Age-Related Macular Degeneration (AMD) Lectures Flashcards
1
Q
What is the main cause of severe visual loss worldwide? How many people are affected globally?
A
AMD, 20-25 million (8 million severe), 2nd to cataract in visual loss
2
Q
Which studies looked at AMD prevalence globally?
A
Beaver Dam, Blue Mountain, Rotterdam
3
Q
What symptoms are seen in AMD?
A
Blurred distorted vision, wavy lines/odd shapes, central vision loss
4
Q
How is AMD diagnosed?
A
VA testing, Amsler grid test, fundoscopy, FFA
5
Q
What are the characteristic clinical findings seen in AMD?
A
Drusen Retinal pigment epithelium (RPE) changes Visual loss (later stages)
6
Q
What are the two main types of AMD?
A
Dry (Geographic Atrophy)
Wet (Neovascular)
7
Q
What fundoscopy signs are visible in geographic atrophy?
A
Pale hypopigmented macula
Choroidal vessels visible (RPE loss)
8
Q
What types of geographic atrophy are there?
A
Normal: Small drusen, normal pigment
At-risk: Reticular drusen, RPE pigment change, thick BM, CC loss
Atrophic: RPE/photoreceptors death, inflamed CC, Muller cells, astrocytes
9
Q
What is the pathogenesis of neovascular AMD?
A
Angiogenesis due to VEGF buildup forms weak, leaky retinal vessels which damage the retina and form scar tissue
10
Q
What else does VEGF cause besides angiogenesis?
A
Capillary leakage
Macrophage and granulocyte chemotaxis
VEGF receptor 1 binds to PIGF, VEGF-B, VEGF-A
11
Q
Which type of late AMD is most common?
A
Dry (90% of cases)
12
Q
Which type of late AMD is treatable? What is the treatment?
A
Wet (neovascular AMD): Anti-VEGF agents
13
Q
What conditions are included under the umbrella term “Neovascular AMD”?
A
Choroidal Neovascularisation (CNV)
Pigment Epithelial Detachment (PED)
Retinal Angiomatous Proliferation (RAP)
Polypoidal Choroidal Vasculopathy (PCV)
14
Q
Which imaging modality highlights vessel leakage in neovascular AMD?
A
Infrared angiography
15
Q
What layers of the retina are affected by early AMD?
A
Retinal pigment epithelium (RPE)
Bruch’s membrane: extracellular matrix
Choriocapillaris: fenestrating capillaries
16
Q
What are the risk factors for developing AMD?
A
Age (biggest) Genetics (1st degree relative with AMD triples risk) Smoking (doubles risk) Ethnicity (Caucasians higher risk) Obesity, high fat diet Hypertension High sunlight exposure Other: Aspirin use, cataract surgery
17
Q
What is a single nucleotide polymorphism (SNP)?
A
Genome variations present in more than 1% of the population
18
Q
What is a haplotype?
A
Polymorphism sets that tend to be inherited together
19
Q
What is a diplotype?
A
2 haplotypes on alleles of homologous chromosomes
20
Q
What are the 3 main gene variants linked to AMD development?
A
Y402H variant of CFH gene (Chromosome 1)
HTRA1, ARMS2 genes (Chromosome 10)
21
Q
Which gene variant on chromosome 1 is linked to an increased risk of developing dry AMD?
A
Y402H variant of CFH gene (4x risk)
22
Q
Which gene variants on chromosome 10 are linked to an increased risk of developing wet AMD?
A
HTRA1, ARMS2 genes (8x risk)
23
Q
Which research paper identified 34 genetic loci associated with increased AMD risk?
A
Fritsche et al. 2016 (Nature Genetics)
24
Q
What factors influence AMD staging?
A
Drusen presence and size
Presence of retinal pigmentary abnormalities
Presence of geographic atrophy or neovascularisation
25
How are drusen formed?
Incomplete photoreceptor breakdown leading to extracellular debris (lipofuscin) buildup in Bruch's membrane, detaches RPE from choroid which causes oxidative stress and drusen formation
26
Where are drusen found?
Between the RPE and Bruch's membrane
27
Which drusen are not associated with AMD?
Small 'hard' drusen (<63μm), linked to normal ageing
28
Which drusen are associated with early AMD?
Medium drusen (63-125μm)
29
Which drusen are associated with intermediate AMD?
Large 'soft' drusen (>125μm)
30
What imaging techniques are used to detect drusen?
```
Fluorescein angiography (FA): Drusen appears hyperfluorescent
Optical Coherence Tomography (OCT)
```
31
What is the complement cascade?
A component of the innate immune system which destroys pathogens and clears away immune complexes
32
What are the 3 main pathways of the complement cascade?
Classical
Lectin
Alternative
33
What is the ultimate goal of these 3 pathways?
