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AREDS SUMMARY GRADING PROTOCOL |
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AREDS SUMMARY GRADING PROTOCOL |
Fundus Photograph Reading Center
Appendix 15B
WISCONSIN AGE-RELATED MACULOPATHY GRADING SYSTEM
9. Myopia
The first goal of the summary grading is to provide information similar to that produced by the detailed grading, but with a smaller investment of grader time. A second goal is to grade in separate items (1) detachment of the sensory retina from the retinal pigment epithelium (RPE) by serous fluid or blood, designated serous or hemorrhagic sensory retinal detachment (RD), and (2) detachment of the RPE from the choroid, designated pigment epithelial detachment (PED), and to distinguish between different types of PED (see Section 15B-7). It is of particular importance to distinguish drusenoid PED from other types of PED (and from RD), because presence of drusenoid PED does not place an eye in the "advanced AMD" category, whereas presence of any of the other types of detachment does.
Sections 15B-2 through 15B-5 summarize major changes from the detailed grading protocol. Section 15B-6 describes briefly the grading form. Sections 15B-7 through 15B-18 deal with specific lesions. Section 15B-19 provides descriptions of example photographs that have been added to those used in conjunction with the detailed grading protocol. These are referred to in other sections when appropriate. Standard and example photographs are on file at the Reading Center, P.O. Box 5240, Madison, Wisconsin 53705.
An additional guideline for grid centration (see Section 15B-7 of the detailed grading protocol) is added for eyes in which RD involving the macula makes the yellow macular pigment more easily recognizable. When this pigment is visible and other landmarks are not helpful, the center of this yellow spot is used to help in grid centration.
Familiarity with the detailed grading protocol is necessary before reading this document. Most of the concepts, conventions, and definitions used in the detailed grading are also used in the summary grading, and only some of them are discussed further here.
The same definitions apply concerning the grades of absent, questionably present, definitely present, and cannot grade. Absent means that the lesion under consideration is not visible in the area being graded and that at least 25% of this area can be seen to be free of the lesion. Cannot grade means that the lesion is not visible and that less than 25% of the area under consideration can be seen to be free of it, either because of an obscuring lesion or poor photo quality (code 8 is assigned in either case). Questionably present means that the grader is > 50 but < 90% certain that the lesion is present in the area under consideration; absent is assigned if the lesion is present with < 50% certainty (and > 25% of the area under consideration is gradable for it). Definitely present means that the grader is > 90% certain that the lesion is present in the area under consideration. A different definition of the questionable grade is used for involvement of the center of the macula by geographic atrophy: questionable means that the grader cannot be > 90% certain that the center is not involved nor > 90% certain that it is involved, usually because of difficulty deciding exactly where the center is located.
As in the detailed grading program, right and left eyes are graded independently.
3.0 SUBDIVISIONS OF FUNDUS TO BE GRADED
In the summary grading the presence and extent of each characteristic graded is not assessed separately in each of the nine subfields of the grid, but in the area of the grid as a whole (or, for some lesions, in Field 2 as a whole instead). In addition, some characteristics are also graded separately in the area within 500 mm of the center of the macula (the central subfield) and/or in the area within 1500 mm of the center of the macula (the central and four inner subfields combined, designated herein "the central zone"). Geographic atrophy (only) is also graded in a fourth location, at the center of the macula. Gradings of a given characteristic in these 3 (or 4) different locations are inclusive, rather than mutually exclusive, e.g. a characteristic present in the central subfield is, by definition, also present in the central zone and within the grid as a whole, while a characteristic present only in one or more of the outer subfields is evaluated within the grid as a whole, but is graded absent in the other locations.
4.0 DRUSEN GRADING, CHANGES FROM DETAILED GRADING PROTOCOL
• Maximum drusen size is graded only for the area within the grid as a whole, as is presence of soft drusen. For soft drusen, the "softest" druse present determines the grade, rather than the predominant type as in the detailed grading. In assessing drusen size, type, and area drusen that are part of a PED are included.
• "Reticular" has been removed from the scales of drusen size and softness. Presence of reticular and calcified drusen are assessed as separate characteristics.
• The grading scale for drusen area has been simplified, in that the same steps are used in each of the 3 locations.
• Drusen confluence has been deleted from the Summary Grading.
5.0 OTHER CHANGES FROM DETAILED GRADING PROTOCOL
Specific items for retinal/choroidal degeneration - other, retinal edema, retinal hemorrhages/microaneurysms, and surface wrinkling retinopathy have been deleted, but presence of these conditions, as well as others, is recorded in the "confounding ocular lesions" or "other ocular lesions" sections. The order of items on the grading form has been modified and gatekeepers added to facilitate the grading process.
The AREDS Summary Maculopathy Grading Form (Exhibit 15B-1) begins with identifying information and a section for recording presence or absence of the fundus photographs specified in the AREDS protocol. Photographic quality is not graded on this form, but on the Photographic Quality and Preliminary Eligibility Assessment Form (Exhibit 15-1).
Section 1 of the Summary Maculopathy Grading Form, "Maculopathy", includes all of the lesions of AMD except drusen, and begins with a gatekeeper allowing it to be bypassed if all of these conditions are absent. The initial items in this section (RD, PED's, hard exudate, subretinal hemorrhage, subretinal fibrosis, and scars thought to represent photocoagulation for AMD) are graded first within all of Field 2 and then within the central zone. The remaining items (geographic atrophy, RPE depigmentation [termed RPE degeneration in the detailed grading protocol and non-geographic atrophy in the Macular Photocoagulation Study], and increased pigment) are graded first in the central subfield, then in the central zone, and finally within the grid as a whole. Geographic atrophy is also graded at the center of the macula.
Sections 2 and 3 of the form are used to record other lesions, Section 2 for those that exclude a subject ("Confounding Ocular Lesions") and Section 3 for those that do not ("Other Ocular Lesions"). Lists of conditions and code numbers are provided for each section (Exhibit 15B-2).
Sections 4 through 11 of the form are concerned with drusen, beginning with a gatekeeper that eliminates grading for drusen area if end-stage AMD is present, defined as presence of any of the following: RD, PED other than drusenoid, subretinal hemorrhage, subretinal fibrosis, scars of photocoagulation for AMD, or geographic atrophy definitely present in the central subfield and questionably or definitely involving the center of the macula. Section 12 is provided for comments.
7.0 SENSORY RETINAL AND RETINAL PIGMENT EPITHELIAL DETACHMENTS
(a) When the sensory retina (this term, or simply retina, is used here to designate all layers of the retina except the pigment epithelium) is normal and in its normal position adjacent to the pigment epithelium, it appears transparent, except for subtle reflections from its inner surface and for blood flowing through the vessels located in its inner layers. Elevation of the retina (i.e. displacement toward the center of the vitreous cavity), an important feature of AMD and several other retinal disorders, is assessed in stereo photographs in part by the position of the retinal blood vessels and in part by partial or complete obscuration of the RPE/choroidal pattern. Obscuration of this pattern occurs when the retina is separated from the RPE, particularly when the fluid responsible for the separation is opaque, but also to some extent when it is clear, because the normal retina is not perfectly transparent and this lack of complete transparency becomes obvious when the retina is separated even slightly from the RPE. Elevation of the retina occurs when it is pushed forward by accumulations of fluid, blood or fibrovascular tissue between it and the RPE, or when the RPE and the overlying sensory retina are pushed forward together by such accumulations (or mounds of drusen) between the RPE and the choroid. The sensory retina also appears elevated when its vessel-containing inner layers are elevated because of thickening within the retina (edema) or splitting of the inner layers of the retina from its outer layers (retinoschisis), processes not usually seen in AMD.
(b) In this grading protocol retinal detachment (RD) is considered to be present when the retina is visibly elevated away from the RPE by an accumulation of clear or turbid fluid (serous sensory retinal [SSR] detachment) or by blood (hemorrhagic RD). In keeping with clinical convention, RD is not considered to be present over a thin layer of subretinal blood, when the retina does not appear visibly elevated. Similarly, by convention, RD is not considered present over a subretinal fibrous scar when the retina appears tightly apposed to the scar tissue without intervening fluid, even though elevation of the retina is clearly visible. Pigment epithelial detachment (PED) is considered to be present when the RPE (and overlying retina) are together visibly elevated away from the underlying choroid. Drusen, which usually lie between the basal lamina of the RPE cells (the inner layer of Bruch's membrane) and the deeper collagenous/elastic layers of Bruch's membrane, often are detached along with the RPE.
(c) In this summary grading, unlike the detailed, subfield-by-subfield grading, RD and PED are graded as separate items, and drusenoid PED's are considered separately from PED's of other types. The principal criterion for recognition of either RD or PED is the perception of elevation of the retina during stereoscopic viewing. This requires normal stereopsis on the part of the grader and good quality stereoscopic fundus photographs. The first task of the grader is to determine whether elevation is present, then, if it is, to characterize its type. RD is distinguished from PED principally by the obscuration of the RPE pattern (and the underlying choroidal pattern as well) that occurs when the translucent retina is separated from the underlying RPE. This obscuration increases both with increasing separation of the retina from the RPE (even when the subretinal fluid is clear) and with increasing turbidity of the subretinal fluid (even if the separation is very slight), becoming most obvious when the subretinal fluid is a thick layer of blood. Thus an area in which the retinal vessels appear elevated is graded as RD if the RPE/choroidal pattern is obscured and the RPE is presumed to be in its normal position, and as PED if the RPE pattern is clearly visible and appears to be elevated along with the retina and in apposition to it. Frequently both types of detachment are present together.
