Letters to the Editor
`
`data collection from a large patient cohort, perhaps with
`collaboration from several centers, would be necessary.
`
`JERRY A. SHIELDS, MD
`HAKAN DEMIRCI, MD
`BRIAN P. MARR, MD
`RALPH C. EAGLE, JR, MD
`CAROL L. SHIELDS, MD
`Philadelphia, Pennsylvania
`
`Reference
`
`1. Shields JA, Demirci H, Marr BP, et al. Sebaceous carcinoma
`of the ocular region: a review. Surv Ophthalmol 2005;
`50:103–22.
`
`Apraclonidine and LASIK
`
`Dear Editor:
`LASIK is a popular and relatively safe surgical procedure
`for the correction of myopia, hyperopia, and astigmatism.1
`The proper adhesion between flap and stromal bed is man-
`datory to restore the corneal integrity and set the back-
`ground for an adequate refractive outcome properly.2 Many
`refractive surgeons started using topical vasoconstrictors to
`reduce postoperative hyperemia and subconjunctival hem-
`orrhages.2,3 However, any positive effect of topical vaso-
`constrictors on subconjunctival hemorrhage would be right-
`fully overshadowed by any flap adherence problems, such
`as flap slippage. Although we greatly enjoyed a study con-
`ducted by Walter and Gilbert,4 we were alarmed by its
`conclusions that the use of a vasoconstrictor, brimonidine,
`might increase the incidence of such complications.
`Moreover, we see several flaws in the report. Apart from
`its not being a prospective, randomized, double-blind clin-
`ical study,
`the sample size seemed inadequate. A total
`number of 279 eyes was divided into 3 groups: the first and
`the last group represented the patients who underwent a
`standard LASIK procedure (2 control groups), whereas only
`the 39 eyes in between (both eyes of all patients) actually
`received brimonidine. Based on our understanding of flap
`complications, whose incidence is reported to be ⬍2%,2,3
`this number of eyes represents an inadequate sample size.
`Moreover, the 3 groups of patients are not statistically
`comparable in terms of preoperative spherical equivalent
`(SE), gender, and age.
`To overcome these problems, we conducted a prospec-
`tive, randomized, double-masked study to detect the potential
`influence of the topical use of apraclonidine just before the
`LASIK procedure on postoperative flap adherence and to
`
`see if it prevents subconjunctival hemorrhage or conjuncti-
`val hyperemia.
`Sixty-six consecutive patients (32 male, 34 female) who
`underwent primary bilateral LASIK were included in this
`study. The mean age was 33⫾11 years (range, 18 – 62),
`whereas the mean SE was ⫺6.43⫾2.03 diopters (range,
`⫺2.375 to ⫺10.625).
`Topical apraclonidine 0.125% was randomly applied
`only to one eye 1 hour before and 30 seconds just before
`placement of the vacuum ring of the microkeratome Moria
`M2 (Moria Surgical, Antony, France), whereas the other eye
`served as control (1 drop of natural tears). After laser
`ablation with the Allegretto Wave excimer laser (Wave-
`Light Laser Technology, Erlangen, Germany), the flap was
`floated back into position with minimal irrigation of bal-
`anced salt solution (Alcon, Fort Worth, TX) by a single
`surgeon (IMA).
`Thirty minutes later, all the patients were examined by an
`independent observer (NST) to identify flap-related compli-
`cations (slippage, dislocation, or flap folds) and evaluate
`hyperemia and subconjunctival hemorrhage.
`None of the eyes from either group had any flap com-
`plications in the postoperative course, including flap adher-
`ence problems. All eyes in the apraclonidine group had a
`slight upper eyelid retraction, which was not present the
`following day. Eyes had less hyperemia and less subcon-
`junctival hemorrhage in the apraclonidine group than in the
`control group (␹2, P⬍0.001), as shown in Table 1 (available
`at http://aaojournal.org).
