A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease.

In response to the 2022 outbreak of mpox driven by unprecedented human-to-human monkeypox virus (MPXV) transmission, we designed BNT166, aiming to create a highly immunogenic, safe, accessible, and scalable next-generation vaccine against MPXV and related orthopoxviruses. To address the multiple viral forms and increase the breadth of immune response, two candidate multivalent mRNA vaccines were evaluated pre-clinically: a quadrivalent vaccine (BNT166a; encoding the MPXV antigens A35, B6, M1, H3) and a trivalent vaccine (BNT166c; without H3). Both candidates induced robust T cell responses and IgG antibodies in mice, including neutralizing antibodies to both MPXV and vaccinia virus. In challenge studies, BNT166a and BNT166c provided complete protection from vaccinia, clade I, and clade IIb MPXV. Furthermore, immunization with BNT166a was 100% effective at preventing death and at suppressing lesions in a lethal clade I MPXV challenge in cynomolgus macaques. These findings support the clinical evaluation of BNT166, now underway (NCT05988203).

Retinoblastoma in Asia: Clinical Presentation and Treatment Outcomes in 2112 Patients from 33 Countries.

PURPOSE: To describe the clinical presentation and treatment outcomes of children who received a diagnosis of retinoblastoma in 2017 throughout Asia. DESIGN: Multinational, prospective study including treatment-naïve patients in Asia who received a diagnosis of retinoblastoma in 2017 and were followed up thereafter. PARTICIPANTS: A total of 2112 patients (2797 eyes) from 96 retinoblastoma treatment centers in 33 Asian countries. INTERVENTIONS: Chemotherapy, radiotherapy, enucleation, and orbital exenteration. MAIN OUTCOME MEASURES: Enucleation and death. RESULTS: Within the cohort, 1021 patients (48%) were from South Asia (SA), 503 patients (24%) were from East Asia (EA), 310 patients (15%) were from Southeast Asia (SEA), 218 patients (10%) were from West Asia (WA), and 60 patients (3%) were from Central Asia (CA). Mean age at presentation was 27 months (median, 23 months; range, < 1-261 months). The cohort included 1195 male patients (57%) and 917 female patients (43%). The most common presenting symptoms were leukocoria (72%) and strabismus (13%). Using the American Joint Committee on Cancer Staging Manual, Eighth Edition, classification, tumors were staged as cT1 (n = 441 [16%]), cT2 (n = 951 [34%]), cT3 (n = 1136 [41%]), cT4 (n = 267 [10%]), N1 (n = 48 [2%]), and M1 (n = 129 [6%]) at presentation. Retinoblastoma was treated with intravenous chemotherapy in 1450 eyes (52%) and 857 eyes (31%) underwent primary enucleation. Three-year Kaplan-Meier estimates for enucleation and death were 33% and 13% for CA, 18% and 4% for EA, 27% and 15% for SA, 32% and 22% for SEA, and 20% and 11% for WA (P < 0.0001 and P < 0.0001), respectively. CONCLUSIONS: At the conclusion of this study, significant heterogeneity was found in treatment outcomes of retinoblastoma among the regions of Asia. East Asia displayed better outcomes with higher rates of globe and life salvage, whereas Southeast Asia showed poorer outcomes compared with the rest of Asia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Antibody-Dependent, Gamma Interferon-Independent Sterilizing Immunity Induced by a Subunit Malaria Vaccine.

