Analysis of the Changes in Keratoplasty Indications and Preferred Techniques

Background Recently, novel techniques introduced to the field of corneal surgery, e.g. Descemet membrane endothelial keratoplasty (DMEK) and corneal crosslinking, extended the therapeutic options. Additionally contact lens fitting has developed new alternatives. We herein investigated, whether these techniques have affected volume and spectrum of indications of keratoplasties in both a center more specialized in treating Fuchs’ dystrophy (center 1) and a second center that is more specialized in treating keratoconus (center 2). Methods We retrospectively reviewed the waiting lists for indication, transplantation technique and the patients’ travel distances to the hospital at both centers. Results We reviewed a total of 3778 procedures. Fuchs’ dystrophy increased at center 1 from 17% (42) to 44% (150) and from 13% (27) to 23% (62) at center 2. In center 1, DMEK increased from zero percent in 2010 to 51% in 2013. In center 2, DMEK was not performed until 2013. The percentage of patients with keratoconus slightly decreased from 15% (36) in 2009 vs. 12% (40) in 2013 in center 1. The respective percentages in center 2 were 28% (57) and 19% (51). In both centers, the patients’ travel distances increased. Conclusions The results from center 1 suggest that DMEK might increase the total number of keratoplasties. The increase in travel distance suggests that this cannot be fully attributed to recruiting the less advanced patients from the hospital proximity. The increase is rather due to more referrals from other regions. The decrease of keratoconus patients in both centers is surprising and may be attributed to optimized contact lens fitting or even to the effect corneal crosslinking procedure.


Introduction
Since the first successful corneal transplantation by Zirm in 1906 [1] the field of keratoplasty has experienced a continuous change and expansion in the spectrum of treated corneal pathologies. Inflammatory corneal diseases used to be one of the most important indications in the mid-20 th century and were then replaced by graft failure and bullous keratopathy [2] with and without intraocular lenses [3]. From the 1980s on, bullous keratopathy remained an important indication for keratoplasty [4,5]. During the 1990s however, in Germany the treatment of keratoconus and Fuchs' dystrophy gained importance and was among the leading indication for keratoplasty [6,7]. From 2000 on, both keratoconus and Fuchs' dystrophy were among the most important indications [8][9][10]. Also in other regions graft failure, keratoconus and Fuchs' endothelial dystrophy were rated among the frequent indications [5,11].
The first anterior lamellar keratoplasty was performed at the end of the 19th century [12]. The first references on lamellar keratoplasty date back from the 1950s [13,14]. The lamellar techniques were reintroduced beginning in 1998 and widely used recently [15,16]. They became the treatment of choice in corneal diseases involving only certain layers of the cornea [17]. Different techniques of endothelial keratoplasty were introduced for treating Fuchs' dystrophy. Descemet stripping with endothelial keratoplasty (DSEK) [18], Descemet stripping automated endothelial keratoplasty (DSAEK) [19] and Descemet membrane endothelial keratoplasty (DMEK) [20] are widely used in treatment of Fuchs' dystrophy. Lamellar techniques are also available for the treatment of keratoconus [21]. Especially the deep anterior lamellar keratoplasty (DALK) appears to be most promising [22,23].
In the treatment of keratoconus conventional penetrating keratoplasty used to be the treatment of choice over more than 60 years. There are several methods of trephination for the penetrating keratoplasty, including manual trephination with freehand trephine blades or suction fixated trephine systems. Laser assisted methods trephination include the excimer laser keratoplasty [24][25][26] or the femtosecond laser assisted keratoplasty [27,28]. These techniques are used in different corneal diseases including keratoconus [29][30][31].
In our opinion the new introduction of surgical techniques might have an impact on the indications for keratoplasty depending on the preferably used techniques and specializations of a center. The lamellar techniques for example might replace the conventional keratoplasty in some indications like Fuchs' dystrophy. Another question is if an eye bank can maintain the demand for corneal transplantation in its area or if the demand decreases over time due to loss of appropriate patients, either due to successful surgery or change in the therapeutic approach. The use of contact lenses and corneal crosslinking for instance might supersede the conventional keratoplasty as treatment of choice for keratoconus. Possible compensatory measures might include recruitment of new patients with a higher mobility from more distant areas, or a change in the surgical spectrum with a focus on a different group of patients.
The purpose of this study was to investigate the volume and spectrum of indications for keratoplasties in a center more specialized in treating Fuchs' dystrophy (center 1) and a second center that is more specialized in treating keratoconus (center 2). In center 1 lamellar keratoplasty with DSAEK and DMEK was adopted early for the treatment of Fuchs' Dystrophie. Center 2 is specialized in excimer keratoplasty, especially for treatment of keratoconus. Air-line distance between both centers is 94 miles.
To determine the mobility of the patients we also registered the patients travel distance from their homes to the respective center.

