The objective of this procedure is to evaluate retinal photographs taken of participants in the Atherosclerotic Risk in Communities (ARIC) Study for hypertensive and/or sclerotic changes. Photographs are evaluated in semi-quantitative fashion by a reader using a magnifying viewer to examine the slide transparencies on a light box. Among the features evaluated are focal narrowing of arterioles, arteriolar sheathing, arterio-venous (AV) crossing abnormalities, and other retinopathy (including microaneurysms, intraretinal hemorrhages, soft exudates or "cotton wool spots," and papillary edema). In addition, photographs are assessed for lesions characteristic of diabetic retinopathy and age-related maculopathy, and other conditions (some of which may affect visual function). Generalized narrowing of arterioles is evaluated separately by measuring vessels upon a digital image processing system, a procedure described in Appendix B.

1.2 Rationale

The major purpose of evaluating changes in the retinal vasculature associated with hypertension and/or arteriolar sclerosis is to explore their prognostic value for cardiovascular outcomes. It may be that changes in the retinal vasculature provide information about status (such as length and severity of exposure to hypertension, and degree of structural damage) not provided by standard measurement of blood pressure, particularly in subjects taking antihypertensive medications. Because the retina can be assessed noninvasively, this procedure may be a practical way to identify risk factors for clinically important pathology.

1.3 Background

Observers have associated retinal changes with hypertension and/or sclerosis for decades. Recently, Freeman and Sperduto reviewed the classification of ocular signs and evaluated their suitability for further research. Focal arteriolar narrowing, AV crossing changes, and hypertensive retinopathy were included in the landmark classification of clusters of signs proposed by Keith, Wagener, and Barker. Later, Sheie, Leishman, and Evelyn also proposed classifications that included several of these features. As Freeman and Sperduto¹ note, focal narrowing and AV crossing changes have been linked with hypertension and other clinical outcomes in various studies. Other changes, particularly the cluster referred to as "malignant" or "fulminant" hyptertensive retinopathy, while also important, have presumably decreased in prevalence as high blood pressure has become better controlled in the general population. Traditionally, changes in arteriolar light reflex have been considered important and were included in early classifications. However, Kagan et al demonstrated that this sign probably cannot be graded with sufficient reproducibility.

2. EQUIPMENT AND MATERIALS

A single 45^o retinal photograph, taken with Ektachrome 100 ASA film on the Canon CR-45UAF non-mydriatic camera, is read for each ARIC participant. The ARIC 45^o photographic field is centered between the optic disc and the macula, providing photographic documentation of the the optic disc, macula, substantial portions of the temporal arcades, and about two disc diameters of retina nasal to the optic disc. The standard ARIC photographic field is diagrammed in Exhibit 1, part A.

The photograph reader views each retinal photograph with a monocular magnifying viewer on a fluorescent light box, and references the written protocol and the photographic standards and examples to evaluate retinal abnormalities. The photograph reader directly enters his/her evaluations in a microcomputer database. The following materials are used in the reading process:

(a) a monocular 8X stand viewer;

(b) a daylight fluorescent light box, Logan #1055 with opal glass cover, modified to hold three 14 watt fluorescent tubes with a Kelvin color rating of 6200^o to approximate normal daylight, and with a modified direct current power source to eliminate flicker;

(d) photographic standards and examples, discussed throughout the protocol and listed in Exhibit 2; and

(e) the direct entry software, a series of data collection screens (Exhibit 3) built in Paradox for Windows (a relational database from Borland International Incorporated) available to the photograph readers on networked IBM-compatible personal computers, and based on the paper data collection form in Exhibit 4.

The Canon 45^o retinal photograph provides about 2X magnification, further magnified by the 8X viewer to about 16X, closely approximating the 15X magnification obtained with Zeiss 30^o photographs and 5X Donaldson stereo viewers.

3. SUBFIELD GRID

The reader overlays a grid of black lines printed on a transparency to determine the grading subfields in each retinal photograph. The grid, developed for use with Canon 45^o retinal photographs, is based on the diameter of an average optic disc as calculated by comparing Zeiss 30^o and Canon 45^o photographs of the same eye from several individuals and appropriately scaling down from the standard disc diameter (DD) for Zeiss 30^o photographs.

The grid consists of three concentric circles centered on the optic disc and four spokes at 12:00, 3:00, 6:00 and 9:00, as diagrammed in Exhibit 1, part B. The inner circle approximates the disc margin assuming an average size disc (diameter = 1 DD or one disc diameter, radius = 1/2 DD); the second circle demarcates a zone extending to 1/2 DD from an average disc margin (radius of circle = 1 DD), hereafter referred to as Zone A; and the outer circle demarcates a zone extending from 1/2 DD to 1 DD from the disc margin (radius of circle = 1 1/2 DD), hereafter referred to as Zone B. The four spokes extend outward from the edge of Zone A and demarcate the four quadrants named for their relationship to the posterior pole (the most posterior retinal region which contains the optic disc and the macula, or center of acute vision). Beginning at the upper left and moving clockwise, the four quadrants in the right eye are the superior temporal, superior nasal, inferior nasal and inferior temporal; in the left eye, the superior nasal, superior temporal, inferior temporal and inferior nasal.

When evaluating any retinal abnormalities present, the photograph reader places the grid over the photograph to determine the subfield in which any lesion occurs. The reader centers the inner circle on the optic disc and places the temporal spoke to evenly bisect the relatively open retina between the major blood vessels of the superior and inferior temporal arcades. In most eyes, the macula will fall just below this spoke. When the temporal spoke extends horizontally from the disc margin at 9:00 (right eye) or 3:00 (left eye), the macula will generally fall on a parallel line intersecting the disc margin at 7:30 (right eye) or 4:30 (left eye). The example photograph PQ1 shows a correctly placed grid.

4. PHOTOGRAPHIC STANDARDS AND EXAMPLES

The ETDRS photographic standards for diabetic retinopathy have been appropriately scaled down for the Canon 45^o photographs by copying the Zeiss 30^o originals of ETDRS standards at a reduced scale appropriate to Canon 45^o photographs, based on comparisons of Zeiss 30^o and Canon 45^o photographs of the same eye of five individuals. Each ETDRS photographic standard is represented by a single scaled down photograph. In the ARIC 45^o photograph, the photograph reader considers an area of retina approximately equal to that of the ARIC reduction of an ETDRS standard when determining if the amount of the lesion present is equal to or greater than the standard. When the reader evaluates the severity of a lesion equal to or greater than a standard, the reader uses the ARIC subfield grid to locate the four quadrants and then compares the total amount of the lesion present in each quadrant to the total amount of the lesion present in the ARIC reduction of the ETDRS standard.

Each photographic example consists of a single Canon 45^o or Topcon 45^o photograph. Many of the photographic examples have corresponding Zeiss 30^o photographs of the same eye, available to the photograph readers as a reference collection in a central location.

5. READING PROCEDURES AND DATA COLLECTION

5.1 Reading Procedures

After computer inventory at the Reading Center, each sheet of up to 10 retinal photographs is handled as one reading list. The photograph reader selects a reading list from his/her workbasket at the beginning of a grading session. Upon completion, the reader initials and dates the mounting sheet label and forwards the list to the basket provided for completed lists.

