Descemet's membrane endothelial keratoplasty versus Descemet's stripping automated endothelial keratoplasty for corneal endothelial failure

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To compare the effectiveness and safety of Descemet's membrane endothelial keratoplasty (DMEK) versus Descemet's stripping automated endothelial keratoplasty (DSAEK) for the treatment of corneal endothelial failure in people with Fuch’s endothelial dystropy (FED) and pseudophakic bullous keratopathy (PBK).

Background

Description of the condition

The cornea is the transparent tissue at the front of the eye. It is a critical component of the eye for vision as the cornea not only constitutes a clear window for the light rays to reach the retina but also provides most of the refractive power of the eye (Ayres 2006). It consists of five layers, the epithelium, the Bowman's membrane, the corneal stroma, Descemet's membrane and the corneal endothelium (from the outer towards the inner surface). The clarity of the cornea is of utmost importance to provide a clear visual image; the endothelial cells of the cornea play a vital role in maintaining corneal transparency. They continuously pump fluid out of the cornea and hence keep it in a dehydrated and transparent state. The average healthy adult cornea has approximately 2500 to 2700 endothelial cells per mm2 lining the inner surface of the cornea. This number falls slowly with age but rarely does this physiological loss of cells result in corneal endothelial failure (Smolin 1994). When, as a result of disease or damage, the number of cells is reduced more markedly below a critical level of around 300 to 500 cells/mm2, then corneal endothelial failure occurs resulting in corneal oedema and loss of vision (Borboli 2002; Smolin 1994).

The leading causes of corneal endothelial failure are pseudophakic bullous keratopathy (PBK) and Fuch’s endothelial dystropy (FED). These conditions are also the two most common indications for corneal transplantation (Boimer 2011; Frigo 2015). PBK refers to the loss of endothelial cells during cataract surgery. This may occur because of direct trauma to endothelial cells during the cataract procedure or indirectly due to the effects of inflammation or high intraocular pressure that occur following cataract surgery (Claesson 2009). In FED (a condition first described by Ernst Fuchs in 1910) there is premature degeneration of corneal endothelial cells. FED commonly affects individuals in the fifth and sixth decade of life (Afshari 2006). It affects both eyes although at its onset it is typically asymmetrical. FED occurs more commonly in females compared to males and can be inherited in an autosomal dominant fashion, although not all cases are familial (Cross 1971; Magovern 1979; Rosenblum 1980). The condition is progressive and irreversible.

Description of the intervention

Treatment for corneal endothelial failure varies according to the severity of the disease and may range from hypertonic saline drops to surgical intervention. In moderate or severe disease, corneal grafting may be required for visual rehabilitation. Previously the gold standard corneal grafting technique for endothelial failure was penetrating keratoplasty (PK). However, over the last 15 years endothelial keratoplasty (EK) has become the treatment of choice (Boimer 2011; Frigo 2015). In EK only the innermost layer of the cornea is replaced during surgery. A variety of EK techniques exist.

The expected benefits of EK techniques over PK are faster visual recovery, less astigmatism and stronger wound integrity (Terry 2001). Graft rejection is an important reason for failure in PK patients (Pineros 1996). Theoretically, there is also less risk of immune rejection of the transplanted corneal tissue with EK because a smaller amount of tissue is transplanted and because the endothelium is located in what is normally an immune privileged location. Finally, with EK there is the potential to make more efficient use of transplant tissue, using the posterior layer of the donor cornea for EK in one patient and the anterior layers for an anterior lamellar graft in another patient (Melles 2003). EK (Descemet’s stripping automated endothelial keratoplasty (DSAEK) and Descemet’s membrane endothelial keratoplasty (DMEK)) now accounts for over 50% of corneal transplants performed in the United States of America (USA) with nearly 25,000 surgeries performed in 2013, a 27% increase over the last 5 years (Eye Bank Association of America 2013). DSAEK is much more commonly performed than DMEK. Of the 24,987 EKs performed in the USA in 2013, 23,465 were DSAEK whilst 1522 were DMEK (Eye Bank Association of America 2013).

