4. DM & Eye
• DR/DME/VH/TRD/rubeosis/NVG
• orbital & ocular infection/blepharitis
• dry eye
• corneal abrasions
• anterior uveitis
• RVO/RAO/OIS
• papillitis/AION
• cranial nerve palsies
DM- General
• 90% T2/Msia 18% population >18yo, 50% unDx, 50% +Cx at presentation, 90% HbA1c >6.5%
• T1DM: retinopathy is rare at diagnosis but present in over 90% after 15 years.
• T2DM: retinopathy is present in 20% at diagnosis but only rises to 60% after 15 years
5. DR & DME- classification
• International classification of DR (ICDR) disease severity scale (DSS)
• mild-mod-severe NDPR, PDR
• DRS & ETDRS
• NPDR severe/very severe, PDR early/high risk
• NVD >/= 1/3 DD
• NVD <1/3 DD with VH/PRH
• NVE >/= ½ DD with VH/PRH
• DME
– center involvement: CMT (center 1mm/100um) >250/300um
– vision impairment: VA =/< 6/9
– focal: micro-aneurysm with circinate ring
– diffuse: cystoid ME
– +- VMT
• International classification of DME (ICDME) disease severity scale (DSS)
• absent vs present (mild-mod-severe: based on center involvement)
• CSME (ETDRS)
– retinal edema within 500um center of fovea
– HE with retinal thickening within 500um center of fovea
– retinal thickening >1DD located within 1DD center of fovea
10. DME Q
• How to detect/diagnose/classify
• Use of OCT
• How to manage
– Between antiVEGF, steroid, laser
• First line, switching, SE
• One more: vitrectomy
– Between different antiVEGF
– Between different treatment response
– Special groups: pregnancy, ATE
• Co-existing condition: PDR, ischemic maculopathy,
NVG, cataract, stable glaucoma, post vitrectomy
11. OCT @ DME
• Normal CRT: 212 ± 19 and 289 ± 16 μm
• DME CRT: vary from 225 to >450 μm.
• Identify subtypes
– Morphologic patterns
• Diffuse retinal thickening
• Cystoid macula edema
• Serous retinal detachment (SRD) without posterior
hyaloidal traction (PHT)
• PHT with tractional retinal detachment (TRD)
– Presence of macula traction
– Localize edema to specific layers of the retina
12. OCT @ DME
• Prognostic Markers
– i. Subretinal fluid (SRF)
– ii. Small intraretinal cystoid fluid
– iii. External limiting membrane (ELM) and Inner
segment/Outer segment (IS/OS) integrity
– iv. Vitreomacular adhesion, no ERM
– hyperreflective foci (HRF) esp for steroid therapy
– No disorganization of retinal inner layers (DRIL)
– Not thin subfoveal choroid at baseline
13. FFA @ DME
• indicating failure or inadequate response to
treatment
• determination of foveal avascular zone (or
use OCTA)
• As a guide for supplemental laser
• diagnosis of co-existing peripheral DR
14. PDR/ADED Mx
• Systemic & Ocular
• Systemic (modifiable)
– lifestyle, medical nutrition therapy (MNT), medications/risk control
–UKPDS (T2)/DCCT (T1) (DM HbA1c <7%/HPT/dyslipidemia)
– HbA1c 1% = DR 40%/laser 25%/blind 15%
– SBP 10mmHg = DR 35%/laser 35%/blind 50%
– TG > DR, LDL/HDL > DME
– BMI >27/<20, waist >90 (M) >80 (F)
– Pregnancy with DM: 50% progress (not GDM)
– IFG (6.1) & IGT (7.8) DM 10%/yr, CVS 2-3x risk
• Ocular
– PRP (DRS/ETDRS/DRCR.net)
– antiVEGF (unsure role, +observed benefit, risk of TRD, adjunct Rx)
– surgery VH
-DRVS study- timing for op- lasered? 4wk? antivegf
- protocol s- high risk pdr- RPR vs Lucentis
young ADED problem- no pvd, need Ga, compliance, bleeding more
15. DME- Pathogenesis
• Inner retinal hypoxia → VEGF → overcomes the natural
inhibitor PEDF (RPE) → increase vascular permeability →
leakage of osmotically active molecules (retinal exudates)
• These exudates siphon water from the capillaries →
intraretinal edema.
• Hypoxic autoregulatory dilatation of the arterioles →
decreases resistance inside the vessels → increasing
downstream capillary hydrostatic pressure
• Fluid movement into the retinal tissues between the
photoreceptors and the horizontal, bipolar and amacrine
cells → disorganization of the retina’s architecture
• Other inflammatory pathways: retinal leukostasis, and
synthesis of proinflammatory mediators (interleukin 6,
monocyte chemoattractant protein-1)
16. DME- treatment
• CPG (Malaysia)
– VA+/CMT+: treat (antiVEGF/IVTA/Ozurdex/laser)
– VA-/CMT+: observe or treat (laser)
– VA-/CMT-: observe
– 6x monthly injection → worsen/stable/improve till
stable/dry/end point x 2 → defer 4-8-16 wk (defer & extend)
– Key factors: access, comorbid, lens status, follow up
• focal/grid laser:
– vs antiVEGF less effective
– indication: >long term effect, not responding to 6x antiVEGF
(rescue laser), before PRP/cataract op
– risk: scotoma/transient worsening/CNV/fibrosis/scar
expansion/fovea burn
•Studies: ETDRS (CSME), rise/ride/resolve/restore (RBZ),
DRCR.net (DME/steroid/antiVEGF)
17.
