Genetic Regulation of SMC Gene Expression and Splicing Predict Causal CAD Genes.

BACKGROUND: Coronary artery disease (CAD) is the leading cause of death worldwide. Recent meta-analyses of genome-wide association studies have identified over 175 loci associated with CAD. The majority of these loci are in noncoding regions and are predicted to regulate gene expression. Given that vascular smooth muscle cells (SMCs) play critical roles in the development and progression of CAD, we aimed to identify the subset of the CAD loci associated with the regulation of transcription in distinct SMC phenotypes. METHODS: We measured gene expression in SMCs isolated from the ascending aortas of 151 heart transplant donors of various genetic ancestries in quiescent or proliferative conditions and calculated the association of their expression and splicing with ~6.3 million imputed single-nucleotide polymorphism markers across the genome. RESULTS: We identified 4910 expression and 4412 splicing quantitative trait loci (sQTLs) representing regions of the genome associated with transcript abundance and splicing. A total of 3660 expression quantitative trait loci (eQTLs) had not been observed in the publicly available Genotype-Tissue Expression dataset. Further, 29 and 880 eQTLs were SMC-specific and sex-biased, respectively. We made these results available for public query on a user-friendly website. To identify the effector transcript(s) regulated by CAD loci, we used 4 distinct colocalization approaches. We identified 84 eQTL and 164 sQTL that colocalized with CAD loci, highlighting the importance of genetic regulation of mRNA splicing as a molecular mechanism for CAD genetic risk. Notably, 20% and 35% of the eQTLs were unique to quiescent or proliferative SMCs, respectively. One CAD locus colocalized with a sex-specific eQTL (TERF2IP), and another locus colocalized with SMC-specific eQTL (ALKBH8). The most significantly associated CAD locus, 9p21, was an sQTL for the long noncoding RNA CDKN2B-AS1, also known as ANRIL, in proliferative SMCs. CONCLUSIONS: Collectively, our results provide evidence for the molecular mechanisms of genetic susceptibility to CAD in distinct SMC phenotypes.

FHL5 Controls Vascular Disease-Associated Gene Programs in Smooth Muscle Cells.

BACKGROUND: Genome-wide association studies have identified hundreds of loci associated with common vascular diseases, such as coronary artery disease, myocardial infarction, and hypertension. However, the lack of mechanistic insights for many GWAS loci limits their translation into the clinic. Among these loci with unknown functions is UFL1-four-and-a-half LIM (LIN-11, Isl-1, MEC-3) domain 5 (FHL5; chr6q16.1), which reached genome-wide significance in a recent coronary artery disease/ myocardial infarction GWAS meta-analysis. UFL1-FHL5 is also associated with several vascular diseases, consistent with the widespread pleiotropy observed for GWAS loci. METHODS: We apply a multimodal approach leveraging statistical fine-mapping, epigenomic profiling, and ex vivo analysis of human coronary artery tissues to implicate FHL5 as the top candidate causal gene. We unravel the molecular mechanisms of the cross-phenotype genetic associations through in vitro functional analyses and epigenomic profiling experiments in coronary artery smooth muscle cells. RESULTS: We prioritized FHL5 as the top candidate causal gene at the UFL1-FHL5 locus through expression quantitative trait locus colocalization methods. FHL5 gene expression was enriched in the smooth muscle cells and pericyte population in human artery tissues with coexpression network analyses supporting a functional role in regulating smooth muscle cell contraction. Unexpectedly, under procalcifying conditions, FHL5 overexpression promoted vascular calcification and dysregulated processes related to extracellular matrix organization and calcium handling. Lastly, by mapping FHL5 binding sites and inferring FHL5 target gene function using artery tissue gene regulatory network analyses, we highlight regulatory interactions between FHL5 and downstream coronary artery disease/myocardial infarction loci, such as FOXL1 and FN1 that have roles in vascular remodeling. CONCLUSIONS: Taken together, these studies provide mechanistic insights into the pleiotropic genetic associations of UFL1-FHL5. We show that FHL5 mediates vascular disease risk through transcriptional regulation of downstream vascular remodeling gene programs. These transacting mechanisms may explain a portion of the heritable risk for complex vascular diseases.

Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.

