Ophthalmic Surgery, Lasers and Imaging Retina

Clinical Science 

Evaluating the Effect of Intravitreal Ranibizumab on Retrobulbar Hemodynamics by Color Doppler Ultrasonography in Neovascular AMD

Sabri Raza, MD; Sule Berk Ergun, MD; Yasin Toklu, MD; Hasan Basri Cakmak, MD; Ali Ipek, MD; Nurullah Cagil, MD

Abstract

BACKGROUND AND OBJECTIVE:

To evaluate changes in retrobulbar blood flow by using color Doppler ultrasonography (CDUS) after intravitreal ranibizumab injection in patients with neovascular age-related macular degeneration (AMD).

PATIENTS AND METHODS:

Eighteen patients who had undergone intravitreal ranibizumab (0.05 mg/0.05 mL) injection due to choroidal neovascular membrane (CNVM) were included in the study. Contralateral eyes of the patients were also analyzed. Peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) were measured from the ophthalmic artery (OA), central retinal artery (CRA), lateral posterior ciliary artery (LPCA), and medial posterior ciliary artery (MPCA) for all patients pre-injection, and at 1 day, 1 week, and 1 month after ranibizumab injection.

RESULTS:

The mean age of the 18 patients included in the study was 66.94 years (± 8.3 years). Of these 18 patients, eight were female and 10 were male. After Bonferroni's correction for multiple comparisons was carried out, there were significant differences only in some values of LPCA; these included the decrease in EDV and an increase in PI values of LPCA between the pre-injection and post-injection of the first month measurements in uninjected eyes (P = .002, P = .002), and a decrease in PI value of LPCA between post-injection first day and first week measurements in injected eyes (P = .004). There were no statistically significant differences in other parameters.

CONCLUSION:

Ocular blood flow velocities may change after intravitreal ranibizumab injection in patients with CNVM.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:437–443.]

Abstract

BACKGROUND AND OBJECTIVE:

To evaluate changes in retrobulbar blood flow by using color Doppler ultrasonography (CDUS) after intravitreal ranibizumab injection in patients with neovascular age-related macular degeneration (AMD).

PATIENTS AND METHODS:

Eighteen patients who had undergone intravitreal ranibizumab (0.05 mg/0.05 mL) injection due to choroidal neovascular membrane (CNVM) were included in the study. Contralateral eyes of the patients were also analyzed. Peak systolic velocity (PSV), end diastolic velocity (EDV), pulsatility index (PI), and resistivity index (RI) were measured from the ophthalmic artery (OA), central retinal artery (CRA), lateral posterior ciliary artery (LPCA), and medial posterior ciliary artery (MPCA) for all patients pre-injection, and at 1 day, 1 week, and 1 month after ranibizumab injection.

RESULTS:

The mean age of the 18 patients included in the study was 66.94 years (± 8.3 years). Of these 18 patients, eight were female and 10 were male. After Bonferroni's correction for multiple comparisons was carried out, there were significant differences only in some values of LPCA; these included the decrease in EDV and an increase in PI values of LPCA between the pre-injection and post-injection of the first month measurements in uninjected eyes (P = .002, P = .002), and a decrease in PI value of LPCA between post-injection first day and first week measurements in injected eyes (P = .004). There were no statistically significant differences in other parameters.

CONCLUSION:

Ocular blood flow velocities may change after intravitreal ranibizumab injection in patients with CNVM.

[Ophthalmic Surg Lasers Imaging Retina. 2019;50:437–443.]

Introduction

Age-related macular degeneration (AMD) is one of the leading causes of vision loss in developed countries.1–3 The visual impairment in patients with AMD is mostly related to choroidal neovascularization,4,5 and there is an essential role of vascular endothelial growth factor (VEGF) in the disease pathogenesis.6,7 In recent years, anti-VEGF agents have been widely used in the treatment of choroidal neovascular membrane (CNVM).8–10 Ranibizumab (Lucentis; Genentech, South San Francisco, CA) is one of the VEGF inhibitors approved by the U.S. Food and Drug Administration for the treatment of neovascular AMD.11 Due to the widely use of anti-VEGF agents, their effect on retrobulbar blood flow has to be explored in addition to other side effects.

