Netarsudil monotherapy as the initial treatment for open-angle glaucoma and ocular hypertension in Indian patients: A real-world evaluation of efficacy and safety.

Purpose: Glaucoma is the second leading cause of blindness worldwide, affecting more than 64 million people aged 40-80. The best way to manage primary open-angle glaucoma (POAG) is by lowering the intraocular pressure (IOP). Netarsudil is a Rho kinase inhibitor, the only class of antiglaucoma medications that reorganizes the extracellular matrix to improve the aqueous outflow through the trabecular pathway. Methods: An open-label, real-world, multicentric, observation-based 3-month study was performed for assessing the safety and ocular hypotensive efficacy of netarsudil ophthalmic solution (0.02% w/v) in patients with elevated IOP. Patients were given netarsudil ophthalmic solution (0.02% w/v) as a first-line therapy. Diurnal IOP measurements, best-corrected visual acuity, and adverse event assessments were recorded at each of the five visits (Day-1: screening day and first dosing day; subsequent observations were taken at 2 weeks, 4 weeks, 6 weeks, and 3 months). Results: Four hundred and sixty-nine patients from 39 centers throughout India completed the study. The mean IOP at baseline of the affected eyes was 24.84 ± 6.39 mmHg (mean ± standard deviation). After the first dose, the IOP was measured after 2, 4, and 6 weeks, with the final measurement taken at 3 months. The percentage reduction in IOP in glaucoma patients after 3 months of once-daily netarsudil 0.02% w/v solution use was 33.34%. The adverse effects experienced by patients were not severe in the majority of cases. Some adverse effects observed were redness, irritation, itching, and others, but only a small number of patients experienced severe reactions, as reported in a decreasing order: redness > irritation > watering > itching > stinging > blurring. Conclusion: We found that netarsudil 0.02% w/v solution monotherapy when used as the first-line treatment in primary open-angle glaucoma and ocular hypertension was both safe and effective.

Open-angle glaucoma in a rural and urban population in Eastern India-the Hooghly river glaucoma study.

Purpose: Glaucoma is the leading cause of irreversible blindness in the world. The current study aims to estimate prevalence, features, and associations of open angle glaucoma (OAG) in a rural and urban East Indian population. Methods: This is a population based cross sectional study with two arms, rural (28 contiguous villages from 13 Gram Panchayats in Balagarh Police Station, Hooghly district) and urban (Kolkata). Individuals residing in the study area aged 40 years and above were included using multistage random cluster sampling. All subjects underwent a detailed ophthalmic examination at our base hospitals including applanation tonometry, ultrasound pachymetry, gonioscopy, and frequency doubling technology perimetry. The primary outcome was the prevalence of POAG (95% CI). Age and gender specific prevalence estimates were calculated. Multiple logistic regressions were used to analyze the risk factors. Results: Data from 7128 and 6964 subjects aged 40 years or older from Kolkata city and Hooghly district, respectively were analyzed. In the urban population, 2.10% (95% CI: 1.99-2.21%) had POAG and 0.15% (95% CI: 0.13-0.17%) had secondary OAG. In the rural population, 1.45% (95% CI: 0.59-2.31%) had POAG and 0.10 ± 0.03% (95% CI: 0.07-0.13%) had secondary OAG. Conclusion: The study concludes that higher age, higher vertical cup disc ratio (VCDR), and lower central corneal thickness (CCT) are important independent predictors of OAG and emphasizes that increased intraocular pressure (IOP) is not POAG. Gonioscopy, disc evaluation, and screening perimetry need to be incorporated in the detection protocol for glaucoma if we intend to lighten the burden of blindness due to glaucoma.

Angle closure glaucoma in rural and urban populations in eastern India-The Hooghly River Glaucoma Study.

Purpose: To estimate the prevalence, features, and associations of primary angle closure disease (PACD) in rural and urban populations from West Bengal in eastern India. Methods: This was a population-based cross-sectional study with two arms, rural and urban. The rural study area consisted of 28 contiguous villages from 13 gram panchayats in Balagarh Police Station, with rural base hospital at Dhobapara, Balagarh Police Station, in the village Kuliapara of Hooghly district. A tertiary eye hospital in central Kolkata was the urban study center. Individuals residing in the study area aged 40 years and above were included in this study using multistage random cluster sampling. All subjects underwent a detailed ophthalmic examination at our base hospitals including applanation tonometry, ultrasound pachymetry, gonioscopy, and frequency doubling technology perimetry. Data collected were analyzed using SPSS 13. Multiple logistic regressions were used to analyze risk factors for PACD. Results: A total of 7,408 and 7,248 subjects aged 40 years or older were enumerated from Hooghly district and Kolkata city, respectively. PACD was detected in 1.9% subjects in rural arm and 1.54% subjects in the urban arm (P < 0.001). In rural arm, 0.3% had PACS, 0.56% had PAC, and 1.03% had PACG. In urban arm, 0.22% had PACS, 0.35% had PAC, and 0.97% had PACG. Conclusion: The study concludes that higher age, higher CCT, and shorter axial length/presence of hyperopia are important independent predictors of ACD. ACD is more common in eastern India than previous estimates.

