Assessing the presence of vascular endothelial growth factor (VEGF) in tears could be a noninvasive way to determine the severity and progression of age-related macular degeneration.
According to a recent study published in Science Reports, the severity and progression of age-related macular degeneration (AMD) could be identified through the level of vascular endothelial growth factor (VEGF) found in the tears of patients with AMD. The objective of the study was to evaluate and compare VEGF levels in the tears and blood of patients with AMD.
A comparative cross-sectional study was conducted in Hospital Universiti Sains Malaysia, a tertiary hospital located in Malaysia, from October 2016 to September 2018. Patients 45 years and older with AMD were recruited for this study, and a control group comprised individuals 45 years and older who did not have any features of AMD.
Early AMD was defined as any retinal drusen or pigmentary changes. Late AMD was defined as the presence of geographic atrophy (GA) or neovascular features.
Patients were excluded from this study for reasons including previous laser photocoagulation, recent intraocular surgery within 6 months of the recruitment period, or prior history of intraocular disease such as uveitis and chorioretinitis. Patients with a history of central serous chorioretinopathy or cystoid macular edema of any cause were excluded, as were patients with uncontrolled hypertension, diabetes, or other medical problems that could cause high circulating blood VEGF levels related to systemic hypoxia and chronic inflammation.
A total of 168 patients were screened: 128 patients with AMD and 40 controls. Among the patients with AMD, 70 had early AMD, 44 had late AMD, and 14 had early AMD in 1 eye and late AMD in another. Of the screened patients, 108 were used in this study: 36 with early AMD, 36 with late AMD, and 36 in the control group.
Demographic data, smoking status, history of alcohol consumption, and systemic illness were obtained from patients through direct questioning and checking medical records. An ophthalmic assessment was performed by the primary investigator. All participants were required to have their fundus photographed and were split into groups with early and late AMD based on those pictures. All blood and tear samples were collected by a designated staff member who was not involved in the study.
To compare VEGF levels among the early AMD, late AMD, and control groups, the analysis of covariance test was used, adjusted for age, sex, smoking status, alcohol use, and systemic illness. The Bonferroni post hoc test was used to compare tear and blood serum VEGF levels using simple and multiple linear regression analyses.
The mean (SD) age of the enrolled subjects was 64.3 (8.3) years. A significant difference in the mean (SD) age was observed among the groups: The control group was youngest at 57.6 (8.1) years, followed by the early AMD (66.6 [7.1] years) and late AMD (68.7 [5.1] years) groups. Of the 108 patients, 85.2% were Malay and the remaining 14.8% were Chinese. Early AMD was more common in women (58.3%) and late AMD was more frequent in men (61.1%).
There were 16 participants who were active smokers, 6 of whom were in the early AMD group and 6 of whom were in the late AMD group. There were 8 participants who had a history of alcohol consumption, 6 of whom were in the late AMD group. Hypertension was the most common comorbidity among participants (61.1% in late AMD, 52.8% in early AMD, and 44.4% in control). There were significant associations between AMD and smoking, alcohol consumption, and chronic kidney disease.
The late AMD group showed the highest mean (SD) level of tear VEGF (292.88 [73.89] pg/mL), followed by the early AMD (161.15 [36.73] pg/mL) and control (117.56 [16.66] pg/mL) groups. The mean (SD) level of VEGF in blood serum was also the highest in the late AMD group (260.10 [76.47] pg/mL) compared with the early AMD (154.90 [39.09] pg/mL) and control (152.11 [36.08] pg/mL) groups.
Significant mean differences in tear VEGF levels between late and early AMD, between late AMD and control, and between early AMD and control were found after Bonferroni post hoc analysis. There was also a significant mean difference in blood VEGF levels between late and early AMD and between late AMD and control, but there was no significant difference between the early AMD and control groups.
The observed area under the receiver operating characteristic curve (AUC) was excellent for tear VEGF (0.996). An excellent AUC (0.900) was also observed for blood VEGF, but the authors noted that there were diagonal segments in that curve, which means the statistics may be biased.
Age and blood VEGF level were identified as significant factors associated with tear VEGF level. The significant factors associated with blood VEGF levels were smoking, diabetes, and tear VEGF level. There was a significant linear and strong correlation between tear and blood VEGF levels among patients with AMD.
There were some limitations to this study. The study had a single-center design and had unequal racial distribution, which makes it hard to generalize these results to other world populations. Residual confounding is still possible despite strict selection criteria given that AMD is a disease common in older adults who often have comorbidities. The researchers were also unable to detect any difference in the VEGF levels of patients with the 2 different forms of late AMD due to the limited number of patients with GA.
The study authors wrote that their findings revealed a significantly higher level of VEGF in the tears of patients with AMD.
“The tear VEGF level has high sensitivity and specificity, and is significantly related to the severity of AMD, whilst serum VEGF level is nonspecific and nonpredictive of AMD severity. Thus, VEGF level in the tears may be used as a noninvasive biomarker for AMD progression,” the researchers concluded.
Shahidatul-Adha M, Zunaina E, Aini-Amalina MN. Evaluation of vascular endothelial growth factor (VEGF) level in the tears and serum of age-related macular degeneration patients. Sci Rep. Published online March 15, 2022. doi:10.1038/s41598-022-08492-7