What's Your Diagnosis?

AMD patient with blurry vision

A 71-year-old Hispanic male presented to the eye clinic with complaints of blurry vision in both eyes of 4 months duration. The patient had been followed in the clinic for dry age-related macular degeneration for numerous years. He was given a home Amsler grid at previous visits and reported no new metamorphopsia, scotoma or decreased vision.

The patient’s medical history was positive for arthritis, hypertension and asthma, which were well controlled medically. He had a history of chronic cigarette use, with failed attempts at cessation through the years.

The patient’s right macula. Note the soft confluent drusen and underlying retinal pigment epithelium changes.
Source: Julie Rodman, OD, MS, FAAO

Best corrected visual acuity was 20/25 OD and OS. Slit lamp exam showed age-appropriate lens changes, with normal intraocular pressure of 18 mm Hg in each eye. Dilated fundus examination revealed moderate optic disc cupping with hypertensive retinopathy not involving the macula or optic disc.

The patient’s left macula. Note the soft confluent drusen and irregular, elevated lesion nasal to the macula.

There was evidence of soft confluent drusen and retinal pigment epithelial atrophy bilaterally. Directly nasal to the fovea in the left eye, there was evidence of an elevated, discolored (orange) lesion. Spectral domain optical coherence tomography (SD-OCT) was performed to obtain cross-sectional images through the lesion. SD-OCT B-scans confirmed the presence of soft, confluent drusen in both eyes. In addition, there was a subretinal heterogeneous hyper-reflective lesion nasal to the fovea with an adjacent cuff of fluid. OCT angiography (OCT-A) was obtained to visualize the choroidal vasculature in more detail and evaluate for the presence of a choroidal neovascular membrane (CNVM).

OCT-A of left eye. Note the hyper-reflective lacy network at the level of the choroid and outer retina. On the lower left panel, the B-scans highlight soft confluent drusen and, directly nasal to the macula, an area of turbidity associated with serous fluid consistent with neovascular activity.

What’s your diagnosis?
See answer on the next page

A number of conditions are associated with CNVM.

Ocular histoplasmosis syndrome (OHS) is a chorioretinal disorder usually encountered in individuals that have lived in or visited the Ohio-Mississippi River Valley, a region endemic for the fungus, Histoplasma capsulatum. Patients are usually in the 20- to 50-year-old age range.

OHS typically presents with a clinical triad including atrophic choroidal scars in the macula or midperiphery (histo spots), a macular CNVM, and peripapillary atrophy or scarring adjacent to the disc. CNVM secondary to OHS is linked to H. capsulatum. The histo spots from which the choroidal neovascularization develop represent focal defects in Bruch’s membrane that provide access for choroidal neovascularization development to invade the subretinal space.

The vector for the fundus is birds, whose droppings carry the fungal spores. These spores enter the human host through airways. Another way to encounter the airborne spores is through close contact with chickens or exotic pet birds.

Angioid streaks appear as subretinal dark or reddish radial bands emanating from the optic disc, sometimes in a spoke-like pattern. Angioid streaks represent breaks in Bruch’s membrane and can be visualized precisely with fundus autofluorescence. These streaks may lead to neovascularization and result in maculopathy.

Julie Rodman

Associated systemic conditions include pseudoxanthoma elasticum, Paget’s disease, sickle-cell disease and Ehlers-Danlos syndrome.

High myopia. Myopic choroidal neovascularization is the most common cause of CNVM in individuals younger than 50 years of age. Patients will typically present with posterior staphyloma, myopic crescent, anomalous optic nerve insertion, Fuchs’ spot and a refractive error greater than 6 D.

Discussion

The present patient did not exhibit or report any risks for choroidal neovascularization other than age and history of chronic cigarette use. OCT-A is a noninvasive technology that employs high-resolution imaging to allow for visualization of the retinal and choroidal circulation. Blood flow detection is achieved using signal decorrelation between consecutive cross-sectional B-scan frames, providing a 3-D angiogram.