Methods
We retrospectively reviewed the eye bank data of 2 centers specialized in the treatment of corneal disorders with penetrating or lamellar keratoplasty. Center 1 is more specialized in the treatment of Fuchs' dystrophy, center 2 is more specialized in the treatment of keratoconus. Ethics Committee approval was obtained at Albert-Ludwigs-University of Freiburg and Saarland University Medical Center. Prior to analysis, all patient records and information were anonymized and de-identified. A descriptive analysis of the data was performed for each year with regard to the indication for the keratoplasty and the surgical technique and is presented as flowcharts and box plots. We also analyzed the travel distance from the patient's home to the hospital and calculated the air plane distance on the basis of the postcode. Unfortunately foreign patients could not be included in the travel distance analysis.

Results
A total of 3778 surgical procedures were analyzed in our study.

Discussion
In both centers keratoconus, Fuchs' dystrophy and bullous keratopathy used to be more or less equally presented. This is in accordance with the results of previous data [6,7]. In the recent years both centers showed a decline in the relative amount of bullous keratopathy cases and of keratoconus patients. This is concordant with the results of other studies, that also showed a decline in bullous keratopathy cases [7,11]. The decline in bullous keratopathy cases may be attributed to the less frequent application of anterior chamber intraocular lenses and the restriction of cataract surgery to experienced surgeons in Germany. Therefore, in other regions the bullous keratopathy may still be a major factor leading to a keratoplasty as was reported in the past years [5,11,17].
The decline in keratoconus patients is surprising since from 1992 until 2010 several authors reported keratoconus among the leading indications for keratoplasty [6][7][8]. In center 1 the total number of keratoconus patients also fell whereas in center 2 the total number of keratoconus patients stayed almost the same but did not parallel the total number of keratoplasties. This may be attributed to optimized contact lens fitting or the widespread application of corneal crosslinking.
Fuchs' dystrophy showed an increase in both centers and was the major indication for keratoplasty in 2013. From the 1980s, where Fuchs' dystrophy ranged among the rare indications for keratoplasty [4,5], there was an increase in Fuchs' dystrophy in many studies. However unitl now, it did not provide the major indication for keratoplasty [8,11].
Both centers showed a decline in the relative number of penetrating keratoplasies while posterior lamellar keratoplasties increased immensely.  Our results show, that a new technique such as DMEK may replace the penetrating keratoplasty as most used technique in a single center. Even though there is a decline in all other major indications like keratoconus or bullous keratopathy the total number of transplantations increased. A reason is that a vast group of patients, which was not suitable for penetrating keratoplasty, now appears to be eligible to transplantation via DMEK. This can be attributed to a recruitment of less advanced patients. It is unclear whether one technique (DMEK or DSAEK) has a crucial advantage over the other [32] or which method of graft preparation is superior [33] or the influence of the selection of the right donor tissue [34] is still subject to current research. In addition, the question is still open for the discussion, what is the appropriate visual acuity Fuchs' dystrophy patients should be offered posterior lamellar keratoplasty.
Another compensatory measure to maintain a steady demand is a recruitment of patients that live further away from the hospital.
The increasing travel distance shows, that the patient mobility is high enough to reach a center specialized in their kind of pathology.
In conclusion the results show that DMEK increases the total number of keratoplasties. This cannot be fully attributed to recruiting the less advanced patients from the proximity of the hospital but rather due to more referrals from other regions. The decrease of keratoconus patients in both centers is surprising and may be attributed to optimized contact lens fitting or to the stabilization effect of corneal crosslinking.