Estimated Rates of Retinal Ganglion Cell Loss in Glaucomatous Eyes with and without Optic Disc Hemorrhages

Purpose: To evaluate whether optic disc hemorrhages are associated with faster rates of estimated retinal ganglion cell (RGC) loss in glaucoma.Methods: A longitudinal observational cohort study of 222 eyes of 122 patients with glaucoma recruited from the Diagnostic Innovations Glaucoma Study (DIGS) followed for an average of 3.74 +/- 0.85 years. All subjects had optical coherence tomography and standard automated perimetry during follow up. Optic disc hemorrhages were detected by masked evaluation of stereophotographs. Rates of change in estimated numbers of RGCs were determined using a previously described method. A random coefficients model was used to investigate the relationship between disc hemorrhages and rates of change in estimated RGC counts over time.Results: 19 eyes of 18 subjects had at least one disc hemorrhage during follow up. At baseline, average estimated RGC counts in eyes with and without disc hemorrhages were 677,994 cells and 682,021 cells, respectively (P = 0.929). Eyes with optic disc hemorrhages during follow-up had significantly faster rates of estimated RGC loss than eyes without disc hemorrhages (22,233 cells/year versus 10,704 cells/year, P = 0.020). the effect of disc hemorrhages on the rates of estimated RGC loss remained significant after adjusting for confounding variables.Conclusion: Eyes with disc hemorrhages showed faster rates of RGC loss compared to eyes without disc hemorrhages. These results provide further evidence that disc hemorrhages should be considered as an indicator of increased risk for faster neural loss in glaucoma.National Institutes of Health/National Eye InstituteResearch to Prevent Blindness (New York, N.Y.)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)AlconAllerganPfizerMerckSantenUniv Calif San Diego, Hamilton Glaucoma Ctr, San Diego, CA 92103 USAUniv Calif San Diego, Dept Ophthalmol, San Diego, CA 92103 USAUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilUniv Edinburgh, Princess Alexandra Eye Pavil, Edinburgh, Midlothian, ScotlandUniv Edinburgh, Dept Ophthalmol, Edinburgh, Midlothian, ScotlandUniversidade Federal de São Paulo, Dept Ophthalmol, São Paulo, BrazilNational Institutes of Health/National Eye Institute: EY021818National Institutes of Health/National Eye Institute: EY11008National Institutes of Health/National Eye Institute: EY14267National Institutes of Health/National Eye Institute: EY019869National Institutes of Health/National Eye Institute: P30EY022589CAPES: 12309-13-3Web of Scienc

Long-Acting Injectable Statins-Is It Time for a Paradigm Shift?

In recent years, advances in pharmaceutical processing technologies have resulted in development of medicines that provide therapeutic pharmacokinetic exposure for a period ranging from weeks to months following a single parenteral administration. Benefits for adherence, dose and patient satisfaction have been witnessed across a range of indications from contraception to schizophrenia, with a range of long-acting medicines also in development for infectious diseases such as HIV. Existing drugs that have successfully been formulated as long-acting injectable formulations have long pharmacokinetic half-lives, low target plasma exposures, and low aqueous solubility. Of the statins that are clinically used currently, atorvastatin, rosuvastatin, and pitavastatin may have compatibility with this approach. The case for development of long-acting injectable statins is set out within this manuscript for this important class of life-saving drugs. An overview of some of the potential development and implementation challenges is also presented

Measuring axial length of the eye from magnetic resonance brain imaging

BACKGROUND: Metrics derived from the human eye are increasingly used as biomarkers and endpoints in studies of cardiovascular, cerebrovascular and neurological disease. In this context, it is important to account for potential confounding that can arise from differences in ocular dimensions between individuals, for example, differences in globe size. METHODS: We measured axial length, a geometric parameter describing eye size from T(2)-weighted brain MRI scans using three different image analysis software packages (Mango, ITK and Carestream) and compared results to biometry measurements from a specialized ophthalmic instrument (IOLMaster 500) as the reference standard. RESULTS: Ninety-three healthy research participants of mean age 51.0 ± SD 5.4 years were analyzed. The level of agreement between the MRI-derived measurements and the reference standard was described by mean differences as follows, Mango − 0.8 mm; ITK − 0.5 mm; and Carestream − 0.1 mm (upper/lower 95% limits of agreement across the three tools ranged from 0.9 mm to − 2.6 mm). Inter-rater reproducibility was between − 0.03 mm and 0.45 mm (ICC 0.65 to 0.93). Intra-rater repeatability was between 0.0 mm and − 0.2 mm (ICC 0.90 to 0.95). CONCLUSIONS: We demonstrate that axial measurements of the eye derived from brain MRI are within 3.5% of the reference standard globe length of 24.1 mm. However, the limits of agreement could be considered clinically significant. Axial length of the eye obtained from MRI is not a replacement for the precision of biometry, but in the absence of biometry it could provide sufficient accuracy to act as a proxy. We recommend measuring eye axial length from MRI in studies that do not have biometry but use retinal imaging to study neurodegenerative changes so as to control for differing eye size across individuals. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12886-022-02289-y

A method for quantifying sectoral optic disc pallor in fundus photographs and its association with peripapillary RNFL thickness

Purpose: To develop an automatic method of quantifying optic disc pallor in fundus photographs and determine associations with peripapillary retinal nerve fibre layer (pRNFL) thickness. Methods: We used deep learning to segment the optic disc, fovea, and vessels in fundus photographs, and measured pallor. We assessed the relationship between pallor and pRNFL thickness derived from optical coherence tomography scans in 118 participants. Separately, we used images diagnosed by clinical inspection as pale (N=45) and assessed how measurements compared to healthy controls (N=46). We also developed automatic rejection thresholds, and tested the software for robustness to camera type, image format, and resolution. Results: We developed software that automatically quantified disc pallor across several zones in fundus photographs. Pallor was associated with pRNFL thickness globally (\b{eta} = -9.81 (SE = 3.16), p < 0.05), in the temporal inferior zone (\b{eta} = -29.78 (SE = 8.32), p < 0.01), with the nasal/temporal ratio (\b{eta} = 0.88 (SE = 0.34), p < 0.05), and in the whole disc (\b{eta} = -8.22 (SE = 2.92), p < 0.05). Furthermore, pallor was significantly higher in the patient group. Lastly, we demonstrate the analysis to be robust to camera type, image format, and resolution. Conclusions: We developed software that automatically locates and quantifies disc pallor in fundus photographs and found associations between pallor measurements and pRNFL thickness. Translational relevance: We think our method will be useful for the identification, monitoring and progression of diseases characterized by disc pallor/optic atrophy, including glaucoma, compression, and potentially in neurodegenerative disorders.Comment: 44 pages, 20 figures, 7 tables, submitte