Forming C3 convertase to cleave C3 into C3b
34
How do the Classical and Lectin pathways produce C3 convertase?
C4b cleaves C2 into C2a + C2b
| C4b and C2b combine, forming Classical/MBL pathway C3 convertase
35
How does the Classical pathway form C4b?
C1q activated by binding to IgG + IgM
C1q activates C1r which activates C1s
C1s cleaves C4 into C4a and C4b
36
How does the Lectin pathway form C4b?
Mannose-binding Lectin (MBL) binds to carbohydrates on microbial surfaces
MASP2 is activated and cleaves C4 into C4a and C4b
37
What is the difference between the Alternative complement pathway and the other 2 pathways?
Alternative pathway is always active, not dependent on microbes being present
38
How does the Alternative pathway form C3 convertase?
C3 is hydrolysed into C3(H2O)
Factor B cleaves C3(H2O) into C3(H2O)B
Factor D cleaves Factor B, forming C3(H2O)Bb
C3 converts to C3b, forming C3 convertase: C3bBb
39
How is the Alternative pathway regulated?
It is regulated through a cascade loop:
C3 convertase + C3b form C5 convertase
C5 convertase binds to C5 to form C5a + C5b
C5b recruits C6 and C7 to form C5b67
C5b67 inserts C8 into membrane, C9 makes pores in it
A membrane attack complex (MAC) has formed
40
Which protein also regulates the Alternative pathway besides the cascade loop?
Complement Factor H (bloodborne)
| Inactivates C3b via Complement Factor I
41
Where else does the mechanism of AMD occur in the body?
Kidneys (type 2 glomerulonephritis)
42
What substance recruits Complement Factor H from the blood into Bruch's membrane?
Heparan sulphate
43
Which polymorphism prevents Complement Factor H binding onto Bruch's membrane?
Y402H
44
Which protein can pass through the blood-retinal barrier (BRB) in place of Complement Factor H?
Factor H-like protein 1 (FHL-1), potential future AMD therapy
45
What medium is used to create OCT images?
Near infrared light
46
How is the OCT image produced?
Reference and sampling beams reflect off tissue into the detector
Echo time delay and light intensity is measured after the beams are combined by an interferometer
47
What parameters are observed in OCT imaging?
```
Axial resolution
Transverse resolution
Measurement time
Detection sensitivity
Image penetration depth by tissue
Image contrast
```
48
What is the most superficial retinal layer?
Internal limiting membrane
49
What is the deepest retinal layer?
Choroid sclera junction (Choroidal stroma)
50
Which retinal layers are found between the internal and external limiting membranes? (Superficial to deep)
```
Retinal nerve fibre layer
Ganglion cell layer
Inner plexiform layer
Inner nuclear layer
Outer plexiform layer
Henle fibre layer
Outer nuclear layer
```
51
Which retinal layers are found between the external limiting membrane and the choroid sclera junction? (Superficial to deep)
```
Photoreceptors
Retinal Pigment Epithelium (RPE)
Bruch's membrane
Choriocapillaris
Inner choroid layer (Sattler’s)
Outer choroid layer (Haller’s)
```
52
Which photoreceptor inner segment layer contains mitochondria?
Ellipsoid
53
Which photoreceptor inner segment layer contains ribosomes (protein synthesis organelles)?
Myoid
54
Which imaging type highlights the posterior border of the choroid layers
Enhanced depth imaging (EDI)
55
What are the key steps in OCT analysis?
Identifying normal, abnormal and artefacts in the image
Observing all line scans
Qualitative retinal image (good/bad?)
Quantitative measures (retinal thickness/volume)
56
What OCT signs are seen in early phase AMD?
Hyperfluorescence between the RPE and Bruce’s membrane surrounded by a margin of hypofluorescence
57
What OCT signs are seen in occult phase AMD?
Irregular RPE elevation
| Stippled fluorescence with diffuse leakage visible
58
Who first identified retinal angiomatous proliferation (RAP) as a form of neovascular AMD?
Yannuzzi
59
What are the 3 main types of retinal angiomatous proliferation (RAP)?
RPE
Choroidal
Intraretinal
60
What are the 3 stages of retinal angiomatous proliferation?
```
Intraretinal neovascularisation (IRN)
Subretinal neovascularisation (SRN)
Choroidal neovascularisation (CRN)
```
61
What form of neovascular AMD involves orange-reddish choroidal lesions invading the subretinal space?
Idiopathic polypoidal choroidal vasculopathy (IPCV)
62
What are the features of polyps in IPCV?
Orange-reddish
Nodular
Hypofluorescent halo
Branching vascular network
63
Besides polyps what other features are seen in IPCV?
RPE and retinal detachment
Haemorrhages (invading vitreous)
Exudates
64
Besides OCT what imaging modality is used to detect IPCV?
