Effect of preoperative vitreoretinal adhesion on pseudophakic cystoid macular edema and choroidal expansion response

DOI: https://doi.org/10.21203/rs.3.rs-1865485/v1

Abstract

Purpose

To evaluate the changes in thickness of central retina, thickness of choroidal layers before and after cataract surgery and determine the impact of vitreoretinal surface status on these parameters.

Methods

Prospective and interventional study included 64 patients (64 eyes) with no macular disorder who underwent phacoemulsification, and had stored spectral domain optical coherence tomography (OCT) imagings within 1 week preoperatively as well as at 1 and 3 months postoperatively. The evaluated SD-OCT parameters were central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), the large choroidal vessel layer thickness (LCVL) and the Sattler’s layer/choriocapillaris complex thickness (SCVL), vitreoretinal status including “vitreomacular adhesion”(VMA), “no vitreoretinal contact visible”, and pseudophakic cystoid macular edema (PCME).

Results

Seventeen eyes (26.6%) had VMA. The preoperative SD-OCT parameters of the two groups were not statistically significant (p > 0.05). The mean CFT values at postoperative first month were statistically significantly higher in VMA group (p = 0.01). Pseudophakic cystoid macular edema was observed in the postoperative first month in two eyes (3.1%) which also had VMA. Statistically significant difference was found between LCVL values of VMA and non-VMA group on the first- and third-month visits (p = 0.02, 0.04, respectively). No statistically significant difference was found between preoperative and postoperative SFCT values.

Conclusions

Pre-surgical vitreomacular adhesion may be a risk factor for development of PCME after uncomplicated cataract surgery. Choroidal expansion response after cataract surgery was not associated with pseudophakic cystoid edema.

Introduction

Pseudophakic cystoid macular edema (PCME) is a common cause of decreased vision following cataract surgery.1 Although the incidence of clinically diagnosed PCME is low, it may reach up to 41% when optical coherence tomography is used.2 Choroidal thickness of the eyes with PCME is a topic of interest.3 Increased choroidal thickness following uneventful cataract surgery has been shown in the literature4 and this finding confirms the inflammatory processes. Inflammatory mediators, which are upregulated in aqueous and vitreous humors, may cause increased vascular permeability and macular edema.2

Anterior-posterior traction during phacoemulsification has also been considered a risk factor.5 A retrospective study of 81 984 eyes showed that a diagnosis of epiretinal membrane (ERM) before cataract surgery was indeed associated with an increased risk of development of PCME.5 The advent of enhanced depth OCT (EDI-OCT) has enabled clinicians to observe choroidal structure, choroidal thickness and vitreoretinal interface, in addition to retinal layers. The aim of this study was to evaluate the changes in thickness of central retina, thickness of choroidal layers before and after cataract surgery and to determine the impact of vitreoretinal surface status on these parameters.

Materials And Methods

Data was collected at the *** Education and Research Hospital, in Antalya, Turkey. The study was approved by the Ethics Committee of the University (2020/20 − 14) and conducted in accordance with the principles of the Declaration of Helsinki.

Patients

The records of the patients who had had uneventful cataract surgery were reviewed for the presence of PCME. Pseudophakic cystoid macular edema was defined as visual impairment or new onset metamorphopsia, associated with the presence of CME in the fundus examination and detection of CME via OCT imaging.1

Ocular diseases, including glaucoma, retinal vascular disorders, macular degeneration, diabetic retinopathy, uveitis, epiretinal membrane, myopic refractive error exceeding − 6.0 diopters, axial length > 25.5 mm, were all considered an exclusion criteria. The cases requiring additional iris and/or capsule manipulation during surgery were not included into the study. Each patient underwent an ophthalmological examination that included best corrected visual acuity (BCVA) with the Snellen eye chart, intraocular pressure (IOP) measurement, slit-lamp evaluation and fundus examination. Preoperative and postoperative values of intraocular pressure, central foveal thickness (CFT), subfoveal choroidal thickness (SFCT), large choroidal vessel layer thickness (LCVL) and the Sattler’s layer/choriocapillaris thickness (SCVL) were recorded.

