Glaucoma is an ophthalmological condition with several diseases, for which diagnostic strategies, drugs and surgical procedures are in constant development. This information is assessed, analyzed and summarized in CPG, which creates the need of continuous updates. Few CPG make specific recommendations for the indications and use of MIGS, even when several systematic reviews, or network meta-analyses (NMA) have been published in the last years.
NMA allows simultaneous comparisons of three or more interventions in a single analysis, even when they were not directly compared in head-to-head clinical trials, combining direct or indirect evidence29. Rigorously conducted NMA provide useful evidence-based information, as long as included primary trials are not deficient30. NMA are useful for a pathology such as glaucoma, which has several treatment options (pharmacological, laser or incisional surgery). In July 2021 Bicket et al. published a NMA that assessed 6 Cochrane systematic reviews of randomized clinical trials (RCT) describing 6 to 60-month outcomes from MIGS31. They reported that the Hydrus microstent bypass device was superior to iStent in achieving IOP reduction and better glaucoma control without the need of medication, compared with cataract surgery alone, although the effect sizes were small31.
National Institute for Health and Care Excellence (NICE) guidelines 202223 (update of the previous version published in 2017) only addresses selective laser trabeculoplasty. NICE has different types of reports for eye conditions for instance, interventional procedures guidance (IPG) for specific procedures, where they assess the safety and efficacy of new interventional procedures for its wide use by the National Health System. Three IPG address MIGS: “Trabecular stent bypass microsurgery for open-angle glaucoma” (IPG575) published in 201718, “Microinvasive subconjunctival insertion of a trans-scleral gelatin stent for primary open-angle glaucoma” (IPG612) published in 201817, and “Ab-interno canaloplasty for open-angle glaucoma” (IPG745) published in 202216. The last one was supported by 7 studies with a before-after design, because no randomized studies were found, and the longest follow-up was of 4 years, some of them with an attenuation of treatment effect over time16.
Even when FCCG and NSG are the latest published CPG, they are English versions of their native language CPG; in both, search dates were not reported, and the evidence was discussed in January 2021–February 2022. In December 2023 EGS published the guide on surgical innovation for glaucoma (EGS-SI)5, where for the first time, based on an expert consensus, CPG make recommendations for several innovative glaucoma surgeries; however, they do not cover all procedures. They leave aside dilating and disrupting trabecular procedures (Trabectome, Kahook, catheter-assisted surgeries, etc.) and address a broad chapter about bleb forming devices, not defined as MIGS by the same CPG. EGS-SI limited the evidence search to December 2018 – February 2021 (evidence gap of 790 records), stating that “There was too little experience among participants to reach a consensus and inform practice”, and that “The evidence available in the literature is limited” (from RCT and systematic reviews) about dilating and disrupting procedures. However NICE-IPG-AIC (2022)16, recommended ab-interno canaloplasty based on 7 non-randomized studies (only 2 of them published in 2022), evidence that could have been included by guidelines published in 2023 (FCCG and EGSI) if they performed a re-run search.
Re-run search is a key step to guarantee the guideline update, and in topics addressing new procedures it is critical to perform or to set database auto-alerts, to avoid the fast outdating of the recommendations. When developing a CPG, during the step “Identifying the evidence”, the Guideline Development Group (GDG) performs the literature search establishing date parameters, information that should be described in the CPG (Details of the question, names of the databases, database coverage dates, the search dates, search strategy and limits)32. Re-run searches allow to identify any further evidence that has been published since the search was run initially; and according to NICE, it should be done 6–8 weeks before submission of the draft guideline32. This strategy is also used by Health Technology Assessment (HTA), with database auto-alerts and updating with new evidence7,26.
Only 2 guidelines reported a search update (Table 1). Last published guidelines available online in 2023 (FCCG and EGS-SI), were developed with the support of a methodological team; however, both guidelines included studies until 2021, and did not report a re-run search, leading to an evidence gap of 2 years (Table 1). This is an important bias for the recommendations made, considering that the last 2–3 years accounted for the higher number of MIGS publications, leading to an important evidence gap.
Several guidelines did not perform or report a re-run or updated search, probably because they addressed a disease (most of the assessed CPG, make recommendations for the diagnosis and treatment of glaucoma or open angle glaucoma) and that evidence had to be discussed for several key questions (epidemiology, diagnosis, treatment, etc.), making the update process more difficult. However, specific procedures' guidelines like EGS-SI5 could have performed an updated search, as performed by other procedures' guidelines (NICE-IPG AIC16, NICE-IPG TSBM17) or HTA reports like CADTH26 (“Regular alerts were established to update the searches until the publication of the final report”), AAO28(“Search was conducted in February 2021 and updated in April 2023”) or Ontario health7(Search was conducted on March 6, 2023 and database auto-alerts monitored until June 12, 2023).
