DR WANI'S TALK ON Diabetic Retinopathy Part II december 31 2022 for KLE RESIDENTS.pptx

Diabetic Retinopathy Part II
Dr. Vivek B Wani MS FRCSEd
Consultant Vitreoretina Surgeon
KLES Dr. Prabhakar Kore Hospital
Belagavi
14-4-2020 DR WANI'S LECTURE ON DR PART II 1

In this talk we will cover
DME
Investigations
Treatment of DR, DME and PDR and its
complications
Prognosis

I) Diabetic Macular Edema(DME)
• Diabetic Macular edema is defined as retinal thickening or
hard exudates (or both)at or within 1 disc diameter of the
center of the macula
Early treatment diabetic retinopathy study group Archives of Ophthalmology;1985: 1796-1806

DME
Can be present in both
NPDR
PDR

DME- Clinically detected by
• Slit lamp biomicroscopic fundus examination with
90D or contact lens examination
• Gives stereoscopic view of macula
Look for
• Loss of foveal reflex
• Retinal thickening and extent
• Cystoid changes
• Subretinal fluid –gentle elevation of retina over
some area with loss of choroidal pattern under it

DME classification
Clinical
DME
CSME
NO CSME

What is Clinically Significant Macular
Edema (CSME)?
Early treatment diabetic retinopathy study group,” Archives of
Ophthalmology;1985: 1796-1806

DME classification-FFA
DME
Focal
Diffuse
Ischemic

Diabetic Macular Edema: What is
Focal and What is Diffuse?
• These terms as they are not well defined in
the literature
Browing et al Am J Ophthalmol. 2008 November ; 146(5): 649–655

Diffuse versus Focal DME
FOCAL
Localized area of retinal thickening usually in
the form of few hard exudate rings and there
are MA in the center of the hard exudate ring
FFA shows leakage from these MA

Focal

Diffuse ME
• The retinal thickening covers large area with
few MA
• FFA shows leakage from mainly dilated
capillaries and less from MA
• Cystoid changes may be seen

Flower petal appearance

Ischemic maculopathy
• FFA shows enlarged FAZ which is normally
<500 mu (foveal avascular zone)
• VA and fundus appearance do not correlate
• Macula may show hemorrhages

DME classification-OCT -Clinical
Studies
DME
Center involving
Non Center
involving

What is Center involving DME(CI-
DME)?
OCT thickness of >250mu in the
central subfield of TD OCT (or its
equivalent on SD OCT )
Central subfield has 1 mm diameter

Central Subfield 1 mm diameter average
thickness differ in different OCTs
• Stratus OCT -- 212 +/-19-250
• Spectralis HRA --289 +/- 16
• Cirrus HD-OCT ---- 277 +/- 19
• SOCT Copernicus 246 +/- 23
• RTVue100- 245 +/- 28
• Topcon 3d 1000- 231+/-16- 263
Ute E. K. Wolf-Schnurrbusch et al Invest Ophthalmol Vis Sci.
2009;50:3432–3437

1 1 mm

center involving DME
center not involving DME

II) Investigations for DR
• General investigations
 FBS, HbA1c –to assess the control
 Blood pressure
• Specific Ocular investigations
 FFA
 OCT
 OCTA
 Ultra-wide field FFA
 USB scan
 Microperimetry, visual fields

a) FFA
• When should we do FFA?
Routine use of FFA in all cases of DR and DME
has reduced with introduction of OCT and anti
VEGFs
When we want to do focal or grid laser
treatment for CSME -to identify leakage points
Do FFA where ischemic maculopathy is
suspected- VA is poor but fundus findings do
not match

Focal

Enlarged FAZ –macular ischemia

b) OCT in DIABETIC MACUAR EDEMA
OCT plays a great role in
• Diagnosis
• Decision of treatment
• Follow up and
• Prognostication of DME

