Customized disposable kit versus a conventional stainless steel instrument for an intravitreal injection: A comparison.

Comparison of a customized disposable kit with a conventional stainless steel instrument was performed for an intravitreal injection. A total of 2700 eyes of 2250 patients were enrolled in two groups. Comfort level of the patients was assessed using a 'Pain Scale' and any post intravitreal injection complications were examined clinically by a slit lamp biomicroscopy. Surgeon's ease was assessed by a questionnaire. In group A, no pain was recorded in 1231(82.06%) eyes, mild pain was d escribed in 184(12.27%), moderate pain was documented in 78 (5.2%) while, severe pain was noticed in 7(0.47%). In group B, no pain was seen in 1014(84.5%), mild pain was present in 123(10.25%), moderate pain was perceived in 58 (4.83%) while, severe pain was recorded in 5 (0.42%). With respect to surgeon's ease, 6 out of the 7 surgeons found the kit to be more convenient and cost effective as compared to the conventional instruments. Disposable intravitreal kit is beneficial for both the patients as well as the surgeons.

ACCURACY AND PRECISION OF INTRAVITREAL INJECTIONS OF ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR AGENTS IN REAL LIFE: What Is Actually in the Syringe?

PURPOSE: To evaluate the accuracy and precision of anti-vascular endothelial growth factor volume delivery by intravitreal injections in the clinical setup. METHODS: Volume output was measured in 669 intravitreal injections administered to patients, calculated from the difference in syringe weight before and after expelling the drug. Three groups were included: prefilled bevacizumab 1.0 mL syringe (Group 1, n = 432), pre-filled ranibizumab in a small-volume syringe with low dead-space plunger design (Group 2, n = 125), and aflibercept drawn and injected using a 1.0-mL syringe (Group 3, n = 112). Accuracy was analyzed by mean absolute percentage error, and precision by coefficient of variation. RESULTS: Volume outputs in all 3 groups were significantly different from the target of 50 µL (P < 0.0001 for all), and mean absolute percentage error values were 12.25% ± 5.92% in Group 1, 13.60% ± 8.75% in Group 2, and 24.69% ± 14.84% in Group 3. No difference was found between groups 1 and 2, but both were significantly more accurate than Group 3 (P < 0.0001 for both). CONCLUSION: The current practices used for intravitreal injections are highly variable, with overdelivery of the anti-vascular endothelial growth factor drugs measured in most cases, but underdelivery in 16.3% of injections. Use of a prefilled syringe was associated with improved accuracy, and low dead-space plunger design may improve precision.

CLINICAL EVALUATION OF THE RAPID ACCESS VITREAL INJECTION GUIDE: A Handheld Instrument for Assisting Intravitreal Injections.

PURPOSE: The Rapid Access Vitreal Injection (RAVI) guide combines the function of an eyelid speculum and measuring caliper into a single instrument for assisting intravitreal injections. This study clinically evaluated the RAVI guide with respect to patient acceptance, complication rates, and operative goals. METHODS: A prospective study was performed on 54 patients undergoing intravitreal injections using the RAVI guide (n = 32) or the speculum/caliper (n = 22). Device-related pain was assessed using the Wong-Baker scoring system, scaled from 0 (no pain) to 10 (agonizing pain). RESULTS: Mean device-related pain score did not differ significantly between the 2 groups, with scores of 0.6 and 0.7 for the RAVI guide and speculum groups, respectively. The rate of significant pain (score of ≥2) was twice as high in the speculum group (7 of 22, 32%) compared with the RAVI guide group (5 of 32, 16%), but this difference was not statistically significant (P = 0.19, Fisher's exact test). Operative goals of avoiding needle touch to lashes/lids and guiding needle insertion to the intended site were achieved in all patients. CONCLUSION: The RAVI guide appeared equivalent to the eyelid speculum in achieving operative goals, with similarly low pain scores. It has the potential for facilitating efficient, accurate, and safe intravitreal injections.

LOW ENDOPHTHALMITIS RATES AFTER INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTIONS IN AN OPERATION ROOM: A Retrospective Multicenter Study.

