The vitreomacular interface in retinal vein occlusion

Authors


Thomas Bertelmann, MD
Department of Ophthalmology
Philipps University Marburg
Robert-Koch-Strasse 4
35037 Marburg
Germany
Tel: + 49 6421 5862600
Fax: + 49 6421 5865678
Email: thomas.bertelmann@staff.uni-marburg.de

Abstract.

Purpose:  To evaluate the posterior vitreous adhesion status in patients with a history of central or branch retinal vein occlusion and to compare the results with the natural time-course of posterior vitreous detachment in healthy age-related controls.

Methods:  A retrospective chart review in terms of the posterior vitreous adhesion status was performed in 132 patients (133 eyes) with a history of a central (CRVO) or branch (BRVO) retinal vein occlusion. All patients underwent vitrectomy. Based on the operation reports, the vitreous adhesion status was classified as attached, partially detached or completely detached. The results were compared to the natural time-course of posterior vitreous detachment development in healthy age-related controls.

Results:  Eighty-one eyes met the inclusion and exclusion criteria. Fifty-two eyes (64%) had a history of CRVO and 29 eyes (36%) a history of BRVO, respectively. In the CRVO group, the posterior vitreous was attached in 47 eyes (90%) and completely detached in five eyes (10%). In the BRVO group, the posterior vitreous was attached in 27 eyes (93%), partially detached in 1 eye (3%) and completely detached in another eye (3%). A subdivision into age classes and a comparison with healthy age-related controls [data by Weber-Krause & Eckardt (1997) Ophthalmologe, 94, 619–623] showed in patients between 65 and 69 years of age an attached posterior vitreous cortex in 72% in healthy eyes, in 100% in CRVO (p = 0.109) and in 89% in BRVO (p = 0.440), in patients between 70 and 79 years of age an attached posterior vitreous cortex in 56% in healthy eyes, in 86% in CRVO (p = 0.010) and in 100% in BRVO (p = 0.038) and in patients between 80 and 89 years of age an attached posterior vitreous cortex in 43% in healthy eyes, in 100% in CRVO (p = 0.191) and in 67% in BRVO (p = 0.582) (Fisher’s exact t-test).

Conclusion:  In patients with a history of CRVO or BRVO, the posterior vitreous cortex stays attached more frequently in all age groups in comparison with the healthy age-related controls.

Introduction

Central (CRVO) and branch (BRVO) retinal vein occlusions are one of the most frequently occurring retinal vascular disorders that can lead to severe visual loss (Rogers et al. 2010a,b; McIntosh et al. 2010).

Recently, the vitreomacular interface and the adhesion status of the posterior vitreous cortex towards the internal limiting membrane (ILM) of the retina is getting more and more into the focus of interest as the adhesion status of the posterior vitreous may play an important role in the pathogenesis of different posterior pole pathologies such as diabetic macular oedema (Stefánsson & Loftsson 2006; Stefánsson 2009), exudative age-related macular degeneration (Krebs et al. 2007; Schulze et al. 2008; Robison et al. 2009; Mennel et al. 2010) and retinal vein occlusion (Stefánsson 1990; Hikichi et al. 1995; Tachi et al. 1999; Charbonnel et al. 2004; Yamamoto et al. 2004; Murakami et al. 2007). Many authors have shown that a completely or partially attached posterior vitreous boosts vitreoretinal pathologies, whereas a completely detached posterior vitreous may serve as a beneficial factor in the development and the progression of above-addressed diseases (Krebs et al. 2007; Schulze et al. 2008; Stefánsson 2009).

The purpose of our analysis is to investigate whether eyes with a history of CRVO or BRVO reveal a higher incidence of an attached and a lower incidence of a completely detached posterior vitreous cortex, respectively, emphasizing the hypothesis that the status of the posterior vitreous plays an important role in the development and the progression of both diseases. To clarify the difference in the adhesion status compared to healthy age-related eyes, we compared our findings to those of Weber-Krause & Eckardt (1997), who investigated the adhesion status of the posterior vitreous in an ultrasonographic study of 712 eyes.

Methods

In this retrospective case study, we analysed the surgical reports of 132 patients (133 eyes), who underwent vitrectomy in combination with RON for CRVO or vitrectomy with AVS for BRVO, respectively, between January 2000 and May 2010 at the University Eye Hospital Marburg, Germany. Eighty patients and 81 eyes met the inclusion and exclusion criteria and were therefore included in our analysis. Fifty-two patients with a medical history of CRVO or BRVO and a performed vitrectomy in combination with RON or AVS had to be excluded because of imprecise descriptions of the posterior vitreous status during the surgical procedure. To be included, the surgical report needed to have a precise description of the status of the posterior vitreous cortex, classifying the posterior vitreous as attached, partially detached or completely detached. To compare our findings with the natural time-course of posterior vitreous detachment (PVD) in healthy age-related eyes, we subdivided the analysed cases into different age groups and compared our findings with ultrasonographic research results from Weber-Krause & Eckardt (1997). We used Fisher’s exact t-test for the statistical analysis. Significant results were assumed if p < 0.05.

