Characteristics of Exudative Age-
`related Macular Degeneration
`Determined In Vivo with
`Confocal and Indirect Infrared
`Imaging
`
`M. Elizabeth Hartnett, MD,"2 Ann E. Elsner, PhD"
`
`Purpose: To evaluate the current and future interventions in age-related macular
`degeneration (AMD), it is essential to delineate the early clinical features associated
`with later visual loss. The authors describe the retinal pigment epithelium (RPE)/Bruch
`membrane region in ten patients with advanced exudative AMD using current angio-
`graphic techniques and a noninvasive method: infrared (IR) imaging with the scanning
`laser ophthalmoscope.
`Methods: Ten patients with exudative AMD, evidenced by choroidal neovascular-
`ization (CNV), fibrovascular scar formation, pigment epithelial detachment, or serous
`subretinal fluid, were examined using IR imaging, fluorescein angiography, indocyanine
`green angiography, and stereoscopic viewing of fundus slides. The authors determined
`the number and size of drusen and subretinal deposits and the topographic character
`of the RPE/Bruch membrane area and of CNV.
`In all patients, IR imaging yielded the greatest number of drusen and sub-
`Results:
`retinal deposits. Sheets of subretinal material, but few lesions consistent with soft drusen,
`were seen. Infrared imaging provided topographic information of evolving CNV. Choroidal
`neovascularization appeared as a complex with a dark central core, an enveloping re-
`flective structure which created a halo-like appearance in the plane of focus, and outer
`retinal/subretinal striae.
`Infrared imaging provides a noninvasive, in vivo method to image
`Conclusions:
`early changes in the RPE/Bruch membrane. It offers advantages over current imaging
`techniques by minimizing light scatter through cloudy media and enhancing the ability
`to image through small pupils, retinal hyperpigmentation, blood, heavy exudation, or
`subretinal fluid. It provides additional information regarding early CNV, and the character
`of drusen and subretinal deposits. Ophthalmology 1996;103:58-71
`
`Originally received: October 6, 1994.
`Revision accepted: July 3, 1995.
`Harvard University, Cambridge.
`
`2 Schepens Retina Associates, Boston.
`
`3 Schepens Eye Research Institute, Boston.
`
`Presented at the ARVO Annual Meeting, Sarasota, May 1994.
`
`Supported by DOE DE-FG 02-91ER61229, EY08794-01A1, and the
`Perkin Fund, New Canaan, Connecticut.
`The authors have no proprietary interest in the equipment or technology
`used in this study, other than grant support for research.
`
`The clinical features of patients with age-related macular
`degeneration (AMD) have been classified to determine
`early findings predictive of later sight loss, namely cho-
`roidal neovascularization (CNV), retinal atrophy, and
`pigment epithelial detachments. I-3 Yet, many classifica-
`tion schemes fail to provide reliable and repeated infor-
`mation predictive of the subsequent anatomic and visual
`outcomes in all patients. Greater understanding of the
`
`Reprint requests to M. Elizabeth Hartnett, MD, Schepens Retina As-
`sociates, 100 Charles River Plaza, Boston, MA 02114.
`
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`Hartnett and Elsner • In Vivo Infrared Imaging in Exudative AMD
`
`pathophysiology of AMD is needed. Further insight into
`the nature of drusen and subretinal topography may help
`to differentiate among the varying precursor stages in
`AMD and their corresponding outcomes. Appropriate
`medical intervention then can be determined and tested
`for effectiveness.
`Information about size, extent, and composition of
`drusen and the choroidal vasculature may be masked in
`clinical examination and stereoscopic fundus photography
`by the overlying retina, retinal pigment epithelium (RPE),
`or by the lack of contrast in heavily or lightly4 pigmented
`fundi. In fluorescein angiography, masking occurs because
`of the melanin and xanthophyll pigments, blood, heavy
`exudation, dense subretinal fluid, or overlying retinal vas-
`cular hyperfluorescence. The choroidal circulation and
`choriocapillaris are not well resolved. Through indocy-
`anine green angiography (ICGA), some drusen are im-
`aged,5 but most drusen are not demonstrated, and the
`choriocapillaris is not well visualized. Recent clinicohis-
`topathologic correlations suggest that clinical definitions
`of drusen do not correspond to their presumed histo-
`pathologic determinants.' There is a need to obtain a bet-
`ter image of the RPE/Bruch membrane region in a non-
`invasive way in vivo and to define and follow the early
`precursor lesions of patients with AMD longitudinally.
