In this work, we assessed the scientific benefit of the OCT in rodent models featuring retinal neurodegeneration, perturbed retinal structure, neovascular conditions, and developmental aberrations, all likely fields of interest to a wide range of academic and industrial researchers.
The results in the light damaged retina show the benefit of the combination of surface imaging with the SLO for aiming at sites of interest (like here demarcated by autofluorescence) and the OCT. We found a close correlation of the site of autofluorescence in the 488 nm SLO images (attributed to the lipid-rich remnants of the photoreceptor outer segments) with the outer retinal damage in the OCT sections. For the first time, we were able to demonstrate edema formation in these rodents (), which appears to be part of the dynamic processes associated with acute light exposure and, because of the tissue processing, is not detectable in conventional morphological analyses.
An example of perturbed retinal structure is the rosette formation in the Nrl
knockout mouse (). Whereas the relatively even topographical distribution of the lesions became visible in SLO imaging (similar to a retinal whole-mount, ), details of the structure were accessible in vivo
with OCT sections (). The formation of rosettes in Nrl mutants is not yet fully understood, but it is known that cones are a major component of these dysmorphic structures, with their inner and outer segments pointing towards the center of each rosette 
. The respective photoreceptor nuclei around the center of the rosette in (similar to the ONL ones) correspond in the OCT to an area of low reflectivity in (similar to the ONL band). The center of rosettes was further shown to contain RPE proteins and have connections to the RPE layer 
. In the OCT, we found that this tissue has reflective properties close to plexiform layers (). Rosette formation occurs postnatally 
, apparently driven by a metabolic need of the retina, leading to an increased surface area between RPE and photoreceptors. To better understand this process, we will examine the time course in individual animals in a separate study.
In mutants lacking the Crumbs1 gene, lesions are commonly sparse (), which makes an histological analysis laborious and demanding. An in vivo screening with the SLO has proven to be very effective the overall assessment as well as a preselection for immunostainings, saving time, money, and animals. Now, with the OCT, the nature and extent of the lesions can be assessed in real time. The particular example in illustrates the capability to detect intraretinal (black arrows) as well as choroidal vessels (white arrows), which so far required a full histological work-up of such lesion sites (). Having the morphological information available in vivo permits to study the dynamics of such sites in more detail (together with the use of dyes) before the animal is sacrificed.
The results in the RbloxP/loxP;α-Cre
mice illustrate how the developmental apoptosis due to an imbalance of RB and the E2Fs 
affects the different layers ().
However, developmental apoptosis only occurs in areas where Rb
is missing, which in this conditional knock-out is the area of Cre expression 
. Since the retina-specific α-Cre
mice used here do show a central-peripheral expression gradient, so does the apoptosis and, subsequently, retinal thickness. So, besides the Rb
-specific findings, this model also helped to assess the feasibility of a topographical mapping of retinal thickness based on a set of consecutive serial sections (“volume scan”). The color-coded map () reveals regular retinal thickness values mainly around the optic disc (image center), which reflects the inverse topography of the α-Cre
transgene expression 
. Thickness maps are further useful to follow thickness changes over time.
The prime advantage of OCT is certainly the ability to non-invasively produce histology-analogue retinal sections. As we have shown, these are both useful for the assessment and numerical quantification of generalized changes and for the detection and analysis of sporadic, localized lesions.
In many cases, standard histology may be replaced or at least its extent reduced by OCT, diminishing the amount of study animals needed. Even if histological sections are required (e.g. immunostains), OCT may help to preselect and to determine the optimal time point in individual animals in case of progressive changes.
As most degenerative processes are dynamic in nature, the non-invasive examination has substantial advantages for the understanding of short–term alterations like edema formation. A requirement for preclinical and long-term studies is that markers of potential degenerative changes or therapeutic effects may be analyzed numerically. The OCT, for the first time, allows an accurate quantitative description of the retinal layers in vivo as shown in . As the majority of lesions primarily compromise the outer retina but leave the inner retina unchanged, it is a fundamental improvement that these layers are now accessible to separate quantification.
In summary, our results present the OCT as an important new tool for the in vivo analysis of rodent eyes. It is not only a methodological step forward but will also significantly help to reduce standard histology and thus the amount of animals needed. The ability to monitor developmental as well as inherited and induced degenerative processes and respective therapeutic intervention in the same individual animals opens a wide field of applicability in future long-term and preclinical studies. In conjunction with other non-invasive tests like electroretinography (ERG), OCT allows for a refined morphological and functional follow-up over time.