Evaluation of the Factors Affect Vision Related Quality of Life and Level of Depression in the Patients with Age-Related Macular Degeneration

Abstract

Purpose: To determine the effect of age-related macular degeneration (AMD) on Vision Related Quality of Life (VRQOL) and depression level.

Method: 108 patients followed up or newly diagnosed with AMD in Ophthalmology Clinic at Gaziantep University had been included in this cross-sectional study. The Turkish version of the National Eye Institute Visual Functioning Questionnaire-25 (NEI VFQ-25) and Geriatric Depression Scale-15 (GDS-15) were assessed to the patients. The results of these two questionnaires were evaluated according to the demographic findings of the patients, the severity, and treatment procedures of the AMD.

Results: The scores obtained from subscales varied from 43.48 for ‘Near activities’ to 81.48 for ‘Color vision’ subscales in NEI VFQ-25 test. According to the results of GDS-15 questionnaire, we detected that 62.9% of all the patients were compatible with depression when the cut-off value was accepted as ‘5’. Intravitreal anti-VEGF injection as a treatment procedure had no correlation with depression (p>0.05).

Conclusion: The lowest and highest scores had been obtained in ‘Near activities’ and ‘Color vision’ respectively. The patients with AMD had higher depression levels. The female AMD patients had higher rates of depression and lower visual acuity levels.

Introduction

 Age-related macular degeneration (AMD) is a progressive neurodegenerative disease affecting the central retina and causing loss of central vision. Age-related macular degeneration is commonly seen in patients over 60 years old and the prevalence of the disease increases with aging[1]. The best-known risk factors are age, tobacco, obesity, female gender, ultraviolet light[2, 3]. AMD is the most common retinal disease in Western countries[4]. According to Beaver Dam Eye Study incidence of early or late-stage AMD in 43-54 years old is 3.9%, but in people older than 75 years old this incidence is %22.8[1].

The most common signs of AMD are distorted vision, metamorphopsia, central scotoma, decrease in visual acuity, and decrease in contrast sensitivity. There are two basic subtypes of AMD: non-neovascular or dry AMD and neovascular AMD (nAMD) or called as wet AMD[5]. Dry AMD can be presented with drusen, retinal pigmentation abnormalities, and geographic atrophy in the macula. Dry AMD is much more common and the decline in visual acuity is more slowly compared with neovascular AMD[5]. Wet AMD is generally characterized by choroidal neovascularization, with the formation of abnormal new blood vessels. Hence, macular edema and hemorrhage can be the reason of the acute central vision loss. Up to date, there is no treatment procedure that can reverse completely the effects of AMD.  The early stages of AMD are managed by modifying the risk factors. In the intermediate stage AMD, antioxidant and mineral supplementation can be suggested [6, 7]. Advanced stage AMD with choroidal neovascularization commonly managed with intravitreal injection of anti-vascular endothelial growth factor inhibitors (anti-VEGF)[8].

NEI VFQ-25 questionnaire was developed by Mangione et al. in the USA[9]. It is a shorter form of NEI VFQ-51 which contains 51 items. NEI VFQ-25 questionnaire is for evaluating the quality of life in patients with chronic eye diseases in a wide age range. The first part of the questionnaire aims to measure the general health and vision, the second part measures the difficulties in performing daily activities. The validity and reliability of this questionnaire in the Turkish population were assessed by Toprak et al.[10]. Moreover, Yesavage et al. developed the first GDS questionnaire which contains 30 questions[11]. Then, to shorten the questionnaire time GDS-15 was started to be used. Its validity and reliability of GDS-15 in the Turkish population were assessed by Durmaz et al.[12]

Visual impairment is one of the leading causes of disability in old ages. Additionally, depression is one of the most important reasons for morbidity and a decline in the quality of life. Herein, we presented the factors that can affect the vision-related quality of life and severity of depression level in patients with AMD by using NEI VFQ-25 and GDS-15 questionnaires.

Method

In this cross-sectional study, we recruited 108 patients being followed up or recently diagnosed with AMD in Ophthalmology Clinic at Gaziantep University, Turkey between October 2019, and January 2020. The patients with cataract, glaucoma, optic neuropathy, diabetic retinopathy, amblyopia, uveitis, degenerative myopia, or another ocular pathology diminish visual acuity or quality of vision were excluded. In addition to that, the patients did not have enough cognitive capacity to understand and answer the questions were excluded. All attendees left a written consent form before taking part in this study. We obtained ethical approval from Gaziantep University Clinical Research Ethics Board. 