`Many patients with AMD and visual impairment have
`other concomitant ocular disorders, such as glaucoma,
`cataract, or pseudophakia. Such patients may be rejected
`from studies because of the technical inability to image
`their maculas adequately. Yet, their eyes may provide
`valuable information and are representative of eyes typ-
`ically found in this age group and in AMD.
`We chose a group of patients seen consecutively by the
`same retinal specialist, all of whom had AMD with visual
`impairment. Although small in number, this population
`represents a realistic cross-section of patients referred to
`retinal specialists for visual loss secondary to AMD. We
`used infrared (IR) imaging with the scanning laser
`ophthalmoscope (SLO) in direct confocal and indirect
`modes' to compare drusen and the subretinal topogra-
`phy seen in these patients with clinical evaluation and
`more standard methods of imaging, fluorescein angiog-
`raphy (FA), stereoscopic fundus slides (FS), and, in some
`cases, ICGA. We found that drusen seen on clinical ex-
`amination correspond to some elevated, discrete subret-
`inal deposits seen with IR imaging. Yet, we were able to
`see a greater number of similar-appearing subretinal de-
`posits and of the RPE/Bruch membrane topography with
`IR imaging than what we saw by clinical evaluation. We
`believe that IR imaging may be a valuable in vivo method
`that provides greater information and thus a greater un-
`derstanding of the RPE/Bruch membrane region.
`
`Patients and Methods
`
`Patients
`
`Our study population included ten consecutive patients
`referred for retinal evaluation because of visual impair-
`
`ment from AMD (Table 1). All patients had wet AMD
`diagnosed because of large confluent soft drusen,' pigment
`epithelial detachment (PED), CNV, subretinal fluid, and/
`or fibrovascular scar formation in one or both eyes. In
`two patients, the less-involved eye had either presumed
`pigment (case 1) or large confluent drusen (case 3). In
`case 1, there was initially no clinical suspicion of wet AMD
`in the fellow, less-involved eye before IR imaging. In the
`remaining eight patients in whom extensive pathology in
`one eye precluded the imaging of drusen and subretinal
`deposits in the macula, only the fellow, less-involved eye
`was studied. In these eight study eyes, wet AMD mani-
`fested by drusen, PED, CNV, or subretinal hemorrhage.
`No patient was excluded due to media opacity, small pu-
`pil, or intraocular lens (IOL) because these conditions of-
`ten coexist with AMD in this age group. A sampled mac-
`ular region of each of the study eyes allowed viewing of
`drusen and subretinal deposits by the greatest number of
`methods possible by avoiding areas masked by the exu-
`dative process. The imaging data were collected prospec-
`tively and analyzed at a later time.
`No patient had a previously known allergy to fluores-
`cein. No patient with an allergy to ICG or iodine under-
`went ICGA. Written informed consent before participa-
`tion was obtained from all patients. The protocol was
`reviewed and approved by the Institutional Review Board
`of the Schepens Eye Research Institute and included con-
`fidentiality of results.