Various subtypes of EK have been described but the most commonly performed are DSAEK and DMEK transplant. DSAEK was first described in 2006 by Mark Gorovoy (Gorovoy 2006) whilst DMEK was pioneered by Gerrit Melles in the same year (Melles 2006).

In DSAEK the surgeon uses an automated machine called a microkeratome to separate a thin layer (50 to 150 microns thick) from the back of the donor cornea containing corneal stroma, Descemet's membrane and endothelial cells. This thin layer of posterior cornea is then transplanted into the recipient eye and attached to the posterior cornea of the recipient. By contrast, in DMEK the surgeon carefully peels Descemet's membrane and endothelial cells from the back of the donor cornea and transplants this thin sheet (around 15 um) into the recipient's eye (Dapena 2011). The relative advantages and disadvantages of these procedures are discussed below.

How the intervention might work

Endothelial cells cannot regenerate in vivo (though they have been shown to do so in vitro (Joyce 2004)) so endothelial failiure results in corneal swelling, that is corneal oedema, which causes blurring of vision. The fluid in the cornea causes bullae (small blisters on the surface of the cornea) which may rupture, causing pain. Medical management of the corneal oedema is limited to regular use of lubrication, hyperosmolar agents (such as sodium chloride 5% ointment) and bandage contact lenses that reduce the pain due to rupturing of surface bullae. When the condition becomes intolerable for the patient then corneal transplantation is the treatment of choice. This surgical procedure can restore the vision or alleviate the symptoms, or both.

The aim of both DMEK and DSAEK is to transplant a healthy endothelial cell layer that will pump the fluid out of the cornea and result in restoration of corneal clarity and improvement in vision. It has been suggested that the visual rehabilitation and final visual acuity of DMEK may be better than DSAEK Guerra 2011. This is thought to be due to the stromal layers, which cause optical irregularities, not being transplanted in the DMEK procedure (Maier 2013). Indeed, there are data to suggest that the thickness of DSAEK grafts influences the outcomes of the procedure. Thinner grafts have been associated with quicker visual rehabilitation and better overall visual outcomes (Busin 2013). It is not clear which method is associated with higher rates of idiopathic primary graft failure (IPGF). Maier suggested this was lower in DMEK compared to DSAEK (Maier 2013) whilst another retrospective comparison of 100 DSAEK cases with 100 DMEK cases found the IPGF rate to be higher in the DMEK group (Hamzaoglu 2015). As DSAEK is a more established surgical procedure, most corneal surgeons have already overcome the technical learning curve whereas DMEK is still a relatively new technique. It is generally accepted that DMEK is a more technically difficult and challenging procedure (Parekh 2013). In DMEK, the graft thickness is not variable, as by definition it is just one layer of cells. The main difficulty is during the preparation of the donor tissue as it is so thin and fragile. It is reported that between 4.2% and 8% of DMEK grafts cannot be prepared successfully (Price 2009). Moreover, postoperative graft dislocation is a more common complication associated with DMEK (33% to 81%) than DSAEK (7% to 20%) (Guerra 2011; Tourtas 2012). Endothelial cell loss after DSAEK procedures has been quoted to range from 13.5% at six months (Khor 2013) to over 50% at 12 months (Dooren 2011). There are several different types of injector systems for insertion of DSAEK grafts and each is associated with different rates of endothelial cell loss. Endothelial cell density loss associated with DMEK has been described to range between 24.7% (Maier 2015) and 41% (Tourtas 2012) at six months. Clearly any comparison of endothelial cell counts must take into account the post-operative time point at which the counts are assessed.

Why it is important to do this review

PBK is the indication for up to 50% and FED the indication for up to 25% of all corneal transplants (Afshari 2006; Eye Bank Association of America 2013; Frigo 2015). Both conditions commonly affect patients in the fifth and sixth decades of life. Population demographics are changing in the developed world, with an aging population. It is possible that many cases of subclinical Fuchs will become clinically apparent as people live longer; therefore, the incidence and prevalence of corneal endothelial failure due to FED may rise. Similarly, PBK is inherently more common in elderly patients, as it is this population which most commonly undergoes intraocular surgery, primarily for cataract. It is, therefore, possible that the incidence of PBK may rise with an aging population.

