7th Consensus Meeting:
Medical Treatment of Glaucoma

Fort Lauderdale, FL, May 1, 2010

cons7
edited by Robert N. Weinreb, Makoto Araie, remo Susanna, Ivan Goldberg, Clive Migdal and Jeffrey Liebmann
2010. 9 tables, 4 figures and 57 photos of with 1 in full color. Hardbound.
ISBN-10: 90 62992 226 9.
ISBN-13: 978-90-6299-226-3
Published by: Kugler Publications.
Click here for more information on all publications in the Consensus series.

See meeting photos

Summary Consensus Points

Section 1 – Who should be treated?

 

  • In general, treatment is indicated for patients with glaucoma or glaucoma
    suspects who are at risk for developing functional impairment or decrease
    in vision-related quality of life from the disease.
    Comment: Treatment is generally indicated when the risks of progressive
    disease outweigh the risks and potential side effects of treatment.
  • All treatment decisions should take into account the presence of coexisting
    ocular conditions, the patient’s life expectancy and general health status,
    as well as his/her perceptions and expectations about treatment.
  • The rate of disease progression is of fundamental importance in considerations
    of treatment for glaucoma patients. Treatment is indicated for patients
    whose rates of progression will most likely result in loss in vision-related
    quality of life over the projected remaining years of life.
  • Treatment is generally indicated for patients with definitive glaucomatous
    visual field loss, particularly in circumstances when such loss has been
    determined to be progressive at a measurable rate.
  • Changes of the optic nerve and/or retinal nerve fiber layer (RNFL) characteristic
    of glaucoma predict functional vision loss in glaucoma and thus patients
    with such documented structural evidence of progressive damage should generally
    be treated with intraocular pressure lowering therapy.
  • The decision regarding whether or not to treat glaucoma suspects should
    involve a consideration of risk factors for disease development, including
    age, family history of glaucoma, intraocular pressure, central corneal thickness,
    presence of pseudoexfoliation, disc hemorrhages and measures of structural
    and functional integrity of the optic nerve head and retinal nerve fiber
    layer.
    Comment: While it is clear that progress has been made in establishing
    risk factors for glaucoma progression, much work remains to be done to better
    refine risk models. Nonetheless, the factors that affect the risk of progression
    help decide the expected prognosis of the individual’s untreated disease
    and thereby the frequency of follow-up and aggressiveness of the therapy
    to be undertaken.
  • Imaging of the optic nerve head and retinal nerve fiber layer can provide
    useful predictive information about the risk of developing functional loss
    from glaucoma and thus can serve as a surrogate predictor of such vision
    loss.
  • Selective visual function tests may be predictive of functional loss
    in glaucoma patients and thus may be used as complementary tests to assist
    in treatment decisions.
  • Predictive models or risk calculators may assist clinicians in providing
    more objective estimates of the risk of glaucoma development for individual
    patients.
    Comment: Predictive models are based on restricted populations of
    patients that were selected based on strict inclusion and exclusion criteria
    and that may not be representative of all patients seen in everyday clinical
    settings. Use of these models should be restricted to those patients who
    are similar to the ones included in the studies used to develop and validate
    such models and calculators.

Section 2 – Treatment goals

 

  • The target IOP is the IOP range at which the clinician judges that the
    estimated rate of progression is unlikely to affect the patient’s quality
    of life.
    Comment: Although recommended by most experts, there is insufficient
    evidence that using target IOP is associated with better clinical outcomes.
  • The determination of a target IOP is based upon consideration of the
    amount of glaucoma damage, the rate of progression, the IOP at which the
    damage has occurred, the life expectancy of the patient, and other factors
    including status of the fellow eye and family history of severe glaucoma.
  • The use of a target IOP in glaucoma requires ongoing re-evaluation and
    adjustment.
  • The benefits and risks of escalating treatment to reach a target IOP
    must be balanced.
    Comment: Uncertainties regarding the short- and long-term variations
    of IOP, accuracy of tonometer readings, patient’s life expectancy, adherence
    to therapy and estimated progression rates remain unresolved.
  • Treatment goals include IOP, visual function and structural (optic disc,
    RNFL) outcomes and QOL.
    Comment: It is uncertain whether patient reported outcomes of glaucoma
    can be applied in clinical practice, and whether they capture clinically
    meaningful progressive changes.

Section 3 – Drugs

 

  • All eye drops have the potential for systemic effects, which may be
    decreased with a lower concentration, reduced frequency of administration
    and using nasolacrimal occlusion or gentle eyelid closure.
    Comment: During pregnancy and lactation, the risks and benefits of
    these medications should be evaluated for each patient.
  • Topical cholinergic agents can effectively reduce intraocular pressure.