OCT-A uses the concept of motion contrast to visualize vascular patterns and is achieved by rapidly acquiring repeated OCT B-scans at the same retinal loci. If the tissue is stationary, the consecutive B-scan images will be identical; however, if there is blood flow, the moving red blood cells will cause pixels in the repeated B-scans to become decorrelated, resulting in a map of capillary patterns. Artifacts from patient movement are eliminated so that motion between successive B-scans represents strictly red blood cell motion through the blood vessels. OCT-A requires higher imaging speeds than conventional OCT due to the higher imaging speeds necessary need to achieve successive B-scans.

OCT-A has several advantages, including ease of use, rapid scan acquisition, 3-D imaging allowing for depth resolution of pathology and segmentation among individual capillary layers. For these reasons, OCT-A is a unique and complementary methodology to stereoscopic observation, fundus photography, SD-OCT, fundus autofluorescence, dark adaptation and other conventional diagnostic evaluations.

Due to the segmentation properties of the device, the en-face OCT images (OCT angiograms) can be analyzed from the internal limiting membrane to the choroid to precisely identify the location of the microvascular abnormality and can be cross-referenced with the B-scan images. In addition, the angiograms provide blood flow information (but not vessel-wall integrity data) at different depths within the retina and choroid.

The superficial retinal vascular plexus includes vasculature from the inner limiting membrane through the inner plexiform layer, the deep vascular plexus includes the inner nuclear layer through outer plexiform layer, the outer retinal vascular plexus images the outer nuclear layer through Bruch’s membrane and finally the choriocapillaris slab illustrates the choroidal vasculature.

Fluorescein angiography (FA) remains the gold standard for the detection of retinal and choroidal neovascularization, as it measures the transit of venous contrast over time, allowing for direct visualization from leakage and dye pooling. However, it is important to note that pathologies can be obscured by leakage, hemorrhage or media opacities, thus making accurate interpretation difficult with FA.

FA provides a planar or flat image, thus depth and size of the lesion may be masked by dye leakage. Consequently, segmentation of retinal and choroidal vasculature is not possible with routine FA. In contrast, OCT-A provides a volumetric presentation of capillary density without the use of dye. FA is also invasive, which can be associated with systemic side effects, contraindications and anaphylaxis.

The present case

Structural OCT (SD-OCT) has emerged as an indispensable technology in the diagnosis and management of AMD. Fluid, exudates, cysts, retinal thickening and subretinal fluid are readily visible with this technology. However, SD-OCT is unable to visualize actual neovascular networks.

While not a direct substitute for FA, OCT-A is particularly useful for CNVM, as it allows for precise evaluation of the extent and morphology of the neovascularization inside the fibrovascular network without the problems linked to dye dynamics. The membrane may appear tree-like or sea fan-like in appearance with fine branches that appear to penetrate into the deeper retinal space. Because OCT-A provides a segmentation map of the retinal and choroidal vasculature, precise identification and classification of the CNVM is possible.

Neovascularization that occurs below the level of the RPE is classified as type 1, type 2 would course above the RPE, and type 3 would be intraretinal in nature. Thus, a type 1 membrane originates in the choriocapillaris with a feeder vessel that perforates through Bruch’s membrane and develops under the RPE. A type 2 membrane develops above the RPE but below the retina, but can course anterior into the retinal space.

Evaluation of the OCT-A images for the aforementioned patient demonstrated a hyper-reflective lacy network originating at the level of the choriocapillaris and extending anterior into Bruch’s membrane/outer retina. Viewing the OCT-A images alongside the B-scans not only provided outstanding resolution of the membrane, but allowed for its classification and measurement. Despite the quiescent nature of this gentleman’s condition for years, OCT-A was used to confirm the diagnosis and allow for timely referral and management.

Disclosures: Rodman reports she is a consultant and speaker for Optovue. Semes is an advisor or on the speakers bureau for Alcon, Allergan, Bausch + Lomb, Genentech, Maculogix, OptoVue, Shire and ZeaVision. He is a stockholder with HPO.

