Effects of Antiglaucoma Drugs on Refractive Outcomes in Eyes with Myopic Regression after Laser In Situ Keratomileusis

1
Effects of Antiglaucoma Drugs on Refractive
Outcomes in Eyes with Myopic Regression after
Laser In Situ Keratomileusis
Kazutaka Kamiya, MD, PhD1), Daisuke Aizawa1),
Akihito Igarashi2), Mari Komatsu2), and Kimiya
Shimizu1) Department of Ophthalmology, Kitasato
University, JAPAN1) Department of Ophthalmology,
Sanno Hospital, JAPAN2)
2
Purpose

• Forward shift of the cornea can be one of the
  factors responsible for regression after excimer
  laser surgery.1,2)
• There have been case reports of transient
  keratectasia associated with marked elevation of
  IOP.3,4)
• The preoperative IOP was significantly higher in
  regressive eyes than in non-regressive eyes after
  LASIK.5)
• These results indicated that lowering the IOP
  might be an effective treatment for myopic
  regression after keratorefractive surgery.
• The purpose of the study is prospectively to
  investigate the effects of the antiglaucoma drugs
  on the correction of regression in relation to
  corneal geometry and refractive power after
  LASIK.

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Patients

• 27 eyes of 17 patients (male, 7 female, 20 eyes)
  
• with regression (changes from the first
  postoperative month)
• -1.26 0.48 (SD) D(-0.50 to -2.25 D) after
  LASIK (VISX STAR S2)
• Age 37.3 9.6 years (23 to 57 years)
• Preoperative manifest refraction -6.31 2.51 D
  (-3.0 to -11.0 D)
• Topical administration of antiglaucoma drugs
  (2.5 nipradilol, Kowa, Japan) was consecutively
  applied twice a day.
• Postoperative periods 9.4 2.8 months (6 to 13
  months)
• Informed consent was obtained from all patients.
• The study adhered to the tenets of the
  Declaration of Helsinki.

4
Methods

• Before and 3 months after application
• log MAR UCVA, log MAR BSCVA
• manifest and cycloplegic refraction
• IOP with a Goldmann applanation tonometer
• central corneal pachymetry (DGH-500, DGH Tech)
• corneal geometry6) measured with scanning-slit
  corneal topography (Orbscan, Bausch Lomb)
• total corneal refractive power within a central
  zone 3 mm in diameter measured with scanning-slit
  corneal topography

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Results

• Log MAR UCVA was significantly improved (plt0.001,
  Fig 1).
• Log MAR BSCVA was not significantly changed
  (p0.22, Fig 2).
• Manifest and cycloplegic refraction was
  significantly improved (plt0.001, Fig 3).
• Twenty-three (85), 16 (59) of 27 eyes showed
  refraction improvement of over 0.25 and 0.5D,
  respectively.
• Manifest and cycloplegic astigmatism was not
  significantly changed (p0.23, p0.15, Fig 4).
• IOP was significantly decreased from 11.4 2.4
  to 9.4 1.3 mmHg (plt0.001). CCT was not
  significantly changed from 505.2 39.3 to 503.6
  38.7 µm (p0.61).
• The posterior surface was shifted posteriorly by
  9.1 8.2 µm.
• Refractive power of the total cornea within a
  3-mm zone was significantly decreased from 38.4
  2.0 to 37.7 2.0 D (plt0.001).
• No serious complications occurred throughout
  follow-up periods.

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Discussion

• Topical application of the IOP-lowering drug was
  effective in reducing the refractive regression,
  especially of the spherical errors after LASIK.
• Until now, enhancement ablation has been the sole
  treatment for the correction of residual
  refractive error after excimer surgery.
• The current approach is unique in simply taking
  IOP-lowering eye drops, and thus it is clinically
  applicable to regressive eyes after refractive
  surgery.
• Moreover, it has advantages over enhancement
  ablation because it appeared to be less invasive
  and to cause fewer side effects (e.g.,
  keratectasia).
• We could first attempt this new treatment before
  considering enhancement surgery, especially when
  the amount of myopic regression is not very large
  (approximately 0.5 D).

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Nipradilol

• Nipradilol, a nonselective alpha-1 beta
  adrenergic antagonist, is widely used in Japan as
  a safe and useful long-term antihypertensive drug
  which lowers IOP by decreasing the aqueous flow
  rate, and by increasing uveoscleral outflow.7,8)
• If the refractive effects depend on the degree of
  IOP reduction, stronger IOP-lowering drugs such
  as prostaglandin derivatives may be more
  effective for the reduction of regression.
• Nipradilol has been reported to inhibit corneal
  epithelial migration and proliferation.9,10)
  However, it did not induce a significant change
  in CCT and pupil diameter.
• Although we cannot refute the possibility that
  the long-term use of nipradilol may affect
  corneal epithelium or tear film function, it was
  seen that nipradilol did not induce in the ocular
  surface a significant change capable of
  influencing refraction.

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Mechanism

• IOP reduction may have induced a backward shift
  of the cornea and reduction of corneal refractive
  power, resulting in refractive improvement in
  post-LASIK eyes.
• It may be that the morphological properties of
  the cornea are easily affected by subtle changes
  in IOP and atmospheric pressure when corneal
  rigidity is impaired by flap manipulation and
  laser ablation.
• In our preliminarily data, refraction improvement
  was more prominent in eyes with thinner
  preoperative CCT or high myopic eyes requiring
  greater correction, suggesting that this
  treatment may be effective especially for
  biomechanically weakened eyes.
• There were non-significant changes in CCT,
  indicating that corneal hydration might not play
  an important role in regression in these eyes.
• Epithelial hyperplasia, development of new
  stromal collagen, and nuclear sclerosis might
  play a significant role in regression, but many
  cases may be unexpectedly caused by corneal
  geometric changes.

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Limitation

• The limitation of this study is that sample data
  are comparatively small in amount and follow-up
  time is short, and that the study is unmasked and
  has no placebo group.
• A double-masked study with a control group
  receiving placebo might be appropriate for
  confirming the authenticity of the results.
• Because it is unclear when the biomechanical
  properties of the cornea have stabilized, it is
  also unknown how long this treatment needs to be
  continued.
• If the refractive effects depend simply on the
  degree of IOP reduction, the patients could be
  required to use the antiglaucoma drugs
  continuously.
• We are currently conducting a further study to
  clarify whether this effect is maintained after
  long-term cessation of the medication.

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Conclusions

• The preliminary data show that antiglaucoma drugs
  are effective for the reduction of the refractive
  regression, especially of the spherical errors,
  after LASIK.
• It is suggested that backward movement of the
  cornea may occur, possibly flattening the corneal
  curvature by lowering the IOP.
• Although we accepted that there were some
  non-effective cases, this new approach to
  regression may be capable of improving refractive
  outcomes after keratorefractive surgery.

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References

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