Recent advances in ophthalmology - Dr. Parag Apte

RECENT ADVANCES IN
OPHTHALMOLOGY
By Dr Parag Apte

What will be covered
1. Lasers in Ophthalmology
2. Intravitreal injections in Ophthalmology
3. Microsurgical techniques in Ophthalmology

LASERS IN OPHTHALMOLOGY
• Lasers emit electromagnetic waves of characteristic properties and
energies.
• Laser term consist of light amplification of stimulated emission of
radiation.
• They consist of coherent monochromatic electromagnetic waves.
• Common types of lasers are:
• Eximer laser – 193 NM wavelength – PRK, LASIK
• Double frequency Yag Laser – 532 NM wavelength – Focal and Pan Retinal
Photocoagulation
• Diode laser – 810 NM wavelength – Cyclo Photcoagulation
• Nd : YAG laser – 1063 NM wavelength – Iridotomy and posterior capsulotomy

Pattern Scan Laser(PASCAL)
• The PASCAL Photocoagulator is an
integrated semi-automatic pattern
scan laser photocoagulation system
designed to treat ocular diseases
using a single shot or multiple shots
at a single click to predetermined
pattern array.
• Laser source :Nd:YAG laser (green
or yellow)
• Delivery device: slit lamp or laser
indirect ophthalmoscope (LIO)
• It has Control system for selecting
power , duration and spot size
• It also has micropulse technology to
deliver sub threshold burns by
reducing the duty cycle and thus
less damage to tissue & less heat
production in macular area
• Used for PRP and macular lasers

FEMTOSECOND LASER
• Mode-locking -pulses of light of extremely short duration, in the order of
picoseconds (10−12s) or femtoseconds (10−15s) are produced.
• Femtosecond laser technology systems use neodymium:glass 1053 nm
(near-infrared) wavelength lightto cause photoablation
Indications
• In femto-LASIK to creat Clear Corneal Incisions
• It replaces a mechanical device (microkeratome) to create a precise
corneal flap
• Femto-cataract surgery to create
Corneal incision
Capsulotomy
Phacofragmentation

DIAGNOSTIC
• Scanning Laser Ophthalmoscopy
• Laser Interferometry
• Optical Coherence Tomography
• Wavefront Analysis

Scanning Laser Ophthalmoscopy
• In the scanning laser ophthalmoscope (SLO), a narrow laser beam
illuminates the retina one spot at a time, and the amount of
reflected light at each point is measured. The amount of light
reflected back to the observer depends on the physical
properties of the tissue, which, in turn, define its reflective,
refractive, and absorptive properties. Media opacities, such as
retinal haemorrhage, vitreous haemorrhage, and cataract, also
affect the amount of light transmitted back to the observer.
Because the SLO uses laser light, which has coherent properties,
the retinal images produced have a much higher image resolution
than conventional fundus photography.
• Used to study
• SLAP test
• retinal and choroidal blood flow
• microperimetry,

Tests Performed on the Scanning Laser
Ophthalmoscope
1) Scanning Laser Acuity Potential (SLAP) Test: The
letter E corresponding to different levels of visual acuity (ranging
from 20/1000 to 20/60) is projected directly on the patient’s
retina. The examiner directs the test letters to foveal and/or
extrafoveal locations within the macula, and determines a subject’s
potential visual acuity.
This is especially helpful in individuals who have lost central
fixation but still possess significant eccentric vision.

2) Microperimetry / Scotometry
The SLO could visualize a particular area of the retina and test its
sensitivity to visual stimuli, thereby generating a map of the seeing
and non-seeing areas.

3) Hi-Speed FA / ICG
• Fluorescein and Indocyanine Green Angiography (FA/ICG)
performed using the SLO is recorded at 30 images per
second, producing a real-time video sequence of the
ocular blood flow

Optical Coherence Tomography(OCT)
• Diode laser light in the near-infrared spectrum (810 nm)
• Partially reflective mirror is used to split a single laser beam into two, the
measuring beam and the reference beam
• Measuring beam is directed to the retina , laser beam passes through the
neurosensory retina to the retinal pigment epithelium (RPE) and the choriocapillaris. At
each optical interface, some of the laser light is reflected back to the OCT’s
photodetector
• Reference beam is reflected off a reference mirror at a known distance from the
beam splitter, back to the photodetector. The position of the reference mirror can be
adjusted to make the path traversed by the reference beam equal to the distance
traversed by the measuring beam to the retinal surface. When this occurs, the wave
patterns of the measuring and reference beams are in precise synchronization,
resulting in constructive interference. This appears as a bright area on the resulting
cross-sectional image. However, some of the light from the measuring beam will pass
through the retinal surface and will be reflected off deeper layers in the retina. This
light will have traversed a longer distance than the reference beam, and when the two
beams are brought back together to be measured by the photodetector, some degree
of destructive interference will occur, depending on how much further the measuring
beam has traveled. The amount of destructive interference at each point measured
by the OCT is translated into a measurement of retinal depth and graphically
displayed as the retinal cross-section.
• OCT images are displayed in false color to enhance differentiation of retinal
structures. Bright colors (red to white) correspond to tissues with high reflectivity,
whereas darker colors (blue to black) correspond to areas of minimal or no reflectivity.
The OCT can differentiate structures with a spatial resolution of only 10 μm

Anterior segment OCT
• Measures accurately the tear meniscus. Anything
below 164 um is abnormal.
• Useful to quantify dry eye, compare efficacy of
treatments.