Despite the fact that studying ocular blood flow is very complicated, color Doppler ultrasonography (CDUS) is a noninvasive diagnostic method that can give information about flow velocities of retrobulbar blood vessels and vascular downstream resistance.12 Additionally, reproducibility and repeatability of CDUS is very high, although it is an ultrasonographic procedure.13

In this study, we aimed to evaluate retrobulbar hemodynamics in patients who had been treated with intravitreal ranibizumab for neovascular AMD with CDUS.

Patients and Methods

This study was approved by the local ethics committee of the hospital and was carried out in accordance with the Declaration of Helsinki.

The first dose of intravitreal ranibizumab injections was given to 18 patients for the treatment of CNVM and assessed prospectively. The fellow uninjected eyes of these patients were also analyzed.

Exclusion criteria were previous intraocular surgery; an ocular disease other than AMD; history of retinal vein or artery occlusion, diabetes, carotid artery stenosis; or any known systemic vascular disease.

All patients underwent a complete ophthalmologic examination including best-corrected visual acuity (BCVA), evaluation of the anterior and posterior segments, intraocular pressure (IOP) measurement using Goldman applanation, fluorescein angiography (FA), and optical coherence tomography (OCT). The diagnosis of neovascular AMD was made basically depending on the clinical examination, FA, and OCT findings. All patients were informed about their diseases and the treatment options, as well as about the benefits and risks of ranibizumab injection. Informed consent was taken from all patients. The injection procedures were performed using 30-gauge needle, 0.05 mL containing 0.5 mg ranibizumab through the pars plana (inferotemporal quadrant, 4 mm away from the limbus) under sterile conditions in the operating room. After the injections, a topical antibiotic was prescribed four times a day for 1 week for each patient.

Follow-up visits were performed post-injection on days 1, 7, and 30. During these visits, examination of BCVA, anterior and posterior segments, and IOP were routinely carried out. FA was performed if needed.

To evaluate the changes in ocular blood flow after intravitreal ranibizumab injection, both eyes of the patients were examined by CDUS four times (before the injection and at 1 day, 1 week, and 1 month after the injection). In parallel to the ultrasound imaging, IOP, systolic and diastolic blood pressures (BPs), and heart rate were evaluated simultaneously at each visit.

All CDUS measurements were performed by the same radiologist using a 9 MHz to 12 MHz linear probe of the same device (Logiq 9; GE Healthcare, Chicago, IL). To minimize the effect of diurnal variation, the examinations were performed at the same time of the day (between 1:30 p.m. and 3:30 p.m.). For the scan, patients were kept at a in the supine position for 5 minutes before the examination, and examinations were performed with the eyes closed and gaze directed upright. A sampling gate of 0.2mm × 0.2mm was used and the Doppler spectral patterns of ophthalmic artery (OA), central retinal artery (CRA), lateral posterior ciliary artery (LPCA), and medial posterior ciliary artery (MPCA) were analyzed. For each vessel, the peak systolic velocity (PSV), end diastolic velocity (EDV), resistance index (RI), and pulsatility index (PI) were recorded.

The statistical analyses were performed using Minitab Release 14 (Microsoft, Redmond, WA), and a P value of less than .05 was considered significant. The Friedman test was used to evaluate the ocular blood flow, IOP, heart rate, and systolic and diastolic BPs.

Due to the repeated measurements in different arteries, Wilcoxon test was used for comparisons. After Bonferroni's correction was introduced .05/6 = .008 was defined as the cutoff for a significant P value.

Results

A total of 36 eyes of 18 patients were examined. The mean age of the 18 patients was 66.94 years ± 8.3 years. Of these, 18 patients eight were female, 10 were male.

