From Scylla to Charybdis: Fixed drug combinations for tuberculosis and increased ethambutol-induced optic neuropathy in India.

Purpose: To describe the increase in prevalence of ethambutol-induced optic neuropathy (EON) in patients presenting to a single tertiary referral eye care center in India after introduction of weight-based fixed dose combinations and an increase in duration of ethambutol use from 2016 in the Revised National Tuberculosis Control Program. Methods: This was a retrospective, observational, referral hospital-based study of 156 patients with a diagnosis of EON presenting to a single tertiary referral eye care center between January 2016 and December 2019. The main outcome measure was to assess the increase in prevalence of EON cases presenting to our tertiary care institute. Results: During the 4-year study period, 156 new patients were diagnosed with EON. A total of 101 patients (64.7%) were males and 55 (35.3%) were females. The most common age group affected was 41-60 years. The significant complaint at presentation was decreased vision in all the patients. A rising trend in the number of patients diagnosed as EON was seen, with the prevalence increasing from 16 cases in 2016, 13 cases in 2017, and 31 cases in 2018 to 96 cases in 2019. Conclusion: The results of this study indicated an alarming increase in the trend of EON cases presenting to our tertiary care institute.

Vitamin B12 deficiency in a large cohort of healthcare professionals across the network of an eyecare organization in India.

Purpose: To evaluate Vitamin B12 levels in healthcare professionals at a tertiary eyecare centre in India. Methods: This was a cross-sectional study conducted among healthcare professionals working at a tertiary eyecare centre in India. The sample included 2,374 employees. Chemiluminescent immunoassay method (reference range, 211-911 pg/ml) was used to assess serum vitamin B12 levels. Effect of age and gender was analyzed in vitamin B12 normal and vitamin B12 deficient groups. To evaluate risk factors, questions related to vitamin B12 deficiency were asked to the study participants in a survey. Results: The mean age of employees was 29.2 ± 0.7 years. Around 26% of them were vitamin B12 deficient. The proportion of males in the vitamin B12 deficient group (61.2%) was significantly higher (P < 0.0001) than that of the vitamin B12 normal group (44.9%). There was no effect of age on vitamin B12 levels in both vitamin B12 normal and vitamin B12 deficient groups. Mean vitamin B12 levels in males (289.1 ± 22.2 pg/ml) was significantly lower (P < 0.0001) than that of females (338.7 ± 30.0 pg/ml). Conclusion: This is the first such study on eyecare professionals. One-fourth of the eyecare professionals were vitamin B12 deficient. The proportion of males was higher in the vitamin B12 deficiency group. Males had lower vitamin B12 levels than females. Annual blood tests for vitamin B12 are recommended for timely diagnosis and management of vitamin B12 deficiency, particularly in males.

Alterations in the gut bacterial microbiome in people with type 2 diabetes mellitus and diabetic retinopathy.

Gut bacterial microbiome dysbiosis in type 2 Diabetes Mellitus (T2DM) has been reported, but such an association with Diabetic Retinopathy (DR) is not known. We explored possible link between gut bacterial microbiome dysbiosis and DR. Using fecal samples of healthy controls (HC) and people with T2DM with/without DR, gut bacterial communities were analysed using 16S rRNA gene sequencing and data analysed using QIIME and R software. Dysbiosis in the gut microbiomes, at phyla and genera level, was observed in people with T2DM and DR compared to HC. People with DR exhibited greater discrimination from HC. Microbiomes of people with T2DM and DR were also significantly different. Both DM and DR microbiomes showed a decrease in anti-inflammatory, probiotic and other bacteria that could be pathogenic, compared to HC, and the observed change was more pronounced in people with DR. This is the first report demonstrating dysbiosis in the gut microbiome (alteration in the diversity and abundance at the phyla and genera level) in people with DR compared to HC. Such studies would help in developing novel and targeted therapies to improve treatment of DR.

Gut mycobiomes are altered in people with type 2 Diabetes Mellitus and Diabetic Retinopathy.