At present there are several different EK techniques. DMEK and DSAEK are the most commonly used and each has its advantages and disadvantages. In this review we aim to determine the effectiveness and safety of DMEK compared to DSAEK.

Objectives

To compare the effectiveness and safety of Descemet's membrane endothelial keratoplasty (DMEK) versus Descemet's stripping automated endothelial keratoplasty (DSAEK) for the treatment of corneal endothelial failure in people with Fuch’s endothelial dystropy (FED) and pseudophakic bullous keratopathy (PBK).

Methods

Criteria for considering studies for this review

Types of studies

We will include all randomised controlled trials (RCTs) of DMEK versus DSAEK that meet our inclusion criteria.

We anticipate that there may be few, if any, RCTs. The way in which these surgical procedures have evolved means that there are more likely to be studies in which patients underwent DSAEK in the past, as the procedure of choice, before undergoing DMEK in their fellow eye. Such non-randomised contralateral eye studies have obvious limitations, but nonetheless the data from these studies may be of value because they will be at lower risk of selection and allocation bias than that from cohort studies. We will, therefore, also include data from non-randomised contralateral eye studies in which patients undergo DSAEK in one eye and DMEK in the other eye. We will not include data from any other study designs.

In the first instance data from RCTs and non-randomised contralateral eye studies will be analysed separately and then, in the absence of heterogeneity, we will perform an analysis of the combined data.

Types of participants

There will be no age or gender restrictions.

Inclusion criteria
  • We will include people with a clinical diagnosis of FED or PBK requiring a corneal transplant for the treatment of corneal endothelial failure. People undergoing combined cataract surgery and corneal transplant (phaco-DMEK/DSAEK) will be included

Exclusion criteria
  • Trials with included participants with visually significant co-morbidities (e.g. glaucoma, glaucoma filtration surgeries, aphakia, anterior chamber intraocular lenses, scleral fixated intraocular lenses)

Types of interventions

Studies in which participants or eyes undergo a DMEK or DSAEK procedure, with or without simultaneous cataract surgery as a primary procedure.

Types of outcome measures

Primary outcomes
  • Mean logarithm of the Minimum Angle of Resolution (LogMAR) best corrected visual acuity (BCVA) at 12 months postoperatively

Secondary outcomes
  • Mean logMAR BCVA at one month and three months post-treatment (to indicate speed of visual recovery)

  • Mean unaided LogMAR visual acuity at six months post-treatment (to evaluate effect of treatment on unaided vision)

  • Mean endothelial cell count as measured by specular microscopy at 6 months, 12 months, 24 months and 5 years post-treatment

  • Mean spherical equivalent refraction in dioptres at 24 months post-treatment

  • Mean regular refractive astigmatism in dioptres at 24 months post-treatment

  • Mean irregular astigmatism in dioptres at 24 months post-treatment, measured by corneal topography

Harms

Information will be collected on all harms but we will specifically analyse the following:

  • Corneal graft rejection at any time up to five years post surgery. Corneal graft rejection is defined as clinical evidence of endothelial dysfunction (increase in corneal thickness) in the presence of cells in the anterior chamber with or without the presence of keratic precipitates

  • Primary graft failure (defined as failure of postoperative corneal oedema to resolve within 3 months of surgery)

  • Graft dislocation within one week of surgery

  • Endophthalmitis within one month of surgery

  • Loss of 10 or more letters (LogMAR) versus preoperative BCVA

Search methods for identification of studies

Electronic searches

We will search CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (latest issue), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to present), EMBASE (January 1980 to present), Latin American and Caribbean Health Sciences Literature Database (LILACS) (January 1982 to present), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We will not use any date or language restrictions in the electronic search for trials.

See: Appendices for details of search strategies for CENTRAL (Appendix 1), MEDLINE (Appendix 2), EMBASE (Appendix 3), LILACS (Appendix 4), ISRCTN (Appendix 5), ClinicalTrials.gov (Appendix 6) and the ICTRP (Appendix 7).

Searching other resources

We will search the reference lists of includable studies to identify any other potentially relevant studies. We will not undertake manual handsearching of conference proceedings or journals for this review.

