Dr Gordana Sunaric Mégevand 

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When Cairns and Watson first described trabeculectomy in 1968, it was the only surgical procedure on offer for patients with progressive 

 or those unable to use topical medication.

 In recent years, precision—or personalised—medicine has emerged as a new and appealing concept to meet the need for individualised patient management that integrates a patient’s specific data such as clinical, lifestyle, genetic and other biomarker information.

With respect to glaucoma surgery, the concept of personalised management is extremely relevant because we have to adapt not only to different patients—their age and life expectancy, potential systemic diseases, psychological state and social environment—but also to each individual eye with its specific stage of disease, the initial untreated intraocular pressure (IOP), optic nerve susceptibility and the presence of other potentially relevant risk factors.

 Today, we have a wide range of different procedures that can be adapted to a patient’s individual profile and to the surgeon’s experience.

Recent research has focused on combining deep clinical phenotyping with genomics, proteomics and metabolomics in order to find new biomarkers that could help stratify patients at risk of scarring.

 This approach is promising and will certainly bring new opportunities to the personalisation and choice of surgical therapy.

Over the years, trabeculectomy has evolved in terms of safety and efficacy, particularly with the use of antimetabolites, representing today the gold standard to which all other surgeries are compared. Well-performed trabeculectomy with antifibrotics reaches an overall success rate of 87% at 2 years

 and performs better than tubes as primary surgery.

 When reaching postoperative IOPs in the low teens, levels targeted in particular for advanced disease, the technique has been reported to reduce the rate of progression on longer follow-up.

However, there are cases with a higher risk of failure or complications following trabeculectomy, particularly with the use of mitomycin-C or 5-fluorouracil. Patients with multiple operations, secondary glaucoma or complex anterior segment dysgenesis as well as aphakia would be better candidates for tubes,

 whereas cases with advanced glaucoma or highly myopic eyes or young male patients with myopia should be offered a less-invasive approach in order to reduce complication rates.

Precision management to revolutionise glaucoma diagnosis and treatment

Non-penetrating surgery is a reasonable alternative to trabeculectomy for primary and secondary open-angle glaucoma. It significantly reduces postoperative complications while providing good long-term IOP control.

Deep sclerectomy and canaloplasty with 360° probing of the Schlemm’s canal can be performed as standalone procedures or in combination; however, in general these interventions are performed by only a handful of surgeons because of their surgical complexity or difficulty and the long learning curve needed to master the techniques. In addition, these procedures are rather time consuming in the learning phase, which is usually not compatible with a busy outpatient surgical theatre.

A new group of very heterogeneous surgical modalities has emerged recently: minimally invasive glaucoma surgery (MIGS) is supposed to be minimally or micro-invasive thus safer and quicker than conventional glaucoma surgery. This makes these procedures particularly appealing for early and moderate disease and for younger, professionally active patients who seek few complications and a quick recovery. In addition, MIGS is supposed to lower the burden of medication, which appears to be an important factor for most patients with mild to moderate glaucoma, for whom most MIGS devices are approved.

Endoscopic cyclophotocoagulation adds cumulative advantage to MIGS

Although the hope generated by these innovations for both patients and surgeons is indisputable, there should be a clear definition of the real value, position and indication of these new techniques based on scientific, medical and economic arguments, and we are not there yet. There are several unmet needs with MIGS and other devices that are often wrongly referred to MIGS, discussed as follows.

Different devices and techniques are coined MIGS although each has physical and surgical particularities that affect the associated learning curve, the invasiveness of the procedure and, of course, its safety and efficacy. The term ‘micro-invasive or minimally invasive’ is based on the notion of the extent of conjunctival dissection: only techniques and devices with minimal scleral and conjunctival manipulation should be named MIGS.

Devices that need substantial conjunctival preparation, additional use of high concentrations of mitomycin C or invasive postoperative manipulation performed in operating rooms should not be named MIGS. This is in line with the fifth edition of the EGS Guidelines: MIGS devices are defined as those that enter the anterior chamber, targeting the trabecular meshwork, Schlemm’s canal or subchoroidal space without manipulating the conjunctiva and sclera. Thus, the Xen and PreserFlo devices are excluded.

We need more robust studies to compare MIGS techniques and devices with conventional surgeries and with one other. MIGS devices have been used in combination with cataract surgery in some studies, thereby confounding the IOP-lowering effect of the device and the effect of phacoemulsification. Others carry biases that range from conflict of interest, selection and performance bias to detection, attrition and reporting biases.