The development of effective malaria vaccines is hampered by incomplete understanding of the immunological correlates of protective immunity. Recently, the moderate clinical efficacy of the Plasmodium falciparum circumsporozoite protein (CSP)-based RTS,S/AS01E vaccine in phase 3 studies highlighted the urgency to design and test more efficacious next-generation malaria vaccines. In this study, we report that immunization with recombinant CSP from Plasmodium yoelii (rPyCSP), when delivered in Montanide ISA 51, induced sterilizing immunity against sporozoite challenge in C57BL/6 and BALB/c strains of mice. This immunity was antibody dependent, as evidenced by the complete loss of immunity in B-cell-knockout (KO) mice and by the ability of immune sera to neutralize sporozoite infectivity in mice. Th2-type isotype IgG1 antibody levels were associated with protective immunity. The fact that immunized gamma interferon (IFN-γ)-KO mice and wild-type (WT) mice have similar levels of protective immunity and the absence of IFN-γ-producing CD4+ and CD8+ T cells in protected mice, as shown by flow cytometry, indicate that the immunity is IFN-γ independent. Protection against sporozoite challenge correlated with higher frequencies of CD4+ T cells that express interleukin-2 (IL-2), IL-4, and tumor necrosis factor alpha (TNF-α). In the RTS,S study, clinical immunity was associated with higher IgG levels and frequencies of IL-2- and TNF-α-producing CD4+ T cells. The other hallmarks of immunity in our study included an increased number of follicular B cells but a loss in follicular T helper cells. These results provide an excellent model system to evaluate the efficacy of novel adjuvants and vaccine dosage and determine the correlates of immunity in the search for superior malaria vaccine candidates.

Absence of IQGAP1 Protein Leads to Insulin Resistance.

Insulin binds to the insulin receptor (IR) and induces tyrosine phosphorylation of the receptor and insulin receptor substrate-1 (IRS-1), leading to activation of the PKB/Akt and MAPK/ERK pathways. IQGAP1 is a scaffold protein that interacts with multiple binding partners and integrates diverse signaling cascades. Here we show that IQGAP1 associates with both IR and IRS-1 and influences insulin action. In vitro analysis with pure proteins revealed that the IQ region of IQGAP1 binds directly to the intracellular domain of IR. Similarly, the phosphotyrosine-binding domain of IRS-1 mediates a direct interaction with the C-terminal tail of IQGAP1. Consistent with these observations, both IR and IRS-1 co-immunoprecipitated with IQGAP1 from cells. Investigation of the functional effects of the interactions revealed that in the absence of IQGAP1, insulin-stimulated phosphorylation of Akt and ERK, as well as the association of phosphatidylinositol 3-kinase with IRS-1, were significantly decreased. Importantly, loss of IQGAP1 results in impaired insulin signaling and glucose homeostasis in vivo Collectively, these data reveal that IQGAP1 is a scaffold for IR and IRS-1 and implicate IQGAP1 as a participant in insulin signaling.

Multimodal Therapy for Stage III Retinoblastoma (International Retinoblastoma Staging System): A Prospective Comparative Study.

PURPOSE: To compare the efficacy of 2 chemotherapeutic drug combinations as part of multimodal therapy for orbital retinoblastoma. DESIGN: Prospective, comparative, study. PARTICIPANTS: Patients with stage III retinoblastoma (International Retinoblastoma Staging System). METHODS: Demographic and clinical features were recorded at presentation. Treatment consisted of a multimodal protocol with neoadjuvant chemotherapy, enucleation, orbital external-beam radiotherapy, and adjuvant chemotherapy. For chemotherapy, patients were randomized into 2 groups: group A patients were treated with vincristine, etoposide, and carboplatin (VEC) and group B patients were treated with carboplatin and etoposide, alternating with cyclophosphamide, idarubicin, and vincristine. Treatment outcomes and adverse effects were recorded. Efficacy parameters were compared between the groups. MAIN OUTCOME MEASURES: Survival probability, cause of death, and chemotherapy-related toxicity. RESULTS: A total of 54 children were recruited (27 in each group). The mean ± SD follow-up was 21.3±11.34 months. The overall Kaplan-Meier survival probability was 80% (95% confidence interval [CI], 0.67-0.89) and 42% (95% CI, 0.24-0.59) at 1 year and 4 years, respectively. There were 9 deaths in group A and 15 deaths in group B. The Kaplan-Meier survival probability at 1 year was similar between the groups: 81% (95% CI, 0.60-0.91) and 79% (95% CI, 0.58-0.9) for groups A and B, respectively. At 4 years, the survival probability for group A was higher (63% [95% CI, 0.41-0.79] vs. 25% [95% CI, 0.08-0.46] for groups A and B, respectively), with a strong trend of better survival in group A over time (P = 0.05). The major cause of death was central nervous system relapse (8 patients in group A and 7 patients in group B). Two patients in group B died of sepsis after febrile neutropenia. Grade 3 and grade 4 hematologic toxicities were more common in group B, with a significant difference in grade 4 neutropenia (P = 0.002). CONCLUSIONS: This study compared the outcomes of VEC chemotherapy with a 5-drug combination of etoposide and carboplatin, alternating with cyclophosphamide, idarubicin, and vincristine, for stage III retinoblastoma. The VEC combination was found to be more effective and may be recommended as neoadjuvant and adjuvant chemotherapy.

Expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins in human retinoblastoma.

BACKGROUND: Regulation of apoptosis is a complex process that involves a number of genes, including Bcl-2, Bcl-x, Bax and other Bcl-2 family members. The aim of the present study is to assess the expression of Bcl- 2 and Bax in retinoblastoma, and correlate them with clinical and histopathological parameters. METHODS: The expression of Bcl-2 and Bax proteins were examined using immunohistochemistry, Western blotting and reverse transcriptase-polymerase chain reaction in a series of 60 prospective cases of primary retinoblastoma tissues. RESULTS: Immunohistochemistry showed expression of Bcl-2 in 40/60 (66.6%), whereas Bax expression was found only in 18/60 (30%) cases, and these correlated with mRNA expression. The Western blotting results also correlated well with the immunohistochemical expression of Bcl-2 (25 kDa) and Bax (21 kDa) proteins. Bcl-2 was expressed in 96% (24/25) of invasive tumours and in 45.7% (16/35) of non-invasive tumours. Expression of Bcl-2 significantly correlated with tumour invasiveness (P = 0.0274) and poor differentiation (P = 0.0163), whereas loss of Bax correlated with massive choroidal invasion and Pathological Tumor-Node-Metastasis (pTNM) (P = 0.0341). However, no correlation was found between Bax and Bcl-2 expression. CONCLUSIONS: Our findings suggest that these apoptotic regulatory proteins may serve as poor prognostic markers and can be used as a therapeutic target for the treatment of invasive retinoblastoma. Further functional studies are required to explore the role of Bax and Bcl-2 in retinoblastoma.

Lateral eyelid rotation flap: a novel technique for reconstruction of full thickness eyelid defect.

The purpose of this study was to study anatomical, functional, and cosmetic outcomes of a novel technique, 'Lateral Eyelid Rotation Flap' for reconstruction of full thickness eyelid defect. In this prospective interventional study, 10 patients with full thickness eyelid defect measuring 1/2-2/3rd of eyelid width were included. Eyelid reconstruction was performed by single surgeon, using lateral eyelid rotation flap. Anatomic outcome was assessed by analyzing horizontal and vertical palpebral apertures (HPA and VPA), eyelid contour, and lateral canthus. Functional outcome was assessed by measuring tear film break-up time (TBUT) and Schirmer's test in both the eyes. Cosmetic outcome was evaluated by patients. Median age of patients was 56 years. Nine cases had full thickness defect following the excision of eyelid malignancy. The mean horizontal defect size was 17 ± 4.2 mm. HPA did not change significantly after surgery. VPA was statistically comparable to contralateral eye at 1-month follow-up. Lateral canthus angle recovered by 3rd month after surgery. TBUT and Schirmer's tests were comparable to contralateral eye. Eight patients graded cosmetic outcome as good to excellent. This is a new, single-stage technique for reconstruction of full thickness eyelid defects, with full thickness eyelid tissue including margin.

Orbital schwannoma: a clinicopathologic study.

The aim of the study was to study the clinical, radiological and histopathological characteristics of orbital schwannomas. It is a retrospective study conducted at a tertiary eye care hospital. A review of histopathological records of the orbital tumors operated between 1993 and 2011 was done. The clinical, imaging and histopathological details of cases of orbital schwannoma were analyzed. Forty-nine cases of orbital schwannomas identified. The age ranged from 8 to 65 years with a female preponderance. The median duration of symptoms was 3 years. Computed tomography findings varied from a hypodense to hyperdense lesion with nil to marked contrast enhancement. USG demonstrated a defined lesion with variable internal reflectivity. Varied proportions of Antoni A and Antoni B areas were found on histopathology of the masses. Hypodense or cystic areas on imaging significantly correlated with Antoni B areas on histopathology. Orbital schwannoma is a rare tumor. The incidence of schwannoma in our institution is 6.5 %. Variable imaging features were found. The definite diagnosis can be established on the basis of histopathological and immunohistochemical studies.