5.2 Data Collection Form

The data collection form exists in both an original paper format (Exhibit 4) and the derived direct entry screens (Exhibit 3). In both, the data collection begins with identifying information and an evaluation of photographic quality, and is followed by the collection of substantive grading data and information on retinal notifications.

The identifying information (field center, participant identification number and eye) is entered in screen 1 of the direct entry screens and at the top of page 1 on the paper data collection form. In direct entry, the reader must correctly enter the field center and participant identification number, which are then checked against the photograph inventory, before entering data for the eye. The direct entry software does not permit data entry for an uninventoried identification number, and shows the grader if data are already present for the identification number.

The reader completes all questions for photographic quality (screen 2 of direct entry, page 1 of paper form) and arteriolar abnormalities (screen 3 of direct entry, page 1 of paper form). The questions regarding diabetic retinopathy and other ocular lesions are organized under gatekeeper questions. The first gatekeeper asks the reader if any lesions of diabetic retinopathy are questionably or definitely present, or ungradable (screen 4 in direct entry, page 2 on paper form). If yes, the reader completes all questions for lesions of diabetic retinopathy (screens 4 and 5 in direct entry, page 2 of paper form). If no, the reader proceeds directly to the overall diabetic retinal level (screens 6 and 7 in direct entry, page 3 of paper form). In all cases, the reader completes the overall diabetic retinal level. Another gatekeeper asks if there are any other ocular lesions questionably or definitely present in the eye (screen 8 of direct entry, page 4 of paper form). If yes, the reader completes all questions for other ocular lesions. If no, the reader proceeds to the comment section (same page as the other ocular lesion questions). Comments may annotate arteriolar abnormalities, lesions of diabetic retinopathy or other ocular lesions.

Finally, the photograph reader records information about retinal notifications to the field centers on screen 9 of direct entry or on page 4 of the paper form.

6. GRADING RULES

Photograph readers (graders) at the Reading Center use the following conventions in evaluating the presence and severity of abnormalities:

a) None is used to indicate that a lesion is absent. If there is a suggestion that a lesion may be present, but the reader is less than 50% certain that the lesion is in fact present, the reader uses none, or absent, for that lesion.

b) Questionable is used to indicate the probable presence of the lesion. If the reader is more than 50% certain but less than 90% certain that the lesion is present, he/she selects questionable as the answer. Stated alternatively, if the reader thinks that the lesion is present but is unsure that all observers would agree, he/she marks the lesion as questionably present.

When an abnormality is present but the reader is uncertain of its identity, the reader chooses questionable for the lesion considered most likely and answers none, or absent, for the lesion(s) considered less likely.

c) Definite indicates the definite presence of a lesion. If the reader is at least 90% certain that the lesion is present, he/she marks the lesion as definitely present.

d) In questions with several codes for definite presence of the lesion, there may be several steps to indicate ascending severity of the lesion. The ascending severities may be described in general terms as mild, moderate and severe. The severities of a lesion are usually defined either in terms of the number, length, or area present, or in relation to photographic standards.

e) Cannot grade is used to indicate that the lesion is ungradable due to impaired photographic quality or a confounding condition. In general, if no evidence of the lesion is seen and more than 50% of the subfield is missing or obscured, the reader selects cannot grade rather than none. For focal narrowing and sheathing of arterioles in the quadrants, at least 1 1/2 DD total length of arterioles should be visible in the quadrant; if no abnormality of the arteriole is seen and less than 1 1/2 DD of arterioles are available for assessment, the reader selects cannot grade as the appropriate answer. Cannot grade is also used where the subfield is present and unobscured but impaired to a degree that the typical appearance of the lesion in question could not be identified.

If a specific lesion can be seen in any part of the subfield, it should be assessed as such even if the remainder of the subfield is ungradable.

f) Lesions occupying more than one subfield are assessed as present in each subfield and the number, length, or area involved is estimated in each subfield separately.

7. PHOTOGRAPHIC QUALITY

The photograph reader separately evaluates the four aspects of photographic quality which most affect how useable the photograph is for light box reading: focus and clarity, field definition, visibility of the optic disc and visibility of the macula. The reader also marks the presence of any photographic artifacts. Presence of artifacts sometimes offers further explanation of the four major aspects of quality. Information on artifacts is also useful to the photographic consultant in providing feedback to the field centers. Finally, the reader evaluates the overall gradability of the retinal photograph.

Example photograph PQ 1 provides an example of ideal photographic quality. Example photographs PQ2 through PQ11 show common photographic problems. A photographic quality evaluation for all of these is contained in Exhibit 5.

7.1 Focus and Clarity

The photograph reader evaluates the focus and clarity for the retinal photograph as a whole, based on the impact of focus and clarity on the detection and assessment of subtle abnormalities such as focal narrowing of arterioles or retinal microaneurysms. In some cases, the clarity may be impaired due to overall haze, possibly from lens or vitreous opacity. Such photographs are marked as having reduced focus and clarity; this reflects the useability of the photograph rather than adequacy of photographic technique. For example, PQ 5 and PQ 6, both taken of the same individual, show overall haze suggesting media opacity. In PQ 5 the camera is focused, but the overall haze reduces the focus and clarity to borderline. In PQ 6 the haze is compounded by true focus problems, resulting in inadequate focus and clarity. If some portions of the photograph are well-focused but other portions are problematic for grading, the reader may describe the overall focus and clarity as fair or borderline. Each reader is provided with Canon 45^o photographic originals showing good, fair, borderline and inadequate focus, in addition to the examples here.

Code Definition

1 Good - Crisp and well-focused throughout (see PQ 1).

2 Fair - Slightly soft, or soft only in some areas; subtle abnormalities such as arteriolar narrowing and microaneurysms are fully gradable (see PQ 3).

3 Borderline - Impaired focus and clarity complicates the reader's decision-making process, but ultimately is adequate to assess arteriolar narrowing and microaneurysms; or, some portions are good and others are inadequate (see PQ 4).

4 Inadequate - Impaired focus and clarity prevent the assessment of arteriolar narrowing and microaneurysms (see PQ 6).

8 Cannot grade - Cannot evaluate focus and clarity, usually because of an obscurity such as a total blink (see PQ 9).

7.2 Field Definition

The reader evaluates field definition on the basis of correct positioning of the two major retinal landmarks, the optic disc and the macula, within the retinal photograph. Ideally, the optic disc should be from 1 1/2 DD to 2 1/2 DD from the nasal edge of the photograph and should be centered vertically between top and bottom of the photograph (see Exhibit 1 and example photograph PQ 1). If any portion of the disc or its surrounding Zones A and B is omitted from the photograph, it is inadequate for the measuring process and the field definition is evaluated as poor; as in example photograph PQ 2. If either disc or macula is omitted from the photograph, it is inadequate for the light box reading and the field definition is evaluated as poor. If the disc is not centered between top and bottom of the photograph, the evaluation of arteriolar abnormalities in some quadrants may be compromised and the field definition is evaluated as fair.

Code Definition

1 Good - Disc is 1 1/2 DD to 2 1/2 DD from nasal edge, and centered vertically; macula is within photograph (see PQ 1).

2 Fair - Disc is at least 1 DD from nasal edge; macula is within photograph.

3 Poor - Disc is omitted or less than 1 DD from nasal edge of photograph (see PQ 2); or macula is omitted from photograph.

