Yong Meng Hsien Lecturer & Ophthalmologist, UKM & HCTM, Malaysia yongmenghsien@ppukm.ukm.edu.my Last edited: Feb 202

1. MR
Dr Yong Meng Hsien
Lecturer & Ophthalmologist, UKM & HCTM
yongmenghsien@ppukm.ukm.edu.my
Last edited: Feb 2022

2. Contents
• DR/DME
• RVO
• RAO
• ARMD
• PCV
• CSCR
• MacTel
• Vascular & Ischemic retinopathy
• Fundus Dystrophy
• Others (Solar/myopia)
• FFA
• Macula basic/SSx/DDx
• Macular hole

3. DR/DME

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

9. Other classification DR/DME
• Vision-threatening DR: severe NPDR, PDR, DME
• DME Rx parameters
– anatomical (CMT) & functional (VA)
• DME pre Rx classification
– proliferative/non-proliferative
– ischaemic/non-ischaemic
• DME Rx response
– target, adequate, non, inadequate
– 60% good, 40% suboptimal
• severe edema
– >500mm: warrant steroid therapy

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)

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

30. DM- Key History/Ix/Mx
• Diagnosis- when & how (Ix+-Sx), type/duration/treatment
– Sx: no  polyuria/dipsia, ifx, LOW
• Complication (chronic)
– macrovascular (CVS/CVA/PVD)
– microvascular (retino/nephro/dermato/neuro & autonomic)
• Complication (acute)
– Hypo (<4.0/Sx autonomic/neuroglycopenic/mild-mod-severe <2.8)  RX :15g CHO/D50 20-50ml 1-3min/DXT 15min
– DKA (DXT >11 + ketone >3/urine2+ + VBG pH<7.3/HCO3<15)  RX: IVD, IVII 0.1unit/kg/h, TRO ifx/CVA/MI
– HHS (DXT >30 + hypovolemia + >32-mosmol/kg  IVD, IVII 0.05unit/kg/h aim DXT reduce <5/hour till <15  change
IVD to D5/10 keep DXT 8-12
– Immuno down/ifx
• Screen: symptom, risk (overwt BMI 23 or waist 80/90, Fhx, GDM), comorbid (HPT/CVD/dyslipidemia/PCOS),
or >30yo
– DXT: only for screening- 5.6)
– FBS/RBS/OGTT: 6.1 – 7 & 7.8 – 11.1, (OGTT dose= 1.75g/kg, max 75g)  control 4.4/7/8.5
– HbA1c: 5.6 to 6.2% (38-44), not for anemia/iron supplement/Hb-pathy  control 6.5%
• Baseline & f/up
– Risk score: CVS (Framingham FRS, SCORE-high)
– Baseline PE: BMI/BP, fundus, foot/toe, sensory 10-g monofilament/128Hz tuning fork
– Baseline Ix: lipid profile, RP, LFT, UFEME/microalbuminemia, ECG, dental
• Mx
– Lifestyle: diet/MNT, exercise/LOW, education
– Pharm: OAD, insulin (0.5mg/kg/day  50% bedtime), lipid/BP
• Special term: metabolic memory (legacy effect), hypoglycemic unawareness

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

34. RVO/RAO/OIS

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)

48. AMD/PCV

49. AMD Classification & AREDS Staging

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

56. Dry ARMD- Rx/Mx
• Lifestyle/diet: antioxidant/green
leafy/smoking/exercise/sunlight/CVS
• Antioxidant supplement: formula AREDS1/2 (target grp/smoker)
– AREDS2: beta-carotene  lutein (10 mg) and zeaxanthin (2 mg) + lower dose
(25 mg) of zinc oxide
• Amsler grid
• advanced case: low vision aids/intraocular telescope/retinal
translocation/bionic eye
• new (for dry ARMD):
– IVT lampalizumab monthly (complement inhibitor): reduce GA 44%
– visual cycle modulation with fenretinide/emixustat: reduce cytotoxic
end product
– nanosec pulse non thermal laser on drusen: rejuvenate RPE
– oral saffron 20mg/day, steroid/brimonidine inserts: neuroprotective
– stem cell transplant