AIMS: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. METHODS AND RESULTS: We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1ß (vs. vehicle), and associated with smooth muscle cell migration in vitro. CONCLUSIONS: A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.

Coral reef aorta: a rare form of obstruction of the ascending aorta in adolescent with aortopathy- case report.

BACKGROUND: Supra aortic obstruction in children is uncommon and is seen in certain unique conditions. While intraluminal obstruction due to heavy calcification is seen in older populations, it is not described in pediatric populations. The coral reef aorta is a rare and distinct calcifying disease causing luminal obstruction of the suprarenal aorta in adults. The definition of this diagnosis relies entirely on the unique aspects and consistency of the lesions, which are rock-hard, irregular, gritty plaques with a white luminal surface resembling a coral reef. However, no such case has been described in children. CASE PRESENTATION: We present an adolescent boy who presented with a heavily calcified ascending aortic lesion associated with aortopathy and hypertension, 12 years after an aortic coarctation repair. The investigations included echocardiography, magnetic resonance and computer-tomographic imaging. A 3-D model was printed in order to visualize and plan surgical steps in advance for safe placement of clamps and defining the extent of resection. In addition, it provided an idea about tissue quality, thickness, spatial relationship, and orientation in relation to surrounding structures. Successful resection and replacement of the diseased segment of the aorta were achieved on cardiopulmonary bypass support. Post-operative recovery was uneventful, and at 6-month follow-up, the patient is doing well. In this report, various aspects of such lesions have been discussed, including clinical presentations, complications, planning and conduct of a safe cardiopulmonary bypass, and precautions during surgery for a successful outcome. CONCLUSION: Complicated obstructive aortic lesions in children require careful assessment, appropriate advanced imaging, and the use of 3-D printing technology in order to plan and perform safe and effective surgical management. The etiology of severe calcified aorta in children may be related to metabolic factors, previous surgery, use of a homograft, or an inflammatory process. However, it has yet to be proven.

Multi-ancestry genetic analysis of gene regulation in coronary arteries prioritizes disease risk loci.

Genome-wide association studies (GWASs) have identified hundreds of risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWASs, and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotypes to identify quantitative trait loci for expression (eQTLs) and splicing (sQTLs) in coronary arteries from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were previously unreported in coronary artery; 19% exhibited cell-type-specific expression. Colocalization revealed subgroups of eGenes unique to CAD and blood pressure GWAS. Fine-mapping highlighted additional eGenes, including TBX20 and IL5. We also identified sQTLs for 1,690 genes, among which TOR1AIP1 and ULK3 sQTLs demonstrated the importance of evaluating splicing to accurately identify disease-relevant isoform expression. Our work provides a patient-derived coronary artery eQTL resource and exemplifies the need for diverse study populations and multifaceted approaches to characterize gene regulation in disease processes.

Integrative multi-ancestry genetic analysis of gene regulation in coronary arteries prioritizes disease risk loci.

Genome-wide association studies (GWAS) have identified hundreds of genetic risk loci for coronary artery disease (CAD). However, non-European populations are underrepresented in GWAS and the causal gene-regulatory mechanisms of these risk loci during atherosclerosis remain unclear. We incorporated local ancestry and haplotype information to identify quantitative trait loci (QTL) for gene expression and splicing in coronary arteries obtained from 138 ancestrally diverse Americans. Of 2,132 eQTL-associated genes (eGenes), 47% were previously unreported in coronary arteries and 19% exhibited cell-type-specific expression. Colocalization analysis with GWAS identified subgroups of eGenes unique to CAD and blood pressure. Fine-mapping highlighted additional eGenes of interest, including TBX20 and IL5 . Splicing (s)QTLs for 1,690 genes were also identified, among which TOR1AIP1 and ULK3 sQTLs demonstrated the importance of evaluating splicing events to accurately identify disease-relevant gene expression. Our work provides the first human coronary artery eQTL resource from a patient sample and exemplifies the necessity of diverse study populations and multi-omic approaches to characterize gene regulation in critical disease processes.

Transcriptomic-based clustering of human atherosclerotic plaques identifies subgroups with different underlying biology and clinical presentation.