`
`Clinical Examination and Angiography
`All patients underwent a thorough ophthalmologic ex-
`amination, including funduscopic biomicroscopy of both
`maculas. Stereoscopic color FS, FA, and, in seven eyes in
`which FA alone failed to provide adequate clinical infor-
`mation, ICGA using the SLO, were performed. In patients
`referred from outside areas, photographs and imaging
`studies were requested. Testing was performed at this in-
`stitution based on the individual clinical need of the pa-
`tients to be cost effective in today's healthcare environ-
`ment. Photographic FAs were performed in standard
`fashion with an intravenous, antecubital injection of 5
`ml 10% sodium fluorescein, followed by sequential fundus
`photographs using a Zeiss (Oberkochen, Germany), Top-
`con (Tokyo, Japan), or Kowa (Tokyo, Japan) fundus
`camera. Stereo pairs of the macula were taken during the
`transit phases. Scanning laser ophthalmoscope FAs (cases
`7 and 9; Table 1) were performed using 488-nm excitation
`light, 160 /./W at the cornea, and a Schott OG 515 filter
`(Glass Technologies, Inc, Duryea, PA). Scanning laser
`ophthalmoscope ICGAs were performed in seven patients
`using an 805-nm excitation light, 0.7 to 1 mW at the
`cornea, and an 810-nm long-pass filter. Indocyanine green,
`reconstituted with 3 to 5 ml diluent, was given as a 3-ml
`injection into the antecubital vein, followed by a saline
`flush, and viewed as a 40° field of view. A repeat injection
`of 2 ml was given for a 20° field of view after allowing
`sufficient time for recirculation of the original bolus of
`ICG. This was done only in those patients in whom min-
`imal pooling of dye was present, and the additional bolus
`
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`Ophthalmology Volume 103, Number 1, January 1996
`
`Table 1. Demographics of Patients*
`
`Indocyanine Green
`Angiography
`
`Case
`No.
`
`Age
`(yrs)
`
`Sex
`
`Hypertensiont
`
`1
`
`2
`3
`
`4
`5±
`
`6
`
`7
`
`8
`9
`10§
`
`59
`
`79
`73
`
`86
`92
`
`79
`
`74
`
`86
`91
`81
`
`M
`
`M
`M
`
`F
`F
`
`F
`
`F
`
`F
`F
`M
`
`—
`+
`—
`
`Eye
`OD
`OS
`OD
`OD
`OS
`OS
`OS
`
`OD
`
`OD
`
`OD
`OS
`OD
`
`Clincal Macular
`Appearance
`Pigment
`CNV
`Treated CNV
`Drusen
`Subretinal fluid
`PED
`Subretinal fluid,
`occult CNV
`PED, occult
`CNV
`Drusen, shallow
`PED
`Subretinal heme
`Occult CNV
`PED, subfoveal
`occult CNV
`
`PED = pigment epithelial detachment; CNV = choroidal neovascularization.
`The fellow eyes of cases 2 and 4 through 10 had fibrovascular scars precluding adequate viewing of drusen and
`subretinal deposits; therefore, only one study eye in each of these patients was included in the study.
`t All hypertension was controlled with medications.
`f Patient had glaucoma.
`§ Patient had a history of cardiovascular disease.
`
`was believed to be needed for information in the 20° field
`after the 40° videoangiogram was reviewed. Indocyanine
`green angiography was not performed in three patients.
`Case 1 had a well-defined CNV in the left eye, and ICGA
`was not required for diagnosis. Cases 3 and 9 had iodine
`allergies. All patients underwent IR imaging using the
`SLO. Infrared imaging was performed before ICGA when
`both were to be performed.
`
`Stereoscopic Fundus Photographs
`Color stereo pairs of FS were viewed on a light box with
`stereo viewers (X4 magnification) by the same observer,
`with the room lights off to achieve the best contrast pos-
`sible.
`The more focused slide of the stereo pair from the FS,
`or red-free slide when the FS was not available, was viewed
`on a slidex (approximately X8 magnification). A trans-
`parent grid with 1-mm2 boxes was superimposed onto the
`image on the slidex. Outlines of the drusen, optic nerve,
`and blood vessels were drawn onto the overlay. A sampled
`macular region was determined and drawn in to represent
`the largest area of the macula that provided the best avail-
`able quality data by all methods. From this area, counting
`of drusen and subretinal deposits was performed. The ap-
`proximate area of the sampled macular region in deg2 was
`calculated by dividing the area in each slide (number of
`millimeter-squared boxes from the transparent grid over-
`lays) by the normalized area of the entire slide (number
`
`of millimeter-squared boxes per deg2 of field; 30°, Zeiss;
`50°, Topcon or Kowa). The sampled macular region in
`relation to the center of the foveal avascular zone for each
`eye was superotemporal in three eyes of three patients,
`superonasal in one eye or one patient, superior hemi-
`macular in one eye of one patient, temporal in one eye
`of one patient, inferior nasal in four eyes of four patients,
`and included the entire macula in two eyes of one patient.
