Secondary Logo

Journal Logo


Incidence of corneal transplantation after phacoemulsification in patients with corneal guttata: a registry-based cohort study

Viberg, Andreas MD; Samolov, Branka MD, PhD; Claesson Armitage, Margareta MD, PhD; Behndig, Anders MD, PhD; Byström, Berit MD, PhD

Author Information
Journal of Cataract & Refractive Surgery: July 2020 - Volume 46 - Issue 7 - p 961-966
doi: 10.1097/j.jcrs.0000000000000207
  • Free

Fuchs endothelial corneal dystrophy (FECD) is a bilateral degenerative corneal disease. With progression, endothelial decompensation with corneal swelling occurs, leading to visual impairment. Blisters, painful epithelial ulcers, and corneal scarring can develop in advanced disease with severe impact on quality of life.1,2 The established curative treatment today is corneal transplantation. Nowadays, endothelial keratoplasty is the most common type of corneal transplantation, which is less traumatic than penetrating keratoplasty (PKP).3–6 Endothelial keratoplasty in FECD has a better long-term visual acuity (VA), more rapid visual recovery, and a lower rejection rate compared with PKP.7,8 All corneal transplantations performed in Sweden since 1996 are registered in the Swedish Cornea Transplant Registry (SCTR).A

The irregularity of the corneal endothelium known as corneal guttata is seen early in FECD but can also occur with aging, trauma, inflammation, and glaucoma.1 The prevalence of corneal guttata in the population varies in studies from 4.1% to 11%.9–11 Different populations and classification criteria probably explain the wide prevalence range. It has been shown that increasing age, female sex, thinner cornea, and smoking correlate with higher risk for corneal guttata.9,11

Cataract extraction with phacoemulsification is associated with an endothelial cell loss between 4.2% and 16.1% and even higher under conditions such as long phacoemulsification time, hard nucleus, short axial length, pseudoexfoliation, diabetes mellitus, and posterior capsule rupture.12–22 The risk can be reduced by different surgical techniques, such as soft-shell technique, but not ameliorated.23 Postoperative corneal endothelial cell damage and loss are reflected in the degree of corneal swelling early postoperatively.13

In Sweden, more than 125 000 cataract extractions are performed annually, and phacoemulsification is the method of choice in more than 98% of cases.B The Swedish National Cataract Registry (NCR) has coverage of over 95.6% of the cataract surgeries performed in Sweden, and the presence of corneal guttata is one of the variables reported.24

Our previous study with a large sample size showed that corneal guttata was associated with inferior results after cataract surgery, compared with patients without guttata.25 Furthermore, currently, FECD is the main indication for corneal transplantation in Germany, the United Kingdom, the United States, and Sweden.3–5,A The aim of this study was to investigate the risk for corneal transplantation after phacoemulsification in patients with or without corneal guttata based on large-scale unselected data from two national registries with a high coverage rate.


This registry-based cohort study involves data from 49 Swedish cataract surgical units and 7 Swedish cornea transplantation units. The regional ethics committee and the Swedish Data Inspection Board approved the study, which was performed according to the tenets of the Declaration of Helsinki.

In this study, 276 362 consecutive patients who had cataract surgery between 2010 and 2012 were linked with 2091 patients who underwent corneal transplantation between 2010 and September 2017. If both eyes had cataract surgery during the study, 1 eye was randomly selected to obtain unrelated samples and avoid paired organ bias. Fellow-eye surgery did not differ related to the presence of corneal guttata, and most of the patients in both groups had cataract surgery because of vision loss irrespective of whether they had corneal guttata or not. Cases with a surgical method other than phacoemulsification with the posterior intraocular lens were excluded. Triple procedures (simultaneous phacoemulsification and keratoplasty) and keratoplasty before cataract surgery were also excluded, as the purpose of the study was to investigate the risk for corneal transplantation after phacoemulsification.26 All excluded patients are shown in Figure 1. Altogether, 192 253 eyes that underwent phacoemulsification remained for the analysis, and 293 of those underwent corneal transplantation because of primary (203 eyes) or secondary (90 eyes) endothelial failure. To analyze the impact of phacoemulsification on the rate of corneal transplantation, primary and secondary endothelial failures were merged into an outcome variable, indicating whether corneal transplantation was performed or not. The corneal transplant methods used were Descemet-stripping automated endothelial keratoplasty in 234 cases, PKP in 40 cases, Descemet membrane endothelial keratoplasty in 17 cases, and other methods in 2 cases.

