2/12/19

1

KeratoconjunctivitisSicca

David A. Wilkie DVM, MS, Diplomate ACVO

Professor EmeritusThe Ohio State University

Wilkie.1@osu.edu

Dry Eye is massively under

diagnosed

Keratoconjunctivitis siccan Keratoconjunctivitis Sicca (KCS)

n 6-34% prevalence in humans >50yr (Thelin, 2012)

n 4-35% prevalence in canine (Williams, 2008; Kaswan, 1998)

n Prevalence varies by breed, age, definition of KCS

Keratoconjunctivitis siccan KCS

n Consequencesn Cornea

n Ulcerationn Vascularizationn Pigmentationn Keratinizationn SCC

n Discomfortn Dischargen Blindnessn Lifelong therapy

n expensive drugs/Sx

Do you see these breeds???

When do I treat???

STT

051015202530

STT

STT

Time

Why do you wait to get to here??

Why not treat here??

2/12/19

2

Lacrimationn Lacrimal glands

n Majority of reflex tearsn Accessory glands

n Basal tear secretionn Conjunctiva/Cornea epithelial cells

n Basal tear secretionn Mucosal hydration regulated via Na+ absorption

and Cl- secretion

Precorneal Tear Film

Cornea

Precorneal Tear Film

STT

TBUT

Keratoconjunctivitis sicca (KCS)

n Progressive inflammatory condition of the cornea and conjunctiva caused by the deficiency of tears n Aqueousn Mucin

Keratoconjunctivitis sicca (KCS)

n Two types – Qualitative vs Quantitative

Keratoconjunctivitis sicca (KCS)

n Decreased Aqueous Tear Productionn Quantitative – determined by STT

2/12/19

3

Keratoconjunctivitis sicca (KCS)

n Decreased Mucin Productionn Qualitative - determined using TBUT

Keratoconjunctivitis sicca (KCS)

n Decreased Mucin Productionn Qualitative - determined using TBUT

Clinical signsn most severe in the

dogn cats have minimal

signs

Clinical signsn Acute - pain, blepharospasm,

ulceration

Clinical signsn Chronic - conjunctivitis (hyperemia,

thickening)

2/12/19

4

Clinical signs:n Chronic - keratitis

n vascularization, pigmentation, fibrosis and superficial haze

2/12/19

5

Clinical signs:n discharge - mucoid to mucopurulent

n mucus produced by the goblet cells

Clinical signsn 70 % bilateral

Clinical signsn neutered animals predisposedn breed incidence

n Eng. Bulldogn Min Schnauzern Yorkshire terriern West Highland terriern Pugn Shih tzun Lhasa apson Am Cocker Spanieln Cavalier King Charlesn Boston terriern Other

2/12/19

6

Etiology of KCS:n Congenital alacrimia due to lacrimal

gland hypoplasia (rare)

Keratoconjunctivitis siccan KCS

n Etiologies- numerousn Breed-associatedn Immune-mediatedn Associated with endocrinopathiesn Age-relatedn Neurogenicn Drug-inducedn Iatrogenicn Post-anesthesia – transient?n Other

Breed Associated Neurologicn Denervation of the parasympathetic fibers in

the lacrimal nerven Pre-ganglionic parasympathetic denervation

leads to dry nose (xeromycteria)

Neurologicn Facial nerve palsy (CN VII)

n Otitis media/internan Hypothyroidn Diabetes mellitus

2/12/19

7

n STT preop is lower in diabetes mellitus vs non-diabetic patients

n STT is lower in all patients in the first 2 weeks post opn Diabetics -26.3%; Non-diabetics -14%

n Diabetic dogs ≤10kg 1.7x more likely to have KCS than non-diabetic

n Preop STT <15mm/min or 15-22mm/min correlates with increase post op KCS in all dogs

Lu J, Gemensky-Metzler AJ, Wilkie DA: Retrospective study of the incidence of KCS in diabetic and non-diabetic dogs after phacoemulsification. 43rd Annual Meeting of the American College of Veterinary Ophthalmology, Portland, OR 2012

Post-op Diabetics

n Incidence of peripheral neuropathiesn Diabetics - 12.5% (24/196 dogs, 30

eyes)n Horners – 20n Neurogenic KCS – 5n Facial palsy - 5

n Non-diabetics – 0.7%

INCIDENCE OF PERIPHERAL NEUROPATHIES AFFECTING THE EYE IN DIABETIC PATIENTSPOST-PHACOEMULSIFICATION. (BC Foote 1, TM Michau 1, A Welihozkiy 1, JM Stine 1) 1BluePearl Veterinary Partners, Tampa FL. ACVO 2016

Neuro-ophthalmic Exam

CN- 2, 3, 4, 5, 6, 7

2/12/19

8

Viral infectionsn canine distempern Feline Herpes

Iatrogenic n Removal of a prolapsed GNMn Irradiationn Drug-induced

n Options:n Surgically replacen Leave alonen Excise

n All are at risk for KCSn Excise (48%) > Leave alone (43%) > Replace

(14%)*n Control (5%)

n Monitor STT for life*Morgan R: JAAHA1997

2/12/19

9

2/12/19

10

Drug-inducedn atropinen anestheticsn phenazopyridinen aminosalicyclic acidn sulfonamidesn Etogesic®

Conjunctivitis - acute or chronic

n obstruction of the lacrimal gland ductules in the conjunctiva

2/12/19

11

Diagnosisn Clinical signsn Schirmer tear test (STT)

n quantitative

Schirmer Tear Test n Strip allowed to remain in place for

exactly 1 minute.

