Cheryl Guttman is a medical writer based in Deerfield, Ill.

Cheryl Guttman Krader, BS, Pharm

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This article was reviewed by Gustavo B. Melo, MD, PhD

The ideal syringe for administering intravitreal injections does not exist. With improved awareness of the drawbacks of existing devices and the characteristics desired for intravitreal use, however, syringe manufacturers are stepping up to design products that will help maximize the safety and efficiency of intravitreal injection, said Gustavo B. Melo, MD, PhD.

“Retina specialists are well aware that intravitreal injection can lead to the presence of silicone droplets in the vitreous. The droplets come from the syringes used for injection because most are manufactured with silicone oil to allow for better glide of the plunger. In addition, almost all needles are dipped in a silicone oil bath to coat the outer surface to enable tissue penetration,” said Melo, an associate researcher at the Federal University of São Paulo and the head of the ophthalmology residency at Sergipe Eye Hospital, Brazil.

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“Available data show these droplets matter,” he said. “In the 2018 American Society of Retina Specialists PAT [Preferences and Trends] survey, 5% of US retina specialists said they had done vitrectomy for symptomatic droplets and 2% have patients seeking legal action for their floaters. In addition, silicone droplets are linked to inflammatory reactions after aflibercept injection.”



According to Melo, the ideal syringe for intravitreal injections would be silicone oil free; have negligible dead space to minimize expensive medication waste; use an attachable needle, giving physicians the option to choose their needle; and feature a Luer lock tip that allows for an attachable needle and prevents liquid leakage along with accidental needle removal.

“Preferably, it would also be designed for ophthalmic use,” Melo said.


Melo and Geoffrey G. Emerson, MD, PhD, an ophthalmologist in private practice at The Retina Center in Minnesota, reviewed the advantages and disadvantages of syringes used for intravitreal injections, including those most commonly used in the Americas and Europe, along with emerging products. 



Eliminating risk of endophthalmitis during intravitreal injections for patients wearing masks

They based their information on the silicone oil released by each syringe on scientific publications and personal research. Clinical and scientific experiences were the foundation for comments on additional features.

“Our review included the syringes that we are aware are being used for intravitreal injection. Other syringes, both good and bad, may be available,” Melo said.


The OcuJect syringe (SJJ Solutions), which is expected to receive CE and FDA certification in mid 2021, seems to meet all the ideal criteria outlined by Melo. It is silicone oil free, has a low volume of dead space and a Luer lock tip, and is designed for ophthalmic use.

The StaClear syringe (TriboFilm Research) recently received FDA clearance for marketing for use in intravitreal injections. It has low dead space and low particulates, complying with USP Chapter 789 testing for ophthalmic solutions. 

The syringe is manufactured with a silicone lubricant, but the lubricant is fixed to the syringe’s lumen.

The Zero Residual Luer Lock syringe (SJJ Solutions) is another syringe that has a lot of positive characteristics. It has a low volume of dead space and a Luer lock tip, can be prefilled air free, and is designed for ophthalmic use. It is not silicone oil free, as it is lubricated with a small amount of oil.



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The Daikyo Crystal Zenith (West Pharmaceutical Services) and Plajex (Terumo) syringes have the advantages of being silicone oil free and having a Luer lock tip. In addition, the Daikyo Crystal Zenith complies with USP Chapter 789. However, both syringes have significant dead space and are not available to be filled at point of care.

The Injekt-F (B. Braun Medical Inc) and Norm-Ject (Henke-Sass Wolf) syringes have the advantage of being silicone free. However, they both have moderate dead space and a Luer slip tip.

“The protruding tip of the Injekt-F syringe helps to minimize dead space. However, the design of this syringe can lead to some confusion regarding the injected volume,” Melo noted.



The BD Luer-Lok syringe (Becton, Dickinson and Company), which is distributed with aflibercept in some markets, has a Luer lock tip. On the downside, it is siliconized, albeit with a small amount of silicone oil. In addition, this syringe has a large dead space that wastes expensive drugs, and it is heavy.