57. Wet ARMD- Rx/Mx
• PED
– observe if: no CNV/no SRF/young/drusenoid PED
– IVT antiVEGF (5-20% risk of RPE tear)
• CNV (active & sub/juxta-foveal)
– IVT antiVEGF
• Monthly (MARINA & ANCHOR, Pier/Excite)
• treat & PRN: monthly x 3 → PRN (VA 5 letters/1line/CMT 100um) [HARBOUR/Pronto/CATT]
• treat & extend: monthly x 3 → 6/8/10/12 wk…. (TREX AMD, SALUTE)
• treat & fixed 2mthly → monthly x 3 → q8wk (Eylea)
– alternative: PDT/laser (MPS/TAP/VIP studies) or IVTA
– Also offered for: PED/PCV/RAP
– Prognostic factor: young/low SRF/high choroidal thickness/minimal classic
– If untreated/natural Hx: 1-2-3-4 lines loss @ 3/6/12/24mth
• Macula hemorrhage/hrge PED
– IVT antiVEGF/IVT or subretinal rtPA/pneumatic displacement/ppv
– KIV stop anticoagulant/aspirin or change
• New
– RTH258 (antiVEGF/6mg/smaller molecule): HAWK, HARRIER studies
– Fovista (antiVEGF + antiPDGF)

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

64. Msia CPG AMD & PCV
• Dx & DDx
– Classification: AMD, nAMD (AMD-CNV – PCV – RAP), CNV (I/II/III)
– Clinical (fluid/HE/scar @any level)
– OCT
– FFA/ICG
• Mx
– Laser photocoagulation
– Anti VEGF
– PDT
• Rx algorithm
• Not commencing Rx
• Retreatment criteria
• Hold/Stop Rx
• Pneumatic displacement

71. ARMD- DDX
• Drusen
– cuticular/basal laminar drusen (30-40s/small/cluster/vitelliform/starry night/increase-
progress-serous PED/CFH gene)
– AD radial drusen/Doyne honeycomb retinal dystrophy (20-30s yo)
– Type 2 membranoproliferative GN related drusen (adolescent/CFH gene)
• GA
– chloroquine toxicity
– high myopia
• CNV
– Degenerative:
• wet ARMD/IPCV, chronic CSCR
• high myopia, angioid streaks +-OD drusen
– Traumatic/iatrogenic
• Choroidal rupture, laser
– Inflammation
• POHS, post uveitis (VKH/toxoplasmosis), white dot syndrome
– Dystrophy
• Best’s dz
– Tumour
• Choroidal nevus/hemangioma
– idopathic
• younger pt, UL, spontaneous resolution/better prognosis

72. AREDS Risk Classification

74. New
• Hyperreflective dots (HRD)
– = activated microglial  inflammatory & activity marker
– @ inflame/DR/DME/AMD/RVO
• Muller cell @ DME
– Cystoid space = Muller cell intracellular swelling
– Inflammatory component
• OCT IS/OS Jx = ellipsoid zone = EZ band
• Outer retinal tubulation (ORT)
• Multicolour imaging w CSLO (Spectalis)
– Blue, green, infrared

75. GA
• New classification (OCT)
–Outer ret atrophy (ORA) only or with RPE
(RORA)
–Complete vs incomplete
–cRORA = GA
–iRORA = early GA
–cORA
–iORA

76. Brolucizumab studies
• RTH 258/fragment/- VEGF-A/26kDa small MW but >concentrated
• Molar basis: dose 6mg  12x > Eylea 2mg, 22x > RBZ 0.5mg
• HAWK (3mg/6mg VS Eylea)
– VS Eylea, 48wk
• HARRIER (3mg VS Eylea)
• Brolucizumab 3mg/6mg VS Eylea
– 3 loading deses  extend Beovu q8wk/q12wk VS Eylea q8wk
– First 4mth to 48wk: VA same, CRT better, AE more (4 vs 1%)
– 50% able to maintain 3mth-dosing (another 50% 2mth-dosing) at
yr-1
– 30% gained 15 letter at yr-1

