Refractive error in children in a rural population in India

PURPOSE: To assess the prevalence of refractive error and related visual impairment in school-aged children in the rural population of the Mahabubnagar district in the southern Indian state of Andhra Pradesh. METHODS: Random selection of village-based clusters was used to identify a sample of children 7 to 15 years of age. From April 2000 through February 2001, children in the 25 selected clusters were enumerated in a door-to-door survey and examined at a rural eye center in the district. The examination included visual acuity measurements, ocular motility evaluation, retinoscopy and autorefraction under cycloplegia, and examination of the anterior segment, media, and fundus. Myopia was defined as spherical equivalent refractive error of at least -0.50 D and hyperopia as +2.00 D or more. Children with reduced vision and a sample of those with normal vision underwent independent replicate examinations for quality assurance in seven clusters. RESULTS: A total of 4414 children from 4876 households was enumerated, and 4074 (92.3%) were examined. The prevalence of uncorrected, baseline (presenting), and best corrected visual acuity of 20/40 or worse in the better eye was 2.7%, 2.6%, and 0.78%, respectively. Refractive error was the cause in 61% of eyes with vision impairment, amblyopia in 12%, other causes in 15%, and unexplained causes in the remaining 13%. A gradual shift toward less-positive values of refractive error occurred with increasing age in both boys and girls. Myopia in one or both eyes was present in 4.1% of the children. Myopia risk was associated with female gender and having a father with a higher level of schooling. Higher risk of myopia in children of older age was of borderline statistical significance (P = 0.069). Hyperopia in at least one eye was present in 0.8% of children, with no significant predictors. CONCLUSIONS: Refractive error was the main cause of visual impairment in children aged between 7 and 15 years in rural India. There was a benefit of spectacles in 70% of those who had visual acuity of 20/40 or worse in the better eye at baseline examination. Because visual impairment can have a significant impact on a child's life in terms of education and development, it is important that effective strategies be developed to eliminate this easily treated cause of visual impairment.     

Moderate visual impairment in India: the Andhra Pradesh Eye Disease Study

AIM: To assess the prevalence and demographic associations of moderate visual impairment in the population of the southern Indian state of Andhra Pradesh. METHODS: From 94 clusters in one urban and three rural areas of Andhra Pradesh, 11 786 people of all ages were sampled using a stratified, random, cluster, systematic sampling strategy. The eligible people were invited for interview and detailed dilated eye examination by trained professionals. Moderate visual impairment was defined as presenting distance visual acuity less than 6/18 to 6/60 or equivalent visual field loss in the better eye. RESULTS: Of those sampled, 10,293 (87.3%) people participated in the study. In addition to the previously reported 1.84% prevalence of blindness (presenting distance visual acuity less than 6/60 or central visual field less than 20 degrees in the better eye) in this sample, 1237 people had moderate visual impairment, an adjusted prevalence of 8.09% (95% CI 6.89 to 9.30%). The majority of this moderate visual impairment was caused by refractive error (45.8%) and cataract (39.9%). Increasing age, female sex, decreasing socioeconomic status, and rural area of residence had significantly higher odds of being associated with moderate visual impairment. CONCLUSIONS: These data suggest that there is a significant burden of moderate visual impairment in this population in addition to blindness. Extrapolation of these data to the population of India suggests that there were 82 million people with moderate visual impairment in the year 2000, and this number is likely to be 139 million by the year 2020 if the current trend continues. This impending large burden of moderate visual impairment, the majority of which is due to the relatively easily treatable refractive error and cataract, would have to be taken into account while estimating the eye care needs in India, in addition to dealing with blindness. Specific strategies targeting the elderly population, people with low socioeconomic status, those living in the rural areas, and females would have to be implemented in the long term to reduce moderate visual impairment.     