No ocular or systemic complications were observed related to injections. IOP, heart rate, and systolic and diastolic BPs did not change significantly during the follow-up period (Table 1). Hemodynamic parameters (PSV, EDV, RI, PI) measured from the OA, MPCA, LPCA, and CRA are shown in Table 2.

IOP, Heart Rate, and Systolic and Diastolic BP of Patients (n = 18) With AMD Before and After Day 1, Week 1, and Month 1 of Ranibizumab Injection

Table 1:

IOP, Heart Rate, and Systolic and Diastolic BP of Patients (n = 18) With AMD Before and After Day 1, Week 1, and Month 1 of Ranibizumab Injection

Hemodynamic Doppler Parameters in the OA, CRA, LPCA, and MPCA in Both Eyes of Patients With AMD (n = 18) Before and After Day 1, Week 1, and Month 1 Post-Injection of RanibizumabHemodynamic Doppler Parameters in the OA, CRA, LPCA, and MPCA in Both Eyes of Patients With AMD (n = 18) Before and After Day 1, Week 1, and Month 1 Post-Injection of Ranibizumab

Table 2:

Hemodynamic Doppler Parameters in the OA, CRA, LPCA, and MPCA in Both Eyes of Patients With AMD (n = 18) Before and After Day 1, Week 1, and Month 1 Post-Injection of Ranibizumab

There was a significant change between the pre-injection and post-injection values of EDV and PI measured from LPCA both in injected and uninjected eyes (Table 2). There was also a significant decrease in the pre-injection and post-injection PSV and EDV values of MPCA measured from uninjected eyes as shown in Table 2.

Nonetheless, after having applied Bonferroni's correction, there was no statistically significant difference between pre-injection and post-injection parameters measured in the retrobulbar arteries of the injected and uninjected eyes other than in some values of LPCA.

These differences are the decrease in EDV and an increase in PI values of LPCA between the pre-injection and post-injection of the first month measurements in uninjected eyes (P = .002, P = .002), as well as a decrease in PI value of LPCA between post-injection day 1 and day 7 measurements in injected eyes (P = .004).

Discussion

Anti-VEGF therapy has recently been used for the treatment of neovascular AMD. Ranibizumab is one of the important anti-VEGF agents that has been found to be effective for neovascular AMD.14,15 Hence, it is of utmost importance for an ophthalmologist to know the safety profile of this agent.

It is well-known that there is a compromise in the retrobulbar blood flow rates in elderly people.12 Dimitrova reported in his study that a reduction occurs in the ciliary vessels, suggesting that choroidal perfusion is compromised in AMD patients.16 It is also suggested that this blood flow changes may also play a role in the disease mechanism. Furthermore, and more importantly, there is a potential ischemia that may arise from using anti-VEGF agents.16–19 Investigation of the effect of intravitreal injections on retrobulbar hemodynamics has become more crucial.

In this prospective study, effects of intravitreal ranibizumab injections in patients with neovascular AMD on the retrobulbar hemodynamics was investigated.

There are three known studies that have reported decrease in some retrobulbar blood flow parameters following intravitreal bevacizumab (Avastin; Genentech, South San Francisco, CA) injections in patients with neovascular AMD.20–22

Some theories exist that may bring clarification to this issue. Firstly, it has been shown that intravitreal bevacizumab injection may reduce the number of fenestrations of the normal choriocapillaris.23 Thus, the decreased number of fenestrations of the choriocapillaris may cause resistance to the blood flow. Secondly, bevacizumab may induce arterial thrombosis by exposing subendothelial procoagulant phospholipids.23,24 At the same time, bevacizumab may reduce the production of nitric oxide and prostacyclin, thus predisposing to thromboembolic events.24 This may lead to thrombus formation and occlusion of the choriocapillaris lumen. This effect that bevacizumab has on the whole choroid may explain the decrease in blood flow velocities.

