Deep anterior laminar keratoplasty (DALK) consists of replacing the anterior corneal tissue to a depth close to the Descemet’s membrane (DM) by a donor tissue. The integrity of the eyeball and the recipient's endothelium – which must be healthy – is respected, together with DM and, depending on the case, some of the deeper stromal lamellae.

Depending on whether or not the stroma has been completely separated from DM, a distinction has been made between descemetic and predescemetic techniques^1,2. Since the discovery of the so-called predescemetic layer of Dua (PDL), we know that this remains linked to DM in the descemetic techniques. In the predescemetic ones, in addition to the DM/PDL, it remains in the bed a more or less thin sheet of residual stroma. The maximum acceptable limit for this is not completely defined, but it is usually accepted that it should not exceed 10% of the total corneal thickness (50-60 μm).

The indications of DALK can be considered in two senses: in relation to the technique itself – the problems it is able to solve – and in comparison to penetrating keratoplasty (PK) and superficial anterior lamellar keratoplasty (SALK). The latter can be considered in lesions up to 200 μm deep. The advantages and disadvantages of DALK with respect to PK (table 1) will determine not so much the indications as their application by a particular surgeon. While most of the advantages of DALK are objective (extraocular procedure, respecting the endothelium, etc.), its drawbacks refer to the technique and skill of the surgeon. Only in the field of visual results and certain risks (relapse, dystrophy, interphase invasion) do objective elements of comparison persist. Regarding vision, it is important to specify the technique (descemetic or predescemetic) when making comparisons. But in case of equality, the objective advantages of DALK give it a clear primacy.

Stromal dystrophies, by their nature, tend to recur in the graft over time, although some, such as granular dystrophy, usually do so at superficial levels. The presence of the interphase and the persistence of the receptor stroma also influence the DALK. With macular dystrophy, the first results showed a relapse rate after DALK clearly superior to PK³, although this has been questioned, together with greater stability of the ocular surface and fewer postoperative complications with DALK⁴. In this dystrophy – which affects all corneal layers including the endothelium – achieving a clean DM seems an essential requirement, since leaving residual stroma can compromise the visual result and favor an early relapse (Figure 1).

In cases of corneal leukomas after herpetic keratitis, the risk of recurrence is never abolished, even with prophylactic oral antiviral treatment for prolonged periods. However, in cases treated with DALK, recurrences appear to be less frequent than in PK cases⁶. In the face of possible recurrences of both dystrophies and herpetic keratitis, a DALK has the advantage of being able to replace the graft simply and safely (Figure 2).

In advanced keratoconus (not accessible to conservative treatments), in the past a main indication of PK, the current trend points to DALK as the treatment of choice. Several studies have shown that there are no statistically significant differences in terms of graft survival, visual acuity (VA) and refractive outcome^7,8. The PK would be reserved for cases with deep scars or a history of hydrops, which pose a high risk of perforation during the dissection of the DALK.

Tectonic purpose: in those diseases in which an important loss of the corneal parenchyma occurs, until the descemetocele, with risk of perforation but without it having occurred. Includes situations after non-superficial therapeutic resections (table 2).

Therapeutic purpose: as a treatment of infectious "hot" keratitis, in order to eradicate the infectious agent located in the corneal stroma and resistant to medical treatment. It is essential that the infection does not affect the deep layer that we are going to leave behind. Because it is an extraocular procedure, DALK avoids the risk, associated with hot PK, of provoking the intraocular extension of the infection. Cases of treatment of active bacterial⁹, herpetic¹⁰, fungal¹¹ and Acanthamoeba¹² processes have been reported.

PATIENT SELECTION

When selecting the patient for a DALK we must assess the following aspects:

- State of the endothelium: If the endothelium is not healthy, a DALK loses much of its meaning. It is important to evaluate its condition even in conditions where it is not obvious that it is affected, such as in keratoconus or stromal opacity (e.g. a band degeneration may be the sign of a latent endothelial failure).

- Depth of the lesion: Especially in keratoconus, deep scars can be a sign of old hydrops, which poses a great risk of rupture during the dissection of DM. Although this is reduced with a predescemetic technique, the visual prognosis will be more limited. Before a post-traumatic scar, determine if it can be penetrating at some point. Superficial scars (<200 μm) can be the objects of a SALK.

- Condition of the ocular surface: If there are alterations such as dry eye, active blepharitis, malposition of the eyelids, etc., they should be resolved or stabilized before surgery, as they may delay epithelization or cause other superficial complications. In the presence of limbal insufficiency (S. Stevens-Johnson, pemphigoid, aniridia, neurotrophic keratopathy, severe dry eye, chemical injuries, etc.), the risk of failure of a DALK is not less than with PK. The vascularization of the recipient cornea must be treated previously or simultaneously, since it involves a risk of stromal rejection or invasion of the interface.

- Impact of the pathology on the technique: There is great disparity in the visual results of DALK, especially when compared with those of PK^7,8,13-16. This can be due to several factors: on the one hand the surgical techniques, on the other the pathologies. When comparing the Anwar technique with that of Melles, one study found no differences in VA, refraction, aberrometry, corneal thickness or endothelial count; only the first presented better contrast sensitivity¹⁷. In another study, the pre-descemetic technique improved the parameters of corneal biomechanics versus the descemetic one¹⁸. The best visual results are achieved when the dissection reaches the DM/PDL, leaving no residual stroma. The possibility of achieving this depends on the indication: it is easier in advanced keratoconus, chemical or thermal burns, stromal dystrophies and herpetic keratitis; in moderate keratoconus and in scars after bacterial keratitis, it is more difficult¹⁹. This would be due to a greater adherence between the DM/PDL and the posterior stroma in the second group. In cases of burns, herpes and dystrophies, there is usually a certain corneal edema that would facilitate this separation²⁰.