(d) There is one exception to the general rule that elevation must be perceived stereoscopically for RD to be recognized. When it is necessary to grade photographs with little or no stereoscopic effect (rather than having them retaken), obscuration of the RPE/choroidal pattern in a localized area may be sufficiently suggestive of RD to merit a grade of definitely present or questionable.
7.2 Total area of detachment (RD plus PED)
If detachment of one or more types (including drusenoid PED) is definitely present, the total area within Field 2 occupied by detachment is estimated to the nearest disc area (if definitely present but < .5 DA, recorded as 0 to indicate the range 0.1 to 0.4).
Drusenoid PED's are usually easily identified as elevated mounds that appear to be made up of one or more large soft indistinct drusen or many confluent drusen. See Examples #22 (59-385 RE) and #26 (61-398 RE). Deposits of pigment may be visible on the surface of the PED, but for the most part the RPE overlying the mound of drusen appears depigmented (and in histologic sections often appears thinned), so that the predominant color of a drusenoid PED is pale yellow to white. The margins of a drusenoid PED are usually fairly well-defined and its elevation low to moderate. Large drusen or clumps of confluent drusen must be at least the diameter of Circle I-2 in narrowest diameter and must appear elevated to be classified as drusenoid PED (see Example #21 [60-347 RE]). In very large drusenoid PED's there may be small areas between or adjacent to large drusen where the color is like that of normal RPE and the appearance suggests presence of a small amount of subRPE or subretinal fluid (see Example #27 [55-346 RE]). Such areas are not classified as serous PED or RD. Drusenoid PED is graded absent, questionable, or definite, first in all of Field 2 and then in the central zone.
(a) Serous or hemorrhagic PED's
Serous PED's are characterized by sharply defined, solid-looking, typically dome-shaped but sometimes shallow elevations of the RPE, usually 500 to 3000 mm in diameter (see Example #29, 58-011 RE, and Standard #12). These elevations are round, oval or kidney-shaped and usually have clearly visible margins and a smooth surface contour. They have a uniform orange color of normal RPE with or without visible drusen and/or pigment deposits. When many large drusen are present, the appearance may be similar to drusenoid PED (see Example #30, 61-431 RE). Shallow serous PED's typically have a smooth, gently sloping surface that thins to a narrow, somewhat less well-defined border (the PED has the cross sectional shape of a strong plano-convex lens, see Example #36, 61-364 LE). The term "hemorrhagic" is used clinically for PED's that are dark gray or black in color, indicating subRPE blood, but in this classification hemorrhagic and serous PED's are placed in the same category, and presence of subRPE or subretinal blood is graded as a separate item.
(b) Irregular (fibrovascular) PED's
Irregular (fibrovascular) PED's can be recognized reliably in color photographs only if good stereoscopic effect is present, and even then are subtle and easily overlooked, because their elevation is low, their color is often similar to that of the surrounding RPE, and their margins are not well defined. See Example #33 (53-006 RE). The term "irregular" applies mainly to the surface contour of the PED. The surface contour of an irregular PED typically varies irregularly from one area to another, an appearance leading to the descriptive term "lumpy, bumpy RPE". Alternatively, the surface contour may be quite smooth, but the cross sectional shape of the PED is more like a low plateau than a plano-convex lens, i.e. the edges do not thin to a narrow border. The "plateau" may be tilted, i.e. higher along one edge than another, and its edges are often ill-defined. The color of an irregular PED may also be irregular, with foci of increased pigment intermixed with areas of depigmentation and/or drusen, but in some cases is more uniform and similar to a serous PED. See also Examples #32 (52-071 LE), #34 (58-327 LE) and, #35 (58-353 RE).
(c) Grading of non-drusenoid PED's
Typical, dome-shaped serous PED's are easily distinguished from typical irregular PED's, but many shallow PED's have an intermediate appearance and are difficult to classify. See Standard #16, Example #36 (61-364 LE), and Example #37 (59-058 RE). In grading serous and irregular PED's the grader first decides whether a PED of either type is absent, questionably present (> 50% but < 90% certain) or definitely present, first in Field 2 as a whole and then within the central zone. If questionably or definitely present in one or both areas, a second item is completed indicating (for all of Field 2) the predominant type of PED: (1) dome-shaped serous or hemorrhagic, (2) shallow (with some features suggestive of serous/hemorrhagic or irregular, but without the degree of elevation typical of dome-shaped serous/hemorrhagic PED and without the unevenness of surface contour typical of an irregular PED), or (3) irregular (with obviously irregular surface contour).
RD's may be seen alone or in combination with PED's. In AMD the most commonly observed RD is serous (serous sensory retinal [SSR] detachment). These RD's are slightly more pale in color than serous PED's, with decreased visibility of the underlying RPE pattern. Their margins are often ill-defined (see Standard #11, Example #41 [54-372 LE], and Example #45 [52-512 RE]). When subretinal hemorrhage is so extensive as to cause definite elevation of the retina, this area is included as RD (see Standard #15).
The reader should review the special conventions regarding classification of RD contained in Sections 15B-7.1.b & d at this point.
RD is graded absent, questionable, or definitely present, first in Field 2 as a whole and then in the central zone.
Hard exudates are small white or yellowish white punctate or linear deposits with distinct margins. When related to AMD, hard exudates are often arranged adjacent to PED's and/or under the peripheral parts of RD's. Pale spots that appear to be deposits on the posterior surface of detached sensory retina are included in the estimate of hard exudates. Hard exudates are graded absent, questionable, or definitely present, first in Field 2 as a whole and then in the central zone.
9.0 SUBRETINAL OR SUBRPE HEMORRHAGE
Hemorrhage between the sensory retina and the RPE usually appears red, like the color of venous blood, retinal hemorrhage or preretinal hemorrhage. When a layer of subretinal or preretinal hemorrhage is particularly thick, however, it may look reddish-black. SubRPE hemorrhage usually appears dark gray and may be difficult to distinguish from pigment. Often both may appear together. Subretinal/subRPE hemorrhage is graded absent, questionable, definitely present, or cannot grade, first in Field 2 as a whole and then in the central zone.
10.0 SUBRETINAL FIBROUS SCAR (OR FIBRIN)
Sheets or mounds of white material under the retina in eyes with age-related macular degeneration usually represent fibrous or fibrovascular tissue that has proliferated in areas previously occupied by serous or hemorrhagic subretinal fluid. Early in the development of such scars the white material may sometimes be fibrin. No attempt is made to distinguish between fibrin and fibrous tissue in the classification. See Example #47, 52-516 RE, and Example #45, 52-512 RE. Subretinal fibrous tissue is graded absent, questionable, definitely present, or cannot grade, first in Field 2 as a whole and then in the central zone.
If subretinal new vessels are visible, their presence is recorded in the "Comments" section.
11.0 SCARS OF PHOTOCOAGULATION FOR AMD
Scars classified as representing photocoagulation for AMD may be difficult to differentiate from geographic atrophy or other chorioretinal scarring. Factors to be considered are location, margins, and degree of preservation of the RPE and choroid. Photocoagulation scars are often located so as to avoid or minimize involvement of the center of the macula. Other locations may be central, resulting from treatment of a subfoveal neovascular membrane, or peripapillary, resulting from treatment of new vessels here. Within such scars the RPE usually appears to have been completely destroyed and the choroid severely damaged and/or obscured by fibrous tissue, with loss of the normal pattern of large choroidal vessels. This degree of destruction is greater than that usually seen in geographic atrophy or in the RPE depigmentation that occurs adjacent to subretinal fibrous scars. In some cases, however, a narrow zone of less severely damaged RPE and choroid may be seen adjacent to a typical photocoagulation scar. Large deposits of pigment may also be seen at the margin of photocoagulation scars. Photocoagulation scars are graded absent, questionable, definitely present, or cannot grade, first in Field 2 as a whole and then in the central zone.
Geographic atrophy is one or more sharply defined, usually more or less circular patches of partial or complete depigmentation of the RPE, typically with exposure of underlying large choroidal blood vessels. To be classified as geographic atrophy, a patch must be at least as large in area as Circle I-1. In general, at least two of the characteristics mentioned above (sharp edges, more or less circular shape, and visibility of underlying choroidal vessels) are required for a patch to be classified as geographic atrophy. Thus, even if much of the RPE appears to be preserved and large choroidal vessels are not visible, a roundish patch of RPE depigmentation with sharp edges may still be classified as geographic atrophy. The criterion of "edge sharpness" may be fulfilled in either of two ways: (1) when the depigmentation within the patch is subtle, a "sharp" edge must be abrupt and smooth, like one made with a cookie-cutter, but (2) when contrast between depigmentation within a patch and the normal pigmentation around it is substantial, the edge of the patch may still be considered "sharp", even if the transition occurs gradually or irregularly over a zone 125 to 250 mm in width. In the latter case, observation of the patch without magnification may be helpful in supporting the overall impression that the edge is "sharp". However, increased visibility of large choroidal vessels is the single most important criterion and, when present, it is not necessary for all the edges of the patch to be sharp; 25% of its circumference may be sufficient.