Results

The medical charts of 80 patients with a total of 81 eyes were enrolled in our analysis. The mean patient age at the onset of retinal vein occlusion was 66.43 years (SD 9.712). Sex distribution revealed 35 female patients (44%) and 45 male patients (56%). Fifty-two eyes (64%) had a history of CRVO and 29 eyes (36%) had a history of BRVO (Fig. 1).

Figure 1.

 Type of retinal vein occlusion (n = 81). CRVO = central retinal vein occlusion in 64% (n = 52), BRVO = branch retinal vein occlusion in 36% (n = 29).

In the CRVO group, the mean patient age at the onset of symptoms was 66.21 years (SD 9.884). Nineteen patients (37%) were women and 33 (63%) were men. The time period between the occurrence of symptoms and the performance of the vitrectomy with RON ranged from 1 to 79 weeks (average 16.02 weeks). During vitrectomy, the posterior vitreous cortex was classified as attached in 47 cases (90%) and as completely detached in five cases (10%) (Fig. 2). In five cases (10%), the adhesion between the posterior vitreous cortex and the ILM was described as extremely strong. We performed a subdivision into age classes to compare our data with the incidence of PVD in the literature. Nine patients (17%) were between 65 and 69 years, 21 patients (40%) between 70 and 79 years and two patients (4%) between 80 and 89 years of age (Table 1). Patients between 65 and 69 years of age showed an attached posterior vitreous cortex in 100% compared to 72% in healthy age-related controls (p = 0.109), patients between 70 and 79 years of age in 86% compared to 56% in healthy age-related controls (p = 0.010) and patients between 80 and 89 years of age in 100% compared to 43% in healthy age-related controls (p = 0.191) (Tables 1 and 2) (Fig. 3).

Figure 2.

 Status of the vitreomacular interface. CRVO = central retinal vein occlusion, BRVO = branch retinal vein occlusion.

Table 1.   Subdivision into age groups, type of retinal vein occlusion and posterior vitreous adhesion status.
Vitreous statusAttachedCompletely detachedPartially detached
Age/yearsCRVO (n = 52), %BRVO (n = 29), %CRVO (%)BRVO (%)CRVO (%)BRVO (%)CRVO (%)BRVO (%)
  1. BRVO, branch retinal vein occlusion; CRVO, central retinal vein occlusion.

30–391 (2)0 (0)1 (100)0 (0)0 (0)0 (0)0 (0)0 (0)
40–493 (6)2 (7)3 (100)2 (100)0 (0)0 (0)0 (0)0 (0)
50–597 (13)3 (10)5 (71)3 (100)2 (29)0 (0)0 (0)0 (0)
60–6918 (35)15 (52)18 (100)14 (93)0 (0)0 (0)0 (0)1 (7)
65–699 (17)9 (31)9 (100)8 (89)0 (0)0 (0)0 (0)1 (11)
70–7921 (40)6 (21)18 (86)6 (100)3 (14)0 (0)0 (0)0 (0)
80–892 (4)3 (10)2 (100)2 (67)0 (0)1 (33)0 (0)0 (0)
Table 2.   Results of B-scan ultrasound investigation into vitreoretinal interface by Weber-Krause & Eckardt, subdivision into age groups.
Vitreous statusAttached (%)Completely detached (%)Partially detached (%)Altogether (%)
65–6975 (72)12 (11)18 (17)105 (100)
70–79166 (56)104 (35)27 (9)297 (100)
80–89114 (43)121 (46)28 (11)263 (100)
>9016 (39)20 (49)5 (12)41 (100)
Figure 3.

 Percentage of attached posterior vitreous cortex in different age groups. Comparison between healthy eyes (results by Weber-Krause & Eckard, control), CRVO and BRVO, *Statistically significant differences.