8 Cannot grade - Cannot evaluate field definition, usually because of an obscurity such as a total blink (see PQ 9).

7.3 Disc Obscured or Missing

The photograph reader evaluates the disc as obscured or missing if any portion of the disc is either obscured by artifact such as a dark shadow or a blink, or omitted from the photograph because of poor field definition. If the disc is obscured or missing, the following lesions should be marked as ungradable: focal narrowing within the disc margin, papillary swelling, new vessels on the disc and overall diabetic retinal level.

Code Definition

0 No - disc is visible.

2 Yes - disc is either obscured or missing (see PQ 9).

7.4 Macula Obscured or Missing

The reader evaluates the macula as obscured or missing if the macula is either obscured, most commonly by the dark shadow resulting from small pupillary dilation, or omitted because of poor field definition. To be recorded as obscured, the area should be greater than one disc area (1 DA) and, in the case of uneven illumination, truly obscured rather than merely shadowed. The dark artifact over the macula only shadows about 1 DA in example photograph PQ 10, but definitely obscures more than 1 DA in example photograph PQ 11. When the area obscured is substantial, the number of microaneurysms, overall diabetic retinal level, and macular edema should be marked as ungradable.

Code Definition

0 No - macular area is visible.

2 Yes - macular area is either obscured or missing (see PQ 11).

7.5 Artifacts

Photographic artifacts are evaluated as either present or absent; severity is not considered. The photograph reader uses example photographs of the various artifacts to aid decisions about their presence.

Code Definition

0 No - absent.

2 Yes - present.

7.5.1 Haze

Two types of haze are noted: overall haze and edge haze. Overall haze is characterized by an overall reduction in clarity and generally produces a dimmer and yellower color than is usually seen. The affect is one of something sheer or gauzy between the retina and the observer. Example photographs PQ 5 and PQ 6 exhibit overall haze. As discussed in section 7.1, the clarity of these two photographs is reduced. Edge haze is a white, hazy appearance at the edge of the retinal photograph, generally whitest and most opaque at the periphery and diffusing towards the center of the photograph. Example photographs PQ 3 and PQ 4 show edge haze. In PQ 4, arteriolar abnormalities are ungradable in the two nasal quadrants because of the edge haze, lowering the overall photographic quality to impaired.

7.5.2 Dust and Dirt

The artifacts resulting from dust spots on the camera lens are usually small gray-white, soft-edged circular spots. Example photograph PQ 1, although excellent in every other way, exhibits one small dust spot at 5:00 near the field periphery. Larger irregular artifacts may result from body oil smudges if the lens has been touched by a nose or finger. If the lens has been improperly cleaned, the resulting artifact may form an arc or arcs following the circular motion used to clean the lens, as shown in photographic examples PQ 10 and PQ 11. Dust and dirt artifacts are soft-edged and out of focus because dirt on the lens is far anterior to the retina and therefore in a very different plane of focus than retinal features.

7.5.2 Lashes

Artifacts from lashes or partial blinks are a bright yellow-white and flare from the edge of the field toward the center, most often extending upwards from the bottom edge of the photograph, as in example photographs PQ 7 and PQ 8. Linear or rounded shapes from the individual lashes are frequently evident. Lash artifacts are soft-edged and out of focus because the lashes are anterior to the retina and in a different plane of focus.

7.5.3 Arc

Arcs are hard-edged white, yellow, or rainbow-shaded artifacts at the field periphery.

7.5.4 Uneven illumination/Macula

Uneven illumination refers to the dark shadow which occurs in non-mydriatic photographs when the pupillary dilation is less than optimal. This dark shadow is usually centered over the macula. The photograph reader assesses uneven illumination as present in the macula if the macular area is lightly shadowed, darkly shadowed or totally obscured. Uneven illumination over the macula is seen in example photographs PQ 8, PQ 10 and PQ 11.

7.5.5 Uneven illumination/Edge

If the dark shadow is placed on the edge or periphery of the field, or extends from the center of the field to the edge, then uneven illumination is marked as present on the edge. Example photographs PQ 8 and PQ 11 show illumination problems on the edge of the field nasally.

7.5.6 Uneven illumination/Disc

If any dark shadow extends over any part of the optic disc, then uneven illumination is marked as present on the disc.

7.5.7 Total Blink

A total blink results in bright yellow-white artifact obscuring all or most of the field. A total blink will sometimes have uneven color or linear shapes from the individual lashes. If the retinal photograph is obscured by a total blink, focus and field definition are usually ungradable. Both disc and macula are obscured resulting in an ungradable photograph. Example photograph PQ 9 shows a total blink.

7.6 Gradability

The overall gradability of the retinal photograph is based on all aspects of photographic quality and the degree to which they impact the reading of retinal abnormalities. The retinal photograph is assessed as gradable if most of the substantive questions can be answered.

In general, the important substantive questions in the retinal light box reading can be grouped under two headings: arteriolar abnormalities and lesions of diabetic retinopathy. If photographic quality negatively impacts only one of these two groupings, the photograph is assessed as gradable but impaired. For example, if the number of microaneurysms and diabetic retinal level are ungradable because the macular area is obscured by dark shadow, but good focus and field definition allow accurate assessment of arteriolar abnormalities, then the photograph is gradable but impaired. Alternatively, if artifacts and obscurities on the field periphery prevent assessment of arteriolar abnormalities in several subfields, but the central retinal landmarks (disc and macula) are clearly visible and the diabetic retinal level can be established, then the photograph is gradable but impaired.

If both major groupings of questions cannot be answered, then the the retinal photograph is assessed as ungradable. The most common causes of ungradable retinal photographs are inadequate focus and clarity, dark shadows obscuring both macula and field periphery, and total blinks. Some photographs may be ungradable because they are obscured by media problems (such as asteroid hyalosis); the assignment of ungradable reflects the usefulness of the photograph for data collection, not necessarily photographic technique.

8. ARTERIOLAR ABNORMALITIES

The arteriolar abnormalities assessed are: focal narrowing of arterioles, generalized narrowing of arterioles, sheathing of arterioles, and arterio-venous crossing abnormalities (arterio-venous nicking). The reader uses the ARIC normotensive examples N1 to N4, the ARIC arteriolar abnormality examples A1 to A8, and a reduction of ETDRS Standard Photograph #9 as references (all listed in Exhibit 2). Exhibit 6 is a table showing assessment of focal narrowing and arterio-venous nicking in example photographs A1 to A8.

8.1 Focal Narrowing

The photograph reader assesses all marked constrictions of arteries and arterioles as focal narrowing. Focal narrowing is assessed separately for the disc and Zone A, where the vessels may be more arterial in nature, and the quadrants beyond Zone A where the vessels are arteriolar in nature. Definite focal narrowing is marked when the involved vessel is at least 50u (42u ETDRS) in diameter, or about 1/3 of the diameter of a vein at the disc margin, and the constricted area has a caliber less than or equal to 2/3 the caliber of proximal and distal vessel segments. If the reader observes constriction in vessels less than 50u (42u ETDRS) in diameter, such constrictions should be assessed as questionable focal narrowing. If the reader feels that subtle constriction of vessels is present, but the segment in question has a diameter greater than 2/3 of the diameter of adjacent segments, then the reader marks questionable focal narrowing.