Figure 1.
Figure 1.:
Flow diagram outlining the exclusion of patients who underwent cataract surgery during the years 2010 to 2012. A patient might have met more than 1 exclusion criterion within each of the exclusion boxes.

The analyzed variables from the NCR reported by the cataract surgeon at the day of the surgery were patient identity, age and sex, operated eye, preoperative VA, surgery date, indication, surgical method, and ocular comorbidity, including corneal guttata, age-related macular degeneration, glaucoma, and diabetic retinopathy. The analyzed data from the SCTR reported by the surgeon at the day of the surgery included patient identity, operated eye, indication for transplantation, surgical method, and surgery date. For patient data at the time of phacoemulsification stratified by the presence of corneal guttata and by corneal transplantation, see Table 1 and Table 2, respectively.

Table 1.
Table 1.:
Baseline patient data at phacoemulsification years 2010 to 2012 stratified by the presence of corneal guttata.
Table 2.
Table 2.:
Patient data at phacoemulsification years 2010 to 2012 stratified by future corneal transplantation.

Statistical Analyses

Each study participant's time at risk for corneal transplantation was calculated as time from phacoemulsification until corneal transplantation or the end of the observation period. Time of risk was censored by death (Table 1), based on data from the Swedish Population Register (Navet). The incidence rate of corneal transplantation after phacoemulsification was calculated by the number of corneal transplants divided by the person years at risk. Poisson regression was used to estimate relative risk for corneal transplantation comparing patients with corneal guttata with those without corneal guttata, while adjusting for age, sex, age-related macular degeneration, glaucoma, and diabetic retinopathy. Age was modeled using cubic restricted splines with 3 knots at the 10th, 50th, and 90th percentile of age distribution, allowing nonlinear effects on the dependent variable. The descriptive data were analyzed using the Pearson χ2 test for categorical variables and the Welch independent sample t test for age. The VA was analyzed using the Mann-Whitney U test. The data were analyzed using the computing environment R (R Development Core Team). Effects with a P value less than 0.05 were considered statistically significant.


A total of 192 253 patients who had undergone phacoemulsification contributed to 1 041 134 person years at risk. Corneal guttata was registered in 3338 patients (1.7%), of which 152 (4.6%) underwent a corneal transplantation during the study period. The overall incidence rate of corneal transplantation after phacoemulsification among patients with corneal guttata was 88 per 10 000 person years (95% CI, 74.5-103.1). During the first year after phacoemulsification, 171.6 per 10 000 person years (95% CI, 129.6-222.8) underwent corneal transplantation in the guttata group. The annual incidence rate diminished thereafter (Figure 2). In comparison, among the 188 915 patients without registered corneal guttata, 141 (0.1%) underwent a corneal transplantation during the study period. The overall incidence rate of corneal transplantation among the patients without corneal guttata was 1.4 per 10 000 person years (95% CI, 1.2-1.6). The overall and annual incidence rates of corneal transplantation at different time points after the phacoemulsification are tabulated in Table 3. Phacoemulsification in patients with corneal guttata was associated with corneal transplantation with an adjusted relative risk of 68.2 (95% CI, 54.0-86.2, P < .001) (Table 4). An increasing age of the patients with corneal guttata at the time of phacoemulsification had a gradually decreasing probability of corneal transplantation (Figure 3).

Figure 2.
Figure 2.:
Annual corneal transplantation incidence rate per 10 000 person years after phacoemulsification in patients with corneal guttata with 95% CI. Note that the incidence of corneal transplantation is highest within the first year postoperatively and decreases thereafter; see also Table 3.
Table 3.
Table 3.:
Overall and annual incidence rates (per 10 000 person years) of corneal transplantation among phacoemulsification patients with and without corneal guttata.*
Table 4.
Table 4.:
Associations between corneal transplantation and corneal guttata at phacoemulsification and possible confounders, presented as adjusted relative risk.*
Figure 3.
Figure 3.:
The nonlinear relation between the incidence of corneal transplantation among patients with corneal guttata and their age at the time of phacoemulsification with 95% CI. Note that the age-related decrease in probability of corneal transplantation is adjusted for sex, age-related macular degeneration, glaucoma, and diabetic retinopathy.

