Molecular epidemiology of lumpy skin disease outbreak in Odisha, India.

Lumpy skin disease virus (LSDV) is the causative agent of lumpy skin disease (LSD) which is a member of Capripoxvirus. It is an economically critical transboundary disease affecting cattle. This study records an LSD outbreak in Ganjam district of Odisha, India during August 2020. The epidemiological data were analysed and LSDV was genetically characterized. Out of the 452 animals clinically examined (59 farms), 63 animals were clinically affected with LSD, with a total morbidity rate of 13.93%. The morbidity rates in the surveyed villages (n = 10) varied from 5.55 to 21.62%. The multivariable logistic regression analysis showed that grazing of animals (P = 0.013; OR: 2.04; 95% CI: 1.16-3.57) and age of cows > 3 years old (P = 0.001; OR: 2.90; 95% CI: 1.65- 5.07) were potential risk factors for the presence of LSD. Out of the 53 clinically suspected animals' samples, 18 samples (33.96%) were found positive for both the P32 and F genes of Capripoxvirus by PCR. Phylogenetic analysis of the P32 gene of LSDV (MW147486) showed 100% similarity with other isolates from India, Bangladesh, Egypt and Saudi Arabia. Additionally, phylogenetic analysis of the F gene of LSDV (MW147485) revealed a similarity of 97.99%, with Odisha India (MT074110) isolate and located in the same cluster with other Indian isolates.

Patterns of Antifungal Resistance in Adult Patients With Fungal Keratitis in South India: A Post Hoc Analysis of 3 Randomized Clinical Trials.

IMPORTANCE: Antifungal resistance has been shown to impact treatment success, but research analyzing antifungal resistance is scarce. OBJECTIVE: To evaluate changes in antifungal resistance over time. DESIGN, SETTING, AND PARTICIPANTS: Ad hoc analysis of 3 randomized clinical trials including consecutive patients 18 years and older presenting with smear-positive fungal ulcers to Aravind Eye Hospitals in Madurai, Coimbatore, Pondicherry, and Tirunelveli in South India who participated in 1 of 3 clinical trials: the Mycotic Ulcer Treatment Trials (MUTT) I (2010 to 2011) or II (2010 to 2015) or the Cross-Linking Assisted Infection Reduction (CLAIR) trial (2016 to 2018). This post hoc analysis was designed in March 2021 and data were analyzed in May and November 2021. INTERVENTIONS: Minimum inhibitory concentration (MIC) of natamycin and voriconazole was determined from corneal cultures obtained using standardized methods outlined in the Clinical and Laboratory Standards Institute. MAIN OUTCOMES AND MEASURES: The primary outcome of this post hoc analysis was MIC of natamycin and voriconazole. RESULTS: A total of 890 fungal isolates were obtained from 651 patients (mean [SD] age, 49.6 [13.0]; 191 [43.3%] female) from 2010 to 2018. MICs were available for 522 samples in 446 patients. Fungal isolates overall demonstrated a 1.02-fold increase per year in voriconazole resistance as measured by MICs (95% CI, 1.00-1.04; P = .06). In subgroup analyses, Fusarium species demonstrated a 1.04-fold increase in voriconazole resistance per year (95% CI, 1.00-1.06; P = .01). Fungal isolates showed a 1.06-fold increase in natamycin resistance per year overall (95% CI, 1.03-1.09; P < .001). Fusarium species had a 1.06-fold increase in natamycin resistance (95% CI, 1.05-1.08; P < .001), Aspergillus had a 1.09-fold increase in resistance (95% CI, 1.05-1.15; P < .001), and other filamentous fungi had a 1.07-fold increase in resistance to natamycin per year (95% CI, 1.04-1.10; P < .001). CONCLUSIONS AND RELEVANCE: This post hoc analysis suggests that susceptibility to both natamycin and voriconazole may be decreasing over the last decade in South India. While a trend of increasing resistance could impact treatment of mycoses in general and infectious fungal keratitis in particular, further study is needed to confirm these findings and determine their generalizability to other regions of the world. TRIAL REGISTRATION: ClinicalTrials.gov Identifiers: NCT00996736 and NCT02570321.

