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Reference(s) ⬇

Wilkinson CP, Ferris FL III, Klein RE, et al. Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003;110:1677-1682.Mitchell P, Bandello F, Schmidt-Erfurth U, et al. The RESTORE Study ranibizumab monotherapy or combined with laser versus laser monotherapy for diabetic macular edema. Ophthalmology. 2011;118:615-625.Korobelnik JF, Do DV, Schmidt-Erfurth U, et al. Intravitreal aflibercept for diabetic macular edema. Ophthalmology. 2014;121(11):2247-2254.Boyer DS, Yoon YH, Belfort R Jr, et al. Three-year, randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with diabetic macular edema. Ophthalmology. 2014;121(10):1904-1914.Cunha-Vaz J, Ashton P, Iezzi R, et al. Sustained delivery fluocinolone acetonide vitreous implants: long-term benefit in patients with chronic diabetic macular edema. Ophthalmology. 2014;121(10):1892-1903.Diabetic Retinopathy Clinical Research Network. Panretinal photocoagulation vs intravitreous ranibizumab for proliferative diabetic retinopathy: a randomized trial. J Am Med Assoc. 2015;314(20):2137-2146.Obeid A, Su D, Patel SN, et al. Outcomes of eyes lost to follow-up with proliferative diabetic retinopathy that received panretinal photocoagulation versus intravitreal anti-vascular endothelial growth factor. Ophthalmology. 2019;126(3):407-413.

Diabetic Retinopathy Disease Severity Scale

  • No apparent retinopathy.
  • Mild nonproliferative diabetic retinopathy (NPDR): Microaneurysms only.
  • Moderate NPDR: More than mild NPDR, but less than severe NPDR (see Figure 11.12.1). May have CWSs and venous beading.
  • Severe NPDR: Any of the following in the absence of PDR: Diffuse (traditionally >20) intraretinal hemorrhages in all four quadrants, two quadrants of venous beading, or one quadrant of prominent intraretinal microvascular abnormalities (see Figure 11.12.2).
  • PDR: Neovascularization of one or more of the following: iris, angle, optic disc, or elsewhere in retina; or vitreous/preretinal hemorrhage (see Figures 11.12.3 and 11.12.4).
  • Diabetic macular edema (DME): May be present in any of the stages listed above. DME affecting or threatening the fovea is an indication for treatment (see Figures 11.12.5 and 11.12.6).

11-12.6 Clinically significant macular edema.

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11-12.5 Nonproliferative diabetic retinopathy with clinically significant macular edema.

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11-12.4 Proliferative diabetic retinopathy with neovascularization of the optic disc.

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11-12.3 Proliferative diabetic retinopathy with neovascularization and scattered microaneurysms.

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11-12.2 Intravenous fluorescein angiography of intraretinal microvascular abnormality.

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11-12.1 Moderate nonproliferative diabetic retinopathy with microaneurysms and cotton–wool spots.

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Differential Diagnosis for Nonproliferative Diabetic Retinopathy

  • CRVO: Optic disc swelling, veins are more dilated and tortuous, hard exudates and microaneurysms usually not found, hemorrhages are nearly always in the NFL (“splinter hemorrhages”). CRVO is generally unilateral and of more sudden onset. See 11.8, CENTRAL RETINAL VEIN OCCLUSION.
  • BRVO: Hemorrhages are distributed along a vein and do not cross the horizontal raphe (midline). See 11.9, BRANCH RETINAL VEIN OCCLUSION.
  • OIS: Hemorrhages mostly in the midperiphery and larger; exudates are absent. Usually accompanied by pain; mild anterior chamber reaction; corneal edema; episcleral vascular congestion; a mid-dilated, poorly reactive pupil; iris neovascularization. See 11.11, OCULAR ISCHEMIC SYNDROME/CAROTID OCCLUSIVE DISEASE.
  • Hypertensive retinopathy: Hemorrhages fewer and typically flame-shaped, microaneurysms rare, and arteriolar narrowing present often with arteriovenous crossing changes (“AV nicking”). See 11.10, HYPERTENSIVE RETINOPATHY.
  • Radiation retinopathy: Usually develops within a few years of radiation. Microaneurysms are rarely present. See 11.5, COTTON–WOOL SPOT.

Differential Diagnosis for Proliferative Diabetic Retinopathy

Work Up ⬆ ⬇

Workup
  1. Slit lamp examination using gonioscopy with careful attention for NVI and NVA, preferably before pharmacologic dilation.
  2. Dilated fundus examination by using a 90- or 60-diopter or fundus contact lens with a slit lamp to rule out neovascularization and ME. Use indirect ophthalmoscopy to examine the retinal periphery.
  3. Check fasting blood sugar, hemoglobin A1c, and lipid panel.
  4. Check blood pressure.
  5. Consider IVFA to determine areas of perfusion abnormalities, foveal ischemia, microaneurysms, and subclinical neovascularization, especially if considering focal macular laser therapy.
  6. Consider OCT to evaluate for presence and extent of DME. OCT angiography (OCTA) can be useful to check for presence of significant central macular ischemia.

