Ocular Pulse Amplitude and Retinal Vessel Caliber Changes after Intravitreal Dexamethasone Implant.

PURPOSE: The purpose of this study is to evaluate possible changes in ocular pulse amplitude (OPA), retinal arteriole caliber (RAC), and retinal venule caliber (RVC), following the intravitreal injection of dexamethasone implants (DIs).
METHODS: Thirty-four eyes of 34 patients with macular edema were included. All participants received a full ophthalmologic examination at baseline. RAC and RVC were measured via optical coherence tomography; OPA and intraocular pressure (IOP) were measured via dynamic contour tonometry at baseline, month 1, and month 3. Statistical analysis was performed for before-after comparison of OPA, IOP, RAC, and RVC measurements.
RESULTS: The mean OPA (in order to baseline, month 1, month 3) was 2.8 ± 0.8, 2.9 ± 1.0, 2.9 ± 0.9. The mean IOP was 16.8 ± 2.9, 17.3 ± 2.7, 18.4 ± 2.9 mmHg. The mean RAC was 97.8 ± 9.2, 97.2 ± 9.0, 97.6 ± 9.4. The mean RVC was 124.4 ± 8.2, 124.8 ± 8.8, 123.8 ± 8.2. There were no statistically significant changes in RAC (P = 0.688), RVC (P = 0.714), OPA (P = 0.348), and IOP (P = 0.115). There was also no correlation between RAC and OPA (r = 0.12, P = 0.62) or RVC and OPA (r = 0.16, P = 0.68) at the last visit.
CONCLUSION: The intravitreal injection of DI does not significantly affect RAC, RVC, or OPA, which indicates that the treatment does not alter overall retinal-choroidal vasculature or hemodynamics.

INTRODUCTION

The dexamethasone drug delivery system (Ozurdex®, Allergan, Irvine, CA, USA) is a biodegradable, intravitreal implant that provides a sustained-release delivery of 0.7 mg of preservative-free dexamethasone to the vitreous.1

Ocular pulse amplitude (OPA) signifies the difference between systolic and diastolic values of pulsatile intraocular pressure (IOP) and thus indirectly reflects choroidal blood flow.2 Studies have also shown that intravitreal anti-vascular endothelial growth factor (VEGF) agents affect ocular blood flow.3

Reflective of retinal blood flow,4 retinal arteriole caliber (RAC), and retinal venule caliber (RVC) can be measured using color fundus photography,5 retinal angiography photographs,6 and optical coherence tomography (OCT) scans.2 Earlier research found that intravitreal anti-VEGF agents significantly dilate retinal venules and constrict retinal arterioles although the underlying mechanisms remain unclear.7 Further, it has been shown that anti-VEGF agent may induce a reduction in choroidal thickness.8

All corticosteroids, including dexamethasone, inhibit the expression of VEGF and other pro-inflammatory cytokines such as ICAM-1, interleukin-6, and MCP-1.9 Dexamethasone implants (DIs) may therefore affect choroidal blood flow and retinal vessels a similar to anti-VEGF agents. In response, we aimed in this study to evaluate possible changes in RAC, RVC, and OPA, following the intravitreal injection of DI.

METHODS

The eyes of 34 consecutive patients who fulfilled the present study's inclusion criteria were included for participation. OCT scans (Spectralis, Heidelberg Engineering, Heidelberg, Germany) and dynamic contour tonometry (DCT) measurements (Pascal DCT, Swiss Microtechnology AG, Port, Switzerland) were performed at baseline, month 1, and month 3.

Criteria for inclusion were age exceeding 18 years, diabetic macular edema (DME) or macular edema secondary to retinal vein occlusion (RVO), and recently planned intravitreal Ozurdex® implantation. All patients with history of treatment for macular edema, history of ocular surgery in the past 6 months, history of laser photocoagulation, or uncontrolled systemic disease or other contraindication for a DI were excluded. This study was conducted according to the principles of the Declaration of Helsinki. All patients were volunteers, each of whom provided his or her informed consent after the study was explained.

Ocular pulse amplitude and retinal venule caliber measurements

RAC and RVC were calculated from OCT scans. The caliber of temporal retinal arterioles and venules were measured at a distance of the diameter of one disc from the margin of the optic disc using the caliber tools of Spectralis software [Figure 1].

