Ocular and systemic causes of retinopathy in patients without diabetes mellitus
http://www.100md.com
《英国医生杂志》
1 Department of Ophthalmology, National University of Singapore, Singapore, 2 Centre for Vision Research, University of Sydney, Australia
Correspondence to: P Mitchell, Centre for Vision Research, Westmead Millennium Institute, Westmead Hospital, Hawkesbury Road, Westmead, NSW 2145, Australia paul_mitchell@wmi.usyd.edu.au
Introduction
We reviewed studies on ocular and systemic causes of "retinopathy" from Medline and textbooks. We specifically excluded "diabetic retinopathy."
Non-diabetic retinopathy
Retinal vein occlusion
Central retinal vein occlusion and branch retinal vein occlusion can present with non-diabetic retinopathy. The appearance on funduscopy is usually characteristic, with flame shaped haemorrhages present within the distribution of the affected vein (fig 1). The patient may complain of a sudden painless unilateral loss of vision or visual field (for example, inferior field defects for superior branch retinal vein occlusion) or may be asymptomatic. If loss of vision is severe a relative afferent pupillary defect may exist, indicating retinal ischaemia. Important systemic risk factors for retinal vein occlusion include hypertension, diabetes mellitus, and other conditions such as hyperhomocystinaemia.5 Glaucoma is an important ocular risk factor. The prevalence of retinal vein occlusion was noted in one study to be 1.6% in people above 49 years of age.6 Given the possible severe associations of this condition and its relatively high prevalence, retinal vein occlusion should not be overlooked.
Fig 1 Branch retinal vein occlusion in a patient with hypertension
Summary points
Many people without diabetes may have signs of retinopathy (microaneurysms, retinal haemorrhages, cotton wool spots)
Ocular conditions associated with retinopathy in non-diabetic patients include retinal vein occlusions, retinal telangiectasia, and retinal macroaneurysms
Systemic conditions associated with retinopathy in non-diabetic patients include systemic hypertension, carotid atherosclerotic diseases, blood dyscrasias, systemic infections, and past radiotherapy to the head
Doctors should be aware of the common causes and clinical significance of these conditions, as retinopathy may be associated with visual loss (for example, retinal vein occlusion) or increased incidence of cardiovascular diseases (for example, hypertensive retinopathy)
Appropriate investigations and referral, if necessary, are advisable in the management of patients presenting with non-diabetic retinopathy
Retinal telangiectasia
Patients with retinal telangiectasia may present with retinopathy. In younger patients this is referred to as Coats' disease. It usually occurs in young men aged less than 20 years (median age 5 years7). Vision may be greatly affected in advanced cases. A milder form of the same disease, termed Leber's miliary aneurysms, can present later in life as a localised cluster of dilated capillaries, aneurysms, and telangiectasia, typically in the temporal quadrants of the retina. Either of these conditions should be suspected in young patients with retinopathy. About 8% of cases are asymptomatic.
Retinal macroaneurysm
Retinal macroaneurysm refers to an isolated aneurysmal dilatation of a major arterial or arteriolar branch that is often associated with leakage of exudate and multiple retinal haemorrhages. It usually occurs in older women and is strongly associated with hypertension and an increased incidence of cardiovascular and atherosclerotic vessel disease.8
Systemic causes of non-diabetic retinopathy
Whereas diabetic retinopathy is often associated with impairment of vision and blindness, the clinical significance of retinopathy in patients without diabetes is varied, particularly in cases of systemic disease.
