Noninvasive method to reduce vitreous reflux following intravitreal injection

Raouf Gaber; Mina Nassif; Wesam S Shalaby; Osama Sorour

doi:10.4103/ejos.ejos_93_22

ORIGINAL ARTICLE

Year : 2023 | Volume : 116 | Issue : 1 | Page : 24-27

Noninvasive method to reduce vitreous reflux following intravitreal injection

Raouf Gaber, Mina Nassif, Wesam S Shalaby, Osama Sorour
Department of Ophthalmology, Tanta University, Tanta, Egypt

Date of Submission	13-Nov-2022
Date of Decision	30-Nov-2022
Date of Acceptance	30-Nov-2022
Date of Web Publication	30-Mar-2023

Correspondence Address:
MD Raouf Gaber
Tanta University Eye Hospital, El-Gash Street, Medical Campus the Faculty of Medicine, Tanta, Gharbeya Province 31527
Egypt

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/ejos.ejos_93_22

Abstract

Aim To investigate the role of pre-injection antiglaucoma medications as a noninvasive method to prevent reflux following intravitreal injection (IVI).
Patients and methods This single-center prospective randomized study included patients who were planned to receive an IVI of anti-vascular endothelial growth factor ranibizumab 0.05 ml for macular edema for diabetic macular edema, branch retinal vein occlusion, or choroidal neovascular membrane. Patients were randomized into five groups: no intervention (group 1), pre-injection topical brimonidine (group 2), pre-injection oral acetazolamide (Diamox) (group 3), pre-injection topical brimonidine and oral Diamox (group 4), and pre-injection paracentesis (group 5). The primary outcomes were the occurrence and degree of reflux following IVI. In addition, the evaluation of conjunctival bleb estimated the degree of reflux. Patient self-rated pain and early complications were secondary outcome measures.
Results A total of 150 eyes of 150 patients were included. Vitreous reflux occurred in 13 (43%), 14 (46.7%), 19 (63.3%), six (20.0%), and four (13.3%) eyes in groups 1–5, respectively (P<0.001). Additionally, higher degrees of reflux were observed in group 1 compared with other groups.
Discussion In our study, we raised the question of whether the intraocular pressure (IOP) before injection affects vitreous reflux. Therefore, we compared the effect of different antiglaucomatous medications on lowering the pre-injection IOP, and so decrease the vitreous reflux. We found that in both the paracentesis group and group of combined topical brimonidine and oral Diamox group, vitreous reflux rate is reduced significantly (P<0.001) because in these two groups, the IOP just before the injection was the lowest. Unfortunately, we could not measure the IOP after paracentesis and before the injection to avoid any risk of endophthalmitis, but we consider the paracentesis as a gold standard group for lowering IOP, although it is an invasive procedure. Interestingly, the self-rated pain rate was the same in all groups.
Conclusion Pre-injection topical brimonidine combined with oral Diamox may be an effective and noninvasive method to prevent/reduce vitreous reflux following IVI.

Keywords: anti-vascular endothelial growth factor, intraocular pressure, intravitreal injection, vitreous reflux

How to cite this article:
Gaber R, Nassif M, Shalaby WS, Sorour O. Noninvasive method to reduce vitreous reflux following intravitreal injection. J Egypt Ophthalmol Soc 2023;116:24-7

How to cite this URL:
Gaber R, Nassif M, Shalaby WS, Sorour O. Noninvasive method to reduce vitreous reflux following intravitreal injection. J Egypt Ophthalmol Soc [serial online] 2023 [cited 2023 May 30];116:24-7. Available from: http://www.jeos.eg.net/text.asp?2023/116/1/24/372952

Introduction

Intravitreal injection (IVI) of various medications is a widely used and safe ophthalmologic intervention for many pathological disorders, such as macular edema secondary to retinal vascular or degenerative diseases [1]. However, major complications may follow, and on top of these is infectious endophthalmitis. Other complications include lens injury, vitreous hemorrhage, and retinal detachment. Chen et al. [2] reported that vitreous reflux, which appears as a subconjunctival bleb, is a common incident and might be a risk factor for endophthalmitis following IVI. Prior studies reported a strong relationship between the intraocular pressure (IOP) spike and vitreous reflux [3],[4],[5],[6],[7]. In addition, the momentary rise of IOP may be very high following IVI, which may be injurious to the retinal ganglion cells, especially in glaucomatous patients [4]. Some authors suggested that paracentesis may effectively reduce both complications [3],[4],[5],[6],[7].

Some studies evaluated potential methods to decrease vitreous reflux. For example, needle diameter may be an important factor that affects the incidence of vitreous reflux. Pang et al. [8] demonstrated that the rate of vitreous reflux after IVI of anti-vascular endothelial growth factor (anti-VEGF) was 53% when using a 30-G needle and 13% when using a 32 G. Additionally, tunneled IVI seems to be less associated with vitreous reflux than straight injection [9].

In this study, we evaluated the efficacy of pre-injection antiglaucoma medications as a noninvasive method to reduce the postinjection IOP spikes and vitreous reflux following IVI. In addition, we compared them with paracentesis, which is an effective but more invasive method.

Patients and methods

Study design

This was a single-center prospective randomized study conducted at the Ophthalmology Department, Tanta University, the largest tertiary care eye hospital in the region. The study was approved by the Institution’s Review Board (number 34942/9/21) and was in accordance with Health Insurance Portability and Accountability Act regulations. An effort was made to recruit consecutively every eligible patient into the study. Written informed consent was obtained from all patients. After informed consent was given and confirmation of patient eligibility, each enrolled patient was assigned a study number and randomized to one of the five study arms according to a block randomization scheme (1 : 1 : 1 : 1 : 1).

