Risk factors for eye disease and injury: literature review

Table 4.1 Summary of results for eye diseases

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Risk factor

Condition

Finding

Group a

Summary sheet
number b

SmokingCataractSmoking is strongly associated with development of nuclear cataract, possibly associated with posterior subcapsular cataract and apparently not associated with cortical cataract. Risk increases with number of cigarettes smoked. Ex-smokers have a lower risk than current smokers, particularly after prolonged quitting.11
SmokingAmblyopiaNo relevant studies found 7NA
SmokingDiabetic retinopathyNo relevant studies found 7NA
SmokingGlaucomaA systematic review of cross-sectional and case–control studies showed a positive association between current smokers (but not past smokers) and glaucoma. However, a very large prospective cohort study, as well as two studies that were excluded from the systematic review, did not show this association and those with more than 10 pack-years of smoking experience had a reduced risk of glaucoma.
(1 pack-year = 1 pack of cigarettes per day for 1 year)
54
SmokingAge-related macular degeneration (AMD)In two studies, current smoking was associated with an increased risk of developing AMD compared to past smokers and never smokers. Smoking is also associated with a progression to late AMD among those with early or intermediate AMD. For one study which did not show these effects, deaths from other causes may have masked the effect.15
SmokingRetinitis pigmentosaNo relevant studies found7NA
SmokingTrachomaNo relevant studies found7NA
Age/ageing CataractPrevalence of cataract increased with ageing, 0particularly post-60 years old when the prevalence increased from 1% to 12% at 65–69 years.18
Age/ageingAmblyopiaIn a case-series of children with anisometropia, depth of amblyopia increased with ageing; prevalence also increased up to three years of age.29
Age/ageingDiabetic retinopathyThere are conflicting results as to whether or not age or ageing is associated with development of diabetic retinopathy. The best quality study in this group (Blue Mountains Eye Study) showed no statistically significant association with ageing. Further research is needed on the relationship between the incidence of DR with the time since onset of diabetes and an ongoing increase in DR with ageing in diabetic patients. 510
Age/ageingGlaucomaCross sectional studies (level IV) show that prevalence of glaucoma (primary open-angle glaucoma, POAG) increases with ageing.211
Age/ageingAMDLink already establishedNANA
Age/ageingRetinitis pigmentosaNo relevant studies found7NA
Age/ageingTrachomaNo relevant studies found7NA
AlcoholCataractDrinking increases the risk of nuclear, cortical and posterior subcapsular cataracts. Both the Blue Mountains Eye Study and the Beaver Dam Study found this effect at ‘heavy’drinking levels, defined as ≥ 4 drinks/day (equivalent to approximately 280 g ethanol per week). However, a further study found that drinking at lower levels (≥ 91 g pure ethanol per week) increased the risk of posterior subcapsular opacities.115
AlcoholAmblyopiaNo relevant studies found7NA
AlcoholDiabetic retinopathyAlcohol consumption may be associated with an increased risk of retinopathy in diabetics. More research is needed on the long-term effects of alcohol consumption on the noncardiac complications of diabetes mellitus.217
AlcoholGlaucomaThere are conflicting results on the effect that alcohol has on the development of glaucoma and its major risk factor, ocular hypertension.518
AlcoholAMDThe relationship between alcohol and AMD is difficult to evaluate due to the number of variables, including the different types and symptoms of AMD, definitions of alcohol intake and types of alcohol. However, the majority of the included literature suggests that drinking more than 6 beers per week increases the risk of developing drusen and drinking more than about 3 drinks per week, particularly of wine or spirits is associated with development of AMD.219
AlcoholRetinitis pigmentosaNo relevant studies found7NA
AlcoholTrachomaNo relevant studies found7NA
Eye infectionsCataractEye infections (conjunctivitis and toxoplasmosis) appear to be linked to cataract.222
Eye infectionsAmblyopiaAmblyopia appears to occur in some cases of eye infection.223
Eye infectionsDiabetic retinopathyEye infection appears to be associated with the development of retinopathy in people with diabetes.224