It has been shown that the intravitreal half-life of bevacizumab is 9.82 days,25 whereas for ranibizumab, it is 2.88 days in an experimental rabbit model, approximately 3 days in monkeys, and 7.19 days in humans.26–28 Studies have shown that intravitreal bevacizumab concentration was found to be more than 10 g/mL for up to 30 days, whereas it was found to be more than 0.1μg/mL for up to 29 days for ranibizumab.26,29 In addition, unlike bevacizumab; little or no passage of ranibizumab to the systemic circulation after intravitreal injections was observed in those studies.26,27,29 The difference in the pharmacokinetics of ranibizumab and bevacizumab mentioned above leads to a question of whether the intravitreal ranibizumab injections have minor effects on retrobulbar hemodynamics.

The study revealed some changes in retrobulbar blood flow after intravitreal ranibizumab injections. These are a decrement in EDV and an increment in PI values of LPCA between the pre-injection and post-injection of first-month measurements in uninjected eyes; and a decrease in PI value of LPCA between the post-injection day 1 and day 7 measurements in injected eyes. Other parameters did not show any significant changes after intravitreal ranibizumab injection.

Those changes in EDV and PI values of LPCA in uninjected eyes is an interesting finding of the study, for which systemic spread of intravitreal ranibizumab injections was unanticipated. The only parameter that was found to be significantly changed in the injected eyes was the decrease in PI value of LPCA in the first week. However, the lack of significant change in all other PI values decreases the importance of this finding.

To date, there are also two studies reporting the effects of intravitreal ranibizumab injections on retrobulbar hemodynamics.30,31 Sakalar et al. observed no significant changes in PSV, EDV, or RI values of OA, CRA, and LPCA between pre-injection and post-injection at 7 days and 30 days,30 whereas Mete et al. found statistically significant difference in EDV of MPCA and LPCA, and RI of LPCA between pre-injection and post-injection the first day.31

The study has some limitations, including a limited number of cases, a lack of a control group with no injection in any eye, or a control group composed of patients treated with bevacizumab/aflibercept (Eylea; Regeneron, Tarrytown, NY). Furthermore, angiographic types of choroidal neovascularization and OCT patterns of macular edema were taken into consideration for diagnosis but not categorized in the study design. The correlation of these findings with the changes in the blood flow parameters will give additional knowledge about the hemodynamics. Future studies require larger study groups to make such subgroup analyses.

CDUS was used for measurements of ocular blood flow. The CDUS can only measure velocity of blood flow, and therefore, does not provide information about intravascular blood flow volume;32 however, the correlation between the blood flow velocity and volume has been demonstrated.33 Reproducibility and repeatability of CDUS is very high despite it being an ultrasonographic procedure.13 CDUS is not a tool for the assessment of microcirculation. OCT angiography (OCTA), which is one of the important imaging innovations in ophthalmology in recent years, is a noninvasive technique for the detection and quantification of both the retinal and the choroidal microcirculation, providing volumetric blood flow information and generating high-quality images with shorter acquisition times.34–36 If it is aimed to evaluate the detailed view of the retinal and choroidal vasculature, OCTA may be the imaging method of choice. However, the retrobulbar blood vessels are generally not visible by OCTA because a large part of the energy of the examining light is blocked by the retina, choroid, and sclera.37–39 It is the advantage of CDUS to assess the retrobulbar hemodynamics regardless of the thickness of these structures. It can also be used in any patient regardless of the translucency of optical structures.32,40 If it is aimed to evaluate both retrobulbar and choroidal/retinal blood flow, CDUS and OCTA should be used together, and the results can be correlated to understand the details about hemodynamics.

The cases in this study do not have any documented cardiovascular disease such as atherosclerosis. Possible adverse effects of intravitreal ranibizumab may be different in cases with atherosclerosis, where the endothelium of the vessels is already abnormal and more susceptible to external effects.

