Diabetic retinopathy: screening and management

Introduction

Diabetes affects around 4.5 million adults in the UK^​1​. Diabetic retinopathy — a type of diabetic eye disease — is a microvascular complication of diabetes affecting retinal blood vessels. It’s a leading cause of visual impairment and blindness, particularly in working-age adults (i.e. those aged 20-65 years) with the condition, who have a 20-fold risk increase of blindness compared with individuals without diabetes^​2​.

The UK prevalence of retinopathy in individuals with diabetes is estimated to be around 34%, with 12% classified as sight-threatening^​3​. Higher rates of diabetic retinopathy are observed in men, people of South Asian and Afro-Caribbean ethnicity, as well as those from socioeconomically deprived backgrounds^​4​.

Chronic hyperglycaemia is a key driver of retinopathy, while most patients with diabetes will develop retinopathy to some extent within 20 years of diagnosis^​5​. People with both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are at risk.

Owing to later diagnosis, retinopathy is more common at the initial presentation of T2DM. However, the cumulative long-term risk is higher in people with T1DM (95% versus 60% over 15 years)^​2​. Additional risk factors include a longer duration of disease, poor glycaemic control and diabetes-related comorbidities^​2​. Other ocular conditions — including cataracts and glaucoma — are also more prevalent in people with diabetes^​2​.

People with, or at risk of, diabetic retinopathy often experience substantial healthcare burden, which has a significant impact on those in work or education. This is because they are required to attend regular appointments across multiple health services and need lifelong management of their condition^​6​.

Visual impairment resulting from diabetic retinopathy also impacts psychological wellbeing and the ability to complete everyday tasks such as driving and reading^​7​. A national screening programme was established in 2003 to enable early detection and timely referral for treatment^​8​, while National Institute for Health and Care Excellence (NICE) guidelines have been published to optimise management^​5​.

Pharmacists play an important part in optimising patient outcomes. Contributions may include supporting lifestyle changes, improving glycaemic control (i.e. with and without medication), promoting attendance to regular eye screening appointments, assessing adherence to treatment and identifying ‘red flags’ that require urgent referral.

Risk factors

Anyone with T1DM or T2DM is at risk of developing diabetic retinopathy, with additional risk increased by the following:

• Poor glycaemic control (i.e. raised HbA1c);
• Duration of diabetes or late diagnosis;
• Hypertension;
• Dyslipidaemia;
• Smoking;
• Obesity;
• Diabetes-related comorbidities (e.g. nephropathy);
• Pregnancy with pre-existing diabetes;
• Ethnicity, as there is a higher risk in South Asian and Afro-Caribbean populations;
• Male gender;
• Family history^​2,9​.

Pathophysiology

The retina has a high metabolic demand, with oxygen and nutrients supplied through the central retinal artery and its capillaries^​10​.

Persistently raised blood glucose levels can lead to biochemical and structural changes to the retinal vasculature such as oxidative stress, inflammation and the accumulation of advanced glycation end-products formed through the non-enzymatic glycation of proteins and lipids^{​10–12​}.

Capillaries become more fragile, microaneurysms form and vascular permeability increases^​12​. This results in the leakage of fluid, lipids and blood into retinal tissue and can cause diabetic macular oedema (DMO), with the macula being the part of the retina responsible for central vision. This leakage distorts the layers of the retina, which subsequently affects vision^​11,12​.

Additionally, in response to vascular damage, angiogenic factors, such as vascular endothelial growth factor (VEGF), are released, which stimulates the formation of new, fragile and highly permeable blood vessels prone to haemorrhage^​12​.

This is known as proliferative diabetic retinopathy (PDR), which can lead to further sight-threatening complications, including vitreous haemorrhage, fibrosis (i.e. scar formation), retinal detachment and neovascularisation of the iris, which may cause glaucoma (see Figure 1^{​10–12​}).

Figure 1: Diabetic retinopathy compared with healthy retina

Screening considerations

Early diabetic retinopathy is frequently asymptomatic and usually detected through routine screening^​2,11​. Patients with more advanced disease may present with reduced, blurred, fluctuating vision or floaters^​2​.

Early detection of diabetic eye disease is vital. The more prompt the treatment, the more outcomes are improved for patients. The NHS Diabetic Eye Screening Programme (DES) has been established by the UK National Screening Committee (UK NSC) to provide screening in anyone with T1DM and T2DM aged 12 years and over, which is identified through GP records^​8​.

Each nation within the UK has its own screening policy based on these recommendations — although, there may be slight differences between them. For example, Scotland offers six-monthly screening in some high-risk cases^​13​.

