Evaluation of the initial implementation of a nationwide diabetic retinopathy screening programme in primary care: A multimethod study

Objectives The Australian Government funded a nationwide diabetic retinopathy screening programme to improve visual outcomes for people with diabetes. This study examined the benefits and barriers of the programme, image interpretation pathways and assessed the characteristics of people who had their fundus photos graded by a telereading service which was available as a part of the programme. Design Multimethod: survey and retrospective review of referral forms. Setting Twenty-two primary healthcare facilities from urban, regional, rural and remote areas of Australia, and one telereading service operated by a referral-only eye clinic in metropolitan Sydney, Australia. Participants Twenty-seven primary healthcare workers out of 110 contacted completed a survey, and 145 patient referrals were reviewed. Results Manifest qualitative content analysis showed that primary healthcare workers reported that the benefits of the screening programme included improved patient outcomes and increased awareness and knowledge of diabetic retinopathy. Barriers related to staffing issues and limited referral pathways. Image grading was performed by a variety of primary healthcare workers, with one responder indicating the utilisation of a diabetic retinopathy reading service. Of the people with fundus photos graded by the reading service, 26.2% were reported to have diabetes. Overall, 12.3% of eyes were diagnosed with diabetic retinopathy. Photo quality was rated as excellent in 46.2% of photos. Referral to an optometrist for diabetic retinopathy was recommended in 4.1% of cases, and to an ophthalmologist in 6.9% of cases. Conclusions This nationwide diabetic retinopathy screening programme was perceived to increase access to diabetic retinopathy screening in regional, rural and remote areas of Australia. The telereading service has diagnosed diabetic retinopathy and other ocular pathologies in images it has received. Key barriers, such as access to ophthalmologists and optometrists, must be overcome to improve visual outcomes

Anterior Chamber Angle Evaluation Using Gonioscopy: Consistency and Agreement between Optometrists and Ophthalmologists

SIGNIFICANCE In our intermediate-tier glaucoma care clinic, we demonstrate fair to moderate agreement in gonioscopy examination between optometrists and ophthalmologists, but excellent agreement when considering open versus closed angles. We highlight the need for increased consistency in the evaluation and recording of angle status using gonioscopy. PURPOSE The consistency of gonioscopy results obtained by different clinicians is not known but is important in moving toward practice modalities such as telemedicine and collaborative care clinics. The purpose of this study was to evaluate the description and concordance of gonioscopy results among different practitioners. METHODS The medical records of 101 patients seen within a collaborative care glaucoma clinic who had undergone gonioscopic assessment by two clinicians (one optometrist and either one general ophthalmologist [n = 50] or one glaucoma specialist [n = 51]) were reviewed. The gonioscopy records were evaluated for their descriptions of deepest structure seen, trabecular pigmentation, iris configuration, and other features. These were compared between clinicians (optometrist vs. ophthalmologist) and against the final diagnosis. RESULTS Overall, 51.9 and 59.8% of angles were graded identically in terms of deepest visible structure when comparing between optometrist versus general ophthalmologist and optometrist versus glaucoma specialist, respectively. The concordance increased when considering ±1 of the grade (67.4 and 78.5%, respectively), and agreement with the final diagnosis was high (>90%). Variations in angle grading other than naming structures were observed (2.0, 30, and 3.9% for optometrist, general ophthalmologist, and glaucoma specialist, respectively). Most of the time, trabecular pigmentation or iris configuration was not described. CONCLUSIONS Fair to moderate concordance in gonioscopy was achieved between optometrists and ophthalmologists in a collaborative care clinic in which there is consistent feedback and clinical review. To move toward unified medical records and a telemedicine model, improved consistency of record keeping and angle description is required

Comparative genomic mapping of uncharacterized canine retinal ESTs to identify novel candidate genes for hereditary retinal disorders

Purpose: To identify the genomic location of previously uncharacterized canine retina-expressed expressed sequence tags (ESTs), and thus identify potential candidate genes for heritable retinal disorders. Methods: A set of over 500 retinal canine ESTs were mapped onto the canine genome using the RHDF ₅₀₀₀₋₂ radiation hybrid (RH) panel, and the resulting map positions were compared to their respective localization in the CanFam2 assembly of the canine genome sequence. Results: Unique map positions could be assigned for 99% of the mapped clones, of which only 29% showed significant homology to known RefSeq sequences. A comparison between RH map and sequence assembly indicated some areas of discrepancy. Retinal expressed genes were not concentrated in particular areas of the canine genome, and also were located on the canine Y chromosome (CFAY). Several of the EST clones were located within areas of conserved synteny to human retinal disease loci. Conclusions: RH mapping of canine retinal ESTs provides insight into the location of potential candidate genes for hereditary retinal disorders, and, by comparison with the assembled canine genome sequence, highlights inconsistencies with the current assembly. Regions of conserved synteny between the canine and the human genomes allow this information to be extrapolated to identify potential positional candidate genes for mapped human retinal disorders. Furthermore, these ESTs can help identify novel or uncharacterized genes of significance for better understanding of retinal morphology, physiology, and pathology.10 page(s

