January-February 2020


Review of “The risk of posterior capsule rupture during phacoemulsification cataract surgery in eyes with previous intravitreal anti-vascular endothelial growth factor injections”

by Jennifer Barger, MD, Alcina Lidder, MD, and Laurence Sperber, MD

Laurence Sperber, MD
Clinical professor
Department of Ophthalmology
New York University Langone Eye Center
New York, New York

Jennifer Barger, MD

Alcina Lidder, MD

Do intravitreal injections increase the risk of posterior capsular rupture during subsequent cataract surgery? I asked the NYU residents to review this study from the February JCRS that attempts to quantify the risk.

—David F. Chang, MD, EyeWorld Journal
Club Editor

The study performed by Nagar et al.1 addresses concerns regarding increased cataract surgery complication rates in patients who received prior anti-vascular endothelial growth factor (anti- VEGF) intravitreal injections. These medications are the standard of care for several retinal conditions, with a significant proportion of patients requiring repeated intravitreal injections to achieve adequate control.2–6 As the authors describe, the proximity of the needle to the lens during the injection process may correlate with increased intraoperative risk when these patients subsequently undergo cataract surgery, particularly with regard to posterior capsule rupture (PCR). Other studies have examined this risk, including Shalchi et al.7 who observed a PCR rate of 1.88% in 1,035 eyes undergoing cataract surgery that had previously received intravitreal injections (of anti-VEGF agents or corticosteroid), and Lee et al.8 who observed a PCR rate of 2.22% in 1,935 eyes that had previously received intravitreal injections (also of anti-VEGF agents or corticosteroid) across 20 different centers in the United Kingdom.
This single center retrospective review of electronic medical record data included 4,047 eyes of which 108 (or 2.7%) had prior intravitreal injections of anti-VEGF agents, representing a similar proportion to what the aforementioned studies reported,7–8 though the sample size was comparatively much smaller. Nagar et al. observed an increased rate of PCR in patients with prior intravitreal injections compared to those without prior injections of 6.67% versus 1.88%, which increases to 9.26% with the inclusion of three eyes in the intravitreal injection group that had documented PCR preoperatively.1 Though the raw incidence of PCR was low in the intravitreal injection group, it is proportionally much higher than in prior studies as noted above,7–8 with an absolute risk increase of 5–7%. Posterior capsular damage has been previously observed preoperatively after intravitreal injections of anti-VEGF agents.9–10 We think that the cases of preoperatively observed PCR should be included in the PCR rate in this study in order to best reflect the risk of posterior capsular compromise potentially associated with intravitreal injections. Still, the authors’ stated aim was to understand the risk of intraoperative PCR in the absence of visible signs of posterior capsule trauma, which would imply a preference to exclude these three cases from analysis. In either case, the authors did not comment on the presence or absence of PCR on preoperative examination in eyes without prior injections. In addition, even the most careful observer may miss preoperative PCR especially in patients who have dense nuclear sclerosis, dense posterior subcapsular cataracts, or white cataracts. Although the authors noted the proportion of patients with “brunescent/white cataract,” they do not specify further cataract grading despite prior studies showing that advanced cataract is a significant predictor of PCR.8 It is possible that there may have been a disparate number of patients in this study’s intravitreal injection group with higher grade cataracts, which would artificially increase the PCR rate. The authors also did not exclude other groups at high risk for posterior capsule compromise such as those with prior trauma, prior intraocular surgery, pseudoexfoliation syndrome, or Marfan syndrome. Similarly, it is possible that other variables such as increased age may independently relate to a higher risk of PCR; this study’s population of patients who had received intravitreal anti-VEGF injections was approximately 2 years older than those patients who had not received injections, which approached statistical significance (p=0.053). It seems likely that the relatively lower sample size compared to prior studies limits the current study’s statistical power, which certainly could influence the reported higher rates of PCR compared to the larger studies.
Nagar et al. did not observe a statistically significant difference in the rate of PCR based on the grade of the operating surgeon, although it is unclear whether this finding was in reference to the clinician administering the intravitreal injection versus performing the cataract surgery. While it is likely the authors were referring to the surgeon performing the surgery, this distinction should ideally be clarified particularly due to the authors’ proposed mechanism of trauma during the intravitreal injection as a means to disrupt the posterior capsule or cause inadvertent zonular trauma, which theoretically would be more likely in less experienced trainees. It appears likely that the study was not sufficiently powered to identify such an association given that a similar larger study demonstrated a significantly increased incidence of PCR in less experienced grades of cataract surgeons.8 The current study was powered to identify a dose-dependent relationship of increasing PCR risk per intravitreal injection received (OR 1.086). However, the reported finding that the PCR rate was higher in patients with greater than 10 injections compared to those who received less than 10, as a grouped variable, does not appear to be statistically significant (p=0.18). Therefore, this interpretation should be evaluated with additional caution.
This study and similar studies do not address the clinical centers’ protocols for administering anti-VEGF injections, which may relate to the future risk of PCR. Although the authors report guidelines including supine positioning of the patient and generally recommended distance from the limbus for injection of phakic eyes, it is unclear whether these recommendations were followed. It is also unclear how one eye was selected for analysis from patients who underwent bilateral cataract surgeries.
Despite the study’s weaknesses, its moderate sample size compared to the current literature and findings make it a useful addition to the literature. Moreover, the results may allow physicians to improve preoperative counseling when explaining the risks of cataract surgery to patients with prior intravitreal injections and potentially allow for closer monitoring intraoperatively to help prevent posterior capsule rupture in these higher risk patients. It would be worthwhile to consider a meta-analysis of these studies or a multicenter study with sufficient sample size to power multivariate logistic regression analysis to better quantify the increased risk of PCR in patients who have received intravitreal injections.

