Tanuj Dada

Evaluation of retinal nerve fiber layer thickness measurement following laser in situ keratomileusis using scanning laser polarimetry

AIM To evaluate the effect of laser-assisted in situ keratomileusis (LASIK) on the measurement of retinal nerve fiber layer thickness by scanning laser polarimetry using customized corneal compensation in myopes. MATERIALS AND METHODS Scanning laser polarimetry was performed on 54 eyes of 54 healthy patients with myopia using the glaucoma diagnostics variable corneal compensation (GDx VCC) instrument (Laser Diagnostic Technologies, San Diego, California) before and a week after LASIK. The various parameters were compared using the Students t test. RESULTS No statistically significant change was observed in any of the retinal nerve fiber layer parameters before and after LASIK. CONCLUSIONS While the measurement of retinal nerve fiber layer thickness by scanning laser polarimetry is affected by anterior segment birefringent properties and LASIK would be expected to produce changes in the same, customized corneal compensation using the GDx VCC seems to adequately compensate for these changes.

CYP1B1-mediated Pathobiology of Primary Congenital Glaucoma.

ABSTRACT CYP1B1 is a dioxin-inducible enzyme belonging to the cytochrome P450 superfamily. It has been observed to be important in a variety of developmental processes including in utero development of ocular structures. Owing to its role in the developmental biology of eye, its dysfunction can lead to ocular developmental defects. This has been found to be true and CYP1B1 mutations have been observed in a majority of primary congenital glaucoma (PCG) patients from all over the globe. Primary congenital glaucoma is an irreversibly blinding childhood disorder (onset at birth or early infancy) typified by anomalous development of trabecular meshwork (TM). How CYP1B1 causes PCG is not known; however, some basic investigations have been reported. Understanding the CYP1B1 mediated etiopathomechanism of PCG is very important to identify targets for therapy and preventive management. In this perspective, we will make an effort to reconstruct the pathomechanism of PCG in the light of already reported information about the disease and the CYP1B1 gene. How to cite this article: Faiq MA, Dada R, Qadri R, Dada T. CYP1 B1-mediated Pathobiology of Primary Congenital Glaucoma. J Curr Glaucoma Pract 2015;9(3):77-80.

Spinocerebellar ataxia 7 (SCA7) in Indian population: predilection of ATXN7-CAG expansion mutation in an ethnic population

Background & objectives: Spinocerebellar ataxia 7 (SCA7) is a rare form of neurodegenerative disorder with the clinical manifestation of cerebellar ataxia and retinal degeneration. In this study we describe the clinico-genetic characteristics of nine SCA7 families of Indian origin and cross compare these with other available worldwide studies. Methods: Thirty five individuals from nine SCA7 families were clinico-genetically characterized and CAG repeat distribution analysis was carried out in 382 control DNA samples from healthy controls (derived from 21 diverse Indian populations based on ethnic and linguistic and geographical location). Results: Of the nine families studied, 22 affected individuals and one asymptomatic carrier were identified. The average age at disease onset was 23.4±12.6 yr. The length of expanded CAG ranged from 40-94 with mean value of 53.2±13.9. The main clinical findings in affecteds individuals included cerebellar ataxia, and retinal degeneration along with hyper-reflexia (95%), slow saccades (85%) and spasticity (45%). Analysis of the association of number of CAG repeats with disease onset revealed that<49 repeats were associated with earlier age at onset in South East Asians compared to European populations. Further analysis of CAG repeats from 21 diverse Indian populations showed pre-mutable repeats (28-34) alleles in the IE-N-LP2 population. Six of the nine families identified in this study belonged to the same ethnic population. Interpretations & conclusion: Our results show that presenece of SCA7 is relatively rare and confined to one ethnic group from Haryana region of India. We observed a homogeneous phenotypic expression of SCA7 mutation as described earlier and an earlier age of onset in our patients with CAG <49. The identification of pre-mutable allele in IE-N-LP2 suggests this population to be at the risk of SCA7.

