Impact of topographic localization of corneal ectasia on the outcomes of deep anterior lamellar keratoplasty employing large (9 mm) versus conventional diameter (8 mm) grafts

Visual and topographic outcomes of large (9.0 mm) versus conventional (8.0 mm) deep anterior lamellar keratoplasty (DALK) for the treatment of keratoconus (KC) were compared in relation to the different localization of the corneal ectasia (within or beyond the central 8.0 mm). This is a retrospective, comparative case series. Preoperatively, the topographic extension of the conus was calculated by measuring the distance from the geometric center of the cornea and the outermost point of the corneal ectasia (ectasia <8.0 mm, group A; ectasia ≥8.0 mm, group B). DALK was performed using both small grafts (8.0 mm, group 1) and large grafts (9.0 mm, group 2). Best-corrected visual acuity and topographic astigmatism were evaluated preoperatively (T0) and postoperatively after complete suture removal (1 year, T1). Data from 224 eyes of 196 patients (mean age 37.6 ± 15.1 years) were evaluated. Topographic astigmatism improved from T0 to T1 (4.94 ± 2.92 diopters (D) [95% CI, 4.56–5.33] vs 4.19 ± 2.45 D [95% CI, 3.87–4.51], p = 0.001). There was no significant difference in postoperative topographic cylinder between group 1 and group 2 when considering eyes with corneal ectasia <8.0 mm (group 1 A, 4.15 ± 2.19 D [95% CI, 3.64–4.66] vs group 2 A, 3.65 ± 2.13 D [95% CI, 2.92–4.38], p = 0.14); conversely, the difference was significant considering eyes with corneal ectasia ≥8.0 mm (group 1B, 4.74 ± 2.90 D [95% CI, 4.09-5.38] vs group 2B, 3.68 ± 1.94 D [95% CI, 3.10–4.26], p = 0.02). Large 9.0-mm DALK provided better anatomical outcomes compared to conventional 8.0-mm DALK, particularly in eyes with corneal ectasia extending beyond the central 8.0 mm.


INTRODUCTION
According to the last report of the Eye Banking Association of America, penetrating keratoplasty (PK) is the most performed surgical procedure for keratoconus (KC), accounting for about 90% of the total number of corneal transplantations [1].In the last two decades, deep anterior lamellar keratoplasty (DALK) has been introduced as an alternative to PK for eyes affected by KC with a healthy endothelium.This technique involves the selective transplantation of anterior corneal layers preserving the recipient endothelium.The main advantage of DALK is the elimination of the risk of endothelial rejection that is a major cause of graft failure; however, it should be pointed out that visual outcomes do not favorably compare to PK [2][3][4][5][6].The lack of superiority in terms of visual outcomes along with the technical difficulty of the surgery that is poorly standardized and requires a steep learning curve represent the main obstacles to the widespread adoption of DALK.As a matter of fact, it still represents only 1.5% of the corneal transplantations performed for KC in the United States [1].Significant efforts have been made to overcome these issues and novel surgical approaches aiming at standardizing the procedure, minimizing the risk of complications and improving both anatomical and functional results have been described [6][7][8][9][10][11].
Thanks to the elimination of the risk of endothelial rejection, DALK technique offers the possibility to employ larger graft in order to try to reduce postoperative astigmatism, thus improving overall visual outcomes.This is, on the contrary, not possible for PK because the higher proximity to limbus increases significantly the risk of immune rejection and graft failure.It has been recently reported that employing large-diameter (9.0 mm) lamellar grafts may provide better functional outcomes compared to conventional sized grafts of 8.0 mm due to the lower postoperative astigmatism [12][13][14].
We hypothesize that the advantage obtained using largediameter grafts might vary according to the characteristics of the keratoconic cornea, in terms of size and location of the conus [15].Therefore, the purpose of this study is to evaluate the impact of topographic localization of corneal ectasia on 1-year visual and topographic outcomes of DALK employing large (9.0 mm) versus conventional diameter (8.0 mm) grafts.

