Efficacy of Thin and Ultrathin Descemet Stripping Automated Endothelial Keratoplasty and Influence of Graft Thickness on Postoperative Outcomes: Systematic Review and Meta-analysis





HIGHLIGHTS





  • Thin and ultrathin DSAEKs (T/UT-DSAEKs) were developed to increase the visual outcomes of DSAEK, retaining their technical accessibility.



  • Conducting a systematic review and meta-analysis on postoperative outcomes of T/UT-DSAEK stratified by graft thickness (<80 μm, 80-100 μm, and 100-130 μm), we included 47 articles (2141 eyes from 2040 patients).



  • We showed that T/UT-DSAEK globally improved postoperative outcomes, without difference depending on graft thickness.



  • Performing the first meta-analysis on T/UT-DSAEK, we showed that visual acuity, pachymetry, endothelial cell count, and rejection and rebubbling rates were similar regardless of graft thickness.



Purpose


To conduct a systematic review and meta-analysis on the efficacy of thin and ultrathin Descemet stripping automated endothelial keratoplasty (T-DSAEK and UT-DSAEK, with graft thickness <130 and <100 µm, respectively), depending on graft thickness.


Design


Systematic review and meta-analysis.


Method


PubMed, Cochrane Library, Embase, ClinicalTrials.gov, and ScienceDirect databases were searched until October 1, 2021. We computed random-effect meta-analysis on postoperative outcomes of T/UT-DSAEK, stratified by graft thickness (<80 μm, 80-100 μm, and 100-130 μm). The main postoperative outcome was visual acuity (logarithm of the minimum angle of resolution [logMAR]). Secondary outcomes were pachymetry (μm), endothelial cell count (cell/mm 2 ), spherical equivalent (diopter [D]), rebubbling rate (%), and rejection rate (%). Meta-regressions compared postoperative outcomes depending on graft thickness and search for putative confusion factors.


Results


We included 47 articles for a total of 2141 eyes of 2040 patients. T/UT-DSAEK globally improved visual acuity (effect size = −0.38 logMAR [95% confidence interval {CI} −0.46 to −0.30 logMAR]), without difference depending on graft thickness. Overall, pachymetry improved (−60.6 µm [95% CI −101 to −19.7 µm]), endothelial cell count decreased (−1039 cells/mm 2 [95% CI −1209 to −868 cells/mm 2 ), spherical equivalent resulted in a hyperopic shift (0.74 D [95% CI −0.50 to 1.97 D), the graft rejection rate was 0.2% (95% CI −0.1% to 0.4%), and the rebubbling rate was 8.7% (95% CI 6.8%-10.5%). Grafts >100 μm induced a hyperopic shift. Metaregressions did not demonstrate differences between the 3 groups (<80 μm, 80-100 μm, or 100-130 μm) in any outcomes.


Conclusion


All T/UT-DSAEK thickness groups provided similar visual acuity, pachymetry, endothelial cell count, rejection rate, and rebubbling rate regardless of graft thickness. A hyperopic shift was induced by grafts >100 μm.


E ndothelial keratoplasty (EK) is becoming the criterion standard surgery for the treatment of endothelial corneal failure, replacing penetrating keratoplasty. Descemet stripping automated EK (DSAEK), with corneal endothelium and Descemet membrane being grafted with a thin layer of donor stroma, , currently remains the most performed EK in both the United States and Europe. , Recently, interesting results highlighted that DSAEK with grafts thinner than 130 µm could involve better postoperative visual acuity, suggesting relationships between graft thickness and visual outcomes. Thereby, thin and ultrathin DSAEK (T/UT-DSAEK) (ie, DSAEK with graft thickness <130 µm 7 ) were developed to increase the visual outcomes of DSAEK and to maintain their technical accessibility. , Further studies supported these findings while showing a similar complication rate and endothelial cell loss to DSAEK. , However, the link between graft thickness and visual outcomes is not consistent, which could therefore question the pertinence of T/UT-DSAEK. Most of the published results relate to grafts generally >100 µm. , , Currently, no data are available for grafts <100 µm. Thus, to assess the influence of graft thickness within T/UT-DSAEK grafts, we conducted a systematic review and meta-analysis on the efficacy of T/UT-DSAEK on postoperative outcomes (ie, visual acuity, pachymetry, cell count, spherical equivalent, and rebubbling and rejection rates), depending on the graft thickness.