Similarly, the company’s BD Plastipak syringe, which is available worldwide, and BD Tuberculin syringe, which is more commonly used in the US, are also siliconized and have significant dead space. Another disadvantage is that they have a Luer slip tip.



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Available in many markets, the BD Ultra-Fine syringe is an insulin syringe that has negligible dead space. However, it is siliconized with a large amount of oil.

“This syringe is notorious for its association with silicone oil droplets in the vitreous,” Melo pointed out. “It has a fixed needle that cannot be substituted.”


Distributed with ranibizumab (Lucentis, Genentech/Roche) in some markets, the Omnifix-F syringe (B. Braun Medical Inc) is siliconized but with just a small amount of silicone oil. However, it has significant dead space and a Luer slip tip.

The Comfort Point insulin syringe (Exel) is available in the US. It has negligible dead space but a fixed needle, and although it is also siliconized, it releases less oil than the BD Ultra-Fine syringe, according to Melo.

Available in many markets, the insulin syringe manufactured by Terumo Medical also has a low volume of dead space. However, it has a fixed needle and releases a large amount of silicone oil.

This article is based on Melo’s video presentation at the European Society of Retina Specialists 2020 Virtual meeting. Melo and Emerson have no financial interests to declare.

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BIGH3 (transforming growth factor-β-Induced Gene Human Clone 30) is a promising serum biomarker for 

 in patients with nonproliferative diabetic retinopathy (NPDR), said Andric Perez-Ortiz, MD, MPH, who presented research at ARVO 2020.

Perez-Ortiz and colleagues conducted a case-control study analyzing levels of BIGH3, transforming growth factor-β1 (TGF-β1), and TGF-β2 in the aqueous humor and serum of patients with 

and unaffected controls. 

The results showed that BIGH3 was the only cytokine that was present in a significantly different concentration in both fluids in

 patients compared with controls and the only cytokine with a positive significant correlation between its level in aqueous humor and serum. 



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None of the three cytokines, however, correlated with macular thickness or OCT phenotype among patients with

“Studies investigating expression and levels of these cytokines have all been performed in vitro. The aim of our study was to measure the concentrations of TGF-β1, TGF-β2, and BIGH3 in aqueous humor of patients with NPDR with and without DME and to assess their clinical applicability as serum markers by testing their correlation in aqueous humor and serum and association with macular thickness and DME phenotype,” said Perez-Ortiz, associate professor, Department of Public Health Universidad Panamericana Sede México, Mexico City, and research fellow, Department of Surgery, Massachusetts General Hospital, Boston, MA. “The predictive capacity of BIGH3 warrants further study, especially its sensitivity and specificity and/or predictive use as an early biomarker for DME development.”

Interest in exploring the potential for TGF-β1, TGF-β2, and BIGH3 to serve as biomarkers for DME is based on understanding of their role in the pathogenesis of DR and 

. 

Perez-Ortiz explained that pericyte dropout and increased inflammation and activation of proinflammatory transcription factors that induce monocyte and macrophage infiltration occur early in the pathogenesis of these diabetic eye diseases. 

Macrophages predominantly secrete TGF-β1 and TGF-β2 that induce apoptosis of retinal pigment epithelial (RPE) and upregulation of the gene encoding for BIGH3.



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BIGH3 is an extracellular matrix protein that can act in an autocrine or paracrine manner to induce apoptosis of RPE cells, pericytes, and retinal endothelial cells in a time and dose-dependent fashion. 

The presence of BIGH3 has been observed in the histopathologic retinal section of a post-mortem globe with documented NPDR deposited predominantly around retinal vessels and occasionally in choroidal vessels.

“Hence, it has been hypothesized that monocyte/macrophage-induced BIGH3 expression is an important progressive step in the pathophysiology of pericyte loss,” Perez-Ortiz said.