18.
19.
20.
21.
22.
23.
24. AntiVEGF @ DME
• 1st line: symptomatic (VA 6/9) central involved (300um thinkness
& within 100um), phakic, glaucoma, <60
– X pregnancy, recent ATE, cant follow up
• loading dose of 3 injections
– Monthly, PRN, T&E, defer & extend
– Switching (to steroid) after 5-6inj
– Progression: optimal, stable, worsening
– Response: target, adequate, non/inadequate)
– 6/15 (20/50) or worse:> Aflibercept
• Ideal 5-6 initial monthly doses
• total 8-9 injections in year 1
• arterial thromboembolic events (ATEs)- CVA/MI
– maybe related to cumulative drug exposure
25. Steroid @ DME
• Can be 1st line in pseudophakic with prior stroke/MI
• Generally not for phakic + younger than 60yo, glaucoma not optimised/unastable
• IOP Monitor: 6 weeks (IOP) months 2-3 (IOP) retreatment 4-6 monthly
– Stable glaucoma + Ozurdex IOP check 1, 2, 4wk
– MEAD study: IOP >10 mmHg in 28%, >35 mmHg in 7%.
– No rise in IOP @ first injection = unlikely to rise in subsequent (no cumulative effect)
• 50% phakic cataract
– between 12 and 24 months (after treatment with 2–4 injections)
• considered during cataract surgery (after IOL is implanted and wound is stable)
26. Focal/Grid laser @ DME
• Rescue laser after 6mth antiVEGF
• Ci-DME with good VA
• Non CI-DME with
– pregnancy
– rapid worsen cataract
– rapid progress/central threatening
–Prior cataract surgery
27. DME Rx Response
Anatomy (CMT) & functional parameter (VA)
i. Target: 6/6 or CMT of <300mm.
ii. Adequate: 6/12 or better and CMT <300mm, or
improvement in CMT as a percentage (>10%) after
treatment
iii. Inadequate: <6/6 and CMT still >300mm or change
in CMT <10% after 1 to 3 anti-VEGF injections.
– if visual acuity of 1–2 lines and 10%–20% improvement
in OCT measurement is not achieved in 3 injections.
iv. Nonresponse: <6/6 and CMT still >300mm or
change in CMT <10% after 3 injections.
28. Different in AntiVEGF Mx
nAMD vs DME
• response of Rx
• Need of frequent inj & visit
• Treat-defer & extend (no inj) vs treat & extend (+inj)
• Defer when stable x 2 (despite some fluid) VS extend
when dry/very little fluid
• VA if delayed/extended
• Regime of Rx
• Best antiVEGF in general VS different VA grps
(baseline)
• Final VA in AMD less than baseline
• Rescue laser & steroid
29. DME- other points
• 34% resolve spontaneously aft 6mth
• hba1c reduce 2 unit in 6mth- better
• laser can improve vision 30% in 2yr- need longer to work, but last
longer. if cmt kess than 400 laser or not central involving-- more cost
effective (NICE)
• subthreshold micropulse laser
• fenofibrate 160mg/day PPAR-ALPHA
- Study FIELD ACCORD
- DR reduce progress
• antivegf- 60%respond well but-
- many 50% need long term Rx,,ffa still leak etc..