OCT and DME –Its advantages
 It is non-invasive and quick 2-5 minutes
 It objectively measures thickness of retina-foveal subfield
thickness
 So follow up OCTs after treatment are useful to see
reduction in thickness
 In vivo optical biopsy-detects cystoid changes, SRF,
tractional changes and ERM and the important four lines in
the outer retina
 Great educational tool to motivate patients to accept
treatment and control their DM
 Teaching tool

OCT types of DME
DME
OCT
Diffuse
Cystoid
Subretinal Fluid
Mixed
Tractional & ERM

Characteristics of lesions on OCT
• Hard exudates and hgs -hyper-reflective white
• Intraretinal edema, cystoid spaces and
subretinal fluid -hypo-reflective-dark
• Shadow effect –hard exudates, vessels and hgs

Diffuse macular edema

RE CSME-Diffuse n cystoid

Cystoid SRF and diffuse Edema

OCT 13TH MAY 2010

January 2011

April 2011

Sept 2011

PRE AND POST IVA LE CSME

Tractional maculopathy

ERM

Prognostic factors of OCT IN DME
• Disturbed ELM and Ellipsoid zone
• Cystoid spaces increased number and size
• Deranged Retinal inner layers or DRIL SIGN
• Retinal thickness -------weak sign
• RPE atrophy

DERANGED RETINAL INNER LAYER
SIGN- DRIL SIGN

c) Investigations-OCT Angiography
• It is a non-invasive method to image retinal
vasculature at various levels
• It uses swept source OCT to image the
vasculature

RE OCT ANGIO
25th August 2018 KLE RETINA UPDATE 49

OCT-A IN DME
• Detects microaneurysms 67% vs FFA
• Does not detect leakage –diffuse edema
• Detects FAZ and capillary drop out areas
• But limited to central 3-6 mm only
• Advantage is it is non-invasive

d) Ultra Wide field FFA is a new
addition
• Images up to 200 d vs 60 d in present FFA
instruments
• Confocal selective laser ophthalmoscope c-
SLO) with panoramic ellipsoid mirror (Optos
from Ireland)
• 82% of retina is imaged in one take 200d
• FFA may reveal areas of drop out areas in the
periphery hitherto not seen

From IJO 2016

Ultrasound B scan
• To assess the retina in cases where the media
is not clear
Cataract
NVI/ NVA with cataract
Vitreous hemorrhage
Helps to diagnose V Hg, RD, TRD or PVD

III) Treatment of DME, DR and PDR
A. Treatment of DME –evidence
based medicine

Treatment of DME
• General measures-
Control DM,HBP and other risk factors
• Medications for DM that may worsen DME
Tab. Pioglitazone or Rosiglitazone- SO CHANGE
THEM if they are being taken by patient

Modalities of treatment of DME
a)Oral medications
b)Laser photocoagulation
c)Anti VEGF injections given intravitreally
d) Steroids -intravitreally /subtenon/supra-
choroidal
e) New drug –faricimab (VABYSMO) dual
antibody

a) Oral medications
• It is a peroxisome proliferator-activated receptor
alpha (PPARα) agonist
• It reduces triglycerides and increases HDL
cholesterol
• Fenofibrate tablets given 200mg/day was
beneficial in reducing the need for laser in
patients with DR in FIELD study
• However the medicine is not used routinely
• Serum creatinine may rise after treatment with
fenofibrate
Keech et al Lancet 2007; 370: 1687–97

LASER in Clinically Significant Macular
Edema (CSME)?
Early treatment diabetic retinopathy study group,” Archives of
Ophthalmology;1985: 1796-1806

The first established treatment for
DME was laser treatment
• Eyes with and without CSME were randomized
to receive
focal or grid laser treatment
Versus
observation
ETDRS study

24% versus 12%

b)Laser photocoagulation treatment for DME
Early Treatment of Diabetic Retinopathy Study
(ETDRS) -RCT
The risk of visual loss of 3 or more lines was
reduced by half if laser treatment was carried
out in
Eyes with CSME with
VA of 20/15 to 20/200 (6/4 to 6/60)
ETDRS REPORT NUMBER1 Arch Ophthalmol 1985;103:1796-1806
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So laser treatment for
CSME became standard
of care from mid 1980s

63 yrs old F DM, LE VA 6/6P with CSFT 271 mu
APRIL 2018 post laser Dec 2018 VA 6/6
20-09-2019 3 D LIVE 2.0 64
How should we treat?

