27 research outputs found

    7-Ketocholesterol increases retinal microglial migration, activation, and angiogenicity: a potential pathogenic mechanism underlying age-related macular degeneration.

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    Age-related macular degeneration (AMD) has been associated with both accumulation of lipid and lipid oxidative products, as well as increased neuroinflammatory changes and microglial activation in the outer retina. However, the relationships between these factors are incompletely understood. 7-Ketocholesterol (7KCh) is a cholesterol oxidation product localized to the outer retina with prominent pro-inflammatory effects. To explore the potential relationship between 7KCh and microglial activation, we localized 7KCh and microglia to the outer retina of aged mice and investigated 7KCh effects on retinal microglia in both in vitro and in vivo systems. We found that retinal microglia demonstrated a prominent chemotropism to 7KCh and readily internalized 7KCh. Sublethal concentrations of 7KCh resulted in microglial activation and polarization to a pro-inflammatory M1 state via NLRP3 inflammasome activation. Microglia exposed to 7KCh reduced expression of neurotrophic growth factors but increased expression of angiogenic factors, transitioning to a more neurotoxic and pro-angiogenic phenotype. Finally, subretinal transplantation of 7KCh-exposed microglia promoted choroidal neovascularization (CNV) relative to control microglia in a Matrigel-CNV model. The interaction of retinal microglia with 7KCh in the aged retina may thus underlie how outer retinal lipid accumulation in intermediate AMD results in neuroinflammation that ultimately drives progression towards advanced AMD

    Unilateral progressive keratoconus associated with ipsilateral craniofacial fibrous dysplasia treated with corneal cross-linking

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    Purpose: The purpose of this study is to describe a case of unilateral keratoconus associated with ipsilateral craniofacial fibrous dysplasia and its subsequent management with corneal collagen cross-linking. Observations: This is an interventional case report of a 16-year-old male with a history of polyostotic fibrous dysplasia of the left frontal bone and orbital roof status post partial resection six years prior who presented to the pediatric ophthalmology clinic with progressively blurry vision in the left eye. Refraction in this eye revealed an increase in cylinder by > 3D from his last refraction two years prior. Pentacam corneal tomography confirmed the diagnosis of keratoconus in the left eye. The patient underwent corneal collagen cross-linking in the affected eye. Postoperatively, he experienced marked improvement in corrected visual acuity with scleral contact lenses and maintained stable astigmatism and keratometry values on Pentacam corneal tomography at his most recent visit 12 months postoperatively. Conclusions: While it is otherwise felt to be a bilateral disease, unilateral keratoconus may present in the context of ipsilateral orbital pathology. Corneal collagen cross-linking may be used to successfully prevent keratoconus progression in the setting of stable orbital pathology

    Recurrent divergence-insufficiency esotropia in Machado-Joseph disease (spinocerebellar ataxia type 3)

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    Purpose: To describe a case of incomitant divergence insufficiency esotropia in the setting of Machado-Joseph disease (spinocerebellar ataxia type 3) that recurred completely within one week after augmented bilateral medial rectus recession. Observations: A 53-year-old female with a history of Machado-Joseph disease presented with horizontal diplopia primarily at distance consistent with divergence insufficiency esotropia. Augmented bilateral medial rectus recessions were performed which initially produced orthotropia, but recurrence of the esodeviation to the full preoperative amount occurred by post-operative week one. The patient subsequently underwent bilateral lateral rectus resections with excellent result. Conclusions and importance: Divergence insufficiency is common in the spinocerebellar ataxia variants and is thought to be secondary to atrophy of brainstem structures involved in the control of ocular vergence. Strabismus surgery in these patients may be complicated by limited response or even rapid regression despite augmented surgery as suggested for divergence insufficiency in the setting of neurologic disease. Patients should be counseled on these risks as well as the potential for multiple procedures in order to achieve surgical success

