eMedicine Specialties > Ophthalmology > Choroid
Neovascularization, Choroidal: Differential Diagnoses & Workup
Updated: Jul 25, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Differential Diagnoses
Other Problems to Be Considered
Lacquer crack with adjacent hemorrhage secondary to myopic macular degeneration
Atrophic macular scar with adjacent hemorrhage
Workup
Laboratory Studies
- Laboratory studies may be indicated if certain underlying medical conditions, such as pseudoxanthoma elasticum (PXE), are present.
Imaging Studies
- Fluorescein angiography
- Fluorescein angiography (FA) is an essential tool in diagnosing and managing CNV.
- Several angiographic patterns have been described for CNV.
- A lesion that hyperfluoresces in the early phases of the angiogram, maintains well-demarcated borders, and leaks late (obscuring its borders) is a classic CNV.
- A lesion whose borders cannot be determined by FA is an occult CNV.
- Fibrovascular pigment epithelial detachment (PED) and late leakage of undetermined source (LLUS) represent patterns of occult CNV.
- A fibrovascular PED is a lesion that is elevated solidly and hyperfluoresces irregularly to different degrees.
- The lesion may be well demarcated or poorly demarcated. LLUS is seen during FA as an irregular, indistinct, late, sub-RPE leakage.
- According to its location relative to the center of the fovea, CNV has been classified as extrafoveal (200-1500 µm), juxtafoveal (1-199 µm), and subfoveal.
- Indocyanine green angiography
- Indocyanine green (ICG) is a water-soluble tricarbocyanine dye that contains 5% sodium iodide; it rapidly binds almost completely to globulins after intravenous injection. ICG has a peak absorption and fluorescence in the near infrared range. This allows visualization of choroidal pathology through overlying serosanguineous fluid, pigment, or a thin layer of hemorrhage that usually blocks visualization during FA. Because ICG is bound tightly to the plasma proteins, less dye escapes from the choroidal circulation, allowing better definition of choroidal vasculature.
- Three types of ICG patterns that are assumed to represent CNV may be imaged. A hot spot is a well-defined focal hyperfluorescent area that is less than one disc area in size. Hot spots usually fluoresce early. A plaque refers to a hyperfluorescent lesion that is larger than one disc area in size. A plaque usually does not fluoresce early, and its intensity diminishes late. Finally, some eyes harbor a combination of plaques and hot spots. In these eyes, the hot spots may be at the edge of the plaque, may overlie the plaque, or may be far from the plaque.
- High-speed or dynamic ICG angiography uses a scanning laser ophthalmoscope that takes up to 32 frames per second. These images are recorded like a movie, and the flow in and out of the vessels can actually be seen. The main use of dynamic ICG angiography is in the identification of CNV feeder vessels that are located in the Sattler layer of the choroid.
- Optical coherence tomography
- CNV causes thickening and fragmentation of the highly reflective RPE-choriocapillaris band. If the CNV is well defined, it is seen as a fusiform thickening of the RPE-choriocapillaris band. In contrast, poorly defined CNV is seen as a diffuse area of choroidal hyperreflectivity that blends into the normal contour of the normal RPE band. A normal boundary cannot be defined.
- A subretinal hemorrhage is seen as a layer of moderate reflectivity that elevates the neurosensory retina and causes optical shadowing, resulting in a lower reflectivity of the underlying RPE and choroid. Serous, hemorrhagic, or fibrovascular RPE detachments reveal focal RPE elevations with shadowing of the structures beneath the elevated areas. Serous detachments are characterized by complete shadowing of the underlying structures. A hemorrhagic RPE detachment shows a moderately reflective layer beneath the detached RPE. Fibrovascular RPE detachments demonstrate moderate reflectivity throughout the entire sub-RPE space under the elevation.