Wavefront Analysis and Aberrometery
• Lasers are used in the measurement of complex
optical aberrations of the eye using wavefront
analysis and Hartmann-Shack aberrometer

Therapeutic Uses
• Lids and Adnexa
• Anterior Segment
• Posterior Segment

Lids and Adnexa
Skin: (usually CO2 laser)
 Lid Tumours : carbon dioxide laser ,benign and
malignant ,bloodless but scarring, lack of a
histologic specimen, and inability to assess margins.
 Blepharoplasty (carbon dioxide or erbium:YAG laser
)
 Xanthalesma ( green laser)
 Aseptic Phototherapy
 Pigmentation lesion
 Laser Hair Removal Technique
 Tattoo Removal
 Resurfacing
Lacrimal Surgery Endoscopic Laser
Dacryocystorhinostomy

Anterior Segment
• Conjunctival Growths and Neovascularization
• Corneal Growths and Neovascularization
• Refractive Surgery
• Laser in Glaucoma
• Laser in Lens

Refractive Surgeries
• Photorefractive
keratectomy
• Laser subepithelial
keratomileusis (LASEK)
• Laser-assisted in situ
keratomileusis (LASIK)
• FEMTO LASIK
• RELEX SMILE

Femto -LASIK
In laser assisted in situ keratomileusis (LASIK), a hinged partial
thickness corneal stromal flap is first created with a rapidly moving
automated femto laser, the flap is lifted and the laser applied onto
the stromal bed.
Lamellar dissection with the microkeratome
Refractive ablation with the excimer laser
In Intra-LASIK or Femto-LASIK or All-Laser LASIK, corneal flap is
made with Femtosecond laser instead of microkeratome
INDICATION
myopia (up to 8D)
low hyperopia (up to 3D)
Astigmatism upto 3D
COMP;ICATION
Wrinkles in flap
Cellular interface proliferation

Lasers in Glaucoma
• Laser treatment for internal flow
block
• Laser peripheral iridotomy
• Laser iridopLasty (GoniopLasty)
• Laser treatment for outflow obstruction
• Laser Trabeculoplasty
• Excimer Laser Trabeculostomy
• Laser Sclerostomy
• Miscellaneous laser procedures
• Cyclophotocoagulation
• Laser suture lysis (LSL)
• Reopening Failed Filtration sites
• Laser synechialysis
• Goniophotocoagulation
• Photomydriasis (pupilloplasty)

Laser treatment for internal flow block
•Laser peripheral
iridotomy
•Laser
iridopLasty
(GoniopLasty)

ND YAG laser Iridotomy
• Laser- Q-switched Nd:YAG
lasers (1064 nm)
• Area- Peripheral third of the
iris but inside the arcus
• Site- Iris crypt or a thinned
area of the iris
• Location - Between 11 o’clock
and 1 o’clock
• Size -200 - 500 μm in size
• Power - 4-8 mJ
• Pulses/burst - 1-3
• Spot size – Fixed
• Gush of pigment and fluid is
noted at the end of t/t

Laser Iridoplasty (Gonioplasty)
Indication is Plateau
iris & Nanophthalmos
Spot size-100–200µm
Power-100–300 mW
duration -0.1 second
Number -10- 20 spots
evenly
distributed over360º

Laser treatment for outflow
obstruction
•Laser Trabeculoplasty
•Excimer Laser Trabeculostomy
•Laser Sclerostomy

Laser trabeculosplasty (LTP)
a) Argon laser trabeculoplasty (ALT) : 50 µm spot size
and 1000-mW power for 0.1 second , 3–4° apart 20–
25 spots per quadrant
b) Selective Laser trabecuLopLasty (SLT) : Q-
switched, frequency-doubled 532-nm Nd:YAG laser,
400-µm spot , 0.8 mJ power , 180° with 50 spots or
360° with 100 spots , 3–10 ns duration
COMPLICATIONS
Iritis
Pressure elevation
Peripheral anterior
synechiae
Hyphema

Excimer Laser Trabeculostomy((ELT)
• precise and no thermal damage to surrounding tissues
• ab-interno (used intracamerally) : 308-nm xenon-
chloride (XeCl) excimer laser delivers photoablative
energy

Laser sclerostomy
• Nd:YAG laser, the dye
laser, 308-nm XeCl
excimer laser, argon
fluoride excimer laser,
erbium:YAG laser,
diode lasers, the
holmium:YAG laser etc
. are used
• Ab-externo : probe
applied to the scleral
surface under a
conjunctival flap.
• Ab-interno : through a
goniolens

Miscellaneous laser procedures
• Cyclophotocoagulation
• Laser suture lysis (LSL)
• Reopening Failed Filtration sites
• Laser synechialysis
• Goniophotocoagulation
• Photomydriasis (pupilloplasty)

Cyclophotocoagulation
• Trans-scleral Cyclophotocoagulation
A) Noncontact Nd:YAG laser cyclophotocoagulation
B) Contact Nd:YAG laser cyclophotocoagulation
C) Semiconductor diode laser trans-scleral
cyclophotocoagulation
• Endoscopic cyclophotocoagulation (ECP)

• Laser synechialysis : lyse iris adhesions
• Goniophotocoagulation: anterior
segment neovascularization , rubeosis ,
fragile vessels in a surgical wound
• Photomydriasis (pupilloplasty) : enlarge
the pupillary area by contracting the
collagen fibers of the iris

Lasers In Lens
•Posterior Capsular Opacification :
•T/t- (Nd:YAG) laser posterior capsulectomy
•laser- source used is the Nd:YAG 1064-nm.
•Use minimum energy: 1 mJ if possible.
•Identify and cut across tension lines.
•Perform a cruciate opening: Begin at 12 o'clock
in the periphery, progress toward 6 o'clock, and
cut across at 3 and 9 o'clock.
•Clean up any residual tags.
•Avoid freely floating fragments.
•capsulotomy should be as large as the pupil in
isotopic conditions
•COMPLICATIONS
•Iop elevation
•Iritis
•Cystoid macular elevation
•Retinal detachment
•Iol pitting
•P Acne endophthalmitis

Femto-lasers in cataract surgery
• New level of precision and
reproducibility is achived.
• Femtosecond laser technology
systems use neodymium:glass 1053
nm (near-infrared) wavelength light.
• This feature allows the light to be
focused at a 3 mm spot size,
accurate within 5 mm in the anterior
segment
• The Laser creates
a) Corneal incisions with precise
dimensions and geometry.
b) anterior capsulotomies with
accurate centration and intended
diameter, with no radial tears.
c) lens fragmentation (customized
fragmentation patterns)

Posterior Segment
• Laser in vitreous
• Laser in Retinal vascular
diseases
• Other Retinal diseases