The parameters were measured, similarly to Sakalar et al.,30 on the first day after injection. It has been shown that the intravitreal half-life of ranibizumab is approximately 7 days, and the peak concentration is achieved in the first day after injection.28 Based on this knowledge, it is possible that side effects of ranibizumab may be more prominent in the first days after the intravitreal injection. This may be the reason why intravitreal ranibizumab injections had no effect on ocular blood flow in the study by Sakalar et al.30 However, another issue that makes the situation more complicated is the effect of acute IOP rise on the retrobulbar hemodynamics that may occur immediately after intravitreal ranibizumab injections,41 so evaluation of the hemodynamics right after the injections, as in the study by Mete et al.,31 may change the results. This is an advantage of the study, that frequent evaluations allow us to draw a complete picture of events occurring in the retrobulbar circulation after intravitreal ranibizumab injections.

Another advantage of this study is that all the cases were receiving intravitreal injections for the first time. Consequently, the uniformity of the group has been ensured in this aspect. Yet, the question of “What will happen to retrobulbar hemodynamics in repeated and following injections?” remains to be answered. This current study was not designed for this purpose so future studies focusing on this issue may help to answer this question.

In conclusion, our results suggest that intravitreal ranibizumab injections make some changes in the retrobulbar blood flow velocities measured by CDUS in patients with neovascular AMD. Further prospective clinical studies are needed to understand the exact effect of ranibizumab as it is used more widely in ophthalmology.

