Diagnosis of Retinitis Pigmentosa from Retinal Images

Retinitis pigmentosa is a genetic disorder that results in nyctalopia and its progression leads to complete loss of vision. The analysis and the study of retinal images are necessary, so as to help ophthalmologist in early detection of the retinitis pigmentosa. In this paper fundus images and Optical Coherence Tomography images are comprehensively analyzed, so as to obtain the various morphological features that characterize the retinitis pigmentosa. Pigment Deposits, important trait of RP is investigated. Degree of darkness and entropy are the features used for analysis of PD. The darkness and entropy of the PD is compared with the different regions of the fundus image which is used to detect the pigments in the retinal image. Also the performance of the proposed algorithm is evaluated by using various performance metrics. The performance metrics are calculated for all 120 images of RIPS dataset. The performance metrics such as sensitivity, sensibility, specificity, accuracy, F-score, equal error rate, conformity coefficient, Jaccard's coefficient, dice coefficient, universal quality index were calculated as 0.72, 0.96, 0.97, 0.62, 0.12, 0.09, 0.59, 0.45 and 0.62, respectively

Diagnosis of Retinitis Pigmentosa from Retinal Images

Retinitis pigmentosa is a genetic disorder that results in nyctalopia and its progression leads to complete loss of vision. The analysis and the study of retinal images are necessary, so as to help ophthalmologist in early detection of the retinitis pigmentosa. In this paper fundus images and Optical Coherence Tomography images are comprehensively analyzed, so as to obtain the various morphological features that characterize the retinitis pigmentosa. Pigment Deposits, important trait of RP is investigated. Degree of darkness and entropy are the features used for analysis of PD. The darkness and entropy of the PD is compared with the different regions of the fundus image which is used to detect the pigments in the retinal image. Also the performance of the proposed algorithm is evaluated by using various performance metrics. The performance metrics are calculated for all 120 images of RIPS dataset. The performance metrics such as sensitivity, sensibility, specificity, accuracy, F-score, equal error rate, conformity coefficient, Jaccard\u27s coefficient, dice coefficient, universal quality index were calculated as 0.72, 0.96, 0.97, 0.62, 0.12, 0.09, 0.59, 0.45 and 0.62, respectively

A Foundation LAnguage-Image model of the Retina (FLAIR): Encoding expert knowledge in text supervision

Foundation vision-language models are currently transforming computer vision, and are on the rise in medical imaging fueled by their very promising generalization capabilities. However, the initial attempts to transfer this new paradigm to medical imaging have shown less impressive performances than those observed in other domains, due to the significant domain shift and the complex, expert domain knowledge inherent to medical-imaging tasks. Motivated by the need for domain-expert foundation models, we present FLAIR, a pre-trained vision-language model for universal retinal fundus image understanding. To this end, we compiled 37 open-access, mostly categorical fundus imaging datasets from various sources, with up to 97 different target conditions and 284,660 images. We integrate the expert's domain knowledge in the form of descriptive textual prompts, during both pre-training and zero-shot inference, enhancing the less-informative categorical supervision of the data. Such a textual expert's knowledge, which we compiled from the relevant clinical literature and community standards, describes the fine-grained features of the pathologies as well as the hierarchies and dependencies between them. We report comprehensive evaluations, which illustrate the benefit of integrating expert knowledge and the strong generalization capabilities of FLAIR under difficult scenarios with domain shifts or unseen categories. When adapted with a lightweight linear probe, FLAIR outperforms fully-trained, dataset-focused models, more so in the few-shot regimes. Interestingly, FLAIR outperforms by a large margin more generalist, larger-scale image-language models, which emphasizes the potential of embedding experts' domain knowledge and the limitations of generalist models in medical imaging.Comment: The pre-trained model is available at: https://github.com/jusiro/FLAI

Defining inclusion criteria and endpoints for clinical trials: a prospective cross-sectional study in CRB1-associated retinal dystrophies

Purpose: To investigate the retinal structure and function in patients with CRB1-associated retinal dystrophies (RD) and to explore potential clinical endpoints. Methods: In this prospective cross-sectional study, 22 patients with genetically confirmed CRB1-RD (aged 6–74 years), and who had a decimal best-corrected visual acuit

Adaptive optics: principles and applications in ophthalmology

This is a comprehensive review of the principles and applications of adaptive optics (AO) in ophthalmology. It has been combined with flood illumination ophthalmoscopy, scanning laser ophthalmoscopy, as well as optical coherence tomography to image photoreceptors, retinal pigment epithelium (RPE), retinal ganglion cells, lamina cribrosa and the retinal vasculature. In this review, we highlight the clinical studies that have utilised AO to understand disease mechanisms. However, there are some limitations to using AO in a clinical setting including the cost of running an AO imaging service, the time needed to scan patients, the lack of normative databases and the very small size of area imaged. However, it is undoubtedly an exceptional research tool that enables visualisation of the retina at a cellular level