Studies have documented dysbiosis in the gut mycobiome in people with Type 2 diabetes mellitus (T2DM). However, it is not known whether dysbiosis in the gut mycobiome of T2DM patients would be reflected in people with diabetic retinopathy (DR) and if so, is the observed mycobiome dysbiosis similar in people with T2DM and DR. Gut mycobiomes were generated from healthy controls (HC), people with T2DM and people with DR through Illumina sequencing of ITS2 region. Data were analysed using QIIME and R software. Dysbiotic changes were observed in people with T2DM and DR compared to HC at the phyla and genera level. Mycobiomes of HC, T2DM and DR could be discriminated by heat map analysis, Beta diversity analysis and LEfSE analysis. Spearman correlation of fungal genera indicated more negative correlation in HC compared to T2DM and DR mycobiomes. This study demonstrates dysbiosis in the gut mycobiomes in people with T2DM and DR compared to HC. These differences were significant both at the phyla and genera level between people with T2DM and DR as well. Such studies on mycobiomes may provide new insights and directions to identification of specific fungi associated with T2DM and DR and help developing novel therapies for Diabetes Mellitus and DR.

Pachymeter Use and Disinfection Practice in the United Kingdom: A National Survey.

OBJECTIVE: Pachymetry plays a crucial role in the diagnosis and management of glaucoma and corneal diseases. There have been several outbreaks of epidemic ocular infections in ophthalmology clinics worldwide with reports of viral, parasitic, and prion disease. Contact pachymetry is a possible vehicle of transmission due to its risk of contamination. We aim to identify the types of pachymetry used and methods employed for cleaning and disinfection in eye units throughout the United Kingdom. METHODS: A telephone survey was carried out, and a senior nurse or sister questioned based on the proforma created. A follow-up email was sent to units that did not respond with the questionnaire attached. RESULTS: Of 109 responses, 10 eye units were unaware of the device name and 4 were unaware of the cleaning method used. Overall, 69/105 (66%) were cleaned with some form of alcohol wipe between patients, 12/105 (11%) used presept solution to soak the pachymetry head mainly 5 to 10 minutes, with 2 units soaking for 20 to 30 minutes. Milton solution was used by 4 units (4%) (10 s to 10 min). Three used a hydrogen peroxide solution for 10 minutes (3%). Three (3%) used an alcohol solution. Fifteen (14%) units used some chlorine-based solution (actichlor/chloraprep) for 5 to 10 minutes. Two (2%) units combined an alcohol-based wipe with solution to soak afterward. CONCLUSIONS: There is a large variation in methods and duration of tip disinfection with only a few units following the Royal College of Ophthalmologists (RCOphth) guidelines on pachymeter disinfection. The majority of eye units use alcohol/chlorine-based wipes for cleaning the pachymetry heads which is against the current recommended guidelines. The average immersion time when solutions were used was 5 to 10 minutes.

Precipitants of 5-Fluorouracil in Trabeculectomy Bleb Management: A Comparative Laboratory Study.

AIM: Concerns regarding 5-Fluorouracil (5-FU) corneal toxicity have resulted in various ways of reducing its corneal exposure during post-operative trabeculectomy bleb manipulation. This study investigates the properties of various topical agents used to induce the precipitation of this compound. MATERIALS AND METHODS: This is a double-blind, descriptive, laboratory study comparing five different potential precipitants of 5-FU (proxymetacaine (proxy), oxybuprocaine (oxy), ametho-caine (ameth), fluorescein (flor), proxymetacaine + fluorescein (proxy-flor) to a control group (normal saline). A 0.01 mL of each anonymized agent was applied next to a clear round comparison marker in a transparent sterile container set on a dark background. 5-FU (0.01 mL of 50 mg/mL) was subsequently applied to each agent. The induced changes in transparency were imaged and compared to the transparency of the central marker. For each application, pH changes were also noted. RESULTS: Proxy, flor and proxy + flor did not result in any discernible 5-FU precipitation. Oxy resulted in a moderate visible change, and ameth produced very significant precipitation. Application of proxy, oxy, ameth, and proxy + flor resulted in the neutralization of the 5-FU's alkaline pH. CONCLUSION: We propose using a cotton-tipped bud dipped in ameth applied at the injection site as the recommended method to avoid 5-FU corneal exposure in these cases. CLINICAL SIGNIFICANCE: Practitioners should be aware of the differences in precipitation of 5-FU by different types of topical anesthetics and modify techniques of anesthesia and 5-FU administration accordingly.How to cite this article: Mercieca KJ, Fenerty CH, Steeples LR, Drury B, Bhargava A. Precipitants of 5-Fluorouracil in Trabeculectomy Bleb Management : A Comparative Laboratory StudyJ Curr Glaucoma Pract 2018;12(2):64-66.

