Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

nonproliferative diabetic retinopathy

1st line – observation

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ACUTE
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nonproliferative diabetic retinopathy
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no diabetic macular edema or non-center-involving diabetic macular edema
1st line – 

observation

Nonproliferative diabetic retinopathy (NPDR) with no diabetic macular edema or non-center-involving diabetic macular edema requires surveillance only.

Patients should be advised to consult their physician to achieve adequate hypertensive, glycemic, and lipid control.

1st line – observation

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ACUTE
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nonproliferative diabetic retinopathy
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center-involving diabetic macular edema with visual acuity better than 6/9
1st line – 

observation

Center-involving diabetic macular edema with good vision (visual acuity better than 6/9) responds equally well to macular laser therapy, intravitreal aflibercept injection, and observation.[96]

Therefore, observation without treatment is reasonable in these patients unless visual acuity becomes worse.[96]

1st line – intravitreal anti-VEGF therapy

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ACUTE
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nonproliferative diabetic retinopathy
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center-involving diabetic macular edema with visual acuity ≥6/9 and <6/18
1st line – 

intravitreal anti-VEGF therapy

Center-involving diabetic macular edema with vision ≥6/9 and <6/18 responds equally well to intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection (aflibercept, ranibizumab, or bevacizumab). Visual acuity was found to improve approximately 1.4 times, on average.[35]

If the patient responds to anti-VEGF therapy, then it should be continued according to regimen, visual acuity, and optical coherence tomography findings.

Intravitreal aflibercept (as-needed, and as fixed loading doses followed by regular injection every two months) has been shown to be effective in patients with diabetic macular edema.​[35][104][111][112][113]

Faricimab, a bispecific angiopoietin-2 and VEGF inhibitor, was noninferior to aflibercept (mean change in best-corrected visual acuity at 1 year) in phase 3 randomized trials of patients with diabetic macular edema.​​[114]​ Incidence of ocular adverse events was comparable.

One systematic review and network meta-analysis found that faricimab, used in a treat and extend protocol for diabetic macular edema with intervals up to every 16 weeks, was associated with a statistically greater increase in mean change in best-corrected visual acuity compared with flexible regimens of ranibizumab and bevacizumab.[115]​ The analyses indicated that the faricimab treat and extend protocol decreased retinal thickness compared with other flexible dosing regimens (aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy). Faricimab injection frequency was numerically lower versus other treatments using a flexible dosing regimen.[115]

The principal ocular complication of any intravitreal anti-VEGF injection is endophthalmitis, intraocular infection, which without prompt treatment may lead to loss of sight. It occurs following approximately 0.5% of injections.[98]

There is no definite evidence of systemic adverse effects with intravitreal anti-VEGF injection.

Primary options

aflibercept intravitreal: 2 mg intravitreally into the affected eye(s) every 4 weeks for 5 doses, followed by 2 mg every 8 weeks

More

OR

ranibizumab intravitreal: 0.3 mg intravitreally into the affected eye(s) once monthly

OR

bevacizumab: 1.25 mg intravitreally into the affected eye(s) once monthly

OR

faricimab intravitreal: 6 mg intravitreally into the affected eye(s) once monthly for at least 4 doses, then adjust dose interval based on response; or 6 mg intravitreally into the affected eye(s) once monthly for 6 doses, followed by 6 mg every 8 weeks for 28 weeks

1st line – intravitreal anti-VEGF therapy

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ACUTE
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nonproliferative diabetic retinopathy
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center-involving diabetic macular edema with visual acuity ≥6/18 and <6/96
1st line – 

intravitreal anti-VEGF therapy

Center-involving diabetic macular edema with visual acuity ≥6/18 and <6/96 responded better to intravitreal aflibercept injection than to ranibizumab or bevacizumab at 1 year. At 2 years, ranibizumab and aflibercept were superior to bevacizumab, and were equally effective. Considering its area-under-the-curve superiority over ranibizumab, aflibercept is the drug of choice in this patient group. Visual acuity improved on average 1.8 times from baseline to 2 years.[97]​ 

If the patient responds to anti-VEGF therapy, then it should be continued according to regimen, visual acuity, and optical coherence tomography findings.

Intravitreal aflibercept (as-needed, and fixed loading doses followed by regular injection every two months) has been shown to be effective in patients with diabetic macular edema.[35][104][111][112][113]​​​​

Faricimab, a bispecific angiopoietin-2 and VEGF inhibitor, was noninferior to aflibercept (mean change in best-corrected visual acuity at 1 year) in phase 3 randomized trials of patients with diabetic macular edema.[114]​ Incidence of ocular adverse events was comparable.

