https://orcid.org/0000-0001-9978-6215
Figures
Abstract
Purpose
To determine whether uneventful cataract surgery in patients with diabetic macular edema (DME) affects the course of the disease, and its relationship with postoperative clinical outcomes in real-world settings.
Materials and Methods
This retrospective cohort study included patients of center-involving DME and a prior history of periocular injection in the operative eye before cataract surgery with a follow-up of at least 6 months. Patients were assigned to active and inactive DME group according to preoperative status. Patients’ clinical outcome measurements before and after cataract surgery were compared between the groups. Cox-proportional hazards model was performed to identify risk factors of DME recurrence or progression after cataract surgery.
Results
The study included 153 eyes in 153 patients. No significant differences were observed in the trend of the groups’ clinical outcomes, including best-corrected visual acuity, central macular thickness and central choroidal thickness (P = .763,.872, and.127, respectively). Patients with higher HbA1c were more likely to develop recurrence or progression of DME after cataract surgery (hazard ratio = 1.407, P = .039).
Conclusion
The clinical outcomes following cataract surgery in patients with inactive or actively treated DME did not show significant differences at any postoperative period. Recurrence or progression of DME after cataract surgery was found to be associated with high HbA1c. Clinicians do not have to delay the cataract surgery in patients with DME who have good glycemic control and are undergoing treatment as needed.
Citation: Kim M, Park Y-G, Park Y-H (2025) Cataract surgery and the risk of developing recurrence or progression of diabetic macular edema. PLoS One 20(8): e0328874. https://doi.org/10.1371/journal.pone.0328874
Editor: Ram Nagaraj, University of Colorado Denver School of Medicine, UNITED STATES OF AMERICA
Received: October 16, 2024; Accepted: July 8, 2025; Published: August 18, 2025
Copyright: © 2025 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript.
Funding: This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF-2020R1F1A1074898). This research was also supported by the Catholic Medical Center Research Foundation made in the program year of 2023. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Introduction
Diabetes mellitus (DM) is associated with an approximately 5-fold increased prevalence of cataract with cortical and posterior subcapsular opacities, compared with the non-diabetic population [1–5]. In the Wisconsin Epidemiologic Study of Diabetic Retinopathy, cataract was a significant cause of legal blindness, second only to proliferative diabetic retinopathy, in younger-onset patients with diabetes, and the most frequent cause of visual loss in older-onset patients with diabetes [6]. Given the epidemiologic trends of cataracts and DM, ophthalmologists will likely encounter patients with comorbidities requiring cataract surgery. In deciding the appropriate timing of cataract surgery, clinicians have many considerations compared to patients without DM who have cataracts. Major considerations include the presence of macular edema or vitreous/preretinal hemorrhage and glycemic control status.
In our clinical practice, determining the appropriate timing for cataract surgery in patients with a history of diabetic macular edema (DME) poses substantial challenges. Several studies have evaluated the impact of cataract surgery on DME exacerbation in patients with diabetes [7–11]. Uneventful cataract surgery is also associated with an increased risk of developing macular edema or worsening of the preexisting one due to alterations in the aqueous levels of angiogenic and anti-angiogenic factors following the surgical procedure [7–9]. According to DRCR network reports, in eyes with diabetic retinopathy without center-involving DME, any history of DME may increase the risk of developing DME after cataract surgery [10]. However, Starr et al. recently reported significant visual acuity improvements after cataract surgery in patients with DME who were actively managed with perioperative intravitreal anti-VEGF injections [11]. If DME is a risk factor for developing macular edema after cataract surgery, the question arises: should cataract surgery be delayed in patients receiving treatment for DME?
This study aimed to determine whether uneventful cataract surgery in patients with DME affects the course of the disease, and its relationship with postoperative clinical outcomes in real-world settings.
Materials and methods
Study population
The study protocol was approved by the Institutional Review Board of the Catholic University of Korea (approval number: KC24RISI0625) and adhered to the tenets of the Declaration of Helsinki. The requirement for written informed consent was waived because of the retrospective nature of this study. Data were accessed for this study from September 20th, 2024 to October 10th, 2024 in accordance with IRB approval.