Histopathological studies have revealed key processes of atherosclerotic plaque thrombosis. However, the diversity and complexity of lesion types highlight the need for improved sub-phenotyping. Here we analyze the gene expression profiles of 654 advanced human carotid plaques. The unsupervised, transcriptome-driven clustering revealed five dominant plaque types. These plaque phenotypes were associated with clinical presentation and showed differences in cellular compositions. Validation in coronary segments showed that the molecular signature of these plaques was linked to coronary ischemia. One of the plaque types with the most severe clinical symptoms pointed to both inflammatory and fibrotic cell lineages. Further, we did a preliminary analysis of potential circulating biomarkers that mark the different plaques phenotypes. In conclusion, the definition of the plaque at risk for a thrombotic event can be fine-tuned by in-depth transcriptomic-based phenotyping. These differential plaque phenotypes prove clinically relevant for both carotid and coronary artery plaques and point to distinct underlying biology of symptomatic lesions.

Long-term follow-up after recanalisation of aortic arch atresia.

AIMS: Aortic arch atresia (AAA) is one of the rarest obstructive defects. The presence of this anomaly in adult age is uncommon. The typical anatomic feature consists of a complete occlusion of the membranous obstruction resulting in an acquired atresia without flow continuity between the proximal and distal segments. This feature is important in determining the feasibility of percutaneous intervention. The aim of the present study was to share long-term follow-up data of adult patients with AAA requiring percutaneous interventions for the management of this rare anomaly involving five different centres. METHODS AND RESULTS: Retrospective data of 19 patients (12 males, 63.2%, mean age 32.2±18.9 years) diagnosed with AAA treated in five different centres between 1999 and 2017 were collected. All patients underwent percutaneous recanalisation by (1) radiofrequency (RF) system (five patients, 26.3%), (2) extra-stiff guidewire (12 patients, 63.2%), and (3) transseptal needle (two patients, 10.5%). All procedures were subsequently followed by covered stent implantation. Two patients developed complications during the procedure and one of them died. Over a median follow-up of 4.94 years, four (21%) patients were able to be weaned from medications for hypertension. All the patients underwent reassessment for recurrence or restenosis during the follow-up. Seven (36.8%) patients underwent successful stent dilatation with a balloon. After the intervention, one patient experienced a late complication; however, one patient died due to an unknown cause believed to be unrelated to the previous recanalisation procedure. CONCLUSIONS: Percutaneous treatment of AAA is feasible with good long-term survival. This study reports the largest case series so far available in the literature.

Complications of conventional scleral buckling occuring during and after treatment of rhegmatogenous retinal detachment.

OBJECTIVE: To identify and determine the frequency of the intra-operative and early postoperative complications of Conventional Scleral Buckling (CSB) as the primary surgical intervention in patients with Rhegmatogenous Retinal Detachment (RRD). STUDY DESIGN: A quasi-interventional study. PLACE AND DURATION OF STUDY: Khyber Institute of Ophthalmic Medical Sciences (KIOMS), Postgraduate Medical Institute (PGMI), Hayatabad Medial Complex (HMC), Peshawar, from April 2005 to June 2006. METHODOLOGY: Fifty consecutive patients who underwent CSB and fulfilled the inclusion criteria, were included in the study. Operative details and any intra-operative complications were noted. The patients underwent another detailed clinical examination and pain assessment on the first postoperative day. All the patients were followed-up minimum for 3 months. Postoperative complications were identified and recorded. The data was analyzed on SPSS 12.0 for measures of central tendency and dispersion. RESULTS: There were 36 male and 14 female subjects. Mean age was 37.18 + or - 20.045 years. Encirclement (56%) was the most frequently used CSB technique. Sixteen (32%) patients had at least one intra-operative complication. Intra-operative complications were iatrogenic scleral break (2%), accidental Sub Retinal Fluid (SRF) drainage (8%), choroidal haemorrhage (2%), subretinal haemorrhage (14%), retinal incarceration (2%), vitreous haemorrhage (6%), raised (4%) or very low (2%), intra-operative IOP and hyphema (2%). Postoperative complications included systemic complications (24%), choroidal detachment (8%), vitreous haemorrahge (16%), raised IOP (22%), angle closure (2%), conjunctivitis (4%), orbital cellulitis (2%), suspected endophthalmitis (2%), ocular movement disorders (2%) and explant exposure (6%). Mean refractive change in spherical equivalent was -1.478 + or - 0.698 D. Final re-attachment rate was (82%) and final BCVA of > 6/60 was achieved in 62% of the subjects in the treated eyes. CONCLUSION: CSB is a safe and effective option for treating uncomplicated RRD, but it is associated with certain complications. Sub-retinal bleed was the most common intra-operative complication. Raised IOP was most the common early postoperative complication followed by choroidal detachment.

Risk factors of preseptal and orbital cellulitis.

OBJECTIVE: To estimate the frequency and major risk factors of preseptal and orbital cellulitis. STUDY DESIGN: A cross-sectional analytical study. PLACE AND DURATION OF STUDY: The Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar from July 2003 to December 2006. METHODOLOGY: All consecutive patients between ages 6 and 40 years, admitted to the institute with the diagnosis of preseptal and orbital cellulitis were included in the study. The patients were divided into two groups. Group I included patients with ages 6-16 years and group II with ages 17-40 years. The clinical features, diagnosis and risk factors were entered on a specially-designed proforma. The risk factors included were trauma, insect bite, localized or systemic infection and postsurgical. Odd ratio and p-values were calculated for potential risk factors. RESULTS: The frequency of orbital cellulitis was 0.1% of total admission. Out of 26 patients, 42.30% patients were in group I and 57 in group II. In group I, insect bite was the most common risk factor identified in 40% of patients with preseptal cellulitis and trauma as a common cause in 50% with orbital cellulitis. In group II, trauma was the leading cause in 50% of patients with preseptal cellulitis and sinusitis as a common cause in 18.1% with those of orbital cellulitis. In both groups the p-values were found insignificant (p>0.5). Complications included cicatricial ectropion in 44.4% and orbital abscess in 41.1%. CONCLUSION: For preseptal cellulitis, insect bite was the most common cause in group I and trauma was the leading cause in group II. For orbital cellulitis, trauma was important cause in group I and sinusitis in group II.

Multi-Omics Approaches to Study Long Non-coding RNA Function in Atherosclerosis.

Atherosclerosis is a complex inflammatory disease of the vessel wall involving the interplay of multiple cell types including vascular smooth muscle cells, endothelial cells, and macrophages. Large-scale genome-wide association studies (GWAS) and the advancement of next generation sequencing technologies have rapidly expanded the number of long non-coding RNA (lncRNA) transcripts predicted to play critical roles in the pathogenesis of the disease. In this review, we highlight several lncRNAs whose functional role in atherosclerosis is well-documented through traditional biochemical approaches as well as those identified through RNA-sequencing and other high-throughput assays. We describe novel genomics approaches to study both evolutionarily conserved and divergent lncRNA functions and interactions with DNA, RNA, and proteins. We also highlight assays to resolve the complex spatial and temporal regulation of lncRNAs. Finally, we summarize the latest suite of computational tools designed to improve genomic and functional annotation of these transcripts in the human genome. Deep characterization of lncRNAs is fundamental to unravel coronary atherosclerosis and other cardiovascular diseases, as these regulatory molecules represent a new class of potential therapeutic targets and/or diagnostic markers to mitigate both genetic and environmental risk factors.

Lens opacities in adults in Pakistan: prevalence and risk factors.

PURPOSE: To investigate the prevalence and risk factors for lens opacity (LO) amongst a nationally representative sample of the adult population of Pakistan. METHODS: This national study of blindness and visual impairment (adults > or =30 years) used multistage, stratified, cluster random sampling. Grading of LO was conducted using the Mehra/Minassian classification system. LO, partly or wholly obscuring the red reflex, or previous cataract surgery were indicators of opacity. RESULTS: 16,402 (94.7%) adults were included in this analysis (study conducted 2002-2003). A total of 4,096 (standardized prevalence 20.9%, 95%CI: 20.3, 21.5%) adults were found to have LO. The highest prevalence of LO was found in Punjab province (22.2%), the lowest in Balochistan Province (18.0%). Significant positive associations were increasing age (multivariable odds ratio (OR) 3.2: 95%CI: 3.1, 3.4), hypertension (OR 1.2, 95%CI: 1.1, 1.3), history of diabetes (OR 2.6: 95%CI 2.0, 3.2) and smoking (OR 1.3: 95%CI: 1.1, 1.5). Higher body mass index (BMI) (OR 0.8: 95%CI 0.7, 0.9, heavy vs. normal BMI) and attendance to school (OR 0.6: 95%CI: 0.5, 0.8) were associated with lower risk of LO. Individuals in districts classified as hot were at significantly increased risk (OR 1.3: 95%CI: 1.1, 1.5), and those in wet districts (> 600 mm annual rainfall) had lower odds than individuals living in dry districts (OR 0.7: 95%CI: 0.6, 0.8). CONCLUSIONS: Almost a fifth of the adult population had LO. Significant positive associations were age, smoking status, hypertension, diabetes, and increased deprivation level. Protective factors included high BMI and educational achievement. The climatic associations offer novel hypothesis for further research into cataractogenesis.