`Norden5 conducted a double-masked study and concluded
`that ␣-agonists applied topically may decrease hyperemia
`and subconjunctival hemorrhage after LASIK surgery sig-
`nificantly, without increasing the risk of flap slippage.
`There are several hypotheses for possible flap adhesion
`problems. An explanation, considering its pharmacological
`mechanism of action, could be that there was a desiccation
`or ischemic effect on the anterior segment due to anterior
`ocular vessel constriction. Another possibility is a direct
`toxic effect on the endothelial cells,5 impairing the normal
`functioning of the endothelial water pump and increasing
`the hydration of the stroma for a prolonged time, which
`would influence negatively the flap adherence.
`However, considering the fact that there was not a proper
`control group in which a placebo drop would have been
`applied, we are led to suspect that a direct lubricant impact
`of the additional drop of brimonidine was not properly
`considered during the surgical procedure. Thus, we tend to
`agree with Norden5 that a simpler reason, like excess of
`moisture on the bed and insufficient flap stroking, may be
`
`Table 1. Postoperative Hyperemia and Subconjunctival Hemorrhage with the Topical Use
`of Apraclonidine in 132 LASIK Eyes
`
`None
`
`Mild
`
`Hyperemia
`Moderate
`
`Hyperemia
`Apraclonidine
`Control
`
`48
`7
`
`16
`37
`
`2
`22
`
`Severe
`
`0
`1
`P⬍0.001
`
`0
`
`44
`19
`
`Subconjunctival Hemorrhage
`1
`2
`3
`
`19
`13
`
`2
`20
`
`1
`14
`P⬍0.001
`
`2238.e8
`
`Slayback Exhibit 1102, Page 1 of 2
`Slayback v. Eye Therapies - IPR2022-00142
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`

`

`Ophthalmology Volume 112, Number 12, December 2005
`
`responsible for the poor flap adherence described before by
`Walter and Gilbert.4
`In conclusion, topical apraclonidine before LASIK sur-
`gery may prevent early postoperative hyperemia and sub-
`conjunctival hemorrhage, without adverse effects on the
`flap adherence.
`
`IOANNIS M. ASLANIDES, MD, PHD
`NIKOLAOS S. TSIKLIS, MD
`IOANNIS G. PALLIKARIS, MD, PHD
`MIRKO R. JANKOV, MD
`Crete, Greece
`
`EFEKAN COSKUNSEVEN, MD
`EFEKAN OZKILIC, MD
`Istanbul, Turkey
`
`References
`
`1. Pallikaris IG, Papatzanaki ME, Stathi EZ, et al. Laser in situ
`keratomileusis. Lasers Surg Med 1990;10:463– 8.
`2. Gimbel HV, Anderson Penno EE, van Westenbrugge JA, et al.
`Incidence and management of intraoperative and early postoper-
`ative complications in 1000 consecutive laser in situ keratom-
`ileusis cases. Ophthalmology 1998;105:1839 – 47, discussion
`1847– 8.
`3. Dada T, Sharma N, Vajpayee RB, Dada VK. Subconjunctival
`hemorrhages after LASIK. Laser in situ keratomileusis. J Cata-
`ract Refract Surg 2000;26:1570–1.
`4. Walter KA, Gilbert DD. The adverse effect of perioperative
`brimonidine tartrate 0.2% on flap adherence and enhancement
`rates in laser in situ keratomileusis patients. Ophthalmology
`2001;108:1434 – 8.
`5. Norden RA. Effect of prophylactic brimonidine on bleeding
`complications and flap adherence after laser in situ keratom-
`ileusis. J Refract Surg 2003;18:468 –71.