Figure 1

Retinal arteriole caliber and retinal venule caliber measurements via optical coherence tomography

Statistical analysis

For each variable, normality was checked via the Shapiro-Wilk test. To compare RAC, RVC, OPA, and IOP values from before and after injection, a one-way ANOVA was employed. Pearson's correlation coefficient analysis was applied to detect correlations of RAC and RVC to OPA. Statistical Package for the Social Sciences version 20 (SPSS, Chicago, IL, USA) was used for data analysis, and values of P < 0.05 were considered statistically significant.

RESULTS

Participant characteristics

The mean age was 63.6 ± 8.2 years (48–84). Nineteen participants (55.9%) were female and 15 participants (44.1%) were male. Twenty-three eyes (67.6%) had DME, 8 eyes (23.5%) had BRVO, and 3 eyes (8.8%) had CRVO. The mean BCVA was 0.2 ± 0.1 decimal (0.01–0.4). The mean axial length was 22.7 ± 0.7 mm (21.6–24.3). The mean central corneal thickness was 536 ± 43 μm (461–634). The mean IOP was 16.8 ± 2.9 mmHg (11.2–20.0). The mean CMT was 515 ± 166 μm (231–986). The mean SCT was 330 ± 51 μm (241–433).

Ocular pulse amplitude and intraocular pressure measurements

The mean OPA (in order to baseline, month 1, month 3) was 2.8 ± 0.8 (1.5–4.8), 2.9 ± 1.0 (1.7–5.1), and 2.9 ± 0.9 (1.6–4.9). The mean IOP (mmHg) was 16.8 ± 2.9 (11.2–20.0), 17.3 ± 2.7 (13.5–25.0), and 18.4 ± 2.9 (14.0–23.0). Pascal tonometry revealed no statistically significant changes in OPA and IOP from baseline to month 1 and month 3 (P = 0.348, P = 0.115).

Retinal arteriole caliber and retinal venule caliber measurements

The mean RAC (μm) (in order to baseline, month 1, month 3) was 97.8 ± 9.2 (78–110), 97.2 ± 9.0 (80–108), and 97.6 ± 9.4 (82–108). The mean RVC (μm) was 124.4 ± 8.2 (119–132), 124.8 ± 8.8 (118–130), and 123.8 ± 8.2 (116–132). There was no statistically significant change in RAC and RVC measured via OCT from baseline to month 1 and month 3 (P = 0.688, P = 0.714).

There was also no correlation between RAC and OPA (r = 0.12, P = 0.62) or RVC and OPA (r = 0.16, P = 0.68) at the last visit.

DISCUSSION

The results of this study show that DI poses no significant effects on RAC, RVC, and OPA in patients with DME and macular edema secondary to RVO. Although all corticosteroids, including dexamethasone, inhibit the expression of VEGF and other pro-inflammatory cytokines and reduce vascular permeability, they do not catalyze overall alterations in ocular vasculature.

Previous studies have shown that ocular vasculature and ocular blood flow may be affected by anti-VEGF injections.47 Wickremasinghe et al. found in two studies that intravitreal ranibizumab significantly dilates retinal venules.47 By contrast, Pekel et al. showed that RAC and RVC remained unaffected following three intravitreal ranibizumab injections,2 as well as that neither OPA nor RAC and RVC changed significantly.2

Some other previous studies have shown that ocular vasculature and ocular blood flow may be affected by steroid injections.10 Lee et al. reported that high-dose systemic corticosteroid treatment also significantly reduces choroidal thickness.10 These results suggest that the implants might impact choroidal circulation although the results of our study have shown the opposite.

This study poses a few limitations. Its sample was small; it did not present any anatomical or functional result of the treatment, and it involved only a brief follow-up period.

To the best of our knowledge, with this study, we have demonstrated for the first time that DI does not affect RAC, RVC, or OPA. Although corticosteroids such as dexamethasone inhibit the expression of VEGF, unchanged RAC, RVC, and OPA indicate that the implants do not change ocular vasculature in the short term and do not alter overall retinal-choroidal vasculature or hemodynamics in patients with DME and RVO. We are confident that further studies with longer follow-up periods can support our findings.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.