Abstract
Since the choroid is a highly vasculature structure, it may potentially be affected by a wide range of systemic conditions. Recently, there have been a surge of studies to assess the structural changes in the choroid both qualitatively and quantitatively using noninvasive enhanced depth imaging technology based on optical coherence tomography. In this chapter, we look at the various diseases and the effect they have on the choroid. The study of the choroid may give us insight into the systemic health of a patient.
Keywords
Pregnancy, Metabolic diseases, Cardiovascular, Respiratory diseases, Systemic inflammatory conditions, Hematological diseases
Introduction
The choroid is a highly vascular tissue, per unit weight, the choroid is the tissue with the highest blood flow in the body. The choroid is an integral part of the nutrient and oxygen exchange with the outer third of the retina, retinal pigment epithelium, a portion of the optic nerve, and it acts as the sole source of metabolic exchange for the fovea. Choroidal thickness is considered a proxy measure of choroidal blood flow, thus, compromised choroidal circulation might lead to structural changes in the choroid including changes in choroidal thickness. Due to the vascular nature of the choroid, potentially any disease that affects systemic vasculature could potentially affect choroid health. The high flow of blood in the choroid also predisposes it as a site for embolic and metastatic spread of infections and tumors.
By using enhanced depth imaging (EDI) technique based on optical coherence tomography (OCT) (EDI-OCT), we have been able to image the choroid, application of advanced image analysis tools has allowed us to study the architectural changes in the choroid and hence allowing the EDI-OCT scans for quantitative assessment of the choroidal stroma and choroidal vasculature. This chapter will look at our current understanding of how systemic conditions can be associated with choroidal changes and have influence on choroid thickness, and provide insights on how we might interpret choroid thickness as an indicator of systemic health.
Introduction
The choroid is a highly vascular tissue, per unit weight, the choroid is the tissue with the highest blood flow in the body. The choroid is an integral part of the nutrient and oxygen exchange with the outer third of the retina, retinal pigment epithelium, a portion of the optic nerve, and it acts as the sole source of metabolic exchange for the fovea. Choroidal thickness is considered a proxy measure of choroidal blood flow, thus, compromised choroidal circulation might lead to structural changes in the choroid including changes in choroidal thickness. Due to the vascular nature of the choroid, potentially any disease that affects systemic vasculature could potentially affect choroid health. The high flow of blood in the choroid also predisposes it as a site for embolic and metastatic spread of infections and tumors.
By using enhanced depth imaging (EDI) technique based on optical coherence tomography (OCT) (EDI-OCT), we have been able to image the choroid, application of advanced image analysis tools has allowed us to study the architectural changes in the choroid and hence allowing the EDI-OCT scans for quantitative assessment of the choroidal stroma and choroidal vasculature. This chapter will look at our current understanding of how systemic conditions can be associated with choroidal changes and have influence on choroid thickness, and provide insights on how we might interpret choroid thickness as an indicator of systemic health.
Pregnancy
Pregnancy
Pregnancy induces various ocular changes, including visual changes, ocular blood flow, fall in intraocular pressure, and an increase in curvature and central cornea thickness. During pregnancy, there may be an increase of pregnancy-related fluid retention in the choroid, causing increased choroidal thickness in normal pregnant women than in normal nonpregnant women, particularly in the second trimester.
Preeclampsia
Preeclampsia is an obstetrical complication affecting multiple systems, characterized by placental ischemia, systemic inflammation and vascular changes that causes widespread vasoconstriction, new onset systemic hypertension and proteinuria. Complications of severe preeclampsia are cerebral or visual disturbances, impaired liver function, pulmonary edema, and thrombocytopenia. Subjective visual disturbances are reported in 40% of women with preeclampsia.
The systemically increased vasospasm in preeclampsia causes choroidal vascular spasm, resulting in decreased choroidal thickness in preeclampsia as compared to normal pregnant women. The choroidal thickness in women with preeclampsia may be comparable to that of normal nonpregnant women.
Introduction
The choroid is a highly vascular tissue, per unit weight, the choroid is the tissue with the highest blood flow in the body. The choroid is an integral part of the nutrient and oxygen exchange with the outer third of the retina, retinal pigment epithelium, a portion of the optic nerve, and it acts as the sole source of metabolic exchange for the fovea. Choroidal thickness is considered a proxy measure of choroidal blood flow, thus, compromised choroidal circulation might lead to structural changes in the choroid including changes in choroidal thickness. Due to the vascular nature of the choroid, potentially any disease that affects systemic vasculature could potentially affect choroid health. The high flow of blood in the choroid also predisposes it as a site for embolic and metastatic spread of infections and tumors.
By using enhanced depth imaging (EDI) technique based on optical coherence tomography (OCT) (EDI-OCT), we have been able to image the choroid, application of advanced image analysis tools has allowed us to study the architectural changes in the choroid and hence allowing the EDI-OCT scans for quantitative assessment of the choroidal stroma and choroidal vasculature. This chapter will look at our current understanding of how systemic conditions can be associated with choroidal changes and have influence on choroid thickness, and provide insights on how we might interpret choroid thickness as an indicator of systemic health.