A potential area of disagreement is the categorization of areas of RPE atrophy adjacent to (or forming the peripheral part of) disciform scars. These areas may have an appearance very similar to that of geographic atrophy. Because such areas have not conventionally been described as geographic atrophy, they will not be so classified here. Sarks & Sarks state, "Use of the term geographic atrophy should be restricted to the end result of the atrophic form of age-related macular degeneration" (Ryan, Ed., Retina, Vol. 2, pp. 167-171). RPE atrophy adjacent to disciform scars will be included in the estimate of RPE depigmentation, with a grade of questionable assigned to geographic atrophy if an appearance typical of geographic atrophy is present in such a location.
Presence of geographic atrophy is graded first at the center of the macula: grade 0 if the center is definitely uninvolved; grade 1 (questionable) if the grader can not be > 90% certain whether the center is or is not involved; and grade 2 if the center is definitely involved. After grading the center point, the central subfield, central zone, and area within the grid are graded, according to total area of geographic atrophy within the zone being graded. The steps in the scale are listed below.
Grade |
Definition |
0 |
None |
1 |
Questionable |
2 |
Present, < Circle I-2 |
3 |
Present, > Circle I-2, < Circle O-2 |
4 |
Present, > Circle O-2, < 1/2 disc area |
5 |
Present, > 1/2 disc area, < 1 disc area |
6 |
Present, > 1 disc area, < 2 disc areas |
7 |
Present, > 2 disc areas |
8 |
Cannot grade |
13.0 RPE DEPIGMENTATION (RPE DEGENERATION, NON-GEOGRAPHIC ATROPHY)
Areas of depigmentation (atrophy) of the RPE that do not meet the requirements for geographic atrophy are placed in this category. Such areas are less well defined (i.e. have less sharp edges), less regular in shape (i.e. less circular or oval), and/or less severe (i.e. the underlying choroid is less visible) than geographic atrophy. Small areas of RPE depigmentation are often seen adjacent to foci of increased pigment. Detection of these sometimes subtle abnormalities is facilitated by careful examination of Fields 1M or 3M, where the central zone is less directly illuminated ("proximal illumination") and increased/decreased pigmentation located here is often more clearly visible (see Example #34, 58-327 LE). Large areas of RPE depigmentation are often seen partially or completely surrounding subretinal fibrous scar tissue (see Example #47, 52-516 RE). RPE depigmentation is graded in the central subfield, central zone, and area within the grid, according to total area involved in each. The steps in the scale are listed below.
Grade |
Definition |
0 |
None |
1 |
Questionable |
2 |
Present, < Circle I-2 |
3 |
Present, > Circle I-2, < Circle O-2 |
4 |
Present, > Circle O-2, < 1/2 disc area |
5 |
Present, > 1/2 disc area, < 1 disc area |
6 |
Present, > 1 disc area, < 2 disc areas |
7 |
Present, > 2 disc areas |
8 |
Cannot grade |
Disturbances of the RPE sometimes lead to deposition of granules or clumps of gray or black pigment in or beneath the retina. Such pigment deposits are found in some eyes with age-related maculopathy, but may also be a result of previous traumatic, inflammatory, toxic, or congenital processes. Pigment deposits that the grader believes to be the result of such processes, or of photocoagulation, are graded 7 (cannot grade - pigment other), except that the halos of pigment surrounding drusen are excluded from consideration, as are peripapillary pigment deposits. Care must also be taken to distinguish pigment deposits from dirt on the viewing box or mounting sheet, or from other artifacts. Increased pigment is frequently most easily detected with proximal illumination. It is graded in the central subfield, central zone, and area within the grid, according to total area involved in each. The steps in the scale are listed below.
Grade |
Definition |
0 |
None |
1 |
Questionable |
2 |
Present, < Circle C-0 |
3 |
Present, > Circle C-0, < Circle C-1 |
4 |
Present, > Circle C-1, < Circle C-2 |
5 |
Present, > Circle C-2, < Circle O-2 |
6 |
Present, > Circle O-2 |
7 |
Pigment, other |
8 |
Cannot grade |
Presence of one or more non-AMD lesions that might interfere with assessment of AMD and its causal role in visual loss is indicated by a "yes" response to this item, followed by recording of the code number for the lesion(s) from a list (Exhibit 15B-2) and a grade of questionably or definitely present. As many as three lesions can be listed.
15.1 Surface wrinkling retinopathy
The mildest degree of this condition (cellophane reflexes) is seen as a patch or patches of irregular increased reflection from the inner surface of the retina, resulting from slight contraction of a thin transparent glial membrane on the inner surface of the retina, as seen in Standard Photograph #19 in the central and inner subfields. In some cases, shrinkage is sufficient to produce fine retinal traction lines, as in Standard Photograph #20. Visible fibrous (glial) tissue may also be present.
If traction lines (folds) are present, or if there is a patch of cellophane reflexes > 1 DA in extent even without traction lines, this lesion is recorded in Section 2, Confounding Ocular Lesions, and disqualifies the subject from entry into the AREDS.
15.2 Abnormalities attributable to myopia
Subjects are excluded from AREDS if either eye is highly myopic as defined by any of the following: (1) refractive error of -8.00 diopters (spherical equivalent) or more, (2) myopic peripapillary crescent equalling or exceeding in width one-half the greatest diameter of the disc (vertical, horizontal, or oblique), (3) pigmentary abnormalities in the posterior pole considered by the clinic ophthalmologist or the Reading Center more likely due to myopia than AMD. It is unlikely that eyes with typical myopic degenerative lesions (lacquer cracks, gyrate atrophy of the RPE and choroid, Foerster-Fuchs spots) will be submitted for entry into AREDS (see Gass' Stereoscopic Atlas of Macular Diseases for examples).
Non-AMD lesions that do not exclude a subject are recorded here as described in Section 15B-15, using the list shown in Exhibit 15B-2.
17.0 DRUSEN (See also Section 15B-4)
This is a gate-keeper question for items 5 through 7 on the Summary Grading Form. If the grade is 0 (none) or 8 (cannot grade), items 5 through 7 are omitted. If the grade is 7 (presence of advanced AMD), items 5 and 6 are completed, but drusen area (item 7) is omitted. If the grade is 2 (drusen questionably or definitely present and advanced AMD absent), all of items 5 through 7 are completed.
Maximum drusen size is graded only within the grid as a whole, according to the guidelines in Sections 9 and 10 of the Detailed Grading Protocol.
Grade 0 is selected when maximum drusen size is < Circle C-0. When drusen size is > Circle C-0 but < Circle C-1, drusen are placed in either a hard or soft category on the basis of uniformity of density (color) from center to periphery, sharpness of edges, and thickness: those with decreasing density from center to periphery and fuzzy edges generally are placed in the soft-indistinct category; those with uniform density, sharp edges, and a solid, thick appearance in the soft-distinct category; and those with sharp edges but without a solid, thick, nodular appearance in the hard category. Drusen as large as or larger than Circle C-1 are placed in either of the soft categories.
Grade 0 is selected when maximum drusen size is < Circle C-0, or when maximum size is > Circle C-0 but < Circle C-1 and no drusen belonging to the soft-distinct or soft-indistinct category are present. Grade 1 is selected when one or more soft distinct drusen, but no soft-indistinct drusen, are present. Grade 2 is selected when one or more soft-indistinct drusen are present. Reticular drusen are included in the soft-indistinct category.
17.4 Drusen area within the grid
Area covered by drusen is estimated by mentally moving together all drusen graded 2 through 5 for size and comparing this area to areas of standard circles, and to the area of the standard disc (using the subfields of the grid as an aid: central subfield = 4/9 DA, each inner subfield = 8/9 DA). Three areas are graded, the central subfield, the central zone, and the area within the grid. The steps in the scale are listed below.
Grade |
Definition |
0 |
Drusen absent or questionable, or area covered by drusen < Circle C-0 but < Circle C-1 |
1 |
Area covered by drusen > Circle C-0 but < Circle C-1 |
2 |
Area covered by drusen > Circle C-1 but < Circle C-2 |
3 |
Area covered by drusen > Circle C-2 but < Circle I-2 |
4 |
Area covered by drusen > Circle I-2 but < Circle O-2 |
5 |
Area covered by drusen > Circle O-2 but < 1/2 disc area |
6 |
Area covered by drusen > 1/2 disc area but < 1 disc area |
7 |
Area covered by drusen > 1 disc area |
8 |
Cannot grade |
17.5 Drusen area outside the grid
All area outside the grid is considered, including Fields 1M and 3. The goal is only to identify eyes with drusen > Circle O-2 in extent, all lesser amounts being pooled with absent.
