This document discusses intravitreal injections for drug delivery to the posterior segment of the eye. It begins by explaining the challenges of drug delivery due to the blood-ocular barrier and how sustained release systems and nano-particles were developed. It then provides details on the procedure of intravitreal injection, including indications, agents used, aseptic technique, complications, and anti-VEGF agents like bevacizumab, ranibizumab, pegaptanib, and aflibercept.

1. Dr . MAHESHWARI S

3. INTRODUCTION
 Drug delivery into the posterior segment of the eye is
complicated by the blood-ocular-barrier
 Prescribed drugs have to overcome these barriers to
deliver therapeutic concentrations
 Thus, bio-degradable and non-biodegradable,
sustained release system for injection (or)
transplantations into the vitreous as well as drug
loaded nano-particles, micro- spheres, and liposomes
emerged .

4. INTRODUCTION
 Intravitreal injection is a highly targeted drug
therapy
 It involves injecting therapeutic agents
(drugs/air/gases) inside the vitreous cavity
through pars plana under aseptic precautions.
 It maximizes therapeutic drug delivery and
minimizes systemic complications.
 It is one of the most commonly performed
ophthalmic procedures at present.

5. HISTORY
 1911- Intravitreal injection was first described by
Deutschmann and Ohm. First used intravitreal injection was
air bubble to tamponade a retinal detachment.
 Triamcinolone acetonide (Kenalog) became the first
intravitreal drug with widespread application, used as a
treatment for macular edema associated with a variety of
etiologies

6.  1944- Von Sallmann first demonstrated efficasy of
intravitreal antibiotic injection for the treatment of
endophthalmitis
 1970-1974- PEYMAN et al heralded the use of
intravitreal antibiotics for the successful treatment of
bacterial and fungal endophthalmitis infection and
determined the non-toxic doses of various intravitreal
antibiotics.

7.  Anti VEGFs-
a. Pegaptanib sodium
b. Bevacizumab
c. Ranibizumab
d. Aflibircept
 Intravitreal steroids- Triamcinolone acetate
 Steroid implants-
a. Dexamethasone
b. Fluocinolone
 Antbiotics
a. Vancomycin
b. Cefazoline
c. Ceftazidine
d. Amikacin

8.  ANTIVIRALS
a. Ganciclovir
b. Foscarnet
c. Cidofovir
 ANTIFUNGALS
a. Amphotericine B
b. Fluconazole
c. Voriconazole
 AIR AND EXPANSILE GASES
a. Sulfur hexafluoride(SF6)
b. Perfluoropropane (C3F8)
c. Hexafluoroethane(C2F6)
 ANTI METABOLITES
a. Melphalan
b. Topotecan
c. Methotrexate

9. INDICATIONS
 ANTI VEGF
ARMD
Diabetic Retinopathy
Vascular Occlusion
Retinopathy of Prematurity
Neovascular Glaucoma
IPCV, Coats Disease etc
 ANTIBIOTICS AND ANTI FUNGALS- Endophthalmitis
 ANTI VIRALS – Viral retinitis in immunocompromised
patients
 ANTI METABOLITES- Chemotherapy
 STEROIDS- Macular edema, uveitis

10. PROCEDURE

11. INFORMED CONSENT
 Specific mention of the off-label use.
 Anti-VEGF agents- specific mentioning data regarding
thromboembolic events, particularly in high-risk individuals.
 Triamcinolone acetonide - consent should specifically
mention the increased risk of cataract formation, as well as
ocular hypertension or glaucoma.

12. ANESTHESIA
 Should be given prior to application of a sterile
preparation
 Topical medications such as proparacaine 0.5% drops
or lidocaine jelly to achieve adequate anesthesia
 If the patient has a low threshold for pain,
subconjunctival lidocaine can be administered
adjunctively
 Rarely, peribulbar , retrobulbar or general anesthesia is
required

13. ASEPSIS
 Several precautions are strongly recommended
to minimize the risk of infection.
 The instruments should be removed from sterile
packaging and dropped onto a sterile field.
 Take a procedural time-out to verify patient,
agent and laterality (2014)
 Once anesthesia has been applied, a 5%
povidone-iodine solution should be applied to the
ocular surface. It is the last agent applied to the
intended injection site before injection. (2014)
Bactericidal with rapid cytotoxicity