8.1.1 Focal Narrowing, Disc and Zone A

The reader assesses focal narrowing within the disc margin, using the natural disc margin even if it is smaller or larger than an average disc (as approximated by the inner circle of the ARIC grid), and in Zone A, defined as the zone from the natural disc margin to the second circle on the grid (1/2 DD from an average disc, radius of second circle = 1 DD from a point at the center of the disc).

Special care must be taken to exclude apparent changes in the diameter of arteries as they come up through the optic cup and course over the margin of the optic disc. The normotensive example N1 shows an artery crossing the disc margin at 12:00 where the apparent diameter of the artery within the disc margin is less than the apparent diameter in Zone A. The Zeiss stereo view shows that the apparent tapering of the artery on the disc is due to its position down the slope of the rim into the optic cup. The nerve fiber layer is frequently more visible near the disc margin and may subtly obscure vessel margins, giving the illusion of a decrease in vessel caliber. Such appearances are excluded. The normotensive examples N2 and N3 show arteries leaving the disc nasally which appear subtly smaller in caliber immediately distal to the disc margin. Close examination of both Canon and Zeiss photographs reveals that these arteries are partially obscured by the feathery, sheer white of the nerve fiber layer; focal narrowing in Zone A of these eyes would be marked as absent.

The severity of focal narrowing within the disc margin and in Zone A is determined by the number of substantial vessels affected, substantial vessels being defined as arteries with a diameter greater than or equal to 50u (42u ETDRS), or about 1/3 the diameter of a vein at the disc margin. If only one or two substantial vessels are affected, the abnormalities are considered definite, mild; if three or more substantial vessels are affected, the abnormalities are severe.

Example photograph A1 shows definite focal narrowing of the arteries leaving the disc margin at 1:00 and 2:00. The artery leaving the disc at 1:00 exhibits two distinct pinched areas, one just within the disc margin and one in Zone A. (Moving towards the center of the disc, this vessel is more subtly narrowed just after it splits off the superior arterial branch.) The artery leaving the disc at 2:00 is distinctly pinched shortly after it splits from the superior arterial branch. This vessel appears "beaded" in Zone A, an appearance usually noted as questionable because the constrictions are not definitively less than 2/3 the normal vessel caliber, but in this case the vessel appears subtly narrower through all of Zone A and possibly into the superior nasal (SN) quadrant when contrasted with more distal lengths of the same vessel. This vessel would be assessed as having definite focal narrowing in Zone A, and questionable narrowing in the SN quadrant.

Example photograph A2 exhibits a trifurcation of the inferior artery within the disc margin. All three of the branches are constricted immediately after the trifurcation. The temporal branch is only subtly narrowed and quickly regains a larger caliber which is then maintained in Zone A and the inferior temporal (IT) quadrant; the appearance of this branch alone would be graded as questionable narrowing within the disc margin. The middle branch is markedly irregular within the disc, showing two definite focal narrowings, and may also exhibit a thickened wall. This vessel is questionably narrowed in Zone A: it is more subtly irregular here and may be narrower than in the inferior nasal quadrant (IN) distally. The nasal branch exhibits a very robust caliber after the initial constriction, and then narrows as it leaves the disc margin at 3:00, courses through Zone A and branches in the superior nasal quadrant, never regaining a caliber close to that within the disc margin. The change in caliber seems too great to be explained by undulations of the vessel within the optic disc; both the initial constriction of this branch and the narrowing at the disc margin are evaluated as definite narrowing. It is difficult to say if this vessel should be evaluated as focally narrowed in Zone A, because the appearances in the superior nasal quadrant suggest generalized narrowing (see section 8.4).

The superior artery in example photograph A2 has two large branches feeding the superior temporal (ST) quadrant. The temporal branch narrows shortly after the branching point within the disc and remains narrow well into Zone A, and then approximately doubles in caliber. This definite focal narrowing in the disc brings the number of vessels with definite narrowing within the disc to three, meeting the requirement for severe focal narrowing within the disc. Focal narrowing in Zone A is definite. This vessel may be subtly irregular and narrower between Zone A and the macula; this appearance would be marked as questionable focal narrowing in the ST if it was the only segment in question. However, the superior branch (leaving the disc margin at 12:00) appears relatively constant in caliber within the disc margin and in Zone A, but exhibits four short segments of distinct focal narrowing in the ST quadrant.

Code Definition

0 No focal narrowing.

1 Questionable focal narrowing.

2 Definite focal narrowing in one or two substantial arterioles (definite).

3 Definite focal narrowing in three or more substantial arterioles (severe).

8 Cannot grade.

8.1.2 Focal Narrowing in Quadrants

Focal narrowing or constriction of arterioles is assessed in each of the four quadrants, excluding the area within 1/2 DD of the disc (Zone A). The photograph reader carefully examines all arterioles greater than or equal to 50u (42u ETDRS) in diameter, or about 1/3 the diameter of a vein at the disc margin, and estimates the combined length of all constricted segments. There is sometimes a gradual tapering from the original caliber of the arteriole to the most constricted caliber; only the length of constriction to 2/3 or less of the original caliber is considered definite. If a quadrant has more than one focally narrowed segment, the lengths of all narrowed segments are added together. If focal narrowing extends from one quadrant to another, the length involved is estimated separately in each quadrant.

Example photograph A2, chosen for pronounced focal narrowing of the arteries on the disc, also exhibits definite focal narrowing of the arterioles in the ST quadrant, as discussed in section 8.1.1.

Example photograph A3 exhibits classic focal narrowing in both superior quadrants. The superior temporal arteriole bifurcates in Zone A, and the more robust branch exhibits two segments of focal narrowing, one in Zone B and one just distal to Zone B. In the superior nasal (SN) quadrant, there is a short but distinct area of focal narrowing about 1/2 DD from the nasal edge of the photograph at 10:30. (Please note that the SN arteriole is also narrowed in Zone A.)

Example photograph A4 demonstrates more pronounced focal narrowing. The more superior arteriole in the superior nasal (SN) quadrant exhibits one segment of distinct focal narrowing, about 1/3 DD in length and beginning about 2/3 DD from the disc margin. The inferior nasal (IN) quadrant exhibits a subtle constriction in the arteriole leaving the disc at 4:00, about 3/4 DD from the disc margin. In the inferior temporal (IT) quadrant, there are constricted segments in three arterioles. The arteriole leaving the disc at 7:30 (note that the entire length within the disc margin is markedly narrowed) is subtly constricted beyond Zone A. The artery leaving the disc at 6:00 immediately bifurcates, giving rise to two arteriolar branches. The more temporal branch exhibits at least two short segments of focal narrowing. The arteriole coursing straight inferiorly exhibits a segment of focal narrowing, beginning about 1 1/4 DD from the disc margin, which exceeds 1/2 DD in length. The total length of focal narrowing in the IT quadrant may be as much as 1 1/4 or 1 1/2 DD, meeting the definition of moderate focal narrowing.