    Penetrating Keratoplasty at a Tertiary Referral Center in Ethiopia

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    PurposeTo describe the indications, visual acuity outcomes, and graft survival after penetrating keratoplasty (PKP) in Addis Ababa, Ethiopia.MethodsThe medical records of patients who underwent PKP at Menelik II Hospital between September 2000 and September 2013 were retrospectively reviewed. The prespecified outcomes were graft survival, visual acuity, and complication rates.ResultsA total of 321 patients underwent PKP during the study period and were included in the analysis. Indications for surgery were trachoma or leukoma in 141 (44%), keratoconus in 45 (14%), corneal dystrophy in 46 (14%), pseudophakic or aphakic bullous keratopathy in 28 (9%), trauma in 27 (8%), previous graft failure in 18 (6%), active ulcer, burn, or perforation in 9 (3%), and others in 7 (2%). The graft survival rate was 80% overall at 2 years but varied considerably depending on the indication for surgery. Uncorrected visual acuity improved from baseline mean logarithm of the minimum angle of resolution 2.09 (SD 0.67) to mean logarithm of the minimum angle of resolution of 1.53 (SD 1.03) at 2 years. A number of factors affected the visual acuity outcomes. Patients were not routinely refracted, and only 18% (N = 60) of patients had access to corrective spectacles or contact lenses postoperatively. Complication rates were high with infectious keratitis being the most common.ConclusionsPKP is becoming a viable treatment for corneal opacity in developing countries. However, the high burden of disease and lack of corrective lenses remain significant obstacles to overcome

    Trends in Corneal Topography and Tomography Imaging for Keratoconus Management.

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    PurposeTo describe trends in the use of corneal topography and tomography for the management of keratoconus patients at a single academic institution and to identify how these trends may be associated with different procedural interventions.Patients and methodsIn this retrospective cohort study, keratoconus patients treated from 2012 to 2019 were identified. The electronic health record was reviewed for the presence of corneal topography or tomography imaging completed within seven days of the first visit and the highest level of intervention at the first and most recent visit. Patients were grouped as pediatric (<18 years) or adult (≥18 years). Chi-square tests and linear regressions were used to evaluate trends and to determine which factors were predictive for receiving corneal collagen cross-linking (CXL) versus other surgical interventions (intrastromal corneal ring segments, lamellar keratoplasty, or penetrating keratoplasty) by the most recent visit.ResultsA total of 873 keratoconus patients met inclusion criteria. The use of corneal topography at the first visit remained relatively consistent from 2012 to 2019, while corneal tomography usage at the first visit increased from 3.9% in 2015, when corneal tomography was introduced, to 52.8% in 2019. Each year was associated with an 11.2% ± 1.9% increase in the use of corneal tomography at the first visit in pediatric patients and 6.7% ± 0.5% in adult patients. Use of corneal tomography at the first visit was a significant predictor for receiving CXL procedures (P < 0.001) and a negative predictor for requiring other surgical interventions (P = 0.032) when controlling for the year of the first visit.ConclusionObtaining corneal tomography at the first visit has become the standard of care in keratoconus, especially for pediatric patients. Moreover, the increase in corneal tomography imaging has coincided with an increase in CXL procedures and decrease in other surgical interventions

    Drusen Regression is Associated With Local Changes in Fundus Autofluorescence in Intermediate Age-Related Macular Degeneration

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    PurposeTo investigate the association of spontaneous drusen regression in intermediate age-related macular degeneration (AMD) with changes on fundus photography and fundus autofluorescence (FAF) imaging.DesignProspective observational case series.MethodsFundus images from 58 eyes (in 58 patients) with intermediate AMD and large drusen were assessed over 2 years for areas of drusen regression that exceeded the area of circle C1 (diameter 125 μm; Age-Related Eye Disease Study grading protocol). Manual segmentation and computer-based image analysis were used to detect and delineate areas of drusen regression. Delineated regions were graded as to their appearance on fundus photographs and FAF images, and changes in FAF signal were graded manually and quantitated using automated image analysis.ResultsDrusen regression was detected in approximately half of study eyes using manual (48%) and computer-assisted (50%) techniques. At year-2, the clinical appearance of areas of drusen regression on fundus photography was mostly unremarkable, with a majority of eyes (71%) demonstrating no detectable clinical abnormalities, and the remainder (29%) showing minor pigmentary changes. However, drusen regression areas were associated with local changes in FAF that were significantly more prominent than changes on fundus photography. A majority of eyes (64%-66%) demonstrated a predominant decrease in overall FAF signal, while 14%-21% of eyes demonstrated a predominant increase in overall FAF signal.ConclusionsFAF imaging demonstrated that drusen regression in intermediate AMD was often accompanied by changes in local autofluorescence signal. Drusen regression may be associated with concurrent structural and physiologic changes in the outer retina
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