Data collection and analysis

Selection of studies

Two review authors will work independently to assess the titles and abstracts resulting from the searches. We will then obtain full-text reports of all possibly or definitely relevant studies for further assessment. The two review authors will assess these full-text copies to see whether they meet the inclusion criteria. We will resolve discrepancies through discussion. We will document excluded trials which were thought to be possibly relevant on the basis of the abstract but not eligible based on the assessment of the full-text copy, and record the reasons for exclusion in the ’Characteristics of excluded studies’ table.

Data extraction and management

Two review authors will extract the data independently using pre-piloted forms and web-based software Covidence (Covidence 2015).

We will collect the following information on study characteristics and summarise these in Table 1.

Table 1. Data on study characteristics
Mandatory items Optional items
Methods  
Study design
  • Parallel group RCTi.e. people randomised to treatment

  • Within-person RCTi.e. eyes randomised to treatment

  • Non-randomised contralateral eye studies i.e. one eye in same participant randomised to one intervention and other eye to other intervention

Number randomised/analysed (RCT)

or
Number recruited/analysed

(Contralateral eye studies)

Reported power calculation (Y/N), if yes, sample size and power

Eyes or

Unit of randomisation/ unit of analysis

Unit of randomisation: participants or eyes

One eye included in study, specify how eye selected

  • Both eyes included in study, both eyes received same treatment, briefly specify how analysed (best/worst/average/both and adjusted for within person correlation/both and not adjusted for within person correlation) and specify if mixture one eye and two eye

  • Both eyes included in study, eyes received different treatments,specify if correct pair-matched analysis done

Participants  
Country 

Setting

Ethnic group

Total number of participants

This information will be collected for total number of study participants who received the intervention and follow up data was reported. We collect the average age of the participants and also the age range

If only one eye from one participant is selected we will record why and when this decision was made

 
Average age and age range
Inclusion criteria
  • People with a clinical diagnosis of endothelial decompensation secondary to FED or PBK and who required a corneal transplant

  • People with co-existent cataracts undergoing combined cataract surgery and corneal transplant (phaco-DMEK/phaco-DSAEK) will be included

Exclusion criteria
  • People who have corneal endothelial failure as a result of a pathology other than FED or PBK

  • Visually significant co-morbidities, especially glaucoma

  • People with visually significant cataract which is not treated prior to, or at the time of, corneal transplant

InterventionsDMEK or DSAEK with or without simultaneous phacoemulsification and lens implant 

Intervention (n= )

Comparator (n= )

See MECIR 65 and 70

  • Number of people randomised to DSAEK

  • Number of people randomised to DMEK

 
Outcomes

Primary outcomes

  • Mean logarithm of the Minimum Angle of Resolution (LogMAR) best corrected visual acuity (BCVA) at 12 months postoperatively

Secondary outcomes

  • Mean logMAR BCVA at 1 month and 3 months post-treatment (to indicate speed of visual recovery)

  • Mean endothelial cell count as measured by specular microscopy at 6 months, 12 months, 24 months and 5 years post-treatment

  • Corneal graft rejection

  • Primary graft failure

  • Graft dislocation

  • Loss of 10 or more letters (LogMAR) versus preoperative BCVA

 

Primary and secondary outcomes as defined in study reports

See MECIR R70

We will collect data on adverse events

A 6, 12 and 24 month follow-up schedule will be collected

 
Notes  

Declaration of interest

See MECIR 69

  
  • Study design: parallel group RCT/within-person RCT/one or both eyes reported

  • Unit of randomisation: (participants or eyes)

  • Participants: country, total number of participants, total number of eyes, age, sex, inclusion and exclusion criteria

  • Intervention and comparator details: including number of people (eyes) randomised to each group

  • Primary and secondary outcomes as measured and reported in the trials, adverse events

  • Length of follow-up

  • Date study conducted

  • Funding and conflicts of interest

We will extract data on all of the outcomes pre-specified in our Methods (Types of outcome measures) section. We will resolve discrepancies through discussion amongst all authors. One review author will enter the data into Review Manager (RevMan 2014), and a second review author will check the entered data for errors and inconsistencies.