Retinal vein occlusion and other retinal vascular disorders
Retinal vein occlusions and other retinal vascular disorders with signs of retinopathy are potentially sight threatening conditions. Ischaemic central retinal vein occlusion is associated with an increased risk of new vessel formation in the iris and subsequent secondary neovascular glaucoma, which can develop up to 24 months after initial presentation.5 Branch retinal vein occlusion can also lead to new vessel formation in the retina or optic disc, and both central retinal vein occlusion and branch retinal vein occlusion may lead to persistent macular oedema, causing permanent loss of vision. Prompt diagnosis and referral to an ophthalmologist for consideration of appropriate laser treatment are warranted. Retinal macroaneurysms may resolve spontaneously by thrombosis, or may be associated with recurrent leakage with retinal and vitreous haemorrhage. Laser photocoagulation may be indicated.8 Early treatment of Coats' disease can reduce the extent of visual loss.21
Severity of hypertension, cardiovascular disease, and mortality
Retinopathy is a prognostic marker in patients with hypertension. In the Keith-Wagener-Barker classification, presence of retinal haemorrhages and cotton wool spots, when present with other retinal changes, is categorised as grade 3 retinopathy, signifying severe hypertensive disease.9 In epidemiological studies, retinopathy has consistently been reported to occur more often in people with uncontrolled or undetected and untreated hypertension than in normotensive people and those with adequately treated hypertension.2 3 22
Retinopathy has been linked with lower glomerular filtration rates and microalbuminuria, and it occurs in parallel with left ventricular hypertrophy early in the course of blood pressure elevation.8 More recent studies have also shown an independent association between the presence of retinopathy and cerebrovascular disease.22 Furthermore, retinopathy has been found to be independently associated with increased all cause mortality.23 The association between non-diabetic retinopathy and ischaemic heart disease, however, is not well established.4
Preclinical diabetes
An interesting question is whether retinopathy is a marker of future risk of diabetes. Few data are available on this subject. One study found that retinopathy was associated with increasing fasting blood sugar concentrations in people not classified as having diabetes mellitus,24 although another study did not find this association.3
Other systemic diseases
Retinopathy in a patient with systemic lupus erythematosis is a known marker for the active phase of the disease.12 Severe retinopathy and other ischaemic retinal changes have also been associated with central nervous system systemic lupus erythematosis.25 White patches of retinitis in Behcet's disease may be indicative of reactivation of the disease process.15
Non-diabetic retinopathy in an AIDS patient is associated with increased systemic severity of the disease.19 A specific correlation of the number of cotton wool spots with increasing systemic severity of AIDS and decreased cerebral blood flow is not well established.
Clinical approach to management
Retinopathy lesions are commonly seen in middle aged and elderly people without diabetes. Common ocular conditions associated with retinopathy in non-diabetic patients include retinal vein occlusions, retinal telangiectasia, and retinal macroaneurysms. Common systemic causes include systemic hypertension, carotid atherosclerotic diseases, blood dyscrasias, systemic infections, and past radiotherapy. Doctors should be aware of these conditions and should appropriately investigate, refer, and manage these patients.
Additional education resources
Websites for doctors
www.emedicine.com—comprehensive, established, and regularly updated website containing extensively peer reviewed articles written by specialists on diseases spanning 62 medical specialties, including retinopathy
www.revoptom.com/HANDBOOK/default.htm—good site developed by optometrists outlining salient clinical and management principles of ocular disease, including many of the conditions predisposing to retinopathy
www.eyeweb.org—site developed and maintained by resident ophthalmologists at the American University of Beirut Medical Centre, providing short outlines of common ophthalmological conditions, including hypertensive retinopathy and retinal vein occlusion, tailored to primary care physicians
Websites for patients
www.emedicinehealth.com—recently developed branch website of the established web based medical reference emedicine.com, providing basic, well reviewed medical information on many conditions, including some diseases associated with retinopathy
www.intelihealth.com/IH/ihtIH/WSIHW000/408/408.html—website providing patients with basic information on various medical conditions, including some retinopathy related diseases, from sources such as Harvard Medical School
www.pennhealth.com/ency/content/index.html—website managed by the University of Pennsylvania Health System, containing information for patients on a multitude of medical conditions, including some retinopathy related diseases
www.eyemdlink.com/Conditions.asp—website dedicated to providing relevant information, contributed by American board certified ophthalmologists, to patients on ocular conditions, including retinopathy
Investigation of retinopathy
Medical history
Diabetes mellitus
Hypertension
History of cardiovascular disease (stroke, ischaemic heart disease, peripheral vascular disease)
History of thrombosis
Anaemia (for example, sickle cell disease)
Drug history (for example, aplastic anaemia)
Connective tissue disease (for example systemic lupus erythematosis)
Radiotherapy (for example, central nervous system or nasopharyngeal tumours, thyroid eye disease)
Malignancy (for example, leukaemia)
AIDS
Physical examination
General health (pallor, cachexia, lymphadenopathy)
Blood pressure assessment
Cardiovascular assessment
Neurological assessment
Investigations
Full blood count, erythrocyte sedimentation rate
Fasting glucose concentrations and oral glucose tolerance test
Lipids (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides)
Infectious disease investigations (for example, chest x ray, syphilis and HIV serology)
Neurological investigations (for example, carotid ultrasound)
Connective tissue investigations (C reactive protein, antinuclear antibodies, anti-dsDNA)
Haematological investigations (activated protein C resistance, protein C activity, protein S activity, antithrombin III activity, antiphospholipid antibodies, and anticardiolipin antibodies)
Further special diagnostic investigations as indicated from preliminary results
A table appears on bmj.com
We thank Tien Y Wong for his critical review of the paper.