METHODS


LITERATURE SEARCH


We searched for articles in PubMed, Cochrane Library, ScienceDirect, Embase, and ClinicalTrial.gov databases until October 1, 2021 with the following keywords: Descemet*


OR endothelial keratoplasty OR DSAEK OR DSEK AND thickness OR thin OR ultrathin OR


UT-DSAEK (details of search strategy used within each database are presented in Appendix 1). The search was not limited to specific years. No language restrictions were applied. We imposed no limitation on sample size or regional origin. To be included, articles had to report clinical outcomes (ie, visual acuity, pachymetry, endothelial cell count, spherical equivalent, or rebubbling or rejection rates) of T/UT DSAEK, defined as DSAEK with preoperative graft thicknesses <130 µm and <100 µm, respectively. Animal studies were excluded. In addition, references of all publications meeting the inclusion criteria were manually searched to identify any further studies. The search strategy is presented in Figure 1 . Two authors (L.B., V.N.) conducted literature searches, collated and separately reviewed the abstracts and, based on the selection criteria, decided the suitability of the articles for inclusion. A third author (F.D.) was asked to review the articles where consensus on suitability was debated. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (Appendix 2).




FIGURE 1


Literature search strategy. DSAEK = Descemet stripping automated endothelial keratoplasty; DSEK = Descemet stripping endothelial keratoplasty; SD = standard deviation; UT = ultrathin.


DATA COLLECTION


The data collected included first author’s name, publication year, country, study design, aims, outcomes of included articles, inclusion and exclusion criteria, sample size, number of eyes, age, percentage of males, endothelial disease, graft cutting technique, type of surgery (simple or triple EK), characteristics of donors (age, sex), measurement time, central graft thickness, central corneal thickness, spherical equivalent, best spectacle-corrected visual acuity, endothelial cell count, graft rejection rate, and rebubbling rate.


OUTCOMES


The primary outcome was best spectacle-corrected visual acuity (logMAR). Secondary outcomes were pachymetry as central corneal thickness (µm), endothelial cell count (cells per square millimeter), spherical equivalent (diopters [D]), graft rejection rate (%), and rebubbling rate (%).


QUALITY OF ASSESSMENT


We used the Scottish Intercollegiate Guidelines Network (SIGN) criteria to assess the methodological quality of the included articles, both for randomized clinical trials and cohort studies, with the dedicated evaluation grids. SIGN Controlled Trials and SIGN Cohort Studies checklists consisting of respectively 10 and 14 items. We presented an overall quality score for each included study, based on the main causes of bias evaluated in section 1 of the checklist through 4 possibilities of answers (yes, no, can’t say, or not applicable).


STATISTICAL CONSIDERATIONS


Statistical analyses were conducted using Stata software (StataCorp). Characteristics of subjects and parameters evaluated were reported for each study sample as mean ± standard deviation (SD) and number (%) for continuous and categorical variables, respectively. We computed random-effects meta-analysis (DerSimonian and Laird approach) on changes between after the intervention and baseline measures, for each efficacy outcome: best spectacle-corrected visual acuity in logMAR, central corneal thickness in µm, endothelial cell count from donor in cell/mm 2 , and SE in D. For graft rejection and rebubbling, meta-analysis was expressed in rates (%). When a study presented several time measurements, the last follow-up time was retained for the main analysis. When visual acuity was evaluated with a Snellen chart or a decimal scale, it was converted to logMAR using the formula: logMAR visual acuity = −log10 (decimal visual acuity). Changes were calculated using the method from Borenstein and associates. This approach has the advantage to express results—ie, effect sizes (ESs) as natural values (logMAR, µm, cell/mm 2 , and D, respectively—but suffers from statistical issues because the number of eyes is only taken into account from SD, and by choosing an arbitrary correlation coefficient of 0.5. Therefore, to be statistically accurate, we further computed aforementioned meta-analysis using standardized mean differences (SMD) by comparing measures of efficacy after the intervention to baseline measures (before the intervention). SMD with their 95% CIs were represented graphically on forest plots. A SMD was defined as an unitless measure of the effects of T/UT-DSAEK on outcomes. A SMD centered at 0 reflects the absence of effect, 0.2 a small effect, 0.5 a moderate effect, and 0.8 a large effect. We stratified our meta-analyses on the thickness of corneal grafts in T/UT-DSAEK (<80 μm, 80-100 μm, and 100-130 μm), according to the preoperative thickness (or the earliest postoperative graft thickness). Lastly, we performed several sensitivity analyses to verify the strength of our results. First, we repeated meta-analyses with all measurement times. Then, as recovery from surgery is likely to be achieved over the long term, we computed previous meta-analyses using only studies with a follow-up >1 year. As the most common surgery is the microkeratome technique for Fuchs endothelial dystrophy, we also computed sensitivity meta-analyses on those studies. Heterogeneity in our results was evaluated by examining forest plots, 95% CIs, and the I 2 statistic. Heterogeneity between studies is considered low for 0% < I 2 <25%, modest for 25% < I 2 < 50%, and high for 50% < I 2 < 100%. For rigor, funnel plots (metafunnels) of meta-analyses were used to search for publication bias, and meta-analyses were conducted excluding studies not evenly distributed around the base of the funnel. When possible (sufficient sample size), metaregressions were proposed to study the relationship between clinical outcomes and clinically relevant parameters such as characteristics of subjects and donors (age, sex), pathology causing endothelial failure, time, and characteristics of surgery. Results of meta-regressions were expressed as regression coefficients and 95% CIs. P values < .05 were considered statistically significant.