    Comment: In open-angle glaucoma, cholinergics enhance aqueous outflow
    through the trabecular meshwork by means of ciliary muscle contraction.

    Comment: Cholinergics may open the drainage angle in certain instances
    of angle closure by stimulating the iris sphincter muscle.
    Comment: The effects of pilocarpine are representative of this class.
    Pilocarpine has an additive hypotensive effect to β-blockers, alpha-2 adrenergic
    agonists, and carbonic anhydrase inhibitors. It can be additive to prostaglandin
    analogues in some patients.
    Comment: Common ocular side effects of pilocarpine, which limit its
    use, include brow-ache, induced myopia, and dimness of vision. Comment:
    TID or QID dosing is associated with poor adherence.

  • Indirect cholinergic agents are reserved for open-angle glaucomas in
    aphakic or pseudophakic eyes.
    Comment: Indirect cholinergic agents are cataractogenic and also
    may cause adverse systemic effects.
  • Topical β-blockers are effective IOP-lowering agents.
    Comment: Topical β-blockers decrease IOP by reducing aqueous humor
    formation. All non-selective β-blockers have comparable IOP-lowering efficacy.

    Comment: Topical and systemic β-blockers are poorly additive with
    respect to lowering IOP.
    Comment: Although some β-blockers have intrinsic sympathomimetic
    activity (ISA) or α-blocking properties, their clinical properties are similar
    to those of other non-selective β-antagonists. However, ISA may reduce respiratory
    and cardiovascular side-effects related to β-blockade.

  • Timolol, and possibly all other β-blockers, have minimal IOP-lowering
    efficacy during sleep.
    Comment: Non-selective topical β-blockers are contraindicated in
    patients with asthma, chronic obstructive pulmonary disease (emphysema and
    bronchitis) some cases of congestive heart failure, bradycardia, and heart
    block.
  • The IOP-lowering efficacy of betaxolol, a relatively selective β-1-blocker,
    is less than that of non-selective β-blockers.
    Comment: Betaxolol is relatively safer than a non-selective β-blocker
    in patients with known reactive airway disease.
  • Carbonic anhydrase inhibitors (CAIs) are effective IOP-lowering agents.

    Comment: CAIs reduce IOP by suppressing aqueous humor production
    through inhibition of the isoenzyme carbonic anhydrase II.
    Comment: CAIs are the only category of drugs available commercially
    in both topical and systemic formulations to lower IOP.
    Comment: For systemic CAIs, major side effects include paresthesia,
    malaise, gastrointestinal disturbances, renal disorder, blood dyscrasia,
    and metabolic acidosis.
    Comment:
    For topical CAIs, side effects include
    ocular burning, stinging, bitter taste, superficial punctuate keratopathy,
    blurred vision, tearing, headache, and transient myopia.
    Comment: CAIs may increase ocular blood velocity; however, there
    is insufficient evidence for any clinical benefit of this effect for glaucoma
    patients.
    Comment: Topical CAIs and systemic CAIs are poorly additive with
    respect to lowering IOP.

  • Systemic CAIs are contraindicated with sulfonamide allergy, with depressed
    sodium and/or potassium blood levels, and in metabolic acidosis.
  • The non-selective adrenergic agonists, epinephrine and its pro-drug
    (dipivefrin) are effective IOP-lowering agents.
    Comment: Adrenergic agonists reduce IOP by decreasing aqueous formation
    and increasing outflow.
    Comment: Adrenergic agonists are contraindicated in infants and children
    because of systemic side effects.
    Comment: IOP-lowering efficacy of adrenergic agonists is less than
    that with timolol. This class is often additive to prostaglandin analogues
    but not to non-selective β-blockers.
    Comment:
    Local side effects
    include hyperemia and blepharoconjunctivitis. Systemic circulatory effects
    include hypertension and tachyarrhythmias.
  • Selective alpha-2 adrenergic agonists reduce IOP by suppressing aqueous
    inflow and increasing outflow. They also may affect episcleral venous pressure.

    Comment: Systemic side effects with selective alpha-2 adrenergic
    agonists include dry mouth, drowsiness and hypotension.

  • There is insufficient evidence for neuroprotection by selective alpha-2
    adrenergic agonists in humans.
  • Bunazosin, a selective α1A antagonist, increases uveoscleral outflow.

