Corneal Imaging and Densitometry Measurements in Patients with Fuchs' Dystrophy Undergoing Penetrating Keratoplasty and Descemet's Striping Automated Endothelial Keratoplasty

Aims: In the present study, we used the densitometry software from the Oculus Pentacam to compare postoperative corneal clarity between penetrating keratoplasty (PK) and Descemet's stripping endothelial keratoplasty (DSAEK) in patients with Fuchs' dystrophy. Methods: A retrospective comparative study was carried out at Manchester Royal Eye Hospital. In 28 patients with Fuchs' dystrophy, corneal densitometry measurements were performed 12–18 months after corneal transplantation. The correlations of the densitometry measurements with the best corrected visual acuity (BCVA) and central corneal thickness (CCT) were analysed and compared between eyes that underwent PK and those that underwent DSAEK Results: Corneal densitometry measurements in the 33 eyes showed no signicant differences between the PK and DSAEK post-surgery groups. There was no signicant correlation between CCT and corneal densitometry measurements in either group (P > 0.05 in both cases). After DSAEK, corneal densitometry measurements were signicantly correlated with BCVA in the central (P = 0.01), posterior (P = 0.007), and full-depth (P = 0.008) 0–2 mm zones of the cornea but not in PK group. The postoperative CCT was signicantly different between the two groups (P (cid:0) 0.01). measurements. Improved visual acuity DSAEK was found to positively correlate with improvements in corneal clarity. Oculus Pentacam provides objective corneal after surgery.


Introduction
Fuchs' endothelial dystrophy (FED) is usually treated using corneal transplantation [1,2], which restores healthy endothelial function [3]. The rst description of FED was published in 1900 by Ernst Fuchs, who described deposits known as guttata on the Descemet's membrane beneath the corneal endothelium; an abnormal extracellular matrix and endothelial cell loss were also apparent [4].
During the initial phase of the FED, epithelial oedema is absent. However, it builds up progressively in later stages. The degree of epithelial oedema is estimated by measuring the central corneal thickness (CCT).
Corneal oedema begins within the central optical area and is a key cause of reduced vision in FED [5]. This is particularly severe in the morning due to reduced tear evaporation during sleep [6]. As the cornea becomes more oedematous, discomfort occurs, followed by extreme pain and photophobia. The eventual effects of extreme endothelial cell loss include stromal swelling, the creation of connective tissue in the stroma and epithelium, corneal oedema, and a clear vision reduction.{Kim, 2004, Laser in situ keratomileusis versus laser-assisted subepithelial keratectomy for the correction of high myopia In 1900, the rst successful full-thickness keratoplasty was performed by Edward Zirm. Since then, this approach has seen considerable alteration and progress. Currently, over 3,000 corneal transplants are conducted annually in the United Kingdom alone [7]. FED transplants account for 25.8% of the overall proposed number for corneal transplant [8] .Historically, FED was treated using full-thickness (penetrating) keratoplasty (PK), which replaces all ve corneal layers. However, as only the endothelial layer is diseased in FED, it is possible to use Descemet's stripping automated endothelial keratoplasty (DSAEK), whereby only the posterior stroma and endothelium are replaced [9].
The success of these surgical procedures is evaluated in terms of best-corrected visual acuity (BCVA) and CCT. Clinically, Pentacam (OCULUS Optikgerate GmbH, Wetzlar, Germany) images are routinely used to assess patients undergoing transplant surgery. However, an update in computer software now allows corneal clarity to be measured in the same image. In the present study, we aimed to evaluate the use of corneal densitometry using Pentacam to assess the outcome of PK and DSAEK.