`The mean ± standard deviation for the sampled macular
`region was 152 ± 79.6 deg2.
`The slide then was projected using a Kodak slide pro-
`jector (Rochester, NY) (approximately X33 magnifica-
`tion).
`
`Red-free Fundus Photographs and Fluorescein
`Angiography
`Red-free photographs and FA were viewed in a similar
`manner to FS slides. Drusen were seen either as subretinal
`low-density lesions (on red-free photographs) or as early
`hyperfluorescing or late staining subretinal lesions (on
`FAs). In two eyes (cases 7 and 9; Table 2), drusen were
`counted from a red-free or FA still frame from a videoan-
`giogram.
`
`Infrared Imaging
`Video images were obtained using the SLOT with a tune-
`able infrared laser (Ti:Sapphire SEO, Concord, MA; 795-
`
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`Hartnett and Elsner • In Vivo Infrared Imaging in Exudative AMD
`
`Table 2. Subretinal Deposit and Drusen Characteristics and Number by Different Imaging Techniques
`
`FA
`Fluorescence
`Late
`Early
`
`NA
`
`NA
`
`Case
`No.
`1
`
`2
`3
`
`4
`5
`6
`7
`8
`9
`10
`
`Eye
`OD*
`OS*
`OD
`OD
`OS
`OS
`OS
`OD
`ODt
`OD
`OSt
`OD
`
`Lens
`Status
`Phakic
`Phakic
`IOL
`Phakic, NS
`Phakic, NS
`Phakic, NS
`IOL
`Phakic, NS
`Phakic, NS
`Aphakic
`IOL
`Phakic
`
`FS
`(4X)
`0
`2
`NA
`76
`64
`8
`20
`42
`NA
`19
`NA
`NA
`
`Red-free
`(4X)
`0
`1
`9
`28
`21
`12
`0
`24
`9
`21
`56
`0
`
`FA
`(4X)
`8
`37
`15
`0
`0
`3
`71
`38
`32
`7
`24
`3
`
`8X
`0
`2
`28
`62
`80
`8
`24
`45
`NA
`21
`NA
`3
`
`33X
`0
`6
`45
`82
`92
`10
`24
`42
`NA
`30
`NA
`NA
`
`IR >80 lam
`2
`15
`5
`43
`6
`188
`3
`125
`12
`104
`3
`35
`53
`4
`19
`87
`17
`384
`77
`7
`79
`7
`69
`1
`
`Sampled Macular
`Region (deg2)*
`237
`293
`93
`136
`79
`156
`274
`102
`121
`96
`50
`190
`
`FA = fluorescein anigiogram; FS = fundus slide; IR = infrared image; OD = right eye; OS = left eye; IOL = intraocular lens; NA = not applicable;
`NS = nuclear sclerosis.
`* Based on fundus slide field of view 30° (Zeiss), 50° (Topton, Kowa).
`t Subretinal deposits and drusen counted from FA videoangiogram.
`t Poor-quality FA secondary to small pupil and IOL precluded adequate imaging.
`
`895 nm)."° Typically, 805-, 835-, 865-, and 895-nm
`wavelengths were used with powers from 40 to 200 µW.
`This is noninvasive and not uncomfortable or fatiguing
`to the patient. Although parametric data were collected
`in this article, clinically useful data could be obtained
`quickly.
`Confocal imaging was performed initially (Fig 1A).
