Journal of Cataract and Refractive Surgery Publish Ahead of Print

DOI:10.1097/j.jcrs.0000000000001256

Safety and Efficacy of Laser Refractive Procedure in eyes with previous keratoplasty - A
Systematic Review and meta-analysis

Authors list:
Abdulrahman Hameed Alsubhi, MBBS
Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia
[email protected]

Nawaf Alhindi, MBBS

Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia.
[email protected]

Abdulrahman Abukhudair, MBBS

Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia.
[email protected]

Abdulrahman Alsulami, MBBS

Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia.
[email protected]

Hadeel Seraj, MBBS

Department of Ophthalmology, King Abdulaziz University hospital, Jeddah, Saudi Arabia.
[email protected]

Hussein Morfeq, DES, FEBO

Assistant professor. Department of Ophthalmology, King Abdulaziz University, Jeddah, Saudi
Arabia.
[email protected]

Corresponding author:
Abdulrahman Alsubhi
Faculty of Medicine, King Abdulaziz University, Rabigh, Saudi Arabia
[email protected]
P.O. BOX: 46356
Mobile: +966532914541
Running head: “Post-keratoplasty laser vision correction”
Financial Support:
None
Conflict of interest:
The authors do not have any conflict of interest to declare
Acknowledgement:
None.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Abstract

Post-keratoplasty patients’ visual acuity can be severely limited by ametropia. Irregular

astigmatisms are frequently encountered in these patients and is commonly associated with

high degrees of hyperopia or myopia. This systematic review investigates the safety and

efficacy of laser refractive surgery for post keratoplasty vision correction. Thirty-one studies with

683 participants (732 eyes) enrolled in this review. Mean astigmatism improved significantly

(MD = -2.70, 95%CI, -3.13 to -2.28, p < 0.0001). As well as Mean spherical equivalent (MD = -

3.35, 95%CI, -3.92 to -2.78, p < 0.0001). from 586 participants 5.8% lost two or more lines of

CDVA after treatment. The proportion of eyes with 20/40 UCVA or better was reported and the

percentage was 46.79% overall. Laser refractive procedures (LASIK or PRK or T-PRK) on eyes

with corneal transplantation were found to be relatively safe and effective. Our systematic

review shows there is improvement in all outcomes. Main adverse effects were haze for PRK

and epithelial ingrowth for LASIK.

Keyword
Post-keratoplasty, Laser refractive surgery, LASIK, PRK

Introduction

Keratoplasty (KP) is a surgical procedure that replaces damaged or diseased layers of the

cornea with healthy donor tissue. The main purpose of KP is to improve visual acuity.

Advancements in eye banking and microsurgical techniques have improved the survivability and

optical clarity of corneal grafts, however patients’ visual acuity can be limited by postoperative

ametropia 1. A big factor that affects visual acuity is astigmatism as it is estimated to affect 20%

to 40% of eyes following KP 2. The range of post-keratoplasty astigmatism has been reported to

be between 2 and 8 diopters and is commonly associated with high degrees of hyperopia or

myopia 3,4. These errors often arise from corneal surface irregularity which is caused by multiple

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
factors. These factors can be preoperative such as the etiology for keratoplasty, intra operative

as in eccentric trephination or failure to excise the peripheral pathology of the cornea, or

postoperative as the timing of sutures removal or the healing of the wound.

Poor postoperative refractive results can be managed with sutures adjustments or selective

removal 5,6. The use of optical correction methods such as glasses and contact lenses can

reduce astigmatism and aniseikonia to an acceptable level, however, this may not be successful

with patients that cannot handle them or in cases with high irregular astigmatism. It has been

reported that 8% to 20% of patients with post KP astigmatism do not tolerate glasses or contact

lenses and require surgical intervention7,8,9. Fortunately, a variety of refractive surgical options

can be used. Relaxing incisions 10, relaxing incisions plus compression sutures 11, wedge

resections 12, intraocular lens (IOL) implantation 13, intracorneal ring segments 14 and laser

vision correction in the form of photorefractive keratectomy (PRK) and laser in situ

keratomileusis (LASIK) are treatment options that may be considered 15,16. Repeat keratoplasty

may be considered as a final option 17.

Both LASIK and PRK are commonly used to correct different types of refractive errors, LASIK

involves the creation of a lamellar corneal flap which is followed by laser ablation on the stromal

surface. The flap can be created using a microkeratome or, more recently, with a femtosecond

laser (FS-LASIK). In PRK the corneal epithelial layer is removed, and the eye is then irradiated

by the laser 18,19. For patients with post-keratoplasty astigmatism undergoing laser refractive

surgery, preoperative assessment and comprehensive corneal/lens evaluation are crucial for

proposing an adequate treatment. The magnitude of cylinder, topographical irregularity,

internal/corneal aberrations, and lens opacity must be evaluated for accurate treatment

planning.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Ablation profiles (planoscan, apheric, cross-cylinder, bi-toric, WFG, WFO) and planning tools

(Q-custom, ORK-Scan, CIPTA, Contoura, Phorcides, etc.) are important considerations in post-

keratoplasty astigmatism surgery. Selection of the most appropriate ablation profile and

planning tool based on the patient's individual needs and characteristics is crucial for optimal

surgical outcomes.