The term reticular drusen has been chosen for the yellowish material that looks like soft drusen arranged in ill-defined networks of broad interlacing ribbons. A good example of reticular drusen is visible in Standard Photograph #10 in the outer superior and temporal subfields on either side of the 1:30 meridian. When reticular drusen are present, they are often more prominent outside than inside the grid. Grade 1 is selected for eyes with questionable reticular drusen, grade 2 when reticular drusen are definitely present but only in the area outside the grid, grade 3 when reticular drusen are present within the grid (with or without presence outside the grid).
This term is used for drusen that are chalky-white or shiny, suggesting deposition of calcium. Absence, questionable presence, or definite presence is indicated, considering all of the area included in the fundus photographs.
The form concludes with a section for comments.
These photographs and their descriptions are provided to assist graders in applying the protocol in a standard way that will be reproducible within and between graders and over time. Many borderline cases have been included deliberately to help define the limits of the "questionable" grade and the choices between different types of detachments (RD versus PED, types of PED) and different degrees of depigmentation (RPE degeneration versus geographic atrophy).
19.1 Drusenoid PED's (Review Section 15B-7.3)
(a) Example #21 (60-347 RE)
Small, intermediate, and large drusen are present in this eye. In the inner inferior subfield near the 4:30 meridian, there is a small mound of drusen material larger than Circle I-2 in diameter, with pigment clumps on its surface. It is slightly but definitely elevated and should be graded as a definite drusenoid PED.
(b) Example #22 (59-385 RE)
A small drusenoid PED with pigment on its surface can be seen in the central, inner nasal, and inner inferior subfields in the 4:30 meridian. It is larger and a little more elevated than the PED in Example #21. Total area of detachment is < 0.5 DA.
(c) Example #23 (52-071 RE)
In the central subfield in the 4:30 meridian there is an accumulation of drusen with overlying pigment. Although there is some substance to this lesion, it is not elevated enough to be called even a questionable drusenoid PED.
(d) Standard #13 (UW/C14318-34 LE)
There is a large druse in the central subfield that shows slight elevation. In the detailed grading protocol grade 1, questionable, or perhaps even grade 2, definite, was considered appropriate, but 3 of 5 experienced graders now consider the correct grade to be absent, while 2 favor questionable.
(e) Example #24 (58-366 RE)
In the lower part of the central subfield there is a mass of confluent large drusen large enough (> Circle I-2) to be considered a definite drusenoid PED, but not elevated enough. Of 5 experienced graders, 3 chose absent, 2 questionable. Compare with Examples #21 and #22.
(f) Example #25 (55-344 RE)
Most of the drusen appear to be of intermediate size. Just above the center of the macula there is a small, low mound about 400-500 mm in diameter that appears to be made up mainly of confluent drusen. Other smaller mounds are present nasal, inferior, and temporal to the center of the macula. Although these mounds appear to be made up mostly of confluent drusen < Circle C-1 in size, the largest mound has drusen material spreading beyond the central confluent clump, and this would lead most graders to choose > Circle C-2 for maximum drusen size and soft indistinct for type. This largest mound meets the minimum size criterion for drusenoid PED (> Circle I-2), but its degree of elevation is borderline. Of 5 experienced graders 2 chose absent, 3 questionable for drusenoid PED. One of the graders choosing absent commented that the camera artefact overlying the nasal part of the mound may be exaggerating the degree of elevation.
(g) Example #26 (61-398)
A low drusenoid PED is present in the inner nasal and inner inferior subfields, extending almost to the 1:30 and 7:30 meridians. The contrast between the choroidal background and the color of the drusenoid PED is not quite as marked as it is in Example #22, perhaps making the elevation less obvious. However, definite elevation is present and this area should be graded definite drusenoid PED. There is perhaps a suggestion of RD (SSR detachment) in the inferior and nasal part of the central subfield adjacent to the PED, but this was considered less than 50% likely and RD was graded absent. Total area of detachment is slightly less than 0.5 DA (the area of each inner subfield is 8/9 DA, that of the central subfield 4/9 DA).
(h) Examples #27 (55-346 RE) & 28 (55-346 LE, Fields 1M & 2)
In both eyes there are many large soft drusen, some of which form confluent masses occupying most of the area with 1 disc diameter of the center of the macula. In the right eye there is good stereoscopic effect and definite RPE elevation, most of which appears to be made up of yellowish-white drusen, although the superior nasal aspect of the mound has a darker appearance suggestive of detachment of intact RPE (serous PED). The Reading Center considered this to be a drusenoid (only) PED. Some observers suggested that serous RD might be present temporal to the PED. Note, however, that the quality of the left member of the stereo pair is poor, especially temporally. This makes it impossible to be sure whether serous RD is present or not; the Reading Center considered it less than 50% likely and thus graded it absent.
In the left eye the elevation of the large confluent masses of drusen is not so obvious, particularly when Field 2 only is considered. Field 1 is helpful (and would be more so if it were centered at the temporal disc margin, as specified for Field 1M in the revised protocol) in documenting a low PED, which the Reading Center considered to be definite. The total area of detachment is about 3 DA in each eye. Compare with Example #30 (61-431 RE).
19.2 Dome-shaped serous PED's (Review Section 15B-7.4.a)
(a) Example #29 (58-011 RE)
There is a dome-shaped serous PED centered in the temporal part of the outer inferior subfield, with a narrow rim of RD (SSR detachment) adjacent to it (most prominent in the outer temporal subfield and below the outer inferior subfield). A thin light line just temporal to the 7:30 meridian defines the temporal edge of the PED (beyond this line is SSR detachment). The edge of the PED can be followed most easily upwards along the 7:30 meridian. It then crosses into the lower corner of the inner temporal subfield, then into the lower portion of the inner inferior subfield, then cuts diagonally through the center of the outer inferior subfield, extends just below its lower edge at about 7 o'clock, and returns to cross the 7:30 meridian again. The shallow SSR detachment extends for another 500-700 mm below and temporal to the PED. The surface of the PED is very smooth, with the reddish-orange color and finely granular pattern of intact RPE visible over its entire elevated dome. This granular RPE pattern is blurred in the areas of SSR detachment. The total area of detachment is 3 or 4 DA. Centered in the lower posterior part of the inner nasal subfield some observers suggest that there is a small, low, subtle elevation of the RPE that might be a PED of the irregular type. If this alone were present, some graders might assign a grade of questionable for PED, but most would consider the likelihood less than 50% and assign a grade of absent.
(b) Standard #12 (FES/3605 LE)
A sharply defined, dome-shaped serous PED is centered near the upper edge of the inner inferior subfield and extends into the remaining inner subfields, the central subfield, the outer inferior subfield, and a very small part of the outer nasal subfield. The intermittent light areas, most prominent in the inner inferior subfield, are drusen material pulled up along with the RPE. Several clumps of pigment are present on the surface of the PED. In the central subfield the color of the PED is reddish-orange and the fine granular RPE pattern is visible. Elsewhere the color is more pale and the RPE pattern is less visible, suggesting SSR detachment, but the presence of drusen leaves no doubt that the RPE is detached from the choroid, not the retina from the RPE. The surface of the PED is smooth, its edges are easily defined, and there is no surrounding SSR detachment. Total area of detachment is 2 DA.
(c) Example #30 (61-431 RE)
A dome-shaped serous PED is centered near the junction of the central and inner temporal subfields and extends also into the inner superior and inner inferior subfields. Its edges are well defined and there is no obvious surrounding or overlying RD. Perhaps there is a suggestion of SSR detachment at the junction of the inner and outer nasal subfields in Field 2, but this is not confirmed in Field 1M. The surface of the PED is smooth and in most areas its color is the reddish-orange of normal RPE. However, near the center of the PED there are several foci of pigment and a hint of several large drusen buried within it. If all of the PED had this appearance, it might be classified as drusenoid, rather than dome-shaped serous. Total area of detachment is 1 DA.
(d) Example #31 (60-345 RE)
A large "U" shaped, shallow to moderately elevated serous PED can be seen encircling the center of the macula from about 2 to 10 o'clock. It occupies part of the central subfield as well as all of the inner inferior subfield, most of the inner nasal and temporal subfields, and parts of the outer nasal, inferior, and temporal subfields. The surface of the elevated area is smooth and its edges fairly well demarcated in some, but not all, areas. There is subretinal and/or subRPE hemorrhage near the edge of the PED, and a vertical streak of subretinal hemorrhage in the inner and outer inferior subfields. There are scattered foci of pigment and a few drusen on the surface of the PED, but otherwise its color is the reddish-orange of intact RPE, except for a tiny light area in the inner temporal subfield at 10:30, which would be graded questionable or definite RPE depigmentation. There appears to be RD (SSR detachment) adjacent to the PED in the outer inferior subfield. Total area of detachment is 6 or 7 DA (including both PED and RD). There is little doubt that this PED is serous, as opposed to irregular, and its elevation is sufficient to place it in the dome-shaped category.