Lysosomal Ca(2+) stores in bovine corneal endothelium

PURPOSE: Acidic organelles, including Golgi bodies and lysosomes, are known to operate as Ca(2+) storage sites in many cell types. This study demonstrates the presence of Ca(2+) stores in lysosomes of bovine corneal endothelial cells (BCECs) and examines their interaction with Ins(1,4,5)P(3)-sensitive Ca(2+) stores. METHODS: Glycyl-L-phenylalanine-beta-naphthylamide (GPN) was used to release Ca(2+) from lysosomes by inducing their selective osmotic swelling. Ca(2+) released into the cytoplasm was measured with fura-2 or fura-PE3 fluorescent dyes. Fluorescence of acridine orange (AO), which selectively sequesters into acidic organelles, was used to establish swelling of lysosomes in response to GPN. RESULTS: Exposure to GPN (100-200 microM) in cultured BCECs produced an increase in free cytosolic Ca(2+) ([Ca(2+)](i)) equivalent to approximately 79% of the peak response to uridine triphosphate (UTP), a P2Y agonist (n = 19). The endothelium of the freshly isolated cornea also produced [Ca(2+)](i) transients similar to those in cultured BCECs; however, the peak [Ca(2+)](i) increase was smaller ( approximately 43% of the peak response to UTP; n = 13). In cultured BCECs, the response to UTP was unaffected by pretreatment with GPN with extracellular calcium ([Ca(2+)](o)) at 0 and 1.2 mM (n = 10). Neither pretreatment with thapsigargin (5 microM) nor with U73122 (a phospholipase C inhibitor; 10 microM) blocked the peak GPN response (n = 6). Exposure to 20 microM monensin produced a [Ca(2+)](i) increase with [Ca(2+)](o) at 0 and 1.2 mM and also reduced the subsequent peak response to GPN (n = 6). CONCLUSIONS: GPN-sensitive lysosomal Ca(2+) stores, distinct from Ins(1,4,5)P(3)-sensitive Ca(2+) stores, are found in both cultured cells and fresh tissue. These stores are susceptible to depletion by the loss of the pH gradient across lysosomes and P2 agonists. The latter occurs through mechanisms independent of phospholipase C (PLC) activation or Ins(1,4,5)P(3). The GPN stores also induce [Ca(2+)](o) influx in response to their depletion.     

Terson's syndrome presenting as an ophthalmic emergency

PURPOSE: To report an unusual case of Terson's syndrome caused by a ruptured intracranial aneurysm presenting as an ophthalmic emergency with visual loss, without any neurological features at the time of presentation. METHODS: Case report. A 38-year-old man was referred to the eye emergency department with sudden loss of vision in both eyes. Vitreous haemorrhage was noted in both eyes. There was no history of loss of consciousness or headaches and no signs of meningeal irritation at presentation. The patient subsequently developed progressive neck stiffness and headache. RESULTS: Neuro-imaging studies revealed a subarachnoid haemorrhage resulting from a ruptured carotid-ophthalmic artery aneurysm. CONCLUSIONS: It is important to consider Terson's syndrome, a potentially life-threatening condition, in any patient presenting with bilateral vitreous haemorrhage. Some patients may not show any headache, neurological deficits or signs of meningeal irritation at presentation but may develop them later on.     

Synthesis and alpha 1-adrenoceptor antagonistic activity of some 4-amino-5,7-dimethyl-2-(substituted) aminopyrido (2,3-d) pyrimidines

A series of new 4-amino-5,7-dimethyl-2- (substituted)aminopyrido(2,3-d)pyrimidines (5) have been synthesized and tested for selective alpha 1-adrenoreceptor antagonistic activity. Some of the compounds were found to antagonize alpha 1-adrenoreceptor in a competitive and reversible manner. When screened on rat anococcygeus muscle some of the compounds exhibited significant alpha 1-adrenoreceptor antagonistic activity (pA2 values in the range of 5.2-7.8). The most potent compound (5j) was evaluated by an in vivo method and was found to reduce the systolic and diastolic blood pressure of spontaneously hypertensive rats. The percentage reduction in blood pressure by test compound 5j was found to be higher than that of the standard drug prazosin (CAS 19216-56-9) at the same dose level (1 mg/kg p.o.). Chemically, prazosin is a 4-aminoquinazolin derivative. Pyridopyrimidine is a known bioisostere of quinazoline. The study revealed that isosteric replacement of the benzene ring of prazosin by a pyridine ring increases the potency.     