79. DME RVOCMO nAMD/PCV
Risk DM HPT Smoke/age
SSx HRF, DRIL HRF, DRIL SHRM
1st line AntiVEGF
Ix OCT/OCTA/FFA
2nd line Steroid Steroid PDT
Prognosis ++ +++ +
Relevant eye DR HPT ret,
glaucoma
Myopia

80. Pachychoroid Spectrum
• CSCR
• IPCV

81. Pachychoroid Spectrum
• thick choroid/dilated vessel
• spectrum
– pachychoroid pigment epitheliopathy PPE (RPE changes)
– CSCR (PED/SRF)
– pachychoroid neovasculopathy PN (type 1 CNV)
– IPCV (type 1 CNV polyp)
• primary or secondary (VKH/MEWDS/MFC)
• fundus: reduced tesselation
• OCT (EDI): think choroid +- 300um, dilated
Haller/attenuation of choriocap-Sattler layer, reduce ratio
choriocap-Sattler vs total thickness
• DDX: ARMD (occult CNV), pattern dystrophy, RPE
epithelitis, PIC
• choroidal thickness
– depends area (thickest subfoveal), age (reduce 10-15um/10yr)
– medium 260um: Sattler 100, Haller 141

82. PCV
• Def: abn choroidal vessel/terminal aneurysm
• Grp: AMD subtype (type I CNV), pachychoroid
spectrum
• Risk (age/F/asian)
• SSx- serosanguinous/bleed, maculopathy, orange
nodule
• Ix: OCT/FFA/ICG/OCT-A
• Diagnostic criteria (JSG/Everest)
• Mx: Sx/active/location, PDT/antiVEGF/Argon
• Study: Everest I & II, PLANET (Eylea +- rescue
deferred PDT)

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

85. PCV Mx
• PLANET + EVEREST II
–Combine RBZ + PDT from beginning
–Or AFB monoT
–RBZ alone (less @ EVEREST II), AFB + PDT from
beginning (less @new trial)
• T&E

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

90. CSCR potential Rx
• Anti-corticosteroid
– eplerenone
–

91. RPE Epithelitis
• Acute RPE inflam → self limiting 6-12 wk
• EpiD: young
• SSx: macular pigmentary changes (fine
stippling hyperP + hypoP halo)
– No PED/SRF/drusen (DDX ARMD/pachychoroid)
• OCT: IS/OS/RPE jx disruption/hyper-
reflective band
• FFA: hyperF halo + hypoF stippling (no leak)
• Mx: observe (self limit)

92. Others

93. Pathological Myopia- Causes
Def: high/progressive myopia (>-6D/>26mm AXL) with ocular
changes
Pathogenesis x 4:
 Genetic (CFI/PEDF)
 Hemodymamic theory (low choroidal flow/thickness- hypoxia and
more VEGF)
 Mechanical (stretch  RPE expansion  VEGF release
 Immuno/inflam  high CRP/C3 release
Causes:
• Idiopathic
– Hereditary/environmental/intensive near work
• systemic association
– Prem/ROP/Congenital rubella
– Down/Noonan/Pierre Robin
– Stickler/Marfan/Ehlers-Danlos
– Albinism/Gyrate Atrophy
Mx: optical (glasses/CL), refractive procedure (cornea vs
lens), medication (atropine 0.5-1%), Cx Mx
(CNV/break/RD)

94. Pathological Myopia- Signs
• OD/peripapillary
– Tilted OD/temporal flattening/PPA
→ OD pit
– Peripapillary intrachoroidal
cavitation/staphyloma/detachment
• Macula
– Staphyloma
– Lacquer crack (Bruch) → CNV/coin
hrge/Fuch’s spot
– Foveolysis/foveal schisis
– Macular hole/RRD (low success op-
+thin retina/stretched w recoil
force)
• Peripheral
– Tessellated/tigroid fundus
– Focal/geographical atrophy
– Lattice degeneration/RRD/PVD
• Others
– Cataract- PSCC/early
NS
– Glaucoma-
POAG/PDS/steroid
responder
– Lens dislocation (rare)
– Amblyopia
(heterometropia)
• A/w (ocular)
– RVO/RAO
– AION
– Ret artery
macroaneurysm

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.