    Comment: Although it is well-tolerated, the hypotensive effect of
    topical bunazosin is weaker than that of topical timolol.

  • Prostaglandin analogues (PGAs) are the most effective IOP-lowering agents
    of all topical glaucoma medications, and generally are first line therapy.

    Comment: PGAs lower IOP by increasing uveoscleral aqueous humor outflow,
    and may also have an effect on outflow facility.
    Comment: Common side effects of prostaglandin analogue drops include
    conjunctival hyperemia, reversible increase of eyelash length, thickness
    and pigmentation, irreversible increase of iris pigmentation, and increase
    of eyelid skin pigmentation. Rare side effects include uveitis, reactivation
    of herpetic keratitis and cystoid macula edema.
    Comment: PGAs are systemically safe, but are relatively contraindicated
    in pregnancy, as are all glaucoma medications.

  • Preservatives used for multi-dose topical ophthalmic medications can
    cause ocular surface changes.
    Comment: Benzalkonium chloride (BAK), in particular, has been associated
    with ocular surface changes in chronic use. Alternative preservative systems
    are increasingly used in multi-dose bottles in an effort to decrease the
    potential for deleterious effects on ocular surface. However, direct comparisons
    between these agents are lacking.
    Comment: Preservative free systems, in the form of unit dose packages,
    are a viable alternative to traditional multi-dose bottles. In theory, they
    may have fewer ocular surface effects, however, direct comparisons with
    preserved agents are lacking.

Section 4 – Selection of drugs

 

  • Only the IOP lowering effect should be considered to define the comparative
    efficacy of an ocular hypotensive agent.
  • Initiation of therapy: prostaglandin analogues (PGA) are recommended
    as first choice agents for most eyes with glaucoma.
  • IOP reduction with initial monotherapy should be at least 20% from baseline.

    Comment: IOP reduction of less than 10% should be considered as nonresponse.
    Comment:
    Switching drugs within the PGA class may, upon occasion,
    provide greater IOP lowering.

  • Adjunctive therapy is indicated when existing therapy fails to reach
    the target IOP.
    Comment:
    Adjunctive therapy should be limited to
    one drug from each class.
    Comment: The efficacy of a drug when used as monotherapy is usually
    less when used as an adjunctive agent.
  • Provided the use of the combination product is as efficacious as the
    two components administered independently, fixed-combinations are preferred
    when possible over the use of two separate bottles due to convenience, reduced
    amount of preservative instillation and possible improved adherence.
    Comment: Evidence is lacking that fixed combination products provide
    better outcomes than the individual components delivered separately.
  • Surgery is indicated when medical therapy fails to adequately lower
    the intraocular pressure or prevent progression, the risk of progression
    remains too high despite the use of medical therapy, or is not possible
    due to allergy, intolerance, poor adherence or lack of availability.

Section 5 – Medical treatments of other types of open-angle glaucomas

 

  • PG analogs are first choices for monotherapy in pseudoexfoliative glaucoma
    and pseudoexfoliation syndrome with ocular hypertension when treatment is
    required.
    Comment:
    Pilocarpine can reduce iris movements in eyes
    with pseudoexfoliation and, therefore, may reduce deposition of exfoliation
    material or pigment in the trabecular meshwork.
  • PGAs are first choices for monotherapy in pigmentary glaucoma.
    Comment: Pilocarpine can be effective in pigmentary glaucoma in reducing
    reverse pupillary block and diminishing iris movements.
  • Medical treatment of inflammation is first line treatment for uveitic
    glaucoma.

Section 6 – Drug delivery

 

  • Poor adherence / perseverance / dyscompliance are major problems in
    glaucoma. Patients taking fewer doses than prescribed are at risk of having
    worse outcomes than those taking a higher proportion.
    Comment: On average, most studies of glaucoma patients estimate that
    about 70% of doses are taken. This may vary depending on duration of treatment,
    number of medications taken and severity of the disease.
  • Patient self-report of adherence is often overestimated.
    Comment: Physicians do not accurately predict which patients are
    poorly compliant.
    Comment:
    While not readily available, better systems
    to reliably and easily monitor patient drop taking behavior are desirable
    since they would provide feedback for physicians to better identify patients
    with difficulty adhering to drop regimens.
  • Risk factors for lower adherence rates have been identified and include
    younger and older age, race/ethnicity, and depression.
    Comment: While poor adherence can occur in all patients, additional
    efforts may be required in patients with these risk factors.
  • Patients often have difficulty properly administering drops to their
    eyes.
    Comment: Efforts to improve adherence should address physical barriers.

