Ординатура / Офтальмология / Учебные материалы / Retinal Vascular Disease Joussen Springer

ty levels are represented, ideally, as a one-dimensional hierarchic scale ranging from absence of retinopathy to the most advanced stages associated with severe visual loss. The levels of the scale reflect the natural progression of the disease in that the higher the retinopathy level, the greater the risk of visual loss or, in other words, the closer the patient is to losing sight.

19 III Diabetic retinopathy grading has a practical application in fundus photographic screening systems, where photography substitutes for examination by an ophthalmologist. It can be argued that a comprehensive clinical examination by a fully trained ophthalmologist, repeated at regular intervals for the entire duration of diabetes, with fundus photography used for documentation only, is the best standard of care. The practical experience is, however, that diabetic retinopathy remains the leading cause of blindness, most of it probably preventable, in the working age population in industrialized nations. The major problems appear to be poor compliance, uneven access to examination by ophthalmologist, and uncoordinated management of the many specialist services that combine to make good diabetes care [13]. In consequence, photographic screening programs have been instituted in settings that range from remote rural primary health care centers to highly specialized diabetology centers. The screening protocols are much simpler than the research protocols, consisting for instance of only two-field non-stereoscopic digital fundus photography, visual acuity with refractometer correction, a simplified grading system, and decision algorithms mandating referral to an ophthalmologist at varying levels of retinopathy, ranging from any retinopathy to retinopathy that closely approaches treatment threshold.

Digital image analysis has been developed in an attempt to supplement or substitute the visual evaluation of fundus photographs [9, 10]. Despite good results in clinical tests, their utility in a practical setting remains to be fully evaluated.

19.01Early Treatment Diabetic Retinopathy Study Grading – An Extension of the Modified Airlie House Classification

The best validated grading system for diabetic retinopathy, in terms of its outcome-related evidence base, is the extension of the Airlie House classification that was developed for the Early Treatment Diabetic Retinopathy Study (ETDRS) [5]. On the basis of a prospective evaluation of the relative risk of retinopathy progression and visual loss, a scale was developed that divides diabetic retinopathy into 13 levels ranging from absence of retinopathy to severe

Fig. 19.1. ETDRS fundus photography: location of the seven 30degree fields. Field 1 is centered on the optic disk. Field 2 is centered on the center of the macula. Field 3 is centered just temporal to the macula. Fields 4 – 7 are tangential to horizontal lines passing through the upper and lower poles of the disk and to a vertical line passing through its center

vitreous hemorrhage [6]. The scale can be used to describe overall retinopathy severity and change in severity over time [7].

ETDRS grading is based on the classification of various types of lesions on a multi-step scale (absent, questionable, definitely present but less than standard photograph 1 or written definition, equal to or worse than the new standard photograph but less severe than standard photograph 2, equal to or worse than standard photograph 2, etc.). For some lesions a standard photograph provided the dividing lines between grades. For others a written definition was used. Five standard photographic fields were defined to include most of the fundus within 30 degrees of the center of the macula.

ETDRS fundus photography includes seven stereoscopic photographic fields, each covering 30 degrees (Fig. 19.1). The photographs are recorded on photographic film as diapositives.

ETDRS fundus photography grading is made by visual inspection of each stereoscopic pair of diapositives on a retroilluminated white glass plate using a stereo viewer (+15 diopters) and comparison, when needed, with reference diapositives. The grade for each lesion is recorded separately for each standard field. The lesions graded in the revised modified Airlie classification comprise:

Lesions graded in Fields 3 – 7 (extramacular area)

–Microaneurysms

–Hemorrhages and/or microaneurysms (H/Ma)

–Drusen

–Hard exudates (HE)

–Soft exudates (cotton-wool patches) (SE)

–Intraretinal microvascular abnormalities (IRMA)

–Venous beading (VB)

–Venous narrowing

–Venous loops and/or reduplication (VLR)

–Venous sheathing

–Perivenous exudates (PVEX)

–Arteriolar narrowing (AN)

–Arteriolar sheathing

–Arteriovenous nicking (AVN)

–New vessels elsewhere (more than one disk diameter from the disk) (NVE) (in fields 3 – 7 and in field 1 outside the area defined for NVD)

–Dilated tips of new vessels elsewhere (in fields 3 – 7 and in field 1 outside the area defined for NVD)

–Fibrous proliferation elsewhere (more than one disk diameter from the disk) (FPE) (in fields 3 – 7 and in field 1 outside the area defined for NVD)

–Plane of proliferation elsewhere (PP) (in fields 3 – 7 and in field 1 outside the area

defined for NVD) Lesions graded in all fields

–Preretinal hemorrhages (PRH)

