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Intravitreal Injections

Common Diseases Treated by Intravitreal Injections

  1. AMD (neovascular age related macular degeneration)
  2. CSME/PDR (clinically significant macular edema/ proliferetive diabetic retinopathy)
  3. Retinal Vein Occlusions
  4. EndophthalmitisUveitis
  5. CME (cystoid macular edema)
  6. CNVM (choroidal neovascular membrane) secondary to multiple retinal diseases
  7. Informed 

Consent and Risks of Intravitreal Injections

Discuss the indications, risks, benefits, and alternatives with patients.  Obtain informed consent, and have the patient's signature on the consent form witnessed. 

The RISKS of intravitreal injections include:

  • PainBleeding (subconjunctival, vitreous hemorrhage)
  • Retinal tear / detachmentCataract (from inadvertently hitting the lens)
  • Infection (Endophthalmitis)Loss of vision (from any of above)
  • Loss of the eye (from a severe infection)Increased IOP, with damage to optic nerve (steroids)
  • Need for surgery (to address some of the complications above)
  • Stroke/Heart-Attack (with Anti-VEGF medications, controversial)
  • Off-label use (for Avastin, Kenalog, other medications)
  • Need for multiple injections in future (patients need to understand this)


BENEFITS of Intravitreal Injections depend on the ocular pathology being treated, but mainly include improvement of vision or prevention of worsening of the vision (in the case of AMD or DR).  In the case of an infection, the benefit is direct delivery of the antibiotic/antifungal into the eye close to the nidus of the infection. 

ALTERNATIVES to intravitreal injection can include observation, surgery (pars plana vitrectomy), or laser treatment (e.g. photodynamic therapy) depending on the ocular disease.  


Common Intravitreal Medications

  • Bevacizumab (Avastin) 1.25mg/0.05ml (0.675mg/0.03ml if considering using for treatment of Zone I+ ROP in an infant)
  • Ranibizumab (Lucentis) 0.5mg/0.05ml
  • Triamcinolone acetonide (Kenalog) 0.1cc of 4mg/ml   (Triesence/ Trivaris is alcohol-free preparation that is FDA approved for intraocular use)
  • Ganciclovir Intravitreal 4mg/0.1mL - administer 2 mg in 0.05 mL (twice weekly for CMV Retinitis for 14 days for induction)

  • ‪Foscarnet Intravitreal 2.4mg/0.1ml ‬‪- administer 1.2 mg in 0.05 mL
  • Cidofovir - 20 micrograms
  • Fomvirsen - 330 micrograms
  • Methotrexate - 400 micrograms
  • Vancomycin 1mg/0.1ml
  • Ceftazidime 2.25mg/0.1ml
  • Amikacin 0.4mg/0.1ml
  • Amphotericin B; 5 micrograms/0.1 mL
  • Voriconazole - 50-100 micrograms/0.1 mL
  • Dexamethasone 0.4mg/0.1ml


Anesthesia

Retina Specialists usually use topical, subconjunctival, or pledgets for common in-office intravitreal injections.  The choice of anesthetic depends on the Retina Specialists' preference, and also dictated by how the patient tolerated prior injections.  Retrobulbar block may need to be used for an inflamed eye in the case of endophthalmitis requiring a tap and inject.  In case of intravitreal bevacizumab or ranibizumab an acute inflammed eye is an contraindication for intravitreal injection. 

Several studies have looked at the different choices of intravitreal injections.  One randomized controlled trial found that topical anesthesia was effective for most patients[1]In this study, patients felt the least pain with the actually injection when a subconjunctival anesthetic was given.  However, they felt more pain when the actual anesthetic was being administered subconjunctivally.  Therefore the collective pain score (anesthesia pain + intravitreal injection pain) was greater for the subconjunctival group compared to the topical group (inwhich patients had less pain during the administration of the anesthetic, but slightly higher pain score during the actual intravitreal injection).

Topical tetracaine or proparacaine eyedrops can also be effective.  In a similar fashion, pledgets soaked with lidocaine or tetracaine can be placed in the inferotemporal fornix and allowed to rest on the globe. 

Another option is to use a gel type anesthetic, such as lidocaine 2% or 4% jelly, or Tetravisc.  Other points to remember:

  • Subconjunctival anesthesia has higher risk of a subconjunctival hemorrhage
  • Allow adequate time for anesthetic to take effect (can be as fast as 1 - 2 minutes for subconj, but would wait longer for topical lidocaine jelly, such as 5 min)
  • If a patient is very nervous or "jumpy" consider doing subconjunctival injection so they do not move during the actual intravitreal injection
  • If using topical anesthesia (since patients feel the injection more), remind them immediately before the injection that they will feel pressure, so that they do not get surprised and move their eye. 