14.  The surgeon should have proper scrubbing as a
part of universal precautions.( 2014)
 Either surgical masks should be used or both the
patient and providers should minimize speaking
during the injection preparation and procedure to
limit aerosolized droplets containing oral
contaminants from the patient and/or provider
(2014)
 Once gloved( sterile/unsterile), the surgeon
applies a fenestrated lid drape similar to those
used in cataract surgery.
 There is no evidence to support the routine use of
a sterile drape.(2014)

15.  A lid speculum is then applied in
order to retract the eyelid and prevent
the patient from blinking.
 Avoid contamination of the needle
and injection site by the eyelashes or
the eyelid margins.
 Avoid extensive massage of the
eyelids either pre- or post-injection (to
avoid meibomian gland expression).

16.  Needle size varies according to the substance
injected:
 27-gauge needles used for crystalline
substances such as triamcinolone acetonide
 30-gauge needles commonly used for
the anti-VEGF agents.

17.  Needle length between ½ - 5/8 inches (12.7 to 15.75 mm) is
recommended
 Separate needles should be used to remove the medication
from the vial and to perform the actual injection. This helps
prevent both contamination and dulling of the needle.
 Studies suggest that smaller, sharper needles require less
force for penetration and result in less drug reflux.
 Longer needles may increase risk of retinal injury if the patient
accidentally moves forward during the procedure

18.  Any clock hour of the eye can be used
 Injection in the inferotemporal quadrant is
common
AGE INJECTION SITE FROM LIMBUS
1-6 months 1.5mm
6 months – 1 year 2mm
1-2year 2.5mm
2-6years 3mm
>6years 3-3.5mm in pseudophakic/aphakic eyes
3.5 – 4 mm in phakic eyes

19. NEEDLE INTRODUCTION AND INJECTION
 Sterile ophthalmic calipers used to mark the
injection site and to verify that adequate
anesthesia has been achieved.
 Patient is instructed to look 180° away from
the site in order to better visualize the
quadrant
 The surgeon introduces the needle through
the marked site smoothly and in a single
motion with the needle aimed toward the mid-
vitreous cavity.

20.  Once the surgeon is assured the needle is in the
vitreous and not within the subretinal space, the
plunger should be pushed in slow, steady
maneuver to prevent a sudden reflux through the
vitreous cavity, as this may disrupt vitreoretinal
adhesions
 The needle is removed, and a sterile cotton swab
is immediately placed over the injection site to
prevent reflux. (2014)
 Routine anterior chamber paracentesis is not
recommended (2014)
 Irrigation of the ocular periocular surface to
remove the povidone- iodine should be performed

21. INJECTION TECHNIQUE
STEP LIKE ENTRY PATH
- Pulling the conjunctiva
over the injection site with
forceps or a sterile cotton
swab to create a steplike
entry path.
- Decreases drug reflux and
risk of infection
STRAIGHT INJECTION
PATH

23.  An injection volume of 0.05 mL is most commonly used.
 Maximum safe volume to inject without preinjection paracentesis
is believed to be 0.1 mL to 0.2 mL.
 Larger injection volumes are uncommon, with two exceptions:
• Injection of gas for pneumatic retinopexy
• Injection of multiple intravitreal agents in one session
 Routine anterior chamber paracentesis is not recommended
(2014)

24. POST-INJECTION ANTIBIOTICS
 Currently, no data clearly demonstrates a reduced risk of endophthalmitis
following intravitreal injection when using post-injection antibiotics.
 Pre-, peri- or post-injection topical antibiotics are unnecessary. (2014)
 Although not required, the use of post-injection antibiotics is left to the discretion
of the treating physician, and typically does not extend beyond 72 hours
 The choice of antibiotic should be determined by community resistance profiles
and the patient’s allergies.
 A broad-spectrum fluoroquinolone is commonly used; however, the clinician may
need to consider other factors including medication allergies.