Study examines pairing phacoemulsification with implantation of stents

Contradictory results reported in some publications may affect the credibility of the authors and companies: in one article in which the authors report 22 cases (11.9%) of reformation of the anterior chamber, they state that only three cases had hypotonia and no cases had a narrow anterior chamber.

In addition, only a minority of the published studies on MIGS respect the World Glaucoma Association guidelines for reporting results in relation to compliance, methodology, ethics and statistical reporting. A recent publication in a journal with a high impact factor reported the pleasant sensation of the ocular surface stated by the five patients included in the trial but omitted to mention postoperative IOP as one of the most important endpoints.

A poorly established cost-effectiveness balance

The author of a recent publication stated that some devices increase the cost of cataract surgery without any benefit, and that phacoemulsification alone is better than most MIGS in early-stage glaucoma, giving a drop in IOP that can last for several years.

 The cost of MIGS devices in most European countries is around 1,000 Euros, far higher than the usual cost of surgical glaucoma management.

Monitoring blood reflux during gonioscopy in glaucoma

MIGS and other new devices would be cost-effective in cases where they would allow for complete and prolonged cessation of topical drugs. Two recent Cochrane reviews stated that the iStent (Glaukos) and Hydrus MIGS devices reduce the need for drugs to some extent but do not erase the need for medication completely.

 In addition, the number of postoperative visits and manipulations as well as reoperations is not reduced, in particular for those devices relaying on subconjunctival blebs (Xen gel stent, Allergan and PreserFlo microshunt, Santen).

It is common and highly desirable in our profession for key opinion leaders (KOLs) and societies to advise companies on new developments and to promote their utilisation. However, some suspicion can arise when, during industry-sponsored meetings or publications, a KOL praises devices/MIGS from different manufacturers with the same enthusiasm: this may raise the question of interests other than scientific. Transparency at all levels is of the utmost importance for the sake of scientific rigour and patient safety.

The pseudo-ease of the technique praised by the manufacturer, in particular when combined with phacoemulsification, may lead to misinterpretation by ophthalmologists and bring confusion between treating a disease (glaucoma) and treating its risk factor, ocular hypertension. Most MIGS and subconjunctival devices lower IOP to the mid-teens and are therefore indicated for early or moderate glaucoma. However, in many such cases, instead of the combined phaco-MIGS surgery, a simple lens extraction would have been sufficient to lower the IOP.

Indeed, a recent article based on Medicare data reported that 41.2% of the operated patients had not received IOP-lowering treatment before the combined phaco-MIGS surgery and 29.5% had received only monotherapy.

 This seems to disregard the usual algorithm that indicates combined surgery when the IOP is not well controlled with topical treatment, the disease is advanced or progressing, or the patient experiences intolerance to topical medication.

Considering the best surgical approach in angle closure patients

It would be of interest to know whether the 70.7% of these reported combined procedures had solid indications. It is a fact that fees for surgery in different countries and continents vary significantly when MIGS is added to cataract surgery. On the other hand, it will be of interest to establish whether MIGS in the long run will be able to lower the rate of progression of the disease while reducing IOP only marginally.

Although innovation goes along with anecdotal reports, it is important to validate the technique in a controlled manner before accepting the results. One example is the association of a Xen device with a traditional tube in cases of congenital glaucoma.

 Further studies are needed to validate this approach.

We are certainly advancing in the process of a personalised approach to glaucoma surgery; one size cannot fit all. The many options available today allow us to better stratify surgical treatment according to the stage of the disease, the age of the patient and the presence of other systemic and/or local conditions as well as the expectations of each patient.

Although the hopes of the patients and the target of the clinician are the same, the expression of the requirements may differ. For a patient, the main priorities may include keeping their independence and their driving license as well as using the least possible topical medication, whereas the surgeon’s priorities are target IOP, reduced disease progression and the safety of the procedure.

The aims are complementary and it should be possible to achieve both in a particular patient via a customised intervention. However, the choice of surgical treatment should be evidence-based, in particular with new techniques, and this can only be achieved by performing robust randomised controlled trials as well as analysing patient-related outcomes to confirm the validity and indication of each of the new techniques compared with conventional glaucoma surgery.

