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HOW OPTICAL COHERENCE

TOMOGRAPHY (OCT) INFLUENCE OUR


CLINICAL DECISION IN AGE-RELATED
MACULAR DEGENERATION (AMD)?

Dr Elvioza SpM(K)
*Head of Vitreo-Retina division
Dept. Of Opthalmology
FKUI – RSCM Kirana
*Head of Retina Service Jakarta Eye Center
Eye Hospital
OCT

 Supporting diagnostic tool

 Immediate quantification

 Non invasive procedure

 Cross sectional and two dimensional slices


OCT : A Dynamic Tool

 Routine use
 Making an initial diagnosis
 Detecting disease progression
 Planning treatment approaches
 Monitoring postoperative results
 Educating patients
Normal Macula

Optical Biopsy of the Retina


(in vivo)
OPTICAL COHERENCE TOMOGRAPHY
(OCT)

 Optical coherence tomography (OCT) evaluation of


macular structure has a central function in the clinical
diagnosis and management of patients with age-related
macular degeneration (AMD).

 In particular, OCT imaging has been important in


decisions regarding treatment with intravitreal anti-
angiogenic agents.

 The ability of OCT imaging to present the necessary data


in a reliable and reproducible manner for clinical
interpretation is essential.
AGE-RELATED MACULAR
DEGENERATION (AMD)

Drusen are seen as undulations and elevations in the hyperreflective


band of the RPE with less reflective material beneath them, while the
inner retinal layers remain generally intact
ATROPHIC MACULAR DEGENERATION

In a case of retinal atrophy, the OCT shows a highly reflective choroidal


signal due to retinal thinning and RPE hypopigmentation, which allows
greater beam penetration into the choroid and greater reflectivity. The
retinal map allows quantification of the decreased retinal thickness
EXUDATIVE MACULAR DEGENERATION

OCT visualizes the components of the neovascular membrane, a retinal


pigment epithelial detachment (PED), detachment of the neuroepithelium
(NED), intraretinal fluid, and subretinal hemorrhage. D: Drusenoid RPE
detachments (∆), subrretinal hemorrhage (*), dense particles present in the
subrretinal fluid (↓), intrarretinal migration of RPE cells (>)
 Because OCT represents a new imaging modality, a
more refined classification of neovascularization has
been proposed by Freund et al.:
 Type 1 corresponds to neovascularization below the RPE
monolayer
 Type 2 corresponds to neovascularization in the subretinal
space
 Type 3 corresponds to an intraretinal lesion.
Type 1 Type 2 Type 3
Occult CNV Classic CNV RAP
RPE DETACHMENT

Serous Detachment of the RPE


associated with a Neurosensory
Retinal Detachment Hemorrhagic detachment of the RPE
NEUROSENSORY RETINAL
DETACHMENT

 Subretinal fluid
INTRARETINAL FLUID

Intraretinal cysts
RPE TEAR

RPE tears, sudden disruptions in the continuity of the hyperreflectivity


layer of the pigment epithelium, show strong reflectivity from the choroid
in the absence of the pigment epithelium, followed by sudden
interruption of the band’s pigment epithelial hyperreflectivity. C: (↓)
Intrarretinal fluid. D: (↓) RPE interruption site, (*) RPE tear bent over itself
POLYPOIDAL CHOROIDOPATHY

Polypoidal Choroidopathy. A: Color photography shows hemorrhagic retinal pigment


detachment (RPED). B: Fluorescein angiography shows the RPED and signs of occult
choroidal neovascularization. C: Indocyanine green angiography shows the presence
of hot spots corresponding to polypoidal structures. D: OCT shows small cup-shaped
RPE elevations corresponding to polypoidal choroidopathy. Subretinal fluid (*) and
blood under the RPED (^)
RETINAL ANOMALOUS PROLIFERATION (RAP)

A (fluorescein angiography) and B (OCT) of a RAP lesion. OCT shows RAP (*)
associated with edema, intraretinal cysts (↘) and subretinal fluid (∆), C
(OCT), OCT shows the RPE and the retinal neurosensory layer detachments.
Intrarretinal cysts (∆), dense retinal particles (↘), the posterior hyaloid
membrane (v) and a vessel (*) can be appreciated too
DISCIFORM SCARS