25.  Patients should be examined on post injection day 1 and 3.
 Monitoring of post injection IOP (2014)
 Anterior segment examination
 Post-injection dilated examination of the posterior segment (although some
viewed the return of formed vision as sufficient, others routinely dilate the
pupil and examine the posterior segment after injection ) 2014
 Symptoms of infection to be explained
 To share contact information
 To avoid head bath for 1 day and swimming for 3 days
 The use of post-injection antibiotics is left to the discretion of the treating
physician, and typically does not extend beyond 72 hours
 Follow up customised according to the patients status

26. COMPLICATIONS

27. ENDOPHTHALMITIS
 Endophthalmitis after injection of triamcinolone acetonide - 0.6%
 All other therapeutics had a risk of 0.1% per injection.
 Staphylococcus and streptococcus is a known cause of endophthalmitis
which has been suggested to be a possible contaminant due to
nasopharyngeal droplets.
 Vitreous wick syndrome is a theory that suggests vitreous incarceration into
a scleral wound which may act as a conduit for bacteria.
Prevention:
 A tunneled injection
 smaller gauge needle
 Placement of a sterile cotton tip applicator over the injection site

28. HEMORRHAGE
 Subconjunctival hemorrhage may occur due to laceration of
subconjunctival or episcleral vessels
 Vitreous hemorrhage may occur
 If the needle touches the ciliary body or retina
 In patients with abnormal neovascularization such as in
proliferative diabetic retinopathy.
 According to MARINA trial- Patients on warfarin did not have
significant ocular hemorrhagic complications, and
discontinuation of systemic anticoagulation is not
recommended.

29. INTRAOCULAR PRESSURE CHANGES
 Transient elevations in IOP following intravitreal injections are a
known side effect
 Repeated injections of anti-VEGF have been shown to have elevated
IOP readings over several visits.
 Ocular hypertension is a known side-effect of corticosteroids, but this
mechanism of sustained ocular hypertension is related to the steroid
rather than the injection itself.
 Hypotony has been reported after uncomplicated intravitreal
injections but was believed to be secondary to ciliary body toxicity
from the injected medication.

30. OTHER COMPLICATIONS
 Retinal vascular occlusion
 Corneal abrasion
 Cataract progression
 Retinal pigment epithelium tear
 Retinal tear or detachment
 Intraocular Inflammation - 1.4-2.9%

32. VASCULAR ENDOTHELIAL GROWTH
FACTOR (VEGF)
 VEGF was first identified in 1983
 Originally known as vascular permeability factor (VPF)
 It is a signal protein produced by cells that stimulates the
formation of blood vessels.
 It restores the oxygen supply to tissues when blood
circulation is inadequate such as in hypoxic conditions.

33. .

35. Characteristics of VEGF induced blood vessels:
 Endothelial cell hyperplasia
 Leaky and friable vessels
 Loss of pericytes
 Increase tortousity
 More propensity for hemorrhage and leakage

36. ANTI VEGF
Block the VEGF molecules
Decreasing the abnormal and harmful new blood
vessels formation
Decreasing the leakage and swelling of the retina
Stabilization / improvement in vision

37. INDICATIONS OF
INTRAVITREAL ANTI VEGF
ARMD
Diabetic Retinopathy
Vascular Occlusion
Retinopathy of Prematurity
Neovascular Glaucoma
IPCV,Coats Diseaseetc.

39. PEGAPTANIB(MACUGEN)
 Pegylated Aptamer
 50 Kda
 MACUGEN ( Pegaptanib sodium)
 Specifically binds to 165 isoform of VEGF A
 Discovered by Gilead Sciences and
licensed in 2000 to EyeTech
Pharmaceuticals.
 Approval was granted by the U.S.
Food and Drug Administration (FDA)
in December 2004.

40.  Administered in a 0.3 mgdoseonce every
sixweeks by intravitreal injection
 Marketed asapre-filled syringe
 ABSORPTION : Very SLOW systemic absorption
 Plasmat½isabout 10days
 Vitreoust½isabout94hrs
 METABOLISM:ByendoandexonucleasesexcretedbyKIDNEY
 Presentlynotinusebecauseof lower efficacy (doesn’t inhibit VEGF
completely)

41. BEVACIZUMAB
 Recombinant humanized monoclonal antibody that blocks angiogenesis
by inhibiting VEGFA(allisoforms)
 Received its first approval in 2004, for combination usewith standard
chemotherapy for metastatic coloncancer
 It hassincebeen used for
• Certain lung cancers
• Renalcancers
• Ovarian cancers
• Glioblastoma multiforme of thebrain
 Not yet approved by FDA (Off label use) in Ophthalmology
 Rosenfield et al were the first ones to describe & publish the off label
use of intravitreal Bevacizumab in 2005.