Transplacental transmission of Theileria annulata in cattle confirmed by molecular techniques.

Theileria annulata (T. annulata) is a tick-borne apicomplexan parasite affecting ruminants and causes severe economic loss. The present paper reports the vertical transmission of T. annulata in a three day old crossbred Jersey calf. Molecular diagnosis of tropical theileriosis was done by PCR, cloning, sequencing and phylogenetic analysis of isolated parasites. Calf showed very low hematocrit value (HCT) (17.82%), red blood cells count (RBC) count (6.9 × 106/µL), and hemoglobin concentration (Hb) (6.6 g/dL). Phylogenetic analysis of Tams 1 gene showed that T. annulata Khorda isolate (MW123091) shared 99.23%, 99.23% and 99.11% nucleotide homology with Puri, India (MN818858), Bahrain (AF214797) and Hyderabad, India (MK034702), respectively. This is the first study in Odisha, India to give an insight into the molecular detection, phylogeny and hematological analysis of T. annulata infected crossbred Jersey calf which got the infection through transplacental transmission.

Efficacy of immunization compared to an anticoccidial drug combination in the management of challenged coccidiosis in Japanese quail.

This study was carried out to compare the efficacy of immunization, by a low-dose of live sporulated oocysts of different Eimeria species separately, with the efficacy of amprolium plus sulphaquinoxaline in the management of challenged coccidiosis in Japanese quail. Dropping samples were collected and sent to the laboratory for isolation and identification of Eimeria species. Three Eimeria species were isolated and identified as E. bateri, E. uzura, and E. tsunodai. Single oocyst isolation and propagation were done successfully for each species. For the experimental trial, Japanese quails were divided into 11 groups of thirty birds each and given different treatments. The assessment of each treatment relied on clinical signs, mortality, lesion score, oocyst output, weight gain, feed conversion ratio, and hematological parameters. The results revealed that immunization, with any isolated species, gave the best results regarding all tested parameters. Thus, we concluded that immunization by a low-dose of live sporulated oocysts was better compared to amprolium plus sulphaquinoxaline in the management of coccidiosis in Japanese quail.

Molecular detection of Theileria annulata infection in cattle by conventional PCR and quantitative real time PCR in India.

Theileria annulata (T. annulata) is a tick-borne apicomplexan parasite that affects bovine. It is endemic in many tropical and subtropics areas, including Odisha, India. The objective of this study is to identify T. annulata infection in the peripheral blood of cattle as a biological sample by conventional PCR (cPCR) and quantitative PCR (qPCR). The phylogenetic analysis was done using the T. annulata merozoite surface antigen (Tams 1) gene. Out of 552 samples of examined blood smears by microscopy, 454 (82.24%) animals were positive for Theileria species. Out of 454 samples, 96 samples were further examined by both cPCR and qPCR, 52 samples (54.16%) were found positive for T. annulata in both PCR methodologies. Phylogenetic analysis revealed that T. annulata Odisha isolate was closely related to T. annulata Uttarakhand, India isolate (KM061799) and Hyderabad, India isolate (MK034702) with Nucleotide sequence identity 95.36%, 95.25%, respectively. This is the first study to detect T. annulata by qPCR in Odisha and supported that both PCR techniques were equally effective for the detection of Tams 1 gene of T. annulata in cattle's blood.

Molecular, epidemiological and haematological evaluation in Theileria orientalis infected cattle from an endemic region in India.

