1	IATROGENIC DRY EYE AND ITS MANAGEMENT Frank J. Holly, Ph.D. Dry Eye Institute Yantis, TX 75497 Spring, 2003
2	Refractive Surgery and the Dry Eye The following major procedures are used in refractive surgery: Radial Keratotomy - RK (still around) Photoreafractive Keratectomy - PRK (still fairly common) Laser–Assisted In-situ Keratomileusis - LASIK (most popular) Laser epithelial keratomileusis - LASEK (gaining grounds) They all can cause dry eyes as a – some times long lasting - complication
3	Surgical Complications Related to Dry Eye States [Selected from 80 complication (after Sandy Keller)] Corneal abrasions Corneal necrosis Corneal ulcers Diffuse lamellar keratitis Dry eye Microcystic edema Epithelial sloughing Foreign body sensation Contact lens intolerance Keratitis (noninfectious) Ocular pain (persistent) Headache Exp. palpebral fissure Photophobia Ptosis Recurr. epithelial erosion
4	Poll Results of Members of Surgical Eyes, Inc. Close to 4,000 members of this group of patients have been sent a questionnaire. The questions were related to the post-surgical care of the most common complication of refractive surgery, the dry eye. One hundred sixty-three patients have replied and their responses are shown in the next few slides. Most of these (98%) were post-lasik patients (2 RK and 1 PRK).
5	Provision of Post-Surgical Care
6	Medication/Device employed in post-surgical patients with complications
7	Other Treatments of Dry Eyes in Post-surgical Patients Contact lenses Erythromycin Puncta cauterization Antiallergy medication Bandage contact lenses Cyclosporin Lid therapy Lid surgery Nutrients Holistic approach Artificial tears suggested: any unpreserved drops Refresh, Refresh P.M. TheraTears, Bion Celluvisc, GenTeal Tears Naturale Moisture Tears HypoTears Endura
8	Properties of the Tear Film Characteristics: The tear film is actually a thin fluid film framed by the tear meniscus that are formed against the lid edges. The fluid layer in the tear meniscus is thick enough (>0.1 mm) so gravitational (hydraulic) flow can take place.
9	STABILITY OF THE TEAR FILM Closed Eye In the closed eye, the whole superficial lipid layer is confined between adjacent lid edges. Under the closed lids there is a continuous aqueous layer which also includes the tear meniscus This aqueous layer provides hydrodynamic lubrication for the lid moving over the globe.
10	FACTORS THAT INCREASE TEAR FILM INSTABILITY Local thinning of the tear film Increase polarity of meibomian lipids* Contamination by sebum* Mucin (lacrimal surfactant) deficiency Severely impaired tear secretion Damaged surface epithelium * caused by lid or skin inflammation (blepharitis, acne rosacea)
11	RUPTURE OF THE TEAR FILM Dry Spot Formation “Dry” eyes either have an unstable tear film or, in severe cases, the tear film is unable to form. Does dry spot formation results from evaporation? Unlikely! Rupture of the tear film is most likely results from local non-wetting.
12	TEAR FILM BREAK-UP TIME (BUT in seconds) It is reasonable to assume (Dohlman, 1974) that BUT shorten than the blinking time interval could result in epitheliopathy of the cornea. It is widely accepted (Lemp, 1976) that BUT < 10 sec is indicative of tear film instability. When evaporation is minimized, BUT as long as 3 minutes has been observed in humans (Holly, 1985).
13	VITAL STAINING Vital dyes commonly used for diagnosis stain epithelial surface abnormalities 1. Sodium fluorescein stains frank epithelial defects (punctate-, defect, erosion) 2. Rose-bengal stains hydrophobic spots (lipid-laden mucus, dead, dying cells) 3. Lissamine Green stains the same as Rose bengal but it is much less irritating. Staining patterns are suggestive as to the cause of surface abnormalities.
14	Positive Rose Bengal Stain
15	BLINKING AND THE TEAR FILM Does the Tear Film Re-form? No! The closing lids compress only the lipid layer. The aqueous layer remain continuous and serves as a lubricant protecting the ocular surface from shear forces generated by the rapidly moving eye lid. CAVEAT: increased viscosity of the lubricating layer could damage an already weakened epithelial surface layer.
16	BLINKING (cont.) The average time between two consecutive blinks ranges from 6 to 15 seconds. Not all blinks are complete! Incomplete blinkers may have inferior keratopathy (usually punctate staining). Activity requiring staring decreases blinking frequency considerably. Unless the tear film is highly stable it may be harmful in the long run.
17	TREATMENT MODALITIES Supplementation of aqueous tears (tear substitutes, lacrimal inserts, etc.) Preservation of aqueous tears (goggles, punctal plugs, etc.) Stimulation of aqueous tear secretion (secretagogues, eledoisin, cyclosporin)
18	Tear Supplementation The use of tear substitutes (ophthalmic demulcents) is the mainstay of the treatment of the iatrogenic dry eye. Unfortunately, it is widely believed that: Enhanced viscosity is helpful All eye drops are “created” the same Hypotonic salt solutions are efficacious Preservative-free drops are necessarily better
19	Tear Supplementation, cont. The main role of the eye drop should be to increase tear film stability High viscosity interferes with lid lubrication, can injure loose epithelium In the presence of leaky epithelium, colloid rather than crystalloid osmolality is important Lack of preservative does not improve efficacy!
