEYE-SIGHT 20/20
September 14, 2014
Jimmy D. Bartlett, O.D., D.Sc., FAAO
Professor Emeritus, The University of Alabama at Birmingham
President, PHARMAKON Group
Birmingham, Alabama
ANTERIOR SEGMENT GRAND
ROUNDSCourse Title:
DISCLOSURE STATEMENT
Please silence all mobile devices.
Alcon
Allergan
Bausch & Lomb
Jobson Medical Publishing
Lecturer: Jimmy D. Bartlett, O.D., D.Sc., FAAO
Professor Emeritus, School of Optometry
The University of Alabama at
Birmingham
Commercial Break (Simbrinza) Disclosure Statement� Alcon
� Allergan
� Bausch & Lomb Pharmaceuticals
� Jobson Publishing Group
� United States Pharmacopeia
� Wolter Kluwers Health
Please silence all mobile devices.
Swollen Painful Eyelid
3/6/2015
2
MRSA UPDATE
Methicillin-Resistant Staphylococcus
Aureus
Penicillins
� Gram-positive
� Penicillins G and V
� Penicillinase-resistant penicillins
� Methicillin, nafcillin, cloxicillin, dicloxacillin
� Extended spectra
� Ampicillin, amoxicillin
3/6/2015
3
The acronym MRSA signifies
that the isolates are resistant to all
beta-lactam antibiotics, not just
methicillin
Evolving Prevalence of MRSA
� S. aureus resistance was first discovered in
1944
� MRSA prevalence is now 3%-53%
� In the US, approx 14% of S. aureus isolates
(bacterial conjunctivitis) are methicillin-
resistant
� Excluding endophthalmitis, nationally the
prevalence of ocular MRSA is about 40%
Range of MRSA Eye Infections
� Blepharoconjunctivitis (78%)
� Keratitis (15%)
� Cellulitis (2.5%)
� Dacryocystitis (2.5%)
� Endophthalmitis (2%)
Freidlin J., et al. Am J Ophthalmol 2007; 144: 313-315.
Best Therapeutic Options
Ocular TRUST
� A longitudinal nationwide antimicrobial
susceptibility surveillance program specific
to ocular isolates
�S. aureus
�Coagulase-negative staphylococci
�S. pneumoniae
�H. influenzae
Asbell, PA, et al. Am J Ophthalmol 2008; 145: 951-958.
Susceptibility Testing
� In vitro susceptibility testing to nine antimicrobials
� Ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin
� Azithromycin
� Trimethoprim
� Tobramycin
� Polymyxin B
� Penicillin
3/6/2015
4
8
50
959389
62
17
100 99
Ocular TRUST 2: S. aureus
Susceptibility
MSSA (N=71) MRSA (N=84)
20
40
60
80
100
% S
us
ce
pti
ble
18
Asbell PA, ASCRS 2008
Antibiotic Resistance Monitoring
in Ocular MicRorganisms
(ARMOR)
• Ocular Surveillance Program across the US
• Profiles in vitro activity of ophthalmic agents against ocular isolates:
‒ Staphylococcus aureus
‒ Coagulase-negative staphylococci
‒ Streptococcus pneumoniae
‒ Haemophilus influenzae
• Tested concurrently for susceptibility to besifloxacin, moxifloxacin, gatifloxacin, ciprofloxacin, azithromycin, tobramycin, trimethoprim, vancomycin
Antibiotic MIC Range MIC50
MIC90
Vancomycin ≤0.25 – 2 0.5 1
Besifloxacin ≤0.008 – 4 0.03 1
Moxifloxacin ≤0.008 – 64 0.06 8
Gatifloxacin ≤0.03 – 256 0.12 8
Ciprofloxacin ≤0.015 – 512 0.5 256
Tobramycin ≤0.06 – >256 0.5 256
Azithromycin ≤0.25 – >512 128 >512
Haas W et al. Presented at: ARVO 2011; May 1-5, 2011; Ft Lauderdale, FL; Poster D1129.
� 50.0% of ocular S aureus isolates were MRSA
� 39.9% of ocular S aureus isolates were FQ resistant
Besifloxacin MIC90 for All
Staphylococcus aureus Isolates
*N=228.Percent resistance based on oxacillin and ciprofloxacin breakpoints.
