Retinal vein occlusion (RVO), including both branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), is a common sight-threatening retinal vascular disorder with significant morbidity [1]. Major causes of vision loss include macular edema and neovascularization with secondary vitreous hemorrhage and/or neovascular glaucoma [1].

Open-angle glaucoma is a progressive retinal ganglion cells degeneration characterized by a specific pattern of visual field and optic nerve head damage [2,3]. Clinical trials confirmed the importance of intraocular pressure (IOP) in the development and progression of open-angle glaucoma, even if evidence suggests the existence of ocular and systemic factors, in addition to IOP, that can be responsible of this development and progression [4].

An association between primary open angle glaucoma (POAG) or ocular hypertension (OHT) and RVO has been found in many studies [5]. Many authors have underlined this association on the basis of different etiopathogenetic theories. In their review, Sonnsjio and Krakau [6] observed an high incidence of RVOs, both central and branch, in a wider group of patients suffering from POAG. According to these authors, the little flame shaped peripapillary hemorrhages, usually seen in patients suffering from glaucoma, correspond to little vein occlusions. The coexistence of these signs suggests a common aetiology, a hypothesis that has always gained great popularity supported by the vascular theory at the basis of the glaucoma damage [7]. Beside the vascular component, many studies have suggested that alterations of the normal anatomy of the optic nerve head could cause a site particularly susceptible to the vein occlusion.

So it can be useful to analyze the optic disc morphologic features in subjects suffering from a retinal vein occlusion, also combined with the diagnosis of primary open-angle glaucoma, with the aim to understand if some anatomic features are associated or not to a determinate occlusion site.

Purposes of our study are:

• to evaluate morphology of the optic disc in eyes suffering from RVO also combined with the diagnosis of POAG;
• to search possible differences in the optic disc parameters studied through the imaging supplied by the HRT II (Heidelberg Retina Tomograph – Heidelberg Engineering – Germany) between the fellow eyes suffering from RVO (not suffering from glaucoma) and a control group of healthy eyes; between the different occlusion sites and finally to study optic disc morphology in the group of patients with papillary edema;
• to define if some morphologic features of the optic disc can or not suggest an etiopathogenetic relation with the retinal vein occlusions considering both the occlusion site and the POAG presence.

The study has been carried out on a group of patients with retinal vein occlusion diagnosis sent to our Ophthalmologic Clinic in the last 5 years.

The study has been conducted with ethical standards, it followed all principles approved in the Declaration of Helsinki and its later amendments, it has been conducted with written informed consent of all the subjects.

48 consecutive patients with diagnosis of unilateral RVO have been included. 18 among them presented a positive clinical history for POAG.

Patients were classified as having POAG when they had a typical glaucomatous visual field, possibility of typical abnormal optic nerve head (before RVO diagnosis), open angle at gonioscopy, IOP > 21 mmHg with no treatment and no clinically apparent secondary cause for their glaucoma [2,3]. Visual fields have been assessed by an Humphrey Field Analyzer 750 (HFA, Humphrey, Inc, San Leandro, CA, USA), 24-2 SITA (Swedish Interactive Threshold Algorithm) standard. A glaucomatous visual field defect was defined as:

• three adjacent points depressed by 5 dB, with one of the points depressed by at least 10 dB or
• two adjacent points depressed by 10 dB or
• 10 dB difference across the nasal horizontal meridian in two adjacent points.

None of the points could be edge points unless immediately above or below the nasal horizontal meridian. In addition, visual field testing was considered reliable only when false-negative and false-positive responses were less than 30% and fixation losses were less than 20% on HFA.

Of the 48 patients included in the study, in 30 patients we diagnosed unilateral RVO and in 18 patients we diagnosed unilateral RVO and positive clinical history of POAG. We selected a control group of 25 healthy subjects (analysis of 25 eyes), age and sex matched to the group of patients with unilateral retinal vein thrombosis without POAG.

Occlusions of the venous drainage of the retina classically have been divided into CRVO and BRVO. More recently RVOs that involve approximately half of the retina have been recognised as a distinct type of RVOs, but there is still confusion as to wheter this group are variants of BRVO or CRVO. We decided, according to Beaumont [8], to define three anatomic occlusion sites on the basis of the fluorescein angiography aspect: arteriovenous crossing (AV-RVO), optic cup (OC-RVO) and optic nerve (ON-RVO). In case of occlusion at the level of an arteriovenous crossing or of the optic cup, the point where the vein calibre changes, is well visible, unless it is obscured by hemorrhages, exudates or retinal edema. The occlusions localized at the optic nerve level have been identified by the fact that the vein enters in a dilated form into the nervous fibers. They have been subdivided in two categories, on the basis of the presence (Optic Nerve Head Swelling; ONHS-RVO) or not (Non Optic Nerve Swelling; NONHS-RVO) of optic nerve head (ONH) edema. The ONH edema is defined as a swelling of the optic nerve compared to the surrounding retina, associated to edema, exudates and hemorrhages. The simple presence of blurred margins without disc swelling was not considered a sufficient sign to include the case in the group with ONH edema.

We excluded from our study those uncommon retinal occlusions without a precise anatomic reference point, defined “no site” RVO (7 patients). We excluded also: patients that had ocular surgery or trauma in the previous year before the study; patients that had ocular infections within 3 months before the study; pregnant or nursing women; inability to understand and/or complete the informed consent and the study; patients less than 18 years old.