Eye infectionsGlaucomaA range of infectious agents (eg herpes zoster, cytomegalovirus and nematodes) appear to be associated with glaucoma.225
Eye infectionsAMDThere may be a link between infection with Chlamydia pneumoniae and macular degeneration.226
Eye infectionsRetinitis pigmentosaNo relevant studies found7NA
Eye infectionsTrachomaNo relevant studies found7NA
UV damageCataractA large number of epidemiological studies support an association between medium-wave ultraviolet light (UVB) and the development of cortical cataract.136
UV damageAmblyopiaNo relevant studies found7NA
UV damageDiabetic retinopathyNo relevant studies found7NA
UV damageGlaucomaNo relevant studies found7NA
UV damageAMDDespite experimental evidence that the retina is susceptible to UV damage there has been no evidence that UV exposure per se is a risk for AMD. However, sunlight exposure in the teenage years and 30s is associated with increased risk of AMD-related pathologies (drusen and pigmentation) and early AMD. Other outdoor exposures did not increase risks (eg working outdoors). Wearing sunglasses and hats for at least half the time was protective for people with the highest levels of exposure when measured at 10 years (but not at five years).240
UV damageRetinitis pigmentosaNo relevant studies found7NA
UV damageTrachomaNo relevant studies found7NA
UV damagePterygiaCurrent and past exposure to UV light appears to increase the population prevalence of pterygia and the risk of developing pterygia. Exposure to UV light also increases re-development of pterygia after surgical removal. 141
UV damageOcular surface neoplasia Some epidemiology studies indicate that ocular surface neoplasms may be associated with exposure to UVB/sunlight. A causal effect of UV is further substantiated by molecular evidence of UV-induced mutations. Other risk factors include fair skin, light coloured iris, HIV infection, HPV infection and smoking.142
Injuries and accidentsCataractCataract can be caused by ocular trauma.143
Injuries and accidentsAmblyopiaOcular injuries and accidents can cause young children to develop amblyopia, either from visual deprivation or anisometropia. These injuries can have a wide range of causes, including dangerous toys and shaken baby syndrome.144
Injuries and accidentsDiabetic retinopathyNo relevant studies found7NA
Injuries and accidentsGlaucomaGlaucoma can occur as a complication of ocular trauma by a number of mechanisms. The risk of developing post-traumatic glaucoma after contusion is associated with increased age, poor visual acuity, iris injury, lens injury, hyphema and angle recession. The original trauma may be the result of any type of injury, including sporting injuries and automobile injuries.146
Injuries and accidentsAMDMacular degeneration does not appear to be linked to ocular injury.447
Injuries and accidentsRetinitis pigmentosaNo relevant studies found7NA
Injuries and accidentsTrachomaNo relevant studies found7NA
CorticosteroidsCataractInhaled corticosteroids may be associated with cataracts250
CorticosteroidsAmblyopiaNo relevant studies found7NA
CorticosteroidsDiabetic retinopathyNo relevant studies found7NA
Oral corticosteroidsGlaucomaThe use of oral glucocortoids increases the risk of ocular hypertension or open-angle glaucoma in older people. 153
Topical corticosteroidsGlaucomaThe long-term use of potent formulations of topical corticosteroids near the eyes may increase the risk of glaucoma. 253
Inhaled corticosteroidsGlaucomaInhaled corticosteroid use may present an increased risk of glaucoma and ocular hypertension for people who are on high doses for long periods of time, or for those with a family history of glaucoma. 153
CorticosteroidsAMDNo association was found between the use of systemic anti-inflammatory medications and the cross-sectional incidence or prevalence of age-related macular degeneration.454
CorticosteroidsRetinitis pigmentosaNo relevant studies found7NA
CorticosteroidsTrachomaNo relevant studies found7NA
High myopiaCataractMyopia, particularly high myopia, is associated with cortical, nuclear and posterior subcapsular cataract, although the causal mechanism remains unknown.157
High myopiaAmblyopiaIt is not clear whether children with high myopia are at increased risk of amblyopia.558
High myopiaDiabetic retinopathyThe relationship between high myopia and diabetic retinopathy remains unclear.559
High myopiaGlaucomaThere in an increased risk of POAG in myopic eyes. In studies of patients with ocular hypertension, myopic patients appear more susceptible to developing POAG than nonmyopic patients. Myopic patients may also be more likely to develop glaucoma early in life.260