All of the above can influence the variability of the results. In general, better VA is obtained in keratoconus compared to other indications such as deep stromal scars²¹. In those, preoperative factors have been identified, such as greater axial length and greater corneal curvature, and postoperative factors such as early removal of sutures, which are associated with poorer refractive results²².

PREPARATION OF THE PATIENT

The purpose of the preoperative study of the patient is to verify that the indication and selection have been correct, to exclude new data that may suppose contraindications or risk factors and to decide if the patient will need any special care or treatment, be it prior or postoperative, or if foresees some special operative maneuver. In addition to a detailed clinical history, the clinical and complementary examinations should be attentive to the characteristics of the cornea, especially to confirm the diagnosis and review the aspects mentioned in the preceding section.

Slit lamp examination: Determine the extension and depth of the corneal opacities (Figure 3). Evaluate if they only affect the stroma or if the DM may be damaged: locate possible breaks or lines of fibrosis at its level that could break during surgery. Locate the areas of greatest ectasia and/or thinning (Figure 4). If there are corneal neovessels, assess their caliber and depth to decide if they should be treated previously or in the same surgical act. Assess the condition of the lens and the possible indication of a combined procedure.

Optical coherence tomography (OCT) of the anterior pole: It allows visualization and measuring of the depth of the opacities (Figure 5), to specify the areas of thinning by topographic pachymetry and to measure the corneal diameters, to plan the dimensions of the graft and depth of trepanation. In the presence of dense opacities that prevent biomicroscopic observation, OCT can inform us of the existence of anterior synechiae or other abnormalities in the anterior chamber^23,24. The OCT systems of spectral technology (Optovue, Casia) have higher resolution and some also perform topography, even in corneas whose irregularity prevents it with other devices.

Corneal topography and Scheimpflug tomography: While the classic Placido systems measure only the anterior surface of the cornea, the tomographs (Orbscan) add the posterior surface and therefore the pachymetric map, and the dimensions of the cornea (white to white). Those based on the Scheimpflug camera (Pentacam, Galilei, Sirius) have better resolution and other functions such as corneal and crystalline densitometry. This helps to measure the extension, depth and density of the opacities (Figure 6). The Pentacam has a program for the detection and classification of keratoconus in grades 1 to 4 (Figure 7). Following its pachymetric map to plan the "big bubble" technique, a greater percentage of successes has been obtained²⁵.

Endothelial specular microscopy: A low endothelial count, below 1000 cells/mm², is a contraindication for DALK.

Confocal microscopy: In cases of active or past inflammation, it allows the cornea to be scanned to rule out amoebic or fungal elements and assess their depth. It can be effective to study the endothelium in patients in whom it is not possible to visualize this with the specular microscope – especially in borderline cases in which we doubt between a DALK or a PK depending on its condition. In the postoperative period it allows to study the graft-host interface and its possible interference in visual recovery².

State of the ocular surface and annexes: Assess lacrimal and palpebral functions. If there is a mild to moderate dry eye, it should be stabilized prior to the intervention. Likewise, the alterations of the closure or the eyelid function must be corrected before or in combination in the surgery itself. Some may require an additional maneuver, such as partial tarsorrhaphy in the case of lagophthalmos or punctum occlusion in the case of stable lacrimal hyposecretion.

Corneal sensitivity: It is advisable to measure it with an esthesiometer or at least with a cotton thread. In eyes with partial anesthesia, e.g. after herpes, assess associated procedures such as a tarsorrhaphy or an amniotic membrane graft. A total corneal anesthesia can be an absolute contraindication. The possible utility of nerve growth factor (NGF) is still under study.

Limbal insufficiency: Patients who present a partial limbal insufficiency syndrome (LIS) should be treated prior to keratoplasty to improve as much as possible the state of the ocular surface (with artificial tears, autologous serum and other blood derivatives, etc.). In these situations, consider a graft or amniotic membrane patch at the end of the transplant, to help its epithelization. If the LIS is greater than 50%, it must be corrected by limbus or expanded stem cell transplant before addressing a keratoplasty.

Corneal Vascularization: It is one of the best-established risk factors for the rejection of corneal grafts. The Collaborative Corneal Transplantation Study found high risk in case of more than 2 quadrants of vascularization. To this are added surgical factors such as mechanical trepanation and sutures that, by inducing inflammation, generate an imbalance between the angiogenic and anti-angiogenic factors.

In vascularized corneas it is advisable to use independent sutures and remove them as soon as possible. Anti-VEGF agents, subconjunctival or intrastromal (bevacizumab 2.5 mg/0.1ml) and, somewhat less effective, in eye drops (25 mg/ml 2-5 times/day), allow to reduce corneal vascularization previously to the intervention (Figure 8). The antiangiogenic effect of topical corticosteroids is known, especially if they are applied before surgery or in the immediate postoperative period. However, corticosteroids are not considered angio-regressive drugs.

Since the vascular endothelial growth factor (VEGF) only has an effect on the initial growth of the neovessel up to the recruitment of pericytes, anti-VEGF agents are not effective in eliminating already mature vessels. To suppress these, photodynamic therapy, argon or dye laser photocoagulation and fine needle electro-diathermy have been tried. The latter is the one that seems to have been most successful, combined with anti-VEGF²⁶.