    Comment: Observation of patient eye drop administration can detect
    patients that are unable to instill them.

  • For at least the next several years, topical IOP-lowering medication
    will remain the mainstay for glaucoma treatment.
    Comment: Despite limitations (inconvenience, dependence on the compliance
    of the patients and well-described adverse events in particular on the conjunctiva),
    topical anti-glaucomatous medication is (relatively) cheap, easily available,
    and generally safe, and it is reversible, should side effects arise.
  • A change in the preservatives of eye drops to a less toxic and more
    tissuefriendly formulation, and/or the development of preservative free
    drug delivery systems is needed to reduce the preservative related side-effects
    and tissue toxicity while delivering enough drug to control the intraocular
    pressure.
  • Non-IOP dependent therapy for glaucoma and also new drug delivery systems
    remain a high priority unmet medical need in glaucoma management.

Section 7 – Health economics

 

  • There are wide variations in reported costs of glaucoma therapy across
    nations.
    Comment:
    There is little information from developing countries.

    Comment: With the exception of the US, the differences in costs of
    therapy are largely related to the level of economic development in various
    regions of the world.

  • Cost of one time surgery is substantially greater than medication in
    the short term, but lower in the long term.
    Comment: Changes in medication costs may alter this.
    Comment: Surgical failure may alter this because of the need for
    additional medication and/or surgery.
  • Generic drugs potentially can reduce direct treatment costs.
    Comment: More studies are needed comparing generic and branded drugs.
  • Side effects of glaucoma medications have minimal economic impact.
  • There do not appear to be significant differences in the cost of fixed
    combination products compared with individual components.
  • Failed medical therapy is defined differently in each country and depends
    on the cost and availability of medical therapy and surgical alternatives
    in that country.
    Comment: Pricing of glaucoma medications is not transparent.

Section 8 – Non-pharmaceutical medications and approaches

 

  • There is a paucity of clinical trial information examining neuroprotective
    effects of non-pharmaceutical compounds (alternative or complementary therapies)
    for glaucoma.
    Comment: Bio-availability of these natural compounds has not been
    well studied, and clinical studies of their efficacy and safety are needed.
  • Exercise reduces IOP, but the extent, duration and clinical significance
    are unclear.
    Comment: Exercise also can increase ocular blood flow, but the significance
    of this is unknown.
  • Acupuncture has been reported to lower IOP and increase ocular blood
    flow.
    Comment: The reported results are inconsistent and additional studies
    are needed before it is employed in clinical practice.

Section 9 – Neuroprotective therapies

 

  • A neuroprotective strategy for glaucoma is defined as a therapy that
    prevents the occurrence or progression of optic neuropathy and preserves
    visual function by mechanisms other than IOP lowering.
  • Agents that lower IOP have been shown to protect the optic nerve from
    glaucoma progression.
    Comment: Some agents that lower IOP might additionally confer protection
    to the optic nerve through mechanisms that are independent of IOP lowering,
    but there is insufficient evidence for this dual effect with any agent at
    the present time.
  • Therapeutic approaches for preventing RGC death may aim to prevent primary
    or secondary degeneration of retinal ganglion cells.
  • Evidence from experimental models suggests that neuroprotection could
    be conferred by:
    a. Inhibiting the pathogenic mechanisms that injure or kill RGCs.

    b. Rendering the optic nerve more resistant to injury.

  • Numerous studies have demonstrated neuroprotection in experimental models
    of glaucoma or optic nerve injury, but good evidence demonstrating neuroprotection
    in clinical studies is lacking.
  • Challenges in translating experimental evidence of neuroprotection into
    clinical proof may be due to:
    a. The therapy may not be effective in humans.
    b. The lack of sufficiently robust tools to assess clinically
    the state of optic nerve
    health.
    c. The lack of animal models that are good representatives of
    human glaucoma.
    d. The lack of well-designed and well-conducted clinical studies.
  • Current testing paradigms are insufficiently sensitive and specific
    to detect change in a logistically feasible time frame. The development
    of accurate, sensitive, specific and reproducible clinical tests that provide
    information on the current state of health of the optic nerve are required
    to increase the feasibility of clinical development of neuroprotective agents.

    Comment: A desired embodiment of such clinical testing would allow
    detection of progression before the damage is irreversible.

Section 10 – Medical management of glaucoma in infants and children

 

  • The primary treatment of glaucoma in infants and young children is surgery.

    Comment: In many situations, however, the clinician must treat elevated
    IOP medically while awaiting surgery or after a partially-successful procedure.