Disinsert, retract and rotate technique of plaque brachytherapy.

BACKGROUND: Plaque brachytherapy is commonly used in the management of choroidal melanomas. The surgical steps usually involve creating a conjunctival peritomy, fixing the recti muscles, with or without disinserting them based on the location of the lesion, and placing the plaque. The inferior oblique muscle is attached close to the macula, and in cases of perimacular or peripapillary lesions, the muscle needs to be sacrificed. PURPOSE: The authors here demonstrate a novel technique of placing radioactive plaque without disinserting the inferior oblique muscle in cases of perimacular or peripapillary choroidal melanomas. SYNOPSIS: The video demonstrates how the "disinsert, retract, and rotate technique" of brachytherapy plaque placement can be performed and what are the fundamentals behind this technique. The authors have performed this procedure multiple times and there has been no incidence of plaque tilt or migration. HIGHLIGHTS: In perimacular and peripapillary choroidal melanoma brachytherapy plaque placement, the inferior oblique muscle can be spared. The simple technique does not lead to any tilt or migration of the radioactive plaque. VIDEO LINK: https://youtu.be/YMIg3rYyp2o.

Adjuvanted subunit intranasal vaccine prevents SARS-CoV-2 onward transmission in hamsters.

Most COVID-19 vaccine trials have focused on recipient protection, not protection of their contacts, a critical need. As a subunit intranasal COVID-19 vaccine reduced nasopharyngeal virus more than did an intramuscular (IM) vaccine, we hypothesized that this vaccine might reduce onward transmission to others. We vaccinated hamsters with either the IM-administrated Moderna mRNA vaccine twice or one dose of mRNA IM followed by adjuvanted subunit intranasal vaccine. 24 hours after SARS-CoV-2 challenge, these animals were housed with naïve recipients in a contactless chamber that allows airborne transmission. Onward airborne transmission was profoundly blocked: the donor and recipients of the intranasal vaccine-boosted group had lower oral and lung viral loads (VL), which correlated with mucosal ACE2 inhibition activity. These data strongly support the use of the intranasal vaccine as a boost to protect not only the vaccinated person, but also people exposed to the vaccinated person, a key public health goal. Author summary: Natural transmission of SARS-CoV-2 is primarily airborne, through the respiratory mucosal route. However, current licensed COVID-19 vaccines are all intramuscular and induce more systemic than mucosal immunity. Here, we did a head-to-head comparison of COVID-19 booster vaccines on SARS-CoV-2 onward transmission. We found that compared to boosting with a Moderna mRNA systemic vaccine, a nanoparticle intranasal COVID-19 vaccine much more effectively prevents onward airborne transmission to naïve recipient hamsters. The protection was correlated with local mucosal antibody. Thus, a mucosal nanoparticle vaccine should be considered for preventing onward airborne transmission, a key public health necessity that has not been adequately studied.

Strong immunogenicity & protection in mice with PlaCCine: A COVID-19 DNA vaccine formulated with a functional polymer.

DNA- based vaccines have demonstrated the potential as a safe and effective modality. PlaCCine, a DNA-based vaccine approach described subsequently relies on a synthetic DNA delivery system and is independent of virus or device. The synthetic functionalized polymer combined with DNA demonstrated stability over 12 months at 4C and for one month at 25C. Transfection efficiency compared to naked DNA increased by 5-15-fold in murine skeletal muscle. Studies of DNA vaccines expressing spike proteins from variants D614G (pVAC15), Delta (pVAC16), or a D614G + Delta combination (pVAC17) were conducted. Mice immunized intramuscular injection (IM) with pVAC15, pVAC16 or pVAC17 formulated with functionalized polymer and adjuvant resulted in induction of spike-specific humoral and cellular responses. Antibody responses were observed after one immunization. And endpoint IgG titers increased to greater than 1x 105 two weeks after the second injection. Neutralizing antibodies as determined by a pseudovirus competition assay were observed following vaccination with pVAC15, pVAC16 or pVAC17. Spike specific T cell immune responses were also observed following vaccination and flow cytometry analysis demonstrated the cellular immune responses included both CD4 and CD8 spike specific T cells. The immune responses in vaccinated mice were maintained for up to 14 months after vaccination. In an immunization and challenge study of K18 hACE2 transgenic mice pVAC15, pVAC16 and pVAC17 induced immune responses lead to decreased lung viral loads by greater than 90 % along with improved clinical score. These findings suggest that PlaCCine DNA vaccines are effective and stable and further development against emerging SARS-CoV-2 variants is warranted.