NEI VFQ-25 contains 12 subscales: general vision, difficulty with near-vision activities, difficulty with distance-vision activities, limitations in social functioning, role limitations, dependency on others, mental health symptoms, driving difficulties, limitations with peripheral and color vision, ocular pain, and general health The score produced for the NEI VFQ-25 converts the pre-coded numeric values of items to a score from 0 to 100. Higher scores reflect better quality of life[9]. Although Marella et. al suggest that the VFQ-25 is a better performing instrument when split into visual functioning and socioemotional scales in low vision group using Rash model to determine the validity of the VFQ-25, Revicki et. al defined that the VFQ-25 has a good reliability and construct validity as a measure of vision related functioning outcomes in patients with AMD[13, 14]. The patients have taken ‘0’ or ‘1’ point for each question in GDS-15 according to their answers and the total scores were calculated. The cut-off value was accepted as ‘5’ for depression in the GDS-15 test.

All the patients in the present study were given a complete ocular examination, including best corrected visual acuity (BCVA), slit-lamp examination, Goldmann applanation tonometry, dilated posterior segment examination. NEI VFQ-25 and GDS-15 questionnaires were assessed to the patients by the same doctor (LD). We recorded the age, gender, marital status of the patients. The duration of AMD, treatment procedures, and the number of anti-VEGF injections were also recorded, and the relationship between these parameters and NEI VFQ-25 and GDS-15 questionnaires was evaluated. 

Statistical Methods

Data were analysed by IBM using SPSS for PC, version 25 (SPSS Inc., Chicago, IL, USA). Descriptive statistics were used to determine the distribution of clinical and demographic characteristics. The t-test was used to compare mean values between the groups. We used the Kolmogorov-Smirnov test to assess the normality of distribution. We employed the Spearman approach to analyse the correlation between the NEI VFQ-25 subscales scores. The existence of statistical significance was established at a p-value of < 0.05, and the confidence interval was taken to be 95%.

Results

108 patients completed the NEI VFQ-25 and GDS-15 questionnaires. The mean age of the patients was 72.96 (±6.6) years. 48.14% (52/108) of the participants were female. Of the patients, 88 (81.4%) were married and, the others (18.6%) were single. 70.4% (76/108) of the participants reported their income level as middle, and 24.1% (16/108) of the patients reported as low. The patient’s characteristics are summarized in Table 1. The mean follow-up time of the patients was 4.16 ± 2.42 years. Of the patients 61 had wet AMD and 47 had dry AMD findings. At least one-time intravitreal injection treatment procedure had been applied to 58 patients during the follow-up time. The scores obtained from NEI VFQ-25 questionnaire varied from 43.48 for ‘Near activities’ to 81.48 for ‘Color vision’ subscales. We are unable to evaluate ‘Driving difficulties’ subscale, hence many of the patients were not drivers even before onset the disease. The mean binocular best-corrected visual acuity (BCVA) (according to Snellen chart) of all patients was 0.26 ± 0.19. The ratio of the patients has visual acuity worse than 20/200 was 51.9% (27/52), and 28.5% (16/56) in females and males, sincerely. 

Although the binocular best-corrected visual acuity (BCVA) was significantly lower in female gender (table 5), there was not statistically difference in NEI VFQ-25 subscale scores between two gender groups (p>0.05). The scores obtained from NEI VFQ-25 subscales except ‘Ocular pain’ and ‘Vision specific dependency’ were negatively correlated with aging (p<0.05).

According to the results of the GDS-15 questionnaire, we detected that 62.9% (68/108) of the patients compatible with depression. In our study, the depression ratio in females was significantly higher than males (p<0.05) (table 3). When considering the presence of depression, the patients with depression had obtained lower scores from all the subscales of NEI VFQ-25 questionnaire, and we found statistically significant differences in subscales of NEI VFQ-25 except ‘Ocular pain’, ‘Vision specific role difficulties’, ‘Color and Peripheral’ vision subscales between the patients with depression and non-depression (table 4). 

