Anuradha Ganesh

Orbital involvement in sickle cell disease: A report of five cases and review literature

Purpose To present five cases of orbital infarction in sickle cell disease and review relevant literature.Method We reviewed the hospital records of 5 patients with sickle cell disease who developed a periorbital swelling during a vaso-occlusive crisis and were managed at our hospital between April 1992 and June 2000.Results The 5 patients (4 with homozygous sickle cell disease and 1 with sickle cell-β-thalassaemia disease) were aged 6-15 years with a history of multiple admissions for vaso-occlusive crises. The periorbital swelling spread to the orbit in 4 cases and resulted in proptosis (2 cases), restriction of ocular motility and visual impairment. In all 4 cases, computed tomography and/or magnetic resonance imaging of the orbits showed a mass adjacent to the orbital wall. In 2 cases the mass was identified as a haematoma. Orbital wall infarction was demonstrated in 3 cases by bone/bone marrow scintigraphy. Epidural haematomas were detected by computed tomography in one case. All patients received intravenous fluids, analgesics, broad spectrum antibiotics and steroids, as well as simple or exchange transfusion, and responded well to medical management.Conclusions Infarction of orbital bones during vaso-occlusive crises in sickle cell disease presents acutely with a rapidly progressive periorbital swelling. Haematomas frequently complicate the condition and, along with the inflammatory swelling, may lead to orbital compression syndrome. The condition is therefore sight-threatening, and necessitates prompt diagnosis and appropriate management for resolution without adverse sequelae. Imaging techniques are invaluable in the evaluation of patients. The majority of cases resolve with conservative treatment that includes steps to combat the vaso-occlusive crisis and use of systemic steroids under antibiotic cover.

Consecutive exotropia after surgical treatment of childhood esotropia: a 40-year follow-up study

Purpose:  To determine the incidence of consecutive exotropia (XT) following successful surgical correction of childhood esotropia (ET) and identify factors associated with its development.

Autozygosity mapping of Bardet–Biedl syndrome to 12q21.2 and confirmation of FLJ23560 as BBS10

Bardet–Biedl syndrome (BBS) is a genetically heterogeneous autosomal recessive disorder characterized by variable obesity, pigmentary retinopathy, polydactyly, mental retardation, hypogonadism and renal failure. In order to identify novel BBS loci we undertook autozygosity mapping studies using high-density SNP microarrays in consanguineous kindreds. We mapped a BBS locus to a 10.1 Mb region at 12q15–q21.2 in a large Omani BBS family (peak lod score 8.3 at θ=0.0 for marker D12S1722) that contained the recently described BBS10 locus. Mutation analysis of candidate genes within the target interval, including the BBS10 gene, revealed a homozygous frameshift mutation in FLJ23560 and mutations were also detected in four smaller consanguineous families with regions of autozygosity at 12q21.2. These findings (a) confirm a previous report that FLJ23560 (BBS10) mutations are a significant cause of BBS, and (b) further demonstrate the utility of high-density SNP array mapping in consanguineous families for the mapping and identification of recessive disease genes.

Orbital Infarction in Sickle Cell Disease

PURPOSE To determine the role of hematological and genetic factors in the development of orbital infarction in sickle cell disease. DESIGN Retrospective, noncomparative case series. METHODS Fourteen sickle cell disease patients were diagnosed with orbital infarction during a vaso-occlusive crisis. Clinical and radiological findings were reviewed retrospectively. Sickle cell disease patients without orbital infarction were recruited as controls after matching for disease severity. Sickle haplotypes were determined for all patients. Differences between groups were evaluated statistically. RESULTS Patients with orbital infarction in sickle cell disease presented with acute periorbital pain and swelling with or without proptosis, ophthalmoplegia, and visual impairment during a vaso-occlusive crisis. Radiological findings included orbital soft tissue swelling (100%), hematoma (orbital, 36%; intracranial, 21%), and abnormal bone marrow intensities. Severity of orbital involvement was unrelated to that of the systemic disease (Pearson correlation coefficient, -0.1567). Affected patients predominantly had the Benin haplotype (P < .00782). CONCLUSIONS Orbital infarction is a potential threat to vision in sickle cell disease patients. Magnetic resonance imaging is more specific than computed tomography or nuclear scintigraphy in the evaluation of orbital changes. The degree of severity of the orbital manifestations appears unrelated to the severity of sickle cell disease. Patients with the Benin haplotype are more likely to develop orbital infarction during vaso-occlusive crises.

