Introduction

• ◾
  

  Prevalence: (a) the overall prevalence of diabetic retinopathy (DR) in individuals with diabetes is approximately 40%, (b) DR is more common in type 1 than in type 2 diabetes, (c) proliferative disease affects 5–10% of the diabetic population (60% after 30 years in type 1), (d) sight-threatening disease is present in up to 10%.

  
  
• ◾
  

  Risk factors: (a) duration of diabetes (50% after 10 years if diagnosed before age 30 years; 5% of type 2 diabetics have DR at presentation), (b) poor control of diabetes, (c) pregnancy, (d) hypertension, (e) nephropathy, (f) hyperlipidaemia, (g) smoking, (h) obesity, (i) anaemia.

Classification

The classification proposed in the Early Treatment Diabetic Retinopathy Study is widely used internationally. An abbreviated version is set out in Table 13.1 ; other commonly used clinical categories are as follows:

• ◾
  

  Background diabetic retinopathy: (a) microaneurysms, (b) dot and blot haemorrhages, (c) hard exudates.

  
  
• ◾
  

  Diabetic maculopathy: vision-threatening macular oedema or ischaemia.

  
  
• ◾
  

  Preproliferative diabetic retinopathy: (a) cotton wool spots, (b) venous changes, (c) intraretinal microvascular anomalies (IRMA), (d) deep retinal haemorrhages.

  
  
• ◾
  

  Proliferative diabetic retinopathy (PDR): (a) neovascularization on or within one disc diameter of the disc (NVD) and/or (b) new vessels elsewhere (NVE) in the fundus.

  
  
• ◾
  

  Advanced diabetic eye disease: (a) tractional retinal detachment, (b) persistent vitreous haemorrhage, (c) neovascular glaucoma.

Signs

• ◾
  

  Microaneurysms: tiny red dots ( Fig. 13.1A ) that tend to be the earliest signs. They represent saccular outpouching of the capillary wall.

  
  

  
  

  
  

  

  
  

  
  

  Background diabetic retinopathy: (A) microaneurysms, (B) retinal nerve fibre layer haemorrhages, (C) dot/blot haemorrhages, (D) exudates forming a circinate pattern.

  
  

  (From Salmon JF, Kanski’s Clinical Ophthalmology: A Systematic Approach , 9th edition. Oxford, UK: Elsevier; 2020.)

  
  
  
  
• ◾
  

  Retinal nerve fibre layer haemorrhages: superficial and flame-shaped ( Fig. 13.1B ).

  
  
• ◾
  

  Intraretinal haemorrhages: located in the compact middle layers of the retina, manifesting with a red ‘dot/blot’ configuration ( Fig. 13.1C ).

  
  
• ◾
  

  Deeper dark round haemorrhages: haemorrhagic infarcts located within the middle retinal layers and are a risk marker for progression to retinal neovascularization.

  
  
• ◾
  

  Hard exudates: waxy yellow lesions with distinct margins, often arranged in clumps and/or rings surrounding leaking microaneurysms ( Fig. 13.1D ).

  
  
• ◾
  

  Diabetic maculopathy: this the most common cause of visual impairment in diabetes; (a) localized macular oedema is caused by focal leakage ( Fig. 13.2A ), (b) diffuse oedema is caused by leakage, often with accumulation of fluid at the fovea in cystoid configuration (CMO). FA shows diffuse late hyperfluorescence with a flower-petal pattern and OCT shows retinal thickening and cystoid spaces ( Fig. 13.2B ), (c) in ischaemic maculopathy, the macula may appear relatively normal despite reduced VA ( Fig. 13.2C ). FA shows capillary nonperfusion and an enlarged foveal avascular zone (FAZ) ( Fig. 13.2D ).

  
  

  
  

  
  

  

  
  

  
  

  Diabetic maculopathy: (A) ring of hard exudates, (B) OCT showing retinal thickening and cystoid spaces, (C) ischaemic changes showing cotton wool spots, (D) FA venous phase of (C) showing hypofluorescence due to capillary nonperfusion.

  
  

  (From Salmon JF, Kanski’s Clinical Ophthalmology: A Systematic Approach , 9th edition. Oxford, UK: Elsevier; 2020.)

  
  
  
  
• ◾
  

  Cotton wool spots: small whitish fluffy lesions consisting of focal accumulations of neuronal debris within the nerve fibre layer ( Fig. 13.3A ); an important sign of retinal ischaemia.

  
  

  
  

  
  

  

  
  

  
  

  Preproliferative changes: (A) cotton wool spots, (B) venous looping, (C) venous beading, (D) intraretinal microvascular abnormalities.

  
  

  (From Salmon JF, Kanski’s Clinical Ophthalmology: A Systematic Approach, 9th edition . Oxford, UK: Elsevier; 2020.)