One systematic review and network meta-analysis found that faricimab, used in a treat and extend protocol for diabetic macular edema with intervals up to every 16 weeks, was associated with a statistically greater increase in mean change in best-corrected visual acuity compared with flexible regimens of ranibizumab and bevacizumab.[115]​ The analyses indicated that the faricimab treat and extend protocol decreased retinal thickness compared with other flexible dosing regimens (aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy). Faricimab injection frequency was numerically lower versus other treatments using a flexible dosing regimen.[115]

The principal ocular complication of any intravitreal anti-VEGF injection is endophthalmitis, intraocular infection, which without prompt treatment may lead to loss of sight. It occurs following approximately 0.5% of injections.[98]

There is no definite evidence of systemic adverse effects with intravitreal anti-VEGF injection.

Primary options

aflibercept intravitreal: 2 mg intravitreally into the affected eye(s) every 4 weeks for 5 doses, followed by 2 mg every 8 weeks

More

OR

faricimab intravitreal: 6 mg intravitreally into the affected eye(s) once monthly for at least 4 doses, then adjust dose interval based on response; or 6 mg intravitreally into the affected eye(s) once monthly for 6 doses, followed by 6 mg every 8 weeks for 28 weeks

proliferative diabetic retinopathy

1st line – urgent panretinal photocoagulation

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ACUTE
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proliferative diabetic retinopathy
1st line – 

urgent panretinal photocoagulation

In patients with proliferative retinopathy, panretinal photocoagulation approximately halves the rate of severe visual loss (worse than 1/60).[74][99]​​[100][101]

Indications for laser treatment for proliferative retinopathy include: mild vessels on the optic disk (greater than one quarter to one third disk area) with vitreous or preretinal hemorrhage; moderate to severe new vessels on the optic disk with or without preretinal hemorrhage; moderate to severe new vessels elsewhere with vitreous or preretinal hemorrhage.[102]

Adverse ocular effects include macular edema, restriction of visual field (in some cases severe enough to lead to the loss of driving license), glare, and loss of night vision.

Supplementary intravitreal anti-VEGF agents may improve the likelihood of neovascular regression. In all major studies examining the effect of intravitreal anti-VEGF agents on macular edema, the proportion of patients with proliferative retinopathy is small. To extrapolate the findings of these studies to patients with proliferative retinopathy and macular edema is of questionable validity, though it is common in clinical practice.[35]​ ​

iris neovascularization

1st line – urgent panretinal photocoagulation plus intravitreal anti-VEGF therapy

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ACUTE
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iris neovascularization
1st line – 

urgent panretinal photocoagulation plus intravitreal anti-VEGF therapy

​Iris neovascularization can be identified on slit-lamp examination. However, it is nearly always associated with proliferative retinopathy. Panretinal photocoagulation is considered a matter of urgency in patients with iris neovascularization, despite only modest supporting evidence.[103]

In patients with proliferative retinopathy, panretinal photocoagulation approximately halves the rate of severe visual loss (worse than 1/60).[74][99]​​​[100][101]​​

Adverse ocular effects include macular edema, restriction of visual field (in some cases severe enough to lead to the loss of driving license), glare, and loss of night vision.

Supplementary intravitreal anti-VEGF agents may improve the likelihood of neovascular regression. There are no studies examining the effect of intravitreal anti-VEGF agents in the management of macular edema in patients with iris neovascularization. In clinical practice, however, the results of studies of anti-VEGF agents are commonly applied to macular edema in patients with iris neovascularization.[35]​​[91]​​[104]

If the patient responds to anti-VEGF therapy, then it should be continued according to regimen, visual acuity, and optical coherence tomography findings.

Intravitreal aflibercept (as-needed, and fixed loading doses followed by regular injection every two months) has been shown to be effective in patients with diabetic macular edema.[35][104]​​​[111][112][113]

Faricimab, a bispecific angiopoietin-2 and VEGF inhibitor, was noninferior to aflibercept (mean change in best-corrected visual acuity at 1 year) in phase 3 randomized trials of patients with diabetic macular edema.[114]​ Incidence of ocular adverse events was comparable.

One systematic review and network meta-analysis found that faricimab, used in a treat and extend protocol for diabetic macular edema with intervals up to every 16 weeks, was associated with a statistically greater increase in mean change in best-corrected visual acuity compared with flexible regimens of ranibizumab and bevacizumab.[115]​ The analyses indicated that the faricimab treat and extend protocol decreased retinal thickness compared with other flexible dosing regimens (aflibercept, ranibizumab, bevacizumab, dexamethasone and laser therapy). Faricimab injection frequency was numerically lower versus other treatments using a flexible dosing regimen.[115]

The principal ocular complication of any intravitreal anti-VEGF injection is endophthalmitis, intraocular infection, which without prompt treatment may lead to loss of sight. It occurs following approximately 0.5% of injections.[98]

There is no definite evidence of systemic adverse effects with intravitreal anti-VEGF injection.