The study investigated the levels of the TGF-β cytokines and BIGH3 in patients with NPDR included adults 18 years and older with type 2 diabetes mellitus who were undergoing a surgical procedure (initiation of intravitreal injection for DME patients and cataract surgery for controls). It included 26 patients with DME and 27 patients without 

. 

Patients were excluded if they had systemic inflammatory disease or a history of any vitreous procedure. 

The aqueous humor sample of approximately 1 µL was collected in all eyes prior to any surgical intervention, and the cytokine levels in serum and aqueous humor were quantified with cytometric-bead assays.



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The two groups were similar in mean age (~63 years) and sex distribution, but the average time since diabetes diagnosis was significantly longer in the DME patients than in the controls. 

As would be expected, maximum central macular thickness (CMT) was also significantly greater in the cases compared with controls. 

Among patients with 

, cystic changes and spongiform changes were the most common phenotypes identified on OCT.

The cytokine analyses showed that the aqueous humor concentration of TGF-β1 was significantly greater in the DME eyes compared with the controls, whereas the reverse relationship was observed in serum. 

TGF-β2 was also present in a significantly higher concentration in the aqueous humor of the cases compared with controls, but its concentration in serum did not differ significantly between the two groups.



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Further analyses showed that the ratio of TGF-β1 in aqueous humor:serum was disproportionately elevated in the DME cases compared with controls. 

In addition, a significant positive correlation was found in the 

 group between aqueous humor concentration and maximal CMT. 

The correlation between serum concentration and maximal central macular thickness was negative for TGF-β1 and positive for TGF-β2.

The concentration of BIGH3 was significantly higher in both serum and aqueous humor in the DME group compared with controls. 

The ratio of BIGH3 concentration in aqueous humor:serum was not significantly different comparing cases and controls, and it did not correlate with CMT or OCT subtypes in the eyes with DME.


None of the investigators has any relevant financial interests to disclose.

BIGH3 is an extracellular matrix protein that can act in an autocrine, paracrine manner.

Investigators explore pathogenic cytokines as biomarkers for DME


This article was reviewed by Yusen Huang, MD



Adding cefuroxime to the irrigating solution used during cataract surgery appears to be a safe and effective method for reducing the risk of postoperative endophthalmitis, according to researchers who reported their experience with this technique in a recently published retrospective study.

The investigation included 61,299 eyes. Of the total cohort, 15,948 eyes were operated on between January 1, 2012, and December 31, 2014, using plain balanced salt solution (BSS) as the irrigating solution (control group), and 45,351 eyes underwent cataract surgery between January 1, 2015, and December 31, 2019, using irrigating solution that contained cefuroxime 1500 µg/mL. 



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The mixture was prepared by withdrawing 10 mL BSS from the irrigating solution and injecting it into a vial of cefuroxime 750 mg. The reconstituted solution was injected back into the BSS container.

The rate of endophthalmitis was significantly decreased after the transition to intraoperative irrigation with cefuroxime. Endophthalmitis occurred in 11 eyes (0.07%) in the group that did not receive intraoperative cefuroxime and in 5 eyes (0.01%) when cefuroxime was used in the irrigating solution (

 < .01). 

Cultures were positive for bacteria in 4 of the 11 cases in the control group and in 1 of the 5 eyes in the intraoperative cefuroxime group (

 > .05). No safety issues were associated with intraoperative cefuroxime irrigation.

Discussing the research, Yusen Huang, MD, PhD, of the Shandong Eye Institute, Shandong First Medical University and Shandong Academy of Medical Sciences in Qingdao, People’s Republic of China, pointed out that although intracameral antibiotics are already widely accepted as a method for endophthalmitis prophylaxis in patients undergoing cataract surgery, the optimal choice of prophylactic routes and antibiotics is controversial.

