MODULO 3 | Lezione 1
DIAGNOSTICA DELLA RETINA
Giovanni Staurenghi, Alessandro Invernizzi, Marco Pellegrini Clinica Oculistica Ospedale Sacco
Dipartimento di Scienze Biomediche e Cliniche “Luigi Sacco”
Università degli Studi di Milano
ARGOMENTI DI QUESTA LEZIONE : Retinografia Infrarosso
Autofluorescenza del fondo oculare
Angiografia con indocianina verde
Tomografia ottica a coerenza - OCT
Heidelberg Engineering 1,2 , OD-OS 1,2 , Optos 1,2 ,
Ocular Instruments 4 , Quantel Medical 1,2 , Carl Zeiss Meditec 1 , Alcon 1,3 , Allergan 1,3 , Bayer 1,3 ,
Boheringer 1 , Genentech 1 , GSK 1,3 , QLT 1 , Novartis 1,3 , Roche 1,3
Conflitti di interesse:
1 consulente, 2 finanziamenti per ricerca, 3 rimborsi per letture, 4 brevetti
ACCURATA DIAGNOSI
TERAPIA MIRATA
MIGLIORI RISULTATI, MAGGIORE
COMPLIANCE DEL PAZIENTE , NOTEVOLE RISPARMIO ECONOMICO
A seguire una flow-chart che indica le più appropriate strategie diagnostiche secondo le varie tipologie di paziente
LE TECNICHE DI IMAGING:
APPROPRIATEZZA D’USO
© Giovanni Staurenghi 2014 - Tutti i diritti riservati
Optical Coherence Tomography (OCT)
Retinografia con radiazione infrarossa
Autofluorescenza del fondo
Fluorangiografia (FA)
Angiografia con indocianina verde (ICGA)
Retinografia con luce aneritra con SLO (luce monocromatica blu)
Imaging non invasivo Imaging invasivo
1 2 3 4
8 9
FA ad ampio campo (Wide field FA)
10
ICGA ad ampio campo (Wide field ICGA)
11
Foto a colori
5
Enhanced Depth Imaging OCT (EDI-OCT)
6
Ecografia
7
FC IR RF FAF OCT
EDI US
FA ICG
WF
WFI
* solo in caso di emovitreo
Degenerazione maculare senile
OCT FAF FA ICG RF IR
Retinopatia diabetica
RF
FC OCT FA WF US *
Corioretinopatia sierosa centrale
OCT EDI ICG FAF
Occlusioni vascolari
FC OCT FA WF
Prima Visita
FC
Tumori oculari
FC OCT EDI FAF ICG WFI US WF
© Giovanni Staurenghi 2014 - Tutti i diritti riservati
OCT
Follow-up
FA ICG
Degenerazione maculare senile
OCT FAF
IR FC + * *
Retinopatia diabetica
RF
FC OCT + FA * WF *
Corioretinopatia sierosa centrale
OCT EDI FAF + ICG °
* solo in caso di non risposta ° solo se necessità di ritrattamento # almeno ogni sei mesi durante trattamento per ischemia
Occlusioni vascolari
FC OCT + FA WF
# #Tumori oculari
FC OCT EDI FAF US
Retinografia Infrarosso
400 500 600 700 800 900 1000
Lens
Wavelenght (nm)
Abso rptio n Co ef ficie nt o f Ocu lar Pigme nts
H
2O HbO
2Melanin
Hb
Metodi e strumenti
HRA Spectralis Nidek F10 Optos
Zeiss Cirrus
Strumenti
Heidelberg
Spectralis Nidek F10 Heidelberg HRA2 with polarized filter
~830 nm ~780 nm ~830 nm
wavelength
Blu Light Green Light Infrared Light
Modo confocale
Retro mode
luce visibile mezzi diottrici
pigmenti oculari emoglobina
melanina in EP melanina in Ch
infrarosso si
si si si si
no no no no assorbimento
a 500 nm 59-75% della luce è assorbita da EPR e coroide a 800 nm solo il 21-38%
Differente assorbimento della luce visibile e infrarossa
no
Vasi re9nici Vasi corideali
Filtri polarizza9
Visulizzazione di liquido intrare9nico
02.09.2001 10.10.2001 15.01.2002 18.03.2002 09.09.2002 21.11.2001
...follow up delle lesioni senza iniezione di colorante o
mappa OCT
Drusen
So*
Drusen
Re,cular
Drusen
Re,cular
Pseudodrusen
Subre,nal drusenoid debris
(SSD)
Chris&ne Curcio
disc in 46% of right and 55% of left eyes, while they were never visible in the center of macula.
D
ISCUSSIONIn the present report the prevalence of RDR was much higher than that previously reported. Furthermore, in this study, the prevalence was much higher on cSLO images (62%) when compared with conventional fundus photography (18%).