Primary options

aflibercept intravitreal: 2 mg intravitreally into the affected eye(s) every 4 weeks for 5 doses, followed by 2 mg every 8 weeks

More

OR

ranibizumab intravitreal: 0.3 mg intravitreally into the affected eye(s) once monthly

OR

bevacizumab: 1.25 mg intravitreally into the affected eye(s) once monthly

OR

faricimab intravitreal: 6 mg intravitreally into the affected eye(s) once monthly for at least 4 doses, then adjust dose interval based on response; or 6 mg intravitreally into the affected eye(s) once monthly for 6 doses, followed by 6 mg every 8 weeks for 28 weeks

advanced proliferative diabetic retinopathy

1st line – consider vitrectomy surgery ± preoperative intravitreal bevacizumab

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ACUTE
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advanced proliferative diabetic retinopathy
1st line – 

consider vitrectomy surgery ± preoperative intravitreal bevacizumab

Patients with macular traction retinal detachment or traction-rhegmatogenous retinal detachment may benefit from vitrectomy.[105][106]​ Nonclearing vitreous hemorrhage is usually treated with vitrectomy, which is best carried out early in patients with type 1 diabetes with a diabetes duration of less than 20 years.[93][94][107]​​

One review has suggested that vitrectomy may be beneficial in patients with no or incomplete posterior vitreous detachment, vitrectomy may be beneficial.[108]​ Preoperative intravitreal bevacizumab may improve surgical outcomes.[109]

Adverse effects of vitrectomy in proliferative retinopathy include cataracts, raised intraocular pressure, entry-site neovascularization, iris neovascularization, vitreous cavity hemorrhage, retinal tear formation, retinal detachment, and endophthalmitis. Crunch syndrome, the rapid development of traction retinal detachment, may follow preoperative intravitreal anti-VEGF injection.[110]

ONGOING

macular edema unresponsive to intravitreal anti-VEGF therapy

1st line – intravitreal corticosteroid or macular laser therapy

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ONGOING
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macular edema unresponsive to intravitreal anti-VEGF therapy
1st line – 

intravitreal corticosteroid or macular laser therapy

Intravitreal corticosteroid therapy (dexamethasone, fluocinolone acetonide) may be considered for edema unresponsive to intravitreal anti-VEGF treatment, particularly in eyes that have undergone cataract extraction.[44][117] One systematic review reported that intravitreal corticosteroids may improve vision in people with diabetic macular edema compared with sham or control.[118]​​ However, the effects were small, about one line of vision or less in most comparisons.[118]

Adverse effects of intravitreal corticosteroid injection include endophthalmitis, cataract, elevated intraocular pressure, and migration of implant.

In patients treated with intravitreal corticosteroid therapy, it should be continued subject to visual acuity, presence of cataract, intraocular pressure, and optical coherence tomography findings; consider switching to intravitreal anti-VEGF agents or macular laser therapy if unresponsive.

The modified Early Treatment Diabetic Retinopathy Study (ETDRS) direct/grid laser photocoagulation technique may be considered for macular edema unresponsive to intravitreal anti-VEGF treatment.[116]

Adverse effects of macular laser therapy include paracentral visual loss, visible scotomata, and, occasionally, choroidal neovascularization or foveal injury.

In patients treated with macular laser therapy, it should be continued according to visual acuity and optical coherence tomography findings; consider switching to intravitreal anti-VEGF agents or intravitreal corticosteroids (dexamethasone, fluocinolone acetonide) if unresponsive.

Primary options

dexamethasone intravitreal: 0.7 mg intravitreally (implant) into the affected eye(s)

OR

fluocinolone intravitreal: 0.19 mg intravitreally (implant) into the affected eye(s)

macular edema with anteroposterior vitreomacular traction

1st line – vitrectomy surgery

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ONGOING
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macular edema with anteroposterior vitreomacular traction
1st line – 

vitrectomy surgery

Some patients with anteroposterior vitreomacular traction benefit from vitrectomy surgery.[119]

Adverse effects of vitrectomy include cataracts, raised intraocular pressure, vitreous cavity hemorrhage, retinal tear formation, retinal detachment, and endophthalmitis.

chronic macular edema, macular ischemia, chronic macular detachment, optic atrophy secondary to neovascular glaucoma

1st line – low vision assessment plus visual rehabilitation

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ONGOING
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chronic macular edema, macular ischemia, chronic macular detachment, optic atrophy secondary to neovascular glaucoma
1st line – 

low vision assessment plus visual rehabilitation

​Some forms of retinopathy are profoundly refractory to therapy. These include macular ischemia, chronic macular edema, chronic macular detachment, and advanced optic atrophy from neovascular glaucoma. If both eyes are affected, such patients should be offered low vision assessment and benefits associated with visual disability.[62][87]​​[120][121]​​

Patients should be advised to consult their physician to achieve adequate hypertensive, glycemic, and lipid control.[62][87]

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Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer