Optical coherence tomography angiography findings in patients undergoing transcorneal electrical stimulation for treating retinitis pigmentosa

Abstract

Purpose: Transcorneal electrical stimulation (TES) is a novel treatment approach for patients with retinitis pigmentosa (RP). The aim of our study was to observe changes in optical coherence tomography angiography (OCTA) that would be attributed to TES treatment.

Methods: A total of 73 eyes were included: 43 eyes of 22 subjects (11 ♀, 11 ♂) suffering from RP were examined at baseline (BL), after first stimulation (TS), 1 week (1W), and 6 months (6M) after treatment initiation and were compared with 30 control eyes of 15 subjects (8 ♀, 7 ♂). TES was performed simultaneously on both eyes for 30 min weekly. OCTA scans of 9 × 15 mm were recorded with a PLEX Elite 9000 swept-source OCTA device (Carl Zeiss Meditec AG, Jena). Vascular density metrics such as perfusion density (PD) and vessel density (VD) were calculated automatically for the macular area by using standardised extended early treatment diabetic retinopathy study (ETDRS) grids centred around the fovea. In addition, the capillary perfusion density (CPD) and the capillary flux index (CFI) of the peripapillary nerve fibre layer microvasculature in all four quadrants of an annulus centred at the optic disc were measured. All parameters were determined over all retinal layers and separately for the superficial (SCP) and deep capillary plexus (DCP). ANOVA-based linear mixed-effects models were calculated with SPSS®.

Results: Throughout the course of TES treatment, the macular VD and PD of all retinal layers in all subsections showed a slight decrement without reaching statistical significance, also when analysed separately in the SCP and DCP (p > 0.08). In analogy, the average CPD and CFI also presented with a slight decrement (p > 0.20). However, when compared with controls, most OCTA parameters showed a significant decrement (p < 0.05). When analysed systematically in all subsections of the extended ETDRS grid, the temporal macular subsections within the outer ring (radius 1.5-3 mm) and also of the peripheral C1, C2, and C3 rings (radius 3-7.5 mm) showed lower VD and PD values when compared with the other subsections (p < 0.05).

Conclusion: Vascular density metrics in the macular region and the peripapillary microvasculature appear to remain unaffected by continuous TES treatment within a period of 6 months.

Keywords: Inherited retinal diseases; Macular vessel density; OkuStim; Optical coherence tomography angiography; Peripapillary microvasculature; Retinitis pigmentosa; TES; Transcorneal electrical stimulation.

Conflict of interest statement

Dr. Scholl is member of the Scientific Advisory Board of Astellas Institute for Regenerative Medicine; Gensight Biologics; Ionis Pharmaceuticals, Inc.; Gyroscope Therapeutics Ltd.; Janssen Research & Development, LLC (Johnson & Johnson); Pharma Research and Early Development (pRED) of F. Hoffmann-La Roche Ltd.; Novartis Pharma AG (CORE); and Retinagenix LLC. Dr. Scholl is a paid consultant of Boehringer Ingelheim Pharma GmbH & Co, Gerson Lehrman Group, and Guidepoint.

Dr. Scholl is member of the Data Monitoring and Safety Board/Committee of ReNeuron Group Plc/Ora Inc. and member of the Steering Committee of Novo Nordisk (FOCUS trial).

Dr. Scholl is co-director of the Institute of Molecular and Clinical Ophthalmology Basel (IOB) which is constituted as a non-profit foundation and receives funding from the University of Basel, the University Hospital Basel, Novartis, and the government of Basel-Stadt.

These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Johns Hopkins University and Bayer Pharma AG have an active research collaboration and option agreement. These arrangements have also been reviewed and approved by the University of Basel (Universitätsspital Basel, USB) in accordance with its conflict of interest policies.

Dr. Hendrik Scholl is a principal investigator of grants at the USB sponsored by the following entity: IVERIC bio (Ophthotech Corporation), Kinarus AG, and Novartis Pharma AG. Grants at USB are negotiated and administered by the institution (USB) which receives them on its proper accounts. Individual investigators who participate in the sponsored project(s) are not directly compensated by the sponsor but may receive salary or other support from the institution to support their effort on the project(s).

All other authors certify that they have no affiliations with or involvement in any organisation or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licencing arrangements) or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Figures

Fig. 1

Example for a vessel density (VD) calculation within different sectors of a standardised extended ETDRS grid on a retinal OCTA slab in the right eye of a healthy subject. The colour bar represents the VD measurements as a colour code in mm/mm2. Results of the VD analysis are averaged values for both the entire scan area, but also for subsections of the ETDRS grid in different regions of measurement: (C) centrally in the foveal area within 1-mm diameter, (I) within an inner ring with a radius of 0.5–1.5 mm divided in four quadrants ((IS) superior, (II) inferior, (IT) temporal, and (IN) nasal quadrant), (O) within an outer ring of 1.5–3-mm radius divided in four quadrants ((OS) superior, (OI) inferior, (OT) temporal, and (ON) nasal quadrant). In addition, further subsections in extended rings C1 (radius 3–4.5 mm), C2 (radius 4.5–6 mm), and C3 (radius 6–7.5 mm) are calculated as well, using the labels (S) superior, (I) inferior, (T) temporal, and (N) nasal

Fig. 2

Example for the calculation of peripapillary microvasculature parameters in the right eye of a healthy subject. An optic disc–centred image protocol is applied, where two concentric rings are created in the peripapillary area: one with a diameter of 2 mm and second with a diameter of 6 mm. The region between these two circles defined the area of interest, in which all calculations were automatically performed. The results are presented as averaged values within four different sectors: (S) superior, (N) nasal, (I) inferior, and (T) temporal

Fig. 3

A, B Box plot analysis illustrates the average vessel density (VD, A) and average perfusion density (PD, B) of all retinal layers (retina slab, white), SCP (light grey), and DCP (dark grey). The y-axis shows the VD in mm/mm2, and the PD without unit for all follow-up visits (BL, TS, 1W, 6M) and control eyes are shown on the x-axis. C Box plot analysis illustrates the average capillary perfusion density (CPD, light grey) and the average capillary flux index (CFI, dark grey). The y-axis shows the CPD and CFI without units for all follow-up visits (BL, TS, 1W, 6M), and control eyes are shown on the x-axis. The upper and lower whiskers of the box plots present the minimum and maximum value, the upper and lower boarders of the box itself represent the 25th and 75th percentile, and the black horizontal bar within the box represents the median. The grey points indicate outliers