Preparation for Intravitreal Injection

  • Patient should be supine with neck well supported
  • Ensure that the headrest is secure and will not unlock during the injection (as patients have a tendency to get nervous and extend their necks and push on the headrest)Close the door and make sure there are no distractions during the injection which could cause the patient to have a saccade and move their eyes
  • Ensure that you have all required instruments before starting, as it is very uncomfortable for patient to wait with Betadine on their eyes if you have to leave the room to get something needed for the injection
  • Do a surgical "timeout" before the procedure to confirm the correct patient, correct eye, and any allergies.  Preferably the timeout should be done with a technician or a nurse to confirm with the patient the procedure.


Injection Site

  • Usually inferotemporal for ease of access
  • Some Retina Specialists will do the injection in the superotemporal quadrant, as they feel that should a complication such as a retinal detachment form, it can be easier treated with a pneumatic retinopexy.  

Asepsis

  • Most important is povidone-iodine 5% solution as it has evidence based data showing risk reduction for endophthalmitis in ocular surgery.
  • Antibiotic use is controversial, and most Retina Specialists do not pre-treat with antibiotics; however most do use it postoperatively for approximately 3 days (which is likely for medico-legal reasons).  A study from Bascom-Palmer suggested that post-injection antibiotics do not reduce the incidence of endophthalmitis[2].  More and more Retina Specialists are abandoning the use of post-injection antibiotics, and this practice may be stopped in the near future.  Studies are also showing resistance developing in use of antibiotics[3].
  • 5% povidone-iodine solution should be placed on the globe and allowed to sit on the eye for at least 30-60 seconds.  One may also use 10% Betadine swabs to gently clean the eye and eyelashes, however 10% Betadine is associated with more corneal toxicity. Sterile lid speculum with closed blades (to isolate lashes better)
  • Gloves are optional, however patients may feel more comfortable if the surgeon uses gloves.
  • Do not talk (or cough, or sneeze) while preparing or performing the intravitreal injection, as Dr. McCannel from UCLA showed at AAO (Chicago 2010) that the most common source of the bacteria causing endophthalmitis was from the surgeon's mouth.  One should consider wearing a mask, and not minimize talking during the injection.  If you have to talk, turn your head away from the surgical field.   


Injection Technique

Variations in technique exist, and the following is an example of how the author does intravitreal injections:

