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• Response to letter
  Tsontcho Ianchule
  Published on: 20 March 2019
• Concerns regarding complication rates of recent prospective investigation
  David Fleischman, Andrzej Grzybowski
  Published on: 20 March 2019

• Published on: 20 March 2019

  Response to letter

  • Tsontcho Ianchule, MD MPH, Ophthalmic Surgeon, Professor of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai Mount Sinai Hospital System

  We thank the authors for their careful perusal of our study report and thoughtful observations. We agree that as demonstrated by the large population study1,2 referenced by us and by them, the rate of complications with cataract surgery is non-homogenous and increases dramatically with advanced stage cataracts – as much as 200%+ increase in rate of PCT in cases with high grade cataract, pseudoexfoliation and other comorbidities. In fact, with the co-existence of multiple factors, the compound rate can be even higher.

  Our pilot study was in patients with advanced cataracts and multiple co-existing ocular pathologies and given the small sample size we are not surprised that the study point estimate for the PCT rate may be on the higher end of the overall range demonstrated by the larger population study. In addition, the randomized control design of the clinical trial further validates a PCT rate which was similar for both treatment and control groups. Certainly, an informed reader would appreciate that such a small trial is underpowered to be conclusive regarding the small difference between the two groups so no claims should be made about the slightly better rate of PCT and lower trend demonstrated in the miLOOP group.

  What is important to appreciate from both the population study and our pilot data is that the rate of PCT is not the same for all cataract surgeries and there is a multiplier effect in certain subgroups and subpopulations. Our authorship team...

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  We thank the authors for their careful perusal of our study report and thoughtful observations. We agree that as demonstrated by the large population study1,2 referenced by us and by them, the rate of complications with cataract surgery is non-homogenous and increases dramatically with advanced stage cataracts – as much as 200%+ increase in rate of PCT in cases with high grade cataract, pseudoexfoliation and other comorbidities. In fact, with the co-existence of multiple factors, the compound rate can be even higher.

  Our pilot study was in patients with advanced cataracts and multiple co-existing ocular pathologies and given the small sample size we are not surprised that the study point estimate for the PCT rate may be on the higher end of the overall range demonstrated by the larger population study. In addition, the randomized control design of the clinical trial further validates a PCT rate which was similar for both treatment and control groups. Certainly, an informed reader would appreciate that such a small trial is underpowered to be conclusive regarding the small difference between the two groups so no claims should be made about the slightly better rate of PCT and lower trend demonstrated in the miLOOP group.

  What is important to appreciate from both the population study and our pilot data is that the rate of PCT is not the same for all cataract surgeries and there is a multiplier effect in certain subgroups and subpopulations. Our authorship team felt that for investigational transparency and authenticity it is important to report all results, including the ones we don’t like and the ones that give us pause in order to stimulate thoughtful discourse such as the one unfolding through the comments in your letter.

  Sean Ianchulev, MD MPH
  Professor of Ophthalmology
  New York Eye and Ear Infirmary of Mount Sinai

  References
  1. Jaycock P, Johnston RL, Taylor H, et al. The Cataract National Dataset electronic multi-centre audit of 55,567 operations: updating benchmark standards of care in the United Kingdom and internationally. Eye 2009 23(1):38-49.
  2. Narendran N, Jaycock P, Johnston RL, et al. The Cataract National Dataset electronic multicenter audit of 55,567 operations: risk stratification for posterior capsule rupture and vitreous loss. Eye 2009 23(1):31-7.

