Inas F. Aboobakar

Major review: Exfoliation syndrome; advances in disease genetics, molecular biology, and epidemiology.

ABSTRACT Exfoliation syndrome (XFS) is a common age‐related disorder that leads to deposition of extracellular fibrillar material throughout the body. The most recognized disease manifestation is exfoliation glaucoma (XFG), which is a common cause of blindness worldwide. Recent developments in XFS genetics, cell biology and epidemiology have greatly improved our understanding of the etiology of this complex inherited disease. This review summarizes current knowledge of XFS pathogenesis, identifies gaps in knowledge, and discusses areas for future research. HighlightsExfoliation glaucoma (XFG) is the most common secondary form of glaucoma worldwide.Exfoliation syndrome (XFS) is increasingly associated with non‐ocular systemic disorders.The LOXL1 and CACNA1A loci are associated with XFG but not other forms of glaucoma.Abnormal levels of TGF‐&bgr;1 and homocysteine are consistently present in XFS.Environmental factors, including UV exposure, geography, and diet may influence XFS risk.

Developments in Ocular Genetics: 2013 Annual Review.

PurposeTo highlight major advancements in ocular genetics from the year 2013. DesignLiterature review. MethodsA literature search was conducted on PubMed to identify articles pertaining to genetic influences on human eye diseases. This review focuses on articles published in print or online in the English language between January 1, 2013, and December 31, 2013. A total of 120 articles from 2013 were included in this review. ResultsSignificant progress has been made in our understanding of the genetic basis of a broad group of ocular disorders, including glaucoma, age-related macular degeneration, cataract, diabetic retinopathy, keratoconus, Fuchs endothelial dystrophy, and refractive error. ConclusionsThe latest next-generation sequencing technologies have become extremely effective tools for identifying gene mutations associated with ocular disease. These technological advancements have also paved the way for utilization of genetic information in clinical practice, including disease diagnosis, prediction of treatment response, and molecular interventions guided by gene-based knowledge.

Genetics of exfoliation syndrome and glaucoma.

Exfoliation glaucoma (XFG) is the most common identifiable secondary form of open-angle glaucoma in the world. It is an ocular manifestation of exfoliation syndrome (XFS), an age-related systemic disease characterized by deposition of extracellular fibrillar material in various tissues and organs. XFS/XFG has been studied in populations around the world, which has led to identification of genetic factors that play a significant role in disease pathogenesis. Here, we summarize current knowledge of the genetics of XFS/XFG and identify areas for future research.

Association of Baseline Anterior Segment Parameters With the Development of Incident Gonioscopic Angle Closure

Importance Baseline anterior segment imaging parameters associated with incident gonioscopic angle closure, to our knowledge, are unknown. Objective To identify baseline quantitative anterior segment optical coherence tomography parameters associated with the development of incident gonioscopic angle closure after 4 years among participants with gonioscopically open angles at baseline. Design, Setting, and Participants Three hundred forty-two participants aged 50 years or older were recruited to participate in this prospective, community-based observational study. Participants underwent gonioscopy and anterior segment optical coherence tomography imaging at baseline and after 4 years. Custom image analysis software was used to quantify anterior chamber parameters from anterior segment optical coherence tomography images. Main Outcomes and Measures Baseline anterior segment optical coherence tomography measurements among participants with gonioscopically open vs closed angles at follow-up. Results Of the 342 participants, 187 (55%) were women and 297 (87%) were Chinese. The response rate was 62.4%. Forty-nine participants (14.3%) developed gonioscopic angle closure after 4 years. The mean age (SD) at baseline of the 49 participants was 62.9 (8.0) years, 15 (30.6%) were men, and 43 (87.8%) were Chinese. These participants had a smaller baseline angle opening distance at 750 µm (AOD750) (0.15 mm; 95% CI, 0.12-0.18), trabecular iris surface area at 750 µm (0.07 mm2; 95% CI, 0.05-0.08), anterior chamber area (30 mm2; 95% CI, 2.27-3.74), and anterior chamber volume (24.32 mm2; 95% CI, 18.20-30.44) (all P < .001). Baseline iris curvature (−0.08; 95% CI, −0.12 to −0.04) and lens vault (LV) measurements (−0.29 mm; 95% CI, −0.37 to −0.21) were larger among these participants ( all P < .001). A model consisting of the LV and AOD750 measurements explained 38% of the variance in gonioscopic angle closure occurring at 4 years, with LV accounting for 28% of this variance. For every 0.1 mm increase in LV and 0.1 mm decrease in AOD750, the odds of developing gonioscopic angle closure was 1.29 (95% CI, 1.07-1.57) and 3.27 (95% CI, 1.87-5.69), respectively. In terms of per SD change in LV and AOD750, this translates to an odds ratio of 2.14 (95% CI, 2.48-12.34) and 5.53 (95% CI, 1.22-3.77), respectively. A baseline LV cut-off value of >0.56 mm had 64.6% sensitivity and 84.0% specificity for identifying participants who developed angle closure. Conclusions and Relevance These findings suggest that smaller AOD750 and larger LV measurements are associated with the development of incident gonioscopic angle closure after 4 years among participants with gonioscopically open angles at baseline.