Our study was a retrospective cohort analysis of consecutive cataract surgeries performed on patients with DME at Seoul St. Mary’s Hospital between January 2013 and December 2021. Inclusion criteria included a diagnosis of center-involving DME and a prior history of periocular injection in the operative eye before cataract surgery with a follow-up of at least 6 months. Patients who had received periocular injection in the operative eye within 6 months before surgery were allocated to the active DME group, while those who had received the same injection in the operative eye more than 6 months before surgery were allocated to the inactive DME group. We also included age- and sex-matched patients with DME who did not undergo cataract surgery as a control group. Exclusion criteria included (1) complicated cataract surgery or postoperative complication including endophthalmitis; (2) history of intravitreal injection treatment other than diabetes (i.e., retinal vein occlusion, exudative age-related macular degeneration); (3) history of uveitis; (4) presence of glaucoma or other concomitant retinal diseases that could affect central macular thickness; and (5) patients who did not complete 6 months of follow-up.
Patient evaluation and image analysis
Patient characteristics, including age, sex, follow-up duration, medical history, history of panretinal photocoagulation or ocular surgeries, and blood test results, including HbA1c, eGFR, and creatine, were retrieved from medical records. All patients underwent comprehensive baseline and follow-up ocular examinations. Best-corrected visual acuity (BCVA) was measured using a standard Snellen chart and converted to logarithm of the minimal angle of resolution (logMAR) units before analysis. Slit-lamp examination and fundus examination was performed using a Haag-Streit BQ 900 slit lamp (Haag-Streit AG, Köniz, Switzerland). Intraocular pressure (IOP) was measured by pneumatic tonometry (TX-20P, Canon, Japan). Optical coherence tomography (OCT) images were recorded at preoperative, 1-month, 3-month, 6-month, and 12-month intervals postoperatively. Eyes were scanned using either a spectral domain OCT (Spectralis HRA OCT; Heidelberg Engineering, Heidelberg, Germany) or a swept-source OCT (DRI-OCT; Topcon Corp, Tokyo, Japan). The same OCT device was used for each patient throughout the follow-up period. Central macular thickness (CMT) and central choroidal thickness (CCT) were measured using either a circular map analysis provided by the spectral domain OCT software or the macular volume scan of the swept-source OCT device.
We analyzed the recurrence or progression of DME as a composite outcome. Recurrence or progression of DME after cataract surgery was defined according to the categorization outlined in the DRCR network report [10]. The definition of recurrence or progression of DME at follow-up was as follows; study eye meeting any 1 of the following (1) ≥1 inner subfield (ISF) thickness ≥310 μm at 16 week and the corresponding ISF thickness increased ≥1 logOCT unit from baseline to 16 week or ≥1 outer subfield (OSF) thickness ≥290 μm at 16 week and the corresponding OSF thickness increased ≥1 logOCT unit from baseline to 16 week; (2) ≥1 ISF thickness increased ≥2 logOCT units from baseline to 16 week or ≥1 OSF thickness increased ≥2 logOCT units from baseline to 16 week; or (3) any treatment for DME or CME other than topical eyedrops received after surgery and criterion 1 or 2 met prior to starting treatment.
Statistical analysis
Categorical data were expressed as absolute numbers, and continuous data as mean ± standard deviation (95% confidence interval). Kruskal-Wallis test was used to compare baseline characteristics between the three groups. The repeated measures ANOVA with Bonferroni post-hoc correction was used to compare the patients’ clinical outcome measurements before and after cataract surgery. Cox proportional hazards models were used to identify the factors on DME recurrence or progression after cataract surgery. Hazard ratios (HRs) were estimated using univariable Cox regression analysis to evaluate the association between individual clinical variables and DME recurrence or progression. The cumulative probabilities of DME recurrence or progression after cataract surgery were assessed using Kaplan–Meier analysis. A log-rank test was used to compare the survival rates between the two groups.
All statistical analyses were performed using SPSS for Windows (version 24.0; IBM, Armonk, New York, USA). Kaplan–Meier survival curves were created using GraphPad Prism version 8.4.2 for Windows (San Diego, California, USA). Results with P-values less than.05 were considered statistically significant and adjusted P-value less than 0.01 was set as the cutoff value in Bonferroni’s post hoc analysis.
Results
Demographic and clinical characteristics
This study included 95 eyes of active DME and 58 of inactive DME. The baseline demographics and clinical characteristics of study participants are presented in Table 1. The mean age of the patients was 61.06 ± 9.15 years in the active DME group and 61.89 ± 9.40 years in the inactive DME group. The age at the time of cataract surgery and sex distribution were comparable among the groups. No significant differences were observed in HbA1c, serum creatinine level, eGFR, severity of diabetic retinopathy, type of previous DME, and axial length between the two groups (all P > .05). Baseline CMT was 314.09 ± 76.30 µm in active DME group and 278.03 ± 56.07 µm in inactive DME group (P = .002). However, the baseline BCVA did not differ significantly between both groups (0.82 ± 0.37 in the active DME group vs 0.74 ± 0.37 in the inactive DME group, P = .211). Within 3 months after cataract surgery, recurrence or progression of DME was observed in 50 eyes (52.5%) in the active DME group, and 23 eyes (39.7%) in the inactive DME group, but with no statistical significance observed (P = .177).