High myopiaAMDMyopia does not appear to be a risk factor for age-related macular degeneration.461
High myopiaRetinitis pigmentosaNo relevant studies found7NA
High myopiaTrachomaNo relevant studies found7NA
Ocular hypertensionCataractThere are conflicting results from studies of possible links between ocular hypertension and development of cataract.564
Ocular hypertensionAmblyopiaNo relevant studies found7NA
Ocular hypertensionDiabetic retinopathyNo relevant studies found7NA
Ocular hypertensionGlaucomaIncreased ocular hypertension (OHT) can lead to glaucoma; treatment of even mild and moderate OHT may help to prevent the onset of glaucoma.267
Ocular hypertensionAMDNo relevant studies found7NA
Ocular hypertensionRetinitis pigmentosaNo relevant studies found7NA
Ocular hypertensionTrachomaNo relevant studies found7NA
Poor living conditionsCataractIt is not clear whether or not poor living conditions are linked to cataracts. Two studies found an association between low socioeconomic status and cataract (confined to nuclear cataract in one study and type not specified in the other) and a third study did not. Possible reasons for the discrepancy are the lack of a standard classification system for socioeconomic status, and the use of cataract surgery as a surrogate for cataract.571
Poor living conditionsAmblyopiaNo relevant studies found772
Poor living conditionsDiabetic retinopathyLower socioeconomic status may be linked to a higher incidence of diabetic retinopathy.273
Poor living conditionsGlaucomaLow income may be associated with glaucoma.274
Poor living conditionsAMDIt is not clear whether or not poor living conditions are associated with AMD. Two studies found an association between socioeconomic factors (income, education and occupation) and AMD; two did not. Possible reasons for the discrepancy are the lack of a standard classification system for socioeconomic status and the different factors measured in the different studies.575
Poor living conditionsRetinitis pigmentosaNo relevant studies found7NA
Poor living conditionsTrachomaNo relevant studies found7NA
DiabetesCataractType 1 and type 2 diabetes are both significantly associated with cataract formation (all three types). If diagnosed early, diabetic cataract can be reversed with a change in diet and medication.178
DiabetesAmblyopiaNo relevant studies found7NA
DiabetesDiabetic retinopathyLink already establishedNANA
DiabetesGlaucomaA systematic review with meta-analysis indicates that diabetes is a risk factor for open-angle glaucoma; however, some prospective cohort studies suggest the opposite.581
DiabetesAMDDiabetes appears not to be a risk factor for macular degeneration.482
DiabetesRetinitis pigmentosaNo relevant studies found7NA
DiabetesTrachomaThere are high rates of diabetes in patients with trachoma, but causality is not clear. Both diseases are poverty-related and this single study looked at a very poor population. Diabetic retinopathy appears to make people more susceptible to poor visual acuity after trachoma.284
HeredityCataractHeredity is the major factor in determining cataract development.185
HeredityAmblyopiaHeredity strabismus appears to be linked with amblyopia.286
HeredityDiabetic retinopathyNo relevant studies found7NA
HeredityGlaucomaDevelopment of primary open-angle glaucoma appears to be strongly linked to heredity factors in some cases. Secondary open-angle glaucoma may not be as strongly linked to heredity factors. Ethnic variations in physiology also account for differences in rates of glaucoma across different ethnic groups.188
HeredityAMDNo relevant studies found7NA
HeredityRetinitis pigmentosaNo relevant studies found7NA
HeredityTrachomaNo relevant studies found7NA
HypertensionCataractThere are conflicting results on the relationship between hypertension and cataract. Further studies are required, and should distinguish between different types of cataract in their analysis.592
HypertensionAmblyopiaNo relevant studies found7NA
HypertensionDiabetic retinopathyHypertension is a risk factor for retinopathy in both people with diabetes and people without diabetes.194
HypertensionGlaucomaOcular hypertension is a risk factor for glaucoma in the general population.195