98. Goldberg staging:
Proliferative Sickle Cell Retinopathy

99. HPT retinopathy:
Keith-Wagener-Barker classification

100. Mitchell-Wong simplification of the Keith-Wagener-Barret system​
• Grade 1 (mild retinopathy) - Arteriolar narrowing (generalized and focal), AV nicking, and/or
arteriolar wall opacity
• Grade 2 (moderate retinopathy) - Hemorrhage, microaneurysm, cotton wool spot, and/or
hard exudate
• Grade 3 (malignant retinopathy) - Moderate retinopathy plus optic disc swelling
Modified Scheie classification
• Grade 0 - No changes
• Grade 1 - Barely detectable arterial narrowing
• Grade 2 - Obvious arterial narrowing with focal irregularities
• Grade 3 - Grade 2 plus retinal hemorrhages and/or exudates
• Grade 4 - Grade 3 plus disc swelling
The Scheie classification also grades the light reflex changes from arteriolosclerotic changes
• Grade 0 - Normal
• Grade 1 - Broadening of light reflex with minimal arteriolovenous compression
• Grade 2 - Light reflex changes and crossing changes more prominent
• Grade 3 - Copper-wire appearance; more prominent arteriolovenous compression
• Grade 4 - Silver-wire appearance; severe arteriolovenous crossing changes

101. Small Print
• Solar/eclipse retinopathy
– key: few hours post exposure → small yellow/red foveolar
spot (variable VA) → fades in weeks/lamellar hole/foveola
defect (irregular margin)
• Focal choroidal excavation (FCE)
– key: OCT conforming vs not- RPE/PRC layer follow
indentation or separated
• Peripheral exudative haemorrhagic chorioretinopathy
(PEHCR)
– key: peripheral wet ARMD/PCV?variant, > elderly F, UL >BL

102. MacTel2
• Loss of luteal pigment, loss of muller cells
• Characteristic Central hypoF loss in FAF

103. CSCR
• Eplerenone
• Micropulse subthreshold
• PED @ CSCR >small (VS PCV)

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.

105. Ix
• OCT
• FFA
• ICG
• ERG

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

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

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

115. FAF/RAF (AutoFluorescence)
• Emit longer WL light aft absorb/stimulated by shorter WL light
(blue 488/green 532  yellow)
• By lipofuscin (+ fluorophores) @ RPE
• Topcon/Optos/Heidellberg Spectalis)
• Technique:
– pre bleached 30sec blue light (avoid bright light/flash/angiogram
prior  ++ bleach ++ false hyperAF)
– Defocus -1D (focus @ RPE) + eye tracking + atleast 10 frames for
averaging
• RAF N: hypoAF @ OD/BV/fovea (lutein)
• HyperAF: RPE sick/high lipofuscin (drusen/AMD/ macular
dystrophies e.g. Best/Stargardt), retina thin/damage PRC-visual
pigment), retinal/mascular dystrophies, active WDS, new GA,
chronic CSCR with gravitational tracking
• HypoAF: RPE atrophy (GA/WDS/rips/angiod streak), mask/block
(blood/exudate/fluid/fibrosis/scar)

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)