  1. Confirm informed consent obtained
  2. Confirm the eye.
  3. Do not talk during injection.
  4. Surgical time-out to confirm correct medication and correct eye
  5. Place patient in near supine position; make sure the headrest of the chair is stable
  6. Topical proparacaine (wait 10-15 seconds before placing Betadine)
  7. 10% Betadine swab to inferior cul-de-sac, to allow the Betadine to start working; ask patient to blink multiple times to spread the Betadine
  8. Place 2% lidocaine jelly on the eye, focusing on inferotemporal quadrant.  (Note:  Betadine placed prior to lidocaine jelly to sterilize the globe prior to placing the jelly so as not to have bacteria trapped in the jelly and possibly increase risk of endophthalmitis).
  9. Ask patient to close their eyes, and return in 2-5 minutes.
  10. Apply Betadine swab again to inferotemporal quadrant and inferior cul-de-sac, as well as to eyelashes (do not manipulate much so as not to liberate bacteria from the lashes)
  11. Place sterile closed-blade eyelid speculum (careful not to cause corneal abrasion and save yourself a phone call from the patient with a painful corneal abrasion). 
  12. Clean again with Betadine
  13. Mark the location of injection:  3-3.5mm for pseudophakes, 3.5-4.0 mm for phakic patients.  Tip:  Can use the end of a TB syringe (without needle attached) to mark 3.5-4.0 mm.  After marking and causing an indentation with the TB syringe, you can place Betadine again -- the Betadine will sit in the indentation ring and nicely highlight the injection site.  Careful with subconj anesthesia so as not to cause too much chemosis or subconj hemorrhage as this case affect your visibility of the injection site mark.
  14. Have the patient look 180 degrees away from the injection site.  For example, if injecting the right eye in the inferotemporal quadrant, ask the patient to look up and to the left. 
  15. Hold syringe in dominant hand, and a Q-tip in the non-dominant hand
  16. Do not talk and ask patient not to talk during the injection.  Make sure the needle tip (which is usually short 30g) is always kept absolutely sterile
  17. Using your dominant hand, rest your wrist on the patient's cheek for hand stabilization
  18. Insert the needle at the marked site in a smooth and single motion, aiming for the mid-vitreous cavity
  19. Insert the short 30g needle about 1/2 length in (to make sure you are in the vitreous cavity and not in subretinal space)
  20. Swing over with your non-dominant hand to push down on the plunger in a smooth fashion.  (Note:  some surgeons prefer to inject with one-hand; the author feels that using two hands is more stable).  Do not move the needle while inside the eye so as to not cause traction on the vitreous and potentially cause a retinal tear/detachment.
  21. As you remove the needle out, cover the injection site with a Q-tip that is in your non-dominant hand
  22. Rinse the Betadine off of the patients eye
  23. Ensure optic nerve perfusion (patient should be at least light perception).  Paracentesis is usually not required, unless a large volume of medication is injected.  Some Retina Specialists prefer to check and document the IOP and not let the patient leave until the IOP has reduced to an acceptable level.  When injecting Kenalog or Triesence which is 0.1cc, this causes a rapid and high IOP and it is not uncommon for patients to be temporarily NLP after the injection.  Warn patients about this.  Tip:  One can try to place pressure on the globe (e.g., Lidocaine 4% anesthetic solution on a Q-tip at the proposed injection site) to squeeze some aqeous out of the eye and lower the IOP prior to injection and possibly prevent the NLP scare that the patient may get.  
  24. Optional:  Place topical antibiotic and have patient use the antibiotic qid x 3 days
  25. Review endophthalmitis and retinal detachment precautions with the patient.


Post-Injection Care Tips

  • Make sure to wash off Betadine well so the patient does not have irritation/corneal toxicity
  • Reassure patients that they may see floaters which can be an air bubble, or can be the medication (in the case of Kenalog or Triesence)
  • Review endophthalmitis and RD precautionsSome practices will do a phone follow-up with patients 3-7 days after the injection; one week in-office follow-up is at the Surgeon's discretion, but likely not needed.


Follow up

Depends on the disease being treated, but is usually in the order of 4-6 weeks.


Similar safety and efficacy of intravitreal bevacizumab compared to ranibizumab

Numerous trials (CATT trial, IVAN trial, GEFAL, MANTA, LUCAS) conducted worldwide have shown Bevacizumab injection in the eye to be non-inferior to Ranibizumab injection in the eye in terms of efficacy and safety in AMD. Bevacizumab on the other hand has the advantage of significantly reducing the cost of therapy. However, intravitreal bavacizumab injection has not been approved by the Food and Drug Administration (FDA) and the use in the eye is hence 'off label'. All patients need to be clearly informed when taking written consent for intraocular bevacizumab.

The possible drawback of AvastinTM may be that as the company does not manufacture and pack it for ocular use the drug does not come in a single use vial. Despite all the precautions there is an increased risk of serious eye infection to a small extent after intravitreal injection.


Additional Resources

Video:  Univeristy of Iowa, Intravitreal Injection Technique:  https://video.google.com/videoplay?docid=-4029538953224029219

Article: Preventing infections: injection technique: https://dx.doi.org/10.4172/2327-5073.1000118

American Academy of Ophthalmology. Retina/Vitreous: Intravitreal Injections Practicing Ophthalmologists Learning System, 2017 - 2019 San Francisco: American Academy of Ophthalmology, 2017.


References 

  1. Blaha GR, Tilton EP, Barouch FC, Marx JL.Randomized trial of anesthetic methods for intravitreal injections. Retina. 2011 Mar;31(3):535-9. 
  2. Rumya R. Rao, Golnaz Javey, Philip J. Rosenfeld, William J. Feue.  Elimination of Post-Injection Topical Antibiotics after Intravitreal Injections.  ARVO May, 2011 
  3. 3. Kim SJ, Toma HS.  Ophthalmic antibiotics and antimicrobial resistance a randomized, controlled study of patients undergoing intravitreal injections.Ophthalmology. 2011 Jul;118(7):1358-63. Epub 2011 Mar 21.
  4. Intravitreal Injections, Focal Points, Volume XXVII, Number 8, September 2009.

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