Besifloxacin (Besivance)
Suspension
� NOT used systemically
� FDA-approved for bacterial
conjunctivitis
� FDA-approved dosage: TID for 7 days
� Pediatric approval: ages 1 and older
� Preserved with 0.01% BAK
� Durasite vehicle for long retention time
on ocular surface
First and Only Ophthalmic
Chlorofluoroquinolone
� Fluorine at C6
� Chlorine at C8
Durasite Vehicle
� Mucoadhesive polymer matrix
3/6/2015
5
Besifloxacin Tear Concentrations
Relative to MIC90 for Ciprofloxacin-
Resistant MRSA and MRSE
� At 12 hours
postinstillation,
concentration of
besifloxacin
remains higher than
the MIC90 for
MRSA-CR and
MRSE-CR
Proksch JW , et al. J Ocul Pharmacol Ther. 2009;25:335-343.
Haas W, et al. Antimicrob Agents Chemother. 2009;53(8):3552-3560.
.
1
10
100
1000
0 4 8 12
Con
cen
trati
on
, µ
g/m
L
Time, h
MIC90 for MRSA-CR and MRSE-CR
Treatment Options for Initial
Empirical Therapy of MRSA
� Topical
�Vancomycin
�Besifloxacin
�Trimethoprim/polymyxin B
Antibiotic Combinations
Trimethoprim/Sulfamethoxazole
Trimethoprim/Sulfamethoxazole
Name Formulation
Trimethoprim/sulfamethoxazole
(generic)
80 mg trim/400 mg sulf
160/800 mg (double
strength)
40/200 mg/5ml
Bactrim, Bactrim DS
Cotrim, Cotrim DS
Septra, Septra DS
Same as above
Case Report
� 35 year-old WF
� Internal hordeolum, right upper lid
� Severe allergy to penicillin
� “Mycin drugs” upset stomach
� “Can’t swallow pills”
3/6/2015
6
Bactrim is a Sulfonamide!
Treatment Options for Initial
Empirical Therapy of MRSA
� Oral
�Trimethoprim/sulfamethoxazole
�Clindamycin
�Doxycycline
�Tedizolid (Sivextro)
Rivera AM, et al. Mayo Clin Proc 2011; 86: 1230-1243.
Treatment Options for Initial
Empirical Therapy of MRSA
� Intravenous (monotherapy)
�Vancomycin
�Daptomycin
�Linezolid
�Telavancin
�Ceftaroline
�Tigecycline
Rivera AM, et al. Mayo Clin Proc 2011; 86: 1230-1243.
β-Blocker Allergy?
3/6/2015
7
Preservative-Free TimololBAK-Free Glaucoma
Medications
� Timoptic in Ocudose
� Timoptic XE
� Alphagan-P
� Travatan Z
� Zioptan
� Cosopt-PF
Contact Allergy� Type IV reaction
� Suspect contact allergy if
�No history of allergy
�Lower lid and inferior conjunctiva most
affected
Management of Contact Dermatitis
� Steroid dermatologic ointments or creams
� Triamcinolone 0.1% crmor ung
� Loteprednol 0.5% ung
� Hydrocortisone 1.0% crm, ung, gel
Case Example
Before One Week Later
3/6/2015
8
Hole-y Cornea!
Case Report
Dellen
� Small area of corneal thinning located at the limbus
� Caused by localized drying of the cornea
� Causes of tearfilm disruption leading to dellen
�Local elevations (pterygium, pinguecula, chemosis, bleb, etc.)
�Systemic medications with anticholinergic side effects
Drugs Causing Dry Eye (and
Possibly Dellen)
� Anticholinergics
� Antihistamines
� Phenothiazines
� Anti-anxiety agents
� Tricyclic antidepressants
� Vitamin A analogs
Anticholinergics
• 1-2 mg oral atropine reduces aqueous tear
secretion from 15 µl/min to 3 µl/min
• 1-2 mg oral scopolamine reduces tear
secretion from 5 µl/min to 0.8 µl/min
Other Anticholinergic Agents
� Sominex (diphenhydramine)
� Lomotil (diphenoxylate and atropine)
� Detrol LA (tolterodine)
3/6/2015
9
Why Do Antihistamines
(and many other meds!)
Cause Dry Eye?
Parasympathetic (Cholinergic)
Innervation of Lacrimal Gland
Antihistamines
• H1 blockers reduce both aqueous and mucinproduction
• As little as 4 mg daily of chlorpheniramine maleate can produce positive Schirmer test
• Four days of once-daily loratadine (Claritin) can induce dry eye and corneal staining
• Can aggravate underlying condition of dry eye
Oxybutynin (Oxytrol) Transdermal
(Rx to OTC January 25, 2013)
Pulmonary Drugs with
Anticholinergic Activity
• Atrovent (ipratropium)
• Spiriva (tiotropium)
Miscellaneous Agents
• Phenothiazines
• Antianxiety agents
• Most antidepressants
have anticholinergic
activity
3/6/2015
10
Antidepressants Causing Dry Eye
• Celexa
• Cymbalta
• Effexor XR
• Lexapro
• Nardil
• Paxil
• Prozac
• Sinequan
• Wellbutrin
• Zoloft
Accutane Has Been
Discontinued– New Isotretinoin
Trade Names:
� Amnesteem
� Claravis
� Sotret
� Myorisan
� Absorica
Descriptive Words in Package
Insert Suggesting “Dry Eye”
� Anticholinergic
� Cholinergic antagonist
� Antimuscarinic
� Muscarinic antagonist
� Parasympatholytic
PI for Oxytrol Transdermal
� http://www.accessdata.fda.gov/scripts/cder/drugsatfda/
� Or just Google “Drugs at FDA”
So Where Do I Find Package
Inserts?