Types of Laser Treatment
• i) Focal and ii) modified grid laser
i) Focal-when localized edema is treated by treating
leaking MA
• These are usually in the center of rings of hard
exudates or isolated MA that are seen to be leaking on
FFA
ii) Modified Grid- Diffuse area of edema is treated by
mainly applying burns in oedematous area along with
treatment of MA where visible
• In diffuse edema dilated capillaries are leaking

How does laser work for DME
• DIRECT treatment of leaking MA stops leakage in
focal laser
• Grid laser is supposed to act at RPE level
RPE is stimulated by the treatment and gets
reactivated some times regeneration
The RPE pumps fluid from edematous retina and
subretinal fluid in to choroid
The stimulated RPE is postulated to produce
cytokines that help in resolving the edema

Laser machines used
• ARGON laser –not in use anymore
• YAG double frequency laser with 532nm
green laser
• Yellow laser
• NAVILAS
• SUBTHRESHOLD laser

NAVILAS- navigated laser photocoagulator
• The retinal eye-tracking laser delivery system
• Uses prelaser photographs-color, FFA with
planned laser spots
• The machine places the laser spots using
tracking system in real time
• No contact lens is use

Sub threshold laser-we don’t see the laser burns!
3RD NOVEMBER 2022 UG CLASS JNMC DR VIVEK WANI 70
The laser is delivered in short pulses with intervals
between them
It is effective at RPE level and the energy does not spread
beyond the RPE
The off time allows the retina to cool
It does not produce any white spots like conventional
laser n pascal laser
It acts by stimulating RPE
We can do laser in fovea also without fear of producing
any scars
Central serous retinopathy –leaking points are lasered
DME
Macular edema due to branch retinal vein occlusion

SUB THRESHOLD MICRO PULSE LASER
• The laser burns are not visible on this laser
• It acts mainly at RPE level by stimulating it
• So laser burns can be place in the fovea too
• Cost and not enough evidence that it is better
than anti VEGF have limited its use

Laser parameters focal or grid in 532
green laser
Focal –for focal edema
• Topical anesthesia & consent
• Mainster standard lens/high mag lens
• Laser burn to mild blanching of the MA to be seen
• Spot size is 50-100 mu size
• Power 50 mw to 100 mw
• Duration of laser – 0.05 to 0.1 sec
• All microaneurysms outside of 500 mu from foveal
center
• Microaneruysms become blanched faint white burn

Modified grid-diffuse edema
• Treat the edematous area
• 50-200 mu spot size
• Power 50-100mw
• Duration of laser 0.1 second
• The laser is applied one burn width apart in the
edematous area
• Usually at RPE level
• Central 1 mm is avoided and papillomacular bundle
avoided
• Faint burns that are just visible are placed

PASCAL LASERPattern Scan
Laser)

Disadvantages of laser
Risk of visual loss reduced from24% to 12%
• But only 3% had VA gain of ≥3 lines
• Microperimetry - field defects near fixation
• Contrast sensitivity-decreases
• The laser scars creep close to fovea with time
• Accidental burn to fovea
• CNV occasionally due to laser causing Bruch’s
membrane rupture
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KLE RETINA UPDATE

Creeping laser scars
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Anything better?
• Search for better alternatives
• Anti VEGFs make entry -2005
• RISE and RIDE were the first RCT to treat DME
with ranibizumab
• Ranibizumab was approved for use in DME by
FDA in 2012