Evidence has been reviewed for other refractive surgeries, but no comprehensive review on

laser refractive procedures is available 20. Therefore, we aim through this systematic review to

evaluate the safety and efficacy of laser refractive procedures (LASIK or PRK) on eyes with

refractive errors following corneal transplantation.

Methods and Materials

Literature Search

This systematic review study seeks to identify the reported studies of excimer laser vision

correction in post-keratoplasty patients. Our systematic review was conducted per the Preferred

Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines 21. This study

was registered in the International Prospective Register of Systematic Reviews (PROSPERO),

ID Number: CRD42022326450 The need for ethical approval was waived due to the type of

the study. In April 2022, we performed a comprehensive systematic review of the online

literature using the following electronic databases: Cochrane, MEDLINE, and EMBASE. We

systematically reviewed the literature from inception without time limitations. We used the

following keywords: (Postkeratoplasty OR post-keratoplasty) AND ( photorefractive keratectomy

OR PRK OR Laser-Assisted Subepithelial Keratectomy OR epipolis laser in situ keratomileusis

OR Epi-LASIK OR transepithelial photorefractive keratectomy OR TransPRK OR laser in situ

keratomileusis OR refractive surgery).

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Study selection

All the included articles in this systematic review met the previously set inclusion criteria: (1)

studies published without time frame limitations in April 2022; (2) articles published in the

English language; (3) Studies of the following designs (RCT, case-control, cohort, or case

series); (4) post-keratoplasty (mostly PK and DALK) patients received laser surgery for the

correction of any refractive error ; (5) Studies reported outcomes of interest for the clinical

question. Our exclusion criteria were as follows: (1) the study used improper methods (meta-

analysis, systematic review, animal study, cadaver study, case reports, narrative review, or

editorial); (2) non-post keratoplasty refractive error correction; (3) used other surgical options

than laser surgery; (4) languages other than English.

Screening and Data extraction

The screening process started with the title and abstract by four independent reviewers, and

then full-text screening was done on the included articles. Outcome measures were extracted

and uploaded into Excel sheet, including study characteristics (author, publication year, country,

study design), sample Characteristics (size, gender, laterality, age of the patients at the time of

presentation, type of keratoplasty, time since keratoplasty, and type of procedure), pre- and

post-laser investigation (SE, cylindrical equivalent, higher-order aberrations, uncorrected visual

acuity, and corrected distant visual acuity), and outcomes (complication, recurrence, and length

of follow-up). Two senior independent reviewers (AS, NH) resolved disagreements regarding

the data extraction and screening. To eliminate duplication, the retrieved data was double-

checked.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Assessment of Methodological Quality

Two authors evaluated the risk of bias of the included articles using two main assessment tools

(methodological quality of case report and case series for the assessment of observational

studies, and the methodological index for non-randomized studies (MINORs) for the

assessment of interventional studies 22, 23. The first consisted of four domains (Selection,

Ascertainment, Causality, and Reporting) and each domain consisted of 1-4 items explained in

Supplemental table 1. The other tool (MINORs) consisted of at least 12-items and shown in the

Supplemental tables 2,3. The two authors assessed each article individually and in spite of the

item's suggestion of bias, both authors obtained identical results.

Outcomes measures and statistical Analysis

Primary outcome measures were postoperative mean spherical equivalent, mean astigmatism,

and proportion of eyes with 2 or more lines of CDVA loss. Proportion of eyes within 0.5D and

1.0D of target spherical equivalent were included as secondary outcomes. Adverse events were

considered as reported by the included articles. The differences between pre- and post-

treatment values of the spherical equivalent (SE) and astigmatism were assessed using mean

difference (MD) and the respective 95% confidence intervals (95%CIs). We used the inverse

variance method with restricted maximum likelihood estimator for tau2. Additionally, we used a

Q test to assess the differences between LASIK and PRK groups. The pooled proportions of

eyes within ±0.5 D and ±1.0 D of the target, as well as the overall proportions of complications

were estimated using a random intercept logistic regression model with a maximum-likelihood

estimator for tau2. Heterogeneity assessments was performed using the I2 test, where a

significant heterogeneity was deemed at I2 > 50%. A random-effects model was applied in the

instance of significant heterogeneity; otherwise, we applied a fixed-effects model. Statistical

significance was considered at p < 0.05.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Results

