Age-Related Macular Degeneration - part 4 docx

C Late-phase ICG study 6 weeks after laser treatment demonstrating resolution of the active CNV and of the serous PED after ICG-guide laser treatment.These polypoidal structures correspo

is complete flattening of the PED and resolution of the lipids No change is noted in the central lesion (F) Late-phase ICG study 3 months after treatment demonstrating hypofluorescence at the site of the active CNV and of the previous PED The large plaque of CNV is unchanged See also color insert, Fig 7.19A, E.

In a recent report by Kuhn et al., RCAs were identified as occurring in 93% of tients with CNV associated with a serous PED These authors reported a poor success ratefrom laser treatment as well (38).

pa-Slakter and co-workers followed prospectively 150 patients with newly diagnosedexudative AMD(37) All had clinical and fluorescein angiographic evidence of occultCNV, and each demonstrated focal areas of hyperfluorescence on ICG angiography, felt to

be representative of CNV Thirty-one (21%) of the 150 eyes were found to have a RCA In

82 eyes the occult CNV was associated with a serous PED Twenty-two (27%) of these tients were noted to have RCA In the remaining 68 cases (occult CNV without serousPED), nine eyes (13%) were found to have a RCA Associated clinical features of RCAswere identified in preretinal or intraretinal hemorrhages at the site of the lesion, dilated tor-tuous retinal vessels, sudden termination of a retinal vessel, and cystoid macular edema.The same authors found that the success rate of laser photocoagulation of RCAs with-out serous PED was 66%, while with serous PED it dropped to 14% Thus the presence of

pa-a RCA mpa-ay well provide pa-a key to understpa-anding the poor outcome for lpa-aser trepa-atment inthis subgroup of patients

In conclusion, from the work of Freund et al (51), it is known that approximatelyonly 13% of patients with CNV secondary to AMD have a classic or well-defined ex-trafoveal choroidal neovascularization by fluorescein angiography that is eligible for lasertreatment With a recurrence rate of approximately 50% following laser photocoagulationunder fluorescein guidance for classic CNV, only approximately 6.5% of patients will ben-efit from treatment

The remaining 87% of patients have occult CNV by fluorescein imaging About 30%

of these eyes have a potentially treatable focal spot by ICG angiography Therefore, 87%

⫻ 29% or 25% of all eyes with exudative maculopathy may be treated by ICG-guided laserphotocoagulation With a success rate of 35%, this means that an additional 9% of patientscan be successfully treated using ICG-guided laser photocoagulation Although this figuresignificantly increases the 6.5% of patients successfully treated by fluorescein-guided laserphotocoagulation, there are still 84.5% of patients who continue to be untreatable or areunsuccessfully treated by thermal laser photocoagulation of the CNV (52)

Lim et al reported on the visual acuity outcome after ICG angiography-guided laserphotocoagulation of choroidal neovascularization associated with pigment epithelialdetachment in 20 eyes with age-related macular degeneration At 3 months after laser pho-tocoagulation, visual acuity had improved two or more Snellen lines in two eyes (10%),worsened by two or more lines in 10 (50%), and remained unchanged in eight of 20 (40%)

At 9 months after laser photocoagulation, visual acuity had improved by two or more lines

in one eye (9%), worsened by two or more lines in nine (82%), and remained unchanged inone of 11 (9%) Lim et al concluded that ICG-guided laser photocoagulation may tem-porarily stabilize visual acuity in some eyes with choroidal neovascularization associatedwith pigment epithelial detachments, but final visual acuity decreases with time (53)

XI RECURRENT OCCULT CHOROIDAL

NEOVASCULARIZATION

Recurrent CNV following photocoagulation treatment is a major cause of failure oflaser therapy Although most recurrences can be detected and imaged with clinicalbiomicroscopic examination and FA, a significant number of patients demonstrate new ex-

udative manifestation and visual symptoms without a clearly defined area of recurrent vascularization identified by FA These patients may exhibit diffuse staining and leakage

neo-at the site of previous treneo-atment or may demonstrneo-ate no FA evidence of recurrence despitethe new exudative manifestations identified clinically ICG angiography has often proven

to be useful in detecting the recurrent CNV (Figs 20–30)

Figure 20 Classic recurrent CNV (A) FA study demonstrating classic recurrent CNV on the nasal margin of an atrophic scar (B) Midphase ICG study of the recurrent CNV; the nasal edge of the recurrence (black arrows), and the feeder vessel (white arrows) are seen (C) Late-phase ICG study demonstrating staining of the CNV.

at the temporal margin of a laser photocoagulation scar A choroidal nevus is partially visible superotemporally (B) Midphase FA study demonstrating hyperfluorescence of the PED and a halo

of hyperfluorescence surrounding the photocoagulation scar (C) Late-phase FA demonstrating further pooling of dye in the sub-RPE space and increased hyperfluorescent halo around the laser photocoagulation scar (D) Late-phase ICG study revealing the presence of a hot spot of recurrent CNV at the temporal margin of the laser scar The PED is hypofluorescent See also color insert, Fig 7.22A.

