Structural Changes in Retinal Vein Occlusion: Implications for Functional Outcomes and Visual Field Deficits

Abstract

Objectives

To investigate the relationship between structural retinal changes and functional visual field (VF) deficits in patients with branch retinal vein occlusion (BRVO), aiming to identify potential biomarkers for predicting visual impairment.

Materials and methods

This cross-sectional study included 34 patients with unilateral BRVO who were recruited from two tertiary centers in Greece. Comprehensive ophthalmic examinations were performed, including visual acuity, intraocular pressure (IOP) and imaging studies such as optical coherence tomography (OCT), OCT angiography (OCT-A), and fundus photography. Retinal alterations, including atrophy, edema, hemorrhages and neovascularization, were assessed by two masked graders. Visual field testing was performed using Humphrey perimetry. Logistic regression analyses were employed to examine associations between imaging biomarkers and the presence of VF defects.

Results

Patients included in the present study had a mean age of 69.1 ± 10.6 years and 58.8% of them were females. Visual field defects were present in 26.5% (9/34) of patients. Structural changes such as retinal atrophy and neovascularization were more prevalent in patients with VF defects. Univariate analysis did not identify OCT-A vessel density or central retinal thickness as significant predictors. Similarly, multivariate logistic regression found no statistically significant associations at the 0.05 level, although trends suggested a relationship between structural damage and functional impairment.

Conclusions

Structural retinal changes, particularly atrophy and neovascularization, appear to be associated with VF defects in BRVO. Despite the lack of statistically significant predictors in multivariate models, these findings highlight the importance of comprehensive functional assessments beyond visual acuity. Future advancements in VF testing technologies may enhance early detection and management of functional deficits in BRVO patients.

INTRODUCTION

Branch retinal vein occlusion (BRVO) typically occurs when a venule is compressed at an arteriovenous crossing point near the lamina cribrosa. It is a relatively common condition, with a global prevalence of approximately 23.38 million people, making it four times more common than central retinal vein occlusion (CRVO). Key risk factors for BRVO include advanced age, hypertension, hyperlipidemia, obesity and glaucoma. While BRVO typically affects older adults, it can occasionally occur in younger individuals with underlying blood hypercoagulability disorders, such as hyperhomocysteinemia and antiphospholipid syndrome (1–3).

This vascular event can lead to significant structural changes in the retina, often associated with functional impairments such as visual field (VF) defects and decreased visual acuity. Understanding the relationship between these structural alterations and clinical outcomes is crucial for guiding treatment and predicting prognosis in affected individuals. The BRVO on retinal function is closely tied to the location and extent of venous occlusion, which can lead to a range of visual symptoms, including metamorphopsia, painless central and/or peripheral vision loss (4–6). Clinically, BRVO manifests with various retinal changes such as retinal hemorrhages, cotton wool spots, macular edema, venous engorgement and tortuosity, as well as complications like iris and retinal neovascularization and collateral vessel formation (7).

The use of ophthalmic imaging technologies such as optical coherence tomography (OCT), OCT-A and fluorescein angiography (FA) has unveiled the anatomical and histological impact of vein occlusions on the retina; specific features include areas of capillary non-perfusion and leakage, retinal layer disorganization and oedema. However, while the anatomical effects of BRVO have been well-documented, there remains a notable gap in understanding how these changes translate to patients' visual function (8, 9).

The routine clinical measurement of central visual acuity, though commonly used, offers limited insight into the severity or specific localization of retinal damage caused by BRVO. For example, visual acuity tests may miss significant peripheral VF loss, which can considerably affect daily functioning. Although VF testing can detect peripheral vision deficits and provide a more comprehensive understanding of visual impairment, it is infrequently performed due to its time-consuming and labor-intensive nature (10). This lack of routine VF testing further obscures the full scope of visual dysfunction in BRVO patients, leaving gaps in the assessment of functional outcomes (11).

Understanding the broader impact of BRVO on both central and peripheral vision is essential for improving diagnostic accuracy and tailoring treatment strategies to enhance patient quality of life. To the best of our knowledge, this is the first study that explores the association between specific retinal changes and function changes as expressed by VF perimetry.

