All you need on ARMD. Studies, Management guidelines etc.. Study material for MD Ophthalmology

2. Normal aging changes in the macula
• Reduced density and distribution of photoreceptors
• Changes in RPE
• Loss of melanin granules
• Formation of lipofuscin granules
• Accumulation of residual bodies
• Granular, lipid rich material on either side of the
RPE basement membrane
• Between plasma membrane and BM – basal lamina
deposits
• Inner collagenous layer – basal linear deposits
• Involutional changes in choriocapillaris

3. RISK FACTORS
• AGE – in 10% over 65yrs, in 25% over 75 yrs
• FEMALE SEX
• HYPERTENSION
• HYPERCHOLESTEROLEMIA
• CARDIOVASCULAR DISEASE
• HIGH WAIST TO HIP RATIO IN MALES
• POSITIVE FAMILY HISTORY
• CIGARETTE SMOKING
• HIGH CRP
• HYPEROPIA
• LIGHT IRIS COLOUR
MULTI-ETHNIC STUDY OF ATHEROSCLEROSIS
(MESA)
Prevalence of AMD highest in WHITES (5.4%)
Lowest in AFRICAN AMERICANS (2.4%)
ASIANS (4.6%)
OTHER RISKS
- Hormonal status
- Sunlight exposure
- Alcohol use
- Vit B, D status
- High plasma fibrinogen

4. Genetics
• Complement factor H (CFH)Y402H (1q31)
• ARMS2 (10q26)

5. NON NEOVASCULAR
AMD

6. •DRUSEN
•RPE CHANGES
USUAL SEQUALE –
Large drusen >> hyperpigmentation >> regression of drusen
>> hypopigmentation >> GA

7. DRUSEN
• Clinical
• Small, round, yellow lesions located along the basal
surface of the RPE – postequatorial retina
• Histology
• Abnormal thickening of the inner aspect of Bruch
membrane
• Ultrastructure
• Basal laminar deposits – granular, lipid-rich and widely
spaced collagen fibres (between plasma membrane and
BM of RPE)
• Basal linear deposits – phospholipid vesicles and
electron dense granules (within the inner collagenous
layer)

9. • Thickened inner aspect of Bruch membrane, along
with the RPE, may separate from the rest of the
Bruch – PED
• Small – large/ soft drusen
• Large – drusenoid PED
• Effects the overlying photoreceptors
• Mild-moderate vision loss
• Decreased contrast contrast sensitivity
• Impaired colour vision
• Impaired dark adaptation
• Increased number, size and confluency increases
the progression to CNV or GA

10. • SMALL: < 63 um diameter
• INTERMEDIATE: 63-124 um diameter
• LARGE: > 125um diameter (diameter of retinal vein
at the optic disc)
• DRUSENOID PED: confluent large drusen ( >350um)
AREDS STAGE 1 STAGE 2 STAGE 3 STAGE 4
AMD NO AMD EARLY AMD
INTEREMEDIATE
AMD
ADVANCED
AMD
No
drusen
OR few
small
Multiple
small + few
intermediate
OR RPE
abnormalities
Extensive
intermediate +
atleast 1 large
OR
Extrafoveal GA
Foveal GA OR
any
neovascular
AMD
5 year risk
of stage 4
1.3% 18%

11. • HARD – discrete and well demarcated
• Focal areas of lipidization or hyalinization of the RPE-
Bruch membrane complex
• SOFT – amorphous and poorly demarcated
• Diffuse thickening of the inner aspects of Bruch (basal
linear deposits)
• CONFLUENT – contiguous drusen without clear
boundaries
Soft / confluent drusen are more likely to progress
to GA or CNV
(Recent study shows small hard drusen are at increase risk of
developing soft / confluent drusen, hence advanced AMD)

12. SOFT, CONFLUENT, LARGE DRUSEN
A. Fundal photo
B. SD-OCT
C. AF

13. Reticular Pseudodrusen
(subretinal drusenoid deposits)
• Reticular like network seen best in fundus
autofluorescence
• Smaller than soft drusen
• Located on the apical surface of the RPE
• Commonly distributed in the superior macular
region
• Share some proteins with drusen (apolipoprotein E,
complement factor H, vitronectin)
• Associated with greater risk of GA and CNV