Literature Findings

Electronic databases searches in April 2022 gave 631 records (Figure 1). Title and abstract

screening were conducted on 449 after the removal of duplicates and 53 articles were

potentially eligible for inclusion in our review. We incorporated 31 articles after a full manuscript

review, later we searched references of the included studies however, no articles were found to

fulfill our inclusion criteria. Added studies characteristics are summarized in table 1. Comprised

studies were published between 1992 and 2022, 23 were prospective clinical trials 4,15,16,24-35,37-
39,42,46,48,49,51,52
and 8 were retrospective 36,40,41,43-45,47,50. Almost all studies had one treatment arm

except Huang et al 36 which had two arms. six studies were conducted in the USA, 5 in Brazil, 4

in Canada, 3 in Italy, 3 in Turkey, 3 in Germany, and 1 in Australia, Egypt, Iran, Japan, Korea,

England, and Spain. A total of 683 participants (732 eyes) met our inclusion criteria. Four

prospective clinical trials 25,34,40,42 had 27,14,16, and 26 participants; but only 6,7,13 and 18 had

refractive errors after undergoing keratoplasty. Mean age was reported in all studies but

three;15,28,40 the age mean was (44.1) years. 23 studies 4,15,16.24,26,27,29-33,35-37,39,41,43-47,49,50,52

reported patients’ gender; the female percentage was (43.6%) of the total number of

participants. Follow-ups ranged from 1 month to 56 months. 17 studies performed LASIK

4,15,24,27,29-31,33,38,41,43,45,47,50-52
, 12 studies performed PRK; of which two performed additional

refractive procedures (PTK, ICRS) 42,48 and one performed LASEK on a comparison group 36.

three studies performed T-PRK 25,37,42. Three of the included papers reported using multiple

sequential laser ablations to reach the desired refraction 35, 38, 44. Only one study used femto-

LASIK instead of mechanical LASIK 52. The average time between keratoplasty and laser

treatment was 50.9 months in the 18 studies that reported it. The number of studies that

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
reported the proportion of eyes achieving 20/20 UCVA or better is 22 studies 15,16,25-33,37,39-43,45-
48,51
. Out of 432 eyes in these studies 9.49% achieved 20/20. Among LASIK studies 11 reported

this outcome and had a total of 247 eyes with 8.09% achieving 20/20. For PRK 8 studies with

151 eyes had a 9.27% of eyes achieving 20/20. The proportion of eyes with 20/40 UCVA or

better was reported by 24 studies with 530 eyes 4,15,16,25-33,35,37-44,46-48,51, and the percentage was

46.79% overall. For LASIK 12 studies reported this outcome with 51.85% of 270 participants

having 20/40 or better. Among 226 eyes from 9 studies in which PRK was done, 39.38% had

20/40 or better UCVA.

Quality Assessment and Risk of Bias

The authors (ِAT, AA) assessed the risk of bias separately and simultaneously using the two

tools mentioned earlier. We used a methodological quality assessment tool based on eight

components that are divided into four domains: selection, ascertainment, causation, and

reporting (Supplemental Table 1). The findings of both reviewers were identical, regardless of

whether the material seemed biased. MINORs were at least 70% in all retrospective and

prospective studies considered. There were two comparative studies, which scored a total of 16

and 24 out of 24. The twelve noncomparative studies had an average score of 12.0 (range 10-

14). The results are summarized in Supplemental tables 2 and 3. The assessment of publication

bias showed a significant risk of bias in the outcomes of SE, astigmatism, proportion of eyes

within ±1.0 D of the target and the proportion of eyes with ≥2 lines CDVA loss. This was

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
confirmed by the results of the Egger’s test (p=0.042, p=0.002, p= 0.001 and p < 0.0001,

respectively, Supplemental Figure 1).

Spherical equivalent and astigmatism

The difference between pre- and post-treatment spherical equivalent (SE) was statistically

significant for all patients (MD = -3.35, 95%CI, -3.92 to -2.78, p < 0.0001), and the between-

study heterogeneity was significant (I2 = 91%). The statistical difference remained significant

among patients who underwent customized PRK procedures (MD = -2.74, 95%CI, -3.82 to -

1.67), conventional PRK procedures (MD = -3.02, 95%CI, -4.57 to -1.47), customized LASIK

procedures (MD = -3.30, 95%CI, -5.15 to -1.44) and conventional LASIK procedures (MD = -

4.06, 95%CI, -4.57 to -3.56). The difference between subgroups was not significant (p = 0.117,

Figure 2).

For the astigmatism, the pooled difference between pre- and post-treatment outcome was

statistically significant (MD = -2.70, 95%CI, -3.13 to -2.28, p < 0.0001) with a significant

heterogeneity between studies (I2 = 87%). The difference between pre- and post-treatment

measures was significant in the customized PRK group (MD = -1.95, 95%CI, -2.14 to -1.76),

conventional PRK group (MD = -2.78, 95%CI, -3.93 to -1.63), customized LASIK group (MD = -

2.66, 95%CI, -3.32 to -1.99) and conventional LASIK group (MD = -3.16, 95%CI, -3.86 to -2.46).

Subgroup differences were statistically significant (p = 0.002, Figure 3).

