Ozempic and Eye Problems: Diabetic Retinopathy, Vision Changes, and Screening Guidance

The SUSTAIN 6 cardiovascular outcomes trial flagged a statistically significant increase in diabetic retinopathy complications with semaglutide compared to placebo.

Key data from SUSTAIN 6:

• Retinopathy complications (vitreous haemorrhage, blindness, or need for intravitreal injection or photocoagulation) occurred in 3.0% of the semaglutide group versus 1.8% of the placebo group
• Hazard ratio: 1.76 (95% CI 1.11 to 2.78)
• The excess events were concentrated in patients with pre-existing retinopathy at baseline and in those who experienced the most rapid HbA1c reductions

Interpretation:

This finding is consistent with the long-established "early worsening" phenomenon seen with any rapid glycaemic improvement. The same pattern has been documented with insulin intensification.

The mechanism relates to retinal vascular autoregulation: chronic hyperglycaemia causes compensatory changes in retinal blood flow, and rapid normalisation disrupts these adaptations, temporarily worsening ischaemia.

Important context:

• Patients without baseline retinopathy showed no increased risk
• The SUSTAIN 6 population was high-risk (long diabetes duration, established CVD), not representative of all Ozempic users
• Long-term data beyond 2 years suggest the initial worsening stabilises and overall retinopathy progression is not accelerated by semaglutide

The SmPC lists diabetic retinopathy complications as a known adverse reaction with semaglutide.

Diabetic retinopathy is the leading cause of preventable blindness in working-age adults in the UK. Approximately 30% of patients with type 2 diabetes have some degree of retinopathy at diagnosis.

Stages of diabetic retinopathy:

• Background retinopathy (R1): microaneurysms and small dot haemorrhages. Vision is unaffected. Most common stage at diabetes diagnosis
• Pre-proliferative retinopathy (R2): cotton wool spots, venous beading, and intraretinal microvascular abnormalities (IRMA). Indicates significant retinal ischaemia
• Proliferative retinopathy (R3): new blood vessel formation (neovascularisation) on the disc or elsewhere. High risk of vitreous haemorrhage and tractional retinal detachment
• Diabetic maculopathy (M1): oedema or exudates within one disc diameter of the fovea. Can cause central vision loss at any retinopathy stage

Why rapid HbA1c reduction worsens retinopathy:

• Chronic hyperglycaemia causes retinal capillary pericyte loss and basement membrane thickening
• The retina adapts to high glucose by increasing blood flow (a compensatory mechanism)
• Rapid glucose normalisation removes this compensatory drive, unmasking ischaemia
• Ischaemic retina releases VEGF (vascular endothelial growth factor), promoting neovascularisation and macular oedema
• The risk correlates with the magnitude and speed of HbA1c reduction, not with the specific drug used

Patients whose HbA1c drops by more than 22 mmol/mol (2.0%) within 3 months are at highest risk of early worsening.

Not all patients starting Ozempic face retinopathy risk. Identifying those who do allows targeted screening and monitoring.

Higher risk patients:

• Pre-existing proliferative or pre-proliferative retinopathy (R2 or R3)
• Long duration of diabetes (more than 10 years)
• HbA1c above 75 mmol/mol (9.0%) at Ozempic initiation, where large reductions are anticipated
• Previous laser photocoagulation or intravitreal anti-VEGF treatment
• Concurrent hypertension (systolic above 140 mmHg), which independently worsens retinopathy
• Pregnancy (not applicable for Ozempic, which is contraindicated, but relevant if switching from Ozempic to insulin)

Pre-treatment assessment:

• Confirm retinal screening is up to date. The NHS Diabetic Eye Screening Programme (DESP) invites patients annually
• If the most recent screening was more than 12 months ago, arrange an updated retinal photograph before starting Ozempic
• Review the most recent screening grade. Patients with R2 or worse should be discussed with ophthalmology before initiating treatment
• Document baseline visual acuity. A simple Snellen chart check in the GP surgery provides a reference point

Lower risk patients:

• No baseline retinopathy (R0) or background retinopathy only (R1)
• HbA1c below 64 mmol/mol (8.0%), where HbA1c reductions will be modest
• Diabetes duration under 5 years
• Well-controlled blood pressure

These patients can start Ozempic with standard annual screening and no additional ophthalmic review.