Differential expression of coding and long noncoding rnas in keratoconus-affected corneas

Purpose Keratoconus (KC) is the most common corneal ectasia. We aimed to determine the differential expression of coding and long noncoding RNAs (lncRNAs) in human corneas affected with KC. Methods From the corneas of 10 KC patients and 8 non-KC healthy controls, 200 ng total RNA was used to prepare sequencing libraries with the SMARTer Stranded RNA-Seq kit after ribosomal RNA depletion, followed by paired-end 50-bp sequencing with Illumina Sequencer. Differential analysis was done using TopHat/Cufflinks with a gene file from Ensembl and a lncRNA file from NONCODE. Pathway analysis was performed using WebGestalt. Using the expression level of differentially expressed coding and noncoding RNAs in each sample, we correlated their expression levels in KC and controls separately and identified significantly different correlations in KC against controls followed by visualization using Cytoscape. Results Using |fold change| ≥ 2 and a false discovery rate ≤ 0.05, we identified 436 coding RNAs and 584 lncRNAs with differential expression in the KC-affected corneas. Pathway analysis indicated the enrichment of genes involved in extracellular matrix, protein binding, glycosaminoglycan binding, and cell migration. Our correlation analysis identified 296 pairs of significant KC-specific correlations containing 117 coding genes enriched in functions related to cell migration/motility, extracellular space, cytokine response, and cell adhesion. Our study highlighted the potential roles of several genes (CTGF, SFRP1, AQP5, lnc-WNT4-2:1, and lnc-ALDH3A2-2:1) and pathways (TGF-β, WNT signaling, and PI3K/AKT pathways) in KC pathogenesis. Conclusions Our RNA-Seq–based differential expression and correlation analyses have identified many potential KC contributing coding and noncoding RNAs.

Optic Nerve Head Pit With Sectoral Inner Retinal Hypoplasia: A Bottomless Pit

Awoman inher late30sdiagnosed inchildhoodashavingamblyopia in the lefteyepresented forexamination.Visual acuitywasstable since childhood: 20/20OD and 20/100OSwith a relative afferent pupillary defect in the left eye, stereopsis of 100 arc-seconds, and 10 of 10 Ishihara color plates in each eye. Ophthalmoscopic examinationof the lefteyeshowedatemporalopticnerveheadpit (ONHP) and optical coherence tomography showed absence of the internal limiting membrane, ganglion cell, and nerve fiber layers in the distribution of the papillomacular bundle (Figure). Discussion Thinning of the peripapillary retinal nerve fiber layer has been described in ONHP,1,2 but this is the first case, to our knowledge, to demonstrate absence of the 3 innermost macular layers. Despite lack of earlier pictures, the stability of vision suggests this finding is congenital. This case suggests a possible association between ONHP and sectoral hypoplasia of the inner retina, which may be important to recognize in eyes with ONHP treated for amblyopia or glaucoma.3

Nonglaucomatous Cupping: Fundus Photography and Spectral Domain Optical Coherence Tomography Imaging Features.

Nonglaucomatous cupping is commonly encountered in neuro-ophthalmic practice. However, the progression of clinical and imaging findings over time has not been well described. We present serial fundus photographs and spectral domain optical coherence tomography from a pediatric patient with neuromyelitis optic spectrum disorder, which demonstrated progression of both cupping and optic atrophy in the setting of normal intraocular pressure.