All patients have been subjected to:

• complete eyes examination with measure of the intraocular pressure with Goldmann Applanation Tonometer (GAT). The IOP measure was carried out between 8:00 a.m. and 10:00 a.m.;
• fluorescein angiography test through H.R.A. (Heidelberg Retina Angiograph);
• morphologic test of the optic nerve head through HRT II (Heidelberg Retina Tomograph II).

The HRT II is a confocal laser scanning microscope which allows the acquisition and the analysis of three-dimensional images of the retinal surface at multiple focal planes. The laser source used for the scanning is a diodes-laser with wave length of 670 nm. Using confocal scanning principles, a 3-dimensional topographic image is constructed from a series of optical image sections at consecutive focal planes. The stereometric analysis of the images gives a set of parameters which describe the optic nerve head. Iester et al. [9] noted a statistically significant correlation (Pearson's r, p < 0.001) between cup area, cup/disc area ratio, rim area, rim volume, cup shape measure, and retinal nerve fibre layer cross-section area with Humphrey’s visual field (Carl Zeiss Meditec, Dublin, California) mean deviation (MD) and corrected pattern standard deviation (CPSD). Multiple linear regression analysis demonstrated that rim area was the most important predictor of mean deviation and pattern standard deviation (PSD).

For the group of patients suffering from optic nerve vein occlusion with papilla edema (ONHS-CRVO) we have used the prominence analysis protocol of the HRT software because the papilla swelling on the retinal plane doesn’t allow the use of the standard processing.

A paired t test between RVO and RVO associated with POAG analyzed differences in the occlusion site frequency. The comparison among the HRT parameters has been obtained with Student’s t test and repeated-measures of ANOVA. The value of p < 0.05 was considered statistically significant.

Of the 48 patients included in the study;

• in 30 patients we diagnosed unilateral RVO (30 eyes), 17 males (56,6%) and 13 females (43,3%) with mean age of 62,3±10,9 years. The average IOP of this group was equal to 15,5±1,8 mmHg (GAT).
• in 18 patients we diagnosed unilateral RVO and positive clinical history for POAG, 10 males (55,5%) and 8 females (44,4%), mean age of 68,5±7,4 years. The average IOP of this group was 18,8±2,0 mmHg (GAT).

We selected a control group of 25 healthy subjects (analysis of 25 eyes), 15 males (60%) and 10 females (10%) with average age 62,9±4,7 years, age and sex matched to the group of patients with unilateral retinal vein thrombosis without POAG. The average IOP of this control group was 15,1±1,7 mmHg.

The features of the patients included in the study have been summed up in Tables 1 and 2.

Comparison of HRT Parameters in Relation to Occlusion Sites

We studied the correlation between the HRT parameters in relation to the occlusion site (Tables 4 and 5).

In Table 4 we note a statistically significant difference (p<0.05) in four parameters in the comparison between the OC group and the AV group: Cup Area, Cup/Disc Ratio, Rim Volume and Cup Shape Measure. We note a statistically significant difference in seven parameters comparing the OC group and the NONHS group: Cup Area, Cup/Disc ratio, Height Variation Contour, Rim Volume, Cup Shape Measure, Mean RNLF thickness and RNFL Cross Sectional Area (CSA).

In Table 5 we note a statistically significant difference similar to the previous one concerning the comparison between the OC group and the AV group. We note a significant difference in five parameters in the comparison between the OC group and the NONHS group: Cup Area, Cup/Disc ratio, Rim Volume, mean Cup Depth and Cup Shape Measure.

In Figs. (1, 2) the frequency of the occlusion site is depicted in the groups without or associated with POAG, respectively.

Fig. (1). Frequency of the occlusion sites of RVO group without POAG.

Fig. (2). Frequency of the occlusion sites of RVO group with POAG.

Our study has got several limitations, particularly a small group of patients. This study will be widened in the involved patients number, using also other methods to evaluate disc morphology.

Our study highlighted how fundamental is to subdivide and classify the RVOs on the basis of the occlusion site. The particular anatomic site of the occlusion determines which factors, like a pathology of the vascular wall and the IOP, have a significant effect on the wall of the vein in that point. While the more frequent occlusion site is the arteriovenous crossing in the non glaucomatous eyes suffering from RVO, the occlusion is localized at the level of the optic disc excavation in half of the glaucomatous eyes of this study. In these occlusions we have observed the presence of several altered HRT morphologic parameters beside a higher IOP level. For this reasons an increased IOP and the glaucomatous cup can be associated with the forms defined OC-RVO.

In the RVO group a statistically significant difference was found (p<0.05) in four parameters in the comparison between the OC group and the AV group: Cup Area, Cup/Disc Ratio, Rim Volume and Cup Shape Measure, in seven parameters comparing the OC group and the NONHS group: Cup Area, Cup/Disc ratio, Height Variation Contour, Rim Volume, Cup Shape Measure, Mean RNLF thickness and RNFL Cross Sectional Area (CSA).

In the RVO with POAG group we note a statistically significant difference similar to the previous one concerning the comparison between the OC group and the AV group. We note a significant difference in five parameters in the comparison between the OC group and the NONHS group: Cup Area, Cup/Disc ratio, Rim Volume, mean Cup Depth and Cup Shape Measure.

In conclusion, the classification on the basis of the occlusion site could positively contribute in lowering the confusion that may arise from the classical subdivision between central vein and branch occlusions, helping in reducing the erroneous diagnosis, creating a logic support on which research on causal factors and the possible associations with the risk factors can be based on.