Clinical outcomes after cataract surgery
Table 2 shows the groups’ clinical outcomes, including BCVA, CMT, and CCT. BCVA showed a significant improvement from 1 month after surgery, with no significant difference in the trend of improvement between the two groups (P = .763). CMT increased at 1 month after cataract surgery, gradually decreased, and tended to return to a level similar to preoperative CMT value at 12 months. No significant difference was observed in the trend between the two groups (P = .872). The mean number of injections in the postoperative period did not differ significantly between the two groups (2.43 ± 1.74 and 1.93 ± 1.84 in the active and inactive DME groups, respectively; P = .093). (Table 1) Additionally, no difference was observed in CCT over time and between the two groups (P = .127).
Fig 1 shows the Kaplan–Meier curve of time to recurrence or progression of DME after cataract surgery. No statistical difference was observed between the two groups
(P = .228, log-rank test), and the median survival time to recurrence was 6 months in the active DME group and 6.5 months in the inactive DME group.
Cox proportional hazards model
We subsequently evaluated the risk factors of recurrence or progression of DME after cataract surgery (Table 3). The cox proportional hazards model revealed that patients with higher HbA1c were more likely to develop recurrence or progression of DME after cataract surgery (hazard ratio = 1.407, P = .039). Age, sex, DM duration, serum creatinine, axial length, severity of DR, previous number of injections, preoperative BCVA, preoperative CMT, or preoperative CCT were not associated with an increased risk of recurrence or progression of DME after cataract surgery.
Discussion
In this study, we assessed the clinical outcomes in patients with DME undergoing cataract surgery by categorizing DME eyes into active and inactive DME groups based on previous treatment. The clinical outcomes, including BCVA and CMT, demonstrated no inferiority in actively treated DME eyes. Notably, preoperative HbA1c emerged as the single risk factor for the recurrence or progression of DME after uncomplicated cataract surgery.
The relationship between uneventful cataract surgery and DME progression or aggravation has been a subject of debate with conflicting evidence. In a large database study of 81,984 eyes, the risk of developing macular edema after cataract surgery was higher in the presence of any DR, even in eyes without DME [12]. In the DRCR network reports, clinical outcomes of cataract surgery in patients without center-involving DME at the time of cataract surgery [10] and with center-involving DME [13] were reported. In the first report, including those eyes without center-involving DME, any history of DME before cataract surgery increased the risk of developing DME afterward. In the second report, including those eyes with center-involving DME, a small percentage of eyes had substantial VA loss or definitive worsening in central retinal thickening. A recent real-world data by Starr et al. [11] examined the clinical outcomes of cataract surgery in active DME managed with anti-VEGF. The study reported that 46% of patients with DME, actively managed with perioperative intravitreal anti-VEGF injections, developed new or worsening DME but still experienced a significant improvement in VA. In our study population, we found that clinical outcomes of cataract surgery in patients in the inactive and active DME groups were comparable and showed significant visual improvements postoperatively. Our findings suggest that clinicians may not have to delay cataract surgery in patients with DME if actively managed with periocular injection.
In patients with diabetes, cataract surgery may induce macular edema due to increased inflammatory mediators in the aqueous and vitreous humor after surgical manipulation. Shimura et al. [14] and Ching et al. [15] reported that macular thickening after cataract surgery peaks at 4–8 weeks after surgery in patients with diabetes. However, in our study population, CMT peaked at 1 month after cataract surgery. Critical clinical evaluations, including OCT scans at 1 month after surgery, play a vital role in determining the necessity of intravitreal injection treatment. Many studies focused on the efficacy of preoperative or perioperative treatment for DME using intravitreal anti-VEGF or periocular steroid injections [16–22]. Intravitreal injections administered preoperatively, postoperatively, and concomitantly with cataract surgery showed comparable efficacy in preventing the worsening of macular edema. Preoperative intravitreal injections are often initiated 1–2 weeks prior to cataract surgery, and adjunctive use of topical nonsteroidal anti-inflammatory drugs (NSAIDs) is common in patients with diabetes [23–27].