Accuracy

The pooled proportion of eyes within ±0.5 D of the target refraction was 41.7% (95%CI, 31.3 to

53.0), and the studies showed a significant heterogeneity (I2 = 57.7%). The pooled estimates in

the LASIK and PRK groups were 37.5% (95%CI, 26.1 to 50.4) and 47.7% (95%CI, 29.8 to

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
66.2), respectively, and the between-study difference was not statistically significant (p = 0.375,

Figure 4A). Regarding the eyes within ±1.0 D of the target, we reported a pooled proportion of

55.0% (95%CI, 43.4 to 66.1), and the studies were significantly heterogenous (I2 = 64.7%). The

LASIK and PRK groups had proportions of 57.0% (95%CI, 46.3 to 67.0) and 54.7% (95%CI,

32.9 to 74.8), respectively, and there was no difference between the groups (p = 0.856, Figure

4B).

Safety

The overall proportion of eyes with ≥2 lines CDVA (correction with either glasses or contact

lenses) loss was 5.8% (95%CI, 4.2 to 8.1), and the heterogeneity was not statistically significant

(I2 = 0%). The proportion in the LASIK group was 4.9% (95%CI, 3.1 to 7.7) and in the PRK

group was 7.5% (95%CI, 4.6 to 12.0). The difference between studies was not significant (p =

0.216, Figure 5). Change in CDVA is displayed on Supplemental Figure 2

Complications and Adverse Events

No complications were reported in ten studies, of which PRK surgeries were performed in four
32, 36, 37, 42
studies and LASIK surgeries in the remaining investigations15, 24, 31, 38, 50, 52
. Other

studies which reported complications employed 409 patients with an overall incidence of 14.3%

(95%CI, 9.3 to 21.4), and the heterogeneity was significant for the pooled calculation (I2 =

51.7%). The overall incidence rates of complications were 17.1% (95%CI, 9.8 to 28.0) in PRK

studies and 11.3% (95%CI, 6.2 to 19.6) in LASIK studies with no significant difference between

groups (p = 0.299, Figure 5). The reported complications were Haze (n=22, 5.4%), epithelial

ingrowth (n=14, 3.4%), regression (n=12, 2.9%), graft rejection (n=10, 2.4%) and perforation

(n=5, 1.2%).

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Discussion

We included 31 articles in our review that had 683 participants (732 eyes) who underwent laser

refractive surgery (LASIK, PRK, T-PRK, LASEK) for correction of post-keratoplasty ametropia

and astigmatism. We found evidence of significant improvement in SE means and astigmatism

means between the preoperative and postoperative period, with 50% in the 1.0D range of target

refraction. The report of loss in CDVA of 2 lines or more was 5.8% overall, with the main

adverse effects that could impact vision being haze and regression for PRK and epithelial

ingrowth for LASIK, which are known complications even in virgin eyes. The potential

complication of an increased rate of graft rejection was not found (2.1%) when compared with

other studies 53,26. Outcomes were comparable between LASIK and PRK, but with more concern

for developing haze after PRK. Pedrotti 37 et al demonstrated excellent results with T-PRK,

which is considered simpler and safer than the traditional PRK, and with no cases developing

significant haze. AK is the most used refractive surgery for post-KP astigmatism, but it was

found to be unpredictable and often patients require additional procedures to achieve significant

improvement in vision as it only offers cylindrical correction 20. We found consistent

improvement in all outcomes and the interventions as being relatively safe throughout the

studies. The studies in this review enrolled participants with refractive errors that ranged from

moderate hyperopia to high myopia with both regular and irregular astigmatism, but all of them

had a mean refractive error of moderate to high myopia and astigmatism. Primarily participants

had penetrating keratoplasty, but few studies had eyes with deep anterior lamellar keratoplasty.

Therefore, the results in this study are mainly applicable to eyes with these characteristics. The

interventions performed included LASIK, PRK, LASEK, and T-PRK with the earlier two being the

most used. Some patients have undergone different refractive procedures before laser

treatment for various reasons. These include unsatisfactory results, pre-planned reduction of

corneal irregularity, and very high refractive errors32,40,42,48. In this concept, two steps techniques

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
have been demonstrated. For LASIK the creation of a lamellar flap alone followed by laser

ablation in two consecutive procedures has been proposed to be more predictable than the one-

step procedure 15,50. Sorkin 44 et al used a first surface ablation to regularize the cornea and a

second for refractive correction. We reviewed the studies included in our meta-analysis to

determine if they took into consideration the posterior astigmatism and investigated the graft-

host transition with an OCT. We found that only two studies used OCT, one to measure the

corneal thickness and the other to evaluate the graft. Unfortunately, we were not able to identify

any correlation between these findings and the differences in results among techniques 31, 48.

Almost all the studies had one arm of intervention with heterogeneity between the procedures.