• chronic dme- rvo/ mactel/ mac ischemia, vmt, thin choroidal thickness
• RBZ 20x affinity >BCZ
• Pegaptanib (Macugen)
– 28-base ribonucleixribonucleotide aptamer
– with high affinity for VEGF165 isoform
32. Protocol V (very good VA ci-DME)
• 20/25 or better:
– observe vs laser vs antiVEGF: same VA outcome in 2yr
– Recommendation: observe then TCA 2mth – 2mth –
4mth (if VA still stable)
– If VA worsened: treat (with AFB)
– new def for VA worsened: =/> 10 letters or 2 lines
dropped from baseline, or 5-9 letter loss at 2 consecutive
visits
– If OCT worsen but VA stable: observe still but shortened
TCA to 1mth if OCT stable back then TCA 2mth – 4mth
• 20/32 or 78 ETDRS letters or 6/9 Protocol I & T
– = visual impairment, antiVEGF better than laser
33. Protocol U (Rescue Ozurdex)
• 3 inj if inadequate reponse 3 extra inj
then assess response
• If still inadequate response (55%)
–Add Ozurdex. VS Continue RBZ
–Outcome VA: same (+2.7 VS +3.0)
• Sub phakic grp VA: worse (+1.1 VS +4.1)
• Sub pseudophakic grp VA: better (+5.1 VS +2.0)
–CMT reduction: better (-110 vs -62)
–SE: IOP 30% at any point
35. Approach to RVO
• Diagnosis, monitor, prognosis
– Cause – Dx – Complication
– OCT & OCTA & FFA
– VA, iris, fundus
– Key: DDx, edema/CMO, ischemia (retina & macula)
• Systemic workup
• Treatment
– leakage & ischaemia
– AntiVEGF
– Steroid
– Surgery
– Laser
36. RVO
• BRVO 3x more than CRVO
• BRVO 63% superotemporal
• ischemia/CFO: BRVO 5DD, CRVO 10DD
• CRVO: 1/3 ischemic, 2/3 non ischemic
• non ischemic ischemic: 15% at 4/12, 1/3 at 3yr
• Ischemia CRVO: NVI (1/3 at 4/12) > NVD (23%) > NVE
(5%)
• Ischemia BRVO: NVE (20% at 6/12) > NVD > NVI
• collateral with reduced edema in 60% cases (> if VA
better than 6/12)
37. RVO- Special Signs
• Chronicity
– Collateral: circulation @BRVO or ONH @CRVO
– Large capillary aneurysms with exudation
• CLRAO
– low perfusion pressure in cilioretinal arteries
compared with the increased retinal capillary bed
pressure
• PAMM
– paracentral acute middle maculopathy
– whitish appearance of the retina around veins
38. Biomarker for Prognosis
• Baseline VA
• CRT/IRF/SRF
• Hyperreflective foci (HRF)
– In DME, HRF usually accumulate around fluid departments,
– in RVO, HRF accumulate around the OPL regardless of location
• Disorganization of the inner retinal layers (DRIL): inner and outer
photoreceptor segment line, ELM
• prominent middle limiting membrane (p-MLM)
• PAMM
• Macular ischaemia/atrophy
• Response to treatment in a spatiotemporal morphologic analysis.
• First three inj response
39. Specific Diagnosis
• Ischemic CRVO
– >10DD CFO
• Delayed FFA/masking by hemorrhage
• Standard 55degree/7field (not UWF)
– clinical signs: prominent CWS/deep hrge, low VA (≤0.1) and RAPD
• CMO
– Central retinal thickness (CRT) @central 1-mm area
– Mainly treatment response, unclear for prognostic value
– IRF, SRF, HRF, DRIL/disruption (morphologic changes VS VA/prognosis= unclear)
– HRF= negative VA prognosis
• Macular ischaemia (FFA/OCTA)
– No consensus exists on the extent/location of macular non-perfusion that can
cause loss of vision treat
• Hemispheric RVO
– arteriovenous crossing is visible and are considered a variant of BRVO
• Hemi-central RVO
– If behind the lamina cribrosa, considered as BRVO or CRVO
40. Investigation @ RVO
• Key: atherosclerosis or hyperviscosity or abn
blood flow
• Minimum: medical history, BP & DXT, FBC
ESR CRP
• Young & bilateral cases:
– thrombophilia
– inflammatory/autoimmune
41. RVO- Mx
• CRVO: CFO >/=10DD vs NeoV, CMO
• BRVO: CFO >5DD vs NeoV (type), CMO
• HRVO=CRVO/BRVO
Study
• CVOS: full PRP @NVI/NVA, no laser for CMO, close observe
biweekly if ischemic but no NV
• BVOS: sectoral PRP @NVE, grid laser @CMO
• BRAVO & CRUISE: RBZ (6+PRN) improve VA/CMT
• CRUISE/HORIZON/RETAIN: RBZ (6+PRN till 12/24/48mth)
• SCORE: IVTA @CMO
• GENEVA: Ozurdex (IOP peak 2mth, 20%>6mth, cataract 70%
@6mth)
• COPERNICUS/GALILEO: Aflibercept (6+PRN, cross/no cross
over, early Rx better)
42. RVO CMO- Rx
• AntiVEGF
– first line for both C/BRVO
– least monthly x 3-6 till VA good and stable x 3 (2
visits) PRN/T&E
• IVT steroid
– 2nd line: after 3-6 inj/CI to antiVEGF
– 1st line: if unable to do month inj (still need IOP
check 2-4weekly) + pseudophakia
– Improvement D7 max D60 retreat 3-4mth
• Resolution= no IRF and SRF at least 6 months
after the last injection
43. AntiVEGF @ CMO/RVO
• Key: start earlier, give enough (till VA
stable), close monitor (1-2mth in 1st year for
ischemic case)
• Regime: monthly until VA stability (expect
good response) 1-2monthly follow-up for
at least 1 year (for ischemic case) OR
3monthly (for non-ischemic) subsequent
extension (up to 3 years)
44. Laser @ RVO
• CRVO
– PRP for NV (not for ischemic/>10DD CFO) in CVOS (biweekly follow
up)
• + AntiVEGF (adjunct)
• PRP first: same day (prior to anti-VEGF) or delay antiVEGF 1-2 weeks.
