Identifying patients at high risk of acute endophthalmitis after cataract surgery is important from both public health and clinical perspectives as this would facilitate detection of disease before the onset of irreversible visual loss enabling earlier intervention. Of the nine risk factors identified in our systematic review and meta-analysis, ECCE / ICCE, a clear corneal incision, without intracameral cefazolin (1 mg in 0.1 ml solution) , without intracameral cefuroxime (1 mg in 0.1 ml solution), PCR, silicone intraocular lens and intraoperative complications were strongly and consistently associated with acute endophthalmiytis. All of these are easily assessed through discussions with patients and do not entail a lengthy medical history taking or laboratory evaluations. Other significant factors with a lower strength of association (risk estimates generally 1.5 or less) were male gender and old individuals (85 years and older). All of these factors are likely to be measured and monitored in the primary care setting.
As we and others have previously reported, we found that patient factors such as older age and male gender are associated with a higher risk of endophthalmitis after cataract surgery. The increased risk with age was only true for the very old ages (85 years) and this result might be explained by a reduced natural immunity in this advanced age group 
. Several studies have reported increased rates of adverse postsurgical events among men 
. Using the analysis data, researchers noted that men had 41% higher odds of postoperative endophthalmitis, compared with women. Possible explanations for the higher complication rates in male patients include behavioral differences (e.g., adherence to postoperative instructions and antibiotic use) 
; differences in bacterial flora between the genders 
; and use of a-antagonists, which can increase the surgical complexity, as they can lead to intraoperative floppy iris syndrome 
Although small-incision phacoemulsification has remained the standard of care, surgeons continue to debate whether modifications in surgical technique have affected complication rates. Our pooled analysis of six studies confirmed the increased risks of acute POE associated with ECCE/ICCE compared with phacoemulsification surgery from both developed and developing countries. It was consistent with the reports of western Australia in 2011 
and southern India in 2009 
. While other studies have found on difference [62 ~ 64] or the opposite conclusion 
comparing postoperative complication rates with the transition from ECCE to phacoemulsification techniques. In a setting with phacoemulsification as the standard method, a selection bias for ECCE/ICCE in particularly difficult cases, e.g. instrumental surgical intervention for mature and hypermature cataracts is possible to lead to some complications concerning zonular fiber damaging, is introduced that may very well influence the results. The larger incision and the longer duration of the operation in ECCE than in phacoemulsification, together with the use of perioperative intracameral antibiotics in the phacoemulsification operation may explain this difference.
Is a clear corneal incision associated with greater odds of endophthalmitis compared with a scleral tunnel or limbal incision? Controversy exists regarding the problem. Theories to account for more frequent POE with sutureless clear corneal incisions are centered on the stability of the surgical wound because its integrity is believed to be a critical factor. A stable, self-sealing incision may be technically more difficult in the cornea than in the sclera. Many reports concluded that postoperative wound defects were a risk factor for the development of endophthalmitis 
and the corneal incision at least 2.0mm in length had substantially greater resistance to incision failure 
. This suggests that the integrity of a self-sealing incision depends to some extent on length. This may be more difficult in a clear corneal incision. If the incision is too short, the cataract wound may be susceptible to a postoperative perturbation (such as rubbing of the eye) and wound abnormality. According to the innovations in phacoemulsification technology, the types of instruments available to better manage complex cases (pupil stretchers, capsular tension rings, dyes to stain the capsule), increased use of topical anesthesia, improvements in intraocular lenses, changes in preoperative or postoperative medication regimens, and better strategies to deal with intraoperative complications, two more recent studies showed the rates of adverse events, including endophthalmitis, decreased among patients undergoing small-incision phacoemulsification from 1994 to 2006 
. The incision location, structure and length should be more thoroughly studied in large prospective trials in the future.