19.3 Irregular (fibrovascular) PED's ("lumpy-bumpy RPE") (Review Section 15B-7.4.b)
(a) Example #32 (52-071 LE)
There is a subtle, shallow elevation of the RPE centered in the inner temporal subfield and extending into adjacent subfields. The highest part of this elevation is in the inner temporal subfield, and it slopes gradually into the outer temporal, inner superior, and inner inferior subfields. Just after entering the central subfield the PED dips to a lower plateau, and the elevation gradually disappears in the inner nasal subfield. There are many pigment clumps on the surface of this detachment, and in the central subfield there is a faint whitish haze that is probably subretinal fibrous tissue. This PED is very shallow, its surface contour is irregular, and its edges are poorly defined, as is characteristic of irregular (fibrovascular) PED's. Total area of detachment is 2 or 3 DA.
(b) Example #33 (53-006 RE)
There is a very subtle, low elevation best seen near the junction of the inner superior, inner temporal, and central subfields. The temporal and superior edges of this elevation can be recognized about 3/4 of the way from the posterior to the peripheral limits of the inner temporal and inner superior subfields, and parallel to them. The nasal and inferior edges of the elevation are very ill-defined. There are scattered foci of pigment, drusen, and some small depigmented spots (RPE depigmentation) over and adjacent to the area of elevation. In the surface contour of the elevated area there appear to be many very subtle irregularities, but perhaps the impression of irregular contour results from the irregular surface pigmentation. At any rate, this elevated area does not have the smooth, "inflated" appearance of a shallow serous PED (see Example #36 61-364 LE) and there is little doubt that it fits best in the irregular (fibrovascular) category. There is no suggestion of any SSR detachment. Total area of detachment is a little greater than 1 DA. Good stereopsis is essential to the above description; monocular viewing of the right member of the pair gives little or no hint that a PED is present.
(c) Example #34 (58-327 LE, Fields 1M, 2, & 3M)
Even though both members of the Field 2 stereo pair have borderline to poor focus/clarity, there is excellent stereoscopic effect, which allows recognition of a low, donut-shaped elevation encircling the center of the macula in the central subfield and involving one-half or more of each inner subfield. A further portion of this elevation, shaped like a linear Indian burial mound oriented East to West, extends into the outer temporal subfield just above the 3 o'clock meridian. This extension, too, is low, making its edges difficult to define. In the 2:30 to 7:30 segment of the donut the elevation appears to involve mainly the RPE (i.e. to be a low PED). In the 7:30 to 1:00 segment the retina appears slightly pale and the underlying RPE/choroidal pattern is more blurred than elsewhere, and in the 1:00 to 2:30 segment the retina appears slightly elevated away from the RPE. From Field 2 alone, the best interpretation would appear to be that this is definitely an irregular PED (at least the 2:30 to 7:30 segment of the donut and its temporal extension) with associated definite low SSR detachment (the 7:30 to 2:30 segment of the donut, where the presence of underlying PED is uncertain). Fields 1M and 3 M confirm the impression of pallor and blurring of the RPE/choroidal pattern in the upper nasal part of the "donut", but are not otherwise very helpful, in spite of fairly good stereoscopic effect in Field 1M. Substituting Field 3M for the left member of the Field 2 stereo pair is also not very helpful; if anything, the impression of SSR detachment is strengthened and that of PED weakened. Total area of detachment is 3 DA.
(d) Example #35 (58-353 RE, Fields 1M, 2, & 3M)
There is a very shallow, plateau-like elevation of the RPE involving most of the area included in the central and inner subfields (the "central zone") and extending into the outer temporal and perhaps the outer superior subfield. The surface of this elevation has an irregular contour. There are heavy deposits of increased pigment and more subtle areas of decreased pigment (RPE depigmentation) over most of the surface of the elevated area. There are more extensive areas of RPE depigmentation involving most of the area included in the outer subfields and particularly prominent in the outer nasal subfield, where the appearance is very similar to that of geographic atrophy. At the lower nasal corner of the inner nasal subfield (and extending slightly into the adjacent subfields) there is an elevated nubbin of subretinal fibrous tissue, with no more than a suggestion of SSR detachment just temporal to it. In the lower nasal corner of the outer temporal subfield there is also perhaps a suggestion of SSR detachment, in that a small distance can be seen between the vertically-running small venule and the underlying choroidal pattern. There is also a suggestion of obscuration of the RPE/choroidal pattern in the posterior one-half of the inner temporal and inner superior subfields from 9 to 12 or 1 o'clock. None of these three "suggestions", nor all of them taken together, is enough to support a grade of even questionable RD. Field 1 M is helpful in confirming that the upper nasal edge of the PED is indeed elevated; substituting Field 3M for the right member of the Field 2 stereo pair is not helpful. All of 5 experienced graders agreed that this was a definite PED, of the typical irregular type ("lumpy-bumpy RPE"). Total area of detachment is 3 DA.
19.4 Shallow PED's (Review Section 15B-7.4)
This category includes shallow PED's that may be either serous (or hemorrhagic) or irregular. This category is provided because of the frequent difficulty in distinguishing between shallow serous and irregular PED's in color stereo photographs alone.
(a) Example #36 (61-364 LE, Fields 1M, 2, & 3M)
A shallow but definite elevation of the RPE occupies essentially all of the inner inferior subfield and extends into adjacent subfields. Its shape is similar to that of a strong convex lens, with a smooth surface that curves gradually to its thin, sharp, fairly well defined edges. Its color is the reddish-orange of intact RPE and similar to that of the uninvolved fundus. These characteristics indicate that this is definitely a PED, probably of the shallow serous type. However, it is possible this could be an irregular fibrovascular PED with an unusually smooth surface. Because of the difficulty in making this distinction both types are included in the "shallow" category. Field 1m is helpful (but unnecessary) in confirming the definite, but shallow, elevation of the PED.
In a narrow ring adjacent to the PED for most of its circumference the RPE/choroidal pattern is slightly blurred and/or pale, and in the upper one-half of the inner temporal subfield the retinal vessels appear slightly elevated and out of focus. All of these features suggest accompanying SSR detachment. In the lower part of the outer inferior subfield and below it there are many small white spots that appear to be either hard exudates or drusen. Their white color, and the slightly linear (i.e. not perfectly round) contour of some of them suggest hard exudate. Field 1M is helpful in showing that at least some of these spots, those near the branching of the small vein that approaches the PED from below, are on the posterior surface (or within) the retina, which is slightly elevated in this area, indicating that the spots are hard exudates. Field 3M is also helpful in documenting RD adjacent to the PED; when the left member of the Field 2 stereo pair is replaced by it, the elevation of the retina in the area described above and in the upper part of the inner temporal subfield are more clearly evident (definite SSR detachment).
There are two areas of subretinal hemorrhage, a sheet centered near the lower nasal corner of the inner nasal subfield and extending into adjacent subfields, and a small round spot near the upper border of the inner inferior subfield. The small linear hemorrhages in the lower part of the central subfield and the lower temporal corner of the inner nasal subfield look more superficial and are probably in the retina (record in "other ocular lesions" section). There are streaks of dark pigmentation in the central and inner nasal subfields over and adjacent to the PED. These appear deep and probably represent merely exaggerated choroidal pattern, rather than actual foci of increased pigment, or subRPE hemorrhage. Total area of detachment is 4 DA.
(b) Standard #16 (CSC/637625-5 RE)
A shallow oval elevation of the RPE occupies all of the central subfield and most of each of the inner subfields. Most of the temporal margin of this shallow PED is clearly visible, but much of its nasal margin is obscured by overlying SSR detachment, which forms a narrow rim adjacent to the PED nasally and then extends inferiorly into the outer nasal and outer inferior subfields (and below the latter). The contour of the PED appears to be plateau-like, sloping slightly from a thicker (more elevated) upper edge downwards to a thin lower edge. The color of the PED is that of intact RPE, with occasional drusen. There are sheets of subretinal hemorrhage nasal and temporal to the PED and perhaps one horizontally linear intraretinal hemorrhage at 3 o'clock in the outer part of the inner nasal subfield. This eye has a definite PED, which is probably best placed in the shallow category, and definite RD. Total area of detachment is 7 DA.
(c) Example #37 (59-058 RE)
A shallow elevation of the RPE occupies almost all of the central zone. Its edges are well defined, except from 4 to 6 o'clock, where shallow SSR detachment overlies the edge of the PED and extends slightly beyond it. There is a linear retinal hemorrhage in the area of RD and hard exudates temporal to and below it. Much of the surface of the PED has the reddish-orange color and fine granularity of intact RPE, but there are some paler areas (particularly in the central subfield) that appear to be confluent drusen and some foci of increased pigment. The surface contour (not color) of the PED is fairly smooth, and it slopes gradually to a thin edge (like a strong convex lens). This definite PED should be placed in the shallow category. Total area of detachment is about 4 DA.
(d) Example #38 (53-543 LE)
In this eye the shallow PED, which occupies small parts of the inner and outer superior and temporal subfields where they intersect, is overshadowed by the low SSR detachment that surrounds it and extends across nearly all of the central zone and into the upper edge of the outer inferior subfield. Surrounding the superior and temporal sides of the PED there is a red fringe, beneath the shallow SSR detachment; this could well be the edge of a subretinal neovascular network. Stringy subretinal vessels also appear to be present inferonasal to the PED. Fine hard exudates are present in and/or beneath the retina over parts of the PED and in the inner nasal, superior and temporal subfields and in the outer superior subfield. The yellow-orange color normally present in and around the center of the macula is more prominent because of the low SSR detachment. Both PED and RD are definitely present. The surface contour of the PED appears fairly smooth (and slopes to thin margins), indicating that it should be placed in the shallow, rather than the irregular category, although this may well actually be an irregular (fibrovascular) PED. Total area of detachment is about 6 DA.