The objective of the present study was to investigate the epidemiological and haematological parameters with simultaneous molecular detection of Theileria orientalis infection of crossbred jersey (CBJ) cattle. Haematological values like mean hemoglobin (Hb) (7.31 ± 2.3 g/dl), packed cell volume (PCV) (21.69 ± 6.11%), red blood cells count (RBCs) (4.40 ± 1.6 M/µl), white blood cells count (WBCs) (6.93 ± 3.06 103/µl) and mean corpuscular hemoglobin concentration (MCHC) (33.56 ± 3.51 g/dl) were decreased significantly (p < 0.05), whereas mean corpuscular volume (MCV) (51.06 ± 6.14fl) and eosinophil count (0.39 ± 0.44 103/µl) were significantly (p < 0.05) increased in cattle infected with T. orientalis. Analysis of major piroplasm surface protein (MPSP) of 110 blood samples randomly collected from cattle from seven districts by PCR indicated that an average of 70% of cattle was positive for T. orientalis infection. In particular, Puri and Khorda districts were identified as relatively high-risk areas for T. orientalis infection, with infection rates of 76.66% and 72.4%, respectively. The phylogenetic analysis of isolated T. orientalis MPSP gene (MN334767) classified it into type 5. Earlier Indian isolates were classified into three types viz.type 1, type 3 and type 7 and this is the first time to detect type 5 in Odisha, India.

Descemet Membrane Suturing for Large Descemet Membrane Detachment After Cataract Surgery.

PURPOSE: To study the outcomes of Descemet membrane (DM) suturing for moderate to severe Descemet membrane detachment (DMD) after cataract surgery. METHODS: This is a retrospective case review of all patients who underwent DM suturing for moderate to severe DMD after cataract surgery in a tertiary training eye care hospital from January 2017 to December 2017. Demographic details, type of cataract, type of cataract surgery, intraoperative complications, severity of DMD, time to repair, and post-DM suturing visual and clinical outcomes were documented. RESULTS: Forty-nine patients were included during the study period with a mean age of 67.7 ± 9.7 years. In total, 79.5% had immature cataracts. Median precataract LogMAR visual acuity was 0.78 (IQR 0.69-1.13). In total, 61.2% underwent manual small-incision cataract surgery, 32.6% had phacoemulsification, 2% had extracapsular cataract extraction (ECCE), and 6% underwent small-incision cataract surgery with trabeculectomy. In total, 44.9% were operated on by trainees and 55.1% were operated on by consultants. In total, 22.4% had primary air descemetopexy during the cataract surgery and failed treatment. All patients had attached DM in the immediate postoperative period. None of them had secondary angle closure glaucoma. At the final follow-up, 42 (85.7%) had clear corneas and 7 (14.3%) had corneal decompensation needing endothelial keratoplasty. Of these 7 patients, 2 (28.5%) had Fuchs dystrophy and 3 (42.8%) had associated DM loss. The median LogMAR visual acuity at the final follow-up was 0.39 (IQR 0.3-0.78). CONCLUSIONS: DM suturing can reattach DM, especially in moderate to severe, recurrent DMD with fewer postoperative complications and thereby reduce the need for corneal transplantation.

Association of Postfungal Keratitis Corneal Scar Features With Visual Acuity.

Importance: Corneal opacity is a leading cause of visual impairment worldwide; however, the specific features of corneal scars, which decrease visual acuity, have not been well characterized. Objective: To investigate which features of a postfungal keratitis corneal scar contribute to decreased visual acuity after an episode of infectious keratitis and evaluate whether any corneal features may be used as outcomes for clinical trials. Design, Setting, and Participants: In this ancillary, prospective cross-sectional study, a subset of study participants treated for fungal keratitis (n = 71) as part of the Mycotic Ulcer Treatment Trial I (MUTT I) underwent best spectacle-corrected visual acuity (BSCVA) and best contact lens-corrected visual acuity examination, Scheimpflug imaging, and anterior segment optical coherence tomography at a referral hospital in India approximately 2 years after enrollment. Data were collected from December 3, 2012, to December 19, 2012, and analyses were performed from December 2, 2013, to October 2, 2019. Main Outcomes and Measures: Linear regression models were used to evaluate the importance of various corneal features for BSCVA and to assess whether these features could be used to differentiate the 2 treatment arms of the MUTT I trial. Results: Seventy-one patients (42 men [59.1%]; median age, 48 [range, 39-60] years) were examined at a median (IQR) time of 1.8 (1.4-2.2) years after enrollment. The mean (SD) logMAR BSCVA was 0.17 (0.19) (Snellen equivalent, 20/32). In multivariable linear regression models, BSCVA was most associated with irregular astigmatism (1.0 line of worse BSCVA per 1-line difference between BSCVA and contact lens visual acuity; 95% CI, 0.6-1.4) and corneal scar density (1.5 lines of worse vision per 10-unit increase in the mean central corneal density; 95% CI, 0.8-2.3). The thinnest point of the cornea was the metric that best discriminated between the natamycin- and voriconazole-treated ulcers in MUTT I, with 29.3 µm (95% CI, 7.1-51.6 µm) less thinning in natamycin-treated eyes. Conclusions and Relevance: Both irregular astigmatism and corneal scar density may be important risk factors for BSCVA in a population with relatively mild, healed fungal corneal ulcers. The thinnest point of the corneal scar may be a cornea-specific outcome that could be used to evaluate treatments for corneal ulcers.