- Detachments of the neurosensory retina appear as elevations of a moderately reflective band above the RPE band. RPE tears can be seen as thick elevated areas of high reflectivity. The underlying choroid is completely shadowed, whereas the adjacent choroid reveals a hyperreflective image because of the absence of RPE. Retinal edema or thickness can be measured objectively by defining the anterior and posterior borders of the retina.
- Rogers and coworkers have proposed an optical coherence tomography (OCT) classification scheme of CNV following photodynamic therapy (PDT).30
- Stage I occurs shortly after PDT and lasts for about a week. It is characterized by an inflammatory reaction that causes an increase in intraretinal fluid in a circular fashion that corresponds with the treatment spot.
- Stage II represents the restoration of a near-normal foveal contour with diminished subretinal fluid occurring 1-4 weeks after treatment.
- Stage III represents reperfusion and involution of CNV. It typically occurs 4-12 weeks following treatment and is subdivided into 2 categories based on the ratio of subretinal fibrosis to fluid present. Stage IIIa contains a greater subretinal fluid to fibrosis ratio, indicating active CNV. Lesions in Stage IIIb have more prominent fibrosis with minimal intraretinal fluid, indicating inactive CNV.
- Further involution of CNV may lead to cystoid macular edema, signifying Stage IV.
- In Stage V, CNV and the subretinal fluid resolve, leading to fibrosis and retinal thinning.
- Despite the many advantages of OCT, FA remains the imaging modality of choice in the management of CNV. Currently, OCT cannot replace FA in the management of CNV.
- CNV causes thickening and fragmentation of the highly reflective RPE-choriocapillaris band. If the CNV is well defined, it is seen as a fusiform thickening of the RPE-choriocapillaris band. In contrast, poorly defined CNV is seen as a diffuse area of choroidal hyperreflectivity that blends into the normal contour of the normal RPE band. A normal boundary cannot be defined.
Histologic Findings
New capillaries and fibroblasts originate from the choroid and grow through a defect in the Bruch membrane into the subretinal space (type 2 CNV) or the sub-RPE space (type 1 CNV). Reactive hyperplastic RPE is present at the advancing edge of CNV.
Specimens obtained from surgical excision of CNV reveal that the most common cellular components are vascular endothelium and RPE. These were present in more than 85% of samples. Fibrocytes and macrophages also have been identified in more than 50% of specimens. Extracellular components include collagen and fibrin. VEGF has been identified in the specimens obtained during submacular surgery.
More on Neovascularization, Choroidal |
| Overview: Neovascularization, Choroidal |
Differential Diagnoses & Workup: Neovascularization, Choroidal |
| Treatment & Medication: Neovascularization, Choroidal |
| Follow-up: Neovascularization, Choroidal |
| References |
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References
Blinder KJ, Blumenkranz MS, Bressler NM, Bressler SB, Donato G, Lewis H, et al. Verteporfin therapy of subfoveal choroidal neovascularization in pathologic myopia: 2-year results of a randomized clinical trial--VIP report no. 3. Ophthalmology. Apr 2003;110(4):667-73. [Medline].
Blinder KJ, Bradley S, Bressler NM, Bressler SB, Donati G, Hao Y. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Am J Ophthalmol. Sep 2003;136(3):407-18. [Medline].
Bressler NM, Bressler SB, Childs AL, Haller JA, Hawkins BS, Lewis H, et al. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings: SST report no. 13. Ophthalmology. Nov 2004;111(11):1993-2006. [Medline].
Bressler NM, Bressler SB, Gragoudas ES. Clinical characteristics of choroidal neovascular membranes. Arch Ophthalmol. Feb 1987;105(2):209-13. [Medline].
Bressler SB, Bressler NM, Fine SL, Hillis A, Murphy RP, Olk RJ, et al. Natural course of choroidal neovascular membranes within the foveal avascular zone in senile macular degeneration. Am J Ophthalmol. Feb 1982;93(2):157-63. [Medline].
Chakravarthy U, Houston RF, Archer DB. Treatment of age-related subfoveal neovascular membranes by teletherapy: a pilot study. Br J Ophthalmol. May 1993;77(5):265-73. [Medline].