    Comment: Only rarely should medical therapy be the primary treatment
    of glaucoma in infants and young children.
    Comment: A young child is not a small adult: systemic adverse reactions
    rarely seen in adults can occur in young children.

  • Outflow medications (pilocarpine and prostaglandin analogues) are variably
    effective in pediatric glaucomas, whereas aqueous suppressants lower IOP
    more consistently.
    Comment:
    Systemic and topical carbonic anhydrase
    inhibitors can be safe and effective. If possible, systemic use should be
    monitored by a pediatrician.
    Comment: Topical beta-blockers are effective; systemic safety is
    the major concern. Betaxolol is safer than timolol.
    Comment: Topical brimonidine is absolutely contraindicated in children
    under two years, and must be used with great caution in older children.
    Apraclonidine may be safer, for short-term use, but clinical data is lacking.

    Comment: Prostaglandin agonists are less effective in children than
    in adults, and are more likely to be effective in older children.
    Comment: Miotics are rarely used in phakic children.

Section 11 – Treatment of glaucoma in pregnancy

 

  • Appropriate management of the pregnant/lactating glaucoma patient requires
    balancing the risk to the fetus of treatment against the risk to the mother
    if treatment is reduced or suspended.
    Comment: While a complete lack of prospective human data complicates
    this decision-making process, publications provide a guide.
  • Like all systemically-absorbed medications that are used during pregnancy
    and lactation, the maternal use of topical anti-glaucoma medications carries
    risks of teratogenicity, of interference with establishment or maintenance
    of pregnancy, or of side effects in the neonate.
    Comment: Prostaglandin analogues may be associated with uterine contraction.
    Comment:
    Beta-blockers and alpha agonists can cause serious toxicity
    (re spiratory and CNS depression) When possible, these agents should be
    withdrawn during the last few weeks of pregnancy.
    Comment: Topical CAIs are generally well tolerated.
  • Laser trabeculoplasty can be a reasonable initial or adjunctive intervention
    in pregnant and nursing women.
  • Filtering surgery, preferably without anti-fibrosis chemotherapy, can
    be considered in certain cases.

Section 12 – Unmet needs

 

  • Identification of biomarkers of retinal ganglion cell dysfunction:

    • A more reliable tool for measuring the health of retinal ganglion cells
    is needed for more effective evaluation of treatment outcome.
    • There is a need to identify new models to test drugs.

  • Identification of novel targets for glaucoma treatments that lower IOP
    and preserve retinal ganglion cell function should be sought.
    Comment: Structural changes in the optic disc or retinal nerve fiber
    layer often precede functional changes and could be useful for primary endpoints
    in clinical trials.
  • New agents need not necessarily have enhanced pressure-lowering efficacy
    compared with prostaglandin analogues, particularly if they have an additive
    effect when used with existing medications.
  • Continuous IOP monitoring and home tonometry: There are currently no
    commercially available devices that allow continuous monitoring of IOP in
    humans. Comment: There is insufficient evidence at this time to show that
    home tonometry with any device provides accurate and reliable IOP measurement.

    Comment: Drugs that provide sustained lowering of IOP throughout
    the 24-hour day may be advantageous.
    Comment: However, it still is uncertain if additional IOP data from
    continuous IOP monitoring or home tonometry provides additional clinical
    information to the current measures of IOP peak, mean and fluctuation.

  • Objective measurement of patient adherence to glaucoma medication: Nonadherence
    to treatment regimens is common in glaucoma patients. Addressing the risk
    factors for poor adherence and developing new methods to improve adherence
    are pivotal to effective delivery of glaucoma treatment.
  • There is insufficient information regarding current treatment practices
    and the most appropriate glaucoma treatment strategies for developing countries.
  • Regulatory agencies should develop uniform standards for preservatives
    and unpreserved medications that could be applied worldwide.
  • A worldwide color-coding scheme for caps of classes and fixed combination
    of glaucoma medications is recommended.
  • Additional studies of the effects of different treatments on ocular
    blood flow and its relationship to glaucoma are needed.
  • Biomarkers for glaucoma diagnosis and progression are needed.
  • Improved delivery methods for drug therapies are needed.
  • A medical treatment is needed to restore retinal ganglion cell function
    or regenerate the optic nerve.

WGC-2017

e-igr

Search


WGA Newsletter

Don’t miss any WGA news! Subscribe now to the WGA newsletter to stay up to date with all WGA activities.

Subscribe

Consensus Meetings


wga