Repeatability and Reproducibility of Slit Lamp, Optical Coherence Tomography, and Scheimpflug Measurements of Corneal Scars.

Purpose: To determine the repeatability and reproducibility of anterior segment optical coherence tomography (AS-OCT) and Scheimpflug photography for several measurements of corneal scars, including scar size, scar depth, and corneal thickness. Methods: A series of patients treated for fungal keratitis at a tertiary eye care center in South India were recalled two years after successful treatment. Eyes with corneal scars had a slit lamp examination performed by two ophthalmologists masked to the other's examination. For AS-OCT and Scheimpflug photography, each eye had two scans taken by one technician and a third scan taken by a separate technician. Scar measurements were subsequently assessed from AS-OCT images by three graders masked to each other's results. Repeatability and reproducibility were assessed by calculating the intra-class correlation coefficient (ICC) from mixed effects linear regression models. Results: Fifty eyes had all measurements taken. The corneal scar size, measured as the geometric mean of the two longest perpendicular meridians, ranged from 0.8 to 5.4 (mean 2.8 mm, 95%CI 2.6 to 3.1). Scar size measurements taken by two separate individuals were most reproducible when the border of the scar was traced from the OCT (ICC 0.90, 95%CI 0.86 to 0.94), and least repeatable when assessed from slit lamp examination (ICC 0.80, 95%CI 0.70 to 0.90). Conclusions: AS-OCT and Scheimpflug imaging of corneal scars produced measurements with acceptable reproducibility that could be useful as cornea-specific outcomes for clinical trials.

Colonization of therapeutic contact lens by dematiaceous fungi.

PURPOSE: To report 2 patients with colonization of therapeutic contact lens with dematiaceous fungi. METHODS: Case report. RESULTS: The first patient had a retained soft contact lens on an opaque cornea for 4 years with brownish black multiple colonies on the soft contact lens and culture grew Bipolaris spp. The second patient was on therapeutic contact lens for pseudophakic bullous keratopathy for 4 months and developed a brownish colonization of contact lens with unidentified dematiaceous fungi. Both the patients had conjunctivitis but did not develop fungal keratitis. CONCLUSION: Judicious use of therapeutic contact lens is required in agrarian countries with adequate emphasis on strict adherence to the standard protocols and frequent replacement of the lens.

Influence of extraction parameters and stability of betacyanins extracted from red amaranth during storage.

Natural colorants are important alternatives to synthetic colorants. They are considered harmless and positively affect biological activities owing to their antioxidant potential. The present study deals with the assessment of the extraction processes and the effects of pH (1.0, 3.0, and 5.0), extraction media (water and 50% ethanol) and storage condition (ambient and refrigeration) on betacyanin content, color values, as well as degradation kinetics of total betacyanins in red amaranth. Betacyanin content was more stable at higher than at lower pH. The degradation rate constant (K) was higher and the half-life (t1/2) was lower at ambient temperature compared to refrigeration temperature. Betacyanin degradation was higher at ambient temperature (30 ± 2 °C) than at refrigeration temperature (4 °C). The pH, storage time, and temperature affected the stability of the color attributes. Therefore, this work suggests that water and lower temperature (4 °C) could be applied to extract more betacyanins from red amaranth and betacyanins might be used as an alternative to synthetic color.