Surgery

Phacoemulsification of all eyes were performed by the same experienced surgeon (FA). Under topical anesthesia, surgery was performed with a 2.8-mm clear corneal incision. After phacoemulsification (Infiniti Vision System, Alcon Laboratories, Inc., USA), intracapsular lens implantation (AcrySof IQ, Alcon Laboratories, Inc.) was performed. Dexamethasone and tobramycin eye drops (Alcon, Hunenberg, Switzerland) were used in the postoperative period. The drops were used 6 times a day for the first week and 4 times a day for the following three weeks.

Optic coherence tomography imaging

Optic coherence tomography imaging (Optovue Inc., Fremont, CA, USA) was used to measure central retinal and subfoveal choroidal thickness. Horizontal B-scan images, which are centered on the fovea, were used to obtain the necessary measurements. The “chorioretinal” acquisition mode of the RTVue software was studied to measure the choroidal vascular layers. The choroid-sclera interface was assigned as the outmost dark-to-bright border. The choroidal thickness measurements were achieved manually by two physicians (NS and FA).The method designed by Branchini et al. was used to determine the large choroidal vessel layer thickness (LCVL) and the Sattler’s layer/choriocapillaris thickness (SCVL) at the subfoveal location (Fig. 1).6 A vessel within the choroid having a lumen of minimum 100 µm in diameter was designated as a large vessel. Using the RTVue software’s “chorioretinal imaging mode”, choroidal thickness was measured perpendicularly from Bruch’s membrane, underneath the foveal region. Measurements that were taken before surgery, 1 week after surgery, 1 month after surgery and 3 months after surgery were recorded. All of the OCT imaging measurements were performed in the morning at 9:00 to 11:00 in our clinic, thus the circadian change of choroidal thickness was eliminated. Two observers (NSK and FA) took three readings at different times, averaged the values and recorded them. The interobserver reproducibility of the measurements was interpreted by calculating the interclass correlation coefficient (ICC). Fovea-centered macular measurements with the E-MM5 scanning mode available in the device (0.9 seconds, external 6x6 mm grid pattern, internal 4x4 mm grid pattern scanning 13 horizontal and 13 vertical lines consisting of 668 A-scans and 8 horizontal and 8 vertical lines, each consisting of 400 A-scans) were used for the CFT measurements.

The criteria established by the International Vitreomacular Traction Study Group were used to evaluate the vitreomacular interface status.7 Spectral domain OCT macular images were classified into following categories: no vitreoretinal contact visible, focal or diffuse vitreomacular adhesion (VMA). Posterior vitreous detachment (PVD) was assessed clinically and by OCT. Two observers (NSK and FA) reviewed all images which were taken by the RTVue software’s “vitreoretinal imaging mode”. Total choroidal thickness, large choroidal vessel layer thickness (LCVL) and the Sattler’s layer/choriocapillaris thickness (SCVL) at the subfoveal location, preoperative status of vitreomacular adhesion was recorded.

Statistical Analyses

Statistical analysis was performed using the statistical package SPSS software (Version 25.0, SPSS Inc., Chicago, IL, USA). If continuous variables were normal, they were describe as the mean ± standard deviation (p > 0.05 in Kolmogorov-Smirnov test or Shapira-Wilk (n < 30)), and if the continuous variables were not normal, they were described as the median. Comparisons between groups were applied using Student T test for normally distributed data. Pre-post measures data were analyzing Paired T test and Repeated Measure Analyses. Values of p < 0.05 were considered statistically.

Results

Fourty two males and 22 females with a mean age of 64.5 ± 7.3 years (range 50–79 years) were included (Table 1). The mean axial length was 23.3 ± 0.7 mm. Considering all patients, median CFT values were 251.2 ± 19.9 µ, 251.7 ± 26.2 µ, 265.8 ± 47.3 µ and 258.8 ± 25.5 µ, on preoperative, postoperative first week, first month and third month respectively (p = 0.005). The median SFCT values of the patients on preoperative, first week, first month and third month examination were 257.2 ± 58.1 µ, 262.4 ± 55.6 µ, 262.0 ± 56.0 µ and 254.6 ± 53.8 µ, respectively (p = 0.4). Seventeen patients had broad/focal vitreomacular adhesion (VMA group) (26.6%) and the SD-OCT imaging of the other patients showed no vitreoretinal contact visible (non-VMA group). There was no statistically significant difference between the preoperative SD-OCT parameters of VMA group and non-VMA group (All p values > 0.05) (Table 1). The mean age of VMA group was lower than non-VMA group (p = 0.01). The mean CFT values at postoperative first month were statistically significantly higher in VMA group (p = 0.01). Statistically significant difference was found between LCVL values of VMA and non-VMA group on the first- and third-month visits (p = 0.02, 0.04, respectively). PCME occurred in two eyes (3.1%) at the first month visit (Fig. 2). Both of these eyes had vitreomacular adhesion and their CFT were 515 and 481, the SFCT values were 256 and 292 µm. With the usage of nepafenac ophthalmic drops four times a day, macular edema was resolved in one month.