In the BRVO group, the mean patient age at the onset of symptoms was 66.83 years (SD 9.555). Seventeen patients (59%) were women and 12 (41%) were men. The time period between the occurrence of symptoms and the performance of the vitrectomy with AVS ranged from 2 to 76 weeks (average 15.28 weeks). During vitrectomy, the posterior vitreous cortex was classified as attached in 27 (93%) cases and as partially or completely detached in one case each (3% each) (Fig. 2). In one case (3%), the adhesion between the posterior vitreous cortex and the ILM was described as extremely strong. The case showing a partial PVD had a strong adhesion towards the ILM at the site of the occlusion and was detached all around. We performed a subdivision into age classes to compare our data with the incidence of PVD with the literature as well. Nine patients (31%) were between 65 and 69 years, six patients (21%) between 70 and 79 years and three patients (10%) between 80 and 89 years of age (Table 1). Patients between 65 and 69 years of age showed an attached posterior vitreous cortex in 89% compared to 72% in healthy age-related controls (p = 0.440), patients between 70 and 79 years of age in 100% compared to 56% in healthy age-related controls (p = 0.038) and patients between 80 and 89 years of age in 67% compared to 43% in healthy age-related controls (p = 0.582) (Tables 1 and 2) (Fig. 3).

Discussion

The vitreomacular interface and the status of the posterior vitreous cortex increasingly get into the focus of interest in vitreoretinal ophthalmology. For several posterior pole pathologies, there appears to be the evidence that an attached or partially detached posterior vitreous cortex can boost the occurrence and the progression rate of various vitreoretinal diseases.

An attached posterior vitreous cortex exerts tangential forces on the neuroretina and the retinal pigment epithelium monolayer. This may result in an increased production and release of growth factors (Noma et al. 2010a,b) and inflammation mediators at the site of a low-grade inflammation (Krebs et al. 2007; Mennel et al. 2010) owing to the mechanical stimulus. An attached vitreous may serve as reservoir for growth factors at the adhesion site by binding vascular endothelial growth factor to altered collagen fibrils (Robison et al. 2009; Stefánsson 2009). Further, an attached posterior vitreous cortex reduces oxygen tension at the vitreoretinal interface (Krebs et al. 2007; Stefánsson 2009), whereas a completely detached posterior vitreous allows a more sufficient oxygenation of the retina (Stefánsson 2009) by a higher diffusion rate of oxygen from the anterior segment (Stefánsson et al. 1981).

In contrast, a complete PVD shows a beneficial impact on the recovery of visual acuity and the deterioration of macular thickness (Stefánsson 2009). This interrelation has been shown for diabetic patients suffering from a clinically significant macular oedema (Stefánsson & Loftsson 2006) and for patients diagnosed with the exudative form of an age-related macular degeneration (Krebs et al. 2007; Schulze et al. 2008; Robison et al. 2009). Recent research results show consistent coherences in eyes with CRVO (Hikichi et al. 1995; Tachi et al. 1999; Murakami et al. 2007) and BRVO (Stefánsson et al. 1990; Tachi et al. 1999; Charbonnel et al. 2004; Yamamoto et al. 2004).

In the literature, the results vary between different studies, showing an overall attached posterior vitreous cortex in patients with CRVO or BRVO in 45–100% (Hikichi et al. 1995; Takahashi et al. 1997; Hayreh & Jonas 2004; Park & Taek 2010), a partially detached posterior vitreous in 2% (Hikichi et al. 1995) and a completely detached posterior vitreous cortex in 35.4–39.1% of cases (Hikichi et al. 1995; Hayreh & Jonas 2004). We performed a subdivision into various age groups. This enables us to compare the incidence of PVD between healthy eyes and eyes with retinal vein occlusions in accordance with the natural time-course of PVD as shown by Weber-Krause & Eckardt. These studies classified the vitreoretinal interface by performing slit-lamp examinations, direct funduscopy (Hikichi & Trempe 1994; Yonemoto et al. 1994; Hayreh & Jonas 2004; Hikichi & Yoshida. 2004) or a B-scan ultrasonographic study (Weber-Krause & Eckardt 1997), and the results varied within the different studies especially in patients at a higher age. This diversity might, at least partially, be explained by different modes of examination.

Our results reveal a more frequently attached posterior vitreous cortex in eyes with retinal vein occlusions compared to healthy age-related controls in all analysed age groups and for both types of retinal vein occlusion, except the study by Park et al. (Park & Taek 2010). Despite these obvious differences in all analysed age groups, we found a statistically significant difference for both types of retinal vein occlusion only in the age group 70–79 years. We attribute this result to the small number of eyes that were included in the other age groups.

The strength of the present study is the use of a direct ‘indicator’ of PVD instead of indirect examination methods, such as funduscopy, ultrasound or OCT. Indeed, we found the evaluation of the vitreoretinal interface during triamcinolone-assisted vitrectomy to be the most appropriate procedure to safely classify the posterior vitreous cortex as attached, partially or completely detached. To the best of our knowledge, our study is the first to describe the state of the vitreomacular interface according to the intraoperative findings during pars plana vitrectomy. Our results disclose that an attached posterior vitreous cortex in eyes with both types of retinal vein occlusion occurs more frequently than assumed so far, except the study by Park et al. Thus, our study endorse the suspicion that an attached posterior vitreous cortex might represent a cofactor in the development of retinal vein occlusion.

