Comparative efficacy of fixed dose combination of brinzolamide 1% and timolol 0.5% without versus with benzalkonium chloride following single ocular instillation in New Zealand white rabbits

Background: Benzalkonium chloride (BAK) is the most used preservative in topical ophthalmic formulations. BAK causes dry eye and trabecular meshwork degeneration. Hence, BAK-free formulations are desirable for chronic conditions like glaucoma. The objective of this study was to compare the efficacy of BAK-free versus BAK-containing ophthalmic suspension of fixed dose combination (FDC) of brinzolamide and timolol on their intraocular pressure (IOP) lowering effect following a single ocular instillation in New Zealand White (NZW) rabbits. Methods: Twelve normotensive NZW rabbits (male) between 9-12 months of age (3.4-4.4 kg) received a single ocular instillation (35 ml) in left eye of either ophthalmic suspension containing FDC of brinzolamide (1% w/v)/timolol (0.5% w/v) without BAK (n=6, test) or with BAK 0.01% w/v (n=6, reference). IOP was measured before ocular instillation (baseline) and at 2, 4, 6, 8 and 24 hours after instillation using a pneumatonometer. Change in IOP from baseline were calculated and analysed using repeated measures analysis of variance (ANOVA) followed by Bonferroni post-test for pairwise comparisons. Results: Significant IOP reduction (p<0.05) from baseline was seen in both test and reference groups, up to 6 hours after instillation. Maximum IOP reduction was 25.5% and 22.6% at 2 hours in the test and reference group respectively. No significant differences (p>0.05) were observed between the test and reference group for the change in IOP at all time points. Conclusions: BAK-free and BAK-containing ophthalmic suspension of FDC of brinzolamide 1% and timolol 0.5% after a single ocular instillation in normotensive NZW rabbits produces similar reductions in IOP.

First case report of tongue squamous cell carcinoma in a neurofibromatosis type 1 patient and review of pathogenesis of carcinoma in neurofibromatosis type 1

Neurofibromatosis type 1 (NF1), also known as von Recklinghausen's disease, is a type of genodermatoses having an autosomal dominant inheritance pattern and is recently considered as a RASopathy. Such patients are very much prone to develop mesenchymal tumors. However, carcinomas are quite rare in NF1 patients. This case study is the first case of oral squamous cell carcinoma (SCC) in tongue of an NF1 patient. A 35-year-old male reported to the Department of Oral Pathology in a tertiary care center with a chief complain of a painful ulcer on tongue for last 1 month. For confirmation of diagnosis of NF1, the “Diagnostic Criteria for Neurofibromatosis Type 1” was followed. Biopsied specimen of the tongue lesion was examined under microscope and histopathological features were suggestive of infiltrating SCC. Immunohistochemistry with Pan CK and beta-catenin was positive. RASopathy, WNT–beta-catenin pathway alteration, heat shock factor 1 production, and miRNA activity are investigated to explain the pathogenesis of malignancies in NF1 patients. In this first case of tongue SCC, we have found out the altered WNT–beta-catenin pathway.

Protection from ultraviolet radiation by spectacle lenses available in India: a comparative study.

BACKGROUND: Exposure to ultraviolet radiation (UVR) can result in several ocular ailments. We studied the UV absorption (UV-A and -B bands) in 20 lenses (11 hard resin and 9 glass) commonly available in India as uncut lenses for the purpose of prescription as well as non-prescription wear. METHODS: Using a UV-visible spectrophotometer (Thermo-Spectronic, UV-1 model, Thermo Electron Corporation, USA), the percentage transmittance was scanned between 190 and 400 nm, from which the results at 280, 320, 340, 360, 380 and 400 nm were analysed. RESULTS: At 360 nm (UV-A), 75% of the lenses studied failed to offer 95% protection as recommended by the United States Food and Drug Administration (US FDA). At 280 nm (UV-B), 35% of the lenses failed to offer 99% protection against UV-B. Hard resin lenses showed a higher degree of variation in protection from UV-A. CONCLUSONS: Most of the lenses studied failed to meet the US FDA recommendations in terms of protection from UV-A. Glass lenses afforded better protection up to 320 nm compared with hard resin lenses. As the claims of lens manufacturers regarding UVR protection fall short of international standards, certification of UVR protection for different lenses should be introduced in India.

Anatomic variations of foramen ovale.