RESULTS


An initial search produced 2926 possibly corresponding articles ( Figure 1 ). After removal of the duplicates and applying selection criteria, we included 47 articles , , , published between 2009 and 2021 ( Table 1 ). All articles were written in English, except for 2 in French, , 1 in Russian, and 1 in German.



TABLE 1

Characteristics of Included Studies





















































































































































































































































































































































































































































































































































































































































































































































































































































































































































































Study Country Study design Eyes, n (No. of Patients) Mean Age, Years Sex (% Male) Pathology Triple EK (%) Graft Dissection Mean CGT, µm (Range) CGT Assessment, Months Outcomes Follow-Up, Months
BSCVA CCT ECC SE Rejection Rebubbling
Asif and associates, 2021 India Retrospective 39 9.9 45 CHED 3 Microkeratome (single pass) 119.4 Immediately after dissection X X 17.3
Bertino and associates, 2020 Brazil Retrospective 15 53 FED, PBK, regraft 13 Manual 94.6 6 X X 12
Bhandari and associates, 2015 India Retrospective case series 30 55.1 60 FED 0 Microkeratome (single pass) 91.1 Immediately after dissection X X X X X 12
Bielefeld and associates, 2020 France Retrospective 79 (75) 72 FED, PBK, regraft, other Microkeratome 91 Immediately after dissection X X X X X 12
Bonissent and associates, 2016 France Retrospective 70 68.1 38.6 FED, PBK, regraft, HSV, ICE Manual + Excimer laser 84.1 1 X X X X 12
Busin and associates, 2013 Italy Prospective case series 285 (250) 67.9 38.4 FED, PBK, regraft, HSV, PPD, ICE, congenital glaucoma 33.7 Microkeratome (double pass) 78.3 3 X X X 24
Castellucci and associates, 2021 Italy Retrospective cohort 26 (13) 67.6 46 FED 58 Microkeratome (single pass) 99.3 Immediately after dissection X X 19.6
Chamberlain and associates, 2019 USA RCT 25 (19) 68 36 FED, PBK 68 Microkeratome 73 Immediately after dissection X X X X X 12
Dickman and associates, 2016 Netherlands RCT 34 73 FED 29 Microkeratome (single pass) 101 Immediately after dissection X X X X 12
Dimitry and associates, 2017 UK Prospective case series 12 65 16.7 FED, PBK 67 Microkeratome (single pass) 78.9 Immediately after dissection X 12
Dunker and associates, 2020 Netherlands RCT 25 71 FED 0 Microkeratome (single pass) 101 Immediately after dissection X X X X X 12
El Hadad and associates, 2016 Italy RCT 51 70.7 FED, PBK, regraft, PPD 49 Microkeratome (double pass) 89.3 1 X X X 12
Gormsen and associates, 2019 Denmark Retrospective registry study 89 71 40 Microkeratome (single pass) 86 Immediately after dissection X X 12
Graffi and associates, 2018 Italy Retrospective case series 21 69.2 48 Regraft 5 Microkeratome 82 6 X X X 12
Guerra and associates, 2011 USA Retrospective case series 15 67 40 FED 0 Microkeratome (single pass) aim to 120 X X 12
Jansen and Zetterberg, 2021 Sweden Retrospective 116 75.1 38.8 FED, PBK, regraft 12 Microkeratome (single pass) (100 – 130) Immediately after dissection X X X 24
Jun and associates, 2009 USA Retrospective case series 28 67 39.3 FED, PBK 39.3 106.9 Immediately after dissection X X 4.7
Kurji and associates, 2018 USA Prospective case series 28 (26) 67.1 39.3 FED 64.3 41 Immediately after dissection X X X 12