Figure 23 Occult recurrent CNV (A) Late-phase FA study demonstrating occult recurrent CNV There is diffuse staining surrounding two previous photocoagulation scars in a patient with recurrence 6 weeks after laser treatment (B) Late-phase ICG study demonstrating localized hyperfluorescence along the superotemporal margin of one of the previous treatment sites consistent with a localized, well-defined, area of recurrent CNV.

A B

Figure 24 Occult recurrent CNV (A) Clinical photograph demonstrating an exudative macular detachment following two previous laser treatments for CNV—one inferonasally and one inferotemporally to the fovea (B) FA study revealing staining of the atrophic photocoagulation scar in the inferonasal macula (C) Midphase ICG study demonstrating a hot spot of recurrent active CNV adjacent to the temporal photocoagulation scar (D) Late-phase ICG study demonstrating widespread hyperfluorescence bridging and surrounding the previous photocoagulation sites, representing a large plaque of occult CNV This plaque serves to explain the multiple recurrences See also color insert, Fig 7.24A.

Sorenson et al reported on ICG-guided laser treatment of recurrent occult CNV ondary to AMD Of 66 eyes that entered in the study, only 29 (44%) were eligible for lasertreatment, and of these 29 eyes 18 (62%) had anatomical success with an average follow-

sec-up of 6 months (54) Interestingly, 56% of the patients remained untreatable by ICG giography guidance, and even with treatment, 11 of 29 patients had incomplete resolution

an-or wan-orsening of the exudative manifestations

XII IDIOPATHIC POLYPOIDAL CHOROIDAL

VASCULOPATHY

Idiopathic polypoidal choroidal vasculopatby (IPCV) is a primary abnormality of thechoroidal circulation characterized by an inner choroidal vascular network of vessels end-

Indocyanine Green 157

Figure 25 Occult recurrent CNV with serous PED (A) Clinical photograph demonstrating a serosanguineous PED in the central macula (B) Late-phase FA study demonstrating a serous PED There is evidence of occult CNV in the papillomacular bundle (C) Early-phase ICG study demonstrating a focal hot spot of CNV at the nasal margin of the PED (D) Clinical photograph after treatment demonstrating a serosanguineous PED and exudative macular detachment (E) Late-phase

FA study demonstrating hyperfluorescence of the serous component of the PED and blocked fluorescence of the hemorrhagic component of the PED There is also ill-defined hyperfluorescence around the treatment scar (F) Late-phase ICG study demonstrating recurrence of the CNV at the temporal edge of the treatment scar in the papillomacular bundle See also color insert, Fig 7.25A, D.

C

D

ing in an aneurysmal bulge or outward projection, visible clinically as a reddish-orange,spheroid, polyp-like structure The disorder is associated with multiple, recurrent serosan-guineous detachments of the RPE and neurosensory retina, secondary to leakage and bleed-ing from the peculiar choroidal vascular abnormality (55–58).

ICG angiography has been used to detect and characterize the IPCV abnormality withenhanced sensitivity and specificity (Figs 31, 32) (58–60) In the initial phases of the ICGstudy, a distinct network of vessels within the choroid becomes visible In patients with jux-tapapillary involvement, the vascular channels extend in a radial, arching pattern and areinterconnected with smaller spanning branches that become more evident and numerous atthe edge of the IPCV lesion

Early in the course of the ICG study, the larger vessels of IPCV network start to fillbefore the retinal vessels, but the area within and surrounding the network is relatively hy-pofluorescent compared with the uninvolved choroid The vessels of the network appear tofill more slowly than the retinal vessels Shortly after the network can be identified on theICG angiogram, small hyperfluorescent “polyps” become visible within the choroid

A

B

Figure 26 Occult recurrent CNV with serous PED and hemorrhage (A) Midphase FA study in

a patient with recurrent CNV demonstrating early filling of the serous component of a PED and blocked fluorescence by subretinal hemorrhage (B) Late-phase FA study demonstrating intense hyperfluorescence of the serous PED The previous treatment site appears hypofluorescent superiorly No clear area of recurrent CNV is identified (C) Midphase ICG study demonstrating a well-defined area of recurrent CNV at the inferior edge of the treatment scar (D) Late-phase ICG study demonstrating leakage of the recurrent CNV in the serous PED.

