qticn Carc
`
`The Once and Future Treatment Of Dry
`Eye
`
`You have
`broad range of therapies to alleviate the symptoms of
`keratoconjunctivitis sicca and other forms of dry eye Researchers and
`drug manufacturers hope to expand your therapeutic arsenal
`
`Rob Murphy
`Managing Editor
`
`Up to 10 million Americans suffer the daily misery of chronic dry eye syndrome
`Unrelenting ocular irritation and photophobia are way of life Dry eye syndrome
`whether stemming from aqueous deficiency or accelerated tear evaporation is the most
`common treatable eye condition you encounter in the clinic In the face of such
`stubborn and implacable malady savvy clinicians use every conceivable countermeasure
`to bring some relief to their patients Current treatments are essentially palliative New
`therapies target the root causes of the disease See table
`
`Causes and Defects
`
`The first step in managing dry eye is to determine whats causing it
`lacrimal gland and denervation of the cornea can curb tear production Meibomian gland
`dysfunction and incomplete lid closure are frequently to blame for rapid tear evaporation
`Obtain
`
`probing history for systemic health factors Sj ogrens syndrome other collagen
`vascular diseases allergies medications antihistamines oral NSAIDs oral beta
`factors dust smoke pets and anything else that may trigger or
`blockers environmental
`worsen symptoms
`
`inflammation of the
`
`lot of patients in this area who are taking
`variety of over-the-counter
`see
`medications for allergies or sinus problems and those typically are antihistamines and
`Fanelli OD private practitioner
`in Wilmington N.C
`says James
`decongestants
`These people will get
`induced dry eye because of all
`medications The dryness stems from the parasympatholytic
`effects of these agents if
`patients can discontinue their medications they may find relief from their ocular
`symptoms
`
`pharmacologically
`
`the
`
`Encourage patients to avoid environments that may exacerbate their discomfort say
`dusty attic Maybe they can change their environment One thingi
`smoky barroom or
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`that helps for people with really severe dry eye is to have them use
`humidifier in their
`Ajamian O.D says
`bedroom at night and moisten the air Atlanta clinician Paul
`
`Be sure to do
`careful check of the lids Meibomian gland stenosis and blepharitis are
`common triggers of dry eye Look at the lid margins for signs of chronic staph lid
`disease Dr Ajamian advises
`lot of dry eye patients have chronic staph and yet we
`just focus on the dry eye portion and ignore the lid-hygiene portion
`
`Many patients who have had LASIK experience dry eye symptoms following the
`Gilbard M.D attributes this to corneal
`procedure Dry eye researcher Jeffrey
`denervation When you cut the flap you cut the corneal nerves he says And just as
`irritated eyes tear more eyes that are numb tear less
`recent study in Australia found
`that 100% of LASIK patients receiving TheraTearsthe artificial
`tears developed by Dr
`Gilbardwere symptom-free at one month post-op compared to just 20% of the
`Donnenfeld M.D is now
`untreated control group New York surgeon Eric
`investigating the efficacy of cyclosporine Restasis Allergan Pharmaceuticals
`
`in treating
`
`post-LASIK dry eye
`
`Whats Happening Now
`
`Dry eye therapy is
`
`sequence of palliative measures tailored to the severity of the
`presentation Clinicians typically begin with non-preserved low-viscosity artificial
`prescribed every two hours or so Among the more popular choices are GenTeal CIBA
`Vision Hypotears PF CIBA Vision Moisture Eyes Bausch
`Lomb
`Pharmaceuticals Refresh Plus Allergan Refresh Tears Allergan Tears Naturale Free
`Alcon and TheraTears Advanced Vision Research Patients may especially like the
`convenience of GenTeal and Refresh Tears which come bottled in multi-dose
`formulation with
`relatively non-toxic preservative thats neutralized upon instillation
`Look for multi-dose formulation of TheraTears
`come spring
`
`tears
`
`TheraTears
`
`seems to be winning more and more support Dr Fanelli says Rabbit
`studies showed that its electrolyte solutionsodium potassium bicarbonate chloride
`magnesium and phosphatelowers
`elevated tear osmolarity and improves the eyes
`electrolyte balance Even so while Dr Fanelli favors GenTeal and Refresh Plus he says
`it usually comes down to trial-and-error Theres no magic involved he says Its
`matter of finding the drop that gives you the longest-lasting and most-comfortable
`relief Seattle clinician Kathy Yang Williams O.D favors preservative- and