14. OCT and
AUTOFLUORESCENCE
of pseudodrusen

15. • FFA –
• Small, Hard drusen – hyperfluoresce early because of
window defect
• Large, soft and confluent drusen, drusenoid PED –
slowly and homogenous staining late due to pooling
• OCT –
• Sub RPE nodular elevations or
• Small RPE detachments with absence of intra/ sub
retinal fluid
• Enhanced depth imaging (EDI) OCT show more details of
choroid – choroidal thickness is REDUCED in AMD

16. RPE CHANGES
• FOCAL RPE HYPERPIGMENTATION
• Increased pigmentation in the outer retina
• Blocks fluorescence on FFA
• Hyperreflective outer retinal foci on OCT
• Increases with age
• Associated with greater risk of progression to more
advanced AMD
• FOCAL ATROPHY
• Pigment mottling / frank depigmentation
(noncontiguous)
• Diameter > 175um = Geographic atrophy (GA)

17. • GEOGRAPHIC ATROPHY
• Absence/ depigmentation of RPE unmasks the choroidal
vessels making them visible
• Overlying outer retina appears thin
• Underlying choriocapillaris is attenuated or atrophied
• On FFA – well circumscribed round to oval window
defect
• SD OCT – progressive loss of – RPE, inner segment
ellipsoid, photoreceptor layer
• Densely hypoautofluorescence
• Often spares the fovea until late in the disease
• Decrease contrast sensitivity and reduced perimetric
sensitivity reflects the presence of pseudodrusen prior
to progression to GA
• 3 line visual loss in 53% at 4 years

18. AUTOFLUORESCENCE
FUNDAL
PHOTO

19. DIFFERENTIAL DIAGNOSIS
• CENTRAL SEROUS CHORIORETINOPATHY
• EDI OCT reveals thickened choroid in both eyes
• PATTERN DYSTROPHIES OF RPE
• Reticular/ butterfly shaped macular hyperpigmentation
• Symmetrical in each eye
• ADULT ONSET VITILLIFORM MACULOPATHY
• Yellow subretinal lesion beneath outer retina
• OCT – hyperreflective, dome shaped central lesion
• FFA – late staining
• Occur in younger adults
• DRUG TOXICITY
• Hx of drug ingestion (HCQ, deferoxamine, cisplatin)
• Lack of large drusen

20. MANGEMENT
• EDUCATION AND FOLLOW UP
• AMSLER GRID TESTING
• HYPERACUITY TESTING
• MICRONUTRIENTS
• LIFESTYLE CHANGES
• LOW VISION THERAPY
• LOW VISION REHABILITATION
Laser treatment is currently under investigation

21. Education and Followup
• Educating the patient regarding the progression
and the prognosis of the condition (p.91, RCOPTH)
• Fundus Autofluorescence is the method of choice in
imaging and monitoring the progression of non-
neovascular AMD

22. Amsler Grid testing
• White grid lines on a black background
• Eyes are tested individually
• With reading glasses on, at reading distance (near
vision)
• Check for new,
• Metamorphopsia
• Scotoma
• Other changes in central vision
• Smart phone apps are available

23. Hyperacuity (vernier) testing
• Extremely sensitive to any geographic shift in the
outer retinal morphology
• Preferential hyperacuity perimetry (PHP)
• Detect recent onset CNV in intermediate AMD patients
with high sensitivity and specificity (HOME study)
• Shape discrimination hyperacuity (SDH)
• Ability to discern a perfect circle from a distorted
contour
• Handheld test – (smart phone apps) can be used at
home

24. Micronutrients
• Age Related Eye Disease Study (AREDS)
• Patients with intermediate or advanced AMD showed a
25% risk reduction for progression, 19% risk reduction in
rates of moderate vision loss at 5 years
• At 10 years, 44% of placebo group and 34% of
supplement group had advanced AMD
• No measureable benefit in no AMD or early stage AMD

25. • AREDS 2
• Replaced β-carotene with xanthophylls (lutein and
zeaxanthin)
• Added omega 3 long chain polyunsaturated fatty acids
(DHA and EPA)
• Lower dose of Zinc (high dose of zinc causes anaemia
and GUT conditions in men)
• Xanthophylls had a similar effect with no increase risk of
lung cancer in smokers
• No added benefit of fatty acids
• 80mg or 25mg of zinc is equally effective in reducing the
progression

