Shashikant Shetty

Mutational Screening of LCA Genes Emphasizing RPE65 in South Indian Cohort of Patients

Background Leber congenital amaurosis (LCA) is the most severe form of inherited retinal visual impairment in children. So far, mutations in more than 20 genes have been known to cause LCA and among them, RPE65 is a suitable candidate for gene therapy. The mutational screenings of RPE65 and other LCA genes are requisite in support of emerging gene specific therapy for LCA. Therefore, we have carried out a comprehensive LCA genes screening using a combined approach of direct sequencing and DNA microarray based Asper chip analysis. Methodology/Principal Findings Thirty clinically diagnosed index LCA cases from Southern India were screened for coding and flanking intronic regions of RPE65 through direct sequencing. Among thirty, 25 cases excluded from RPE65 mutations were subjected to Asper chip analysis, testing 784 known pathogenic variations in 15 major LCA genes. In RPE65 screening, four different pathogenic variations including two novel (c.361insT & c.939T>A) and two known (c.394G>A & c.361delT) mutations were identified in five index cases. In the chip analysis, seven known pathogenic mutations were identified in six index cases, involving genes GUCY2D, RPGRIP1, AIPL1, CRX and IQCB1. Overall, 11 out of 30 LCA cases (36.6%) revealed pathogenic variations with the involvement of RPE65 (16.6%), GUCY2D (10%), RPGRIP1 (3.3%), AIPL1 (3.3%) and CRX & IQCB1 (3.3%). Conclusions/Significance Our study suggests that such combined screening approach is productive and cost-effective for mutation detection and can be applied in Indian LCA cohort for molecular diagnosis and genetic counselling.

Bilateral persistent fetal vasculature: A study of 11 cases

PURPOSE To describe the clinical and radiologic features of patients with bilateral persistent fetal vasculature (PFV). METHODS All patients diagnosed with symmetric, bilateral PFV over a 3.5-year period were included in this representative, observational case series. Only patients with more or less symmetrical disease in both eyes were included. Examination under anesthesia was performed in all but 1 case. B-scan ultrasonography of the eye was performed in all cases. A computed tomographic or magnetic resonance imaging scan was done if the ocular ultrasonography was inconclusive. A systemic workup was performed to rule out associated systemic anomalies. RESULTS The study group included 11 patients. Of the 22 eyes studied, 20 (91%) showed features of both the anterior and the posterior forms of PFV. Two children tested positive for IgM rubella antibodies. Ten eyes (45.5%) had a horizontal corneal diameter of less than 10 mm. Fifteen eyes (68.2%) had cataract at presentation. Intraocular pressure was >21 mm Hg in 17 eyes (77.3%). CONCLUSIONS Microcornea and cataract were common findings. Bilateral PFV cases were more commonly associated with combined anterior and posterior PFV. Bilateral PFV, although infrequent, should be considered in the differential diagnosis of bilateral leukocoria.

Surgical outcome in monocular elevation deficit: A retrospective interventional study

Background and Aim: Monocular elevation deficiency (MED) is characterized by a unilateral defect in elevation, caused by paretic, restrictive or combined etiology. Treatment of this multifactorial entity is therefore varied. In this study, we performed different surgical procedures in patients of MED and evaluated their outcome, based on ocular alignment, improvement in elevation and binocular functions. Study Design: Retrospective interventional study. Materials and Methods: Twenty-eight patients were included in this study, from June 2003 to August 2006. Five patients underwent Knapp procedure, with or without horizontal squint surgery, 17 patients had inferior rectus recession, with or without horizontal squint surgery, three patients had combined inferior rectus recession and Knapp procedure and three patients had inferior rectus recession combined with contralateral superior rectus or inferior oblique surgery. The choice of procedure was based on the results of forced duction test (FDT). Results: Forced duction test was positive in 23 cases (82%). Twenty-four of 28 patients (86%) were aligned to within 10 prism diopters. Elevation improved in 10 patients (36%) from no elevation above primary position (-4) to only slight limitation of elevation (-1). Five patients had preoperative binocular vision and none gained it postoperatively. No significant postoperative complications or duction abnormalities were observed during the follow-up period. Conclusion: Management of MED depends upon selection of the correct surgical technique based on employing the results of FDT, for a satisfactory outcome.

Improvement in visual acuity following surgery for correction of head posture in infantile nystagmus syndrome.