• Glaucoma backup (surgery) esp IOP raise/NVG/close angle
– Prophylactic PRP (before NV)
• If biweekly follow up not practical
• prevent iris neovascularization in ischemic CRVO
• 80% develop neovascularisation
• BRVO
– Focal laser for CMO (but antiVEGF >effective)
– Sectoral PRP for NeoV
45. CRVO follow up & discharge
• Non-ischaemic CRVO
– q3 months @first 6 months
– at least 18 months is usually recommended, or
– disc collaterals and spontaneous resolution of macular oedema
for at least 6 months
• Ischaemic CRVO
– Monthly for first 6mth then 1-2mthly (if antiVEGF) or 3monthly
(if no antiVEGF needed)
– 3 years (30% conversion)
• BRVO
– three to four monthly intervals for patients with one quadrant
or more retinal ischaemia.
– Up to 24mth
46. RVO- Ix/Mx/Studies (new)
• Ix:
– ultra-widefield FA (UWF-FA): ischemic index
– OCTA
• Mx:
• CRA (venous)- risk of CNV/fibrosis/TRD/VH
• radial optic neurotomy (RON) with TPPV @CRVO
• Sheathotomy @BRVO
• thrombolytic therapies
• anticoagulation or antiplatelet: no high quality evidence
• HRT/oestrogen containing therapies: do not start, if started +- continue
(discuss)
• Studies
– SCORE II: CRVO with CMO
• monthly RBZ vs Eylea x 6mth → Ozurdex as 2nd line
– LEAVO: CRVO with CMO
• RBZ vs Eylea
- CRYSTAL and BRIGHTER
• VA stabilization criteria (defined as three consecutive visits with stable VA)
50. ARMD- Type & Classification
• Dry vs wet- 90 vs 10% (blindness opposite)
• Normal/normal aging/early/intermediate/late AMD
– drusen size + pigmentary changes → CNV/GA
• Dry- drusen/GA
• Drusen- size (drupelets/63/125=vein diameter at OD margin), morphology
(hard/soft/confluent), +- dystrophic calcification +- pigmentary changes
• PED- x 4 (drusenoid/serous/hrge/FVC)
• Wet- CNV/PED/RAP/PCV
• CNV (FFA/MPS study)
– classic (20%, predominant/minimal), (location: extra/juxta/subfovea, 200um
vs foveola)
– occult (80%, FV PED/LLUS)
• CNV (ICG)
– Hot spot <1DD (less common, for laser)
– Plaque >1DD (more common, poor natural history)
– Combination (rare)
• Wet (CNV)- type 1/2 (subRPE/subretina) or type 3 (RCA with RAP)
• CNV (active/not)- +fluid/hrge/leak on FFA/enlarging CNV membrane/deteriorating
vision
• Variant- RAP x 3 stages (1-3: IRN/SRN/RCA), IPCV
51. ARMD- Risk
• Risk of ARMD:
– Non- modifiable- age/race/FHx (3x)/genetic (CFH/ARMS2/lipid
metabolism)
– Modifiable- smoking (2x), HPT/CVS/obese/diet, aspirin (for cnv)
– Minor- female, blue iris, cataract op, sunlight exposure
• Risk of Drusen (5yr to late ARMD):
– intermediate size + pigmentary changes → 10%
– large size/soft → 13%
– large size/soft + pigmentary changes >1/2 DD → 50% (blue mountain
eye study)
• Risk of PED (to CNV)
– serous PED → 33% to CNV in 2yr
– drusenoid → 25% to CNV, 75% to GA in 10yr (33% to GA/CNV in 3yr)
• Risk reduction with antioxidant (AREDS1/2 formula)
52. ARMD- S&Sx
• BL gradual painless BOV
– asymmetrical
– vision better with bright light
– central +ve scotoma/metamorphosia (PED/CNV)
• Acute on chronic unilateral BOV
– CNV bleed (SRF/PED)
– RPE tear from PED (crescent pale area=tear + adjacent pigmented area=retracted folded RPE)
• Drusen (progress/increase/confluent)
• Pigmentary changes (hyper/hypo, focal/diffuse) → GA
• SRF (serous/hrge), lipid exudation
• PED
– orange nodule with paler halo (SRF), dark red if hrge PED
– +- pigment band (chronic) +- RPE tear
– FV PED (>irregular), if drusenoid (>shallow/pale/scalloped edge)
– if no drusen → DDX IPCV (for ICGA)
– RPE rip- risk: height/size, antiVEGF/PDT/laser at edge of PED
• CNV
– greyish/pink-yellowish lesion
– +- fluid/hrge/lipid exudate → disciform scar
• Relevant negative
– Myopic changes (PPA/tessellated fundus)
– Choroidal mass
– Laser mark
– OD drusen/angioid streaks
53. ARMD- Ix
• OCT
– drusen/PED (content/CNV notch/irregular fibrous)/SRF
– RPE loss/RPE tear/PRC loss
– outer retinal tubulation (round hypoR space due to PRC loss) & outer retinal corrugation
(hyperR layer due to basal laminar deposit)