NICE NG 28 and the Royal College of Ophthalmologists recommend enhanced retinal surveillance when intensifying glycaemic treatment in patients with existing retinopathy.

Recommended screening schedule while on Ozempic:

• No baseline retinopathy (R0): continue standard annual DESP screening. No additional monitoring required
• Background retinopathy (R1): annual screening remains appropriate. Consider a 6-month interim screen if HbA1c drops by more than 15 mmol/mol (1.5%) in the first 3 months
• Pre-proliferative retinopathy (R2): arrange ophthalmology review before starting Ozempic. Screen at 3 to 4 monthly intervals during the first year of treatment
• Proliferative retinopathy (R3) or maculopathy (M1): active ophthalmological management should be in place. Discuss with the retinal specialist before initiating semaglutide. More frequent monitoring (every 2 to 3 months) is advisable

Practical considerations:

• The NHS DESP uses digital retinal photography, which is adequate for screening
• Patients with R2 or higher may need optical coherence tomography (OCT) to assess macular oedema
• If new visual symptoms develop during treatment (blurred vision, floaters, visual field loss), urgent ophthalmology referral is indicated regardless of the most recent screening result
• Document retinal screening dates in the diabetes care plan to ensure follow-up is not missed

Slower dose titration (extending each dose step to 8 weeks rather than 4) may reduce the speed of HbA1c improvement and lower the risk of retinopathy worsening, though this approach is not formally validated in trials.

Beyond the diabetic retinopathy concern, patients occasionally report visual symptoms while taking Ozempic. Most are benign and related to glycaemic changes rather than direct ocular toxicity.

Blurred vision during dose changes:

• Refractive changes occur when blood glucose levels shift significantly. The lens of the eye absorbs glucose and swells or contracts with plasma glucose fluctuations
• Patients starting Ozempic may notice temporary blurred vision during the first 2 to 4 weeks as blood glucose improves
• This effect is self-limiting and resolves once glucose levels stabilise. Patients should be advised not to change their spectacle or contact lens prescription during this period

Dry eyes:

• Reported by some patients, though not listed as a common adverse reaction in the SmPC
• May be secondary to dehydration from reduced fluid intake (nausea-related) or from the medication itself
• Lubricating eye drops (artificial tears) provide symptomatic relief

Floaters:

• New floaters, particularly if associated with flashing lights or visual field loss, require urgent assessment to exclude vitreous haemorrhage or retinal detachment
• In patients with known proliferative retinopathy, new floaters are a red flag and should prompt same-day ophthalmology review

Visual disturbance from hypoglycaemia:

• Blurred or double vision can occur during hypoglycaemic episodes, particularly in patients also taking sulfonylureas or insulin
• This resolves once blood glucose is corrected above 4.0 mmol/L

The SmPC does not list semaglutide as causing direct optic nerve or retinal toxicity outside the context of rapid glycaemic change.

The retinopathy signal from SUSTAIN 6 must be weighed against the substantial glycaemic and cardiovascular benefits of semaglutide.

For most patients, the risk-benefit balance strongly favours treatment.

Arguments for starting Ozempic despite retinopathy concerns:

• SUSTAIN 6 demonstrated a 26% reduction in major adverse cardiovascular events, driven by a 39% reduction in non-fatal stroke
• Long-term glycaemic control reduces lifetime retinopathy risk. The UKPDS demonstrated that every 11 mmol/mol (1%) reduction in HbA1c reduces microvascular complications by 37%
• The early worsening phenomenon is typically temporary (3 to 6 months) and manageable with ophthalmological monitoring
• Patients who develop macular oedema during rapid glycaemic improvement respond well to anti-VEGF injections (ranibizumab, aflibercept)

Risk mitigation strategies:

• Start at 0.25 mg and consider extending each titration step to 8 weeks in high-risk patients to slow the rate of HbA1c decline
• Optimise blood pressure control (target below 140/80 mmHg, or below 130/80 mmHg if retinopathy is present, per NICE NG 136)
• Ensure retinal screening is current before initiation
• Consider an HbA1c target that permits gradual rather than abrupt improvement

When to avoid Ozempic:

• Active proliferative retinopathy awaiting laser treatment or anti-VEGF injections. Stabilise the retinopathy first, then reconsider
• Patients who decline or cannot access retinal screening

For the majority of patients with type 2 diabetes, particularly those without baseline retinopathy, the eye-related risk from Ozempic is minimal and should not deter prescribing.