Dawson DW, Volpert OV, Gillis P, Crawford SE, Xu H, Benedict W, et al. Pigment epithelium-derived factor: a potent inhibitor of angiogenesis. Science. Jul 9 1999;285(5425):245-8. [Medline].
de Juan E Jr, Loewenstein A, Bressler NM, Alexander J. Translocation of the retina for management of subfoveal choroidal neovascularization II: a preliminary report in humans. Am J Ophthalmol. May 1998;125(5):635-46. [Medline].
Emerson MV, Lauer AK, Flaxel CJ, Wilson DJ, Francis PJ, Stout JT, et al. Intravitreal bevacizumab (Avastin) treatment of neovascular age-related macular degeneration. Retina. Apr-May 2007;27(4):439-44. [Medline].
Eyetech Study Group. Anti-vascular endothelial growth factor therapy for subfoveal choroidal neovascularization secondary to age-related macular degeneration: phase II study results. Ophthalmology. May 2003;110(5):979-86. [Medline].
Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. Nov 1984;102(11):1640-2. [Medline].
Folk JC, Reddy CV. White dot chorioretinal inflammatory syndromes. In: Medical and Surgical Retina Advances, Controversies, and Management. 1994;385-399.
Fuller B, Gitter KA. Traumatic choroidal rupture with late serous detachment of macula. Report of successful argon laser treatment. Arch Ophthalmol. Apr 1973;89(4):354-5. [Medline].
Goff MJ, Johnson RN, McDonald HR, Ai E, Jumper JM, Fu A. Intravitreal bevacizumab for previously treated choroidal neovascularization from age-related macular degeneration. Retina. Apr-May 2007;27(4):432-8. [Medline].
Gragoudas ES, Adamis AP, Cunningham ET, Feinsod M, Guyer DR. Pegaptanib for neovascular age-related macular degeneration. N Engl J Med. Dec 30 2004;351(27):2805-16. [Medline].
Gross JG, King LP, de Juan E Jr, Powers T. Subfoveal neovascular membrane removal in patients with traumatic choroidal rupture. Ophthalmology. Apr 1996;103(4):579-85. [Medline].
Grossniklaus HE, Green WR. Histopathologic and ultrastructural findings of surgically excised choroidal neovascularization. Submacular Surgery Trials Research Group. Arch Ophthalmol. Jun 1998;116(6):745-9. [Medline].
Hawkins BS, Bressler NM, Bressler SB, Davidorf FH, Hoskins JC, Marsh MJ, et al. Surgical removal vs observation for subfoveal choroidal neovascularization, either associated with the ocular histoplasmosis syndrome or idiopathic: I. Ophthalmic findings from a randomized clinical trial: Submacular Surgery Trials (SST) Group H Trial: SST Report No. 9. Arch Ophthalmol. Nov 2004;122(11):1597-611. [Medline].
Hawkins BS, Bressler NM, Miskala PH, Bressler SB, Holekamp NM, Marsh MJ, et al. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: ophthalmic findings: SST report no. 11. Ophthalmology. Nov 2004;111(11):1967-80. [Medline].
Ho AC, Yannuzzi LA, Pisicano K, DeRosa J. The natural history of idiopathic subfoveal choroidal neovascularization. Ophthalmology. May 1995;102(5):782-9. [Medline].
Klein R, Klein BE, Linton KL. Prevalence of age-related maculopathy. The Beaver Dam Eye Study. Ophthalmology. Jun 1992;99(6):933-43. [Medline].
Lambert HM, Capone A Jr, Aaberg TM, Sternberg P Jr, Mandell BA, Lopez PF. Surgical excision of subfoveal neovascular membranes in age-related macular degeneration. Am J Ophthalmol. Mar 15 1992;113(3):257-62. [Medline].