26. •Recommended supplementation for
stage 3/ 4 AMD in at least 1 eye (daily
dose)
• Vitamin C 500 mg
• Vitamin E 400 IU
• Lutein 10 mg
• Zeaxanthin 2 mg
• Zinc 80 mg or 25 mg
• Cupric oxide 2 mg
To reduce Zn induced
Cu deficiency anaemia

27. Lifestyle changes
• Smoking cessation (3x risk of AMD)
• Diet rich in fruits, vegetables, oily fish, eggs etc..
• Obesity reduction
• Blood pressure control
• ? Anti-glare spectacles
Cataract surgery does not progress AMD ?
UV A, UV B exposure does not progress AMD ?

28. Low vision rehabilitation
• Near vision is affected more than the distance
vision
• Preferential retinal locus (PRL) develops with time
in foveal vision loss
• Should be started early in the disease process
• Magnifiers and low vision aids
• Computers/ tablets with enhanced contrast, zoom,
background options etc..

29. NEOVASCULAR AMD

30. • The presence of CNV
• Degerative changes in Bruch membrane (accumulation
of drusen + progressive thickening) provide a
proangiogenic environment that stimulate
neovascularization in the choriocapillaris
• Perforation of membrane
• New vessels are accompanied by fibroblasts >>
hypertrophic fibrotic disciform scar

31. Signs and Symptoms
• Sudden onset of decreased vision
• Metamorphopsia
• Paracentral scotomas
• Sub/ Intra retinal fluid
• Exudates/ blood (unrelated to other pathologies)
• Pigment ring or gray green membrane
• Irregular elevation of the RPE or a PED
• RPE tear
• Sea-fan pattern of subretinal vessels

32. Anatomical CLASSIFICATION
• TYPE 1
• New vessels originate from the choriocapillaris >> grow
through a defect in the Bruch >> sub RPE space >> fluid
leakage and bleeding >> vascularized serous/ fibrovascular
PED
• More common (80%)
• TYPE 2
• CNV originates between the RPE and neurosensory retina
• Lacy / gray green lesion
• TYPE 3
• New vessels from the deep capillary plexus of the retina and
grows towards the RPE
• Originally named retinal angiomatous proliferation (RAP)
• Small area of red discolouration with exudates or SRF

33. Fluorescein Angiography
• OCCULT CNV
• Consistent with type 1 neovascularization
• Diffuse hyperfluorescence
• Fibrovascular PED –
• Irregular elevation of RPE, progressive stippled leakage on FFA
• Vascularized serous PED –
• Pool dye rapidly in a homogenous ground glass pattern (like a
serous PED), has a notch or hot spot due to the vascularization
• Late leakage from undetermined source –
• Fluorescence at the level of RPE poorly defined in the early
phase, better appreciated in late phases (after 2 minutes)

34. • CLASSIC CNV
• Consistent with type 2 neovascularization
• Bright, lacy, well defined hyperfluorescent lesion that
appears in the early phase and progressively leaks in the
late phases
• TYPE 3 (RAP)
• A spot of retinal haemorrhage in the macula, focal hot
spot with late CME/ pooling into a PED
• Associated with large serous PEDs and extensive areas of
drusen
• Leak aggressively, hence the adjacent retina is disrupted
with cystoid spaces

37. •In common practice…..
• Classic with no occult (100% classic)
• Occult with no classic (100% occult)
• Predominantly classic (classic > 50%)
• Minimally classic (classic 1 - 49%)

38. • SUB FOVEAL – involving the geometric center of the fovea
• JUXTAFOVEAL – immediately adjacent to the center but
within FAZ (1- 199um from center)
• EXTRAFOVEAL – outside FAZ (> 200um from fixation)

39. ICGA
• Longer wavelengths in the infrared spectrum,
penetrates through haem/ pigments to reveal a
hotspot
• 90% protein binding can differentiate between scar
tissue or serous RPE fluid to reveal an active
vascular lesion
• Should be considered in suspected,
• RAP
• iPCV
• Occult peripapillary choroidal neovascular membranes