Spectrum of ocular surface squamous neoplasia.

OBJECTIVE: To describe the pattern of ocular surface squamous neoplasia (OSSN), clinical presentations, the risk factors and treatment options. DESIGN: An observational case series. PLACE AND DURATION OF STUDY: Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar, from April 2003 till August 2006. PATIENTS AND METHODS: The study included 36 eyes of 35 patients with biopsy-proven ocular surface neoplasia. The details of patients regarding age, gender, laterality and risk factors were entered into a specially-designed proforma. Each patient was also assessed biomicroscopically for type and complications of ocular surface neoplasia. RESULTS: The frequency of OSSN was 0.37 among admitted hospital patients. Among 36 cases of OSSN, squamous cell carcinoma of the conjunctiva was the most common type of OSSN seen in 63.9%, followed by carcinoma in situ of conjunctiva in 25% and carcinoma in situ of cornea in 11.1%. Male patients outnumbered female (65.7% vs 34.3%) with 71.42% of patients above 60 years of age. The risk factors identified were: old age, ultraviolet B exposure and xeroderma pigmentosa. Treatment consisted of local resection with or without adjuvant therapy in 61.1%, exenteration in 30.5%, enucleation in 5.5% and chemo/radiotherapy in 2.7%. Intraocular invasion was seen in 5.5% and orbital spread in 30.5%. CONCLUSION: The frequency of OSSN was 0.37% among admitted patients. Identification of exact etiological factors will enable to formulate strategies that are likely to decrease the incidence of this disease and the associated morbidity and mortality.

Patterns of ocular trauma.

OBJECTIVE: To describe the patterns of ocular trauma, cause of injury and its effects on eye. DESIGN: A retrospective case series. PLACE AND DURATION OF STUDY: Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar, from January 1999 to June 2004. PATIENTS AND METHODS: Medical records of 1105 patients admitted with ocular trauma were reviewed. The details of patients regarding age, gender, literacy, cause of injury and its effects on eye were entered into specially-designed performa. Sample selection consisted of all patients with history of ocular trauma and who were admitted to hospital. Population details consisted patients who were referred to the hospital from all parts of N.W.F.P. Thus, the frequency of trauma in the hospital admissions was analysed. RESULTS: Ophthalmic trauma comprised 6.78% of the hospital admission. One thousand one hundred and five patients presented with eye injuries. Out of them, 21 patients suffered from trauma to both eyes. Almost 80% patients were male and 69% patients were below 30 years of age. Delayed presentation was more common and 63.61% patients presented after one week. Open globe injuries were more common [520 eyes (46.18%)] than closed globe injuries [484 eyes (42.98%)]. 23.26% of open globe injuries were associated with intraocular and intra-orbital foreign bodies. Superficial non-perforating, eyelid and adnexal and burns were seen in 122 eyes (10.83%). Among the complications, lens damage and hyphema was seen in more than 50% of the patients, 16.60% eyes were infected at the time of admission and 4.88% of eyes needed enucleation or evisceration. The common causes of injury were violence in 37.37%, occupational in 24.43% and domestic accidents in 19.18%. CONCLUSION: Ophthalmic trauma is a major public health problem. Majority of the involved are male and under 30 years of age. Delayed presentation is more common. Open globe injuries are more frequent. Violence and occupational injuries are the major causes.

Frequency and causes of bilateral occular trauma.