Figure 27 Treatment of recurrent occult CNV with hemorrhage (A) Clinical photograph of a case of recurrent CNV 4 years after laser treatment Note the presence of subretinal hemorrhage and neurosensory detachment (B) Early-phase FA study demonstrating irregular hyperfluorescence surrounding the treatment scar No classic CNV is seen (C) Late-phase FA study demonstrating diffuse leakage in the neurosensory detachment (D) Early-phase ICG study clearly demonstrating the recurrent CNV at the inferior edge of the treatment scar (E) Midphase ICG study demonstrating leakage of the CNV (F) Clinical photograph 6 weeks after ICG-guided laser treatment There is complete resolution of the neurosensory detachment.

to the treatment scar (C) Late-phase ICG study 6 weeks after laser treatment demonstrating resolution of the active CNV and of the serous PED after ICG-guide laser treatment.

These polypoidal structures correspond to the reddish-orange choroidal excrescenceseen on clinical examination They appear to leak slowly and the surrounding hypofluo-rescent area becomes increasingly hyperfluorescent In the later phase of the angiogramthere is a uniform disappearance of the dye (“washout”) from the bulging polypoidal le-sions The late ICG staining characteristic of occult CNV is not seen in the IPCV vascularabnormality

ICG angiography has also proven useful in recognizing cases of IPCV masquerading

as CSR (61), and also in differentiating chronic cases of CSR from AMD (62–65) Spaide

et al demonstrated that in chronic CSR there is a characteristic hyperfluorescence of thechoroidal vessels in the midphase of the ICG study, which disappear in the late phase of thestudy This background hyperfluorescence in CSR has been attributed to hyperpermeabil-ity of the choroidal vasculature

XIII NEW TECHNIQUES IN ICG ANGIOGRAPHY

Recent advances in ICG angiography are real-time angiography (66), wide-angle raphy (66), digital subtraction ICG angiography (67), and dynamic ICG-guided feedervessel laser treatment of CNV (68)

angiog-Real-time ICG angiography uses a modified Topcon 50IA camera with a diode laserillumination system that has an output at 805 nm (Topcon 501AL camera) that can produceimages at 30 frames per second, and allows high-speed recording The images can be ac-quired either as videotape, or as a single image at a frequency of 30 images per second To

C

D B

Figure 30 Treatment of recurrent occult CNV with serous PED (A) Clinical photograph of a serosanguineous PED in a patient with AMD (B) Late-phase FA study demonstrating blockage by the subretinal hemorrhage and leakage in the serous component of the PED No well-defined CNV

is identified (C) Late-phase ICG study demonstrating a hot spot of well-defined CNV temporal to the optic disc (D) Late-phase ICG study 2 weeks after laser treatment demonstrating hypofluorescence of the treatment site (E) Clinical photograph 8 weeks after treatment demonstrating recurrence of the neurosensory macular detachment (F) Late-phase ICG study demonstrating a hot spot of recurrent CNV just temporal to the previous laser treatment scar See also color insert, Fig 7.30A, E, G.

make printed copies of these images, single frames are digitized, but the resolution is ited to 640 by 480 pixels.

lim-Wide-angle images of the fundus can be obtained by performing ICG angiographywith the aid of wide-angle contact lenses The contact lenses used are the Volk SuperQuad

160, the Volk Quadraspheric, or the Volk Transequator (Volk, Mentor OH) Because theimage formed by these lenses is located about 1 cm in front of the lens, the fundus camera

is set on A or + so that the camera is focused on the image plane of the contact lens Thistechnique allows instantaneous imaging of a large area of the fundus The combined usage

of the contact lens and of the laser illumination system allows real-time imaging of a widefield of the choroidal circulation, up to 160 degrees of field of view (Figs 33–36).Digital subtraction ICG angiography (DS-ICGA) uses digital subtraction of sequen-tially acquired ICG angiographic frames to image the progression of the dye front in thechoroidal circulation A method of pseudocolor imaging of the choroid allows differentia-tion and identification of choroidal arteries and veins DS-ICGA allows imaging of occultchoroidal neovascularization (CNV) with greater detail and in a shorter period of time thanwith conventional ICG angiography

Staurenghi et al considered a series of 15 patients with subfoveal CNVM in whomfeeder vessels (FVs) could be clearly detected by means of dynamic ICG angiography butnot necessarily with FA On the basis of the indications of the pilot study, the authors alsostudied a second series of 16 patients with FVs smaller than 85 microns Treatment of FVusing argon green laser was performed The ICGA was performed immediately after treat-ment, after 2, 7, and 30 days, and then every 3 months, to assess FV closure If a FV ap-peared to be still patent, it was immediately retreated and the follow-up was started again.The follow-up time ranged from 23 to 34 months for the pilot study and from 4 to 12months for the second series In the pilot study, the CNVM was obliterated after the firsttreatment in only one patient, five patients needed more than one treatment, and oblitera-tion failed in nine patients (40% success rate) The rate of success was affected by the widthand number of the FVs The success rate in the second series of 16 patients was higher(75%) The authors concluded that dynamic ICGA may detect smaller FVs and makes itpossible to control the laser effect and initiate immediate retreatment in the case of incom-plete FV closure and should be considered mandatory for this type of treatment (68)

Figure 30 (cont.) (G) Clinical photograph 2 months after treatment of the recurrence demonstrating resolution of the neurosensory detachment (H) Late-phase ICG study demonstrating complete elimination of the recurrent CNV.