Indocyanine green angiography (ICGA)
65
Which 3 or more OCT findings are diagnostic for IPCV?
Multiple RPE detachments
Sharp RPED notch/peak
Hypofluorescent lumen (polyps)
Hyperfluorescent intraretinal exudates
66
Which neovascular AMD signs may be left untreated depending on severity?
```
Pigment epithelial detachment (PED)
Intraretinal fluid (IR) up to 200μm
```
67
Which cause of subretinal fluid has a worse prognosis: neovascularisation or vitreous degeneration?
Vitreous degeneration due to retinal detachment
68
What lesions are a result of inflammation due to microglial cell activation?
Subretinal hyperreflective exudative (SHE) lesions
69
What signs indicate a retinal pseudocyst?
Thinner overlying retina
Squared off lesion
Surrounding atrophy
70
What signs indicate retinal tubulation?
```
Retinal rosettes (photoreceptor degeneration)
Atrophic change (late stage)
```
71
How are OCT-A images produced?
Laser light reflected off moving red blood cells in retinal vessels creating multiples images which are then combined
72
What types of OCT-A artefact are there?
Vessel thickness (overestimated)
Projection
Thresholding
Fringe washout (microsaccade)
73
What vasculopathy is identified better by OCT-A than FA?
DR microaneurysms
74
What are some OCT-A segmentation errors?
Superficial vessels interfering with deep vessel images
Vessel leakage not visible
Image size smaller than that of FA
75
OCT-A is good at identifying what retinal vascular features?
Chorioretinal anastamoses
Small areas of PED
CNV
CSR
76
What is the pathogenesis of fibrosis in neovascular AMD?
Inflammatory mediator release following CNV
| Fibroblast aggregation
77
What are the consequences of fibrosis in neovascular AMD?
Photoreceptor, RPE and choroidal vessel destruction
| Visual acuity drop (especially if external limiting membrane intact)
78
What are the main challenges in neovascular AMD fibrosis management?
Existing therapy resistance
Quantifying subretinal fibrosis
Identifying types of fibrosis
Timing of therapy
79
How does AMD impact peoples’ daily lives?
```
Difficulty in driving, reading and recognising faces
Increased falling and injury risk
Greater need for supportive care
Lower quality of life
Exacerbation of existing co-morbidities
Increased risk of depression
```
80
What is the estimated cost of AMD detection and treatment for 2010-2020?
£16.4 billion
81
What is the percentage risk of an AMD patient developing AMD in the contralateral eye over 2 years?
28.9%
82
What forms of diet supplementation could aid AMD treatment?
High dietary carotenoid and omega-3 levels
83
What is the name of the main diet-related AMD study?
AREDS (Bird et al)
84
What AMD categories are highlighted by the AREDS1 study?
1: No AMD, >20/32 VA in both eyes
2: Many small/1+ intermediate drusen or pigment changes in 1/both eyes, >20/32 VA in both eyes
3: Many intermediate/1+ large drusen, GA outside fovea
4: Advanced AMD in 1 eye
85
Which dietary supplements were included in the AREDS1 study?
Vitamin C, E
Beta-carotene
Zinc
Copper
86
What were the results of the AREDS1 study?
Antioxidants and zinc reduced AMD risk by 25% in AMD category 3/4 participants
87
What cautions were associated with the AREDS1 study?
Beta-carotene: Lung cancer risk (smokers)
Zinc: Alzheimer’s, genitourinary hospital admission risk
Vitamin E: Heart failure risk (HOPE study)
88
Which additional dietary supplements were added to AREDS1 for AREDS2?
Lutein
Zeaxanthin
Omega-3 (DHA and EPA)
89
What were the results of the AREDS2 study?
Lutein/zeaxanthin: 26% more AMD risk reduction
Zinc: Higher doses higher benefit
Omega-3: No effect on AMD risk
90
What dietary recommendations followed the AREDS studies?
Dark green leafy vegetables
“Colour on the plate”
Eggs, fish
91
What factors affect the simplified AREDS risk score?
Drusen >125μm in 1 eye
Drusen 63-125μm in both eyes
Pigment changes
92
What are the two most common forms of CNV in neovascular AMD?
Occult (>85%)
| Classic (12%)
93
What are the symptoms of neovascular AMD?
Blurred, distorted vision
Decreased central vision
Increased glare sensitivity
Reduced night vision
94
Which type of CNV responds to anti-VEGF and photodynamic therapy?
IPCV
95
Which type of CNV responds well to therapy but can be aggressive?
Classic
96
Which type of CNV responds to therapy but requires many injections?
RAP
97
Which type of CNV progresses slowly?
Occult
98
What are the main types of RPE detachment?
Drusenoid
Serous
Haemorrhagic
Fibrovascular (Occult)
99
Which retinal layer is affected by drusenoid PED?