Contributors: JV conducted the literature review and wrote the initial and final drafts. PM reviewed the manuscript and provided additional intellectual content and overall supervision.
Funding: None.
Competing interests: None declared.
References
Van Leiden HA, Dekker JM, Moll AC, Nijpels G, Heine RJ, Bouter LM, et al. Risk factors for incident retinopathy in a diabetic and nondiabetic population: the Hoorn study. Arch Ophthalmol 2003;121: 245-51.
Klein R, Klein BE, Moss SE, Wang Q. Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population. Arch Ophthalmol 1994;112: 92-8.
Yu T, Mitchell P, Berry G, Li W, Wang JJ. Retinopathy in older persons without diabetes and its relationship to hypertension. Arch Ophthalmol 1998;116: 83-9.
Wong TY, Klein R, Sharrett AR, Manolio TA, Hubbard LD, Marino EK, et al. The prevalence and risk factors of retinal microvascular abnormalities in older persons: the cardiovascular health study. Ophthalmology 2003;110: 658-66.
Williamson TH. Central retinal vein occlusion: what's the story? Br J Ophthalmol 1997;81: 698-704.
Mitchell P, Smith W, Chang A. Prevalence and associations of retinal vein occlusion in Australia: the Blue Mountains eye study. Arch Ophthalmol 1996;114: 1243-7.
Shields JA, Shields CL, Honavar SG, Demirci H. Clinical variations and complications of Coats disease in 150 cases: the 2000 Sanford Gifford memorial lecture. Am J Ophthalmol 2001;131: 561-71.
Rabb MF, Gagliano DA, Teske MP. Retinal arterial macroaneurysms. Surv Ophthalmol 1988;33: 73-96.
Chatterjee S, Chattopadhya S, Hope-Ross M, Lip PL. Hypertension and the eye: changing perspectives. J Hum Hypertens 2002;16: 667-75.
Brown GC, Magargal LE. The ocular ischemic syndrome: clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11: 239-51.
Klein R, Sharrett AR, Klein BE, Chambless LE, Cooper LS, Hubbard LD, et al. Are retinal arteriolar abnormalities related to atherosclerosis? The atherosclerosis risk in communities study. Arterioscler Thromb Vasc Biol 2000;20: 1644-50.
Jabs DA. Rheumatic diseases. In: Ryan SJ, Schachat AP, eds. Retina, 3rd ed, vol 2. St Louis, MO: Mosby, 2001: 1410-33.
Klinkhoff AV, Beattie CW, Chalmers A. Retinopathy in systemic lupus erythematosus: relationship to disease activity. Arthritis Rheum 1986;29: 1152-6.
Demirci FY, Kucukkaya R, Akarcay K, Kir N, Atamer T, Demirci H, et al. Ocular involvement in primary antiphospholipid syndrome: ocular involvement in primary APS. Int Ophthalmol 1998;22: 323-9.