Another source of heterogeneity is the etiology for performing KP as well as the pretreatment

regularity status of the corneal surface. In most studies, we had difficulty extracting the time

points that different outcome measures were reported at. Nonetheless, studies with longer

duration of follow up showed that the refractive results are mostly stable with minor regression

in vision which was explained by other conditions 33, 36, 45. Additionally, selection bias may be a

concern due to the design of included studies. In this review, we followed the PRISMA

guidelines, and studies were screened by two separate reviewers. We did an electronic

database search without publication date restrictions; however, we limited the inclusion to only

studies that were published in English. This systematic review on an important clinical area is of

value as the literature is almost exclusively small case series. We reviewed the traditional

outcomes for refractive surgery patients, however irregular astigmatism is often the main feature

in these patients and often indicates the presence of higher order aberrations which is missing

from our review. Due to the limited data availability, comparison of studies that presented a

vectorial analysis of surgically induced astigmatism was not possible. This method assumes a

regular toric surface, and this may not be the case for post-keratoplasty eyes. With these prior

mentioned limitations, we suggest that future research could investigate the use of vectorial

analysis in post-keratoplasty eyes, with consideration for the irregular astigmatism that can

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
occur after this procedure. This could help to better understand the impact of surgically induced

astigmatism on visual outcomes in this population. Furthermore, evidence would benefit from

high-quality studies that make direct comparisons between these different types of

interventions.

Conclusion

In conclusion, this systematic review gathered the literature to evaluate the safety and efficacy

of laser refractive procedures (LASIK or PRK or T-PRK) on eyes with refractive errors following

corneal transplantation. The literature shows these procedures are relatively safe and effective,

with improvement in all the outcomes measured. We found significant improvement in

astigmatism and SE means. The loss in CDVA of 2 lines or more was 5.8% overall. Main

adverse effects were haze for PRK and epithelial ingrowth for LASIK. Future high-quality studies

that compare between these different types of interventions are recommended.

Acknowledgement:
None.

Financial Support:
None
Conflict of interest:
The authors do not have any conflict of interest to declare

Supplemental Figure 1-http://links.lww.com/JRS/A942

Supplemental Figure 2-http://links.lww.com/JRS/A943
Supplemental Table 1-http://links.lww.com/JRS/A944
Supplemental Table 2-http://links.lww.com/JRS/A945
Supplemental Table 3-http://links.lww.com/JRS/A946

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
References

1. Riddle HK Jr, Parker DA, Price FW Jr. Management of postkeratoplasty astigmatism. Curr
Opin Ophthalmol. 1998 Aug;9(4):15-28. doi: 10.1097/00055735-199808000-00004. PMID:
10387463.

2. Williams KA, Ash JK, Pararajasegaram P, Harris S, Coster DJ. Long-term outcome after
corneal transplantation. Visual result and patient perception of success. Ophthalmology. 1991
May;98(5):651-7. doi: 10.1016/s0161-6420(91)32238-3. PMID: 2062497.

3. Hoffart L, Proust H, Matonti F, Conrath J, Ridings B. Correction of postkeratoplasty

astigmatism by femtosecond laser compared with mechanized astigmatic keratotomy. Am J
Ophthalmol. 2009 May;147(5):779-87, 787.e1. doi: 10.1016/j.ajo.2008.12.017. Epub 2009 Feb
20. PMID: 19232560.

4. Donnenfeld ED, Kornstein HS, Amin A, Speaker MD, Seedor JA, Sforza PD, Landrio LM,
Perry HD. Laser in situ keratomileusis for correction of myopia and astigmatism after
penetrating keratoplasty. Ophthalmology. 1999 Oct;106(10):1966-74; discussion 1974-5. doi:
10.1016/S0161-6420(99)90410-4. PMID: 10519594.

5. Binder PS. The effect of suture removal on postkeratoplasty astigmatism. Am J Ophthalmol.

1988 Jun 15;105(6):637-45. doi: 10.1016/0002-9394(88)90057-8. PMID: 3287939.

6. Sarhan AR, Dua HS, Beach M. Effect of disagreement between refractive, keratometric, and
topographic determination of astigmatic axis on suture removal after penetrating keratoplasty.
Br J Ophthalmol. 2000 Aug;84(8):837-41. doi: 10.1136/bjo.84.8.837. PMID: 10906087; PMCID:
PMC1723594.

7. Hardten DR, Lindstrom RL. Surgical correction of refractive errors after penetrating
keratoplasty. Int Ophthalmol Clin. 1997 Winter;37(1):1-35. doi: 10.1097/00004397-199703710-
00003. PMID: 9101343.

8. Price FW Jr, Whitson WE, Marks RG. Progression of visual acuity after penetrating
keratoplasty. Ophthalmology. 1991 Aug;98(8):1177-85. doi: 10.1016/s0161-6420(91)32136-5.
PMID: 1923353.

9. Rajan MS, O'Brart DP, Patel P, Falcon MG, Marshall J. Topography-guided customized laser-
assisted subepithelial keratectomy for the treatment of postkeratoplasty astigmatism. J Cataract
Refract Surg. 2006 Jun;32(6):949-57. doi: 10.1016/j.jcrs.2006.02.036. PMID: 16814052.