We had applied the intravitreal anti-VEGF injections to 58 of the patients at least one time in during their follow-up time. The range of the injection numbers was quite wide (1-41).  We had separated the patients into two separate groups depending on whether the intravitreal injection was applied (injection and non-injection groups). There were no significant differences between the two groups in terms of subscales of the NEI VFQ-25 questionnaire (p>0.05). According to the depression scale, we noticed that the depression ratio was statistically significantly higher in the non-injected group (p<0.05) (table 6). 

66 patients had at least one known systemic disease. The most common diseases were systemic hypertension and diabetes mellitus, but these patients did not have diabetic or hypertensive retinopathy signs. The only scores in the ‘General health’, ‘Near-distance activities’, and ‘Vision specific role difficulties’ subscale scores were statistically significantly lower in patients with systemic disease (p<0.05). Also, we had not found any effect on the subscales of the NEI VFQ-25 test by marital and income status of the patients (p>0.05).

Discussion

Age-related macular degeneration (AMD) is a chronic, progressive disease and one of the most important reasons for irreversible visual impairment over 60 years old[15]. Older patients with impaired vision have more difficulties in daily activities for maintaining an independent lifestyle. With the advancing age, comorbidities, and loss of central vision by AMD, the quality of life diminishes. The relation between aging and depression is a well-known fact[16]. Depression becomes an inevitable problem when the effects of low vision are also added to these conditions.

Our study was a cross-sectional study. In this study, 48.1% of all AMD patients was female. This finding was not suitable with literature. In a study presented from America, %65 of the AMD patients was female[1]. The other conspicuous finding is that, in our study, the patients with dry AMD were 43.51% of all the patients. The patients with wet AMD are more commonly referred to our clinic for anti-VEGF injections and as a result they come to the clinic more commonly for applying of anti-VEGF treatment and control examination for possible complications of the injections. Hence, the ratio of patients with dry AMD was lower in our study. 

In the present study, the lowest scores were obtained in the ‘Near activities’, ‘General health’, ‘General vision’ subscales, and the highest scores were obtained in the ‘Color vision’, ‘Ocular pain’, ‘Peripheral vision’ subscales. Schippert et al. published a report includes the association of demographic findings of Norwegian AMD patients and vision-related quality of life[17].  The highest score was obtained in ‘Ocular pain’ and the lowest score was obtained in ‘General vision’ and ‘Near activities’ in Norway population. In fact, the compatibility of our and this study can be based on pathophysiology of the age-related macular degeneration. AMD affects especially central vision, so peripheral vision can be protected at the acceptable levels and near vision can be effected also in the early stages of the disease[18]. 

The score of ‘General health’ subscale was 51.31 (±18.91) in our study. In Schippert and co-workers’ study, the score of ‘General health’ was 47.28 (±22.33). This condition can be explained with the differences in mean age of the participants between the two studies. Hence, the mean age of the patients was 72.94 in our study, and 81.7 in the other study. In the other subscales except ‘General health’, our NEI VFQ-25 scores were lower than the Norwegian population. The most remarkable difference was in the ‘Vision specific social functioning’ subscale of which scores were 66.07 (±26.64), 83.33 (±20.3), 85.5 (±20.4) in our study, Norwegian and American population; sincerely[19]. We know that NEI VFQ-25 test had been prepared for the American population and culture. Life expectancy may differ between different countries and cultures.

 Depression in advanced ages might be the initial sign of other diseases[20]. Therefore, early diagnosis of depression is important for geriatric practice. The diagnosis of depression is difficult, and affective symptoms are uncommon in elderly patients[21].  The short form of Geriatric Depression Scale includes 15 items (GDS-15), which is effective for the diagnosis of depression in elderly people and it is more brief, simple ,and time-effective than the original geriatric depression scale includes 30 items (GDS-30)[12]. Because of these advantages, we had used GDS-15 in the detection of depression. According to our study, the prevalence of depression was 62.96% in our patients. In a recently published study, Inan et al. presented the depression prevalence in the AMD group as 63.5%[22]. The previous studies have presented different ratios of depression in patients with AMD[23]. Mathew et al. found that, 44% of the patients with low vision associated with AMD have depression signs[23]. Durmaz et al. had applied the GDS-15 test to 329 patients who had admitted to the geriatric clinic for routine examination. In their study, depression ratio was 29.2%, but they had not considered any ocular or systemic disease, and the difference in the depression ratio between this and our study may be explained with low vision related to AMD. In addition to that, the female gender is one of the risk factors for the depression. According to several published studies, females are twice more depressive[24]. We found that the ratio of depression in females was significantly more than males (p<0.05). In the patients with depression, the all scores of the subscales of the NEI VFQ-25 test were lower than the non-depressive group, and the only scores of ‘Ocular pain’, ‘Color and Peripheral vision’ subscales were not statistically significantly different between the two groups.