Anti VEGF use in DME –EBM guidelines
• If eyes have CI DME on OCT WITH CSFT >250 MU and
• VA of 6/9 TO 6/96 (20/32 to 20/320 )
• Anti VEGF is better than laser treatment
 8 letter gain in anti VEGF eyes vs
 -1 letter in laser treated eyes
• 7-9 injections are needed in the first year to get this benefit
Anti VEGF treatment for DME is better than laser in
patients with above characteristics
Virgili G et al Cochrane Database of Systematic Reviews 2014, Issue 10.
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Bevacizumab Ranibizumab Aflibercept
Size 149 kDa6 48 kDa1 97-115 kDa3
Structure Full-length antibody Antibody fragment Recombinant fusion
protein
Target All VEGF-A isoforms6 All VEGF-A isoforms2 All VEGF-A isoforms,
VEGF-B and placental
growth factor3
Half-life in humans
Ocular
Systemic
6.7 days7
20 days6
9 days1
~2 hours1
Unknown
4-5 days4,5
Pharmacological characteristics of commonly
used anti-VEGF therapies
1. www.ema.europa.eu/docs/en_GB/document _library/EPAR_-_Scientific_Discussion/human/000715/WC500043550.pdf;
2. Lucentis® prescribing information, www.ema.europe.eu; 3. EYLEA® prescribing information, www.fda.gov;
4. Dixon JA et al. Expert Opin Investig Drugs 2009;18:1573-80; 5. Tew WP et al. Clin Cancer Res 2010;16:358-66;
6. Avastin® prescribing information, www.ema.europe.eu; 7. Zhu Q et al. Ophthalmology 2008;115:1750-5
Fc domain
Fc domain
Brolucizumab and FARICIMAB

47 years F, type II DM, HT
3 monthly anti VEGF injections (razumab biosimilar) April to June
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APRIL 2018 6/12, CFT 389 MU
September 2018 6/9 CFT 333MU

A question remained
All anti VEGF trials excluded eyes with VA of 6/6 or
6/7.5
Laser treatment trial ETDRS included eyes with VA up
to 6/4
So if there is an eye with CI-DME and VA better than
6/9 can we use anti VEGF instead of laser?
Virgili G et al Cochrane Database of Systematic Reviews 2014, Issue 10.
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Protocol V study by DRCR net April 2019
Eyes with VA 6/7.5 (20/25) or better & CI DME CSFT>250mu
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Treatment % of eyes with loss of 5 letters or more at
the end of two years
aflibercept 16
laser 17
observation 19
If VA is 20/25 or better and CI DME -observation is a valid option
Initiate anti VEGF only when vision decreases to 20/30 or worse
Baker et al JAMA 2019;321(19):1880-94

Decision
making
Mitchell et al Am J
Ophthalmol
2014;157:505–513.
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observation
protocol V
If CSME present

Anti VEGFs in DME
Advantages
• Vision improves
• Reduce the central
foveal thickness
• Severity of DR ↓
• Development of PDR ↓
Disadvantages
• Repeated injections
• Many visits
• Cost
• Risk of endophthalmitis,
vitr hg, cataract, RD
• Systemic considerations
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Which anti VEGF to use?
• PROTOCOL T study by DRCR net compared
afliberecept(2mg) vs bevacizumab(1.25mg) vs
ranibizumab (0.3mg)
• Eyes with VA 20/30 or worse with center
involving DME with OCT CSF>250mu
• At the end of two years the visual results of all
the three Anti VEGFs were similar
DRCR network . N Engl J Med. 2015 ; 372(13): 1193–1203
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Protocol T -1 & 2 year results -VA gains
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VA gain A-13.3 , B- 9.7 ,R-11.2
Significant A vs B and A vs R At 2 yrs- A-12.8, B-12 R-12.3 NS
DRCR network N Engl J Med. 2015 ; 372(13): 1193–1203
Wells et al Ophthalmology 2016;123:1351-1359

Which drug is cost effective?
• Cost analysis by DRCT net concluded
that aflibercept and ranibizumab are
not cost-effective relative
to bevacizumab for CI DME
• Bevacizumab is not approved by FDA
and is used off label
JAMA Ophthalmol 2016;134(8):888-96
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How to start the treatment and how to
continue?
• Initially monthly injections for three months
• After the three injections
• PRN or Treat and extend strategies are used
• PRN –pro ra nata-as needed- every month
check VA AND OCT if edema+ give inj and call
next month stop inj- if stable VA and OCT n
call next month –pt visits monthly