Preoperative Visual Acuity

The median VA before the phacoemulsification for the 293 patients who later underwent a corneal transplantation was the same for both patients with and without corneal guttata (0.52 logarithm of the minimum angle of resolution [logMAR]). The median VA before the corneal transplantation was 1.0 logMAR (interquartile range, 1.35) among the patients with corneal guttata, compared with 2.0 logMAR (interquartile range, 1.3) for the patients without corneal guttata (P < .001).


Approximately 20 million people are blind because of cataract worldwide, and although cataract surgery is limited in developing countries, it is the most common surgery today, with phacoemulsification getting increasingly common.27 Although both patients with and without corneal guttata benefit from cataract surgery, they suffer from endothelial cell loss, and the results for the corneal guttata group are worse.12–14,25 FECD and pseudophakic bullous keratopathy (PBK) are the most common causes for corneal transplantation in western countries today.3–5 It is of great interest to study the risk for corneal transplantation during the first years after cataract surgery in patients with corneal guttata because a transplantation deals with a more complex postoperative course that, in a way, lasts for life. Many of the patients are older people, and if their corneas do not decompensate for several years, one can argue that phacoemulsification is a good vision-improving option even in this patient group. On the other hand, these patients must be aware of the risk for failed vision improvement or even deterioration with the need for subsequent corneal transplantation. Modern endothelial keratoplasty is less traumatic than the penetrating technique, but it still involves a risk for rejection, other perioperative and postoperative complications, longer healing time, and rehabilitation compared with cataract surgery alone.28,29 Are we doing these patients a disservice by treating them with phacoemulsification, which may lead to a worsening in FECD and the need for corneal transplantation, or are the results good enough and the frequency of transplantation so low that phacoemulsification is advisable in this group?

The incidence rate of corneal transplantation after phacoemulsification among patients with corneal guttata was 88 per 10 000 person years, highest within the first year and diminished thereafter. The already planned corneal transplantation as a secondary step after cataract surgery might be a factor in the increased likelihood of transplantation during the first year. The early corneal transplants might also reflect a more severe endothelial failure after cataract surgery, and the outcome for PBK after corneal transplantation is known to be better if the duration of the edema after the cataract surgery is shorter.30 Different events and factors after the cataract surgery could have influenced the risk for corneal transplantation. The effect of patients who have died or emigrated during the study has been managed, but other unknown events that the registries do not comprise might have affected the outcome as well. The influence of other unknown factors increases, the longer the time interval is between the surgeries. There was a 68-fold increased risk for subsequent corneal transplantation after phacoemulsification in patients with corneal guttata compared with those without guttata. The high relative risk is not that surprising, as the main indication for corneal transplantation is FECD.

The association between increasing age and a lower probability of corneal transplantation can partially be interpreted as a selection bias, at least in the upper part of the age range. The decision to perform a corneal transplantation is based on an overall evaluation, where the patient's chance to benefit from the transplant is important along with the ability to go through the surgery and the postoperative treatment with a longer healing time.

The NCR and the SCTR receive data from the whole country and, thereby, include virtually all cases going through surgery in Sweden, which makes the study less biased by local and regional variations. The large number of consecutive cases offers a high statistical power for this study, but a weakness is that neither corneal guttata in the NCR nor the indication for surgery in the SCTR is a validated variable, and conflicting data between the registries have been discovered. The registration is made by the surgeon based on the medical record from the preoperative examination, in many cases not done by the surgeon themselves. The low corneal guttata prevalence of 1.7% compared with the literature could indicate that the threshold for reporting was higher and probably led to a concentration of more advanced disease states.9–11 In registry-based studies such as this, inaccurate registration is an inherent problem that needs to be actively and continuously limited by the registry and those who register the data. A grading of the corneal guttata or FECD and more perioperative data, such as the choice of ophthalmic viscosurgical device and phacoemulsification energy, would probably improve the risk analysis, but such data are currently not available in the registries. Another consequence of probable underreporting of corneal guttata is an overestimation of the risk for PBK in need of transplantation, which means that the incidence rate of corneal transplantation among patients without corneal guttata might be even lower than 1.4 per 10 000 person years. The triple procedures (63 cases) were not included in the analysis because the study aimed to evaluate the risk for corneal transplantation after phacoemulsification in patients with corneal guttata. These patients might represent advanced forms of FECD, and their exclusion probably underestimates the risk for transplantation after phacoemulsification. However, they can also illustrate the difference in the experience and the preference of the surgeons making the treatment plan and decision.