XIV SUMMARY

ICG videoangiography is a useful adjunctive technique to FA for the diagnosis of AMD.This is especially true in the presence of occult CNV Furthermore, ICG allows betterrecognition of subtypes of occult CNV such as vascularized PED, hot spots, plaques, andRCA Preliminary studies suggest that ICG-guided laser photocoagulation may be benefi-cial in the treatment of CNV Further research is necessary to improve our understanding

of all the information obtained by ICG angiography Real-time ICG angiography, gle ICG angiography, and digital subtraction ICG angiography may improve ourdiagnostic ability in AMD

MD, New York From Yannuzzi LA, Flower RW, Slakter JS Indocyanine Green Angiography St Louis: CV Mosby, 1997:332–333.) See also color insert, Fig 7.31A.

Indocyanine Green 165

Figure 32 Idiopathic polypoidal choroidal vasculopathy This patient presented with submacular hemorrhage ICG angiography shows poly-like bulging of the inner choroidal circulation in the papillomacular bundle.

Figure 33 Wide-angle ICG angiography A Volk SuperQuad 160-fundus lens is held in contact with the patient’s eye to perform wide-angle ICG angiography of the fundus.

Figure 34 Wide-angle ICG angiography Wide-angle ICG angiography picture of a patient with

a choroidal nevus Note the typical butterfly distribution of the choroidal circulation (Courtesy of Richard F Spaide, MD, New York From Yannuzzi LA, Slakter JS, Flower RW Indocyanine Green Angiography St Louis: CV Mosby, 1997.)

Figure 35 Wide-angle ICG angiography Wide-angle ICG angiography picture of a patient with subretinal hemorrhage secondary to idiopathic polypoidal choroidal vasculopathy The image shows

160 degrees of the fundus (Courtesy of Richard F Spaide, MD, New York, New York.)

Angiogra-2 Yannuzzi LA, ed Laser Photocoagulation of the Macula Philadelphia: JB Lippincott, 1989.

3 Guyer DR, Puliafito CP, Mones JM, Friedman E, Chang W, Verdooner SR Digital indocyanine green angiography in chorioretinal disorders Ophthalmology 1992;99:287–290.

4 Yannuzzi LA, Slakter JS, Sorenso JS, Guyer DR, Orlock DA Digital indocyanine green videoangiography and choroidal neovascularization, Retina 1992;12:191–223.

5 Geeraets WJ, Berry ER Ocular spectral characteristics as related to hazards from lasers and other light sources Am J Ophthalmol 1968;66:15–20.

6 Fox IJ, Wood EH Application of dilution curves recorded from the right side of the heart or nous circulation with the aid of a new indicator dye Proc Mayo Clin 1957;32:541.

ve-7 Fox IJ, Wodd EH Indocyanine green: physical and physiological properties Mayo Clin Proc 1960;35:732.

8 Kogure K, David NJ, Yamanouchi U, Choromokos E Infrared absorption angiography of the fundus circulation Arch Ophthalmol 1970;83:209–214.

9 David NJ Infrared absorption fundus angiography In: Proceedings of International sium on Fluorescein Angiography, Albi, France, 1969 Basel: Karger, 1971:189–192.

Sympo-10 Hochheimer BF Angiography of the retina with indocyanine green Arch Ophthalmol 1971;86:564–565.

11 Flower RW Infrared absorption angiography of the choroid and some observations on the fects of high intraocular pressures, Am J Ophthalmol 1972;74:600–614.

ef-12 Flower, RW, Hochheimer BF Clinical infrared absorption angiography of the choroid (letter).

Am J Ophthalmol 1972;73:458–459.

13 Flower RW, Hochheimer BF A clinical technique and apparatus for simultaneous angiography

of the separate retinal and choroidal circulation Invest Ophthalmol 1973;12:248–261.

14 Flower RW, Hochheimer BF Indocyanine green dye fluorescence and infrared absorption choroidal angiography performed simultaneously with fluorescein angiography Johns Hopkins Med J 1976;138:3–42.

15 Hyvarinen L, Flower RW lndocyanine green fluorescent angiography Arch Ophthalmol 1980;58:528–538.

16 Bischoff PM, Flower RW Ten Years experience with choroidal angiography using indocyanine green dye: a new routine examination or an epilogue? Doc Ophthalmol 1985;60:235–291.

