Glaucoma- side effects

Glaucoma Editorial

Side Effects from Glaucoma Therapy

ANNALS OF OPHTHALMOLOGY---1980? p. 964-5

Medical therapy of glaucoma is often compromised by adverse
reactions. Unwanted side effects from orally or parentally administered
agents, such as the carbonic anhydrase inhibitors, are expected and well
known to all prescribing ophthalmologists. Sometimes overlooked, however,
is the fact that ocular therapy, in addition to its inconvenient visual and
irritative side effects, may occasionally induce adverse reactions that
account for significant ocular or systemic morbidity. While many other
factors are contributory, it is possible that patient rejection of
therapeutic regimens because of their side effects may lead to
noncompliance, a principal reason for failure to achieve medical control of
glaucoma. (1) Advance consideration of possible adverse effects is helpful
in planning glaucoma regimens that are compatible with both the life-style
of the patient and with successful management of the disease.

The establishment of the National Registry for Drug Induced Ocular
Side Effects, now at the University of Oregon Health Sciences Center in
Portland, has increased our awareness of the many adverse effects from
medications we use in ophthalmology. (2) The Registry collects preliminary
data on those effects and warns of potentially serious reactions to new and
established medications. In most cases, the incidence of side effects is
unknown, and proof of direct causal relationships requires long-term,
controlled prospective studies.

Compendiums of the spectrum of glaucoma drug side effects are
available elsewhere and are not the subject of this discussion. (2-6)
Examples of potentially occult and serious effects, however, may encourage
ophthalmologists to be wary about the development of unwanted, and
sometimes avoidable, adverse reactions to glaucoma medications.

Patients on miotics should be observed, not only for the
development of possible cataract and retinal detachment, but also for
changes in the iridocorneal angle. The combination of advancing nuclear
sclerosis and miotic-induced changes in lens shape and position may induce
intermittent relative pupillary block which may lead to subacute or chronic
angle closure. Failure to perform gonioscopy on such patients may lead the
ophthalmologist to mistakenly attribute a rise in intraocular pressure to
loss of medical control of open angle glaucoma rather than to the
introduction of pupillary block. To raise the concentration of the miotic
in this situation will only increase the pupillary block, converting
medically controllable open angle glaucoma into intractable chronic angle
closure. Probably, this is a more common cause of the development of angle
closure in patients with open angle glaucoma than that brought about by the
administration of mydriatic glaucoma agents, such as epinephrine.

Timolol has been available for the treatment of glaucoma for nearly
2 years and has proved to be efficacious and safe in many cases. Some
patients, however, have developed side effects. Although a few have
complained of the external ocular irritation common with many collyria,
most patients have had system adverse reactions, especially of the
cardiovascular, respiratory, and central nervous systems. (4,5)
Epinephrine also has the potential for producing cardiotoxicity, although
few cases have been reported. It should be remembered that many ocularly
administered agents, including epinephrine and timolol, may be rapidly
absorbed via the lacrimal tract and nasopharyngeal mucose. The usual
hepatic detoxification that occurs with gastrointestinal absorption is thus
bypassed, making the ocular route of systemic administration more similar
to intravenous than to gastrointestinal absorption. This consideration may
help to explain the high incidence of systemic effects from ocularly
applied timolol. Moreover, recent studies have demonstrated that more than
50% of ocularly applied epinephrine is absorbed systemically, making the
usual ocular dosage comparable to regularly used therapeutic systemic
dosages. (8) Hence, neither of these agents is an ideal first choice for
patients with cardiovascular disease. Moreover, the importance of lacrimal
canalicular compression should be emphasized to all glaucoma patients on
topical therapy, but particularly to those for whom epinephrine and timolol
are necessary.

Those with lacrimal shunts, such as Jones Pyrex tubes, especially
need to be reminded of the potential systemic effects of using eye drops.
These patients experience the rapid nasopharyngeal absorption of collyria
and could find themselves hospitalized with unrecognized cholinergic,
adrenergic, or other drug toxicity. (9-10)

Because many of our patients seem to be treated successfully with
the same agent for many years, we may occasionally be lured into
unjustified complacency about the efficacy and safety of their therapy.
The example of miotic-induced angle closure is most clear-cut, but we have
also seen patients develop cholinergic, adrenergic, or allergic symptoms
after previously tolerating certain agents for many years. Hence, even
with what seems to be adequate control, it is worthwhile occasionally to
stop and reconsider the appropriateness of any therapeutic regimen.

Prospective studies are needed to determine the incidence of
adverse effects and their causal relationship to ocular drugs.
Tentatively, however, we can state that, in our glaucoma patients, the side
effects seem to be somewhat more common with miotics, and possibly with
epinephrine, than with timolol. However, it is more important to consider
that the side effects from Timolol and possibly from epinephrine are more
likely to be systemic and thus to be associated with significant morbidity.
Active research into new methods of drug delivery may permit the
achievement of adequate therapeutic intraocular dosage while minimizing
that available for systemic absorption. Meanwhile, many glaucoma patients
will require a combination of agents; it is important to keep in mind the
possible adverse reactions of each. Rather than seek an ideal first-line
drug for glaucoma, it is preferable to design specific regimens for
individual patients based upon their ocular needs and their general medical
condition.
The National Registry is grateful for the many reports it receives
from ophthalmologists and urges the continued reporting of adverse effects
observed after the administration of glaucoma and other ophthalmic
medications.

E. Michael Van Buskirk, MD
The National Registry for Drug-Induced
Ocular Side Effects
Department of Ophthalmology
University of Oregon Health Sciences Center
Portland, OR 97201


References

1. Vincent A: Patient's viewpoint of glaucoma therapy. Sight Sav Rev
1972-1973.

2. Fraunfelder FT: Drug-induced Ocular Side Effects and Drug
Interactions. Philadelphia, Lea & Febiger, 1976.

3. Grant W: Toxicology of the Eye. Springfield, Ill, Charles C Thomas,
1974.

4. Van Buskirk EM: Adverse reactions from timolol administration.
Ophthalmol, to be published.

5. Van Buskirk EM: ADverse reactions from topical glaucoma therapy and
their clinical implications. Paper presented at a symposium held by
Exerpta Medica, Cancun, Mexico, March 28-29, 1980.

6. Epstein DL, Grant W: Carbonic anhydrase inhibitor side effects. Arch
Ophthalmol 95: 1378-1382, 1977.

7. Shell JW, Fraunfelder FT: Letter to the editor. New Engl J Med, to be
published.

8. Anderson JA: Systemic absorption of topical ocularly applied
epinephrine and dipivefrin. Arch Ophthalmol 98: 350-353, 1980.

9. According to a letter from J.L. Wobig, in 1980.

10. Wood JR, Anderson RL, Edwards JJ: Phospholine iodide toxicity and
Jones' tubes. Ophthalmol 87 (4): 346-348, 1980

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