For severe focal narrowing, all segments of focal narrowing in a quadrant are similarly added up and must total 2 DD or more. Given that the Canon 45^o photographs usually provide about 6 DD of arterioles for evaluation in each temporal quadrant and only about 3 DD in each nasal quadrant, it is unusual to find more than 2 DD of focal narrowing in any given quadrant.

Example photographs 5 and 6 show cases that, although less pronounced, are evaluated as definite focal narrowing. In example photograph A5, the superior nasal artery bifurcates at the disc margin. The more superior arteriolar branch is irregular along its length. This vessel is probably about 60u (50u ETDRS) in caliber, approaching the lower limit at which focal narrowing can be confidently assessed at this magnification, and the narrowings are brief, making an assessment of the degree of constriction difficult. The appearances in this eye suggest possible generalized narrowing. However, there are two areas of definite focal narrowing: one in the SN quadrant about 1 DD from the disc margin in the more superior vessel, and one in Zone A in the vessel coursing nasally.

Example photograph A6 is also subtle. The arteriolar branch leaving the photographic field at 2:30 shows one short segment of definite focal narrowing about 1 DD from the edge of the field.

If the total length of arterioles available for examination in a quadrant totals less than 1 1/2 DD, then the reader marks that quadrant ungradable, code 8. Cannot grade is also used if the arterioles in a given subfield are out-of-focus or obscured by artifact.

Code Definition

0 No focal narrowing.

1 Questionable focal narrowing.

2 Definite focal narrowing, combined length < 1/2 DD (mild).

3 Definite focal narrowing, combined length > 1/2 DD, but < 2 DD (moderate).

4 Definite focal narrowing, combined length > 2 DD (severe).

8 Cannot grade.

8.2 Arteriolar Sheathing

The reader assesses opacification of the arteriolar column as arteriolar sheathing in the four quadrants, excluding the area within 1/2 DD of the disc (Zone A). Arteriolar walls which are partially opaque, that is, a ribbon of blood can still be seen with white lines on one or both sides, and complete opacification of the arteriolar column, or white threads, are assessed as definite arteriolar sheathing. The lengths of all sheathed segments are added for each quadrant, as described for focal narrowing above.

If the total length of arterioles available for examination in a quadrant totals less than 1 1/2 DD, then the reader marks that quadrant ungradable, code 8.

Code Definition

0 No arteriolar sheathing.

1 Questionable arteriolar sheathing.

2 Definite arteriolar sheathing, combined length < 1/2 DD (mild).

3 Definite arteriolar sheathing, combined length > 1/2 DD, but < 2 DD (moderate).

4 Definite arteriolar sheathing, combined length > 2 DD (severe).

8 Cannot grade.

8.3 Arterio-venous Crossing Abnormalities

The photograph reader assesses abnormalities of arterio-venous crossings, or arterio-venous nicking, in each quadrant. Crossings within 1/2 DD of the disc margins are excluded, as are the atypical crossings where the vein crosses over the artery. The reader examines all crossings of artery over vein, and evaluates crossings where the venous blood column is narrowed as abnormal.

Tapering or narrowing of the venous blood column on both sides of the crossing is required for definite AV nicking. If the venous blood column appears tapered on only one side of the crossing, and the appearance is not due to normal vessel undulation, then the reader assesses AV nicking as questionable. The grader discounts any apparent diminishments in venous caliber if the vein appears to be partially obscured by nerve fiber reflex as it approaches and crosses under the artery.

The reader compares any definite arterio-venous nicking to that in the ARIC reduction of ETDRS Standard Photograph #9; if the appearance is as pronounced as that in ETDRS Standard Photograph #9, it is assessed as severe. In ETDRS Standard Photograph #9, the venous blood column is reduced to about 1/2 its original diameter on both sides of the crossing.

Example photograph A6 exhibits one definite arterio-venous crossing abnormality in the superior temporal (ST) quadrant. Subtle tapering of the venous blood column can be seen on both sides of the crossing, and the Z-shaped deviation in the path of the vein further suggests that the pressure relationships at the crossing are not normal. The arterio-venous crossing in the inferior temporal (IT) quadrant is similar in appearance but the tapering of the venous blood column cannot be seen distinctly on the proximal side of the crossing; therefore, the IT quadrant would be marked questionable for arterio-venous crossing abnormalities.

The arterio-venous crossing abnormalities in example photograph A7 are more pronounced. Both the inferior nasal (IN) and superior temporal (ST) quadrants exhibit marked narrowing of the venous caliber on both sides of the arterio-venous crossing in question. In the ST quadrant, the caliber of the vein narrows to about 1/3 of its normal caliber, resulting in a grade of severe. The inferior temporal (IT) quadrant has an arterio-venous crossing immediately adjacent to a venous trifurcation. The venous branch involved in the this crossing is visibly narrowed distally, but the proximal side cannot be assessed because of the proximity to the trifurcation. Because the venous narrowing is visible on only one side, arterio-venous nicking would be assessed as questionable in the IT quadrant.

Example photograph A8 exhibits definite, although somewhat more subtle, arterio-venous nicking in both temporal quadrants. The abnormal arterio-venous crossing in the IT quadrant is adjacent to a venous bifurcation. In this case, the crossing is somewhat distal to the bifurcation and the venous caliber can be assessed on both sides of the crossing. The venous caliber on both sides is narrower than the caliber of the vein distally in the field. The ST quadrant shows narrowing of the vein on both sides of the crossing, although the narrowing on the proximal side is subtler than that seen in the other examples.

Code Definition

0 No A/V nicking.

1 Questionable A/V nicking.

2 Definite A/V nicking, < ETDRS Std Photo #9 (definite).

3 Definite A/V nicking, > ETDRS Std Photo #9 (severe).

8 Cannot grade.

8.4 Generalized Narrowing

Generalized narrowing is difficult to evaluate, given that normal arterioles in the same eye may not be available for comparison. The reader provides an estimate of generalized narrowing based on comparison with the corresponding veins in the eye or, where the arterioles appear normal in some quadrants, with other arterioles.

If the reader has a general impression that the arterioles in the eye are narrow in comparison with the veins, he/she marks generalized narrowing as questionable. If some arterioles in the eye are markedly narrowed, or thready, but other quadrants appear more normal, then the reader marks generalized narrowing as definite. Sometimes only the nasal quadrants may have thready arterioles. Example photograph A8 may have questionable generalized narrowing: the arterioles in the SN quadrant are narrower than one might expect given the caliber of the parent artery. If the arterioles are small threads throughout the entire eye, then the reader assesses generalized narrowing as severe.

Code Definition

0 No generalized narrowing.

1 Questionable generalized narrowing.

2 Definite generalized narrowing.

3 Severe generalized narrowing, threads throughout.

8 Cannot grade.

9. LESIONS OF DIABETIC RETINOPATHY

The photograph reader assesses all lesions of diabetic retinopathy for presence or absence. Individual lesions are assessed for severity where relevant to the supporting evidence for the diabetic retinal level. A brief description of each lesion and special considerations for non-stereo 45^o photographs are provided here; more detailed descriptions of the individual lesions are available in ETDRS Report #10, An Extension of the Modified Airlie House Classification.