119. OCTA
• Compare cross sectional w cube
• Projection artefact
–Compare superficial image 1st
• OCTA RVO

120. AntiVEGF
YMH

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,

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

125. New RX
• Iluvien (fluocinolone acetonide intravitreal
implant 0.19 mg)

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

134. Macula- Part II
YMH

135. Macula- special (anatomy)
• Macula- fovea/peri/para- FAZ- foveola- umbo
• Inner retinal- higher xanthophyll/yellow pigment
(lutein/zeaxanthin)
• GCL- multiple (except foveola zero GCL)
• RPE- taller/thinner/more regular/more & bigger
melanosomes
• ILM- thick in fovea
• PRC- cone predominant (foveola only cone
150k/mm2)

136. Retina- number (anatomy)
• Thickness
– Post pole/parafovea/papillomacula bundle= 0.23mm
– Ora serrata/foveola = 0.1mm
– Equator 0.20mm
• Diameter
– Total retina area 266mm2
– Macula 5-6mm
– Fovea 1.5mm/parafovea +0.5mm/perifovea +1.5mm
– Foveola 0.35mm/umbo 0.15mm
– FAZ 0.6mm
– OD 1.5mm
– 1DD = 1.5mm = 4.5 degree (0.3mm = 1 degree)
• Location/Distance
– Fovea= 3mm from temporal margin of OD, 0.8mm inferior center of OD
– Periphery (from arcades):
• Near periphery/Equator = 1.5mm
• Mid periphery= 3.0mm
• Far periphery= till ora
– Ora serrata: 8.5mm from arcades. 7.0mm from equator
• Central vision (degree) (x3 of diameter/mm)
– Macula 15-20, fovea 5-6, foveola 1.25

137. Macula- Symptoms
• Reduce VA/Central +ve scotoma (-ve in Oneuropathy)
• Metamorphopsia
• Macropsia/micropsia
• Dyschromatopsia (>Oneuropathy/cone dystrophy)
• Impaired dark adaptation
• RAPD- only if very extensive (> Oneuropathy)
• Hypermetropic shift (for CSCR)
• Worse VA with pin hole
• Amsler grid defect (20 degree)
• Plus lens (+1) test (for CSCR)
• Watzke Allen test (distorted/thinned/broken)

138. Macula- Signs
• Preretinal
– blood/ERM sheen (cellophane/pucker)/operculum
• Intraretinal
– blood/HE/fluid/CMO, hole/thinning/thickening
– loss of foveal reflex/scar/fibrosis
• Subretinal
– blood/SRF
• SubRPE
– drusen/PED/orange nodule
– Choroid- choroid nodule/CNV grey nodule, fold
– Bruch- angioid streaks
• Macular Ischemia
– FAZ normal 250-550
– FAZ > 600 = abn
– FAZ > 1000 = clinical significant/VA loss

139. Macular Function Tests
Clear Media
• VA (+-RAPD/CV/Contrast)
• OCT
– Time domain < spectra/Fourier
< swept source
– ED-OCT, OCT-A, wide field,
intraop, functional, doppler
• Microperimetry/HVF 10-2
• Photostress
– VA → light 10sec → VA (1 line
above pretest) → N= 30sec
• FAF
• FFA/ICG
– petalloid (CMO), ink blot/smoke
stack (CSCR), stippled granular
(CNV)
Opaque Media
• Maddox rod
• Multifocal ERG
• Laser interferometry
– 2 coherent light → fringe pattern
(progressive finer/different
orientation)
• Flying corpuscles/Entoptic
phenomenon test
– Entoptoscope (blue) → WCC @
perifoveal capillary (number &
speed) → N >15 corpuscles/fast
moving
• Potential acuity meter
– Project mini Snellen into
retina/macula (avoiding other
media problem)

140. Macula SSx: DDX
DDX: N VA but reduced contrast sensi
• amblyopia
• optic neuropathy
• some cataracts
• higher-order aberrations
• By: Pelli-Robson, sinusoidal grafting
DDX: Central Scotoma
•Macula (+ve): CMO
(DME/RVO/uveitis),
ARMD/IPCV/CSCR/Mactel,
hole/ERM/schisis (absolute)
•ON (-ve): AION, Oneuritis
•DDX: +ve/-ve/relative/absolute/
central/peripheral scotoma, VS defect
DDX: Micropsia
•Optical: refraction/glassess
•Ocular: cornea, macula
•Brain/psy