Methods
Participants:This study was a retrospective, comparative, non-randomised cross-sectional study. It was approved by the Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom, and by the local national research ethics committee. The study followed the tenets of the Declaration of Helsinki, and written, informed consent was obtained from all subjects after the study's nature had been explained to them. The study included patients with FED who had been visiting the Clinical notes were examined, and relevant information such as age, sex, date of surgery, and type of surgery was recorded for descriptive data analysis, as were postoperative parameters, including BCVA (in LogMAR) and clinical details.
Pentacam Imaging:All imaging was performed by the same trained staff in a dark room 12-16 months after surgery. A single image that met the quality requirements of Pentacam analysis was taken from each patient. This study's inclusion criteria were: age ≥ 18 years, history of FED corneal transplantation (PK or DSAEK), completion of a 1-year post-treatment follow-up, availability of a Pentacam image from that time.
Surgical Procedures:The surgical procedures (DSAEK and PK) were each performed by one of two surgeons; they used identical techniques during the respective procedures to minimise variation [10]. PK was performed using a standard technique that employs a Hessburg-Barron trephine (JedMed Instrument Co., St. Louis, MO) [11]. DSAEK was conducted according to standard techniques [12][13][14]. As FED is a corneal disease associated with ageing, a triple procedure of cataract extraction, intraocular lens implantation, and corneal transplantation was performed in that order when necessary.
Statistical Analysis:Data analyses were carried out using SPSS V22.0 statistics software package for Windows. Descriptive statistics were presented as means ± standard deviation. The data normality was examined using the Shapiro-Wilk test, which is more appropriate for small sample sizes (N < 50). When parametric analysis was possible, the Student's t-test for two independent samples was used. All P-Values less than 0.05 were considered statistically signi cant.

Results
A total of 33 eyes of 28 patients were studied. The sample characteristics were comparable between the groups; however, there were more women than men in both groups (PK, 11:2; DSAEK, 15:5); importantly, this did not constitute a signi cant difference between the groups (P=0.96). The mean age of patients in the PK group was 70.0 ± 10.0 years, while that in the DSAEK group was 69.9 ± 9.84 years (P=0.96).
In the PK group, seven eyes (53.8%) achieved a postoperative BCVA of 0.3 LogMAR or better, while in the DSAEK group, 15 eyes (75%) achieved a postoperative BCVA of 0.3 LogMAR or better. The mean postoperative BCVA in the DSAEK group was 0.19 ± 0.12 LogMAR, which was better than that in the PK group (0.37 ± 0.22 LogMAR; P= 0.01).
Densitometry measurements showed that DSAEK causes less light scattering than PK in all layers of both the inner 0-2 mm zone of the cornea and the surrounding 2-6 mm annulus zone. However, further statistical analysis showed that none of the densitometry measurements' differences were signi cant (P 0.05 in all cases; Table 1). The mean CCT 1 year after PK treatment was 510.8 ± 54.9 μm, while that 1 year after DSAEK treatment was 639.55 ± 59.0 μm. Both CCT and the thinnest corneal area thickness were signi cantly different between the PK and DSAEK groups (P 0.05) ( Table 2).