Treat and extend-
• Initial loading doses of after 3 or more injections
• One mo after last inj- check if VA OCT stabilized
give inj call at six weeks
• Check VA OCT and if stable still give inj and call
after 8 weeks so on till 4 months interval is
reached
• Intervals between visits increase gradually up to
16 weeks but at each visit pt gets injection
• If VA or OCT worsen during these extensions
revert to every month injections till stable

Aiello LP, DRCR network et al Ophthalmology. 2011 ; 118(12): e5–e14.
Mitchell et al Am J Ophthalmol 2014;157:505–513
DRCR.net N Engl J Med. 2015; 372(13): 1193–1203
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May Add laser
VA ↑ by 5 or > letters
CFT ↓10% or >
VA ↓by 5 or > letters
CFT ↑10% or >

Treatment of DME
• Can be frustrating as it recurs back in 50%
cases
• Good counselling is needed from the
beginning
• Switching to other anti VEGFS or steroids can
be done if response is not optimum

When to switch to steroids ?
• If anti VEGF Treatment failure -
 loss of 10 letters or more after at least 4 anti VEGF
injections monthly OR
 after one year of treatment with anti VEGFs there is
no improvement in VA or CSFT from baseline
• If patient is not compliant with the rigorous regimen
of anti VEGF treatment OR
• If anti VEGFs contraindicated-recent MI or stroke
• Or a pregnant patient
Aiello LP, DRCR network et al Ophthalmology. 2011 ; 118(12): e5–e14.
Mitchell et al Am J Ophthalmol 2014;157:505–513
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Jan 2019 VA 6/9 after three mo of ozurdex inj
April 2018
Sept 2018

Available intraocular steroids
• Triamcinolone acetonide dose-1-4 mg –very
cheap but, not more effective >laser
• Cataract and glaucoma very common so used
sparingly only for pseudophakic patients
• Dexamethasone implant(0.7mg)(ozurdex,
Allergan Inc, Irvine, USA)- 28000 rs
• Is approved by FDA for DME
• Fluocinolone acetonide 0. 19 mg (Iluvien, Alimera
Sciences limited, UK)-not available in India
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2 years results of Triamcinolone acetonide for DME
DRCR NET et al Ophthalmology 2008;115:1447–1459
Group MEAN ±SD
CHANGE IN
VA
STAT SIGNI % of pts
who lost 15
or more
letters
STAT SIGNI
Laser 1±17 LASER VS 1 mg
3.5 LETTERS
P=0.02
14 P=0.03 vs 1 mg
P=0.01 vs 4 mg
1 mg
Triamci
-2±18 LASER VS 4mg
4.6 LETTER
P=0.002
20 1mg vs 4 mg
0.82
4 mg
Trimcin
-3+/-22 1 mg vs 4 mg
1.1 letter
P=0.49
20
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DRCR NET PROTOCOL I-Pseudophakic eyes-
subgroup analysis
DRCR network Ophthalmology 2012;119:2312-2318
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Results of slow release steroid inserts
Characteristic Dexam 0.7 mg
OZURDEX
Fluoc 0.19mg
ILUVIEN
Years studied 3 3
BCVA letter gain average 3.5 5.3
≥15 letters 22.2% 28.7%
Number of injections 4.1 1.1
OCT decrease in CSFT 116 280
Cataract surgery 59.2% 80%
BCVA in psuedophakes 6.5 NR
Use of IOP lowering medications 41.5% 38.4%
Need for glaucoma surgery <1% 4.8%
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Campochiaro et al Ophthalmology
2012;119:2125-32
Boyer et al Ophthalmology
2014; 121:1904-14

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VA gains were comparable
CFT thickness decrease more in Dexa vs anti VEGF
Cataract and glaucoma > in Dexa
Anti VEGF or Ozurdex?