PURPOSE: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections in three European hospitals performed in an operation room (OR) under sterile conditions. METHODS: A retrospective multicenter study between 2003 and 2016 at three European sites, City Hospital Triemli Zurich, Switzerland (CHT), Zealand University Hospital Roskilde, Denmark (ZUH) and University Clinic Bern, Switzerland (UCB). Intravitreal injection (IVI) database of each department was reviewed. All anti-vascular endothelial growth factor injections were performed using a standardized sterile technique in an operation room. Injection protocols were similar between the three sites. No preinjection antibiotics were given. Postoperative antibiotics varied among sites. RESULTS: A total of 134,701 intravitreal injections were performed at the 3 sites between 2003 and 2016. Ten cases of presumed endophthalmitis were documented: 4 in 50,721 at CHT (95% CI: 0.0071-0.0087%), 2 in 44,666 at ZUH (95% CI: 0.0039-0.0051%), and 4 in 39,314 at UCB (95% CI: 0.0092-0.011%). This results in one case in 13,470 intravitreal injections and a combined incidence of 0.0074% per injection (95% CI: 0.0070-0.0078%). Positive cultures were found in 4 out of 10 presumed endophthalmitis cases. CONCLUSION: The standardized sterile technique in an operation room with laminar airflow showed very low rates of endophthalmitis at three European sites.

Real-time measurement of needle forces and acute pressure changes during intravitreal injections.

BACKGROUND: The purpose of this study was to use a physiological pressure transducer to measure real-time, continuous pressure changes in an ex vivo study model of porcine eyes to record the amount of force needed for scleral penetration and to measure acute intraocular pressure rise during intravitreal injections. METHODS: A pressure transducer was inserted into the anterior chamber of 30 fresh porcine eyes, and intraocular pressure was measured 2 s prior to intravitreal injection until 2 s after. A force transducer plate was used to insert various gauge needles into the vitreous cavity and the amount of force in Newtons (N) required for scleral penetration was recorded. RESULTS: For scleral perforation, 32- and 30-gauge needles required 0.44 N and 0.45 N, significantly less than larger gauge needles (P < 0.05). Similarly, 27- and 25-gauge needles required more force than smaller gauge needles but less than 19 gauge (P < 0.05). Intraocular pressure increased an average of 64.5 mmHg during intravitreal injection. Two seconds postinjection intraocular pressure readings showed a residual intraocular pressure increase of 11.1 mmHg from pre-injection baseline. CONCLUSION: Real-time continuous recordings of pressure reveal that an instantaneous intraocular pressure spike occurs during intravitreal injection and appears to be separate from the intraocular pressure spike that occurs during needle insertion. This pressure spike is transient and has not been captured by previous methods of intraocular pressure measurement, which rely on single time point measurements. The clinical significance of this brief intraocular pressure spike is unclear and warrants further investigation.

ARE INTRAVITREAL INJECTIONS WITH ULTRATHIN 33-G NEEDLES LESS PAINFUL THAN THE COMMONLY USED 30-G NEEDLES?

PURPOSE: This study investigated whether pain from intravitreal injections (IVIs) can be reduced by injecting with a 33-G needle instead of the commonly used 30-G needle. Additionally, several pain-related psychological factors were explored as predictors of outcome. METHODS: This randomized crossover trial included 36 patients who received injections with both needles in randomized order. After the injection, patients rated IVI pain on a 0 to 10 scale. Before injection, distress and pain expectations were assessed. Afterward, patients rated the IVI procedure and anticipated consequences. In addition, we assessed the force necessary to penetrate the sclera for both needles in porcine eyes. RESULTS: The 33-G needle did not result in lower IVI pain (2.8 vs. 3.1, P = 0.758) but tended to cause less vitreal reflux (0 vs. 5 times, P = 0.054). Factors related to more pain were distress, expecting IVI pain and discomfort, dissatisfaction with the preparation procedure, anticipating negative consequences, and female gender. Patients regarded povidone-iodine disinfection as particularly unpleasant. Exploration of the needles' mechanical properties showed that 33-G needles penetrate the sclera more easily. CONCLUSION: The thinner 33-G needle does not reduce IVI pain but may limit scleral damage. Future efforts could be aimed at optimizing patient information, reducing distress, and the use of better tolerable disinfectants.

Needle contamination in the setting of intravitreal injections.

