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Clinical science
The impact of typical neovascular age-related macular degeneration and polypoidal choroidal vasculopathy on vision-related quality of life in Asian patients
  1. Eva K Fenwick1,2,
  2. Chui Ming Gemmy Cheung2,3,
  3. Peng Guan Ong2,
  4. Gavin Tan2,3,
  5. Shu Yen Lee2,3,
  6. Ian Yeo2,3,
  7. Ching Yu Cheng2,3,
  8. Tien Y Wong1,2,3,
  9. Ecosse L Lamoureux1,2,3
  1. 1Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, University of Melbourne, East Melbourne, Victoria, Australia
  2. 2Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore
  3. 3Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Medical School, National University of Singapore, Singapore, Singapore
  1. Correspondence to Dr Gemmy Cheung, Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore 168751, Singapore; gemmy.cheung.c.m{at}snec.com.sg

Abstract

Aims To determine the impact of neovascular age-related macular degeneration (nAMD) on vision-related quality of life (VRQoL) in an Asian population.

Methods In this cross-sectional study, 162 subjects with nAMD from the Asian AMD Phenotyping Study and 105 randomly sampled age-matched and gender-matched controls from the population-based Singapore Chinese Eye Study were recruited. nAMD was categorised as either polypoidal choroidal vasculopathy (PCV) or ‘typical’ AMD (tAMD). The reading, mobility and emotional well-being subscales of the impact of vision impairment (IVI) scale were validated using Rasch analysis and used as the main outcome measures and collectively referred to as VRQoL. Multivariate linear regression analyses were performed to assess the impact of nAMD overall, and PCV and tAMD subtypes, on the three IVI domains.

Results Of the 162 with nAMD, 103 (63.6%) had PCV and 59 (36.4%) had tAMD. In multivariate models, nAMD overall was independently associated with a 21% reduction in reading (β=−1.08; CI −1.58 to −0.57); 16% reduction in mobility (β=−0.74; −1.14 to −0.33) and 44% reduction in emotional well-being (β=−2.15; −2.83 to −1.47) compared with controls. There were significant VRQoL deficits (p<0.05) associated with both PCV and tAMD; these deficits were similar and not statistically different between the two nAMD subtypes (p>0.05).

Conclusions Neovascular AMD, including both PCV and tAMD subtypes, has a detrimental impact on VRQoL in Asian subjects independent of level of vision impairment. Interventions to increase reading capacity, enhance mobility and independence and improve mental health outcomes for subjects with neovascular AMD further address the impact of the condition on VRQoL in addition to pharmacological therapies.

  • Macula
  • Degeneration
  • Public health
  • Vision

http://dx.doi.org/10.1136/bjophthalmol-2016-308541

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    Introduction

    Age-related macular degeneration (AMD) is a progressive disease of the macula and a major cause of blindness in older adults in the West.1 Recent evidence suggests that AMD is also highly prevalent in Asia,2 with the prevalence likely to increase due to the rapidly ageing population, increasing prevalence of cigarette smoking, urbanisation and adoption of Western dietary habits. Thus, half of patients with AMD globally will reside in Asia by 2050.2 AMD has been consistently linked to poor vision-related quality of life (VRQoL) in Western populations.3 ,4 However, the impact of AMD on VRQoL in Asian populations is less well understood. Some QoL domains often measured in Western-developed questionnaires, such as driving, may not be as important in Asian populations.5

    There are few studies on Asian patients with late AMD, particularly neovascular AMD (nAMD), which presents differently in Asian compared with Western populations.6 For example, a major subtype of nAMD in Asian people is polypoidal choroidal vasculopathy (PCV),7 which affects up to 50% of Asians with nAMD and tends to present in younger patients sometimes acutely with massive subretinal haemorrhage and severe vision loss. In a previous study, Asian patients with nAMD presented with significantly poorer vision compared with that reported from Western data registries.8 As a result, patients' final visual acuity remained substantially lower than their Western counterparts 1 year following treatment,8 and this may translate into substantial QoL detriments. This information, not currently available, is vital to inform the monitoring and treatment of AMD in Asian patients and to develop interventions to improve VRQoL outcomes.

    Therefore, we determined the impact of nAMD and associated vision impairment on VRQoL in a predominantly Chinese population in Singapore using the reading, mobility and emotional scales of the impact of vision impairment (IVI) questionnaire. We specifically investigated the individual impact of PCV and typical AMD (tAMD) subtypes of nAMD and determined whether particular VRQoL domains were more affected than others.

