Sterile Caliper Anterior Chamber Decompression Mitigates Intraocular Pressure Spikes in Intravitreal Injections

Abstract

Purpose: To investigate the efficacy of a novel approach using a sterile caliper for anterior chamber (AC) decompression in reducing post-intravitreal injection (IVI) intraocular pressure (IOP) spikes.

Methods: A prospective interventional case series conducted at the Iowa City Veterans Affairs Medical Center (VAMC) with Institutional Review Board approval. Patients were randomized to receive conventional IVI or IVI with sterile caliper decompression. Fifty eyes from 47 patients underwent IVI for various retinal pathologies. Subjects were randomly assigned to the intervention or control arm. Two resident physician providers performed injections, with one applying sterile caliper decompression (intervention) and the other following the standard technique (control). Baseline and postinjection IOP were measured using Tonopen (Reichert, Depew, NY).

Results: In both groups there was a significant IOP rise following IVI (P < 0.0001). There was no significant difference in baseline IOP between groups (P = 0.082), but postinjection IOP was significantly lower in the intervention group (23.52 ± 5.98 mm Hg) compared to the control group (44.08 ± 8.48 mm Hg). There were no patients with an IOP spike >25 mm Hg in the intervention arm. The technique was effective regardless of lens status.

Conclusions: Sterile caliper AC decompression significantly reduced post-IVI IOP spikes presenting an efficient and cost-effective alternative to previously proposed methods of IOP reduction. Further studies are warranted to validate these findings and explore broader applications in ophthalmic interventions.

Translational Relevance: The caliper decompression technique presents potential benefit in preventing short-term morbidity associated with IOP spikes after IVI and addressing long-term concerns in patients with pre-existing glaucoma.

Introduction

Intravitreal injections (IVI) are one of the most common procedures in ophthalmology with over 7 million injections performed in the United States annually.¹ This number continues to rise with an aging population and as medical management of the most common retinal diseases relies on repeated injections for treatment. Short-term intraocular pressure (IOP) elevation is a well-recognized risk of IVI and the average IOP within one minute of an injection can be as high as >40 mm Hg.^2,3 Usually the IOP decreases without intervention, but it often requires prolonged monitoring of the patient with repeated IOP measurements. Rarely, patients can experience transient occlusion of the central retinal artery, and this may lead to visual loss if not recognized; in these cases, intervention with anterior chamber paracentesis (ACP) can be performed to quickly lower the IOP.³ Even though most patients return to a safe IOP within 30 minutes of injection,^2,4 the long-term effects of this transient IOP spike is not well understood. Several large studies have identified a dose-related association of IVI and open angle glaucoma along with gradual thinning of the retinal nerve fiber layer (RNFL).^3,5,6 Furthermore, patients with a history of glaucoma have been shown to take significantly longer time to normalize IOP after IVI and have been reported to require ACP more frequently.^2,7 

As a result of these sequalae and the interplay of retinal and glaucomatous pathologies, many approaches have been attempted to mitigate the IOP elevation. These approaches include but are not limited to modifying needle size, use of topical IOP-lowering medications, cotton swab decompression, and digital ocular massage.^8–14 

We propose a novel, efficient, and cost-effective approach, using the same sterile caliper, commonly used for marking injection sites, to lower the postinjection IOP spikes seen in IVI. We hypothesize that applying sustained pressure on the limbus for ten seconds with the caliper before IVI can provide moderate AC decompression thereby reducing IOP spikes when compared to conventional IVI techniques. 

Methods

This was an Institutional Review Board approved prospective interventional case series conducted at the Iowa City Veterans Affairs Medical Center (VAMC). All research adhered to the tenets of the Declaration of Helsinki. Data was collected from July 2023 to September 2023. Patients were randomly assigned to injection technique method on the day of treatment and all patients were consecutively enrolled during the study period. The method of randomization involved random assignment of patients to the resident physician based on the clinic schedule for the day. This approach minimized bias, as it depended on the pre-established clinic schedule rather than any specific patient characteristics or predetermined criteria. Intravitreal injections were performed by two resident physician providers using a 30-gauge needle. The same physician (SBA) treated patients in the intervention arm with use of sterile caliper decompression, while a different physician (ST) treated those in the control arm, where no deliberate decompression was performed. Other than sterile caliper decompression, both physicians adopted the same injection technique as detailed below. A total of 25 eyes were included in each arm. 

In the control arm, the standard-of-care technique at our center was used: 

• 1. Topical anesthesia with 0.5% proparacaine followed by 4% lidocaine.
• 2. Placement of a standard style sterile eyelid speculum between the eyelids to allow for injection. The eyelid speculum is placed by the treatment provider wearing sterile gloves.
• 3. Installation of 5% povidone-iodine for disinfection of the eye that is to be injected.
• 4. Marking of the injection site, most commonly superotemporally, at a distance of 3.5 mm from the limbus in patients with pseudophakia or at 4.0 mm in phakic patients. The disposable caliper (Moria Instruments, Paris, France) is used to mark the injection site for <1 second in the standard technique.
• 5. Intravitreal injection of medication verified by the treating physician.
• 6. Prompt removal of the eyelid speculum.
• 7. Measurement of IOP within 30 seconds after IVI using Tonopen (Reicher, Depew, NY, USA).