Retinopathy of prematurity in VLBW and extreme LBW babies

Objective : This is a hospital-based, prospective clinical study to determine the incidence, risk factors, and outcome of extreme low birth weight and very low birth weight pre-term babies with retinopathy of prematurity (ROP) at the Sultan Qaboos University Hospital, Oman.Methods : All babies with a birth weight=/ <1500 g and gestational age =/ < 32 weeks admitted in the Neonatal Unit, were screened for ROP between 4 to 6 weeks of age and staged according to the international classification and were followed up until complete vascularization of the retina. Fifty nine babies formed the study group.Results : The overall incidence of ROP was 25.4% (15 out of 59), of which 6 babies had severe ROP and underwent cryotherapy/laser. All babies with ROP had a birth weight <1250 g and were born before 31 weeks of gestation.Conclusion: ROP is a multifactorial disease, the immature retina of the pre-term baby being the primary factor. Incidence and severity was inversely proportional to birth weight and gestational age. Multiple logistic regression analysis showed that sepsis and total parenteral nutrition to be highly significant risk factors. Repeated blood transfusions, hypotension and congenital heart disease with left to right shunt were seen to be considerably associated with the development of ROP. A decrease in overall incidence and severity of ROP was observed in this study.

Macular cysts in retinal dystrophy

Purpose of review To describe the entity of macular cysts in retinal dystrophy, differentiate it from cystoid macular edema (CME), and review the role of carbonic anhydrase inhibitors in management. Recent findings Macular cysts in retinal dystrophy are seen in retinopathies caused by mutations in the NR2E3 gene, juvenile X-linked retinoschisis (XLRS), and some other retinal dystrophies. These must be distinguished from CME. Optical coherence tomography can clearly demonstrate intraretinal cysts which may not be clinically detectable. Intravenous fluorescein angiography (IVFA) does not show macular hyperfluorescence (i.e. leakage). Molecular genetic testing aids in the diagnosis and elucidation of pathophysiology. Carbonic anhydrase inhibitors may promote resolution of the cysts resulting in visual improvement. Summary Non-CME macular cysts in retinal dystrophies can be differentiated from CME by a combination of clinical examination, IVFA, and molecular genetic testing to identify causative phenotype. Carbonic anhydrase inhibitors may be effective in promoting resolution.

Escobar variant with pursed mouth, creased tongue, ophthalmologic features, and scoliosis in 6 children from Oman

We report on six Omani children from two consanguineous families, with a multiple congenital anomaly syndrome defined by arthrogryposis multiplex congenita, typical facial appearance, ophthalmologic anomalies, atrophic calf muscles, and interdigital, neck and axillar pterygia. In addition, the patients present unique features as a furrowed tongue and enlarged corneal nerves, undescribed previously in association with other distal arhtrogryposis syndromes (DA). The patients can be classified as multiple pterygium syndrome (Escobar syndrome) but display overlapping features with Freeman–Sheldon syndrome and arthrogryposis with ophthalmologic abnormalities. We excluded two known arthrogryposis loci on chromosome 9p13 (TPM2) and 11p15 (TNNI2, TNNT3). We conclude that our patients display a subtype of multiple pterygium syndrome with overlapping features to other DAs.

Sickle cell–haemoglobin E (HbSE) compound heterozygosity: a clinical and haematological study

The paucity of clinical reports in the world literature suggests that, as a disease entity, haemoglobin SE compound heterozygosity is of negligible importance. In view of the significant community prevalence of this haemoglobinopathy in the Sultanate of Oman where it is the second most prevalent sickling disorder, a hospital study of 12 SE compound heterozygotes from six unrelated Arab families was undertaken to determine their clinico‐haematological features. Our findings were compared with those reviewed in the literature. Clinical and haematological evaluation was carried out by conventional methods including chromatographic haemoglobin analysis. At least 50% of those studied were asymptomatic throughout the study period but sickling‐related complications occurred in the rest and included the acute chest syndrome (1/12), severe vaso‐occlusive skeletal pain (2/12), frontal bossing (1/12) possibly indicative of significant chronic haemolysis and recurrent infections of the urinary tract (1/12). Steady‐state haemoglobin levels fell within the reference range while MCV and MCH values were, as expected, reduced in most cases; nevertheless, concomitant inheritance of α‐thalassaemia trait was also likely. Red cell morphology was striking by the absence or rarity of pseudo‐sickled cells in the blood films of many patients during the steady state and in crises. Bearing in mind the prevalence of 0.05% of SE compound heterozygosity in Oman, the findings in this single study of the largest number of SE patients and their relatives confirm the predominantly asymptomatic nature of this sickling disorder in individuals in the community at large. HbF levels do not appear to explain the heterogeneous nature of this haemoglobinopathy. Correlation of the variable clinical and haematological features of SE cases with their α‐globin gene status and β‐cluster haplotypes (linked to the βs‐ and βe‐genes) merits a separate investigation, which is being currently organized.

