title: Perioperative medications for preventing temporarily increased intraocular pressure after laser trabeculoplasty.
abstract: Glaucoma is the international leading cause of irreversible blindness. Intraocular pressure (IOP) is the only currently known modifiable risk factor; it can be reduced by medications, incisional surgery, or laser trabeculoplasty (LTP). LTP reduces IOP by 25% to 30% from baseline, but early acute IOP elevation after LTP is a common adverse effect. Most of these IOP elevations are transient, but temporarily elevated IOP may cause further optic nerve damage, worsening of glaucoma requiring additional therapy, and permanent vision loss. Antihypertensive prophylaxis with medications such as acetazolamide, apraclonidine, brimonidine, dipivefrin, pilocarpine, and timolol have been recommended to blunt and treat the postoperative IOP spike and associated pain and discomfort. Conversely, other researchers have observed that early postoperative IOP rise happens regardless of whether people receive perioperative glaucoma medications. It is unclear whether perioperative administration of antiglaucoma medications may be helpful in preventing or reducing the occurrence of postoperative IOP elevation.
  
  
  
  To assess the effectiveness of medications administered perioperatively to prevent temporarily increased intraocular pressure (IOP) after laser trabeculoplasty (LTP) in people with open-angle glaucoma (OAG).
  
  
  
  We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 11), MEDLINE Ovid (1946 to 18 November 2016), Embase.com (1947 to 18 November 2016), PubMed (1948 to 18 November 2016), LILACS (Latin American and Caribbean Health Sciences Literature Database) (1982 to 18 November 2016), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com); last searched 17 September 2013, ClinicalTrials.gov (www.clinicaltrials.gov); searched 18 November 2016 and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en); searched 18 November 2016. We did not use any date or language restrictions.
  
  
  
  We included randomized controlled trials (RCTs) in which participants with OAG received LTP. We included trials which compared any antiglaucoma medication with no medication, one type of antiglaucoma medication compared with another type of antiglaucoma medication, or different timings of medication.
  
  
  
  Two review authors independently screened records retrieved by the database searches, assessed the risk of bias, and abstracted data. We graded the certainty of the evidence using GRADE.
  
  
  
  We included 22 trials that analyzed 2112 participants and identified no ongoing trials. We performed several comparisons of outcomes: one comparison of any antiglaucoma medication versus no medication or placebo, three comparisons of one antiglaucoma medication versus a different antiglaucoma mediation, and one comparison of antiglaucoma medication given before LTP to the same antiglaucoma medication given after LTP. Only one of the included trials used selective laser trabeculoplasty (SLT); the remaining trials used argon laser trabeculoplasty (ALT). Risk of bias issues were primarily in detection bias, reporting bias, and other potential bias due to studies funded by industry. Two potentially relevant studies are awaiting classification due to needing translation.In the comparison of any medication versus no medication/placebo, there was moderate-certainty evidence that the medication group had a lower risk of IOP increase of 10 mmHg or greater within two hours compared with the no medication/placebo group (risk ratio (RR) 0.05, 95% confidence interval (CI) 0.01 to 0.20). This trend favoring medication continued between two and 24 hours, but the evidence was of low and very low-certainty for an IOP increase of 5 mmHg or greater (RR 0.17, 95% CI 0.09 to 0.31) and 10 mmHg or greater (RR 0.22, 95% CI 0.11 to 0.42). Medication was favored over placebo/no medication with moderate-certainty in reducing IOP from the pre-LTP measurements for both within two hours and between two and 24 hours. At two hours, the mean difference (MD) in IOP between the medication group and the placebo/no medication group was -7.43 mmHg (95% CI -10.60 to -4.27); at between two and 24 hours, the medication group had a mean reduction in IOP of 5.32 mmHg more than the mean change in the placebo/no medication group (95% CI -7.37 to -3.28). Conjunctival blanching was an ocular adverse effect that was more common when brimonidine was given perioperatively compared with placebo in three studies.In our comparison of brimonidine versus apraclonidine, neither medication resulted in a lower risk of increased IOP of 5 mmHg or greater two hours of surgery; however, we were very uncertain about the estimate. There may be a greater mean decrease in IOP within two hours after LTP. We were unable to perform any meta-analyses for other review outcomes for this comparison.In our comparison of apraclonidine versus pilocarpine, we had insufficient data to perform meta-analyses to estimate effects on either of the primary outcomes. There was moderate-certainty evidence that neither medication was favored based on the mean change in IOP measurements from pre-LTP to two hours after surgery.In the comparison of medication given before LTP versus the same medication given after LTP, we had insufficient data for meta-analysis of IOP increase within two hours. For the risk of IOP increase of 5 mmHg or greater and 10 mmHg or greater at time points between two and 24 hours, there was no advantage of medication administration before or after LTP regarding the proportion of participants with an IOP spike (5 mmHg or greater: RR 0.82, 95% CI 0.25 to 2.63; 10 mmHg or greater: RR 1.55, 95% CI 0.19 to 12.43). For an IOP increase of 10 mmHg or greater, we had very low-certainty in the estimate, it would likely change with data from new studies.
  
  
  
  Perioperative medications are superior to no medication or placebo to prevent IOP spikes during the first two hours and up to 24 hours after LTP, but some medications can cause temporary conjunctival blanching, a short-term cosmetic effect. Overall, perioperative treatment was well tolerated and safe. Alpha-2 agonists are useful in helping to prevent IOP increases after LTP, but it is unclear whether one medication in this class of drugs is better than another. There was no notable difference between apraclonidine and pilocarpine in the outcomes we were able to assess. Future research should include participants who have been using these antiglaucoma medications for daily treatment of glaucoma before LTP was performed.
authors.affiliation: The Eye Center, 65 Mountain Blvd Extension, Warren, New Jersey, USA, 07059.
authors.forename: Linda
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, Michigan, USA, 48105.
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Weizer
authors.affiliation: Ophthalmology and Visual Sciences, Kellogg Eye Center, University of Michigan, 1000 Wall Street, Ann Arbor, Michigan, USA, 48105.
authors.forename: David C
authors.initials: DC
authors.lastname: Musch
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000068438:Brimonidine Tartrate / Q000627:therapeutic use; D003000:Clonidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D003228:Conjunctiva / Q000187:drug effects; D005902:Glaucoma, Open-Angle / Q000601:surgery*; D006801:Humans; D007429:Intraocular Pressure / Q000187:drug effects*; D009798:Ocular Hypertension / Q000517:prevention & control*; D010862:Pilocarpine / Q000627:therapeutic use; D011183:Postoperative Complications / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D014130:Trabeculectomy / Q000009:adverse effects*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D000959:Antihypertensive Agents; D010862:Pilocarpine; D000068438:Brimonidine Tartrate; C016986:apraclonidine; D003000:Clonidine