MATERIALS AND METHODS
In this retrospective, comparative, interventional case series, the anatomical and functional outcomes of eyes affected by KC who underwent DALK between June 2010 and November 2020 performed by the same experienced surgeon (V.S.) at "Magna Graecia" University, Catanzaro (Italy), were analyzed.The study followed the tenets of the 2013 Declaration of Helsinki and was approved by the local ethics committee (Comitato Etico Area Centro, Regione Calabria).A detailed informed consent was provided to all patients undergoing surgery.
The topographic extension of the conus was classified as within (group A) or beyond (group B) the central 8.0 mm diameter measuring the distance between the geometric center of the cornea and the outermost point of the corneal ectasia with keratometric axial power ≥50.5 D (Fig. 1).
To assess the validity of the topographic extension of the conus as a parameter to stage conus characteristics, the correlation between the topographic localization of the conus, spherical equivalent, mean central K readings, minimum corneal thickness, topographic cylinder and BCVA was calculated.
DALK surgery was performed according to the technique previously reported [12] using grafts of conventional diameter (8.0 mm, group 1) from June 2010 to December 2016; afterwards, large-diameter DALK (9.0 mm, group 2) had become our preferred technique of lamellar keratoplasty for KC.Briefly, pneumatic dissection was attempted in all eyes.The bubble formed was classified in type 1 (predescemetic) and type 2 (descemetic) according to the classification reported by Dua et al. [16][17][18].In case of failure, dissection by ophthalmic viscoelastic devices (OVDs) (I.SPACE, Vivacy, Kestrel Ophthalmics, UK) was attempted.In the remaining cases in which the OVD-assisted dissection also failed, manual dissection was executed.Upon successful dissection, donor cornea was punched from the endothelial side with a Barron donor punch (Katena Products, Parsippany, NJ) to the same diameter as the trephination.The endothelium and DM were gently stripped off.The graft was secured to the recipient bed by double running 10-0 nylon sutures in all cases.In all patients, one of the sutures was removed approximately 6 months postoperatively, while the second was removed after 12 months.
A complete ophthalmological evaluation, including all preoperative examinations, was performed postoperatively after the complete removal of the sutures at 12 months (T1).Both intraoperative and postoperative complications were recorded.
Postoperative outcomes were compared according to graft size (groups 1 and 2) and topographic localization of the conus (groups A and B).

Statistical analysis
All data were entered into an electronic database via Microsoft Office Excel 365 (Microsoft Corp., Redmond, WA) and analyzed with IBM SPSS Statistics (version 26.0;IBM, Armonk, New York).BCVA was assessed with a Snellen chart and converted into the logarithm of the minimum angle of resolution (LogMAR) for the purpose of statistical analysis.The Shapiro-Wilk test and the Kolmogorov-Smirnov test were used to determine the normality of data.Paired Student's t test was used to compare variables between preoperative and postoperative time points within the same group of eyes.Independent Student's t test was used to compare variables between different groups, both preoperatively and postoperatively.One-way analysis of variance (ANOVA) was used to determine statistically significant differences for variables between three or more independent groups.Chisquare test was used for the analysis of categoric variables.Univariate and multivariate analyses were performed to evaluate the statistical correlation between topographic localization of the conus, spherical equivalent, mean central K readings, minimum corneal thickness, topographic cylinder and BCVA.Variation inflation factor (VIF) was calculated to exclude multicollinearity.Values are expressed as mean ± standard deviation.All tests were two-sided and a p < 0.05 was considered statistically significant.
Topographic localization of the conus was within the central 8.0 mm of the cornea in 104 eyes (46.4% of the total) (group A) and beyond 8.0 mm from the corneal center in 120 eyes (53.6%) (group B).

Preoperative evaluation
Preoperative values of BCVA did not differ significantly between group 1 and group 2 (p > 0.05), while a significant difference was found between group A and group B (p < 0.001).There was no statistically significant difference in preoperative BCVA of eyes with the same topographic localization of conus who received grafts of different diameter, neither between group 1 A and group 2 A (p = 0.15), nor between group 1B and group 2B (p = 0.07).
Preoperative values of topographic cylinder did not differ significantly between group 1 and group 2 (p > 0.05), while a significant difference was found between group A and group B (p < 0.001).
There was no statistically significant difference in preoperative topographic cylinder of eyes receiving grafts of different diameter in the presence of similar corneal ectasia localization, neither between group 1A and group 2A (p = 0.30), nor between group 1B and group 2B (p = 0.19).
Detailed preoperative and postoperative values concerning BCVA and topographic cylinder are reported in Table 1.

Surgery
DALK was completed in all cases and no conversion to PK was needed.Pneumatic dissection formed a type 1 bubble in 151 out of 224 eyes (67.4%), while type 2 bubble in 12 eyes (5.4%), all belonging to group B. In case of pneumatic dissection failure, OVD-assisted dissection was performed successfully in 21 eyes (34.4% of the attempts), while the remaining 40 eyes (65.6%) underwent manual dissection.
Considering eyes that underwent manual dissection, no significant difference was found when comparing the two groups (always p > 0.05).

