Improvements in technique are delivering on promise of improved graft survival

Roibeard O’hEineachain

Posted: Sunday, April 1, 2018

Bruce Allan FRCS

Adoption of the Descemet’s-baring big-bubble technique appears to improve the short-term survival of deep anterior lamellar keratoplasty (DALK) grafts, raising hopes of lifelong graft longevity even in young keratoconus patients, said Bruce Allan FRCS, Moorfields Hospital, London, UK.

“The key message here is that if you have good technique you will have good results,” Dr Allan told the 22nd ESCRS Winter Meeting in Belgrade, Serbia.

DALK and penetrating keratoplasty (PK) appear to perform equally well in terms of visual outcomes, he noted. However, DALK has several theoretical advantages over PK. Since it leaves the host endothelium intact, DALK reduces the risk of immune rejection and endothelial cell loss and should therefore extend graft longevity potentially for the life of the patient.

Registry studies show that PK grafts have a good survival rate during the first 10 years of around 90%, but by 20 years the survival rate drops to around 50% and by 23 years to 17%. Moreover, second and third penetrating grafts have a 10-year survival rate of only around 50% and 33% respectively.

Therefore, keratoconus patients who undergo penetrating keratoplasty are at a greater risk of corneal blindness in their later years, since they generally undergo their first graft when they are in their 20s.

Accelerated endothelial cell loss
The reasons for graft failure following PK procedures include not only immune rejection but also an accelerated endothelial cell loss. In contrast, although there is some endothelial cell loss during the first six months following DALK procedures, thereafter the rate drops to normal physiological levels, as occurs with phacoemulsification. On that basis, one could extrapolate that a successful DALK graft could last the lifetime of a young patient, compared to the 17-year median survival of PK grafts, Dr Allan said.

However, what the registry studies have actually shown is that DALK has historically had a poorer graft survival in the short term, with 12% of DALK grafts failing in the first three years in the Australian registry and similar results in the UK (OTAG) database. The principal causes for failure of DALK grafts include perforation, persistent double anterior chambers and fibrosis in the stromal interface. Immune stromal rejection can also occur, and although it is usually easy to treat, it can cause neovascularisation and graft failure.

Nonetheless, Dr Allan pointed out that the historic nature of the registries should be taken into account when considering these findings. The data covers the early years of DALK surgery, when surgeons primarily used deep stromal dissection and when the precision of surgery and the understanding of the cornea’s lamellar anatomy were less advanced than today.

Since that time, the DALK technique has evolved considerably, particularly with the advent of Descemet’s membrane-baring techniques like the big-bubble technique, introduced by Mohammed Anwar MD in the early years of the current century. As data accumulates, DALK with the newer techniques appears to be on an equal footing with PK in terms of early graft survival.

For example, in a single-surgeon series of 158 patients undergoing the big-bubble DALK technique, the failure rate at four years was only 2%, and in a multi-surgeon study at Moorfields involving 350 cases the rate was 3% at three years.

“Now that we understand the techniques better we are getting better early results, and I think that is the key to understanding why the registry data which is quite historic is showing relatively poor results for DALK,” he explained.

Dr Allan noted that the air-reflection manual dissection approach, introduced by Dr Gerrit Melles in the late 1990s, is still very useful in some cases, particularly when there is a scar in the posterior stroma. It involves using an air bubble in the anterior chamber to create a mirror image of the dissector blade. The apparent width of a dark band between the leading edge of the blade and its bright reflection is twice the residual stromal thickness. The technique has also been used to help locate the cannula tip deep in the corneal stroma for the big-bubble technique.

Regarding the big-bubble technique itself, he notes that he and his associates have developed a variant they call the “mini-bubble technique”. Inspired in part by Harminder Dua’s description of the pre-Descemet’s layer anatomy, it involves using the femtosecond laser to create a mushroom graft with a 6.0mm Descemet’s membrane baring optical centre and a 9.0mm outer diameter.

He noted that perforations during the big-bubble technique generally occur in the periphery as the bubble extends outward to 8.0mm. The pre-Descemet’s layer inserts into the stroma with about 6-to-8mm diameter. The narrow optical zone of the mini-bubble dissection respects the anatomy of the pre-Descemet’s layer, and the 9.0mm graft provides good optical quality and should help prevent late ectasia resulting from continued thinning of the host-side corneal periphery, which commonly occurs decades after conventional 7.5-8mm diameter PK.

He added that the technique also has the advantage of being easy to perform and that procedure could still be feasible in corneal surgical centres that don’t have femtosecond lasers, since the laser part of the procedure could be carried out at a centre that does have the laser.

“You’ve heard of pre-cut donors, I think in the future we may be seeing pre-cut patients,” Dr Allan concluded.

Bruce Allan:

Caption information: The donor cornea is supported on an artificial anterior chamber filled with air to facilitate applantation and laser cutting shown here using the J&J iFS femtolaser. Drying excess fluid before application facilitates accurate visualisation of the application meniscus; The air injection cannula is introduced into the deep stroma in the 6mm central ‘mushroom stalk’ zone of the host cornea prior to air injection and big bubble formation; Because the pre-Descemet’s layer inserts into the stroma at 6-8mm diameter, bubble formation often covers the entire 6mm-diameter central zone; The overlying stroma can be removed relatively easily along the track of the 6mm posterior side cut to expose the pre-Descemet’s layer in the central host cornea;After removal of the donor Descemet’s membrane, the donor cornea is washed in balanced salt solution and placed ready for fixation with 10/0 nylon interrupted sutures; Topical steroid drops are tailed over slowly in the first four months post surgery. Rejection reactions, as seen with mild superficial stromal haze here, generally respond easily to further topical steroid treatment