Decision making -When to chose
OZURDEX for center involving DME
• Primary therapy
 for patients refusing repeated inj of anti VEGFs
 For patients with unstable angina, recent MI OR stroke
 For pseudophakic patients with no glaucoma
 For naive chronic DME of >3 yrs duration
 For pregnant women with DME
• Secondary therapy -DME not responding to anti VEGFs
Campochiaro et al Ophthalmology 2012;119:2125-32
Boyer et al Ophthalmology 2014; 121:1904-14
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Advantages
• Long lasting effect
OZURDEX-3-4 MO
Iluvien 12-36 mo
• Treatment burden reduces and costs reduce!
• Effective in chronic edema
• Systemic side effects are not a concern
Campochiaro et al Ophthalmology 2012;119:2125-32
Boyer et al Ophthalmology 2014; 121:1904-14
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Disadvantages
• Increased IOP
• Cataract
• Susceptibility to ocular infections -CMV
retinitis, ARN
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Can we get better results by using both anti
VEGFs and steroid depots together ?
• Protocol u study by DRCR.net
• The VA results were same in Dexa+Ranibizumab
group and Ranibizumab alone group
JAMA Ophthalmol. doi:10.1001/jamaophthalmol.2017.4914
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Pars plana vitrectomy with ILM peeling
for DME
• Major surgery with risks
• Usually used when all other measures fail-
recalcitrant cases of DME
• Results are not consistently good

PPV for DME
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A patient with about 10 injections of
anti VEGF
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NEW ANTI VEGF-brolucizumab
Brolucizumab
humanized monoclonal single-chain variable
fragment (scFv)
Binds and inhibits vascular endothelial growth
factor A (VEGF-A)
Mol weight 26 so more molecules can be packed
per unit weight
KITE AND KESTREL trials proved its efficacy in
DME and is now approved for DME
ADVANTAGE IS its action lasts for up to 12 weeks

Brolucizumab in INDIA is PAGENAX
• Five 6 weekly injections
• Later every 12 weeks

New molecule for DME-FARICIMAB-
VABYSMO

Dual effects
The anti-VEGF-A effect
• reduces vascular permeability
• inhibits endothelial proliferation so suppresses
neovascularization
The anti-Angiopoeitin 2 effect is thought to
• improve vascular stability and
• desensitize the vessels to the actions of VEGF-
A

Angiopoetin 1 and 2
• They are proteins that bind to TIE 2 receptor on
the cell membrane
• They compete with each other
• Angio 2 inhibits the TIE 2 receptor linked enzyme
mechanisms and promotes vascular permeability
to increase and neovascularization
• So inhibiting angio2 will stimulate TIE 2 SYSTEM
AND decrease vascular permeability and suppress
neovascularization
• Angio 1 has stimulates the TIE 2 receptor linked
enzyme mechanisms

FARICIMAB
• APPROVED FOR DME treatment by FDA after
results of YOSEMITE AND RHINE trials were
submitted
• Advantage is treatment intervals are 12 weeks
and can be extended to 16 weekly also
• Visual gains and effect of CFT are same as that
of aflibercept

Treatment of PDR
• PDR WITH HRC, advanced PDR
• Treatment is recommended at PDR WITH HRC
but it may be done earlier if pt follow up is
questionable or one eyed
• DRS study
If we treat eyes with HRC PDR by Pan retinal
photocoagulation PRPC-the risk of severe visual
loss is reduced by >50%
Diabetic Retinopathy Study Research Group.
Ophthalmology 1978;85:82–106.

D. Early PDR
E. High risk PDR
New vessels present (criteria not
met E)
Any one or more of the following
criteria :
1. NVD with VH
2. NVD > ¼ - 1/3 DD without VH
3. NVE > ½ with VH
Stages of Proliferative Diabetic Retinopathy - PDR
26% 4%
(<5/200) within 2 yrs
Without treatment With treatment
26% 9%
30% 7%
Risk of severe visual loss
Diabetic Retinopathy Study Research
Group. Ophthalmology
1978;85:82–106.