OCT shows a hyperreflective fibrotic nodular area that corresponds to


the fibrotic area and easily detects diffuse or cystoid edema. In the wet
form, OCT shows diffuse or cystoid edema involving the RPE detachment
TIME-DOMAIN vs SPECTRAL-DOMAIN
OCT

Time-Domain OCT Spectral-Domain OCT


 Reference mirror position  Uses a high-speed
and delay are spectrometer to measure light
mechanically scanned to echoes from all time delays
produce axial scans (A-
scans) of light echoes  Greater than 20,000 A-scans
per second
 Scan rates of 400 A- scans
per second  Axial resolution of 3 to 7 μm

 Axial resolution of 8 to 10  Precise anatomic detection of


μm structural changes
TIME-DOMAIN vs SPECTRAL-DOMAIN

SD- vs. TD-OCT. A, TD-OCT (Stratus). B, SD-OCT (Cirrus). Foveal cysts


are barely distinguishable with the TD-OCT but are clearly identified
by SD-OCT
OCT and ANGIOGRAPHY

The retinography corresponds to a


polypoidal choroidopathy (A)
where you can observe the
presence of intraretinal
haemorrhages. In the red-free
image (B) you can observe the
tomographic cut line. The OCT
shows a marked elevation of the
cup-shaped RPE (C). By
indocyanine green angiography
you can observe a hot spot that
confirms the diagnosis (DE)
OCT vs. FA

“ Intraretinal and sub-retinal fluid (OCT) have


excellent sensitivity and moderate specificity
in detecting CNV activity with FA leakage as
the standard test ”.
 Because of the widespread use of OCT, the use of FA has
dropped to second place in routine consultations, but it is
still an essential examination for studying CNV in patients
with AMD, and FA and ICGA are especially important for
identifying occult disease.

 Krebs et al and Saddu et al proposed that OCT can


detect signs of activity similar to FA.
CLINICAL & THERAPEUTIC
IMPLICATIONS OF OCT IN AMD

 OCT is now a routine examination for patients with AMD.


Although some studies have advocated a role for OCT in
the dry forms of the disease, its use is greater in patients
with the neovascular forms, and it is now a main method
of study in these patients.

 In recent years, OCT has become increasingly important,


to the extent that recent studies have based the need
for retreatment on the findings in OCT images.
DRY AMD

(A) Central soft drusen may be seen in the retinography. (B) Drusen are
observed as undulations and elevations of RPE hyperreflective band
with less reflective material below them.
(A) Central hard drusen surrounded by atrophic areas of the RPE are seen in the
retinography. (B) In the autofluorescence image, a hypofluorescence area
corresponding to atrophic areas of the RPE may be apreciated. (C) In the OCT, two
hyperreflectant points corresponding to hard drusen observed in the retinography are
seen. (D) Infrared image captured by the OCT which shows the tomographic section
line of figure C.
PrONTO study

 Prospective Optical coherence tomography imaging of


patients with Neovascular AMD Treated with intraocular
ranibizumab (Lucentis) [PrONTO] study :

 Investigate the role of OCT imaging in a variable dosing


regimen with ranibizumab

 Intravitreal injections of ranibizumab were administered


to all patients at baseline, month 1, and month 2.
• Additional reinjections were given if any of the following
changes were observed by the evaluating physician:
WET AMD
PrONTO clinical trial criteria
of retreatment, based in
the analysis by OCT:

• Decrease of more than 5


letters of VA (ETDRS) with
fluid detected in the
macula by OCT(A),

• Increase of more than


100 µm in the central
retinal thickness respect to
the lowest previous value
measured by OCT (B1, B2)

• Fuid reappearance in the


OCT in a previous dry
lesion. (C1, C2)
Wet or Dry ?
Dry

Wet
OCT : response to ranibizumab injection
in an eye with neovascular AMD

Ranibizumab
injection

Ranibizumab
injection
In the second year of the study, the presence of qualitative
changes in the OCT images that suggested fluid recurrence was
included, such as intraretinal cysts (A), subretinal fluid (B), or
progression of a PED (C1 and C2).
Ophthalmology Volume 121, Number
1, January 2014

Grunwald et al Risk of Geographic


Atrophy in CATT
Risk Factors of Macular Atrophy
Based on Harbor Post Hoc Study
LESSER RISK GREATER RISK