`Focusing was determined at the optical plane of the major
`retinal blood vessel walls for each wavelength tested. The
`light reflected from the macula was allowed to return
`through a central annulus of 200 or 800 µm. In the highly
`confocal image (200-µm aperture) light focused at the de-
`sired optical plane returned to the detector with little light
`from other tissue planes. In the direct mode, a larger ap-
`erture of 400 to 800 Am allowed a higher proportion of
`light from deeper layers of the retina to return to the de-
`tector. This direct mode was helpful in determining the
`optical plane desired for viewing subretinal structures and
`pathology 1° and will represent the aperture used when the
`term confocal is used. Highly confocal will indicate the
`200-µm aperture. We found that 835- and 865-nm wave-
`lengths were the most helpful in evaluating the RPE/Bruch
`region membrane and deep retinal region.
`Once the desired optical plane was set, indirect mode
`imaging of the macula was performed (Fig 1B). Here, the
`aperture was of a larger diameter with the central circular
`area occluded. Directly reflected light was blocked, allow-
`ing light scattered from the deeper retinal layers to return
`to the detector. The central occluded areas were 200 or
`800 Am in diameter. The 800-µm diameter stop was used
`in this article to count subretinal deposits in digitally stored
`images.
`
`Each transparent grid overlay derived from the slidex
`( X8 magnification) indicating the drusen in the sampled
`macular region of a study eye was compared with captured
`computer videoimages indicating subretinal deposits seen
`on IR imaging.
`
`Determination of the Number of Drusen and
`Subretinal Deposits
`Drusen and subretinal deposits were counted separately
`using color FS, FA, red-free slides, and IR imaging from
`the sampled macular region as described. Subretinal de-
`posits, were defined as areas of elevation viewed on IR
`images that may or may not correspond directly to clinical
`drusen. Those subretinal deposits seen on IR images that
`corresponded directly to subretinal deposits viewed by FS
`and defined as clinical drusen also were referred to as
`subretinal deposits in the IR images. Other subretinal de-
`posits, viewed on IR imaging, although similar in ap-
`pearance to deposits corresponding to clinical drusen, were
`not called drusen if no clinical counterparts were noted,
`but were included with subretinal deposits. Therefore,
`drusen was retained as a clinical term and used in de-
`scribing subretinal structures with FS, red-free slides, and
`FA. Subretinal deposits described clinical drusen and other
`small, discrete, elevated lesions seen on IR imaging alone.
`All drusen and subretinal deposits were counted and re-
`corded.
`Drusen and subretinal deposits were counted by the
`same individual (MEH) three times. The variability of
`counts was 2% or less for FS, FA, and red-free slides and
`4% or less for IR videoimages. On FS, FA, and red-free
`
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`A
`
`ap,atturi, r..osItion
`
`traction
`Intr
`
`t
`
`Bruch's mernbrarre
`
`r
`choriocapillarls law
`
`Top, Figure 1. A, confocal imaging, direct mode. Directly reflected light enters central annulus. Fibrin at the edges of the choroidal neovascularization
`(CNV) complex reflects more light (thick arrow). Less light is reflected from the active neovascular areas because hemoglobin absorbs light (thin
`arrow). We believe the halo-like appearance seen at the plane of focus represents the greater reflected light and the central dark area represents
`neovascular channels. B, indirect mode. Scattered light from deeper layers (small diagonal arrows) passes through the annular aperture, whereas
`reflected light is blocked by the central stop. Little light is reflected from the center of the CNV because it is absorbed by hemoglobin (thin arrows).
`A higher degree of scattering of light is likely where fibrin density is greatest (thick arrows).
`Center and bottom, Figure 2. Fundus photography (center left) and late frame of fluorescein angiogram (center right) of case 1 (right eye), initial
`evaluation, show a pigmented, deep, flat area inferior to the fovea. Bottom left, an indirect infrared image (865 nm) of the same eye, visit 1, shows
`an elevated lesion with a dark central core and a surrounding elevated lighter halo-like appearance in the plane of focus. Bottom right, fluorescein
`angiogram of case 1 (right eye), visit 2, 4 months later, shows choroidal neovascularization. Note similarity of this fluorescein angiogram to the previous
`infrared image, visit 1.
