A Global Assessment of Eye Health and Quality of Life

1At least 2.2 billion people worldwide have a vision impairment, of whom more than 1 billion have moderate or severe vision impairment or blindness from a preventable or potentially correctable cause, including refractive error, presbyopia, and cataract. Existing evidence suggests that vision impairment is associated with lower quality of life, defined as physical, emotional, and social well-being. Visual impairment is also linked to lower vision-related quality of life or daily visual function and the ability to perform visual tasks.

2Over the past decade, quality-of-life measures have gained popularity in ophthalmology research, including clinical trials, as the value of patient-reported outcomes in measuring well-being and visual function is being recognized. However, to our knowledge, there has yet to be a global synthesis of the evidence about quality of life and eye health, despite the numerous systematic reviews about vision impairment, eye diseases, or ophthalmic interventions and quality of life.,,

3Therefore, the objective of this umbrella review, which is a systematic review of systematic reviews, is to examine the association between vision impairment or specific eye diseases and reduced quality of life, and the effectiveness that ophthalmic interventions can have on improving quality of life.

4This study forms part of the work for the forthcoming Lancet Global Health Commission on Global Eye Health. We followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) reporting guidelines (eAppendix 1 in the Supplement). A protocol was published and registered on the Open Science Framework Registries (https://osf.io/qhv9g). Changes to the protocol are noted in eAppendix 2 in the Supplement.

5A comprehensive search was performed using the electronic databases MEDLINE, Ovid, Embase, Cochrane Database of Systematic Reviews, Proquest Dissertations, and Theses Global from inception through June 29, 2020 (a sample search strategy is in the eFigure in the Supplement). OpenGrey, the Agency for Healthcare Research and Quality, and references of included reviews were searched for additional articles. Inclusion and exclusion criteria are listed in Table 1.

6Study selection, quality appraisal, and data collection were performed by 4 reviewers (L.A., F.C., P.I., and H.S.) independently and in duplicate using Covidence software (Covidence Inc). Titles and abstracts were screened to identify potentially relevant articles. Full texts of these articles were assessed for eligibility based on the inclusion and exclusion criteria. Reviews that aimed to identify studies with quality-of-life outcomes but did not find any were excluded, since they had no results to be extracted.

7Reviews underwent quality appraisal using the Joanna Briggs Institute Critical Appraisal Checklist for Systematic Reviews and Research Syntheses. Reviews for which any of the items “clear review question,” “appropriate inclusion criteria,” “appropriate search strategy,” or “appropriate criteria for critical appraisal” were graded as unclear or no were excluded. Data collection was performed using the Joanna Briggs Institute Data Extraction Form for Systematic Reviews and Research Syntheses.

8Results of the reviews on vision impairment or eye diseases and ophthalmic interventions were presented separately. Within the reviews on ophthalmic interventions, 2 types of comparisons were identified: (1) those that compared the quality of life of a group receiving an intervention with baseline quality of life in the same group or a control group receiving no intervention, a placebo, or sham therapy and (2) those that compared the quality of life of a group receiving 1 intervention with a group receiving another intervention, without comparison with a baseline or a group that received no intervention. Results from each type of comparison were described separately, and only comparisons with baseline or a group receiving no intervention were included in the Tables summarizing findings (Table 2 and Table 3).

9When the same intervention or outcome was assessed by more than 1 review, the primary studies used by the reviews to inform the results were compared to assess the extent to which individual studies were included in more than 1 review. Results about associations were based on the reviews’ interpretation of the estimates and accompanied by the measure of association and quality of the evidence assessment when available in the published review. Overall findings were presented in Table 2 and Table 3.

10As described in the PRISMA flowchart (eTable 1 in the Supplement), 8070 unique titles and abstracts were screened; of these, 685 relevant full-text articles were assessed for eligibility. Ten eligible systematic reviews addressed quality of life and vision impairment or eye diseases, and 205 assessed ophthalmic interventions. Of the reviews concerning ophthalmic interventions, 143 were excluded because they did not identify any eligible studies with quality-of-life data in the literature.

