Development and validation of a RP-UPLC method for the determination of betamethasone dipropionate impurities in topical formulations using a multivariate central composite design.

The current study presents a specific, accurate, simple, and rapid UPLC method for the determination of impurities present in cream and ointment formulations of betamethasone dipropionate (BMD). The analytical method was optimized using central composite design (CCD) prior to the method validation. Critical Process Parameters (CPPs) and Critical Quality Attributes (CQAs) were identified for the analytical method. A total of 17 experiments were carried out and verified the individual and interaction effects of CPPs. The CPPs were optimized using a numerical method by keeping the CQAs within the desired range (R1-R2: minimize & R3-R5: maximize) as an optimization goal. Optimized chromatographic separation was achieved using a Waters Acquity UPLC BEH C18, 100 mm × 2.1 mm, 1.7 µm column with a gradient mode of elution comprising 20 mM phosphate buffer: ACN 70 : 30, v/v as mobile phase-A and 20 mM phosphate buffer: ACN 30 : 70, v/v as mobile phase-B. The developed method was validated in accordance with ICH guidelines. The validation data conclude that the developed method is specific, accurate, linear, precise, rugged, and robust for the quantification of impurities in BMD topical formulations.

Effects of intraoperative steroid injection on the outcome of pterygium surgery.

PURPOSE: To evaluate the effects of intraoperative triamcinolone injection on the outcome of pterygium surgery. METHODS: This prospective study included 54 eyes with primary nasal pterygia that underwent pterygium surgery with a bare-sclera technique and intraoperative mitomycin C application. Patients were randomized into two groups; the steroid group that received subconjunctival injection of 12 mg triamcinolone acetonide at the end of surgery, and the control group that did not receive such steroid injection. Main outcome measures included presence of conjunctival inflammation at 1 month postoperatively as well as recurrence of pterygium. RESULTS: Twelve-month follow-up was completed in 48 eyes (23 in the steroid group and 25 in the control group). At 1 month postoperatively, different grades of conjunctival inflammation were present in 11 (47.8%) of the steroid group and in 14 (56%) of the control group (P=0.39). For eyes with moderate or severe postoperative inflammation, subconjunctival triamcinolone was injected; these included 6 (26.1%) and 9 (36%) in the steroid and control groups, respectively (P=0.54). During follow-up, surgical area showed fine episcleral vessels without fibrous tissue in 1 (4.3%) of the steroid group and 3 (12.0%) of the control group (P=0.33), which all regressed after triamcinolone injection. Conjunctival recurrence of pterygium was seen in 2 (8.7%) of the steroid group and in 1 (4.0%) of the control group (P=0.47). No eye developed corneal recurrence in either group. CONCLUSIONS: In pterygium surgery with a bare-sclera technique and mitomycin C application, intraoperative triamcinolone injection did not significantly reduce postoperative conjunctival inflammation or pterygium recurrence.

Ocular demodicosis.

We present a case of blepharitis with symptoms lasting two years in duration and refractory to a host of prior medical treatments, including antibiotics, corticosteroids, cyclosporine, and baby shampoo. We recognized the clinical presentation as pathogomonic for demodicosis caused by the parasitic mite, demodex folliculorum, confirmed with light microscopy, and treated appropriately with tea tree oil and hygiene measures--achieving full resolution of symptoms. We highlight the presentation, treatment, and underscore demodicosis as an important, under recognized cause of blepharitis.

Coverage of the vitamin A supplementation programme for child survival in Nepal: success and challenges.

BACKGROUND: Nepal's national vitamin A programme, which began in 1993 and continues twice yearly, targets pre-school-aged children in all districts of the country in an effort to reduce morbidity, mortality and nutritional blindness. OBJECTIVE: To characterize the coverage of the Nepal National Vitamin A Programme (NVAP) for pre-school-aged children in Nepal and to identify risk factors for failure to receive vitamin A supplementation. METHODS: The relationship between receipt of a vitamin A capsule and demographic and health indicators was examined in a cross-sectional study of 4013 children aged 12-59 months and their families who participated in the 2011 Nepal Demographic and Health Survey (NDHS), a nationally representative survey. Coverage of the vitamin A programme was compared with coverage estimates from surveys in 2001 and 2006. RESULTS: Coverage estimates of the national vitamin A programme for children aged 12-59 months as assessed by the 2001, 2006 and 2011 NDHS were 84.3%, 96.6% and 92.1%, respectively. Children who missed a vitamin A capsule were more likely to be younger and anaemic, have less educated parents, live in rural areas, and have higher child and infant mortality in the family. CONCLUSIONS: The national vitamin A supplementation programme in Nepal has relatively high coverage of children aged 12-59 months but still misses children in families with high child mortality. Further measures might be needed to sustain a high level of programme coverage.