`
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`Hartnett and Elsner • In Vivo Infrared Imaging in Exudative AMD
`
`slides, there was minimal confluence of drusen. The
`greatest obstacles in counting drusen were small pupils
`and media opacities precluding good-quality photographs.
`Although small pupils and media opacities did not present
`obstacles to imaging the macular area by IR imaging, the
`confluence of clinical drusen made it more difficult to
`appreciate individual subretinal deposits.
`Statistical determination of the number of drusen and
`subretinal deposits and the effects of magnification or im-
`aging method were determined using nonparametric
`methods. Where two eyes were quantified, results were
`averaged so that sample sizes were determined by the
`number of patients. No data were pooled across method,
`so that the sample size for each data analysis depended
`on the number of patients who had good-quality images
`for each method in the analysis.
`
`Determination of Subretinal Deposit Size and
`Character (elevation, fluorescence)
`
`Approximate size of subretinal deposits was determined
`by counting the pixels on the computer images of captured
`IR indirect images and multiplying by 20 Am/pixel (based
`on optical data from Rodenstock (Ottobrunn-Riemerling,
`Germany) and our calibration for the emmetropic eye).
`The IR indirect images provided the best views from which
`to count elevated subretinal deposits. Small subretinal de-
`posits were designated as having diameters 80 Am or less,
`because this was the smallest diameter believed to accu-
`rately reflect the size of the deposit, given the resolution
`of the IR images, and to meet the definition of hard drusen
`less than 63 Am in diameter." The borders of clinically
`apparent drusen on FS were appreciated easily on IR im-
`ages. However, the distinct borders of smaller subretinal
`deposits that were not visible on FS are not always well
`appreciated by IR imaging because of the small size of
`the deposits (the accuracy in quantifying size of small
`subretinal deposits is 20% or lower).
`The characteristics of drusen and subretinal deposits
`were evaluated as follows. Size determination was used
`to define hard drusen ( 80 Am in diameter)." The pres-
`ence of elevation was determined using the stereo viewers
`when viewing stereo pairs of FS, FA, and red-free slides,
`and by shadows cast by thickened regions or motion par-
`allax in video using IR imaging in the indirect mode. The
`fluorescence characteristics of drusen were determined as
`early hyperfluorescence occurring during the arteriolar to
`venous flow stages, and late fluorescence as that occurring
`after arteriolar—venous phases. Drusen were counted as
`hyperfluorescent only if their fluorescence was greater than
`the background choroidal fluorescence.3
`
`Figure 3. Top, fluorescein angiogram of a well-defined subfoveal choroidal
`neovascularization (CNV) in the left eye of case 1, with surrounding
`window defects, some of which correspond to fundus slide drusen and
`infrared (IR) subretinal deposits. Bottom, indirect IR image (865 nm) of
`subfoveal CNV in the left of case 1 shows a dark central core with a
`surrounding elevated halo-like area with an additional dark area sur-
`rounded by a lighter area. This appearance suggested a multilayered CNV
`complex. Also notice that subretinal deposits nasal to the CNV appear
`as elevated lighter lesions. The window defects noted on fluorescein
`angiography are outlined in black. Notice good correspondence but a
`greater number of subretinal deposits noted by IR imaging, as evidenced
`by elevated areas of the same size with shadowing.
`
`Case Reports
`
`Case 1. A 59-year-old man noted gradual blurring of his
`central vision in the left eye 1 month previously. His medical
`history included a previous cholecystectomy and appendectomy.
`Otherwise, he had good health. He had two siblings with AMD.