Outer nuclear layer
100
What OCT findings indicate serous PED?
Optically empty, smooth-domed elevation
101
What OCT findings indicate vascularised PED?
Irregular hyperreflective elevation
| Serous PED may also be present
102
Which types of RPE detachment are treated with anti-VEGF?
Fibrovascular
| Haemorrhagic (with PDT)
103
What studies introduced PDT and what were the conditions for treatment?
2001 TAP study, 2003 NICE study
| Classic CNV, >6/60 VA
104
What is the name of the drug used in PDT?
Verteporfin
105
Which study introduced anti-VEGF and what was the drug name?
2008 NICE study
| Ranibizumab (Lucentis)
106
How is anti-VEGF better than PDT in treating AMD?
PDT only slows deterioration
| Anti-VEGF stabilises/improves vision
107
Which cells proliferate to form new vessels due to VEGF-A?
Endothelial cells
108
Who first discovered angiogenic growth factors?
Judah Folkman (1970’s)
109
When was VEGF then its isomers (e.g. VEGF-A) identified?
VEGF (and VPF): 1980’s
| VEGF-A and other isomers: 1990’s
110
Who pioneered intravitreal anti-VEGF injections?
Rosenfeld
111
Where is VEGF found in the eye and what is its normal function?
RPE
| Embryonic, skeletal and reproductive angiogenesis
112
What factors stimulate VEGF accumulation?
Growth factors, hormones, cytokines
| Hypoxia
113
What are the pathological effects of VEGF?
Endothelial cell proliferation
Inappropriate angiogenesis
Vascular leakage and oedema
114
What is the role of placental growth factor (PlGF)?
Enhances angiogenesis
| Binds to VEGF-R1 so VEGF-A binds to VEGF-R2
115
Which VEGF receptor has the greatest effect in neovascular AMD?
VEGF-R2 (binds VEGF-A, C, D)
116
What are the 3 main anti-VEGF drugs?
Lucentis (Ranibizumab)
Avastin (Bevacizumab)
Eylea (Aflibercept)
117
Which studies provided evidence for Lucentis (Ranibizumab) use?
ANCHOR (Monthly vs PDT)
MARINA (Monthly vs sham)
PIER (3-monthly vs sham)
PrONTO/SUSTAIN (PRN)
118
What indicated “stable” vision according to the ANCHOR and MARINA studies?
Losing <15 letters from baseline
119
What were the results of the MARINA study?
20.3-21.4 letters gained over sham after 2 years
120
What were the results of the PIER study?
19.1-2 letters improvement over sham after 2 years
121
What was the extended PIER study called?
HORIZON
122
What were the results of the ANCHOR study?
17.9-20.5 letters gained over PDT after 2 years
VFQ-25: 15-point mean difference
15-42.1% >6/12 VA after 2 years
123
What were the results of the EXCITE study?
8. 3 letters improvement from monthly Lucentis (1 year)
| - 105μm retinal thickness (1 year)
124
What was the patient criteria for the PrONTO/SUSTAIN studies?
>5 letters vision loss + fluid
| >100μm central retinal thickness
125
Which study investigated 3-monthly vs monthly Lucentis use?
EXCITE
126
Which studies involved 3 loading doses followed by monthly review?
PrONTO
SUSTAIN
Mont-BLANC
127
What was the retreatment criteria in the PrONTO study?
New Classic CNV/haemorrhage
| Persistent fluid following last injection (2nd year: any more fluid)
128
Why was the SUSTAIN study less successful than the PrONTO study?
Too rigid retreatment criteria
Too many Occult CNV cases (40%)
0.3mg rather than 0.5mg dose
129
Which treatment interval yielded the best results? Which studies did these involve?
Monthly: 8 letters gained
| ANCHOR, MARINA, EXCITE
130
Which treatment interval yielded the worst results? Which studies did these involve?
3-monthly: 2.2 letters gained
| PIER, EXCITE, SAILOR
131
What were the results of the HARBOR study?
10.1 and 8.2 letters gained for Lucentis monthly and PRN respectively after 12 months
132
Which studies were combined to outline long term PRN Lucentis use?
PIER, HORIZON, SEVEN-UP
133
What are the 3 types of treatment responses seen in the Lucentis studies?
Gained/maintained
Gained/not maintained
No gain
134
Which dosing approaches are examples of individualised dosing?
PRN
| Treat and Extend
135
What is the Treat and Extend approach?
Treat at all visits
Inactive disease: longer treatment intervals and vice versa
Individualising patient care
136
What is the maximum interval between treatments in the Treat and Extend approach?
12 weeks
137
What are the potential benefits of the Treat and Extend approach?
Greater capacity through longer review intervals
| Large vision drops unlikely
138
What are the potential drawbacks of the Treat and Extend approach?