Pregnancy
Pregnancy
Pregnancy induces various ocular changes, including visual changes, ocular blood flow, fall in intraocular pressure, and an increase in curvature and central cornea thickness. During pregnancy, there may be an increase of pregnancy-related fluid retention in the choroid, causing increased choroidal thickness in normal pregnant women than in normal nonpregnant women, particularly in the second trimester.
Preeclampsia
Preeclampsia is an obstetrical complication affecting multiple systems, characterized by placental ischemia, systemic inflammation and vascular changes that causes widespread vasoconstriction, new onset systemic hypertension and proteinuria. Complications of severe preeclampsia are cerebral or visual disturbances, impaired liver function, pulmonary edema, and thrombocytopenia. Subjective visual disturbances are reported in 40% of women with preeclampsia.
The systemically increased vasospasm in preeclampsia causes choroidal vascular spasm, resulting in decreased choroidal thickness in preeclampsia as compared to normal pregnant women. The choroidal thickness in women with preeclampsia may be comparable to that of normal nonpregnant women.
Metabolic Diseases
Diabetes Mellitus
Diabetes mellitus is primarily a vascular disease, and its complications can be divided into macrovascular and microvascular abnormities. In diabetes, other than changes in retinal blood flow, the changes in choroidal vasculature may play a vital role in the pathogenesis of diabetic eye disease. Various choroidal abnormalities have been reported in studies on diabetics, including choroidal neovascularization, choroidal vascular degeneration, obstruction of the choriocapillaris, choroidal aneurysms, and increased tortuosity and narrowing of the choroidal vessels.
Many studies have been done with regards to choroidal thickness in diabetes, but results have been varied. One study did not find any significant difference in the mean choroidal thickness between their controls and diabetic patients. Another study reported similar choroidal thickness between their controls and nonproliferative diabetic retinopathy. Meanwhile, two studies showed that patients with diabetes mellitus had significantly thinner choroid than nondiabetics regardless of their diabetic retinopathy status. In contrast, another study showed that early diabetic retinopathy patients had thinner choroid compared to nondiabetics, but it progressively thickened with increasing severity of diabetic retinopathy. In the Beijing Eye Study, choroidal thickness was measured in 246 subjects with diabetes mellitus. The study found that there is increased choroidal thickness in subjects with diabetes, and no association between the presence and severity of diabetic retinopathy and the change in subfoveal choroidal thickness. Due to controversial reports, the effect of diabetes on choroid is still not clear; other ocular parameters may be explored to understand the pathophysiology of diabetes mellitus in the choroid.
Hypercholesterolemia
Atherosclerotic changes may occur in the choroid due to its high blood flow. These changes occur in presence of hypercholesterolemia. A single study showed that there was significantly higher subfoveal choroidal thickness in subjects with hypercholesterolemia than in controls. Further studies need to be conducted to confirm this association and determine the possible mechanisms involved. It might be important to consider hypercholesterolemia while analyzing choroidal thickness.
Cardiovascular Diseases
Hypertension
Hypertension causes disease in vascular systems in the brain, heart, kidneys, and eyes. In the eyes, it can cause retinal hemorrhages, cotton wool spots, vessel closure in the retinal capillaries and choriocapillaris, and intraretinal lipid accumulation. Retinal and choroidal changes occur with hypertension; however, the pathophysiology behind choroidal changes remains unknown. A single study demonstrated a significant increase in subfoveal choroid thickness in patients with hypertensive retinopathy. This could be due to accumulation of interstitial fluid in the choroid because of choroid permeability changes. Hypertension is a possible determinant of choroidal thickness; however, further studies are required to confirm this finding.
Respiratory Diseases
Smoking
Smoking is a significant modifiable risk factor for many systemic diseases, especially in the cardiovascular and respiratory systems. In the eye, smoking causes alterations in vasculature, including decrease in choroidal and retinal blood flow. It is a risk factor for ocular vascular diseases such as age-related macular degeneration, anterior ischemic optic neuropathy, and hypertensive retinopathy. The changes in vasculature in the choroid may in turn affect its structure, including choroidal thickness. Smoking causes a significant decrease in choroidal thickness. The proposed mechanism of this decrease is vascular dysfunction secondary to a decrease in nitric oxide bioavailability. This causes peripheral vasoconstriction, which leads to increased resistance to blood flow peripherally, eventually causing a decrease in choroidal thickness.
Systemic Inflammatory Conditions
Systemic inflammatory conditions may affect choroidal tissue structure, and this often relates to disease activity. In the active inflammatory phase, there is generally increased choroidal thickness, which may decrease in the chronic phase.
Ankylosing Spondylitis
Ankylosing spondylitis is a systemic inflammatory disease which involves the eye, causing anterior uveitis. Uveitis is the most common extraarticular manifestation of seronegative spondyloarthritis and is one of the classification criteria for the disease. One study showed that ankylosing spondylitis causes an increased choroidal thickness; however, disease duration and severity had no association with choroidal thickness. The increase in choroidal thickness may be explained by inflammation of the uveal tract.
