IVT

Intravitréal Therapy (IVT)

Clarification: Endophthalmitis, increased risk of endophthalmitis due to blepharitis, keratitis, conjunctivitis, infection of the lacrimal tract -> treatment of the source of infection before injection

Declaration of consent

• Before the first injection
• When changing the preparation
• Once a year

ONO: KoGU only necessary for secondary CNVs or other indications (cave: C-Statsus Clinic). Primary preparation Eylea pre-filled syringe.

Anti-VEGF

Relative contraindication: TIA, stroke, miyocardial infarction over the last 6 months

Preparations

Avastin®: Off Lable Use
ONO: not approved
See below for approved products

Lucentis® (ranibizumab)

Approvals: wAMD, DME, RVO, myopic CNV, other CNVs

Eylea® (aflibercept)

Approval: wAMD, DME, RVO, myopic CNV

Beovu® (brolucizumab)

Approval: wAMD, DR
ONO: not approved (cave: serious side effects such as vasculitis)

Vabysmo®

Approval: wAMD, DME
Indication: Low responder
Follow-up after 2-5 days is absolutely necessary (side effects)
ONO: do not treat new patients with Vabysmo, not as an initial treatment (cave: side effects such as uveitis, vasculitis)

Eylea® 8 mg

Approval: wAMD, DME
Indication: Low responders
Application: 8mg = 0.07 mL (cave: other preparations are 0.05 mL)
Follow-up in 2-5 days is absolutely necessary (side effects)
ONO: not approved as initial treatment (cave: side effects unclear)

Afqlir®

Biosimilar anti-VEGF to Aflibercept 2 mg (Eylea®)
Manufacturer: Swiss manufacturer Sandoz®
Approval: WaMD, DME, RVO, myope CNV
Very high structural, functional and clinical resemblance to Eyle® a
Safety and effectiveness evidence: Approval study, real world data still limited
‍Dodeller F et al, Curr Ther Res Clin Exp 08/25_Development of Biosimilar Aflibercept SDZ-AFL
Bordon A F et al, Retina 10/24_Efficacy and Safety of Aflibercept SDZ-AFL Study
Zhou Y et al, Front Pharmacol 02/26_META-Analysis: Efficacy and Safety of Aflibercept Biosimilars

Current: ONO internal study by Dr. Berisha and Dr. Ray

Treatment regimens

Treat and Extend scheme (see diagram below)

Usual scheme (ONO: basic scheme)

1st diagnosis (always in consultation with ophthalmic surgery specialist)
Diagnosis can be confirmed before the first IVT using OCT-A (Angio-OCT) or angiography for patients from remote locations (e.g. laughing/Einsiedeln) OCT-A on IVT day

2. First IVT as soon as possible (if applicable, see above for KoGU)

3. Follow-up after first IVT with OCT M after 2-5 days

4. Second IVT 1 month after first IVT (same procedure for the first three injections for saturation)

5. Third IVT with follow-up after 2-5 days with OCT M, decide when the next IVT should take place

• No activity -> extend by 2 weeks
• Recurrent activity -> shorten by 1 week
• In case of visual acuity reduction -> 5 letters/lots of IRF/SRF -> shorten the interval to 4w

minimum interval 4 weeks

wAMD: Maximum control/IVT interval 16 weeks (completion of IVT after 3x 16 weeks), followed by follow-up with OCT M every 4-6 months

DME/RVO: no maximum control/IVT interval, extend by 4 weeks (instead of 2 weeks) after 16 weeks

Graduation

IVT for wAMD after an interval of 3x 16 weeks
NK after graduation from WaMD after 3 months with OCT M P and photos
After that, NK every 6 months

Questionable response to IVT

Evaluation of the maximum effect 10-14 days after IVI with OCT M > If applicable Switch to another anti-vegt

Unplanned treatment interruption

Detailed information and documentation in KG, NK with OCT M at the time when the next IVT would be planned with the responsible ophthalmic surgery specialist to discuss and determine further treatment intervals.