Invitations for screening are sent to eligible patients annually; however, if no signs of diabetic retinopathy are seen on two consecutive visits, this will reduce to once every two years as the risk of developing sight-threatening disease is lower^​14,15​. Attendance is not mandatory but should be encouraged^​8​. Those not wishing to attend regularly may request that invitations be deferred for up to three years^​16​.

Appointments and diagnosis

The diabetic eye screening appointment involves the following:

• Measurement of patient’s visual acuity in each eye against a Snellen chart or equivalent;
• Instillation of dilating eye drops such as phenylephrine or tropicamide;
• Digital imaging taken of each retina using specialist equipment^​16​.

Patients should be advised not to drive themselves to appointments as their vision may be blurry for up to four hours afterwards, while contact details should be provided for reporting unexpected adverse events^​17​.

Patients who must avoid dilating eye drops — for example, if patients have acute angle-closure glaucoma — may have images taken without dilation. However, this should be noted as the quality of imaging is likely to be poorer^​17​. If images cannot be taken successfully, referral for further assessment should be made^​18​.

The administration of dilating eye drops by both registered and non-registered healthcare professionals during the screening process falls within the Medicines Act 1968 and may be permitted without the need for a prescription or patient group direction (PGD) — provided the eye drops are obtained within legislation^​17​.

Images are graded against national standards to classify the extent of retinopathy and maculopathy (i.e. the presence of macular oedema) into ‘referable’ and ‘non-referable’ disease (see Table 1^​2​). Images of the retina are reviewed for presence of microaneurysms, haemorrhages or other exudates from leaking vessels, increased tortuosity of the retinal vasculature and the presence of neovascularisation.

Table 1: Grading of diabetic retinopathy

If referral to secondary care is made, further assessment and imaging may be undertaken, including:

• Slit-lamp and fundus examination of the eyes;
• Fundus fluorescein angiography, where fluorescein dye is injected intravenously and images taken of the retinal vasculature to identify venous haemorrhages, occlusions or neovascularisation;
• OCT, which shows a cross-section image of the retinal layers and is used to measure the thickness of the macula and monitor presence of oedema or structural changes^​2​.

Pharmacists may encourage patients to attend regular eye screening and hospital appointments during structured medicine reviews or through health promotion campaigns involving diabetes care.

For example, ask: “Have you attended your diabetic eye screening appointment recently?” If not, discuss that retinopathy may develop or worsen without symptoms, as well as that early detection and treatment reduces the long-term risk of visual impairment. Pharmacists may also signpost patients to seek urgent advice if ‘red flag’ ocular symptoms are present. Local optometrists may offer urgent assessment under the Minor Eye Conditions Service (MECS). Otherwise, referral to the local A&E or eye casualty unit, if available, should be made (see Box)^​19​.

Diabetic retinopathy management

In 2024, NICE published guidelines on the management and monitoring of patients with diabetic retinopathy^​5​. These guidelines recommend that all clinicians involved in patients’ diabetes care support them to optimise long-term control of their condition to reduce the impact of diabetic retinopathy^​5​.

Non-pharmaceutical management in primary care

Lifestyle changes related to smoking, weight and exercise should be recommended^​2​. Tight control of both HbA1c and blood pressure has been shown to reduce the incidence of microvascular disease, including retinopathy. A reduction in HbA1c from 9% to 7.2% in people with T1DM was shown to reduce the incidence of retinopathy by 76%^​2,21​.

The results of a Cochrane review, published in 2023, demonstrated that interventions to control blood pressure reduced the five-year incidence of retinopathy; although, they did not significantly slow the progression of disease unless patients were hypertensive at presentation^​22​. Off-label use of fenofibrate may reverse diabetes-induced retinal effects and may delay the progression of retinopathy in patients with T2DM. However, no evidence currently exists in T1DM^​23​.

It should also be noted that there are concerns that a rapid reduction in HbA1c (e.g. with medication) can lead to the worsening of diabetic retinopathy and vision loss in the short term^​2,21​. However, evidence reviewed by NICE did not demonstrate this — although it was of poor quality. It is therefore recommended that the patient’s ophthalmologist is made aware of any change to treatment that may lead to a rapid change in HbA1c, to allow appropriate assessment and monitoring^​5​. Recent treatment developments, including GLP-1 inhibitors, require ongoing surveillance owing to evidence suggesting they may lead to early worsening of retinopathy^​24​.

Pharmacists can educate people with diabetes on the risk of retinopathy and provide advice on optimising glycaemic control with or without medication. This may include support with quitting smoking, monitoring weight, blood pressure and blood glucose, as well as tailoring advice accordingly.

Management in secondary care

Monitoring and treatment of diabetic retinopathy is managed in secondary care by medical retina specialists. In patients with bilateral disease, eyes should be monitored and treated separately as they may show different stages of retinopathy^​5​.