PRPC –how to do?
• Take consent
• Topical anesthesia/PB
• Usually slit lamp laser machine delivery is
used/indirect laser ophthalmoscope can also +
• Mainster wide field lens/ 165 d lens
• Spot size 200-500 mu
• Duration of laser spot 0.1 sec
• Power start from 200 mw and titrate it to get
mild white burns

Lenses used in slit lamp delivery
of laser
119
Lenses used in indirect
ophthalmoscope delivery of laser

Effect of laser in retinal tissues
• When we apply the laser burns to the retina the laser is absorbed by
a) Melanin pigment in the retinal pigment epithelium(RPE) , melanin in
choroid
b) Haemoglobin in retinal capillaries, choroidal capillaries to lesser extent
• This causes the temperature to increase in the RPE and overlying retina
usually by 10-15 d C above body temperature
• This leads to protein denaturation in the RPE cells and vacuolation in
overlying photoreceptors leading to their death
• This is thermal effect-photocoagulation
• Hemoglobin in retinal capillaries also absorb laser and this may lead to
closure of capillaries of retina due to thermal effect

PRPC
• Whole procedure is done usually in 3-4 sittings at weekly
intervals
• Start inferiorly so that IF vitreous hg occurs will clear last
from inferior area
• Start about 1 dd away from disc nasally and 2 DD away
from fovea temporally and outside arcade
• All the retina way up to equator or beyond is covered by
laser burns in 3-4 sittings
• Burns are placed 1 burn width apart
• Usually 1200-1500 spots are needed per sitting if 200 mu
size is used and half if we use 500 mu size
• Additional laser sittings are done later if there is no
regression of NV or there is recurrence

From IJO 2016

Signs of regression
• New vessels shrink and fibrose
• Venous dilatation reduces
• Hgs, MA reduce
• Disc pallor
• Laser scars develop in to pigmented and some
atrophic scars

Complications of PRPC
• Corneal abrasions
• Worsening of DME
• Choroidal detachment, hypotony if extensive
PRPC is done
• Vitreous hemorrhage
• TRD increase
• Peripheral Field constriction -15 d of field is lost
• Disc pallor
• Pupillary atrophy

Anti VEGF for PDR
• VEGF is a known to promote
neovascularization
• So anti VEGF will arrest that process

Protocol S study compared ranibizumab injection with
PRPC for high risk PDR
Excluded eyes with TRD
• It showed that ranibizumab was better than
PRPC in eyes with PDR in terms of
Less loss of Visual field
Less need for vitrectomy surgery
Less chances of DME
Final VA results were same in both groups
DRCR network. JAMA. 2015;314(20):2137-2146.

RE PDR before and after avastin injection

Inform patient about pros and cons
PRP VS ANTI VEGF FOR PDR
PRP
 3-4 sittings
 Destructive
 Less costly
 Non invasive
 No Endophthalmitis
 Peripheral field lost ++
 Dark adaptation
 DME worsens+
 PPV –need more+
• Long term follow up less
rigorous
Ranibizumab/anti VEGF
 7 inj /first year
 Not a destructive
 More costly
 Invasive
 Endo, RD possible
 VF changes less
 Not affected
 DME less
 PPV need less
 Long term follow up needed
recurrence
 Side effects systemic +

When anti VEGF injections are stopped
• PDR may come back and have disastrous
results if not follow up
• Anti VEGF effect lasts only one month
• The hypoxic retina starts producing VEGF
again when anti VEGF treatment is stopped

So is Ranibizumab approved for
treatment of PDR?
FDA approved for not only PDR but also ALL
FORMs OF DR-MODERATE, SEVERE, VERY
SEVERE
• Ranibizumab in APRIL 2017
• Aflibercept in May 2019 (PANORAMA STUDY)
• So it is valid to give anti VEGF for moderate or
severe NPDR even without DME