OBJECTIVES: Foramen ovale is of great surgical and diagnostic importance in procedures like percutaneous trigeminal rhizotomy for trigeminal neuralgia, transfacial fine needle aspiration technique in perineural spread of tumour and electroencephalographic analysis for seizure. This study presents the anatomic variations in dimensions, appearance and number of foramen ovale. METHODS: We studied 35 dried human skulls available in the Department of Anatomy, Manipal college of Medical Sciences, Pokhara, Nepal. Variations in appearance and number of foramen ovale were noted. Length and width of foramen ovale was measured. Comparison with other races and differences between right and left sides were also discussed. RESULTS: Out of 70 sides in 35 adult skulls, mean length and width of foramen ovale was 7.46+/-1.41 mm and 3.21+/-1.02 mm on right side and 7.01+/-1.41 mm and 3.29+/-0.85 mm on left side. Shape of foramen ovale was typically oval in 43, (22 on right, 21 on left) almond shape in 24 (Fig.1, arrowhead; 11 right, 13 left), round in 2(1 right, 1 left) and slit-like in 1(Fig.1, arrow). Bilateral oval foramen was observed in 15 and bilateral almond was in 7. Out of 70 sides in 35 adult skulls 3 (2 left, 1 right) sides had spine on the margin of the foramen (Fig.2, arrow), 3 (2 left, 1 right) had tubercle protruding from the margin (Fig. 3, arrow), 2 (1 left, 1 right) sides had bridge like bony spur dividing the foramen into two compartments(Fig. 2, arrowhead), 9 (5 left, 4 right) had bony plate on the margin of foramen ovale (Fig. 4, arrow). Variant foramen ovale was observed in 24.2%. CONCLUSION: Anatomical variations in size and shape of foramen ovale could be explained by developmental reasons. Considering the immense surgical and diagnostic importance of foramen ovale, this study was worthwhile.

Childhood proptosis: the invaluable but overlooked peripheral blood smear.

Two cases of granulocytic sarcoma presenting as childhood proptosis are described. This highlights the significance of peripheral blood smear examination in establishing the diagnosis of Acute Myeloid Leukaemia (AML).

Management of retinoblastoma with radiation.

OBJECTIVE: To evaluate the role of radiation therapy in the management of retinoblastoma. DESIGN: Retrospective analysis. METHOD: From January 1993 to March 1994, one hundred and eleven children (150 eyes) of retinoblastoma were referred for radiotherapy. The diagnosis was based on clinical examination and ocular ultrasonogram for both the eyes. The radiation treatment policy involved 40 Gy in 20 fractions over 4 weeks delivered with sedation for children under 1 year of age, 36 Gy in 9 fractions over 3 weeks under ketamine anesthesia for 1-4 years of age and for >4 years of age, a dose of 50 Gy in 25 fractions over 5 weeks. The initial tumor regression was evaluated by A and B mode ultrasonography and/or CT scan. RESULTS: The age distribution ranged from two months to six years (median - 20 months). Bilaterality was observed in 39 out of 111 cases (35%). The male to female ratio was 1.8:1. Eighty two of the 111 children were treated by definitive external beam radiation to one or both eyes. Fifteen cases received adjuvant radiotherapy after enucleation, and 14 had extensive disease for which palliative radiotherapy was offered. We observed a complete response in 54% of cases, partial response in 32%, and none in 14% of cases. Forty per cent (40%) eye survival was documented at the end of 28 months. The complication rate encountered was about 15%. CONCLUSION: Radiotherapy is an effective modality of treatment in significant number of patients with retinoblastoma. However, it requires appropriate fractionation, precise colimation and careful immobilization with general anesthesia.

Fungal flora in congenital dacryocystitis.

In this study, 86 eyes in 66 cases (20 bilateral) of congenital dacryocystitis were analysed for fungal growth. Fungi alone were isolated in 12 eyes (13.95%) and in 14 eyes (16.28%) together with bacteria--a total of 26 positive for fungus in 86 eyes (30.23%). These 26 eyes yielded on fungal culture a total of 28 isolates (in 2 eyes, another fungus was isolated on repeat culture). 11 types of fungi were cultured--C. albicans and A. niger accounted for 5 each out of 28. To the best of our knowledge this is the first report in the literature of fungal flora analysed in congenital dacryocystitis--not surprisingly, more than 30% of eyes were positive for fungus. Systemic studies of fungal flora in dacryocystitis are very few, and hardly any literature on this subject exists in congenital dacryocystitis. This study is an attempt to determine the frequency and clinical significance of fungi isolated from cases of congenital dacryocystitis.

Clinicobacteriological correlates of congenital dacryocystitis.

One hundred and fourteen eyes with congenital dacryocystitis have been studied clinically and bacteriologically. Gram positive cocci constituted the major bacterial isolates (57.9%) with streptococcus pneumoniae predominating (28.9%). The most effective antibiotic was cloxacillin with an overall efficacy of 77%. Normal conjunctival flora was sterile in majority (75%) of cases. Positive cases showed preponderance of gram positive cocci (21.6%) with staphylococcus albus (13.3%) being the major isolate. Normal nasal flora revealed diphtheroids (alone or in combination) to be the commonest bacteria (62.1%). A statistically significant correlation was not observed between the normal conjunctival or nasal flora and flora from the affected eyes.