In the present study, 51.9% of the females had a worse visual acuity than 20/200 (Snellen test), and this ratio was only 28.5% in males. Although Rudnica et al. presented that, there was some evidence to suggest a higher risk of neovascular AMD and late AMD in women compared with men[25], the difference in the visual acuity between the genders was more remarkable in our study. The scores obtained from NEI VFQ-25 subscales except ‘Ocular pain’ and ‘Vision specific dependency’ were negatively correlated with aging (p<0.05). Although, we have noticed that ‘Color-Peripheral vision’ and ‘Ocular pain’ subscales were the least affected parameters in AMD, with the effect of aging, color vision and peripheral vision scores decreased. Previous research has shown that the useful field of view seems to decline with aging[26] and Pinkers et al reported that, test error scores in the FM 100 Hue test had been increasing with aging[27].

Additionally, we evaluated the scores of NEI VFQ-25 subscales in anti-VEGF injected and non-injected patients separately. There were not any statistically significantly different scores in the subscales between the groups, and the visual acuity of the patients was not correlated with the number of the injections (p>0.05). At the same time, the non-injected group was more depressive (p<0.05). Senra et al. presented that, depression levels were significantly higher in patients who received up to 3 injections compared with patients who received from 4 to 12 injections and with patients who received more than 12 injections in the patients with wet AMD[28]. We hypothesised that, the anxiety levels against the anti-VEGF injections decrease as the number of intravitreal injections increase and they experience the rising in the visual acuity related to injections. 

Lastly, we had not found any statistically significant differences in the NEI VFQ-25 subscales and GDS-15 test by the marital and income status of the patients (p>0.05). Schippert et al, also showed that there is no relationship between marital status and vision-related quality of life subscales[17].

The limitations of this study include the small size of the sample that was used to investigate the outcome variables. We did not have a control group, with visual impairment associated with another ocular disease or with no visual impairment. On the other hand, the NEI VFQ-25 test had been prepared for the American population and culture.

Conclusion

According to our results, the lowest score obtained in ‘Near activities’ and the highest score obtained in ‘Color vision’ subscale. Depression was quite common in patients with AMD. Depressive patients had taken lower scores in quality of life (QOL) test than non-depressive patients. Female patients were more depressive and had worse visual acuity levels than males. Intravitreal injection treatment or the number of the injections did not affect the result of the QOL test and depression scale.

Declarations

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources 

The authors received no funding for this study

Authorship Contributions

Involved in design and conduct of the study (LD, DT, KG); preparation and review of the study (LD, DT, KG); and data collection (LD).

References

1.            Friedman, D.S., et al., Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol, 2004. 122(4): p. 564-72.

2.            Smith, W., et al., Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology, 2001. 108(4): p. 697-704.

3.            Heesterbeek, T., et al., Risk factors for progression of age-related macular degeneration: Risk factors for progression of AMD. Ophthalmic and Physiological Optics, 2020. 40.

4.            Chakravarthy, U., et al., Clinical risk factors for age-related macular degeneration: a systematic review and meta-analysis. BMC Ophthalmol, 2010. 10(31): p. 1471-2415.

5.            Lindsley, K., et al., Interventions for Age-Related Macular Degeneration: Are Practice Guidelines Based on Systematic Reviews? Ophthalmology, 2016. 123(4): p. 884-897.

6.            Evans, J.R. and J.G. Lawrenson, Antioxidant vitamin and mineral supplements for preventing age-related macular degeneration. The Cochrane database of systematic reviews, 2017. 7(7): p. CD000253-CD000253.

7.            Lawrenson, J.G. and J.R. Evans, Omega 3 fatty acids for preventing or slowing the progression of age‐related macular degeneration. Cochrane Database of Systematic Reviews, 2015(4).