Functional and Morphological Characteristics of the Retina of Patients with Drusen-like Deposits and Systemic Lupus Erythematosus Treated with Hydroxychloroquine: A Retrospective Study

Purpose: To evaluate the impact of drusen-like deposits (DLD) on retinal layer integrity and retinal function by optical coherence tomography (OCT) and multifocal electroretinography (mfERG) in patients with systemic lupus erythematosus (SLE). Methods: We identified 66 eyes of 33 SLE patients treated with hydroxychloroquine (HCQ) that were categorized into two groups according to whether DLDs were present (34 eyes, Group One) or absent (32 eyes, Group Two). The groups were matched for age, sex, HCQ treatment duration, daily, and cumulative dosage. OCT (retinal layer thicknesses, central retinal thickness, CRT) and mfERG concentric ring analysis were analyzed and compared. Results: CRT was significantly thicker in Group One compared to Group Two (273.21 ± 3.96 vs. 254.5 ± 7.62) (p = 0.023). Group One also demonstrated an overall thicker retinal pigment epithelium compared to Group Two; however, the other outer retinal layers, outer nuclear layer, and photoreceptor layer were found to be significantly thinner in Group One compared to Group Two. We found no differences in mfERG parameters between the two groups. Conclusions: DLDs in SLE patients lead to abnormal central retinal layer thickness, which has no measurable impact on cone-mediated retinal function assessed by mfERG

Snapshot Hyperspectral Imaging for Complete Fundus Oximetry

In this work, a snapshot hyperspectral imager capable of tuning its average spectral resolution from 22.7 nm to 13.9 nm in a single integrated form is presented. The principle of this system will enable future snapshot systems to dynamically adapt to a wide range of imaging situations. Additionally, the system overcomes datacube size limitations imposed by detector array size limits. The work done in this thesis also advances oximetry of the retina using data collected by the Image Mapping spectrometer (IMS), a snapshot spectrometer. Hyperspectral images of the retina are acquired, and oximetry of individual vessels in four diseased eyes is presented. Further, oximetry of the entire fundus is performed using a novel algorithm with data collected with the IMS. We present oxyhemoglobin concentration maps of the eye and demonstrate oxygen sensitivity of the maps by comparing normal and diseased eyes. The aim of this work is to advance the general capabilities of snapshot hyperspectral imagers and to advance the integration of retinal oximetry into the standard ophthalmology instrument repertoire

Retinal plasticity in the context of a partially rescued retinitis pigmentosa mouse model

Retinitis pigmentosa (RP) is a major cause of hereditary blindness and visual disability. The prevalence of RP is estimated to be 1/4000, affecting approximately 2.5 million people worldwide. RP is a very slow-progressing disease, and its symptoms start usually during adolescence. Mutations in over 70 different genes can cause photoreceptor cell degeneration leading to retinitis pigmentosa. A common RP-related gene is PDE6B which encodes a β-subunit of PDE6-enzyme which has a crucial function in rod-mediated vision. No cure is available currently for RP patients. Treatment options are few, but the most promising one is gene therapy. Since retinal gene therapy is delivered by a single sub-retinal injection, it does not rescue all the diseased photoreceptor cells. The impact of the non-rescued photoreceptor cells on the rescued ones is not fully understood. This remains a challenge for the therapy. The project aimed to study the retinal morphology and the function of the retinal pigment epithelium (RPE) in 48-week-old diseased (RP) and partially rescued mice. Pde6bST/WT mice have a functional Pde6b allele and were used as a control in the experiments. Pde6bST/ST mice have a loxP-flanked stop cassette in the intron 1 of both loci of the Pde6b gene. The stop cassette contains multiple polyadenylation signals which prevent gene expression. Pde6bST/ST exhibit progressive rod degeneration. In Pde6bST/ST Pax6αCre mice, stop cassettes are partially removed by the Cre recombinase which is expressed under a Pax6α promoter. Both Pde6b alleles are functional in the distal retina whereas the non-recombined retina in the center remains mutant. Retinal sections were stained with multiple antibodies to study the retinal morphology. RPE morphology was studied by quantifying fluorescence images from RPE wholemounts. Apoptotic cell death in the RPE cells was studied by using a commercial TUNEL assay. In normal physiology, RPE cells phagocytose photoreceptor cell outer segments and this process was studied by using an ex vivo assay. According to the results, the partially rescued retina of Pde6bST/ST Pax6αCre showed signs of retinal remodelling. This can be seen as beneficial for the retinal gene therapies conducted by a single injection if the partially rescued retina can regenerate and expand the rescued area. The diseased retina of Pde6bST/ST showed large-scale retinal degeneration and revealed heterogeneity of the RPE

Accuracy of fundus autofluorescence imaging for the diagnosis and monitoring of retinal conditions: a systematic review