Raynaud’s Phenomenon
In Raynaud’s phenomenon, the extremities experience a reversible vasospastic response to cold or emotion. It is an early manifestation of systemic sclerosis. The vasoconstriction and vasodilation affects not only the peripheries, but other organs such as the eye as well. Thinning of the choroid is observed in patients with primary Raynaud’s phenomenon. When the Raynaud’s phenomenon is secondary to systemic sclerosis, the thinning is more severe. This may be because the thickness of the choroid reflects systemic hemodynamic changes. Raynaud’s phenomenon affects the basal sympathetic tone, which affects blood circulation.
Vogt–Koyanagi–Harada Syndrome
Vogt–Koyanagi–Harada (VKH) Syndrome is an autoimmune disease that affects melanocyte-containing tissues like the skin, meninges, and uvea. The disease has four phases; prodromal, acute uveitis, convalescent, and chronic-recurrent phases. VKH causes bilateral granulomatous panuveitis, presenting as diffuse choroiditis in the beginning, with multifocal serous detachments that may lead to serious retinal detachment. VKH may progress to cause chorioretinal depigmentation, perilimbal vitiligo, and sunset glow fundus.
VKH causes a markedly increased choroid thickness during active disease; however, the choroid thickness decreased with longer disease duration and increased degree of depigmentation in chronic disease. Choroidal thickness also decreases in response to corticosteroid treatment in patients with active inflammation. Serial measurements of choroidal thickness may provide a noninvasive tool to monitor disease progression and guide treatment in VKH ( Figs. 15.1 and 15.2 ).
Behçet’s Disease
Behcet’s disease is characterized by recurrent oral ulceration and the presence of other systemic manifestations such as genital ulcers, ocular complications, skin lesions, vascular disease, gastrointestinal complications, neurological disease, or arthritis. Ocular complications occur in 70% of women and 95% of men and generally presents bilaterally. Complications include retinitis, retinal vasculitis, vitritis, and panuveitis. In the end stage of the disease, there is optic atrophy, vascular occlusion, and gliotic sheathing.
Subfoveal choroidal thickness is increased in affected eyes in patients during the acute phase of Behçet’s disease as compared to the quiescent phase. Choroidal thickness is also increased in the quiescent phase, and even in the uninvolved eye in patients with Behçet’s disease as compared to the general population. Choroidal thickness significantly decreased when the patient was treated with infliximab.
Sarcoidosis
Sarcoidosis is an idiopathic multisystem granulomatous disorder, characterized by noncaseating granulomas in various organs such as eyes, lungs, liver, spleen, parotid glands, skin, mediastinal and superficial lymph nodes, and pharyngeal bones. In the eye, it may present with choroidal and optic disk granulomas, anterior, intermediate or panuveitis, segmental or occlusive phlebitis, and multifocal choroiditis.
To date, only individual case reports have been done on choroid involvement in sarcoidosis. Choroidal granulomas present as a homogenous hyporeflective lesion on EDI-OCT scans, sparing surrounding choroid. The thickness of the choroid varies, and more research must be done to determine the effect this disease has on the choroid. The choroidal granulomas decreased in size after treatment with immunosuppressants.
Tumors
Metastatic Cancer
Approximately 90% of uveal metastases occur in the choroid, making it the most common site, followed by the iris and ciliary body. The most common primary sites are the breast and bronchus. Other primary sites are the kidney, gastrointestinal tract, skin, and rarely the prostate. Metastasis to the choroid may be unilateral or bilateral and multifocal or unifocal, thus choroidal metastases do not cause generalized increase or decrease in choroidal thickness.
On studying the imaging features of choroidal metastasis using EDI-OCT, it was found that the tumors had a characteristic lumpy bumpy anterior surface, with disruption of the outer retina layer, but the inner layers of the retina were preserved.
A large study was done, showing that most metastatic choroid tumors are plateau or some shaped and approximately 3 mm thick. Choroidal metastatic tumors from breast cancer are usually bilateral, multifocal, and flatter, measuring 2 mm at the thickest tumor focus. Thicker tumors are more commonly found in lung, gastrointestinal, kidney, and prostate cancers; the mean thickness in kidney and gastrointestinal tumors is 4 mm. The flattest tumors are secondary to metastasis from skin melanomas, with a mean thickness of 1 mm.
Sturge–Weber Syndrome
Sturge–Weber syndrome (SWS) is a congenital vascular disorder with capillary-venous malformations affecting the central nervous system and eye. It is characterized by facial capillary malformation (port wine stain). The most common ocular presentation is the choroidal hemangioma, which typically enlarges slowly and involves over half of the choroid. Diffuse choroidal hemangiomas almost only occur in patients with SWS and is associated with serous retinal detachment. Because of the vascular malformations in the choroid, it is known to cause increased choroidal thickness ( Fig. 15.3 ). The choroidal thickness decreases when the eye is treated with photodynamic therapy, thus choroidal thickness may be a useful marker for follow-up in patients with SWS posttreatment.