• FFA
– drusen: hyper (window/late stain) or hypo (hydrophopic/lipid rich), starry sky in DDX
cuticular drusen), autoF in redfree/FAF
– serous PED: hyperF (pooling), indentation/notch = CNV
– FV PED (occult CNV): stippled/granular hyperF, PED fill then leak later
– drusenoid PED: hypoF then late irregular staining
– hrge PED: hypoF (masking)
– RPE tear: hyperF (folded RPE) + hypoF (tear)
– CNV: confirm Dx (occult/classic), TRO RAP/IPCV, scar (late stain)
• ICGA
– PED: hypoF with hyperF rim, focal hyperF if occult CNV/FV PED
– CNV: focal hyperF hotspot/plaque, delineate occult CNV, better view with
hrge/fluid/pigment, DDX PCV/CSCR/RAP
– RAP: hairpin loop (hot spot in mid phase + perfusing arteriole + draining venule
54. CNV: OCT vs FFA
• OCT – FFA
• Type 1 CNV (subRPE) occult CNV
• Type 2 CNV (subretina) classic CNV
• Type 3 CNV (intraretinal) RAP
55. Management of AMD
• observation and early detection
• antioxidant vitamin and mineral
supplements
• intravitreal injection of anti-VEGF agents
• PDT
• laser photocoagulation surgery
• encouragement of smoking cessation
58. nAMD Rx
• Rx classification
– Standard/fix dosing, reactive (PRN), proactive (T&E), mixed
(T& defer/PRN)
• Fix? Best result vs over Rx/$/choroidal atrophy
• T&E studies
– LUCAS, TREX, TREND, ARIES, ALTAIR, FLUID
• ALTAIR: AFB 2wk vs 4wk T&E
– VA/OCT same
• ARIES: T&E after loading VS after 1yr- same
• FLUID: T&E start after bone-dry or minimal fluid (200um)
= relaxed T&E- almost same
– Controversial theory of minimal fluid less risk of GA
59. AMD T&E
• Standard 2wk extension when bone dry up to
12wk max 2wk shortened when worsened
• Variation
– +defer
– +maintain if stable fluid ALTAIR
– +extend 4wk with AFB (ALTAIR)
– +extend with min fluid FLUID
• Non responder
– Tolerance: shorten visit freq/inj or increase dose
– Tachyphylasis: usually after many inj, good initial
response, acute drop in response later
60. Rx responder in nAMD
• Types of response
– Good, partial, poor, non
– Early & consistent (50%)
– Early & non consistent
– Late & non consistent
– Non responder
• Def of non responder?
– VA/OCT/FFA leak over 6/12? with best std treatment
– Or VA still decline despite best care/monthly inj
– ANCHOR/MARINA best care/monthly inj still decline VA in
5% (1st yr), 10% (2nd yr)
– CATT 8% VA decline, 60% still fluid, 20% FFA leak
61. AMD- activity
• Quantitative VS qualitative
• CMT 10% or 50-100um
• SHRM- subretinal hyperrefractive material
(activity + >fibrosis w poor VA)
• Fluid at any level (hypolucent/reflective)
• Reduced VA that corresponded to disease
• H’rge (new)
• Leak @ FFA
62. Non response case
• Why
– Fibrosis ++
– Block/treated but new CNV
• Types
– True non responder (from beginning)
– Tolerance (initial good then poor response)
– Tachyphylaxis (early reduce response)
– Poor/late responder (need time)
• How
– Reduce interval of injection (if already extended) and check response
– Switch drug
– Combine PDT (ICG TRO IPCV)
– Combine steroid (no study)
– Stop & monitor (if ++ fibrosis/scar)
• To stop antiVEGF Rx if
– GA/fibrosis/scar @ fovea
– Pre/Submacular hrge/VH (if small for pneumatic, if large for TPPV +- drain)
– H/o ATE/CVA/IHD in 6/12 with poor response (risk > benefit)
63. Approach to non-responder
• Evaluate adherence/persistent! (pt factor & Rx
regime)
• Continue Rx
• Same agent with better/different regime
• Shorter interval +- <4wk
• Switch agent
• Combination for PCV (rpt FFA/ICG if needed)
• DDX
• Stop
83. PCV- Diagnosis
• Clinical
– Orange nodule, massive hrge
– + DDX ARMD: no drusen/GA/pigment changes
• ICGA (Everest criteria)
– focal hyperF (@red-orange nodule) 1st 6min
– HypoF halo
– nodular (@stereoscopic)
– pulsatile (@dynamic)
– BVN
– massive submacular h’rge
• OCT
– thumb like projection/peaked PED/double hump, ring like lesion,
double layer/undulating RPE, abn internal reflectivity at PED,
pachychoroid (EDI)
• OCTA- high flow under PED/notch
84. PCV- Mx
• Active?