Laud K, Spaide RF, Freund KB, Slakter J, Klancnik JM Jr. Treatment of choroidal neovascularization in pathologic myopia with intravitreal bevacizumab. Retina. Oct 2006;26(8):960-3. [Medline].
Lazic R, Gabric N. Verteporfin therapy and intravitreal bevacizumab combined and alone in choroidal neovascularization due to age-related macular degeneration. Ophthalmology. Jun 2007;114(6):1179-85. [Medline].
Machemer R, Steinhorst UH. Retinal separation, retinotomy, and macular relocation: II. A surgical approach for age-related macular degeneration?. Graefes Arch Clin Exp Ophthalmol. Nov 1993;231(11):635-41. [Medline].
Macular Photocoagulation Study Group. Argon laser photocoagulation for neovascular maculopathy. Five-year results from randomized clinical trials. Arch Ophthalmol. Aug 1991;109(8):1109-14. [Medline].
Macular Photocoagulation Study Group. Laser photocoagulation for juxtafoveal choroidal neovascularization. Five-year results from randomized clinical trials. Arch Ophthalmol. Apr 1994;112(4):500-9. [Medline].
Pharmacological Therapy for Macular Degeneration Study Group. Interferon alfa-2a is ineffective for patients with choroidal neovascularization secondary to age-related macular degeneration. Results of a prospective randomized placebo-controlled clinical trial. Pharmacological Therapy for Macular Degeneration Study Group. Arch Ophthalmol. Jul 1997;115(7):865-72. [Medline].
Photodynamic Therapy Study Group. Photodynamic therapy of subfoveal choroidal neovascularization in age-related macular degeneration with verteporfin: one-year results of 2 randomized clinical trials--TAP report. Arch Ophthalmol. Oct 1999;117(10):1329-45. [Medline].
Rogers AH, Martidis A, Greenberg PB, Puliafito CA. Optical coherence tomography findings following photodynamic therapy of choroidal neovascularization. Am J Ophthalmol. Oct 2002;134(4):566-76. [Medline].
Rosenfeld PJ. Intravitreal avastin: the low cost alternative to lucentis?. Am J Ophthalmol. Jul 2006;142(1):141-3. [Medline].
[Best Evidence] Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. Oct 5 2006;355(14):1419-31. [Medline].
Rosenfeld PJ, Moshfeghi AA, Puliafito CA. Optical coherence tomography findings after an intravitreal injection of bevacizumab (avastin) for neovascular age-related macular degeneration. Ophthalmic Surg Lasers Imaging. Jul-Aug 2005;36(4):331-5. [Medline].
Rosenfeld PJ, Rich RM, Lalwani GA. Ranibizumab: Phase III clinical trial results. Ophthalmol Clin North Am. Sep 2006;19(3):361-72. [Medline].
Roth DB, Downie AA, Charles ST. Visual results after submacular surgery for neovascularization in age-related macular degeneration. Ophthalmic Surg Lasers. Nov 1997;28(11):920-5. [Medline].
Schmidt-Erfurth U, Miller J, Sickenberg M, Bunse A, Laqua H, Gragoudas E, et al. Photodynamic therapy of subfoveal choroidal neovascularization: clinical and angiographic examples. Graefes Arch Clin Exp Ophthalmol. May 1998;236(5):365-74. [Medline].
Sears J, Capone A Jr, Aaberg T Sr, Lewis H, Grossniklaus H, Sternberg P Jr, et al. Surgical management of subfoveal neovascularization in children. Ophthalmology. May 1999;106(5):920-4. [Medline].
Shiraga F, Ojima Y, Matsuo T, Takasu I, Matsuo N. Feeder vessel photocoagulation of subfoveal choroidal neovascularization secondary to age-related macular degeneration. Ophthalmology. Apr 1998;105(4):662-9. [Medline].
Sivagnanavel V, Evans JR, Ockrim Z, Chong V. Radiotherapy for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2004;(4):CD004004. [Medline].