Effect of age on dental plaque deposition and its control by ultrasonic scaling, dental hygiene chew, and chlorhexidine (0.2%w/v) in dogs.

BACKGROUND AND AIM: Periodontitis is the most prevalent inflammatory dental disease caused by a lack of oral hygiene measures in domestic animals. The periodontal disease complex arises as a result of bacterial biofilm deposition termed as plaque on the tooth surface. Lack of cleaning measures either mechanical or chemical credit for the condition. The present study was conducted to screen the animals for the presence of plaque deposition, gingivitis, along with various control measures for the same. MATERIALS AND METHODS: Thirty-two dogs of different age groups were evaluated for the presence of plaque and gingivitis by scoring method to estimate the extent of severity. Scaling of the tooth surface was done by ultrasonic scaling machine to remove the plaques, and the animals were divided into four treatment groups to study the effects of dental hygiene chew and chlorhexidine for control of plaque. RESULTS: Present study revealed 71.87% and 34.37% of the screened animals were having plaque deposition and varied degrees of gingivitis respectively. A positive coefficient of correlation (r) of 0.89 (p<0.05) between advancing age and plaque deposition and 0.85 (p<0.05) between age and level of gingivitis was obtained. Two groups receiving dental chew and 0.2% w/v chlorhexidine showed lower plaque deposits, and the fourth treatment group receiving both dental chew and chlorhexidine showed 100% animals remained free from fresh plaque deposits. CONCLUSION: The present study showed a strong positive relationship between age and plaque deposition and gingivitis. The study also showed that oral hygiene measures such as use of dental hygiene chew and chlorhexidine application can reduce plaque deposition and periodontitis in domesticated canines.

The Significance of Repeat Cultures in the Treatment of Severe Fungal Keratitis.

PURPOSE: To identify fungal keratitis patients who are at risk of a poor outcome and may benefit from closer follow-up or more aggressive treatment. DESIGN: Secondary analysis of randomized clinical trial data. METHODS: We compared the clinical outcomes of patients who had positive 6-day fungal cultures with those who did not, using backward stepwise regression with covariates for all baseline clinical characteristics. SUBJECTS: Patients presenting with a smear-positive filamentous fungal ulcer and visual acuity of 20/400 or worse, and who subsequently had a 6-day fungal culture performed at the Aravind Eye Care system (India), Lumbini Eye Hospital (Nepal), or Bharatpur Eye Hospital (Nepal). MAIN OUTCOME MEASURES: The primary outcome is rate of corneal perforation and/or the need for therapeutic penetrating keratoplasty. Secondary outcomes include 3-month best spectacle-corrected visual acuity (BSCVA), 3-month infiltrate and/or scar size, and rate of re-epithelialization. RESULTS: Patients who tested positive at their 6-day culture had twice the hazard of experiencing a corneal perforation or the need for therapeutic penetrating keratoplasty (P = .002) than those who tested negative, even after controlling for baseline ulcer characteristics. These patients also had on average 0.26 logMAR lines worse BSCVA at 3 months (P = .001). Culture positivity at day 6 was not a statistically significant predictor of 3-month infiltrate/scar-size (-0.24 mm1; P = .45) or time to re-epithelialization (hazard ratio = .81; P = .31). CONCLUSIONS: Here we identify a uniquely valuable clinical tool, day 6 culture results, for the treatment of severe fungal keratitis. Risk stratification based on repeat culture positivity is an objective way to assess response to medical therapy and identify patients who are at high risk of a poor clinical outcome. This establishes a new standard of care for severe fungal keratitis management.

Ocular manifestations of isolated corneal bee sting injury, management strategies, and clinical outcomes.

