DOI: https://doi.org/10.21203/rs.2.23918/v2
Background:To quantitatively evaluate the possible effects of phacoemulsification cataract surgery on macular hemodynamics using optical coherence tomography angiography (OCTA).
Methods:Prospective observational study. Superficial and deep macular vascular densities as well as parameters of foveal avascular zone (FAZ) were measured preoperatively (baseline) and at 1 day, 1 week and 4 weeks postoperatively in normal eyes (≥22 mm and ≤24 mm) of patients scheduled for phacoemulsification cataract surgery with intraocular lens implantation. Correlations between the rate of change of pre- and post-operative vascular densities and surgical parameters were analyzed.
Results: 123 eyes of 107 patients were recruited. Compared with baseline measurements, no statistically significant variation was found in macular vascular densities of 1 day after surgery (P>0.05). While both superficial and deep macular vascular densities were significantly increased postoperatively on week 1 and week 4 (P<0.05; P<0.05). There were no statistically significant differences in any of the FAZ parameters between the baseline measurements and the entire follow-up period (P>0.05 for all). There were no statistically significant correlations between main surgical parameters and the changes of macular vascular densities.
Conclusions: In normal eyes, macular blood perfusion gradually increased after phacoemulsification cataract surgery and was stabilized in one week. Foveal avascular zone was basically stable before and after surgery. Main parameters and intraoperative perfusion of phacoemulsification surgery may not be the key factors affecting macular hemodynamics.
Since the first phacoemulsifier was invented by Kelman in 1967, with the technological innovation during half a century, phacoemulsification cataract surgery with intraocular lens implantation has become the most commonly used procedure for the treatment of cataract as a result of its small incision, short operation time, and rapid postoperative recovery. Specific perfusion is necessary to maintain the stability of the anterior chamber during cataract extraction. And this may cause transient intraocular pressure (IOP) fluctuations during surgery which consequently result in corneal edema, poor visual acuity and longer time to recovery after surgery[1-2]. Whether the intraoperative perfusion and other surgical factors may cause fundus hemodynamic changes, especially macular microcirculation changes is worth exploring. However, there has been little research of this issue due to technical limitations[3-4]. Therefore, this study was designed to prospectively evaluate hemodynamic changes of the macular microcirculation in patients before and after phacoemulsification cataract surgery using OCTA.
2.1 Participants
All subjects were from a Han Chinese population and were recruited from May 5, 2019 to June 22, 2019 in Tianjin Eye Hospital (Tianjin, China). All participants were informed of the purpose of the research and provided written informed consent prior to entering the study. This prospective study was approved by the Ethical Review Committee of the Tianjin Eye Hospital and adhered to the provisions of the Declaration of Helsinki for research involving human subjects.
All subjects underwent a comprehensive preoperative ophthalmologic examination. Cataract severity was assessed using the Lens Opacities Classification System III (LOCS scale)[5]. Demographic information and medical history were recorded for all subjects, and their heart rates (HR), blood pressures (BP) and best-corrected visual acuity (BCVA) were measured before the time of the OCTA imaging. Subjects were included if they met the following criteria: patients diagnosed with age-related cataracts; age 60-70 years old; normal eyes (≥ 22 mm and ≤ 24 mm) and normal IOP; LOCS-N: 2-3+. Exclusion criteria were patients with diabetes, hypertension and other systemic vascular disease; history of intraocular surgery or history of ocular trauma; history of laser treatment of the eye; history of high intraocular pressure or glaucoma; history of any fundus disease. In addition, patients with obvious postoperative anterior chamber inflammation or corneal edema under slit lamp examination were also excluded.
A single experienced surgeon operated in all patients included in the study. Tropicamide eye drops (Santen Pharmaceutical Co., Ltd., Osaka, Japan) were used for mydriasis 30 min before surgery, and cimetidine hydrochloride eye drops (Alcon, Fort Worth, TX, USA) were used for surface anesthesia. A 3.0-mm clear corneal tunnel incision was made above the temporal or the nasal of eyes with a scalpel. Continuous circular capsulorhexis were made, and nuclear hydrodissection were carried out. The lens was removed by phacoemulsification (Stellaris, Bausch & lomb Incorporated Rochester, NY, USA) with the bottle height of 90 cm. After polishing, IOLs were placed to the capsular bag and the incision was sealed. The effective phacoemulsification time (EPT) and cumulative dissipated energy (CDE) were noted at the end of each case from the metrics of the phacoemulsification machine.