    Materials and methods

    Study design and population

    The Asian AMD Phenotyping Study is a prospective clinical study of Asian patients in Singapore that aims to provide longitudinal data on the clinical features, risk factors, natural history, treatment pattern and response, and QoL impact of nAMD.9 Patients with nAMD who had received no treatment for macular diseases in the last 12 months were recruited from a public outpatient retinal clinic of a major Singapore hospital. The current study reports on data from 162 participants who completed the IVI questionnaire between 2010 and 2012. In order to establish the comparative impact of nAMD on QoL, a sample of age-matched (matched to within 5 years where possible) and gender-matched controls with no ocular disease or vision impairment from the population-based Singapore Chinese Eye Study (SCES)10 was also included in the analysis (n=105). Both studies adhered to the tenets of the Declaration of Helsinki, and all participants provided written informed consent. Ethics approval was obtained from SingHealth centralised Institutional Review Board (#R697/47/2009) for the Asian AMD Phenotyping study and from the Singapore Eye Research Institutional Review Board (#2006/612/A) for the SCES.

    Clinical examination and assessment of AMD

    All participants and controls underwent a comprehensive ophthalmic examination. This included visual acuity, dilated fundus examination, colour fundus photography, autofluorescence imaging, spectral-domain optical coherence tomography (SD-OCT) (Cirrus OCT, Carl Zeiss Meditec, Dublin, California, USA) using the 512×128-volume cube setting and (Spectralis OCT, Heidelberg Engineering, Heidelberg, Germany), fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA) (TRC-50X/IMAGEnet 2000, Topcon, Tokyo, Japan), according to a standardised protocol.

    nAMD was diagnosed clinically using FFA and ICGA. Choroidal neovascularisation was graded using criteria from the Macular Photocoagulation Study.11 The diagnosis of definitive PCV lesions was based on the angiographic criteria for the Japanese Study Group guidelines,12 which defined PCV as characteristic polypoidal lesions on ICGA. Presenting visual acuity (PVA) was measured for each eye using a Snellen chart and converted to logarithm of the minimum angle of resolution (LogMAR). PVA in the better eye was the better presenting distance vision of the right or left eye.

    Vision-related quality of life

    The 32-item IVI questionnaire was used to assess VRQoL. The IVI has undergone extensive psychometric validation in the past,13 and our group has recently validated the Chinese version in the SCES using Rasch analysis.14 Based on a priori evidence from our Chinese validation study that the total IVI was multidimensional,14 its three component scales were analysed separately. These were reading and accessing information; mobility and independence; and emotional well-being. We use ‘VRQoL’ to describe the overarching construct of QoL, and reading, mobility and emotional to describe the three subtraits of VRQoL (study outcomes). Rasch analysis was used to assess the psychometric properties of the three IVI scales in our current sample using the Andrich rating scale model with Winsteps software (V.3.90, Chicago, Illinois, USA).15 ,16 Following minor amendments, including collapsing two response categories to resolve disordered thresholds, and deletion of items 25–28 due to misfit, items 11 and 14 due to differential item functioning, and items 5 and 20 due to multidimensionality, the three scales showed excellent fit statistics. Ordinal ratings of the three scales were then transformed to estimates of interval measures, which were used in subsequent regression models.

    Other assessments

    Sociodemographic information, self-reported medical history and lifestyle risk factors were collected by an interviewer-administered questionnaire that was identical for cases and controls. Blood pressure (BP) was measured by an automated BP machine. Height and weight were measured using a wall-mounted adjustable measuring scale and a calibrated scientific weight scale, respectively. Body mass index (BMI) was calculated as weight (kg) divided by height in metres squared (kg/m2).

    Statistical analysis

    Patients' demographics and baseline characteristics were summarised by mean and SD for normally distributed continuous data, or the median and IQR for skewed distributed data, and counts and percentages for categorical data. Key covariates included age (years), gender, education, income, socioeconomic status, smoking status, alcohol status, can read and write, driving status, comorbidity (ie, stroke, myocardial infarction, hypertension, thyroid, hypercholesterolaemia, diabetes), BMI and systolic BP (mm Hg) and diastolic BP (DBP, mm Hg). PVA (better eye) was analysed first as a continuous variable and then categorised into none or mild (<0.5 LogMAR), moderate (≥0.5 LogMAR >1.0) and severe (>1.0 LogMAR) vision impairment.

    χ2 statistics, t-test and analysis of variance were used to determine univariate associations. Multivariable logistic regression analysis was used to examine the relationship between nAMD and reading, mobility and emotional. Models were adjusted for age, gender, categories of vision impairment, BMI, low socioeconomic status, income, alcohol and smoking status, DBP and ability to read, write and drive. Associations were considered statistically significant if p<0.05.