40. SD – OCT
• TYPE 1
• SEROUS PED – Sharply elevated, dome shaped lesions
with hollow internal reflectivity; No SRF / IRF
• FIBROVASCULAR PED – May or may not be sharply
elevated; demonstrates lacy/ polyp like hyperreflective
lesions on the undersurface of RPE; +/- signs of
contraction
• CHRONIC FIBROVASCULAR PED – Multilayered
appearance due to sub RPE cholesterol crystal
precipitation; “onion sign”; “bridge arch shape”
following anti VEGF denotes poor visual outcome
INCOMPLETE response to antiVEGF

41. SEROUS PED
FIBROVASCULAR PED
CHRONIC FIBROVASCULAR PED

42. • TYPE 2
• Hyperreflective band or plaque in the subneurosensory
space, with sub/ intra retinal fluid
COMPLETE/ GOOD response to antiVEGF

43. • TYPE 3
• Hyperreflective foci emanating from the deep capillary
plexus of the retina; +/- CME and PED
Sensitive to antiVEGF early in the disease
RAP with PED

44. OCT Angiography
• Non invasive
• Reveals structural details of CNV
• Free of blur caused by fluorescein leakage in FFA

45. Polypoidal Choroidal Vasculopathy (PCV)
• Initially called posterior uveal bleeding syndrome
• A variant if type 1 CNV; Often in the peripapillary region
• Multiple, recurrent, serosanguineous RPE detachments
• Network of polyps with feeder vessels that adhere to the
RPE monolayer of the fibrovascular PED (“string of pearls”
appearance)
• Asia – 20-50% on nvAMD are PCV type (<5% in white)
• Vitreous haemorrhage is more common
• Soft drusen +/-
• Pachychoroid
• Visual outcome better except in severe subretinal
haemorrhage
• Ix- ICGA, SD OCT, OCTA
• Less responsive to anti VEGF

46. Diagnostic criteria of PCV (EVEREST II)
Early subretinal ICGA hyperfuorescence (appearing
within 5 mins of injection) with at least one of,
1. Nodular appearance of the polyp on stereoscopic
viewing
2. Hypofluorescent halo around the nodule
3. Abnormal vascular channel(s) supplying the polyps
4. Pulsatile filling of polyps
5. Orange subretinal nodules corresponding to the
hyperfluorescent area on ICGA
6. Massive submacular haemorrhage

47. EVEREST STUDY
• PDT +/- ranibizumab has a better response than ranibizumab
alone
PLANET STUDY
• Aflibercept monotherapy is non inferior to aflibercept + vPDT

48. OCT in PCV
• Sub retinal fluid
• PED
• Fluid / haemorrhage beneath
• Notched PED (sharped peaked) – denotes polyp
• Thumb like polyp
• Polyps attached to the undersurface of PED
• Double layer sign in the PED margins
1. Shallow irregular RPE
2. Bruch membrane
• Pachychoroid
• Intraretinal cystoid spaces LESS COMMON
ACTIVE PCV
- Intra/ sub retinal fluid
- Sub RPE/ subretinal haemorrhage
- Vision loss > 1 line (5 letters ETDRS)

50. PCV vs CNV
• Seen in a younger age group than AMD
• Often occurs in the nasal macula
• May leak and bleed but less likely to invade the
retina than CNV
• Pachychoroid
• Has a strong association with hypertension and
ischemic heart disease

51. DIFFERENTIAL DIAGNOSIS
• DIABETIC MACULOPATHY
• Presence of extensive vascular signs outside the macular
arcade along with venous engorgement or beeding
• Visual function is less markedly reduced
• FFA – absence of neovascularization and subRPE pathology
• Sometimes both can coexist
• CENTRAL SEROUS CHORIORETINOPATHY
• Subretinal fluid can be seen in both
• No subretinal haemorrhages (no neovascularization)
• Thick choroidal layer (pachychoroid)
• Geographic patches of RPE pigment mottling that extends to
the inferior periphery in a gravitational configuration.
(“guttering”)
• CNV and IPCV can occur as a complication

52. • HIGH MYOPIA
• Minute cracks in thinned Bruch membrane allowing choroidal
vessels to access the subretinal space
• INFLAMMATORY CNV
• MACULAR TELANGIECTASIA
• Type 1 – middle aged, unilateral, exudative features, cystic
maculopathy, surrounding exuadates
• Type 2 – older, bilatetral, crystalline deposits, pigmentary
changes
• FFA leakage present but no retinal thickening
• Cystic spaces present on OCT
• Occasionally subretinal neovascularization develops and
arises from the retinal circulation
• Difficult to differentiate from RAP