LASER TREATMENT OF
FUNDUS DISORDERS
 Diabetic Retinopathy
 Retinal Vascular Diseases
 Choroidal Neovascularization (CNV)
 Clinical Significant Macular Edema (CSME)
 Central Serous Retinopathy (CSR)
 Retinal Break/Detachment
 Tumour

Focal and Grid laser
Focal Grid
• Spot size -50 to 100u size 50 to 200u size.
• Duration -0.05 to 0.1sec. 0.05 to 0.1 sec.
• Intensity -Moderate Light to medium
• Power – 70 to 100 mW 70 to 100 mW
Wavelength– argon green, db.fq. YAG green, dye
yellow or diode red
Area of treatment – within 500um of center of
macula avoiding the fovea
Lense used – area centralis, meinster standar or
goldman 3 mirror lens

Indication of Focal or grid
photocoagulation
1. Macular edema from diabetes or branch vein occlusion
2. Retinopathy of prematurity(ROP)
3. Closure of retinal microvascular abnormalities such as
microaneurysms, telangiectasia or angiomas
4. Focal ablation of extrafoveal choroidal neovascular
membrane
5. Creation of chorioretinal adhesions surrounding retinal
breaks and detached areas.
6. Focal treatment of pigment abnormalities such as RPE
leakage in central serous chorioretinopathy(CSR}
7. Treatment of ocular tumors
8. Posterior hyloidotomy in large sub hyloid haemorrhage

Focal or grid laser treatment
Modified grid laser in dme
Laser to ischemic areas in ROP
Posterior
hyloidotomy
Laser barrage arouind retinal tear. 3
rows of laser burns given .

Pan retinal photocoagulation
• Number - 2000-3000 spots distributed in 3 to 4 sittings
• Spot size- 500 mm size with goldmann lense and 200-300
mm size with panfunduscopic lens.
• Duration- 0.05-0.10 sec.
• Intensity- moderate intensity laser burns
• Wavelength– argon green, db.fq. YAG green, dye yellow or
diode red.
• Lens used – PRP 165 or goldman 3 mirror lens
• Pattern- Scatter pattern PRP. Place laser spots in the
peripheral retina for 360 degrees sparing the central 30
degrees of the retina.
• Laser spots are given 1 spot apart 1 DD away from the disc
nasally , 2DD away from macula temporally and beyond the
arcades superiorly and inferiorly

Indications of Panretinal
photocoagulation (PRP)
1. Proliferative diabetic retinopathy with high risk
characteristics
2. Severe non proliferative diabetic retinopathy associated
with-poor compliance for follow up or before cataract
surgery or renal failure or one eyed patient or pregnancy
3. Central retinal vein occlusion and branch retinal vein
occlusion with nvd or nve or nvi
4. Sickle cell retinopathy,
5. Eales disease and IRVAN (idiopathic retinal vasculitis,
aneurysms, and neuroretinitis )
6. Retinopathy of prematurity (ROP)
7. Coats Disease
8. Radiation retinopathy
9. Neovascularisation of iris in ocular iscemoc syndrome

Transpupillary thermotherapy(TTT)
• Thermotherapy involves using ultrasound, microwave, or
infrared radiation to deliver heat to the eye.
• It involves application of diode (infrared) laser to the tumor
surface or in regions of CNVM activity.
• Retinoblastoma It cause tumor cell death by raising the
temperature of tumor cells to above 45°C for ~1 min., thus
reducing blood supply and producing apoptosis.
• Classic subfoveal or extrafoveal choroidal neovacular
membrane

Transpupillary thermotherapy (TTT)
Retinoblastoma after
thermotherapy
Retinoblastoma
before themotherapy

Photodynamic therapy (PDT)
Light application

Indications of PDT
• Classic CNVs due to
• age-related macular degeneration
• idiopathic polypoidal choroidal vasculopathy,
• pathologic myopia,
• angioid streaks
• presumed ocular histoplasmosis syndrome
• Retinal capillary hemangioma
• Vasoproliferative tumor
• Parafoveal teleangiectasis
• CSR with subfoveal leak

PDT Procedure
• For age-related macular
degeneration and pathologic
myopia : i.v Verteporfin at
6mg/m2 BSA over 10 mins.
Five minutes after the
cessation of infusion, light
exposure (laser emitting light
of 692 nm) with an irradiance
of 600 mW/m2 is started,
delivering 50 J/cm2 within
83 s .
• Angiod Streaks and CSR
light dose of 100 J/cm2 over
an interval of 166 s

Shrinkage of retino-chroidal haemangioma after PDT

INTRAVITREAL THERAPY
• Drugs are introduced in the vitreous cavity
by different modalities
1. Intravitreal injection
2. Microsphere delivery device (> 1micron)
3. Nanoparticle delivery device (< 1micron)
4. Iontophoresis
5. Sustained release implants.

INDICATIONS FOR INTRAVITREAL THERAPY
• Endophthalmitis
• CMV retinitis
• Unresponsive post uveitis
• PDR
• AMD a/w CNV
• Diabetic macular edema
• Macular edema
• Recalcitrant macular edema
• CRVO
• Macular hole

How to perform intravitreal therapy.
• Location: OT set up.
aseptic precautions
• Pre-operative preparation
• informed written consent for intravitreal therapy.
• The pupil should be dilated
• Prepare intravitreal injection in tuberculin syringes/insulin
syringes .26 guage or 30 guage needle is used to inject.
• The pupil should be dilated
• Topical anaesthetic agents or peribulbar anaesthesia.
• use 10% povidone iodine to clean the Eyelids and to irrigate
the ocular surface and conjunctival sac.
• use lid speculum

Injection technique
• Tuberculin syringes with 26 or 30 gauge needle
• conjunctiva be displaced slightly with a cotton bud
• SITE
• 4mm from limbus in aphakic eye
• 3.5mm from limbus in a pseudophakic eye.
• 3 mm from limbus in aphakic eye
• Take the syringe with 0.1ml drugs. Puncture the globe
at pars plana Slowly inject the content.
• Put a pad and bandage for at least an hour. Analgesic
and a tablet of acetazolamide is optional
• Post injection look for
• IOP increase
• Retinal vascular occlusion

Intravitreal pharmacokinetics
• Drugs spread through vitreous at same rate as they will
through a free solution
• A mathematical model develop using FICK’S second law of
diffusion assumes vitreous body is a cylinder with 3 major
pathways of drug elimination
Aqueous retinochoroidoscleral lens
drainage membrane
(Hyrophillic ( lipohillic
Drugs) drugs)
• Drug decay rate is greater in diseased eye than in normal
eye.

• Need for intrvireal therapy
• Poor ocular especially post segment penetration of systemically administered drugs
attributed to
• BLOOD AQUEOUS BARRIER
• BLOOD RETINAL BARRIER
• Higher efficacy of local treatment-desired dose at target site
• Reduced systemic toxicity
• Disadvantage of intravitreal therapy
• Compromised protection to the other eye
• Compromised protection to other organs
• Local complications
• Endophthalmitis
• Vitreous haemorrhage
• Retinal detachment
• Retinal necrosis
• Vascular shutdown
• Local drug toxicity
• Need of expertise

• Presently used intravitreal drugs
• Antibiotics-antibacterials,antivirals,antifungals
• Steroids-
dexamethasone,triamcenolone,flucinolone
• Anti VEGF-pegaptanib(macugen)
bevacizumab( avastin)
ranibizumab( lucentis)
• Immunosuppressants-cyclosporine

ANTIBIOTICS-ANTIBACTERIAL.
1) AMINOGLYCOSIDES
• Bacteriocidal
• Amino sugars in a glycosidic linkages
• intrvitreal t ½ is 8 hrs
• Main route of elimination is renal
• MOA
binds to 30 S of bacterial ribosomes
blocks translation in mRNA
Blocks bacterial protein synthesis
cell death

• Spectrum – gram positive cocci ,staph. Aureus ,aerobic
gram negative organisms ,P. aeuruginosa ,P. mirabillis
,klebsiella ,serratia , enterobacteria ,acinetobacter spp.
And mycobacteria
• Resistance developes Due To
• Decreased transport across the cell membrane
• Plasmid transmitted ability to inactivate the drug
• Low affinity of the bacterial rhibozome to the drug.
Commonly use aminoglycosides intrvitreally
• gentamycin
• Amikacin
• tobramycin

GENTAMYCIN
• Hydrophillic drug
• Highly active against staph.aureus and pseuomonas, niesseria
• Indication- bacterial endophthalmitis
• Dosage 0.2 to 0.4 mg/ 0.1 ml
• a/e ocular punctate keratitis
macular infarct
Tobramycin
• Active aditionally against H.aegypticus
• Dose 0.15 mg/0.1ml
Amikacin
• Same spectrum as gentamycin.
• Used to treat infections resistant to gentamycin and tobramycin
• Less maculotoxic
• Dose 0.4mg/0.1ml

• Amikacin reconstitution for ivt
injection
• 250mg/2ml
• Withdraw 0.1ml in 1ml syringe
• Dilute with 0.9mlof BSS
• Discard 0.9ml and redilute
with 0.9 ml BSS
• Discard 0.9ml
• Final conc-125 microgram/o.1ml

2)Cephalosporins
• Structure-7 aminocephalosporanic acid nucleus compounds
with a beta lactum ring
• bacteriocidal
• MOA- react with bacterial transpeptidase and inhibit cell
wall synthesis
• Spectrum-gram positive org.esp streptococcus
some gram negative org
• Indication- bacterial enophthalmitis
• Common intravitreal used
• Cefazolin
• ceftazidime

Cefazolin
• First generation drug
• Available as a 500 mg powder
• Commonly used intracamerally postcataract surgery to reduce risk of
endophthalmitis
• A/E ocular—surgical complications

Ceftazidime
• Third generation
• More active against gram negative organisms
• Separate syringes to be use for cephalosporins and vancomycin as
precipitation occurs if mixed
• Reconstitution of Ceftazidime
• 500mg/vial
• Add 2ml BSS
• Withdraw 0.1ml
• Dilute with 0.9ml of BSS
• Discard 0.9ml
• Final conc-2.5mg/0.1ml

3. Fluroquinolones
• Bacteriocidal
• Flurinated derivatives of nalidixic acid
• MOA
inhibits DNA gyrase and Topoisomerase 4
inhibits DNA replication and translation
cell death
• Spectrum—gram positive, gram negative, anaerobes,
atypical mycobacteria, listeria
• Intrvitreally used drug-ciprofloxacin

Ciprofloxacin
• c/I hypersensitivity
• A/E
rash
cataract
macular bullae
crystal deposits in cornea
renal failure
• Dose 0.15 mg /0.1ml

MOXIFLOXACIN
• Most commonly used antibiotic post operatively in India
• Also used for Intracameral injection as well as Intravitreal injections.
• 0.03ml of MOXIFLOXACIN (preservative free) is taken into tuberculin
syringe and with the aid of thirty gauge needle is injected into the
eye.
• It is effective against both gram positive and gram negative
organinsms.

4) MACROLIDES
• Bacteriostatic and bacteriocidal at high conc
• MOA
bind irreversibly to 23tRNA of 50S ribizomal subunit
Blocks peptide chain elongation
blocks protein synthesis
Cellular death
• Show good tissue distribution
• Metabolized mainly by liver and excreted through bile

Vancomycin
• Tricyclic glycopeptide derived from nocardia orientalis
• Indication: MRSA endophthalmitis
• Used in empirical treatment of bacterial endoph.with aminoglycosides
• Dose 1mg/0.1ml
• S/E: CME
anaphylaxis
Effetive against-Spectrum-gram positive cocci ,gram negative bacill ,Neisseria,
mycoplasma ,chlamydia , ricketssia , bartonella sp , clostridium species ,
propionobacterium acnae ,atypical mycobacteria
Reconstitution -vancomycin
500mg/vial
Add 5 ml of BSS
Withdraw 0.1ml in 1ml syringe
Dilute with 0.9ml of BSS
Mix for 30 sec
Discard 0.9ml
Final conc-1mg/0.1ml