References

  1. Bird AC, Bressler NM, Bressler SB, et al. An international classification and grading system for age-related maculopathy and age-related macular degeneration. The international ARM Epidemiological Study Group. Surv Ophthalmol. 1995;39(5):367–374. doi:10.1016/S0039-6257(05)80092-X [CrossRef]
  2. Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. 1992;99(6):933–943. doi:10.1016/S0161-6420(92)31871-8 [CrossRef]
  3. Kulkarni AD, Kuppermann BD. Wet age-related macular degeneration. Adv Drug Deliv Rev. 2005;57(14):1994–2009. doi:10.1016/j.addr.2005.09.003 [CrossRef]
  4. Chakravarthy U, Augood C, Bentham GC, et al. Cigarette smoking and age-related macular degeneration in the EUREYE Study. Ophthalmology. 2007;114(6):1157–1163. doi:10.1016/j.ophtha.2006.09.022 [CrossRef]
  5. Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984;102(11):1640–1642. doi:10.1001/archopht.1984.01040031330019 [CrossRef]
  6. Kvanta A, Algvere PV, Berglin L, Seregard S. Subfoveal fibrovascular membranes in age-related macular degeneration express vascular endothelial growth factor. Invest Ophthalmol Vis Sci. 1996;37(9):1929–1934.
  7. Kliffen M, Sharma HS, Mooy CM, Kerkvliet S, de Jong PT. Increased expression of angiogenic growth factors in age-related maculopathy. Br J Ophthalmol. 1997;81(2):154–162. doi:10.1136/bjo.81.2.154 [CrossRef]
  8. Andreoli CM, Miller JW. Anti-vascular endothelial growth factor therapy for ocular neovascular disease. Curr Opin Ophtalmol. 2007;18(6):502–508. doi:10.1097/ICU.0b013e3282f0ca54 [CrossRef]
  9. Ciulla TA, Rosenfeld PJ. Antivascular endothelial growth factor therapy for neovascular age-related macular degeneration. Curr Opin Ophtalmol. 2009;20(3):158–165. doi:10.1097/ICU.0b013e32832d25b3 [CrossRef]
  10. Jeganathan VSE, Verma N. Safety and efficacy of intravitreal anti-VEGF injections for age-related macular degeneration. Curr Opin Ophtalmol. 2009;20(3):223–225. doi:10.1097/ICU.0b013e328329b656 [CrossRef]
  11. Chang TS, Bressler NM, Fine JT, et al. Improved vision-related function after ranibizumab treatment of neovascular age-related macular degeneration: results of a randomized clinical trial. Arch Ophthalmol. 2007;125(11):1460–1469. doi:10.1001/archopht.125.11.1460 [CrossRef]
  12. Greenfield DS, Heggerick PA, Hedges TR 3rd, . Color Doppler imaging of normal orbital vasculature. Ophthalmology. 1995;102(11):1598–1605. doi:10.1016/S0161-6420(95)30822-6 [CrossRef]
  13. Matthiessen ET, Zeitz O, Richard G, Klemm M. Reproducibility of blood flow velocity measurements using colour decoded doppler imaging. Eye (Lond). 2004;18(4):400–405. doi:10.1038/sj.eye.6700651 [CrossRef]
  14. Rosenfeld PJ, Brown DM, Heier JS, et al. MARINA Study. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1419–1431. doi:10.1056/NEJMoa054481 [CrossRef]
  15. Brown DM, Kaiser PK, Michels M, et al. Ranibizumab versus verteprofin for neovascular age-related macular degeneration. N Engl J Med. 2006;355(14):1432–1444. doi:10.1056/NEJMoa062655 [CrossRef]
  16. Dimitrova G, Tamaki Y, Kato S. Retrobulbar circulation in patients with age-related maculopathy. Eye (Lond). 2002;16(5):580–586. doi:10.1038/sj.eye.6700161 [CrossRef]
  17. Dimitrova G, Kato S. Color Doppler imaging of retinal diseases. Surv Ophthalmol. 2010;55(3):193–214. doi:10.1016/j.survophthal.2009.06.010 [CrossRef]
  18. Friedman E, Krupsky S, Lane AM, et al. Ocular blood flow velocity in age-related macular degeneration. Ophthalmology. 1995;102(4):640–646. doi:10.1016/S0161-6420(95)30974-8 [CrossRef]
  19. Mori F, Konno S, Hikichi T, Yamaguchi Y, Ishiko S, Yoshida A. Pulsatile ocular blood flow study: Decreases in exudative age related macular degeneration. Br J Ophthamol. 2001;85(5):531–533. doi:10.1136/bjo.85.5.531 [CrossRef]
  20. Mete A, Saygili O, Mete A, Bayram M, Bekir N. Effects of intravitreal bevacizumab (Avastin) therapy on retrobulbar blood flow parameters in patients with neovascular age-related macular degeneration. J Clin Ultrasound. 2010;38(2):66–70.
  21. Bonnin P, Pournaras JA, Lazrak Z, et al. Ultrasound assessment of short-term ocular vascular effects of intravitreal injection of bevacizumab (Avastin) in neovascular age-related macular degeneration. Acta Ophthalmol. 2010;88(6):641–645. doi:10.1111/j.1755-3768.2009.01526.x [CrossRef]