Prevalence of glaucoma in Eastern India: The Hooghly River Glaucoma Study.

CONTEXT: Glaucoma is the leading cause of global irreversible blindness. No recent study with adequate sample size has been carried out to estimate glaucoma prevalence in Eastern India. AIMS: The aim of this study was to assess and compare the prevalence and types of glaucoma in a rural and urban East Indian population. SETTINGS AND DESIGN: The Hooghly River Glaucoma Study (HRGS) is a population-based cross-sectional study from West Bengal. A tertiary hospital in Kolkata was our urban study center. Our rural study area included 28 contiguous villages from the district of Hooghly surrounding the rural base hospital located at Dhobapara in village Bakulia. Individuals aged 40 years and above were included in this study. SUBJECTS AND METHODS: All subjects underwent a detailed ophthalmic examination at our base hospitals including applanation tonometry, ultrasound pachymetry, gonioscopy, and frequency doubling technology perimetry. Glaucoma was defined using modified International Society of Geographical and Epidemiological Ophthalmology criteria. STATISTICAL ANALYSIS USED: Analysis was performed using Chi-square test and multiple logistic regression using SPSS. RESULTS: Totally, 14,092 individuals participated; 2.7% were detected to have glaucoma in rural arm and 3.23% in urban arm (P < 0.001). In urban population, 2.10% had primary open angle glaucoma (POAG), 0.97% had primary angle closure glaucoma (PACG), and 0.15% had secondary glaucoma. In rural population, 1.45% had POAG, 1.15% had ACG, and 0.10% had secondary glaucoma. CONCLUSIONS: HRGS is the largest population-based glaucoma study in India to date with glaucoma prevalence comparable to other landmark Indian studies. POAG was the most common form of glaucoma in our study population as well. PACG was more common in this region than previously thought.

Effect of bridgehead substitution in the Grob fragmentation of norbornyl ketones: a new route to substituted halophenols.

Grob fragmentation of suitably designed bicyclic species often generates novel organic skeletons in a facile manner. Herein, we report a comprehensive account of an effective acid-catalyzed Grob fragmentation of trihalonorbornyl ketones to dihalophenol derivatives in good yields. The transformation entails tri-n-butyltin hydride (TBTH) mediated regioselective reduction of one of the two bridgehead halogens of readily available Diels-Alder adducts resulting from 1,2,3,4-tetrahalo-5,5-dimethoxycyclopentadiene and vinyl acetate derivatives, followed by its conversion to substituted halophenol species via a three-step hydrolysis-oxidation-rearrangement/aromatization strategy. Both alkyl and aryl substituted norbornyl ketones were studied. A detailed mechanistic analysis employing an isotope labeling experiment revealed plausible mechanistic pathways. Among the two bridgehead substituents, when halogen (X = Cl, Br) stays at C-1 and hydrogen (H, or deuterium, D) at C-4, then product formation takes place via exclusive protonation (supplied by an external acid) at ß carbon (i.e. C-1) of a dienol moiety formed in situ during the Grob-fragmentation, followed by the removal of acidic 4-H (or 4-D) and halide ion (X(-)) from the resulting cyclohexenone intermediate prior to nucleophilic attack on the oxocarbenium ion by X(-) and final enolisation of cyclohexadienone species. A sharp deviation was observed with the regioisomeric bicyclic ketone, wherein the 4-X triggers a facile removal of X(-) and forms the end products without necessitating the involvement of the C-1 substituent (i.e. 1-H/D), thereby retaining it in the final halophenols. It clearly demonstrates how the bridgehead substituents in the two regioisomeric trihalo-norbornyl ketones steer the bicyclic systems to follow entirely different reaction pathways thus suggesting their crucial yet distinct roles in the overall reaction. The present transformation thus manifests the relevance of bridgehead substituents in the Grob fragmentation of such norbornyl systems. Our current strategy also allows one to access ortho-deuterated halophenol compounds.