≤ 15mm/min consider Rx Tear break-up time (TBUT)n Fluorescein dye is placed on the cornea and

the eyelids are held closedn Qualitative

STT

TBUT

Tear break-up time (TBUT)n Eyelids are then opened, and held openn Tear film break-up is prevented by the

mucinn Normal TBUT for the dog >20 sec

2/12/19

12

Tear Break-up

Tear Break-up20 seconds

Tear Break-up - Human

Tear Break-up - Canine Treatmentn Medical Therapy

n Lacrimogenicsn Tear supplementsn Antiinflammatories

n Surgical Therapyn PDT

2/12/19

13

Lacrimogenicsn The use of topical cyclosporine (CSA) and

Tacrolimus has revolutionalized our approach to the medical management of KCS

Lacrimogenicsn If successful, therapy with CSA/Tacrolimus will

eliminate the need for other medicationsn Optimmune® - 0.2% cyclosporine ointment

n Often too low a concentrationn 1-2% cyclosporine solution – compoundedn 0.02-0.03% Tacrolimus - compounded

75-82% response rate (CSA optimmune)85%-96% response rate (Tacro)36% with STT <2mm/min fail to respond

Lacrimogenicsn Often treat both eyes, even if only 1 eye has

KCS to get maximal responsen Decreases the T-helper cell�s response.

Decreases the recognition and afferent phase of auto-immunity to the lacrimal tissue

n Also has lacrimogenic, anti-inflammatory, anti-angiogenic and pigment-thinning and pigment-preventative effects.

Lacrimogenics

n Tacrolimusn Similar to cyclosporin, but more potent

n FK506 was the test namen Compounded

n 0.02-0.03% ointment/solution

STT

051015202530

STT

STT

Time

Why do you wait to get to here??

Why not treat here??

2/12/19

14

Lacrimogenicsn Pilocarpine

n Direct-acting parasympathomimetic

Lacrimogenicsn Pilocarpine

n Direct-acting parasympathomimeticn 1 drop of 2% pilocarpine orally BID for

each 10 lbs body weight - the dose can be increased slowly

n Signs of toxicity are hypersalivation, vomiting, diarrhea

n In my experience, this mode of therapy is rarely beneficial, except perhaps in neurogenic KCS

Tear replacementn Long-lasting viscous

preparationsn Preservative free

Tear Replacement

Corticosteroids

Antibioticsn Probably the most common medication

prescribed for KCS and the least indicated

2/12/19

15

Surgical Therapy for KCSn Medical therapy should always be attempted

firstn Surgical therapy is rarely indicated with the

improved efficacy of medical therapy (i.e, cyclosporine, tacrolimus and long-lasting viscous tear supplements)

Surgical Therapy for KCSn A parotid salivary duct transposition may be

indicated if medical therapy does not workn Tears and saliva are not identical in composition and

side effects and intolerance occur.

Surgical Therapy for KCS

PDT – side effects PDT – side effects

2/12/19

16

PDT – side effects Decreased Mucin Production (qualitative)

n Mucin deficiency results in a break in the contact (adsorption) of the precorneal tear fim with the cornea with a resultant �dry spot�

Loss of corneal luster

Flour + dry spot

TBUT < 5 seconds Decreased Mucin Production (qualitative)

n Chronic inflammation or primary disease of the conjunctival goblet cells

Decreased Mucin Production

(qualitative)n Reduced/more rapid tear BUT (<20 seconds)

n Chronic keratoconjunctivitis, but the STT is

normal or near normal and there is very little

mucoid discharge.

Decreased Mucin Production (qualitative)

n Treat using n CSA, Tacrolimusn Viscous tear replacers

2/12/19

17

Sequelae - chronic KCSWhat is your #1 Diff Dx?

Canine Corneal SCC

SCC pre surgery

SCC post surgery plus 5-FUSCC beta radiation

2/12/19

18

Researchn Water soluble CSA-like compounds

n Gilger BC, Wilkie DA, Salmon JH, Peel MR: A topical aqueous calcineurin inhibitor for the

treatment of naturally-occurring keratoconjunctivitis sicca in dogs. Vet Ophth 2012

n ENaC- Epithelial Na channel pump inhibitorsn OSU Clinical Trial n Thelin WR et al: Effect of Topically Applied Epithelial Sodium Channel Inhibitors on Tear

Production in Normal Mice and in Mice with Induced Aqueous Tear Deficiency. J Ocular

Pharm Therapeutics 2012

Lacrimationn Net fluid movement across the conjunctiva is a

balance between: n Ion secretion – Cl- channelsn Ion absorption – Epithelial Na+ Channel (ENaC)

n Works independently of the lacrimal gland status

Levin, IOVS 2006, 47:306-316

Refractory Pre ZP-1 Refractory Post ZP-1

Naïve Pre ZP-1 Naïve Post ZP-1STT 0 mm; TBUT 2 sec STT 0 mm; TBUT 2 sec

STT 8 mm; TBUT 7 sec STT 10 mm; TBUT 14 sec

CSA Implant

CSA Implant