Dominguez LN, Irvine AR. Fundus changes in Behcet's disease. Trans Am Ophthalmol Soc 1997;95: 367-82, discussion 382-6.
Charache S. Eye disease in sickling disorders. Hematol Oncol Clin North Am 1996;10: 1357-62.
Mansour AM, Salti HI, Han DP, Khoury A, Friedman SM, Salem Z, et al. Ocular findings in aplastic anaemia. Ophthalmologica 2000;214: 399-402.
Schachat AP, Markowitz JA, Guyer DR, Burke PJ, Karp JE, Graham ML. Ophthalmic manifestations of leukaemia. Arch Ophthalmol 1989;107: 697-700.
Jabs DA, Green WR, Fox R, Polk BF, Bartlett JG. Ocular manifestations of acquired immune deficiency syndrome. Ophthalmology 1989;96: 1092-9.
Brown GC, Shields JA, Sanborn G, Augsburger JJ, Savino PJ, Schatz NJ. Radiation retinopathy. Ophthalmology 1982;89: 1494-501.
Budning AS, Heon E, Gallie BL. Visual prognosis of Coats' disease. J AAPOS 1998;2: 356-9.
Wong TY, Klein R, Klein BE, Tielsch JM, Hubbard L, Nieto FJ. Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality. Surv Ophthalmol 2001;46: 59-80.
Schouten EG, Vandenbroucke JP, van der Heide-Wessel C, van der Heide RM. Retinopathy as an independent indicator of all-causes mortality. Int J Epidemiol 1986;15: 234-6.
Stolk RP, Vingerling JR, de Jong PT, Dielemans I, Hofman A, Lamberts SW, et al. Retinopathy, glucose, and insulin in an elderly population: the Rotterdam study. Diabetes 1995;44: 11-5.
Jabs DA, Miller NR, Newman SA, Johnson MA, Stevens MB. Optic neuropathy in systemic lupus erythematosus. Arch Ophthalmol 1986;104: 564-8.(Jayant Venkatramani, medi)
Correspondence to: P Mitchell, Centre for Vision Research, Westmead Millennium Institute, Westmead Hospital, Hawkesbury Road, Westmead, NSW 2145, Australia paul_mitchell@wmi.usyd.edu.au
Introduction
We reviewed studies on ocular and systemic causes of "retinopathy" from Medline and textbooks. We specifically excluded "diabetic retinopathy."
Non-diabetic retinopathy
Retinal vein occlusion
Central retinal vein occlusion and branch retinal vein occlusion can present with non-diabetic retinopathy. The appearance on funduscopy is usually characteristic, with flame shaped haemorrhages present within the distribution of the affected vein (fig 1). The patient may complain of a sudden painless unilateral loss of vision or visual field (for example, inferior field defects for superior branch retinal vein occlusion) or may be asymptomatic. If loss of vision is severe a relative afferent pupillary defect may exist, indicating retinal ischaemia. Important systemic risk factors for retinal vein occlusion include hypertension, diabetes mellitus, and other conditions such as hyperhomocystinaemia.5 Glaucoma is an important ocular risk factor. The prevalence of retinal vein occlusion was noted in one study to be 1.6% in people above 49 years of age.6 Given the possible severe associations of this condition and its relatively high prevalence, retinal vein occlusion should not be overlooked.
Fig 1 Branch retinal vein occlusion in a patient with hypertension
Summary points
Many people without diabetes may have signs of retinopathy (microaneurysms, retinal haemorrhages, cotton wool spots)
Ocular conditions associated with retinopathy in non-diabetic patients include retinal vein occlusions, retinal telangiectasia, and retinal macroaneurysms
Systemic conditions associated with retinopathy in non-diabetic patients include systemic hypertension, carotid atherosclerotic diseases, blood dyscrasias, systemic infections, and past radiotherapy to the head
Doctors should be aware of the common causes and clinical significance of these conditions, as retinopathy may be associated with visual loss (for example, retinal vein occlusion) or increased incidence of cardiovascular diseases (for example, hypertensive retinopathy)
Appropriate investigations and referral, if necessary, are advisable in the management of patients presenting with non-diabetic retinopathy
Retinal telangiectasia
Patients with retinal telangiectasia may present with retinopathy. In younger patients this is referred to as Coats' disease. It usually occurs in young men aged less than 20 years (median age 5 years7). Vision may be greatly affected in advanced cases. A milder form of the same disease, termed Leber's miliary aneurysms, can present later in life as a localised cluster of dilated capillaries, aneurysms, and telangiectasia, typically in the temporal quadrants of the retina. Either of these conditions should be suspected in young patients with retinopathy. About 8% of cases are asymptomatic.