It could be argued that the low median VA before corneal transplantation in both patients with corneal guttata (1.0 logMAR) and those without (2.0 logMAR) indicates that there is a need for more corneal transplants. Improved and refined corneal surgical techniques can shift the risk-benefit evaluation further toward earlier corneal transplantation. An increase in transplantation volumes would consequently increase the transplantation incidence rates. Nevertheless, cataract surgery is less complex than lamellar corneal transplantation, especially regarding postoperative care and the need for donor tissue.

In conclusion, this study shows that the risk for undergoing a corneal transplantation after phacoemulsification is much higher for patients with corneal guttata than that for those without, particularly during the first postoperative year. Despite that, most of the patients with corneal guttata do not undergo a corneal transplantation. Therefore, it seems reasonable to start with cataract surgery in most cases when vision impairing cataract is present.


  • Cataract patients with corneal guttata both benefit from cataract surgery and have an increased risk for inferior results compared with patients without corneal guttata, but the incidence of subsequent corneal transplantation has not been studied.


  • There is a 68-fold increased risk for corneal transplantation after phacoemulsification in patients with corneal guttata compared with those without.
  • Despite that, most of the patients with corneal guttata do not undergo corneal transplantation after phacoemulsification.
  • The incidence of corneal transplantation in the corneal guttata group decreases annually after phacoemulsification.