BACKGROUND/PURPOSE: To evaluate the risk of intravitreal needle contamination through speaking versus breathing in an office setting. METHODS: This was a prospective sampling assay. Participants held a sterile 30-gauge half-inch needle 25 cm from their mouth for 30 seconds under 2 conditions: (1) while speaking and (2) while breathing silently. Needles were then cultured and assayed after 6 days of incubation. Absolute colony-forming units were compared between conditions and against control sterile needles and oral swab cultures. RESULTS: Ten physicians were sampled with 15 samples per physician. Participants grew an average of 0.21 colonies (median = 1 CFU) from their talking samples and 0.07 colonies (median = 1 CFU) from their silent breathing samples. Oral swab plates grew an average of 373.4 colonies. None of the control needle plates grew colony-forming units. A nominal regression analysis showed no significant difference between talking and silent samples (P = 0.457). CONCLUSION: No significant difference in needle contamination was found between talking and breathing. Compared with oral swab plates, a significant difference exists between the amount of flora colonizing the oropharynx and that which was found on the needle cultures (P < 0.0001). These findings suggest that speaking versus remaining silent makes no difference in regard to needle contamination with oral flora during intravitreal injection.

Tower microneedle minimizes vitreal reflux in intravitreal injection.

Intravitreal injection is widely used for easy control of drug levels in posterior segment of the eye by injecting the drug directly with hypodermic needles. Patients, however, often experience complications from intravitreal injection due to repeated injections, increased intraocular pressure, and infection. In addition, injected drug reflux after intravitreal injection makes it challenging to maintain predetermined drug dose due to the drug loss through backward effusions. Here, we described that the Tower Microneedle can reduce initial reflux and bleb formation due to its smaller outer diameter compared to a traditional hypodermic needle. Furthermore, we use phenylephrine hydrochloride for pupil expansion and demonstrated that Tower Microneedle induced similar pupil expansions using only half the drug volume, in the same period of time, compared to the 31 Gauge hypodermic needle. Consequently, Tower Microneedle achieves the same therapeutic effect in the vitreous body using fewer drugs than a traditional hypodermic needle due to the decreased backward drug effusion. Tower Microneedle described herein holds great promise for intravitreal injection with less reflux and lower drug dosage.

Bimanual assisted eyelid retraction technique for intravitreal injections.

PURPOSE: To describe an alternative technique for avoiding contact with the lids and eyelashes without the use of a metal lid speculum along with the results in clinical practice. METHODS: Retrospective review of the medical records of all patients undergoing intravitreal injections of bevacizumab and ranibizumab with lid retraction achieved by bimanual assisted eyelid retraction between November 2010 and December 2011. RESULTS: A total of 10,164 consecutive intravitreal injections were performed, of which 3,834 were bevacizumab and 6,330 were ranibizumab. In this cohort of patients, 3 suspected cases of endophthalmitis developed (2 culture-negative), corresponding to a rate of 0.03%. CONCLUSION: The technique of bimanual assisted eyelid retraction for intravitreal injection has a low rate of infection similar to the reported rates using a metal lid speculum.

A micro-advancer device for vitreal injection and retinal recording and stimulation.

A micro-advancer device that positions a narrow-gauge needle within the vitreous humor of the rat eye is described. The device is compact, simple and inexpensive to manufacture. It consists of an outer guard needle and an inner injection needle that is advanced through the guard needle. With the rat held in a stereotaxic holder and the globe fixed to a stabilizing ring, the outer 25-gauge guard needle is advanced through the sclera using a standard micromanipulator. The inner 31-gauge injection needle is then advanced through the guard needle with a manually controlled leadscrew and carriage mechanism. The inner injection needle is attached to a Hamilton syringe and can be positioned to within microns of the retinal surface under visual observation through a microscope. The injection needle is fixed to the device by a quick-release clamp on the carriage and can be rapidly exchanged while the guard needle remains in place in the vitreous. This permits different solutions to be injected sequentially into the vitreous humor. Recording electrodes, stimulating electrodes, and optical fibers can also be advanced through the guard needle and positioned accurately near the retinal surface or within the retina.

Experimental investigation of needles, syringes and techniques for intravitreal injections.