11Results of the quality assessment are presented in eTable 2 in the Supplement. Three reviews were excluded, 2 for not having appropriate critical appraisal criteria, and 1 for not having appropriate inclusion criteria. This left 9 reviews on vision impairment or eye diseases and 60 reviews on ophthalmic interventions included in the current analysis. Review characteristics are summarized in eTable 2 in the Supplement.

12In total, 9 systematic reviews,,,,,,,, published between 2010 and 2020 evaluated the association between vision impairment or eye disease and quality of life. Four of them had corresponding authors in the UK,,,; the rest were in the US, Netherlands, Taiwan, China, and Singapore. Five,,,, were systematic reviews of observational quantitative studies, 3,, were reviews of qualitative studies, and 1 was a review of both quantitative and qualitative studies (Table 3). None of the reviews graded the quality of the evidence.

13The systematic reviews of observational quantitative studies focused on people with vision impairment, including adults and specifically working-age and older adults, people with glaucoma, diabetic retinopathy, and children and adults with mendelian eye conditions, including retinitis pigmentosa, Usher syndrome, and mixed retinal dystrophies. Among all the populations examined, vision impairment or eye diseases were associated with lower quality of life, including vision-related and health-related and glaucoma-specific quality of life. Moreover, people with vision impairment had poorer scores on quality-of-life subscales, such as mental health, psychosocial functioning, and fatigue (odds ratio, 2.61 [95% CI, 1.69-4.04]).

14The systematic reviews of qualitative studies assessed emotional well-being and daily functioning among older adults with vision impairment and age-related macular degeneration (AMD) and children and adults with mendelian eye conditions, including retinitis pigmentosa specifically in a second review. The 2 reviews, that addressed retinitis pigmentosa included 2 overlapping primary studies. Emotional well-being among people with vision impairment, AMD, and retinitis pigmentosa was especially affected at the initial diagnosis, which was described as a shocking or traumatic event in the 3 reviews.,, Moreover, coping with AMD and retinitis pigmentosa was associated with negative thoughts, including depressive symptoms, fatigue, and isolation., Vision impairment and mendelian eye conditions specifically also affected general daily functioning; people reported having to relinquish their independence and giving up on leisure activities.,, Difficulties performing visual tasks, such as reading and seeing in changing light conditions, were also reported by people with retinitis pigmentosa.

15Overall, 5 exposures (vision impairment; AMD; diabetic retinopathy; mendelian eye conditions, including retinitis pigmentosa; and glaucoma) were evaluated for their association with quality of life. A summary of findings is presented in the Box.

16Vitality subscale (fatigue) of health-related quality of life among adults with vision impairment

17Mental health subscale of health-related and vision-related quality of life among working-age adults with vision impairment

18Vision-related and health-related quality of life among older adults with vision impairment

19Emotional well-being and general functioning among older adults with vision impairment

20Emotional well-being among people with age-related macular degeneration

21Psychosocial functioning among people with diabetic retinopathy

22Emotional well-being among people with retinitis pigmentosa

23General and visual functioning among people with mendelian eye conditions, including retinitis pigmentosa

24Glaucoma-specific quality of life among people with glaucoma

25In total, 60 systematic reviews published between 2005 and 2020 evaluated ophthalmic interventions using quality-of-life outcomes. Seventeen had corresponding authors in the UK,,,,,,,,,,,,,,,,,, 13 in the US,,,,,,,,,,,,, 6 in China,,,,,, 6 in Italy,,,,,, 3 in Brazil,,, 3 in Canada,,, 2 in Denmark,, 2 in Spain,, and 1 each in Uruguay, Switzerland, Bahrain, Germany, Belgium, the Netherlands, Taiwan, and Australia. Thirty-nine reviews reported vision-related quality-of-life measures,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,; 7, disease-specific measures,,,,,,; 4, generic measures,,,; and 10, more than 1 measure type.,,,,,,,,, Reviews that assessed and reported the quality of the evidence either used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) tool with 4 possible levels of evidence (very low, low, moderate, or high) or the US Preventive Services Task Force scale for overall quality of the evidence (poor, fair, or good).

