Medical Retina: Notes

Yong Meng Hsien
Lecturer & Ophthalmologist, UKM & HCTM, Malaysia
[email protected]
Last edited: Feb 202

1. MR Dr Yong Meng Hsien Lecturer & Ophthalmologist, UKM & HCTM [email protected] 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

6. 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

7. 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

8. OCT @ DME Normal CRT: 212 ± 19 and 289 ± 16 μ m DME CRT: vary from 225 to >450 μ m. 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

9. 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

10. 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

11. 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

12. 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)

13. 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 )

14. AntiVEGF @ DME 1 st 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

15. Steroid @ DME Can be 1 st 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)

16. 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

17. 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.

18. 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

19. 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

20. 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

21. 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

22. 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

23. RVO/RAO/OIS

24. 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

25. 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)

26. 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

27. 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

28. 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

29. Investigation @ RVO Key: atherosclerosis or hyperviscosity or abn blood flow Minimum: medical history, BP & DXT, FBC ESR CRP Young & bilateral cases: thrombophilia inflammatory/autoimmune

30. 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)

31. 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 2 nd line: after 3-6 inj /CI to antiVEGF 1 st 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

32. AntiVEGF @ CMO/RVO Key: start earlier, give enough (till VA stable), close monitor (1-2mth in 1 st year for ischemic case) Regime: monthly until VA stability (expect good response)  1-2 monthly follow-up for at least 1 year (for ischemic case) OR 3monthly (for non-ischemic)  subsequent extension (up to 3 years)

33. 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

34. 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

35. 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 Sheathoto my @BRVO thrombolytic therapies anticoagulation or antiplatelet : no high quality evidence HRT/oestrogen containing therapies: do not start, if started +- continue (discuss) S tudies SCORE II: CRVO with CMO monthly RBZ vs Eylea x 6mth → Ozurdex as 2 nd line LEAVO: CRVO with CMO RBZ vs Eylea - CRYSTAL and BRIGHTER VA stabilization criteria (defined as three consecutive visits with stable VA)

36. AMD/PCV

37. AMD Classification & AREDS Staging

38. 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

39. 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)

40. 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

41. 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

42. CNV: OCT vs FFA OCT – FFA Type 1 CNV ( subRPE )  occult CNV Type 2 CNV ( subretina )  classic CNV Type 3 CNV (intraretinal)  RAP

43. 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 

44. 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

45. 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] t reat & 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 )

46. 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

47. 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

48. 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% (1 st yr ), 10% (2 nd yr ) CATT  8% VA decline, 60% still fluid, 20% FFA leak

49. 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

50. 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)

51. 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

52. 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

53. 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

54. AREDS Risk Classification

55. 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

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

57. 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

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

59. Pachychoroid Spectrum CSCR IPCV

60. 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

61. 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)

62. PCV- Diagnosis Clinical Orange nodule, massive hrge + DDX ARMD: no drusen/GA/pigment changes ICGA (Everest criteria) focal hyperF (@red-orange nodule) 1 st 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

63. 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

64. 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

65. 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%1 st yr ), 4mth KIV laser/PDT (half)/ antiVEGF /Diamox Mx: risk modification (steroid reduction/withdraw) Cx : 50% recur, chronic +- visual loss, CNV (DDx or Cx )

66. CSCR- the S Serous Subretinal Scotoma Smaller (micropsia) Stress Steroid Self limited

67. 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  

68. CSCR potential Rx Anti-corticosteroid eplerenone

69. 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)

70. Others

71. 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)

72. 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

73. 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

74. 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)

75. 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.

76. Goldberg staging: Proliferative Sickle Cell Retinopathy

77. HPT retinopathy: Keith-Wagener-Barker classification

78. 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

79. 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

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

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

82. 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. 

83. Ix OCT FFA ICG ERG

84. 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

85. 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

86. 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

87. 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

88. 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

89. 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

90. 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

91. 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)

92. 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)

93. 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)

94. OCTA Compare cross sectional w cube Projection artefact Compare superficial image 1 st OCTA RVO

95. AntiVEGF YMH

96. 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,

97. 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)

98. 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

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

100. 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

101. New Protocols W, AA, AB, TX, AC, and AE Protocol AC- switching antiVEGF Protocol AB- VH with immediate PPV vs antiVEGF

102. 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. 

103. 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

104. 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

105. wAMD 6mg in 0.05mL monthly x3  q 8-12 weeks Store  2°C to 8°C (room air only 24H)

106. 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

107. Macula- Part II YMH

108. 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)

109. 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

110. 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)

111. 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

112. 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)

113. 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

114. 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 T ree N ever M anage To Grow Tall in Sand= CRAO, Tay Sachs, Niemann Pick, Macular hole, Toxicity Gaucher , Trauma/Berlin, Sandhoff

115. 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

116. 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

117. 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

118. 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

119. Vascular & Ischemic Retinopathy

120. 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/ uveitis 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

121. 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

122. 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

123. Sickle Cell Anemia (SCA) Salmon patch @ retina

124. 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)

125. Cotton Wool Spots = Capillary Retinal Arteriole Obstruction Acute obstruction @ radial peripapillary capillary net  R NFL 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)

126. Fundus Dystrophies

127. 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…

128. 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