Despite the disappointments, market withdrawals of several devices and their current limitations, MIGS still represents a reasonable hope for some glaucoma patients with well-defined indications. Indeed, MIGS has brought new options to the management of glaucoma and has revived interest in the disease not only for glaucoma specialists but also for general ophthalmologists.

However, we should not sacrifice good practice and evidence for misplaced interest or misjudgement. In the interest of our patients, we must retain evidence and transparency; although all innovation is paved with difficulty, the effort is worthwhile.

Further steps to improve precision in surgical management of glaucoma may come with new diagnostic assessment tools of the outflow pathways, with better knowledge of genetic influence of the healing process as well as with the use of big data and artificial intelligence. However, although fascinating and expanding, these novelties are not yet designed for daily clinical practice.

1. Cairns JE. Trabeculectomy. Preliminary report of a new method. 

2. Bell K, Gramlich OW, Von Thun Und Hohenstein-Blaul N, et al. Does autoimmunity play a part in the pathogenesis of glaucoma? 

3. Yu-Wai-Man C, Khaw PT. Personalized medicine in ocular fibrosis: myth or future biomarkers. 

4. Sunaric Megevand G, Bron AM. Personalising surgical treatments for glaucoma patients. 

5. Kirwan JF, Lockwood AJ, Shah P, et al. Trabeculectomy in the 21st century: a multicenter analysis. 

6. Gedde SJ, Feuer WJ, Lim KS, et al. Treatment outcomes in the primary tube versus trabeculectomy study after 3 years of follow-up.

7. Iverson SM, Schultz SK, Shi W, et al. Effectiveness of single-digit IOP targets on decreasing global and localized visual field progression after filtration surgery in eyes with progressive normal-tension glaucoma. 

8. Mataki N, Murata H, Sawada A, et al. Visual field progressive rate in normal tension glaucoma before and after trabeculectomy: a subfield-based analysis. 

9. Bissig A, Rivier D, Zaninetti M, et al. Ten years follow-up after deep sclerectomy with collagen implant.

10. Grieshaber MC, Peckar C, Pienaar A, et al. Long-term results of up to 12 years of over 700 cases of viscocanalostomy for open-angle glaucoma. 

11. Le JT, Mohanty K, Bicket AK, et al. Identifying outcomes that are important to patients with ocular hypertension or primary open-angle glaucoma: a qualitative interview study. 

. 4th ed. Savona, Italy: Publicomm; 2020.

13. Agrawal P, Bradshaw SE. Systematic literature review of clinical and economic outcomes of micro-invasive glaucoma surgery (MIGS) in Primary open-angle glaucoma. 

14. Schlenker MB, Gulamhusein H, Conrad-Hengerer I, et al. Efficacy, safety, and risk factors for failure of standalone ab interno gelatin microstent implantation versus standalone trabeculectomy. 

15. Schultz T, Schojai M, Kersten-Gomez I, et al. Ab externo device for the treatment of glaucoma: direct flow from the anterior chamber to the ocular surface. 

16. Quigley HA. 21st century glaucoma care. 

17. Le JT, Bicket AK, Wang L, Li T. Ab interno trabecular bypass surgery with iStent for open-angle glaucoma. 

18. Otarola F, Virgili G, Shah A, et al. Ab interno trabecular bypass surgery with Schlemm’s canal microstent (Hydrus) for open angle glaucoma. 

19. Wang SY, Singh K, Stein JD, Chang RT. Ocular antihypertensive medication use after iStent implantation concurrent with cataract surgery vs cataract surgery alone in a large US health care claims database. 

20. Arad T, Hoffmann EM, Prokosch-Willing V, et al. XEN-augmented Baerveldt implantation for refractory childhood glaucoma: a retrospective case series. 

Dr Gordana Sunaric Mégevand is medical director of the Florissant Eye Centre and director of the Eye Research Centre A de Rothschild in Geneva, Switzerland. She has no financial disclosures to make.

Dr Alain Bron is professor of ophthalmology and leads the Glaucoma Unit at the University Hospital in Dijon, France. He acts as consultant for Aerie, Allergan, Bausch & Lomb, Santen and Théa.

Articles

Minimally invasive glaucoma surgery (MIGS) is appealing to glaucoma patients and surgeons; however, it should not be adopted without further high-quality research and careful reporting. Selection of the appropriate treatment for individual patients must be evidence based.

Author | Dr Gordana Sunaric Mégevand

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Personalising glaucoma surgery: The role of MIGS