From Rise and Ride studies
Ip et al Ophthalmology 2015;122(2) 367-374

Panorama Study for Aflibercept

Anti VEGF treatment for NPDR
• So offer anti VEGF injections to patients with
DR (Severe NPDR) to stop its progression and
also reverse the disease process
• Eylea can be given every four months

March 2017
February 2012

Surgical treatment of Advanced PDR
Indications for PPV
• Vitreous hemorrhage, subhyaloid hg that is not
resolving precluding PRPC (TYPE I -1 mo, Type II -3
months)-rule out TRD by USB
• Vitreous hemorrhage with NVI or NVA need sooner
interventions
• TRD that involves macula or threatens macula
• TRD with Combined Rh RD -urgent
• Tractional macular hole
• Thick post hyaloid that has reduced the vision
• Recalcirant DME and tight posterior hyaloid

LE PPV FOR TIGHT HYALOID

Post PPV ILM peeling

Anti VEGF preoperatively
• Especially in TRDs
• Given 1-10 days before surgery
• The new vessels shrink and per operative
bleeding will be less
• Also helps in membrane removal

Goals of PPV
• Remove all opacities- blood membranes
• Remove post hyaloid and all the tractional
membranes without causing any retinal
breaks
• Perform PRPC
• Adequate tamponade

Steps of PPV
• Counsel patient and explain risks
• Local or GA
• 23 or 25 g or 27 g
• Fix the trocars, do core vitrectomy
• Make an opening in post hyaloid in periphery
where it is usually detached & extend it 360d
circumferentially
• Remove membranes from the retina if present
with delamination or segmentation

Delamination

SEGMENTATION
3rd October 2021 KLE RETINA UPDATE 2021 144

Segmentation
• A membrane will have some area detached
from the retina
• This area is opened and cut till the area where
there are firm adherence is there
• So islands of membranes are created from one
membrane

Complications of PPV
• Intraoperative –bleeding , retinal tears, lens
touch, incomplete removal of posterior
hyaloid
• Post operative-rebleeding(30% of VHG cases
rebleed), increased IOP, Cataract, Rh RD,
Recurrent tractional RD, side effects of silicone
oil, NVG, phthisis

TRD
3rd October 2021 KLE RETINA UPDATE 2021 151

Protocol s study inclusion criteria
• Study Eyes
• Inclusion
• Presence of PDR which the investigator intends to
manage with PRP alone but for which PRP can be
deferred for at least 4 weeks in the setting of
intravitreal ranibizumab, in the investigator’s
judgment Best corrected E-ETDRS visual acuity
letter score ≥ 24 (i.e., 20/320 or better) Media
clarity, pupillary dilation, and individual
cooperation sufficient to administer PRP and
obtain adequate fundus photographs and OCT

Protocol S exclusion criteria
• Exclusion History of prior PRP, defined as ≥100 burns
outside of the posterior pole Traction retinal detachment
involving the macula
• Exam evidence of neovascularization of the angle
(neovascularization of the iris alone is not an exclusion if it
does not preclude deferring PRP for at least 4 weeks in the
investigator’s judgment)
• If macular edema is present, it is considered to be
primarily due to a cause other than diabetic macular
edema (e.g. post-surgical macular edema or epiretinal
membrane) An ocular condition is present (other than
diabetic retinopathy) that, in the opinion of the
investigator, might alter visual acuity during the course of
th

20-09-2019 155
3 D LIVE 2.0
Mitchell P et al
Am J Ophthalmol 2014;157:505-513

NORMAL AVERAGE CENTRAL THICKNESS(1MM)
in Adult population
• Stratus OCT ------------- 212 +/-19
• Spectralis HRA OCT ------ 289 +/- 16
• Cirrus HD-OCT ------------ 277 +/- 19
• Spectral OCT/SLO--------- 243 +/- 25
• SOCT Copernicus -------- 246 +/- 23
• RTVue—100------- 245 +/- 28
• Topcon 3d 1000- 231+/-16
IOVS 2009

DR WANI'S TALK ON Diabetic Retinopathy Part II december 31 2022 for KLE RESIDENTS.pptx

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