17 Hayashi K, DeLaey JJ Indocyanine green angiography of neovascular membranes mologica 1985;190:30–39.

Ophthal-18 Hayashi K, Hasegawa Y, Tazawa Y, Delaey JJ Clinical application of indocyanine phy to choroidal neovascularization Jpn J Clin Ophthalmol 1989;33:57–68.

angiogra-19 Hayashi K, Hasegawa Y, Tokoro T Indocyanine green angiography of central serous oretinopathy Int Ophthalmol 1986;9:37–41.

chori-20 Hayashi K, Hasegawa Y, Tokora T, Delaey JJ Value of indocyanine green angiography in the diagnosis of occult choroidal neovascular membrane Jpn J Clin Ophthalmol 1988;42:827–829.

21 Destro M, Puliafito CA Indocyanine green videoangiography of choroidal neovascularization Ophthalmology 1988;96:846–853.

22 Scheider A, Schroedel C High resolution indocyanine green angiography with scanning laser ophthalmoscope Am J Ophthalmol 1989;108:458–459.

23 Patz A, Flower RW, Klein ML, Orth DH, Fleishman JA, MacLeod D Clinical applications of indocyanine green angiography Doc Ophthalmol Proc Series 1976;9:245–251.

24 Cherrick GR, Stein SW, Leevy CM, et el Indocyanine green: observations on its physical erties, plasma decay, and hepatic extraction J Clin Invest 1960;39:592.

prop-25 Baker KJ Binding of sulfobromophthalein (BSP) sodium and indocyanine green (ICG) by plasma al-lipoproteins Proc Soc Exp Biol Med 1966;122:957.

26 Goresky CA Initial distribution and rate of uptake of sulfobromophthalein in the liver Am J Physiol 1964;207:13.

27 Leevy CM, Bender J, Silverberg M, et al Physiology of dye extraction by the liver: tive studies of sulfobromophthalein and indocyanine green Ann NY Acad Sci 1963;111:161.

compara-28 Ketterer SG, Wiengand BD The excretion of indocyanine green and its use in the estimation of hepatic blood flow Clin Res 1959;7:71.

29 Ketterer SG, Wiengand BD Hepatic clearance of indocyanine green Clin Res 1959;7:289.

30 Probst P, Paumgartner G, Caucig H, Frauohlich H, Grabner G Studies on clearance and cental transfer of indocyanine green during labotn Clin Chim Acta 1970;29:157.

pla-31 Leevy CM, Smith F, Kierman T Liver function test In: Bockus HL, ed Gastroenterology, 3rd ed Vol 3 Philadelphia: WB Saunders, 1976:68

32 Shabetai R, Adolph RJ Principles of cardiac catheterization In: Fowler NO, ed Cardiac nosis and Treatment, 3rd ed Hagerstown, MD: Harper & Row, 1980:117.

Diag-33 Hope Ross M., Yannuzzi LA, Gragoudas ES, et al Adverse reactions due to indocyanine green Ophthalmology 1994;101:529–533.

34 Olsen TW, Lim JI, Capone A, Myles RA, Gilman JP Anaphylactic shock following nine green angiography Arch Ophthalmol 1996;114:97.

indocya-35 Macular Photocoagulation Study Group Occult choroidal neovascularization: influence on visual outcome in patients with age-related macular degeneration Arch Ophthalmol 1996;114:400–412.

36 Schwartz S,Guyer DR, Yannuzzi LA, et al Indocyanine green videoangiography guided laser photocoagulation of primary occult choroidal neovascularization in age-related macular degen- eration Invest Ophthalmol Vis Sci 1995;36:186.

37 Slakter JS, Yannuzzi LA, Scheider U, Sorenson JA, Ciardella AP, Guyer DR, Spaide RF, und KB, Orlock DA Retinal choroidal anastomosis and occult choroidal neovascularization Ophthalmology 2000;107:742–753.

Fre-38 Kuhn D, Meunier I, Soubrane G, Coca G Imaging of chorioretinal anastomoses in vascularized retinal pigment epithelium detachments Arch Ophthalmol 1995;113:1392–1396.

39 Lafaut B A, Aisenbrey S, Vanden Broecke C, Bartz-Schmidt KU Clinicopathological tion of deep retinal vascular complex in age related macular degeneration Br J Ophthalmol 2000;84:1269–1274.

correla-40 Scheider A, Kaboth A, Neuhasuer L Detection of subretinal neovascularization membranes with indocyanine green and infrared scanning laser ophthalmoscope, Am J Ophthalmol 1992;113:45–51.

41 Lim JI, Stenberg P, Capone A, Aaberg TM, Gilman JP Selective use of indocyanine green angiography for occult choroidal neovascularization Am J Ophthalmol 1995;120:75–82.

42 Yannuzzi LA, Hope-Ross M, Slakter JS, et al Analysis of vascularized pigment epithelium detachments using indocyanine green videoangiography Retina 1994;14:99–113.