`
`Visual acuity was 20/20 in the right eye and 20/200 in the
`left. Intraocular pressures were 11 mmHg in the right eye and
`12 mmHg in the left. Anterior segment showed no inflammation
`and mild nuclear sclerosis in both eyes. Results of fundus
`examination of the macula in the right eye showed a well-
`demarcated, deeply pigmented area abutting the fovea and
`extending inferior to it (Fig 2, center left). There was no associated
`
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`Figure 4. Top left, red-free image of the right eye shows a treated area below the fovea (visit 1, case 2) with few drusen-like deposits noted in the
`macula. Top right, late frame of fluorescein angiogram in the right eye shows areas of previous photocoagulation and faint fluorescence at the
`boundary between the earlier treated area (rounder, lower area of hypofluorescence) and most recent treatment area (upper, triangular area). Also
`notice hyperfluorescence in the earlier area of treatment (lower). Center left, "highly confocal" infrared (IR) image (835 nm) of case 2 (right eye)
`shows fine, deep, radiating striae extending superonasal from the foveola. Notice the dark central core and halo-like appearance in the plane of focus
`above the area of treatment. This appeared elevated, unlike the clinical appearance. Also notice numerous surrounding elevated subretinal deposits.
`An 835-nm IR image was used for this image to show subretinal features and maintain retinal landmarks for comparison. Center right, indirect
`
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`Hartnett and Elsner • In Vivo Infrared Imaging in Exudative AMD
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`IR image (865 nm) of the same eye. Notice the appearance of elevated, discrete, subretinal deposits and of sheets of subretinal material. Bottom left,
`early phase indocyanine green angiogram shows no clear, lacy filling of choroidal neovascularization. Bottom right, late-phase indocyanine green
`angiogram without evidence of a late hot spot. Notice inferior hypofluorescence of an earlier treated area and superior triangular hypofluorescence,
`corresponding to the most recent area of treatment as seen on the fluorescein angiogram (Fig 4, top right). Any faint hyperfluorescence is believed
`to represent staining between these two areas.
`
`elevation, exudation, hemorrhage, or drusen. The macula in the
`left showed an area of retinal elevation involving the fovea with
`a few drusen located near it. Neither eye had vitreous cells, histo-
`like spots, or peripheral streaks. Both eyes had mild peripapillary
`atrophy.
`A late frame of the FA in the right eye showed a well-
`demarcated hypofluorescent area with surrounding staining but
`no definite leakage, corresponding to the area of pigmentation
`seen clinically (Fig 2, center right). In the left eye, there was a
`lacy area of early hyperfluorescence with leakage consistent with
`a well-defined CNV (Fig 3, top). There were a few window defects
`believed to be drusen, because they corresponded to clinical
`drusen seen surrounding the membrane.
`Infrared imaging of Bruch membrane area by confocal,
`direct, and indirect modes showed numerous subretinal
`deposits that were small and elevated, located temporal to the
`optic nerve and throughout the macula. The area, believed to
`be pigment in the right eye, was elevated on indirect viewing
`with a halo-like appearance in the plane of focus (Fig 2, bottom
`left). The left eye showed a multilayered structure with
`concentric dark and lighter, thickened areas. The surrounding
`macula showed numerous elevated subretinal deposits as seen
`on IR indirect imaging (Fig 3, bottom). These appeared to be
`small, discrete areas determined to be elevated by motion
`parallax and shadowing. The drusen apparent on FS, and FA
`corresponded to a number of subretinal deposits seen on IR
`imaging. However, many more subretinal deposits were seen
`on IR imaging. The patient desired no laser treatment and was
`requested to return in 1 month. He was lost to follow-up until
`4 months later. Visual acuity in the right eye had worsened to
`20/30. The FA showed a well-defined subfoveal CNV (Fig 2,
`bottom right) in the area noted to be elevated by IR imaging
`on previous evaluation.
`Here, the diagnosis was not clearly AMD, although the history
`and results of clinical examination did not support an alternative
`diagnosis. Infrared imaging supported the diagnosis of AMD
`based on a greater number of subretinal deposits/drusen than
`that appreciated clinically on FS or FA. It also imaged the core
`and surrounding halo in the right eye, which had a similar
`appearance to the subfoveal CNV only appreciated on FA 4
`months later (compare Fig 2, bottom).
`Case 2. A 79-year-old man who had had focal laser treat-
`ments three times in the right eye for CNV and subsequent
`recurrences secondary to AMD presented for a second opinion.
`His initial CNV occurred approximately 2 months after un-
`eventful cataract surgery with IOL implantation. He was first
`seen at our laboratory approximately 2 weeks after his last laser.