The intervention arm was the same except that the sterile caliper tip was used to slightly depress the sclera at the limbus for ten seconds prior to injection. The injector was instructed to apply enough pressure to indent the sclera slightly without causing discomfort to the patient, aiming for a consistent approach across all injections within the intervention arm. 

All patients received standardized injections of bevacizumab (1.25 mg/0.05 mL), aflibercept (2 mg/0.05 mL), or ranibizumab (0.5 mg/0.05 mL). All patients had preinjection IOP measured as a routine part of the clinical encounter. The IOP measured as measured by Tonopen during the routine clinical encounter was utilized as the “pre-treatment IOP” reported in the study. There was minimal time (<30 minutes) between the time of IOP measurement and the time of injection. Postinjection IOP was measured immediately by the treating physician using the Tonopen. Visual acuity testing for hand motion or better along with IOP measurements were repeated at approximately three-minute intervals. Once the vision was at least counting fingers and the IOP reached 30 mm Hg or lower, the patient was discharged. No adverse events were noted, and decompression was tolerated well by patients. 

Data analysis was performed using GraphPad Prism Version 9.5.1. Baseline and post-injection IOP (mm Hg, SD) were compared between groups using a paired t-test. A P value <0.05 was considered statistically significant. The presence of a post-injection IOP spike >25 mm Hg from baseline in eyes injected with the standard technique was compared with the interventional arm using Fisher's exact test. 

Results

Fifty eyes from 47 patients were included in the study. The mean age at time of injection was 76.16 ± 6.32 years in the control arm and 72.64 ± 7.41 years in the intervention arm (Table 1). Indications for IVI included diabetic macular edema, exudative age-related macular degeneration, cystoid macular caused by retinal vein occlusion, and others (including idiopathic choroidal neovascular membrane and radiation retinopathy). None of the patients included in our study cohort had a history of glaucoma surgery or required pre-treatment IOP lowering therapy. Detailed data regarding prior gonioscopy (i.e., angle status) and axial length were not collected as part of this study. 

Table 1.

 

Characteristics and Demographics of Study Participants

 

In the control arm, preinjection IOP was 16.24 mm Hg ± 2.95 and post-injection IOP was 44.08 mm Hg ± 8.48, with an average delta IOP of 27.84 mm Hg ± 9.09. In the intervention arm, pre-injection IOP was 14.56 mm Hg ± 3.70 SD and post-injection IOP was 23.52 mm Hg ± 5.98, with an average delta IOP of 8.96 mm Hg ± 7.66 (Table 2). 

Table 2.

 

Intraocular Pressure Before and After Intervention

 

In both groups a significant IOP rise following IVI was observed (P < 0.0001 for control arm, P < 0.0001 for study arm). There was no significant difference in baseline IOP between groups (P = 0.082), but postinjection IOP was significantly higher in the control group than in the intervention group (P < 0.0001) (Fig. 1). There was a significantly higher incidence of significant IOP elevation, defined as a rise of IOP of >25 mm Hg from baseline, in the control arm (72% vs, 0%, Fisher's exact test, P < 0.0001). When stratified by lens status (i.e., phakic versus pseudophakic subjects), post-injection IOP in the intervention group was lower than that in the control group for both phakic and pseudophakic groups (Table 2; Fig. 2). 

Figure 1.

 

Box plot showing the immediate postinjection intraocular pressure after injection in the control arm versus the intervention arm.

Figure 2.

 

Box plots showing the immediate postinjection intraocular pressure after injection in the control arm versus the intervention arm stratified based on lens status.

Figure 3.

 

Bar graphs showing the percentage of eyes with change in intraocular pressure >5 mm Hg, >15 mm Hg and >25 mm Hg after injection in the control arm versus intervention arm.

Post-injection IOP was not significantly different between phakic and pseudophakic patients within either the control (42.73 ± 8.43 vs. 45.14 ± 8.68, P = 0.49) or the intervention (23.31 ± 5.92 vs. 23.75 ± 6.30, P = 0.86) groups. Post-injection spike (delta IOP) was also not significantly different between phakic and pseudophakic patients within either the control (25.73 ± 8.98 vs. 29.50 ± 9.16, P = 0.31) or the intervention (8.92 ± 6.69 vs. 9.00 ± 8.89, P = 0.98) groups. 

Discussion

Our findings demonstrate that sterile caliper AC decompression significantly decreases post-injection IOP compared to conventional IVI technique. Further, the intervention arm had no patients with an IOP spike >25 mm Hg from baseline (Fig. 3). Our study also found no significant difference in the IOP spike between patients that were phakic and pseudophakic, which is consistent with prior studies that stratified based on lens status.¹² 

To our knowledge this method of ocular decompression has not been reported to date. In our study, we show that this is an effective and well-tolerated technique that significantly reduces postinjection IOP elevations. This is not only favorable in short-term morbidities such as amaurosis, but also in the lesser-known long-term morbidities, especially in patients with pre-existing glaucoma. 