METHODS

This cross-sectional study was conducted in two large centers in Greece: the General University Hospital of Patras and the General University Hospital of the Hellenic Red Cross – Korgialenio-Benakio in Athens. The study was approved by the Institutional Review Board and followed the tenets of the Declaration of Helsinki. The purpose of this study was explained to all participants and their signed written consent was obtained.

In total, 34 patients with unilateral BRVO were enrolled. All recruited subjects were Caucasians. Those with co-existing retinal pathology, such as diabetic retinopathy, glaucoma or AMD were excluded. Patients with poor fixation that could potentially affect VF examination testing, those with optical media opacities that could affect image quality as well as patients with severe systemic conditions were excluded.

All 34 study participants underwent a throughout clinical evaluation, including visual acuity, IOP, anterior and posterior segment examination. In addition, all patients underwent the following investigations: OCT imaging of the macular region (Spectralis Imaging platform, Heidelberg Engineering, Germany), fundus photography (Zeiss Clarus 500, Carl Zeiss AG) and OCT-A (RTVue XR Avanti (Optovue, Inc., Fremont, CA). The device has a speed of 70 000 A scans per second and a light source of 840 nm in the scan. Standard 3.0-mm and 6.0-mm HD modes were applied to capture 3.0 × 3.0 mm, 6.0 × 6.0 mm areas, respectively, on the macula centred on the foveola. The FAZ was measured on 3.0 × 3.0 mm scans using an automated tool available on the commercial version of the AngioVue 2.0 software (Optovue, Inc., Fremont, CA, USA), where the built-in algorithm automatically detects and measures the area of FAZ. In cases of incorrect delineation of the FAZ, borders were manually redrawn using the edit tool from the software. Assessment of microvasculature was performed by analyzing vessel density from 6.0 x 6.0 mm HD scans and was calculated as the percentage of area occupied by blood vessels in the selected region. Superficial and deep vessel density (VD; %) were assessed in the macular region.

Two independent masked graders (CGX, GB) reported and analyzed imaging findings and structural alterations, including fundus hemorrhages, retinal edema, retinal atrophy, RPE atrophy, hyperreflective foci and cotton wool spots. Moreover, the presence of IRMA, NVE, NVD, venous beading, shunts and Salus-Gunn sign was noted.

Statistical analysis was performed using SPSS (IBM SPSS Statistics for Windows, Version 22.0; Armonk, NY, USA). Descriptive statistics are presented as mean ± SD. The Shapiro–Wilk test was used to examine normality of all parameter’s distributions. All p values relate to two-sided tests with a significance level of a = 0.05. The sample size for this study was calculated based on an estimated prevalence of 70-80% for mild to moderate VF defects in patients with early-stage BRVO and the inclusion of at least two predictors in the logistic regression model. Following the rule of at least 10 events per predictor, a minimum of 20 events was required. Given the prevalence, a target of 30–40 patients was considered sufficient to meet this criterion while maintaining an acceptable statistical power of 70-80% and a significance level of 0.05.

We employed logistic regression to identify significant predictors of VF defects in patients with branch retinal vein occlusion BRVO. The dependent variable was the presence or absence of VF defects. The independent variables included patient age, hypertension and other relevant clinical factors such as IOP and number of previous injections. The logistic regression model was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between these predictors and the likelihood of developing VF defects. A p-value of <0.05 was considered statistically significant. Optical coherence tomography parameters, such as central macular thickness (CMT) and retinal atrophy, were correlated with the degree of VF depression to explore potential structural-functional relationships.

RESULTS

This study included 34 patients with a mean age of 69.13 ± 10.59 years. A histogram for disease prevalence in different age groups is shown in Figure 1. Disease duration was 3.69 ± 1.99 years.

In total, 58.82% of the study population were women (n=20). The study eye had equal distribution in this study, with 18 right eyes (52.94%) and 16 left eyes (47.06%). Of the study population, 25/34 patients (73.52%) had previously received anti-VEGF injections. Participants’ central retinal thickness (CRT), a variable that had normal distribution according to the Shapiro-Wilk test, was 327.85 ± 94.98 μm (p=0.083). Regarding systemic comorbidities, eight out of the 34 recruited patients (23.5%) had diabetes and hypertension, two (5.9%) only diabetes and 15 (44.1%) only hypertension. The measured IOP during examination was 14.65 ± 2.22 mm Hg. The minimum value was measured at 10 mm Hg and the maximum at 18 mm Hg, without any outliers. The best-corrected visual acuity (BCVA) was 0.30 logMAR (= 20/40).