PURPOSE: The purpose of this study is to describe the presenting features, management strategies, and clinical outcome following bee sting injury to the cornea. METHODS: Retrospective case series involving 11 eyes of 11 patients with corneal bee sting injuries who presented over a period of 2 years. Nine of these 11 eyes had the presence of intact bee stinger in the cornea, which was removed immediately under an operating microscope and sent for microbiological and histopathological evaluation. The patients were managed as per the individual treatment protocol of the respective treating physicians. RESULTS: Six eyes (54.5%) had a good clinical outcome (best-corrected visual acuity [BCVA] >20/40) with medical therapy alone with no need for surgical intervention. Five eyes (45.5%) had a poor clinical outcome (BCVA <20/40) with medical therapy and required surgery; of which three required a combined penetrating keratoplasty with cataract surgery, while one required isolated cataract surgery and one underwent penetrating keratoplasty. Glaucoma was present in 3/5 eyes undergoing surgery, one of which required a trabeculectomy. Five of the six eyes who had a good clinical outcome with medical therapy alone had been treated with concomitant oral steroids, along with topical antibiotic-steroid combination therapy. CONCLUSION: Oral corticosteroid supplementation to the topical steroid antibiotic treatment in patients with corneal bee sting injury where corneal involvement and anterior reaction is severe at presentation or inflammation not ameliorating with topical steroids alone prevents serious vision-threatening complications such as corneal decompensation, cataract, and glaucoma.

Microsporidial infection masquerading as graft rejection post-Descemet's stripping automated endothelial keratoplasty.

A 51-year-old immunocompetent male with a history of Fuchs' endothelial dystrophy and immature cataract who underwent Descemet's stripping automated endothelial keratoplasty with intraocular lens implantation in both eyes presented with redness and defective vision of 1-day duration in his left eye. Slit lamp examination revealed coarse superficial punctate lesions with graft edema. He was diagnosed with acute graft rejection and treated with topical steroids. Two days later, symptoms worsened in his left eye with the involvement of his right eye showing a similar clinical picture. An infectious etiology was suspected and in vivo confocal microscopy ordered, which revealed hyperreflective dots, highly suggestive of microsporidial spores. The patient was prescribed topical fluconazole 0.3% in both eyes. This unique presentation of bilateral graft edema following microsporidial keratoconjunctivitis in postgraft patients requires a high index of suspicion as it can be easily be mistaken for and mismanaged as acute graft rejection.

Predictors of Corneal Perforation or Need for Therapeutic Keratoplasty in Severe Fungal Keratitis: A Secondary Analysis of the Mycotic Ulcer Treatment Trial II.

Importance: Identifying patients with infectious keratitis who are at risk of experiencing a poor outcome may be useful to allocate resources toward high-risk patients, particularly in resource-poor settings. Objective: To determine baseline patient and ulcer characteristics that predict a high risk of developing corneal perforation and/or the need to undergo therapeutic penetrating keratoplasty (TPK). Design, Setting, and Participants: This is a secondary analysis of Mycotic Ulcer Treatment Trial II, a multicenter, double-masked, placebo-controlled randomized clinical trial that enrolled 240 patients with smear-positive filamentous fungal corneal ulcers who enrolled between May 2010 and August 2015. Participants had a baseline visual acuity of 20/400 or worse and were randomized to receive oral voriconazole or a placebo (all participants received topical voriconazole, 1%). After 39 participants (16.3%) were enrolled, topical natamycin, 5%, was also added. Main Outcomes and Measures: The primary outcome of this secondary analysis was the rate of corneal perforation or the need to undergo TPK. Results: The mean (SD) age at enrollment was 49 (13) years, 104 participants (43.3%) were women, and all were of Southeast Asian descent. The presence of hypopyon at baseline indicated 2.28 times the odds of the patient developing corneal perforation and/or needing TPK (95% CI, 1.18-4.40; P = .01). Study participants whose infiltrate involved the posterior one-third had a 71.4% risk of developing corneal perforation and/or needing TPK. For each 1-mm increase in the geometric mean of the infiltrate, there was 1.37 (95% CI, 1.12-1.67; P = .002) increased odds of developing perforation and/or needing TPK. Other clinical features such as visual acuity, baseline culture positivity, type of filamentous fungal organism and duration of symptoms, and demographic characteristics, such as sex and occupation, were not significant predictors in the multivariable regression analysis. Conclusions and Relevance: These results suggest that risk stratification from baseline ulcer characteristics can identify those at highest risk for developing corneal perforation and/or needing TPK. Trial Registration: clinicaltrials.gov Identifier: NCT00996736.