`lanolin-free Hypotears PF for those with associated atopic eye disease to reduce the
`for hypersensitivity reaction
`potential
`For more severe or refractory presentations you may wish to graduate to moderate-
`tears such as Bion Tears Alcon or OcuCoat PF BL
`viscosity artificial
`Pharmaceuticals or high-viscosity products such as AquaSite CIBA Vision Celluvisc
`Allergan or Murocel BL Pharmaceuticals As an alternative these patients may find
`relief with the newer gel formulations GenTeal Gel CIBA Vision or Tears Again
`OcuSoft Ointments may work well for the most severe cases that require nighttime
`therapy
`
`Punctal plugs can be effective for moderate to severe dry eye when artificial
`
`tears alone
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`dont bring relief Some clinicians favor the CIBA Vision line of punctal plugs that come
`preloaded device that makes insertion easy But dont wait too long to plug
`with
`dont think twice anymore about plugging Dr Fanelli says Im not going to put them
`through this regimen where they have to use tears every hour and ointments at night He
`likes to do monocular
`few
`trial by plugging the upper and lower puncta of one eye for
`days to see if it works
`Especially severe and recalcitrant keratoconjunctivitis
`sicca may call for
`1999 study published in Ophthalmology by Peter Marsh
`course of topical steroids
`M.D and Stephen Pflugfelder M.D found that
`2-week course of topical
`relieved the irritation of dry eye and in many patients that relief
`methylprednisolone
`lasted weeks or months after they stopped therapy Loteprednol etabonate 0.2% Alrex
`BL Pharmaceuticals or loteprednol etabonate 0.5% Lotemax BL Pharmaceuticals
`may be well-suited for this purpose because theyre less likely than other steroids to
`increase intraocular pressure With the advent of some of the newer steroids certainly
`its nice to be able to prescribe medications like that without the risk of more serious
`1% used tid or qid for
`complications Dr Williams says Topical methylprednisolone
`3-4 weeks can be
`safe and effective regimen
`
`short-term
`
`Meanwhile you may need to address associated lid disease In cases of staph blepharitis
`Dr Ajamian prescribes lid scrubs and
`broad-spectrum antibiotic ointment such as
`polysporin For dry eye symptoms associated with meibomian gland disease Miami
`clinician Tern Rose O.D favors
`6-8 week course of oral doxycycline Dosing varies
`by physician but an average course might be 100mg bid for 6-8 weeks says Dr Rose
`who is on staff at the Bascom Palmer Eye Institute The use of an antibiotic in
`condition has to do with the effect of doxycycline on lipid production and
`non-infectious
`its effectiveness as an anti-inflammatory agent
`
`Whats to Come
`
`The dry eye treatment thats attracted the most attention in the last year is one that hasnt
`even obtained FDA approval Clinical investigators who have given their patients topical
`cyclosporine 0.05% Restasis Allergan Pharmaceuticals
`say this immunomodulatoiy
`agent effectively reduces the signs and symptoms associated with keratoconjunctivitis
`sicca Although Allergan was rebuffed in its bid last July to win FDA approval the
`company has responded to the agencys concerns and hopes to get
`the green light to
`market the product by summertime see
`
`as
`
`ci
`
`clinical
`
`Cyclosporine targets the immune-based inflammation that shuts down tear production in
`the lacrimal gland T-lymphocytes infiltrate the lacrimal gland and they cause
`for cyclosporine The
`inflammation explains Dr Donnenfeld
`investigator
`acinar cellsthose are the ones that secrete the tearsfibrose and die The tear
`dry eye What cyclosporine does its
`production stops and you end up with
`specific
`T-cell modulator that inhibits T-lymphocytes reversibly and in doing so stops the
`inflammatory cycle so that the inflammatory cells die normal death and stop secreting
`the inflammatory mediators The lacrimal gland tissue thats still viable comes back so
`that the patient starts inducing their own tears
`Although the FDA-mandated phase
`trials showed that cyclosporine was clinically
`effective with negligible side effects transient burning Dr Donnenfeld and other3
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`clinicians say it doesnt work for all patients One of the problems with cyclosporine is
`that we dont know who is going to be
`good candidate for its use and who is not and
`thats one of the things were still working out right now he says
`
`Further back in the pipeline is another potentially fmitful dry eye therapy this one based
`on the sex-hormones known as androgens Animal models show that androgens play
