Effect of Repeated Intravitreal Injections in Glaucoma Spectrum Diseases

Abstract

Purpose

To evaluate whether repeated intravitreal injections (IVI) with an anti-vascular endothelial growth factor (anti-VEGF) agent are associated with glaucomatous progression in eyes with glaucoma spectrum diseases (GSD).

Methods

Single-center, retrospective, longitudinal study of patients with bilateral and similar GSD who: (1) received ≥8 IVI in only one eye during the study period; (2) had ≥2 retinal nerve fiber layer thickness (RNFL) measurements obtained by spectral-domain optical coherence tomography (SD-OCT) at least 12 months apart. The primary outcome was the absolute RNFL thickness change, comparing injected and fellow uninjected eyes. Linear mixed effects models were constructed, including a multivariable model.

Results

Sixty-eight eyes from 34 patients were included, 34 injected and 34 fellow uninjected eyes. Average baseline age was 67.68±21.77 years with a follow-up of 3.66±1.89 years and 25.12±14.49 IVI. RNFL thickness decreased significantly from 80.92±15.78 to 77.20±17.35 μm (p<0.001; −1.18±1.93 μm/year) in injected eyes and from 79.95±17.91 to 76.61±17.97 μm (p<0.001; −1.07±0.98 μm/year) in uninjected eyes. In a multivariable linear mixed model of injected eyes, only higher baseline RNFL thickness (p < 0.001) significantly predicted higher absolute RNFL thickness loss. Neither absolute RNFL thickness variation (p=0.716) nor RNFL rate (p=0.779) was significantly different between paired injected and uninjected eyes. Absolute IOP variation was not significantly different between groups (16.62±4.77 to 15.09±4.34 mmHg in injected eyes and 17.68±5.01 to 14.50±3.39 mmHg in fellow uninjected eyes; p=0.248). The proportion of eyes receiving glaucoma medical treatment increased significantly in both groups (55.9% to 76.5% in injected eyes; p=0.039; 58.8% to 76.5% in uninjected eyes; p = 0.031). The number of glaucoma medications also increased significantly in both groups (1.03±1.11 to 1.59±1.18 glaucoma medications in injected eyes; p=0.003; 1.09±1.11 to 1.56±1.19 glaucoma medications in uninjected eyes; p=0.003).

Conclusion

Repeated IVI do not seem to accelerate glaucomatous progression. Future studies with a longer follow-up are needed.

Keywords:

• glaucoma
• intravitreal injections
• progression
• optical coherence tomography
• retinal nerve fiber layer thickness

Key Points

1. It has been postulated that the immediate (though generally transient) intraocular pressure elevation (IOP) that follows anti-VEGF intravitreal injections (IVI) may promote glaucomatous damage in eyes with glaucoma spectrum diseases (GSD), leading to faster retinal nerve fiber layer (RNFL) thinning over time.

2. To date, only a limited number of studies have been conducted on this matter, with conflicting results, and several only report the injected eye group, with no control for comparison.

3. The main purpose of this study was to ascertain if repeated intravitreal anti-VEGF IVI lead to faster RNFL thickness changes between injected and fellow uninjected eyes of patients with symmetrical GSD.

4. In our study with a follow-up of 3.66±1.89 years, RNFL thickness decreased significantly from 80.92±15.78 to 77.20±17.35 μm (p<0.001; −1.18±1.93 μm/year) in injected eyes and from 79.95±17.91 to 76.61±17.97 μm (p<0.001; −1.07±0.98 μm/year) in fellow uninjected eyes, despite regular follow-up and an escalation in glaucoma treatment. Neither absolute RNFL thickness variation (p=0.716) nor RNFL rate (p=0.779) was significantly different between paired injected and uninjected eyes.

5. Repeated IVI do not seem to accelerate glaucomatous progression in eyes with pre-existing GSD. Future studies with a longer follow-up are needed.

Previous Presentation of Interim Findings

The abstract of this paper was presented at the 2022 ARVO meeting, as a poster presentation, with interim findings. The poster’s abstract was published in “Poster Abstracts” in INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE.

Data Sharing Statement

Access to any supplemental information such as the study protocol or anonymized data can be available upon reasonable request.

Ethics/Ethical Approval

The study was approved by the Institutional Ethics Review Board of Centro Hospitalar Universitário de São João, Porto, Portugal (certificate approval number CES269/2021). The protocol conformed with the canons of the Declaration of Helsinki for research involving human participants, as well as the European Union’s General Data Protection Regulation. Informed consent was waived in view of the retrospective nature of the study. This article was redacted according to the recommendations of The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement.

Acknowledgments

Only the named authors have collaborated in the writing of this paper.

Author Contributions

All authors contributed to the study’s conception and design. Material preparation and data acquisition were performed by Flávio Alves, António Benevides Melo, Sérgio Estrela-Silva, Joana Araújo, João Tavares-Ferreira, Marta Silva, Amândio Rocha-Sousa, Ângela Carneiro and João Barbosa-Breda. Data collection and analysis were performed by Rodrigo Vilares-Morgado, Vera Correia and Ana Margarida Ferreira. The first draft of the manuscript was written by Rodrigo Vilares-Morgado, Vera Correia and João Barbosa-Breda. The remaining authors critically reviewed the article. All authors agreed on the journal to which the article should be submitted. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Thus, all authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

The authors have no conflicts of interest to declare.

Additional information

Funding

The authors declare that they have no financial ties to declare. No funding or sponsors were undertaken in the preparation of the manuscript.