141. Macula SSx DDX- Spots
DDX: foveal yellow spot
• VMT/Stage 1a impending macular
hole
• CMO
• Vitelliform macular dystrophy
• Solar retinopathy
• Laser pointer retinopathy
DDX- Macular hole (red spot)
• FTMH/lamellar hole/pseudohole
(ERM/CMO)
• Idiopathic (old/female)
• VMT
• Trauma
• High myopia
DDX: Cherry red spot
(macular/retina problem)
• CRAO/cilioretinal (@acute)
• commotio retinae/Berlin
• retinotoxic drug (genta/dapsone)
• macular hole
• Metabolic storage d/o
- GMI gangliosidosis & mucolipidosis (+OD
atrophy/CNS/corneal cloud)
- GM2 gangliosidosis (Tay Sachs/Sandhoff)
+CNS
- Niemann Pick (A&B only, C only motility
d/o)
- Farber (corneal cloud/nodule
+skin/LN/psy/renal/CVS)
* Cherry Tree Never Manage To Grow Tall in
Sand= CRAO, Tay Sachs, Niemann Pick,
Macular hole, Toxicity Gaucher,
Trauma/Berlin, Sandhoff

142. Macular SSx- DDx
Bull’s eye
• drug toxicity
(HCQ/Clofazimine)
• macular dystrophy
(Stargardt/cone/ARMD
/pattern/Leber)
• Chronic macular hole
• Bardet-Biedl
• Hallervorden-spatz
• AD cerebellar ataxia
• Lipofuscinosis
Crystalline Maculopathy
• Drugs: tamoxifen,
nitrofurantoin
• Metabolic:
hyperoxaluria, cystinosis
• Dystrophy: Bitti, gyrate
atrophy
• MacTel
• Others: Sjogren-Larsson,
West African Talc Com
Stach emboli

143. Macular SSx DDX: Chorioretinal Fold
• Congestion/compression
– Retroorbital: high ICP (+- papilloedema) TRO!!!
– Orbital: tumour/TED/IOID
• Surrounding effect:
– choroid (tumour)
– sclera (scleritis/buckling)
– vitreous/AC: hypotony/globe rupture
• Tissue contraction (=ocular causes)
– DDX retinal fold (ERM)- choroidal fold > horizontal/
deeper/parallel, a/w RPE changes (peak-trough light-dark
band), OCT/FAF/FFA
• Idiopathic
– >hypermetropic, BL

144. Macular SSx DDX- Angioid Streak
• = Bruch’s membrane break (thickened/calcified)
• sign: red/dark brown/narrow/irregular streaks + serrated
edge + radiating/interconnecting from a peripapillary ring
• +-peau d orange, RPE changes, autoF (FAF), FFA hyperF
(window, CNV)
• Cx: CNV/chroidal rupture (trivial trauma)/foveal involved
BOV/metamorphosia
• Causes (PEPSI HAM)
• Ocular only/idiopathic (50%)- a/w OD drusen (25%)
• Systemic (50%)- abn elastin/collagen/deposit
• CTD: Pseudoxanthoma elasticum (most)/EDS/Marfan
• Endocrine: Paget’s disease (Ca), blood d/o (iron),
acromegaly
• Blood d/o: SCA, Hb-pathy, hereditary spherocytosis
• Genetic: NF, SWS, TSC