2.2 OCTA Image acquisition and data collection
OCTA has emerged as a novel, rapid, non-invasive imaging modality that allows generating volumetric vascular images in seconds with no need to intravenously administer fluorescent dyes. It has broad applicability to retinal choroidal vascular disease and provides quantitative measurements of retinal vascular density[6-8]. This study used the OCTA system (RTVue-XR; Optovue, Inc., Fremont, CA, USA) to detect blood flow. During the study, OCTA measurements were performed four times in each subject eye. The first measurement was performed one day before the cataract surgery (baseline), the second measurement was performed one day after the cataract surgery, and the last two measurements was performed one week and four weeks after the cataract surgery. To evaluate macular vessels, a 6mm × 6mm scanning image centered on the macula was acquired and it was automatically divided into two segments, including the superficial (ILM to IPL-10μm) and deep capillary plexuses (IPL-10μm to OPL+10μm). Superficial and deep vascular density (%) were automatically quantified by the OCT machine’ s inner software (version 2014.2.0.93). Image acquisition and evaluation were performed by two experienced researchers independently, and images with low quality (scan quality < 6) and excessive artifacts were excluded. Subsequently, parameters including superficial and deep macular vascular densities of the whole image, foveal avascular zone (FAZ) area, FAZ perimeter (PERIM) and acircularity index (AI) were derived and recorded. The rate of change in vascular density was calculated by the difference in vascular density before and one day after surgery, divided by preoperative blood vascular density. See Figure 1 for details.
2.3 Statistical analysis
SPSS (IBM, SPSS statistics, Version 20.0; SPSS Inc, Chicago, IL) was used for statistical analysis. The distribution of numeric variables was assessed by inspecting histograms and using Shapiro-Wilk tests of normality. Qualitative data are expressed in terms of frequency and numeric data are presented as the mean ± standard deviation (SD). χ2 test were used for categorical variables. Repeated measures of variance analysis were used to compare the four-time repeated measurements. Correlation analysis were analyzed using Pearson correlation analysis. P< 0.05 was assumed to be statistically significant.
Of all subjects enrolled in the study, 6 eyes were excluded due to unclear optical media or poor fixation which conducted low quality scans. In the end, a total of 123 eyes of 107 patients were included in the study. The mean age of these patients was 63.2 ± 2.7 years. The demographic and clinical characteristics of the subjects were summarized and compared in Table 1.
Table 1. Demographic and clinical characteristics of the included patients.
Parameters |
Subclass |
Numerical value |
||
Gender, n (%) |
Male |
45 (42%) |
||
Female |
62 (58%) |
|||
Age, n (%) |
60<Age≦65 |
52 (49%) |
||
65<Age≦70 |
55 (51%) |
|||
Eye, n (%) |
Right |
73 (60%) |
||
Left |
50 (40%) |
|||
LOCS-N, n (%) |
2≦nuclear<3 |
67 (54%) |
||
3≦nuclear<4 |
56 (46%) |
|||
Intraocular pressure, IOP (mmHg)* |
Baseline |
15.3 ± 4.2 |
||
1 day post-operation |
14.5 ± 3.9 |
|||
1 week post-operation |
12.0 ± 3.1 |
|||
4 weeks post-operation |
12.6 ± 3.3 |
|||
Mean arterial pressure, MAP(mmHg) * |
Baseline |
91.7± 12.4 |
||
1 day post-operation |
93.1± 11.2 |
|||
1 week post-operation |
91.1± 11.8 |
|||
4 weeks post-operation |
92.3± 9.5 |
|||
Heart rate, HR (beats/min) * |
Baseline |
75.6± 10.5 |
||
1 day post-operation |
76.3± 9.7 |
|||
1 week post-operation |
74.1± 12.3 |
|||
4 weeks post-operation |
74.6± 11.4 |
|||
Pre-operative BCVA |
.480 ± .152 |
|||
LOCS = Lens Opacities Classification System; N = nuclear; BCVA = best-corrected visual acuity;
*Repeated measures of variance analysis: IOP: Baseline/1 Day > 1Wk/4Wk; MAP: No statistical difference (all P>0.05); HR: No statistical difference (all P>0.05).