Adjunctive Oral Voriconazole Treatment of Fusarium Keratitis: A Secondary Analysis From the Mycotic Ulcer Treatment Trial II.

Importance: Fusarium keratitis is common and often results in poor outcomes. No new treatments since natamycin have become available. Objective: To explore the role of adjuvant oral voriconazole on clinical outcomes in Fusarium keratitis. Design, Setting, and Participants: In this prespecified subgroup analysis of a multicenter, double-masked, placebo-controlled randomized clinical trial, 240 patients from the Aravind Eye Care System in India, the Lumbini Eye Hospital and Bharatpur Eye Hospital in Nepal, and the University of California, San Francisco, who had culture-positive fungal ulcer and baseline visual acuity of 20/400 or worse were randomized to receive oral voriconazole vs placebo. Enrollment started May 24, 2010, and the last patient study visit was November 23, 2015. All patients received topical voriconazole, 1%, and after the results of the Mycotic Ulcer Treatment Trial (MUTT) II became available, topical natamycin, 5%, was added for all patients. Data analysis was performed from September 2 to October 28, 2016. Main Outcomes and Measures: The primary outcome of the trial was the rate of corneal perforation or the need for therapeutic penetrating keratoplasty. Secondary outcomes included rate of reepithelialization, best spectacle-corrected visual acuity, and infiltrate or scar size at 3 months. Results: Of the 240 study participants, 72 (30.4%) were culture positive for Fusarium species (41 [56.9%] male and 31 [43.1%] female; median [interquartile range] age, 50 [45-57] years). Of these, 33 (45.8%) were randomized to oral voriconazole and 39 (54.2%) to placebo. Fusarium ulcers randomized to oral voriconazole had a 0.43-fold decreased hazard of perforation or therapeutic penetrating keratoplasty compared with placebo after controlling for baseline infiltrate depth (95% CI, 0.22-fold to 0.84-fold; P = .01). Multiple linear regression revealed a 1.89-mm decreased infiltrate and/or scar size at 3 weeks (95% CI, -2.69 to -1.09 mm; P < .001) and a 0.83-mm decreased infiltrate and/or scar size at 3 months after correcting for baseline values (95% CI, -1.33 to -0.32 mm; P = .001) in eyes randomized to oral voriconazole vs placebo. Eyes treated with oral voriconazole also had a mean 0.29 decreased logMAR (improved) (Snellen equivalent 20/40) visual acuity at 3 months after controlling for baseline visual acuity, although this finding was not statistically significant (95% CI, -0.57 to 0.002; P = .052). Conclusions and Relevance: Although MUTT II could not find a benefit for all corneal ulcers, Fusarium keratitis may benefit from the addition of oral voriconazole to topical natamycin, and physicians should consider prescribing oral voriconazole in these cases. Trial Registration: clinicaltrials.gov Identifier: NCT00996736.

Trends in antibiotic resistance in bacterial keratitis isolates from South India.

AIMS: To report trends in antibiotic resistance in cases of bacterial keratitis from a large eye hospital in South India. METHODS: In this retrospective cross-sectional study, the microbiology laboratory records of patients with infectious keratitis diagnosed at an eye hospital in South India from 2002 to 2013 were reviewed to determine the proportion with antibiotic non-susceptibility. RESULTS: 3685 bacterial isolates had susceptibility testing performed over the 12-year period. The two most common organisms with resistance were Streptococcus pneumoniae (n=1204) and Pseudomonas aeruginosa (n=894). Antibiotic non-susceptibility was generally uncommon for these two organisms and no significant trends were detected over the course of the study. In contrast, Staphylococcus aureus (N=211) isolates demonstrated a significant increase in fluoroquinolone non-susceptibility over the 12-year study period. This coincided with a significant increase in methicillin-resistant S. aureus (MRSA) during the study period, though the increase in fluoroquinolone resistance was likewise seen in methicillin-sensitive S. aureus (MSSA). For example, ofloxacin resistance in MSSA increased from 11.1% in 2002 to 66.7% in 2013 (p=0.002). No trends were apparent for the aminoglycosides, cefazolin or vancomycin, for which in vitro non-susceptibility generally appeared to be low. CONCLUSION: Resistance to antibiotics was generally stable for infectious keratitis isolates from a large eye hospital in South India, except for S. aureus, which experienced a significant increase in fluoroquinolone resistance from 2002 to 2013. Fluoroquinolone antibiotics currently have poor in vitro activity against both MRSA and MSSA in South India and are therefore not the ideal therapy for Staphylococcal corneal ulcers.