A 71-year-old Hispanic male presented to the eye clinic with complaints of blurry vision in both eyes of 4 months duration. The patient had been followed in the clinic for dry age-related macular degeneration for numerous years. He was given a home Amsler grid at previous visits and reported no new metamorphopsia, scotoma or decreased vision.

The patient’s medical history was positive for arthritis, hypertension and asthma, which were well controlled medically. He had a history of chronic cigarette use, with failed attempts at cessation through the years.

The patient’s right macula. Note the soft confluent drusen and underlying retinal pigment epithelium changes.
Source: Julie Rodman, OD, MS, FAAO

Best corrected visual acuity was 20/25 OD and OS. Slit lamp exam showed age-appropriate lens changes, with normal intraocular pressure of 18 mm Hg in each eye. Dilated fundus examination revealed moderate optic disc cupping with hypertensive retinopathy not involving the macula or optic disc.

The patient’s left macula. Note the soft confluent drusen and irregular, elevated lesion nasal to the macula.

There was evidence of soft confluent drusen and retinal pigment epithelial atrophy bilaterally. Directly nasal to the fovea in the left eye, there was evidence of an elevated, discolored (orange) lesion. Spectral domain optical coherence tomography (SD-OCT) was performed to obtain cross-sectional images through the lesion. SD-OCT B-scans confirmed the presence of soft, confluent drusen in both eyes. In addition, there was a subretinal heterogeneous hyper-reflective lesion nasal to the fovea with an adjacent cuff of fluid. OCT angiography (OCT-A) was obtained to visualize the choroidal vasculature in more detail and evaluate for the presence of a choroidal neovascular membrane (CNVM).

OCT-A of left eye. Note the hyper-reflective lacy network at the level of the choroid and outer retina. On the lower left panel, the B-scans highlight soft confluent drusen and, directly nasal to the macula, an area of turbidity associated with serous fluid consistent with neovascular activity.

What’s your diagnosis?
See answer on the next page

PAGE BREAK

A number of conditions are associated with CNVM.

Ocular histoplasmosis syndrome (OHS) is a chorioretinal disorder usually encountered in individuals that have lived in or visited the Ohio-Mississippi River Valley, a region endemic for the fungus, Histoplasma capsulatum. Patients are usually in the 20- to 50-year-old age range.

OHS typically presents with a clinical triad including atrophic choroidal scars in the macula or midperiphery (histo spots), a macular CNVM, and peripapillary atrophy or scarring adjacent to the disc. CNVM secondary to OHS is linked to H. capsulatum. The histo spots from which the choroidal neovascularization develop represent focal defects in Bruch’s membrane that provide access for choroidal neovascularization development to invade the subretinal space.

The vector for the fundus is birds, whose droppings carry the fungal spores. These spores enter the human host through airways. Another way to encounter the airborne spores is through close contact with chickens or exotic pet birds.

Angioid streaks appear as subretinal dark or reddish radial bands emanating from the optic disc, sometimes in a spoke-like pattern. Angioid streaks represent breaks in Bruch’s membrane and can be visualized precisely with fundus autofluorescence. These streaks may lead to neovascularization and result in maculopathy.

Julie Rodman

Associated systemic conditions include pseudoxanthoma elasticum, Paget’s disease, sickle-cell disease and Ehlers-Danlos syndrome.

High myopia. Myopic choroidal neovascularization is the most common cause of CNVM in individuals younger than 50 years of age. Patients will typically present with posterior staphyloma, myopic crescent, anomalous optic nerve insertion, Fuchs’ spot and a refractive error greater than 6 D.

Discussion

The present patient did not exhibit or report any risks for choroidal neovascularization other than age and history of chronic cigarette use. OCT-A is a noninvasive technology that employs high-resolution imaging to allow for visualization of the retinal and choroidal circulation. Blood flow detection is achieved using signal decorrelation between consecutive cross-sectional B-scan frames, providing a 3-D angiogram.