Assessment of risk of bias in included studies

Two review authors will assess studies meeting the inclusion criteria for risk of bias. For eligible RCTs we will use the principles described in Cochrane's 'Risk of bias' tool in Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will consider the following domains: random sequence generation (selection bias) and allocation concealment (selection bias), masking of participants, masking of outcome assessment (performance bias and detection bias), completeness of follow-up (attrition bias) and selective reporting (reporting bias). Masking of surgeons performing the procedure is clearly not possible. However, we will consider studies where the participants and the assessors have been masked to be at low risk of performance bias and detection bias. In studies where participants or assessors have not been masked to the intervention, the study will be deemed as having high risk of performance bias and detection bias. We will grade each parameter as: low risk of bias, high risk of bias and unclear. We will resolve any disagreements between the review authors by discussion.

To assess the risk of bias in non-randomised contralateral eye studies (NRS) meeting our inclusion criteria we will use the ACROBAT-NRSI (“A Cochrane Risk Of Bias Assessment Tool for Non-Randomized Studies”) tool (Sterne 2014). This tool requires us to define a hypothetical generic target randomised trial addressing the population, intervention, comparator and outcomes of interest. The conceptualisation of this hypothetical generic target trial allows the research question to be clearly specified, and complexities that may arise with respect to the tools used to measure an outcome domain or the timing of measurements to be identified. Based on the inclusion and exclusion criteria for this review as a whole, we have defined our generic target trial as DMEK versus DSAEK for the treatment of corneal decompensation and visual acuity of 6/12 or less.

When using the ACROBAT-NRS tool, DMEK will be defined as the experimental intervention and DSAEK as the control intervention. In our hypothetical generic target trial, our effect of interest would be the effect of assigning patients to one treatment or other (DMEK or DSAEK) at baseline. This effect would be measured using an intention-to-treat analysis in our generic target trial. We will therefore use the ACROBAT-NRS analogue of starting experimental intervention versus starting control intervention to evaluate risk of bias.

NRS meeting inclusion criteria will likely have confounding domains which predict whether a participant receives the experimental or control intervention. The most likely confounding domain is the differing follow-up periods between eyes. DSAEK is an older procedure and therefore many patients in non-randomised contralateral eye studies will have undergone DSAEK many months or years previously and DMEK (the newer intervention) more recently. It is possible that there could be a difference of many months or even years between the procedures which could confound the results, particularly regarding long-term outcomes. The second confounding domain is ocular co-morbidity. DSAEK is perceived as technically more straight forward than DMEK in cases where the patient has a shallow anterior chamber or anterior chamber lens inserted or has undergone previous glaucoma surgery. Our inclusion and exclusion criteria for this review will exclude such patients. All studies included will be single intervention studies, and subsequently there will be no co-interventions which would have an effect on the outcome of interest.

Measures of treatment effect

In this review, we will treat these outcomes as dichotomous data and we will use the odds ratio (OR) to measure the effect size.

  • Primary graft failure

  • Corneal graft rejection (dichotomous)

  • Graft dislocation

  • Endophthalmitis

  • Loss of 10 or more letters (LogMAR) versus preoperative BCVA

We will treat the following outcomes as continuous data and will use the mean difference.

  • Time to corneal graft rejection

  • BCVA (LogMAR)

  • Unaided visual acuity (LogMAR)

  • Degree of irregular astigmatism

  • Refractive error (spherical equivalent in dioptres and amount of regular astigmatism in dioptres)

  • Endothelial cell density

If we suspect or find that the values for these outcomes are not normally distributed then we will report the median and interquartile ranges.

Unit of analysis issues

Trials may randomise one or both eyes to the intervention or comparator.

If people are randomised and allocated to treatment but only one eye per person is included in the trial, then there will not be a unit of analysis issue. In these cases, we will document how and when the eye was selected in order to determine whether the selection was data driven.

If people are randomly allocated to treatment but both eyes are included and reported, we will analyse as 'clustered data' i.e. adjust for within-person correlation. We may have to contact the trial investigators for further information to do this.