(e) Example #39 (58-038 RE)
There are three small, shallow PED's in this eye, each a bit less than one-half DA in size, in the outer subfields centered in the 5:30, 10:00, and 11:30 meridians. The definite PED at 5:30 is hemorrhagic, and is partially surrounded by a horseshoe of subretinal hemorrhage. It has a smooth, evenly convex surface. The PED's at 10:00 and 11:30 are near the borderline between questionable and definite. The upper part of the PED at 10:00 has an appearance suggestive of early (questionable) subretinal fibrous tissue. Temporal to it there are many hard exudates. The PED at 11:30 is easily overlooked. Its upper edge lies just outside the grid, its lower edge near the more temporal branch of a small vein that bifurcates just above the exact center of the outer superior subfield. Adjacent to it are many large soft indistinct drusen. There appears to be considerable distance between the RPE and the retina in the inner and outer superior subfields, and to a lesser extent in the remaining inner subfields as well. Compare the distance of the retina from the RPE here with that outside the grid temporally. It is difficult to decide whether this appearance is the result of SSR detachment or of unusually good stereoscopic effect. RD should be graded no more than questionable. The predominant PED type is shallow. Total area of detachment is about 1-2 DA.
(f) Example #40 (61-372 RE)
A shallow, round PED centered near the junction of the central and inner temporal subfields occupies most of these two subfields and extends into the inner superior and inferior subfields as well. It has a fairly smooth, evenly convex surface and its margins can be distinguished fairly well (although somewhat obscured by very shallow overlying and adjacent SSR detachment). The otherwise rather darkly pigmented PED appears to be covered in some areas by a grayish-white film of fibrous tissue or fibrin. There is one collection of bright white hard exudate temporal to the PED and another duller collection in the nasal part of the outer inferior subfield. The RD appears to involve nearly all of the central zone and the part of the outer temporal subfield occupied by hard exudate, with total area of detachment about 5 DA. The yellow color of the retina at and around the center of the macula is increased because of the SSR detachment. The dark slightly reddish areas in the inner superior and nasal subfields at 12:30, 1:30, and 3:00 may be subretinal/subRPE hemorrhage (a grade of questionable may be best).
19.5 Retinal detachment (Review Sections 15B-7.1 and 15B-7.5)
Many examples of RD associated with PED have been given above. This section provides examples of eyes in which RD is a more prominent feature than PED, or exists without associated PED.
(a) Example #41 (54-372 LE)
A low SSR detachment covers the entire central subfield, extends a short way into the inner superior subfield, and then fans out to cover approximately one-half or a little more of the inner nasal and inner temporal subfields and all of the inner inferior subfield, as well as the lower one-third of the outer nasal subfield and all but the inferior temporal corner of the outer inferior subfield. The subretinal fluid is fairly turbid throughout, making it difficult to decide whether a shallow PED is present (most likely at the site of the large drusen and adjacent pigment located near the junction of the central and inner inferior and nasal subfields). Of 5 experienced graders, 1 graded PED questionable, 4 PED absent. Total area of detachment is about 5 DA.
(b) Example #42 (54-427 RE, Fields 1M, 2, & 3M)
A disc-shaped, very low SSR detachment occupies the central subfield and about two-thirds of each inner subfield. Its edges are quite well defined as a circle within which the fine granularity of the RPE pattern is blurred and the RPE/choroidal background looks slightly darker. As they cross this circle, the small retinal vessels appear to turn forward slightly as they climb the low sloping elevation of the RD, and they become slightly out of focus. The subretinal fluid is clear enough to allow small drusen to be seen. Field 3M is helpful as a replacement for the left member of the Field 2 stereo pair, providing greater stereoscopic effect (and suggesting that perhaps some of the "drusen" beneath the RD are exudates on the posterior surface of the retina). No PED is present. Total area of detachment is 2 DA.
(c) Example #43 (53-493 RE)
A fairly obvious SSR detachment occupies all of the inner and outer nasal subfields and adjacent parts of the inner and outer inferior, the central, and (barely) the inner and outer superior subfields. Below the horizontal meridian under the posterior part of the RD, drusen can be seen in the plane of the RPE. Between the 1:30 and 3:00 meridians there is an oval pale area with a ring of surrounding pigment (and some drusen partially surrounding the pigment). If the oval pale area appeared elevated, it might be interpreted as a PED or is subretinal fibrous tissue. There is a history of previous photocoagulation, and this lesion may represent a photocoagulation scar.
(d) Example #44 (61-414 LE)
There is a shallow SSR detachment centered near the junction of the central, inner temporal, and inner inferior subfields, and involving nearly all of these subfields and parts of the inner nasal and perhaps the inner superior subfields as well. The good stereoscopic effect provided by this stereo pair makes it easy to detect the elevation of the retinal vessels. The loss of the normal fine granular RPE pattern in the elevated area strongly supports the interpretation that this is RD, not PED, as does the blurring of the few drusen still visible beneath the elevated retina and their apparent position in the plane of the attached RPE. The first two of these features (loss of the RPE pattern and blurring of the drusen) are not dependent on stereoscopic effect and in this case would be sufficient to allow a grade of definite RD, even if only one member of the stereo pair were present. The temporal and inferior edges of the RD are fairly well defined, but the nasal and superior edges are not (compare with the sharp edges of PED's in Example #30 (61-431 RE) and Standard #12. There is a fleck of subretinal hemorrhage near the lower temporal corner of the inner inferior subfield and several tiny dots of such hemorrhage in the temporal part of the inner superior subfield. At the junction of the central and inner superior subfields there is a collection of foci of increased pigment with very subtle adjacent partial depigmentation. This oval area of pigment disturbance appears to be very slightly elevated. Its more posterior part (in the central subfield) is blurred by the overlying RD, while its more peripheral part (in the inner superior subfield) is in contact with the overlying attached (or very slightly detached) retina. There is a history of photocoagulation in this eye, and this lesion probably is a photocoagulation scar. If it were less pigmented and more elevated, it might be interpreted as a shallow PED. Total area of detachment is 2 or perhaps 3 DA.
(e) Standard #11 (UW/G637-5 LE)
There is a shallow elevation of the retina centered near the junction of the inner and outer inferior and the inner and outer temporal subfields and extending into all subfields except the outer superior and outer nasal. The elevation is low and its borders somewhat indistinct, characteristics of SSR detachment. In the central and inner temporal subfields the RPE pattern is obscured and the detachment appears to be purely SSR. This is true as well for the tiny extensions of the detachment into the inner superior and nasal subfields. In the outer temporal and inferior subfields, near the middle circle on either side of the 4:30 meridian, drusen are seen clearly, suggesting that the RPE is elevated. This appearance is different from that seen elsewhere in the detached area, in particular along its lower edge near the outer circle from 3:45 to 5:00, suggesting that the RPE may be detached and close to or in contact with the sensory retina in the area where drusen are clearly visible. All of 5 experienced graders agreed on the presence of SSR detachment; 1 graded PED absent, 1 questionably present, and 3 definitely present (shallow type). Total disc areas of detachment equal approximately 5: outer temporal 2 disc areas, outer inferior 1 disc area; inner temporal and its central extension 1 disc area; inner inferior and its central extension 1 disc area, with room at its inferior nasal corner for the tiny extensions occupying the inner nasal and superior subfields and for part of the superior nasal half of the central subfield not yet accounted for; leaving less than one-half disc area in the central subfield, not enough to bring the total to 5.5 DA (which would be rounded to 6).
(f) Standard #15 (CSC/637625-5 LE)
There is a shallow elevation of the retina involving nearly all of the area within the grid. In the upper one-third of the outer temporal subfield the appearance is that of a very shallow SSR detachment, with slight elevation of the retinal vessels and slight blurring of underlying drusen. In the nasal part of the central subfield, and in adjacent parts of the inner inferior, nasal, and superior subfields, the dark brownish-orange color suggests a very shallow PED. Temporal to this the black color indicates subRPE blood, with some elevation of the RPE and overlying retina (about the same amount of elevation as in the area of SSR detachment described above), i.e. hemorrhagic PED. Most of the remaining area within the grid is occupied by a layer of subretinal blood that is thick enough to elevate the retina to about the same level as the SSR detachment and hemorrhagic PED. This eye would therefore be graded as having: (1) RD (SSRD and hemorrhagic RD are considered together as one lesion), (2) PED (shallow), and (3) subretinal/ subRPE hemorrhage. Total area of detachment within Field 2 is about 15 DA (the grid contains 16 DA).