10. Geggel HS. Arcuate relaxing incisions guided by corneal topography for postkeratoplasty
astigmatism: vector and topographic analysis. Cornea. 2006 Jun;25(5):545-57. doi:
10.1097/01.ico.0000214222.13615.b6. PMID: 16783143.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
11. Javadi MA, Feizi S, Yazdani S, Sharifi A, Sajjadi H. Outcomes of augmented relaxing
incisions for postpenetrating keratoplasty astigmatism in keratoconus. Cornea. 2009
Apr;28(3):280-4. doi: 10.1097/ICO.0b013e3181875496. PMID: 19387228.

12. Ezra DG, Hay-Smith G, Mearza A, Falcon MG. Corneal wedge excision in the treatment of
high astigmatism after penetrating keratoplasty. Cornea. 2007 Aug;26(7):819-25. doi:
10.1097/ICO.0b013e318093de39. PMID: 17667616.

13. Amm M, Halberstadt M. Implantation torischer Intraokularlinsen zur Korrektur hoher

postkeratoplastischer Astigmatismen [Implantation of toric intraocular lenses for correction of
high post-keratoplasty astigmatism]. Ophthalmologe. 2002 Jun;99(6):464-9. German. doi:
10.1007/s003470100542. PMID: 12125415.

14. Arriola-Villalobos P, Díaz-Valle D, Güell JL, Iradier-Urrutia MT, Jiménez-Alfaro I, Cuiña-

Sardiña R, Benítez-del-Castillo JM. Intrastromal corneal ring segment implantation for high
astigmatism after penetrating keratoplasty. J Cataract Refract Surg. 2009 Nov;35(11):1878-84.
doi: 10.1016/j.jcrs.2009.05.060. PMID: 19878819.

15. Alió JL, Javaloy J, Osman AA, Galvis V, Tello A, Haroun HE. Laser in situ keratomileusis to
correct post-keratoplasty astigmatism; 1-step versus 2-step procedure. J Cataract Refract Surg.
2004 Nov;30(11):2303-10. doi: 10.1016/j.jcrs.2004.04.048. PMID: 15519079.

16. Bilgihan K, Ozdek SC, Akata F, Hasanreisoğlu B. Photorefractive keratectomy for post-
penetrating keratoplasty myopia and astigmatism. J Cataract Refract Surg. 2000
Nov;26(11):1590-5. doi: 10.1016/s0886-3350(00)00692-1. PMID: 11084265.

17. Szentmáry N, Seitz B, Langenbucher A, Naumann GO. Repeat keratoplasty for correction of
high or irregular postkeratoplasty astigmatism in clear corneal grafts. Am J Ophthalmol. 2005
May;139(5):826-30. doi: 10.1016/j.ajo.2004.12.008. PMID: 15860287.

18. Sugar A, Rapuano CJ, Culbertson WW, Huang D, Varley GA, Agapitos PJ, de Luise VP,
Koch DD. Laser in situ keratomileusis for myopia and astigmatism: safety and efficacy: a report
by the American Academy of Ophthalmology. Ophthalmology. 2002 Jan;109(1):175-87. doi:
10.1016/s0161-6420(01)00966-6. PMID: 11772601.

19. Epstein D, Fagerholm P, Hamberg-Nyström H, Tengroth B. Twenty-four-month follow-up of

excimer laser photorefractive keratectomy for myopia. Refractive and visual acuity results.
Ophthalmology. 1994 Sep;101(9):1558-63; discussion 1563-4. doi: 10.1016/s0161-
6420(94)31150-x. PMID: 8090458.

20. Ho Wang Yin G, Hoffart L. Post-keratoplasty astigmatism management by relaxing incisions:

a systematic review. Eye Vis (Lond). 2017 Dec 6;4:29. doi: 10.1186/s40662-017-0093-7. PMID:
29238735; PMCID: PMC5725940.