Ocular demodicosis as a potential cause of pediatric blepharoconjunctivitis.

PURPOSE: To report Demodex infestation in pediatric blepharoconjunctivitis. METHODS: A retrospective review of 12 patients, with ages from 2.5-11 years, with chronic blepharoconjunctivitis who failed to respond to conventional treatments. Demodex was detected by lash sampling and microscopic examination. Patients were treated with 50% tea tree oil (TTO) eyelid scrubs or 5% TTO ointment eyelid massages for 4-6 weeks. RESULTS: Demodex mites were found in all, but 1 case had cylindrical dandruff in the lashes. After 1 week of TTO treatment, all patients showed dramatic resolution of ocular irritation and inflammation while Demodex counts dropped. All corneal signs resolved within 2 weeks except for a residual anterior stromal scar in 1 eye. During a follow-up period of 8.3 ± 4.6 months, 1 patient showed recurrent inflammation, which was successfully managed by a second round of TTO treatment. CONCLUSIONS: Demodicosis should be considered as a potential cause of pediatric refractory blepharoconjunctivitis. Eyelid scrubs or massage with TTO could be an effective treatment regimen in these cases.

Coverage of vitamin A capsule programme in Bangladesh and risk factors associated with non-receipt of vitamin A.

Vitamin A supplementation reduces child morbidity, mortality, and blindness. The coverage of the national vitamin A programme and risk factors for not receiving vitamin A were characterized using data from the Bangladesh Demographic and Health Survey 2004. Of 3,745 children aged 18-59 months, 3,237 (86.4%) received a vitamin A capsule each within the last six months. Children who missed vitamin A were more likely to be stunted (prevalence ratio [PR] 0.97, 95% confidence interval [CI] 0.95-1.00) and come from a family with a previous history of mortality of children aged less than five years (PR 0.95, 95% CI 0.91-0.99). Maternal education of > or = 10 years (PR 1.09, 95% CI 1.04-1.13), 7-9 years (PR 1.08, 95% CI 1.04-1.12), and 1-6 years (PR 1.05, 95% CI 1.02-1.08) compared to no formal education was associated with the child not receiving vitamin A in a multivariate model, adjusting for potential confounders. Children missed by the vitamin A programme were more likely to come from families with lower maternal education. Special efforts are required to ensure that the coverage of the national vitamin A programme is increased further so that the most vulnerable children are also better protected against morbidity, mortality, and blindness.

A validated stability-indicating LC method for acetazolamide in the presence of degradation products and its process-related impurities.

The objective of the current study was to develop a validated, specific and stability-indicating reverse phase liquid chromatographic method for the quantitative determination of acetazolamide and its related substances. The determination was done for an active pharmaceutical ingredient, its pharmaceutical dosage form in the presence of degradation products, and its process-related impurities. The drug was subjected to stress conditions of hydrolysis (acid and base), oxidation, photolysis and thermal degradation as per International Conference on Harmonization (ICH) prescribed stress conditions to show the stability-indicating power of the method. Significant degradation was observed during acid and base hydrolysis, and the major degradant was identified by LC-MS, FTIR and (1)H/(13)C NMR spectral analysis. The chromatographic conditions were optimized using an impurity-spiked solution and the generated samples were used for forced degradation studies. In the developed HPLC method, the resolution between acetazolamide and, its process-related impurities (namely imp-1, imp-2, imp-3, imp-4 and its degradation products) was found to be greater than 2. The chromatographic separation was achieved on a C18, 250mmx4.6mm, 5microm column. The LC method employed a linear gradient elution, and the detection wavelength was set at 254nm. The stress samples were assayed against a qualified reference standard and the mass balance was found to be close to 99.6%. The developed RP-LC method was validated with respect to linearity, accuracy, precision and robustness.