Table 1

Descriptive Statistics and Central Foveal Thickness and Subfoveal Choroidal Thickness Measurements of Two Groups

 

VMA

Non-VMA

p

Age, years, mean ± SD

59 ± 6

66 ± 7

0.01

Axial length, mm, mean ± SD

23 ± 1

23,4 ± 1

0.1

Central foveal thickness (CFT), µm, mean ± SD

     

Preoperative CFT

Postoperative CFT first week

Postoperative CFT first month

Postoperative CFT third month

255 ± 22

254 ± 23

290 ± 82

266 ± 31

249 ± 20

251 ± 27

257 ± 21

256 ± 23

0.4

0.7

0.01

0.1

Subfoveal choroidal thickness (SFCT), µm, mean ± SD

     

Preoperative SFCT

Postoperative SFCT first week

Postoperative SFCT first month

Postoperative SFCT third month

275 ± 60

284 ± 48

284 ± 54

280 ± 56

251 ± 57

255 ± 57

254 ± 55

246 ± 51

0.1

0.06

0.06

0.03

Subfoveal large choroidal vessel layer thickness (LCVL), µm, mean ± SD

     

Preoperative LCVL

Postoperative LCVL first week

Postoperative LCVL first month

Postoperative LCVL third month

208 ± 56

215 ± 53

210 ± 51

205 ± 54

181 ± 55

185 ± 51

178 ± 49

177 ± 46

0.08

0.04

0.02

0.04

Subfoveal Sattler’s layer/choriocapillaris thickness (SCVL), µm, mean ± SD

     

Preoperative SCVL

Postoperative SCVL first week

Postoperative SCVL first month

Postoperative SCVL third month

67 ± 16

75 ± 19

74 ± 19

75 ± 14

71 ± 24

70 ± 23

76 ± 30

69 ± 26

0.5

0.4

0.8

0.4

Intraocular Pressure (IOP), mmHg, mean ± SD

     

Preoperative IOP

Postoperative IOP first week

Postoperative IOP first month

Postoperative IOP third month

14 ± 3

14 ± 2

15 ± 3

15 ± 3

15 ± 3

15 ± 3

14 ± 3

14 ± 3

0.4

0.4

0.4

0.4

Discussion

The incidence of PCME is reported to be between 0.1 and 3.8% in the literature8, however the incidence is higher when OCT is used.2 Notably though, the definition of PCME differs between the studies: some researchers define PCME as the 10% increase of CFT or intraretinal cysts appearrance9, while other researchers describe PCME as a 10% increase in CFT over previous PCME, along with a reduction in BCVA.10 In our study we described PCME as visual impairment or new onset metamorphopsia, associated with the presence of CME in fundus examination and OCT imaging such Yonekawa and Kim described in their study.1

In our study, the incidence of PCME was found as 3.1% (two eyes). Kusbeci et al. found 5.5% of cases with PCME, and an increase in CFT at 1 week, 1 month, 3 months and 6 months in their prospective study.11 According to the results of our study, the values of CFT on postoperative first and third months, were statistically significantly higher from preoperative values. Although PCME was seen on first month visits in our both cases, the retinal thicknesses did not return preoperative values on third month. This result shows that the normalization of posterior segment takes long time after phacoemulsification.