–Vitreous hemorrhage (VH)

–Scars of prior photocoagulation

Lesions graded in Fields 2 – 7

– Retinal elevation (traction, detachment) Lesions graded in Field 1

–Neovascularization on or within one disk diameter of the disk (NVD)

–Dilated tips of the new vessels of the disk

–Fibrous proliferation on or within one disk diameter of the disk (FPD)

–Plane of proliferation on or within one disk diameter of the disk

–Papillary swelling

Lesions graded in Field 2

–Hard exudate rings

–Posterior vitreous detachment

–Retinal thickening (edema)

–Hard exudates within one disk diameter of the center of the macula and at the center of the macula

–Cystoid spaces

–Other lesions within one disk diameter of the center of macula

The lesion grades are summarized for each eye into an ETDRS level that defines the diabetic retinopathy severity (Table 19.1).

The scale of ETDRS levels (Table 19.1) does not cover macular edema, which is graded separately [5]. Using a grid overlay on one photograph in the Field 2

stereo pair, the grader evaluates the size and location of thickened retina, the maximum thickness of the thickened retina, the degree of cystoid edema, and the location of the hard exudate that is often found with it. The ETDRS defined diabetic macular edema as thickening and/or hard exudate within 1 disk diameter of the center of the macula (Table 19.2), giv-

en that the total amount of hard exudate within the III 19 Field 1 photograph exceeded that in a certain stan-

dard photograph. The study of diabetic macular edema and the effect of photocoagulation for diabetic macular edema led to the definition of the term clinically significant macular edema (CSME) for edema that involves or threatens the center of the macula (even if visual acuity is not yet reduced) as assessed by stereo contact lens biomicroscopy or stereo photography. CSME currently serves as the reference threshold for intervention by thermal laser photocoagulation. CSME is defined as:

Retinal thickening at or within 500 μm of the center of the macula and/or

hard exudates at or within 500 μm of the center of the macula, if associated with thickening of the adjacent retina and/or

a zone or zones of retinal thickening 1 disk area in size at least part of which is within 1 disk diameter of the center of the macula.

Additional abnormalities evaluated within 1 disk diameter of the foveal center include epiretinal and preretinal new vessels, epiretinal and preretinal fibrosis, abnormal pigmentation, retinal tension lines, and macular hole.

Optical coherence tomography (OCT) is a valuable tool for assessment of retinal thickening. Its inclusion in ongoing trials on the treatment of diabetic macular edema will likely result in the development of methods for translation between visual grading and OCT thickness mapping and in a better understanding of the relation between thickening of the macula and visual function as well as visual prognosis and potential for recovery if the edema is resolved.

ETDRS fundus photography and grading is the scientific and regulatory standard. It places considerable demand on the patient and the resources for photography, and the grading is complex, for which reason simplified protocols have been developed, two of which will be described below.

19.02 EURODIAB Grading

The EURODIAB grading system is a simplified system, based on experience with the seven-field 30° ETDRS grading system, but adapted to enable large epidemiological studies, in which participating cen-

Table 19.1. Revised modified Airlie House diabetic retinopathy classification (ETDRS)

NPDR non-proliferative diabetic retinopathy, PDR proliferative diabetic retinopathy, IRMA intraretinal microvascular abnormalities, NVE new vessels elsewhere, NVD new vessels on or within

1 disk diameter of the optic disk, PRH pre-retinal hemorrhage, VH vitreous hemorrhage. The definition for each level assumes that the definition for any higher level is not met. NPDR levels 35 and above all require presence of microaneurysms. The corresponding EURODIAB classification scale is shown in the left column

a See [5] for definition of standard photographs

ters have a limited experience in fundus photography [1]. The photographic protocol comprises two 45° color diapositive photographs per eye, one macular field photograph with the optic disk just inside the edge of the frame on its horizontal meridian and one disk/nasal field centered nasal of the disk with the disk one disk diameter in from the temporal edge of the frame on its horizontal meridian (Figs. 19.2 – 19.13). The diabetic retinopathy severity scale comprises no retinopathy, non-proliferative retinopathy, and proliferative retinopathy. Non-proliferative retinopathy is defined as the presence of one or more microaneurysms, hemorrhages, and/or hard exudates. Proliferative retinopathy is defined as any new

vessels, fibrous proliferations, preretinal hemorrhage, vitreous hemorrhage, or photocoagulation scars. Per-patient grading is determined by the eye with the most advanced retinopathy [11]. Because fundus photography was not stereoscopic, macular edema (thickening) was not gradable. Retinopathy was assessed after grading of individual lesion types, from top down. This means that the first step is to determine whether proliferative diabetic retinopathy is present. In the event that it is, the retinopathy level of the eye is 5; if not, the level is not 5 and one proceeds to evaluate if the eye is level 4, and so on.