    In addition, for independent significant associations between nAMD and VRQoL, and vision impairment and VRQoL, a pairwise comparison of the p values was performed between the reading, mobility and emotional outcomes to determine whether the difference in β coefficients between outcomes was significant. This provided an indicator of whether one domain of VRQoL had greater impact on patients compared with the other domains. All statistical analyses were performed using Stata V.12.0 (StataCorp, College Station, Texas, USA).

    Results

    We included 162 subjects with nAMD (103 PCV and 59 tAMD) and 105 age-matched and gender-matched controls. Subjects with nAMD had significantly worse PVA in the better eye compared with controls (0.32 vs 0.11, p<0.001; table 1). Moderate and severe vision impairment was seen in 17.8% and 8.2% of nAMD cases, respectively. Of the cases, 127 nAMD subjects had unilateral nAMD (PVA better eye, 0.26); 35 had bilateral nAMD of which 23 presented with a scar in the first eye (PVA better eye, 0.41) and 12 presented with simultaneous active disease (PVA better eye, 0.55; table 1).

    View this table:
    Table 1

    Sociodemographic and clinical characteristics of the participants (n=267)

    Association between nAMD and VRQoL

    In univariate analyses, subjects with nAMD had significantly worse scores in all three IVI domains compared with controls (p<0.001, see online supplementary table S1). There was no statistically significant difference in VRQoL for patients with PCV compared with tAMD (p>0.05). Subjects with moderate or severe vision impairment had significantly worse VRQoL compared with those with none or mild vision impairment (p<0.001).

    Supplementary table

    Association between the Reading, Mobility and Emotional well-being subscales of the Impact of Vision Impairment Questionnaire and sociodemographic and clinical variables

    In multivariate models, nAMD was associated with a 21%, 16% and 44% decline in reading (β (β coefficient)=−1.08; CI −1.58 to −0.57), mobility (β=−0.74; −1.14 to −0.33) and emotional (β=−2.15; −2.83 to −1.47), respectively, compared with controls independent of PVA (figure 1). Regarding the subtypes of nAMD, PCV was independently associated with a 22% decrement in reading (β=−1.14; −1.69 to −0.59), an 18% decline in mobility (β=−0.85; −1.30 to −0.39) and a 49% decrement in emotional (β=−2.31; −3.06 to −1.56). Similar and statistically similar (p>0.05) reductions in reading, mobility and emotional were also observed for tAMD (20%, 12% and 38%, respectively) (table 2). Moderate and severe vision impairment were independently associated with a 28% (β=−1.31) and 37% (β=−1.75) decline in reading and a 17% (β=−0.73) and 32% (β=−1.39) decline in mobility, respectively (figure 1). Although systematic decrements were observed for emotional, these were not statistically significant (figure 1). We also ran the analysis using the worse eye and results were very similar (data not shown) except for emotional where severe VI was associated with a significant 35% −1.39 (−2.39 to −0.30) reduction. The variance explained in the reading, mobility and emotional outcomes by nAMD was 5.6%, 2.1% and 6.9%, respectively, while the variance explained by PVA (better eye) was 8.4%, 11.2% and 12.5%, respectively.

    View this table:
    Table 2

    Association between nAMD, tAMD and PCV, and vision-related quality of life using multivariable regression models

    Figure 1
    Figure 1

    Results of fully adjusted multivariate models showing that subjects with neovascular age-related macular degeneration (nAMD) had significantly worse reading, mobility and emotional scores compared with controls. In subjects with nAMD, moderate and severe vision impairment were significantly associated with reading and mobility, but not with emotional. AMD, age-related macular degeneration; IVI, impact of vision impairment

    Focusing on the association between nAMD and VRQoL, the difference in magnitude between β coefficients for emotional and mobility was statistically significant (p<0.001), as was the difference between emotional and reading (p=0.001), suggesting that subjects with nAMD reported a greater impact on emotional compared with mobility or reading. When considering the association between vision impairment and VRQoL, the difference between β coefficients for reading and mobility (p=0.032) and reading and emotional (p=0.027) was statistically significant, suggesting that vision impairment had a greater impact on reading compared with mobility or emotional.

    Discussion

    We found that people with nAMD had 21%, 15% and 44% reductions in reading, mobility and emotional, respectively, compared with controls without nAMD, even when adjusting for visual acuity. Both PCV and tAMD were similarly and independently associated with substantial declines in VRQoL, with PCV associated with an almost 50% decline in emotional well-being. The QoL impact associated with nAMD was significantly greater for emotional compared with reading and mobility. Interventions to improve VRQoL in subjects with nAMD are warranted, particularly in the area of mental health.