Three multicenter prospective randomized partially masked control study concurred that the most pertinent finding of the protective effect against infection produced by the prophylactic use of intracameral cefuroxime (1 mg in 0.1 ml solution) compared with topical disinfection alone 
. A current prospective observational study reported the intracameral cefazolin (1 mg in 0.1 ml solution) significantly reduced the rate of postoperative endophthalmitis. The magnitude of the ORs shown by our meta-analysis were inconsistent across studies while the pooled estimates were statistically significant for both without intracameral cefuroxime (OR 5.48, 95% CI 3.79~7.92) and without intracameral cefazolin (OR 10.76, 95% CI 6.45~17.95) with no evidence of heterogeneity (I2
0.858 respectively). Coagulase-negative staphylococcus (shown in ) is the most commonly isolated organism and is followed by other gram-positive organisms (such as staphylococcus aureus, streptococcus species) and gram-negative bacteria. Cefuroxime or cefazolin is usually effective against the broad spectrum of bacteria causing acute onset postoperative endophthalmitis. Endophthalmitis caused by coagulase-negative staphylococci may have less inflammatory signs, often creating difficulty in distinguishing between an infective and a noninfective etiology. Many surgeons fear an increased incidence of toxic anterior segment syndrome (TASS) with injected antibiotics, such as the toxic effects of higher concentrations of cefuroxime and vancomycin on human corneal endothelial cells 
. More research on the clinically used concentrations was recommended.
Our meta-analysis confirmed the increased risks of acute endophthalmitis associated with silicone lOLs. This seems to corroborate experimental studies 
and also some clinical data, reporting an increased bacterial adhesion to silicone lenses compared with polymethylmethacrylate lOLs and hydrophobic acrylic IOLs, as the first-line implants in most operating practice due to the favoring of foldable IOLs to avoid induction of astigmatism [74~76]. The future new lens materials or design may confer greater resistance of intraocular organisms to physiological and pharmacological antibacterial protective mechanisms. Evaluation on the uveal and capsular biocompatibility shape of IOL should also be considered to prohibit lens epithelial cell migration and postoperative inflammation.
Posterior capsular rupture caused intraoperative communication with the vitreous cavity, was found to be a significant risk factor for postoperative endophthalmitis, which was well proved by in vitro experiments 
and animal models 
. Our pooled estimates revealed that PCR was associated with an increased risk of more than six-fold for acute endophthalmitis. This risk increased when we excluded the two studies that had a lower cut-off for prospective design. When other intraoperative complications were added, the pooled estimates OR was 5.28 (95% CI, 2.74~10.18), suggesting that PCR may be the common intraoperative risk and do most contribution to the incidence of endophthalmitis.
There are several strengths in our systematic review. We performed a comprehensive search through six databases, had inclusion criteria for the prospective, cross-sectional and retrospective studies. The fully adjusted study-specific ORs were combined to estimate the pooled ORs with 95% CI using the random effects model for analyze the heterogeneity. The uniquely large sample size and inclusion of studies from different ethnic populations around the world could provide a more precise estimate of the perioperative risk factors for POE in the general population because they included known, presumably symptomatic, and unknown risks.
There are potential limitations to the present literature synthesis, some inherent to systematic reviews in general and some particular to our review. First, the studies included in this analysis may be subject to some methodological variation. Definitions of endophthalmitis may have varied; in addition, inherent difficulties in the diagnosis of this complication are apparent secondary to the uncommon manifestation of the “classic” form of postsurgical endophthalmitis. Miscoding of endophthalmitis itself could be a serious concern for data quality of any epidemiological analysis. Second, the overwhelming number of publications showing retrospective data, and the limited number of prospective and case-controlled studies with appropriate randomization methods, negatively affected the proportion of high-quality articles reviewed. Systematic reviews have an intrinsic limitation: the quality of the outcome depends on the quality of the inputs. Therefore, their findings must be interpreted with caution. Nonetheless, many studies included in this review were from Asian populations (e.g. Chinese, Malay Asians, Thailand, India) and thus, we believe our results can be generalizable to different populations in different countries around the world. Finally, the major setback of published studies and meta-analyses of published studies in general is publication bias. Publication bias may be an issue because studies that report statistically significant results are more likely to get published than studies that report nonsignificant results, and this could have distorted the findings of our meta-analyses. Therefore, potentially additional unpublished evidence regarding risk factors of acute endophthalmitis following cataract surgery during the past decade may be unavailable for analysis 
. However, Egger regression asymmetry test and the Begg's test suggested no evidence of publication bias in our study.
Nonetheless, even with these limitations in mind, we believe that our analysis provides clear evidence to support the notion that the nine risk factors for acute endophthalmitis. This study provides additional information for primary care physicians, general ophthalmologists and other eye care professionals to counsel their patients on acute POE risk.