Inactive disease being treated
Costs
Injection risks
139
Which studies have provided evidence for the Treat and Extend approach?
Prospective: LUCAS, Toalster, Abedi
Retrospective: Gupta, Oubraham, Engelbert
Ongoing: TREND, T-REX, RANGE
140
What was the LUCAS T&E study retreatment criteria?
Fluid on OCT
Haemorrhage or dye leakage
Increased lesion size on FA
141
What was the aim of the Fight Retinal Blindness (FRB) project?
Verifying that wet AMD treatment evidence in clinical trials applied in real world settings (Australia/New Zealand)
142
Which study examined the Treat and Extend approach over 2 years?
Arnold et al.
143
What drug treats wet AMD as well as colorectal cancer?
Bevacizumab (Avastin)
144
Which study compared Lucentis vs Avastin monthly/PRN over 2 years?
CATT
145
What are the benefits of using Avastin instead of Lucentis for wet AMD treatment?
Higher rate of SAE
Longer half-life (20 days)
Cheaper
146
What are the drawbacks of using Avastin instead of Lucentis for wet AMD treatment?
Not licensed
| No standard dose: Contamination risks (inflammation, raised IOP)
147
What is the first fully human intravitreal fusion protein?
Eylea (Aflibercept)
148
Which are the main studies providing evidence for Eylea (Aflibercept) use?
VIEW1/2
149
When did NICE permit the use of Eylea (Aflibercept) in treating wet AMD?
July 2013
150
Which study evaluated Eylea (Aflibercept) use in treating wet AMD over 7 years?
Gillies et al.
151
What are the risks associated with intravitreal injections?
```
Endophthalmitis
Retinal detachment
Lens damage
Atrophy
Stroke
MI
```
152
Which ethnic group is more prone to developing PCV in wet AMD?
East Asians
153
What combination therapy is ideal in treating PCV in wet AMD?
Anti-VEGF agents and PDT
154
Which study provided evidence for combination therapy in treating PCV in wet AMD?
EVEREST
155
What potential X-ray based treatment may be used in treating wet AMD?
Stereotactic radiotherapy (Oraya IRay)
156
Which study provided evidence for stereotactic radiotherapy use in treating wet AMD?
INTREPID
157
What were the results of the INTREPID study in treating wet AMD?
33% less injections needed after 1 year
| Treatment response not dependent on dosage
158
According to the Royal College of Ophthalmologists guidelines, where in a hospital can doctors carry out intravitreal injections?
Theatre
| Dedicated outpatient rooms
159
What are the minimum requirements to perform an intravitreal injection?
Surgical scrub
| Sterile mask and gloves
160
What topical anaesthesia can be given before administering intravitreal injections?
Oxybuprocaine
| Tetracaine
161
What substance is used for disinfection before administering intravitreal injections?
5-10% povidone iodine
162
Which scleral injection site is ideal for intravitreal injections and what angle should the needle be inserted at?
3.5-4.0mm from the limbus
| Perpendicular to the sclera
163
What is the maximum appropriate volume for an intravitreal injection
0.1ml
164
Which method should be used for wide-bore injections?
Stepped entry
165
What is the preparation policy for bilateral intravitreal injections?
Each eye prepared separately
| Different set of instruments per eye
166
What are discharged patients no longer prescribed following intravitreal injections?
1-2 topical antibacterial drops after injection then QDS for 3+ days
167
Why are patients no longer given topical antibacterial drops after intravitreal injections?
Increased microbial resistance (63.6%)
168
What are the contraindications for intravitreal injections?
Conjunctivitis
Severe blepharitis
Allergies
169
What are the complications associated with an intravitreal injection volume of >0.05ml
Raised IOP risk
Glaucoma
Sudden no perception of light (NPL)
170
What are the complications associated with ocular injections?
```
Endophthalmitis (very rare, 0.048% risk)
Intraocular inflammation/haemorrhage
Trauma, retinal detachment
Raised IOP
Hypotony
```
171
What is the human visible spectrum?
400-700nm (555nm peak)
172
How does the crystalline lens optical density change with age? Which light does it absorb more with age?
Rises with age, more blue light is absorbed
173
What is macular pigment? Where is it found? What is it made up of?
Yellow oily substance
Central 6 degrees of retina in fibres of Henle
Lutein and zeaxanthin
174
What does macular pigment do?
Absorbs harmful blue light toxic to retina
| Antioxidant, anti-inflammatory (protective in AMD)
175
What factors affect macular pigment levels?
AMD, diet, smoking, obesity, high BP, iris colour (more if darker)
176
What naturally occurring carotenoid has more lutein than zeaxanthin?
Xanthophyl
177
How can macular pigment levels be increased?
Consuming green leafy vegetables
| Lutein/zeaxanthin supplementation
178
Which method is used to measure macular pigment levels?
