The Impact on Glaucoma from the OUTSIDE IN - New York Eye and ...

work of Ammar and Kahook 18,23 and that of Zhang and
colleagues 17 suggest that the toxic effects of BAK may not be
limited to the external surface of the eye, but that BAK may
actually penetrate through corneal skeletal limbal tissue and
thus both trabecular endothelial cells and non-pigmented ciliary
epithelial lines are also affected. What is your belief regarding
this evidence?
Dr Moster: A single drop of a BAK-containing ocular medication
can persist in ocular tissues for an extended period of time 24 ;
thus, I believe there is a strong possibility that BAK can enter
into and persist within internal tissues.
Dr Herndon: Before forming a definitive opinion on this issue, I
would like to see more evidence showing BAK’s toxicity on the
trabecular meshwork.
<strong>The</strong> Effects of Preservatives
on Surgical Outcomes
Dr Parrish: Some evidence suggests that the long-term use of
ocular antihypertensives is associated with failure of traditional
trabeculectomy limbal filtration surgery or with complications
with postoperative healing. 25,26 Do you see poor surgical
outcomes caused by ocular antihypertensives?
Dr Herndon: I believe that preservatives have a deleterious effect
on the conjunctival surface, leading to poor surgical outcomes.
This was demonstrated by the work of Broadway and colleagues
approximately 20 years ago. <strong>The</strong>y found that the long-term use of
multiple ocular antihypertensives induced preoperative subclinical
conjunctival inflammation, and that the long-term multidrug
regimens were associated with lower surgical success rates
compared with shorter-term monotherapy. Both exposure to
preservatives and duration of therapy were cited by the authors
as probable mechanisms that led to poor surgical outcomes. 25
Dr Moster: I recommend a drop holiday prior to surgery, even if
the patient’s IOP is high. Following a drop holiday, I often
observe decreased bleeding, less irritation, and improved
surgical outcomes. An oral agent can be employed to lower the
IOP until the time when the patient can be brought comfortably
to the operating room.
Dr Parrish: Do ocular antihypertensives negatively affect
outcomes of argon laser trabeculoplasty (ALT) or selective laser
trabeculoplasty (SLT)?
Dr Pflugfelder: It is a possibility. Ocular antihypertensive use,
specifically in terms of the inflammatory effects of BAK, has
been found to be a risk factor for failure or rejection of corneal
transplant, suggesting that the drops can gain access to the
anterior chamber. 27
Prostaglandin-Associated Periorbitopathy
Dr Parrish: Recently, prostaglandin-associated periorbitopathy
(PAP), or deepening of the superior lid sulcus, has received
increasing attention as a potential adverse effect of ocular
prostaglandin agonists. Do you observe this phenomenon in
your practice, and if so, what do you do about it?
Dr Herndon: I have clearly seen patients in my practice who
have presented with deeper orbits related to the use of ocular
prostaglandin analogs, particularly those who are treated in
only 1 eye. We should give credit to both Louis R. Pasquale,
MD, and Stanley J. Berke, MD, for bringing this adverse effect
to the attention of the ocular community. In this situation, the
eyelids become tighter and it can be difficult for the clinician to
lift up the patient’s eyelid.
Dr Moster: <strong>The</strong> condition is sometimes referred to as
pharmacologic blepharoplasty.
Dr Parrish: With limited literature on this subject, it is difficult
to ascertain if PAP is an effect of preservatives or of the
prostaglandin analog moiety. Could it be that BAK is enhancing
the penetration of the prostaglandin analog into the periorbital
tissue? Based on this hypothesis, perhaps a preservative-free
prostaglandin analog would have less extensive orbital
penetration? For the present, these scientific questions are
simply speculation.
MANAGING PATIENTS WITH GLAUCOMA
OR OCULAR HYPERTENSION AND
OCULAR SURFACE ISSUES
<strong>The</strong>rapeutic Strategies for Controlling IOP
and Maintaining Ocular Surface Health
Dr Parrish: What are the best practices for maintaining ocular
surface health while managing IOP? What do you do for the
patient who uses ocular antihypertensives and presents with a
myriad of ocular surface findings and complaints?
Dr Pflugfelder: <strong>The</strong> best method to determine if ocular
antihypertensive agents are the cause of ocular surface toxicity
is to initiate a drop holiday. Thus, in patients with ocular surface
toxicity, I discontinue all ocular antihypertensives and begin IOPlowering
therapy with an oral carbonic anhydrase inhibitor. In
severe cases, during the drop holiday, I will prescribe a low-dose,
preservative-free ocular steroid to reduce inflammation of the
ocular surface. <strong>The</strong> steroid typically accelerates improvement of
the ocular surface, and interestingly, usually does not increase
IOP. I typically use dexamethasone, 0.01%, which is compounded
by a specialty pharmacy. In close collaboration with the patient’s
glaucoma specialist, and with careful monitoring of IOP, I typically
continue the drop holiday for a few weeks. <strong>The</strong>n, if the patient’s
ocular surface improves, which it usually does, I resume ocular
antihypertensive therapy, but with non-BAK preserved or
preservative-free ocular antihypertensives. In some cases, I
prescribe the combination of a low-dose oral carbonic anhydrase
inhibitor and an ocular antihypertensive.
<strong>The</strong> best method to determine if ocular
antihypertensive agents are the cause of ocular
surface toxicity is to initiate a drop holiday. Thus, in
patients with ocular surface toxicity, I discontinue
all ocular antihypertensives and begin IOP-lowering
therapy with an oral carbonic anhydrase inhibitor.
—Stephen C. Pflugfelder, MD
Dr Moster: Because glaucoma is a lifelong disease, a drop
holiday makes sense. As does Dr Pflugfelder, I prescribe a lowdose,
preservative-free ocular steroid during the drop holiday,
followed by re-initiation of ocular antihypertensive therapy, but
with a preservative-free formulation.
Dr Parrish: Has anyone used the 1-eye trial to determine which
ocular antihypertensive in a regimen is causing ocular surface
distress? That is, has anyone discontinued 1 medication at a
time, in 1 eye, and followed the patient to observe for
improvement of ocular surface symptoms in the trial eye
compared with the eye that continues to be treated with the
original medical regimen.
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