Molecular Diagnostics and Genetic Counseling in Primary Congenital Glaucoma

ABSTRACT Primary congenital glaucoma (PCG) is a childhood irreversible blinding disorder with onset at birth or in the first year of life. It is characterized by the classical traid of symptoms viz. epiphora (excessive tearing), photophobia (hypersensitivity to light) and blepharospasm (inflammation of eyelids). The only anatomical defect seen in PCG is trabecular meshwork dysgenesis. PCG shows autosomal recessive mode of inheritance with considerable number of sporadic cases. The etiology of this disease has not been fully understood but some genes like CYP1B1, MYOC, FOXC1, LTBP2 have been implicated. Various chromosomal aberrations and mutations in mitochondrial genome have also been reported. Molecular biology has developed novel techniques in order to do genetic and biochemical characterization of many genetic disorders including PCG. Techniques like polymerase chain reaction, single strand conformational polymorphism and sequencing are already in use for diagnosis of PCG and other techniques like protein truncation testing and functional genomics are beginning to find their way into molecular workout of this disorder. In the light of its genetic etiology, it is important to develop methods for genetic counseling for the patients and their families so as to bring down its incidence. In this review, we ought to develop a genetic insight into PCG with possible use of molecular biology and functional genomics in understanding the disease etiology, pathogenesis, pathology and mechanism of inheritance. We will also discuss the possibilities and use of genetic counseling in this disease. How to cite this article: Faiq M, Mohanty K, Dada R, Dada T. Molecular Diagnostics and Genetic Counseling in Primary Congenital Glaucoma. J Current Glau Prac 2013;7(1):25-35.

Cataract Surgery in Eyes with Previous Glaucoma Surgery: Pearls and Pitfalls.

ABSTRACT The problem of cataract management in the patients of glaucoma who have undergone fltering surgery is a challenging proposition for any surgeon, as the surgery can lead to several complications in the already compromised eye. As glaucoma requires lifelong management, the development of cataract is a significant concern because its treatment may lead to loss of intraocular pressure (IOP) control. This review aims to highlight the intra- and postoperative measures that may increase the chances of bleb survival following cataract surgery. How to cite this article: Dada T, Bhartiya S, Baig NB. Cataract Surgery in Eyes with Previous Glaucoma Surgery: Pearls and Pitfalls. J Current Glau Prac 2013;7(3):99-105.

Selective Laser Trabeculoplasty: An Overview.

Given the obvious quality of life concerns with medical and surgical lowering of intraocular pressure (IOP), lasers have received considerable attention as a therapeutic modality for glaucoma. Selective laser trabeculoplasty (SLT) is increasingly being used in clinical practice as both the primary procedure and as an adjunct to medical and surgical therapy. Preliminary published evidence suggests that SLT is an effective, compliance-free, repeatable and safe therapeutic modality having only minor, transient, self-limiting or easily controlled side effects with no sequelae. This review attempts a broad overview of the current knowledge of its mechanism, efficacy, indications and limitations, point out the knowledge lacunae that still exist with respect to this highly promising technology which has captured the attention of glaucoma surgeons all over the world. How to cite this article Jha B, Bhartiya S, Sharma R, Arora T, Dada T. Selective Laser Trabeculoplasty: An Overview. J Current Glau Prac 2012;6(2):79-90.

Identification and genotype phenotype correlation of novel mutations in SIX6 gene in primary open angle glaucoma

ABSTRACT Background: Recently SIX1 and SIX6 genes have been associated with primary open angle glaucoma (POAG). This study was planned to do mutation screening in SIX1 and SIX6 genes in North Indian POAG patients and correlate with clinical phenotypes. Materials and Methods: SIX1 and SIX6 genes were amplified by PCR and sequenced in 115 POAG cases and 105 controls. Four pathogenecity prediction tools (MutationTaster, PolyPhen-2 HumDiv, PolyPhen-2 HumVar and SIFT) were used to predict the pathogenicity of the missense mutations. Protein modeling studies were done to predict the effect of the missense mutations on the protein structure and function. Results: Two novel mutations p.R116G and p.R116E were observed in the SIX6 gene of patients with POAG. The mutations p.R116G and p.R116E were predicted to be pathogenic and replacement of R116 by G or E might lead to loss of interaction between DNA and R116 of wild type SIX6 protein. The patients with the mutation p.R116E had significantly more visual field damage (MD) and early age of onset of the disease. No sequence variations were observed in the SIX1 gene. Conclusion: These results expand the mutation spectrum of SIX6 gene and suggest that SIX6 gene plays an important role in POAG pathogenesis.