Low intake of vitamin A-rich foods among children, aged 12-35 months, in India: association with malnutrition, anemia, and missed child survival interventions.

OBJECTIVE: To determine whether children in India who have a low intake of vitamin A-rich foods are at higher risk of malnutrition, anemia, and not receiving child health interventions. METHODS: We analyzed data from the India National Family Health Survey, 2005-2006. RESULTS: Of 17 847 children (41.9%), aged 12-35 months, 7020 did not receive vitamin A-rich foods, based on 24-h recall. The prevalence of stunting, severe stunting, underweight, and severe underweight among children who did and did not receive vitamin A-rich foods was, respectively, 52.5% versus 59.0%, 26.7% versus 32.9%, 43.8% versus 48.5%, and 17.9% versus 21.6% (all P<0.0001). Children who did not receive vitamin A-rich foods were more likely to be anemic, not have completed childhood immunizations, and not to have received vitamin A supplementation in the previous 6 mo (all P<0.0001). Maternal education of ≥10, 7-9, and 1-6 y, respectively, compared with no formal education was associated with the child receiving vitamin A-rich foods (odds ratio 1.41, 95% confidence interval 1.20-1,67, P<0.0001; odds ratio 1.20, 95% confidence interval 1.04-1.37, P=0.01; odds ratio 1.16, 95% confidence interval 1.02-1.32, P=0.02) in a multivariate logistic regression model adjusting for maternal age, household size, socioeconomic status, and location. CONCLUSION: Children who did not receive vitamin A-rich foods were more likely to be malnourished and to have missed basic child health interventions, including vitamin A supplementation. Children were more likely to receive vitamin A-rich foods if their mothers had previously achieved higher primary or secondary education levels.

The role of expanded coverage of the national vitamin A program in preventing morbidity and mortality among preschool children in India.

Higher food prices increase the risk of vitamin A deficiency among preschool children in poor families, because a larger part of the household food budget is spent on grain foods and less on vitamin A-rich foods. Vitamin A supplementation is an important source of vitamin A for children. Our objective was to characterize coverage of the India national vitamin A program for preschool children and identify risk factors for not receiving vitamin A. Anthropometric and demographic data were examined in 23,008 children aged 12-59 mo in the India National Family Health Survey, 2005-2006. Within the last 6 mo, 20.2% of children received vitamin A supplementation. The prevalence of stunting, severe stunting, underweight, and severe underweight was higher among children who did not receive vitamin A compared with those who received vitamin A (P < 0.0001). In families with a child who did and did not receive vitamin A, respectively, the proportion with a history of under-5 child mortality was 8.4 vs. 11.4% (P < 0.0001). By state, vitamin A program coverage was inversely proportional to the under-5 child mortality rate (r = -0.51; P = 0.004). Maternal education of > or =10 y [odds ratio (OR) 2.22; 95% CI 1.69-2.91], 7-9 y (OR 1.99; 95% CI 1.57-2.53), or 1-6 y (OR 1.65; 95% CI 1.28-2.13) compared with no education was an important factor related to receipt of vitamin A. Poor coverage of the vitamin A supplementation program in India has serious implications in the face of rising food prices. Expanded coverage of the vitamin A program in India will help protect children from morbidity, mortality, and blindness.

Vitamin A supplementation in Cambodia: program coverage and association with greater maternal formal education.

Vitamin A supplementation reduces morbidity, mortality, and blindness among children in developing countries. The objective of this study is to characterize the coverage of the Cambodian national vitamin A program among preschool children and to identify risk factors for not receiving vitamin A supplementation. The study subjects were preschool children and their families who participated in the 2005 Cambodian Demographic and Health Survey (CDHS), a nationally representative survey. Of 1,547 preschool children, aged 12-59 months, 42.8% received a vitamin A capsule within the last six months. There were no significant differences in paternal education, child age, fever within the last 2 weeks, stunting, underweight, or wasting between children who did or did not receive a vitamin A capsule. Maternal education of > or =10 years (Odds Ratio [OR] 2.09, 95% Confidence Interval [CI] 1.02-4.29), 7-9 years (OR 1.46, 95% CI 0.99-2.15), 4-6 years (OR 1.71, 95% CI 1.26-2.32), and 1-3 years (OR 1.50, 95% CI 1.10-2.06) was associated with the child receiving a vitamin A capsule compared to no formal education in multivariate analyses adjusting for other potential confounders. The national vitamin A supplementation program in Cambodia did not reach over one-half of preschool children in 2005. Greater maternal formal education appears to be an important determinant for receipt of a vitamin A capsule by preschool children.