Follow-up checks

Basic checks GK

Every 6 months on both sides (OU)
Anamnesis: new drugs, diseases (e.g. stroke/TIA/MI)
Investigations OU

• OCT M P and photos (scanning laser scanning laser ophthalmoscopy (infrared laser) OU
  • OCT-A, if applicable
• Subjective refraction
  • If necessary, adjustment of glasses
• Amslergitter
• Applanation tonometry and papillary assessment: increased papillary excavation
• Front eye section: rubeosis iridis, cataract
• Incoming fundus copy in mydriasis: bleeding, neovascularization

Short check KK

2-5 days after every IVT

• Subjective refraction if visual acuity on AR is worse than in previous controls
• Air tono/applanation tonometry
• Front eye section: anterior chamber stimulus
• Central fundus copy in miosis: bleeding

Implementation of IVT

instrument table

• Hibidil® solution
• 6x round swab
• clip
• sterile perforated cloth
• eyelid speculum
• Stick swab
• BSS solution
• Medication (needle 30 g, 12mm)

Preoperative preparation

• topical anaesthesia with 3x Tetracaine® eye drops before the procedure in preparation
  
  • Alternatively: lidocaine 2% solution or gel (cavre: effect is slower and lasts less long)
• Disinfecting the operator's hands and putting on sterile gloves
• Disinfect songs, periorbital skin and eyelashes in the operating room three times with Hibidil® solution (do not wipe off)
• cover with sterile perforated cloth
• Using an eyelid blocker
• Irrigation of bulbar conjunctiva, fornices and caruncles with Hibidil® solution, exposure time 30 s
• Flushing the bulbar conjunctiva with BSS
• Medication must be available in sterile form
• Remove air bubbles from the syringe

injection

• Puncture via pars plana 3mm (pseudophak) or 3.5 mm (phac) from limbus
• 30 gauge injection cannula, maximum length 12 mm
• If the patient sees black: massage the bulb and wait a few minutes
• If pressure increase persists: paracentesis of the anterior chamber by surgeon

Post-operative

• No fixed medication
• Optava® eye drops for moisturizing when needed
• If necessary, eye drops 2x/day for four days
• If necessary, further therapy (ointments, pressure-lowering drops, Diamox® tablets, etc.) depending on the indications and only in exceptional cases

cave: no scientific evidence for empirical p.o. antibiotic prophylaxis

Follow-up checks

further control intervals according to clinical findings and injection regimen generally after Treat-and-Extend

Pro Re Nata (PRN) scheme

Only in exceptional cases, e.g. with myoper CNV or secondary CNV, consultation with ophthalmic surgery specialist

IVT depending on activity sign, no IVT if activity sign is missing

Checks usually 4 times a week with new indications

Activity sign

• Intraretinal fluid (IRF)
• Subretinal/sub-RPE liquid (SRF) > 50 μm (< 50 μm can be tolerated if there is no change in fluid AND stable visual acuity during the 3rd treatment visit)
• With DME/RVO: Extension may be possible with dry fovea and extrafoveal IRF as long as there is no visual impairment under extension

cave: IRF for microcystic macular edema and degenerative IRF e.g. via geographic atrophy in AMD should not be regarded as a sign of activity (“outer retinal tubulation”)

IVT basic control billing

• consultation, 10-15 minutes
• Cross-sectional image
• Visual acuity assessment, corrected (part of general basic services)
  • Subjective refraction (when the retina changes)
• Amsler network, on both sides
• Applanation tonometry and stereotactic papillary assessment
• Slit lamp examination of the front eye sections
• Biomicroscopy of the central fundus
  • Supplement for detailed examination of fundus periphery (possibly in mydriasis)

Intravitréal steroids

Ozurdex® (dexamethasone)

Approvals: DME, Uveitis, RVO
Indication: DME, uveitis, RVO (in case of lack of response to anti-VEGF)
Absolute contraindication: Known steroid responses
Relative contraindication: Phaker patient (cave: Cataracta secundaria), iridectomy (implant can enter the anterior chamber through iridectomy and damage the endothelium > Educate patient accordingly, instruct, close follow-up checks)

Check after 1 day (after initial application)
Check-up after 7 days
Check-up after 6-8 weeks

Duration of effect 3-4 months

Kenakort® (triamcinolone)

Approval: off-label use (cave: higher incidence of steroid response than Ozurdex® (Mishra et al. , Int. J.Oph. 2018)

Follow-up

Check after 1 day (only after initial application)
Check-up after 7 days
Check-up after 2-4 weeks

‍

Sources: Will's Eye Manual, Blaubuch Eye Clinic Inselspital Bern