Fig. 19.10. Venous beading (VB) standard fundus photograph according to the EURODIAB diabetic retinopathy grading system

Fig. 19.11. New vessels elsewhere (NVE) and new vessels on the disk (NVD) standard fundus photograph according to the EURODIAB diabetic retinopathy grading system

Table 19.2. EURODIAB single lesion grading

Single standard photograph

0 Lesion absent

1 Lesion questionable (grader > 50 % but less than 90 % sure) 2 Definitely present but < SP1

3 Lesion present SP1

Two standard photographs

0 Lesion absent

1 Lesion questionable (grader > 50 % but less than 90 % sure) 2 Definitely present but < SP1

3 Lesion present SP1 but < SP2

4 Lesion present SP2

Table 19.3. EURODIAB lesion scale definition (estimated number relative to standard photographs)

M macular field, D/N disk/nasal field, SP standard photograph, SM standard measure (50 % or more of field involved)

Table 19.4. EURODIAB overall retinopathy grades

Level Severity

0No retinopathy

1Minimal non-proliferative retinopathy: HMA = grade 2 to 3 in 1 or 2 fields and/or HE = grade 2 to 4 in 1 or 2 fields

2Moderate non-proliferative retinopathy: HMA = grade 4 in only 1 field or

HMA = grade 2 to 3 in 1 or 2 fields plus: CWS = grade 2 to 3 in 1 or 2 fields and/or IRMA = grade 2 in 1 or 2 fields and/or VB = grade 2 in 1 to 2 fields

3Severe non-proliferative (pre-proliferative) retinopathy: HMA = grade 4 in both fields or

HMA =grade 2 to 4 in 1 or 2 fields plus: CWS = grade 4 in 1 or 2 fields and/or IRMA = grade 3 in 1 or 2 fields and/or VB = grade 3 in 1 or 2 fields

4Photocoagulated:

Scars of photocoagulation in any field

5Proliferative:

Any of the following:

New vessels (disk or elsewhere)

Fibrous proliferations (disk of elsewhere) Pre-retinal hemorrhage

Vitreous hemorrhage

NPDR non-proliferative diabetic retinopathy, HMA hemorrhage and microaneurysm, HE hard exudates, CWS cotton wool spots, IRMA intraretinal microvascular abnormalities, VB venous beading. All appearances are in comparison with the EURODIAB standard photographs [1]

19.03International Clinical Diabetic Retinopathy Severity Scale

The proposed International Clinical Diabetic Retinopathy and Diabetic Macular Edema Disease Severity Scale was developed by a consensus panel of experts to provide a severity scale for common usage that is targeted at solving practical clinical issues, for instance in retinopathy screening and to improve communication and coordination of care among physicians who care for patients with diabetes [12].

The five-stage disease severity classification for diabetic retinopathy includes three stages of low risk, a fourth stage of severe non-proliferative retinopathy, and a fifth stage of proliferative retinopathy. Diabetic macular edema is classified as apparently present or apparently absent. If training and equipment allow the screener to make a valid decision, macular edema is further categorized as a function of its distance from the central macula.

The system was developed with reference to the ETDRS grading system. It may help standardize clinical retinopathy grading where many systems are in use that are nominally different but vary little in their fundamental concept.

Table 19.5. Diabetic Retinopathy Disease Severity Scale

References

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2.Davis MD, Fisher MR, Gangnon RE, Barton F, Aiello LM,

3.Diabetic Retinopathy Study Research Group (1981) Diabetic Retinopathy Study. Report Number 6. Design, methods, and baseline results. Report Number 7. A modification of the Airlie House classification of diabetic retinopathy. Invest Ophthalmol Vis Sci 21(1):1 – 226

4.Early Treatment Diabetic Retinopathy Study Research Group (1985) Photocoagulation for diabetic macular edema. Early Treatment Diabetic Retinopathy Study Report Number 1. Arch Ophthalmol 103(12):1796 – 806

5.Early Treatment Diabetic Retinopathy Study Research Group (1991) Grading diabetic retinopathy from stereoscopic color fundus photographs – an extension of the modified Airlie House classification. ETDRS Report Number 10. Ophthalmology 98:786 – 806

6.Early Treatment Diabetic Retinopathy Study Research Group (1991) Fundus photographic risk factors for progression of diabetic retinopathy. ETDRS Report Number 12. Ophthalmology 98:823 – 833