26Findings about quality of life after ophthalmic interventions compared with quality of life at baseline or in a group receiving no intervention are presented in Table 2. Seven systematic reviews,,,,,, addressed interventions for age-associated cataract. One review found improvement in vision-related quality of life after treatment of early vision impairment attributable to cataract in 3 of the 5 studies included (with fair-quality evidence). Two reviews, using results from the same primary studies showed improved vision-related quality of life in the group receiving expedited cataract surgery compared with the control group with a routine waiting time for surgery, and a third found benefits to immediate cataract surgery among people with AMD specifically, compared with those having no or delayed surgery (low-quality evidence). Two reviews, with some overlap of primary studies found a nonclinically meaningful improvement in vision-related quality of life after a second eye cataract surgery compared with surgery in 1 eye only (with moderate-quality evidence in 1 review). Both extracapsular cataract extraction with posterior chamber intraocular lens (IOL) implantation and intracapsular cataract extraction with aphakic glasses were associated with improvement in vision-related quality-of-life outcomes, but extracapsular cataract extraction resulted in greater improvement. Only 1 systematic review assessed interventions associated with refractive error. Using corrective lenses for vision impairment because of uncorrected refractive error improved vision-related quality of life (fair-quality evidence).

27Seven systematic reviews,,,,,, assessed interventions for AMD. Anti–vascular endothelial growth factor (anti-VEGF) therapy was associated with improved vision-related quality of life compared with no anti-VEGF therapy in 2 reviews,,,,,,,, with some overlap in primary studies (described as mild to moderate improvements, with fair-quality evidence and moderate-quality evidence). Treatment using aflibercept and ranibizumab resulted in improved vision-related quality of life from baseline to a similar extent (high-quality evidence that quality of life is similar in both groups). Macular surgery compared with observation (relative risk, 1.35 [95% CI, 1.09-1.68]; low-quality evidence), and antioxidant vitamin supplementation compared with placebo (low-quality evidence) were associated with improved vision-related quality of life, while radiotherapy compared with observation was not. Two reviews, with some overlap of primary studies found that supplementation with lutein and/or zeaxanthin compared with placebo was not associated with better vision-related quality of life (with low-quality evidence in 1 review).

28Nine systematic reviews,,,,,,,, examined interventions for other retinal diseases. One systematic review reported that both anti-VEGF therapy and laser photocoagulation improved vision-related quality of life for diabetic retinopathy, but anti-VEGF therapy resulted in a greater improvement (moderate-quality evidence). Likewise, 3 reviews,, using identical primary studies found that anti-VEGF therapy, compared with a sham treatment, was associated with improvement in vision-related quality of life in people with macular edema secondary to central retinal vein occlusion (high-quality evidence in 1 review and moderate-quality evidence in another review). Anti-VEGF therapy was also found to improve vision-related quality of life in those with branch retinal vein occlusion and choroidal neovascularization secondary to pathological myopia (moderate-quality evidence). Ocriplasmin injection compared with a sham treatment was associated with clinically meaningful improvement in vision-related quality of life among those with symptomatic vitreomacular traction and adhesion (moderate-quality evidence). In people with hereditary retinal dystrophies, vision-related quality of life was similar among those who received nutritional supplementation and placebo.

29Two systematic reviews, addressed glaucoma interventions. Treatment of early open-angle glaucoma with laser trabeculoplasty and topical β-blockers compared with placebo was not associated with differences in vision-related quality of life. Selective laser trabeculoplasty and/or medication use did not result in changes in disease-specific quality of life in open-angle glaucoma.

30One systematic review addressed vision rehabilitation interventions. Compared with a passive control arm (delayed or no care), methods for enhancing vision (eg, low-vision service, customized prism glasses) resulted in an imprecisely estimated benefit in vision-related quality of life (very low-quality evidence), and multidisciplinary rehabilitation resulted in beneficial vision-related quality-of-life effects (with very low-quality evidence).

31One systematic review addressed vision screening. After-school vision screenings and the use of ready-made or custom-made spectacles both resulted in improvement in vision-related quality of life to a similar extent (with moderate-quality evidence that quality of life was similar in both groups).