  22. Toklu Y, Cakmak HB, Raza S, Anayol A, Asik E, Simsek S. Short term effects of intravitreal bevacizumab (Avastin) on retrobulbar hemodynamics in patients with neovascular macular degeneration. Acta Ophthalmol. 2011;89(1):41–45. doi:10.1111/j.1755-3768.2010.02075.x [CrossRef]
  23. Shimomura Y, Hirata A, Ishikawa S, Okinami S. Changes in choriocapillaris fenestration of rat eyes after intravitreal bevacizumab injection. Graefes Arch Clin Exp Ophthalmol. 2009;247(8):1089–1094. doi:10.1007/s00417-009-1054-1 [CrossRef]
  24. Kilickap S, Abali H, Celik I. Bevacizumab, bleeding, thrombosis, and warfarin. J Clin Oncol. 2003;21(18):3542; author reply 3543. doi:10.1200/JCO.2003.99.046 [CrossRef]
  25. Krohne TU, Eter N, Holz FG, Meyer CH. Intraocular pharmacokinetics of bevacizumab after a single intravitreal injection in humans. Am J Ophthalmol. 2008;146(4):508–512. doi:10.1016/j.ajo.2008.05.036 [CrossRef]
  26. Bakri SJ, Sneyder MR, Reid JM, Pulido JS, Ezzat MK, Singh RJ. Pharmacokinetics of intravitreal Ranibizumab (Lucentis). Ophthalmol. 2007;114(12):2179–2182. doi:10.1016/j.ophtha.2007.09.012 [CrossRef]
  27. Gaudreault J, Fei D, Rusit J, Suboc P, Shiu V. Preclinical pharmacokinetics of Ranibizumab (rhuFabV2) after a single intravitreal administration. Invest Ophthalmol Vis Sci. 2005;46(2):726–733. doi:10.1167/iovs.04-0601 [CrossRef]
  28. Krohne TU, Liu Z, Holz FG, Meyer CH. Intraocular pharmacokinetics of Ranibizumab following a single intravitreal injection in humans. Am J Opthalmology. 2012;154(4):682–686. doi:10.1016/j.ajo.2012.03.047 [CrossRef]
  29. Bakri SJ, Sneyder MR, Reid JM, Pulido JS, Singh RJ. Pharmacokinetics of intravitreal bevacizumab (Avastin). Ophthalmol. 2007;114(5):855–859. doi:10.1016/j.ophtha.2007.01.017 [CrossRef]
  30. Sakalar Yb, Senturk S, Yildirim M, Keklikci U, Alakus MF, Unlu K. Evaluation of retrobulbar blood flow by color Doppler ultrasonography after intravitreal ranibizumab injection in patients with neovascular age-related macular degeneration. J Clin Ultrasound. 2013;41(1):32–37. doi:10.1002/jcu.21989 [CrossRef]
  31. Mete A, Saygili O, Mete A, Gungor K, Bayram M, Bekir N. Does ranibizumab (Lucentis) change retrobulbar bloodflow in patients with neovascular age-related macular degeneration?Ophthalmic Res. 2012;47(3):141–145. doi:10.1159/000330509 [CrossRef]
  32. Lieb WE. Color Doppler imaging of the eye and orbit. Radiol Clin North Am. 1998;36(6):1059–1071. doi:10.1016/S0033-8389(05)70231-1 [CrossRef]
  33. Taylor GA, Short BL, Walker LK, Traystman RJ. Intracranial blood flow: quantification with duplex Doppler and colour Doppler flow US. Radiology. 1990;176(1):231–236. doi:10.1148/radiology.176.1.2112768 [CrossRef]
  34. Ferrara D, Waheed NK, Duker JS. Investigating the choriocapillaris and choroidal vasculature with new optical coherence tomography technologies. Prog Retin Eye Res. 2016;52:130–155. doi:10.1016/j.preteyeres.2015.10.002 [CrossRef]
  35. de Carlo TE, Romano A, Waheed NK, Duker JS. A review of optical coherence tomography angiography (OCTA). Int J Retina Vitreous. 2015;1:5. eCollection 2015. doi:10.1186/s40942-015-0005-8 [CrossRef]
  36. Li XX, Wu W, Zhou H, et al. A quantitative comparison of five optical coherence tomography angiography systems in clinical performance. Int J Ophthalmol. 2018;11(11):1784–1795.
  37. Spaide RF, Koizumi H, Pozzoni MC. Enhanced depth imaging spectral-domain optical coherence tomography. Am J Ophthalmol. 2008;146(4):496–500. doi:10.1016/j.ajo.2008.05.032 [CrossRef]
  38. Margolis R, Spaide RF. A pilot study of enhanced depth imaging optical coherence tomography of the choroid in normal eyes. Am J Ophthalmol. 2009;147(5):811–815. doi:10.1016/j.ajo.2008.12.008 [CrossRef]
  39. Ikuno Y, Maruko I, Yasuno Y, et al. Reproducibility of retinal and choroidal thickness measurements in enhanced depth imaging and high-penetration optical coherence tomography. Invest Ophthalmol Vis Sci. 2011;52(8):5536–5540. doi:10.1167/iovs.10-6811 [CrossRef]
  40. Grudzińska E, Modrzejewska M. Modern diagnostic techniques for the assessment of ocular blood flow in myopia: Current state of knowledge. J Ophthalmol. 2018;2018:4694789.
  41. Harris A, Joos K, Kay M, et al. Acute IOP elevation with scleral suction: effects on retrobulbar haemodynamics. Br J Ophthalmol. 1996;80(12):1055–1059. doi:10.1136/bjo.80.12.1055 [CrossRef]