  
  
  
  
• ◾
  

  Venous anomalies: seen in ischaemia, consist of: (a) generalized dilatation and tortuosity, (b) looping ( Fig. 13.3B ), (c) ‘beading’ (focal narrowing and dilatation) ( Fig. 13.3C ), (d) segmentation. The extent of the involved retinal area correlates with the risk of developing PDR.

  
  
• ◾
  

  Intraretinal microvascular abnormalities (IRMA): fine irregular intraretinal arteriovenous shunts often seen adjacent to areas of capillary nonperfusion ( Fig. 13.3D ). FA shows absence of leakage.

  
  
• ◾
  

  Neovascularization: (a) NVD describes neovascularization on or within one disc diameter of the optic nerve head ( Fig. 13.4A ), (b) NVE describes neovascularization further away from the disc ( Fig. 13.4B ), (c) new vessels on the iris (rubeosis iridis) carry a high risk of progression to neovascular glaucoma (see Chapter 11 ).

  
  

  
  

  
  

  

  
  

  
  

  Proliferative retinopathy: (A) disc new vessels, (B) new vessels elsewhere.

  
  

  (From Salmon JF, Kanski’s Clinical Ophthalmology: A Systematic Approach , 9th edition. Oxford, UK: Elsevier; 2020.)

  
  

Treatment of clinically significant macular oedema (CSMO)

• ◾
  

  Definition: (a) retinal thickening within 500 μm of the centre of the macula ( Fig. 13.5A ), (b) exudates within 500 μm of the centre of the macula, if associated with retinal thickening ( Fig. 13.5B ) or (c) retinal thickening one disc area (1500 μm) or larger, any part of which is within one disc diameter of the centre of the macula ( Fig. 13.5C ).

  
  

  
  

  
  

  

  
  

  
  

  Clinically significant macular oedema: (A–C): see text.

  
  

  (From Salmon JF, Kanski’s Clinical Ophthalmology: A Systematic Approach , 9th edition. Oxford, UK: Elsevier; 2020.)

  
  
  
  
• ◾
  

  Pretreatment FA: delineates the area and extent of leakage and detects ischaemic maculo-pathy (poor prognosis).

  
  
• ◾
  

  Intravitreal anti-VEGF agents: are playing a prominent role (a) CSMO involving the centre of the macula, but with a visual acuity of better than 6/15 can be treated with aflibercept, bevacizumab or ranibizumab ( Fig. 13.6A and B ), (b) when the acuity is 6/15 or worse aflibercept should be considered, with initial induction using monthly injections for 3–6 months, followed by an ‘as needed’ approach, (c) patients with CSMO and a visual acuity of 6/7.5 or better who otherwise meet criteria for treatment might prefer to be monitored once the risks of treatment are considered.

  
  

  
  

  
  

  

  
  

  
  

  Anti-VEGF treatment for clinically significant macular oedema: (A) OCT appearance before treatment showing diffuse thickening of the macula (red), (B) 6 months after treatment showing resolution.

  
  

  (From Salmon JF, Kanski’s Clinical Ophthalmology: A Systematic Approach , 9th edition. Oxford, UK: Elsevier; 2020.)

  
  
  
  
• ◾
  

  Focal treatment: light/moderate intensity burns (50–100 μm, 0.1 sec) applied to microaneurysms associated with CSMO ( Fig. 13.7A and B ). Treatment as close as 300 μm from the centre of the macula may be considered in some cases, with a lighter intensity reaction closer to the centre.

  
  

  
  

  
  

  

  
  

  
  

  Laser treatment for macular oedema: (A) pre-treatment appearance, (B) immediate appearance after modified grid.

  
  

  (Courtesy of R. Bates.)

  
  
  
  
• ◾
  

  Grid treatment: burns (100 μm, 0.1 sec) applied to areas of diffuse retinal thickening more than 500 μm from the centre of the macula to give a very light intensity reaction. Treatment should be particularly light if significant macular ischaemia is present.

  
  
• ◾
  

  Results: 70% of eyes achieve stable VA, 15% show improvement and 15% subsequently deteriorate; it may take up to 4 months for oedema to respond.

  
  
• ◾
  

  Poor prognostic factors: (a) significant macular ischaemia, (b) foveal exudates, (c) diffuse macular oedema, (d) CMO, (e) severe retinopathy at presentation, (f) uncontrolled systemic hypertension, (g) renal disease, (h) poorly controlled blood glucose, (i) smoking.

  
  
• ◾
  

  Micropulse diode laser: short duration (microseconds) burns to the RPE without significantly affecting the outer retina and choriocapillaris.

  
  
• ◾
  

  Frequency-doubled micropulse Nd:YAG laser: (e.g. ‘pattern scan laser’ – PASCAL); offers the potential for a less destructive retinal effect than argon, with barely visible burns at the level of the RPE.

  
  
• ◾
  

  Intravitreal triamcinolone: pseudophakic eyes with CSMO may benefit from intravitreal steroid injection followed by prompt laser. Can be considered in pregnancy or where there is a contraindication to anti-VEGF medication (e.g. recent myocardial infarct).