CPG developers should take into account patients’ opinions and experiences for the development and implementation of a CPG. Preferences and values refer to the objectives, expectations and predispositions that could influence patients. (e.g., Fear of ultimate blindness and difficulty managing eye-drop medication led patients to explore other treatment options, such as MIGS” 7).
Several guideline developers address cultural and ethnic diversity33 which play an important role in the adherence in diseases like glaucoma. The CPG should have an adequate assessment of a wide variety of procedures so that they can be adapted in a diverse way in other countries.
New evidence about MIGS devices is available34,35, for instance high frequency deep sclerotomy36 or excimer laser trabeculotomy37. CPGs missed out recommendations about these devices and about several trabecular low cost-procedures not financed by industry, like Bent Ab Interno Needle Goniectomy (BANG) or Gonioscopy-assisted Transluminal Trabeculotomy (GATT) which will be an alternative to expensive MIGS performed worldwide. GATT, described by Grover and Fellman in 201438, is actually performed in America (USA, Canada and Latin America), Asia, Africa or European countries like United Kingdom, Switzerland, Italy, Romania, Poland, etc. According to results from Dar et al.39, GATT is effective in patients with mild, moderate and advanced glaucoma, hence we need to think about going forward in the glaucoma treatment, change the paradigm, in order to develop a new algorithm from mild to advance glaucoma cases.
In the USA, angle-based stenting increased in 2021 and decreased in 2022, so a “surgical shift from angle-based stenting and filtering surgeries toward goniotomy and canaloplasty” has occurred40, probably related with the high cost of these procedures, which are usually device dependent procedures. Most of the CPG recommend industry developed devices, with scarce recommendations for low-cost or non-industry developed devices. High-cost devices could be more recommended in CPG, due to the potential conflict of interest of GDG members, a common situation in several MIGS consensus published in the last years, developed with industry support but reported by authors as “no conflict of interest”. Mooghali et al. reported that financial relationships with industry are common among US authors of CPG and it was frequently not accurately disclosed41. Nguyen et al. reported that more than half of GDG with reports of no financial disclosure had payments reported by industry42. So, an adequate critical appraisal should be performed to evaluate a paper43, especially when assessing a CPG10, preferably using appraisal tools and considering that a non-transparent conflict of interest (COI) declaration might affect recommendations and quality44.
Only NICE IPG guidelines and 4 assessed HTA included in their evidence tables a detailed COI of all the authors, detailing the type of COI when assessing each study. Evidence supporting MIGS is diverse, most of them being observational studies, and few of them RCT, making it difficult to establish recommendations based on low level evidence. When using a GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, strong recommendations can result from low/very low certainty of evidence45. Most available MIGS clinical trials were sponsored by industry, so this represents high certainty studies with an important bias, which can downrate to low certainty; or an observational study with no bias and large effect, can be uprated to a high certainty45. When making recommendations, these issues should have been considered by GDG of CPG addressing MIGS, also including judgments about the balance of benefits and harms of the procedures.
The MIGS safety profile and long-term effects, as with other innovative glaucoma surgeries, are critical for surgeons and patients. Most of the available studies about innovative glaucoma surgeries examine data related to harms and adverse events, but they do not use a validated instrument for reporting the severity46. Stringa et al. (2022) published a list of glaucoma surgery complications with definitions, aiming to unify the criteria for performing and reporting complications after glaucoma surgery, and thus allow the comparison between techniques47(EGS-SI5: Chap. 7). These standards result in more relevant, valid and reliable information. Also, the standards presented by EGS-SI for reporting of studies will be useful to achieve high quality evidence, improving its implementation.
The need to establish standards for performing studies with MIGS is very important. The “World Glaucoma Association” published a guideline for the design and conduct of glaucoma surgical trials48, however the adherence was low for MIGS trials49. EGS-SI established relevant standards for the analysis and reporting of observational or experimental studies about MIGS, to define the comparable outcomes between studies and complications, which will lead to the comparison of different techniques in the future.
Probably, MIGS will be the first surgical procedure instead of subconjunctival surgery in mild or moderate cases to preserve conjunctiva or improve drug-related dry eye, taking in consideration a careful patient selection, stage of the disease, duration of antiglaucoma medication use, age and comorbidities as a way to ensure success. Low-cost MIGS like GATT, BANG and others will become popular in developing countries and will turn out to be the first choice for conjunctiva-sparing surgery. In advanced cases with special conditions, some MIGS or MIBS will be chosen according to the most recent evidence in order to start with a minimally invasive approach.
Finally, little has changed since 2018, when Michaelov et al. performed a systematic review of CPGs related to glaucoma in adults and evaluated the coverage of MIGS devices and procedures which was sparse, non-specific and in many cases absent50. This makes the CPGs a suboptimal source to guide physicians and health policy makers.
In summary, MIGS is a relevant topic that has not been adequately addressed in terms of updated evidence, available procedures, and recommendations in open-angle glaucoma CPG or MIGS procedures CPG.