Treatment ⬆ ⬇

Diabetic Macular Edema

  1. Anti-VEGF agents (FDA-approved ranibizumab and aflibercept, as well as off-label bevacizumab) are first-line therapy for center-involving DME.
  2. Those patients who have a suboptimal response to these anti-VEGF agents or require ongoing, frequent anti-VEGF therapy can consider intravitreal corticosteroid therapy with FDA-approved dexamethasone or long-acting fluocinolone acetonide injectable implants. Off-label intravitreal corticosteroid (e.g., triamcinolone 40 mg/mL, injecting 1 to 4 mg) can also be considered. Complications include cataract formation and elevated IOP.
  3. Focal macular laser treatment can be considered in patients with extrafoveal microaneurysms causing significant edema. Macular laser can also be considered in patients for whom anti-VEGF and intravitreal steroid injections are contraindicated. Most practitioners avoid using anti-VEGF agents in pregnant patients, though no study has definitively shown adverse fetal side effects.

Proliferative Diabetic Retinopathy

  1. PRP is indicated for any one of the following high-risk characteristics (see Figure 11.12.7):
    • NVD greater than one-fourth to one-third of the disc area in size.
    • Any degree of NVD when associated with preretinal hemorrhage or VH.
    • NVE greater than one-half of the disc area in size when associated with preretinal hemorrhage or VH.
    • Any NVI or NVA.

    11-12.7 High-risk characteristics for diabetic retinopathy.

    Gervasio-ch011-image023
  2. Anti-VEGF therapy can be utilized for PDR as an alternative to PRP and is the preferred initial therapy in the presence of DME or if the view to the peripheral retina is limited by VH. Anti-VEGF therapy without PRP should be utilized cautiously, as patients lost to follow up have been shown to have worse anatomic and visual outcomes.
NOTE:

Some physicians treat NVE or any degree of NVD without preretinal hemorrhage or VH, especially in unreliable patients.

Indications for Vitrectomy

Vitrectomy may be indicated for any one of the following conditions:

  1. Dense, nonclearing or recurrent VH causing significant decreased vision.
  2. Traction RD involving and progressing within the macula.
  3. Macular epiretinal membranes (ERMs) or vitreomacular traction causing significant visual symptoms.
  4. Dense premacular hemorrhage.
  5. Chronic DME not responsive to other treatment.
  6. Severe retinal neovascularization and fibrous proliferation that is unresponsive to laser photocoagulation or anti-VEGF therapy.
NOTE:

Young patients with type 1 diabetes are known to have more aggressive PDR and therefore may benefit from earlier vitrectomy, laser photocoagulation, or anti-VEGF therapy. B-scan US may be required to rule out tractional detachment of the macula in eyes with dense VH obscuring a fundus view.

Follow Up ⬆

  1. Diabetes without retinopathy. Annual dilated examination.
  2. Mild NPDR. Dilated examination every 6 to 9 months.
  3. Moderate to severe NPDR. Dilated examination every 4 to 6 months.
  4. PDR (not meeting high-risk criteria). Dilated examination every 2 to 3 months.
  5. Diabetes and pregnancy. Changes that occur during pregnancy have a high likelihood of postpartum regression. See Table 11.12.1 for follow-up recommendations.

11-12.1 Recommendations Based on the Baseline Diabetic Retinopathy in Pregnancy

Baseline Diabetic RetinopathyGestational DiabetesNone or Minimal Nonproliferative Diabetic Retinopathy (NPDR)Mild-to-Moderate NPDRHigh-Risk NPDRProliferative Diabetic Retinopathy (PDR)
Gestational courseNo risk of retinopathyNo progression in vast majority. Of those who progress, only a few have visual impairment.Progression in up to 50%. Postpartum regression in many.Progression in up to 50%. Postpartum regression in some.Tends to progress rapidly.
Eye examinationsNoneFirst and third trimesterEvery trimesterMonthlyMonthly
TreatmentNoneNoneNone, unless high-risk proliferative retinopathy develops.None, unless high-risk proliferative retinopathy develops.Treat PDR with panretinal photocoagulation. Observe diabetic macular edema (high rate of spontaneous postpartum regression).
NOTE:

The Diabetes Control and Complications Trial showed that strict control of blood sugar with insulin (in type 1 diabetes) decreases the progression of diabetic retinopathy, as well as nephropathy and neuropathy.