Purpose To assess for activation of the unfolded protein response in corneal endothelium of Fuchs endothelial corneal dystrophy patients. Design Retrospective comparative case series of laboratory specimens Methods Corneal specimens of patients with Fuchs dystrophy and controls with corneal pathologies other than Fuchs dystrophy were evaluated by transmission electron microscopy (TEM) to evaluate for structural changes of the rough endoplasmic reticulum in corneal endothelium. TEM images were evaluated for alterations of rough endoplasmic reticulum as sign of unfolded protein response. Normal autopsy eyes, Fuchs dystrophy, and keratoconus corneas were used for immunohistochemistry. Immunohistochemistry was performed on formalin-fixed, paraffin-embedded sections of patient corneas for three unfolded protein response markers (GRP78, phospho-eIF2α, CHOP) and two apoptosis markers (Caspase 3 and 9). Immunohistochemistry signal quantitation of corneal endothelium for evaluation of marker expression was performed using automated software. Corneal sections were assessed quantitatively for levels of immunohistochemistry marker expression. Results TEM showed enlargement of rough endoplasmic reticulum in corneal endothelium of all Fuchs dystrophy specimens. Immunohistochemistry quantitation demonstrated a significant increase in mean signal in corneal endothelium from Fuchs dystrophy patients for markers GRP78, phospho-eIF2α, CHOP and caspase 9, compared with non- Fuchs dystrophy corneas (p < 0.05). Conclusions Results of both TEM and immunohistochemistry indicate activation of unfolded protein response in Fuchs dystrophy. Unfolded protein response activation leads to endothelial cell apoptosis in Fuchs dystrophy and may play a central pathogenic role in this disease.
Purpose: To develop and validate a deep learning (DL) algorithm that predicts referable glaucomatous optic neuropathy (GON) and optic nerve head (ONH) features from color fundus images, to determine the relative importance of these features in referral decisions by glaucoma specialists (GSs) and the algorithm, and to compare the performance of the algorithm with eye care providers.Design: Development and validation of an algorithm.Participants: Fundus images from screening programs, studies, and a glaucoma clinic. Methods: A DL algorithm was trained using a retrospective dataset of 86 618 images, assessed for glaucomatous ONH features and referable GON (defined as ONH appearance worrisome enough to justify referral for comprehensive examination) by 43 graders. The algorithm was validated using 3 datasets: dataset A (1205 images, 1 image/patient; 18.1% referable), images adjudicated by panels of GSs; dataset B (9642 images, 1 image/ patient; 9.2% referable), images from a diabetic teleretinal screening program; and dataset C (346 images, 1 image/patient; 81.7% referable), images from a glaucoma clinic.Main Outcome Measures: The algorithm was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for referable GON and glaucomatous ONH features.Results: The algorithm's AUC for referable GON was 0.945 (95% confidence interval [CI], 0.929e0.960) in dataset A, 0.855 (95% CI, 0.841e0.870) in dataset B, and 0.881 (95% CI, 0.838e0.918) in dataset C. Algorithm AUCs ranged between 0.661 and 0.973 for glaucomatous ONH features. The algorithm showed significantly higher sensitivity than 7 of 10 graders not involved in determining the reference standard, including 2 of 3 GSs, and showed higher specificity than 3 graders (including 1 GS), while remaining comparable to others. For both GSs and the algorithm, the most crucial features related to referable GON were: presence of vertical cup-to-disc ratio of 0.7 or more, neuroretinal rim notching, retinal nerve fiber layer defect, and bared circumlinear vessels.Conclusions: A DL algorithm trained on fundus images alone can detect referable GON with higher sensitivity than and comparable specificity to eye care providers. The algorithm maintained good performance on an independent dataset with diagnoses based on a full glaucoma workup.
This review compares and contrasts the surgical management options for IIH.
Intracranial dural arteriovenous fistulas (dAVFs) can produce a variety of symptoms depending on fistula location, size, and venous drainage. Although cavernous sinus fistulas (CCFs) classically present with symptoms of orbital venous congestion due to retrograde venous drainage into the superior ophthalmic vein (i.e. an arterialised ''red eye'') (Miller NR. Neurosurg Focus 2007;23:1-15), dAVFs not localised to the cavernous sinus rarely present with a ''red eye'' and instead produce increased intracranial pressure, which can mimic idiopathic intracranial hypertension (IIH). The authors present a unique case of an intracranial dAVF with clinical features suggestive of both CCF and IIH. Clinicians should be aware of this possibility to avoid delayed diagnosis of the intracranial dAVF.
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