By providing the sectioning capability to differentiate individual retinal layers, optical coherence tomography (OCT) is revolutionizing eye disease diagnosis and treatment evaluation. A better understanding of the hyper- and hypo-reflective bands in retinal OCT is essential for accurate interpretation of clinical outcomes. In this article, we summarize the interpretations of clinical OCT and adaptive optics (AO) OCT (AO-OCT) of the outer retina in the human eye, and briefly review OCT investigation of the outer retina in animal models. Quantitative analysis of outer retinal OCT bands is compared to established parameters of retinal histology. The literature review and comparative analysis support that both inner/outer segment (IS/OS) junction and IS ellipsoid zone nonexclusively contribute to the second band; and OS, OS tips, and retinal pigment epithelium apical processes contribute to the third band in conventional OCT. In contrast, AO-OCT might predominantly detect the IS/OS junction and OS tip signals at the second and third bands due to its improved sectioning capability and possible AO effect on the sensitivities for recording ballistic and diffusive photons from different regions of the outer retina.

Multispectral imaging (MSI) of the retina and choroid has increasing interest for better diagnosis and treatment evaluation of eye diseases. However, currently available MSI systems have a limited field of view (FOV) to evaluate the peripheral retina. This study is to validate trans-pars-planar illumination for a contact-mode ultra-widefield MSI system. By freeing the available pupil for collecting imaging light only, the trans-pars-planar illumination enables a portable, non-mydriatic fundus camera, with 200° FOV in a single fundus image. The trans-pars-planar illumination, delivering illumination light from one side of the eye, naturally enables oblique illumination ophthalmoscopy to enhance the contrast of fundus imaging. A broadband (104 nm) 565 nm light-emitting diode (LED) is used for validating color fundus imaging first. Four narrowband (17-60 nm) 530 nm, 625 nm, 780 nm, and 970 nm LEDs are tested for MSI. With 530 nm illumination, the fundus image reveals retinal vasculature predominantly. 625 nm and 780 nm illuminations enhance the visibility of choroidal vasculature. With further increased wavelength of 970 nm, the fundus image is predominated by large veins in the choroid, with multiple vortex ampullas observed simultaneously in a single fundus image.

PurposeTo conduct longitudinal optical coherence tomography angiography (OCTA) to characterize dynamic changes of trilaminar vascular plexuses in wild-type (WT) and retinal degeneration 10 (rd10) mouse retinas.MethodsLongitudinal in vivo OCT/OCTA measurements of WT and rd10 mouse retinas were conducted at postnatal day 14 (P14), P17, P21, P24, and P28. OCT images were used to quantify retinal thickness changes, while OCTA images were used to investigate vascular dynamics within the trilaminar vascular plexuses, that is, superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP). Blood vessel densities of all three plexus layers were quantitatively evaluated separately. The caliber of first-order blood vessel branches in the SVP layer was also measured.ResultsVascular densities in all three plexuses continuously decreased with aging in both WT and rd10. However, abnormal density reduction in rd10 occurred at P17 in both ICP (P < 0.001) and DCP (P < 0.001). While the ICP of rd10 showed density recovery at P24, the DCP of rd10 showed significantly low density. Remarkable vascular narrowing in rd10 was also observed in the SVP, especially at P28.ConclusionsThe most severe vascular impairment happened in the DCP, while the ICP showed the transient recovery of vascular density after the onset of retinal degeneration. The SVP was most resistant to the retinal degeneration, but the first-order blood vessel branches within the SVP showed progressive narrowing.Translational RelevanceBetter understanding of the vascular changes correlated with retinal development, and retinal degeneration can provide insights in advanced development of treatment protocols of retinal degenerative diseases.

Stimulus-evoked intrinsic optical signal (IOS), which occurs almost immediately after the onset of retinal stimulus has been observed in retinal photoreceptors, promises to be a unique biomarker for objective optoretinography (ORG) of photoreceptor function. We report here the first-time in vivo ORG detection of photoreceptor dysfunction due to retinal degeneration. A custom-designed optical coherence tomography (OCT) was employed for longitudinal ORG monitoring of photoreceptor-IOS distortions in retinal degeneration mice. Depth-resolved OCT analysis confirmed the outer segment (OS) as the physical source of the photoreceptor-IOS. Comparative ERG measurement verified the phototransduction activation as the physiological correlator of the photoreceptor-IOS. Histological examination revealed disorganized OS discs, i.e. the pathological origin of the photoreceptor-IOS distortion.

Age-related macular degeneration (AMD) is the leading cause of severe vision loss and legal blindness. It is known that retinal photoreceptors are the primary target of AMD. Therefore, a reliable method for objective assessment of photoreceptor function is needed for early detection and reliable treatment evaluation of AMD and other eye diseases such as retinitis pigmentosa that are known to cause photoreceptor dysfunctions. Stimulus-evoked intrinsic optical signal (IOS) changes promise a unique opportunity for objective assessment of physiological function of retinal photoreceptor and inner neurons. Instead of a comprehensive review, this mini-review is to provide a brief summary of our recent in vitro and in vivo optical coherence tomography (OCT) studies of stimulus-evoked IOS changes in animal retinas. By providing excellent axial resolution to differentiate individual retinal layers, depth-resolved OCT revealed rapid IOS response at the photoreceptor outer segment. The fast photoreceptor-IOS occurred almost right away (∼ 2 ms) after the onset of retinal stimulation, differentiating itself from slow IOS changes correlated with inner neural and hemodynamic changes. Further development of the functional IOS instruments and retinal stimulation protocols may provide a feasible solution to pursue clinical application of functional IOS imaging for objective assessment of human photoreceptors. Impact statement Retinal photoreceptors are the primary target of age-related macular degeneration (AMD) which is the leading cause of severe vision loss and legal blindness. An objective method for functional assessment of photoreceptor physiology can benefit early detection and better treatment evaluation of AMD and other eye diseases that are known to cause photoreceptor dysfunctions. This article summarizes in vitro study of IOS mechanisms and in vivo demonstration of IOS imaging of intact animals. Further development of the functional IOS imaging may provide a revolutionary solution to achieve objective assessment of human photoreceptors.