Retinal macroaneurysm
Retinal macroaneurysm refers to an isolated aneurysmal dilatation of a major arterial or arteriolar branch that is often associated with leakage of exudate and multiple retinal haemorrhages. It usually occurs in older women and is strongly associated with hypertension and an increased incidence of cardiovascular and atherosclerotic vessel disease.8
Systemic causes of non-diabetic retinopathy
Whereas diabetic retinopathy is often associated with impairment of vision and blindness, the clinical significance of retinopathy in patients without diabetes is varied, particularly in cases of systemic disease.
Retinal vein occlusion and other retinal vascular disorders
Retinal vein occlusions and other retinal vascular disorders with signs of retinopathy are potentially sight threatening conditions. Ischaemic central retinal vein occlusion is associated with an increased risk of new vessel formation in the iris and subsequent secondary neovascular glaucoma, which can develop up to 24 months after initial presentation.5 Branch retinal vein occlusion can also lead to new vessel formation in the retina or optic disc, and both central retinal vein occlusion and branch retinal vein occlusion may lead to persistent macular oedema, causing permanent loss of vision. Prompt diagnosis and referral to an ophthalmologist for consideration of appropriate laser treatment are warranted. Retinal macroaneurysms may resolve spontaneously by thrombosis, or may be associated with recurrent leakage with retinal and vitreous haemorrhage. Laser photocoagulation may be indicated.8 Early treatment of Coats' disease can reduce the extent of visual loss.21
Severity of hypertension, cardiovascular disease, and mortality
Retinopathy is a prognostic marker in patients with hypertension. In the Keith-Wagener-Barker classification, presence of retinal haemorrhages and cotton wool spots, when present with other retinal changes, is categorised as grade 3 retinopathy, signifying severe hypertensive disease.9 In epidemiological studies, retinopathy has consistently been reported to occur more often in people with uncontrolled or undetected and untreated hypertension than in normotensive people and those with adequately treated hypertension.2 3 22
Retinopathy has been linked with lower glomerular filtration rates and microalbuminuria, and it occurs in parallel with left ventricular hypertrophy early in the course of blood pressure elevation.8 More recent studies have also shown an independent association between the presence of retinopathy and cerebrovascular disease.22 Furthermore, retinopathy has been found to be independently associated with increased all cause mortality.23 The association between non-diabetic retinopathy and ischaemic heart disease, however, is not well established.4
Preclinical diabetes
An interesting question is whether retinopathy is a marker of future risk of diabetes. Few data are available on this subject. One study found that retinopathy was associated with increasing fasting blood sugar concentrations in people not classified as having diabetes mellitus,24 although another study did not find this association.3
Other systemic diseases
Retinopathy in a patient with systemic lupus erythematosis is a known marker for the active phase of the disease.12 Severe retinopathy and other ischaemic retinal changes have also been associated with central nervous system systemic lupus erythematosis.25 White patches of retinitis in Behcet's disease may be indicative of reactivation of the disease process.15
Non-diabetic retinopathy in an AIDS patient is associated with increased systemic severity of the disease.19 A specific correlation of the number of cotton wool spots with increasing systemic severity of AIDS and decreased cerebral blood flow is not well established.