43 Guyer DR, Yannuzzi LA, Slakter JS, et al Digital indocyanine-green videoangiography of occult choroidal neovascularization Ophthalmology 1994;101:1727–1737.

44 Guyer DR, Yannuzzi LA, Slakter JS, et al Classification of choroidal neovascularization by digital indocyanine green videoangiography Ophthalmology 1996;103:2054–2060.

45 Chang B, Yannuzzi LA, Ladas ID, et al Choroidal neovascularization in second eyes of patients with unilateral exudative age-related macular degeneration Ophthalmology 1995;102:1380–1386.

46 Lee BL, Lim JI, Grossniklaus HE Clinicopathologic features of indocyanine green angiography-imaged, surgically excised choroidal neovascular membranes Retina 1996;16:64–69.

47 Chang TS, Freund KB, de la Cruz Z, et al Clinicopathologic correlation of choroidal cularization demonstrated by indocyanine green angiography in a patient with retention of good vision for almost four years Retina 1994;14:114–24.

neovas-48 Guyer DR, Yannuzzi LA, Ladas I, et al Indocyanine green guided laser photocoagulation of cal spots at the edge of plaques of choroidal neovascularization: a pilot study Arch Ophthalmol 1996;114:693–697.

fo-49 Slakter, JS, Yannuzzi, LA, Sorenson, JA, et al A pilot study of indocyanine green giography-guided laser photocoagulation of occult choroidal neovascularization in age-related macular degeneration Arch Ophthalmol 1994;112:465–472.

videoan-50 Regillo SD, Benson WE, Maguire JI, et al Indocyanine green angiography and occult choroidal neovascularization Ophthalmology 1994;101:280–288.

51 Freund KB, Yannuzzi LA, Sorenson JA, et al Age-related macular degeneration and choroidal neovascularization Am J Ophthalmol 1993;115:786–791.

52 Mandava N, Guyer DR, Yannuzzi LA, et al Indocyanine green videoangiography-guided laser photocoagulation of occult choroidal neovascularization Ophthal Surg Lasers 1997;28:844–852.

53 Lim JI, Aaberg TM, Sr, Capone A, Jr, Stemberg P Jr Indocyanine green angiography-guided photocoagulation of choroidal neovascularization associated with retinal pigment epithelial de- tachment Am J Ophthalmol 1997;123:524–532.

54 Sorenson JA, Yannuzzi LA, Slakter JS, et al A pilot study of digital indocyanine green giography for recurrent occult choroidal neovascularization in age-related macular degenera- tion Arch Ophthalmol 1994;112:473–479.

videoan-55 Kleiner RC, Brucker AJ, Johnston RL The posterior uveal bleeding syndrome Ophthalmology 1984;91 (Suppl 9):110.

56 Kleiner RC, Brucker AJ, Johnston RL The posterior uveal bleeding syndrome Retina 1990;10:9–17.

57 Yannuzzi LA, Sorenson JS, Spaide RF, et al Idiopathic polypoidal choroidal vasculopathy Retina 1990;10:1–8.

58 Yannuzzi LA, Ciardella AP, Spaide RF, et al The expanding clinical spectrum of idiopathic polypoidal choroidal vasculopathy Arch Ophthalmol 1999;115:478–485.

59 Ross RD, Gitter KA, Cohen G, et al Idiopathic polypoidal choroidal vasculopathy associated with retinal arterial macroaneurysm and hypertensive retinopathy Retina 1996;16:111.

60 Spaide RF, Yannuzzi LA, Slakter JS, et al Indocyanine green videoangiography of idiopathic polypoidal choroidal vasculopathy Retina 1995;15:100–110.

61 Yannuzzi LA, Freund KB, Goldbaum M, Scassellati-Sforzolini B, Guyer DR, Spaide RF, Maberley D, Wong DW, Slakter JS, Sorenson JA, Fisher YL, Orlock DA Polypoidal choroidal vasculopathy masquerading as central serous chorioretinopathy Ophthalmology 2000;107:767–777.

62 Spaide RF, Hall L, Haas A, et al Indocyanine green videoangiography of older patients with central serous chorioretinopathy Retina 1996;16:203–213.

63 Spaide RF, Campeas L, Haas A, et al Central serous chorioretinopathy in younger and older adults Ophthalmology 1996;103:2070–2080.

64 Guyer DR, Yannuzzi LA, Slakter JS, et al Digital indocyanine green videoangiography of tral serous chorioretinopathy Arch Ophthalmol 1994;112:1057–1062.

cen-65 Piccolino FC, Borgia L, Zinicola E, et al Indocyanine green angiographic findings in central serous chorioretinopathy Eye 1995;9:324–332

66 Spaide RF, Orlork DA Herrmann-Delamazure B, et al Wide-angle indocyanine green raphy Retina 1998;18:44–49.

angiog-67 Spaide RF, Orlock DA, Yannuzzi LA, et al Digital subtraction indocyanine green angiography

of occult choroidal neovascularization Ophthalmology 1998;105:680–688.