Trabeculectomy bleb needling and antimetabolite administration practices in the UK: a glaucoma specialist national survey.

AIMS: To evaluate, describe and quantify the diversity in postoperative antimetabolite administration and bleb needling practices among glaucoma specialists performing trabeculectomy surgery within the UK and Ireland. METHODS: A cross-sectional online survey was distributed to all consultant glaucoma specialists who are on the United Kingdom and Eire Glaucoma Society (UKEGS) contact list. Participants were asked specific questions about their current practices for post-trabeculectomy antimetabolite administration followed by questions directly related to bleb needling procedures. RESULTS: 60 (83%) of UKEGS glaucoma subspecialty consultants completed the survey. 70% of respondents administered 5-fluorouracil (5-FU) in their clinic room while 30% used a separate treatment room. Doses of 5-FU varied considerably but 70% used 5 mg as standard. Techniques used to reduce corneal toxicity included precipitation with amethocaine (44%) or benoxinate (14%), saline wash (14%) and modified injection technique (8%). Topical antibiotics and/or betadine were used to prevent infection following 5-FU injection in just over 50%. Bleb needling was exclusively performed in operating theatre by 56% of respondents and solely at the slit lamp in the clinic room by 12%. A further 30% used a combination of both theatre and outpatient clinic rooms. Anti-metabolites used were 5-FU (72%) and mitomycin C (22%) with 12% using either of the two substances. CONCLUSIONS: There is a significantly wide variety of current practices for antimetabolite administration and bleb needling within the UK and Ireland. This may be influenced by a glaucoma surgeon's specific experience and audit results as well as particular clinical set-up, availability of antimetabolite and clinic room space.

Disposable versus non-disposable tonometer prisms: a UK national survey.

PURPOSE: To determine the prevalence of disposable tonometer versus non-disposable tonometer use in the UK and to determine methods of decontamination and frequency of replacement of prisms.A total of 137 ophthalmology departments were interviewed by telephone using a structured questionnaire. The main outcome measured were:types of tonometer prisms used in clinic (disposable, non-disposable and/or other)average disposable prisms used per clinic sessionaverage lifespan of non-disposable prismsprism preference by glaucoma and other teams within department.A cost and benefit analysis was then performed on the data acquired. RESULTS: One hundred and fifty-five departments were identified for the survey. Of these, 137 (88.3%) responded. Eighty-one departments (59.1%) used Tonosafe prisms alone, whereas 22 departments (16.1%) used Goldmann non-disposable prisms exclusively. Thirty-five departments (64%) on average have a change rate of 26.5% per year (range: 0-100, median: 20) attributed to damage, loss or theft. Sixteen departments (29%) reported that prisms were used until damaged or lost. Four departments (7%) were uncertain of their prism usage and could not provide further information. CONCLUSIONS: Majority of eye departments in the UK opt for disposable prisms. This survey shows the perceived cost-effectiveness of disposable prisms is overestimated when the true cost of disinfection and damage is taken into account. Significant cost savings coupled with the low risk of infectivity (if decontaminated properly) should prompt clinicians and ophthalmic departments worldwide to reconsider the use of non-disposable prisms.

Corneal epitheliopathy in congenital methemoglobinemia.