42.  DOSAGE: 1.25 mg/ 0.05ml in adults, and half that dose in
babies.
 HALF LIFE :Approximately 20 days
 INTERVAL BETWEEN INJECTIONS: Typically administered at
4-6 week intervals, although this varies widely based on
disease and response.

43. 1. CVS- Htn, thromboembolism
2. CNS- headache, dizziness, sensory neuropathy
3. GIT- abdominal pain, vomiting
4. Renal – proteinuria (> 3.5mg dose)

44. RANIBIZUMAB(LUCENTIS)
 Monoclonal antibody fragment( fab)
 Binds to all VEGF A isoforms with higher
affinity than bevacizumab
 Developed from the identical parent
antibody as avastin.
 Lucentis was approved for neovascular AMD
in the U.S. In 2006.
 It has a FDA approval for use in DME in
2015.

45.  Dose: 0.5 mg/0.05 ml once every month
 HALF LIFE: approximately 9days
 Safe in renal impairment

46. DIFFERENCE BETWEEN BEVACIZUMAB AND
RANIBIZUMAB
BEVACIZUMAB (AVASTIN) RANIBIZUMAB
(LUCENTIS)
Full sized antibody Antibody fragment
148 kilodaltons 48 kilodaltons
Half life-20 days Half life- 3 days
Clearance is slow Clearance 100 folds faster
Long action & less dosage 140 times higher affinity
Costs less Costly

47. AFLIBERCEPT: EYLEA
 Recombinant fusion protein
 Consist of VEGF-bindingportions from the
extracellular domains of human V E GF
receptors 1 and 2, that are fused to the Fc
portion of the human IgG1 immunoglobulin
 Approval was granted by the U.S.
Food and Drug Administration (FDA)
in December 2011.

48.  DOSAGE: 2 mg/0.05 mL every 4 weeks (monthly) for
the first 12 weeks (3 months), followed by 2 mg/0.05
mL once every 8 weeks (2 months).
 HALF LIFE: 5-6 days

49. BROLUCIZUMAB
 Humanized single-chain antibody fragment
 Inhibits all isoforms of VEGF-A.
 It is the smallest of the anti-vegf antibodies.
 Brolucizumab has a molecular weight of 26 kda, compared
with 48 kda for ranibizumab, 115 kda for aflibercept and
149 kda for bevacizumab.
 It is possible to concentrate brolucizumab up to 120 mg/ml,
allowing the administration of 6 mg in a single 50-ml ivt
injection.
 On a molar basis, 6 mg of brolucizumab equals
approximately 12 times the 2.0-mg dose of aflibercept and
22 times the 0.5-mg dose of ranibizumab.
 Thus this drug has potential advantages in the treatment of
armd. Assuming comparable half-life, higher molar doses of
drug may be cleared more slowly from the eye, thus
prolonging duration of action.
 Small molecular weight + higher molar doses + high drug
concentration gradient between the vitreous and retina may
support support superior drug distribution into the retina.

51. Major systemic events in past 3 months
 Stroke
 Cardiacarrest
 Uncontrolledhypertension
 Anticoagulants
 Fibro vascular proliferation threatening macula
 Active ocular or periocular inflammation
 Known hypersensitivity to Anti VEGF agents

52. ADVERSE OCULAR EVENTS
 Increase in IOP
 Subconjunctival haemorrhage – occurs in 10% of cases,and common
in patients on aspirin
 Intraocular inflammation- 1.4-2.9%
 Cataract
 Rebound macular edema
 CRAO
 Rhegmetogenous RD
 Infectious endophthalmitis- Reported in 0.019 – 1.6% of the cases in
a multicenter trials