“In European countries, commercial cefuroxime formulation (Aprokam) has been widely used, and the dose administered is the same as in the European Society of Cataract and Refractive Surgeons’ (ESCRS’) randomized prospective study demonstrating its efficacy,” Huang said. 

Surgeons have been reluctant to adopt intracameral cefuroxime because it is off label and carries potential risks.



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“In our study, the manner of cefuroxime preparation was modified so that it involved only a 1-step process. This makes it simpler, saves resources, and could reduce the potential risks of both preparation errors and contamination,” Huang pointed out. “Although the intracameral concentration achieved with our approach is estimated to be 1500 µg/mL, or only about 45% of the ESCRS recommendation, we found that it reduced the rate of postcataract surgery endophthalmitis by about sevenfold.”

Furthermore, Huang explained that “during the last 2 years in our hospital where more than 25,000 cases of cataract surgery have been performed using intraoperative cefuroxime irrigation, not a single patient developed endophthalmitis. 

It should be noted, however, that this method is not recommended for use in patients with a history of vitrectomy, [considering] the potential for rapid posterior segment diffusion of the antibiotic and potential macular toxicity.”

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Although adding cefuroxime to the irrigating solution is still an off-label use of the medication, the authors suggested that it represents a good option for countries with no licensed product for intracameral use of endophthalmitis prophylaxis and particularly in developing regions where the risks for both endophthalmitis and a poor outcome may be higher given a variety of contributory factors.

Throughout the entire study period, all patients received the same preoperative antisepsis with application of topical povidone-iodine. 

In addition, all patients started using topical levofloxacin 0.5% solution preoperatively and continued it postoperatively, along with a topical steroid and topical nonsteroidal anti-inflammatory drug.



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Postoperative follow-up visits were scheduled at 1 and 4 days, 4 weeks, and 12 weeks, but patients were instructed to seek care if they developed pain, redness, or loss of vision. 

The analyzed outcome was onset of acute-onset endophthalmitis, which was diagnosed if a patient presented within 6 weeks of surgery with eye pain, anterior chamber reaction or flare, hypopyon, and/or vitritis with causes for intraocular inflammation other than endophthalmitis excluded.

The 16 cases of endophthalmitis recorded during the 9-year study period developed at a median of 7.56 days after cataract surgery (range, 1-21 days). 

None of the cases occurred in a patient who had an intraoperative complication or was noted to have incision leakage at the time endophthalmitis was identified.



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Isolates from the culture-positive cases of endophthalmitis in the control group included 

 was identified as the causative pathogen in the culture-positive case of endophthalmitis among patients who received intraoperative cefuroxime, and the organism was found susceptible to cefuroxime.



1. Ma X, Zie L, Huang Y. Intraoperative irrigation prophylasix for acute-onset endophthalmitis after phacoemulsication surgery. 

Findings from retrospective study support intraoperative cefuroxime irrigation.  


Investigators focus on preventing postcataract surgery endophthalmitis

can benefit from perioperative use of artificial tears, particularly by starting the treatment preoperatively, according to the findings of a retrospective study conducted by Italian investigators.

The researchers analyzed data from the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire, tear breakup time (TBUT) measurements, and corneal fluorescein staining (CFS) in 3 groups of patients. 



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The groups comprised those who did not use any artificial tears perioperatively (n = 140); patients who began to instill artificial tears 1 week preoperatively and continued for 2 months postoperatively (n = 139); and a cohort that used artificial tears postoperatively for 2 months (n = 140). 

The DED-related evaluations were performed preoperatively and at follow-up visits occurring at 1, 4, and 8 weeks after surgery. 

The artificial tear product was a commercially available lubricant formulation containing hydroxypropyl guar and hyaluronic acid, and all patients were treated with the same perioperative regimen of antibiotic and anti-inflammatory medications.

 showed statistically significant benefits of treatment with the artificial tears for mitigating surgically induced signs and symptoms of DED. 

Statistically significant differences favoring the group that started using the artificial tears preoperatively compared with the group using the ocular lubricant only after surgery were seen in analyses of SPEED scores and TBUT.