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  Conflict of Interest:
  patent holder, inventor and founder of the milOOP technology

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• Published on: 20 March 2019

  Concerns regarding complication rates of recent prospective investigation

  • David Fleischman, Assistant Professor, Ophthalmology University of North Carolina at Chapel Hill
  • Other Contributors:
    • Andrzej Grzybowski, Chair of Ophthalmology

  We are interested in the work of Ianchulev et al in their recent interventional randomized controlled trial.[1] What piqued our interest was the rate of posterior capsular tears (PCT). 4/53 (7.5%) patients in the miLOOP+phaco group experienced PCT, and 5/48 (10.4%) phaco-alone controls with PCT. These rates are much higher than standard phacoemulsification reports. The authors refer to a large study that identified advanced cataracts increased risk of PCT at comparable levels.[2] That same group published investigations expounding upon this.[3-4] Advanced cataracts were specifically identified as brunescent/white cataracts, contrasting Grade 3-4 in the miLOOP study (curiously described as LOCSIII classification in the manuscript).

  Using the risk calculation,[3] the range of composite adjusted odds ratio (aOR) for the miLOOP study was 49.93 (25-28% risk) to an aOR of 0.87 (<1% surgical risk). The average patient from the miLOOP investigation had an aOR of 4.43, thus <5% PCT risk.

  Our concerns: First, the authors state that “There was a trend towards a lower rate of capsular tear during the phaco portion with miLOOP-assisted phaco (7.5%) compared to standard phaco (10.4%).” Given the numbers representing these percentages this is an inappropriate description of this relationship.

  Let us assume that a control group presented with a PCT rate similar to that reported in literature: <5%. Here, miLOOP-phaco PCT rate would be higher than the control...

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  We are interested in the work of Ianchulev et al in their recent interventional randomized controlled trial.[1] What piqued our interest was the rate of posterior capsular tears (PCT). 4/53 (7.5%) patients in the miLOOP+phaco group experienced PCT, and 5/48 (10.4%) phaco-alone controls with PCT. These rates are much higher than standard phacoemulsification reports. The authors refer to a large study that identified advanced cataracts increased risk of PCT at comparable levels.[2] That same group published investigations expounding upon this.[3-4] Advanced cataracts were specifically identified as brunescent/white cataracts, contrasting Grade 3-4 in the miLOOP study (curiously described as LOCSIII classification in the manuscript).

  Using the risk calculation,[3] the range of composite adjusted odds ratio (aOR) for the miLOOP study was 49.93 (25-28% risk) to an aOR of 0.87 (<1% surgical risk). The average patient from the miLOOP investigation had an aOR of 4.43, thus <5% PCT risk.

  Our concerns: First, the authors state that “There was a trend towards a lower rate of capsular tear during the phaco portion with miLOOP-assisted phaco (7.5%) compared to standard phaco (10.4%).” Given the numbers representing these percentages this is an inappropriate description of this relationship.

  Let us assume that a control group presented with a PCT rate similar to that reported in literature: <5%. Here, miLOOP-phaco PCT rate would be higher than the control raising safety concerns. Yet the study showed a similarly high complication rate in the control group, statistically maintaining the miLOOP’s safety.

  Finally, this occurs in the setting of considerable financial interest.

  Regardless of the opportunities not otherwise afforded to these patients by their generous work, ethical standards and protection against bias is essential to protect patients. The complication rate was unacceptably high, and the trial should have been stopped and the study should not have been published.

  References

  1. Ianchulev T, Chang DF, Koo E, et al. Microinterventional endocapsular nucleus disassembly: novel technique and results of first-in-human randomized controlled study. Br J Ophthalmol 2019 103(2):176-180.
  2. Jaycock P, Johnston RL, Taylor H, et al. The Cataract National Dataset electronic multi-centre audit of 55,567 operations: updating benchmark standards of care in the United Kingdom and internationally. Eye 2009 23(1):38-49.
  3. Narendran N, Jaycock P, Johnston RL, et al. The Cataract National Dataset electronic multicenter audit of 55,567 operations: risk stratification for posterior capsule rupture and vitreous loss. Eye 2009 23(1):31-7.
  4. Johnston RL, Taylor H, Smith R, et al. The Cataract National Dataset Electronic Multi-center audit of 55,567 operations: variation in posterior capsule rupture rates between surgeons. Eye 2010 24(5):888-93.

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  Conflict of Interest:
  None declared.

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