53. SYSTEMIC ADVERSE
EFFECTS
 Significant non ocular haemorrhagic events like
ecchymosis, GI haemorrhages, subdural hematoma etc
 Potential risk of ATE (Arterial thromboembolic event)
 Non fatal stroke
 Non fatal MI
 Vascular deaths

55.  Intravitreal steroids are used for their anti-inflammatory,
angiostatic, and anti-permeability effects.
 MECHANISM
 Decreases growth factors
 Stabilises endothelial cell tight junctions
 Reduces permeability to water and solutes

56. INTRAVITREAL
STEROIDS
TRIAMCINOLONE
ACETONIDE
DEXAMETHASONE
FLUCINOLONE
ACETONIDE

57. TRIAMCENOLONE
ACETONIDE
 Synthetic steroid of the glucocorticoid family with a fluorine in
the ninth position
 It appears as a white- to cream-colored crystalline powder
and it is practically insoluble in water and very soluble in
alcohol
 Therapeutic effects for approximately three months after
4 mg intravitreal TA injection.
 Maximum effect duration - 140 days
 They are considered as off label for intraocular use.

58.  Kenalog-40 (40 mg/mL, Bristol-Myers
Squibb, NJ) - off-label for intraocular
injections.
 TrivarisTM (80 mg/mL, Allergan Inc.,
Irvine, CA) – FDA approved
 Triesence (40 mg/mL, Alcon Inc., Fort
Worth, TX) - FDA approved

59. DEXAMETHASONE - OZURDEX
 FDA approved drug
 Five times more potent than TA
 Provides sustained distribution of 700 μg of dexamethasone in the
vitreous cavity
 Formed by a solid biodegradable polymer (Novadurtm, Allergan,
Irvine, CA, USA)
 Degradation produces lactic acid and glycolic acid, which are
subsequently converted to and eliminated as carbon dioxide and
water.
 Implanted using a novel 22-gauge injecting applicator
 Peak effect by 2 months
 Effect lasts for 6 months

60. FLUOCINOLONE ACETONIDE
 Non bioerodible
 Releases steroid at submicrogram levels for 36 months
 It has high local activity and least systemic effects
Bausch &
Lomb,
Rochester, NY
0.59mg
Anchored to
sclera
Initial release
0f 0.6mic /day
later 0.3-
0.4mic for 30
months
RETISERT
Alimera
Sciences,
Alpharetta,
GA, USA
190 μg
Free floating
low dose of
0.2 μg per
day, with a
delivery
lifespan of
more than 2
years
ILUVIEN

62.  Intraocular penetration of antibiotics in non vitrectomied
inflamed eyes is unreliable.
 The parameters directing the choice and dosing of intravitreal
antibiotics are
 Ability to achieve and maintain therapeutic levels
 Efficacy and safety of intravitreal antibiotics
 Intraocular distribution
 Clearance from the eye.
 In situations like endophthalmitis intravitreal injections are the
preferred route of drug delivery.

63. INTRAVITREAL DOSE
 The efficacy of intravitreal antibiotics is based on how long the
intraocular drug level exceeds the minimal inhibitory concentration
(MIC) of a particular drug against the implicated organism.
 The safe and therapeutic intravitreal doses of commonly used
antibiotics have been determined in experimental and clinical
studies.
 Increased retinal toxicity to routinely used doses of intravitreal
antibiotics was demonstrated in eyes filled with silicone oil.
 This was possibly due to reduction of the preretinal space. Using
one quarter of the nontoxic dose could prevent retinal toxicity.

67. Activity Spectrum and
Choice of Antibiotics
 Prompt clinical, therapeutic and diagnostic decisions have to be
made based on a thorough history and clinical examination
 Bactericidal agents are preferred to bacteriostatic agents as
eye is an immune privileged site.
 The commonly used empirical antibiotic regimen consists of
vancomycin combined with ceftazidime or amikacin.

68.  THE ENDOPHTHALMITIS VITRECTOMY STUDY
proved the efficacy of the combination of vancomycin to
cover gram-positive bacteria which are the most
common pathogens causing postoperative
endophthalmitis and amikacin to cover gram-negative
bacteria which are rare but cause more fulminant
endophthalmitis
 The choice of antibiotic can be further modified based
on sensitivity spectrum based on the culture reports.