19.6 RD and subretinal fibrous tissue
(a) Example #45 (52-512 RE)
A low elevation of the retina occupies all of the central zone and extends into the outer nasal and inferior subfields and inferiorly beyond them. Perhaps small parts of the outer temporal and superior subfields, on either side of the 10:30 meridian, are also involved; it is difficult to be sure of this because focus/clarity is poor in this area in both members of the stereo pair. The margins of the elevated area are not well defined. There is no doubt that this is an RD (SSR detachment). The subretinal fluid is clear and the choroidal/RPE pattern and flat sheets of subretinal fibrous tissue are clearly visible in the plane of the attached RPE. In fact, these features are so well seen that the presence of RD could not be detected with certainty without stereoscopic effect. In the outer nasal subfield and below it at 4 o'clock there is a solid (3 dimensional) band of subretinal fibrous tissue. Along its nasal edge there is a thin line of subretinal hemorrhage. There are also small spots of subretinal hemorrhage outside the grid at about 6:45, 7:15, and 9:00, and several tiny spots near the temporal end of the outer superior subfield. There is some hard exudate inside, but more outside, of the grid between 7:30 and 9:00. Most of the whitish area within the grid is subretinal fibrous tissue. At least some of the smaller, less intensely white depigmented spots on either side of the 1:30 meridian in the inner superior and nasal subfields and on either side of the 7:30 meridian in the inner inferior and inner temporal subfields represent RPE depigmentation (some may be drusen).
(b) Example #46 (52-500 RE)
In the central subfield and in a portion of all the inner subfields there is dense subretinal fibrous tissue. The elevation of the fibrous tissue is due to the thickness of the subretinal tissue itself, not to the presence of PED pushing it forward. There is also RPE depigmentation surrounding the mound of fibrous tissue. This is evident by the change in the color of the RPE. There are thin fibrous strands in this area as well. The retina appears to be in contact with the fibrous tissue in most areas, but peripheral to the fibrous tissue in some areas the retina is elevated by serous fluid; this is seen most clearly from 11:00 to 12:00 in the inner superior subfield (SSR). All or some of the hemorrhages seen nasally are probably in the retina (they are too high to be subretinal).
(c) Example #47 (52-516 RE)
In the central zone a wad of subretinal fibrous tissue is present, with pigment deposits at its inferotemporal edge and a depression in its center. The elevation of the surface of the fibrous tissue is probably due to the tissue itself and not to an underlying PED. There is a narrow rim of subtle SSR detachment adjacent to the fibrous tissue along its superior and nasal edges. A fairly broad band of RPE depigmentation surrounds this entire area. It is most extensive in the outer temporal subfield, occupying most of it, but being most obvious between 8 and 9 o'clock, where the appearance is very similar to geographic atrophy.
(d) Example #48 (58-357 LE)
A large mass of subretinal fibrous tissue occupies most of the central zone and extends into parts of all the outer subfields. Over much of the fibrous tissue and temporal to it there is a shallow SSR detachment. At about 3 o'clock in the outer temporal subfield there are several faint reddish spots that may be subretinal hemorrhage (graded no more than questionable). It is difficult to decide whether a PED is present beneath the fibrous tissue. Along the temporal edge of the mound, there seems to be a gradual sloping upward of the tissue, suggesting that PED is present. In addition, in the inner superior subfield, beneath the small branch of the venule, some choroidal vessels can be seen. They appear to be on an incline which, again, suggests PED is present (graded questionable).
(e) Example #49 (54-414 LE)
This case is similar to Example #48, but the amount of subretinal fibrous tissue is less and evidence of a PED underlying it stronger (at the borderline between definite and questionable PED, of the shallow type). Shallow SSR detachment is present throughout the central zone and extends part way into each of the outer subfields. The mass beneath the retina is most highly elevated in the inner superior and temporal subfields, where the fibrous tissue is located, and slopes downward into the inner inferior subfield. The hemorrhage partially surrounding the PED is obviously beneath the retinal vessels and is dark red in color rather than grey-black, which indicates that it is subretinal not subRPE. There also appears to be some hard exudate outside the grid at about 11:00 and some in the outer nasal and inferior subfields, most notably at 7:30.
Three types of abnormalities are graded, each as a separate item:
Increased pigment >"pigmentary abnormalities"
RPE depigmentation (degeneration) > " "
Geographic atrophy
There are two principal difficulties in grading: (1) deciding whether to categorize small, flat depigmented spots as drusen or as RPE depigmentation, and (2) deciding whether to categorize depigmented areas that have some, but not all, of the characteristics of geographic atrophy (GA) as GA or as RPE depigmentation. The examples to follow will focus on these problems.
(a) Standards #1 (UW/C246-9 LE), #2 (UW/C9188-7 RE), #4 (UW/G637-16 RE), & #5 (UW/-G2260-14 RE)
Standard Photographs #1 and #4 have no increased pigment, even at the questionable level. All of the pigmentation in Standard Photograph #2, including the more prominent area in the inner inferior subfield, is considered pigment mottling, so that increased pigment is graded 0 here as well. In Standard Photograph #5 in the central subfield at 11:00 touching the edge of the large druse is a grey spot that should be graded questionable. Definite increased pigmentation, however, can be seen in the inner superior subfield.
(b) Example #50 (58-016 RE)
There are several small drusen mainly in the outer temporal subfield. Near the edge of the central subfield from 1 to 4 o'clock there are several foci of increased pigmentation with adjacent decreased pigmentation. Both increased pigment and RPE depigmentation (degeneration) clearly should be graded definitely present (and there is no suggestion of GA).
(c) Example #51 (58-342 LE, Fields 1M, 2, & 3M)
Straddling the inner circle at 9 o'clock there is a small area of depigmentation that could be described equally well as "roundish" or "squarish". Its edges are clearly defined, but not "cookie-cutter" sharp. No large choroidal vessels are visible within it. It should be graded as definite RPE depigmentation. In Field 2, two small foci of pigment are visible, one near the center of the depigmented area and one on its margin at 1:30 o'clock. Many other areas of dark pigmentation are visible, but all of these are part of the choroidal pattern. In Field 1M, focus is better and several pigment dots can be seen within the depigmented area; they appear to be definite increased pigment.
(d) Standard #3 (FES/491-S-1 RE)
There is a pale area straddling the inner circle from 10 to 12 o'clock. Within this area several small drusen are visible, but it does not appear that all of the area can be ascribed to drusen. Therefore RPE depigmentation should be graded definite. This area may well be unrelated to age-related macular degeneration but because the RPE appears to be the principal tissue involved and is depigmented, this area is graded as RPE depigmentation.
(e) Example #52 (53-563 RE)
In the central and inner nasal subfields there are subtle but definite foci of increased pigment. In the nasal one-half of the central subfield and in the posterior part of the inner nasal subfield adjacent to the increased pigment, there is definite RPE depigmentation. In the upper part of the outer temporal subfield there are some obvious drusen (many of them > 63 mm in size). In the inner superior subfield and upper part of the inner nasal subfield there are some smaller, more subtle drusen. The remaining obvious pale areas, in the inner nasal, inferior, and temporal subfields, are less easy to categorize. Most of these are round, intensely white spots, and they should probably be considered to be confluent drusen (most < 63 m, some perhaps > 63 m). Adjacent to these spots, and elsewhere in the inner temporal subfield, there are ill-defined areas of very subtle depigmentation, too subtle to classify even as questionable RPE depigmentation.
(f) Example #53 (54-425 LE, Fields 1M, 2, & 3M)
There are many foci of increased pigment, most prominent in the central subfield but also present in each inner subfield. How should the paler areas adjacent to the pigment be classified, as drusen or as RPE depigmentation? Within the central subfield many of the pale spots are small and round, strongly suggesting drusen (presumably confluent between 6 and 7 o'clock). In the inner subfields the spots are larger, most have fuzzy edges, and there is a suggestion of visible thickness in many of them; all these characteristics suggest large, soft indistinct drusen. From Field 2 it would be difficult to defend an interpretation of RPE depigmentation in any area. From Field 1M, which is in better focus, the pale area in the lower part of the central subfield between 6 to 7 o'clock is suggestive of RPE depigmentation, but should be graded no more than questionable.
(g) Standard #18 (UW/G3229-25 RE)
A roughly round patch of RPE atrophy occupies most of the central zone. Its edges are clearly defined (superotemporally cookie-cutter sharp) and large choroidal vessels are visible at its base. Clearly this is geographic atrophy with the center of the macula involved. There is increased pigment, quite definite along the temporal margin of the atrophic area.
(h) Example #54 (61-394 LE)
All of the atrophic areas have clearly defined edges and exposed choroidal vessels. Most are round, or appear to result from confluence of multiple smaller round areas. Even the smallest round patch at 12:30 is larger (slightly) than Circle I-1. All of these areas are geographic atrophy. The center of the macula is not involved by GA, but there is increased pigment here. There are many large and smaller confluent drusen, some of which are very shiny, meriting a definite grade for calcified drusen.
(i) Example #55 (54-008 RE)
This case has 4 roundish areas of RPE atrophy, all with "cookie-cutter" sharp edges, all > Circle I-1 in size, and with varying degrees of visibility of underlying choroidal vessels (at 7, 10, 1:30, and 3 o'clock in the inner subfields). All of these should be graded as definite GA. If only the 3 o'clock lesion were present, a grade of questionable might be considered. Some of the drusen are calcified.