Evaluation of a hospital-based integrated model of eye care for diabetic retinopathy assessment: A multimethod study

Objectives Diabetic eye disease is a leading cause of blindness but can be mitigated by regular eye assessment. A framework of issues, developed from the literature of barriers to eye assessment, was used to structure an examination of perceptions of a new model of care for diabetic retinopathy from the perspective of staff using the model, and health professionals referring patients to the new service. Design Multimethod: interviews and focus groups, and a separate survey. Setting A new clinic based on an integrated model of care was established at a hospital in outer metropolitan Sydney, Australia in 2017. Funded jointly by Centre for Eye Health (CFEH) and the hospital, the clinic was equipped and staffed by optometrists who work alongside the ophthalmologists in the existing hospital eye clinic. Participants Five (of seven) hospital staff working in the clinic (ophthalmologists and administrative officers) or referring to it from other departments (endocrinologists); nine optometrists from CFEH who developed or worked in the clinic; 10 community-based optometrists as potential referrers. Results The new clinic was considered to have addressed known barriers to eye assessment, including access, assistance for patients unable/unwilling to organise eye checks and efficient management of human resources. The clinic optimised known drivers of this model of care: providing clear scope of practice and protocols for shared care between optometrists and ophthalmologists, good communication between referrers and eye professionals and a collegial approach promoting interprofessional trust. Remaining areas of concern were few referrals from general practitioners, fewer referrals from hospital endocrinologists than expected and issues with stretched administrative capacity. There were also perceived mismatches between the priorities of hospital management and aims of the clinic. Conclusions The new model was considered to have addressed many of the barriers to assessment. While there remain issues with the model, there were also unexpected benefits

Cloning and Characterization of the Canine Photoreceptor Specific Cone-Rod Homeobox (CRX) Gene and Evaluation as a Candidate for Early Onset Photoreceptor Diseases in the Dog

Purpose: The cone-rod homeobox protein (CRX) is a member of the homeodomain-containing protein family expressed in the retinal photoreceptors and pinealocytes; it is involved in the regulation of the coordinate expression of multiple photoreceptor specific genes during retinal development. Mutations in the CRX gene are causally associated with retinal degeneration phenotypes in man. To clone the full length cDNA, characterize the genomic organization of canine CRX, map the gene in a radiation hybrid (RH) panel, and evaluate it as a candidate for canine inherited retinal degenerations. Methods: cDNA representational difference analysis (RDA) was done using normal and cone degeneration (cd) affected retinas. Exonic primers designed from consensus sequences of mammalian CRX cDNA were used to amplify and sequence dog genomic DNA. Canine specific primers were used for RH mapping of CRX on the RH3000 cell line. Linkage, sequencing and/or mapping the disease locus was used to evaluate CRX as a disease associated candidate gene. Results: The gene comprises three exons and two introns and codes for a transcript with a 900 bp open reading frame (ORF). In agreement with human map data, RH mapping placed canine CRX on the proximal end of CFA1, in a region of synteny with HSA19q13-q13.3. Based on RH mapping, meiotic linkage or sequencing data, we excluded CRX as the cause of canine early onset photoreceptor degenerations affecting Alaskan malamutes (cd), collies (rod-cone dysplasia 2, rcd2), American Staffordshire terriers, and Tibetan terriers. Conclusions: Canine CRX has a high level of nucleotide and amino acid sequence identity with ortholgous sequences reported for other species. The gene is excluded from causal association with 4 early onset photoreceptor diseases affecting cones (cd) or rods and cones (rcd2, PRA in American Staffordshire terriers, and Tibetan terriers)

Underdeveloped RPE Apical Domain Underlies Lesion Formation in Canine Bestrophinopathies

Canine bestrophinopathy (cBest) is an important translational model for BEST1-associated maculopathies in man that recapitulates the broad spectrum of clinical and molecular disease aspects observed in patients. Both human and canine bestrophinopathies are characterized by focal to multifocal separations of the retina from the RPE. The lesions can be macular or extramacular, and the specific pathomechanism leading to formation of these lesions remains unclear. We used the naturally occurring canine BEST1 model to examine factors that underlie formation of vitelliform lesions and addressed the susceptibility of the macula to its primary detachment in BEST1-linked maculopathies

Modeling the Structural Consequences of \u3cem\u3eBEST1\u3c/em\u3e Missense Mutations