Heterochromatic flicker photometry
179
How does heterochromatic flicker photometry work in macular pigment testing?
2 superimposed lights (blue 450nm, green 540nm) set with 15Hz flicker, subjects identify point of minimum flicker in central and peripheral fixation
180
How is the luminence ration calculated in macular pigment testing?
Blue light luminence divided by green light luminence
181
What is the critical flicker fusion frequency in macular pigment testing?
Flicker too quick for the human eye to detect
182
Which formula is used in the age-estimate technique for macular pigment testing?
Periphery luminence ratio = 4 + age x 0.02
183
Which study produced the equations used in macular pigment calculations?
Van der Veen et al. (2009)
184
Which study investigated the effect of lutein supplementation on macular pigment and VA? What were the results?
CLEAR study
68% increase in MP
VA increase over 1 year
185
Which type of photoreceptor is lost first in early AMD?
Rods
186
What do RPE cells surrounding photoreceptors do?
Facilitate daily renewal, dispose of outer segment discs across Bruch's membrane into choroid
187
How does Bruch's membrane influence photoreceptors?
It regenerates rhodopsin which make up rods
188
What is dark adaptation?
The process by which eyes become more sensitive to light in reduced illumination
189
In which conditions is dark adaptation abnormal?
AMD, vitamin A deficiency, diabetes, alcoholism, Crohn's, Stargardt disease
190
How is dark adaptation measured?
Target presented at central 8 degrees of vision after bright flash of light dazzles eyes, takes longer for older eyes to adjust
191
Which study compared dark adaptation between normal and AMD-affected eyes?
RapidDA study
192
What are the aims of AMD imaging?
Monitor disease progression and response to treatment
193
What does fundus fluorescein angiography highlight?
Vascular leakage
194
What are the stages of fundus fluorescein angiography?
Red-free, choroidal (8-10s): Backgrounnd flush, patchy/lobe,
| Arterial (10-12s), capillary (10-13s), venous (12-14s): early, mid, late
195
What does indocyanine green angiography highlight? What is contraindicated?
Delineates vasculature beyond RPE
| Iodine, shellfish
196
What are the phases of indocyanine green angiography?
Early-mid (5-10 mins): Choroid vessels
| Late (10-30 mins): Choriocapillaris
197
What does optical coherence tomography highlight?
Retinal structures, CNV activity (thickening/fibrosis)
198
What wide-field imaging device is commonly used? What is the field of view?
Optos
| 200 degrees
199
Which region of the retina yields the highest VEGF production? According to which paper?
Mid-periphery
| Shimizu
200
Which were the first wide-field imaging devices introduced?
Pomerantzeff (1984)
Panoret (2000's)
Staurenghi lens
Optos, RetCam (contact), Spectralis (non-contact)
201
What is autofluorescence?
Spontaneous light emission from cells following exposure to different wavelenghts of light
202
What can be seen using autofluorescence?
Vessel anatomy, leaks, RPE function, cortical vitreous/retina/choroid
203
What types of autofluorescence are there?
Near infrared, fundus and cSLO
204
Which ocular structures are secondary fluorophores?
Sclera, hyaluronic acid, inner retina flavins, choroid, macular pigments
205
What pathologies can increase AF levels?
Photoreceptor outer segment change, RPE loss
206
What pathologies can reduced AF levels?
Photoreceptor death, RPE atrophy (GA)
207
Which study assessed near-infrarer cSLO imaging to examine RPE and choroidal melanin? What were the limitations?
Delori et al.
| Focused on posterior pole, not useful centrally
208
Which 8 FAF patters identified by the FAM study group evaluated advanced AMD progression?
1: Normal
2: Minimal change
3: Focal increase
4: Patchy
5: Linear
6: Lace-like
7: Reticular
8: Speckled
209
How does autofluorescence differentiate drusen types?
Mildly raised AF suggests AMD drusen, hyper-AF suggests other drusen
210
Which study examined GA progression in relation to abnormal AF levels?
Holt et al. (2007)
211
What can AF highlight peripherally?
Photoreceptor loss, serpiginous choroiditis, DR PRP
212
What retina feature are seen in retinitis pigmentosa?
Bone spicules, narrow vessels, optic nerve pallor, CMO
213
What did the OTELLO study examine?
Peripheral AMD changes via Optomap FAF images: better visualisation
214
What were the results of the Bird et al (2001) OCT study?
OCT as sensitive as FA for oedema (acetazolamide response)
215
What types of OCT have there been from 1997 to 2011?
Time domain, spectral domain then swept source
216
What are the benefits of swept source OCT imaging?
Twice as fast as spectral domain, uniform sensitivity, more visibility, less light scatter
217
What does OCT measure in terms of the choroid? How does this change with AMD?