68 Staurenghi G, Orzalesi N, La Capria A, Aschero M Laser treatment of feeder vessels in foveal choroidal neovascular membranes: a revisitation using dynamic indocyanine green an- giography Ophthalmology 1998;105:2297–2305.

8

Optical Coherence Tomography for

Age-Related Macular Degeneration

Mark J Rivellese and Elias Reichel

New England Eye Center, Tufts University School of Medicine, Boston, Massachusetts

II OVERVIEW

The mechanism of OCT is analogous to ultrasound B-mode imaging with several distinctadvantages The use of light instead of acoustic waves allows for spatial resolution in the10–20-micron range, approximately 10 times higher than B-mode ultrasound TraditionalB-mode ultrasound using a sound wave frequency of 10 MHz yields spatial resolutions ofapproximately 150 microns In addition, the use of light allows an image to beobtained noninvasively, without direct contact to the globe Cross-sectional images can beobtained rapidly in approximately 2.5 s

III APPLICATION

OCT has a wide range of applications in ophthalmology, particularly for diseases of themacula The technology has been used to study patients with epiretinal membranes, macu-lar holes, central serous chorioretinopathy, diabetic retinopathy, age-related maculardegeneration, and other disorders A particularly useful application of OCT is in the

localization, detection, and measurement of retinal fluid A fluid collection is accurately picted in its anatomical layer, may it be intraretinal, subretinal, or under the retinal pigmentepithelium OCT can provide clinically useful information about any retinal disease thatmanifests by changing macular thickness or accumulation of fluid in the macula It also hasutility in following response to treatments that alter macular structure.

de-IV OPTICAL COHERENCE TOMOGRAPHY

INTERPRETATION

Interpretation of OCT images of ophthalmic disease such as age-related macular ation requires familiarity with the OCT representation of a normal posterior segment andknowledge of basic OCT principles

degener-The strength of the OCT signal at a particular tissue layer is dependent on several tors Signal strength is defined by the following: the amount of incident light transmitted to

fac-a pfac-articulfac-ar lfac-ayer without being fac-absorbed by intervening tissue, the fac-amount of trfac-ansmittedlight that is backscattered, and the fraction of backscattered light that returns to the detec-tor without being further attenuated The reflectivity is the portion of incident light that isdirectly backscattered by a tissue Therefore, the OCT signal from any particular tissuelayer is a function of its reflectivity and the absorption and scattering properties of the over-lying tissue layers (1) For example, a tissue with a high level of backscatter that lies deep

to a tissue with low absorption and low backscatter will produce a high signal

The signal strength can be represented in gray scale or as the false color tion used for the images that follow Figure 1 shows an OCT image of a normal eye scannedthrough the optic nerve and fovea The vitreoretinal interface is characterized by a demar-cation in contrast from the nonreflective vitreous and the highly reflective nerve fiber layer(NFL) High backscatter is represented by red-orange color and low backscatter appearsblue-black False color is represented by the normal visible spectrum The fovea has a char-acteristic depression with thinning of the retina corresponding to its normal anatomy

representa-Figure 1 OCT of a normal eye through the optic nerve and fovea See also color insert, Fig 8.1.

A bright red-orange layer that delineates the posterior boundary of the retina sponds to the retinal pigment epithelium (RPE) and choriocapillaris Again, there is con-trast between the less reflective photoreceptors and the highly backscattering RPE Thethin, dark layer anterior to the RPE layer represents the photoreceptor layer Relativelyweak backscatter returns from the choroid and appears green on the tomogram The inter-mediate layers between the highly reflective NFL and RPE exhibit moderate backscatterand are represented on the false color scale as yellow-green.

corre-V NONEXUDATIVE MACULAR DEGENERATION

Cross-sectional imaging of eyes with nonexudative age-related macular degeneration(AMD) shows the characteristic appearance of drusen and geographic atrophy Soft drusencause a modulation in the highly reflective posterior boundary of the retina consistent withthe accumulation of material within the RPE (Fig 2) The small elevations of the RPE canappear similar to RPE detachments Geographic atrophy shows thinning of the overlyingretina and the hypopigmented RPE allows deeper penetration of the incident light into thechoroid The choroidal layer will have higher-than-normal backscatter owing to a decrease

in signal absorption from the atrophic retina and RPE (Fig 3)

Figure 2 Soft drusen See also color insert, Fig 8.2.

Figure 3 Geographic atrophy See also color insert, Fig 8.3.