These results suggest that RDR represent a common pheno- typic biomarker in advanced atrophic AMD and that cSLO imaging is superior for detection of RDR compared with con- ventional fundus photography.
The identification of characteristic but subtle changes asso- ciated with RDR requires good image quality and careful anal- ysis. It may be challenging in the majority of subjects to acquire images with even illumination and sharp focus over the entire frame. Despite good image quality, other phenotypic altera- tions such as soft or hard drusen may interfere with RDR detection. In the present study, using a grading system that distinguishes between definite RDR and indefinite, there was moderate to good interobserver agreement (Armstrong JR, et al. IOVS 2005;46:ARVO E-Abstract 220/B194). Because we are not yet able to define a clear-cut image quality threshold that permits one to exclude RDR, we consider the prevalence rate of 62% as the minimum RDR prevalence in our study cohort.
Thus, RDR may be present even more frequently, but current imaging technology may limit their detection.
Given the relatively high RDR prevalence in this cohort of subjects with GA, one could speculate that RDR represent a disease hallmark. Further, their absence might reflect the pres- ence of other diseases that mimic AMD phenotypic features.
Atrophy of outer retinal layers (geographic atrophy) and asso- ciated choroidal neovascularization are obviously not specific for AMD and occur in association with various complex and monogenetic macular as well as diffuse retinal diseases. To further explore the hypothesis that RDR represent an essential disease hallmark, we have initiated a genotype-phenotype study that will assess the correlation between AMD genetic risk factors and the presence of RDR. Given both the markedly
improved detection and the superior interobserver reliability compared with other imaging modalities, we believe that both IR and FAF cSLO imaging are optimal choices for the charac- terization of RDRs in any future AMD natural history studies.
Several recent publications have reported that en face visi- ble RDR are spatially confined to locations that are anterior to the RPE when visualized using an instrument that simultane- ously combines cSLO and SD-OCT imaging.17,28,29 This local- ization suggests that RDR may play a role in disease-relevant processes at the level of the photoreceptors. In contrast, pre- vious hypotheses on AMD pathogenesis have suggested that changes in drusen area or the location of drusen at the level of the RPE and Bruch’s membrane are of predominant impor- tance.
The histologic characterization of RDR is limited to a single case report in which the presence of RDR was related to abnormalities in the inner choroid.19 While frequently re- ported with OCT imaging, characterization of RDR with OCT may be difficult; for example, it remains unclear if and to which extent the highly reflective, focal SD-OCT alterations of variable extension above the RPE are caused by optical inter- ference. Although one might also speculate that RDR may coexist together with already well-described extracellular ac- cumulation of material beneath the RPE as basal laminar de- posits and membranous debris, the latter alterations are not yet detectable by currently imaging technology in the living hu- man eye. The high prevalence of RDR found in the present study should in any case further prompt histopathological and biochemical studies to elucidate the exact morphologic sub- strate of RDR and their molecular composition.
In accordance with previous reports, we confirmed that RDR are most commonly located superior to the foveal center in the outer macula and that they are correlated with increas- ing age and with female sex.19,24 The rare prevalence within 3000 !m from the foveal center in this cross-sectional study in eyes affected from late-stage atrophic AMD does not indicate that this area is an untypical location for RDR. Presence of GA is associated with the absence of RD. From this study it is not possible to address the possible presence of RD in the perifo- veal area before GA developed. Using three-field FAF imaging,
FIGURE 4. Diagrams showing the lo- cation of prevalent RDR as identified by three-field cSLO fundus autofluo- rescence imaging, illustrated sepa- rately for right (A, C: OD) and left eyes (B, D: OS). The top row shows the topographic presence for each of the 17 predefined fields (see also Fig.
2); in the bottom row the presence of drusen by four grouped areas is illustrated. Note that the central 3000
!m were largely involved by atro- phic areas in this study population with all eyes showing patches of GA.
Therefore, it cannot be excluded if RDR were present before the devel- opment of atrophy.
IOVS, August 2011, Vol. 52, No. 9 Reticular Drusen in GA 5013
“RDR were detected with at least one cSLO modality in 286 of 458 (62%)
patients in either eye (bilateral 207 [45%]) and were visible in fundus camera
photographs in 66 of 371 (18%) patients (bilateral 48 [13%])”
Viola, et al. Investigative ophthalmology and visual science. 46:E-Abstract(2005). - p. 244-244 Quentel et al. Br J Ophthalmol 2007;91:354–359
Membrane neovascolari
coroideali
G. Staurenghi et al., Archives of ophthalmology, 114(3), 1996, pp. 365-365 M.E. Hartnett et al. Ophthalmology. 103(1): 1996 pp 58-71.