We found that misalignments of internal GHIs existed in both postsurgical groups, similar to those in previous reports.12,13 Smoothness of the anterior GHI can result from several factors. First, the surgeon can align the epithelial surface of a corneal wound under direct vision during an operation. Other factors include suture traction and the powerful regeneration capacity of corneal epithelium. It has been reported that posterior GHI discontinuity exists universally, but related studies are very limited.13 Lang et al.19 found misalignments of the DM layer in 22 eyes in post-mortem examinations of 25 patients (30 eyes) who had undergone PK. Kaiserman et al.12 reported more post-PK internal graft-host malappositions (76.4%) in keratoconic patients compared with those who received corneal transplantations for other corneal diseases (50%). For keratoconic patients, the higher probability of irregular wound healing might be due to uneven thinning of the cornea before surgery. In our study, 58.3% graft-host junctions were misaligned. The major reasons for the relatively low incidence of misalignment may be the expertise of our experienced surgeons and the use of equal graft-host size. Moreover, unlike previous studies, we enrolled both post-PK and post-DALK patients. The different healing processes of these two procedures might account for the discrepancy in misalignment rates among studies.20
Until now, there have been conflicting opinions about the causes of postoperative astigmatism; these include small intraoperative trephinations, uneven suture tension and graft-recipient misalignments.8,11 Limberg et al.15 proposed that imprecise graft-host matching might result in astigmatism of about 4 to 6 diopters.1 Kaiserman et al.11 reported slight misalignment-associated astigmatism after PK. Jhanji et al.17 categorized the alignment patterns as step and ledge, but failed to describe the relevance of malappositions to postoperative visual outcomes. However, they proposed a theory that an oversized graft would affect the GHI alignment due to the curled shape of the internal surface of the larger graft. In the current study, graft and host beds were prepared isometrically in all cases so size difference was not an issue. Suture tension within each case proved to be almost even, based on the symmetry of postoperative corneal morphology under AS-OCT observation.
Referring to lamellar keratoplasty, the GHI manifest as a moderate-to- highly reflective interface in AS-OCT images.18 However, the incision depth of corneal stroma in our DALK procedure virtually reached the DM layer. Hence, the very thin residual stroma made the AS-OCT cross-sectional images from the PK and DALK groups very similar.18 In our study, the PK group had better logMAR BCVA than did DALK group [(0.25±0.24) vs. (0.47±0.20), P = 0.002] despite similar astigmatism. This is probably due to the shorter postoperative recovery time in the DALK cohort, resulting in thicker junctional graft, with the consequent irregular or optically less clear GHI resulting in lower visual acuity. There have been different opinions about the relative merits of these two surgeries for years. However, there was strong evidence, from a register of controlled trials, suggesting better logMAR BCVA at ≥ 6 months with PK in a recent systematic review.4 Our results concur with that conclusion.10 The more severe SE and DS results in our study might be attirubuted to the relatively worse keratoconus and higher degree of myopia before surgery in our patients.2
Post-keratoplasty alignment patterns can be classified into four basic types: regular apposition, step, protrusion and gape. Moreover, graft step and host step are subtypes of step, while hill and tag are subtypes of protrusion.12 Studies have shown that various preoperative corneal pathologies influence the wound alignment patterns.12,21 Sung et al.13 used AS-OCT to observe the posterior surface of corneal wounds from 13 post-PK keratoconic eyes, and found 78.8% had malapposed junctions, including 22.1% with gape, 22.1% protrusion and 34.6% step. Among the 360 graft-host sections, confined to only keratoconic eyes in the current study, the most common malapposition was graft step (122 cases, 33.9%). Since it has been reported that preoperative corneal pathology can influence the graft-host apposition patterns,14,16 we hold the opinion that asymmetrical pre-operative thinning of the cornea in different disease stages caused increased graft step numbers, because the normal corneal grafts from donors were generally thicker than the recipient beds, which had already thinned.
GHT represented the contact area between the graft and recipient bed. Generally, step and gape significantly reduced GHT, whereas hill increased GHT. In the current study, tag pattern also slightly increased GHT. “Tag” refers to a small piece of DM layer protruding from the corneal wound, while “hill” is a protrusion of both the DM layer and deep corneal stroma.12,13 Hence, we think that tag should increase GHT, but only to a very limited extent.
In present study, various correlations between visual outcomes and characteristics of the corneal alignment patterns were specifically evaluated and quantified. Generally, we found the malappositions that decreased GHT significantly increased the postoperative SE and DS. However, the decreased GHT lowered logMAR BCVA. We speculate that expansion of GHT might enhance stability of the corneal wound, and thus reduce the postoperative SE and DS. However, logMAR BCVA increased slightly with GHT in some unknown way, which needs further exploration. SE and DS significantly increased under the influence of F (step), F (graft step), Pm, Tg, and |Tg-Th|. Specifically, Astig value and SE both showed a slight tendency to increase along with increments of Sm. We speculate that F (step), F (graft step) and Pm may be the major factors responsible for post-keratoplasty ametropia. Moreover, the relationships between |Tg-Th| and visual outcomes indicated that larger graft-host disparity might lead to more-serious ametropia. Hence, we assume that the thinner the recipient bed is, the worse the visual outcomes will be. The increase in graft thickness mainly occurs shortly after surgery, because of tissue edema; hence, this could explain the increase of logMAR BCVA, SE, and DS with Tg, because most cases were observed shortly after operation. Sung et al.13 evaluated the characteristics of GHI after PK using AS-OCT and reported that the graft-host thickness disparity, which closely related to the wound alignment state, showed a positive correlation with keratometric astigmatism (r=0.56, P<0.01). Kaiserman et al.12 analyzed 204 post-PK graft-host sections from 27 eyes, and found that Sm correlated negatively with postoperative SE (r=-0.2, P=0.02) and positively with postoperative DC (r=0.26, P=0.006). Although the correlations were slight, Sm could explain, in part, the astigmatism and ametropia. Herein, Sm increase the degree of astigmatism, if only to a minor extent.
Our study has several limitations. Because it only represented a single-center experience, with relatively few subjects, we may have missed some statistical conclusions that might otherwise have been significant. Next, the study subjects were restricted only to keratoconic patients, so it may not be possible to extrapolate from our results to cases with other corneal diseases. Moreover, we unavoidably missed some information about internal GHIs because data for only eight positions per eye were acquired within a raster scan.
We verified the widespread existence of internal graft-host malappositions using AS-OCT and quantified the relationships between GHI characteristics and visual outcomes in postoperative keratoconic patients for the first time. GHT increased in protrusion alignment and decreased in step and gape patterns. F (step), F (graft step), Pm and |Tg-Th| influenced SE and DS positively. Central corneal keratometric astigmatism increased along with Sm increment. LogMAR BCVA rose with increasing GHT and Tg.