Non-randomised trials included in the review (within-person study) will be analysed as paired data. We may have to contact the trial investigators for further information to do this.

Dealing with missing data

We will evaluate all studies for missing outcome data, missing summary data, missing individuals (e.g. lost to follow-up) and missing study level characteristics such as subgroup analyses.

In the event of missing data we will document the cause and assess whether the data are missing at random (where the fact that the data are missing is not related to the actual values of the data) or whether the data are not missing at random (where the missing data may be related to the treatment administered) such as losses to follow up.

Whenever possible, we will contact the original investigators to request missing data. Where this is not forthcoming we will analyse data as follows:

  1. Where data are missing at random we will analyse only the available data (i.e. ignoring the missing data). In this event we will make explicit our assumption that the data are missing at random.

  2. Imputing the missing data with replacement values, and treating these as if they were observed (e.g. last observation carried forward, imputing an assumed outcome such as assuming all were poor outcomes, imputing the mean, imputing based on predicted values from a regression analysis). Again, where we impute missing data we will make explicit the assumptions made when choosing our method to cope with missing data.

  3. We will perform sensitivity analyses to assess how sensitive our results are to reasonable changes in the assumptions that are made.

  4. We will address the potential impact of missing data on the findings of the review in the Discussion section.

Assessment of heterogeneity

In order to decide whether it is possible to carry out a meta-analysis on the results of the trials found, we will check for heterogeneity by examining:

  • the characteristics of the studies;

  • the forest plot of results of the studies;

  • the results of the Chi2 test for statistical heterogeneity;

  • the I2 statistic computed to quantify inconsistencies between study results.

A Chi2 P value of less than or equal to 0.10 will be regarded as indicating significant heterogeneity.

We will use the following thresholds for the interpretation of I2:

  • 0% to 30%: Unlikely to be any heterogeneity;

  • 30% to 60%: may represent moderate heterogeneity*;

  • 50% to 90%: may represent substantial heterogeneity*;

  • 75% to 100%: considerable heterogeneity

* The I2 value will be interpreted in light of the magnitude and direction of intervention effects and the strength of evidence for heterogeneity (P value from the Chi2 test, or confidence interval for I2).

If heterogeneity is identified, we will not combine results but will report a descriptive summary of results. If no heterogeneity is detected we will calculate summary measures using a fixed-effect model where we have three or fewer studies. Where more than three studies are included we will use a random-effects model.

Assessment of reporting biases

If the protocol for a trial is available, then the outcomes in each trial protocol will be compared with the published report. If not, then the outcomes listed in the methods section of an article will be compared with those reported in the results section. If there are 10 trials or more included in an analysis, we will construct funnel plots and consider tests for asymmetry for bias assessment, according to Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Data synthesis

In the absence of heterogeneity we will perform meta-analysis of data from RCTs and non-randomised contralateral eye studies separately in the first instance. We will then pool the data from both study types and, in the absence of heterogeneity, we will perform a meta-analysis on these pooled data.

We will combine parallel arm studies with studies using paired data by means of generic inverse variance meta-analysis.

Subgroup analysis and investigation of heterogeneity

We will perform subgroup analysis of outcomes in patients with PBK and patients with FED.

We will perform subgroup analysis of combined phaco-DMEK/phaco-DSAEK procedures and DSAEK/DMEK alone.

Sensitivity analysis

We will conduct sensitivity analyses to examine how strongly our review results are related to the decisions and assumptions that have been made during the review. We will evaluate the effect of excluding RCTs deemed as high risk of bias for allocation concealment. We will then examine the effect of excluding trials assessed as high risk of bias on any parameter, unpublished trials or data, and industry-funded studies, by repeating the analysis without these.

We will utilise the NRSI tool to identify non-randomised contralateral eye studies deemed to be at high risk of bias and evaluate the effect of excluding these from the pooled and subgroup analysis.