The full spectrum of persistent fetal vasculature in Aicardi syndrome: an integrated interpretation of ocular malformations

Editor,—Aicardi syndrome (OMIM 304050), a rare genetic disorder of cerebro-ocular development, is characterised by infantile spasms, psychomotor retardation, agenesis of corpus callosum, and lacunar chorio- retinopathy.1 We present an infant girl with Aicardi syndrome. In addition to chorioretinal lacunae, ophthalmic examination revealed microphthalmos, persistent pupillary membrane, posterior synechiae, posterior polar cataract, optic nerve malformation, and epipapillary and epiretinal gliosis. We believe that all these ocular anomalies other than the chorioretinal lacunae, are manifestations of persisting fetal blood vessels and should, therefore, be referred to as “persistent fetal vasculature”.  We discuss the ocular manifestations of Aicardi syndrome and their embryogenesis. We also attempt to link the ocular malformations with those of the brain. ### CASE REPORT A 22 day old baby girl was referred for evaluation of microphthalmos. She was the eighth child born to non-consanguineous parents and was delivered at term by caesarean section. There was no family history of neurological or eye disease. The baby was microcephalic (head circumference 30 cm), but did not have any facial dysmorphism. Neurological examination was unremarkable. On ophthalmic examination, the right eye was found to be microphthalmic with a horizontal corneal diameter of 8 mm. The pupil was irregular with posterior synechiae and persistent pupillary membrane (Fig 1), and the lens had a small, paraxial dot opacity on the posterior surface. Funduscopy revealed a large dysplastic disc with an eccentric coloboma. Glial tissue spread out nasally in a fan-shaped manner along the retinal surface, from the centre of the disc all the way to the ora serrata and posterior surface of the lens. The macula was partially covered …

Compliance of amblyopic patients with occlusion therapy: A pilot study.

Background: Increasing evidence shows that good compliance with occlusion therapy is paramount for successful amblyopia therapy. Purpose: To study the degree of compliance and explore factors affecting compliance in patients undergoing occlusion therapy for amblyopia in our practice. Design: Nonrandomized clinical intervention study. Materials and Methods: A total of 31 families with a child (aged 2-12 years), undergoing unilateral amblyopia treatment at the pediatric ophthalmology clinic of Sultan Qaboos University Hospital, Oman, were recruited for this one month study. Parents were interviewed and completed a closed-ended questionnaire. Clinical data including, visual acuity, refraction, diagnosis and treatment, for each patient was collected from the hospital chart and was entered in a data collection sheet. Compliance with occlusion therapy was assessed by self-report accounts of parents and was graded into good, partial, or poor. Association between various factors and degree of compliance was studied using logistic regression modeling. Results: Only 14 (45%) patients showed good compliance to occlusion therapy. 17 (55%) patients were noncompliant. Improvement in visual acuity strongly correlated with compliance to patching (P = 0.008). Other variables that were studied included, age at onset of therapy; gender; degree of amblyopia; type of amblyopia; use of glasses; and compliance with glasses. These did not emerge as significant predictors of compliance. All but one family with poor compliance stated that the main challenge in following the recommendation to patch for requisite hours was in getting their child to cooperate. Only in one instance, the family cited nonavailability of patches as the main hindrance to compliance. 10/31 (32%) families expressed a desire for more information and 18/31 (58%) parents did not understand that amblyopia meant decreased vision. Conclusion: Poor compliance is a barrier to successful amblyopia therapy in our practice. Improvement in visual acuity is associated with better compliance with patching. Parents find it difficult to comprehend and retain verbal explanations of various components regarding occlusion therapy for amblyopia. Future study with a larger sample of patients is recommended to investigate the factors affecting compliance with amblyopia therapy and determine predictors for poor compliance.