Effect of Oral Voriconazole on Fungal Keratitis in the Mycotic Ulcer Treatment Trial II (MUTT II): A Randomized Clinical Trial.

Objective: To compare oral voriconazole with placebo in addition to topical antifungals in the treatment of filamentous fungal keratitis. Design, Setting, and Participants: The Mycotic Ulcer Treatment Trial II (MUTT II), a multicenter, double-masked, placebo-controlled, randomized clinical trial, was conducted in India and Nepal, with 2133 individuals screened for inclusion. Patients with smear-positive filamentous fungal ulcers and visual acuity of 20/400 (logMAR 1.3) or worse were randomized to receive oral voriconazole vs oral placebo; all participants received topical antifungal eyedrops. The study was conducted from May 24, 2010, to November 23, 2015. All trial end points were analyzed on an intent-to-treat basis. Interventions: Study participants were randomized to receive oral voriconazole vs oral placebo; a voriconazole loading dose of 400 mg was administered twice daily for 24 hours, followed by a maintenance dose of 200 mg twice daily for 20 days, with dosing altered to weight based during the trial. All participants received topical voriconazole, 1%, and natamycin, 5%. Main Outcomes and Measures: The primary outcome of the trial was rate of corneal perforation or the need for therapeutic penetrating keratoplasty (TPK) within 3 months. Secondary outcomes included microbiologic cure at 6 days, rate of re-epithelialization, best-corrected visual acuity and infiltrate and/or scar size at 3 weeks and 3 months, and complication rates associated with voriconazole use. Results: A total of 2133 patients in India and Nepal with smear-positive ulcers were screened; of the 787 who were eligible, 240 (30.5%) were enrolled. Of the 119 patients (49.6%) in the oral voriconazole treatment group, 65 were male (54.6%), and the median age was 54 years (interquartile range, 42-62 years). Overall, no difference in the rate of corneal perforation or the need for TPK was determined for oral voriconazole vs placebo (hazard ratio, 0.82; 95% CI, 0.57-1.18; P = .29). In prespecified subgroup analyses comparing treatment effects among organism subgroups, there was some suggestion that Fusarium species might have a decreased rate of perforation or TPK in the oral voriconazole-treated arm; however, this was not a statistically significant finding after Holms-Sidák correction for multiple comparisons (effect coefficient, 0.49; 95% CI, 0.26-0.92; P = .03). Patients receiving oral voriconazole experienced a total of 58 adverse events (48.7%) compared with 28 adverse events (23.1%) in the placebo group (P < .001 after Holms-Sidák correction for multiple comparisons). Conclusions and Relevance: There appears to be no benefit to adding oral voriconazole to topical antifungal agents in the treatment of severe filamentous fungal ulcers. All patients in this study were enrolled in India and Nepal; therefore, it is possible that organisms in this region may exhibit characteristics different from those in other regions of the world. Trial Registration: clinicaltrials.gov Identifier: NCT00996736.

Bilateral Atypical Granular Corneal Dystrophy Associated with Unilateral Keratoconus in a Male Child.

A 14-year-old male presented with decreased vision. Slit lamp examination indicated multiple anterior corneal stromal opacities with clear intervening spaces accompanied with superficial subepithelial lines arranged in a quasi-whorl-like fashion bilateral with greater prominence in the right eye. Corneal steepening associated with thinning was noted only in the right eye. Genetic analysis confirmed a mutation suggestive of granular corneal dystrophy. Here, we describe a rare case of an atypical granular dystrophy associated with unilateral keratoconus in a male child.