• VA drop 5letters/1line
• leak: SRF/IRF fluid, SR/SubRPE bleed, FFA
• PED
• Laser: for extrafoveal (200um)
– need to treat BVN also (FFA based + 1000um more)
– Cx: recur/persist/CNV/RPE atrophy
• PDT: (must combine with anti VEGF, initial/deferred)
– For polyp regression/BVN regression
– Cx: recur esp BVN/new CNV/new polyp, RPE rip/scar, new bleed,
choroidal infarct
• AntiVEGF: (mono/combine with stat/deferred PDT)
– RBZ: monoT if good VA/high PED (risk of rip)/high grape-like lesion or
BVN (risk of new CNV)
– Eylea: better for less choroidal thickness, polyp closing, PED
• Outcome: VA gain, polyp closure, absence of disease activity, reduce
inj , treatment burden
87. CSCR (General)
• idiopathic subretinal serous fluid at macula
• d2 focal dysfuction RPE + hyperpermeability of
choriocapillary
• Risk: young M/older F, steroid/stress/pregnancy, +- H
pylori/drugs (sildenafil/ecstasy)/OSA
• SSx: UL (BL rare)/central BOV scotoma/metamorphosia,
hyperopic shift, micropsia → well defined serous RD + focal
RPE lesion (PED/depigment) +- exudate/HRF chronic RPE
mottling or recur snail tract
• Ix: OCT macula (EDI), FFA (smoke stack/ink blot/granular),
ICGA (abn choriocap), +- FAF, OCTA
• Mx: observe (3-6mth, 80% N VA, 50%recur- 50%1st yr),
4mth KIV laser/PDT (half)/antiVEGF/Diamox
• Mx: risk modification (steroid reduction/withdraw)
• Cx: 50% recur, chronic +- visual loss, CNV (DDx or Cx)
88. CSCR- the S
• Serous
• Subretinal
• Scotoma
• Smaller (micropsia)
• Stress
• Steroid
• Self limited
89. Central Serous Chorioretinopathy
International Group
• chronic persistent, acute recurrent, acute on
chronic, and subclinical disease when
attempting to address the limitations of using
the simple terms acute and chronic
95. Myopic CNV
• Lacquer crack with SRH VS CNV SRH
–Coin shaped hrge/Fuch spot
–Resolved by time/without Rx
–No leak at FFA
• ICG may not show leak (low activity CNV)
• Dome shaped CNV
96. mCNV- Mx
• 10% of pathological myopia
• depends: location, symptoms
• progression: atrophy/lacquer crack → CNV → coin
hrge → Fuch’s spot → further atrophy
• Extrafoveal: antiVEGF > focal laser (risk of crack/new
CNV/scar + expansion)
• Subfoveal: antiVEGF > PDT (only reduce level of VA
loss)- REPAIR/RADIANCE/MYRROR (Eylea) studies
• AntiVEGF- immediate Rx better than delay (MYRROR),
PRN basis (good prognosis),
• Prognosis: much better than wARMD, fewer inj
• Alternative: surgery (excision, macular translocation)
97. High myopia
META-PM (meta-analysis for pathologic myopia) international classification
• for myopic maculopathy
• OCT and colour fundus photography
• retinal changes + choroid, Bruch’s membrane and the RPE
• “no myopic retinal degenerative lesion” (Category 0), “tessellated
fundus” (Category 1), “diffuse chorioretinal atrophy” (Category 2), “patchy
chorioretinal atrophy” (Category 3), and “macular atrophy” (Category 4).
• “plus” lesions: lacquer cracks, myopic choroidal neovascularisation, and
Fuchs spot.
• Posterior staphyloma was considered as a further important sign
ATN classification
• three factors: atrophy, traction and neovascularisation.
104. • Protocol W
• Protocol W is evaluating intravitreous anti-VEGF for the prevention of vision-threatening outcomes (DME or PDR) in patients who present with
severe nonproliferative DR. This outcome will be important to determine whether preventive anti-VEGF therapy in DR is beneficial. The study is
anticipated to be completed in April 2022.
• Protocol AA
• Protocol AA is comparing ultra-widefield fundus imaging to ETDRS seven-standard-fields imaging for the assessment of DR and prediction rates
for worsening of DR.
• Protocol AB
• Protocol AB is a surgical study evaluating prompt vitrectomy versus anti-VEGF therapy for vitreous hemorrhage due to PDR.
• Protocols TX and AC
• Currently enrolling trials include Protocols TX and AC. Protocol TX is a single-visit 5-year follow-up study of patients who were enrolled in
Protocol T. This study will provide information on long-term VA, changes in treatment, and remission or recurrence of DME after protocol-specified
treatment was stopped.
• Protocol AC is an evolution of Protocol T that is examining the real-world cost burden for patients and insurance systems and considering the
potential results of a step-therapy approach to anti-VEGF therapy. Patients with DME will be randomly assigned to bevacizumab (Avastin, Genentech)
with deferred aflibercept (Eylea, Regeneron) as needed compared with monotherapy aflibercept from the outset. The study will evaluate whether
switching patients to aflibercept only if needed can be a cost-effective option with similar visual results to aflibercept for DME.