In a recent meta-analysis, the use of IOP lowering therapy was confirmed to reduce the IOP spike associated with IVI and several studies have demonstrated that that there are several ways to mitigate the assumed harmful IOP spike.⁵ Despite a valid clinical utility, however, the previously described methods add time to the clinical encounter and increase medication use. These have both implications on both cost and sustainability. Our novel technique repurposes a device, the sterile caliper, that is already being used and adds about ten seconds to the conventional technique. In a similar fashion, although ACP is a cost-effective procedure to immediately lower IOP, it has the potential for many complications including pain, hyphema, inflammation, infection, leakage, and capsular violation in phakic patients. The sterile caliper approach offers advantages in resource conservation and waste reduction compared to alternative methods. 

It is generally accepted that the injection of additional volume to the relatively closed space of the globe is what causes IOP spikes.³ Understanding this equilibrium of inflow and outflow is also critical in understanding the efficacy of decompression in mitigating post-injection IOP spikes. Application of the sterile caliper effectively modifies the facility of outflow in Goldmann's equation,¹⁵ thereby resulting in a pressure gradient that favors aqueous outflow through conventional routes. We believe that the most likely result is a reduced intraocular volume when the pressure from the caliper is released, thus, creating a safety net to restabilize the volume of the globe with the injection with a lesser chance of an IOP spike. The compression by the caliper, in fact, yields AC decompression. 

The long-term effects of repeated IOP spikes in patients undergoing treatment are not yet well characterized. This is of particular consideration in patients with baseline poor ocular perfusion, poor facility of outflow, or a pre-existing diagnosis of glaucoma. There are recent studies that suggest there is accelerated structural RNFL loss in patients receiving intravitreal injections^16,17 and that there is a higher risk of glaucoma surgery in patients receiving repeated injections.¹⁸ Large prospective trials would be useful to fully elucidate the risk of glaucomatous damage in patients undergoing repeated injections, but this has proven difficult to date. As such, prevention of these IOP spikes should be especially considered in eyes that may be particularly vulnerable to fluctuations in IOP. 

At the Iowa City VAMC almost all IVI are performed by resident trainees. The introduction of this technique, beyond its cost-effectiveness and utility, has been helpful in resident performance during training while also reducing complications. Patients in our clinical practice are observed after IVI until IOP returns to <30 mm Hg. This can often result in prolonged visits as patients wait for the IOP to normalize. Although the time-to-discharge between groups was not a measured outcome, this should be considered in overall patient experience and well-being. 

Although our study provides valuable insights, it has some limitations, including a relatively small size and the need for further studies with larger sample sizes to validate our findings. First, there is an inherent potential for inaccuracy when using the Tonopen tonometer. Various methods exist for assessing IOP, and the Tonopen has been reported to potentially mask higher IOP when compared to Goldmann applanation tonometry.^19,20 Therefore using Goldmann applanation tonometry, thus, may have yielded different results between the intervention and control groups. Another limitation to this pilot study is the potential for bias as the clinician measuring the intraocular pressure was also the injector of the drug and was not masked to the study arm. This lack of masking may introduce measurement bias, potentially affecting the accuracy of our findings. To address this concern in future studies, we would incorporate masked observers to measure IOP at subsequent time points, which would minimize bias. Masked measurements would ensure that the observer is unaware of the patient's study arm, thus providing more objective and unbiased results. Additionally, implementing a standardized protocol for IOP measurement at multiple time points postinjection would allow for a more comprehensive assessment of the intervention's effectiveness over time. Lastly, it was not plausible to standardize the forces applied on the globe. The decompression technique was performed by the same treating provider to help reduce variability in pressure applied during caliper indentation. However, the pressure applied with the caliper varied among patients based on the operator's judgment and technique. Because of the lack of a standardized method for measuring the exact amount of pressure exerted on the globe during caliper indentation, this variable could not be quantitatively controlled or reported. Future investigations should both attempt to standardize the pressure and explore whether different injectors can reproduce these results consistently. The predilection of male patients is the result of our patient demographic encountered at the Iowa City VAMC and reduces the generalizability of our results. 

Conclusions

In conclusion, our investigation found that caliper AC decompression preceding intravitreal injections decreased postinjection IOP spikes. The introduction of new protocols, such as caliper decompression, could help reduce the risk of associated morbidity and need for ACP. Beyond its therapeutic impact, the sterile caliper technique showcases a pragmatic avenue for resource conservation and procedural waste reduction, aligning with contemporary demands for sustainable and cost-effective healthcare practices. 

Acknowledgments

Disclosure: M. Mansoor, None; N.-U.-S. Ahmad, None; S.B. Ahmed, None; S. Tadros, None; J. Folk, None; M.D. Abramoff, None