21. Moher D (2009) Preferred reporting items for systematic reviews and meta-analyses: the
PRISMA statement. ACP J Club 151(4):264.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
22. Murad, M. H., Sultan, S., Haffar, S., & Bazerbachi, F. (2018). Methodological quality and
synthesis of case series and case reports. BMJ evidence-based medicine, 23(2), 60–63.
23. Slim K, Nini E, Forestier D, Kwiatkowski F, Panis Y, Chipponi J. Methodological index for
non-randomized studies (minors): development and validation of a new instrument. ANZ J Surg.
2003;73(9):712-716. doi:10.1046/j.1445-2197.2003.02748.x.
24. Shalash RB, Elshazly MI, Salama MM. Combined intrastromal astigmatic keratotomy
and laser in situ keratomileusis flap followed by photoablation to correct post-penetrating
keratoplasty ametropia and high astigmatism: One-year follow-up. J Cataract Refract Surg.
2015;41(10):2251-2257. doi:10.1016/j.jcrs.2015.10.028.
25. Allan BD, Hassan H. Topography-guided transepithelial photorefractive keratectomy for
irregular astigmatism using a 213 nm solid-state laser. J Cataract Refract Surg. 2013;39(1):97-
104. doi:10.1016/j.jcrs.2012.08.056.
26. Sarnicola V, Toro P, Sarnicola C, Sarnicola E, Ruggiero A. Long-term graft survival in
deep anterior lamellar keratoplasty. Cornea. 2012 Jun;31(6):621-6. doi:
10.1097/ICO.0b013e31823d0412. PMID: 22406938. doi:10.1034/j.1600-
0420.2001.079004376.x.
27. Kwitko S, Marinho DR, Rymer S, Ramos Filho S. Laser in situ keratomileusis after
penetrating keratoplasty. J Cataract Refract Surg. 2001;27(3):374-379. doi:10.1016/s0886-
3350(00)00642-8.
28. Yoshida K, Tazawa Y, Demong TT. Refractive results of post penetrating keratoplasty
photorefractive keratectomy. Ophthalmic Surg Lasers. 1999;30(5):354-359.
29. Webber SK, Lawless MA, Sutton GL, Rogers CM. LASIK for post penetrating
keratoplasty astigmatism and myopia. Br J Ophthalmol. 1999;83(9):1013-1018.
doi:10.1136/bjo.83.9.1013.
30. Forseto AS, Francesconi CM, Nosé RA, Nosé W. Laser in situ keratomileusis to correct
refractive errors after keratoplasty. J Cataract Refract Surg. 1999;25(4):479-485.
doi:10.1016/s0886-3350(99)80043-1.
31. Acar BT, Utine CA, Acar S, Ciftci F. Laser in situ keratomileusis to manage refractive
errors after deep anterior lamellar keratoplasty. J Cataract Refract Surg. 2012;38(6):1020-1027.
doi:10.1016/j.jcrs.2011.12.034.

32. Alessio G, Boscia F, La Tegola MG, Sborgia C. Corneal interactive programmed

topographic ablation customized photorefractive keratectomy for correction of postkeratoplasty
astigmatism. Ophthalmology. 2001;108(11):2029-2037. doi:10.1016/s0161-6420(01)00807-7.

33. Imamoglu S, Kaya V, Oral D, Perente I, Basarir B, Yilmaz OF. Corneal wavefront-guided
customized laser in situ keratomileusis after penetrating keratoplasty. J Cataract Refract Surg.
2014;40(5):785-792. doi:10.1016/j.jcrs.2013.10.042.
34. Knorz MC, Jendritza B. Topographically-guided laser in situ keratomileusis to treat
corneal irregularities. Ophthalmology. 2000;107(6):1138-1143. doi:10.1016/s0161-
6420(00)00094-4.
35. Bizrah M, Lin DTC, Babili A, Wirth MA, Arba-Mosquera S, Holland SP. Topography-
Guided Photorefractive Keratectomy for Postkeratoplasty Astigmatism: Long-Term Outcomes.
Cornea. 2021;40(1):78-87. doi:10.1097/ICO.0000000000002403.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
36. Huang PY, Huang PT, Astle WF, et al. Laser-assisted subepithelial keratectomy and
photorefractive keratectomy for post-penetrating keratoplasty myopia and astigmatism in adults.
J Cataract Refract Surg. 2011;37(2):335-340. doi:10.1016/j.jcrs.2010.08.039.
37. Pedrotti E, Sbabo A, Marchini G. Customized transepithelial photorefractive keratectomy
for iatrogenic ametropia after penetrating or deep lamellar keratoplasty. J Cataract Refract Surg.
2006;32(8):1288-1291. doi:10.1016/j.jcrs.2006.03.032.
38. Buzard K, Febbraro JL, Fundingsland BR. Laser in situ keratomileusis for the correction
of residual ametropia after penetrating keratoplasty. J Cataract Refract Surg. 2004;30(5):1006-
1013. doi:10.1016/j.jcrs.2003.08.035.
39. Campos M, Hertzog L, Garbus J, Lee M, McDonnell PJ. Photorefractive keratectomy for
severe postkeratoplasty astigmatism. Am J Ophthalmol. 1992;114(4):429-436.
doi:10.1016/s0002-9394(14)71854-9.
40. Amm M, Duncker GI, Schröder E. Excimer laser correction of high astigmatism after
keratoplasty. J Cataract Refract Surg. 1996;22(3):313-317. doi:10.1016/s0886-3350(96)80242-
2.
41. Lima G da S, Moreira H, Wahab SA. Laser in situ keratomileusis to correct myopia,
hypermetropia and astigmatism after penetrating keratoplasty for keratoconus: a series of 27
cases. Can J Ophthalmol. 2001;36(7):391-397. doi:10.1016/s0008-4182(01)80083-1.
42. Camellin M, Arba Mosquera S. Simultaneous aspheric wavefront-guided transepithelial
photorefractive keratectomy and phototherapeutic keratectomy to correct aberrations and
refractive errors after corneal surgery. J Cataract Refract Surg. 2010;36(7):1173-1180.
doi:10.1016/j.jcrs.2010.01.024.
43. Hardten DR, Chittcharus A, Lindstrom RL. Long term analysis of LASIK for the
correction of refractive errors after penetrating keratoplasty. Cornea. 2004;23(5):479-489.
doi:10.1097/01.ico.0000120783.31977.77.
44. Sorkin N, Einan-Lifshitz A, Abelson S, et al. Stepwise Guided Photorefractive
Keratectomy in Treatment of Irregular Astigmatism After Penetrating Keratoplasty and Deep
Anterior Lamellar Keratoplasty. Cornea. 2017;36(11):1308-1315.
doi:10.1097/ICO.0000000000001359.