'Summary of findings' table

We will prepare a 'Summary of findings' table presenting relative and absolute risks. Two authors will grade independently the overall quality of the evidence for each outcome using the GRADE classification (GRADEpro 2015). We will include the following outcomes in the 'Summary of findings' table:

  • Mean logarithm of the Minimum Angle of Resolution (LogMAR) best corrected visual acuity (BCVA) at 12 months postoperatively in the operated eye

  • Severe visual loss (LogMAR BCVA of 1.0 or less)

  • Mean endothelial cell count as measured by specular microscopy at 6 months, 12 months, 24 months and five years post-treatment

  • Corneal graft rejection

  • Primary graft failure

  • Graft dislocation

Acknowledgements

Cochrane Eyes and Vision (CEV) will create and execute the electronic search strategies. We thank Jod Mehta and Ana Quartilho for their comments on this protocol. We thank Jennifer Evans and Anupa Shah for their support with the editorial process.

Appendices

Appendix 1. CENTRAL search strategy

#1 MeSH descriptor: [Fuchs' Endothelial Dystrophy] this term only
#2 fuchs* near/3 endothelial near/3 dystroph*
#3 fuchs* near/3 dystroph*
#4 bullous keratopath*
#5 pbk
#6 #1 or #2 or #3 or #4 or #5
#7 MeSH descriptor: [Descemet Membrane] this term only
#8 Descemet* near/2 strip* near/5 keratoplast*
#9 Descemet* near/2 membrane* near/5 keratoplast*
#10 DSAEK or DMEK
#11 #7 or #8 or #9 or #10
#12 #6 and #11

Appendix 2. MEDLINE (OvidSP) search strategy

1. Fuchs' Endothelial Dystrophy/
2. (fuchs$ adj3 endothelial adj3 dystroph$).tw.
3. (fuchs$ adj3 dystroph$).tw.
4. bullous keratopath$.tw.
5. pbk.tw.
6. or/1-5
7. Descemet Membrane/
8. (Descemet$ adj2 strip$ adj5 keratoplast$).tw.
9. (Descemet$ adj2 membrane$ adj5 keratoplast$).tw.
10. (DSAEK or DMEK).tw.
11. or/7-10
12. 6 and 11

Appendix 3. EMBASE (OvidSP) search strategy

1. congenital cornea dystrophy/
2. (fuchs$ adj3 endothelial adj3 dystroph$).tw.
3. (fuchs$ adj3 dystroph$).tw.
4. bullous keratopath$.tw.
5. pbk.tw.
6. or/1-5
7. Descemet Membrane/
8. (Descemet$ adj2 strip$ adj5 keratoplast$).tw.
9. (Descemet$ adj2 membrane$ adj5 keratoplast$).tw.
10. (DSAEK or DMEK).tw.
11. or/7-10
12. 6 and 11

Appendix 4. LILACS search strategy

(fuchs$ endothelial dystroph$ or fuchs$ dystroph$) and (Descemet$ strip$ keratoplast$ or Descemet$ membrane$ keratoplast$ or DSAEK or DMEK)

Appendix 5. ISRCTN search strategy

"(fuchs OR endothelial dystrophy OR bullous keratopathy OR pbk) AND (descemet OR DSAEK OR DMEK)"

Appendix 6. ClinicalTrials.gov search strategy

(fuchs OR endothelial dystrophy OR bullous keratopathy OR pbk) AND (descemet OR DSAEK OR DMEK)

Appendix 7. ICTRP search strategy

fuchs OR endothelial dystrophy OR bullous keratopathy OR pbk = Condition AND descemet OR DMEK or DSAEK = Interventions

Contributions of authors

Protocol written by AJ Stuart and edited by AJ Shortt with additions by G Virgili.

Declarations of interest

AJ Stuart: None known
G Virgili: None known
AJ Shortt: None known

Sources of support

Internal sources

  • No sources of support supplied

External sources

  • National Institute for Health Research, UK.

    • Richard Wormald, Co-ordinating Editor for Cochrane Eyes and Vision (CEV) acknowledges financial support for his CEV research sessions from the Department of Health through the award made by the National Institute for Health Research to Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology for a Specialist Biomedical Research Centre for Ophthalmology.

    • The NIHR also funds the CEV Editorial Base in London.

    The views expressed in this publication are those of the authors and not necessarily those of the NIHR, NHS, or the Department of Health.

Ancillary