Complications
Intraoperative microperforations occurred in 5 eyes in group 1 (3.4%) and in 13 eyes in group 2 (17.1%).A statistically higher rate was reported in group 2 (χ 2 = 12.80, p < 0.01).In all cases microperforations were managed conservatively and there was no need for conversion.Two cases of severe corneal neovascularization (defined as corneal neovessels going beyond the graft-host junction) were reported, both in eyes that underwent 9.0-mm DALK.Stromal immune rejection was more common in eyes that underwent 9.0-mm DALK (5 out of 76 eyes, 6.6%) compared to 8.0mm DALK (4 out of 148 eyes, 2.7%) but the difference was not statistically significant (χ 2 = 1.96, p > 0.1).

DISCUSSION
Corneal grafts employed for PK are usually about 8.0 mm in diameter since using larger grafts increases significantly the risk of immune rejection and graft failure.However, using grafts of this diameter may cause not only a higher degree of postoperative astigmatism, but also the possibility of retention of the ectasia itself with a higher risk of long-term KC recurrence [19].The most important advantage obtained with DALK surgery involves the lack of endothelial immune rejection, the most threatening type and the only able to determine irreversible failure of the transplanted graft [20].Therefore, it is possible to safely employ larger DALK grafts, up to 9.0 mm in diameter, instead of conventional 8.0-mm grafts.Our group recently compared the outcomes of a series of 124 large 9.0-mm DALK and 133 conventional 8.0-mm DALK performed for KC and reported that large-diameter DALK provided better visual outcomes and significantly lower degrees of topographic astigmatism without an increased risk of immune rejection and graft failure [14].
According to the univariate and multivariate analyses performed in this study, the topographic extension of the conus was significantly correlated to the preoperative BCVA of keratoconic eyes.To date, there are no studies that compare the outcomes of large versus small grafts for the treatment of KC according to the characteristics of the conus in terms of size and location.In the present large case series, the visual and topographic outcomes of eyes with KC undergone DALK were reported in relation to graft diameter employed and topographic localization of the ectasia.Overall, 9.0-mm DALK determined significantly lower values of postoperative topographic cylinder compared to 8.0-mm DALK.Concerning KC characteristics, large-diameter DALK provided significantly lower values of postoperative topographic astigmatism compared to conventional diameter DALK only in eyes with ectasia exceeding central 8.0 mm.This main finding highlights the importance of removing the entire area of corneal ectasia in order to obtain better postoperative outcomes.In fact, employing a conventional 8.0-mm graft in a case of corneal ectasia extending beyond 8.0 mm does not allow the complete removal of the conus (Fig. 4).Further significant differences recorded in our study concerned the occurrence of bubble formation that, as already known, was statistically lower in mild KC [21], and the rate of intraoperative microperforations that were significantly more frequent in large DALK.The most reasonable explanation for this last finding is that big bubble usually does not extend beyond 8.0 mm and would have to be completed by hand to reach the 9.0 mm circumference, thus posing an additional risk of perforation [12].
Despite the meaningful advantage of DALK surgery is the lack of endothelial immune rejection, stromal and epithelial immune rejections are still possible.In our case series, stromal immune rejection was reported in 6.6% of eyes that underwent 9.0-mm

Fig. 1
Fig. 1 Preoperative assessment of the topographic localization of corneal ectasia.Left: the distance between the geometric center of the cornea and the outermost point of the corneal ectasia (with keratometric axial power ≥ 50.5 diopters [D]) was 2.93 mm (radius) (ectasia < 8.0 mm, group A).Right: the distance between the geometric center of the cornea and the outermost point of the corneal ectasia (with keratometric axial power ≥ 50.5 D) was 4.22 mm (ectasia ≥ 8.0 mm, group B).

Fig. 4
Fig. 4 Both corneal maps show a corneal ectasia extending beyond 8.0 mm.The black circle marks the dimensions of the graft employed for deep anterior lamellar keratoplasty (DALK).Left: employing a conventional 8.0-mm graft corneal ectasia extending beyond 8.0 mm is not completely removed.Right: employing large 9.0-mm graft it is possible to remove the entire amount of the conus.

Table 1 .
Preoperative and postoperative values of BCVA and topographic cylinder for each group.