  
  
• ◾
  

  Pars plana vitrectomy: when macular oedema is associated with tangential traction from a thickened and taut posterior hyaloid and possibly in other circumstances (e.g. vitreous haemorrhage)

  
  
• ◾
  

  Lipid-lowering drugs: may reduce the requirement for laser treatment.

Treatment of proliferative retinopathy

• ◾
  

  Risk characteristics and benefits: the landmark Diabetic Retinopathy Study established the characteristics of high-risk proliferative disease and the effect of PRP, showing that (a) mild NVD with haemorrhage carries a 26% risk of visual loss, reduced to 4% with PRP, (b) severe NVD without haemorrhage has a 26% risk of visual loss, reduced to 9%, (c) severe NVD with haemorrhage carries a 37% risk of visual loss, reduced to 20%, (d) severe NVE with haemorrhage carries a 30% risk of visual loss, reduced to 7% with treatment.

  
  
• ◾
  

  Complications: visual field defects of sufficient severity to legally preclude driving. Patients should also be made aware that there is some risk to central vision and that night and colour vision may be affected.

  
  
• ◾
  

  Laser settings: (a) spot size depends on the contact lens used (e.g. Goldmann 200–500 μm, panfundoscopic lens 100–300 μm), (b) duration 0.05–0.1 sec, and (c) power sufficient to produce only a light intensity burn.

  
  
• ◾
  

  PRP technique: 1500–2000 burns in a scatter pattern extending from the posterior fundus to cover the peripheral retina in one or more sessions. In eyes with severe NVD, 3000 or more burns may be required ( Fig. 13.8A and B ). Many practitioners leave two disc diameters untreated at the nasal side of the disc to preserve paracentral field. Topical anaesthesia is adequate in most patients, although a local block is sometimes necessary. Follow-up after 4–6 weeks.

  
  

  
  

  
  

  

  
  

  
  

  PRP: (A) composite image of ‘pattern scan’ multispot array treatment, (B) retinal appearance several weeks after laser.

  
  

  ( Figure 13.8A courtesy of S. Chen; Figure 13.8D courtesy of Chris Barry, Lions Eye Institute, Perth, Australia.)

  
  
  
  
• ◾
  

  Intravitreal anti-VEGF therapy: used as an adjunct to PRP, especially if there is central-involving DMO.

Advanced diabetic eye disease

Introduction

• ◾
  

  This is the second most common retinal vascular disease after DR.

  
  
• ◾
  

  It is strongly associated with age-related local and systemic factors.

  
  
• ◾
  

  Examination should aim to do the following: (a) distinguish retinal vein occlusion as either branch retinal vein occlusion or central retinal vein occlusion, (b) determine the presence of macular oedema, (c) estimate the amount of retinal ischaemia, (d) check for retinal or iris neovascularization, (e) determine the cause.

Predisposing factors

• ◾
  

  Age: more than 50% of patients are older than 65 years.

  
  
• ◾
  

  Hypertension, particularly in branch retinal vein occlusion (BRVO).

  
  
• ◾
  

  Hyperlipidaemia.

  
  
• ◾
  

  Diabetes mellitus.

  
  
• ◾
  

  Oral contraceptive pill: the most common association in younger females.

  
  
• ◾
  

  Raised IOP in central retinal vein occlusion ( CRVO).

  
  
• ◾
  

  Smoking is a likely risk factor.

  
  
• ◾
  

  Uncommon predispositions may be more important under the age of 50 years: (a) myeloproliferative disorders, (b) acquired hypercoagulable states (e.g. hyperhomocysteinaemia, lupus anticoagulant, antiphospholipid antibodies), (c) inherited hypercoagulation diseases (e.g. activated protein C resistance; protein C and protein S deficiencies), (d) inflammatory disease associated with occlusive periphlebitis (e.g. Behçet syndrome, sarcoidosis), (e) miscellaneous causes (e.g. chronic renal failure, orbital disease, dehydration).

Systemic assessment

• ◾
  

  All patients: (a) blood pressure, (b) erythrocyte sedimentation rate (ESR), (c) full blood count (FBC), (d) blood glucose, (e) serum lipids, (f) plasma protein electrophoresis, (g) urea, electrolytes, and creatinine, (h) thyroid function tests (dysfunction associated) and (i) ECG (left ventricular hypertrophy associated).

  
  
• ◾
  

  Selected patients: (e.g. younger than 50 years, bilateral RVO, previous thromboses, family history of thrombosis); (a) chest X-ray, (b) C-reactive protein (CRP), (c) thrombophilia screen, (d) anticardiolipin antibody (IgG and IgM), lupus anticoagulant, (e) autoantibodies, (f) serum angiotensin-converting enzyme, (g) fasting plasma homocysteine, (h) treponemal serology.

Branch retinal vein occlusion