OBJECTIVE: To determine the frequency and causes of bilateral ocular trauma. DESIGN: A descriptive case series. PLACE AND DURATION OF STUDY: Khyber Institute of Ophthalmic Medical Sciences, Hayatabad Medical Complex, Peshawar from October 1999 to September 2006. PATIENTS AND METHODS: All patients coming to the hospital with bilateral eye trauma and requiring admission were recruited into the study. The details of patients' demographics, risk factors, ocular examination, treatment offered and final visual acuity were noted and described as frequency and percentages. RESULTS: Out of a total of 1551 patients of hospitalized ocular trauma, 46 (2.9%, 92 eyes) had bilateral ocular trauma. The majority (54.3%) were due to landmine blast injuries followed by dynamite blast in 10.8%, coalmine blast and firearm injury in 6.5% each. Pressure cooker explosion and road traffic accident was the cause in 4.3% each. Gas cylinder and automobile battery explosion, alkali and acid burn, assault and incidental trauma occurred in 2.1%. Sixty three percent were between 16 and 40 years of age. Males were affected in 93.4%. Corneal and / or scleral repair was done in 58.6%, conjunctival and or corneal foreign body removal in 26% and extracapular cataract extraction with intraocular lens implantation in 16.3%. The visual acuity was in the range of 6/60 and perception of light in 54.3%, while in 21.7%, there was no perception of light at the time of admission. Due to severity of injury, the final visual acuity was poor and only 28.2% regained vision between 6/18 and 6/60. CONCLUSION: In this series, landmine, dynamite and coalmine blasts were the major causes of bilateral ocular trauma. Victims were usually young males. Due to severity of ocular trauma, majority had poor visual outcome.

Glaucoma admissions and surgery in public sector tertiary care hospitals in pakistan: results of a national study.

PURPOSE: To assess the annual number of glaucoma operations and admissions in the public sector tertiary care hospitals in Pakistan. METHODS: Eye departments in all 18 public tertiary care centers in the country were requested to provide data on the number of glaucoma operations and admissions during 1998. Of these, 13 hospitals agreed to participate. Eye departments' log books or patients' records were used to collect data retrospectively on the total number of eye admissions, the total number of glaucoma admissions, the type of glaucoma, and the total number and type of glaucoma operations. RESULTS: Glaucoma accounted for 8.1% (1,942/23,931) of all eye admissions. Open-angle glaucoma was responsible for 37.6% or 731 glaucoma admissions followed by secondary glaucoma (35.0%) and angle-closure glaucoma (18.2%). During 1998, 1,407 glaucoma-related operations were performed in the selected hospitals. The mean (+/-SD) and the median number of operations performed were 108.2 (+/-59.6) and 112 (range: 17-206), respectively. Trabeculectomies accounted for 1,043 (74.1 %) of all procedures. Their number ranged from 16 to 170 (median: 84) in the selected hospitals. CONCLUSIONS: We believe that the annual number of glaucoma operations performed in the public tertiary care hospitals in Pakistan is far less than required. In-depth research is therefore needed to explain if this is because of gaps in service provision or a genuine shift to medical management of glaucoma on an outpatient basis.

Perceptions of eye health in schools in Pakistan.

BACKGROUND: Research exploring children's and their teachers' perceptions of eye health is lacking. This paper reports for the first time on perceptions of primary schoolchildren and their teachers of healthy and diseased eyes, things that keep eyes healthy and damage them, and what actions to be taken in case of an eye injury. METHODS: Using draw and write technique, 160 boys and girls (9-12 years old) attending four primary schools in Abbottabad district, northern Pakistan, were invited to draw pictures in response to a set of semi-structured questions and then label them. Sixteen teachers who were currently teaching the selected students were interviewed one-on-one. RESULTS: Analysis of text accompanying 800 drawings and of the interview scripts revealed that most children and teachers perceived healthy eyes to be those which could see well, and diseased eyes to be those which have redness, watering, dirty discharge, pain, and itching; or those which have "weak eyesight" and blindness. Among things that students and teachers thought damage the eyes included sun, television, and sharp pointed objects, particularly pencils. Teachers noted that children with eye problems "have difficulty seeing the blackboard well", "screw up their eyes", and "hold their books too close". CONCLUSION: We conclude that schoolchildren and their teachers had a good knowledge of eye health, but many of them had serious misconceptions e.g., use of kohl, medicines and eye drops keeps eyes healthy. Kohl is an important source of lead and can reduce children's intelligence even at low blood levels. Health education in schools must take into account children's existing knowledge of and misconceptions about various aspects of eye health. Such steps if taken could improve the relevance of eye health education to schoolchildren.

