W e read with great interest the article by Ansari et al on the fragility in studies of minimally invasive glaucoma surgery (MIGS), and we would like to comment on mechanisms that may mediate the effect of these procedures and on the design of studies assessing their efficacy.
There is no doubt that cataract surgery lowers intraocular pressure (IOP), although the mechanism remains uncertain. , Distension of the trabecular meshwork by the ophthalmic viscoelastic device, together with irrigation and washout of the trabeculum, may generate a trabeculoplasty-like effect. When MIGS devices are implanted, these changes may be even more pronounced, as marked distension of the anterior chamber is required to visualize the angle structures and to control potential bleeding, and thorough removal of the viscoelastic is also necessary. Furthermore, blood reflux into de Shlemm´s canal, frequently observed in these patients, might itself produce an effect analogous to a canaloplasty.
When MIGS or cataract surgery is performed as a stand-alone procedure, these changes occur only once. However, when both procedures are combined, they may occur twice, as many surgeons use acetylcholine and a second, higher-density viscoelastic to improve visualization of the trabecular meshwork. This may help to explain the greater IOP-lowering effect often observed in combined MIGS–cataract surgery compared with isolated cataract surgery or stand-alone MIGS.
In many cases, treatments do not work through the mechanisms that we initially assume. An important part of the IOP-lowering effect attributed to MIGS procedures may derive from the surgical maneuvers required to implant the device rather than from the device itself.
The steps performed before and after MIGS, release significant amounts of mechanical energy onto the trabecular meshwork through various mechanisms such as deformation, vibration, and shock waves, and may also have a meaningful effect. Future clinical trials should therefore include a control arm in which all of these surgical steps are performed except for device implantation. This would allow a more accurate estimation of the true effect attributable to the implant.
In addition, such a design would also help to minimize the observer-expectancy bias, which inevitably arises in this context, particularly considering that Goldmann applanation tonometry is highly observer dependent. This represents another source of fragility inherent to most glaucoma studies. The entire framework of glaucoma research rests on the foundation of Goldmann applanation tonometry, which is highly observer dependent. Measurements must be rounded on a scale that advances in increments of 2 mm Hg. In routine practice, several readings are typically obtained, from which the observer must round and select the final value. The inherent cherry picking and rounding involved in this process, together with small favorable rounding after surgery, may bias the results in favor of the treated group.
In summary, when the therapeutic effect is so modest, the mechanism of action remains uncertain, and the measurement instrument is so operator dependent, inclusion of a sham-surgery control group may be necessary to reliably determine the efficacy of these procedures.
CRediT authorship contribution statement
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
