• Kanski = Kanski's Clinical Ophthalmology (found in library)
• Khurana = A.K. Khurana's Comprehensive Ophthalmology
• Rynes — likely refers to the ETDRS (Early Treatment Diabetic Retinopathy Study) criteria, sometimes attributed to the study group. The CSME definition originates from the ETDRS.

CSME (Clinically Significant Macular Edema) — Management

Definition (ETDRS Criteria)

1. Retinal thickening at or within 500 µm of the center of the fovea
2. Hard exudates at or within 500 µm of the center of the fovea with adjacent retinal thickening
3. A zone of retinal thickening ≥ 1 disc area (1500 µm), any part of which is within 1 disc diameter of the center of the fovea

CSME can be present at any stage of diabetic retinopathy — NPDR or PDR.

Classification

By OCT morphology (clinically used today):

By foveal involvement:

• Centre-involving DME (CI-DME): Thickening involves the foveal centre → primary indication for anti-VEGF therapy
• Non-centre-involving DME: Thickening spares the foveal centre → may observe or consider focal laser

Investigations

1. Slit-lamp biomicroscopy (90D / 78D lens) — gold standard for clinical diagnosis
2. Optical Coherence Tomography (OCT) — quantifies retinal thickness, identifies morphologic subtype, guides treatment; central subfield thickness (CST) >300 µm (female) / >320 µm (male) is significant
3. Fundus Fluorescein Angiography (FFA/IVFA) — identifies focal leaking microaneurysms, areas of capillary non-perfusion, foveal avascular zone (FAZ) integrity; essential before focal laser
4. OCT Angiography (OCTA) — evaluates macular ischaemia and FAZ enlargement without dye
5. Blood investigations: HbA1c, fasting blood glucose, lipid profile, blood pressure

Management

A. Systemic Control (Foundation of treatment)

• Glycaemic control: Target HbA1c < 7% — the UKPDS and DCCT trials demonstrated that tight glycaemic control reduces risk and progression of DME
• Blood pressure control: Target <130/80 mmHg; ACE inhibitors/ARBs preferred
• Lipid management: Statins reduce hard exudate burden; fenofibrate (FIELD study) reduces DME progression
• Renal status: Proteinuria worsens DME; nephrology co-management important

B. Anti-VEGF Therapy (First-line for CI-DME)

• RISE & RIDE (ranibizumab): ≥2-line BCVA gain in ~45% at 24 months
• PROTOCOL T (DRCR.net): Aflibercept superior to bevacizumab and ranibizumab when initial VA <69 letters; comparable when VA better
• VIVID/VISTA (aflibercept): Significant BCVA gains vs. laser alone

• Initiation: Monthly (4–6 loading doses) until maximum response
• Maintenance: PRN (treat-and-observe) or T&E (treat-and-extend)
• Assess response at 3–4 months; switch agents if <5-letter gain and persistent CI-DME at 6 months

Anti-VEGF agents are also preferred over PRP when DME co-exists with PDR. — Wills Eye Manual

C. Intravitreal Corticosteroids (Second-line / adjunct)

• Suboptimal response to anti-VEGF
• Anti-VEGF contraindicated (pregnancy, recent MI/CVA)
• Pseudophakic eyes (less cataract risk)
• Patient compliance issues (longer-acting implants)

D. Laser Photocoagulation

Focal/Grid Macular Laser

• Non-centre-involving CSME with focal leaking microaneurysms
• Extrafoveal microaneurysms as adjunct to anti-VEGF
• Patients where anti-VEGF/steroids are contraindicated (e.g., pregnancy)
• CSME that is predominantly focal with circinate hard exudates

• Burns applied directly to leaking microaneurysms (500–3000 µm from centre of fovea)
• Spot size: 50–100 µm; duration: 0.05–0.10 s; endpoint: mild whitening of microaneurysm
• FFA essential to localise target lesions

• Burns applied in a grid pattern over areas of diffuse leakage / thickening
• Spot size: 100–200 µm; spacing: 1 burn-width apart
• Avoid within 500 µm of foveal centre and 500 µm of optic disc margin

E. Surgical Management — Vitrectomy

1. Chronic DME unresponsive to anti-VEGF, steroids, and laser
2. Vitreomacular traction (VMT) contributing to DME — traction-induced macular oedema
3. Epiretinal membrane (ERM) with distortion and macular thickening
4. Dense premacular/subhyaloid haemorrhage
5. Co-existing tractional retinal detachment involving the macula

F. Emerging / Adjunct Therapies

• Faricimab (Vabysmo): Dual inhibition of VEGF-A and Angiopoietin-2; allows Q16-week dosing in some patients (YOSEMITE & RHINE trials)
• Port Delivery System (PDS) with ranibizumab: Sustained release intravitreal device
• Neuroprotective agents, gene therapy (investigational)

Treatment Algorithm Summary

CSME diagnosed
      │
      ├─► Centre-involving DME?
      │         │
      │        YES → Anti-VEGF (1st line) ──► Reassess at 3–4 months
      │                                            │
      │                                   Adequate response? → Continue PRN/T&E
      │                                   Inadequate response? → Switch anti-VEGF agent
      │                                                        → Add intravitreal steroid
      │                                                        → Consider focal/grid laser
      │                                                        → Vitrectomy (VMT/ERM/refractory)
      │
      └─► Non-centre-involving DME
                │
               YES → Observe OR Focal laser (extrafoveal microaneurysms)
                    → Anti-VEGF if threatening centre

Follow-Up Schedule

Key Points to Remember

• CSME is a clinical/biomicroscopic diagnosis; OCT confirms and quantifies
• Anti-VEGF is first-line for CI-DME — this is the current standard of care
• Focal laser retains a role for non-CI CSME and as adjunct
• Steroids are second-line; avoid in phakic, glaucoma-prone patients
• Vitrectomy reserved for traction-related or refractory chronic DME
• Systemic control is the backbone — ophthalmology cannot succeed without medical optimisation
• CSME can occur at any stage of diabetic retinopathy