Intravitreal antibiotics in endophthalmitis
broad-spectrum antibiotics
vancomycin- gram +ve coverage
ceftazidime or amikacin - gram –ve coverage
dexamethasone in low virulence endophthalmitis
do not mix drugs in same syringe
• Post op pt positioned on pillow with head turned to
opposite side or face down 15 to 20 min to avoid
precipitation of drugs on macula
• if no clinical improvement/deterioration in condition
in 48-72 hrs then Pars plana vitrectomy or repeat
injections

ANTIVIRALS-ACYCLOVIR
• Acycloguanosie,ACV,zovirax
• Synthetic purine nucleoside analogue with an acyclic side chain.
• Available as white crytalline lyophilized powder completely
unionized
• Store at 15 to 25 deg c protected from light
• Reconstitute 50 mg /ml stable for 12 hrs at 30 deg c
• Excretion by renal filteration
• Spectrum - HSV 1 and 2
HZV
• Binds to DNA polymerase and inhibits DNA synthesis .
Intravitreal dose 10 to 40 microgrms/0.1ml
• Indications: CMV retinitis
ARN ( along with vitrectomy and sceral buckling)

GANCICLOVIR
• DHPG, GCV, Cytovene
• Dihydroxy-propoxy ,methylguanine
• Synthetic purine nucleoside of guanosine
• Spectrum: CMV,HSV 1 and 2,HHV, VZV and EBV
• Indication : CMV retinitis in AIDS
• C/I : pregnancy , hypersensitivity.
Dose :
• induction -2 mg/0.1ml
0.1 ml injected 2 times per week for 3 wks
• Maintanance - 2mg/0.1 ml once a week
• Sites—superotemporal,inferotemporal,superonasal
pars plana 4 mm post to limbus using 30 G needle
uner TA.

VITRASERT
• Gancicovir implant
• Provides local sustained conc. Of the drug with decrease risk of
systemic SE without repeated injections
• Therapeutic levels upto 8 months
• 4.5 mg drug in 2.5 mm pellet completely coated by drug
permeable poly vinyl alcohol and incompletely coated with
impermeable ethyl vinyl acetate
• Releases drug at rate of 1 micro gm/hr
• Insreted through 5 t0 6mm sclerotomy at pars plana and then
secured by scleral sutures f/b partial vitrectomy
• Mean intravitreal conc. Achieved is 4.1 microgm/ml
• Median time of progression of cmv retinitis(8m) is 3 times longer
than intrvitreal injection(42 wks)

• A/E: foreign body sensations
conjunctival haemorrhage
fibrovascular scar , scleral induration
min. blurring of vision
failure
extrusion
pellet separation
VH
catarct
retinal detachment
endophthalmitis
• Response to treatment
• Loss of satellite lesions
• Disappearance of venous sheathing
• Resolution of exudative RD
• Formation of inactive scar
• MAIN USE IS IN CMV RETINITIS IN AIDS
Ocular S/E : rhegmatogenous RD
endophthalmitis
vitreous haemorrhage
cataract
transient increase in IOP
retinal vascular occlusion
retinal necrosis
vacuolation of
photoreceptor cells
uveitis
hypotony

FOSCARNET• Phosphonomethanoic acid / Phosphonoforonic acid/ trisodium PFA/ Foscavir
• Pyrophosphate analogue
• Inhibit herpes virus DNA polymerase, HIV reverse transcriptase
• Directly bind to pyrophosphate binding site on DNA and thus dose not require host
phosphorylation for activation
• Hence use in ACV resistance
• Spectrum-CMV ( FDA approved), HSV ,EBV, VZV
• Virustatic
• Pharmacokinetics
• Poor GI absorption, not used PO
• Indication
• Resistance CMV in AIDS
• CMV in pt. with concurrent zidovudin and other immunosupressive ART
• C/I for ganciclovir
• C/I IV foscarnet in renal failure
• Passed through 0.22μm filter and 1.2 mg in 0.05 ml injected intravitreally
• Induce two injection once per week for 3 weeks
• Maintain one injection per week

• Indication
• Resistance CMV in AIDS
• CMV in pt. with concurrent zidovudin and other immunosupressive ART
• C/I for ganciclovir
• C/I IV foscarnet in renal failure
• Passed through 0.22μm filter and 1.2 mg in 0.05 ml injected
intravitreally
• Induce two injection once per week for 3 weeks
• Maintain one injection per week

CIDOFOVIR
• HPMC, Vistide, Forvade
• Inhibit DNA polymerase- does not req. activation phosphorylation by TK
• persist intracellularly for65h
• Spectrum -HSV 1, 2 ,VZV ,EBV, CMV, adenovirus
• Indication – CMV retinitis in AIDS
• Intravitreal
• 20mg / 0.1ml every 6 weekly
• T 1/2 intravitreal and retinal cells 3 days
• Oral probencid 2gm before injection and 1 gm after post injection
• Precaution- probenacid reduce hypotony as well as uveitis
• Hypotony more severe in pts. With low CD4 counts
• S/E-
• Hypotony (CB atrophy)
• Uveitis 25- 45% , treatment- topical steroid, cycloplegics
• Renal toxicity
• Cataract, cynechia

Fomivirsen
• 21 base synthetic phosphorothiole oligo nucleotie designed to be complimentry to
the CMV viral mRNA that encodes for major immediate early region (IE2) protein of
CMV
• Binding to this location L/T specifie inhibition of gene expression that is critical for
production of essential viral protein
• MIC 0.03+_ 0.02μm
• Pharmacokinetics
• First order
• Vitreal t ½ 55 hr
• S/E
• AC rection……… if given along with idofovir
• Increase IOP
• Retinal pigment epitheliopathy
• Visual field defect
• Cataract
• Dose
• 330 μg intravitreal every 2 weekly for 2 doses for induction
• Maintenance 330 μg intravitreally / month
• 4th line drug treatment of CMV retinitis in AIDS

Antifungals
• Class
• Polyenes –
• ampho B, Natamycin, Ampho B methyl ether
• Imidazole-
• Clotrimazole, Miconazole, Econazole, Ketoconazole, Thabendazole
• Triazoles-
• Fluconazole, Itraconazole, Voriconazole
• Pyrimidines-
• Flucystine
• Other-
• Nystatin, Terbenafine, Caspofungin, Ciepentacin, Pradicincine