BackgroundNatural fluorescence in the eye may be increased or decreased by diseases that affect theretina. Imaging methods based on confocal scanning laser ophthalmoscopy (cSLO) can detect this ‘fundusautofluorescence’ (FAF) by illuminating the retina using a specific light ‘excitation wavelength’. FAFimaging could assist the diagnosis or monitoring of retinal conditions. However, the accuracy of themethod for diagnosis or monitoring is unclear.ObjectiveTo conduct a systematic review to determine the accuracy of FAF imaging using cSLO for thediagnosis or monitoring of retinal conditions, including monitoring of response to therapy.Data sourcesElectronic bibliographic databases; scrutiny of reference lists of included studies andrelevant systematic reviews; and searches of internet pages of relevant organisations, meetings and trialregistries. Databases included MEDLINE, EMBASE, The Cochrane Library, Web of Science and the Mediondatabase of diagnostic accuracy studies. Searches covered 1990 to November 2014 and were limited tothe English language.Review methodsReferences were screened for relevance using prespecified inclusion criteria to capturea broad range of retinal conditions. Two reviewers assessed titles and abstracts independently. Full-textversions of relevant records were retrieved and screened by one reviewer and checked by a second. Datawere extracted and critically appraised using the Quality Assessment of Diagnostic Accuracy Studies criteria(QUADAS) for assessing risk of bias in test accuracy studies by one reviewer and checked by a second.At all stages any reviewer disagreement was resolved through discussion or arbitration by a third reviewer.ResultsEight primary research studies have investigated the diagnostic accuracy of FAF imaging in retinalconditions: choroidal neovascularisation (one study), reticular pseudodrusen (three studies), cystoid macularoedema (two studies) and diabetic macular oedema (two studies). Sensitivity of FAF imaging using anexcitation wavelength of 488 nm was generally high (range 81–100%), but was lower (55% and 32%) intwo studies using longer excitation wavelengths (514 nm and 790 nm, respectively). Specificity rangedfrom 34% to 100%. However, owing to limitations of the data, none of the studies provide conclusiveevidence of the diagnostic accuracy of FAF imaging.LimitationsNo studies on the accuracy of FAF imaging for monitoring the progression of retinalconditions or response to therapy were identified. Owing to study heterogeneity, pooling of diagnosticoutcomes in meta-analysis was not conducted. All included studies had high risk of bias. In most studiesthe patient spectrum was not reflective of those who would present in clinical practice and no studiesadequately reported how FAF images were interpreted.ConclusionsAlthough already in use in clinical practice, it is unclear whether or not FAF imaging isaccurate, and whether or not it is applied and interpreted consistently for the diagnosis and/or monitoringof retinal conditions. Well-designed prospective primary research studies, which conform to the paradigmof diagnostic test accuracy assessment, are required to investigate the accuracy of FAF imaging in diagnosisand monitoring of inherited retinal dystrophies, early age-related macular degeneration, geographicatrophy and central serous chorioretinopathy.Study registrationThis study is registered as PROSPERO CRD42014014997.FundingThe National Institute for Health Research Health Technology Assessment programme

Quantified phenotype analysis in a cell model for Autosomal Dominant Retinitis Pigmentosa

Modern cell biology relies greatly on microscopy to assess distribution and dynamics of fluorescently labelled cellular proteins. Quantified image analysis allows not only measurement of clear differences between individual phenotypes and time points, but also discovery of subtle changes which are not obvious to an observer by visual inspection. In this dissertation, we quantitatively characterise wild type and mutations P23H/A/L in rhodopsin in a cellular model for autosomal dominant retinitis pigmentosa in stable HEK 293S cell lines and in GMK cells. Autosomal dominant retinitis pigmentosa is a genetic disorder which can lead to photoreceptor cell death and result in reduced vision and complete blindness. Endoplasmic Reticulum chaperone calnexin was also quantified from both immune-labelled fixed cells, and from transient co-transfection of live cells. The clinically relevant severity of rhodopsin mutations was in keeping with the phenotypes of the cellular model. The severe mutation P23H showed the lowest volume of rhodopsin-GFP in both cell lines in comparison to wild-type. We also reported a significantly higher calnexin volume in HEK293 and GMK expressing P23H rhodopsin (with p<0.05). Less severe mutants had a phenotype more similar to wildtype. Colocalisation was assessed using a simple approach of overlapping volume. As co-expression of rhodopsin and calnexin during time-lapse acquisition induced cytotoxicity and accelerated cellular death, we assessed phototoxicity caused by blue light illumination. We quantified motility and division rates in PC3 and GMK mammalian cell cultures, respectively. A surprisingly low phototoxicity threshold of 13.9 J/cm2 was determined for imaging unlabelled GMK cells without inducing mitotic delay. To assess the production of reactive oxygen species, which are key to phototoxicity in fluorescence microscopy, the end-product hydrogen peroxide was monitored using a ratiometric biosensor. Finally, all findings are synthesised as practical guidelines for end users