3/6/2015
11
What If I Don’t Have Time For
All That?!!
Use Epocrates on Smartphone
or Tablet
Epocrates Rx Diagnosis of Dellen
� Foreign body sensation or ocular discomfort
� Focal conjunctival injection
� Small, oval, saucer-like excavation usually less than 2.0 mm located on corneal side of limbus, more frequently on temporal side
� Clearly defined borders, but base appears hazy and dry
� Epithelium is typically intact and fluorescein pools in the excavation
� Early, stroma is intact but thin due to loss of fluid
� True scarring with or without vascularization can occur if allowed to persist
3/6/2015
12
Management
� Treatment is directed toward rehydrating the cornea and, if possible, removing the cause
� Non-preserved artificial tears Q2H and lubricating ointment HS usually allow resolution within 48 hours
� Severe dellen may require prophylactic topical antibiotics
� Inflammatory conditions should be treated appropriately
Commercial Break (Prolensa)
What’s That White Spot
on the Cornea?
What is the best management of
this patient? D/C contact lenses +
A. Artificial tears
B. Topical steroid alone
C. Topical antibiotic alone
D. Topical steroid-antibiotic combo
E. Patch the eye with topical antibiotic ung
and cycloplegic
Infiltrative Keratitis/CLARE/CIE
� Initially thought to be primarily due to hypoxia
�An inflammatory response to toxins produced by less virulent strains of gram negative bacteria
�Recurrent episodes common
�CLARE is NOT a marker for microbial keratitis
Sweeney, et al. Eye Contact Lens 2007
3/6/2015
13
Differential Diagnosis of Corneal
Ulcers vs. Sterile InfiltratesUlcer (MK)
� Rare
� Usually painful
� Tend to be central
� 1 to 1 staining defect to
lesion ratio
� Cells in anterior chamber
� Generalized conjunctival
injection
� Usually solitary lesion
� Possible tear lake debris
� Eyelid swollen
Infiltrate
� Common
� Mild pain
� Tend to be peripheral
� Staining defect size relatively
small
� No cells in anterior chamber
� Sector skewed injection
pattern
� Can be multiple lesions
� Clear tear lake
� Eyelid not swollen
Infiltrate
� Common
� Mild pain
� Tend to be peripheral
� Staining defect size relatively
small
� No cells in anterior chamber
� Sector skewed injection
pattern
� Can be multiple lesions
� Clear tear lake
� Eyelid not swollen
3/6/2015
14
Management of CLARE/CIE
� Topical steroid alone
� If cornea is clear/no epithelial compromise
� Combination antibiotic/steroid
�Pulse-dose q2h for 1-2 days, then q.i.d. for 4-5 days
� Address CL hygiene and wearing time: Daily wear only!
�Otherwise, CLARE is likely to recur
Preferred Antibiotic-Steroid
Combos
Treatment of acute ocular surface and
eyelid inflammation in an atopic,
pregnant female
PUFFY (REALLY, REALLY
PUFFY) EYELIDS
32 Year-Old AA Female
� “This morning I was having a permanent in my
hair”
� “Some of the solution dripped into my eyes”
� “My eyes immediately swelled and are
extremely itchy. They are so swollen, I can
hardly see.”
� 4 months pregnant
� Has asthma and eczema, and so does her father
3/6/2015
15
Oral Antihistamines for ACUTE
Allergic Angioedema
Oral H1 Antihistamines
� Often prescribed based on sedative properties
� Formulations include syrups, tablets, capsules and sustained-release
� Indicated for moderate to severe eyelid edema and chemosis
Classification by CNS Sedation� Nonsedating
�Fexofenadine (Allegra)
�Loratadine (Claritin)
�Desloratadine (Clarinex)
�Cetirizine (Zyrtec)
� Mildly sedating
�Chlorpheniramine (Chlor-Trimeton)
�Brompheniramine (Dimetane)
� Strongly sedating
�Diphenhydramine (Benadryl)
Nonsedating Antihistamines
� Loratadine (Claritin)
� Claritin D
� Desloratadine (Clarinex)
� Clarinex D
� Cetirizine (Zyrtec)
� Zyrtec D
� Fexafenadine (Allegra)
� Allegra D
Loratadine (Claritin)
Dosage Formulations:
� 10 mg tablet; QD
� Syrup
� Claritin D-24 h
� Claritin D-12 h
� 10 mg Reditabs
� Alavert
(Dissolves in Mouth)
3/6/2015
16
Mildly Sedating Antihistamines
� Brompheniramine (Dimetane)
�Adult dosage 4 mg q 6-8 h
� Chlorpheniramine (Chlor-Trimeton)
�Adult dosage 4 mg q 6-8 h
Side Effects
� Sedation
�Avoid alcohol and opioids!