Temporary sutureless amniotic membrane patch for acute alkaline burns.

OBJECTIVE: To evaluate the clinical outcome of a new sutureless approach for a temporary amniotic membrane patch (ProKera; Bio-Tissue, Inc, Miami, Florida) in eyes with acute burns. METHODS: Retrospective review of 5 eyes of 5 patients with grades I to III acute alkaline burns, receiving ProKera insertion within 8 days of injury. RESULTS: These eyes had either total (2 cases) or extensive (60%-75%, 3 cases) corneal epithelial defects with limbal (120 degrees -360 degrees ) and conjunctival (30%-60%) epithelial defects. ProKera was inserted within a mean (SD) of 3.7 (3.1) days after burn and repeated 1 to 3 times for 3 cases. Conjunctival defects reepithelialized in 8.2 (5) days (range, 5-17 days), while limbal and corneal defects healed in 13.6 (8.3) days (range, 5-25 days). The latter was completed with circumferential closure of limbal defects followed by centripetal healing of corneal defects. In 3 eyes, early peripheral corneal neovascularization was followed by marked regression on completion of healing. During 16.8 (10.8) months of follow-up, all eyes retained a stable surface with improved corneal clarity, and without limbal deficiency or symblepharon. CONCLUSION: This sutureless application of an amniotic membrane patch allows for early delivery of its biologic actions, which may help preserve remaining limbal stem cells for rapid expansion and prevent late cicatricial complications in eyes with mild and moderate acute alkaline burns.

Coverage of the national vitamin A supplementation program in Ethiopia.

Periodic vitamin A supplementation is a major intervention to reduce morbidity, mortality, and blindness among children in developing countries. The goal was to characterize the coverage of the Ethiopia national vitamin A program among preschool children and to identify risk factors for not receiving vitamin A. In the Ethiopia Demographic and Health Survey of 2005, among 4762 preschool children, aged 12-59 months, 46.8% received a vitamin A capsule within the last 6 months. There were no significant differences in stunting, underweight, or wasting between children who did or did not receive a vitamin A capsule. In multivariate logistic regression analyses, maternal education of > or =10 years [odds ratio (OR) 1.90, 95% confidence interval (CI) 1.23-2.92], 7-9 years (OR 2.47, 95% CI 1.67-3.65), 4-6 years (OR 1.56, 95% CI 1.18-2.07), and 1-3 years (OR 1.11, 95% CI 0.90-1.37), and paternal education of > or =10 years (OR 1.61, 95% CI 1.14-2.29), 7-9 years (OR 1.24, 95% CI 0.94-1.64), 4-6 years (OR 1.26, 95% CI 1.03-1.56), and 1-3 years (OR 1.29, 95% CI 1.05-1.50) were associated with the child receiving a vitamin A capsule compared with no years of formal parental education. Expanded coverage of the national vitamin A capsule program may help protect children from nutritional blindness and to help reach Millennium goals for reducing under-five child mortality in Ethiopia.

New surgical approach for superior conjunctivochalasis.

PURPOSE: To show poor adhesion between the conjunctiva and the sclera in eyes with superior conjunctivochalasis (CCh) and to introduce a new surgical approach by reinforcing adhesion between the conjunctiva and the sclera for correcting this deficiency. METHODS: After conjunctival peritomy and removal of the loose Tenon remnants, "Tenon reinforcement" for conjunctival adhesion to the underlying sclera was achieved by transplantation of cryopreserved amniotic membrane with fibrin glue (group A, 9 eyes of 6 patients) or 10-0 nylon sutures (group B, 8 eyes of 6 patients) in 17 eyes of 12 patients with refractory superior CCh. RESULTS: The mean age of patients was 68.2 +/- 9.8 years (range, 54-80 years). Superior CCh was associated with a superior limbic keratoconjunctivitis (SLK)-like clinical feature before surgery and found to exhibit dissolved Tenon capsule during surgery in all patients. During a mean follow-up of 3.7 +/- 1.9 months after surgery, all eyes achieved smooth conjunctival surface without any sign of CCh. Complete resolution of symptoms was seen in 9 eyes (52.9%) and significant resolution in 8 eyes (47.1%). There was no significant difference between groups A and B in improvement of symptoms and signs. No complications related to surgery were noted during follow-up. CONCLUSIONS: We propose that loose and dissolved Tenon tissue is correlated with the development of superior CCh, which may result in an SLK-like appearance by blink-related microtrauma. Reinforcement of conjunctival adhesion onto the sclera by amniotic membrane with either fibrin glue or sutures is effective in alleviating symptoms and signs in eyes with superior CCh.