32Subcutaneous immunotherapy for rhinoconjunctivitis was shown to result in greater improvement in rhinoconjuctivitis-specific quality of life compared with placebo among children in 1 systematic review (low-quality evidence) and among adults in another review (high-quality evidence). Sublingual immunotherapy was associated with better quality of life in 1 review (moderate-quality evidence), but not in another 1 that focused on children only. Intranasal fluticasone furoate was associated with better rhinoconjunctivitis-specific quality of life compared with placebo in people with allergic rhinoconjunctivitis.

33Two systematic reviews with some overlap of primary studies reported that adults with active uveitis who received adalimumab, relative to those receiving placebo, had a greater improvement in quality of life, but those with inactive uveitis did not have improvements in quality of life with therapy., Surgery for people with trichiasis improved vision-related quality of life regardless of perioperative azithromycin administration in 1 review. There were no differences in quality of life among people with thyroid eye disease who received radiotherapy or sham, according to 2 reviews, based on results from the same primary study.

34Thirty-three interventions among specific populations (eg, people with AMD, people with inactive disease, children only) were identified, after accounting for duplicate interventions assessed by multiple reviews and combining quality-of-life outcomes (health-related, vision-related, or disease-specific quality of life). A summary of findings is presented in Table 4. Overall, only 11 interventions,,,,,,,,,, were not associated with improved quality of life compared with baseline or compared with a group receiving no intervention: radiotherapy and supplementation with lutein and zeaxanthin, for AMD, supplementation with nutrients for hereditary retinal dystrophies, early open-angle glaucoma treatment with laser trabeculoplasty and topical β-blockers, open-angle glaucoma treatment with selective laser trabeculoplasty and/or medications, adalimumab for the treatment of inactive uveitis (treatment improved quality of life among those with active disease),, radiotherapy for the treatment of thyroid eye disease,, and sublingual immunotherapy for rhinoconjunctivitis among children (however, this treatment improved quality of life in a review covering both children and adults).

35Comparisons of quality of life between 2 different ophthalmic interventions are presented in eTable 3 in the Supplement. Similar quality of life was reported across the interventions for most interventions compared. Interventions that were associated with small or moderate improvements in quality of life when compared with other interventions were immediate sequential cataract surgery compared with different date bilateral cataract surgery (moderate-quality evidence), multifocal IOLs compared with monofocal IOLs (very low-quality evidence in 1 review),,, toric IOLs compared with nontoric IOLs, macular translocation compared with photodynamic therapy (described as “insufficient evidence”(p2)), the use of handheld electronic devices with optical devices compared with optical devices alone (moderate-quality evidence), vision rehabilitation using methods for enhancing vision (eg, low-vision service, customized prism glasses) compared with other interventions (moderate-quality evidence), and posterior lamellar tarsal rotation surgery for minor trichiasis compared with epilation.

36In this umbrella review, we performed a global, broad assessment of eye disease, vision impairment, and ophthalmic interventions on quality of life. There was a consistent association between vision impairment and eye disease with reduced quality of life across eye conditions, especially among adults. Seventy-five percent of ophthalmic interventions evaluated had evidence of a positive outcome on quality of life. Most notably, cataract surgery and the use of anti-VEGF therapy for AMD, diabetic macular edema, and macular edema secondary to other causes resulted in improved quality of life.

37Vision impairment and eye diseases, namely glaucoma, diabetic retinopathy, AMD, and retinitis pigmentosa were associated with lower quality of life, using a range of outcome measures. Quantitative studies showed significant associations and sometimes a graded response, with worse vision impairment being associated with worse quality of life. Qualitative studies provided insight into the mechanisms of the associations, specifically on well-being and functioning. While the significant associations were expected, previous literature suggests that even more eye diseases are associated with worse quality of life. Notably, dry eye has been studied extensively, and a systematic review (excluded because of a lack of appropriate criteria for critical appraisal) has suggested that dry eye syndrome has a substantial association with reduced quality of life across countries in Europe, North America, and Asia.