`
`Author reply
`
`Dear Editor:
`I read with great interest the response to our article regarding
`apraclonidine and LASIK. First of all, it is quite ironic that the
`first criticism of our retrospective study was that it was not
`randomized or a masked study, when these authors are pre-
`senting their data as a letter to the editor. Indeed, our study was
`neither randomized nor masked, nor was it ever meant to be. It
`was simply an observation of our clinical findings over time—
`thus, a retrospective review. I did not feel it to be ethical to
`submit patients to a randomized trial of brimonidine, having
`gained the necessary knowledge from this clinical experience,
`nor did our institutional review board. Another criticism of our
`study was the small sample size of the patients having bri-
`monidine before LASIK. Indeed, if you refer to our article, the
`flap slippage rate was 6 of 39 eyes, or 15%, in the brimonidine
`group, versus 0 of 240 eyes in the nonbrimonidine groups.
`Using the Fisher exact test on these 2 groups, the P value was
`highly significant at 0.00001. This powerful statistical tool tells
`us that there was a more than adequate sample size. Addition-
`ally, there were 2 nonbrimonidine groups, one before bri-
`monidine use and one after. Our technique for flap reposition
`never changed during this entire time, so an “excess of mois-
`ture on the bed and insufficient flap stroking” do not explain
`
`2238.e9
`
`this increase in flap dislocation. The one and only variable was
`pretreatment with brimonidine before LASIK.
`This letter to the editor is disconcerting in the lack of
`scientific evidence to support its conclusions. Foremost,
`they too had a small sample size and, by their quoted rate of
`2% slipped flaps, should have found 2 or 3 slipped flaps in 132
`eyes studied. One reason that slipped flaps were not seen in
`this study might have been the extremely short observation
`time (30 minutes) after the procedure. Their report does not
`indicate that additional observations were made on the
`following day. In our study, all flaps were adherent in both
`groups 30 minutes after surgery but were dislocated in 6
`eyes on the following day. Another explanation for not
`observing any dislocated flaps in the apraclonidine group
`could be the use of the drug 1 hour before surgery. All of
`our patients received the drug within 5 minutes of surgery.
`Additionally, the authors used a very weak formulation of
`apraclonidine— 0.125%, versus 0.5% or 1%.
`However, the most likely explanation is that apraclonidine
`and brimonidine are 2 different ␣-agonists, with different po-
`tency and adverse effects.
`
`KEITH A. WALTER, MD
`Winston-Salem, North Carolina
`
`IOP after Triamcinolone Acetonide
`Dear Editor:
`In Jonas et al’s article,1 the authors discuss the treatment of
`raised intraocular pressure (IOP) after intravitreal injection
`of triamcinolone acetonide (TA). They treated 3 patients
`who developed intractable IOP elevation despite maximal
`medical treatment with filtering surgery (trabeculectomy).
`We offer our experience and opinions about the treatment.
`Currently, there are 3 options if full medication is still
`unsuccessful in controlling IOP after TA injection: filtering
`surgery, valve implant, or vitrectomy. Steroid-induced glau-
`coma has been known for a long time and is due mainly to
`decreased outflow of aqueous. Either filtering surgery or a
`valve implant can increase the outflow to reduce the IOP.
`However, we believe it is better to find and treat the cause
`of elevated IOP rather than to treat the effect or complica-
`tion. Therefore, the removal of vitreous TA by vitrectomy
`may be a better option in these cases. In addition, the
`occaisional finding of a pseudohypopyon in the anterior
`chamber (AC) makes us realize that intravitreous TA can
`migrate to the AC and may clog the trabecular meshwork.2,3
`Therefore, in our clinic we performed pars plana vitrectomy
`(PPV) and AC irrigation to treat patients with intractable
`glaucoma, and IOP was well controlled rapidly after surgery.
`Finally, it is of course important to control elevated IOP
`to avoid further optic nerve damage after intravitreal injec-
`tion of TA. The choice of filtering surgery, valve implant, or
`vitrectomy depends on which operation the local ophthal-
`mologist is familiar with. As retina specialists, we recom-
`mend PPV and AC irrigation.
`
`JANE-MING LIN, MD
`YI-YU TSAI, MD
`POR-TYING HUNG, MD
`Taichung, Taiwan
`
`Slayback Exhibit 1102, Page 2 of 2
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