1. Adamis AP, Filatov V, Tripathi BJ, Tripathi RC. Fuchs' endothelial dystrophy of the cornea. Surv Ophthalmol 1993;38:149–168
2. Klintworth GK. Corneal dystrophies. Orphanet J Rare Dis 2009;4:7
3. Flockerzi E, Maier P, Bohringer D, Reinshagen H, Kruse F, Cursiefen C, Reinhard T, Geerling G, Torun N, Seitz B; all German Keratoplasty Registry Contributors. Trends in corneal transplantation from 2001 to 2016 in Germany: a report of the DOG-section cornea and its keratoplasty registry. Am J Ophthalmol 2018;188:91–98
4. Keenan TD, Jones MN, Rushton S, Carley FM; National Health Service Blood and Transplant Ocular Tissue Advisory Group and Contributing Ophthalmologists (Ocular Tissue Advisory Group Audit Study 8). Trends in the indications for corneal graft surgery in the United Kingdom: 1999 through 2009. Arch Ophthalmol 2012;130:621–628
5. Park CY, Lee JK, Gore PK, Lim CY, Chuck RS. Keratoplasty in the United States: a 10-year review from 2005 through 2014. Ophthalmology 2015;122:2432–2442
6. Terry MA, Ousley PJ. Deep lamellar endothelial keratoplasty in the first United States patients: early clinical results. Cornea 2001;20:239–243
7. Fuest M, Ang M, Htoon HM, Tan D, Mehta JS. Long-term visual outcomes comparing Descemet stripping automated endothelial keratoplasty and penetrating keratoplasty. Am J Ophthalmol 2017;182:62–71
8. Ezon I, Shih CY, Rosen LM, Suthar T, Udell IJ. Immunologic graft rejection in Descemet's stripping endothelial keratoplasty and penetrating keratoplasty for endothelial disease. Ophthalmology 2013;120:1360–1365
9. Higa A, Sakai H, Sawaguchi S, Iwase A, Tomidokoro A, Amano S, Araie M. Prevalence of and risk factors for cornea guttata in a population-based study in a southwestern island of Japan: the Kumejima study. Arch Ophthalmol 2011;129:332–336
10. Lorenzetti DW, Uotila MH, Parikh N, Kaufman HE. Central cornea guttata. Incidence in the general population. Am J Ophthalmol 1967;64:1155–1158
11. Zoega GM, Fujisawa A, Sasaki H, Kubota A, Sasaki K, Kitagawa K, Jonasson F. Prevalence and risk factors for cornea guttata in the Reykjavik Eye Study. Ophthalmology 2006;113:565–569
12. Miyata K, Maruoka S, Nakahara M, Otani S, Nejima R, Samejima T, Amano S. Corneal endothelial cell protection during phacoemulsification: low- versus high-molecular-weight sodium hyaluronate. J Cataract Refract Surg 2002;28:1557–1560
13. Lundberg B, Jonsson M, Behndig A. Postoperative corneal swelling correlates strongly to corneal endothelial cell loss after phacoemulsification cataract surgery. Am J Ophthalmol 2005;139:1035–1041
14. Hayashi K, Yoshida M, Manabe S, Hirata A. Cataract surgery in eyes with low corneal endothelial cell density. J Cataract Refract Surg 2011;37:1419–1425
15. Bourne RR, Minassian DC, Dart JK, Rosen P, Kaushal S, Wingate N. Effect of cataract surgery on the corneal endothelium: modern phacoemulsification compared with extracapsular cataract surgery. Ophthalmology 2004;111:679–685
16. Yamazoe K, Yamaguchi T, Hotta K, Satake Y, Konomi K, Den S, Shimazaki J. Outcomes of cataract surgery in eyes with a low corneal endothelial cell density. J Cataract Refract Surg 2011;37:2130–2136
17. Walkow T, Anders N, Klebe S. Endothelial cell loss after phacoemulsification: relation to preoperative and intraoperative parameters. J Cataract Refract Surg 2000;26:727–732
18. O'Brien PD, Fitzpatrick P, Kilmartin DJ, Beatty S. Risk factors for endothelial cell loss after phacoemulsification surgery by a junior resident. J Cataract Refract Surg 2004;30:839–843
19. Morikubo S, Takamura Y, Kubo E, Tsuzuki S, Akagi Y. Corneal changes after small-incision cataract surgery in patients with diabetes mellitus. Arch Ophthalmol 2004;122:966–969
20. Lee JS, Lee JE, Choi HY, Oum BS, Cho BM. Corneal endothelial cell change after phacoemulsification relative to the severity of diabetic retinopathy. J Cataract Refract Surg 2005;31:742–749
21. Hayashi K, Manabe S, Yoshimura K, Kondo H. Corneal endothelial damage after cataract surgery in eyes with pseudoexfoliation syndrome. J Cataract Refract Surg 2013;39:881–887
22. Hayashi K, Hayashi H, Nakao F, Hayashi F. Risk factors for corneal endothelial injury during phacoemulsification. J Cataract Refract Surg 1996;22:1079–1084
23. Seitzman GD. Cataract surgery in Fuchs' dystrophy. Curr Opin Ophthalmol 2005;16:241–245
24. Behndig A, Montan P, Stenevi U, Kugelberg M, Lundstrom M. One million cataract surgeries: Swedish National Cataract Register 1992-2009. J Cataract Refract Surg 2011;37:1539–1545
25. Viberg A, Liv P, Behndig A, Lundstrom M, Bystrom B. The impact of corneal guttata on the results of cataract surgery. J Cataract Refract Surg 2019;45:803–809
26. Muraine M, Gueudry J, Retout A, Genevois O. Keratoplasty combined with cataract surgery. J Fr Ophtalmol 2012;35:546–554
27. Pascolini D, Mariotti SP. Global estimates of visual impairment: 2010. Br J Ophthalmol 2012;96:614
28. Nanavaty MA, Wang X, Shortt AJ. Endothelial keratoplasty versus penetrating keratoplasty for Fuchs endothelial dystrophy. Cochrane Database Syst Rev 2014;2:Cd008420
29. Lee WB, Jacobs DS, Musch DC, Kaufman SC, Reinhart WJ, Shtein RM. Descemet's stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology. Ophthalmology 2009;116:1818–1830
30. Claesson Armitage M, WJ, Stenevi U. Corneal oedema after cataract surgery: predisposing factors and corneal graft outcome. Acta Ophthalmol 2009;87:154–159


A. Claesson Armitage M. Svenska Cornearegistret. Årsrapport 2017. Svenska Cornearegistret, Blekingesjukhuset, Karlskrona 2017
B. Zetterström C, Lundström M, Behndig A, Serring I, Montan P, Kugelberg M, Nilsson I. Svensk Kataraktkirurgi. Årsrapport 2016 baserad på data från Nationella Kataraktregistret. Nationella Kataraktregistret, Blekingesjukhuset, Karlskrona 2017
Copyright © 2020 Published by Wolters Kluwer on behalf of ASCRS and ESCRS