    The 15–43% VRQoL reductions associated with nAMD in our study exceed those reported in the Singapore Malay Eye Study (SiMES; ∼6%),17 which may be due to the small number of subjects with late AMD in SiMES (n=23) and the different questionnaires used (VF-14 vs IVI). Our results mirror those from Western studies that have reported significant declines in VRQoL associated with AMD18–20 or related vision impairment.21–23 Interestingly, the observed associations between AMD and VRQoL in all previous studies were either dependent on visual acuity4 ,17 ,23 or visual acuity was not adjusted for.18–20 ,22 In contrast, in our study, nAMD remained independently associated with worse VRQoL even when we included vision impairment in our regression models. Studies in diabetic retinopathy have also reported an independent association between disease severity and VRQoL.24 Moreover, while moderate and severe vision impairment was associated with declines in reading and mobility in our study, neither was significantly associated with emotional. However, when we ran the same analyses using the worse eye instead of the better eye, we found that severe VI had a substantial impact on emotional well-being. This is likely due to loss of visual field and depth perception, and anxiety related to having one seeing eye; indeed, other studies have found reduced QoL impact associated with the worse seeing eye.25 This suggests that the general clinical maxim of ‘still got one good eye’ may not be appropriate as participants may experience reduced emotional well-being even when only one eye is bad, despite not experiencing restrictions in mobility or reading. Similarly, treating the worse as well as the better eye may be important for the mental health outcomes of patients with nAMD.26

    Taken together, our findings suggest that distance visual acuity is not the main factor responsible for the deficits in VRQoL reported by our Asian participants with nAMD; rather there appear to be disease-specific aspects (eg, loss of near central vision, metamorphosia, scotoma, contrast sensitivity, depth perception and adaptation) and psychosocial factors (eg, fear of going blind, losing independence, frustration and treatment burden) that more strongly influence VRQoL in this group. This is supported by the small variance in VRQoL explained by both nAMD and vision impairment (∼20%), which suggests that other factors may be more strongly associated with VRQoL.

    Ours is the first study to specifically assess the VRQoL impact of PCV, a common subtype of nAMD in Asians.6 We found independent substantial declines in VRQoL associated with PCV, particularly in relation to emotional. Our findings are important for clinicians and researchers in Asia as PCV represents more than half of the nAMD cases in Asia.7

    The emotional impact of nAMD was significantly greater compared with reading and mobility. Crucially, severity of vision impairment was not independently related to emotional in those with nAMD, which suggests that factors unrelated to visual acuity are contributing to the emotional impact of nAMD. A recent study evaluating the VRQoL of subjects with exudative AMD has also found that mental health was the most affected QoL domain.20 Interventions to improve nAMD patients' mental health should use evidence-based strategies such as collaborative care, cognitive behavioural therapy and problem-solving therapy.27

    Strengths of our study include the well-characterised clinical sample of patients with late AMD and a high proportion of patients with PCV, adjustment for a range of risk factors including PVA and use of Rasch analysis on our IVI data. One limitation is that we were unable to make comparisons with patients with early AMD. Due to differences in study design between our clinical and population based studies, we were unable to obtain age-matched and gender-matched controls for all 162 nAMD cases and, despite matching age within 5 years, we had significantly fewer participants aged >70 in the control group; however, as we adjusted for age in our multiple regression analyses, this is unlikely to have affected our results. Finally, this is a cross-sectional study, so inferences about causality are not possible.

    In conclusion, our clinical study demonstrates that Asian patients with nAMD have substantially worse VRQoL, particularly emotional well-being, with similar decrements observed for PCV and tAMD. Our study re-emphasises the need for preventative strategies to slow the progression to nAMD where the VRQoL deficit is considerable and for interventions with a strong focus on improving mental health for patients with nAMD.

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    Footnotes

    • Contributors EKF and CMGC contributed equally, conceived of the study, interpreted the data and drafted and edited the manuscript. PGO performed data analysis and interpretation and drafted the statistical sections of the manuscript. GT, SYL, IY, CYC and TYW provided revisions to the manuscript. ELL conceived of the study, interpreted the data and edited the manuscript. All authors approved the final version of the manuscript.

    • Funding This study was supported by grants from the National Medical Research Council (STaR/0003/2008 and NIG/1003/2009), National Medical Research Council grant NMRC/NIG/1003/2009; the Singapore Bio Imaging Consortium (C-011/2006) and the Biomedical Research Council (08/1/35/19/550). EF is funded by a National Health and Medical Research Council (NHMRC) Early Career Fellowship (#1072987). The Centre for Eye Research Australia receives Operational Infrastructure Support from the Victorian Government.

    • Competing interests None declared.

    • Patient consent Obtained.

    • Ethics approval SingHealth Centralised Institutional Review Board (#R697/47/2009) for the Asian AMD Phenotyping study, and from the Singapore Eye Research Institutional Review Board (#2006/612/A) for the SCES.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement Unpublished data from the study are available to researchers upon email request from the corresponding author.