53. MANAGEMENT
• Laser photocoagulation
• Photodynamic therapy
• Anti angiogenic therapy
• Steroids
• Combination treatment
• Surgical treatment
• Low vision therapies
• Low vision rehabilitation

54. Laser photocoagulation (thermal
laser)
• High recurrence rates (MACULAR
PHOTOCOAGULATION STUDY TRIALS – MPS)
• Severe vision loss +/-
• Now used very rarely
• Peripheral lesions might benefit, but must be
warned regarding permanent scotoma
• Must follow up at 2 weeks and 6 weeks with repeat
FFA to confirm CNV ablation

55. Photodynamic therapy (cold laser)
• Localized photochemical reaction induces CNV
thrombosis
• PDT slows progression
• Doesn’t prevent significant vision loss in most eyes
• Upregulates VEGF in the treated area
• Rarely used now
• Have to avoid direct sunlight for 5 days
• C/I in porphyria, allergy
• Caution in liver dysfunction, pregnancy, breast
feeding, paediatrics

56. • No longer justifiable as monotherapy for nvAMD
• Recommended only in iPCV
• Performed within 2 weeks of FFA and then as
required 3 monthly
• Severe vision loss immediately post Rx in 4% and
may be permanent
• Idiosyncratic back pain occurs in 1-2% which
resolves when the infusion is stopped
• Should avoid direct sunlight exposure for 2 – 5 days
RCOPHTH GUIDELINES

57. Antiangiogenic therapy
• Activators of angiogenesis
• Vascular endothelial growth factor (VEGF)
• Fibroblast growth factor (FGF)
• Transforming growth factor α (TGF α)
• TGF β
• Angiopoietin 1, 2
• Inhibitors of angiogenesis
• Thrombospondin
• Angiostatin
• Endostatin
• Pigment epithelium derived factor (PEDF)

58. • VEGF
• Homodimeric glycoprotein
• Heparin binding growth factor specificity for
vascular endothelial cells
• Induces –
• Vascular permeability
• Angiogenesis
• Lymphangiogenesis
• Prevents apoptosis
• 4 major isoforms – in CNV most dominant is
VEGF165

59. PEGATANIB SODIUM
• First approved intravitreal anti VEGF
• RNA oligonucleotide ligand (aptamer) that binds
human VEGF165 isoform of VEGF-A
• No longer in use, supplanted by more effective
agents
MACUGEN – 0.3mg
VISION study
• Used six weekly Pegatanib sodium
• Recommended dosage 0.3mg

60. RANIBIZUMAB
• Recombinant humanized antibody fragment (Fab)
that binds VEGF
• Binds to and inhibits all active forms of VEGF-A as
well as their active degradation products
ANCHOR
Ranibizumab monthly vs PDT as needed quarterly; Ranibizumab
superior
MARINA
Ranibizumab monthly vs sham injectons; Ranibizumab superior
LUCENTIS – 0.5mg / 0.05mL

61. PIER / EXCITE
Treatment efficacy declined in participants undergoing
quarterly (every 3 month) injections as opposed to monthly
PrONTO / SAILOR / SUSTAIN / HORIZON
3x monthly injections followed by various as needed
treatment regimens based on clinical/ OCT criteria
HARBOR
No difference in VA/ anatomical gain between 2.0mg (high
dose) vs 0.5mg (standard)

62. • TREATMENT REGIMEN
Monthly injections until the macula is dry
(initial 3 +)
Then;
• AS NEEDED – inject when signs reappear
• TREAT AND EXTEND – inject with decreasing
frequency even if the retina is dry
• No disease activity: + 2 weeks
• Disease activity: - 2 weeks
Fibrovascular PEDs may be at increased risk for the development
of an RPE tear following anti VEGF therapy (esp PEDs > 600um in
height); Due to the contraction of underlying type 1 CNV
Not a contraindication for anti-VEGF