Discussion
DSAEK is a comparatively new method for transplanting the endothelium from a donor cornea, and it is now the primary surgical treatment of FED [10,15,16]. DSAEK has several advantages over PK in patients with endothelial dystrophy; it is associated with fewer complications and a shorter recovery time [10,17,18]. Several studies have reported that PK and DSAEK differ in several areas [18], including rates of rejection and post-operation BCVA. Updates from Nanavaty have reported similar ndings [17]. However, up to our knowledge, the present study was the rst to nd that postoperative densitometry measurements differed between DSAEK and PK in patients with FED, which show a signi cant correlation to BCVA in the DSAEK group.
Scheimp ug imaging has numerous applications in corneal assessment. Moreover, with the updated software, it may be possible to measure the amount of backscattered light in diverse cornea regions [19,20]. In this regard, corneal transparency is attributable to complex mechanisms, including size, regularity, and collagen brils arrangement [21].
The present study established that 12-18 months after surgery, the mean corneal densitometry in FED patients was somewhat higher than the normative value quanti ed in a previously published agematched set [22,23]. Patients who undergo PK still receive sutures that must be extracted, while patients who undergo DSAEK do not. Overall, in patients with PK, the corneal graft/host intersection requires 12-24 months of recovery and complete suture extraction. Moreover, as PK involves full-thickness grafting, it contradicts the eyes' structural and immunological integrity and can cause more signi cant harm than DSAEK. Indeed, PK causes greater damage to corneal tissue. The greater activation of keratocytes likely occurs as a reaction to trauma, leading to raised corneal densitometry measurements.
The average endothelial cell density loss per year after successful PK ranges from 7.8% between 3 and 5 years after surgery [24] to 4.2% between 5 and 10 years after surgery [25]. This is contrasted with a remarkable 50% loss of endothelial cells just 6 months after successful DSAEK [26]. Because the present study involved only a small sample and was retrospective, we had limited ability to research this matter. Therefore, future research must conduct a well-planned research that explores the function of the endothelium pump or alternative factors contributing to enhanced corneal transparency in FED following DSAEK.
The present research con rmed that postoperative BCVA is signi cantly better after DSAEK than after PK, probably because partial suture extraction is necessary during PK. Regarding postoperative BCVA measurement, comparisons between DSAEK and PK are best carried out after entire suture extraction; an additional review of each patient's clinical notes revealed that postoperative BCVA is improved after entire suture extraction. The present study found a considerable association between postoperative BCVA and densitometry quanti cation in the DSAEK group, corroborating previous studies [27,28]. However, this correlation did not occur in the PK group. Positive correlations were also found in the central, posterior, and full depth layers.
We should clarify that we excluded patients from our data analysis if they experienced complications during or after surgery. DSAEK is renowned for providing swifter visual rehabilitation than PK. Nonetheless, this has to be con rmed through additional research employing signals that are more dependable than visual results (e.g. contrast susceptibility and higher order aberration HOA steps following procedures), as well as larger sample sizes.
After surgery, visual acuity improvements can take several months or even years [26,29,30]. In this regard, visual acuity can be affected by the lamellar graft's thickness and the interfere optical quality of the graft/host interface [28, 31,32]. However, there was no correlation between BCVA and corneal thickness in the current study compared to the previous studies [33].
Increased corneal densitometry was found in the stroma, the anterior cornea; overall, corneal thickness was also improved. Therefore, the changes detected using densitometry appeared to affect the whole stroma and consisted of more than simply an increase in light scatter as a result of sub-epithelial brosis or augmented scatter from the graft/host interface, although both components still can cause light scattering in post-DSAEK patients.{Kim, 2004, Laser in situ keratomileusis versus laser-assisted subepithelial keratectomy for the correction of high myopia A signi cant relationship between visual outcome and corneal densitometry was recently discovered after DSAEK [27], corroborating observations of the present study. To some extent, Koh et al. reported higher values than we did. However, their study did not clearly de ne which thickness and diameter the densitometry measurements were acquired from. For this reason, the measurements are not directly comparable with those of the present study.
Poor graft interface can lead to graft failure. This illustrates the importance of maintaining a pristine graft interface and avoiding wrinkles in the graft across the pupillary area. In this regard, greater curvature disparities between recipient and donor corneas may promote wrinkle development [15,34].
After surgery, gradual improvements in visual acuity are associated with increases in optical aberrations and corneal backscatter, which signify that the cornea is steadily restored after corneal oedema, with an average total corneal breadth of about 700 mm. In fact, reduced BCVA after DSAEK is sometimes believed to be caused by corneal backscatter (haze) [33,35,36]. However, backscatter cannot in uence vision since it is not distributed around the retina. In contrast, forward scatter does alter vision, but it naturally causes glare rather than diminished visual acuity [37][38][39][40].
The present study found that the patients' average CCT was 510.8 ± 54.9 μm 1 year after PK and 639.55 ± 59.0 μm 1 year after DSAEK. This constituted a signi cant difference (P=0.0001) and is similar to the results of [41] who documented an average CCT of 535.0 ± 45.0 μm 6 months after PK; this had increased to 580.0 ± 59 μm 5 years later. Nonetheless, the present study found no statistical correlation between BCVA and CCT in either group. Furthermore, CCT varies greatly among normal eyes.
The present study results agree with those of Terry et al. with regards to DSAEK graft thickness. They stated the following: 'graft thickness may have a small effect on visual outcomes in the extremes of thickness, but not in the common range of 100 mm to 200 mm', and 'donor thickness has a tenuous relationship with visual outcomes, accounting for only 5% of the variance in vision between patients, and should play a minimal role in surgical planning' [39].
The present study was limited by its relatively small sample size and the possibility that suture removal may have affected the outcome, especially with respect to BCVA.
In conclusion, the present study showed that corneal densitometry can be used to detect subtle changes that occur in the cornea after transplantation and to monitor recovery. Densitometry may also further our understanding of the cornea in both normal and diseased conditions.

Declarations
Competing intrests No con ect of intrest to be disclore by all the authors  Figure 1 The correlation between BCVA and Corneal densitometry in PK and DSAEK (* represent signi cant at Pvalue of <0.05).