`He had no further distortion. His left eye had lost central vision
`7 years earlier from subfoveal CNV successfully closed with
`photocoagulation.
`On examination, visual acuity was 20/30 in the right eye
`and counting fingers in the left. Intraocular pressures were
`15 mmHg in the right eye and 18 mmHg in the left. Anterior
`segment biomicroscopy was significant only for a well-posi-
`tioned posterior chamber IOL in the right eye and nuclear
`sclerosis in the left. The clinical appearance and red-free slide
`
`showed a flat, dry, atrophic area with few surrounding drusen
`(Fig 4, top left). The FA showed an early hypofluorescent area
`inferior to the foveola extending into the foveal avascular
`zone, representing previous photocoagulation and faint flu-
`orescence at the boundary between the earlier treated area
`and the most recent treatment area. In the late phases of the
`FA, there was an area of hyperfluorescence in the center of
`the earlier treated area inferior to the fovea (Fig 4, top right).
`Small, discrete, hyperfluorescing drusen were viewed early in
`the FA surrounding the treatment area. There was leakage
`from a fibrovascular scar in the left eye.
`Highly confocal IR imaging showed the treatment area with
`an elevated area superiorly. Fine, radiating, retinal striae were
`noted off the superior aspect of the treated area (Fig 4, center
`left). The indirect mode showed a halo-like appearance sur-
`rounding the treatment area. Surrounding this halo-like ap-
`pearance were sheets of elevated subretinal deposits throughout
`the macula (Fig 4, center right). Indocyanine green angiography
`showed a dark area corresponding to previous laser and to the
`hypofluorescent area on FA. An area of faint hyperfluorescence
`between early laser treatment and the most recent treatment
`corresponded to a similar area on FA, but no hyperfluorescence
`was noted inferior to this within the old treatment scar where
`an area of hyperfluorescence was of concern on FA (Fig 4, bot-
`tom). The patient was followed.
`He returned 21 months later with a drop in visual acuity to
`20/70. Results of his clinical examination showed the dry scar
`as noted previously, with retinal elevation and a subretinal hem-
`orrhage extending under the fovea in the foveal avascular zone.
`Confocal imaging showed elevation above the treatment scar
`with fine, radiating striae extending superior and nasal to the
`scar (Fig 5, top left). On ICGA, a subfoveal CNV with a feeding
`vessel extending from within the scar was appreciated (Fig 5,
`top right). Treatment of the feeding vessels and recurrent CNV
`was only initially successful. The patient returned 11 months
`later with another recurrence. Note the red-free image with re-
`currence through the fovea with subretinal hemorrhage in Figure
`5, bottom left. Highly confocal IR imaging showed deep retinal
`striae, elevation of subretinal deposits, and thickened areas (Fig
`5, bottom right), which appeared more expansive than the IR
`image from the previous examination.
`Here, IR imaging provided earlier topographic information
`of a questionable area of recurrence of CNV within the laser
`treatment area on visit 1.
`
`Results
`
`We studied ten patients (6 women, 4 men), ranging in
`age from 59 to 92 years (mean, 80 years). Three patients
`had medically controlled hypertension and one had a his-
`tory of cardiovascular disease (Table 1).
`A total of 12 eyes (7 right eyes and 5 left eyes) are
`described. One patient had glaucoma. Six patients were
`phakic (7 eyes), 3 patients had IOLs (3 eyes), and 1
`
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`Ophthalmology Volume 103, Number 1, January 1996
`
`patient was aphakic (Table 2). One patient (1 eye) had
`asteroid hyalosis. These reflectile particles were noted
`at the shorter IR wavelengths (e.g., 805 nm) but did not
`interfere with FA, ICGA, or IR imaging at longer wave-
`lengths.
`
`Subretinal Deposit Number
`Drusen defined by clinical FS, FA, and red-free images
`corresponded in location with some subretinal deposits
`seen on IR imaging, and we therefore believe that these
`deposits represent the topographic appearances of drusen
`(Table 2). Although we do not know the nature of the
`other subretinal deposits