Lanza and associates, 2021 Italy Retrospective 111 (96) 70.3 45.8 FED, PBK 48.6 90.3 Immediately after dissection X X X X X 8.5
Liarakos and associates, 2013 Netherlands Retrospective case series 7 72.4 57.1 PBK 0 Manual 107 Immediately after dissection X X X X 12
Matsou and associates, 2020 UK RCT 28 72 50 FED 71 Microkeratome (single pass) 63 Immediately after dissection X X X X X 12
McKee and Jhanji, 2015 Australia Case series 5 80.2 40 FED, PBK, regraft Femtosecond laser 82.8 6 X 6
Mencucci and associates, 2020 Italy Retrospective 18 73.5 11 FED 0 Microkeratome (single pass) 80.3 Immediately after dissection X X X X X 12
Mimouni and associates, 2021 Austria Retrospective 28 73.9 25 FED, PBK 88.5 Immediately after dissection X
Muijzer and associates, 2019 Netherlands Prospective cohort 21 68 39 FED, regraft 47.6 Microkeratome (single pass) or manual 105 Immediately after dissection X X X X 12
Muijzer and associates, 2019 Netherlands Prospective cohort 53 68 39 FED, PBK, regraft 39.6 Microkeratome (single pass) or manual 106 Immediately after dissection X X X X 12
Nahum and associates, 2015 Italy Retrospective 42 FED, PBK, regraft Microkeratome (single) pass 63 3 X 3
Parekh and associates, 2019 UK Retrospective cohort 39 33.3 Microkeratome (single) pass 83.5 Immediately after dissection X X 8.5
Roberts and associates, 2015 UK Prospective cohort 130 (114) 72 50 FED, other 53 Microkeratome (single) pass 95 Immediately after dissection X X X X 12
Romano and associates, 2017 UK Case series 10 Microkeratome (single) pass 83.2 Immediately after dissection X 3
Romano and associates, 2020 UK Retrospective case series 31 69.3 42.9 FED, PBK 35.5 75.3 Immediately after dissection X X 12
Rosa and associates, 2013 Portugal Prospective 25 65 32 FED, PBK 32 Microkeratome + Femtosecond laser 83.1 1 X X X 6
Ruzza and associates, 2015 Italy Prospective case series 14 FED, PBK, regraft, PPD Microkeratome (single pass) 102 Immediately after dissection X 6
Ruzza and associates, 2021 Italy Retrospective case series 9 FED, PBK 22.2 83 8.5 X X X 8.5
Saunier and associates, 2016 France Prospective 49 67.5 40.8 FED, PBK, other 36.7 Microkeratome (single pass) 116.5 Immediately after dissection X X 6
Schaub and associates, 2016 Germany Retrospective case series 5 60 60 Microkeratome (single pass) 64.5 Immediately after dissection X X X X 3
Tereshchenko and associates, 2017 Russia 5 72 0 PBK 0 Femtosecond laser 52 6 X X 6
Terry and associates, 2012 USA Retrospective case series 45 64.8 31 FED Microkeratome (single pass) (80 – 124) Immediately after dissection X 6
Thannhäuser and associates, 2014 Germany Prospective 18 76 FED, PBK, other Microkeratome + Excimer laser 111 Immediately after dissection X X X 6
Tomida and associates, 2015 Japan 21 70 62 FED, PBK, other Femtosecond laser Aim to 120 X X X 6
Torras-Sanvicens and associates, 2021 Spain Retrospective case series 10 75.4 40 FED 20 91.1 Immediately after dissection X X 45.5
Tourkmani and associates, 2019 UK Retrospective 29 FED, PBK, regraft, HSV 17.2 Manual 106 2 X 2
Tsatsos and associates, 2014 UK Prospective 10 FED, PBK 0 Manual 90.7 1 X 1
Vajpayee and associates, 2013 Australia Case series 15 FED, PBK, regraft, CHED 20 Microkeratome (single pass) 111 6 X X 6
Villarrubia and Cano-Ortiz, 2015 Spain Prospective case series 60 (51) Microkeratome (single or double pass) 99.3 1 X 1
Walter and associates, 2020 USA Retrospective cohort 170 72 30 FED, PBK (70 – 110) Immediately after dissection X 48
Wang and associates, 2021 China Prospective 85 (84) 58 52.4 FED, PBK, regraft, HSV, ICE, other 27.1 Femtosecond laser 113 3 X X X X 24
Woo and associates, 2019 Singapore Retrospective cohort 60 68.6 46.7 FED, PBK Microkeratome 80.6 Immediately after dissection X 60

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Sep 11, 2022 | Posted by in OPHTHALMOLOGY | Comments Off on Efficacy of Thin and Ultrathin Descemet Stripping Automated Endothelial Keratoplasty and Influence of Graft Thickness on Postoperative Outcomes: Systematic Review and Meta-analysis
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