Prevalence of dry eye diseases in hospital-based population in West Bengal, Eastern India.

To determine the prevalence of dry eye diseases in general clinical ophthalmic practice in a hospital-based population in West Bengal, Eastern India, a cross-sectional study was undertaken among 3023 subjects with the age of > or = 30 years, attending general ophthalmic clinic in a tertiary eye hospital. Demographics, detailed history and 6-items McMonnies' dry eye questionnaire were asked. Tear film break-up time (TBUT), Schirmer-I test, Rose Bengal (RB) staining, slit lamp examination and Meibomian gland dysfunction (MGD) were studied. Dry eye diseases were significantly higher in women than in men ie, 51.9% versus 48.1% (p < 0.01). Symptom-based dry eye (one or more symptoms present often or most of the time) was diagnosed in 1234 subjects (40.8%). With symptoms and at least one sign [TBUT < 10 seconds, RB staining (van Bjisterveld score: 4 or more) and Schirmer-I test = 5 mm in 5 minutes], the prevalence of dry eye was 786 (26%). Different grades of MeibOmian gland dysfunction (MGD) were detected in 957 cases (31.7%). Primary Sjogren syndrome was found in 21.5%; and 10.9% patients of dry eye had some form of systemic collagen vascular disorders. Using computers was not a risk factor in this geographical area. No significant correlation was seen between significant symptoms and positive signs in the study population. The prevalence of dry eye disease is high in West Bengal, Eastern India in hospital-based population. The risk is higher with age, female gender, systemic collagen diseases and with oral antidepressant/anxiolytic medication. Meibomian gland dysfunction is found to be common among dry eye subjects.

Mutations in MYOC gene of Indian primary open angle glaucoma patients.

PURPOSE: Glaucoma is the second leading cause of blindness worldwide after cataract. Defects in the myocilin gene (MYOC) have been shown to be associated with Primary Open Angle Glaucoma (POAG), the most common form of the disease, especially in its juvenile form. Most of the reported mutations in MYOC are in POAG patients of Caucasian origin. A few studies have been reported on Asian patients (such as Chinese, Japanese, and Koreans) but none from the Indian subcontinent. The purpose of this study was to investigate the molecular basis of POAG among Indians, using MYOC as the candidate gene, and broaden our understanding on the pathogenesis caused by MYOC. METHODS: Fifty-six unrelated POAG patients, comprising 39 sporadic cases and 17 patients having familial history for POAG were enrolled in this study. The coding sequence of the gene was amplified by polymerase chain reaction (PCR) using genomic DNA from 30 POAG patients, followed by sequencing of the PCR products. Nucleotide changes were detected by identifying double peaks in the chromatogram due to heterozygosity and pairwise BLAST analysis of the sequence output data against the normal copy of the MYOC cDNA. Alteration of restriction sites due to nucleotide changes was identified. Twenty-six patients (not sequenced) and controls were screened for nucleotide changes by allele specific restriction digestion of the PCR products followed by separation of the digested DNA fragments by polyacrylamide gel electrophoresis. RESULTS: From a pool of 56 unrelated POAG patients two mutations were identified. A putative novel mutation (144 G->T; Gln48His) of a conserved amino acid was detected in the exon 1 of MYOC from three unrelated patients but none in the 51 control samples examined. The other mutation (1109 C->T; Pro370Leu), located in exon 3 and detected in a family affected with POAG, cosegregated with the disease and was not present in control samples. Two single nucleotide polymorphisms (SNPs) were identified; one in the promoter region (-83 G->A) and the other in the coding sequence (227 G->A; Arg76Lys). These two SNPs were found to be highly heterozygous both in the control (0.480) and the patient (0.477) populations, and were observed to be in linkage disequilibrium. CONCLUSIONS: The presence of a novel non-conservative change in codon 48 of MYOC in 3 POAG patients, but none in the healthy controls, suggests a causal association of the mutation with the disease, either singly or in combination with other genetic loci. The other point mutation (Pro370Leu) detected in the members of an affected POAG family represents a hotspot of mutation in the gene. Two identified SNPs (-83 G->A and 227 G->A) are not associated with the disease phenotype but could be used as highly informative markers in POAG affected families to determine any causal association of MYOC with the disease, and for identification of presymptomatic carriers in the family, where applicable. A comparison of our data with other studies revealed that these two polymorphisms are in complete linkage disequilibrium among Asians, but not among other ethnic groups studied so far.