145. Macular SSx DDX: Submacular H’rge
• Causes/Origin
– choroidal V: CNV (ARMD/IPCV/PED tear/myopia/trauma/OHS/angioid
streak/inflam/neoplasm/idiopathic)
– retinal V: intra/sub-retinal
– Systemic risk: anticoagulant, HPT
• Damage
– Depends: extend (size/thickness) & duration
– Iron/hemosiderin/fibrin- cytotoxic to PRC
– Physical separation btw PRC-RPE- RPE/PRC atrophy
– Clot retraction- PRC damage
– PRC edema <24H> → ONL damage 1/52 → PRC/ONL absence 2/52 +- scar
• Prognosis
– No Rx: 6 lines LOV @3yr (50%), with scar to observe 2yr
• Mx
– Pneumatic displacement (SF6/C3F8)- can position, new <3wk>, inf to fovea
– TPPV/retinostomy/SRH evacuation/gas or air tamponade +-
subretinal/microcannula rtPA/antiVEGF- Submacular Surgery Trial (no benefit
& high risk for AMD related hrge)
– IVT antiVEGF
– IVT rtPA (2.5-10ug = 0.1-0.4ml)
– PDT

148. Vascular & Ischemic Retinopathy

149. Retinal Vascular Disease
1. Metabolic/athelosclerotic
– DR/HPT
– RVO/RAO/OIS
2. Blood
– SCA/thalassemia/anemia
– leukemia/lipaemia/hyperviscosity
3. Abn vessel
– macroaneurysm (arteriole)
– telangiectasia (cap/Coat/MacTel)
– Inflam/Vasculitis/Eales
4. U/lying RPE-choriocap
– CNV/RAP/IPCV
– ARMD/myopia/trauma/POHS/uvei
tis
– CSCR
5. Precipitating factor
– Prem- ROP
– Radiation R
– Trauma- Purtscher
(flecken, OD hrge/edema,
complement 5a)
– Fat/amniotic fluid-
Purtscher –like
– Weight lift- Valsalva
(premacular hrge)
– Sun- Solar R
– NAI- Shaken baby
– High ICP- Terson
6. Neoplasm
- Phakomatoses- VHL/SWS
- Paraneoplastic
- blood d/o

150. Ischemic Retinopathy- Causes
Bilateral
• Metabolic/Vascular:
DR > RVO/RAO/OIS
• Blood: SCA/thalassemia,
hyperviscosity
• Paeds: ROP/FEVR
• Inflam/vasculitis
• Abn vessels
• Radiation/trauma/tumour
Unilateral
• Metabolic/Vascular:
OIS/RVO/RAO > DR
(aggravating factor+)
• RD (long)
• Inflam/vasculitis (long)
• Radiation
• Tumour
• Trauma/Purtscher
• Abn vessel:
macroaneurysm,
telangiectasia

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

153. Sickle Cell Anemia (SCA)
• Salmon patch @ retina

154. Retinal SSx: Roth spots
What: haemorrhages (round/oval/flame-shaped), with centre white spot
How: blood disorder/bleeding tendency, capillary ischemia, increased
vessel permeability, high venous pressure → retinal capillaries rupture
→ extrusion of whole blood → coagulation cascade → platelet-fibrin
thrombus.
Causes:
* subacute bacterial endocarditis/DIVC/leukaemias (thrombocytopenia)
* anaemia/anoxia/carbon monoxide poisoning/prolonged intubation
(ischemia)
* hypertensive retinopathy/pre-eclampsia/DR/ocular decompression
following trabeculectomy (capillary fragility)
* birth trauma/traumatic deliveries/battered children/shaken baby
syndrome/intracranial haemorrhage/AVM (high venous pressure)

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)

156. Fundus Dystrophies

157. RP
• PSEUDO RP:
- Drug toxicities: chloroquine
- Resolved exudative RD
- Previous hx of blunt trauma (severe commotio)
• Systemic association with RP
- Ptosis and EOM: CPEO, KS
- Deafness: Usher, KS,Refsum, Bardet-Biedl
- Heart: KS syndrome, Refsum
- Fingers: polydactyl
- Mental handicap…

158. Night Blindness
• Congenital
– Rod dystrophy: RP, CSNB, Oguchi’s dz, cone-rod
dystrophy
– Choroid dystrophy: choroideremia, gyrate atrophy
– VR dystrophy: Goldman Farve
• Acquired
– Glaucoma (advanced)
– PRP
– Drug, phenothiazines, quinie
– Vit A deficency