38Ophthalmic interventions differed in their association with quality of life. In general, treating cataract immediately after diagnosis, even in those with competing eye conditions such as AMD and who had already received a first cataract surgery, improved quality of life. Moreover, anti-VEGF therapy for a number of conditions, including AMD and diabetic macular edema, and the use of corrective lenses for refractive error were associated with improved quality of life. Projections from 2015 suggested that in 2020, 127.7 million people will have moderate or severe vision impairment because of uncorrected refractive error, 57.1 million because of cataract, 8.8 million because of AMD, and 3.2 million because of diabetic retinopathy. Three interventions (cataract surgery, corrective lenses, and anti-VEGF therapy) provide opportunities to improve the quality of life of more than 150 million individuals globally. Other interventions, such as treating rhinoconjunctivitis in children and adults, trichiasis in endemic areas, and uveitis in those with active and inactive disease, and low-vision rehabilitation, also have the potential to improve quality of life.

39The 8 interventions that were not found to improve quality of life included 2 that focused on specific populations. This included the use of adalimumab, which did not improve quality of life among people with inactive uveitis but improved it in those with active disease, and sublingual immunotherapy for rhinoconjunctivitis, which did not improve quality of life among children but improved it when people of all ages were included in another review. Two of the interventions involved nutritional supplements; one was lutein or zeaxanthin for AMD, and the other was nutritional supplements for hereditary retinal dystrophies.

40There were gaps in the evidence available on the outcomes of leading causes of visual impairment (eg, cataract, refractive error), among particular groups (eg, children, people from racial/ethnic minorities), and in low- and middle-income countries compared with high-income countries. Interventions for dry eye, refractive error, glaucoma, and diabetic retinopathy were underrepresented in this review in comparison with their prevalence globally. While systematic reviews about some topics may be lacking, there may be a lack of primary studies as well: 70% of the interventional systematic reviews that aimed to assess quality of life outcomes were subsequently excluded because they did not identify any primary studies reporting quality-of-life outcomes. Moreover, almost half of the interventions and outcomes identified in this review were comparing one intervention with another without presenting information about the change in quality of life from baseline in any of the groups, making it impossible to know whether any of the interventions had an association with quality of life to begin with. While this may be standard practice, as more and more eye diseases have well-established treatments, delaying treatment or using placebo control arms will not be possible. Thinking of ways to answer questions about potential advantages of interventions without depriving a group of beneficial therapy will be important. Researchers could be encouraged to analyze and present data such as overall changes from baseline values by treatment arm, or regardless of treatment arm, even if they are not the primary outcomes.

41The review process highlighted the need for a unified definition for quality of life to study and understand the association with vision impairment and ophthalmic interventions on well-being and vision function from the patient perspective. Many systematic reviews were excluded because they considered patient satisfaction or patient-reported symptoms and discomfort as quality-of-life measures. While these measures fall under the umbrella of patient-reported outcomes and capture valuable information, they do not describe general well-being or vision function in day-to-day life. Moreover, in the included reviews, a wide range of quality of life measures were used between and within the systematic reviews, which limits the ability to compare findings between studies or combine them into meta-analyses.

42Umbrella reviews findings are limited to results that have been synthesized in published reviews, which may be affected by publication bias themselves. Although this may have limited the availability of studies about specific topics, it is this approach that allowed for a global assessment of a broad topic in a systematic manner. Moreover, umbrella reviews are limited by the quality of the reviews and the data reported by the reviews; not all reviews reported specific estimates, tools used to measure outcomes, or enough context to interpret the results. However, we applied strict criteria for systematic reviews, including the working definition and critical appraisal criteria used, and excluded reviews with case series. This approach may have further limited the number of systematic reviews included, but it ensured the inclusion of reviews of higher quality. Finally, there were overlaps in primary studies used by the reviews, and many reviews reported findings based on results from 1 or 2 primary studies only; these were presented in both the text and Tables to allow readers to take them into account when interpreting the findings.

43There is evidence that vision impairment and eye diseases in general are associated with lower quality of life, and most ophthalmic interventions are associated with improved quality of life. Reviews and primary studies addressing underrepresented diseases and reviews focusing on specific populations, such as people from low- and middle-income countries, are needed to expand generalizable knowledge on the association between eye health and quality of life.

44Vision impairment and eye conditions are associated with lower quality of life, and ophthalmic interventions can lead to significant improvement in quality of life. Scaling up interventions, such as cataract surgery, refractive error correction, and anti-VEGF therapy at a global level, has the potential to improve the quality of life of millions of people worldwide.