HypertensionAMDThere may be an association between hypertension/blood pressure and age-related macular degeneration (AMD). One study showed no association between hypertension and ARM; others showed that hypertension/high blood pressure were risk factors for ARM/AMD. Beaver Dam Eye study had a smaller number of incident cases of ARM than Klein et al 2003 (see results column). Van Leeuwen study had a much larger study sample than other two studies (other 2 were of comparable size).596
HypertensionRetinitis pigmentosaNo relevant studies found7NA
HypertensionTrachomaNo relevant studies found7NA
SquintCataractNo relevant studies found7NA
SquintAmblyopiaAlthough there is debate about different intervention and screening programs, strabismus is clearly a cause of amblyopia.1100
SquintDiabetic retinopathyNo relevant studies found7NA
SquintGlaucomaNo relevant studies found7NA
SquintAMDNo relevant studies found7NA
SquintRetinitis pigmentosaNo relevant studies found7NA
SquintTrachomaNo relevant studies found7NA
AnisometropiaCataractThis study shows that anisometropia is associated with the presence of cataract. Further research would be required, however, to confirm causality.2106
AnisometropiaAmblyopiaIt is well-established that anisometropia can lead to amblyopia, although it is not the only cause of this condition. Australian studies have shown that amblyopia is a significant cause of reduced visual acuity in the adult population.1107
AnisometropiaDiabetic retinopathyNo relevant studies found7NA
AnisometropiaGlaucomaNo relevant studies found7NA
AnisometropiaAMDNo relevant studies found7NA
AnisometropiaRetinitis pigmentosaNo relevant studies found7NA
AnisometropiaTrachomaNo relevant studies found7NA
CataractAmblyopiaCongenital cataracts cause abnormal or reduced visual stimulation during the sensitive period of visual development, which can result in amblyopia.1114
CataractDiabetic retinopathyNo relevant studies found7NA
CataractGlaucomaNo relevant studies found7NA
CataractAMDIt is not clear whether incidence of cataracts or cataract surgery is linked to age-related macular degeneration.5117
CataractRetinitis pigmentosaNo relevant studies found7NA
CataractTrachomaNo relevant studies found7NA
Physical activityCataractPhysically active people may be less likely to develop cataract than those who are inactive, although more research is needed.6120
Physical activityAmblyopiaNo relevant studies found7NA
Physical activityDiabetic retinopathyNo relevant studies found7NA
Physical activityGlaucomaNo relevant studies found7NA
Physical activityAMDPhysical activity may have a protective effect against exudative AMD, independent of body mass index and other confounders.6124
Physical activityRetinitis pigmentosaNo relevant studies found7NA
Physical activityTrachomaNo relevant studies found7NA
Diet (Fruit and vegetables)CataractThese studies suggest that diet high in fruit and vegetables has a modest protective effect on cataract. This is especially true for spinach and kale, which are naturally high in the antioxidant lutein, found to be protective against nuclear cataract. 1258
Diet (Glycaemic load)CataractGlycaemic load does not appear related to the incidence of cataract.4258
Diet (Other nutrients)CataractOther nutrients such as riboflavin, thiamin, vitamin C and vitamin E may protect against cataract but further studies are required.2258
DietAmblyopiaNo relevant studies found7NA
DietDiabetic retinopathyAlthough in vitro and animal studies have suggested that vitamins E and C may protect against the development of retinopathy, there is insufficient evidence from epidemiological studies to confirm this protective effect.6260
DietGlaucomaThese prospective studies suggest that diet, specifically fatty acids and antioxidants, is neither a causative nor a protective factor for primary open-angle glaucoma.3261
DietMacular degenerationA low-fat, low-glycaemic diet high in fruit, fish and nuts may be protective against the onset of age-related macular degeneration. Other factors, such as zinc, coffee or carbohydrate intake, were not related to AMD. Further research is required before any supplements could be recommended.6262
DietRetinitis pigmentosaNo relevant studies found7NA
DietTrachomaNumerous studies have shown that malnutrition predisposes an individual to infections, due to immunological deficits. Although malnutrition and trachoma share risk factors, such as poor hygiene and low socioeconomic status, this study did not find a direct causal relationship between malnutrition and trachoma.4264
Nutritional supplementsCataractMajor studies show no association between vitaimns E, C and -carotene; vitamin E alone; vitamin C alone; or carotenoid supplements and the risk of any type of cataract development.