Impact of Childhood Glaucoma and Glaucoma Surgery on Quality of Life

There has been a fundamental shift in pediatric medicine toward patient- and family-centered care to develop collaborative partnership between patients, families, and their health-care providers. Literature, albeit limited, shows that childhood glaucoma has a significant negative effect on quality of life (QoL) of affected children. As the affected children are usually younger and require intensive long-term medical care with frequent interventions and follow-up, this may lead to significant stress in the personnel responsible for primary caregiving to these young individuals (parents or caregivers). Surgical intervention for childhood glaucoma has been found to improve the QoL of affected children and their caregivers. However, there is an unmet need to develop glaucoma-specific child-reported outcome questionnaires and to develop large studies with robust methodology which include QoL measures to help identify and further understand this pertinent aspect for holistic management of this sight-threatening condition. In the management of childhood glaucoma, ophthalmologists need to incorporate QoL tools to investigate and better understand the psychological effects in both the affected population and their caregivers. There is also a need to adapt and offer various psychological therapeutic measures to the affected population to help them cope with an important but relatively overlooked facet of this vision-threatening illness.

Evaluation of Physical Properties of Generic and Branded Travoprost Formulations

ABSTRACT Purpose: Comparative evaluation of pharmaceutical characteristics of three marketed generic vs branded travoprost formulations. Materials and methods: Three generic travoprost formulations and one branded (Travatan without benzalkonium chloride) formulation (10 vials each), obtained from authorized agents from the respective companies and having the same batch number, were used. These formulations were coded and labels were removed. At a standardized room temperature of 25°C, the drop size, pH, relative viscosity, and total drops per vial were determined for Travatan (Alcon, Fort Worth, TX, USA) and all the generic formulations. Travoprost concentration in all four brands was estimated by using liquid chromatography-coupled tandem mass spectrometry LCMS. Results: Out of the four formulations, two drugs (TP 1 and TP 4) were found to follow the United States Pharmacopoeia (USP) limits for ophthalmic formulation regarding drug concentration, while the remaining two drugs failed due to the limits being either above 110% (TP 2) or below 90% (TP 3). Two of them (TP 1 and TP 2) had osmolality of 313 and 262 mOsm respectively, which did not comply with the osmolality limits within 300 mOsm (+ 10%). The pH of all the formulations ranged between 4.7 and 5.9, and the mean drop size was 30.23 ± 6.03 uL. The total amount of drug volume in the bottles varied from 2.58 ± 0.15 to 3.38 ± 0.06 mL/bottle. Conclusion: There are wide variations in the physical properties of generic formulations available in India. Although some generic drugs are compliant with the pharmacopeia standards, this study underscores the need for a better quality control in the production of generic travoprost formulations. How to cite this article: Wadhwani M, Mishra SK, Angmo D, Velpandian T, Sihota R, Kotnala A, Bhartiya S, Dada T. Evaluation of Physical Properties of Generic and Branded Travoprost Formulations. J Curr Glaucoma Pract. 2016;10(2):49-55.

Biodegradable Collagen Implants in Trabeculectomy.

ABSTRACT Subconjunctival and subscleral fibrosis are the major causes of failure of filtering surgery. Antiproliferative agents have been successfully used to improve the long-term success of this surgery. Recent advancement in the field of glaucoma surgery has been the use of bioengineered, biodegradable, porous collagen-glycosaminoglycan matrix implant in the subconjunctival and/or subscleral space to modify the wound-healing process and reduce scar formation, hence improving the surgical success without the need for anti-fibrotic agents. Biodegradable, collagen implants have shown favorable results when used with deep sclerectomy. There have been variable results regarding the success of trabeculectomy when combined with these implants. These implants also decrease the dose of mitomycin C required with trabeculectomy and hence, decrease the side effect associated with these drugs. The use of the biodegradable implants in glaucoma surgery is still evolving and further studies are needed to find the appropriate surgical technique, the ideal size and site of placement and determine their long-term impact on trabeculectomy outcomes and complications. How to cite this article: Ichhpujani P, Dada T, Bhartiya S. Biodegradable Collagen Implants in Trabeculectomy. J Curr Glaucoma Pract 2015;9(1):24-27.