ORCA study: real-world versus reading centre assessment of disease activity of neovascular age-related macular degeneration (nAMD)

Abstract

Background/aims: The prospective, non-interventional ORCA module of the OCEAN study (Observation of Treatment Patterns with Lucentis in Approved Indications) evaluated the qualiy of spectral domain-optical coherence tomography (SD-OCT) image interpretation and treatment decisions by clinicians in Germany and the impact on visual outcomes over 24 months in patients with neovascular age-related macular degeneration (nAMD).

Methods: 2286 SD-OCT scans of 205 eyes were independently evaluated by clinicians and reading centres (RCs) regarding signs of choroidal neovascularisation (CNV) activity, including presence of intraretinal fluid, subretinal fluid, and/or increase in pigment epithelial detachments. Agreement between clinicians and RCs was calculated. Treatment decisions by clinicians and the impact on treatment outcomes were evaluated.

Results: CNV activity was detected by RCs on 1578 scans (69.0%) and by clinicians on 1392 scans (60.9%), with agreement in 74.9% of cases. Of the 1578 scans with RC detected CNV activity, anti-vascular endothelial growth factor injections were performed by clinicians in only 35.5% (560/1578). In 19.7% of cases (311/1578), lack of treatment was justified by patients request, termination criteria or chronic cystoid spaces without other signs for CNV activity. In 44.8% of cases (707/1578) with RC detected CNV activity, clinicians claimed no treatment was necessary despite having correctly detected CNV activity in about 2/3 of these cases. In 34% of cases with presumed undertreatment, visual acuity declined in the following visit.

Conclusion: Although broad agreement on CNV activity parameters was observed between clinicians and RCs, correct identification of CNV activity did not always lead to the initiation of (re-)treatment. To preserve vision over time, correct interpretation of SD-OCT scans and careful retreatment decisions are required.

Trial registration number: NCT02194803.

Keywords: macula; neovascularisation; retina.

Conflict of interest statement

Competing interests: SL received personal fees from Novartis, Heidelberg Engineering, Carl Zeiss Meditec, Allergan, Bayer, and was member of an advisory board for Novartis. GS received personal fees from Bayer Healthcare, Novartis, Zeiss, OD-OS and Allergan Pharma. CKB has received grants from Heidelberg Engineering, Newtricious, Novartis, Zeiss Meditec; and personal fees from Heidelberg Engineering, Newtricious and Novartis. TS received personal fees from Novartis. FZ received grants and personal fees from Alimera, Allergan, Bayer Healthcare, Biogen and Roche, grants from Clearside, personal fees from Boehringer Ingelheim, Novartis, NovoNordisk and MSD Sharp & Dohme. JV and MK are employees of Novartis. BK received grants from Novartis and personal fees from Novartis, Pfizer and Bayer. FGH received grants from Acucela, Alcon, Allergan, Bayer, Genentech, Heidelberg Engineering, Novartis, Ophthotech, Roche and personal fees from Allergan, Bayer, Genentech, Novartis, Ophthotech; he was a member of advisory boards for Acucela, Allergan, Avalanche, Bayer, Genentech, Heidelberg Engineering, Johnson & Johnson, Novartis, Ophthotech and Roche. DP received grants from Novartis, Ophthotech, Acucela, Genentech, Roche, Bayer and personal fees from Novartis, Bayer, Allergan; he was a member of advisory boards for Novartis, Bayer and Allergan. SS-V received grants and non-financial research funding from Acucela, Alcon/Novartis, Allergan, Bayer, Bioeq/Formycon, Centervue, Galimedix, Genentech/Roche, Heidelberg Engineering, Optos, Carl Zeiss MediTec, and personal fees and honoraria from Alcon/Novartis, Bayer, Genentech/Roche and Carl Zeiss MediTec.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Example OCT scans of the minimal standard for clear identification of signs for CNV activity. CNV, choroidal neovascularisation; OCT, optical coherence tomography.

Figure 2

Agreement between RCs and clinicians regarding presence of SD-OCT parameters in scans from follow-up visits. Evaluations of (a) intraretinal fluid, (b) subretinal fluid and (c) pigment epithelium detachments were compared. The percentages shown are calculated based on a 100% ‘Yes’ or 100% ‘No/questionable/cannot grade’ evaluations of the clinician for each parameter. for some scans, information on the parameter was missing/not assessable by the clinician or the RCS: intraretinal fluid, n=23; subretinal fluid, n=36; pigment epithelium detachments, n=29. CG, cannot grade; RC, reading centre; SD-OCT, spectral domain-optical coherence tomography.

Figure 3

Central retinal thickness parameters (mean of foveal central subfield, foveal centre point) as measured by RCs and clinicians. Mean±SD is shown for each parameter. For a number of scans, information on retinal thickness was missing/not assessable by the clinicians (central subfield: n=252; central point: n=114) or the RCS (central subfield: n=292; central point: n=39). Note: foveal central subfield was measured from internal limiting membrane to the photoreceptors and foveal centre point was measured from the internal limiting membrane to the Bruch’s membrane. RCs, reading centres.

Figure 4

Identification of CNV activity parameters on SD-OCT volume scans and treatment decisions by clinicians for 1578 scans with RC confirmed CNV activity. presumed reasons for decisions not to perform injection are presented. *At least one parameter (IRF, SRF or PED increase) was observed by the clinician, and at least one parameter (IRF or SRF) was observed as strongly visible by RC and at least one parameter (IRF or SRF) was assessed as present within the central subfield by RC. **Multiple responses possible as for some visits more than one of these criteria were Met. ***Other reasons included patient preference, that the visit was planned to be only for monitoring, that the injection was planned for later visit and other reason without further clarification. ****Missing information were classified under ‘Watch and wait justified’ to avoid over-estimating undertreatment. CNV, choroidal neovascularisation; IRF, intraretinal fluid; PED, pigment epithelial detachments; RC, reading centre; SD-OCT, spectral domain optical coherence tomography, SRF, subretinal fluid.