Mutations in the bestrophin-1 gene (BEST1) are an important cause of inherited retinal disorders. Hitherto, over 100 unique allelic variants have been linked to the human BEST1 (hBEST1), and associated with disease phenotypes, broadly termed as bestrophinopathies. A spontaneous animal model recapitulating BEST1-related phenotypes, canine multifocal retinopathy (cmr), is caused by mutations in the canine gene ortholog (cBEST1). We have recently characterized molecular consequences of cmr, demonstrating defective protein trafficking as a result of G161D (cmr2) mutation. To further investigate the pathological effects of BEST1 missense mutations, canine and human peptide fragments derived from the protein sequence have been studied in silico as models for early events in the protein folding. The results showed that G161D as well as I201T substitutions cause severe conformational changes in the structure of bestrophin-1, suggesting protein misfolding as an underlying disease mechanism. The comparative modeling studies expand our insights into BEST1 pathogenesis

Differential Allocation of Constitutive and Induced Chemical Defenses in Pine Tree Juveniles: A Test of the Optimal Defense Theory

Optimal defense theory (ODT) predicts that the within-plant quantitative allocation of defenses is not random, but driven by the potential relative contribution of particular plant tissues to overall fitness. These predictions have been poorly tested on long-lived woody plants. We explored the allocation of constitutive and methyl-jasmonate (MJ) inducible chemical defenses in six half-sib families of Pinus radiata juveniles. Specifically, we studied the quantitative allocation of resin and polyphenolics (the two major secondary chemicals in pine trees) to tissues with contrasting fitness value (stem phloem, stem xylem and needles) across three parts of the plants (basal, middle and apical upper part), using nitrogen concentration as a proxy of tissue value. Concentration of nitrogen in the phloem, xylem and needles was found to be greater higher up the plant. As predicted by the ODT, the same pattern was found for the concentration of non-volatile resin in the stem. However, in leaf tissues the concentrations of both resin and total phenolics were greater towards the base of the plant. Two weeks after MJ application, the concentrations of nitrogen in the phloem, resin in the stem and total phenolics in the needles increased by roughly 25% compared with the control plants, inducibility was similar across all plant parts, and families differed in the inducibility of resin compounds in the stem. In contrast, no significant changes were observed either for phenolics in the stems, or for resin in the needles after MJ application. Concentration of resin in the phloem was double that in the xylem and MJ-inducible, with inducibility being greater towards the base of the stem. In contrast, resin in the xylem was not MJ-inducible and increased in concentration higher up the plant. The pattern of inducibility by MJ-signaling in juvenile P. radiata is tissue, chemical-defense and plant-part specific, and is genetically variable

A symmoriiform chondrichthyan braincase and the origin of chimaeroid fishes

Chimaeroid fishes (Holocephali) are one of the four principal divisions of modern gnathostomes (jawed vertebrates). Despite only 47 described living species1, chimaeroids are the focus of resurgent interest as potential archives of genomic data2 and for the unique perspective they provide on chondrichthyan and gnathostome ancestral conditions. Chimaeroids are also noteworthy for their highly derived body plan1,3,4. However, like other living groups with distinctive anatomies5, fossils have been of limited use in unravelling their evolutionary origin, as the earliest recognized examples already exhibit many of the specializations present in modern forms6,7. Here we report the results of a computed tomography analysis of Dwykaselachus, an enigmatic chondrichthyan braincase from the ~280 million year old Karoo sediments of South Africa8. Externally, the braincase is that of a symmoriid shark9,10,11,12,13and is by far the most complete uncrushed example yet discovered. Internally, the morphology exhibits otherwise characteristically chimaeroid specializations, including the otic labyrinth arrangement and the brain space configuration relative to exceptionally large orbits. These results have important implications for our view of modern chondrichthyan origins, add robust structure to the phylogeny of early crown group gnathostomes, reveal preconditions that suggest an initial morpho-functional basis for the derived chimaeroid cranium, and shed new light on the chondrichthyan response to the extinction at the end of the Devonian period

Understanding hereditary diseases using the dog and human as companion model systems

Animal models are requisite for genetic dissection of, and improved treatment regimens for, human hereditary diseases. While several animals have been used in academic and industrial research, the primary model for dissection of hereditary diseases has been the many strains of the laboratory mouse. However, given its greater (than the mouse) genetic similarity to the human, high number of naturally occurring hereditary diseases, unique population structure, and the availability of the complete genome sequence, the purebred dog has emerged as a powerful model for study of diseases. The major advantage the dog provides is that it is afflicted with approximately 450 hereditary diseases, about half of which have remarkable clinical similarities to corresponding diseases of the human. In addition, humankind has a strong desire to cure diseases of the dog so these two facts make the dog an ideal clinical and genetic model. This review highlights several of these shared hereditary diseases. Specifically, the canine models discussed herein have played important roles in identification of causative genes and/or have been utilized in novel therapeutic approaches of interest to the dog and human