Numeric data are presented as means ± standard deviations where applicable.
Vascular density is defined as the percentage of the area occupied by blood vessels in the en face image. The preoperative superficial and deep macular vascular densities were (45.29±4.06)% and (44.15±5.67)%. The postoperative superficial macular vascular densities were (44.59±3.85)%, (47.92±3.45)%, and (48.10±3.67)%, respectively. Meanwhile, the postoperative deep macular vascular densities were (43.12±6.13)%, (46.46±4.47)%, and (47.35±5.42)%, respectively. The results indicated that macular vascular densities changed significantly over time in the two layers (both P < 0.05). The minimum macular vascular densities were both at 1 day after surgery, but no significant difference compared with parameters before surgery (both P > 0.05). Then, marked increases were subsequently exhibited on week one and week four (all P < 0.05). The trend of vascular density is shown in Figure 2.
The preoperative FAZ area, PERIM and AI were (0.35±0.13) mm2, (2.25±0.46) mm and 1.14±0.02, respectively. The postoperative FAZ area were (0.38±0.15) mm2, (0.35±0.16) mm2 and (0.33±0.17) mm2 in the next three visits. The postoperative PERIM values were (2.34±0.59) mm, (2.17±0.59) mm and (2.12±0.58) mm. And postoperative AI values were 1.12±0.61, 1.10±0.26 and 1.12±0.04, respectively. There were no statistically significant differences in any of the FAZ measurements for the entire study period (P >0.05). The trend of FAZ parameters is shown in Figure 3.
Correlation analyses of the measurement parameters are presented in Table 2, 3 and Figure 4. The rate of change in vascular density was calculated by the difference in vascular density before and one day after surgery, divided by preoperative blood vascular density. No statistically significant correlations were observed between EPT and rate of change in both superficial and deep macular vascular densities. And no statistically significant correlations were found between CDE and the changes of macular vascular densities. There were no statistically significant correlations between postoperative BCVA and macular vascular densities (all P>0.05).
Table 2 Relationships between the surgical parameters and changes of macular vascular densities
Surgical parameters |
Rate of change in superficial macular vascular density |
Rate of change in deep macular vascular density |
||
r |
P |
r |
P |
|
EPT |
.008 |
.960 |
-.029 |
.856 |
CDE |
-.112 |
.478 |
-.066 |
.667 |
P< 0.05 was assumed to be statistically significant.
Table 3 Relationships between postoperative BCVA and macular vascular densities
Vascular density |
BCVA |
||
1 day |
1 week |
4 weeks |
|
Superficial macular vascular density |
P=0.334; r=0.171 |
P=0.955; r=0.010 |
P=0.218; r=0.250 |
Deep macular vascular density |
P=0.653; r=0.080 |
P=0.910; r=0.019 |
P=0.458; r=0.152 |
P< 0.05 was assumed to be statistically significant.
In this study, we performed a quantitative assessment of macular vascular density using OCTA and compared the macular blood perfusion before and after phacoemulsification cataract surgery in Chinese normal eyes. We limited the patient's axial length, age and IOP to a small range, because these factors may affect the fundus blood flow [9]. And there was no statistical difference in blood pressure and heart rate of all patients during each examination. Of note, we found that blood flow parameters in the macula area increased gradually and stabilized in about one week after surgery. FAZ related parameters are stable before and after surgery. Main parameters of phacoemulsification surgery have no statistically significant correlations with changes of macular hemodynamics. No statistically significant correlations were found between postoperative BCVA and macular vascular densities.