CYST YES VS NO

FELLOW EYE MA YES VS NO Higher risk of


developing MA with
IRF YES VS NO
cysts, fellow eye MA
Baseline

PED YES VS NO at baseline


CNV SIZE (2 DA INCREASE)

PED THICKNESS (100 µM INCREASE)

SRF THICKNESS (100 µM INCREASE)


Lower risk of
MIN. CLASSIC VS OCCULT CNV
developing MA with
PREDOM. CLASSIC VS OCCULT CNV Subretinal Fluid (SRF)
SRF YES VS NO

0 .1 2 5 0 .2 5 0 .5 1 2 4 8

H a z a r d R a tio
95% confidence intervals are shown.
Sadda et al. 2014. Presented at the American Academy of Ophthalmology Annual Meeting, Subspecialty Day, Chicago, IL, October
17, 2014
Predictors for Visual Acuity score change or gain ≥ 3 line
from baseline at 1 Year

Older age is
significant predictors
of less gain VA score
at 1 year

Larger CNV area at


baseline significant
predictors of less gain
VA score at 1 year

Absence of RAP lesion


at baseline significant
predictors of less gain
VA score at 1 year

Presence of RPE
elevation at baseline
significant predictors of
less gain VA score at 1
year
Sub analysis of CATT study
Integrity of inner-segment /outer-
segment (IS/OS) junction, and external
limiting membrane (ELM)

 Eyes with more ELM damage at the baseline when measured on SD-OCT
manifested poorer visual improvement than the eyes that with less ELM
damage

 Pretreatment BCVA, IS/OS junction, and ELM integrity on SD-OCT together


predict 37% of visual improvement

Chhablani J. et al. 2013.Int J. Ophthalmo


Quantitative OCT
Central Foveal Thickness (CFT) < 200 mm and
CFT ≥ 200 mm

CFT ≥ 200 mm will


immediate worsen if given
quarterly maintenance
regimen after 3 months
loading dose

Intravitreal Injection 3 months loading


dose and quarterly for maintenance
Sub analysis PIER study
Brown DM. , 2013. RETINA 33:23–3
OCT & REVIEWS: “TREAT and EXTEND”

Treatment schedule and revisions of Treat & Extend


 A variable dosing regimen with ranibizumab resulted in an
average of 5.6 injections over one year with visual acuity
and OCT improvements that were statistically and clinically
significant.

 These results were similar to the outcomes obtained using 13


monthly injections over one year in the fixed-dosing Phase III
regimens.

 OCT can be useful for guiding retreatment with intravitreal


ranibizumab in neovascular AMD, and the use of such an
OCT-guided, variable-dosing regimen should decrease the
injection burden without sacrificing improvements in visual
acuity.
PROGNOSTIC FACTORS IN OCT as
identified by various authors
Parameter Author, year
Total retinal thickness Singh, 2009
Subretinal tissue volume Keane, 2008
Neurosensory retina thickening
RPE status Kiss, 2009
Integrity of IS/OS Junction Sayanagi, 2009. Kaluzny, 2009.
Chen, 2009. Witkins, 2009. Kwon,
2014
Posterior vitreomacular adhesion Lee, 2009. Mojana, 2008.
Optical density ratio Ahlers, 2009
Integrity of external limiting Chhablani, 2012. Kwon, 2014.
membrane
Presence of subretinal fluid (SRF) Regillo, 2015
Presence of intraretinal cyst (IRC) Ritter, 2015
Subretinal hyperreflectivity Willoughby, 2015
material (SRHM)
OCT & WET AMD IN CLINICAL
PRACTICE

 To reach a consensus on the criteria of treatment and


frequency of revisions, daily management of these patients
is individualized, and the decisions are based on clinical
examination and qualitative analysis of OCT images.

 The main signs of activity of the neovascular membranes in


the OCT are the presence of intraretinal or subretinal fluid
and RPE detachments and tears.

 The presence of any of these tomographic signs, the


patient’s VA, and the ophthalmoscopic and angiographic
appearance of the lesions should be evaluated by
ophthalmologists to reach treatment decisions and revisions
in each case until the current prospective multicenter
studies shed light on results based on conclusive evidence.
Conclusion

 OCT is a valuable clinical tool


 Complements the FFA
 In some cases, replaces FFA
 Improves patient understanding/
satisfaction
 Improves clinical decision making

 Improves quality