One randomised controlled trial (RCT) from China and a number of observational studies have shown a reduction in all types of cataracts after multivitamin use or supplements with riboflavin and niacin.
NB: Adverse effects of supplements need to be taken into account (eg -carotene has been shown to increase risk of lung cancer in smokers; vitamin E has increased heart disease in people with vascular disease or diabetes).
6222
Nutritional supplementsAmblyopiaNo relevant studies found7NA
Nutritional supplementsDiabetic retinopathyNo relevant studies found7NA
Nutritional supplementsGlaucomaSupplements (in the form of antioxidants) do not significantly reduce the risk of glaucoma.3224
Nutritional supplementsAMDIt is not clear whether supplements (vitamins, antioxidants, lutein, zeaxanthin and zinc) have a positive, negative or no effect on macular degeneration.
Other adverse effects of supplements should be taken into account (eg -carotene has been shown to increase risk of lung cancer in smokers; vitamin E has increased heart disease in people with vascular disease or diabetes).
5226
Nutritional supplementsRetinitis pigmentosaIt is not clear whether lutein supplements are beneficial in retinitis pigmentosa. Docosa-hexaenoic acid (DHA, long chain omega-3 fatty acid) supplements do not appear to be beneficial.5227
Nutritional supplementsTrachomaNo relevant studies found7NA
Fatty acidsCataractMost types of dietary fat do not appear associated with cataract. The Nurses’ Health Study found that high intakes of the 18-carbon polyunsaturated fatty acids linoleic acid and linolenic acid were significantly associated with the prevalence of nuclear opacities. This is supported by In vitro studies, which have demonstrated a potential mechanism for epithelial lens cell damage by polyunsaturated fatty acids. However, more detailed studies are required, particularly studies that separate different types of polyunsaturated fatty acids, as there is conflicting evidence from cross-sectional studies. 5251
Fatty acidsAmblyopiaNo relevant studies found7NA
Fatty acidsDiabetic retinopathyNo relevant studies found7NA
Fatty acidsGlaucomaThe association of fatty acids and glaucoma is unclear from this literature. Further randomised control trials would be required to support recommending fatty acids as a treatment.5254
Fatty acidsMacular degenerationAlthough some studies suggest that omega 3 fatty acid consumption has a protective effect against AMD, the studies that have been done on this issue are not of very good quality and the results have been inconsistent. Further research with well-designed RCTs or prospective cohort studies is required to resolve this issue.5255
Fatty acidsRetinitis pigmentosaAlthough trends of improvement in some retinitis pigmentosa outcomes were found in randomised control trials, more research is required in this area before fatty acids can be recommended as a therapy for retinitis pigmentosa.6256
Fatty acidsTrachomaNo relevant studies found7NA
ObesityCataractAlthough causality has not been established, these studies suggest that obesity is associated with an increased risk of cataract, especially posterior subcapsular cataract.2244
ObesityAmblyopiaNo relevant studies found7NA
ObesityDiabetic retinopathyAbdominal obesity appears to be a risk factor for retinopathy in people with and without diabetes; however, body mass index is not.2246
ObesityGlaucomaObesity does not appear to be a risk factor for glaucoma, although more research is required in this area.4247
ObesityMacular degenerationHigh body mass index (BMI) is a risk factor for visually significant AMD (but possibly not neovascular) in males; however, a low BMI is also associated with increased risk of visually significant ARM. A BMI within the normal range offers the lowest risk of ARM in men.1248
ObesityRetinitis pigmentosaNo relevant studies found7NA
ObesityTrachomaNo relevant studies found7NA
a Groups are as follows:
Group 1 — Clear association/causality
Group 2 — Possible association/causality (more research needed)
Group 3 — Lack of association/causality
Group 4 — Possible lack of association/causality (more research needed)
Group 5 — Conflicting results
Group 6 — Possible protection
Group 7 — No studies
b Summary sheets number refers to the results tables in Appendix 3.
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