(j) Example #56 (56-389 LE, Fields 1M & 2)
There are several foci of increased pigment in the upper part of the inner inferior subfield. Nasal to this pigment there is an ill-defined area almost as large as the disc (centered above the lower nasal corner of the inner nasal subfield) in which there is a subtle increase in the visibility of the choroidal vessels. Only in the upper part of this area (between the 8 and 9 o'clock meridians in the nasal part of the inner nasal subfield) is there definite RPE depigmentation (and increased pigment within it); the rest of the area might well be considered within normal limits.
(k) Example #57 (58-368 LE, Fields 1M, 2 & 3M)
There is a roundish depigmented area in the lower part of the central subfield, with some increased visibility of choroidal vessels within it. Its nasal and temporal edges are sharp, its upper and lower edges less well defined. There are many foci of increased pigment superior to the depigmented spot and one within it. It is difficult to decide whether to classify this as geographic atrophy or RPE depigmentation. A questionable grade for GA and definite for RPE depigmentation would be appropriate.
(l) Example #58 (61-349 RE)
In the area outside the grid, in most of the outer temporal subfield, and in some outer parts of the remaining outer subfields the brownish-orange color of the RPE is visible. This color is also present in most of the upper nasal one-half of the central subfield, in adjacent parts of the inner superior and nasal subfields, and extending across the inner and outer nasal subfields between the 3:45 and 4:30 meridians. In much of this area large soft drusen are visible. In the remainder of the photo, the large choroidal vessels are faintly visible, the color is more reddish-orange, and there are few or no drusen; this appearance presumably results from partial atrophy of the RPE and strongly suggests geographic atrophy. However, the atrophic area is not round or oval and its edges are ill defined. Compare with Example #55 (54-008 RE). Grades of definite for RPE depigmentation and questionable or absent for geographic atrophy best categorize this eye. The foci of pigment in the temporal one-half of the central subfield merit a grade of definite for increased pigment. It is less clear how the pigment in the nasal one-half of the central subfield and in adjacent parts of the inner superior and nasal subfields should be graded (if it alone were present); either questionable or definite would be appropriate.
(m) Example #59 (52-509 RE)
There are about 6 or 7 roundish spots of (partial) atrophy of the RPE contiguous with one another lying mostly in the inner superior and nasal subfields. The margin of these areas are sharp and the reddish-orange color of the choroidal vessels barely visible in some areas. These lesions are probably best classified as definite geographic atrophy, although near the borderline of questionable. There are many foci of increased pigment.
(n) Example #60 (53-490 LE)
Occupying all of the central subfield and adjacent parts of all the inner subfields is a roughly oval area of RPE atrophy with exposure of large choroidal vessels beneath most of its base. Its nasal and upper edges are sharp (with pigment foci) and its temporal and lower edges somewhat ill-defined. It meets the criteria for definite geographic atrophy, with involvement of the center.
(o) Example #61 (56-364 LE)
Straddling the junction of the inner and outer nasal subfields is a patch of definite geographic atrophy, over which some drusen are still present. In a corresponding position temporally is an ill-defined area with some increase in visibility of choroidal vessels. This would not meet the criteria for geographic atrophy and it is doubtful whether RPE atrophy is definite enough for a grade of more than questionable RPE depigmentation. Compare with Examples #55 (54-008 RE) and #58 (61-349 RE).
(p) Example #62 (61-389 LE)
A low mound of subretinal fibrous tissue occupies a large part of the outer superior subfield and extends into adjoining subfields. There is little or no RD over or adjacent to it. An area of partial RPE atrophy involves all of the central zone, most of the outer temporal subfield, and smaller parts of the outer inferior and nasal subfields. Scattered over this atrophic area there are additional more subtle flat patches and bands of subretinal fibrous tissue, as well as foci of increased pigment. The atrophic area is roughly circular and there is some increased visibility of choroidal vessels, but its edges are ill-defined. It should be graded as RPE depigmentation, not geographic atrophy. The prominent vessels in the central subfield may be subretinal/subRPE new vessels. There are some tension lines in the retina, probably related to contraction in the fibrous tissue.
(q) Example #63 (58-366)
Rather faint subretinal fibrous tissue (or fibrin) straddles the inner circle from 10 to 4:30 o'clock. Peripheral to it there is a narrow parallel band of SSR detachment. There are areas of RPE atrophy occupying much of the central zone with extensions into adjoining parts of the outer subfields. The most clearly defined patch of atrophy straddles the middle circle at 9 o'clock; it is round, has fairly well defined edges, and exposed choroidal vessels are visible in it. This could be a patch of geographic atrophy, as could some (or all) of the other patches, and the exudative features could have occurred subsequent to development of the GA. On the other hand, exudative AMD could have occurred first, with the RPE atrophy occurring as part of the disciform scar. The clearly defined patch at 9 o'clock could be a photocoagulation scar (but there is no history of such treatment). All of the atrophy should be graded RPE depigmentation, because it appears to be related to the fibrous scar, except perhaps for the round patch at 9 o'clock, which should be graded questionable or definite GA, definite if it is known that this eye did not have photocoagulation.
19.8 Surface wrinkling retinopathy (epiretinal membrane) (Review Section 15B-15.1)
(a) Standard #20 (UW/C19179-8 LE)
There are obvious tension lines in all subfields.
(b) Example #64 (59-369 RE)
There are subtle tensions lines about 1 disc diameter temporal to the temporal margin of the disc, running through parts of the inner and outer nasal and inner and outer superior subfields. Although subtle, these are enough to disqualify the subject. The pigment beneath the tension lines between 3 and 4 o'clock is part of the choroidal pattern and would not be graded as increased pigment (nor would the nevus at 7:30 at the edge of the photo).
(c) Example #65 (59-326 LE)
Even though there are no tension lines, an area of visible epiretinal membrane occupying one disc area or more is sufficient to disqualify a subject from AREDS.
19.9 Myopia (Review Section 15B-15.2)
(a) Example #66 (53-505 RE)
The disc appears fairly typical of high myopia, with a temporal crescent slightly wider than one-half the vertical disc diameter. There are also fine areas of depigmentation in the macula and few, if any, obvious drusen. The temporal crescent is sufficient to exclude the subject, and this decision is perhaps supported to some extent by the pigmentary changes.
(b) Example #67 (60-160 LE)
The disc qualifies (barely) for exclusion on the basis of myopia. Just nasal to the center of the macula there is a pale area (it is difficult to decide whether to grade this as drusen or RPE depigmentation). Superonasal to the center of the macula there is a suggestion of tension lines, which should be graded questionable SWR. If the disc were more normal and myopia were < 8.00, the eye would be eligible.
Exhibit 15B-1. SUMMARY MACULOPATHY GRADING FORM
Exhibit 15B-1. SUMMARY MACULOPATHY GRADING FORM continued
Exhibit 15B-2. APPENDIX FOR THE AREDS SUMMARY GRADING FORM
2. Confounding ocular lesions (use only for non-AMD)
18 Pup Sz Pupil < 5 mm diameter
19 Media Media opacity precludes adequate photos
20 Ang stk Angioid streaks
21 DR>10RS Diabetes ³ 10 red spots (Ma's and/or small RHS) and/or < 10 red spots with more severe lesion(s)
23 Drug Drug related maculopathy (e.g. chloroquine)
24 Nevus + Nevus within grid with associated pigmentation, depigmentation or drusen
25 H/T/C Healed chorioretinal scar to include Histo, Toxo, Chorioretinitis
26 Mac ed Macular edema < 1500 microns from center
27 Mac hle Macular hole/cyst < 1500 microns from center
28 Mac scr Macular scar < 1500 microns from center
29 Mac oth Macular other lesion < 1500 microns from center
30 Occ art Occlusion, central or branch artery
31 Occ vn Occlusion, central or branch vein
32 Op at Optic atrophy
33 Op ed Optic disc edema
34 PC oth Photocoagulation scars, other (i.e. non-AMD)
35 P/V hem Preretinal or vitreous hemorrhage
36 Ret det Retinal detachment
37 Dq oth Other disqualifying lesions (specify under comment)
38 SWR>Stds Surface wrinkling retinopathy more severe than that in examples 68-71
39 Cat Cataracts preclude satisfactory photos
40 Myope Myopic crescent > 1/2 longest diameter of disc
3. Other ocular lesions
41 Ast hyl Asteroid hyalosis
42 Art nar Arteriolar narrowing ³ Std 19
43 Chr scr Chorioretinal scar > 1500 microns from center
44 DR < 10RS Diabetic retinopathy level 20 or 30 or < 10 small red spots
45 Op dr Drusen of the optic nerve
46 Hollenh Hollenhorst plaque
47 Nevus Only Nevus (< #24 of Confounding ocular lesions)
48 Peri at Peripapillary atrophy
49 Cello R Cellophane reflex only, no patch ³ 1 disc area in extent
50 Vit/gl Vitreous opacity or glial remnant
51 Other Other (specify under comment)
52 Lg Cup Large cup (add under comment if present; asymmetry, undercutting, notching, or cup-to-rim)
53 SWR£Stds Surface wrinkling retinopathy w/traction lines £ examples 68-71 and OS 9 and 13 (any category)
29Feb2000