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Based on the findings, the investigators concluded that the artificial tears were effective in protecting the ocular surface, particularly if initiated in the preoperative period. 

Noting that DED can lead to biometric errors and adversely affect patient comfort and vision after surgery, they stated that the findings highlight the importance of improving the homeostasis of the ocular surface not only in patients with established DED but also in those without frank disease or evident DED risk factors.



The study identified patients who had undergone unilateral cataract surgery across 17 centers in Italy. 

A total of 419 patients met the inclusion criteria that required eligible patients to be aged at least 50 years and have undergone an uncomplicated procedure with a clear corneal incision, IOL implantation in the capsular bag, and postoperative treatment with dexamethasone and tobramycin 4 times a day for 10 days and nepafenac 0.1% 3 times a day for 1 month.



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In addition, patients needed to have data from DED diagnostic tests conducted between 30 and 7 days before surgery and at 1, 4, and 8 weeks postoperatively. 

Patients were excluded if they had preexisting DED, which was diagnosed based on a Schirmer test without anesthesia less than 7 mm/5 min, TBUT less than 10 seconds, SPEED score greater than 4, and CFS score greater than 1, or if they had any other findings that could confound the results.

Preoperatively, the 3 study groups were well matched with respect to mean age ( ~ 72 years), mean Schirmer test score ( ~ 13 mm/5 min), mean TBUT ( ~ 12 sec), and percentage of eyes with a CFS score equal to 0 (65% to 76%). 

The postoperative data from all groups were consistent with previous reports showing that cataract surgery can induce signs and symptoms of DED.

Mean SPEED questionnaire scores did not change significantly in groups that were using artificial tears but increased significantly (worsened) at week 4 in the untreated patients. 

The differences in mean SPEED scores were statistically significant favoring both groups using the artificial tears versus the untreated group at all follow-up visits. 

The investigators noted that 25% of the patients in the untreated group had SPEED scores corresponding to mild-moderate dry eye symptoms at 8 weeks after surgery.


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In addition, a statistically significant difference favoring the group starting artificial tear use preoperatively compared with the group treated only postoperatively was noted at postoperative weeks 1 and 4.

The TBUT was significantly higher in both groups using the artificial tears compared with the controls at all follow-up visits, and mean TBUT fell to below 10 seconds postoperatively only in the control group. 

In addition, TBUT recovered faster in the group using artificial tears preoperatively compared with the group that was treated only after surgery. At the week 4 postoperative visit, the TBUT was higher in the group that started artificial tear use preoperatively compared with the group treated only postoperatively.

The investigators noted the difference was statistically significant, but it was not clinically significant.

The results for CFS showed that patients using artificial tears had less corneal damage after surgery than their untreated counterparts. 

Among patients who used the artificial tears preoperatively and postoperatively, a small minority had CFS scores of 2 (7.2%) or 3 (0.7%) at the week 1 postoperative visit. 

In this same group by week 4, more patients had a CFS score of 0 compared with baseline, and the percentage was increased further at week 8.

A similar pattern of early worsening in CFS scores and subsequent progressive improvement was noted in the group that used artificial tears postoperatively only and in the untreated group.

However, among patients who used the artificial tears after surgery, approximately 6% of patients had a CFS score greater than 1 at week 4, whereas in the untreated group a CFS score greater than 1 was found in 20% of eyes at week 1, 13% at week 4, and 6.4% at week 8. 


1. Favuzza E, Cennamo M, Vicchio L, Giansanti F, Mencucci R. Protecting the ocular surface in cataract surgery: the efficacy of the perioperative use of a hydroxypropyl guar and hyaluronic acid ophthalmic solution.

2020;14:1769-1775. doi:10.2147/OPTH.S259704

Study supports preoperative ocular surface optimization with artificial tears.

Cheryl Guttman Krader, BS, Pharm

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