This study has a few limitations. First, its retrospective nature resulted in variable use of perioperative topical eyedrops, including NSAIDs, within the study populations. In patients with diabetes, prophylactic preoperative or postoperative NSAIDs may have a role in preventing macular edema following cataract surgery [24,27]. Second, we did not include patients with diabetes without a history of DME as an additional control group. However, the diverse spectrum of patients with diabetes without a history of DME could introduce additional confounding factors. Third, the intravitreal injections were administered according to the PRN protocol, with treatment decisions and follow-up intervals left to the physician’s judgment. Differentiating new-onset pseudophakic cystoid macular edema and aggravation of DME may also pose challenges. Fourth, there may be selection bias as the study only targeted patients who visited a tertiary care center. Lastly, although the recurrence and progression of DME may represent distinct clinical courses with potentially different risk profiles, we reported them as a combined outcome in our analysis. This decision was made because the number of events in each category was too small to allow for meaningful statistical comparison. Although the differences in recurrence rates and CMT between the two groups did not reach statistical significance, the magnitude of these differences may still carry clinical relevance. Specifically, the recurrence rate was higher in the active group (52%) compared to the non-active group (39%), and the mean difference in CMT between the groups was approximately 50 µm. While these findings were not statistically significant, they suggest a potential trend toward worse anatomical outcomes in eyes with active DME. Further studies with larger sample sizes are needed to confirm the clinical significance of these observations. Despite these limitations, the main strengths of our study lie in the extended postoperative evaluation periods for BCVA and CMT, as well as the analysis of predictive factors for the recurrence or progression of DME after cataract surgery in a real-world setting.
In summary, the clinical outcomes following uneventful cataract surgery in patients with inactive or actively treated DME did not show significant differences at any postoperative period. Recurrence or progression of DME after cataract surgery was found to be associated with high HbA1c. Based on these findings, we concluded that clinicians do not have to delay the cataract surgery in patients with DME who have good glycemic control and are undergoing treatment as needed.
References
- 1. Klein BE, Klein R, Wang Q, Moss SE. Older-onset diabetes and lens opacities. The Beaver Dam Eye Study. Ophthalmic Epidemiol. 1995;2(1):49–55. pmid:7585233
- 2. Leske MC, Wu SY, Hennis A, Connell AM, Hyman L, Schachat A. Diabetes, hypertension, and central obesity as cataract risk factors in a black population. The Barbados Eye Study. Ophthalmology. 1999;106(1):35–41. pmid:9917778
- 3. Delcourt C, Cristol JP, Tessier F, Léger CL, Michel F, Papoz L. Risk factors for cortical, nuclear, and posterior subcapsular cataracts: the POLA study. Pathologies Oculaires Liées à l’Age. Am J Epidemiol. 2000;151(5):497–504. pmid:10707918
- 4. Rowe NG, Mitchell PG, Cumming RG, Wans JJ. Diabetes, fasting blood glucose and age-related cataract: the Blue Mountains Eye Study. Ophthalmic Epidemiol. 2000;7(2):103–14. pmid:10934461
- 5. Rotimi C, Daniel H, Zhou J, Obisesan A, Chen G, Chen Y, et al. Prevalence and determinants of diabetic retinopathy and cataracts in West African type 2 diabetes patients. Ethn Dis. 2003;13(2 Suppl 2):S110–7. pmid:13677425
- 6. Klein BE, Klein R, Moss SE. Prevalence of cataracts in a population-based study of persons with diabetes mellitus. Ophthalmology. 1985;92(9):1191–6. pmid:4058882
- 7. Kim SJ, Equi R, Bressler NM. Analysis of macular edema after cataract surgery in patients with diabetes using optical coherence tomography. Ophthalmology. 2007;114(5):881–9. pmid:17275910
- 8. Meyer CH. Current treatment approaches in diabetic macular edema. Ophthalmologica. 2007;221(2):118–31. pmid:17380066
- 9. Patel JI, Hykin PG, Cree IA. Diabetic cataract removal: postoperative progression of maculopathy--growth factor and clinical analysis. Br J Ophthalmol. 2006;90(6):697–701. pmid:16540489