• Protocol AE
• The DRCR Retina Network will soon begin a pilot study investigating photobiomodulation. Protocol AE will investigate the role of daily
photobiomodulation therapy for patients with center-involved DME. Recent preclinical and small phase 1 trials have shown photobiomodulation to
affect the pathogenesis of DR and to improve DME. This would potentially be the first at-home therapy to treat DR and DME.
106. OCT Macula
• time domain → spectral → swept source
• Script:
– loss of foveal contour with
– destruction/loss of normal architecture of outer /inner
retina, RPE, IS/OS junction
– hyper/hypo reflectivity
– at subRPE or sub/intra/epi retina
• hyperR: epiretina (ERM/hrge/CWS), intraretina (hrge/HE/inflam
cell), deep (drusen/CNV/RPE hyperplasia)
• hypoR: fluid/cyst @intraretina/PED, shadow
– with PED/cystic change/inflam cell/hole….
– +- vitreous postetrior face
– +- choroidal vessels dilated
107.
108. OCT Macula
• Qualitative (morphology and reflectivity)
• Quantitative (thickness, mapping and volume)
• ELM band (ELM)- btw nuclei & IS of PR (+Müller cells)
• Ellipsoid zone (EZ)- prev IS/OS jx, mitochondria
@outer portion of IS of PR.
– distance EZ-ELM shorter than EZ-RPE @fovea
• Interdigitation zone (IZ)- contact of OS-RPE
• RPE band- RPE-Bruch, thicker in fovea
• Damage: IZ EZ ELM
• Recovery: ELM EZ IZ
109.
110. FFA
• Clinical use (F) & indication (FFA)
• Principles- fluorescence & BRB
• Peocedure- 5ml 10%
• SE/CI
• Phases
• Pseudo-/Auto-/Hyper/Hypo-F
• why fovea dark
• vs ICGA
• specific pattern: petalloid, lacy/stippled pin point/no
demarcation, ink blot/smoke stack/granular, starry night
111. ICGA
• phases
– early <1min: filing of choroidal vessels
– early mid 1-3min:
– late mid 3-15min: fading of choroidal vessels
–Late >15min: choroidal vessels dark
112. FFA vs ICGA
FA ICGA
Molecular
Hydroxyxanthene 5ml/10% Tricarbocycline (+iodine)
Stimulation- blue/490nm IR/805nm
Emission- yellow/530nm IR/835nm (better penetration)
MW- 376 D 775 D
Protein bind- 80% 98%
Met @liver, excrete @kidney Met @liver, excrete @biliary
Washout few minutes Washout 30min
Uses
FFA (BRB) ICGA- choroidal lesion, penetrate blood/HE
Ant seg/tear/IOP/siedel/surface +- diode laser (photosensitised)
SE
N&V/discolouration/allergy Iodine allergy but better tolerated
Features
OD white, FAZ, pseudoF OD dark, no FAZ
113. FFA comments
• Classic CNV (>type II/subretinal CNV)
– there is a early (<30sec) & well delineated uniform/lacy pattern
hyperF at macula +- hypoF halo
– which increase in intensity and size
• Occult CNV (>type 1/subRPE CNV)
– there is a slightly late hyperF with indistinct margin/stippled pattern
@macula,
– which increase in size & intensity
– i would like to look at stereoscopic view for elevated RPE
• IPCV @ ICG
– there is a hot spot/focal hyperF with hypoF halo in the
macula/periphery, within 6min of ICG
– which increase in size & intensity, area of suspicious BVN
– area of hypoF due to masking by hrge
– i would like to see the dynamic for pulsation
– and stereoscopic photos for nodular shape
– and fundus exam/photo for orange pigment
• I would like to compare FFA with fundus photo/autoF photo to
differentiate masking/CFO, autoF/hyperF
114. FFA
• DR: NV vs IRMA, microaneurysm
• RVO: AV transit, collateral flow,
• OIS: delayed choroidal filling in 60% of eyes,
prolonged arteriovenous transit time in 95%
of eyes, and prominent vascular staining
(particularly of the arteries) in 85% of eyes.
• Others: macular ischeamia, CFO, NV,
macular edema
117. ERG
• Types x 3
– full flash
– pattern
– multifocal
• Test (separate
rod/cone)
– Rod: dark adapt
– Cone: high flicker
30Hz, light adapt
• Wave x 3
–A: -ve/outer retina (PRC)
–B: +ve/inner retina
(Muller/bipolar)
–C: RPE + PRC
• Reading
–Amplitude
• N35/P50/N95
–Latency (to beginning of A)
–Implicit time (to peak of B)
118. OCTA
• Compare slab VS cross sectional
• Projection artefact: compare superficial image
• OCTA for RVO: ischemia @ periphery & macula. NeoV
@VRI
• OCTA for CNV: Dx/subtype, still need FFA
• OCTA for mCNV: good, clean image to visualise CNV
– New algorithm: SD OCT +- OCTA as first line treat if
positive if both negative then only FFA
• OCTA vessels
– Above RPE: white
– Below RPE: dark (choroidal vessels), unable to penetrate RPE
for flow image)
121. About Avastin (Bevacizumab)
• IndiC: CA of colorectal (mets), lung (non sq
non small), breast (HER 2 –ve)
• Msia CPG (2009): can use for wARMD &
DME, cost effective,
122.