69. CLEARANCE OF DRUGS
FROM THE EYE
 Clearance of the drug depends on:
 Molecular size
 Solubility coefficient
 Ionic nature
 Surgical status of the eye
 Ocular inflammation

70.  For the drugs eliminated through posterior route the
drug clearance is retarded and elimination life
prolonged in inflamed eye due to compromise of RPE
pump.
 Drugs eliminated through anterior route have enhanced
removal in an inflamed eye
 Inflammation increases rate of elimination of
vancomycin in aphakic eyes only.

71. FREQUENCY AND SAFETY OF REPEATED
INTRAVITREAL ANTIBIOTIC INJECTIONS
 Most endophthalmitis cases recover with single intravitreal antibiotic
administration with or without vitrectomy
 Repeat antibiotic injections are required for persistent endophthalmitis and
known to have a worse outcome.
 Decision to repeat intravitreal injections of antibiotics depend on subjective
assessment of the clinical response, microbiological results and toxicity of
the drugs to be given.
 The aim of repeat dosing should be to optimize the duration of drug
exposure to concentrations above the MIC, rather than to aim at higher peak
levels.

72.  Adequate and safe antibiotic levels can be better
achieved by more frequent rather than higher dosages
with reduced risk of retinal toxicity.
 Retreatment with intravitreal antibiotics with or without
vitrectomy should be considered where stabilization or
improvement is not noted after first 36 to 48 hours or
signs of worsening appear.
 If possible choice of repeat antibiotics should be guided
by culture results of vitreous or aqueous tap.

74. ANTI FUNGAL INTRAVITREAL
DOSAGE
HALF LIFE IN
VITREOUS (IN
HOURS)
COVERAGE
AMPHOTERICIN B 5-10 mic g 7-15 Candida
Aspergillus
Penicillium
Rhizopus
FLUCANOZOLE 100mic g 3 Candida
Aspergillus
Histoplasma
fusarium
ITRACONOAZOLE 10 mic g As above
VORICONAZOLE 50-100 mic g 2.5 As above

77.  Intravitreal antiviral medications have been usedfor
treatment of viralretinitis.
 Typically occurs in immunosuppressed patients suffering
from debilitating illnesses
 Canceror AIDSor in patients receiving
systemic corticosteroids
 Immunosuppressive medications for organtransplantattion

78. ANTI VIRAL INTRAVITREAL
DOSAGE
HALF LIFE IN
VITREOUS (IN
HOURS)
COVERAGE
ACICLOVIR 240mic g HSV, VZV
GANICICLOVIR 2-5MG 7-8 HSV, VZV,CMV
FOSCARNET 1-2.4mg 77 HSV, VZV,CMV
CIDOFOVIR 20-100mic g 24.4 HSV, VZV,CMV

79. VITRASERT
 Gancicovirimplant.
 Indicated for the treatment of CMV retinitis in
patients with acquired immunodeficiency
syndrome (AIDS)
 4.5 mg drug in 2.5 mm pellet completelycoatedby
drug permeable polyvinylalcoholandincompletely
coatedwith impermeable ethyl vinylacetate.
 Releasesdrug at rate of 1 microgm/hr.
 Mean intravitreal conc. achieved is 4.1
microgm/ml.
 Therapeutic levels upto 8months

81.  Thefirst IVIof gaswasperformed by Ohmin 1911.
 Ohmpunctured the sclera, drained the fluid, and injected air
into the vitreous cavity to hold the retina in place, but made
aretinal break by administering the injection through the
retina. Hewassuccessfulin two of his fourcases.

82. COMMONLY USEDGASES
 Sulfur hexafluoride gasexpands2.5 times its volume in 48
hours and maintains aneffective volume for 7daysto 10days
 Perfluoropropane (C3F8)expandsfour times its volume in
96hours and maintains an effective volume for 35days.

83. PNEUMATIC RETINOPEXY
Usedto manage RDresulting from either
a single break smaller than 1-o’clock hour
and located within the superior 8 hours of
the ocular fundus or by several small
retinal breakswithin1-o’clock hour.