Clinical approach to management
Retinopathy lesions are commonly seen in middle aged and elderly people without diabetes. Common ocular conditions associated with retinopathy in non-diabetic patients include retinal vein occlusions, retinal telangiectasia, and retinal macroaneurysms. Common systemic causes include systemic hypertension, carotid atherosclerotic diseases, blood dyscrasias, systemic infections, and past radiotherapy. Doctors should be aware of these conditions and should appropriately investigate, refer, and manage these patients.
Additional education resources
Websites for doctors
www.emedicine.com—comprehensive, established, and regularly updated website containing extensively peer reviewed articles written by specialists on diseases spanning 62 medical specialties, including retinopathy
www.revoptom.com/HANDBOOK/default.htm—good site developed by optometrists outlining salient clinical and management principles of ocular disease, including many of the conditions predisposing to retinopathy
www.eyeweb.org—site developed and maintained by resident ophthalmologists at the American University of Beirut Medical Centre, providing short outlines of common ophthalmological conditions, including hypertensive retinopathy and retinal vein occlusion, tailored to primary care physicians
Websites for patients
www.emedicinehealth.com—recently developed branch website of the established web based medical reference emedicine.com, providing basic, well reviewed medical information on many conditions, including some diseases associated with retinopathy
www.intelihealth.com/IH/ihtIH/WSIHW000/408/408.html—website providing patients with basic information on various medical conditions, including some retinopathy related diseases, from sources such as Harvard Medical School
www.pennhealth.com/ency/content/index.html—website managed by the University of Pennsylvania Health System, containing information for patients on a multitude of medical conditions, including some retinopathy related diseases
www.eyemdlink.com/Conditions.asp—website dedicated to providing relevant information, contributed by American board certified ophthalmologists, to patients on ocular conditions, including retinopathy
Investigation of retinopathy
Medical history
Diabetes mellitus
Hypertension
History of cardiovascular disease (stroke, ischaemic heart disease, peripheral vascular disease)
History of thrombosis
Anaemia (for example, sickle cell disease)
Drug history (for example, aplastic anaemia)
Connective tissue disease (for example systemic lupus erythematosis)
Radiotherapy (for example, central nervous system or nasopharyngeal tumours, thyroid eye disease)
Malignancy (for example, leukaemia)
AIDS
Physical examination
General health (pallor, cachexia, lymphadenopathy)
Blood pressure assessment
Cardiovascular assessment
Neurological assessment
Investigations
Full blood count, erythrocyte sedimentation rate
Fasting glucose concentrations and oral glucose tolerance test
Lipids (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides)
Infectious disease investigations (for example, chest x ray, syphilis and HIV serology)
Neurological investigations (for example, carotid ultrasound)
Connective tissue investigations (C reactive protein, antinuclear antibodies, anti-dsDNA)
Haematological investigations (activated protein C resistance, protein C activity, protein S activity, antithrombin III activity, antiphospholipid antibodies, and anticardiolipin antibodies)
Further special diagnostic investigations as indicated from preliminary results
A table appears on bmj.com
We thank Tien Y Wong for his critical review of the paper.
Contributors: JV conducted the literature review and wrote the initial and final drafts. PM reviewed the manuscript and provided additional intellectual content and overall supervision.
Funding: None.
Competing interests: None declared.
References
Van Leiden HA, Dekker JM, Moll AC, Nijpels G, Heine RJ, Bouter LM, et al. Risk factors for incident retinopathy in a diabetic and nondiabetic population: the Hoorn study. Arch Ophthalmol 2003;121: 245-51.
Klein R, Klein BE, Moss SE, Wang Q. Hypertension and retinopathy, arteriolar narrowing, and arteriovenous nicking in a population. Arch Ophthalmol 1994;112: 92-8.
Yu T, Mitchell P, Berry G, Li W, Wang JJ. Retinopathy in older persons without diabetes and its relationship to hypertension. Arch Ophthalmol 1998;116: 83-9.
Wong TY, Klein R, Sharrett AR, Manolio TA, Hubbard LD, Marino EK, et al. The prevalence and risk factors of retinal microvascular abnormalities in older persons: the cardiovascular health study. Ophthalmology 2003;110: 658-66.