Choroidal thickness
| Gets thinner with AMD
218
What features can be identified using Topcon En-Face?
Epiretinal membranes, DMO
219
How do classic CNV lesions appear?
Subfoveal, all between RPE and Bruch's membrane (FFA)
220
How do occult CNV lesions appear?
Stippled lacy membrane, irregular dye leak (FFA)
221
How does fibrovascular PED appear on OCT?
Blister, RPE rip: Hyperreflective, hyporeflection due to blockage
222
What can Fourier domain OCT highlight?
Sub/intraretinal fibrosis
223
How does polypoidal choroidopathy (IPCV) appear on indocyanine green angiography?
PED, exudates, subhyaloid blood, choroid polyps, RD
224
How do retinal angiomatous proliferation (RAP) lesions appear on OCT, FFA and ICG?
OCT: Superficial haemorrage, IR fluid, PED, CMO
FFA: Early IR leak, occult
ICG: Visible mid-late, anterior to RPE
225
How does geographic atrophy appear on AF?
RPE atrophy, high edge? Progression risk
226
What lesions can be seen with OCT and FFA +/- ICG?
CNV, IPCV, RAP lesions
227
What lesions can be seen with OCT and AF?
Drusen, GA
228
What was the resolution of the first OCT image? How deep did it penetrate tissue?
17μm, 1.5mm
229
What is the order of colours from low to high reflectivity on OCT?
Black, blue, green, yellow, red, white
230
Which retinal layers are found from the internal to the external limiting membrane?
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Nerve fibre layer
Ganglion cell layer
Inner plexiform layer
Inner nuclear layer
Outer plexiform layer
Fibres of Henle layer
Outer nuclear layer
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231
Which retinal layers are found below the external limiting membrane?
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Ellipsoid zone
Retinal pigment epithelium
Bruch's membrane
Choriocapillaris
Choroid (Sattler's, Haller's layers)
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232
What are the main components of photoreceptors?
Synaptic body, nuclear segment, fibre, myoid zone, ellipsoid zone, outer segment
233
What does Stratus OCT highlight? Which is the deepest layer it can image?
Sub-retinal fluid
| Stops at RPE
234
What does Cirrus/Topcon OCT highlight? Which is the deepest layer it can image?
Sub-retinal fluid, CNV
| Stops at RPE
235
What does Spectralis OCT highlight? Which is the deepest layer it can image?
Sub-retinal fluid, CNV, PED
| Stops at Bruch's membrane
236
Changes in which retinal layer most closely suggest wet AMD?
Retinal pigment epithelium
237
What RPE changes may occur?
Thickening, thinning, detachment
238
What types of RPE detachment are there?
Drusenoid
Serous (fluid)
Haemorrhagic
Fibrovascular (occult)
239
How does drusenoid PED appear on OCT?
RPE elevation, outer nuclear alteration
240
How does serous PED appear on OCT?
Optically empty RPE elevation, smooth-domed +/- CNV
241
How does fibrovascular PED appear on OCT?
Irregular RPE elevation, hyper-reflective +/- serous
242
How does haemorrhagic PED appear on OCT?
1+ dome-like RPE elevations, hyperreflective top
243
How is drusenoid PED treated?
Dry AMD advice
244
What CNV type is being treated in fibrovascular PED? How?
Occult membranes, CNV
| Anti-VEGF
245
What CNV type is being treated in haemorrhagic PED? How?
IPCV
| Anti-VEGF, PDT
246
What changes can occur in the neurosensory retina?
Fluid, thickening
| Intra-retinal cysts
247
What disease causes fluid build-up in the ellipsoid layer?
Adult vitelliform dystrophy (juvenile: Best's disease)
248
How can lipofuscin deposits produce false positives?
Optically empty, mask choroid, mistaken for fluid
249
What is schisis?
Mechanical stretching of the retina due to myopia
250
What is central serous retinopathy?
Idiopathic sub-retinal fluid between ellipsoid and RPE layers
251
Which structures surround photoreceptors in a wall-like appearance?
Outer retinal tubulations
252
What are the aim of AMD retreatment?
Ideally curing CNV effects, mitigating damage caused by it, stabilising vision
253
In AMD retreatment which two strategies are used?
PRN
| Treat and extend
254
What questions are asked before AMD retreatment?
Is the disease due to CNV active? Worse, stable or improving? Is the diagnosis correct?
255
When would AMD treatment be continued (PRN) or interval kept the same (T&E)?
Persistent lesion activity
| No contraindications
256
When would AMD treatment stop (PRN) or the interval extend (T&E)?
Inactive disease
| Adverse events
257
In AMD retreatment, how is the disease defined as inactive?
No reappearance of CNV indicators post-treatment (OCT), no deterioration in VA, no leak on FFA (if done)
258
What adverse events can occur with AMD treatment?