With the development of phacoemulsification technology, surgeons use maximum vacuum to reduce direct damage by the power of phacoemulsification. But it brings the effect of high perfusion pressure at the same time. Previous reports have reported that the instability of the fluidics system during cataract surgery results in a longer operation time and an increase in CDE, which in turn will lead to longer recovery time and even poor visual function in postoperative patients [1-2]. So we wonder whether the fluctuation of intraocular perfusion pressure during phacoemulsification affect fundus microcirculation and then affect the patient's postoperative vision. Many literatures have reported the effects of phacoemulsification cataract surgery on ocular hemodynamics by using various techniques [10-13]. Nevertheless, due to the limitations of these devices, there is no consistent conclusion currently. Meanwhile, the emergence of OCTA provides us with new ideas to explore.
A non-invasive and quantitative research of fundus blood vessels could be obtained by OCTA in seconds[6-8]. Good reproducibility and repeatability of OCTA on vascular and FAZ measurements have already been demonstrated[14-15]. The inner retina which supplied by the central retinal vascular system can be segmented into two layers on OCTA image. One is the superficial capillary plexuses (SCP) mainly located in the retinal nerve fiber layer, including arterioles, venules and capillaries. The other is the deep retinal vascular plexus (DCP), which is mainly located in the inner nuclear layer of the retina and consists of capillary network[6,7].Researches used OCTA has indicated that fundus vessel density is negatively correlated with the axial length or age[16]. Abnormal vessel densities of SCP and DCP has been observed in various eye or systemic diseases. And the changes are often closely related to the decline of visual function[6,17].
In this study,vascular densities in the macula area increased gradually in 1 day to 1 week after surgery, which is consistent with the results of Siqing Yu[18]. They used OCTA to study 13 cataract eyes and observed that there was a increase of either perfusion or vessel density on SCP and DCP in a 3 mm×3 mm en face image one week after surgery[18]. But Siqing Yu et al. attributed this increase as the result of the different refractive medium before and after surgery, they did not measure patients’ ocular blood flow status immediately after the surgical intervention, which ignored the impact of cataract surgery on the macular hemodynamics. Moreover, Zhennan Zhao et al. studied 32 cases of uncomplicated phacoemulsification surgeries by using OCTA[19]. Significant increases in macular vessel density and macular thickness were found in one month and three months postoperatively. This is basically consistent with the conclusions of our larger sample study. Previous studies have pointed out that fundus perfusion will eventually improve due to the IOP-lowering effect of cataract surgery, which is believed to result from the widening of the anterior chamber[20-23]. This is consistent with our research since patients' IOP decreased significantly one week after surgery. Previous study indicated that several inflammatory factors could be released as the result of the destruction of the blood-aqueous barrier and many of them had vasodilator effect[24, 25]. The interpretation of these studies is in support of our findings. In addition, most of the subjects had earlier cataracts (LOCS scale,median: N3, C4, P3) in current study in order to ensure the imaging quality of larger en face images (6mm×6mm). The scan qualities of all included patients were more than 6, which was considered acceptable. We also manually excluded images with good scan quality but more artifacts, so we believed that the effect of lens opacities were diminished and the results of this study should be reliable.
Previous clinical studies of FAZ have many limitations due to the invasiveness, equipment complexity and long scanning time[26-29]. Some clinical studies using OCTA to analyze FAZ[30-34] are mainly focused on diabetic retinopathy(DR) have shown a decrease in total retinal blood flow associated with an increase in FAZ area with increasing age[35, 36]. And they have showed that the size of FAZ was negatively correlated with both the macular vascular density and BCVA[31, 37]. Therefore, FAZ parameters may detect the impairments of macular micro-vessels and visual function to some extent. In our study, the influence of age had been avoided and the FAZ area of subjects after cataract surgery increased first and then decreased, while the differences were not significant (P>0.05). This difference may be due to participants in our study have no systemic vascular disease. The postoperative microcirculation change was only transient and mild, with no qualitative vascular changes. Our result is consistent with the findings of Siqing Yu et al.[18] that there were no significant differences in FAZ area and perimeter between preoperative measurements and one week after cataract surgery. However, unlike our findings, Zhennan Zhao et al[19] found a decrease in the foveal avascular zone after cataract surgery in 32 patients with the axial length between 20mm and 25mm. We analyzed this difference may be contributed to the inconsistency in the axial length of enrolled patients included in the two studies. Since the axial length is the influencing factor of fundus blood vessel density [3] and the eye volume is smaller in short eyes, so the IOP fluctuation is much more severe in surgery. Besides, fundus vessels are straight and fragile in long eyes, being stretched as the result of the extension of eyeball[38]. Moreover, because of the large eye volume, the pressure on the eyeball wall is uneven during the operation[39].