Williamson TH. Central retinal vein occlusion: what's the story? Br J Ophthalmol 1997;81: 698-704.
Mitchell P, Smith W, Chang A. Prevalence and associations of retinal vein occlusion in Australia: the Blue Mountains eye study. Arch Ophthalmol 1996;114: 1243-7.
Shields JA, Shields CL, Honavar SG, Demirci H. Clinical variations and complications of Coats disease in 150 cases: the 2000 Sanford Gifford memorial lecture. Am J Ophthalmol 2001;131: 561-71.
Rabb MF, Gagliano DA, Teske MP. Retinal arterial macroaneurysms. Surv Ophthalmol 1988;33: 73-96.
Chatterjee S, Chattopadhya S, Hope-Ross M, Lip PL. Hypertension and the eye: changing perspectives. J Hum Hypertens 2002;16: 667-75.
Brown GC, Magargal LE. The ocular ischemic syndrome: clinical, fluorescein angiographic and carotid angiographic features. Int Ophthalmol 1988;11: 239-51.
Klein R, Sharrett AR, Klein BE, Chambless LE, Cooper LS, Hubbard LD, et al. Are retinal arteriolar abnormalities related to atherosclerosis? The atherosclerosis risk in communities study. Arterioscler Thromb Vasc Biol 2000;20: 1644-50.
Jabs DA. Rheumatic diseases. In: Ryan SJ, Schachat AP, eds. Retina, 3rd ed, vol 2. St Louis, MO: Mosby, 2001: 1410-33.
Klinkhoff AV, Beattie CW, Chalmers A. Retinopathy in systemic lupus erythematosus: relationship to disease activity. Arthritis Rheum 1986;29: 1152-6.
Demirci FY, Kucukkaya R, Akarcay K, Kir N, Atamer T, Demirci H, et al. Ocular involvement in primary antiphospholipid syndrome: ocular involvement in primary APS. Int Ophthalmol 1998;22: 323-9.
Dominguez LN, Irvine AR. Fundus changes in Behcet's disease. Trans Am Ophthalmol Soc 1997;95: 367-82, discussion 382-6.
Charache S. Eye disease in sickling disorders. Hematol Oncol Clin North Am 1996;10: 1357-62.
Mansour AM, Salti HI, Han DP, Khoury A, Friedman SM, Salem Z, et al. Ocular findings in aplastic anaemia. Ophthalmologica 2000;214: 399-402.
Schachat AP, Markowitz JA, Guyer DR, Burke PJ, Karp JE, Graham ML. Ophthalmic manifestations of leukaemia. Arch Ophthalmol 1989;107: 697-700.
Jabs DA, Green WR, Fox R, Polk BF, Bartlett JG. Ocular manifestations of acquired immune deficiency syndrome. Ophthalmology 1989;96: 1092-9.
Brown GC, Shields JA, Sanborn G, Augsburger JJ, Savino PJ, Schatz NJ. Radiation retinopathy. Ophthalmology 1982;89: 1494-501.
Budning AS, Heon E, Gallie BL. Visual prognosis of Coats' disease. J AAPOS 1998;2: 356-9.
Wong TY, Klein R, Klein BE, Tielsch JM, Hubbard L, Nieto FJ. Retinal microvascular abnormalities and their relationship with hypertension, cardiovascular disease, and mortality. Surv Ophthalmol 2001;46: 59-80.
Schouten EG, Vandenbroucke JP, van der Heide-Wessel C, van der Heide RM. Retinopathy as an independent indicator of all-causes mortality. Int J Epidemiol 1986;15: 234-6.
Stolk RP, Vingerling JR, de Jong PT, Dielemans I, Hofman A, Lamberts SW, et al. Retinopathy, glucose, and insulin in an elderly population: the Rotterdam study. Diabetes 1995;44: 11-5.
Jabs DA, Miller NR, Newman SA, Johnson MA, Stevens MB. Optic neuropathy in systemic lupus erythematosus. Arch Ophthalmol 1986;104: 564-8.(Jayant Venkatramani, medi)