� Palpitations
� Drying of throat/bronchi AND EYES
� Mydriasis
� GI/GU disturbances
�Take with meals or adjust dose
Contraindications
� Alcohol, opioid analgesics
� Avoid antihistamines with strong anticholinergic effects in peptic ulcer disease, prostatic hypertrophy (BPH), bladder obstruction, angle-closureglaucoma
� Lactation/3rd trimester pregnancy
What is the Best (Safest) Allergy
Treatment During Pregnancy?
Generic Name Trade Name Pregnancy
Category
Dosing
Frequency
Alcaftadine Lastacaft B QD
Nedocromil Alocril B BID-QID
Lodoxamide Alomide B QID
Cromolyn sodium Opticrom, Crolom B QID
Chlorpheniramine Chlor-Trimeton B QID
Loratadine Claritin B QD
Cetirizine Zyrtec B QD
Diphenhydramine Benadryl B QID
Avoid Oral Antihistamines for
Long-Term Therapy
Potential Issues
� Elevated blood pressure when used with
decongestants
� Dry eye
3/6/2015
18
Differential Between HSK and
HZKHerpes Simplex Herpes Zoster
Pain Mild to moderate Severe
Dendrite appearance Larger, more branching,
discrete, delicate pattern,
more central
Smaller, less branching,
coarse, blunted pattern,
usually peripheral
Epithelium Ulcerated Blunted dendrite with
slightly raised edges
Fluorescein staining Prominent Dull and irregular
End bulbs Present Absent
Recurrence Common Rare
Herpes Zoster Ophthalmicus
Etiology
� Recurrent varicella-zoster virus
� Occurs most often in immunocompromised patients
� Physical and emotional trauma, immunosuppressive medications, irradiation, cancer, TB, and HIV can reactivate the virus
� Diagnosis of HZO in patients younger than 45 years warrants testing for HIV
Diagnosis
� Headache, malaise, fever, chills
� Followed in one or two days by neuralgic pain
� Followed in 2 or 3 days by hot, hyperesthesia and edema of dermatomes
� Unilateral vesicular eruption
� Vesicles become yellow and turbid and form eschars by day 7-10
3/6/2015
19
Treatment of Skin Lesions
� Avoid drying lotions
� Oral antihistamines may
prevent itching
� Warm solution of aluminum
acetate (Burow’s)
�Apply 15-30 min, QD to
TID
� Oculoplastic consultation
Ophthalmic Management
� No therapy may
be required
� Topical steroids
for corneal
edema and
anterior uveitis
� Oral analgesics
Acyclovir
� Should be started within 72 hours of skin
lesions
� 800 mg 5 times daily for 7-10 days
Acyclovir Formulations
� 200 mg capsule
� 400 mg tablet
� 800 mg tablet
� 200 mg/5 ml suspension
(banana flavor)
Benefits of Acyclovir Therapy
� Dendriform
keratopathy
� Stromal keratitis
� Anterior uveitis
� Acute and chronic
pain
3/6/2015
20
Valacyclovir (Valtrex)
� Prodrug of acyclovir
� Available as 500 mg
tablet
� Dosage is 1000 mg
tid x 7 days
Famciclovir (Famvir)
� Prodrug of penciclovir
� Available as 125, 250, 500 mg tablet
� Dosage is 500 mg tid x 7 days
Side Effects of Antivirals
� GI
�Nausea
�Diarrhea
3/6/2015
21
Contraindications
� Hypersensitivity
� Intolerance
� For immunocompromised patients, avoid
valacyclovir
�Risk of thrombocytopenia, which can be
fatal
�Famciclovir is okay
Don’t Forget These!
� Slit lamp exam
�Uveitis?
� IOP
� Dilated fundus exam
�Retinitis?
Herpes Zoster Neuralgia
� Varies from minor tingling and numbness to
excruciating pain
� Postherpetic neuralgia
Capsaicin for Postherpetic
Neuralgic PainNot For Use In The Eye!