63. AFLIBERCEPT
• Known as VEGF Trap
• Soluble protein which acts as a VEGF decoy
• Ligand binding elements of the extracellular
domains of VEGF receptors are fused to the Fc
region of IgG
• Binds both VEGF-A and placenta like growth factor
(PGF)
• Fully penetrates all the retinal layers (small
molecule)
EYLEA – 2mg / 0.05mL

64. VIEW 1 / VIEW 2 (VEGF Trap-Eye: Investigation of efficacy
and safety in Wet AMD 1 and 2)
• Aflibercept is non inferior to Ranibizumab
• Aflibercept every 2 monthly showed similar efficacy to
ranibizumab administered monthly
• Safety profiles are similar for both

65. BEVACIZUMAB
• Full length monoclonal antibody against VEGF
• Used to treat metastatic colorectal cancer
• Large molecule; But cheaper
• Longer systemic half life (21 days)
BRAMD / CATT / GEFAL / IVAN / LUCAS / MANTA
Bevacizumab non inferior to Ranibizumab
CATT
Systemic side effects were significantly greater in the
bevacizumab group (40%) than the ranibizumab group (31%)
AVASTIN – 1.25mg / 0.05mL

66. COMPLICATIONS OF INTRAVITREAL ANTI-
ANGIOGENICS THERAPY
• Subconjunctival haemorrhage
• Local irritation
• Inflammation
• Persistent ocular hypertension
• Retinal detachment
• Vitreous haemorrhage
• Endophthalmitis (1:2000)
• Geographic atrophy
• Arteriothrombotic events (in high risk patients only)

67. Steroids
• Anecortave acetate
• Angiostatic cortisone
• Does not produce increased IOP, cataracts
• Administered every 6 monthly PST
• Triamcinolone acetate
• Intravitrial +/- PDT (VERITAS)
• NO EVIDENCE TO SUPPORT STEROID THERAPY FOR
nvAMD

68. Combination treatment
RADICAL / DENALI / MONT BLANC
Ranibizumab monotherapy vs combined with PDT
• Combination reduced retreatment rates
Visual outcomes were inferior to monotherapy
• Combination can be beneficial in PCV but VA was
inferior (EVEREST)

69. Surgical treatment
• Intravitreal/ subretinal t-PA injection with
pneumatic displacement
• In thick submacular haemorrhage
• Macular translocation surgery
• Radiotherapy
• Externally (teletherapy)
• Locally (brachytherapy)
Not recommended for the management on
nvAMD

70. Low vision therapy
• Implantable miniature telescope (IMT)
• Enlarges the retinal image of the central field
• Can lead to corneal decompensation
• IOL-VIP system
• High minus in bag and a high plus in the AC

71. Low vision rehabilitation
• Optical / non optical devices
• High plus lenses, video magnifiers
• Optimal lighting, contrast enhancement
• Training of the use of eccentric fixation

72. OTHER CAUSES OF CNV
• OCULAR HISTOPLASMOSIS SYNDROME
• 90% react positively to histolplasmin skin testing
• Small, atrophic, “punched out” chorioretinal scars in
midperiphery and posterior pole (histo spots)
• Linear peripheral atrophic tracks
• Juxtapapillary chorioretinal scarring
• +/- CNV in the macula
• B/L in 60%
• Absent vitreous inflammation
• Rx – no specific medical Mx, Anti VEGF if CNV develops

74. • ANGIOID STREAKS
• Irregular dark red/ brown lines radiating from a ring of
peripapillary atrophy surrounding the optic nerve head
• FFA – characteristic window defect with late staining
• Dehiscences or cracks in the thickened and calcified
Bruch membrane
• Associations :
• Pseudoxanthoma elasticum
• Grondbald-Strandberg syndrome
• Paget disease of bone
• Beta thalasaemia
• Sickle cell anaemia
• Ehlers-Dalos syndrome
• Asymptomatic unless they are sub foveal
• Rx- Safety glasses; Medical R/V; If CNV anti VEGF

76. • PATHOLOGIC MYOPIA
• CNV develops in 5-10% with an axial length >26.5 mm
• +/- lacquer cracks / widespread degeneration
• Laser scars can expand over time (atrophy creep)
• Rx – anti VEGF
• Sustained regression after 1 or 2 injections