84.  Thevolume of gasto be injected (0.3– 0.5 mL)isdrawn
through amillipore filter into asyringe.
 Oncethe needle is located in the globe, it is pulled back to
leave only 2 mm in the vitreous, and the volume of the gasis
injected suchthat onlyonebubbleisformed.
 Paracentesis is commonly performed.

86. METHOTREXATE
 INDICATION:
a. Intraocular lymphoma
b. Noninfectious posterior or panuveitis
 Half life in vitreous – 5 days
 DOSAGE:
400µg/0.1ml Once a month for 3 months

87. MELPHALAN
 Used for retinoblastoma seeding in vitreous
 DOSAGE:
 20-30micro gram / 0.1 ml
 Half life: 90 min
 PROCEDURE:

88. With strict asepsis under general anaesthesia
The clock hour of injection was selected based on vitreous
seed activity, with the goal to inject 1 to 2 clock-hours’
distance from the vitreous seeds to avoid direct contact with
the seeds and avoid extraocular extension
Intravitreal injection through pars plana approximately 2.5-
3mm from limbus based on patients age
cryotherapy was applied to the injection site to include the
needle in the ice ball.
The needle was withdrawn through the ice ball during the first
freeze.
Triple-freeze-thaw cryotherapy was completed.
The eyeball was gently moved with forceps back and forth
to cause drug dispersion throughout the vitreous cavity and
preferably to the site of vitreous seeds

89. TOPOTECAN
 Topoisomerase I inhibitor that can produce lethal
damage in DNA replication of cells
 INDICATION: Used in vitreal seedings of
retinoblastoma adjunctive to melphalan
 DOSAGE: up to 20 µg Intravitreally


91. INFLIXIMAB
 Acts against Tumour Necrosis
Factor- Alpha (TNF-ά)
 INDICATION:
Chronic non-infectious uveitis
 DOSE: 2mg/0.05ml

92. SIROLIMUS (RAPAMYCIN)
 Bacteria-derived immunosuppressant
 Inhibits the activation of T cells and B cells and
reduces cytokine production
 INDICATION: Chronic non-infectious uveitis
 DOSAGE:
 Given every 2 months for non infectious Post. Uveitis
 2 different doses: 880µg or 440µg

94. MARINA STUDY
Minimally Classic/Occult Trial of the Anti-VEGF Antibody
Ranibizumab in the Treatment of Neovascular AMD
 Phase 3, randomized, multicenter, double-masked, sham-
controlled study
 Enrolled 716 patients with minimally classic lesions or occult
with no classic lesions.
 Patients were randomized 1:1:1 to either sham (n=238),
ranibizumab 0.3 mg (n=238), or ranibizumab 0.5 mg (n=240).
 Primary endpoint- Proportion of subjects losing less than 15
ETDRS letters at one year.
 Secondary endpoint- Change in VA from baseline

95. RESULTS
MAINTAINING VISION
patients losing fewer than 15 letters
95% (452/478) of treated
Vs
62 % (148/238) of control
group (p<.0001)
IMPROVING VISION
patients gaining 15 letters or more
25% (59/238) of 0.3 mg Ranibizumab
vs
34 % (81/240) of 0.5 mg of Ranibizumab
vs
5 % (11/238) of controls
• Ranibizumab therapy was associated with clinically and statistically significant
benefits with respect to visual acuity and angiographic lesions during 2 years of
follow-up in patients with minimally classic or occult lesions with no classic choroidal
neovascularization.
• These efficacy outcomes were achieved with a low rate of serious ocular adverse
events and with no clear difference from the sham-treated group in the rate of
nonocular adverse events.