Even if one eye is affected more severely, treating both is important to help reduce progression of disease in either eye, which could have significant consequences^​5​. Non-proliferative diabetic retinopathy (NPDR) should be monitored every 6–12 months if moderate, or every 3 months if severe, to detect progression to PDR or DMO early^​5​. Evidence for active treatment of NPDR is currently lacking^​5​.

PDR treatment

Treatment options for PDR include laser treatment (i.e. pan-retinal photocoagulation [PRP]) or injection of biologic agents targeting VEGF into the vitreous cavity of the eye (i.e. intravitreal route).

PRP involves using laser to burn areas of neovascularisation and haemorrhage, reducing fluid leakage into the retina. It does not improve vision by itself but can delay progression^​11​. Anti-VEGF treatments are usually offered if PDR remains despite a complete course of PRP, which work by inhibiting VEGF and stopping the growth of new vessels^​5​.

Only one anti-VEGF agent — ranibizumab — is currently licensed for patients with diabetic retinopathy without macular oedema; although, other medications may be used off-label depending on local commissioning agreements^​5​.

If significant vitreous haemorrhage (i.e. not clearing within three months) or retinal detachment is present, removal of the vitreous gel and temporary replacement with gas or silicone (i.e. vitrectomy) may help. Vitreous gel will naturally turn over and replace itself over time^​5​.

DMO treatment

Treatment options for DMO include intravitreal injection of anti-VEGF agents or steroid implants, or laser treatment to the macula^​5​.

A macular laser aimed at areas of oedema rather than new vessels is recommended where oedema is not affecting central vision or where the patient’s visual is still good^​5​.

Anti-VEGF agents

Where central vision is threatened and central retinal thickness (CRT) is larger than 400 microns — measured by OCT — anti-VEGF agents are recommended^​25​. However, health inequalities may be avoided by offering treatment earlier to patient populations with naturally thinner retinas who may take longer to reach the CRT threshold. For example, those of South Asian and Afro-Caribbean descent, especially women^​5​.

Anti-VEGF agents require initial loading — monthly injections for three to five months depending on the drug — followed by regimes tailored to the initial response to treatment^​25​. This may be at fixed intervals or following a ‘treat and extend’ protocol where dosing intervals are increased between each injection until no further response is seen^​25​.

Treatment should stop if there is significant worsening of oedema despite treatment or if irreversible damage occurs^​25​. Newer agents, including high-dose aflibercept (8 mg) or faricimab, may offer longer dosing intervals of up to 16 weeks, which may help to reduce capacity issues in busy injection clinics and treatment burden for patients^​25​.

Lower-cost, therapeutically equivalent biosimilar agents are available for ranibizumab and aflibercept (2 mg), but these may not achieve the same treatment intervals as newer agents^​25​.

Overall, a balance between lower-cost and longer-acting agents needs to be found to optimise cost-effectiveness without overburdening services. NHS England has produced guidance to support both commissioners and ophthalmology services^​25​.

Potential risks of intravitreal injections include endophthalmitis (i.e. an infection inside the eye), intraocular inflammation, retinal detachment and cataract. Injections should be administered only by trained healthcare professionals^​26​.

Anti-VEGF agents carry a theoretical risk of systemic effects, including non-ocular bleeding and arterial thromboembolic events. Treatment should be withheld in patients with a recent history of stroke, transient ischaemic attack or myocardial infarction^​26​. There is limited evidence for their use during pregnancy^​26​.

Intravitreal corticosteroids

Intravitreal steroid implants offer an alternative where anti-VEGF treatment is contraindicated. This can include during pregnancy or where less frequent administration may be beneficial, if an individual has dementia or learning difficulties, for example. These implants release steroids slowly over time.

Dexamethasone is licensed for administration every six months, although in practice four-monthly administration is used owing to early loss of effect^​25​. Fluocinolone implants release the drug over three years, although rescue treatment with anti-VEGF or dexamethasone is often required, which reduces cost-effectiveness^​25,27​.

Additional risks for steroids can include cataract formation and raised intraocular pressure, which requires close monitoring^​27​.

A summary of the available treatments for PDR and DMO can be seen in Table 2^​4​.

Table 2: Treatments recommended for diabetic retinopathy, as per NICE guidance

The pharmacist’s role

Pharmacists in secondary care settings may provide advice to patients regarding risks and benefits of intravitreal injections, as patients often report high anxiety levels and lack of understanding around intravitreal injections, especially before their first dose^​28​.

They can also support services to switch treatments to biosimilar agents, where appropriate, to improve cost-effectiveness.