20	ONCOTIC PRESSURE determined directly and expressed in mmHg Colloid osmolality can only be determind by direct measurement of the oncotic pressure. Such a solution can exert an osmotic effect even in the absence of a semi-permeable membrane (such as leaky epithelium) Eye drops having an oncotic pressure higher than the stromal imbibition pressure and IOP are efficacious in healing damaged, leaky surface epithelium and improve epithelial adhesion to stroma.
21	Preservation of Aqueous Tears The approach to preserve existing tears can be two-fold: diminish drainage through the puncta diminish evaporation by goggles or ointments
22	WHAT ABOUT LIPID OINTMENTS? Do they adversely affect tear film stability? This problem has not been adequately studied. Lipids used in ointments are mostly apolar and does not spread on hydrophilic surfaces. The quantity applied is enormous compared to the mucus layer capacity to handle lipid contamination. So, the hydrophobic contamination may be more than the lacrimal system can handle… ….resulting in blurry vision and interfering with the hydrodynamic lubrication of the lids.
23	PUNCTAL PLUGS to improve the tear meniscus Discontinuous, even scanty or narrow (<0.10 mm) tear meniscus is indicative of insufficient tear volume The placement of punctum plugs or sealing of the puncta may ameliorate the condition. Punctal plugs are not a panacea, however. In case of epiphora they should be removed. All the four puncta should only be plugged in desperate cases.
24	Stimulation of Tear Secretion Such drugs have been used in Europe for decades. Most intriguing is eledoisin prepared from the salivary glands of the mediterranean octopus. Cyclosporin-containig drops (Restasis) will soon be avavilable in the U.S.A from Allergan.
25	EFFICACIOUS ARTIFICIAL TEARS The following properties/components have found to be important to ensure efficacy: Achieve complete wetting of hydrophobic surfaces Elevated oncotic pressure Nutrients and antioxidants such as retinoids and cyanocobalamine
26	AQUEOUS PHARMA EYE DROPS A: Dwelle®, B: Dakrina®, C: REDKOTE™; D: FRESHKOTE ™ All four have complete wetting ability Three have high oncotic pressure (except REDKOTE™) Dakrina also contains vitamin A REDKOTE™ also contains cyanocobalamine FRESHKOTE™ also contains lipids Available only through a compounding pharmacy
27	THE IATROGENIC DRY EYE At least temporary dry eyes are diagnosed in about 50% of patients after refractive surgery Surgery aggravates existing dry eye condition Poor contact lens tolerance is a red flag for pre-lasik Cosmetic surgery of the eye lid – ditto Autoimmune disease in patient history - ditto Certain medications: beta blockers, accutane, psychotropic drugs, antihistamine, antifungal, etc.
28	SURGICAL EYES FOUNDATION, DRY EYE INSTITUTE&AQUEOUS PHARMA joined forces and used various combinations of Aqueous Pharma eye drops to find out whether higher efficacy can be demonstrated in iatrogenic eyes as well as it could in traditional dry eye patients. Volunteers were asked to keep a diary or report regularly by e-mail to the Dry Eye Institute. Many of the patients were regularly checked by their physicians or optometrists for the condition of their surface epithelium in the eye.
29	Rational Approach to Post-lasik Dry Eye Management Eliminate the use of lipid ointment Eliminate the use hypertonic salt solution Employ collyrium that contains wetting polymers (A, B, C, or D) Employ collyrium w/ high colloidal osmotic pressure (A, B, or D) Employ collyrium that contains bioavailable vitamin A (B) Employ collyrium with cyanocobalamine. (C) Employ collyrium with phospholipids (D) A=DwelleÒ, B=DakrinaÒ, C=REDKOTE™, D=FRESHKOTE™
30	Results obtained with Surgical Foundation Members 76% participants reported: Diminished discomfort Better visual acuity Improved epithelial integrity Sharply increased incidence of epithelial erosion Similar observations were made at one of the TLC by the optometrist in charge of post-lasik care.
31	Efficacy of Aqueous Pharma Drops in Post-Lasik Patients (n =48)
32	Management of Iatrogenic Dry Eyes Diagnostic Methods Conduct the following tests: Thorough slit-lamp examination Fluorescein staining (viewed with cobalt blue filter) Tear film break-up time in seconds Tear meniscus width and continuity Corneal sensitivity Lacrimation rate ability (Schirmer) mm/5 min Rose bengal (lissamine green) staining Goblet cell density (by impression cytology) Lid-examination (lipid interference patter)
33	Management of Iatrogenic Dry Eyes Treatment Modalities Supplementation of aqueous tears with REDKOTE™ (increase BUT, heal surface) DwelleÒ (increase BUT, impact eoithelium DakrinaÒ (increase BUT, improve mucin deficiency) FRESHKOTE™ (as before plus improve lipid abnromality) Preservation of aqueous tears with Goggles, transparent patches Punctal plugs (start with two) Avoid ointments and hypertonic preparations Stimulation of tear secretion with secretagogues, eledoisin, pilocarpine, cyclosporin
34	AND DO NOT FORGET TO KEEP REMINDING YOUR PATIENTS: BLINK FREQUENTLY AND COMPLETELY! Thank you!