123. New Rx
• New Generation Anti-VEGF Agents
– brolucizumab (RTH258, Novartis)
– abiciparpegol, a designated ankyrin repeat protein, or
DARP (Allergan)
– Conbercept (Lumitin, China)- fusion protein with 3x
domains for VEGF A/B/PGF, longer t ½ (3+q3mth dosing),
>affinity, > wARMD
– RG7716 (Roche/ Genentech), a single-molecule,
bispecific agent that inhibits both VEGF and angiopoetin-2,
or Ang-2
– Ziv-aflibercept (Zaltrap, Sanofi, Paris, France)- systemic
antiVEGF for metastatic colon cancer, higher osmolarity of
815–829 mOsm (risk of retinal toxicity)
124. New Rx
• Anti-integrin (anti oxidative)
– SF0166, a topical anti-integrin agent being explored by
SciFluor Life Sciences selectively blocks the alpha-V beta-
3 receptor two dose strengths (2.5% or 5%), gutt BD 1/12
– risuteganib (Luminate, Allegro Ophthalmics)- IVT
localizes & reservoir @ RPE =greater durability
– Integrin receptors are upregulated when a cell is under
stress, and they play a role in signaling all the downstream
effects of oxidative stress.
• Tie-2 activator AKB-9778 (Aerpio) subcutaneous- > DR
126. Protocol S
• antiVEGF (RBZ) vs PRP for PDR
– Outcome: 2yr vs 5yr, VA, VF loss, visit, DME, injection, VH/significant VA
loss/RD
– VA same in 2&5 yr (2yr RBZ >0.5line)
– PRP > new DME, Cx (VH/need PPV), peripheral VA loss
– antiVEGF > follow up dependent/visit
– Combine is not recommended
– Conclusion: antiVEGF is an alternative Rx for PDR but need =/>monthly f/up
• Protocol S consideration:
– HbA1c <10 as inclusion criteria
– Age av 52
• CLARITY- AFB VS PRP
127. New
• Protocols W, AA, AB, TX, AC, and AE
• Protocol AC- switching antiVEGF
• Protocol AB- VH with immediate PPV vs
antiVEGF
128. • Protocols AG and AH are sister trials. Protocol
AG is evaluating pneumatic vitreolysis for
vitreomacular traction (VMT). Investigators will
compare clinic-based injection of C3F8 gas with
sham injection for VMT. Protocol AH will evaluate
full thickness macular holes associated with VMT.
Protocol AH does not have a sham group, but it
will evaluate the effectiveness of pneumatic
vitreolysis in closure rates for macular holes
associated with VMT.
129. Eye Pressing Procedure in Ophthal
• Ophthalmodynanometer
• Easily collapsed CRA in OIS
• Scleral buckle TRO CRAO
• Ocular massage for CRAO
• Retropulsion for orbital examination
• Ocular massage for glaucoma shunt
130. Brolucizumab (Beovu/Pagenax)- SE
• Intraocular inflammation
• most after the first or second injection (first 6mth)
• within 1 to 2 weeks of treatment
• Early SE > severe VA loss
• changes in vision, floaters or blurry vision
• package insert:
– 4% rate of intraocular inflammation
– 1% rate of retinal artery occlusion, vasculitis & occlusive
vasculitis (up to 2%)
• VA loss: 30% mod (3line), 20% severe (6line)
• Higher than other antiVEGF
131. • wAMD
• 6mg in 0.05mL
• monthly x3 q8-12 weeks
• Store 2°C to 8°C (room air only 24H)
132. HAWK and HARRIER trials
• 1817 untreated active CNV wARMD
• Beovu 3mg & 6mg Vs Eylea 2mg
• 48wks
• Load x 3 Eylea q8wk, Beovu q12wk (8wk if
+activity)
• VA- non inferior
• Q12wk for 48wk- >50% in Beovu 6mg
• Anatomy: Beovu better > Eylea
• SE same
152. Retinal Vessels Changes & Hrge
Vascular changes
•OIS: A narrowed,
microaneurysm; V dilated
but not tortuous
•RVO: V tortuous
•DR: A microaneurysm, V
beaded not tortuous
Haemorrahages
•OIS: deep, round,
midperiphery
•RVO: flame-shaped
•DR: dot-blot
155. Cotton Wool Spots
• = Capillary Retinal Arteriole Obstruction
• Acute obstruction @ radial peripapillary
capillary net RNFL infarct cotton-wool spot
impaired axoplasmic transport
• Typical: superficial, white, ¼ OD size or less,
fade in 5–7 weeks (longer in DR).
• +- subtle retinal depression (inner retinal
ischemic atrophy) in an area of prior ischemia.
• +- loss of VA/VF (related to the size and location
of the occluded area)