Assessment of age-related macular degeneration (AMD) risk factors in AMD patients and healthy people over 40 years old in the Polish population

INTRODUCTION

The main cause of blindness in Western populations is age-related macular degeneration (AMD) [1]. It is also the most prevalent retinal disease in this part of the world [2]. Globally, the number of AMD patients is predicted to increase from approximately 196 million in 2020 to 288 million in 2040 [3]. Recently, major improvement has been made in the compre-hension as well as the treatment of this eye condition. Especially, intravitreal injections of antiangiogenic agents make it pos-sible to stabilize or even reverse progression of neovascular AMD. However, early diagnosis is crucial for their efficacy [4]. As a consequence, there is a need for a test which will enable doctors to determine high risk populations, observe them and start treatment as soon as possible. Therefore, the aim of our study was to assess the prevalence of AMD risk factors in the Polish population of AMD patients and healthy individuals over 40 years of age. Thus, after analyzing articles on that topic, the decision to use the Simplified Thea AMD Risk-Assessment Scale (STARS) questionnaire was made. STARS is simple, short, translated into Polish and self-administered [5].

MATERIAL AND METHODS

The STARS questionnaire was performed on people aged over 40 years old including self-reported AMD patients in the outpatient clinics in University Clinical Center Prof. Kornel Gibiński of the Medical University of Silesia in Katowice and in Provincial Specialist Hospital Blessed Virgin Mary in Czestochowa as well as through an online survey posted on social media with a short invitation. The questionnaire contained 14 questions about demographics and AMD risk factors stated in STARS – Figure 1A (in Polish) and Figure 1B (in English). We provided every interviewee with the opportunity to learn their STARS score with details on which modifiable factors influenced the result. The data were collected from October 2019 to October 2020 and analyzed anonymously in the program Statistica 13.3. A total of 233 questionnaires were obtained. Statistical analyses included descriptive methods as well as association and significance of difference methods. Chi-square tests were performed for the categorical data. When class size was less than five, the exact Fisher’s test was used. For quantitative data the Shapiro-Wilk test was used to assess data distribution normality. We applied Mann-Whitney U-test test to compare the differences among the groups because they were found to be non-normally distributed. A p-value of 0.05 was considered statistically significant.

RESULTS

Data were obtained from 233 adults. Of these 65% were female (F). Women accounted for 61% of patients and 67% of the healthy group (p = 0.35). 54% of people were in the age range 40 to 64, 23% in the range 65 to 74 and 23% were over 74 years old. Ninety cases of AMD were reported. AMD was observed more often in adults over 65 years old (p < 0.001). All respondents were of Caucasian descent. Self-reported AMD family history prevalence was 10%, 11% in AMD patients and 9% in people without this disease (p = 0.6).
Mean body mass index (BMI) was 26. It did not differ significantly between the groups (p = 0.07). Sixty percent of partici-pants had abnormal BMI indicating overweight (AMD: 52%, healthy: 39%) or obesity (AMD: 16%, healthy: 16%). One percent of participants in both groups were underweight.
Current, former ≤10 years, former >10 years and never smokers made up respectively 16%, 9%, 39% and 37% of the AMD group and 11%, 8%, 20% and 61% of the no AMD group (p = 0.009). Smoking was more common in people with AMD (p = 0.004). AMD patients were more often diagnosed with hypertension (p < 0.001) compared to adults without AMD. People re-ported myocardial infarction in 9% in the AMD and 3% in the healthy group but the difference was not statistically significant (p = 0.08). Also, hypercholesterolemia (p < 0.001) and arteriosclerosis (p < 0.001) were correlated with AMD.
Phacoemulsification procedures had been performed more often in the AMD patients compared to the other group (p < 0.001). However, it was apparent in the 40-64 years of age group (p < 0.001) but not in the older age groups (p > 0.05). There were no statistical differences in occurrence of myopia, hyperopia and no refractive errors between the groups (p > 0.05).
STARS median score in the overall group was 9.5 points (0-30). Median score in the AMD group was 14 points and in the no AMD group 5 points (p < 0.001). The distribution between low, moderate and high risk groups was respectively 32%, 60% and 13% in the AMD group, 75%, 24% and 1% in the no AMD; and the difference was statistically significant (p < 0.001).