AZD3152 neutralizes SARS-CoV-2 historical and contemporary variants and is protective in hamsters and well tolerated in adults.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in variants that can escape neutralization by therapeutic antibodies. Here, we describe AZD3152, a SARS-CoV-2-neutralizing monoclonal antibody designed to provide improved potency and coverage against emerging variants. AZD3152 binds to the back left shoulder of the SARS-CoV-2 spike protein receptor binding domain and prevents interaction with the human angiotensin-converting enzyme 2 receptor. AZD3152 potently neutralized a broad panel of pseudovirus variants, including the currently dominant Omicron variant JN.1 but has reduced potency against XBB subvariants containing F456L. In vitro studies confirmed F456L resistance and additionally identified T415I and K458E as escape mutations. In a Syrian hamster challenge model, prophylactic administration of AZD3152 protected hamsters from weight loss and inflammation-related lung pathologies and reduced lung viral load. In the phase 1 sentinel safety cohort of the ongoing SUPERNOVA study (ClinicalTrials.gov: NCT05648110), a single 600-mg intramuscular injection of AZD5156 (containing 300 mg each of AZD3152 and cilgavimab) was well tolerated in adults through day 91. Observed serum concentrations of AZD3152 through day 91 were similar to those observed with cilgavimab and consistent with predictions for AZD7442, a SARS-CoV-2-neutralizing antibody combination of cilgavimab and tixagevimab, in a population pharmacokinetic model. On the basis of its pharmacokinetic characteristics, AZD3152 is predicted to provide durable protection against symptomatic coronavirus disease 2019 caused by susceptible SARS-CoV-2 variants, such as JN.1, in humans.

Giant cell reparative granuloma of the orbit.

Giant cell reparative granuloma is a rare fibro-osseous benign lesion. Only a few isolated cases of giant cell reparative granuloma of the orbit have been reported previously. The authors report an interesting case of giant cell reparative granuloma of the orbit in an 8-year-old girl. Surgical resection was performed, and no recurrence was noted at 18-month follow up.

Clinicopathologic review of epithelial tumors of the lacrimal gland.

OBJECTIVE: To study the clinicopathologic features of epithelial tumors of the lacrimal gland diagnosed at a tertiary care center in India during a 10-year period. METHODS: Medical records of cases with histopathologically proven epithelial tumors of the lacrimal gland were reviewed for demographic details and clinical features at the time of presentation. For histopathologic findings, slides with hemotoxylin and eosin-stained sections of the tumors were reviewed. Special stains, including histochemical and immunohistochemical stains, and additional sections were studied, whenever needed. RESULTS: Of 66 cases with epithelial tumors of the lacrimal gland identified during the study period, 50 (76%) cases were benign and 16 (24%) cases were malignant tumors. Histopathologic examination was consistent with the diagnosis of pleomorphic adenoma (PA) in all 50 cases of benign tumors. The mean age at diagnosis in PA cases was 37.7 years. Microscopic examination of PA tumors showed cystic degeneration in 18 (36%) cases, squamous metaplasia in 16 (32%) cases, calcification in 6 (12%) cases, and ossification in 1 (2%) case. Among malignant tumors, adenoid cystic carcinoma (ACC) was the most common tumor (n = 12, 18%), with an average age at diagnosis of 32.4 years. Microscopic examination of ACC revealed that most cases were grade I tumors. Solid areas were noted in 4 (33.3%) cases and perineural invasion was identified in 2 (16.7%) cases. Other malignant tumors included 1 case each of carcinoma ex-PA (1.5%), lacrimal duct carcinoma (1.5%), mucoepidermoid carcinoma (1.5%), and basal cell adenocarcinoma (1.5%). CONCLUSIONS: As far as the authors are aware, this is the largest series on clinicopathologic features of epithelial tumors of the lacrimal gland from South Asia. The incidence of PA was significantly higher in this study than reported in the Caucasian population. Among malignant tumors, ACCs were the most common, although rare tumors were also identified.