Some of these lesions, notably microaneurysms, retinal hemorrhages and soft exudates, or cotton-wool spots, are also characteristic of hypertensive retinopathy. Recent data from a study by Klein et al suggest that a single retinal microaneurysm is more typically found in hypertensive rather than diabetic individuals.

9.1 Retinal Hemorrhages and Microaneurysms

The photograph reader counts microaneurysms up to a total of five, counts retinal hemorrhages up to two, characterizes the retinal hemorrhage(s) as blot or flame, and estimates the total area of retina covered by retinal hemorrhages and microaneurysms.

9.1.1 Number of Microaneurysms

Retinal microaneurysms, small sacs or balloonings of the retinal capillaries, appear as small red dots. A red spot which is less than 150u (125u ETDRS) in its longest dimension (approximately the width of a vein at the disc margin) and which has sharp margins and even density is considered a microaneurysm. A red spot which is equal to or greater than 150u (125u ETDRS) in its longest dimension is assessed as a microaneurysm only if features such as round shape, smooth margins and a central light reflex suggest that it is probably a microaneurysm; otherwise, it is assessed as a retinal hemorrhage. Microaneurysms are typically round, but may more rarely appear fusiform, or sausage-shaped. They are typically red, but more rarely appear pink or dull white if opacified.

Code Definition

0 No microaneurysms.

1 Questionable microaneurysm.

2 One microaneurysm.

3 Two microaneurysms.

4 Three microaneurysms.

5 Four microaneurysms.

6 Five or more microaneurysms.

8 Cannot grade.

9.1.2 Number of Retinal Hemorrhages

Retinal hemorrhages, the leaking of blood into the retina, typically appear as red spots in the retina with irregular margins and shapes. A red spot less than 150u (125u ETDRS) in its longest dimension is assessed as a retinal hemorrhage only if it has irregular margins and/or uneven density. Any red spot greater than or equal to 150u (125u ETDRS) in its longest dimension is considered a retinal hemorrhage, unless its features strongly suggest that it is a microaneurysm as described above.

Code Definition

0 No retinal hemorrhage.

1 Questionable retinal hemorrhage.

2 One retinal hemorrhage.

3 Two or more retinal hemorrhages.

8 Cannot grade.

9.1.3 Type of retinal hemorrhage

The reader characterizes any retinal hemorrhage present as either flame-shaped or blot-shaped, or notes that both types are present. Flame-shaped hemorrhages are elongated and pointed at one or both ends; if small, they may appear linear. The density of the hemorrhage may be greater centrally, and it may have a central white spot (Roth's spot). Flame-shaped hemorrhages are oriented parallel to the nerve fiber layer and characteristically appear in the vessel arcades or radiating from the optic disc. Blot hemorrhages are roughly round or irregular in outline, and may occur anywhere within the retina. Example Photograph T2, diabetic retinal level 35, shows retinal hemorrhages and microaneurysms, including a linear flame hemorrhage in the inferior temporal arcade and several blot hemorrhages.

Code Definition

0 No retinal hemorrhage.

1 Questionable retinal hemorrhage (retinal hemorrhage questionably present).

2 Definite retinal hemorrhage(s), flame-shaped only.

3 Definite hemorrhage(s), blot only.

4 Definite hemorrhages, blot and flame-shaped.

8 Cannot grade.

9.1.4 Hemorrhages and Microaneurysms (H/Ma)

The photograph reader estimates the total area of retina covered by hemorrhages and/or microaneurysms (H/Ma), in comparison to the ARIC reductions of ETDRS Standard Photographs #1 and #2A. All punctate, blot and linear hemorrhages, and all microaneurysms are included. The amount of retinal hemorrhage and microaneurysms is assessed in some detail because of its importance in determining diabetic retinal level.

Code Definition

0 No hemorrhages or microaneurysms.

1 Questionable microaneurysm and/or retinal hemorrhage.

2 Definite microaneurysms and/or retinal hemorrhages, but the amount is < ETDRS Std Photo #1, or > ETDRS Std Photo #1 in only one to three quadrants.

3 Definite, > ETDRS Std Photo #1 in all four quadrants.

4 Definite, > ETDRS Std Photo #2A in an area approximating an ETDRS field.

5 Definite, > ETDRS Std Photo #2A in two or three quadrants.

6 Definite, > ETDRS Std Photo #2A in all four quadrants.

9.2 Hard Exudates and Macular Edema

9.2.1 Hard Exudates (HE)

Hard exudates are lipid deposits within the retina. They are characteristically bright yellow-white deposits with sharp margins, and often appear waxy, shiny or glistening. Hard exudates may be arranged as individual dots, confluent patches, or in rings partially surrounding zones of retinal edema and/or groups of microaneurysms. Hard exudates are shown in Example Photographs T3, T4, T6, and T8.

Code Definition

0 No hard exudate.

1 Questionable hard exudate.

2 Definite hard exudate.

8 Cannot grade.

9.2.2 Macular edema

Macular edema is thickening of the retina in the macular area, resulting from the leakage of fluid into the retina from microaneurysms and/or compromised capillaries. In a non-stereo photograph, the reader cannot directly assess thickening of the retina and must rely on other appearances to estimate areas of edema.

Hard exudates, particularly confluent hard exudates or hard exudate rings, are characteristic of eyes with macula edema. More rarely, edematous eyes have large amounts of retinal hemorrhages and microaneurysms concentrated temporally or arranged concentrically around the macula. In addition, changes in the transparency of the retina within hard exudate rings or at the center of the macula may suggest retinal thickening.

Example Photographs T6, T8 and T10 show hard exudate patterns suggestive of macular edema. T6 exhibits a hard exudate ring superior to the macula with one confluence of hard exudate adjacent to the macula at 10:00, suggesting retinal thickening in this area; the Zeiss stereo photographs confirm thickening in this area. The proximity of the hard exudates to the center suggests "clinically significant macular edema" by the ETDRS definition, in the Topcon 45^o photograph. T8 exhibits massive edema throughout the posterior pole; the presence of edema extending to center can easily be deduced from the hard exudate rings and the several patches of confluent hard exudate encroaching on the center. The partial ring of hard exudate in T10 is a more subtle appearance and, in the absence of stereo in the 45^o photograph, the grade of choice may be questionable macular edema.

The photograph reader assesses any inferred edema within the temporal arcades, but less than clinically significant macular edema, as definite. Clinically significant macular edema is defined as: (a) an area of edema greater than or equal to 1 DA and extending within 1 DD of center, or (b) edema extending within 500u of center. The reader may assess definite thickening at center based on the presence of hard exudates at center, a central color change or loss of transparency, or cystoid spaces at center. Example Photograph T8 exhibits definite thickening at center, based on the proximity of the hard exudates to center.

Code Definition

0 No macular edema.

1 Questionable macular edema.

2 Macular edema present but less than clinically significant, inferred from hard exudates and/or other appearances.

3 Clinically significant macular edema present, but center is not definitely involved, inferred from hard exudates and/or other appearances.

4 Clinically significant macular edema with center definitely involved, inferred from hard exudates and/or other appearances.

8 Cannot grade.

1. Other non-proliferative lesions.

9.3.1 Soft exudate (SE)

Soft exudates indicate areas of ischemia in the retina. They appear as superficial white, pale yellow-white or gray-white areas with feathery edges, frequently showing striations parallel to the nerve fibers.