- 10. Diabetic Retinopathy Clinical Research Network Authors/Writing Committee, Baker CW, Almukhtar T, Bressler NM, Glassman AR, Grover S, et al. Macular edema after cataract surgery in eyes without preoperative central-involved diabetic macular edema. JAMA Ophthalmol. 2013;131(7):870–9. pmid:23599174
- 11. Starr MR, Mahr MA, Smith WM, Iezzi R, Barkmeier AJ, Bakri SJ. Outcomes of Patients With Active Diabetic Macular Edema at the Time of Cataract Surgery Managed With Intravitreal Anti-Vascular Endothelial Growth Factor Injections. Am J Ophthalmol. 2021;229:194–9. pmid:33852907
- 12. Chu CJ, Johnston RL, Buscombe C, Sallam AB, Mohamed Q, Yang YC, et al. Risk Factors and Incidence of Macular Edema after Cataract Surgery: A Database Study of 81984 Eyes. Ophthalmology. 2016;123(2):316–23. pmid:26681390
- 13. Diabetic Retinopathy Clinical Research Network Authors/Writing Committee, Bressler SB, Baker CW, Almukhtar T, Bressler NM, Edwards PA, et al. Pilot study of individuals with diabetic macular edema undergoing cataract surgery. JAMA Ophthalmol. 2014;132(2):224–6. pmid:24309926
- 14. Shimura M, Nakazawa T, Yasuda K, Nishida K. Diclofenac prevents an early event of macular thickening after cataract surgery in patients with diabetes. J Ocul Pharmacol Ther. 2007;23(3):284–91. pmid:17593013
- 15. Ching H-Y, Wong AC, Wong C-C, Woo DC, Chan CW. Cystoid macular oedema and changes in retinal thickness after phacoemulsification with optical coherence tomography. Eye (Lond). 2006;20(3):297–303. pmid:15818389
- 16. Lanzagorta-Aresti A, Palacios-Pozo E, Menezo Rozalen JL, Navea-Tejerina A. Prevention of vision loss after cataract surgery in diabetic macular edema with intravitreal bevacizumab: a pilot study. Retina. 2009;29(4):530–5. pmid:19357559
- 17. Takamura Y, Kubo E, Akagi Y. Analysis of the effect of intravitreal bevacizumab injection on diabetic macular edema after cataract surgery. Ophthalmology. 2009;116(6):1151–7. pmid:19376589
- 18. Fard MA, Yazdanei Abyane A, Malihi M. Prophylactic intravitreal bevacizumab for diabetic macular edema (thickening) after cataract surgery: prospective randomized study. Eur J Ophthalmol. 2011;21(3):276–81. pmid:20853269
- 19. Cetin EN, Yıldırım C. Adjuvant treatment modalities to control macular edema in diabetic patients undergoing cataract surgery. Int Ophthalmol. 2013;33(5):605–10. pmid:23248073
- 20. Furino C, Boscia F, Niro A, D’Addario M, Grassi MO, Saglimbene V, et al. DIABETIC MACULAR EDEMA AND CATARACT SURGERY: Phacoemulsification Combined With Dexamethasone Intravitreal Implant Compared With Standard Phacoemulsification. Retina. 2021;41(5):1102–9. pmid:32897932
- 21. Fallico M, Lotery A, Maugeri A, Favara G, Barchitta M, Agodi A, et al. Intravitreal dexamethasone implant versus anti-vascular endothelial growth factor therapy combined with cataract surgery in patients with diabetic macular oedema: a systematic review with meta-analysis. Eye (Lond). 2022;36(12):2239–46. pmid:34795415
- 22. Fallico M, Avitabile T, Castellino N, Longo A, Russo A, Bonfiglio V, et al. Intravitreal dexamethasone implant one month before versus concomitant with cataract surgery in patients with diabetic macular oedema: the dexcat study. Acta Ophthalmol. 2021;99(1):e74–80. pmid:32588978
- 23. Sheppard JD. Topical bromfenac for prevention and treatment of cystoid macular edema following cataract surgery: a review. Clin Ophthalmol. 2016;10:2099–111.
- 24. Yüksel B, Karti Ö, Kusbeci T. Topical nepafenac for prevention of post-cataract surgery macular edema in diabetic patients: patient selection and perspectives. Clin Ophthalmol. 2017;11:2183–90. pmid:29269999
- 25. Wingert AM, Liu SH, Lin JC, Sridhar J. Non-steroidal anti-inflammatory agents for treating cystoid macular edema following cataract surgery. Cochrane Database Syst Rev. 2022;12(12):Cd004239.
- 26. Laursen SB, Erichsen JH, Holm LM, Kessel L. Prevention of macular edema in patients with diabetes after cataract surgery. J Cataract Refract Surg. 2019;45(6):854–69. pmid:31146934
- 27. Alnagdy AA, Abouelkheir HY, El-Khouly SE, Tarshouby SM. Impact of topical nonsteroidal anti-inflammatory drugs in prevention of macular edema following cataract surgery in diabetic patients. Int J Ophthalmol. 2018;11(4):616–22. pmid:29675380