Prevalence of diabetic retinopathy among individuals screened positive for diabetes in five community-based eye camps in northern Karachi, Pakistan.

BACKGROUND: Population-based data on the prevalence of diabetic retinopathy in Pakistan are lacking. We determined the prevalence of diabetic retinopathy among individuals screened positive for diabetes in five community-based eye camps in northern Karachi, Pakistan. METHODS: In summer 2002, five community-based eye camps were set up in Karachi, Pakistan's largest city. All individuals aged 30 years or older who visited the camps were requested to participate in the study. Those who agreed were screened for diabetes and those found to have the disease were referred to an eye hospital for diabetic retinopathy screening. Verbal informed consent was obtained from all participants at the examination site. Our main outcome measure was diabetic retinopathy, which was classified as non-proliferative diabetic retinopathy (NPDR), severe NPDR, and proliferative diabetic retinopathy (PDR). Our grading was based on clinical examination. RESULTS: A total of 912 subjects were screened for diabetes mellitus. Of these, 160 (17.5%) had diabetes- 1.8% had type I diabetes and 15.9% had type II diabetes. One hundred and eight individuals visited the hospital for ophthalmic examination. Of them, 15.7% had diabetic retinopathy. The prevalence of diabetic retinopathy was higher among individuals with type I diabetes, with greater duration of diabetes, and among women. The commonest form of diabetic retinopathy was non-proliferative (76.5% [mild: 35.3%, moderate: 29.4%, and severe: 11.8%]), followed by maculopathy (17.6%) and proliferative diabetic retinopathy (5.9%). CONCLUSION: More systematic and population-based research is needed to estimate the prevalence of and identify risk factors for diabetic retinopathy in Pakistan.

Stent dilatation of atretic aortic coarctation in an adult-case report and literature review.

BACKGROUND: Patients with functional aortic interruption of the descending thoracic aorta at the isthmus due to severe coarctation in association with atretic lumen are extremely rare in the adult population. The management is challenging and carries high morbidity and mortality. CASE PRESENTATION: We describe successful percutaneous reconstruction using a covered stent in a similar patient who is doing well two-years after intervention. A literature search was done to explore management strategies and their long-term outcomes for better understanding. CONCLUSIONS: This report is an attempt to highlight the role of minimal invasive approach in the management of rare, severe coarctation of the aorta in adult patients to avoid morbidity and mortality associated with more invasive procedures.

Prevalence and causes of blindness and low vision in a rural setting in Pakistan.

PURPOSE: To determine the prevalence and causes of blindness and visual impairment in people 40 years of age and older in Budni, Peshawar, Pakistan. METHODS: A population-based cross-sectional study was carried out involving 1,106 men and women 40 years of age and older in a rural area in Pakistan's North West Frontier Province (NWFP). All subjects with a presenting visual acuity < 6/18 in either eye were referred to a centralized clinic for a standardized eye examination that included refraction and dilated fundal examination. The main outcome was blindness (presenting visual acuity < 3/60 in the better eye) and low vision (presenting VA < 6/18-3/60 in the better eye). RESULTS: Of 1,106 people examined, 21 (1.9%; 95% CI: 1.1-2.7%) were blind, while another 27 (2.4%) and 62 (5.5%) subjects had severe visual impairment (< 6/60-3/60) and visual impairment (< 6/18-6/60), respectively. Women, as compared to men, had a higher prevalence of visual impairment and severe visual impairment; but they had a lower prevalence of blindness (1.6 vs. 2.2%); however, the difference was not statistically significant (0.6%; 95% CI: -0.9-2.1%). Similarly farmers had the highest prevalence of blindness. The leading cause of blindness and low vision was cataract, which accounted for 14 of 21 (66.6%) cases of blindness and 49 of 89 (55.5%) cases of low vision. The second leading cause of blindness was uncorrected aphakia. CONCLUSION: Much of the blindness was due to unoperated cataract and uncorrected aphakia. Thus, there is an urgent need to develop ways in which cataract surgical output could be increased, and glasses provided to those who need them.