BACKGROUND: To assess the techniques and materials used in intravitreal injections. DESIGN: Descriptive study realized at the Vision Institute of the Federal University of São Paulo, Brazil. SAMPLES: Different brands of needles and syringes, as well as enucleated porcine eyeballs. METHODS: The ultra-structures of commonly used needles were analysed by scanning electron microscope, and they were compared using different criteria, such as irregularities and debris from the lubrication process. The scleral incision was also assessed using needles of different brands and sizes. Accuracies in drug administration were studied by comparing the residual and delivered volume of needles and also by the analysis of reflux after intravitreal injections. MAIN OUTCOME MEASURES: Efficiency and quality of materials used in intravitreal injections. RESULTS: Ultra-structure analyses showed that all needles had different types of irregularities. Some photographs showed debris from the lubrication process, especially in BD needles. Scleral incision analysis showed a tendency of reducing the ocular damage with increasing gauge (P=0.024). The investigation of delivery accuracy showed that almost all needles underdosed the amount injected (P<0.05), and that the reflux could be minimized by tunnelled injections with thinner needles. CONCLUSION: Needles used in intravitreal injections possess many irregularities in their structures, which may cause different injection outcomes. Analyses of scleral incisions showed that the larger the needle gauge, the lesser the scleral damage and the risk of complications. Moreover, drug administration inaccuracies might be one of the causes for some unsuccessful attempts of treatment.

Critical analysis of techniques and materials used in devices, syringes, and needles used for intravitreal injections.

Intravitreal injections have become the most commonly performed intraocular treatments worldwide. Because intravitreal injections may induce severe adverse events, such as infectious and noninfectious endophthalmitis, cataract, ocular hypertension, vitreous hemorrhage, or retinal detachment, appropriate awareness of the materials and techniques used are essential to reduce these sight-threatening complications. This review provides insights into the needles, syringes, silicone oil coating, sterilization methods, devices to assist intravitreal injections, scleral piercing techniques using needles, syringe handling, anesthesia, and safety issues related to materials and techniques. It is paramount that physicians be aware of every step involved in intravitreal injections and consider the roles and implications of all materials and techniques used. The ability to understand the theoretical and practical circumstances may definitely lead to state-of-the-art treatments delivered to patients. The most important practical recommendations are: choosing syringes with as little silicone oil as possible, or, preferably, none; avoiding agitation of syringes; awareness that most biologics (e.g., antiangiogenic proteins) are susceptible to changes in molecular properties under some conditions, such as agitation and temperature variation; understanding that improper materials and techniques may lead to complications after intravitreal injections, e.g., inflammation; and recognizing that some devices may contribute to an enhanced, safer, and faster intravitreal injection technique.

Real-time measurement of intraocular pressure variation during automatic intravitreal injections: An ex-vivo experimental study using porcine eyes.

PURPOSE: To measure needle insertion force and change in intraocular pressure (IOP) in real-time during intravitreal injection (IVI). The effects of needle size, insertion speed, and injection rate to IOP change were investigated. METHODS: Needle insertion and fluid injection were performed on 90 porcine eyeballs using an automatic IVI device. The IVI conditions were divided according to needle sizes of 27-gauge (G), 30G, and 33G; insertion speeds of 1, 2, and 5 mm/s; and injection rates of 0.01, 0.02, and 0.05 mL/s. Insertion force and IOP were measured in real-time using a force sensor and a pressure transducer. RESULTS: The peak IOP was observed when the needle penetrated the sclera; the average IOP elevation was 96.3, 67.1, and 59.4 mmHg for 27G, 30G, and 33G needles, respectively. An increase in insertion speed caused IOP elevation at the moment of penetration, but this effect was reduced as needle size decreased: 109.8-85.9 mmHg in 27G for 5-1 mm/s (p = 0.0149) and 61.8-60.7 mmHg in 33G for 5-1 mm/s (p = 0.8979). Injection speed was also related to IOP elevation during the stage of drug injection: 16.65 and 11.78 mmHg for injection rates of 0.05 and 0.01 mL/s (p < 0.001). CONCLUSION: The presented data offers an understanding of IOP changes during each step of IVI. Slow needle insertion can reduce IOP elevation when using a 27G needle. Further, the injection rate must be kept low to avoid IOP elevations during the injection stage.

The influence of dead spaces and the designs of injectors on the amount of drug dose in intra-vitreal injection.