Uveitis, RD, endophthalmitis, periocular infection, thrombo-emboli
259
What should be considered before discontinuing AMD treatment?
Drug hypersensitivity
<15 letters BCVA in 2 visits, >30 letters drop
Lesion shape worse despite treatment
260
What should be considered before discharging AMD patients?
Treatment discontinuation, no other issues, low reactivation risk (poor central vision, scar)
261
How is disease activity judged in AMD retreatment?
VA, OCT: retinal oedema, haemorrhages, exudation
262
When would you consider treating in AMD retreatment?
Vision drop, SR/IR fluid, fresh haemorrhage, worse symptoms,
263
When would you consider not treating in AMD retreatment?
Severe vision drop, dry macula, stable vision, adverse event
264
When was the certificate of visual impairment (formerly BD8) introduced in England and Wales?
England: September 2005, Wales: April 2007
265
What is the purpose of the certificate of visual impairment?
Provides a reliable route for those with sight loss to be brought to the attention of social care
266
How many UK individuals are visually impaired? How many have certificates of visual impairment? Which age group has the most registrants?
2 million
Approximately 300000
>75 year old's
267
What is main cause of visual impairment for (a.) >65's, (b.) working age, (c.) children?
(a. ) AMD
(b. ) DR/DMO
(c. ) Optic neuropathy
268
What is the definition of sight impaired?
Substantial, permanently handicapped by defective vision due to congenital illness or injury
269
What are the criteria for sight impaired registration?
VA 6/24-6/60 (0.6-1.0 logMAR), large field restriction, media opacity/aphakia or
VA <6/18 (0.5 logMAR), gross field defect and constriction
270
What is the definition of severely sight impaired?
So blind as to be unable to perform any work for which eyesight is essential
271
What are the criteria for severely sight impaired registration?
VA <3/60 or VA <1/18 (1.30 logMAR) with restricted visual field
272
How are low vision assessments carried out? Which organisation approves these? Which eye specialist provides the visual impairment letter? Who signs it?
Eye clinic appointments
Royal National Institute of Blind People (RNIB)
Optometrists
Consultant ophthalmologist
273
What is considered in visual impairment needs assessments?
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Domestic tasks
Safe transport
Accommodation
Communication
Finances, jobs
Leisure
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274
Who carries out mobility assessments for the visually impaired?
Rehabilitation officer
275
What is included in visually impaired quality of life assessments?
Physical, psychological, functional, social, economic well-being
Personality, religion, social support, health, education level
276
What visually impaired quality of life questionnaires are there?
Low Vision Quality of Life
Adaptation to Age-Related Vision Loss (AVL-12)
Keele Participation Restriction Questionnaire (KAP)
277
What benefits are there in registering for CVI?
Needs assessment, assistance, concessions, sight tests, early detection
278
What direct and indirect costs are linked to impaired vision?
Direct: Productivity, care, medical support
Indirect: Falls, exacerbations, depresssion
279
Which quality of life assessments were used in the Manchester conventional vs enhanced low vision rehab RCT?
Generic: SF-36
Vision-specific: VCM1 Psychological: NAS
Self-rated activity restriction: MLVQ
280
Besides QoL assessments, what outcome measures were used in the Manchester conventional vs enhanced low vision rehab RCT?
LVR device use
| AMD/VI knowledge at start and 1 year later
281
What were the results of the Manchester conventional vs enhanced low vision rehab RCT?
Home visits ineffective for QoL, LVR high benefit
282
What are the goals in low vision patient rehabilitation?
Restoration
Optimal function levels
Maximise residual vision for independence, LVA: Reading, magnifying, illuminating
283
What other impairments is low vision linked to?
Daily activity dependence, low physical activity, isolation, depression
284
Why are logMAR charts preferred to Snellen for low vision assessment?
Standardised, logarithmic letter size progression
285
How is the magnification required for visually impaired children calculated?
Actual near visual acuity divided by required near visual acuity
286
Which study investigated the reliability of VA measures?
Intersession Repeatability of VA Scores in AMD (Patel et al, 2008)
287
What clinical contrast sensitivity tests are there?
Arden Grating Vistech/FACT
Cambridge
Bailey-Lovie/Regan Pelli-Robson
288
Which electronic vision enhancement systems are there for the visually impaired?
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Contrast, reduced glare, tints, task lighting
Software: Supernova, Jaws (DSS)
Audio description
Eccentric viewing
Steady Eye Strategy
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289
How does Charles Bonnet syndrome commonly present? How is it managed?
Visual hallucinations in those with vision loss
| Treat cause, reassurance, changing environment
290
What can cause homonymous hemianopia? How does it present?
Stroke, brain tumour, trauma
| Navigation issues, tripping, bumping into obstacles
291
Which triaging method uses a 'custom and practice' appoach for low vision assessment?
Telephone review