PURPOSE To report the effect of the abnormal head posture (AHP) correcting procedures on the visual acuity improvement in patients with infantile nystagmus syndrome (INS) and the visual acuity improvement outcomes in different AHP correcting surgeries in INS. METHODS This was a prospective, non-randomized, interventional study. Twenty-eight patients underwent the Anderson-Kestenbaum procedure or the modified Anderson procedure with or without tenotomy of at least one horizontal recti for correction of AHP. Best-corrected binocular null zone acuity and degree of AHP was recorded preoperatively and compared with those done 1 month postoperatively. RESULTS The average null zone logarithm of the minimum angle of resolution acuity was 0.42 preoperatively, which improved significantly to 0.33 postoperatively (P = .002). The AHP ranged from 10° to 40° (mean: 20.89°), which improved significantly to a mean of 3.21° (P = .000). No significant difference (P = .65) was found in the visual acuity improvement among patients who underwent the Anderson-Kestenbaum procedure or the modified Anderson procedure with or without tenotomy. No significant difference in the visual acuity improvement was seen in patients who underwent tenotomy of at least one horizontal rectus muscle along with the modified Anderson procedure compared to those who underwent the modified Anderson procedure alone (P = .28). CONCLUSION The procedures used mainly for correction of AHP in INS do yield significant improvement in the visual acuity. This improvement is seen in patients undergoing surgery for both horizontal and vertical AHP.

Wildervanck syndrome associated with cleft palate and short stature.

We report a case of Wildervanck syndrome exhibiting Klippel-Feil anomaly, Duane retraction syndrome and deafness. Since the first case was reported in 1952, there have been more reports describing this triad, either complete or incomplete. Our patient had the complete triad of the syndrome along with cleft palate and short stature. Also, a review of the literature regarding this syndrome is presented here.

Pupillary-iris-lens membrane with goniodysgenesis: a case report.

We describe a rare case of pupillary-iris-lens membrane with goniodysgenesis, a unilateral neurocristopathy. The membrane represents ectopic iris on the lens with abnormal iris stroma and anterior chamber angle from aberrant induction, migration or regression of neural crest cells. The membrane can be progressive. Catastrophic vision loss from angle closure can occur and may be controlled with surgery. This subject needed treatment for amblyopia.

Analysis of the SALL4 gene in patients with Duane retraction syndrome in a South Indian population.

Duane retraction syndrome (DRS) is a congenital eye movement disorder characterized most typically by partial or complete failure of abduction and narrowing of palpebral fissure with globe retraction on adduction. Recently mutations of the SALL4 gene on chromosome 20 have been linked to DRS associated with radial forearm malformations (Okihiro syndrome). In this prospective, non-interventional study we screened for SALL4 mutations in 72 patients clinically diagnosed as having isolated DRS or DRS associated syndromes. All four exonic and the neighboring intronic regions of SALL4 gene were amplified by sixteen sets of primers using polymerase chain reaction and were subjected to bi-directional sequencing and BLAST analysis. No genetic variations were detected in the coding region and in the neighboring intronic regions of the SALL4 gene suggesting an alternative mechanism in the pathogenesis of these disorders in the South Indian population.

Atypical presentation of an unusual foreign body.

A 14-year-old boy presented with intractable diplopia for 10 days following an assault. A thorough history revealed that he was unaware of any penetrating injury. However, imaging demonstrated a radiolucent foreign body between the globe and the orbital floor. On surgical exploration, it was found to be the proximal part of a ball point pen. Its removal resulted in complete resolution of diplopia. Thorough clinical and radiological examination is recommended when a foreign body is suspected in pediatric patients. Prompt diagnosis will aid in early intervention and prevention of long-term complications.

Bilateral spontaneous hyphaema in juvenile xanthogranuloma

This report describes a rare occurrence of bilateral, spontaneous, nontraumatic hyphema in a 6 weeks old infant, associated with a small, multiple skin lesions. The diagnosis of juvenile xanthogranuloma was confirmed by histopathological examination of the cutaneous lesions. The hyphaema cleared gradually in 2 weeks time with conservative management.

Atypical association of Duane retraction syndrome and Bardet Biedl syndrome.

Duanes retraction syndrome (DRS) includes changes in palpebral fissure width along with restriction of ocular motility. Bardet Biedl syndrome (BBS) includes presence of retinitis pigmentosa (RP) with obesity, mental retardation, polydactyly and renal abnormalities. We report a case of rare association of DRS with BBS in a seven-year-old child. The ocular motility examination revealed left DRS with esotropia. Fundus examination revealed findings characteristic of an atypical retinitis pigmentosa. The electro-retinogram waveforms were extinguished both for rods and cones. He was diagnosed as a case of BBS on the basis of the ophthalmological findings plus association with the systemic features of obesity, polydactyly, hypogonadism, mental retardation and renal abnormalities. This case gives further evidence of the fact that BBS may be associated with abnormalities of eye movements.