The effects of various surgical parameters on ocular structures have been of concern and efforts have been made to evaluate the same[40, 41]. However,there is a shortage of literature on the effect of different flow parameters on the posterior segment. Previous studies[42] demonstrated that phacoemulsification ultrasound energy can induce the production of some cytokines, which in turn affects ocular hemodynamics. This prompts us to explore the correlations between surgical parameters and changes in ocular blood flow. In our study, no statistically significant correlations were observed between the two parameters (EPT and CDE) and rate of change in both superficial and deep macular vascular densities. It suggests that the main parameters of phacoemulsification surgery may not be the key factors affecting macular hemodynamics in normal eyes. However, the LOCS nuclear opalescence score of our subjects were mainly concentrated between 2+ and 3+, which may result in a very small fluctuation of surgical parameter and reduce its influence. And the included patients had no vascular disease, so the good vascular elasticity may cause a rapid recovery after surgery.
Previous studies on various ocular vascular diseases such as retinal vein occlusion (RVO), diabetic retinopathy (DR) and macular telangiectasia have demonstrated that the macular vacular densities is positively correlated with BCVA [16-17, 43]. However, in this study, there was no correlation between BCVA and macular vascular density at each follow-up after surgery. This difference may be caused by the different vascular conditions of the included patients. Unlike the above studies, physiological function of the fundus blood vessel in patients included in this study was intact and did not have organic changes. The effect of fundus vascular density on visual function in patients after surgery needs further investigation
The main limitation of this study is the lack of research on patients with more severe cataracts. However, this study is the basis for exploring the effects of phacoemulsification on macular hemodynamics in different populations in the future. Furthermore, studies in the future are needed to focus on abnormal eyes, especially patients who with high myopia, glaucoma and systemic vascular disease. This will give clinicians more reference for practice. For example, a highly myopic patients who have long eyes, weak eyeball wall and liquefying vitreum, will have greater intraoperative IOP fluctuations. Comparison of ocular vasculature changes between long eyes and normal eyes before and after surgery can guide clinicians to further optimize surgical parameters and clinical medication. This study can also be a basis for further studies of fundus hemodynamic changes after vacuum application in femtosecond laser-assisted cataract surgery.
In our study, macular blood perfusion in normal eyes gradually rose one day to one week after phacoemulsification cataract surgery in Chinese normal eyes. Finally, it stabilized in one week. FAZ measurements seems to be stable before and after surgery. Main parameters and intraoperative perfusion of phacoemulsification surgery may not be the key factors affecting macular hemodynamics.
OCTA Optical coherence tomography angiography
FAZ Foveal avascular zone
IOP Intraocular pressure
HR Heart rates
BP Blood pressures
BCVA Best-corrected visual acuity
EPT Effective phacoemulsification time
CDE Cumulative dissipated energy
PERIM FAZ perimeter
AI Acircularity index
MAP Mean arterial pressure
LOCS Lens opacities olassification system
SCP Superficial capillary plexuses
DCP Deep retinal vascular plexus
DR Diabetic retinopathy
RVO Retinal vein occlusion
7.1 Ethics approval and consent to participate
This prospective observational study was approved by the ethics committee of Tianjin Eye Hospital, and written informed consent was obtained from all patients.
7.2 Consent for publication
Not applicable.
7.3 Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
7.4 Competing interests
The authors declare that they have no competing interests.
7.5 Funding
No funding received.
7.6 Authors' contributions
Design of the study (XJ, YW); data collection (XJ, YW); statistical analysis (XJ, YW); drafting of the manuscript (XJ); critical revision (YW,HS). All authors read and approved the manuscript to be published.
7.7 Acknowledgements
Not applicable.
8. Footnotes
Xinyu Jia and Yingjuan Wei contributed equally to this work.
Xinyu Jia and Yingjuan Wei are co-first authors.