In vitro and in vivo killing of ocular Demodex by tea tree oil.

AIMS: To compare the in vitro killing effect of different agents on Demodex and to report the in vivo killing effect of tea tree oil (TTO) on ocular Demodex. METHODS: Survival time of Demodex was measured under the microscope. Sampling and counting of Demodex was performed by a modified method. RESULTS: Demodex folliculorum survived for more than 150 minutes in 10% povidone-iodine, 75% alcohol, 50% baby shampoo, and 4% pilocarpine. However, the survival time was significantly shortened to within 15 minutes in 100% alcohol, 100% TTO, 100% caraway oil, or 100% dill weed oil. TTO's in vitro killing effect was dose dependent. Lid scrub with 50% TTO, but not with 50% baby shampoo, can further stimulate Demodex to move out to the skin. The Demodex count did not reach zero in any of the seven patients receiving daily lid scrub with baby shampoo for 40-350 days. In contrast, the Demodex count dropped to zero in seven of nine patients receiving TTO scrub in 4 weeks without recurrence. CONCLUSIONS: Demodex is resistant to a wide range of antiseptic solutions. Weekly lid scrub with 50% TTO and daily lid scrub with tea tree shampoo is effective in eradicating ocular Demodex.

Correlation of corneal complications with eyelid cicatricial pathologies in patients with Stevens-Johnson syndrome and toxic epidermal necrolysis syndrome.

PURPOSE: To look at the correlation between many factors (time of hospitalization, floppy eyelid syndrome, trichiasis, open lacrimal puncta, symblepharon, and aqueous tear deficiency) and corneal complications in Stevens-Johnson syndrome (SJS). DESIGN: Observational cases series. PATIENTS: Clinical data were retrospectively reviewed from 38 patients (32.7+/-20.1 years old) with SJS (n = 11) and with toxic epidermal necrolysis (TENS) (n = 27) from January 2002 to August 2004. One case report with SJS was included to verify the presence of tarsal/lid margin ulceration at the acute stage. METHODS: The medical history was retrieved regarding presumed causative medications used within 15 days and the duration of hospitalization. Data of the latest photographic documentation and eye examination were compared and correlated in a masked fashion. MAIN OUTCOME MEASURES: Floppy eyelid, trichiasis, lid margin keratinization, meibomian gland orifice metaplasia, symblepharon, tarsal scar, and corneal complications. RESULTS: Acute SJS/TENS was characterized by tarsal conjunctival ulceration. Keratinization of the eyelid margin with variable degrees of meibomian gland dysfunction was observed in all cases. Floppy eyelid, trichiasis, partially or totally opened lacrimal punctum, symblepharon, and aqueous tear deficiency were not significantly correlated with corneal complications. In contrast, there was a strong correlation between the severity of eyelid margin and tarsal pathology and the extent of corneal complications (Spearman r, 0.54; P = 0.0005). A multivariable regression analysis also showed that the extent of eyelid and tarsal pathology had a significant effect on corneal complications (coefficient, 0.84; P = 0.006). CONCLUSIONS: Patients with acute SJS/TENS are characterized by severe inflammation and ulceration of the tarsal conjunctiva and lid margins. If left unattended, lid margin keratinization and tarsal scar, together with lipid tear deficiency, contribute to corneal complications because of blink-related microtrauma. Attempts to suppress inflammation and scarring by amniotic membrane transplantation at the acute stage and to prevent microtrauma at the chronic stage are vital to avoid sight-threatening complications.