In our study, we aimed to query the effect of vitreomacular adhesion on existence of macular edema. The CFT of the eyes with VMA was thicker than non-VMA group on first month visit. This result confirmed our hypothesis. Duker et al. defined vitreomacular adhesion as perifoveal vitreous detachment with remaining vitreomacular attachment and unperturbed foveal morphologic features.7 This condition appears with OCT and is nearly always a result of vitreous aging. However in our study, the VMA group was younger than non-VMA group.

The etiology of PCME is thought to be inflammatory mediators which rise in the aqueous and vitreous humors, causing increased vascular permeability: destroyed retinal barrier leads fluids to extend to the fovea and causes macular edema.2 The changes in choroidal thickness after uneventful cataract surgery is a topic of interest. Previous studies have reported the changes in the choroid after successful cataract surgery. Odrobina and Lauda Ńska-Olszewska measured the choroidal thickness of the operated eye and fellow eye of the 28 patients who underwent uneventful cataract surgery and found that the average choroidal thickness of the operated eye, was statistically significantly lower than the fellow eye.12 The authors concluded that lower blood flow in operated eye may lead to PCME, however the effect of decreased blood flow on PCME is controversial. There are several studies demonstrating choroidal thickening after phacoemulsification cataract surgery.4,13 Falcao et al14, showed that there was no change in choroid in patients without retinal pathology after cataract surgery. Similarly in our study, we did not find any change in total choroidal thickness.

Ohsugi et al.demonstrated that after phacoemulsification of 100 eyes, IOP was significantly reduced at the postoperative 3 weeks, 3 months, and 6 months; CFT, SFCT were significantly increased and both CFT and SFCT were found to be inversely correlated with IOP increase.15 In our study, there was no statistically significant difference between the IOP values; the stability of IOP may be the cause of the constant values of total choroidal thickness.

Analysis of choroidal vascular layers as SCVL and LCVL has been a common method to clarify the effects of systemic and ocular disorders.16,17 The strength of our study was to investigate the two vascular layers of choroid after uneventful cataract surgery. In patients with vitreomacular adhesion, the LCVL was found to be thicker one week after cataract surgery. The thickening of large vessel layer continued on first and third month. We conclude that this change should be a result of tractional effect on choriocapillaris during surgery. Choriocapillaris layer might be pulled anteriorly by vitreous after completing phacoemulsification of lenticular fragments and the LCVL might be relatively thicker in the patients with VMA.

In our study, two eyes had PCME one month after phacoemulsification and both of these had vitreomacular adhesion. Vitreomacular adhesion, which is an early stage of vitreomacular traction, may have a mechanical effect on macula and induce macular edema. Copete et al. investigated the relationship among the existence of vitreoretinal interface abnormalities and the PCME formation after cataract operation.18 The researchers stated that VMA or vitreomacular traction detected by SD-OCT was not connected to the development of PCME and that the only factor associated with PCME was found to be the existence of nonsurgical ERM.18 On the contrary, with this study, we showed that the eyes having vitreomacular adhesion have higher risk of PCME after cataract surgery.

Anastasilakis et al. investigated the potential correlation between PCME incidence and vitreoretinal interface status, and found no significant relationship, however they found that the incidence of PCME was higher in patients with attached posterior vitreous.19 The authors concluded that intact vitreoretinal interface on macula may promote the transmission of the phaco energy.19 In our study, two patients with PCME had VMA and we concluded that the phaco energy may facilitate the traction on the areas of VMA and causes PCME.

Limitations

Limitations of our study include the small number of patients and not counting on the phacoemulsification time and power. On the other hand, the strengths of this study were evaluating the different layers of choroid before and after phacoemulsification, investigating nearly all components of posterior segment before and after operation, and the fact that all operations were performed by the same experienced surgeon.

Conclusion

Pre-surgical vitreomacular adhesion established by SD-OCT is a risk factor for the development of PCME after uncomplicated cataract surgery. Choroidal expansion response after cataract surgery was not associated with pseudophakic cystoid edema.

Declarations

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Competing Interests

The authors have no relevant financial or non-financial interests to disclose.

Author Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Nedime Sahinoglu-Keskek and Fatih Aslan. The first draft of the manuscript was written by Nedime Sahinoglu-Keskek and Fatih Aslan commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

I would like to extend my gratitude to Cagla Sariturk for his precious assistance in our statistical analysis.

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