Augmented trabeculectomy – The surgical journey and road trip forward

In the 1950s, mitomycin C (MMC) was discovered by Mongolian scientists. It is produced from the actinobacteria Streptomyces caespitosus. Ophthalmic use of MMC dates back to the 1960s. It was used to treat recurrent pterygia in 1969 in Japan. MMC is being widely used in various fields of ophthalmology. It has become the gold standard medication for glaucoma filtration surgeries.[1] In a recent article, the author has reported on visual field changes in patients who underwent augmented trabeculectomy on a long-term follow-up of 2 years.[2] In this commentary, the journey of MMC in augmenting trabeculectomy surgery is highlighted in great detail with other revolutionary alternatives.

The Inception and Establishment of MMC for Trabeculectomy Surgery

Traditionally, trabeculectomy was augmented with MMC-soaked sponges with concentrations of 0.1, 0.2, or 0.4 mg/ml [Table 1], which involves placing a cellulose sponge soaked in MMC at a standard concentration onto the bare sclera for a predetermined duration. Adequate MMC application during trabeculectomy enhances bleb survival and long-term results.[3] Various factors affecting the efficacy of MMC sponge application include the soakage properties of the cellulose sponge, the dosage of MMC, the surface area of application, duration of exposure, and toxic effects of mitomycin on the corneal, limbal, and scleral surfaces. Currently, we are at a crossroads where we are slowly but surely transitioning toward injectable MMC.

Table 1.

Various concentrations of MMC used in practice and its preparation methodology

MMC Concentration	Materials required	Procedure
0.1 mg/ml	2 mg MMC vial, 10 ml syringe, 1 ml syringe	In 10 ml syringe take 2 ml distilled water add to 2 mg MMC Powder (2 mg in 2 ml). In 10 ml syringe take 1 ml of reconstituted solution (1 mg/1 ml) + 9 ml distilled water (1mg/10 ml=0.1 mg/ml). 0.1 ml of the reconstituted solution is taken for usage.
	10 mg MMC vial, 10 ml syringe, 1 ml syringe	In 10 ml syringe take 10 ml distilled water and add to 10 mg MMC Powder (1 mg/ml). In 10 ml syringe take 1 ml of reconstituted solution and add 9 ml of distilled water (1 mg/10 ml=0.1 mg/ml). 0.1 ml of the reconstituted solution is taken for usage
0.2 mg/ml	2 mg MMC vial, 5 ml syringe, 1 ml syringe	In 5 ml syringe take 2 ml distilled water add to 2 mg MMC Powder (2 mg in 2 ml). In 5 ml syringe take 1 ml of reconstituted solution (1 mg/1 ml) + 4 ml distilled water (1 mg/5 ml=0.2 mg/ml). 0.1 ml of the reconstituted solution is taken for usage
	10 mg MMC vial, 10 ml syringe, 1 ml syringe	In 10 ml syringe take 10 ml distilled water and add to 10 mg MMC powder (1mg/ml). In 10 ml syringe take 2 ml of reconstituted solution and add 8 ml of distilled water (2 mg/10 ml=0.2 mg/ml). 0.1 ml of the reconstituted solution is taken for usage
0.4 mg/ml	2 mg MMC vial, 5 ml syringe, 1 ml syringe	In 5 ml syringe take 5 ml distilled water add to 2 mg MMC Powder (2 mg in 5 ml=0.4 mg/ml). 0.1 ml of the reconstituted solution is taken for usage.
	10 mg MMC vial, 10 ml syringe, 1 ml syringe	In 5 ml syringe take 5 ml distilled water add to 2 mg MMC Powder (2 mg in 5 ml=0.4 mg/ml). 0.1 ml of the reconstituted solution is taken for usage.

Injectable MMC: The Redemption

Injectable MMC is an alternate method for mitomycin-soaked sponge application on the bare sclera and has been proven to be a safe and effective method for administering MMC, especially in patients with ocular surface disease.[4-6] Injectable MMC has tremendous advantages over conventional sponge application in the following ways:

1. Direct and diffuse application of MMC promotes less scarring and vascularization of the bleb

2. Need for multiple sponge applications avoids the risk of retained sponges and facilitates equal exposure to the entire scleral surface intended for application

3. The dosage of injection is very less compared to sponges

4. Less time consuming

5. Titratable drug delivery

6. The need for repeated 5-fluorouracil injections is avoided

The Spongy Conundrum for Actual MMC Dose Delivery – The Unpredictability

The sponge application of MMC was introduced back in the 90s, when the surface area of cut pieces of cellulose sponges was variable, along with the soakage of MMC in the sponge, thereby leading to variable delivery of MMC from the sponge. Different delivery materials like polyvinyl alcohol triangular sponges, polyvinyl alcohol fluid wicks, and absorbable gelatinous sponges have been used to soak MMC for delivering the drug during trabeculectomy. Irrespective of the material, variation of dosage remains.

The quantity of MMC in sponges has also been found to be variable among surgeons. The estimated actual dose delivered in a sponge soaked with MMC 0.2 mg/ml varied between 1.9 µg and 17.3 μg.[7] With this unpredictable sponge dosing, there is an increased risk of overdosage of MMC. Irrigation is often used after the delivery of MMC; however, it helps to reduce MMC concentrations only in the superficial scleral layers, with no effect on MMC concentrations in the deep scleral and subscleral layers.[8]

Also, there is unpredictability in the morphology of the blebs due to variable sponge dosing resulting in unfavorable outcomes. However, the morphologic characteristics of the blebs that received injectable MMC imply a more favorable outcome for patients.[9]

Back to Square One – The Quandary with MMC Molecule

Though injectable MMC seems to be taking over, there are limitations remaining due to the short-term and long-term effects of MMC leading to late-term wound leaks, blebitis, hypotony, and even endophthalmitis. To tackle these setbacks, various other methods of trabeculectomy augmentation were ventured into.

Ologen – A Revolutionary Alternative

This porous, porcine, collagen implant had comparable outcomes similar to MMC-augmented trabeculectomy, without major complications. This implant greatly helped in the formation of organized collage fibers within the porous material by providing a scaffold. It helped to overcome the issues faced with antifibrotic agents.[10] However, due to manufacturing issues owing to the unavailability of the raw material after the coronavirus disease (COVID) pandemic, this product has been out of stock in the market currently.

Viscoelastic-Augmented Trabeculectomy – A Practicable Substitute

Recently, viscoelastic-augmented trabeculectomy (VAT) has been suggested and implemented as an alternative to conventional trabeculectomy. It involves the injection of viscoelastic into the bleb and, if required, into the anterior chamber to augment the belt function by preventing postoperative hypotony and bleb fibrosis.[11]

Visionary Outlook – Combining Trabeculectomy with Minimally Invasive Glaucoma Surgery

Minimally invasive glaucoma surgery (MIGS) is taking over the field with its economic and effective approach. Though it has never been practiced before, food for thought would be the augmentation of procedures like trabeculectomy with bent ab interno needle goniectomy (BANG) and Kahook Dual Blade (KDB; New World Medical, Rancho Cucamonga, CA, USA) ab interno trabeculectomy.[12] The rationale being that, along with the trabeculectomy ostium, internal flow can be augmented further by deroofing of the trabecular meshwork with BANG and KDB. However, further multicentric, randomized control trials are needed to validate the safety profile and long-term results of the same.

Conclusion

It is important to walk toward the future with new and alternative methods of complication-free glaucoma surgeries to improve the quality of vision and life for glaucoma patients.