Spaide RF, Guyer DR, McCormick B, Yannuzzi LA, Burke K, Mendelsohn M, et al. External beam radiation therapy for choroidal neovascularization. Ophthalmology. Jan 1998;105(1):24-30. [Medline].
Spaide RF, Laud K, Fine HF, Klancnik JM, Meyerle CB, Yannuzzi LA, et al. Intravitreal bevacizumab treatment of choroidal neovascularization secondary to age-related macular degeneration. Retina. Apr 2006;26(4):383-90. [Medline].
Spaide RF, Sorenson J, Maranan L. Photodynamic therapy with verteporfin combined with intravitreal injection of triamcinolone acetonide for choroidal neovascularization. Ophthalmology. Feb 2005;112(2):301-4. [Medline].
Staurenghi G, Orzalesi N, La Capria A, Aschero M. Laser treatment of feeder vessels in subfoveal choroidal neovascular membranes: a revisitation using dynamic indocyanine green angiography. Ophthalmology. Dec 1998;105(12):2297-305. [Medline].
Steen B, Sejersen S, Berglin L, Seregard S, Kvanta A. Matrix metalloproteinases and metalloproteinase inhibitors in choroidal neovascular membranes. Invest Ophthalmol Vis Sci. Oct 1998;39(11):2194-200. [Medline].
Sternberg P Jr, Lewis H. Photodynamic therapy for age-related macular degeneration: a candid appraisal. Am J Ophthalmol. Mar 2004;137(3):483-5. [Medline].
Teixeira A, Moraes N, Farah ME, Bonomo PP. Choroidal neovascularization treated with intravitreal injection of bevacizumab (Avastin) in angioid streaks. Acta Ophthalmol Scand. Dec 2006;84(6):835-6. [Medline].
Tewari A, Dhalla MS, Apte RS. Intravitreal bevacizumab for treatment of choroidal neovascularization in pathologic myopia. Retina. Nov-Dec 2006;26(9):1093-4. [Medline].
Thomas MA, Dickinson JD, Melberg NS, Ibanez HE, Dhaliwal RS. Visual results after surgical removal of subfoveal choroidal neovascular membranes. Ophthalmology. Aug 1994;101(8):1384-96. [Medline].
Verteporfin Roundtable Participants. Guidelines for using verteporfin (visudyne) in photodynamic therapy for choroidal neovascularization due to age-related macular degeneration and other causes: update. Retina. February/March 2005;25(2):119-134. [Medline].
Wood CM, Richardson J. Chorioretinal neovascular membranes complicating contusional eye injuries with indirect choroidal ruptures. Br J Ophthalmol. Feb 1990;74(2):93-6. [Medline].
Wormald R, Evans J, Smeeth L, Henshaw K. Photodynamic therapy for neovascular age-related macular degeneration. Cochrane Database Syst Rev. 2003;(2):CD002030. [Medline].
Wu L, Murphy RP. Photodynamic therapy: a new approach to the treatment of choroidal neovascularization secondary to age-related macular degeneration. Curr Opin Ophthalmol. Jun 1999;10(3):217-20. [Medline].
Wyhinny GJ, Jackson JL, Jampol LM, Caro NC. Subretinal neovascularization following multiple evanescent white-dot syndrome. Arch Ophthalmol. Oct 1990;108(10):1384-5. [Medline].
Yamamoto I, Rogers AH, Reichel E, Yates PA, Duker JS. Intravitreal bevacizumab (Avastin) as treatment for subfoveal choroidal neovascularisation secondary to pathological myopia. Br J Ophthalmol. Feb 2007;91(2):157-60. Epub 2006 Jul 26. [Medline].
Further Reading
Keywords
choroidal neovascularization, choroidal NV, CNV, subretinal neovascularization, Bruch's membrane, subretinal space, retinal pigment epithelium, RPE, visual loss, vision loss, vascular endothelium growth factor, VEGF, pigment epithelium derived factor, PEDF
Differential Diagnoses & Workup: Neovascularization, Choroidal