DISCUSSION

To our knowledge, this is the first published study on STARS or different questionnaires related to AMD risk factors used in the Polish population. Other recent studies which involved Polish AMD patients concerned analysis of antioxidative en-zymes related to AMD risk development.
A significant decrease in those enzymes might lead to damage of photoreceptors and retinal pigment epithelium cells and had an important role in AMD progression [6].
The selection as well as the score of each risk factor included in STARS derived from research conducted on approximately twelve thousand Italian patients and validated on a population of over six thousand French [5].
The epidemiological data have been inconsistent regarding the sex-specific risk of AMD. Sex was not significantly associ-ated with AMD in our study. Many studies including meta-analysis [7] have produced similar results to ours in terms of the correlation between sex and AMD [8, 9]. On the other hand GlobalData epidemiologists found that 65.76% of diagnosed in-cident cases of AMD occurred in women while men accounted for 34.24% in the seven major pharmaceutical markets [10]. An explanation for this phenomenon could be the longer life expectancy of women compared to men, which makes them more likely to acquire age-dependent diseases. However, in this Korean cross-sectional study male population was at a greater risk for late-AMD [11]. AMD prevalence rose with the increasing age of the respondents and it was observed more often in adults over 65 years old in our research. Those findings were confirmed by Weih et al. [12] and Klaver et al. [13].
We did not deeply examine race as a risk factor of AMD because all our respondents were Caucasian. Nevertheless, earlier research – by Lazreg et al. [14] indicated that North-African ethnicity was associated with this disease.
In contrast to a previously cited article by Chakravarthy et al. [7], in our study self-reported AMD family history was simi-lar in AMD and no AMD groups despite being one of the risk factors. The possible explanation is that healthy respondents with family members with AMD could have been more interested in our research than people who have never heard about it.
In our study, the difference in the presence of AMD between the BMI groups – underweight, healthy, overweight, obese was not significant. However, the majority – 60% of our respondents were overweight and according to other research – by Clemons et al. [15] the association with AMD was only made with obese patients. Furthermore, physical activity tended to decrease the risk of AMD progressing – Seddon et al. [16]. Therefore, obesity was considered as the modifiable AMD risk factor and losing weight was also recommended.
Chakravarthy et al. [7] and Joachim et al. [17] classified smoking cigarettes currently and in the past as risk factors of AMD. Those findings were proved in the combined analysis based on three similar populations from North America, Europe and Australia – Smith et al. [18]. Our survey supported these results but we did not analyze smoking pack-years like Clemons et al. [15]. Consequently, both AMD patients and people in the risk group for developing AMD were strongly advised against smoking and quitting is recommended [19].
In our study, hypertension (HT) was correlated with AMD incidence. The resembling findings were from the Age-Related Eye Disease Study Research Group [20]. AMD patients with hypertension showed decreased choroidal blood flow in compar-ison to those without history of HT in this study [21]. The impaired choroidal perfusion might result in insufficient elimina-tion of degradation products from retinal pigment epithelium and the formation of drusen. Reduced blood flow contributes to hypoxia and promotes vascular endothelial growth factor (VEGF) upregulation and neovascularization [22].
Accordingly the prevention of hypertension should be considered as an important public health issue. Additionally, the pres-ence of HT is contemplated to reduce the potential for functional improvement caused by the application of anti-VEGF ther-apy in neovascular AMD [23-25] though some studies did not find that correlation [26, 27]. Further research is needed to evaluate the impact of methods of HT treatment on visual outcomes of AMD patients.
Myocardial infarction was more common in the AMD group but the result was not statistically significant probably be-cause of the small group size. Similar results involving cardiovascular diseases were obtained by Chakravarthy et al. [7].
Increased level of total serum cholesterol was correlated with AMD incidence. Similarly to previous research – by Tan et al. [28] and Tomany et al. [29]. That relationship was not readily explained. Arteriosclerosis was correlated with AMD inci-dence. There were no clear results in the literature about that topic. However, arteriosclerosis is obviously connected to hy-percholesterolemia.
Phacoemulsification was more common in AMD patients but only in the 40-64 age group. The findings from epidemiolog-ical studies regarding these associations have been inconsistent. Studies by Chakravarthy et al. [7] and Freeman et al. [30] supported this association. It could reflect shared risk factors and the fact that both are diseases that affect the aging eye, there is concern that surgery may predispose the operated eye to the development of neovascular AMD. However, there are pooled reports which do not support this association [31]. These results also showed no clear effect of cataract surgery on the risk of progression to advanced AMD [31].
Despite the fact that in our study there were no significant differences in occurrence of myopia, hyperopia and no refrac-tive errors between the groups, there was research which found that refractive error, especially hyperopia, was correlated with AMD [32]. Several possible explanations have been proposed over the past few decades. Hyperopic eyes are believed to have increased scleral rigidity, which leads to impairment of the choroidal blood flow in the eyes with shorter axial length [33, 34]. It is possible that decreased flow contributes to the neovascularization, drusen formation, poorer thermoregulation and higher susceptibility to oxidative stress [33, 34]. There could be genetic link between hyperopia and AMD. In this Korean study there was a statistically significant negative correlation of myopia with any AMD in the female group [35]. Myopic eyes are known to have a less rigid sclera compared to hyperopic eyes [34]. Decreased concentration of VEGF in myopic eyes can cause de-creased angiogenesis [36]. A further possible explanation is the use of spectacles by myopic patients resulting in reduced exposure to ultraviolet rays from sunlight, a risk factor for AMD [37].
In our study, the STARS median score was higher in the AMD group than in the no AMD group similarly to Delcourt et al. [5]. What is more, the difference of the distribution between low, moderate and high risk groups was statistically significant. Therefore, it could be useful in determining the high risk population of this disease in the Polish population.
Additionally, all interviewees had the possibility to find out their STARS score as well as discuss the possible ways to im-prove their health and reduce AMD risk or its progression.
Our study has some limitations. Data were self-reported by the participants. Therefore the presence of AMD was not veri-fied. Group size could have played a role in the results.

CONCLUSIONS

Most AMD risk factors included in the STARS questionnaire occurred more often in AMD patients in our study. Therefore, it could be useful in determining the high risk population of this disease. Regrettably, in spite of getting a low risk score in STARS, there was still a possibility to develop this eye condition. Moreover, a wider education about healthy lifestyle which influences AMD risk is necessary. Finally, risk factors and causes of AMD require further attention and investigation.

ACKNOWLEDGMENTS

We would like to thank Dr Katarzyna Grzybek-Oleś, the ophthalmologist in Provincial Specialist Hospital Blessed Virgin Mary in Czestochowa and Prof. Ewa Mrukwa-Kominek, the Chair of the Department of Ophthalmology, Medical University of Silesia in Katowice, for the ability to collect questionnaires from AMD patients in their respective institutions.

DISCLOSURE

The authors declare no conflict of interests.

References