Soft exudates appear in Example Photographs T3, T4, T5, T6, T7 and T9; Example Photograph T2 shows a questionable soft exudate.

Code Definition

0 No soft exudate.

1 Questionable soft exudate.

2 Definite soft exudate.

8 Cannot grade.

9.3.2 IRMA

Intraretinal microvascular abnormalities (IRMA) are tortuous intraretinal vascular segments varying in caliber from barely visible to 35u (30u ETDRS) or larger. In the absence of stereo, it may be difficult to distinguish IRMA from new vessels. In general, IRMA are more delicate, more angular or jagged in their tortuousity, less likely to cross themselves or other retinal vessels, and more likely to occur in relatively open areas between major vessels. The amount of IRMA is assessed relative to the ARIC reduction of ETDRS Standard Photograph #8A.

Example Photographs T5, T6 and T7 show definite IRMA; Example Photograph T9 exhibits IRMA greater than Standard Photograph #8A. in the superior temporal quadrant.

Code Definition

0 No IRMA.

1 Questionable IRMA.

2 Definite IRMA, < ETDRS Std Photo #8A, in one to three quadrants.

3 Definite IRMA, < ETDRS Std Photo #8A, in all four quadrants.

4 Definite IRMA, > ETDRS Std Photo #8A in any given area approximating an ETDRS field.

8 Cannot grade.

9.3.3 Venous beading (VB)

Venous beading refers to localized increases in the venous caliber (segmental dilation), sometimes resembling a string of beads and typical of diabetic retinopathy.

An example of venous beading may be found in Example Photograph T8. Example Photograph T9 suggests the difficulty of assessing venous beading in 45^o photographs: venous beading is evident in the superior temporal arcade in the Zeiss photographs but is more difficult to identify in the Topcon photograph.

Code Definition

0 No venous beading.

1 Questionable venous beading.

2 Definite venous beading in one quadrant only.

3 Definite venous beading in two to four quadrants.

8 Cannot grade.

9.4 Proliferative Lesions

The proliferative lesions assessed include new vessels on the disc, new vessels elsewhere, fibrous proliferations and vitreous and/or preretinal hemorrhage. In a non-stereo photograph, proliferative lesions which are elevated from the retinal surface are in a different plane of focus from the retinal vessels, and may therefore be out of focus when the retinal vessels and other retinal detail are in focus.

9.4.1 New Vessels on the Disc (NVD)

New vessels on the surface of the optic disc or on the retina within 1 DD of the disc margin (within Zone B), or in the vitreous cavity anterior to this area are considered NVD. However, when new vessels originating elsewhere than the disc extend within 1 DD from the disc (within Zone B) but not within 1/2 DD of the disc (within Zone A), and no other new vessels are present closer to or on the disc, they are graded as new vessels elsewhere (NVE). The amount of NVD is assessed in relation to the ARIC reduction of ETDRS Standard Photograph #10A.

Example Photographs T11, T12 and T13 show new vessels on the disc, with that in Examples T12 and T13 greater than Std Photo #10A.

Code Definition

0 No NVD.

1 Questionable NVD.

2 Definite NVD, < ETDRS Std Photo #10A.

3 Definite NVD, > ETDRS Std Photo #10A.

8 Cannot grade.

9.4.2 New Vessels Elsewhere (NVE)

Any new vessels which are on the surface of the retina or further forward in the vitreous cavity are considered new vessels elsewhere, excluding those considered as NVD as described in Section 10.4.1. In the absence of stereo, it may be difficult to distinguish subtle new vessels from IRMA. In general, new vessels are bolder, more curvilinear, more likely to cross and recross both themselves and the retinal vessels, and more likely to be sited over retinal vessels.

Example Photographs T11, T12 and T13 exhibit new vessels elsewhere. Example Photograph T9 has an area in the superior temporal arcade which could reasonably be assessed as either IRMA or NVE from the non-stereo 45^o photograph.

Code Definition

0 No new vessels elsewhere.

1 Questionable new vessels elsewhere.

2 Definite new vessels elsewhere, < 1/2 DA.

3 Definite new vessels elsewhere, > 1/2 DA.

8 Cannot grade.

9.4.3 Vitreous and/or Preretinal Hemorrhage

Vitreous hemorrhage (blood in the vitreous cavity) and preretinal hemorrhage (blood on the surface of the retina) are considered together. Vitreous hemorrhage is frequently diffuse and may obscure part or all of the photographic field. If localized, it is usually irregular in shape and outline. Preretinal hemorrhages may be boat-shaped, indicating a fluid level in a pocket between the retina and the detached posterior hyaloid, or flat and blot-shaped. Small preretinal hemorrhages may be distinguished from intraretinal hemorrhages by their distinctive shape or by a darker, more purple-red color.

Example Photographs T13 and T14 both show diffuse vitreous hemorrhage. Example Photograph T12 exhibits small hemorrhages at 7:00 in the 45^o field. Their distinct edges and dark color suggest that they are not retinal but, without stereo effect to differentiate them, they could be either preretinal or vitreous.

Code Definition

0 No vitreous and/or preretinal hemorrhage.

1 Questionable vitreous and/or preretinal hemorrhage.

2 Definite vitreous and/or preretinal hemorrhage, totalling < 1 DA.

3 Definite vitreous and/or preretinal hemorrhage, totalling more than 1 DA.

8 Cannot grade.

9.4.4 Fibrous Proliferation (FP)

Fibrous proliferations are white sheets or fine strands of fibrotic tissues formed subsequent to neovascularization, and are therefore sited similarly. Fibrous proliferations on the disc (FPD) and elsewhere (FPE) are considered together.

Example Photograph T10 shows an eye where fibrous proliferations are the only evidence of neovascularization.

Code Definition

0 No fibrous proliferation.

1 Questionable fibrous proliferation.

2 Definite fibrous proliferation.

8 Cannot grade.

9.5 Papillary Swelling

Papillary swelling is detectable in non-stereo photographs only by blurring of the disc margin. The reader assesses papillary swelling as severe if at least 270^o of the disc margin is blurred and the appearance of the disc suggests swelling comparable to that in ETDRS Example Photographs E and F.

Marked papillary swelling may be accompanied by engorged capillaries on the disc, retinal hemorrhage and/or soft exudate.

Code Definition

0 No papillary swelling.

1 Questionable papillary swelling.

2 Definite papillary swelling.

3 Severe papillary swelling.

8 Cannot grade.

9.6 Laser Photocoagulation Treatment

The photograph reader assesses the presence of photocoagulation treatment, and its type based on his/her inference of the intent of the treating physician, given the location and appearance of the photocoagulation scars.

Focal photocoagulation treatment for macular edema is characterized by burn scars within the temporal arcades. Focal treatment may be scattered, indicating treatment of microaneurysms or other focal sources of leakage, or, more rarely, arranged in a grid pattern around the macula. Focal burns tend to be smaller and lighter, i.e., with less pigment disturbance, than scatter treatment burns.

Scatter treatment, usually administered for severe non-proliferative or proliferative retinopathy, characteristically consists of an even pattern of burns in all four quadrants and sparing the macula and the papillomacular bundle. Scatter treatment may be accompanied or, rarely, replaced by local treatment, areas of confluent burns used to treat neovascularization directly.