96. ANCHOR STUDY
 Phase III, randomised, multi-centre double-masked active treatment-
controlled trial
 Comparing two different doses of Ranibizumab to verteporfin photodynamic
therapy (PDT) in treating subfoveal neovascular macular degeneration.
 423 patients in the United States, Europe and Australia
 Randomised 1:1:1 to either PDT plus sham injection or to placebo PDT
plus Ranibizumab (0.3 mg or 0.5 mg) monthly for 24 months.
 Fluorescein angiography every three months to determine the need for
additional PDT or placebo PDT
 Primary endpoint- Proportion of subjects losing less than 15 ETDRS
letters at one year.
 Secondary endpoint - Change in VA from baseline

97. RESULTS
MAINTAINING VISION
patients losing fewer than 15 letters at 12
months
94% in Ranibizumab 0.3 mg
Vs
96% in Ranibizumab 0.5 mg
vs.
64% in PDT group (p < 0.0001)
IMPROVING VISION
patients gaining 15 letters or more
36% (Ranibizumab 0.3 mg)
Vs
40% (Ranibizumab 0.5 mg)
Vs
6% (PDT) (p < 0.0001
• The ANCHOR study showed that ranibizumab administered monthly by intravitreal
injection was superior in efficacy to photodynamic therapy with verteporfin in patients
with subfoveal, predominantly classic choroidal neovascularization associated with
age-related macular degeneration.
• The first-year results of our study and the 2-year results of the MARINA study,
considered together, demonstrate that ranibizumab was effective with an acceptable
adverse-event profile in the treatment of all angiographic subtypes of choroidal
neovascularization associated with age-related macular degeneration

98. CATT STUDY
COMPARISON OF AMD TREAMENT TRIAL
 Multicentre, randomised, double-blind, controlled clinical trial
 Recruitment- 1208 patients
 Primary Outcome- Change in visual acuity
 Secondary outcomes
 Number of treatments
 3-line change in visual acuity (15 letters on ETDRS chart)
 Change in subretinal and intraretinal fluid on OCT
 Change in lesion size on fluorescein angiography
 Incidence of complications of treatment (endophthalmitis, retinal
detachment, cataract, uveitis)
 Cost of treatment
 Dosage: 0.50 mg (in 0.05 ml of solution) for ranibizumab and 1.25 mg (in
0.05 ml of solution) for bevacizumab.

99. RESULTS
 The CATT trial provided evidence that bevacizumab is an effective
alternative to ranibizumab in the treatment of wet AMD at the 1-year and 2-
year time-points.
 Visual acuity outcomes were not statistically different between the drugs,
when the same dosing regimes were compared.
 The trial confirmed that as required dosing is an effective means of
administration of both anti-VEGF agents, and was not proven to be inferior
to monthly dosing for either drug.
 From a side-effect standpoint, there was no difference in the rates of death
or thrombo-embolic events between the drugs.
 However, somewhat curiously, and reflecting an area of ongoing concern,
the rate of serious adverse events and hospitalisations was higher in
bevacizumab patients, though this difference occurred over conditions not
previously identified as associated with anti-VEGF therapy.

100. RESTORE study
FOR DME
 Intravitreous injection of ranibizumab (0.5 mg) and
sham laser
 Injection of ranibizumab (0.5 mg) and focal/grid laser
photocoagulation
 sham injection and focal/grid laser photocoagulation
 At 12 months, the mean change in visual acuity in the
group getting ranibizumab alone (+6.1 letters) and in
the group getting ranibizumab plus laser (+5.9 letters)
was significantly better compared with the group
getting laser alone (+0.8 letters; both P <0.0001).

101. BEAT ROP
NUMBER ENROLLED: 150 infants (67 with zone I, 83 with posterior
zone II) enrolled, 143 survived; 75 randomized to conventional laser, 75
to intravitreal bevacizumab
RATIONALE: Anti-VEGF agents are efficacious in the treatment of stage
3+ ROP in zone I and II
OUTCOME MEASURES: Recurrence of ROP (primary outcme), interval
from treatment to recurrence, need for surgery
RESULTS: Significant treatment effect for zone I ROP (4% recurrence
with intravitreal bevacizumab as compared to 22% recurrence with laser)
but not for zone II disease

102. REFERENCES
 AAO- Guidelines and technique Of intravitreal injection
 Intravitreal Injection Guidelines - Ekta Rishi and Pramod Bhende
 Endophthalmitis: Current Trends, Drugs and Protocols -Aditya
Verma, Vinata Muralidharan and Eesh Nigam
 Intravitreal injections - Shalabh Sinha
 Intravitreal steroids – Albert J Augustin
 Updated guidelines for intravitreal injection- Colin et al
 Yanoff