A limitation of our study is the retrospective study design. Furthermore, we compared our intraoperative findings during triamcinolone-assisted vitrectomy with an ultrasound evaluation of the posterior vitreous adhesion status in healthy eyes as shown by Weber-Krause et al. Nevertheless, we found our approach to be reasonable for the following reasons. (i) We believe that the most appropriate way to classify the posterior vitreous adhesion status can be achieved during vitrectomy staining the posterior hyaloid with triamcinolone. (ii) To the best of our knowledge, there is no data available investigating the posterior vitreous adhesion status during triamcinolone-assisted vitrectomy in healthy eyes owing to ethnic concerns. (iii) Kicova et al. demonstrated in patients with epiretinal gliosis undergoing triamcinolone-assisted vitrectomy that a preoperative performed ultrasound examination showed in more than 80% the identic status of the posterior vitreous cortex as found during vitrectomy (article in press). (iv) Weber-Krause et al. showed in their study that the posterior vitreous cortex stays more frequently attached in healthy eyes than believed so far based on biomicroscopic evaluations. (v) As vitrectomy with RON for CRVO or AVS for BRVO are getting more and more unpopular, it seems to be difficult to obtain more results of the posterior vitreous adhesion status during triamcinolone-assisted vitrectomy in the future. For all these reasons, we found it to be the most appropriate way to compare the status of the posterior vitreous cortex during triamcinolone-assisted vitrectomy in patients with retinal vein occlusions with ultrasonographic controls in healthy eyes. A prospective survey is needed to approve our results.

Several former studies, exploring the vitreoretinal interface in eyes with a history of retinal vein occlusion, have demonstrated the interrelationship between the adhesion status of the posterior vitreous cortex and the ILM of the retina. Takahashi et al. (1997) showed that the incidence of macular oedema was significantly higher in eyes with an attached vitreous (93%) than in eyes with a detached posterior vitreous (41%) in BRVO. Avunduk et al. (1997) deduced that total PVD has a clear preventive effect on persistent macular oedema and retinal neovascularization development in BRVO. Other authors demonstrated that in both types of retinal vein occlusion, there was a higher risk of neovascularization development in eyes where the posterior vitreous was attached, whereas eyes with a complete PVD were at significant lower risk (Trempe et al. 1981; Kado et al. 1990; Hikichi et al. 1995).

The surgical detachment of the posterior vitreous cortex during vitrectomy led to a significant reduction in central macular oedema and to a significant increase in visual acuity in both types of retinal vein occlusion (Tachi et al. 1999; Noma et al. 2010a,b). Comparable results were found in eyes who underwent vitrectomy with peeling of the ILM (Leizaola-Fernandez et al. 2005; Raszewska-Steglinska et al. 2009). Yamamoto et al. compared the surgical results of vitrectomized eyes for induction of a PVD with eyes undergoing vitrectomy and AVS. Both groups showed a significant increase in best-corrected visual acuity and a significant decrease in central foveal thickness. Interestingly, there were no differences found regarding visual acuity and central foveal thickness between both groups, indicating that induction of a PVD has the same beneficial effect than a vitrectomy plus AVS in eyes with a history of BRVO (Yamamoto et al. 2004). Charbonnel et al. showed in BRVO eyes, undergoing vitrectomy, peeling of the ILM and AVS, that in eyes with an initial PVD visual acuity worsened postoperatively whereas eyes with an attached posterior vitreous experienced a statistically significant gain in visual acuity postoperatively. The author suggested as a conclusion that ‘the surgical detachment of the posterior hyaloid could be as important (or more) as the sheatotomy itself’ (Charbonnel et al. 2004). Suzuma et al. (2009) reported on a significant improvement in the retinal thickness and visual acuity after intravitreal r-TPA application for induction of a PVD.

In summary, our intraoperative evaluation confirms previously published results using indirect evaluation techniques demonstrating that the posterior vitreous cortex in patients with CRVO or BRVO remains more frequently attached in comparison to an age-related control group. We suggest that an attached posterior vitreous cortex might be a cofactor in the pathogenesis of retinal vein occlusions. As the induction of PVD plays a beneficial role in the occurrence and the etiopathology of both diseases and as new approaches for a PVD induction are available today (enzymatic vitreolysis), the effect of PVD induction should be investigated in further prospective and randomized studies as well as taken into therapeutic consideration as it may play an essential cornerstone in the treatment strategy for patients with CRVO and BRVO.

Acknowledgement

There was no sponsor or funding organization involved in this study. The author indicates no financial conflict of interest.

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