Mature orbital teratoma with an ectopic tooth and primary anophthalmos.

PURPOSE: To describe the clinicopathologic features and management of an unusual case of orbital teratoma. METHODS: A 7-year-old girl presented with a history of an orbital mass since birth. CT scan showed a large mass lesion involving the right orbit, with absence of the eyeball. An ectopic tooth was identified within the tumor. Lid-sparing exenteration surgery was performed. RESULTS: Histopathologic examination of the excised mass showed presence of elements from all three germ layers, consistent with a diagnosis of mature orbital teratoma. Normal ocular structures were not identified on histopathology. At one year follow-up, there was no tumor recurrence. CONCLUSION: We report an extremely rare and interesting case of a mature orbital teratoma, which was associated with primary anophthalmos and an ectopic tooth.

Orbital retinoblastoma in an adult.

PURPOSE: Retinoblastoma is usually seen in children before 5 years of age. We report an unusual case of retinoblastoma in an adult who presented to us with an orbital mass. METHODS: A 24 year-old-male presented to our centre with a history of protrusion of the right eye for 6 months, and associated loss of vision. Ultrasonography B-scan revealed an intraocular mass with calcification and MRI of the orbits showed extra-ocular spread. An incisional biopsy was taken from the orbital mass. RESULTS: On biopsy, histopathologic features and immunohistochemical stains were consistent with retinoblastoma. CONCLUSION: To our knowledge, this is the first report of retinoblastoma presenting as an orbital mass in adulthood and highlights the importance of considering this tumour in the differential diagnosis of an intraocular mass with orbital extension in an adult patient.

Conjunctivodacryocystorhinostomy using a high-density porous polyethylene-coated tear drain tube.

To evaluate the outcome of conjunctivodacryocystorhinostomy using a high-density porous polyethylene (HDPP)-coated tear drain tube. Patients with epiphora due to a proximal lacrimal system block were included in a prospective interventional case study. A total of 22 eyes were treated with lacrimal bypass surgery using the HDPP-coated tube. On follow-up (12-41 months), 21 eyes had a patent well-positioned tube with subjective relief of epiphora. In one eye, a loose sleeve was noted during surgery. The tube dislodged postoperatively and was removed. A high success rate with only a few minor complications is achievable using a HDPP-coated tear drain tube for lacrimal bypass surgery. Long-term follow-up is required to look for tube blockage due to conjunctival or nasal mucosal overgrowth.

Correlation between clinical features, magnetic resonance imaging, and histopathologic findings in retinoblastoma: a prospective study.

OBJECTIVE: To correlate clinical features with histopathology findings in advanced intraocular retinoblastoma and to determine the diagnostic accuracy of magnetic resonance imaging (MRI) in detecting tumor invasion. DESIGN: Prospective, nonrandomized case series. PARTICIPANTS: We included 75 patients with group E retinoblastoma. METHODS: Demographic and clinical features were recorded at presentation. Contrast-enhanced MRI was performed to study tumor characteristics and extent of invasion. Primary enucleation was performed and histopathologic features noted. Statistical analysis was done using the Kruskal-Wallis test to determine correlation between clinical features and histopathology. Sensitivity, specificity, and accuracy of MRI in detecting tumor invasion were determined. MAIN OUTCOME MEASURES: Significant associations between clinical findings at presentation and high-risk histopathology, and correlation between MRI results and histopathologic evidence of tumor invasion. RESULTS: A significant association was found between iris neovascularization and choroidal invasion (P = 0.032), intraocular pressure and optic nerve invasion (P = 0.034), and shallow anterior chamber and iris invasion (P = 0.021). Corneal diameter did not show any significant correlation with high-risk histopathology. On MRI, tumor volume showed a significant association with optic nerve invasion (P = 0.023). The accuracy of MRI in detecting choroidal invasion was 68% (sensitivity, 60%; specificity, 80%). Prelaminar invasion was correctly identified in 9 out of 15 eyes (accuracy, 84%; sensitivity, 60%; specificity, 90%), whereas the accuracy of MRI in detecting postlaminar invasion was 76% (sensitivity, 61.9%; specificity, 81.5%). Ciliary body invasion was correctly identified in 5 out of 7 eyes (accuracy, 93.3%; specificity, 95.6%) and scleral invasion in 5 out of 6 eyes (accuracy, 98.7%; specificity, 100%). CONCLUSIONS: As far as we are aware, this is the first prospective study on the correlation of clinical features and MRI findings with histopathologic risk factors in eyes primarily enucleated for retinoblastoma. Neovascularization of iris, intraocular pressure, shallow anterior chamber, and tumor volume correlated well with high-risk histopathology. Because MRI has limitations in reliably predicting microscopic infiltration of the choroid and optic nerve, decision in favor of neoadjuvant chemotherapy on the basis of suspected postlaminar invasion on MRI is not justified in the absence of histopathologic evidence of disease.