OCT-A uses the concept of motion contrast to visualize vascular patterns and is achieved by rapidly acquiring repeated OCT B-scans at the same retinal loci. If the tissue is stationary, the consecutive B-scan images will be identical; however, if there is blood flow, the moving red blood cells will cause pixels in the repeated B-scans to become decorrelated, resulting in a map of capillary patterns. Artifacts from patient movement are eliminated so that motion between successive B-scans represents strictly red blood cell motion through the blood vessels. OCT-A requires higher imaging speeds than conventional OCT due to the higher imaging speeds necessary need to achieve successive B-scans.

OCT-A has several advantages, including ease of use, rapid scan acquisition, 3-D imaging allowing for depth resolution of pathology and segmentation among individual capillary layers. For these reasons, OCT-A is a unique and complementary methodology to stereoscopic observation, fundus photography, SD-OCT, fundus autofluorescence, dark adaptation and other conventional diagnostic evaluations.

Due to the segmentation properties of the device, the en-face OCT images (OCT angiograms) can be analyzed from the internal limiting membrane to the choroid to precisely identify the location of the microvascular abnormality and can be cross-referenced with the B-scan images. In addition, the angiograms provide blood flow information (but not vessel-wall integrity data) at different depths within the retina and choroid.

PAGE BREAK

The superficial retinal vascular plexus includes vasculature from the inner limiting membrane through the inner plexiform layer, the deep vascular plexus includes the inner nuclear layer through outer plexiform layer, the outer retinal vascular plexus images the outer nuclear layer through Bruch’s membrane and finally the choriocapillaris slab illustrates the choroidal vasculature.

Fluorescein angiography (FA) remains the gold standard for the detection of retinal and choroidal neovascularization, as it measures the transit of venous contrast over time, allowing for direct visualization from leakage and dye pooling. However, it is important to note that pathologies can be obscured by leakage, hemorrhage or media opacities, thus making accurate interpretation difficult with FA.

FA provides a planar or flat image, thus depth and size of the lesion may be masked by dye leakage. Consequently, segmentation of retinal and choroidal vasculature is not possible with routine FA. In contrast, OCT-A provides a volumetric presentation of capillary density without the use of dye. FA is also invasive, which can be associated with systemic side effects, contraindications and anaphylaxis.

The present case

Structural OCT (SD-OCT) has emerged as an indispensable technology in the diagnosis and management of AMD. Fluid, exudates, cysts, retinal thickening and subretinal fluid are readily visible with this technology. However, SD-OCT is unable to visualize actual neovascular networks.

While not a direct substitute for FA, OCT-A is particularly useful for CNVM, as it allows for precise evaluation of the extent and morphology of the neovascularization inside the fibrovascular network without the problems linked to dye dynamics. The membrane may appear tree-like or sea fan-like in appearance with fine branches that appear to penetrate into the deeper retinal space. Because OCT-A provides a segmentation map of the retinal and choroidal vasculature, precise identification and classification of the CNVM is possible.

Neovascularization that occurs below the level of the RPE is classified as type 1, type 2 would course above the RPE, and type 3 would be intraretinal in nature. Thus, a type 1 membrane originates in the choriocapillaris with a feeder vessel that perforates through Bruch’s membrane and develops under the RPE. A type 2 membrane develops above the RPE but below the retina, but can course anterior into the retinal space.

Evaluation of the OCT-A images for the aforementioned patient demonstrated a hyper-reflective lacy network originating at the level of the choriocapillaris and extending anterior into Bruch’s membrane/outer retina. Viewing the OCT-A images alongside the B-scans not only provided outstanding resolution of the membrane, but allowed for its classification and measurement. Despite the quiescent nature of this gentleman’s condition for years, OCT-A was used to confirm the diagnosis and allow for timely referral and management.

Disclosures: Rodman reports she is a consultant and speaker for Optovue. Semes is an advisor or on the speakers bureau for Alcon, Allergan, Bausch + Lomb, Genentech, Maculogix, OptoVue, Shire and ZeaVision. He is a stockholder with HPO.