PURPOSE: The aim of this study was to describe a previously unreported characteristic corneal epitheliopathy in congenital methemoglobinemia (type 1). METHODS: This was an observational case series of ocular findings in congenital methemoglobinemia. RESULTS: Siblings of 2 different affected families (age range, 12-14 years; 3 girls, 1 boy) affected with congenital methemoglobinemia had similar ocular complaints and clinical presentation. All of them had recurrent episodes of irritation and tearing in both eyes. Slit lamp biomicroscopy examination in all of them revealed the presence of dark colored corkscrew conjunctival vessels (prominently seen on the tarsal and forniceal region) and grayish-white raised corneal epithelial lesions. Diagnostic corneal scrapings in 2 of the patients showed the presence of epithelial cells with nonspecific inflammatory cells, and the results were negative for microbes. None of the patients had any abnormality in the lid adnexa, blink response, corneal sensation, or in the tear film. The corneal lesions resolved in 2 to 3 weeks time while on supportive therapy alone and on vitamin C supplements. CONCLUSIONS: Dark colored conjunctival vessels and recurrent corneal epitheliopathy causing irritation and tearing may be ocular features associated with congenital methemoglobinemia. It is pertinent for ophthalmologists, hematologists, and pediatricians to be aware of this association.

Challenge in diagnosis of CD56+ lymphoproliferative disorders: two cases of CD56+CD33+ lymphoma/leukemia.

Two cases of CD56+CD33+ leukemia/lymphoma are reported. The patient in case 1 presented with skin rash, diffuse lymphadenopathy, and hepatosplenomegaly. Blasts with monocytoid and lymphoid features were present in the peripheral blood. The tumor cells expressed HLA-DR, CD4, CD33, CD38, and CD56. Cytogenetic analysis revealed del(2)(p13),del(9)(q22),add(6)(q25),add(12)(p12),-13,-18, and -20. The clinicopathologic features were similar to those of blastic natural killer cell leukemia/lymphoma or type 2 dentritic cell leukemia. The patient in case 2 presented with generalized weakness and skin erythema not responding to antibiotics. Circulating blasts with monocytoid features were seen in the peripheral blood. The tumor cells expressed CD7, CD13, CD33, CD38, and CD56, and cytogenetic analysis revealed -5,add(7)(p22),-8, del(10)(p11.2),-12,der(13; 14)(p10;p10),+14,-16,-18,-19, and del(20)(q13.1). The clinicopathologic features were consistent with a myeloid/ natural killer cell precursor acute leukemia. Both disorders are aggressive hematopoietic malignancies that have similar clinical presentation and morphology but differ in immunophenotype and cytogenetic features.

Prolonged activated partial thromboplastin time in pregnancy: a brief report.

BACKGROUND: Limited data are available regarding causes of prolonged activated partial thromboplastin time (aPTT) in otherwise normal pregnancies. We retrospectively evaluated clinical data of pregnant women in whom an elevated aPTT was noted on routine prenatal testing. Our intent was to identify various causes of prolonged aPTT and to evaluate whether the pregnancies were adversely affected. METHODS: A retrospective review of medical records of 36 pregnant patients with a prolonged aPTT as the sole abnormal coagulation test seen in the outpatient department of a tertiary care hospital over a period of 4 years. RESULTS: Patients' median age was 26 (range, 19-41) years and median duration of gestation period was 19 (range, 8-38) weeks. Fifteen patients were primigravida. Of 36 patients, repeated aPTT values were normal in 24 (67%) patients, whereas 12 (33%) patients had persistently elevated aPTT values. Factor XI deficiency was found in 5 patients, lupus anticoagulant in 3 patients, elevated anticardiolipin antibody in 2 patients, and low von Willebrand Factor level in 1 patient. Overall, 23 patients delivered. No patients experienced excessive bleeding or thromboembolism. CONCLUSION: Factor XI deficiency and antiphospholipid antibody were 2 major abnormalities identified in patients with prolonged aPTT. These coagulopathies were not associated with excessive bleeding or thromboembolism. Repeat normal aPTT in approximately 2 thirds of patients suggests that proper sample collection and processing are important for coagulation assays to avoid erroneous clotting times.