77. • IDIOPATHIC CNV / MISCELLANEOUS CAUSES
• Inflammatory chorioretinopathies
• Choroidal neoplasms
• Traumatic choroidal rupture
• Optic nerve head anomalies
• Rx – anti VEGF

78. Conditions associated with CNV
• Degenerative
• ARMD
• Myopic degeneration
• Angioid streaks
• Heredodegerative
• Vitilliform maculopathy
• Fundus flavimaculatus
• Optic nerve head drusen
• Inflammatory
• Ocular histoplasmic Sx
• Multifocal choroiditis
• Multifocal serpiginoid
choroiditis
• Toxoplasmosis
• Toxocara
• Rubella
• VKH
• Behecet
• Sypathetic ophthalmia
• Tumour
• Choroidal naevus
• Choroidal haemangioma
• Metastatic choroidal
tumours
• Hamartoma of the RPE
• Traumatic
• Choroidal rupture
• Intense photocoagulation
• Idiopathic

79. RCOPHTH……

80. TREATMENT ALGORITHM
• EXTRAFOVEAL CNV –
• Focal laser treatment (MPS protocol)
• Anti VEGF – if laser induces scotoma which affects normal
visual function OR large CNV + progression
• If no progression or not vision threatening OBSERVE
• SUBFOVEAL/ JUXTAFOVEAL –
• Anti VEGF
• PDT can be offered for predominantly classic
• Occult with minimum symptoms OBSERVE until progression
• RAP –
• Anti VEGF
• IPCV –
• Only macular involvement is treated unless large
• PDT +/- anti VEGF (EVEREST)

81. Criteria for initiating treatment
• Active subfoveal neovascularization of any type
• In PROGRESSION (in occult CNV with minimal
symptoms)
1. Appearance of sight threatening CNV which was not
previously suspected or thought to be present
2. Evidence of new haemorrhage and/ or SRF
3. A document recent visual decline
4. An increase in CNV size
• BCVA between 6/12 and 6/96
• No significant structural damage to the fovea
(longstanding fibrosis/atrophy, disciform scar)
• Lesion size ≤ 12 disc area – NICE guidelines

82. Clinical scenarios
• BILATERAL ACTIVE CNV
• Can inject simultaneously
• Different set of instruments, separate vials
• PREDOMONANTLY HAEMORRHAGIC LESIONS
• Not considered a reason to withhold treatment
• RAISED INTRAOCULAR PREASSURE
• Can give even if >30mmHg with concurrent IOP Rx
• INTRAOCULAR SURGERY
• Exudative CNV should be treated prior to cataract Sx

83. Criteria for not commencing
treatment
• Permanent structural damage (further visual loss
not possible)
• Evidence / suspicion of hypersensitivity to antiVEGF

84. Rx regimen
• LOADING PHASE
• Ranibizumab/ aflibercept monthly for 3 months
• MAINTAINANCE PHASE
• Depends on BCVA, Hx, Ex, OCT etc..
• Ranibizumab – 4 weekly
• Aflibercept – 8 weekly
• (Pegaptanib – 6 weekly)
• PRN / treat and extend

85. Criteria for continuation
1. Persistent evidence of lesion activity
(Retinal/ sub retinal/ sub RPE fluid or hemorrhage)
2. Lesion continues to respond to repeated
treatment
3. No contraindications to continuing treatment

86. Temporary discontinuation
• Absence of disease activity (FFA leakage, increase
size, new haemorrhage or exudate) even if there is
persistent fluid (intraretinal cysts/ tabulation) on
OCT
• No reappearance of CNV activity following recent
discontinuation
• No deterioration of vision

87. Permanent discontinuation
• Hypersensitivity reaction
• Can change to Pegaptanib or PDT
• Reduction of BCVA by 15 letters on 2 consecutive
visits
• Reduction of BCVA by 30 letters
• Evidence of deterioration of the lesion over 3
consecutive visits
• Progressive increase of lesion size on FFA
• Worsening of OCT indicators of CNV disease activity
• Significant new hamorrhages or exudates

88. Discharging from clinic
• If permanently discontinued
• No evidence of other ocular pathology
• Low risk of further worsening or reactivation of
nvAMD that could benefit from restarting Rx (poor
central vision and large non progressive scar)
Anti VEGF will improve vision in only 33%
Majority will maintain vision
10% will not respond to treatment