A VF defect as detected by Humphrey perimetry was present in 9/34 patients (26.5%) (Figure 2). Regarding the VF defects, we calculated ORs for different OCT biomarkers, as shown in Table 1. Results are summarized in Figure 3. The X-axis was log-transformed to enhance data visualization. Supplementary univariate logistic regression analysis did not identify OCT-A vessel density in superficial (p=0.33) and deep network (p=0.42) as well as FAZ area (p=0.246) and CRT (p=0.179) as significant predictors for VF defects.

In multivariate logistic regression analysis, examining factors associated with the presence of a VF defect, none of the chosen predictors showed statistically significant associations with the outcome at the 0.05 level (Table 2).

FIGURE 1.

Histogram for branch retinal vein occlusion (BRVO) prevalence in recruited patients across different age groups

FIGURE 2.

Pie charts of visual defect prevalence in the study population as well as the distribution of generalized and peripheral defects. VF=visual field

TABLE 1.

Odds ratios for fundus and optical coherence tomography (OCT) findings in the study group compared to controls

FIGURE 3.

Forest-plot graph of important biomarkers that favor a visual field defect and their relative odds ratios. VF=visual field; NV=neovascularization; Hg=hemorrhage

TABLE 2.

Multivariate analysis regarding demographic, clinical and imaging biomarkers and their significance in visual field (VF) defects

DISCUSSION

In the present study we evaluated functional impairment in BRVO using Humphrey perimetry and explored its association with structural retinal changes. To the best of our knowledge, this is the first study to systematically assess the structure–function relationship in BRVO with perimetry. Our results suggest that retinal atrophy and neovascularization are associated with the presence of VF defects, even though statistical significance has not been achieved in multivariate models. These findings highlight that structural alterations may contribute to functional impairment beyond visual acuity, underscoring the value of comprehensive assessment in BRVO.

The role of neovascularization as a marker of ischemia and disease chronicity has been well established in previous studies and our findings are in agreement with this body of evidence (12–14). Similarly, retinal atrophy reflects long-term vascular compromise and has been correlated with reduced retinal thickness and poor visual outcomes in BRVO (15). These structural changes appear to parallel the functional deterioration captured by perimetry. Although visual acuity remains the standard clinical metric, it does not fully capture the spectrum of functional deficits, particularly those involving peripheral vision. Our study supports the notion that VF testing provides complementary information that may be clinically relevant in the management of BRVO (16–18).

Comparable observations have been reported in other retinal diseases, where ischemic injury correlates with VF impairment. In diabetic retinopathy, capillary non-perfusion has been shown to affect perimetric outcomes (19), while panretinal photocoagulation, although effective in preventing severe vision loss, frequently induces peripheral VF constriction (20, 21). Similar structure–function associations have also been described in myopic peripapillary atrophy and age-related macular degeneration (22–24). By aligning with these observations, our results suggest that BRVO shares a common pathogenic pathway where structural retinal compromise translates into measurable VF deficits.

This study has several limitations that should be acknowledged. Our small sample size limited the statistical power of the analysis and increased the risk of type II error, which may have explained why some of our emerging trends did not reach statistical significance. In particular, the number of events per variable (EPV) in the logistic regression model was below the ideal threshold, which may have reduced the reliability of regression estimates. Furthermore, our sample selection was confined to a specific patient cohort recruited from two tertiary centers in Greece, which may limit the external validity and generalizability of our findings. The cross-sectional design also prevents conclusions regarding causality or disease progression.

Future studies should aim to validate these findings in larger multicenter cohorts with sufficient statistical power to confirm structure–function associations. Longitudinal designs would further clarify the temporal relationship between structural damage and functional decline. Finally, the integration of novel technologies such as microperimetry and virtual reality–based field assessment may improve the feasibility of functional testing in clinical practice, helping establish VF analysis as a routine tool in BRVO management (25–32).

CONCLUSION

In summary, our study provides preliminary evidence that retinal atrophy and neovascularization are associated with functional impairment in BRVO as expressed by visual field defects. While limited by sample size and statistical power, these findings underscore the potential role of VF testing in complementing standard clinical evaluations and guiding individualized patient care.

Financial support

none declared.

Conflicts of interest

none declared.