Example Photograph T6 shows focal treatment only. Scatter photocoagulation treatment is present in all of Example Photographs T10 through T14. Example T12 shows definite focal and scatter treatment. In Example T10, the Zeiss photographs show subtle focal treatment but one is able to assess only scatter treatment as definitely present in the Topcon 45^o photograph.

Code Definition

0 No photocoagulation treatment.

1 Questionable photocoagulation treatment.

2 Definite photocoagulation treatment, focal only.

3 Definite photocoagulation treatment, scatter and/or local only.

4 Definite photocoagulation treatment, focal and scatter and/or local.

8 Cannot grade.

10. DIABETIC RETINAL LEVEL

The photograph reader assigns an overall diabetic retinopathy severity level according to the ETDRS scale and marks the appropriate supporting evidence, based on his/her assessments of the individual lesions of diabetic retinopathy. The table below lists the diabetic retinal levels in ascending severity, along with the supporting evidence and rules for marking that evidence for each level. Levels 14 and 15 indicate retinopathy which is questionably diabetic because of the lack of microaneurysms, the hallmark of diabetic retinopathy. Level 20, or microaneurysms only, is commonly considered the earliest stage of diabetic retinopathy. The ascending severity of the non-proliferative diabetic retinopathy levels 35 to 53 indicate increased risk of the eye becoming proliferative within the next one to five years, based on ETDRS results. Ascending proliferative levels 61 to 85 indicate increased risk of moving to DRS High Risk Characteristics or severe visual loss (need reference).

ETDRS Scale of Diabetic Retinopathy Severity	Supporting Evidence	Rules for Marking Supporting Evidence
10 Diabetic retinopathy absent	101 Microaneurysms (Ma's) and other lesions absent
14 Diabetic retinopathy questionable	141 Hard exudate, no Ma's 142 Soft exudate, no Ma's 143 IRMA, no Ma's	Reader may select one, two or three of the supporting evidence codes.
15 Diabetic retinopathy questionable	151 Retinal hemorrhage, no Ma's
20 Microaneurysms only	201 Microaneurysms only
35 Mild non-proliferative diabetic retinopathy	351 Venous loop > code 2 352 Questionable soft exudate, IRMA or hard exudate 353 Retinal hemorrhage 354 Hard exudate 355 Soft exudate	Reader may select from one to five of the supporting evidence codes.
43 Moderate non-proliferative diabetic retinopathy	431 H/Ma > Std Photo #1 in four quadrants 432 H/Ma > Std Photo #2A in one "field" 433 IRMA in one to three quadrants	Reader may select only one of the supporting evidence codes; reader may not select both 431 and 432, and either 431 or 432 paired with 433 moves the eye up to level 47.
47 Moderately severe non-proliferative diabetic retinopathy	471 Both IRMA and H/Ma characteristics from level 43 472 IRMA in all four quadrants 473 H/Ma > Std Photo #2A in two or three quadrants 474 Venous beading in one quadrant	Reader may select only one of the supporting evidence codes; either 472 or 473 supersedes 471, and any two codes moves the eye up to level 53.
53 Severe non-proliferative diabetic retinopathy	531 Any two or three of level 47 characteristics 532 H/Ma > Std Photo #2A in four quadrants 533 IRMA > Std Photo #8A 534 Venous beading in two to four quadrants	Reader may select only code 531, or any one, two or three of the other codes; any of codes 532, 533 or 534 supersedes code 531.
61 Mild proliferative diabetic retinopathy	611 FPD and/or FPE 612 NVE < 1/2 DA	Reader may select one or both supporting evidence codes.
65 Moderate proliferative diabetic retinopathy	651 VH and/or PRH < 1 DA 652 NVE > 1/2 DA 653 NVD < Std Photo #10A 654 NVE < 1/2 DA, with VH and/or PRH	Reader selects only the highest supporting evidence code.
71 DRS High Risk Characteristics	711 VH and/or PRH > 1 DA 712 NVE > 1/2 DA with VH and/or PRH 713 NVD < Std Photo #10A with VH and/or PRH 714 NVD > Std Photo #10A	Reader selects only the highest supporting evidence code.
75 DRS High Risk Characteristics	751 NVD > Std Photo #10A with VH and/or PRH
81 Advanced proliferative diabetic retinopathy	811 VH and/or PRH partially obscures retina; cannot grade for NVD and/or NVE but the center of the macula is attached
85 Advanced proliferative diabetic retinopathy	851 Macula obscured by VH and/or PRH 852 Retinal detachment at the center of the macula Reader selects only the highest supporting evidence code.	Reader selects only the higher supporting evidence code.
90 Cannot grade	901 Cannot grade for microaneurysms; no other background retinopathy is present 902 Cannot grade for background retinopathy; no proliferative retinopathy is present 903 Cannot grade for proliferative retinopathy	Reader selects only the highest supporting evidence code.

11. OTHER OCULAR LESIONS

Other ocular lesions are evaluated as not seen, questionably present, or definitely present. The other ocular lesions specifically assessed are listed below, loosely grouped by topic:

Occlusions:

Central artery occlusion

Branch artery occlusion

Central vein occlusion

Branch vein occlusion

Lipids:

Hollenhorst plaque

Asteroid hyalosis

Glaucoma indicators:

Large cup/disc ratio (.6 to .69 = questionable, > .7 = definite)

Retinal hemorrhage on the disc or crossing the disc margin

Other disc abnormalities:

Peripapillary atrophy

Other disc abnormality

Non-pathological confounding lesions:

Glial tissue and/or vitreous thickening

Medullated nerve fibers

Surface wrinkling retinopathy:

Cellophane reflex

Surface wrinkling retinopathy with tension lines and/or glial tags

Maculopathy:

Soft drusen within 2 DD of the center of the macula

RPE depigmentation

Hyperpigmentation

SSR detachment

Subretinal hemorrhage

Subretinal fibrosis

Geographic atrophy

Other:

Chorioretinal scar

Nevus

Retinal detachment

Other

12. RETINAL NOTIFICATIONS

The photograph reader prepares letters for retinal alert conditions and routine retinal results, as discussed in the Reading Center Procedures Chapter, Section 7.4. The readers use the guidelines for notification procedures detailed in Exhibits 7 and 8. The direct entry software shows a plus next to all retinal alert conditions and an asterisk next to all routine retinal notification conditions to assist the reader in identifying eyes which need letters. When completing the grading, the reader notes if either a retinal alert or routine notification was sent, and the date of the letter. If either of the two major retinal landmarks, the disc and the macula, is missing or obscured, or if the diabetic retinal level in ungradable for any other reason, and no lesions prompting notification are seen, then the eye is marked cannot grade for notification conditions.

Code Definition

0 No retinal notification sent.

1 Retinal alert notification sent.

2 Routine retinal notification sent.

8 Cannot grade for notification conditions.

Exhibit 1

Part A - Diagram of a Canon 45o Photographic Field

Part B - Diagram of Grid Application

Exhibit 2

ARIC Photographic Standards and Examples

ARIC Canon 45^o Example Photographs for Photographic Quality

PQ 1 Excellent photographic quality; appropriate grid application