IOP, Heart Rate, and Systolic and Diastolic BP of Patients (n = 18) With AMD Before and After Day 1, Week 1, and Month 1 of Ranibizumab Injection

Pre-InjectionPost-Injection First DayPost-Injection First WeekPost-Injection First MonthP Value
Systolic BP126.39 ± 7.44121.94 ± 7.30122.22 ± 10.18129.17 ± 7.12.453
Diastolic BP78.89 ± 5.3078.61 ± 5.8981.94 ± 6.4580.56 ± 4.50.085
Heart Rate77.22 ± 8.5374.00 ± 7.0173.94 ± 8.8773.11 ± 5.30.453
IOP in Injected Eye (mm Hg)14.722 ± 2.02415.000 ± 2.05814.833 ± 1.75715.111 ± 1.023.781
IOP in Uninjected Eye15.000 ± 1.87914.944 ± 1.92414.722 ± 1.77614.833 ± 1.425.970

Hemodynamic Doppler Parameters in the OA, CRA, LPCA, and MPCA in Both Eyes of Patients With AMD (n = 18) Before and After Day 1, Week 1, and Month 1 Post-Injection of Ranibizumab

Pre-InjectionPost-Injection First DayPost-Injection First WeekPost-Injection First MonthP Value

OA of Injected EyePSV (cm/s)46.6740.5039.5942.84.066
EDV (cm/s)10.138.618.6810.21.076
RI1.431.441.431.43.990
PI0.740.760.730.74.745

OA of Uninjected EyePSV (cm/s)47.4839.5842.0342.23.062
EDV (cm/s)10.418.399.149.23.249
RI1.491.511.481.54.777
PI0.740.750.730.73.765

CRA of Injected EyePSV (cm/s)13.3713.8314.0111.74.516
EDV (cm/s)2.402.912.702.34.051
RI0.790.770.770.79.497
PI1.781.571.691.62.215

CRA of Uninjected EyePSV (cm/s)12.3811.6311.1110.86.421
EDV (cm/s)2.562.082.162.08.114
RI0.750.780.770.79.194
PI1.561.621.611.77.204

LPCA of Injected EyePSV (cm/s)14.8214.5314.9312.56.284
EDV (cm/s)3.633.584.122.45.008
RI0.720.750.690.76.138
PI1.481.501.301.56.042

LPCA of Uninjected EyePSV (cm/s)14.4612.6412.0110.79.153
EDV (cm/s)3.733.012.662.3a8.048
RI0.720.750.740.78.094
PI1.401.521.511.63.016

MPCA of Injected EyePSV (cm/s)13.8513.3013.0212.75.186
EDV (cm/s)3.753.683.653.21.559
RI0.730.710.710.74.576
PI1.431.371.381.46.630

MPCA of Uninjected EyePSV (cm/s)20.0115.3712.2011.21.006
EDV (cm/s)4.824.123.573.22.006
RI0.720.720.710.74.440
PI1.351.371.311.54.121
Authors

From Atatürk Training and Research Hospital, Department of Ophthalmology, Ankara, Turkey (SR); Numune Training and Research Hospital, Department of Ophthalmology, Ankara, Turkey (SBE); Yıldırım Beyazıt University Faculty of Medicine, Department of Ophthalmology, Ankara, Turkey (YT, NC); Hitit University Faculty of Medicine, Department of Ophthalmology, Çorum, Turkey (HBC); and Atatürk Training and Research Hospital, Department of Radiology, Ankara, Turkey (AI).

The authors report no relevant financial disclosures.

Address correspondence to Sule Berk Ergun, MD, Numune Eğitim ve Araştırma Hastanesi, Göz Hastalıkları Kliniği, Sıhhiye, Ankara, Turkey; email: suleberk@yahoo.com.

Received: July 26, 2018
Accepted: January 17, 2019

10.3928/23258160-20190703-05

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