8.            Sarwar, S., et al., Aflibercept for neovascular age-related macular degeneration. The Cochrane database of systematic reviews, 2016. 2: p. CD011346-CD011346.

9.            Mangione, C.M., et al., Development of the 25-list-item National Eye Institute Visual Function Questionnaire. Archives of Ophthalmology, 2001. 119(7): p. 1050-1058.

10.         Toprak, A.B., et al., Cross-validation of the Turkish version of the 25-item National Eye Institute Visual Functioning Questionnaire (NEI-VFQ 25). Ophthalmic Epidemiol, 2005. 12(4): p. 259-69.

11.         Yesavage, J.A., Geriatric Depression Scale. Psychopharmacol Bull, 1988. 24(4): p. 709-11.

12.         Durmaz, B., et al., Validity and reliability of geriatric depression scale-15 (short form) in Turkish older adults. North Clin Istanb, 2018. 5(3): p. 216-220.

13.         Marella, M., et al., The Psychometric Validity of the NEI VFQ-25 for Use in a Low-Vision Population. Investigative Ophthalmology & Visual Science, 2010. 51(6): p. 2878-2884.

14.         Revicki, D.A., et al., Reliability and validity of the National Eye Institute Visual Function Questionnaire-25 in patients with age-related macular degeneration. Invest Ophthalmol Vis Sci, 2010. 51(2): p. 712-7.

15.         Wong, W.L., et al., Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health, 2014. 2(2): p. e106-16.

16.         Casten, R.J. and B.W. Rovner, Update on depression and age-related macular degeneration. Current opinion in ophthalmology, 2013. 24(3): p. 239-243.

17.         Schippert, A.C., et al., The Impact of Age-Related Macular Degeneration on Quality of Life and Its Association With Demographic Data: Results From the NEI VFQ-25 Questionnaire in a Norwegian Population. Gerontology & geriatric medicine, 2018. 4: p. 2333721418801601-2333721418801601.

18.         Broman, A.T., et al., The Impact of Visual Impairment and Eye Disease on Vision-Related Quality of Life in a Mexican-American Population: Proyecto VER. Investigative Ophthalmology & Visual Science, 2002. 43(11): p. 3393-3398.

19.         Orr, P., et al., Validation of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) in age-related macular degeneration. Invest Ophthalmol Vis Sci, 2011. 52(6): p. 3354-9.

20.         Blazer, D.G., Depression in late life: review and commentary. J Gerontol A Biol Sci Med Sci, 2003. 58(3): p. 249-65.

21.         Fiske, A., J.L. Wetherell, and M. Gatz, Depression in older adults. Annu Rev Clin Psychol, 2009. 5: p. 363-89.

22.         Inan, S., et al., Quality of life among patients with age-related severe macular degeneration assessed using the NEI-VFQ, HADS-A, HADS-D and SF-36 tests. A cross-sectional study. Sao Paulo Med J, 2019. 137(1): p. 25-32.

23.         Mathew, R.S., et al., Depressive symptoms and quality of life in people with age- related macular degeneration. 2011. 31(4): p. 375-380.

24.         Nolen-Hoeksema, S., Gender Differences in Depression. Current Directions in Psychological Science, 2001. 10(5): p. 173-176.

25.         Rudnicka, A., et al., Age and Gender Variations in Age-related Macular Degeneration Prevalence in Populations of European Ancestry: A Meta-analysis. Ophthalmology, 2011. 119: p. 571-80.

26.         Sekuler, A.B., P.J. Bennett, and M. Mamelak, Effects of aging on the useful field of view. Exp Aging Res, 2000. 26(2): p. 103-20.

27.         Pinckers, A., Color vision and age. Ophthalmologica, 1980. 181(1): p. 23-30.

28.         Senra, H., et al., Experience of Anti-VEGF Treatment and Clinical Levels of Depression and Anxiety in Patients With Wet Age-Related Macular Degeneration. Am J Ophthalmol, 2017. 177: p. 213-224.

Tables

Table 1. Demographic Data

BCVA: best corrected visual acuity, AMD: age related macular degeneration

Table 2. Scores for subscales 

Table 3: Depression by Gender

Table 4: NEI VFQ-25 subscale scores by the presence of depression

Table 5: BCVA by gender

BCVA: best corrected visual acuity

Table 6: Anti-VEGF injections and Depression

VEGF: vascular endothelial growth factor