Editors’ note: Supported in part by an unrestricted grant from Research to Prevent Blindness to New York University Langone Health Department of Ophthalmology. Dr. Barger and Dr. Lidder contributed equally to this review.


1. Nagar AM, et al. The risk of posterior capsular rupture during phacoemulsification cataract surgery in eyes with previous intravitreal anti-vascular endothelial growth factor injections. J Cataract Refract Surg. 2020;46. Article in press.
2. Diabetic Retinopathy Clinical Research Network, Elman MJ, al. Intravitreal ranibizumab for diabetic macular edema with prompt versus deferred laser treatment: three-year randomized trial results. Ophthalmology. 2012;119:2312–8.
3. Brown DM, et al. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1432–44.
4. Rosenfeld PJ, al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419–31.
5. Brown DM, et al. Sustained benefits from ranibizumab for macular edema following branch retinal vein occlusion: 12-month outcomes of a phase III study. Ophthalmology. 2011;118:1594–602.
6. Boyer D, et al. Vascular endothelial growth factor Trap-Eye for macular edema secondary to central retinal vein occlusion: six-month results of the phase 3 COPERNICUS study. Ophthalmology. 2012;119:1024–32.
References continued
7. Shalchi Z, et al. Risk of posterior capsule rupture during cataract surgery in eyes with previous intravitreal injections. Am J Ophthalmol. 2017;177:77–80.
8. Lee AY, et al. Previous intravitreal therapy is associated with increased risk of posterior capsule rupture during cataract surgery. Ophthalmology. 2016;123:1252–6.
9. Khalifa YM, Pantanelli SM. Quiescent posterior capsule trauma after intravitreal injection: implications for the cataract surgeon. J Cataract Refract Surg. 2011;37:1364.
10. Saeed MU, Prasad S. Management of cataract caused by inadvertent capsule penetration during intravitreal injection of ranibizumab. J Cataract Refract Surg. 2009;35:1857–9.


Sperber: Laurence.Sperber@nyulangone.org

Review of “The risk of posterior capsule rupture during phacoemulsification cataract surgery in eyes with previous intravitreal anti-vascular endothelial growth factor injections” Review of “The risk of posterior capsule rupture during phacoemulsification cataract surgery in eyes with
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