1. AMPHOTERICIN B.
• Fungistatic and fungicidal at high concentration.
• Produced from streptomyces species
• MOA
binds to ergosterol in cell wall of fungi
localized lysis
pores in cell wall
leakage of K+ ions
osmotic imbalance
cellular death

• Spectrum: candida ,aspergillus ,blastomyces andcoccidiodes
• Indications: fungal enophthalmitis
• Dose: 5 microgram/ 0.1 ml injected slowly in central vitreal space
mostly combined with vitrectomy
iv test dose 1mg in 150 ml 5 % dextrose
if reaction occurs concurrent iv
hydrocortisone given
• Ocular S/E: retinal necrosis
• Amphotericin B preparation for ivt use
• 50mg/vial
• Add 10ml of BSS
• Withdraw 0.1ml in 1ml syringe
• Dilute with 0.9ml BSS
• Discard 0.9ml and redilute with 0.9ml of BSS
• Discard 0.9ml
• Final conc 5mcg/0.1ml

2. FLUCONAZOLE
• Belongs to triazole group
• Sectrum : candida albicans ,Aspergillus ,cryptococcus
neoformans ,sporothrix shenckii ,Coccidiodes ,Histoplasma
,blastomyces
• MOA: inhibits ergosterol synthesis by
• Decreased activity of cell memb. Asso enymes leading to
increased cellular permeability causing lysis
• Indicated in fungal endophthalmitis
• Usually given along with amphotericin B and fluocystine under
clsoe observation
• Dose intravitreal :25 microgram/0.1 ml
• Has good oral absorption
good ocular penetration
levels in vitreous are almost 70% of serum drug levels
• Dreaded complication is anaphylaxis

3.VORICONAZOLE
• Triazole antifungal
• MOA : interupts ergoaterol synthesis
• Spectrum: additional activity against- sceidiosporiasis,other
candidial species,aspergillus
• Indications
• Endogenous fungal endophthalmitis
• Invasive aspergillosis
• Resistant fungal endophthalmitis
• S/E:transient visual disturbances
photophobia
photopsia
dyschromatopsia
• Dose: total 100 micrograms

STEROIDS
• GLUCOCORTICOSTEROIDS
Short acting—hydrocortisone/ cortisol
(<12h)/ cortisone
Intermediate acting– prednisolone
methylprednisolone
triamcenolone
Long acting-- dexamethasone
(>36h) betamethasone
• MINERELOCORTICOIDS
DOCA
Aldosterone
fludrocortisone

ANTI-INFLAMMATORY STEROIDS
• Induction of LIPOCORTINS in macrophages etc to inhibit PL
A2 to decrease production of PG,LT,PAF
• Negative regulation of genes for CYTOKIENES
• Decreased ACUTE PHASE REACTANTS proudction
• decreased proudction and expression of ICAM 1 and ELAM
adhesion molecules
• Decreased proudction of COLLAGENASES and
STROMOLYSINS
• Inhibition of Ag-Ab reactions

• Indications for intravitreal steroids
• ARMD
• CME
• ARN
• Choroiditis
• Post op. Endophthalmitis
• Vasculitis
• Retinitis

• Ocular S/E
• Cataract (PSC)
• Glaucoma
• Uveitis
• Secondary infections
• Delayed wound healing
• Mydriasis
• Ptosis
• Exophthalmos
• Pseudotumour cerebrii
• C/I - ocular infections

1. TRIAMCENOLONE ACETATE
• Intermediate acting steroid
• Used in AMD
• Suboptimal as monotherapy
• Used in combination with Vertifortin PDT
• Dose 4 mg intraviteal injection following PDT Intravitreal
triamcinolone acetonide (TA) has
• become popular in recent times as a promising treatment
for recalcitrant macular edema,particularly diabetic, in
choroidalneovascularization and to visualize vitreous in
clear gel vitrectomy. The crystals have also found use in
anterior vitrectomy in complicated cataract surgery.
• The drug preparation available most commonly is a
suspension of the triamcenolone crystalin a vehicle
containing benzyl alcohol 0.9%. Commercially available TA
suspension for injection (Kenacort 40 mg/ml and Tricort 40
mg/ml,)

2.DEXAMETHASONE
• Dose 400 micrograms/0.1 ml
• reconstitution
• 8mg/2ml vial
• 0.1ml to be given directly
• Final conc-0.4mg
• Can be mixed with Taxim,
ciplox, amikacin
• INDICATED in endophthalmitis

DEXAMETHASONE IMPLANTS
INDICATIONS AND USAGE
• OZURDEX contains a dexamethasone indicated for the treatment of
macular edema following branch retinal vein occlusion (BRVO) or
central retinal vein occlusion (CRVO).
• Following the intravitreal injection, patients should be monitored for
elevation in intraocular pressure and for endophthalmitis.
DOSAGE FORMS AND STRENGTHS
• Intravitreal implant containing dexamethasone 0.7mg in the NOVADUR
indicated for the treatment of macular edema following branchretinal
vein occlusion (BRVO) or central retinal vein occlusion (CRVO).
• CONTRAINDICATIONS
• Ocular or periocular infections
• Advanced glaucoma
Most common adverse reactions reported
• Increased incidence of cataract
• ≥20% of patients included increased intraocular
pressure and conjunctival hemorrhage.

3. FLUCINOLONE ACETATE
• RETISERT is indicated for the treatment of chronic non-
infectious uveitis affecting the posterior seg.
• DOSAGE AND ADMINISTRATION
• RETISERT (fluocinolone acetonide intravitreal implant)
0.59 mg is implanted into the posterior segment of the
affected eye through a pars plana incision.
• The implant contains one tablet of 0.59 mg of
fluocinolone acetonide. RETISERT is designed to release
fluocinolone acetonide at a nominal initial rate of 0.6
µg/day, decreasing over the first month to a steady
state between 0.3-0.4 µg/day over approximately 30
months. Following depletion of fluocinolone acetonide
as evidenced by recurrence of uveitis, RETISERT may be
replaced.