VI EXUDATIVE MACULAR DEGENERATION

Optical coherence tomograms of exudative macular degeneration may aid in the diagnosisand management of this condition OCT is particularly valuable for detecting subretinal fluidand retinal pigment epithelial detachments, as well as changes in retinal thickness from in-traretinal fluid Measurements of retinal thickness provide an objective method of compar-ing retinal edema and subretinal fluid before and after intervention There is some variabil-ity in the appearance of choroidal neovascularization on OCT However, OCT may represent

a new technique for visualizing angiographically occult choroidal neovascularization

A Intraretinal and Subretinal Fluid

The presence of intraretinal fluid may be represented as retinal thickening or as the mulation of fluid in well-defined spaces (Fig 4, 5) Intraretinal fluid in localized cysts(cystoid macular edema) appears as areas of discrete decreases in backscatter within the in-termediate retinal layers, while diffuse edema will show an increase in thickness withoutdefinite spaces Neurosensory detachments from the accumulation of subretinal, fluid ap-pear in cross-section as elevations of the neurosensory retina above an optically clear space.The fluid space has well-defined boundaries at the fluid-retinal and fluid-RPE interfaces

accu-In contrast to RPE detachments, the highly reflective RPE is imaged at the posterior border

of the detachment (Fig 6)

B Retinal Pigment Epithelial Detachments

It is possible to distinguish between serous and hemorrhagic retinal pigment epithelial tachments (PED) based on OCT images Serous pigment epithelial detachments appear as

de-Figure 4 Retinal thickening See also color insert, Fig 8.4.

dome-shaped elevations of the RPE with an elevated reflective band corresponding to theRPE The intervening nonreflective layer is fluid in the sub-RPE space The margins aresharp and there typically is shadowing of the reflections returning from the deeper choroid.This may be due to increased reflectivity and attenuation of the light through the decom-pensated RPE (Fig 7) Hemorrhagic PEDs have a similar appearance However, images of

Figure 5 Cystoid macular edema secondary to choroidal neovascularization See also color insert, Fig 8.5.

Figure 6 Neurosensory detachment secondary to subretinal fluid See also color insert, Fig 8.6.

hemorrhagic detachments tend to show a band of high backscatter under the RPE band atthe apex of the detachment (Fig 8) This corresponds to the accumulated blood, decreas-ing light penetration, and attenuating choroidal reflection Hemorrhagic PEDs and subreti-nal hemorrhages are sometimes difficult to distinguish on OCT because blood and the de-tached RPE have similar reflectivity.

C Choroidal Neovascularization

The presentation of choroidal neovascularization on OCT typically falls into one of threecategories, but may show variability Neovascular complexes that are angiographicallywell defined typically present as fusiform enlargement of the RPE/choriocapillaris reflec-tive band with discrete borders (Fig 9) Occasionally, the membrane may be imaged in thesubretinal space (Fig 10) Neovascular complexes that are poorly defined angiographically

Figure 7 Serous retinal pigment epithelial detachment See also color insert, Fig 8.7.

Figure 8 Hemorrhagic retinal pigment epithelial detachment See also color insert, Fig 8.8.

and fall into the category of occult fibrovascular PEDs display a well-defined elevation ofthe RPE reflective band with a mildly backscattering region below, corresponding to fi-brous proliferation (Fig 11) No shadowing of the choroidal reflection is present Manychoroidal neovascular complexes display enhanced choroidal reflection without a discrete

Figure 9 Well-defined choroidal neovascularization See also color insert, Fig 8.9.

Figure 10 Choroidal neovascularization in the subretinal space See also color insert, Fig 8.10.

Figure 11 Fibrous pigment epithelial detachment See also color insert, Fig 8.11.

Figure 12 (A) Choroidal neovascularization before photodynamic therapy (B) Same eye after photodynamic therapy See also color insert, Fig 8.12A, B.

A

Optical Coherence Tomography for AMD 179

membrane This may be due to increased optical penetration secondary to retinal pigmentepithelial changes (1)

The ability to detect small changes in retinal thickness and the presence of fluid makeOCT particularly useful for following patients after conventional laser treatment, photody-namic therapy, or transpupillary thermotherapy Figure 12 shows a patient before and aftertreatment with verteporfin photodynamic therapy Note the change in retinal thicknesssecondary to intraretinal fluid absorption

VII SUMMARY AND FUTURE DEVELOPMENT

OCT is a noninvasive imaging modality capable of providing accurate, reproducible ages of the posterior segment The retinal and RPE changes in age-related macular degen-eration have a characteristic appearance on OCT OCT is useful in detecting small changes

im-in retim-inal thickness, subretim-inal and sub-RPE fluid, and choroidal neovascularization It curately localizes these processes and may provide an objective measurement This isparticularly useful in monitoring the response to therapeutic intervention in concert withconventional fluorescein and indocyanine green angiography