45. Park CH, Kim SY, Kim MS. Laser-assisted in situ keratomileusis for correction of
astigmatism and increasing contact lens tolerance after penetrating keratoplasty. Korean J
Ophthalmol. 2014;28(5):359-363. doi:10.3341/kjo.2014.28.5.359.

46. Sorkin N, Kreimei M, Einan-Lifshitz A, et al. Wavefront-Guided Photorefractive

Keratectomy in the Treatment of High Astigmatism Following Keratoplasty. Cornea.
2019;38(3):285-289. doi:10.1097/ICO.0000000000001830.

47. Malecha MA, Holland EJ. Correction of myopia and astigmatism after penetrating
keratoplasty with laser in situ keratomileusis. Cornea. 2002;21(6):564-569.
doi:10.1097/00003226-200208000-00006.

48. Bertino P, Magalhães RS, José de Souza C Jr, Rocha G, Santhiago MR. Intrastromal
corneal ring segments followed by photorefractive keratectomy for high post-keratoplasty

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
astigmatism: A prospective study. J Cataract Refract Surg. 2022 Jan 18. doi:
10.1097/j.jcrs.0000000000000888. Epub ahead of print. PMID: 35067663.

49. Bandeira E Silva F, Hazarbassanov RM, Martines E, Güell JL, Hofling-Lima AL. Visual
Outcomes and Aberrometric Changes With Topography-Guided Photorefractive Keratectomy
Treatment of Irregular Astigmatism After Penetrating Keratoplasty. Cornea. 2018 Mar;37(3):283-
289. doi: 10.1097/ICO.0000000000001474. PMID: 29215394.

50. Kollias AN, Schaumberger MM, Kreutzer TC, Ulbig MW, Lackerbauer CA. Two-step
LASIK after penetrating keratoplasty. Clin Ophthalmol. 2009;3:581-6. doi: 10.2147/opth.s7332.
Epub 2009 Nov 2. PMID: 19898662; PMCID: PMC2773279.

51. Mann E, Zaidman GW, Shukla S. Efficacy of nonsimultaneous bilateral LASIK after
nonsimultaneous bilateral penetrating keratoplasty. Cornea. 2006 Oct;25(9):1053-6. doi:
10.1097/01.ico.0000254199.17302.e5. PMID: 17133052.

52. Ghoreishi M, Naderi Beni A, Naderi Beni Z. Visual outcomes of Femto-LASIK for
correction of residual refractive error after corneal graft. Graefes Arch Clin Exp Ophthalmol.
2013 Nov;251(11):2601-8. doi: 10.1007/s00417-013-2458-5. Epub 2013 Sep 26. PMID:
24068438.

53. Borderie VM, Sandali O, Bullet J, Gaujoux T, Touzeau O, Laroche L. Long-term results of
deep anterior lamellar versus penetrating keratoplasty. Ophthalmology. 2012 Feb;119(2):249-
55. doi: 10.1016/j.ophtha.2011.07.057. Epub 2011 Nov 4. PMID: 22054997.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Figure 1: PRISMA flowchart.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Figure 2: a forest plot showing the standardized mean difference between pre- and post-
treatment differences in the spherical equivalent. Studies in the figure are listed with their
citations in Table 1.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Figure 3: a forest plot showing the standardized mean difference between pre- and post-
treatment differences in the cylindrical equivalent. Studies in the figure are listed with their
citations in Table 1.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Figure 4: a forest plot showing the pooled proportions of eyes with within ±0.5 D (A) and ±1.0 D
of the target (B). Studies in the figure are listed with their citations in Table 1.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.
Figure 5: a forest plot showing the pooled proportions of eyes ≥2 lines CDVA loss. Studies in
the figure are listed with their citations in Table 1.

Supplemental Figure 1: Egger’s test showing risk of bias in the outcome.

Supplemental Figure 2: change in Snellen lines in CDVA.

Copyright © 2023 Published by Wolters Kluwer on behalf of ASCRS and ESCRS. Unauthorized reproduction of this article is prohibited.