Caution should be exercised in handling RETISERT in order to avoid
damage to the implant, which may result in an increased rate of drug
release from the implant. Thus, RETISERT should be handled only by the
suture tab. Care should be taken during implantation and explantation to
avoid sheer forces on the implant that could disengage the silicone cup
reservoir (which contains a fluocinolone acetonide tablet) from the suture
tab. RETISERT should not be resterilized by any method.

• Dosage Forms And Strengths
• 0.59 mg fluocinolone acetonide intravitreal implant.
• The implant consists of a tablet encased in a silicone elastomer cup
containing a release orifice and a polyvinyl alcohol membrane
positioned between the tablet and the orifice. The silicone elastomer
cup assembly is attached to a polyvinyl alcohol suture tab with silicone
adhesive. Each RETISERT is approximately 3 mm x 2 mm x 5 mm.
• Each implant is stored in a clear polycarbonate case within a foil pouch
within a Tyvek peelable overwrap. Each packaged implant is provided in
a carton which includes the package insert.
• FDA approval is awaited

• S/E:
• Ocular SE
• Cataract(psc)
• Transient blurring of vision
• Increase IOP
• VH
• RD
• Maculopathy
• Macular edema
• Hyphaema
• Diplopia
• Ptosis
• Keratitis
• Corneal ulcer
• Blepharitis
• dry eye
Surgical complications
Endophthalmitis
Choroidal detachment
Retinal detachment
Vitreous haemorrhage
Vitreous loss
Hypotony
Increase IOP
Wound dehiscence
Globe perforation
Systemic complications
Headache
Arthargia
Sinusitis,nasopharingitis,URTI
rash

Anti VEGF
Monocytes RPE neurones
Inflammation oxidative hpoxia
stress
VEGF a
VEGF 165
VEGF 121
VEGFr1 VEGFR 2
Inuduction of induction of ICAM 1
uPA,tPA
MMP9
Integrin expression
EC mitosis

ANTI VEGF AGENTS
1.PEGAPTANIB SODIUM/ MACUGEN
• First anti VEGF agent FDA approved for ophthalmic use in dec
2004
• Chemically synthesized ss of nucleic acid with 28 bp ,
complementary to RNA (APTMER)
• MOA : binds to 165 aminoacid isoform of VEGF
• AMD (CNVM)
• Dose: 0.3 mg intravitreally every 6 wks for 2 yrs
• Sustained inhibition achieved for 20 d with single dose
• T ½ in vitreous is 83 to 94 hrs
• Advantage:
• Doesnot elicit immune reaction
• No systemic S/E
• No regression of normal retinal vasculatures

• VISION
• Anti -VEGF inhibited ocular neovascularization.
• 0.3 mg/ 0.1 mg/3.0mg intrvitreal injections v/s placebo
at 6 weeks interval and analysed at 1 yr
Macugen group placebo group
1. % avoided mod. 70 55
Visual loss
2. % gained vision 33 23
Statistically significant
• S/E: pain
puncate keratitis
vitreous floaters
icreased IOP
endophthalmitis (1.3%)
RD(0.7%)
traumatic cataract (0.6%)

2. BEVACIZUMAB/ AVASTIN
• Mouse derived nonselective anti VEGF antibody
• Antagonizes proliferative and permeability
increasing effects of VEGF
• HMW of 150,000 daltons thus cannot cross
retinal ILM and RPE into subretinal space
• Off label drug
• Liscenced for IV use in metastatic colorectal
cancer
• Used in AMD
CRVO
PDR, DME
• Dose : 1.25 mg at 4 weekly interval usually for 6
wks
• Benefits : increase in V/A
decreased retinal thickness

• AVASTIN in PDR and DME
• Ensues rapid regression of new vessels
• Treats actively leaking vessels
• In combination with TA
• Pts unresponsive to PRP
• As an ajunct to PRP
• Prevents laser asso macular edema
• Preop use facilitates:: sx removal of fibrovascular memb
reduces intra op bleeding
accelerates post op vitreous clearing

3.RANIBIZUMAB/LEUCENTIS
• LEUCENTIS , RhuFAB
• Recombinant humanized monoclonal fragment antibody
• LMW 48,000 daltons
• Nonselective VEGF antibody
• Dose: 0.3 to 0.5 mg every 4 weekly
• FDA approved
• 3 initial injections 0.3 mg at monthly interval
• Followed by additional doses as inicated

4.VEGF TRAP/EYLEA/AFLIBERCEPT
• Eylea (aflibercept) is made from a human antibody fragment
• Contains Ig domain of VEGF R1 and 2
• High affinity to the receptors to which it binds an neutralizes it
• 0.05 to 4 mg intrvitreally single injection at end of 6 wks
• 15 % showed stabilization of vision loss
Ocular side effects
• eye pain or redness, swelling around your eyes;
• sudden vision problems;
• seeing flashes of light or "floaters" in your vision, seeing halos around lights;
• increased sensitivity of your eyes to light;
• sudden numbness or weakness, especially on one side of the body; or
• sudden severe headache, confusion, problems with speech or balance

IMMUNOSUPPRESSIVE DRUGS
CYCLOSPORINE
• Impairs t-cell meiated immunity
• Used as steroid sparing agent
• Indications
• Uveitis
• Behecet’s disease
• Scleritis
• Orbital inflammatory disease
• Posterior nonresponding uveitis
• Graft rejection(KP)
• A/E
• Superficial punctate keratitis
• Blurring of vision
• Burning sensations
• Dose: 2mg intrvitreal implant

The cataract comes out in one whole piece

Limitations of ECCE
• Prolonged surgery time
• Trauma leads to inflammation
• Suture distortion of cornea
• Prolonged convalescence
• Restrictions to activity
• Necessitates a regional ‘block’ anaesthetic

The cataract is emulsified then sucked out

Phacoemulsification
• Small incision (1.75 to 3.25mm)
• Can be performed without needles
• Takes only minutes
• Less inflammation
• Faster recovery
• Little restriction to activity
•Topical anesthesia

Aqualase
Lens liquifaction device
• Alcon Infiniti
• Also has ultrasonic phacoemulsification
• 4 micro litre bursts of water
• No heat
• Soft plastic tip
• Advantages:
• No heat at wound, no wound burns
• Less endothelial cell disruption
• Less risk of posterior capsular rupture
• Disadvantages:
• Expensive
• Too slow for hard cataracts