Clinical predictors of high risk histopathology in retinoblastoma.

BACKGROUND: Previous studies show that clinical features at presentation, in retinoblastoma patients, like glaucoma and neovascularization of iris are associated with a higher incidence of high risk histopathology findings (HRF) in enucleated eyes. Herein, we analyze association between clinical features at time of enucleation and occurrence of HRF including invasion of anterior chamber, iris, ciliary body, choroid (massive), sclera, extrascleral tissue, optic nerve beyond lamina cribrosa, and optic nerve cut end, in a large series of eyes enucleated for retinoblastoma. PROCEDURE: We retrospectively studied demographic, clinical, and histopathology findings in all retinoblastoma patients who underwent primary enucleation at our center, over a 5 years duration. Statistical analysis was done to find any association between clinical features at presentation and the presence of HRF. RESULTS: Three hundred twenty-six eyes were studied. Median age of presentation was 2 years. Glaucoma was the most common clinical finding at presentation apart from leucocoria. Out of 326 enucleated eyes, 28 (8.6%) had extrascleral and/or optic nerve transection invasion. Among remaining 298 eyes, with completely resected tumor, 115 (38.6%) had massive choroidal invasion, 54 (17%) had retrolaminar optic nerve invasion, and 24 (7%), 29 (9%), and 23(7%) had anterior chamber, iris, and ciliary body invasion, respectively. Age more than 2 years, lag period more than 3 months, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were associated with occurrence of three or more HRF on univariate analysis. CONCLUSIONS: Clinical variables including older age, longer lag period, hyphema, pseudohypopyon, staphyloma, and orbital cellulitis were strongly associated with occurrence of HRF in this study.

Moxifloxacin resistance: intrinsic to antibiotic or related to mutation?

PURPOSE: To evaluate and compare the pattern of resistance to topical moxifloxacin of ocular isolates recovered during comparable periods within 2 years. METHODS: Records of 611 consecutive cases of bacterial corneal ulcers that presented to our center between April and August 2007 were compared with records of 417 cases that presented in April and August 2006. Records of culture and sensitivity to cefazolin, tobramycin, gatifloxacin, and moxifloxacin at the time of presentation were analyzed. Parameters recorded included total number of cases in each period, culture-positive cases, organisms isolated, and sensitivity by Kirby-Bauer disk-diffusion test. The data from 2007 was compared with those from 2006 using χ test. RESULTS: Culture-positive rate was 70.2% in 2007 compared with 65.0% in 2006 (p = 0.143). The percentage of culture-positive cases resistant to moxifloxacin was 5.46% in 2007 compared with 5.42% in 2006 (p = 0.977). There was no significant difference between resistance against cefazolin during the two periods (p = 0.895). Resistance to gatifloxacin and tobramycin was significantly higher in samples tested in 2007 as compared with those tested in 2006 (gatifloxacin, p = 0.037; tobramycin, p = 0.031). CONCLUSIONS: Resistance to moxifloxacin did not change significantly during a period of 2 years in our study. The static resistance pattern to moxifloxacin may indicate that such resistance to moxifloxacin is intrinsic in the antibiotic rather than new resistance stemming from mutations.