`key role in regulating the function of both the lacrimal and meibomian glands David
`Sullivan Ph.D of the Schepens Eye Research Institute in Boston recently found that
`women who lack functioning androgen receptors had
`significant increase in dry eye
`signs and symptoms Another study revealed that patients with SjOgrens syndrome were
`androgen-deficient Both studies support Dr Sullivans hypothesis that androgen
`therapy may benefit patients with lacrimal and meibomian gland
`
`replacement
`
`dysfunction
`therapy based on Dr Sullivans research The
`Allergan holds the license to any potential
`study originally planned for last summer
`company put on hold multicenter phase
`Still Dr Sullivan remains optimistic We think it
`looks promising he says Every
`study weve been able to throw at it with every control we can so far theyve been
`consistent with the hypothesis
`
`Finally keep an eye on whats happening down at Bascom Palmer Searching for
`target
`therapy Dr Pflugfelder has been looking for molecules that
`at which to aim potential
`in healthy individuals He thinks hes found
`are elevated in dry eye but normal
`collagenase enzyme that fits the bill Theres one specifically called MIVIP9 thats very
`high in dry eye patients in their tear fluid and almost nondetectable in normals he says
`For the first
`time have marker that goes up in dry eye and not in normal eyes
`think
`its definitely something to look into inhibiting that Interestingly we already have
`potent inhibitor of MMP9the tetracyclines Dr Pflugfelder
`medication that acts as
`hopes to develop other therapies based on what hes learning
`
`remain fertile ground for research as long as patients continue to suffer
`Dry eye will
`Chronic keratoconjunctivitis
`sicca is miserable way to go through life Just ask your
`patients Theyll appreciate anything you can do to ameliorate their lot
`
`What Ever Happened to Restasis
`
`good thing going when they
`they had
`The people at Allergan Pharmaceuticals thought
`approached the FDA last July for approval
`to market cyclosporine 0.05% Restasis as
`for dry eye The two arms of the phase
`clinical studies had gone well
`treatment
`demonstrating that the
`T-lymphocyte inhibitor effectively reduces the signs and symptoms of
`sicca with minimal adverse events
`
`keratoconjunctivitis
`
`But then something funny happened The ophthalmic advisory panel
`less than impressed with Allergans clinical data The panelists issued
`so-called
`approvable letter listing several points they wanted the company to address before they
`would recommend approval We have been reviewing the data and looking to see if
`in
`
`for the FDA was
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`fact we could present the data from those studies in way that would better present our
`case Allergan spokesman Ira Haskell says
`
`Unfortunately the two arms of the phase
`trial did not completely replicate themselves
`in terms of the signs and symptoms that reached statistical significance investigator
`Steven Wilson M.D wrote in
`paper presented last September at Research to
`Prevent Blindness seminar One problem was that cyclosporines vehicle
`castor oil
`emulsion may have worked
`little too well
`in the trials
`
`dont know that the panel was that impressed that there was that much difference
`between the drug and the vehicle says investigator Stephen Pflugfelder M.D who
`testified before the FDA panel on behalf of Allergan The vehicle itself
`is better than
`tear You know if they had compared the drug to artificial
`tears they would
`any artificial
`have won hands down Im sure
`
`Allergan expects to hear back from the FDA by June Mr Haskell says In the meantime
`someone should consider packaging castor oil as
`treatment for dry eye Apparently its
`R.M
`
`the next best thing to cyclosporine
`
`Dry Eye Treatments
`
`Low-Viscosity Artificial Tears
`
`GenTeal CIBA Vision
`Hypotears PF CIBA Vision
`Lomb
`Moisture Eyes Bausch
`Pharmaceuticals
`Refresh Plus Allergan
`Refresh Tears Allergan
`Tears Naturale Free Alcon
`TheraTears Advanced Vision Research
`
`Moderate-Viscosity
`Artificial Tears
`
`Bion Tears Alcon
`OcuCoat PF BL Pharmaceuticals
`
`High-Viscosity
`Artificial Tears
`
`AquaSite CIBA Vision
`Celluvisc Allergan
`Murocel BL Pharmaceuticals
`Gel Formulations
`
`GenTeal Gel CIBA Vision
`Tears Again OcuSoft
`Lubricating Ointments
`
`Hypotears CIBA Vision
`Moisture Eyes BL
`
`Pharmaceuticals
`Refresh PM Allergan
`Duratears Naturale Alcon
`
`Return to February Highlights
`Review of Optometry OnLine
`February 15 2000
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`1111
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