6mm
Advances in Intraocular lenses (IOLs)
technology

YELLOW LENS - Contrast Sensitivity is a better

Aspheric IOLs
• CONTRAST SENSITIVITY IS
IMPROVED
• NIGHT VISION IS BETTER
• ABBERATIONS ARE REDUCED
• NIGHT GLARE IS ALSO
REDUCED

Pre op Biometry
Ultrasound B Scan
IOL Master: coherence interferometry
SLO laser technology is used.
Gives accurate IOL power
Accurate readings for multifocal IOL
Accurate readings for post lasik iol
power calculations

Refractive corrections after cararact surgery
• Cataract surgery is increasingly used to reduce peoples dependence on
glasses
• Secondary LASIK can be done to reduce refractive error after cataract
surgery

Secondary LASIK can be done to reduce refractive
error after cataract surgery

Reading without glasses post cataract surgery
• Aim for myopia in both eyes
• Aim for myopia in one eye (monovision)
• Multifocal IOL

Accomodating IOLs
IOL has accomodating capacities
Not very popular

Multifocal IOL
•Addition of refractive lens
causes light to converge to
two points

New Intraocular lenses
However …
•Higher glare and reduced contrast is a
major issue
•Requires careful patient selection
•Optimal distance for reading is short
•Best for hypermetropes with
presbyopia
•Toric IOL for astigmatism is also
gaining popularity

Vitreoretinal microsurgery
• The basic technique involves making small entry ports on the surface
of the eye to gain surgical access to intraocular structures.
• This includes use of illuminating probes, laser probes, infusing and
aspirating devices and surgical manupulators.
• The entry point is 3 – 4 mm posterior to limbus through the pars
plana
• The vitreous body consists of type to collagen and Hyluronic acid
• Various vitreoretinal diseases requiring microsurgery are vascular
disorders of retina (diabetic retinopathy, CRVO, Vasculitis etc.) with
dense vitreous haemorrhage, retinal detachment (Rhegmatoginous,
tractional, combined and exudative) and trauma with retained
Introcular foreign body etc.

Principles of vitreoretinal surgery
• The principles are similar to anterior segment surgery.
• The volume of the eye is maintained with balanced salt solution or linger lactate when
intraocular materials (vitreous gel, blood, foreign body etc.) are removed
• Traction of the vitreous on the retina is removed with the help of vitrectomy cutter .
• External illumination being inadequate to visualize the retina, internal illuminating
systems have to be used.
• First parsplana vitrectiomy was done in 1970 by Robert Macamar
• Modern parsplana vitrectomy consist of 3 port 20 gauge sclerotomies (0.9mm)
• A light probe is passed through one port, infusion canula is fixed to a second port and
vitrectomy is performed under direct visualisation through the third port
• The sclerotomies are closed with absorbable sutures.
• Various lens systems such as macamar lens system and landers lens system are used for
visualisation of the retina through a microscope.

ADVANCES IN VITRECTOMY SURGERY
• The sclerotomy size is reduced to 23 gauge (0.6mm), 25 gauge (0.5mm) and
even 27 gauge trocar and cannula equipment and hence the surgery
becomes a transconjunctival suture less surgery.
• Various vitreoretinal surgical instruments have been reduced in size to 23
gauge, 25 gauge and 27 gauge.
• Modern vitrectomy cutters have high speed cutting rate upto 3000 to 5000
cuts per minute which previously used to be upto 600 cuts per minute. This
reduces the traction the retina and also helps efficient working close to the
retina.
• Modern vitrectomy instruments have a duel numatic and venturi drive
system with improved duty cycle thus producing a very high cut rate
• Advanced lens systems (Biom, E-BIOS etc.) attached to high end
microscopes improve the visualisation of the retina significantly
• Robotic eye surgery is under development.

Advances in glaucoma surgical procedures

Advances in corneal and
refractive surgery

Implantable Contact Lens
• Also called Phakic IOL (intraocular lens)
• Two options in the US
• Visian ICL
• Placed behind the iris
• Verisyse
• Attaches to the iris
• Can be used in cases when patients are not LASIK or PRK
candidates, such as:
• High amounts of nearsightedness or farsightedness
• Thin cornea, corneal scarring
• Reversible
• Requires a laser procedure before surgery
• May develop a cataract or elevated pressure in the eye

Intacs
• Intracorneal ring segments
• Plastic rings that are placed into
the cornea to reshape the
curvature of the cornea.
• Only approved for patients with a
low degree of nearsightedness and
in patients with keratoconus.
• Reversible
• Side effects: cornea scarring,
glare/halos, inflammation, infection

Deep Anterior Lamellar Keratoplasty
• Abbreviated DALK
• Partial thickness corneal transplant of the upper
layers of the cornea (epithelium, bowman’s, and
stroma)
• This surgery is used for patients with keratoconus or a
corneal scar
• This surgery requires normal endothelium

Descemet’s Stripping Endothelial Keratoplasty(DSEK)
• Abbreviated DSEK, DSAEK (automated)
• Partial thickness corneal transplant of the inner layers of the cornea (descemet’s and endo).
• This surgery is used for patients with Fuchs’ corneal dystrophy or Pseudophakic bullous
keratopathy.
• No sutures used on the graft
• An air bubble is used to hold the tissue in place for the first few days.
• Maintains the structural integrity of the eye

Descemet’s Membrane Endothelial Keratoplasty(DMEK)
• Abbreviated DMEK
• Partial thickness corneal transplant of the inner layers of the cornea
(descemet’s and endo, no stroma tissue)
• This surgery is used for patients with Fuchs’ corneal dystrophy or
Pseudophakic bullous keratopathy
• No sutures used on the graft
• An air bubble is used to hold the tissue in place for the first few days
• Maintains the structural integrity of the eye.

Boston Keratoprosthesis (artificial cornea)
• Abbreviated- K- Pro, Boston K-Pro
• Artificial cornea made of plastic and titanium
• Requires sutures around the graft
• This surgery is reserved for patients with extensive scarring
or multiple failed grafts with a potential to have good vision.

Recent advances in ophthalmology - Dr. Parag Apte

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