The study groups were as follows: no intervention (group 1), pre-injection topical brimonidine (group 2), pre-injection oral Diamox 500 mg (group 3), pre-injection topical brimonidine and oral Diamox 500 mg (group 4), and pre-injection paracentesis (group 5). Patients in groups 2, 3, and 4 received treatment 2 h before the IVI^.

Inclusion and exclusion criteria

Inclusion criteria included age more than 18 years and a diagnosis of diabetic macular edema, branch retinal vein occlusion, or choroidal neovascular membrane requiring IVI of anti-VEGF. Eyes diagnosed with glaucoma, conjunctival pathology, or prior intraocular surgery were excluded. Only the right eye was included for patients receiving IVI in both eyes, and prior IVI was not considered an exclusionary criterion.

Outcome measures

The primary outcome measure was the degree of reflux following IVI. The degree of reflux was estimated by evaluation of postinjection conjunctival bleb using caliber: no conjunctival bleb (grade 0 or no reflux), conjunctival bleb with a diameter of less than 2 mm (grade 1 or mild reflux), conjunctival bleb with a diameter of 2–3 mm (grade 2 or moderate reflux), and conjunctival bleb with a diameter of more than 3 mm (grade 3 or severe reflux). Patient self-rated pain and early complications were secondary outcome measures.

Surgical procedure

One surgeon (M.W, a fellowship-trained vitreoretinal specialist) performed all procedures using the same technique. All patients received 0.05 ml of ranibizumab (Lucentis®, Novartis, Basel, Switzerland; Genentech, South San Francisco, CA, USA) treatment, and the drug was injected using a 30-G needle on a 1-ml syringe. An anesthetic eye drops, 0.5% proparacaine hydrochloride, was topically administered for anesthesia before the injection. After the topical instillation of 5% povidone–iodine solution to the conjunctival sac and cleansing of the periocular skin with 10% povidone–iodine, the eye was covered with a sterile drape and opened with a lid speculum. Then, the 30-G needle was inserted into the vitreous cavity 3.5–4 mm (according to the lens status), posterior to the limbus through the supero-temporal quadrant, using a straight injection technique and penetrating the sclera at an angle of 90°. The drug was injected slowly, and the needle was drawn at the same angle.

Statistical analysis

Statistical analyses were performed using SPSS Software, version 27 (IBM Corp., Armonk, New York, USA). Continuous variables were summarized as mean±SD. Proportions (%) were used to describe categorical variables. Between-group comparisons for continuous and categorical variables were performed using one-way analysis of variance and χ² test (Fisher’s exact test), respectively. P values less than 0.05 were considered significant.

Results

Baseline characteristics

A total of 150 eyes of 150 patients were included in the study (30 patients in each group), with a mean age of 63.7±4.5 years. Baseline characteristics are displayed in [Table 1]. Demographics and ophthalmic characteristics were comparable between groups. Most patients (141 or 94%) received IVI for diabetic macular edema, and only 15 (10%) had their first IVI.

Table 1 Baseline characteristics in the study groups

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Outcome measures

The outcome measures in the five study groups are displayed in [Table 2]. Vitreous reflux was observed in 56 (37.3%) eyes and was significantly higher in groups 1, 2, and 3 (51%) as compared with groups 4 and 5 (16.6%) (P≤0.001). In eyes that showed vitreous reflux, the grading was also significantly different among groups (P=0.001), as mild (46%), moderate (30.8), and severe reflux (23%) were observed in group 1, whereas other groups had only mild reflux (100%). Interestingly, self-rated pain was highest in group 1 (40%) versus other groups (0–10%) (P<0.001). No early postinjection complications were observed immediately after the IVI or postinjection day 1.

Table 2 Outcome measures in the study groups

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Discussion

Injection technique, needle size, injected dose, and lens status may indirectly alter short-term postinjection IOP by affecting vitreous reflux, which is the main factor determining IOP in the short term after an injection [8],[9],[10]. As the amount of vitreous reflux decreased, postinjection IOP levels rose [8]. In our study, we raised the question of whether the IOP before injection affects vitreous reflux. Therefore, we compared the effect of different antiglaucomatous medications on lowering the pre-injection IOP, and so decrease the vitreous reflux. One surgeon (M.W.) had injected all of the patients by the same technique using 30-G needle in all cases. We found that in both the paracentesis group and group of combined topical brimonidine and oral Diamox group, the vitreous reflux rate is reduced significantly (P<0.001), because in these two groups, the IOP just before the injection was the lowest. Unfortunately, we could not measure the IOP after paracentesis and before the injection to avoid any risk of endophthalmitis, but we consider the paracentesis as a gold standard group for lowering IOP, although it is an invasive procedure. Interestingly, the self-rated pain rate was the same in all groups.

Based on our results, we advise lowering baseline IOP using combined oral acetazolamide 500 mg and topical brimonidine to decrease the postinjection vitreous reflux and endophthalmitis risk. Moreover, lower reflux means lower drug loss. To the best of our knowledge, this is the first study assessing the effect of lowering the pre-injection IOP on lowering the postinjection vitreous reflux.

Our study has some limitations: we could not assess the IOP after paracentesis and before the injection of anti-VEGF medication to avoid the potential risk of intraocular infection. The study’s use of the conjunctival bleb diameter alone to quantify vitreous reflux is another drawback. The actual volume of vitreous reflux could be affected by the conjunctival bleb’s height, which was not assessed.

Conclusion

Pre-injection topical brimonidine combined with oral Diamox may be an effective and noninvasive method to prevent/reduce vitreous reflux following IVI.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

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