Bilateral macular hemorrhage caused by azathioprine-induced aplastic anemia in a corneal graft recipient

PURPOSE: To report the occurrence of bilateral macular hemorrhage following the use of azathioprine for immunosuppression in a corneal transplant recipient. METHODS: The patient underwent therapeutic penetrating keratoplasty for progressive fungal keratitis in his left eye. Although the infection did not recur, the graft failed with vascularization of the cornea in three quadrants. He underwent repeat penetrating keratoplasty 2 years later and was treated with azathioprine (100 mg daily) to enhance graft survival. Four months after instituting azathioprine therapy, he developed aplastic anemia and macular hemorrhage in both eyes. RESULTS: Fluorescein angiography revealed a preretinal location of the macular hemorrhage. After cessation of azathioprine therapy and treatment with blood component replacement, hematological parameters improved and the macular hemorrhage cleared with good visual recovery during the next 2 months. CONCLUSION: This report highlights the serious ocular and systemic complications that can occur following the use of systemic immunosuppressants after ophthalmic surgery.     

Complications of laser-in-situ-keratomileusis

Laser-in-situ-keratomileusis (LASIK) has become a popular technique of refractive surgery because of lower postoperative discomfort, early visual rehabilitation and decreased postoperative haze. Compared to photorefractive keratectomy (PRK), LASIK involves an additional procedure of creating a corneal flap. This may result in complications related to the flap, interface and underlying stromal bed. The common flap-related complications include thin flap, button holing, free caps, flap dislocation and flap striae. The interface complications of diffuse lamellar keratitis, epithelial ingrowth and microbial keratitis are potentially sight threatening. Compared to PRK, there is less inflammation and faster healing after LASIK, but there is a longer period of sensory denervation leading to the complication of dry eyes. The refractive complications include undercorrection, regression, irregular astigmatism, decentration and visual aberrations. Honest and unbiased reporting is important to understand the aetiology and redefine the management.     

Role of Ca2+ channels on the hypothermic response produced by activation of kappa-opioid receptors

The effect of nimodipine (NIM) and lercanidipine (LER) 1,4-dihydropyridine (DHP) calcium channel blockers (CCBs) on the hypothermic response of selective kappa-opioid receptor agonists U50,488H (U50), PD117,302 (PD) and U69,593 (U69) was determined in rats by recording colonic temperature using digital telethermometer. Intraperitoneal (i.p.) injections of U50 (7.5, 15, 22.5 and 40 mg/kg), PD (7.5, 15 and 22.5 mg/kg) and U69 (5 and 20 mg/kg) produced a dose-dependent hypothermic response. However, higher doses of U50 (60 and 80 mg/kg) produced hypothermia, which is less when compared to that produced by 22.5-mg/kg dose of U50. NIM (1 mg/kg i.p.; 15 min prior) and LER (0.3 mg/kg i.p.; 15 min prior) did not produce any change in basal colonic temperature. Treatment of NIM and LER potentiated the U50 (7.5, 15, 22.5 and 40 mg/kg)-induced hypothermic effect. NIM did not potentiate hypothermia produced by U50 (60 mg/kg). On the other hand, PD (7.5, 15 and 22.5 mg/kg)- and U69 (5 and 20 mg/kg)-induced hypothermia was unaffected by the pretreatment of either NIM or LER. This differential modulation of kappa-opioid agonist-induced hypothermia by CCBs suggest that there may be two mechanisms, Ca(2+)-sensitive and Ca(2+)-insensitive, involved in kappa-opioid agonist-induced hypothermic response.     

Prospects for rational development of pharmacological gap junction channel blockers

Connexin-null mice and human genetic gap junction diseases illustrate the important roles that gap junction channels play under normal conditions, and the neuro- and cardioprotective effects of gap junction blocking agents demonstrate that closure of these channels may be beneficial in certain pathological situations. This overview summarizes studies in which gap junction modifying reagents have been characterized, highlighting examples of agents for which selectivity for gap junction subtypes has been demonstrated. In addition, strategies for targeting connexin domains through peptide inhibitors are outlined, which may ultimately provide agents that are not only connexin-selective in their actions, but also affect only a subset of a gap junction channel's gating responses.