AIM: To evaluate the dead spaces resulting from different designs of the insulin injectors used for intravitreal injections and the amounts of drug doses. METHODS: In the study, five different brands of sterile insulin injectors of 1 mL were used for the test. The weight of the injectors was determined before and after filling the injectors with 0.05 and 0.1 mL distilled water. The weight of the injectors was measured with and without the needle after the water within the injectors had been taken out and weight differences were measured. The difference between the intended amount of fluid to be thrown out and the weight of the fluid remaining in the injector was calculated as percent error. RESULTS: After throwing out 0.05 mL distilled water from the injector, weights of the Beybi®, Traf®, Becton Dickinson®, Ayset®, and Setojet® brands of injectors with 30 G needle were detected to increase the mean 0.0220 ± 0.006 g, 0.0208 ± 0.008 g, 0.0355 ± 0.016 g, 0.0219 ± 0.017 g, and 0.0150 ± 0.007 g, respectively compared to the weights of the dry injectors. The 0.1 mL injector group was found to be mean 0.0350 ± 0.014 g, 0.0264 ± 0.008 g, 0.0405 ± 0.015 g, 0.0272 ± 0.013 g, and 0.0245 ± 0.014 g, respectively. The maximum increase due to the dead spaces in the injectors was found in the Becton Dickinson® injector, both in the 0.05 mL and the 0.1 mL groups (p < 0.000). CONCLUSION: The injector designs may affect the dose of IVI required to be given. More correct amounts of drugs may be administered via the intra-vitreal route through designs that reduce the dead spaces at the end part of the injector and between the inner wall and the plunger.

Silicone oil-free syringes, siliconized syringes and needles: quantitative assessment of silicone oil release with drugs used for intravitreal injection.

PURPOSE: This study aimed to quantify the amount of silicone oil (SO) released across a variety of syringe and needle models routinely used for intravitreal injection. METHODS: The release of SO was assessed in eight models of syringes, two of which were reported to be 'SO-free', and eleven models of needles with unknown SO content. To evaluate SO release within the context of anti-VEGF therapeutics, syringes were evaluated using aflibercept, bevacizumab, buffer, ziv-aflibercept and formulation buffer. All syringe tests were performed with or without agitation by flicking for syringes. Needles were evaluated without agitation only. Samples were fluorescently labelled to identify SO, and triplicate measurements were collected using imaging flow cytometry. RESULTS: Seven out of 8 syringe models showed a statistically significant increase in the SO particle count after agitation. The two SO-free syringe models (HSW Norm-Ject, Daikyo Crystal Zenith) released the least SO particles, with or without agitation, whereas the BD Ultra-Fine and Saldanha-Rodrigues syringes released the most. More SO was released when the syringes were prefilled with formulation buffer than with ziv-aflibercept. Syringes filled with aflibercept and bevacizumab had intermediate levels. Agitation increased the release of SO into each of the drug solutions. Silicone oil (SO) was detected in all needles. CONCLUSIONS: Agitation of the syringe by flicking leads to a substantial increase in the number of SO particles. Silicone oil (SO)-free syringes had the best performance, but physicians must also be aware that needles are siliconized and also contribute to the injection of SO into the vitreous.

Intraocular pressure and injection forces during intravitreal injection into enucleated porcine eyes.

Injection of biological molecules into the intravitreous humor is of increasing interest for the treatment of posterior segment eye diseases such as age-related degenerative macular degeneration. The injection volume is limited by an increase in intraocular pressure (IOP) and 50-100 µL are typically used for most intravitreally (IVT) applied commercial products. Direct measurement of IOP is difficult and has not been studied dependent on solution properties and injection rates. We used an instrumental set-up to study IOP ex vivo using healthy enucleated porcine eyes. IOP was determined as a function of injection volume for viscosities between 1 and 100 mPas, injection rates of 0.1, 1, and 1.5 mL/min, and needle length and diameter (27/30G and 0.5/0.75″) using Dextran solutions. IOP increased exponentially for injection volumes larger than 100 µL. We did not observe differences in IOP dependent on viscosity, injection rate, and needle diameter. However, variability increased significantly for injection volumes larger than 100 µL and, unexpectedly, declined with higher viscosities. We demonstrate that the exponential increase in IOP is not reflected by injection force measurements for typical configurations that are used for IVT application. The present findings may guide injection volumes for intravitreal injection and inform injection force considerations during technical drug product development.